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Laura Manuelidis is a physician and neuropathologist at Yale University.
Career
Dr. Manuelidis earned her B.A. degree from Sarah Lawrence College, where she studied poetry, and her M.D. from Yale Medical School. She is head of the section of Neuropathology in the department of Surgery at Yale. She is also on the faculty of Neurosciences and Virology. Her major contributions include the discovery of complex repeated DNAs at centromeres and on chromosome arms (LINES) in large Giemsa bands that define tissue specific genes. She also illuminated the compact 3-D organization and structure of individual chromosomes in the interphase nucleus (not spaghetti-like chromatin) by developing high resolution non-isotopic in-situ hybridization, and further demonstrated positional specificity in different functional cell types, such as neurons and glia
Achievements
The Manuelidis lab was the first to serially transmit any form of human Creutzfeldt–Jakob disease (CJD) to small rodents. This made it possible to elucidate fundamental mechanisms of infection, including infectious agent uptake and spread by myeloid cells of the blood, lack of maternal transmission, and major strain differences of human Transmissible Spongiform Encephalopathy (TSE) agents such as sporadic CJD, kuru of New Guinea, bovine-linked vCJD in the UK, and Asiatic CJD. Her development of monotypic tissue cultures infected by many different human and sheep scrapie TSE strains along with rapid quantitative assays of infectivity showed that PrP band patterns are cell-type dependent and not specific for the agent-strain. TSE agents replicate every 24 hrs in culture in contrast to their slow replication in brain that has many complex host immune system controls.
Prion Hypothesis
She has challenged the dominant explanation that the host prion protein (PrP), without any nucleic acid, is the causal infectious agent in TSEs. The prion hypothesis was put forth by Stanley B. Prusiner, who won the 1997 Nobel Prize in Physiology or Medicine. In contrast to the amyloid or "infectious form of host PrP", Manuelidis and colleagues showed that infectious CJD brain particles separated from most prion protein with a homogeneous viral density and size, and disruption of CJD nucleic acid-protein complexes destroys infectivity. Comparable 25 nm particles were identified within CJD and scrapie infected cell cultures, but not in uninfected controls. As with 25 nm brain particles, the culture particles did not bind PrP antibodies.
Manuelidis stated that, "Although much work remains to be done, there is a reasonable possibility these are the long sought viral particles that cause transmissible spongiform encephalopathies. The [prion] is probably not infectious, but is a pathological result [of] an infectious virus binding to this host protein.". Much additional recent evidence points to an exogenous source of infectious TSE agents and the claim that recombinant PrP can be made infectious has not been reproduced. In fact, one can remove all detectable forms of PrP from infectious brain particles, yet the brain particles retain their high infectivity. Thus, PrP may not be an integral component of the infectious agent, but instead a host susceptibility factor. Additionally, nucleases that have no effect on PrP are able to obliterate particle-associated nucleic acids and destroy >99% of their infectivity. These findings suggest that TSE agents are viruses that require protected genetic material to infect their hosts. Although novel circular SPHINX DNAs from the microbiome were identified in isolated infectious particles, their role in infection and/or disease is not yet clear.
See also
Frank Bastian
Stanley Prusiner
Prion
Slow virus
Virino
Spiroplasma
References
External links
http://medicine.yale.edu/lab/manuelidis/index.aspx
Sarah Lawrence College alumni
American women biochemists
Prions
Living people
Yale School of Medicine alumni
Year of birth missing (living people)
American pathologists
21st-century American women | en | apollo | train |
These data suggest that aAG appears to be associated with the progression of CKD. aAG might be an independent predictor of CKD progression. | en | apollo | train |
The effective method for investigation meridian tropism theory in rats.
This present work describes an effective new method for study traditional Chinese medicine (TCM) on meridian tropism (MT) theory, which plays an essential role in clinical selection of TCM according to syndromes and strengthens the therapeutic effects. The new thread included material basis foundation and its tissue distribution study. Xiheliu, the most popular TCM on heart tropism, was investigated by simple and accurate high performance liquid chromatography (HPLC) method. The analysis of plasma after oral administration the total flavonoid of Xiheliu (TFX) exhibited that tamarixetin and kaempferide had the highest concentration and approximately the highest level within 25 min. The mixture of them could last accelerating the urine excretion more than 7 h after a single dose and could not cause the disorder of ion in rats, which was observed in diuretic activity experiment. In view of the reported biological activities was consistent with the effects of Xiheliu, tamarixetin and kaempferide were likely to be the material basis of it. Tissue distribution study showed that the highest level of analytes was in heart, lung, kidney and liver, and most tissues reached maximum level at 30 min post-dose. Since liver was the most important blood-supply tissue, the result of this experiment was in accordance with the MT record of Xiheliu and confirmed that tamarixetin and kaempferide was the material bases of it on MT. This is the first report for the illumination of material basis and the mechanism of Xiheliu on MT by analysis the record of Xiheliu in Compendium of Materia Medica and experimental study. | en | apollo | train |
Most TENS devices use biphasic electrical pulse waveforms, resulting in zero net current flow between the electrodes and thus preventing skin irritation.14.3 Fibre recruitment by increasing the amplitude of electrical currents administered during conventional TENS.Fig.In theory, TENS frequencies below 200 pps should be optimal.In 1965, Melzack and Wall provided a physiological rationale for electro-analgesia and this was followed by clinical observations that chronic pain could be relieved in patients by electrical stimulation of nerve fibres in the skin, dorsal columns in the spinal cord and periaquaductal grey in the midbrain. Initially, TENS was used to predict the success of spinal cord stimulation implants but it was quickly realized that TENS could be used successfully as a treatment in its own right. The purpose of TENS is to selectively activate different populations of nerve fibres to initiate physiological responses that lead to pain relief. As the current amplitude of TENS is increased, large diameter myelinated non-nociceptive axons (Aβ) are activated first because they have lower thresholds of excitation (Fig. 14.3). The sensation experienced beneath the electrodes is often described as a 'tingling' or 'pins and needles' sensation (electrical paraesthesia) with an intensity that is non-painful. If current amplitude is increased further smaller diameter myelinated (Aδ) and unmyelinated (C-fibre) afferents become active and the user experiences a painful sensation, which is not desirable. Activation of low threshold (Aβ) axons without concurrent activation of higher threshold (Aδ and C-fibre) afferents is achieved using currents with small amplitudes (i.e. low intensity) and pulse durations between 50 and 500 μs. More nerve impulses can be generated in the axon by increasing the pulse frequency of TENS, although at higher frequencies this is limited by the absolute and relative refractory periods for the axon. In theory, TENS frequencies below 200 pps should be optimal. Fig. 14.3 Fibre recruitment by increasing the amplitude of electrical currents administered during conventional TENS. Most TENS devices use biphasic electrical pulse waveforms, resulting in zero net current flow between the electrodes and thus preventing skin irritation.Also, skin offers high impedance to TENS so currents tend to remain superficial and stimulate cutaneous rather than deep-seated tissue.By reducing pulse duration and placing electrodes over muscles or muscle efferents it is possible to generate muscle contractions without a strong TENS sensation. | en | apollo | train |
For women with early pregnancy body weight outside of 50-90 kg, consider adjusted LMWH dosing. - There is limited evidence to guide the most appropriate dose in obese patients but standard dosing may be inadequate. - Clinicians should refer to their local or jurisdictional guidance on additional VTE risk factors.
For postpartum women who have had COVID-19 during pregnancy, consider using at least 14 days of prophylactic dosing of anticoagulants, preferably LMWH (eg, enoxaparin 40 mg once daily or dalteparin 5000 IU once daily) unless there is a contraindication, such as risk for major bleeding. Increased duration of six weeks should be considered if severe or critical COVID-19 and/or additional risk factors for VTE are present (consensus recommendation) - Dosing of LMWH is dependent on pre-pregnancy body weight and current renal function. For women with early pregnancy body weight outside of 50-90 kg, consider adjusted LMWH dosing. - There is limited evidence to guide the most appropriate dose in obese patients but standard dosing may be inadequate.
# Discussion
The treatment of COVID-19 is a rapidly expanding area of research, with an unprecedented global effort underway. However, with more than 53 000 COVID-19 articles in PubMed, as well as 2100 systematic review protocols and 1600 trial protocols registered online in less than eight months, it is increasingly difficult for clinicians to remain up-to-date on important developments. | en | apollo | train |
In addition to patients in whom it is obvious that admission is necessary at the end of the ED stay, other predictors of those warranting hospitalization include a significant medical history (OR = 2.1, 95% CI 1.1-4.3) and greater than one ALTE in 24 hours (OR = 2.1, 95% CI 1.2-4.6).In a retrospective patient review of 196 ALTE patients, there were no deaths.163 The follow-up revealed a high percentage of asthma and seizures, as well as GERD necessitating Nissen fundoplication. Infants who survive an ALTE generally do well in follow-up. However, some rare complications do occur, including pulmonary edema, aspiration pneumonia, and neurologic sequelae secondary to hypoxia.166
Multiple studies show that 84% of patients with ALTE are admitted by emergency physicians for evaluation and monitoring. Based on the results of a study of 59 infants with ALTE, Claudius and Keens developed a clinical decision rule suggesting that infants younger than 1 month of age and those with recurrent ALTE should be admitted for evaluation, but other well-appearing children with ALTE may be discharged with close follow-up.167 Mittal and colleagues showed in a cohort of 300 infants with ALTE that premature birth (relative risk [RR] 2.8, 95% CI 1.5-5.1); absence of choking (RR 2.6, 95% CI 1.4-4.7), color change to blue (RR 2.1, 95% CI 1.2-3.8), and abnormal examination findings in ED (RR 2.8, 95% CI 1.6-4.9) were significantly associated with the need for admission.168 Fu and Moon suggest other conditions under which it may be safe to discharge a patient with an ALTE, and these include the following: (1) the episode is brief, nonsevere, and self-resolving; (2) the cause is probably a nonprogressive condition such as GERD; and (3) the infant has no comorbidities and appears well.170 Kaji and others170a developed and validated a clinical decision rule for ALTE in 832 infants. In addition to patients in whom it is obvious that admission is necessary at the end of the ED stay, other predictors of those warranting hospitalization include a significant medical history (OR = 2.1, 95% CI 1.1-4.3) and greater than one ALTE in 24 hours (OR = 2.1, 95% CI 1.2-4.6).## Sudden Infant Death Syndrome
The National Center for Health Statistics reports that SIDS is the third leading cause of death in infants, accounting for 8% of deaths in children younger than 1 year.171 SIDS may occur at any time during the first 2 years of life, but it is rare (1%) in children younger than 1 month and in those older than 1 year (2%). | en | apollo | train |
Isolation and electrophoretic study on Mallory bodies from the livers of alcoholic cirrhosis.
Mallory bodies (MBs) were isolated from the livers of eight alcoholic patients. The method consisted of homogenization, velocity sedimentation in 60 per cent sucrose solution and two-phase polymer centrifugation using a polyethylene glycol-dextran system. MBs were isolated in large quantity and high purity (more than 95 per cent in some cases). Isolated MBs maintained the characteristic filamentous structures. They were solubilized in 6 M guanidine hydrochloride in 10 per cent or 1 per cent acetic acid by sonication or in 1 per cent sodium dodecyl sulfate with 5 per cent 2-mercaptoethanol and 8 M urea. The solubilized MB protein produced three peaks on Sephadex G-100 chromatography and at least five intense protein bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The fractions from control livers contained several bands which were identical with the major components of isolated MB protein. These findings suggest that MBs are not homogeneous protein, but that they are probably complexes of various proteins, and that some components of MBs are present in normal hepatocytes. The exact nature of MBs has yet to be established. | en | apollo | train |
Tumor vascularization is an important control point in cancer progression and its inhibition is a promising approach to cancer therapy. Stromal-derived factor-1 alpha (SDF-1 alpha or CXCL12) is a chemoattractant for lymphocytes, hematopoietic progenitor cells, and vascular endothelial cells. SDF-1 alpha binds to the CXCR4 receptor on cell surfaces and to heparan sulfate in cell membranes and the extracellular matrix. We hypothesized that SDF-1 alpha is an important mediator of tumor vasculogenesis, recruiting bone marrow-derived endothelial progenitor cells to tumors. We evaluated the role of SDF-1 alpha in the adhesion of bone marrow-derived lineage-negative cells to the murine Lewis lung adenocarcinoma (LLCaB subclone), both in vitro and in vivo. LLCaB lung and liver metastases expressed significantly elevated levels of SDF-1 alpha compared to normal tissue from naive controls and primary tumors. SDF-1 alpha expression inversely correlated with tumor size, implicating involvement in early tumor development. SDF-1 alpha was detected on ~30% of blood vessels in primary and metastatic tumors by double immunocytochemistry staining and on endothelial cells within primary cultures of dissociated LLCaB tumors (DTC). Lineage-negative BMC enriched for Sca1+cKit+ (LSK) cells, including endothelial progenitors and CXCR4+ cells, were used for subsequent adhesion studies. LSK cells preferentially adhered in vitro to DTC, compared to other target cell types. Pre-incubation with anti-CXCR4 antibody or the CXCR4 antagonist AMD3100 decreased adhesion of LSK cells by 50%. Biolocalization of adoptively-transferred EGFP-Lineage-negative BMC in tumor-bearing wild-type mice was evaluated by qPCR for the egfp-transgene. A significantly greater number of Lineage-negative BMC localized to metastases 2-3 days after intravenous injection than to adjacent healthy tissue, normal organs, or primary tumors. Control CXCR4-negative EGFP-dermal fibroblasts showed significantly less tumor localization. One-week post-injection, Lineage-negative BMC were still detected in every metastasis, suggesting that BMC were retained and/or had replicated. These data support the hypothesis that the biolocalization of circulating Lineage-negative BMC to tumors is SDF-1 alpha-mediated. We have also put forth the novel proposal that SDF-1 alpha promotes early tumor vasculogenesis as a tumor endothelium-associated adhesion molecule for circulating CXCR4+ Lineage-negative BMC. These findings may aid our understanding of the mechanism of tumor vascularization and the design of tumor-targeted therapy.
Joshi, Molishree Umesh. THE ROLE OF SDF-1[alpha] AS A VASCULOGENIC CHEMOKINE AND ENDOTHELIUM-ASSOCIATED CELL ADHESION MOLECULE FOR THE RECRUITMENT OF BONE MARROW-DERIVED PROGENITOR CELLS TO DEVELOPING TUMORS. Doctoral Dissertation. East Carolina University, January 2010. The Scholarship. http://hdl.handle.net/10342/2953. April 24, 2019.
Joshi, Molishree Umesh, “THE ROLE OF SDF-1[alpha] AS A VASCULOGENIC CHEMOKINE AND ENDOTHELIUM-ASSOCIATED CELL ADHESION MOLECULE FOR THE RECRUITMENT OF BONE MARROW-DERIVED PROGENITOR CELLS TO DEVELOPING TUMORS” (Doctoral Dissertation., East Carolina University, January 2010).
Joshi, Molishree Umesh. THE ROLE OF SDF-1[alpha] AS A VASCULOGENIC CHEMOKINE AND ENDOTHELIUM-ASSOCIATED CELL ADHESION MOLECULE FOR THE RECRUITMENT OF BONE MARROW-DERIVED PROGENITOR CELLS TO DEVELOPING TUMORS [Doctoral Dissertation]. Greenville, NC: East Carolina University; January 2010. | en | apollo | train |
QR Pharma Inc (QR Pharma) is a pharmaceutical company that develops novel drugs for the treatment of alzheimer's disease, parkinson's disease and neurodegenerative disorders. The company's product candidate includes posiphen, which inhibits the translation of amyloid precursor protein. Its Posiphen inhibits synthesis of amyloid precursor protein (APP), Tau and a-Synuclein. QR Pharma also develops drugs for huntington's disease, down syndrome, traumatic brain injury and post operative cognitive decline. The company works in partnership with laboratories for technical support to further its pipeline. QR Pharma is headquartered in Chester, Pennsylvania, the US.
QR Pharma Inc-Pharmaceuticals & Healthcare-Deals and Alliances Profile provides you comprehensive data and trend analysis of the company's Mergers and Acquisitions (M&As), partnerships and financings. The report provides detailed information on Mergers and Acquisitions, Equity/Debt Offerings, Private Equity, Venture Financing and Partnership transactions recorded by the company over a five year period. The report offers detailed comparative data on the number of deals and their value categorized into deal types, sub-sector and regions.
QR Pharma Inc, Deal Analysis, Mergers, Acquisitions, Asset Purchases, Asset Divestitures, Company Divestitures, Equity Offerings, Capital Raising, Debt Offerings, IPOs, Initial Public Offering, Private Placement, Private Investment In Public Equities, Secondary Offerings, Follow-On Offerings, Debt Private Placement, Public Debt Placement, Partnerships, Joint Venture, Licensing Agreements, Co-Marketing Agreements, Upfront Payment, Milestone Payment, Phases, Clinical Trials, Private Equity, Venture Capital, PE,VC, Asset Finance, Project Finance, Tax Equity Financing, Bond Financing, Lease Financing, New Build Financing, Deal Analysis By Market/sector, Deal Analysis By Geography, Deal Analysis By Deal Types, Key Employees, Locations And Subsidiaries, Competitors, Recent News, Company Overview, Key Facts, Deals By Year, Deal Details, Recent Developments, Significant Developments. | en | apollo | train |
The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1) is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases.
Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i) the degree of inflammation at day 7; and ii) indexes of fibrosis (assessed by deposition of hydroxyproline in the lung) at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-β1, IFN-γ and TNF-α generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21) or therapeutically (from day 14 onward), ameliorated both signs of inflammation and fibrosis.
Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.
Pulmonary fibrosis, a severe pathological outcome associated with several lung diseases, can be commonly reproduced by intratracheal instillation of bleomycin, a cytotoxic chemotherapeutic agent. The tissue remodeling that ensues is characterized by severe inflammation (evident from edema and leukocyte migration) and a delayed phase with fibroblast proliferation and excess matrix deposition . The pathological events leading to pulmonary fibrosis have been attributed to an overproduction of interstitial collagens by cytokine-activated fibroblasts ; moreover, though a variety of cytokines have been implicated in fibroblast activation, a paramount causative role for transforming growth factor (TGF)-β1 has emerged. This cytokine activates fibroblast differentiation into myofibroblasts and stimulates extracellular matrix (ECM) production . However, besides its pro-fibrotic properties, TGF-β1 exerts a number of other homeostatic functions in immune and cancer biology , so that inhibition of TGF-β1 would provoke a series of adverse effects, making it not that valuable as a therapeutic approach. Other therapeutic interventions include anti-inflammatory drugs (e.g. glucocorticoids as prednisone) that are effective to relieve disease without halting fibrosis progression. Anti-fibrotic drugs do not improve lung function or life expectancy and their use may also be associated with harmful side effects . Nonetheless, our knowledge on the underlying mechanisms of pulmonary fibrosis is increased, and this might help for the identification of targets amenable for the development of novel therapies .
There is great interest on biochemical pathways centered on endogenous inhibitors endowed with counter-regulatory and protective functions . Most of these studies have focused on acute inflammation, elucidating endogenous anti-inflammatory pathways that operate in parallel, and sometimes in a time-delayed fashion, to the more widely studied pro-inflammatory mediators, to ensure rapid resolution of the host response with return to tissue homeostasis . One line of research has focused on the glucocorticoid-regulated protein annexin A1 (AnxA1; 346 amino acids long; 37 kDa protein), a potent modulator of leukocyte trafficking/transmigration in acute and chronic inflammation [10, 11], with a particular ability to inhibit the leukocyte/endothelium interaction in the microvasculature . Characterization of an AnxA1 null mouse colony has revealed, upon stimulation, a dysregulation of pathophysiological mechanisms, with an exacerbation of acute and chronic experimental inflammatory responses [12–15].
The AnxA1 protein is highly expressed in the airways, both in human/animal alveolar macrophages and epithelial cells [16–18], a finding explained by constitutive gene promoter activity in bronchial epithelium and lung endothelial cells [12, 15]. The AnxA1 anti-inflammatory effects can be replicated by a shorter peptide spanning the first 25 amino acids, termed peptide Ac2-26. Both AnxA1 and its N-terminal derived peptides exert potent regulation of the inflammatory reaction by activating its receptor, the formyl-peptide receptor (FPR) [19–21], with consequent inhibition of white blood cell trafficking and promotion of efferocytosis [22, 23]. Of interest in the context of lung inflammation, down-regulation of endogenous AnxA1 expression has been noted in the bronchoalveolar lavage (BAL) fluid of cystic fibrosis patients . More recently, blockade of the transmembrane conductance regulator protein (CFTR) led to the release of AnxA1 from human and mouse neutrophils, a finding associated with an altered acute inflammatory reaction .
Against this background, the present study was undertaken to compare cellular, tissue and macroscopic alterations observed in the model of bleomycin-induced lung fibrosis in wild type and AnxA1 null mice. Moreover, the pattern of expression of the endogenous protein and gene promoter activity were monitored, and the pharmacological potential of AnxA1 peptido-mimetic was assessed.
Male C57bl/6 wild type and AnxA1 null mice [14, 15] (20-25 g of body weight), maintained on a standard chow pellet diet with tap water ad libitum, were used for all experiments. Animals were housed at a density of five animals per cage in a room with controlled lighting (lights on from 8:00 a.m. to 8:00 p.m.) in which the temperature was maintained at 21-23°C. Animal work was performed according to UK Home Office regulations (Guidance on the Operation of Animals, Scientific Procedures Act 1986), Committee of Ethics in Animal Research, FAMERP, SP, Brazil (Protocol n°042407) and along the directives of the European Union.
Pulmonary fibrosis was induced by intratracheal (i.t.) administration of bleomycin (Blenoxane, Mead Johnson, Princeton, NJ) suspended in sterile phosphate-buffered saline (PBS) at 0.15 U/Kg. Control mice received saline vehicle only (N = 5 per group). At different time post intratracheal injection (day 0, 7 and 21) mice were anesthetized with ketamine (Dopalen, Vetbrands, Brazil, 60%) and xylazine (Anasedan, Vetbrands, Brazil, 40%) solution (60 μL in total) for blood and BAL fluid collection. In some cases, animals were perfused with 20 mL of PBS to remove blood contents from tissues, and lung were collected and processed as described below. Animal survival was monitored daily up to 21 days post-bleomycin. In case of death, the experiments were repeated to achieve the minimal number of 5 animals per group.
In some cases, mice were treated daily with 1 mg/kg intraperitoneally (i.p.) of peptide Ac2-26 (Ac-AMVSEFLKQAWFIENEEQEYVQTVK; obtained from Tocris, Huissen, The Netherlands) starting immediately after the first dose of bleomycin (bleo+pep; N = 5). Another group of bleomycin-treated mice received the same dose and route of peptide Ac2-26 from day 14 to day 21 post-bleomycin (bleo+pep 14-21 d; N = 5). Control mice were treated daily with Ac2-26 (i.p.), but were i.t. treated with saline only instead of bleomycin. In all cases, animals were sacrificed at day 21 for lung histology and immunohistochemistry, and Western blotting analyses.
Wild type and AnxA1 null lungs were excised, fixed in 4% paraformaldehyde, 0.1 M sodium phosphate buffer (pH 7.4) for 2 h at 4°C; then, they were fragmented, washed, dehydrated in ethanol, clarified in xylene and embedded in paraplast™ (Sigma, USA). Histological sections were cut (Leica RM2265, Leica, GR), mounted on slides, and stained with Masson's Trichrome. Quantification of leukocyte numbers in tissue samples was performed by the point-counting technique with a high-power objective (×40) and measuring the area of analysis with the software Axiovision (Zeiss, GR). Data was reported as cells/mm2 (analyzing at least 10 distinct histological sections per mouse).
Total lung hydroxyproline contents were determined using a well-accepted assay . Briefly, samples of lung homogenate (500 μL) were added to 1 mL of 6 N hydrochloric acid for 8 h at 120°C. To a 5 μL sample of the digested lung, 5 μl of citrate/acetate buffer (5% citric acid, 7.2% sodium acetate, 3.4% sodium hydroxide, and 1.2% glacial acetic acid, pH 6.0) and 100 μL of chloramine-T solution (282 mg of chloramine-T, 2 ml of N-propanol, 2 ml of distilled water, and 16 mL of citrate/acetate buffer) were added. The resulting samples were then incubated at room temperature for 20 min before addition of 100 μl of Ehrlich's solution (Aldrich, Milwaukee, WI), 9.3 mL of N-propanol, and 3.9 mL of 70% perchloric acid. After a further incubation at 65°C samples for 15 min, samples were read at 550 nm in a DU640 spectrophotometer (Beckman, Fullerton, CA); hydroxyproline concentrations were then calculated from standard curve (0-100 μg/mL hydroxyproline).
Aliquots of blood (20 μL) obtained from the abdominal artery were diluted 1:10 in Turk's solution (0.1% crystal violet in 3% acetic acid) for cell quantification. After semi-excision of the trachea, a plastic cannula was inserted and airspaces were washed with 0.5 mL of 0.9% sodium chloride containing 2.6 mM EDTA with a 1 mL syringe. This operation was repeated twice. BAL was centrifuged (600 g for 10 min, 4°C) and the cell-free supernatants were frozen at -80°C for subsequent cytokine analysis. Cell pellets were re-suspended and an aliquot (190 μL) was diluted 20:1 in Turk's solution (3% crystal violet in 20% acetic acid) for cell quantification.
In both cases, total and differential counting was obtained with a Neubauer chamber using a ×40 objective in the light microscope Axioskop II mot plus (Zeiss, GR). BAL cells were distinguished in polymorphonuclear (PMN), mononuclear phagocytic cells (monocyte/macrophages - MPC) and lymphocytes (LY), whereas blood cells were divided into PMN, peripheral blood monocytes (PBMC) and LY.
Aliquots of blood and BAL fluids were centrifuged at 4000 and 600 g for 10 min, respectively. Concentrations of tumor necrosis factor (TNF)-α, transforming growing factor (TGF)-β and interferon (IFN)-γ were measured using specific enzyme-linked immunosorbent assay kits purchased from R&D System (Abingdon, UK).
AnxA1 protein expression in tissue cells was determined by immunohistochemistry, as reported . Briefly, wild type lung samples were fixed in 4% paraformaldehyde (in 0.1 M sodium phosphate buffer, 2 h at 4°C, pH 7.4) and embedded in LR Gold resin (London Resin, UK). Histological sections (1 μm thick) were blocked with 10% albumin bovine in PBS (PBSA), and a polyclonal rabbit anti-AnxA1 antibody (Zymed Laboratories) added (1:200 in 1% PBSA) overnight at 4°C. As negative control of the reaction, some histological sections of wild type lungs were incubated with non-immune rabbit serum (1:200 working dilution; Sigma-Aldrich) instead of the primary antibody. A goat anti-rabbit IgG (Fc fragment-specific) antibody conjugated to 5 nm colloidal gold (1:100; British BioCell International) was then added. Silver enhancing solution (British BioCell International) was used to augment gold particle staining and histological sections were counterstained with haematoxylin. Analysis of AnxA1 expression was conducted with an Axioskop II microscope (Zeiss, Germany). The stained area was analyzed densitometricaly with the Software Axiovision™ (Zeiss) to determine the values of AnxA1 in the cell. The generate values varied from 0 to 255 arbitrary units.
Spatial and temporal activation of Anxa1 gene promoter in lung was monitored with histochemical X-Gal staining, as reported , monitoring Prussian blue precipitation as a marker of LacZ gene activity [14, 15]. Briefly, tissues were fixed in 4% paraformaldehyde, 0.1 M sodium phosphate buffer, pH 7.4, for 2 h at 4°C, and washed in rinse buffer (0.1 M phosphate buffer pH 8, 2 mM magnesium chloride, 0.1% Triton X-100). Samples were stained overnight at 37°C with 5 mM potassium ferricyanide and 5 mM potassium ferrocyanide in rinse buffer containing 1 mg/mL 5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside and 4% dimethylformamide. Samples were then embedded in LR Gold™ resin for subsequent microscopy analysis. As a negative control for the reaction, wild type lungs were incubated with X-Gal staining. Densitometric analysis for X-Gal staining was performed densitometricaly with the Software Axiovision™ (Zeiss) in lung leukocytes and epithelial cells. The values generated varied from 0 to 255 arbitrary units.
Lung from control or experimental groups of wild type mice were homogenized in EDTA free protease inhibitor (Roche, UK). Protein concentrations were determined by the Bradford assay (Sigma), mixed 1:1 with Laemmli sample buffer , and equal protein amounts (30 μg) electrophoresed in a 10% polyacrylamide gel in running buffer (0.3% Tris base, 1.44% glycine, 0.1% SDS in distilled water) followed by transfer of proteins onto Hybond-C extra nitrocellulose membranes in transfer buffer (0.3% Tris base, 1.44% glycine, 20% methanol in distilled water). After membrane blocking with 5% non-fat milk solution in TBS containing 0.1% Tween 20, AnxA1 immunoreactivity was assessed using specific antibody to detect both cleaved (33 kDa) and intact protein (37 kDa) (1:1000; Invitrogen, USA). The signal was amplified with HRP-linked anti-mouse secondary antibody (1:2000; Amersham Biosciences, USA) and visualized by ECL (Western blotting detection reagent; Amersham Biosciences, USA).
In all cases data are reported as mean ± SEM of five mice per group. Statistical differences between groups were determined by ANOVA followed, if significant, by the Bonferroni test. In all cases, a probability value <0.05 was taken as significant. The survival rate was analyzed using Kaplan-Meier cumulative plots, and comparisons between groups were performed using a log-rank test.
We began this study by monitoring AnxA1 protein expression in wild type and gene promoter activity in AnxA1 null mice, both in bronchiolar epithelial cells, circulating and migrated leukocytes. Table 1 and 2 reports the cumulative data obtained from these densitometric analyses.
AnxA1 protein expression was analyzed, as described in Material and Methods, in wild type mice lung at 0, 7 and 21 days post-bleomycin i.t. administration. Also a group of mice were daily i.p. treated or post-treated with the peptide Ac2-26 as described in Material and Methods section. Values (densitometric units) are mean ± SEM of 10 histological tissue sections analyzed from five mice per group. * P < 0.05 versus sham group values. # P < 0.05 versus corresponding control group values. PMN, polymorphonuclear cells; MPC, monocyte/macrophages.
AnxA1 null mice were treated with bleomycin (0.15 U/Kg i.t.) at time 0 and lung collected at the reported time points. X-Gal staining was done as described in Material and Methods. Values (densitometric units) are mean ± SEM of 10 histological tissue sections analyzed from five mice per group. * P < 0.05 versus sham group values. ** P < 0.01 versus sham group values. *** P < 0.001 versus sham group values.
As predicted , immunohistochemistry revealed intracellular localization for AnxA1 associated to gold particles in bronchiole epithelial cells (Figure 1A), mononuclear phagocytic cell (MPC) and circulating polymorphonuclear (PMN) (Figure 1B). All cells were positive for AnxA1 under basal conditions (Table 1). At day 7 post-bleomycin, an increment of AnxA1 expression was observed in the bronchiolar epithelium (Figure 1C), PMN and MPC of wild type mice (Figure 1D, with quantitative data shown in Table 1); this cellular response was no longer evident at day 21 (Figure 1E and 1F, Table 1). No immunogold staining could be detected in absence of the primary antibody (Figure 1G and 1H), confirming the specificity of the AnxA1 staining.
Analysis of endogenous AnxA1 protein and Anxa1 gene expression during lung fibrosis. (A-H;O-P) Wild type and (I-N) AnxA1 null mice received bleomycin i.t. at time 0. The AnxA1 protein content was analyzed by immunohistochemistry. At 0 time-point, wild type mice exhibit a basal immunostain for AnxA1 protein (A and B). After 7 days post-bleomycin administration, this protein expression was greatly increased (C and D). And, after 21 days, the AnxA1 expression was reduced (E and F) in epithelial cells (arrow) and polymorphonuclear (PMN) (arrowheads) and MPC (curve arrow)(G and H). Control of immunogold reaction (CR) showing no cellular immunostaining. Anxa1 gene promoter activity was visualized by X-Gal staining reaction. AnxA1 null mice lung showing Anxa1 gene expression (I and J) on the epithelial cells (arrow), intravascular PMN (arrowhead) and MPC (curve arrow); an intense positive reaction was attained (K-N) on day 7 and 21 post-bleomycin administration. Control for LacZ reaction (CR) showing wild type mice negative to the X-Gal staining (O and P). Haematoxylin counterstain. Bars, 10 μm.
In lungs taken from sham mice (day 0), basal Anxa1 gene promoter activity could be detected in the bronchiolar epithelium (Figure 1I), PMN and MPC (Figure 1J). This colorimetric reaction was markedly augmented at day 7 (Figure 1K and L) and day 21 (Figure 1M and 1N) post-bleomycin, with the epithelium and MPC resulting strongly positive at the later time-point. Table 2 reports these data in quantitative fashion. As a control for these data, performing the X-Gal staining protocols on lungs taken from wild type mice did not yield any coloration (Figure 1O and 1P).
The early response to bleomycin-induced fibrosis is characterized by a dramatic increase in inflammatory cell recruitment that precedes fibrotic tissue formation . Bleomycin administration induced marked leukocyte influx in wild type mice with no influx of blood cells being found in untreated mice (Figure 2). Quantitative analysis of several histological lung sections of AnxA1 null and wild type mice revealed rapid and intense leukocyte migration not only in peribronchial and perivascular areas but also in the interstitial space, occurring both at day 7 and 21 post-bleomycin (Figure 2). At day 7, mice deficient in AnxA1 displayed a higher degree of PMN and peripheral blood monocytes (PBMC) adhesion to lung microvessels (Figure 2).
Leukocyte influx into the lung tissue. Semiquantitative analysis of the histological sections showing intravascular polymorphonuclear (PMN) and monocytes (mono), and transmigrated PMN and MPC in lung tissue. Wild type and AnxA1 null mice were analyzed at 0, 7 and 21 days post-bleomycin i.t. administration as described in Methods section. Data are mean ± SEM from 5 mice per time point. *P < 0.05 versus 0 time point wild type group values; **P < 0.01 versus 0 time point wild type group values; ***P < 0.001 versus 0 time point wild type group values; #P < 0.05 versus corresponding wild type group values; ###P < 0.01 versus corresponding wild type group values.
Analysis of several tissue parameters was complemented by quantification of blood and BAL total leukocyte numbers. In wild type mice, bleomycin administration caused marked leukocytosis at day 21, with a high number of circulating PMN, PBMN and lymphocytes (LY) being calculated (Additional file 1: Figure S1). These profiles of circulating leukocyte subsets were mildly affected by absence of AnxA1: a reduction in LY at day 7 as well as a less pronounced increase in PMN could be measured at day 21 (Additional file 1: Figure S1). In parallel analyses, a rapid cells influx of blood-borne leukocyte into BAL fluid was detected, with marked changes between wild type and AnxA1 null mice especially for PMN (day 7 and day 21), PBMC (day 21) and LY (day 7) (Additional file 1: Figure S1).
We then assessed the extent of pulmonary fibrosis in both genotypes, using the Masson tri-chrome stain. Administration of saline to either wild type or AnxA1 null did not lead to abnormal deposition of collagen around the bronchiole, vessels or alveoli (Figure 3A and 3D). In contrast, at day 7 post-bleomycin, wild type mice showed no significant increase in the connective tissue (Figure 3B), with signs of severe fibrosis evident at day 21, with greater destruction of alveolar architecture, more pronounced at perivascular and peribronchial sites (Figure 3C). These changes were also evident in AnxA1 null mice, both at 7 and 21 days post-bleomycin (Figures 3E and 3F).
Lung histopathology. (A-C) Wild type and (D-F) AnxA1 null mice lung were analyzed at 0, 7 and 21 days post-bleomycin i.t. administration as described in Material and Methods section. (A and D) Histological analysis of wild type and AnxA1 null mouse lungs showing presence of collagen in the connective tissue in the lung parenchyma (a), near the vessel (v) and bronchiole (b). (B) No major changes in the connective tissue of wild type lung parenchyma, as observed at day 7 post-bleomycin administration. (C) At day 21 post-bleomycin, the alveolar septa thicken because of a significant increase in connective tissue deposit (arrow). (E and F) In the AnxA1 null mice, the fibrosis was evident already at day 7; by day 21 there is evidence of increased connective tissue (arrows). Masson trichrome stain. Bars, 100 μm.
Results obtained with the histopathological method were confirmed by measuring hydroxyproline content in lung tissue samples, to quantify the extent of collagen deposition. Both wild type and AnxA1 null bleomycin-treated mice had significantly higher fibrosis scores than saline-treated corresponding mice (Additional file 2: Figure S2). Moreover, there was a statistically significant difference (+23.5% at day 7; +20% at day 21) between wild type and AnxA1 null bleomycin-treated mice, indicating induction of a higher degree of pulmonary fibrosis in the latter genotype (Additional file 2: Figure S2).
Why the observation is surprising to observe that a proportion of AnxA1 null mice succumbed during the time-course of these experiments, with a progressive incidence of lethality from day 7: at day 21 ~50% of bleomycin-treated mice had died (Figure 4). No lethality was observed in wild type animals up to the day 21.
Bleomycin lethality in AnxA1 null mice. Wild type and AnxA1 null mice received 0.15 U/Kg bleomycin i.t. at time 0 and survival rate was monitored daily up to 21 days. Results are cumulated from three experiments with a total of 15 mice per group.
It is accepted that TGF-β1, IFN-γ and TNF-α are key cytokines in the fibrotic process of the lung initiated by bleomycin [3, 29]. Thus, we analyzed cytokine levels as a possible cause behind the increased signs of fibrosis and collagen accumulation detected in AnxA1 null mice.
Figure 5 shows a marked time-dependent increase (>15-fold) in circulating IFN-γ upon bleomycin treatment, whereas changes in TGF-β1 and TNF-α were more modest (between 2-3 fold over untreated mice, day 0 values). Furthermore, higher serum TGF-β1 and TNF-α levels were measured at day 7 in AnxA1 null mice. Similar changes were seen in BAL fluid samples, with discrete alterations of these values in samples taken from AnxA1 null mice (Figure 5). As an example, BAL TNF-α was higher at day 7, with BAL IFN-γ being increased at day 21. TGF-β1 was mildly affected by the absence of endogenous AnxA1.
Serum and BAL supernatant cytokine levels. Wild type and AnxA1 null mice received bleomycin i.t. at time 0, with blood and BAL samples being collected at the reported time points. The serum and cell-free supernatant BAL concentration of TGF-β1, IFN-γ and TNF-α was determined by ELISA. Results are mean ± SEM from two separate experiments with 5 mice per group. *P < 0.05,**P < 0.01 and ***P < 0.001 versus 0 time point wild type group values; #P 0.05 versus corresponding wild type group values.
Finally, we tested whether treatment of wild type mice with an AnxA1 mimetic would affect the dramatic changes provoked by bleomycin in the lung. Two protocols were used for administration of this peptide.
Histological analyses showed that the peptide Ac2-26 treatment reduced the extracellular deposition of collagen when compared to mice treated with bleomycin alone (Figure 6B and 6C). In the group of mice treated with peptide Ac2-26, daily from day 0, a clear reduction in connective tissue deposition around the bronchiolar epithelium was observed, with some similarity to the morphological structure of the sham group (Figure 6A and 6C). Similar protection of the lung was afforded when the peptide was administered between days 14 to 21 post-bleomycin, as determined by quantification of lung hydroxyproline content (Figure 6D). A control group treated daily with peptide Ac2-26 i.p., and given saline i.t., did not show significant morphological changes in the lung tissue (data not shown).
Effects of treatment with peptide Ac2-26 on lung fibrosis and hydroxyproline content. Lung were analyzed at 0 and 21 days post-bleomycin i.t. administration. Also a group of mice were daily treated i.p. with the peptide Ac2-26 (1 mg/kg) or between the days 14 to 21 post-bleomycin as described in Methods section. (A) Morphological analysis of sham group indicated the reduced content of collagen in the lung parenchyma (a), near the vessels (v) and bronchiole (b). (B) At day 21 after bleomycin administration, the alveolar septa thickening indicated the significantly increasement of collagen deposit (arrows). (C) The daily treatment with peptide Ac2-26 prevents bleomycin-induced lung fibrosis (curve arrows). Masson trichrome stain. Bar, 100 μm. (D) Pulmonary fibrosis was biochemically assessed by measurement of lung hydroxyproline content. Results are expressed as means ± SEM of μg of hydroxyproline per mg of lung tissue. **P < 0.01 versus 0 time point values; #P < 0.05 versus day 21 post-bleomycin time point values.
Treatment of mice with peptide Ac2-26 led to an increased expression of endogenous AnxA1 protein in the lung (Figure 7E and 7F), when compared to bleomycin treatment alone (Figure 7C and 7D). The changes provoked by peptide Ac2-26 occurred in the alveolar macrophage and the epithelial cell and the expressions were higher than sham group (saline treated) (Figure 7E/F and 7A/B, respectively). Western blotting analyses confirmed these histological results, showing augmented AnxA1 in lung protein extracts prepared from mice treated with peptide Ac2-26 over 21 days or only for the 14-21 day period, when compared to bleomycin-treated control mice (Figure 7G). Table 1 reports quantitative data associated with these analyses at single cell level.
Analysis of endogenous AnxA1 expression in wild type mice after treatment with peptide Ac2-26. Mice received bleomycin i.t. at time 0. Immunohistochemistry was performed to visualize the protein expression in epithelial cells (arrows), PMN (arrowheads) and alveolar macrophages (curved arrow). (A and B) Sham mice exhibit a basal immunostain for AnxA1 protein. (C and D) Lung fibrosis induced by bleomycin reduced the AnxA1 expression in epithelial cells (arrow) and PMN (arrowheads). (E and F) Daily treatment with peptide Ac2-26 (1 mg/kg) increased the AnxA1 expression during lung fibrosis. Haematoxylin counterstain. Bar, 10 μm. (G) The AnxA1 protein content was also analyzed by Western blotting (seen as both the native 37 kDa and 33 kDa cleavage products). AnxA1 was down regulated during lung fibrosis. Daily i.p. treatment with peptide Ac2-26, or given only between day 14 and day 21 post-bleomycin, increased expression of this endogenous protein.
Pulmonary fibrosis has a complex etiology involving interactions among multiple cell types and intricate cytokine/chemokine networks. However, the precise role of any one of these cytokines in vivo is hard to identify in view of their pleiotropic biological activities. Studies using animal models afford a well-defined means of addressing this problem since provide the opportunity to target each of these putative mediators using immunological and genetic approaches.
In line with the human fibrosis, the mechanisms underlying bleomycin-induced lung fibrosis are not fully understood, although several studies have identified expression of specific cytokines and mediators with potential functional role(s) during this process. We propose here that investigation of the potential modulation of effectors of endogenous anti-inflammation could provide novel clues to harness the host response during lung fibrosis . Such a novel approach - exploiting the functions of homeostatic and tissue protective mediators - would possibly be more successful than blockade of the actions of pro-inflammatory mediators since anti-cytokine therapy has produced no improvement in lung function and, rather, seemed to be associated with harmful side effects . Few studies in humans and animals have demonstrated down regulation of one endogenous effector of resolution, the protein AnxA1, during the development of cystic fibrosis [24, 25]; the present study was intended to address, for the first time, the potential relevance of AnxA1 in experimental fibrosis using the recently generated AnxA1 null mouse [14, 15].
Analysis of AnxA1 protein expression in the bleomycin-induced fibrosis indicated increased expression in bronchial epithelial cells and leukocytes during the inflammatory phase (7 days) followed by a reduction during the fibrotic phase (21 days), as compared to sham animals: this event is in agreement with changes reported in lung tissue and leukocytes [24, 25] in experimental settings modeling tissue fibrosis.
We could monitor Anxa1 gene promoter activity in leukocytes and epithelial cells using the AnxA1 null mouse colony where a LacZ gene reporter assay is inserted in frame. At day 21 post-bleomycin, the X-Gal staining detected higher Anxa1 gene promoter activity in leukocytes and epithelial cells compared to day 0 lung tissue samples. These data, together with the AnxA1 protein expression, indicate that despite the lower levels of AnxA1 detected in the cells, there is ample Anxa1 gene promoter activity; we wish to postulate that reduction in AnxA1 protein may be associated with a post-transcriptional mechanism(s) which could perhaps lead to AnxA1 proteolysis or leakage (aberrant secretion) from the cells. AnxA1 lacks a signal peptide yet it is released from cells (e.g. activated PMN; see ref. 31). Several non-canonical secretory pathways have been ascribed, possibly in a cell specific fashion, including phosphorylation , proteolysis [24, 33], granule/membrane fusion and microparticles release . Future studies will attempt to establish the 'preferred' mode of AnxA1 secretion in activated lung cells, though it cannot be excluded that alternative mechanisms might be operating in diseased cells.
At day 21, we could also measure a higher degree of fibrosis and collagen deposition in AnxA1 null animals, as detected both morphologically and by hydroxyproline measurement. Therefore, AnxA1 down-regulation might be an important determinant during lung fibrosis development, suggesting that manipulation of local pulmonary concentration of AnxA1, perhaps by adenoviral delivery (a route successfully applied to lung pathologies; , might represent a novel way to afford lung tissue protection.
AnxA1 has been implicated in many aspects of cell physiology including regulation of cell growth and differentiation , signal transduction and arachidonic acid release , as well as intracellular vesicle trafficking . Moreover, it promotes cell apoptosis and, possibly more relevant, phagocytosis of apoptotic cells and subsequent tissue clearance has also been ascribed to this homeostatic mediator.
Croxtall et al. showed that a lung fibroblast cell line derived from the AnxA1 null mouse was refractory to growth inhibition by dexamethasone, indicating that intracellular AnxA1 (though it cannot be excluded also an extracellular role here) can function as a negative regulator of cell growth. In pathology, AnxA1 has been implicated directly or indirectly in tumor cell growth [41, 42]. Our previous results also showed an abnormal growth formation in the AnxA1 null mice skull, probably caused by increased extracellular matrix and a delay in the bone mineralization . Thus, we would postulate that absence of AnxA1 may lead to higher cell proliferation, increasing the extracellular matrix production and fibrosis formation. Studies by Nusrat's lab have identified AnxA1 as a major effector of tissue protection following epithelial damage, an effect requiring externalization of the protein.
In our experimental conditions, absence of AnxA1 affected several indices of the response promoted by bleomycin, characterized by an early inflammatory phase followed by the fibrotic process. The combined effect of AnxA1 absence and bleomycin-induced fibrosis exceeded the sum of the effects of each factor alone on the severity of histological changes. This was visible because the higher degree of activation of circulating leukocyte and a remarkable leukocyte infiltration to the alveolar space and lung parenchyma; these cellular events led, or at least contribute, to: i) a more severe inflammatory response and ii) a greater destruction of alveolar architecture, pronounced in the perivascular and peribronchial areas. This effect is in line with our previous data in different experimental models of inflammation, including acute peritonitis and lipopolysaccharide-induced systemic inflammation . Absence of AnxA1 is conducive to increased leukocyte infiltration leading to a more severe inflammatory reaction. Several studies have associated inflammatory cell recruitment and lung damage with fibrosis formation [7, 45], prompting us to propose that alteration in the early protective role of AnxA1 during the inflammatory phase could lead, downstream, to a higher degree of fibrosis.
So far we have two feasible mechanisms for explaining the impact of AnxA1 in this model: i) direct alteration in the phenotype of lung cells potentially, but not necessarily, related to a ii) more aggressive inflammatory reaction. Analysis of cytokine content favors a functional association between these two readouts. In fact, tightly coupled to the early inflammatory response is a higher cytokine expression. We measured TNF-α, TGF-β1 and IFN-γ since they instrumental for the inflammatory process and/or fibrosis [46, 47]. In wild type mice, levels of these cytokines changed in the blood and BAL fluid samples. TGF-β1 is largely responsible for fibroblast activation/differentiation, as well as collagen over-expression . Furthermore, a lower degree of parenchymal inflammation has been observed in IFN-γ deficient mice subjected to the bleomycin-induced lung fibrosis model . In our samples we could determine a correlation between increased levels of TGF-β1 with TNF-α and IFN-γ up-regulation. Hardie and collaborators showed that TGF-β1 conditional over-expression in epithelial cells, endothelial cells and macrophages induces fibrosis and TNF-α expression even in the absence of inflammation. It is plausible that complex positive loops might be activated locally, since TGF-β1 induction from macrophages occurs in a two-stage process requiring both TNF-α and IL-13 .
Global absence of AnxA1 resulted in dysregulated pulmonary levels of TNF-α, TGF-β1 and IFN-γ, more evident at day 21, yet present also at day 7 post-bleomycin. This association of AnxA1 with TNF-α expression is not totally unexpected as previously reported in a model of systemic endotoxemia induced by LPS [12, 50]. More studies will better address the molecular events behind AnxA1 regulation of cytokine production in lung cells.
Finally, we tested the potential pharmacological benefit of treatment of mice with peptide Ac2-26. This peptide mimics most [10, 31, 51], if not all , of the pharmacological actions of AnxA1. Given daily over 21 days, or from day 14 to 21, peptide Ac2-26 reduced the most remarkable feature of the animal response to bleomycin, which is fibrosis, as quantified both histologically and by determination of lung hydroxyproline content.
An interesting observation stemmed from these experiments, that is the positive effect of treatment of mice with peptide Ac2-26 on tissue levels of AnxA1, indicating that a positive loop might exist in anti-inflammation, whereby AnxA1 activation of its receptor (here the activation is achieved by the AnxA1 pharmacophore peptide Ac2-26) would augment its own synthesis, in epithelial cells and in some leukocytes subsets (Table 1). Such a model is congruent with a recent study in mouse colitis, which revealed the ability of treatment with peptide Ac2-26 to increase tissue mRNA for AnxA1 receptors . The same held true for epithelial cells treated with AnxA1 . Therefore, different studies are coming together with indications for the existence of this positive loop; if extended to other settings; this would indicate possible "auto-reactivity" of endogenous anti-inflammation and resolution, at least with respect to the AnxA1 pathway.
In summary, the striking phenotype we describe here indicates that endogenous and exogenous AnxA1 affects selective aspects of the process of fibrosis development in the lung, a feature that may warrant further investigation on AnxA1 biology in these experimental and pathological settings.
This work was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP 05/56855-8), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 471730/2006-8) and the Wellcome Trust UK (programme grant 086867/Z/08). ASD is funded by FAPESP (06/50015-0), SMO is funded CNPq (302768/2010-6).
ASD: participated in the design of the study, carried out the experiments and participated in the sequence alignment and drafted the manuscript; ALFS: carried out the experiments; CMAGN: carried out the histopathological analysis; RJF: provided de transgenic mice and helped during the discussion of the manuscript; MP: conceived of the study, and participated in its design and coordination and helped to draft the manuscript; SMO: participated in the design of the study and participated in the sequence alignment and drafted the manuscript. | en | apollo | train |
These data suggest that hoptels may help equalize inpatient lengths of stay among domiciled and homeless patients discharged to a hoptel. Public health care systems seeking innovative ways of reducing inpatient lengths of stay among homeless patients ought to consider establishing hoptels. | en | apollo | train |
Lymphoedema and lipoedema of the extremities.
Lymphoedema is a clinical manifestation of an impaired lymphatic drainage with accumulation of lymphatic fluid. Lipoedema is characterized by bilateral enlargement of the legs and/or arms due to abnormal deposition of fatty tissue, which accumulates fluid. Conservative treatment including compressions garments and lymphatic drainage is suitable to prevent ongoing clinical deterioration although both diseases cannot be cured. The ability to properly diagnose lymphoedema and lipoedema is crucial to prevent the significant morbidity and loss of quality of life that is associated with this condition. It is imperative that patients with lymphoedema are referred to specially trained healthcare professionals to ensure optimal treatment. Continuous therapy with strict compliance of the patients is essential, and premature interruption is the most frequent mistake. Lipoedema is a different entity but patients are still fighting for acceptance. The mutual relation of lipoedema and obesity and the poor knowledge of the underlying mechanisms limit the acceptance of lipoedema as a relevant disease. | en | apollo | train |
The antitumor activity of hPRDX5 against pancreatic cancer and the possible mechanisms.
Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer. | en | apollo | train |
2003) and neonatal pneumonia (Auten et al.1991; Robertson 1996; Herting et al. Supraventricu-lar tachycardia and atrial flutter are managed with cath-eter ablation. Pathophysiologyof spironolactone-induced gynecomastia.
392).But scientific evidence “is only helpful to professionals and their clients if health serviceproviders seek it out understand it, and apply it” (Bernstein Ratner, 2006, p. (2008) Imaging amyloid deposi-tion in Lewy body diseases.
When conductingany type of review of the denominations or faiths in a particu-lar community, be aware that a client’s spiritual dimension issubjective and may vary greatly among persons, even personsof the same denomination or faith.
The needle is passed back through the distal embrasure,around the tooth lingually, and then passed back to the facial side through themesial embrasure. Jorgensen is at risk for Deficient Fluid Volume.12.
(2001a) Odor threshold, recognition, discrimination,and identification in centenarians.
The primary way this regulation is accomplished isthrough interaction with Mdm2 [ 26].
Catalase present in tissues speedsdecomposition resulting in foaming—helps in loosening andremoving slough, ear wax, etc.
The imidazoline compounds—naphazoline, xylometazoline and oxymetazolineare relatively selective 2 agonist (like clonidine).They have a longer duration of action (12 hours)than ephedrine. “A Detailed Introduction of H5N1 to New Comers.” Above TopSecret. These fibers havegreat resistance to fatigue but generate less tension thanother fibers. | en | apollo | train |
The main storage form of fat in the body. Most are found in fat tissue, but some circulate in the bloodstream to provide fuel for the body’s cells. The triglyceride molecule is composed of three fatty acid chains attached to a glycerol molecule. The body can break down the triglycerides in the foods you eat and can also break down and recombine other molecules, such as fats, carbohydrates, and proteins, to make triglycerides.
Having high levels of triglycerides in the blood can increase a person’s risk of cardiovascular disease. Having very high triglycerides can also increase the risk of pancreatitis, or inflammation of the pancreas. Because blood triglycerides are naturally higher after a meal, they should be measured after 8–12 hours of fasting for meaningful results.
Limit your intake of saturated fat.
Drink in moderation or not at all.
If lifestyle measures alone don’t adequately control your triglyceride levels — or if your levels are 200 mg/dl or higher to begin with — your doctor may prescribe one of a class of drugs called fibric acid derivatives, such as fenofibrate (brand name TriCor and others) or gemfibrozil (Lopid). Prescription niacin (such as Niaspan) is sometimes also used to lower triglyceride levels.
The class of drugs popularly known as “statins,” which includes atorvastatin (Lipitor, Torvast), fluvastatin (Lescol), lovastatin (Mevacor, Altocor, Altoprev), pravastatin (Pravachol, Selektine, Lipostat), rosuvastatin (Crestor), and simvastatin (Zocor, Lipex), is also sometimes used, especially when a person also has high low-density lipoprotein (LDL, or “bad”) cholesterol levels. | en | apollo | train |
Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity.
Treatment of early relapsing-remitting multiple sclerosis with the lymphocyte-depleting humanized monoclonal antibody alemtuzumab (Campath [registered trade mark]) significantly reduced the risk of relapse and accumulation of disability compared with interferon β-1a in a phase 2 trial [Coles et al., (Alemtuzumab vs. interferon β-1a in early multiple sclerosis. N Engl J Med 2008; 359: 1786-801)]. Patients treated with alemtuzumab experienced an improvement in disability at 6 months that was sustained for at least 3 years. In contrast, those treated with interferon β-1a steadily accumulated disability. Here, by post hoc subgroup analyses of the CAMMS223 trial, we show that among participants with no clinical disease activity immediately before treatment, or any clinical or radiological disease activity on-trial, disability improved after alemtuzumab but not following interferon β-1a. This suggests that disability improvement after alemtuzumab is not solely attributable to its anti-inflammatory effect. So we hypothesized that lymphocytes, reconstituting after alemtuzumab, permit or promote brain repair. Here we show that after alemtuzumab, and only when specifically stimulated with myelin basic protein, peripheral blood mononuclear cell cultures produced increased concentrations of brain-derived neurotrophic factor, platelet-derived growth factor and ciliary neurotrophic factor. Analysis by reverse transcriptase polymerase chain reaction of cell separations showed that the increased production of ciliary neurotrophic factor and brain-derived neurotrophic factor after alemtuzumab is attributable to increased production by T cells. Media from these post-alemtuzumab peripheral blood mononuclear cell cultures promoted survival of rat neurones and increased axonal length in vitro, effects that were partially reversed by neutralizing antibodies against brain-derived nerve growth factor and ciliary neurotrophic factor. This conditioned media also enhanced oligodendrocyte precursor cell survival, maturation and myelination. Taken together, the clinical analyses and laboratory findings support the interpretation that improvement in disability after alemtuzumab may result, in part, from neuroprotection associated with increased lymphocytic delivery of neurotrophins to the central nervous system. | en | apollo | train |
Recovery from ultraviolet-induced growth arrest of primary rat hepatocytes by p53 antisense oligonucleotide treatment.
Recent evidence suggests that wild-type p53 prevents cell-cycle progression after DNA damage, which may provide a sufficient period for the cells to repair the genetic lesions that may otherwise lead to cell death or cellular transformation. We tested whether this hypothesis is generally applicable to parenchymal cells of internal organs. When primary neonatal rat hepatocytes were exposed to a nonlethal dose of ultraviolet light, actinomycin D, or mitomycin C, most cells expressed abundant p53 with an abnormally extended half life in their nuclei, and their growth was arrested despite treatment with growth factors (epidermal growth factor and insulin). When DNA-damaged cells were treated with p53-antisense oligonucleotides, p53 expression was significantly suppressed, and an appreciable fraction of the cells entered S phase. However, when damaged cells were administered p53-sense or retinoblastoma susceptibility gene-antisense oligonucleotides, there was no recovery from growth arrest. The data strongly suggest that p53 is a component of at least one signal transduction pathway leading to growth arrest in DNA-damaged cells. | en | apollo | train |
The neurobiological substrates for conditioned withdrawal also may depend on the basolateral amygdala.The enhancement of conditioned reinforcement produced by psychomotor stimulants appears to involve the basolateral amygdala and its glutamatergic projection to the nucleus accumbens with dopaminergic modulation (Robbins et al., 1989).Another example is drug-induced reinstatement where a small dose of the drug elicits responding for a lever that has been extinguished. _Craving Type 2_ : Craving is conceptualized as a state change characterized by anxiety and dysphoria or a residual negative affective state that combines with Craving Type 1 situations to produce relapse to drug seeking. Animal models of Craving Type 2 include stress-induced reinstatement of drug seeking after extinction or increased drug taking in animals during or after a prolonged deprivation. Craving Type 2 can be conceptualized as a residual negative emotional state or an acute stress-like state, both of which can elicit drug-seeking behavior. Conditioning to the positive affective states induced by drugs has been demonstrated in animals. Stimuli associated with drugs of abuse can maintain responding in rats and monkeys when presented without the drug. It is also possible to demonstrate conditioned withdrawal. For example, when previously neutral stimuli are paired with naloxone-induced withdrawal, the neutral stimuli themselves elicit signs of opioid withdrawal. Conditioned withdrawal has been observed in opioid-dependent animals and humans. Neurobiological substrates for conditioned drug effects have been investigated in some detail (Cardinal, Parkinson, Hall, & Everitt, 2002; Everitt, Cardinal, Hall, Parkinson, & Robbins, 2000). The enhancement of conditioned reinforcement produced by psychomotor stimulants appears to involve the basolateral amygdala and its glutamatergic projection to the nucleus accumbens with dopaminergic modulation (Robbins et al., 1989). The neurobiological substrates for conditioned withdrawal also may depend on the basolateral amygdala.Another powerful source of relapse in human subjects is exposure to a stressor or the state of stress.Both conditions may involve activation of CRF, dynorphin, and noradrenergic systems in the central nucleus of the amygdala and bed nucleus of the stria terminalis. | en | apollo | train |
HOUSTON - Targeted cancer therapy pioneer John Mendelsohn, M.D., researcher and former president of The University of Texas MD Anderson Cancer Center, will share the 2018 Tang Prize in Biopharmaceutical Science for his leadership in developing antibodies to block cancer-promoting growth factor receptors on the surface of cancer cells.
In announcing the award on June 19 in Taiwan, the Tang Foundation noted the three awardees launched the field of targeted therapy - attacking tumors based on their genetic and molecular aberrations -- with their research to understand the role of tyrosine kinase proteins and to design ways to block their activity.
Their work led to "a thorough understanding of the fundamental principles of cell growth and cancer development," the Tang Foundation noted in its announcement, and the therapies they developed "fundamentally changed the practices of cancer clinics."
Mendelsohn, president of MD Anderson from 1996 to 2011, is a professor of Genomic Medicine and director of the Zayed Institute for Personalized Cancer Therapy at MD Anderson, as well as the L.E. & Virginia Simmons Senior Fellow in the Division of Health and Technology Policy at Rice University's Baker Institute.
The honor cites Mendelsohn's role in conceiving the approach of using antibodies to target the epidermal growth factor receptor (EGFR), which is overexpressed or mutated to a cancer-promoting form in a variety of cancers.
Then at the University of California at San Diego, working with colleague Gordon Sato, Ph.D., Mendelsohn's team conducted preclinical research and developed the anti-EGFR antibody cetuximab (Erbitux), which went on to approval by the U.S. Food and Drug Administration for the treatment of colon cancer and head and neck cancer. This first tyrosine kinase-targeting antibody was "a trail-blazer which has spurred many others to follow," the Tang announcement notes.
"It's an honor to be recognized by the Tang Foundation with colleagues who opened such an important chapter of cancer research," Mendelsohn said. "By highlighting the vital connection between basic research and progress in the clinic, the Tang Foundation encourages the progress we need in scientific, translational and clinical research to continue to improve cancer treatment."
The Tang prizes, announced in 2012 by Taiwanese entrepreneur Samuel Yin, have been awarded every two years since 2014.
* Tony Hunter, Ph.D., professor of Biology at the Salk Institute, who discovered tyrosine phosphorylation, found that the Src oncogene is a tyrosine kinase, and demonstrated the role of tyrosine phosphorylation in uncontrolled cancer growth.
* Brian Druker, M.D., director of the Oregon Health Sciences University Knight Cancer Institute, who advocated for and led the successful clinical trial of imatinib (known commercially as Gleevec) for chronic myelogenous leukemia, the first successful small-molecule tyrosine kinase inhibitor.
Tang prizes are awarded in four categories: Biopharmaceutical Science, Sustainable Development, Sinology (the study of Chinese language, history, customs and politics) and Rule of Law. Winners receive a medal and diploma and share a cash award of approximately $1.33 million and a $330,000 research grant. | en | apollo | train |
Virus-induced unfolded protein response attenuates antiviral defenses via phosphorylation-dependent degradation of the type I interferon receptor.
Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of the type I interferon (IFN) receptor is regulated by two different pathways, one of which is ligand independent. We report that this ligand-independent pathway is activated by inducers of unfolded protein responses (UPR), including viral infection, and that such activation requires the endoplasmic reticulum-resident protein kinase PERK. Upon viral infection, activation of this pathway promotes phosphorylation-dependent ubiquitination and degradation of IFNAR1, specifically inhibiting type I IFN signaling and antiviral defenses. Knockin of an IFNAR1 mutant insensitive to virus-induced turnover or conditional knockout of PERK prevented IFNAR1 degradation, whether UPR-induced or virus-induced, and restored cellular responses to type I IFN and resistance to viruses. These data suggest that specific activation of the PERK component of UPR can favor viral replication. Interfering with PERK-dependent IFNAR1 degradation could therefore contribute to therapeutic strategies against viral infections. | en | apollo | train |
Usefulness of 64-slice MDCT for follow-up of young children with coronary artery aneurysm due to Kawasaki disease: initial experience.
To evaluate the initial application and value of 64-slice multidetector computed tomography as an alternative diagnostic modality in the follow-up of young children with coronary artery aneurysm due to Kawasaki disease. Twelve boys (mean age 5.1 years, range 1.8-7.8 years) for follow-up (time range from 1.1 to 5.1 years) of known Kawasaki disease and coronary artery aneurysm underwent 64-slice MDCT ECG-gated coronary angiography. All data were acquired without breath holding. Two pediatric radiologists independently assessed image quality and the diameter of all coronary segments were measured for each patient. The number, position, shape and size of each coronary artery aneurysm were observed and compared with those of ECHO performed previously. A total of 118/156 segments permitted visualization with diagnostic image quality, the CT measurements showed good inter-observer and intra-observer reliability, coefficients were 0.93 and 0.88, respectively. A total of 30 coronary artery aneurysms were identified with measured mean of 7.5+/-3.8 mm in diameter, and of 12.4+/-9.1 mm in longitudinal lengths.10 tumors were small, 8 tumors were medium and 12 tumors were giant aneurysm. The affected segments included LM7/12(58.3%), 9/12(75%) of LAD1, 4/12(33.3%) of LAD2, 2/12(16.7%) of LCX1; 6/12(50%) of RCA1, 9/12(75%) of RCA2 and 4/12(33.3%) of RCA3, including affected two segments in 9 tumors and three segments in 1 tumor. Calcifications were found in 5 aneurysms and 3/5 with thrombosis; six stenotic segments were found. ECHO failed to detect 8 tumors with 2/8 in LAD, 1/8 in LCX and 5/8 in RCA, and those included 4 small aneurysms. The use of 64-slice MDCT angiography proved valuable for monitoring young children with Kawasaki disease. However, further study is necessary to specify the sensitivity and specificity of MDCT in the follow-up. | en | apollo | train |
Posterior circulation stroke presenting as a new continuous cough: not always COVID-19.
A 19-year-old man was admitted with a 2-week history of continuous cough along with a day history of acute onset unsteadiness and hiccups. Given the current pandemic, he was initially suspected to have COVID-19, however he tested negative on two occasions. Subsequent brain magnetic resonance imaging (MRI)confirmed a small left acute and subacute lateral medullary infarction with chest X-ray suggesting aspiration pneumonia with right lower lobe collapse. This is a distinctive case of posterior circulation stroke presenting with a new continuous cough in this era of COVID-19 pandemic. We anticipate based on MRI findings that his persistent cough was likely due to silent aspiration from dysphagia because of the subacute medullary infarction. It is therefore imperative that healthcare workers evaluate people who present with new continuous cough thoroughly to exclude any other sinister pathology. We should also be familiar with the possible presentations of posterior circulation stroke in this pandemic era. | en | apollo | train |
Eagle's syndrome should be kept in mind when the otologist is faced with vague, nonspecific secondary otalgia. The vagueness of symptoms and the infrequent clinical observations are often misleading the clinician to do unnecessary workup, incorrect diagnosis, and wrong treatment.
The vagueness of symptoms and the infrequent clinical observations are often misleading the clinician to do unnecessary workup, incorrect diagnosis, and wrong treatment. Eagle's syndrome should be kept in mind when the otologist is faced with vague, nonspecific secondary otalgia. This study was approved by the Inje University Sanggye Paik Hospital institutional review board (IRB. NO. 2015-12-007).
A 60-year-old woman complained of intermittent right otalgia for over 2 years. She noticed right otalgia shortly after the right pharyngeal foreign body sensation. Over the years, she had been under the care of various medical specialists. She had underwent a right tympanostomy and ventilation tube insertion 1 year before presentation, without relief of her symptoms. Physical examination of her ear, nose, oropharynx, and neck was unremarkable. Contrast-enhanced neck computed tomography (CT) images revealed an asymmetrically long 7 cm-sized right temporal styloid process extending to parapharyngeal space at the hyoid bone level [Figure 1]a. On palpation of the right tonsillar fossa, tender elongated styloid process was felt. Palpation elicited pain sensation down her right neck. She was treated with nonsteroidal anti-inflammatory drugs (NSAIDs). She was also suggested about styloidectomy if the symptoms were not relieved. She was lost to follow-up.
A 61-year-old woman presented with a 4-month history of the right otalgia. She had consulted with many different medical specialists since. Her pain was not related with masticating or head turning. Contrast-enhanced Neck CT images were not specific except 0.3 cm sized tiny enhancing lesion in the right parotid gland. Follow-up sonoguided fine-needle aspiration cytology compatible with lymphoproliferative lesion. One year later, she revisited our clinic for the complaint of the right neck pain which was aggravating by head turning to the left. Sono-guided fine-needle aspiration cytology revealed reactive hyperplasia. MR images of internal auditory canal were not specific. Two years later, she revisited for the complaint of the right submandibular area pain which was aggravating by head turning to the right. During the oropharyngeal examination, a hard, sharp process was palpated intraorally around the anterior pillar of the right tonsil. The pain was exacerbating by palpation of the lateral tonsillar fossa. Then, the previous neck CT images were reviewed thoroughly, the asymmetrically elongated (3.7 cm vs. 2.4 cm) and slightly medially bent right styloid process was identified [Figure 1]b. Final diagnosis of Eagle's syndrome was made. The condition was explained to the patient and operative treatment was recommended. After right tonsillectomy, styloid process was skeletonized by cone ring curette and removed with bone cutter. On the first postoperative visit, rotation of the head did not elicit any pain. 10 days after surgery, she visited for posttonsillectomy bleeding. Bleeding was controlled by conservative manner. 6 months after the surgery, she was asymptomatic even by neck rotation or palpation.
Eagle's syndrome is an important pathology in the differential diagnosis of secondary otalgia. The diagnostic difficulty of this condition is due to the variable and nonspecific vague symptoms. Patients seek diagnosis and treatment in variable clinics such as otology, neurology, dentistry, and even psychiatry. Misdiagnosis of the syndrome can result in various unnecessary workups and treatments. The differential diagnosis of Eagle's syndrome should include tonsillitis, trigeminal, glossopharyngeal and sphenopalatine neuralgia, temporomandibular joint disease, migraine, myofascial pain dysfunction syndrome, laryngopharyngeal reflux, and dental-related problems.
Eagle's syndrome should be suspected in the presence of persistent throat pain triggered or exacerbated by head rotation, lingual movement, swallowing, and chewing. In those cases, digital palpation of the tonsillar fossa to provocative the symptoms should be included in the examination process.
The styloid muscles are a pyramid shape, the tip of which is formed by the attachment of the styloid muscles to the styloid process. The glossopharyngeal nerve crosses to the anterior side of the stylopharyngeus muscle at the junction of the stylopharyngeus, middle constrictor, and hyoglossal muscles, which are at the base of the pyramid. The middle constrictor muscle forms a wall between the glossopharyngeal nerve and the hypoglossal nerve in this region. Then, the glossopharyngeal nerve gives off a lingual branch and deepens to innervate the pharyngeal mucosa.
The nonsurgical treatment of Eagle's syndrome generally involves pharmacotherapy with NSAIDs, anticonvulsant or antidepressants, but the effects are unpromising. Long-lasting symptom relief requires the surgical removal of the long portion of the styloid process. The transoral or recently endoscopic approach involving resection of the styloid process is relatively easy to perform and leaves no external scar.
Eagle's syndrome should be kept in mind when the otologist is faced with vague, nonspecific otalgia.
Prasad KC, Kamath MP, Reddy KJ, Raju K, Agarwal S. Elongated styloid process (Eagle's syndrome): A clinical study. J Oral Maxillofac Surg 2002;60:171-5. | en | apollo | train |
Patients with major medical illnesses such as cancer may also be at risk for lymphedema, a swelling that typically occurs in the extremities. To ease lymphedema discomfort, Little Company of Mary Hospital (LCMH) offers advanced treatment from physical therapy experts who are specially trained as certified lymphedema specialists.
There are two types of Lymphedema: Primary and Secondary Lymphedema. Primary Lymphedema is rare and is caused by the absence of certain vessels at birth or abnormalities in the lymphatic system. Secondary Lymphedema is due to blockage or interruption of the lymphatic system, which can occur from cancer treatment. Many who deal with breast cancer develop Lymphedema due to the fact that at least two or three lymph nodes (sometimes more) are removed from under the arm for surgery. If the cancer spreads and radiation is needed, radiation can cause scarring and inflammation of lymph nodes or lymph vessels which will restrict the flow of lymph fluid.
Lymphedema develops when fluids of the lymph system — the network that carries white blood cells throughout the body to fight infection — are blocked by treatments such as surgery or radiation. This causes a build-up of fluid in the lymph system, which then leads to uncomfortable or painful swelling and limited range of motion, usually in the arms, fingers, legs or toes.
Certified lymphedema specialists Janelle Trippany, D.P.T., and Charmaine Boncalon, P.T., provide intensive lymphedema services for patients who struggle with swelling that ranges from moderate to severe. “After their first lymphedema treatment many patients feel relief right away,” says Boncalon. “Their affected area feels lighter and they can move easier, which means a lot when they are performing activities of daily living, such as dressing or bathing.” Therapy requires a physician referral. Treatment focuses on lymphatic drainage, in which the lymphedema therapist manually redirects the buildup of fluid to help significantly reduce swelling. Therapy also includes compression bandaging of the affected area, skin care, exercises to promote lymphatic flow and an emphasis on patient education. “Intensive therapy ‘gets the juices flowing and has a huge impact on patients,” says Trippany. “Lymphedema is a lifelong condition, but it can be managed with appropriate care and regular follow-up.
LCMH is one of the few medical centers in the area offering cutting-edge lymphedema services. “LCMH responded to the demand for this type of care right here in the community, “says Vince Cesaro, director of Physical Therapy. “We are proud to provide specialized treatment that is convenient for patients and provides them with significant relief from qualified lymphedema experts.
WHO: Two Certified Lymphedema Therapist that treat both Primary and Secondary Lymphedema.
Fitting for long term compression garments.
TREATMENT TIMELINE: Intensive Phase: Attaining as much decongestion as possible through CDT.
Plan for home phase with education and fitting for compression garments.
Home Phase: 2-3 days per week for 2-4 weeks: Transitions patients into independent home management, including self-bandaging, self- MLD, and ability to donn/doff garments independently.
HOW TO REACH US: For more information or an appointment please call 708-229-5525. | en | apollo | train |
• You plan to become pregnant within 3 months.• You have diabetes, asthma, kidney, liver or gallbladder disease.• You have had blood clots, stroke, high blood pressure, congestive heart failure or heart attack.• You have migraine headaches, epilepsy or porphyria.**
| **POSSIBLE ADVERSE REACTIONS OR SIDE EFFECTS**
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**SYMPTOMS** | **WHAT TO DO**
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**Life-threatening:**
Blood clots (severe or sudden headache, severe pain in calf or chest or other body parts, shortness of breath, slurred speech, weakness or numbness, sudden vision changes). | Seek emergency help. ---|---
**Common:**
• Painful or swollen breasts, swollen feet or ankles, rapid weight gain. | Discontinue. Call doctor right away. ---|---
• Appetite loss, nausea, stomach, cramps or bloating, skin irritation in patch or spray users. | Continue. Call doctor when convenient. **Infrequent:**
• Breast lumps or discharge, changes in vaginal bleeding (more, less, spotting, prolonged), migraine headache. | Continue, but call doctor right away. ---|---
• Dizziness, contact lens intolerance, vomiting, mild diarrhea, headache, increased or decreased sexual desire, slow weight gain, other unusual symptoms. | Continue. Call doctor when convenient. **Rare:**
Stomach or side pain, joint or muscle pain, jaundice (yellow skin or eyes). | Discontinue. Call doctor right away. ---|---
| **WARNINGS & PRECAUTIONS**
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**Don't take if:**
You are allergic to any estrogen-containing drugs. Allergic reactions are rare, but may occur. **Before you start, consult your doctor if:**
• You have or have had cancer of the breast or reproductive organs, fibrocystic breast disease, fibroid tumors of the uterus or endometriosis, unexplained vaginal bleeding. • You have migraine headaches, epilepsy or porphyria. • You have had blood clots, stroke, high blood pressure, congestive heart failure or heart attack. • You have diabetes, asthma, kidney, liver or gallbladder disease. • You plan to become pregnant within 3 months.**Pregnancy:**
Consult doctor.Drug should not be used during pregnancy.Can cause harm to unborn baby.Risk category X (see here).**Breastfeeding; Lactation; Nursing Mothers:**
Drugs in this group have some precautions and concerns with breastfeeding.Discuss risks and benefits with your doctor.**Infants & children up to age 18:**
Not recommended in this age group. | en | apollo | train |
Protective effect of caffeine on streptozotocin-induced beta-cell damage in rats.
Many epidemiological studies have shown that coffee consumption reduces the risk of type 2 diabetes mellitus (T2D), although the reasons as to why remain unclear. In this study we investigated the effect of caffeine on pancreatic beta-cell damage in rats using the diabetogenic agent, streptozotocin (STZ). Wistar rats were given intraperitoneal injections of saline or caffeine (10, 50 or 100 mg kg(-1)). After 15 min, the rats were injected with a citrate buffer or 65 mg kg(-1) STZ. Three days after injection, an oral glucose tolerance test (OGTT) was performed on the rats. Furthermore, three days after the OGTT, the pancreas was isolated and homogenized, followed by determination of insulin content. STZ treatment significantly increased the plasma glucose level compared with the control at all times during the OGTT, which was significantly diminished by caffeine pretreatment at all doses. STZ treatment significantly decreased the plasma insulin level, however, which was not recovered by caffeine pretreatment. Pancreatic insulin content was significantly reduced by STZ treatment compared with the control, which was significantly recovered by caffeine pretreatment at a dose of 100 mg kg(-1) (P<0.01). We showed that caffeine protects pancreatic beta-cells against STZ toxicity. Further investigation will be required to understand the protective effect of caffeine against beta-cell destruction in T2D. | en | apollo | train |
PI using a T1-weighted 3D FSPGR sequence shows the best correlation with neurobehavioral performance indicators and is the best measure for detection of blood and airborne Mn concentrations in welders exposed to excessive occupational Mn. | en | apollo | train |
This term is�used to descibe a complex of symptoms that include neck pain with�irradiation to one or both shouldersand beyond, with pain often�extending as far as the fingers. In many cases, there is no specific cause for the pain other than degeneration or arthrosis ov the vertebral column. If the pain is limited to one specific cervical spinal nerve, the pssibility of a niated disc should be considered. Only in rare cases, the pain is caused by a tumor or infectious process. Traditionally we tend to look on pain as "merely a sypmtom"��of an underlying disease, however, pain specialists condider pain to be a disease in its own right. Especially since we usually cannot find a specific cause, ane even when we can we cannot always�treat the cause.�Moreover the treatment of the cause may involve a surgical intervention.�This is not always feasible or desirable. What's left may be termed symptomatic treatment.
Typical features of cervicobrachialgia, include pain that is provoked by movement, such as bending forward or backward and ratation of the head. These movements may case irradiating pain to the shoulders and/or arms. Rotation case pain on either side. People who wuffer from this are likely to have pain when working above shoulder level or carrying weight.
� Physical examination of the shoulder joint. If there is reason to believe that there ar abnormalities of the shoulder joint, referral to an orthopedic surgeon should be considered.
� Consultation by a neurologist should be considered if thare is reason to believe that a herniated disc may be involved. is would require an MRI or a CT-scan.
Headache is commonplace and is among the top ten health complaints. In some cases, patients have only occasional headaches while in others the headache is continuous. In about 10% of all headaches, find their origin in the neck vertebrae. This type of headache is called cervicogenic headache.
The pain is often provoked by certain movements, particularly extension and rotation of the neck. These movements sometimes have a limited range of motion.
The pain radiates from the neck to the back of the head and from there to the forehead.
The classic form�is one-sided, but can also be bilateral.
The pain is sometimes difficult to distinguish from migraine. The two diagnoses are not mutually exclusive.
When a patient has frequent or almost continuous headache for a periods of moere than three months, his headache is considered to be chronic. Chronic headache can be very debilitating, making many daily activities difficult or impossible to perform. Headache experts divide headaches into different categories. Thes can be seen in a separate appendix to this webpage.
Like the aforementioned pain syndromes, WIP finds in origin in the cervical spine. However, the p[ain is caused not by degeneration of the spine, but is initiated by a trauma. The most common trauma is a sudden extention of the neck such as can be expected when sitting in an automobile and getting hit from behind.Other forms of violence may also initiate this sydrome, such as falling over backward or getting into a head grip. The twisting motion may lead to one/sided symptoms, but with most patients the pain is bilateral. The results of such a villent impact can vary from mild pain over a period of several days, to severe lifelong pain and inability to lead a normal life.
2. The trauma must be of such a nature, that it is likely to have had an impact on the cervical spine.
3. The pain symptoms must start within 48 hours of the trauma and there were no symptoms prior to the trauma, are if there were any, they�should have been much less severe.
4. The pain must be present in the neck or emanate from the neck.
5. The pain is aggravated by movement of the neck, by tension or by remaining in one position for a prolonged period (reading watching TV or sitting�at a�computer).
6. Short term memory and ability to concentrate may be impaired.
7. Physical findings and anatomical defects are often lacking.
8. An X-ray of the cervical spine should be taken, preferably with additional lateral projections with the neck in extension and flexion. Generally there are either no abnormal findings, or if there are any, they are likely to be pre-existent.
Treatment of post-whiplash syndrome (whiplash-associated disorder) is similar toe that of cervicobrachialgia. Psychological and social factors require additional attention, since these often play a part in pain behavior and may even be prominent. Medical treatment includes the classic painkillers, but drugs used for treating neuropathic pain should be considered because the pain is often amplified by central nervous system hyperexcitability. Physical therapy may be helpful, for example TENS . Invasive treatmenst include: radiofrequency treatment of the facet joints, pulsed radiofrequency treatment of the dorsal root ganglion and epidural corticosteroid injections adhesiolysis).
When looking at a patient whose symptoms have only recently developed, the prognosis is favorable. 80% of the patients who develop symptoms, will find that the symptoms remit within a year. The remaining 20% can be problematic. The Quebec Task Force has develop a scale of severity for patients with post whiplash syndroom.
Grade 1: complaints of pain, tenderness �and stifness of the neck, without physical abnormalities or limitations. | en | apollo | train |
Our findings added newer insights into the multifaceted role played by miR-199a-5p/CCR7 in bladder cancer, prompting for the first time this miRNA/chemokine axis that regulates cell metastasis. The results strongly supported miR-199a-5p as a potential therapeutic agent and diagnostic marker of bladder cancer. | en | apollo | train |
pneumoniae_ doesn't.**Optochin sensitivity** : Viridans grows in the presence of the chemical optochin; _S.These organisms are α-hemolytic, but so are the viridans group, so two tests can distinguish between the two:
**Quellung reaction** : Detects the presence of the polysaccharide capsule.They cause the following diseases:
Encarditis in a prosthetic heart valve: think _S. epidermidis_ if < 60 days since surgery, Viridans group strep if > 60 days. Dental caries (especially _Streptococcus mutans_ )
Subacute (slow-onset) bacterial endocarditis following a dental procedure, especially on previously damaged or prosthetic heart valves
Brain or abdominal abscesses (especially intermedius and anginosus groups—if these are found in the blood, use computed tomography [CT] to assess for abscess)
**Group D strep** comprises four species, two of which are enterococci ( _Enterococcus faecalis_ and _Enterococcus faecium_ ) and two of which are not ( _Streptococcus bovis_ and _Streptococcus equinus_ ). The enterococci have recently been given their own genus ( _Enterococcus_ ), but will still be discussed here. _**Enterococcus faecalis**_ and _**Enterococcus faecium**_ are normal inhabitants of bowel (grow well in bile) and commonly cause infections in hospitalized patients: UTIs, biliary tract infections, subacute bacterial endocarditis, wound infections, and bacteremia/sepsis from IV catheters. These species are resistant to many antibiotics. Beware of vancomycin-resistant enterococcus (VRE)! _**Streptococcus bovis**_ bacteremia is highly associated with colon cancer—if you find it in the blood, check for cancer. _**Streptococcus pneumoniae**_ has no Lancefield antigen, appears as lancet-shaped cocci in pairs (diplococci), and contains a **polysaccharide capsule**. These organisms are α-hemolytic, but so are the viridans group, so two tests can distinguish between the two:
**Quellung reaction** : Detects the presence of the polysaccharide capsule. **Optochin sensitivity** : Viridans grows in the presence of the chemical optochin; _S. pneumoniae_ doesn't.pneumoniae, H. influenzae, Legionella_
Pneumonia in older adults: _S.pneumoniae_ , gram-negative rods, _H.influenzae_
Meningitis in adults: _S.pneumoniae_ , gram-negative rods, _Listeria_
_S.pneumoniae_ is a common cause of pneumonia and meningitis in adults (like group B strep in babies) and of otitis media and conjunctivitis in children (Fig.5-12). | en | apollo | train |
Samin Hong, Yeon Soo Chung, Hyun Jong Kim, Yang Je Cho, Chan Yun Kim, Gong Je Seong; Pre-Commercialization of Agmatine Antiglaucoma Eye Drops. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1244.
Purpose : To develop a new antiglaucoma ophthalmic solution containing agmatine in the pre-commercialization stage.
Methods : A new antiglaucoma ophthalmic solution containing 1.0 mM agmatine sulfate has been developed in the pre-commercialization stage. Three candidate eye drops were formulated and their stability was checked for 6 months at both room temperature as well as in the refrigerator. Their ocular safety was carefully evaluated on the cornea of Sprague Dawley rats for 4 weeks. For the most promising agmatine candidate, its ocular hypotensive and neuroprotective effects were assessed for 3 weeks. In addition, its antiglaucoma effects were compared to a currently used antiglaucoma agent of brimonidine which is supposed to have most similar action mechanisms with agmatine among all commercialized antiglaucoma eye drops.
Results : Among 7 available sources of raw agmatine sulfate, the highest one with a purity of 99.92% as determined by high-performance liquid chromatography (HPLC) was selected. All three agmatine formulations were completely stable for at least 6 months and did not cause any apparent ophthalmic complications for 4 weeks. In the chronic ocular hypertensive Sprague Dawley rat models established by episcleral vein cauterization, the candidate agmatine eye drops decreased the intraocular pressures by 19.86% (from 36.50±2.38 mmHg to 29.25±2.06 mmHg) and preserved the intensity of retinal ganglion cell axon as assessed by immunofluorescence for alpha-tubulin.
Conclusions : A new antiglaucoma ophthalmic solution containing 1.0 mM agmatine sulfate has been successfully developed in the pre-commercialization stage. These promising eye drops have excellent ocular hypotensive and neuroprotective effects. | en | apollo | train |
_See_ abdominal aortic aneurysm
AAP.**A**
AAA.Page numbers followed by a _t_ or _f_ indicate locations of Tables or Figures, respectively.Published by The McGraw-Hill Companies, Inc. Click here for terms of use.## **INDEX**
Copyright © 2009 by the American Medical Association.1994;271(5):385-388._JAMA_.Does this patient have a serious form of vertigo?The questionnaire alone would have allowed correct categorization of 61% of the patients with true vertigo according to whether they had episodic (<5 minutes, 5 minutes to 24 hours, 1 day to 1 week) vs persistent vertigo (>1 week) and hearing loss or no hearing loss. #### **CONCLUSIONS**
**LEVEL OF EVIDENCE** Level 4. **STRENGTHS** Simplified approach to recording the patient medical history. **LIMITATIONS** Although the clinician did not have the questionnaire answers, the clinician developed the questionnaire and was thus aware of the study hypotheses. This incorporation bias may have made the questionnaire appear to work better than it would once generalized to other settings. The questionnaire requires evaluation in a primary care and emergency department setting. The details of the clinical examination and other tests are not provided. The sample size is small. Although the overall quality of the study means that the results cannot be applied with confidence, the questionnaire does provide a reasonable paradigm for the initial line of questioning the vertiginous patient. Reviewed by David L. Simel, MD, MHS
#### **REFERENCE FOR THE EVIDENCE**
. Froehling DA, Silverstein MD, Mohr DN, Beatty CW. Does this patient have a serious form of vertigo? _JAMA_. 1994;271(5):385-388. ## **INDEX**
Copyright © 2009 by the American Medical Association. Published by The McGraw-Hill Companies, Inc. Click here for terms of use. Page numbers followed by a _t_ or _f_ indicate locations of Tables or Figures, respectively. **A**
AAA. _See_ abdominal aortic aneurysm
AAP. | en | apollo | train |
###### Investigations
Patch testing (see Chapter 128) is carried out to a standard series, a specific stoma series (Table 114.3) and samples of the appliance and any accessory products used.The patient experiences an itchy, sometimes burning, eczematous rash affecting the skin in contact with the material responsible and spreading out from the area.Avoidance of irritants or allergens is dealt with in the sections on allergic contact dermatitis and irritant skin reactions. ### Allergic contact dermatitis
###### Introduction and epidemiology
Allergic contact dermatitis (ACD) affecting the skin around stomas is relatively uncommon [1], being less than 1% of the skin problems seen in almost 1000 patients attending a dedicated dermatology and joint stoma care clinic. Despite this, many patients and stoma nurses suspect allergy to a stoma appliance as the cause of an otherwise unexplained dermatitis before considering any other aetiology. This can be partly explained by the number of individual case reports published in the last 30 years detailing sensitivities to individual components many of which, such as epoxy resin systems, are no longer used in appliance manufacture. These reports have been eloquently summarized by Martin _et al_. [2]. Where ACD occurs it is usually to biocides in cleansers, fragrances in deodorizers or resin systems in pastes used to fill irregularities in the peristomal skin (Gantrez® PMV/MA co-polymers). ###### Pathophysiology
See Chapter 128 for pathogenetic information on allergic contact dermatitis. ###### Clinical features
The symptoms and clinical appearances of ACD and irritant dermatitis are similar in the occluded peristomal environment and are therefore difficult to distinguish on clinical grounds alone. The patient experiences an itchy, sometimes burning, eczematous rash affecting the skin in contact with the material responsible and spreading out from the area. ###### Investigations
Patch testing (see Chapter 128) is carried out to a standard series, a specific stoma series (Table 114.3) and samples of the appliance and any accessory products used.This involves applying a stoma bag together with accessories such as additional hydrocolloid washers or skin pastes to the non-stoma side of the abdomen.The appliances are changed at the same time as that on their stoma and the test continues for 5–7 days. | en | apollo | train |
Protection of mitomycin C induced skin extravasation with the nitroxide, 3-carbamoyl-PROXYL (3-CP).
Extravasation tissue injury from chemotherapeutic drugs is a serious clinical problem. A swine model has been useful for studying skin extravasation and evaluating potential antidotes. Mitomycin C (MMC) skin extravasation was studied. Nitroxides, a class of compounds which are protective against a variety of oxidative stresses in vitro, including MMC, were tested as antidotes. Miniature swine were anesthetized and given intradermal (ID) injections of MMC. MMC alone caused skin necrosis and ulceration. Several nitroxides were screened as protectors of MMC induced skin necrosis. 3-carbamoyl-PROXYL (3-CP) was the lone nitroxide which protected if given 5 min after extravasation. Administration of 3-CP 10 min after MMC injection was not protective. In vitro studies with monolayered V79 cells showed that 3-CP had a direct protective effect against MMC cytotoxicity in a concentration-dependent fashion. Therefore, in the swine model doses of 3-CP ranging from 25-100 mM were tested and found to protect against MMC skin necrosis 90 days after injection. Histologic sections of the 3-CP- and MMC-treated pig skin showed a marked reduction in the degree of acute inflammation and the absence of deep dermal scarring when compared to MMC alone. | en | apollo | train |
Robert Kellogg Crane (December 20, 1919 – October 31, 2010) was an American biochemist best known for his discovery of sodium–glucose cotransport.
Biography
Crane was born on December 20, 1919 in Palmyra, New Jersey, to Wilbur Fiske Crane, Jr. architect and engineer, and Mary Elizabeth McHale Crane. He is the grandson of Stephen Crane's brother Wilbur.
He received a B.S. from Washington College in 1942. After serving in the Navy during World War II, Crane studied in biochemistry with Eric Ball at Harvard from 1946 to 1949, then spent a year with Fritz Lipmann at Harvard Medical School, and received a Ph.D. in Medical Sciences in 1950. He then joined Carl Cori's Department of Biological Chemistry at Washington University School of Medicine in St. Louis, where he began his long interest in glucose metabolism and worked until 1962. After that, he was professor and chairman of the department of Biochemistry at the Chicago Medical School until 1966 and then became professor and chairman of the department of Physiology and Biophysics at Rutgers Medical School (now known as Robert Wood Johnson Medical School) of the University of Medicine and Dentistry of New Jersey until 1986. He received a Sc.D. from Washington College in 1982.
Discovery of cotransport
In the 1950s, Crane played a central role in establishing that glucose transport into the cell was the first step in glucose metabolism and its control. He demonstrated that neither the phosphorylation-dephosphorylation mechanism nor other covalent reactions accounted for glucose transport in the intestine.
In August 1960, in Prague, Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption. Cotransport was the first ever proposal of flux coupling in biology and was the most important event concerning carbohydrate absorption in the 20th century.
Application in oral rehydration therapy
Crane's discovery of cotransport led directly to the development of oral rehydration therapy. This treatment counterbalances the loss of water and electrolytes caused by cholera via a glucose containing salt solution that accelerates water and electrolyte absorption. This is possible because cholera does not interfere with sodium-glucose cotransport.
Oral rehydration therapy saves the lives of millions of cholera patients in underdeveloped countries since the 1980s. In 1978, The Lancet wrote: "the discovery that sodium transport and glucose transport are coupled in the small intestine, so that glucose accelerates absorption of solute and water, was potentially the most important medical advance this century."
Applications in pharmaceutical drugs
Crane's discovery is also used in blockbuster drugs, such as the SSRI Prozac, which treat depression by inhibiting the Na/serotonin cotransporters in the brain.
Furthermore, major pharmaceutical companies are developing inhibitors of the Na/glucose cotransporters to treat diabetes and obesity.
Awards and honors
First Place, Southeast Regional Scholarship Competition, Lehigh University, 1938.
Kent County Scholar, Washington College, 1941–42.
Atomic Energy Commission Predoctoral Fellow, 1948–49.
Fellow, American Association for the Advancement of Science, 1957.
Headmaster's Alumni Medal, St. Andrew's School, 1963.
Alumni Award, Washington College, 1963.
Fellow, American Institute of Chemists, 1968.
Distinguished Achievement Award, American Gastroenterological Association, 1969.
Sir Arthur Hurst Memorial Lectureship, British Society of Gastroenterology, 1969.
Gastrointestinal Section Lectureship, American Physiological Society, 1971.
Fellow, New York Academy of Sciences, 1976.
Dr. Harold Lamport Award, New York Academy of Sciences, 1977.
Doctor of Science (honoris causa), Washington College, 1982.
Honorary Chairman, International Symposium on the 25th Anniversary of the Gradient Hypothesis, Aussois, France, 18, 19 and 20 September 1985.
Selected bibliography
Robert K. Crane and Anna K. Keltch. "Dinitrocresol and phosphate stimulation of the oxygen consumption of a cell-free oxidative system obtained from sea urchin eggs". The Journal of General Physiology 32, 1949, pp. 503–509.
Robert K. Crane and Eric G. Ball. "Factors affecting the fixation of C1402 by animal tissues". Journal of Biological Chemistry 188, 1951, pp. 819-832.
Robert K. Crane and Eric G. Ball. "Relationship of C1402 fixation to carbohydrate metabolism in retina". Journal of Biological Chemistry 189, 1951, pp. 269–276.
Robert K. Crane and Fritz Lipmann. "The relationship of mitochondrial phosphate to aerobic phosphate bond generation". Journal of Biological Chemistry 201, 1953, pp. 245–246.
Robert K. Crane and Fritz Lipmann. "The effect of arsenate on aerobic phosphorylation". Journal of Biological Chemistry 201, 1953, pp. 235–243.
Robert K. Crane and Alberto Sols. "The association of hexokinase with particulate fractions of brain and other tissue homogenates". Journal of Biological Chemistry 203, 1953, pp. 273–292.
Alberto Sols and Robert K. Crane. "The inhibition of brain hexokinase by adenosinediphosphate and sulfhydryl reagents". Journal of Biological Chemistry 206, 1954, pp. 925–936.
Robert K. Crane and Alberto Sols. "The non-competitive inhibition of brain hexokinase by glucose 6-phosphate and related compounds". Journal of Biological Chemistry 210, 1954, pp. 597–606.
Alberto Sols and Robert K. Crane. "Substrate specificity of brain hexokinase". Journal of Biological Chemistry 210, 1954, pp. 581–595.
Robert K. Crane, Richard A. Field and Carl F. Cori. "Studies of tissue permeability I. The penetration of sugars into Ehrlich ascites tumor cells". Journal of Biological Chemistry 224, 1957, pp. 649–662.
Robert K. Crane and T. Hastings Wilson. "In vitro method for the study of the rate of intestinal absorption of sugars". Journal of Applied Physiology, Vol. 12, 1958, pp. 145–146.
Stephen M. Krane and Robert K. Crane. "The accumulation of D-galactose against a concentration gradient by slices of rabbit kidney cortex". Journal of Biological Chemistry 234, 1959, pp. 211–216.
Robert K. Crane. "Intestinal absorption of sugars". Physiological Reviews, Vol. 40, 1960, pp. 789–825.
Robert K. Crane, D. Miller and I. Bihler. "The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439–449.
D. Miller and Robert K. Crane. "The digestive function of epithelium of the small intestine. 1. An intracellular locus of disaccharide and sugar phosphate ester hydrolysis". Biochimica et Biophysica Acta 52, 1961, pp. 281–293.
Robert K. Crane. "Hypothesis for mechanism of intestinal active transport of sugars". Federation Proc. 21, 1962, pp. 891–895.
David Miller and Robert K. Crane. "The digestion of carbohydrates in the small intestine". American Journal of Clinical Nutrition 12, 1963, pp. 220–227.
Alexander Eichholz and Robert K. Crane. "Studies on the organization of the brush border in intestinal epithelial cells I. Tris density gradient disruption of isolated hamster brush borders and separation of fractions" Journal of Cell Biology 26, 1965, pp. 687–691.
Jane Overton, Alexander Eichholz and Robert K. Crane. "Studies on the organization of the brush border in intestinal epithelial cells II. Fine structure of fractions of tris-disrupted hamster brush borders" Journal of Cell Biology 26, 1965, pp. 693–706.
Robert K. Crane. "Structural and functional organization of an epithelial cell brush border". Intracellular Transport, Symp. Intnl. Soc. Cell BioI. Vol. 5, B. Warren, Ed., Academic Press, 1966, pp. 71–102.
Alexander Eichholz, K. E. Howell and Robert K. Crane. "Studies on the organization of the brush border in intestinal epithelial cells VI. Glucose binding to isolated intestinal brush borders and their subfractions". Biochimica et Biophysica Acta 193, 1969, pp. 179–192.
Robert K. Crane. "A perspective of digestive-absorptive function". American Journal of Clinical Nutrition 22, 1969, pp. 242–249.
Robert K. Crane. "Speculations about mechanism: The ecstasy of transport". 21st annual meeting of the Gastrointestinal Section, American Physiological Society, 1971, pp. 1–16.
Alexander Eichholz and Robert K. Crane. "Isolation of plasma membranes from intestinal brush borders in Methods in Enzymology". Vol. 31, part A, Biomembranes, S. Fleischer and L. Packer, Eds., Academic Press, 1974, pp. 123–134.
Robert K. Crane. "The gradient hypothesis and other models of carrier-mediated active transport". Reviews of Physiology, Biochemistry and Pharmacology, Vol. 78, 1977, pp. 99–159.
Robert K. Crane. "Digestion and absorption: water-soluble organics". International review of physiology, Gastrointestinal physiology II, Vol. 12, Robert K. Crane, Ed., University Park Press, 1977, pp. 325–365.
Robert K. Crane. "Intestinal structure and function related to toxicity". Environmental Health Perspectives 33, 1979, pp. 3–8.
Robert K. Crane. "The road to ion-coupled membrane processes". Comprehensive Biochemistry. Vol 35: Selected Topics in the History of Biochemistry, Personal Recollections l. (Neuberger, A., van Deenen, L. L. M. and Semenga, G., Eds.), Elsevier, Amsterdam, 1983, pp. 43–69.
Robert K. Crane. "Questions". In: the proceedings of an International symposium on 25 years of Research on the Brush Border Membrane and Na+ gradient-coupled transport, Editors: Francisco Alvarado and others, INSERM symposium, No. 26, Elsevier-North Holland, Amsterdam, 1986, pp. 431–438.
Robert K. Crane. "Robert Kellogg Crane: A Scientist Remembers". IUBMB Life, Volume 62, Issue 8, August 2010, pp. 642–645.
Further reading
C. A. Pasternak. "A Glance Back Over 30 Years". Bioscience Reports, Vol. 13, No. 4, 1993, pp. 183–190.
Robert Joseph Paton Williams. "The History of Proton-Driven ATP Formation". Bioscience Reports, Vol. 13, No. 4, 1993, pp. 193, 200–201, 203, 207.
Daphne A Christie, E M. Tansey (eds). "Intestinal absorption". Wellcome Witnesses to Twentieth Century Medicine, Vol. 8, The Wellcome Trust, London, 2000, pp. 17–35.
Stephen M. Kavica, Eric J. Frehmb and Alan S. Segalc. "Case Studies in Cholera: Lessons in Medical History and Science". Yale Journal of Biology and Medicine, Vol. 72, Issue 6, 1999, p. 404.
See also
Cotransport
Cotransporter
Sodium-glucose transport proteins
Glucose transporter
Oral rehydration therapy
References
External links
Video interview of Robert K. Crane by Martin Frank, Ph.D., on November 17, 2009, for the American Physiological Society's Living History of Physiology Project. In this interview Crane describes his training, career and professional interactions.
"For Living History" by Robert K. Crane: article for the American Physiological Society's Living History of Physiology Project.
List of published works of Robert K. Crane for the American Physiological Society's Living History of Physiology Project.
1919 births
2010 deaths
American biochemists
Washington College alumni
Harvard Medical School alumni
Rosalind Franklin University of Medicine and Science faculty
University of Medicine and Dentistry of New Jersey faculty
Washington University in St. Louis faculty
People from Palmyra, New Jersey
United States Navy personnel of World War II | en | apollo | train |
This study shows that topical application of Tualang honey on burn wounds contaminated with P. aeruginosa and A. baumannii gave the fastest rate of healing compared with other treatments. | en | apollo | train |
Purification and Properties of Glyoxysomal Cuprozinc Superoxide Dismutase from Watermelon Cotyledons (Citrullus vulgaris Schrad).
A glyoxysomal copper,zinc-containing superoxide dismutase (EC 1.15.1.1) was purified to homogeneity, for the first time, from watermelon cotyledons (Citrullus vulgaris Schrad.). The stepwise purification procedure consisted of acetone precipitation, batch anion-exchange chromatography, anion-exchange Fast Protein Liquid Chromatography and gel-filtration column chromatography. Pure copper,zinc-superoxide dismutase (Cu,Zn-SOD II) had a specific activity of 1211 units per milligram protein and was purified 400-fold, with a yield of 8 micrograms enzyme per gram cotyledon. The glyoxysomal Cu,Zn-SOD had a relative molecular weight of about 33,000 and was composed of two equal subunits of 16,500 Daltons. Metal analysis showed that the enzyme, unlike other Cu,Zn-SODs, contained 1 gram-atom Cu and 1 gram-atom Zn per mole dimer. No iron and manganese were detected. Ultraviolet and visible absorption spectra were reminiscent of other copper,zinc-superoxide dismutases. | en | apollo | train |
What is the secondary prevention method for glycogen storage disease type III? Effective measures for the secondary prevention of glycogen storage disease type 3 include blood glucose monitoring, prevent overtreatment, general medical care recommendations, gastrointestinal / nutritional recommendations, cardiology recommendations, physical therapy, surgery / anesthesia recommendations, and gynecological / obstetrical recommendations. | en | apollo | train |
The normal parathyroid gland is on the right and consists of lobules of chief cells with central connective and vascular tissue.(B) Encapsulated chief cell adenoma in a horse with primary hyperparathyroidism.Scale = 5 mm.Small white foci of C‐cell hyperplasia can be seen in the thyroid parenchyma (arrow).(C) C‐cell hyperplasia (arrowheads) and adenoma (central mass) in a dog with primary hyperparathyroidism. (D) Intra‐ and interfollicular C‐cell hyperplasia in a dog with primary hyperparathyroidism. Hyperplastic C cells can be identified in H&E sections by the amphophilic tinctorial staining of their cytoplasm. (E) Calcitonin IHC. C‐cell adenoma in a dog. Note the variable staining of the neoplastic cells from intensely positive to negative representing the amount of cytoplasmic stored hormone. Differentiation of C‐cell tumors from solid follicular tumors often requires IHC for calcitonin or thyroglobulin. (F) Calcitonin IHC. Intra‐ and interfollicular C‐cell hyperplasia in a dog with primary hyperparathyroidism. The hyperplastic C cells stain intensely to moderately positive for cytoplasmic calcitonin. 27. Figure 18.27 C‐cell carcinoma from a dog with eosinophilic interstitial amyloid production by the neoplastic cells. C‐cell tumors in the dog are usually malignant. Carcinomas that invade into the thyroid capsule have the potential to metastasize to the lungs. 28. Figure 18.28 Parathyroid chief cell adenoma. (A) Chief cell adenoma ( **A** ) in the external parathyroid gland of a dog with primary hyperparathyroidism. This is the most common cause of primary hyperparathyroidism in dogs. The adenoma is sharply demarcated and encapsulated from the adjacent compressed normal parathyroid gland ( **N** ). Small white foci of C‐cell hyperplasia can be seen in the thyroid parenchyma (arrow). Scale = 5 mm. (B) Encapsulated chief cell adenoma in a horse with primary hyperparathyroidism. The normal parathyroid gland is on the right and consists of lobules of chief cells with central connective and vascular tissue.The infarction of the tumor resulted in spontaneous recovery from primary hyperparathyroidism.The thyroid is on the right.(D) Parathyroid adenoma from a dog.The neoplastic chief cells are on the right and consist of large cells with abundant eosinophilic and partially vacuolated cytoplasm. | en | apollo | train |
Molybdenum cofactor deficiency is a rare human disease in which the absence of molybdenum cofactor leads to accumulation of toxic levels of sulphite and neurological damage. Usually this leads to death within months of birth, due to the lack of active sulfite oxidase. Furthermore, a mutational block in molybdenum cofactor biosynthesis causes absence of enyzme activity of xanthine dehydrogenase/oxidase and aldehyde oxidase. | en | apollo | train |
We may recommend dental sealants if you have deep pits or fissures on the surface of your molars (back teeth) that collect plaque. While we often recommend dental sealants for children, adults can also benefit from getting dental sealants.
A sealant covers the entire chewing surface of your tooth, sealing it from food particles, plaque, and tartar. Our dental sealant dentist in Troy, MI will be able to determine if this procedure is right for you.
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Applying dental sealants is fast, easy, and painless. During the dental sealants procedure, we roughen the chewing surface of your molars before painting on the sealant. Doing this allows the sealant to bond strongly to the surface of your teeth so it’ll last for years to come.
Apply acidic gel to roughen chewing surfaces of molars.
Paint liquid sealant solution over grooves in molars.
Harden dental sealants with special curing light.
It’s important to understand that dental sealants are not meant to replace good oral hygiene habits. You’ll need to continue brushing your teeth twice a day and flossing once daily to remove plaque at home. You’ll also need to see our Troy, MI dentist at least every 6 months for a teeth cleaning and oral examination.
Our dentist offers dental sealants and other preventive dentistry services to help you maintain good oral health. To request an appointment with our dental sealant dentist in Troy, MI, call the Premier Dental Center at (248) 457-0500. | en | apollo | train |
Naftidrofuryl-driven regulation of endothelial ICAM-1 involves nitric oxide.
Naftidrofuryl is a selective inhibitor of the 5-HT2 receptor expressed on human endothelial cells. This drug has been used over the years to cope with cerebral or peripheral ischemic accidents; however, no clear mechanism of action of this molecule has been highlighted to explain its vascular effects. In the present work, we demonstrate that the involvement of nitric oxide can account for the effects of naftidrofuryl. Indeed, naftidrofuryl potently inhibited the TNF-alpha-triggered increase of intercellular adhesion molecule-1 (ICAM-1) expression as well as stress fiber formation in human umbilical vein endothelial cells (HUVEC). Moreover, naftidrofuryl induced the expression of type II nitric oxide synthase (NOS II) messenger and protein, leading to a noticeable increase in nitric oxide synthesis. Furthermore, using the specific NOS II inhibitor 1400W, we verified that the observed effects of naftidrofuryl were NOS II-dependent. The biology of nitric oxide accounts for the reduction of the vasospasm associated with stroke and the strong inhibition of platelet aggregation. In conclusion, our work provides evidence for the inhibition of leukocyte recruitment by downregulation of CD54/ICAM-1, an additional key factor to be dealt with during thrombotic accidents. Importantly, it also highlights a novel NOS II-dependent mechanism of action for naftidrofuryl. | en | apollo | train |
Clinical neuropsychology is a sub-field of psychology concerned with the applied science of brain-behaviour relationships. Clinical neuropsychologists use this knowledge in the assessment, diagnosis, treatment, and or rehabilitation of patients across the lifespan with neurological, medical, neurodevelopmental and psychiatric conditions, as well as other cognitive and learning disorders. The branch of neuropsychology associated with children and young people is pediatric neuropsychology.
Clinical neuropsychology is a specialized form of clinical psychology. Strict rules are in place to maintain evidence as a focal point of treatment and research within clinical neuropsychology. The assessment and rehabilitation of neuropsychopathologies is the focus for a clinical neuropsychologist. A clinical neuropsychologist must be able to determine whether a symptom(s) may be caused by an injury to the head through interviewing a patient in order to determine what actions should be taken to best help the patient. Another duty of a clinical neuropsychologist is to find cerebral abnormalities and possible correlations. Evidence based practice in both research and treatment is paramount to appropriate clinical neuropsychological practice.
Assessment is primarily by way of neuropsychological tests, but also includes patient history, qualitative observation and may draw on findings from neuroimaging and other diagnostic medical procedures. Clinical neuropsychology requires an in-depth knowledge of: neuroanatomy, neurobiology, psychopharmacology and neuropathology.
History
During the late 1800s, brain–behavior relationships were interpreted by European physicians who observed and identified behavioural syndromes that were related with focal brain dysfunction.
Clinical neuropsychology is a fairly new practice in comparison to other specialty fields in psychology with history going back to the 1960s. The specialty focus of clinical neuropsychology evolved slowly into a more defined whole as interest grew. Threads from neurology, clinical psychology, psychiatry, cognitive psychology, and psychometrics all have been woven together to create the intricate tapestry of clinical neuropsychology, a practice which is very much so still evolving. The history of clinical neuropsychology is long and complicated due to its ties to so many older practices. Researchers like Thomas Willis (1621–1675) who has been credited with creating neurology, John Hughlings Jackson (1835–1911) who theorized that cognitive processes occurred in specific parts of the brain, Paul Broca (1824–1880) and Karl Wernicke (1848–1905) who studied the human brain in relation to psychopathology, Jean Martin Charcot (1825–1893) who apprenticed Sigmund Freud (1856–1939) who created the psychoanalytic theory all contributed to clinical medicine which later contributed to clinical neuropsychology. The field of psychometrics contributed to clinical neuropsychology through individuals such as Francis Galton (1822–1911) who collected quantitative data on physical and sensory characteristics, Karl Pearson (1857–1936) who established the statistics which psychology now relies on, Wilhelm Wundt (1832–1920) who created the first psychology lab, his student Charles Spearman (1863–1945) who furthered statistics through discoveries like factor analysis, Alfred Binet (1857–1911) and his apprentice Theodore Simon (1872–1961) who together made the Binet-Simon scale of intellectual development, and Jean Piaget (1896–1980) who studied child development. Studies in intelligence testing made by Lewis Terman (1877–1956) who updated the Binet-Simon scale to the Stanford-Binet intelligence scale, Henry Goddard (1866–1957) who developed different classification scales, and Robert Yerkes (1876–1956) who was in charge of the Army Alpha and Beta tests also all contributed to where clinical neuropsychology is today.
Clinical neuropsychology focuses on the brain and goes back to the beginning of the 20th century. As a clinician a clinical neuropsychologist offers their services by addressing three steps; assessment, diagnosis, and treatment. The term clinical neuropsychologist was first made by Sir William Osler on April 16, 1913. While clinical neuropsychology was not a focus until the 20th century evidence of brain and behavior treatment and studies are seen as far back as the neolithic area when trephination, a crude surgery in which a piece of the skull is removed, has been observed in skulls. As a profession, clinical neuropsychology is a subspecialty beneath clinical psychology. During World War I (1914–1918) the early term shell shock was first observed in soldiers who survived the war. This was the beginning of efforts to understand traumatic events and how they affected people. During the Great Depression (1929–1941) further stressors caused shell shock like symptoms to emerge. In World War II (1939–1945) the term shell shock was changed to battle fatigue and clinical neuropsychology became even more involved with attempting to solve the puzzle of peoples' continued signs of trauma and distress. The Veterans Administration or VA was created in 1930 which increased the call for clinical neuropsychologists and by extension the need for training. The Korean (1950–1953) and Vietnam Wars (1960–1973) further solidified the need for treatment by trained clinical neuropsychologists. In 1985 the term post-traumatic stress disorder or PTSD was coined and the understanding that traumatic events of all kinds could cause PTSD started to evolve.
The relationship between human behavior and the brain is the focus of clinical neuropsychology as defined by Meir in 1974. There are two subdivisions of clinical neuropsychology which draw much focus; organic and environmental natures. Ralph M. Reitan, Arthur L. Benton, and A.R. Luria are all past neuropsychologists whom believed and studied the organic nature of clinical neuropsychology. Alexander Luria is the Russian neuropsychologist responsible for the origination of clinical psychoneurological assessment after WWII. Building upon his originative contribution connecting the voluntary and involuntary functions influencing behavior, Luria further conjoins the methodical structures and associations of neurological processes in the brain. Luria developed the ‘combined motor method’ to measure thought processes based on the reaction times when three simultaneous tasks are appointed that require a verbal response. On the other side, environmental nature of clinical neuropsychology did not appear until more recently and is characterized by treatments such as behavior therapy. The relationship between physical brain abnormalities and the presentation of psychopathology is not completely understood, but this is one of the questions which clinical neuropsychologists hope to answer in time. In 1861 the debate over human potentiality versus localization began. The two sides argued over how human behavior presented in the brain. Paul Broca postulated that cognitive problems could be caused by physical damage to specific parts of the brain based on a case study of his in which he found a lesion on the brain of a deceased patient who had presented the symptom of being unable to speak, that portion of the brain is now known as Broca's Area. In 1874 Carl Wernicke also made a similar observation in a case study involving a patient with a brain lesion whom was unable to comprehend speech, the part of the brain with the lesion is now deemed Wernicke's Area. Both Broca and Wernicke believed and studied the theory of localization. On the other hand, equal potentiality theorists believed that brain function was not based on a single piece of the brain but rather on the brain as a whole. Marie J.P Flourens conducted animal studies in which he found that the amount of brain tissue damaged directly affected the amount that behavior ability was altered or damaged. Kurt Goldstein observed the same idea as Flourens except in veterans who had fought in World War I. In the end, despite all of the disagreement, neither theory completely explains the human brains complexity. Thomas Hughlings Jackson created a theory which was thought to be a possible solution. Jackson believed that both potentiality and localization were in part correct and that behavior was made by multiple parts of the brain working collectively to cause behaviors, and Luria (1966–1973) furthered Jackson's theory.
The job
When considering where a clinical neuropsychologist works, hospitals are a common place for practitioners to end up. There are three main variations in which a clinical neuropsychologist may work at a hospital; as an employee, consultant, or independent practitioner. As a clinical neuropsychologist working as an employee of a hospital the individual may receive a salary, benefits, and sign a contract for employment. In the case of an employee of a hospital the hospital is in charge of legal and financial responsibilities. The second option of working as a consultant implies that the clinical neuropsychologist is part of a private practice or is a member of a physicians group. In this scenario, the clinical neuropsychologist may work in the hospital like the employee of the hospital but all financial and legal responsibilities go through the group which the clinical neuropsychologist is a part of. The third option is an independent practitioner whom works alone and may even have their office outside of the hospital or rent a room in the hospital. In the third case, the clinical neuropsychologist is completely on their own and in charge of their own financial and legal responsibilities.
Assessment
Assessments are used in clinical neuropsychology to find brain psychopathologies of the cognitive, behavioral, and emotional variety. Physical evidence is not always readily visible so clinical neuropsychologists must rely on assessments to tell them the extent of the damage. The cognitive strengths and weaknesses of the patient are assessed to help narrow down the possible causes of the brain pathology. A clinical neuropsychologist is expected to help educate the patient on what is happening to them so that the patient can understand how to work with their own cognitive deficits and strengths. An assessment should accomplish many goals such as; gage consequences of impairments to quality of life, compile symptoms and the change in symptoms over time, and assess cognitive strengths and weaknesses. Accumulation of the knowledge earned from the assessment is then dedicated to developing a treatment plan based on the patient's individual needs. An assessment can also help the clinical neuropsychologist gage the impact of medications and neurosurgery on a patient. Behavioral neurology and neuropsychology tools can be standardized or psychometric tests and observational data collected on the patient to help build an understanding of the patient and what is happening with them. There are essential prerequisites which must be present in a patient in order for the assessment to be effective; concentration, comprehension, and motivation and effort.
Lezak lists six primary reasons neuropsychological assessments are carried out: diagnosis, patient care and its planning, treatment planning, treatment evaluation, research and forensic neuropsychology. To conduct a comprehensive assessment will typically take several hours and may need to be conducted over more than a single visit. Even the use of a screening battery covering several cognitive domains may take 1.5–2 hours. At the commencement of the assessment it is important to establish a good rapport with the patient and ensure they understand the nature and aims of the assessment.
Neuropsychological assessment can be carried out from two basic perspectives, depending on the purpose of assessment. These methods are normative or individual. Normative assessment, involves the comparison of the patient’s performance against a representative population. This method may be appropriate in investigation of an adult onset brain insult such as traumatic brain injury or stroke. Individual assessment may involve serial assessment, to establish whether declines beyond those which are expected to occur with normal aging, as with dementia or another neurodegenerative condition.
Assessment can be further subdivided into sub-sections:
History taking
Neuropsychological assessments usually commence with a clinical interview as a means of collecting a history, which is relevant to the interpretation of any later neuropsychological tests. In addition, this interview provides qualitative information about the patient’s ability to act in a socially apt manner, organise and communicate information effectively and provide an indication as to the patient’s mood, insight and motivation. It is only within the context of a patient’s history that an accurate interpretation of their test data and thus a diagnosis can be made. The clinical interview should take place in a quiet area free from distractions. Important elements of a history include demographic information, description of presenting problem, medical history (including any childhood or developmental problems, psychiatric and psychological history), educational and occupational history (and if any legal history and military history.)
Selection of neuropsychological tests
It is not uncommon for patients to be anxious about being tested; explaining that tests are designed so that they will challenge everyone and that no one is expected to answer all questions correctly may be helpful. An important consideration of any neuropsychological assessment is a basic coverage of all major cognitive functions. The most efficient way to achieve this is the administration of a battery of tests covering: attention, visual perception and reasoning, learning and memory, verbal function, construction, concept formation, executive function, motor abilities and emotional status. Beyond this basic battery, choices of neuropsychological tests to be administered are mainly made on the basis of which cognitive functions need to be evaluated in order to fulfill the assessment objectives.
Report writing
Following a neuropsychological assessment it is important to complete a comprehensive report based on the assessment conducted. The report is for other clinicians, as well as the patient and their family so it is important to avoid jargon or the use of language which has different clinical and lay meanings (e.g. intellectually disabled as the correct clinical term for an IQ below 70, but offensive in lay language). The report should cover background to the referral, relevant history, reasons for assessment, neuropsychologists observations of patient’s behaviour, test administered and results for cognitive domains tested, any additional findings (e.g. questionnaires for mood) and finish the report with a summary and recommendations. In the summary it is important to comment on what the profile of results indicates regarding the referral question. The recommendations section contains practical information to assist the patient and family, or improve the management of the patient’s condition.
Educational requirements of different countries
The educational requirements for becoming a clinical neuropsychologist differ between countries. In some countries it may be necessary to complete a clinical psychology degree, before specialising with further studies in clinical neuropsychology. While some countries offer clinical neuropsychology courses to students who have completed 4 years of psychology studies. All clinical neuropsychologists require a postgraduate qualification, whether it be a Masters or Doctorate (Ph.D, Psy.D. or D.Psych).
Australia
To become a clinical neuropsychologist in Australia requires the completion of a 3-year Australian Psychology Accreditation Council (APAC) approved undergraduate degree in psychology, a 1-year psychology honours, followed by a 2-year Masters or 3-year Doctorate of Psychology (D.Psych) in clinical neuropsychology. These courses involve coursework (lectures, tutorials, practicals etc.), supervised practice placements and the completion of a research thesis.
Masters and D.Psych courses involve the same amount of coursework units, but differ in the amount of supervised placements undertaken and length of research thesis. Masters courses require a minimum of 1,000 hours (125 days) and D.Psych courses require a minimum of 1,500 hours (200 days), it is mandatory that these placements expose students to acute neurology/neurosurgery, rehabilitation, psychiatric, geriatric and paediatric populations.
Canada
To become a clinical neuropsychologist in Canada requires the completion of a 4-year honours degree in psychology and a 4-year doctoral degree in clinical neuropsychology. Often a 2-year master's degree is required before commencing the doctoral degree. The doctoral degree involves coursework and practical experience (practicum and internship). Practicum is between 600 and 1,000 hours of practical application of skills acquired in the program. At least 300 hours must be supervised, face-to-face client contact. The practicum is intended to prepare students for the internship/residency. Internships/residencies are a year long experience in which the student functions as a neuropsychologist, under supervision. Currently, there are 3 CPA-accredited Clinical Neuropsychology internships/residencies in Canada, although other unaccredited ones exist. Prior to commencing the internship students must have completed all doctoral coursework, received approval for their thesis proposal (if not completed the thesis) and the 600 hours of practicum.
United Kingdom
To become a clinical neuropsychologist in the UK, requires prior qualification as a clinical or educational psychologist as recognised by the Health Professions Council, followed by further postgraduate study in clinical neuropsychology. In its entirety, education to become a clinical neuropsychologist in the UK consists of the completion of a 3-year British Psychological Society accredited undergraduate degree in psychology, 3-year Doctorate in clinical (usually D.Clin.Psy.) or educational psychology (D.Ed.Psy.), followed by a 1-year Masters (MSc) or 9-month Postgraduate Diploma (PgDip) in Clinical Neuropsychology.
The British Psychological Division of Counselling Psychology are also currently offering training to its members in order to ensure that they can apply to be registered Neuropsychologists also.
United States
In order to become a clinical neuropsychologist in the US and be compliant with Houston Conference Guidelines, the completion of a 4-year undergraduate degree in psychology and a 4 to 5-year doctoral degree (Psy.D. or Ph.D.) must be completed. After the completion of the doctoral coursework, training and dissertation, students must complete a 1-year internship, followed by an additional 2 years of supervised residency. The doctoral degree, internship and residency must all be undertaken at American Psychological Association approved institutions.
After the completion of all training, students must apply to become licensed in their state to practice psychology. The American Board of Clinical Neuropsychology, The American Board of Professional Neuropsychology, and The American Board of Pediatric Neuropsychology all award board certification to neuropsychologists that demonstrate competency in specific areas of neuropsychology, by reviewing the neuropsychologist's training, experience, submitted case samples, and successfully completing both written and oral examinations. Although these requirements are standard according to Houston Conference Guidelines, even these guidelines have stated that the completion of all of these requirements is still aspirational, and other ways of achieving clinical neuropsychologist status are possible.
Journals
The following represents an (incomplete) listing of significant journals in or related to the field of clinical neuropsychology.
Aging, Neuropsychology and Cognition
Applied Neuropsychology
Archives of Clinical Neuropsychology
Archives of Neurology
Brain
Child Neuropsychology
The Clinical Neuropsychologist
Cognitive Neuropsychology
Cortex
Developmental Neuropsychology
Journal of Clinical and Experimental Neuropsychology
Journal of Cognitive Neuroscience
Journal of the International Neuropsychological Society
Journal of Neuropsychology
Neurocase
Neuropsychologia
Neuropsychological Rehabilitation
Neuropsychology
Neuropsychology Review
Psychological Assessment
See also
Abnormal psychology
Neurolaw
Neuropsychological test
Neuropsychological assessment
Neuropsychology
References
Further reading
This standard reference book includes entries by Kimford J. Meador, Ida Sue Baron, Steven J. Loring, Kerry deS. Hamsher, Nils R. Varney, Gregory P. Lee, Esther Strauss, and Tessa Hart.
This handbook for practitioners includes chapters by Michael W. Parsons, Alexander Rae-Grant, Ekaterina Keifer, Marc W. Haut, Harry W. McConnell, Stephen E. Jones, Thomas Krewson, Glenn J. Larrabee, Amy Heffelfinger, Xavier E. Cagigas, Jennifer J. Manly, David Nyenhuis, Sara J. Swanson, Jessica S. Chapin, Julie K. Janecek, Michael McCrea, Matthew R. Powell, Thomas A. Hammeke, Andrew J. Saykin, Laura A. Rabin, Alexander I. Tröster, Sonia Packwood, Peter A. Arnett, Lauren B. Strober, Mariana E. Bradshaw, Jeffrey S. Wefel, Roberta F. White, Maxine Krengel, Rachel Grashow, Brigid Waldron-Perrine, Kenneth M. Adams, Margaret G. O'Connor, Elizabeth Race, David S. Sabsevitz, Russell M. Bauer, Ronald A. Cohen, Paul Malloy, Melissa Jenkins, Robert Paul, Darlene Floden, Lisa L. Conant, Robert M. Bilder, Rishi K. Bhalla, Ruth O'Hara, Ellen Coman, Meryl A. Butters, Michael L. Alosco, Sarah Garcia, Lindsay Miller, John Gunstad, Dawn Bowers, Jenna Dietz, Jacob Jones, Greg J. Lamberty, and Anita H. Sim.
This collection of articles for practitioners includes chapters by Linda A. Reddy, Adam S. Weissman, James B. Hale, Allison Waters, Lara J. Farrell, Elizabeth Schilpzand, Susanna W. Chang, Joseph O’Neill, David Rosenberg, Steven G. Feifer, Gurmal Rattan, Patricia D. Walshaw, Carrie E. Bearden, Carmen Lukie, Andrea N. Schneider, Richard Gallagher, Jennifer L. Rosenblatt, Jean Séguin, Mathieu Pilon, Matthew W. Specht, Susanna W. Chang, Kathleen Armstrong, Jason Hangauer, Heather Agazzi, Justin J. Boseck, Elizabeth L. Roberds, Andrew S. Davis, Joanna Thome, Tina Drossos, Scott J. Hunter, Erin L. Steck-Silvestri, LeAdelle Phelps, William S. MacAllister, Jonelle Ensign, Emilie Crevier-Quintin, Leonard F. Koziol, and Deborah E. Budding.
External links
Neuropsychology | en | apollo | train |
Fasudil inhibited high glucose-induced apoptosis in rat H9c2 cells through activating autophagy. | en | apollo | train |
[Morphological changes in immunogenesis organs in transplantation of Guerin carcinoma to the spleen].
The study was made in 30 male Wistar rats (b.m. 110+/-10 g) with transplanted Guerin carcinoma to their spleen. Morphological changes in the tumour, spleen, thymus and mesenteric lymph nodes on tumour growth day 7, 10, 14, 18, 22, 25 were studied. The elaborated experimental model of tumour growth in the spleen allowed to detect tumor-specific changes in organs of immunogenesis as well as the dynamics of their development. The findings show possibility of renewal of both cellular content in the tumour-activation of proliferation, and in tissue of the spleen-blast transformation with predominance of lymphoblasts. Morphologic changes in the thymus and regional lymph nodes are different this meaning that changes in the organs of immunogenesis are not of a systemic character, their reaction to the presence of tumour in organism is not always the same and has its own features. | en | apollo | train |
Our results show that resuscitation with FFP attenuates circulating nucleosome levels and prevents DNAse1 depletion. These factors may play a role in the neuroprotective effects observed during early resuscitation with FFP. | en | apollo | train |
RanBP3 Regulates Proliferation, Apoptosis and Chemosensitivity of Chronic Myeloid Leukemia Cells <i>via</i> Mediating SMAD2/3 and ERK1/2 Nuclear Transport.
Abnormal subcellular localization of proteins is an important cause of tumorigenesis and drug resistance. Chromosome region maintenance 1 (CRM1), the nuclear export regulator of most proteins, has been confirmed to be over-expressed in various malignancies and is regarded as an efficient target. But the potential role of the CRM1 cofactor RanBP3 (Ran Binding Protein 3) is left unrevealed in chronic myeloid leukemia (CML). Here, we first detected the level of RanBP3 in CML and found an elevated RanBP3 expression in CML compared with control. Then we used shRNA lentivirus to down-regulated RanBP3 in imatinib sensitive K562 cells and resistant K562/G01 cells and found RanBP3 silencing inhibited cell proliferation by up-regulating p21, induced caspase3-related cell apoptosis, and enhanced the drug sensitivity of IM <i>in vitro</i>. Notably, we observed that RanBP3 silencing restored imatinib sensitivity of K562 cells in NOD/SCID mice. Mechanistically, the nuclear aggregation of SMAD2/3 revealed that tumor suppressor axis (TGF-β)-SMAD2/3-p21 was the anti-proliferation program related to RanBP3 knockdown, and the decrease of cytoplasmic ERK1/2 caused by RanBP3 interference leaded to the down-regulation of anti-apoptosis protein p(Ser112)-BAD, which was the mechanism of increased cell apoptosis and enhanced chemosensitivity to imatinib in CML. In summary, this study revealed the expression and potential role of RanBP3 in CML, suggesting that targeting RanBP3 alone or combined with TKIs could improve the clinical response of CML. | en | apollo | train |
Although some conflicting data exist, one very large epidemiologic study has shown that alcohol consumption during the first trimester of pregnancy, at levels as low as three drinks per week, is associated with an increased incidence of spontaneous pregnancy loss (306–308).Exposure to three particular substances—alcohol, cigarettes, and caffeine—deserves specific attention.Programmed cell death (apoptosis) may also play an essential role in normal placental development. Alterations in two important apoptotic pathways—Fas-Fas ligand and bcl2—have both been linked to recurrent pregnancy loss and poor pregnancy outcome (121,295). Environmental Factors A variety of environmental factors have been linked to sporadic and recurrent early spontaneous pregnancy loss. These are difficult studies to perform, because, in humans, they all must be retrospective and all are confounded by alternative or additional environmental exposures. Nevertheless, the following factors have been linked to pregnancy loss: exposure to medications (e.g., antiprogestogens, antineoplastic agents, and inhalation anesthetics), exposure to ionizing radiation, prolonged exposure to organic solvents, and exposure to environmental toxins, especially bisphenol-A and heavy metals (296–299). The latter two exposures have been demonstrated to have both endocrine and immune effects that could lead to poor placentation and subsequent pregnancy loss (300,301). Associations between spontaneous pregnancy loss and exposures to video display terminals, microwave ovens, high-energy electric power lines, and high altitudes (e.g., flight attendants) are not substantiated (302,303). There is no compelling evidence that moderate exercise during pregnancy is associated with spontaneous abortion. In the absence of cervical anatomic abnormalities or incompetent cervix, coitus does not appear to increase the risk for spontaneous pregnancy loss (304,305). Exposure to three particular substances—alcohol, cigarettes, and caffeine—deserves specific attention. Although some conflicting data exist, one very large epidemiologic study has shown that alcohol consumption during the first trimester of pregnancy, at levels as low as three drinks per week, is associated with an increased incidence of spontaneous pregnancy loss (306–308).Alcohol and tobacco intake in the male partner correlates with the incidence of domestic violence, which in turn is associated with early pregnancy loss (312).Finally, recent evidence adds to a growing body of literature that suggests consumption of coffee and other caffeinated beverages during early pregnancy is linked to adverse pregnancy outcome (309,313). | en | apollo | train |
Inactivation of influenza A virus by gentian violet (GV) and GV-dyed cotton cloth, and bactericidal activities of these agents.
Recently we have heard warnings of an outbreak of a highly pathogenic avian influenza virus (H5N1). Although, to prevent such infections we must prepare anti-viral drugs and type-specific vaccines against influenza, we need various simple and effective protection methods, such as the use of face masks for public health. Also, in any consideration of bacterial infections, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and multidrug-resistant Pseudomonas aeruginosa (MDRP) also pose serious concerns which must be addressed. I examined the antiviral activity of gentian violet (GV) and GV-dyed cloth against the influenza A (H1N1) virus. Time-kill studies were carried out, and the virus titer was determined based on the 50% tissue culture infective dose (TCID50). The minimum inhibitory concentrations (MICs) of GV against bacteria were also determined, and the killing activities of the GV-dyed cloth were judged from viable cell counts. GV immediately killed the influenza A virus and this was confirmed by electron microscopy. Moreover, cloth dyed with a combination of GV and copper showed not only excellent antiviral activity but also prominent bactericidal activities. | en | apollo | train |
Importance of arginine 20 of the swine vesicular disease virus 2A protease for activity and virulence.
A major virulence determinant of swine vesicular disease virus (SVDV), an Enterovirus that causes an acute vesicular disease, has been mapped to residue 20 of the 2A protease. The SVDV 2A protease cleaves the 1D-2A junction in the viral polyprotein, induces cleavage of translation initiation factor eIF4GI, and stimulates the activity of enterovirus internal ribosome entry sites (IRESs). The 2A protease from an attenuated strain of SVDV (Ile at residue 20) is significantly defective at inducing cleavage of eIF4GI and the activation of IRES-dependent translation compared to the 2A protease from a pathogenic strain (J1/73, Arg at residue 20), but the two proteases have similar 1D-2A cleavage activities (Y. Sakoda, N. Ross-Smith, T. Inoue, and G. J. Belsham, J. Virol. 75:10643-10650, 2001). Residue 20 has now been modified to every possible amino acid, and the activities of each mutant 2A protease has been analyzed. Selected mutants were reconstructed into full-length SVDV cDNA, and viruses were rescued. The rate of virus growth in cultured swine kidney cells reflected the efficiency of 2A protease activity. In experimentally infected pigs, all four of the mutant viruses tested displayed much-reduced virulence compared to the J1/73 virus but a significant, albeit reduced, level of viral replication and excretion was detected. Direct sequencing of cDNA derived from samples taken early and late in infection indicated that a gradual selection-reversion to a more efficient protease occurred. The data indicated that extensive sequence change and selection may introduce a severe bottleneck in virus replication, leading to a decreased viral load and reduced or no clinical disease. | en | apollo | train |
Rapid screening of TMAs for routine Her-2 FISH testing is safe, economical and time efficient. The technique ensures that all patients receive 'gold standard' testing. | en | apollo | train |
Triazavirin (TZV, Riamilovir) is a broad-spectrum antiviral drug developed in Russia through a joint effort of Ural Federal University, Russian Academy of Sciences, Ural Center for Biopharma Technologies and Medsintez Pharmaceutical. It has a novel triazolotriazine core, which represents a new structural class of non-nucleoside antiviral drugs.
The main principle action of triazavirin is to inhibit the synthesis of viral ribonucleic acid (RNA) and the replication of viral genomic fragments through its synthetic analogue to the bases of purine nucleosides.
Uses
It was originally developed as a potential treatment for pandemic influenza strains such as H5N1, and most of the testing that has been done has focused on its anti-influenza activity. However, triazavirin has also been found to have antiviral activity against a number of other viruses including Tick-borne encephalitis virus, and Forest-Spring Encephalitis virus, and is also being investigated for potential application against a lethal influenza infection and secondary bacterial pneumonia following influenza, Lassa fever and Ebola virus disease. Triazavirin has passed clinical trials and has shown antiviral activity against ARVI. In 2020, testing of triazavirin was started against SARS-CoV-2 in Russia, China, and South Africa.
In August 2014, the Ministry of Health of Russia issued a registration certificate for triazavirin. The active substance of the drug triazavirin is a new active molecule, and can be dispensed by prescription. The production of triazavirin is carried out at a modern pharmaceutical enterprise LLC "Plant Medsintez". The registration procedure for triazavirin has begun in the Republic of South Africa.
See also
BCX4430
Brincidofovir
Favipiravir
Umifenovir
References
Antiviral drugs
Experimental drugs
Lactams
Thioethers
Nitrogen heterocycles
Heterocyclic compounds with 2 rings
Russian drugs
Russian inventions
Triazoles | en | apollo | train |
While circulating ADMA is higher, NO is lower in COPD and both show a strong correlation to the degree of airflow limitation. ADMA seems to be a possible new marker of prognosis of COPD and can be a novel therapeutic target for the treatment of COPD. | en | apollo | train |
DiscoveryoftheRANK/RANKL/OPGsystemhaspresentednewtherapeuticopportunitiesfortreatingosteoporosis.AbiologicalantiresorptivedrugbasedonahumanizedantibodydirectedagainstRANKLisnowavailablefortreatmentofpostmenopausalosteoporosis.Thishasproventobeaneffectivetreatmentthatimprovesbonedensityandreducestheriskoffracture.As the osteoblasts become surrounded by and entrapped within bone, they become osteocytes that sit within small spaces called lacunae. Osteocytes remain interconnected through cell processes that run within canaliculi and form communicating junctions with adjacent cell processes. The new concentric layers of bone, along with the interconnected osteocytes and the central canal, are referred to collectively as a Haversian system or osteon. Emerging evidence indicates that osteocytes are able to sense mechanical stress in bone and signal that additional local bone formation is needed. They can also detect microdamage in bone that serves to initiate remodeling at that location. Asacalciotropichormone,PTHisapotentregulatorofboneresorptioninadults.ThePTH/PTHrPreceptorisexpressedonosteoblastsbutnotonosteoclasts.ThereforePTHactsonosteoblaststoincreaseexpressionofosteoblastparacrinefactors(i.e.,M-CSF,RANKL)thatupregulateosteoclastdifferentiationandboneresorption.1,25-DihydroxyvitaminDalsostimulatesboneresorptionbyupregulatingRANKLexpressioninosteoblasts. ItisimportanttorecognizethatPTH(alongwith1,25-dihydroxyvitaminD)willpromoteboneresorptionwhenPTHlevelsarehigh(i.e.,duringahypocalcemicchallenge).WhenPTHlevelsarenormal,however,boneremodelingisalocallycontrolledprocessbywhicholddamagedboneisreplaced.Interestinglyithasbeenshownthatintermittentadministrationoflow-dosePTHpromotesosteoblastsurvivalandboneanabolicfunctions,increasesbonedensity,andreducestheriskoffractureinhumans. DiscoveryoftheRANK/RANKL/OPGsystemhaspresentednewtherapeuticopportunitiesfortreatingosteoporosis.AbiologicalantiresorptivedrugbasedonahumanizedantibodydirectedagainstRANKLisnowavailablefortreatmentofpostmenopausalosteoporosis.Thishasproventobeaneffectivetreatmentthatimprovesbonedensityandreducestheriskoffracture.°PTH °1,25(OH)2D3 ˜1,25(OH)2D3
Regulation of Serum Phosphate by FGF23
Study of hypophosphatemic disorders has led to the discovery that FGF23, a peptide hormone produced by osteocytes, is a regulator of Pi metabolism.FGF23 binds to a receptor complex in proximal tubule cells and, like PTH, inhibits NPT2 to promote Pi excretion. | en | apollo | train |
Sodium benzoate, 5 g orally twice daily, ornithine aspartate, 9 g orally three times daily, and L-acyl-carnitine (an essential factor in the mitochrondrial transport of long-chain fatty acids), 4 g orally daily, may lower blood ammonia levels, but there is less experience with these drugs than with lactulose.When given orally, the initial dose of lactulose for acute hepatic encephalopathy is 30 mL three or four times daily. The dose should then be titrated so that the patient produces 2–3 soft stools per day. When given rectally because the patient is unable to take medicines orally, the dose is 200 g/300 mL a solution of lactulose in saline or sorbitol as a retention enema for 30–60 minutes; it may be repeated every 4–6 hours. Bowel cleansing with a polyethylene glycol colonoscopy preparation is also effective in patients with acute overt hepatic encephalopathy and may be preferable. Continued use of lactulose after an episode of acute encephalopathy reduces the frequency of recurrences. The ammonia-producing intestinal flora may also be controlled with an oral antibiotic. The nonabsorbable agent rifaximin, 550 mg orally twice daily, is preferred and has been shown as well to maintain remission of and reduce the risk of rehospitalization for hepatic encephalopathy over a 24-month period, with or without the concomitant use of lactulose. Metronidazole, 250 mg orally three times daily, has also shown benefit. Patients who do not respond to lactulose alone may improve with a course of an antibiotic added to treatment with lactulose. Opioids and sedatives metabolized or excreted by the liver should be avoided. If agitation is marked, oxazepam, 10–30 mg, which is not metabolized by the liver, may be given cautiously by mouth or by nasogastric tube. Zinc deficiency should be corrected, if present, with oral zinc sulfate, 600 mg/day in divided doses. Sodium benzoate, 5 g orally twice daily, ornithine aspartate, 9 g orally three times daily, and L-acyl-carnitine (an essential factor in the mitochrondrial transport of long-chain fatty acids), 4 g orally daily, may lower blood ammonia levels, but there is less experience with these drugs than with lactulose.Use of special dietary supplements enriched with branched-chain amino acids is usually unnecessary except in occasional patients who are intolerant of standard protein supplements.**5. | en | apollo | train |
Because the demented patients with fluent aphasia have impaired comprehension, they may seem apathetic and unconcerned with their language deficits, if they are in fact aware of them at all.More commonly, fluent aphasias occur in conjunction with vascular dementia secondary to a temporal-lobe or parietal-lobe cerebrovascular accident (CVA).Estimates vary depending on the age range of the population studied and whether the individuals sampled were in the general community, acute care facilities, or long-term nursing institutions. 17.2.2 Symptoms
Essential to the diagnosis of dementia is the presence of cognitive deficits that include memory impairment and at least one of the following abnormalities of cognition: aphasia, agnosia, apraxia, or a disturbance in executive function. In addition to defects in memory, patients with dementia often exhibit impairments in language, recognition, object naming, and motor skills. Aphasia is an abnormality of language that often occurs in vascular dementias involving the dominant hemisphere. Because this hemisphere controls verbal, written, and sign language, these individuals may have significant problems interacting with people in their environment. People with dementia and aphasia may exhibit paucity of speech, poor articulation, and a telegraphic pattern of speech (nonfluent, Broca's aphasia). Despite faulty communication skills, patients with dementia with nonfluent aphasia have normal comprehension and awareness of their language impairment. As a result, such individuals often present with significant depression, anxiety, and frustration. By contrast, patients with dementia with fluent (Wernicke's) aphasia may be quite verbose and articulate, but much of the language is nonsensical and rife with such paraphasias as neologisms and clang (rhyming) associations. Whereas nonfluent aphasias are usually associated with discrete lesions, fluent aphasia can result from such diffuse conditions as dementia of the Alzheimer type. More commonly, fluent aphasias occur in conjunction with vascular dementia secondary to a temporal-lobe or parietal-lobe cerebrovascular accident (CVA). Because the demented patients with fluent aphasia have impaired comprehension, they may seem apathetic and unconcerned with their language deficits, if they are in fact aware of them at all.Patients with dementia may also lose their ability to recognize.Agnosia is a feature of a dominant hemisphere lesion and involves altered perception in which, despite normal sensations, intellect, and language, the patient cannot recognize objects.This is in contrast to aphasia in which the patient with dementia may not be able to name objects, but can recognize them. | en | apollo | train |
The mission of the NIDA Brain Development Research Consortium is to foster translational science on brain development, cognition, behavior and functioning to advance the understanding of drug abuse and addiction, prevention, treatment and recovery within the scientific mission areas of NIDA.
The Brain Development Research Consortium includes a multidisciplinary group of NIDA staff representing diverse programs and offices working to enhance basic and clinical research on drug abuse by examining neurodevelopment, addiction and the complex interplay of contextual, behavioral, and genetic factors.
drug abuse recovery for youths and young adults.
National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), funded by the NIAAA, NIMH, NICHD and NIDA is a multisite study to examine the effects of alcohol use on the developing adolescent brain and to determine brain characteristics that predict alcohol use.
Adolescent Brain Cognitive Development Study will be the largest long-term study of cognitive and brain development in children across the United States.
Pediatric Imaging, Neurocognition, and Genetics (PING) is a large MRI and genetics data resource shared openly with the scientific community that includes information about the developing mental and emotional functions of the children between the ages of 3 and 20 years so that links between genetic variation and developing patterns of brain connectivity can be examined.
Monitoring the Future (MTF) Survey has measured drug, alcohol, and cigarette use and related attitudes among adolescent students nationwide since 1975.
National Addiction & HIV Data Archive Program (NAHDAP) acquires, preserves and disseminates data relevant to drug addiction and HIV research.
National Drug Abuse Treatment Clinical Trials Network (CTN) Dissemination Library is a digital repository of resources from NIDA's National Drug Abuse Treatment Clinical Trials Network (CTN).
Pediatric HIV/AIDS Cohort Study (PHACS) is a longitudinal cohort study investigating the long-term effects of HIV infection and ARV (antiretroviral) medications in children and young adults who were born with HIV or born exposed to HIV developed by NICHD and co-funded by NIDA, NIAAA, NIAID, NIDCD, NHBLI, NIMH, NIDS, and OAR.
PhenX (consensus measures for Phenotypes and eXposures) Toolkit is a catalog of recommended, standard measures of phenotypes and environmental exposures for use in biomedical research. PhenX measures that are relevant to development, substance abuse and addiction (SAA) research are included in several research domains.
NIH Toolbox is a multidimensional set of brief measures assessing cognitive, emotional, motor and sensory function from ages 3 to 85, meeting the need for a standard set of measures that can be used as a “common currency” across diverse study designs and settings.
Published January 1997. Revised October 2003. Presents research-based drug abuse prevention principles, an overview of program planning, and critical first steps for those learning about prevention.
Published January 2014. Revised January 2014. Presents research-based principles of adolescent substance use disorder treatment; covers treatment for a variety of drugs including, illicit and prescription drugs, alcohol, and tobacco; presents settings and evidence-based approaches unique to treating adolescents.
Published October 2012. Revised August 2015. Provides parents with research-based skills to help keep their children drug-free. | en | apollo | train |
Glutathione and antioxidants protect microsomes against lipid peroxidation and enzyme inactivation.
The study investigated the relationship between lipid peroxidation and enzyme inactivation in rat hepatic microsomes and whether prior inactivation of aldehyde dehydrogenase (ALDH) exacerbated inactivation of other enzymes. In microsomes incubated with 2.5 microM iron as ferric sulfate and 50 microM ascorbate, ALDH, glucose-6-phosphatase (G6Pase) and cytochrome P450 (Cyt-P450) levels decreased rapidly and concurrently with increased levels of thiobarbituric acid-reactive substances. Microsomal glutathione S-transferase and nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were little affected during 1 hr of incubation. Addition of reduced glutathione partially protected and N,N'-diphenyl-p-phenylenediamine and butylated hydroxytoluene completely protected microsomes against inactivation of ALDH, G6Pase and Cyt-P450, as well as lipid peroxidation induced by iron and ascorbate. ALDH was more susceptible than G6Pase to inactivation by iron and ascorbate, and was thus an excellent marker for oxidative stress. Inhibition of ALDH by cyanamide injection of rats exacerbated the inactivation of G6Pase in microsomes incubated with 0.1 mM, but not 25 microM 4-hydroxynonenal (4-HN). 4-HN did not stimulate lipid peroxidation. Thus, 4-HN may play a minor role in microsomal enzyme inactivation. In contrast, lipid peroxyl radicals play an important role in microsomal enzyme inactivation, as evidenced by the prevention of both lipid peroxidation and enzyme inactivation by chain-breaking antioxidants. | en | apollo | train |
"The years have layered onto this term (i.e.Masturbation in the 19th century was thought of as abnormal.Homosexuality was not that long ago considered a mental illness.Psychiatric textbooks reflect this.Yet we know that history and culture shape what is considered abnormal.We would all like the certainty and clarity of a precise distinction between normal and abnormal.Abnormal psychologists are concerned with the assessment, diagnosis and management of psychological problems. They are both scientists and practitioners who often specialize in the treatment of various disorders like anxiety disorders (anxiety, panic, phobias, post-traumatic stress disorders); mood disorders (depression, bipolar disorder, suicide); substance disorders (alcohol, stimulants, hallucinogens, etc. ); or very complex problems like schizophrenia. Clinical psychology is part, but by no means the central part, of psychology. It is certainly associated by lay people as the most interesting and important specialism in applied psychology. **Defining abnormality** While it is relatively easy to spot people who are distressed or acting bizarrely, it is much more difficult to define abnormality. "Abnormal" means departure from the norm. So very tall and very short people are abnormal, as are very backward and very gifted people. Thus, strictly speaking, Einstein and Michelangelo were abnormal, as were Bach and Shakespeare. For clinical psychology, the issue is not so much whether the behavior is abnormal, as whether it is maladaptive, causing a person distress and social impairment. If a person's behavior seems irrational or potentially harmful to themselves and others, we tend to think of that as abnormal. For the psychologist it is called psychopathology; for the lay person, madness or insanity. We would all like the certainty and clarity of a precise distinction between normal and abnormal. Yet we know that history and culture shape what is considered abnormal. Psychiatric textbooks reflect this. Homosexuality was not that long ago considered a mental illness. Masturbation in the 19th century was thought of as abnormal. "The years have layered onto this term (i.e.A. Reber, 1985
Socio-economic status, gender and race are all related to abnormality.Women are more likely to have anorexia, bulimia or anxiety disorders than men, who, in turn, are more likely to be substance abusers.Poor people are more likely to be diagnosed schizophrenic than rich people. | en | apollo | train |
Fibrillation potentials and positive waves on needle EMG are also commonly found in intrinsic foot muscles as a further indicator of frequently subclinical motor involvement.Abnormalities of median and ulnar CMAPs are much less common.Although some studies have suggested that antisulfatide antibodies are common with painful small fiber neuropathy,, subsequent reports suggest that these antibodies have a very low sensitivity and poor specificity., We never order them as we have found them to be of little use clinically, and a pathogenic relationship has never been demonstrated. That is, the presence of these antibodies does not imply that the patients have an immune-mediated neuropathy and that they may respond to treatment with immunotherapy. We also feel that there is no role for screening various antiganglioside and other antinerve antibodies (e.g., GM1 and Hu antibodies) in the workup of patients with chronic, indolent, sensory predominant, length-dependent polyneuropathies. CSF examination is usually normal and is also unwarranted. In people with a large fiber neuropathy, the sensory NCS reveal either absent or reduced amplitudes that are worse in the legs.,,,– Sensory NCV are normal or only mildly slow. Quantitative sensory testing (QST) demonstrates abnormal thermal and vibratory perception in as many as 85% of patients., In addition, autonomic testing (e.g., quantitative sudomotor axon reflex and heart rate testing with deep breathing or Valsalva) is abnormal in some patients. Despite the fact that sensory symptoms predominate, motor NCS are often abnormal. Wolfe et al. reported that 60% of their patients with idiopathic polyneuropathy had abnormal motor NCS. The most common motor abnormalities are reduced peroneal and posterior tibialis compound muscle action potentials (CMAP) amplitudes, while distal latencies and conduction velocities of the peroneal and posterior tibial CMAPs are normal or only slightly impaired. Abnormalities of median and ulnar CMAPs are much less common. Fibrillation potentials and positive waves on needle EMG are also commonly found in intrinsic foot muscles as a further indicator of frequently subclinical motor involvement.In patients with pure small fiber neuropathies, motor and sensory NCS are, by definition, normal.The peripheral autonomic nervous system is often affected in small fiber neuropathies; thus, autonomic testing can be useful.,– The quantitative sudomotor axon reflex test (QSART) can be performed in the distal and proximal aspects of the legs and arms (Fig.22-1). | en | apollo | train |
They are continuously replaced by new chemoreceptor cells that differentiate from basal cells located near the base of the taste bud.Chemoreceptor cells live only about 10 days.The chemoreceptor cells synapse at their bases with primary afferent nerve fibers, and their apices have microvilli that extend toward a taste pore.8.29A ).Vestibular reflexes and clinical tests of vestibular function are described in
The Chemical Senses
The senses of gustation (taste) and olfaction (smell) help detect chemical stimuli that are present either in food and drink or in the air. In the evolution of humans, these chemical senses apparently did not have the survival value of some of the other senses, but they contribute considerably to quality of life and food selection, and they are important stimulants of digestion. In other animals, the chemical senses have greater survival value, and their activation evokes a number of social behaviors, including mating, territoriality, and feeding. The stimuli that we commonly know as tastes are actually mixtures of five elementary taste qualities: salty, sweet, sour, bitter, and umami. Taste stimuli that are particularly effective in eliciting these sensations are, respectively, sodium chloride, sucrose, hydrochloric acid, quinine, and mono-sodium glutamate. Umami has been described as having a proteinaceous, meaty character. bThe existence of a sixth, taste, fat (free fatty acids), is currently being debated. CHAPTER 8 The Special Senses
The sensation of taste depends on the activation of chemoreceptors located in taste buds. A taste bud consists of a group of 50 to 150 receptor cells, as well as supporting cells and basal cells (Fig. 8.29A ). The chemoreceptor cells synapse at their bases with primary afferent nerve fibers, and their apices have microvilli that extend toward a taste pore. Chemoreceptor cells live only about 10 days. They are continuously replaced by new chemoreceptor cells that differentiate from basal cells located near the base of the taste bud.Some stimuli can pass directly into the cell to depolarize it (Na+ for salty and H+ for sour) or open cation channels to generate a receptor potential (also salty and sour), whereas others (sucrose, quinine, and glutamate for sweet, bitter, and umami) activate a second messenger that can either open cation channels or directly activate intracellular Ca++ stores (see
Fig.8.29B ). | en | apollo | train |
Stressor and glucocorticoid-dependent induction of the immediate early gene kruppel-like factor 9: implications for neural development and plasticity.
Krüppel-like factor 9 (KLF9) is a thyroid hormone-induced, immediate early gene implicated in neural development in vertebrates. We analyzed stressor and glucocorticoid (GC)-dependent regulation of KLF9 expression in the brain of the frog Xenopus laevis, and investigated a possible role for KLF9 in neuronal differentiation. Exposure to shaking/confinement stressor increased plasma corticosterone (CORT) concentration, and KLF9 immunoreactivity in several brain regions, which included the medial amygdala and bed nucleus of the stria terminalis, anterior preoptic area (homologous to the mammalian paraventricular nucleus), and optic tectum (homologous to the mammalian superior colliculus). The stressor-induced KLF9 mRNA expression in the brain was blocked by pretreatment with the GC receptor antagonist RU486, or mimicked by injection of CORT. Treatment with CORT also caused a rapid and dose-dependent increase in KLF9 mRNA in X. laevis XTC-2 cells that was resistant to inhibition of protein synthesis. The action of CORT on KLF9 expression in XTC-2 cells was blocked by RU486, but not by the mineralocorticoid receptor antagonist spironolactone. To test for functional consequences of up-regulation of KLF9, we introduced a KLF9 expression plasmid into living tadpole brain by electroporation-mediated gene transfer. Forced expression of KLF9 in tadpole brain caused an increase in Golgi-stained cells, reflective of neuronal differentiation/maturation. Our results support that KLF9 is a direct, GC receptor target gene that is induced by stress, and functions as an intermediary in the actions of GCs on brain gene expression and neuronal structure. | en | apollo | train |
Detection of doxorubicin-induced apoptosis of leukemic T-lymphocytes by laser tweezers Raman spectroscopy.
Laser tweezers Raman spectroscopy (LTRS) was used to acquire the Raman spectra of leukemic T lymphocytes exposed to the chemotherapy drug doxorubicin at different time points over 72 hours. Changes observed in the Raman spectra were dependent on drug exposure time and concentration. The sequence of spectral changes includes an intensity increase in lipid Raman peaks, followed by an intensity increase in DNA Raman peaks, and finally changes in DNA and protein (phenylalanine) Raman vibrations. These Raman signatures are consistent with vesicle formation, cell membrane blebbing, chromatin condensation, and the cytoplasm of dead cells during the different stages of drug-induced apoptosis. These results suggest the potential of LTRS as a real-time single cell tool for monitoring apoptosis, evaluating the efficacy of chemotherapeutic treatments, or pharmaceutical testing. | en | apollo | train |
Identification of amine receptors from a swallowtail butterfly, Papilio xuthus L.: cloning and mRNA localization in foreleg chemosensory organ for recognition of host plants.
The swallowtail butterfly, Papilio xuthus L., feeds exclusively on members of the plant family, Rutaceae. Female butterflies lay eggs in response to specific chemicals contained in their host plants. They perceive a variety of polar compounds as oviposition stimulants through the tarsal chemosensilla of the foreleg by drumming upon the leaf surface. Some biogenic amine analogs have been characterized as oviposition stimulants. We have cloned three amine receptors, serotonin, tyramine, and dopamine, from cDNA derived from foreleg tarsus of P. xuthus, and determined structures of both cDNA and genomic genes. The phenylethylamine (tyramine and dopamine) receptors were expressed preferentially in brain and chemosensory organs. Moreover, we observed the localized expression of dopamine receptors at the base of tarsal chemosensilla by in situ hybridization. These results suggest that amine receptors in tarsal chemosensilla have a functional role in chemoreception for host plant recognition. | en | apollo | train |
1Department of Pharmaceutics, Industrial Pharmacy Laboratory, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, INDIA.
2Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, Maharashtra, INDIA.
3Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, INDIA.
4Department of Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, INDIA.
The modulation of mucoadhesion at the nanoscale is a very challenging task before the formulation scientists. Mucoadhesive nanoparticles are endowed with distinct properties such as increased residence, intimate contact of mucoadhesive dosage form at the mucosal surface and reproducible drug absorption. Large surface area, porous endothelial membrane, high total blood flow, ready accessibility, rapid onset of action, low enzyme level compared to gastrointestinal tract and avoidance of hepatic first pass metabolism are few of the major reasons for preferred drug delivery across the nasal mucosal membrane. There is a limited systematic summarized literature is available which could outline the potential of mucoadhesive nanoparticles for intranasal administration and present review could be an excellent platform to fulfill the voids. The authors put very enthusiastic opinion that the nasal mucoadhesive nanocarriers would meet the criteria set by regulatory authorities and soon such formulations would be available to accomplish the healing desires of the community, provided a successful execution of extensive clinical research with encouraging outcomes.
Key words: Nanomedicine, Nanoparticles, Mucoadhesion, Intranasal, Drug delivery. | en | apollo | train |
Initial-phase serum levels of chemokines in patients with meningococcal sepsis can predict mortality and can correlate strongly with disease severity. Chemokines may play a key role in the pathophysiology of meningococcal disease and are potentially new targets for therapeutic approaches. | en | apollo | train |
Many patients with invasive lobular carcinoma have metastatic disease in bone at the time of first presentation, and this disease is often highly responsive to primary endocrine therapy.What treatment would you recommend at that time? **
1. Continue tamoxifen and Xgeva
2. Surgical resection of primary tumor and radiation, followed by continued tamoxifen and Xgeva
3. Bilateral mastectomy, and continued tamoxifen and Xgeva
Approximately 5% of patients have metastatic disease at the time of initial diagnosis (stage 4). The major focus of treatment of these patients is to control their systemic disease with appropriate drug treatment. Historically, local treatment for the primary tumor and nodes has been reserved for those patients with locally advanced disease, to control local complications such as ulceration, bleeding, and infection. With improvement in systemic treatment, however, many patients who present with metastatic disease are experiencing longer survival. In such patients, the question arises: do they benefit from resection of the primary tumor? And, if so, when? There are numerous retrospective studies that have addressed the issue. Overall these studies suggest an approximately 40% improvement in short-term (3-year) survival in those patients who underwent surgery. Currently there are ongoing randomized prospective trials (in India, in Turkey, and ECOG 2108 in the United States) that will hopefully provide more definitive guidelines. At present, surgical resection of the primary tumor appears most appropriate for younger patients, those who have a favorable response to systemic therapy, and patients who have bone and soft tissue, as opposed to visceral metastases. Many patients with invasive lobular carcinoma have metastatic disease in bone at the time of first presentation, and this disease is often highly responsive to primary endocrine therapy.In the absence of BRCA gene mutation, and with the presence of metastatic disease, bilateral mastectomy is not indicated.* * *
* * *
# Case study 83.5
Locally Advanced and Inflammatory Cancer
A 55-year-old woman presented with a 4-week history of swelling and redness of the right breast, which was unresponsive to two courses of antibiotics from her family doctor. | en | apollo | train |
Saffron is a lovely spritely 13year old cat that we have had in the practice for dental treatment yesterday. Saffron has had problems with her mouth which has required her to have all her molars and premolar teeth extracted.
This procedure is occasionally required when a cat develops an inflammatory problem called Stomatitis or Faucitis. Stomatitis is a general term that refers to inflammation of the oral cavity. Faucitis is a term that has been used to describe inflammation of the tissues behind the teeth in the back of the oral cavity. Both can be due to several different causes, but viral infections such as “Calici Virus” can be involved.
This viral disease results in the cats own body over-reacting and fighting itself and causing inflammation and ulceration of the mouth and throat area (see the photo of Saffrons tongue, with an ulcer, a couple of weeks ago and a more extreme form of ulceration in another cats mouth due to calici Virus) and sometimes even pneumonia and even lameness in young kittens. This can flare up from time to time if the cat becomes a carrier of the virus and sometimes requires just simple treatment during these flare ups. However, sometimes the consequences of the virus are more severe and further, more invasive treatments, are required. This may mean removal of all the teeth and very importantly, removal of the roots of the teeth as well. If this is not successful, then we also sometimes need to use anti-viral medications. We can vaccinate our cats against Calici virus and this usually gives protection for most cats against developing severe clinical signs. Please do take a look at our section on "Vaccinating your Cat" or give us a call at the surgery on 01254 53622 if you require any advice on this or any other subject.
It is estimated that 50 to 80% of animals that are taken into a veterinary practice for any reason, have concurrent dental issues. As such “dental treatment” is a common procedure performed here at Daisy Street. Cat dentistry can be especially difficult and is a skill full, time consuming procedure. Cats teeth are designed to catch and hold prey…not to be removed. As such this can result in the tooth “snapping” whilst being removed. This does not always cause concern, especially in some forms of dental disease such as “Neck Lesions”, but in cases such as Saffron’s, it is very important that we remove all the roots, or the inflammation may not resolve.
Thus due to the difficulty to remove cats teeth, especially when the actual tooth is healthy as in Saffron’s case, we have to resort to surgery where we remove the surrounding bone and gently lift the tooth out. Sutures are then placed to close the wound.
As you can see from the photo, the teeth are designed so as not to be easily pulled out. The bottom part of the tooth that is deep in the jaw bone is wider than higher up the tooth. Also the amount of tooth you see – the “crown”, is only a very small section of the whole tooth (a little like the iceberg phenomenon). Along with the fact that many of the cats teeth have two or even three roots, all pointing in different direction again to oppose removal…you can quickly see why it almost impossible for the tooth and root to come out unless the tooth is diseased or broken.
In Saffron’s case, she recovered very well and was eating again after a couple of hours. We will have to see if this treatment is sufficient to cure her Faucitis but we are all wishing her a speedy recovery here at Daisy Street Vets.
Samantha Purcell, Daisy Street Vets Blackburn. | en | apollo | train |
In vitro antibacterial and morphological effects of the urushiol component of the sap of the Korean lacquer tree (Rhus vernicifera Stokes) on Helicobacter pylori.
Eradication regimens for Helicobacter pylori infection have some side effects, compliance problems, relapses, and antibiotic resistance. Therefore, alternative anti-H. pylori or supportive antimicrobial agents with fewer disadvantages are necessary for the treatment of H. pylori. We investigated the pH-(5.0, 6.0, 7.0, 8.0, 9.0, and 10.0) and concentration (0.032, 0.064, 0.128, 0.256, 0.514, and 1.024 mg/mL)-dependent antibacterial activity of crude urushiol extract from the sap of the Korean lacquer tree (Rhus vernicifera Stokes) against 3 strains (NCTC11637, 69, and 219) of H. pylori by the agar dilution method. In addition, the serial (before incubation, 3, 6, and 10 min after incubation) morphological effects of urushiol on H. pylori were examined by electron microscopy. All strains survived only within pH 6.0-9.0. The minimal inhibitory concentrations of the extract against strains ranged from 0.064 mg/mL to 0.256 mg/mL. Urushiol caused mainly separation of the membrane, vacuolization, and lysis of H. pylori. Interestingly, these changes were observed within 10 min following incubation with the 1xminimal inhibitory concentrations of urushiol. The results of this work suggest that urushiol has potential as a rapid therapeutic against H. pylori infection by disrupting the bacterial cell membrane. | en | apollo | train |
Cancer-Associated Fibroblasts in Mycosis Fungoides Promote Tumor Cell Migration and Drug Resistance through CXCL12/CXCR4.
Cancer cells are known to reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) to act as tumor supporters. The presence and role of CAFs in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, are unknown. This study sought to characterize CAFs in MF and their cross talk with the lymphoma cells using primary fibroblast cultures from punch biopsies of patients with early-stage MF and healthy subjects. MF cultures yielded significantly increased levels of FAPα, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4 axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility. Our data suggest that the fibroblasts in MF lesions are more proliferative than fibroblasts in normal skin and that CAFs protect MF cells from doxorubicin-induced cell death and increase their migration through the secretion of CXCL12. Reversing the CAF-mediated tumor microenvironment in MF may improve the efficiency of anticancer therapy. | en | apollo | train |
Histological Analysis, Bioinformatics Profile, and Expression of Methylenetetrahydrofolate Reductase (MTHFR) in Bovine Testes.
Methylenetetrahydrofolate reductase (MTHFR), an enzyme expressed in mammalian testes, exerts a direct effect on spermatogenesis; however, its protein characteristics in bovine testes remain unknown. Here, we analysed bovine testicular structure, MTHFR bioinformatics profile, mRNA, and protein expression characteristics in yellow-cattle (y-c) and yak testis using histological procedures, bioinformatics analysis, qRT-PCR, and western blot. Testes from 13 bovines, ≤2 years juvenile (y-c, <i>n</i> = 3; yak, <i>n</i> = 3) and ≥3 years adult (y-c, <i>n</i> = 3; yak, <i>n</i> = 4) were collected and analysed. Anatomical characteristics of testis in y-c and yak were similar except the weight or size for which that of y-c was significantly higher or greater than yak. In y-c, an open reading frame (ORF) for 2600 nucleotides sequence, encoding 655 amino acids showed high homology with zebu cattle (99.51%) and wild yak (98.68%). Secondary and 3D protein structures were similar to that of humans with differences in the number of nucleotides, amino acids, and some physico-chemical characteristics. MTHFR mRNA expression in y-c and yak were significantly higher in adult testes compared with juvenile ones. However, its protein expression was higher, but not statistically significant, in adult y-c and yak compared to the juvenile ones. The highlights and inferences of these and other findings are discussed. | en | apollo | train |
• Green tea polyphenols have shown renal protection.### Keywords
Chronic kidney disease; elderly; diet; renal function
Key Facts
• Regular fish consumption, independent of overall dietary and other measured lifestyle habits, seems to be a non-pharmacological means in the maintenance of preserved kidney function, especially among elders.Chapter 31
# How Nutrition Affects Kidney Function in Aging
Christina Chrysohoou1, Georgios A. Georgiopoulos1 and Ekavi N. Georgousopoulou2, 11st Cardiology Clinic, University of Athens, Athens, Greece, 2Department of Nutrition-Dietetics, School of Health and Education, Harokopio University, Athens, Greece
## Abstract
Aging causes deterioration in kidney function leading to chronic kidney disease. Chronic kidney disease has been associated with oxidative stress, increased circulating levels of inflammatory markers, phosphate retention with medial vascular calcification, increased parathyroid hormone concentrations causing valvular calcification and dysfunction, anemia, and left ventricular hypertrophy, all of which can increase cardiovascular risk. Among lifestyle factors, diet plays an important role in the prevention of renal failure. Although, there is no specific dietary pattern for preventing renal failure, excessive intake of protein, sodium, potassium and alcohol have shown to be related with the progression of renal failure even among elderly individuals; while the well-balanced Mediterranean diet has been related with preserved renal function. Fish and polyunsaturated fatty acids (PUFA) consumption has been favorably related to the prognosis of kidney function, mainly due to the anti-inflammatory properties of PUFA, as well as to its negative correlation with blood pressure levels. ### Keywords
Chronic kidney disease; elderly; diet; renal function
Key Facts
• Regular fish consumption, independent of overall dietary and other measured lifestyle habits, seems to be a non-pharmacological means in the maintenance of preserved kidney function, especially among elders. • Green tea polyphenols have shown renal protection.• Excessive intake of protein, sodium, potassium, and alcohol has been associated with the progression of kidney failure.• Omega-3 fatty acids supplementation has shown beneficial impact in chronic kidney disease.• Mediterranean type of diet has been linked with improved rates of renal function, due to its anti-inflammatory and antioxidative properties. | en | apollo | train |
Haemostasis in Thyroid Surgery: Collagen-Fibrinogen-Thrombin Patch versus Cellulose Gauze-Our Experience.
Purpose. Postoperative hemorrhage is fortunately uncommon but potentially life-threatening complication of thyroid surgery that increases the postoperative morbidity and the hospital stay. In this study we compare the efficacy of collagen patch coated with human fibrinogen and human thrombin (CFTP) (group C) and oxidized regenerated cellulose gauze (group B) versus traditional hemostatic procedures (group A) in thyroid surgery. Methods. From January 2011 to December 2013, 226 were eligible for our prospective, nonrandomized, comparative study. Patients requiring a video-assisted thyroidectomy without drain, "near total," or hemithyroidectomy were excluded. Other exclusion criteria were a diagnosis of malignancy, substernal goiter, disorders of hemostasis or coagulation, and Graves or hyperfunctioning thyroid diseases. Outcomes included duration of operation, drainage volume, and postoperative complications. Results. Our results show a significant reduction in drainage volume in group C in comparison with the other two groups. In group C there was no bleeding but the limited numbers do not make this result significant. There were no differences in terms of other complications, except for the incidence of seroma in group B. Conclusion. The use of CFTP reduces the drainage volume, potentially the bleeding complications, and the hospital stay. These findings confirm the efficacy of CFTP, encouraging its use in thyroid surgery. | en | apollo | train |
Interestingly, this same protein is involved in rheumatoid arthritis, another inflammatory condition.It was as if Emily's entire body had become inflamed.Doctors worked tirelessly to determine what had caused Emily's sudden illness and soon learned that a certain protein—interleukin-6 (IL-6)—had become highly elevated, a sign of inflammation caused by her immune system's explosive attack.Several of June's adult patients had already been enrolled in the study and had responded well. After doctors harvested Emily's T cells, they reengineered them in a laboratory using a disabled form of the HIV virus to insert a new gene in these cells' DNA. Her "new and improved" T cells would now make a protein called CD19 that is found only on the surface of B cells, the very cells that had become cancerous in Emily. Once the reengineered cells were infused back into Emily's blood, they would then be able to recognize the CD19 markers on the leukemic B cells that threatened Emily's life. On April 17, 2012, Emily became the first pediatric patient in the world to be treated with the CAR-T immunotherapy then known as CTL019. A sign that this cellular therapy is working is what oncologists call "shake and bake." The patient becomes very ill, with uncontrollable chills and raging fevers, a sign that the therapy had indeed initiated a kind of civil war between the engineered T cells and the leukemic B cells. But as is sometimes the case with experimental treatments, Emily's symptoms were much more severe than doctors anticipated. She became critically ill and was admitted to the pediatric intensive care unit at CHOP and later placed on a ventilator to assist her breathing. At one point, she was very close to death and given only a one-in-a-thousand chance of survival. Doctors worked tirelessly to determine what had caused Emily's sudden illness and soon learned that a certain protein—interleukin-6 (IL-6)—had become highly elevated, a sign of inflammation caused by her immune system's explosive attack. It was as if Emily's entire body had become inflamed. Interestingly, this same protein is involved in rheumatoid arthritis, another inflammatory condition.Serendipitously—as sometimes happens in medical research—June's daughter has rheumatoid arthritis and uses tocilizumab as part of her treatment regimen.Although the drug had never been used in this setting before, the team reasoned that it might dampen the IL-6 storm raging in Emily's body and immediately administered tocilizumab to Emily, with dramatic results. | en | apollo | train |
1C Davila University of Medicine, Bucharest, Romania; 2Institute of Endocrinology, Bucharest, Romania; 3Molecular Endocrinology Laboratory, IURC, Montpellier 1 University, Montpellier, France.
Background: The incidence of metabolic syndrome (MetS) is higher in polycystic ovary syndrome (PCOS) patients than in the general population. However, it is still unclear if MetS is qualitatively different in PCOS.
Aim: To compare the distribution of MetS diagnostic criteria and of insulin-resistance in subjects with MetS (PCOS versus matched controls).
Patients: Of 97 patients with PCOS (Rotterdam criteria) and 31 age- and BMI-matched eumenorrheic, non-hirsute women were recruited at the Institute of Endocrinology, Bucharest, Romania. All subjects were examined and waist circumference, BMI and blood pressure (BP) were recorded. Blood lipids, glycemia and insulinemia were measured after an overnight fast and a standard oral glucose tolerance test (OGTT) was performed. All samples were collected during the early follicular phase of the menstrual cycle.
Results: According to IDF criteria, MetS was present in 33% of PCOS patients and in 29% of controls (P=NS). No significant differences were found between the PCOS patients with MetS (group A, n=32) and controls with MetS (group B, n=9), regarding serum triglycerides, HDL-cholesterol, BP values and waist circumference. Impaired fasting glucose (IFG) or type 2 DM was more frequent in group A than group B (40.63% versus none, P<0.05).
Insulin-resistance (HOMA-IR> 90th percentile of a Romanian female population reference) was more frequent in group A than group B (55.17 vs 12.5%, P=0.04). Insulin-resistance was strongly associated with MetS (P<0.0001, χ2) within the whole PCOS group, but not in the control subjects. Furthermore, PCOS patients with MetS had higher 2hr-glucose during OGTT than patients without MetS (125.2±6 vs 97.8±4.1 mg/dl, P<0.001; mean±S.E.M).
Conclusions: The incidence of each MetS criterion is not different between MetS subjects with PCOS and matched MetS controls, except for IFG / type 2 DM. In PCOS, insulin-resistance is more frequent and correlates strongly with MetS. | en | apollo | train |
For example, _p53_ mutations are frequent in established cancers.Mutations in many of the genes maintaining normal mitosis have been described in cancer.There are many ways in which such instability can be produced, bearing in mind the complexity of the mitotic process.Chromosomal instability is a hallmark of cancer where cells are often aneuploid.A phase of cell growth (G2) occurs before entry into mitosis, which is initiated by proteins known as cyclin-dependent kinases (Figure 3.6). At the onset of mitosis, prometaphase, each member of the pairs attaches at its centromere to proteins that will form part of the mitotic spindle. Unattached chromatids issue a delaying signal until all are attached and the spindle formed (metaphase). The nuclear membrane disappears while this process is occurring. A second group of proteins assembles, the anaphase-promoting complex, which degrades proteins that prevent anaphase from beginning. In anaphase there is enzymic cleavage of the ties (cohesins) that bind the two sister chromatids and the two sets of chromosomes separate to opposite poles of the cell. The cell divides and the daughter cells pass into a prolonged resting phase (G0) or into a first growth phase (G1) that leads to a further cycle of DNA replication. **Figure 3.6** Diagrammatic representation of the process of mitosis and the checkpoints. The terms are explained in the text. At each stage there are checks to ensure the fidelity of the process before it continues. Mitosis does not begin until the presence of DNA damage has been detected by proteins such as _p53_ (see below), ATM and CHK2. The integrity of the mitotic spindle phase is checked by BUB1 and MAD proteins (see Figure 3.6). If these proteins are inactive, the chromosomes fail to segregate correctly. Chromosomal instability is a hallmark of cancer where cells are often aneuploid. There are many ways in which such instability can be produced, bearing in mind the complexity of the mitotic process. Mutations in many of the genes maintaining normal mitosis have been described in cancer. For example, _p53_ mutations are frequent in established cancers.Some of the protective proteins are targets for viral carcinogenesis.For example, HTLV-1 produces a protein (TAX) that degrades MAD1 and results in chromosomal instability.Numerous other proteins are involved in the regulation of mitosis, such as APC (mutated in adenomatous polyposis coli). | en | apollo | train |
As part of the modeling, the researchers used data from the three most recent National Health and Nutrition Examination Surveys, as well as from published sources and meta-analyzes which included demographic information, dietary intakes, policy effects, diet-disease effects, policy costs and healthcare costs.
"Our findings support the implementation and evaluation of healthy food prescriptions . . . to improve the diet and health of Americans," said researcher Yujin Lee, a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts University in Boston.
"We found that partial coverage of the cost of purchasing fruits, vegetables, whole grains, nuts/seeds, seafood and plant oils in Medicare and Medicaid would be highly cost-effective--about the same cost-effectiveness as drug treatments for high cholesterol or high blood pressure," Lee said.
"It's exciting that we are finally having a conversation about this because it needs to happen," said Massart, director of the Primary Care Precision Medicine Clinic at the University of Pittsburgh Medical Center. "It would be so great to see money invested in an intervention that could make a difference in quality of life and in reducing disease burden and potentially cost less."
While the study findings are based on a model rather than an actual trial, "it may convince people to put money into research studies on actual people in real communities," Massart said. "This is part of the whole concept of precision medicine. People are born with a genetic predisposition for diseases that interacts with environmental exposure. Often the risk factors are modifiable."
Massart said she would enthusiastically embrace the concept if it could be proven in trials. "I'd much rather prescribe a cucumber over a pharmaceutical any day," she added. | en | apollo | train |
Mixed or variable threshold angina pectoris is a syndrome in which there is substantial variation in the magnitude of physical activity that induces anginal chest pain. | en | apollo | train |
Dry Beriberi: neuro symptoms caused by thiamine deficiency
Wet Beriberi: cardiac symptoms caused by thiamine deficiency
Infantile Beriberi: neuro/cardiac symptoms caused by thiamine deficiency in <1 year old infant
Anything that causes thiamine (vitamin B1) deficiency: poor dietary intake, malabsorption, increased metabolic requirement
Chronic alcoholism, dieting/fasting/starvation, anorexia, vomiting/diarrhea, unbalanced TPN, GI surgery, malignancy, dialysis, AIDS, IBD, pancreatitis, liver disease, thyrotoxicosis
Chronic alcoholism, dieting/fasting/starvation, anorexia, vomiting/diarrhea, unbalanced TPN, GI surgery, malignancy, dialysis, AIDS, IBD, pancreatitis, liver disease, thyrotoxicosis
Thiamine is a cofactor for enzymes required in:
Krebs cycle
Pentose phosphate pathway
Alpha-ketoglutarate dehydrogenase
Pyruvate dehydrogenase.
Because thiamine is an important cofactor in critical pathways for energy production, deficiency results in lactic acidosis and alteration of brain metabolism.
Thiamine is also important for lipid metabolism and may affect myelin sheath formation. This may explain peripheral neuropathy symptoms in dry beriberi.
Krebs cycle
Pentose phosphate pathway
Alpha-ketoglutarate dehydrogenase
Pyruvate dehydrogenase.
Wernicke-Korsakoff syndrome
Beriberi | en | apollo | train |
AAHS, Merck's adjuvant, forms a chemical bond to antigens (unlike some aluminum-based adjuvants that form an electrostatic bond) and appears to have an "enhanced binding capacity."When aluminum-containing adjuvants bind with antigens, like HPV types—desirable from an antigenicity standpoint—it is more difficult for the body to excrete the aluminum.He believes that once recombinant DNA inserts itself into a human cell, the consequences are hard to predict. The aluminum-containing adjuvants in Gardasil and Cervarix have garnered much-deserved attention, with concerns over aluminum mounting from both experts and the public. Many of the other components of the HPV vaccines need to be studied much more closely, as well. The assumed safety of these ingredients is troubling and potentially dangerous. 22. HPV VACCINES, AUTOIMMUNITY, AND MOLECULAR MIMICRY
"The number of viral matches and their locations makes the occurrence of side autoimmune cross-reactions in the human host following HPV16-based vaccination almost unavoidable." DR. DARJA KANDUC, UNIVERSITY OF BARI, ITALY (2009)
Many people, including scientists, are describing autoimmune diseases devastating once-healthy young people after HPV vaccination. We are learning of new syndromes and disorders we had never heard of before. Could these conditions be related to aluminum-containing adjuvants? While the HPV vaccine clinical trials showed little difference in adverse outcomes between vaccine recipients and those who received aluminum-containing adjuvants as controls, this says nothing about the safety of injected aluminum. When aluminum-containing adjuvants bind with antigens, like HPV types—desirable from an antigenicity standpoint—it is more difficult for the body to excrete the aluminum. AAHS, Merck's adjuvant, forms a chemical bond to antigens (unlike some aluminum-based adjuvants that form an electrostatic bond) and appears to have an "enhanced binding capacity."Dr. Humphries described AAHS as provoking an "immune system bonfire."Repeated exposure to adjuvants and persistence of aluminum from adjuvants may lead to immune system hyperactivation and chronic inflammation.Scientists worldwide are devoting themselves to the study of aluminum's deleterious effects. | en | apollo | train |
Surgery can be performed using this same method, through the use of more than one port.When diagnostic laparoscopy is performed the abdominal cavity is first filled with air or carbon dioxide to create a space in which the organs can be visualized.The information gained from these procedures now often replaces exploratory surgery. Both techniques rely on obtaining cross-sectional images of the anatomy that create a series of sequential images of the patient being X-rayed. The image produced provides detailed information that enables physicians to find problems that could not be detected by normal two-dimensional X-rays such as barium enemas or barium swallows. To be evaluated, the patient lies in a tunnel-like chamber while the test is being performed. The open MRI, a newer design, doesn't require lying in a closed chamber. Basically the MRI measures the spin of your atoms in a very sophisticated procedure that requires no radiation. The information is generated through a signal from a large magnet that changes proton spin. In an evaluation of the digestive tract, the MRI is sometimes limited because it's much more sensitive to movement. For images of the abdomen, CT scanning is often still better because the peristalsis of the bowel creates constant motion that can blur the image. While it takes longer to do an MRI than a CT scan, the MRI is useful in areas of the body where there is little movement, such as the liver. Consequently the MRI is probably the test of choice for the liver because it's able to give a little more definition. One of the problems with the CT scan is that metallic objects can distort the image. For instance, surgical staples give off artifacts, an image caused by reflection on the metal, that can blur a portion of the X-ray. LAPAROSCOPY
This procedure uses a surgical instrument that functions like a telescope, about the thickness of a Magic Marker, inserted in a small port incision in the abdomen. When diagnostic laparoscopy is performed the abdominal cavity is first filled with air or carbon dioxide to create a space in which the organs can be visualized. Surgery can be performed using this same method, through the use of more than one port.Laparoscopy can also be used surgically in the treatment of ulcerative colitis and in the removal of colon tumors.The use of this instrument eliminates the necessity of large incisions in the abdominal wall, promoting more rapid healing.Laparoscopy can allow the surgeon to gently shift organs within the abdominal cavity through the use of probes. | en | apollo | train |
Lung volumes and lung capacities refer to the volume of air associated with different phases of the respiratory cycle. Lung volumes are directly measured; lung capacities are inferred from lung volumes.
↑ Scott L. DeBoer (4 November 2004). Emergency Newborn Care. Trafford Publishing. p. 30. ISBN 978-1-4120-3089-2.
↑ Wilburta Q. Lindh; Marilyn Pooler; Carol Tamparo; Barbara M. Dahl (9 March 2009). Delmar's Comprehensive Medical Assisting: Administrative and Clinical Competencies. Cengage Learning. p. 573. ISBN 978-1-4354-1914-8.
↑ Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest. 2006 Sep; 130 (3) :827–33. PubMed PMID 16963682.
1 2 3 4 5 6 Simpson, Kathleen Rice; Patricia A Creehan (2007). Perinatal Nursing (3rd ed.). Lippincott Williams & Wilkins. pp. 65–66. ISBN 978-0-7817-6759-0.
↑ Guyton and hall (2005). Textbook of Medical Physiology (11 ed.). Philadelphia: Saunders. pp. 103g. ISBN 81-8147-920-3.
1 2 Ganong, William. "Fig. 35-7". Review of Medical Physiology (21st ed.).
↑ Morris, Mohy G. (2010). "Comprehensive integrated spirometry using raised volume passive and forced expirations and multiple-breath nitrogen washout in infants". Respiratory Physiology & Neurobiology. 170 (2): 123–140. doi:10.1016/j.resp.2009.10.010. ISSN 1569-9048. PMC 2858579 . PMID 19897058.
↑ Wilmore, J. H. (1969). "The use of actual predicted and constant residual volumes in the assessment of body composition by underwater weighing". Med Sci Sports. 1: 87–90. doi:10.1249/00005768-196906000-00006.
↑ MILLER, WAYNE C.; SWENSEN, THOMAS; WALLACE, JANET P. (February 1998). "Derivation of prediction equations for RV in overweight men and women". Medicine & Science in Sports & Exercise. 30 (2): 322–327. doi:10.1097/00005768-199802000-00023. PMID 9502364.
↑ Morrow JR Jr; Jackson AS; Bradley PW; Hartung GH. (Dec 1986). "Accuracy of measured and predicted residual lung volume on body density measurement". Med Sci Sports Exerc. 18 (6): 647–52. doi:10.1249/00005768-198612000-00007. PMID 3784877. | en | apollo | train |
This lining is the blood you see each month.If the lining is not conducive to support the fertilized egg, or if there is no fertilized egg that month, then this endometrium is discharged during menstruation.The uterus then acts as the incubator for the developing embryo and subsequent baby.This blockage acts like a wreck on the highway and prevents the egg from traveling south or the sperm from traveling north. If egg and sperm don't meet, you don't conceive. You can still conceive if only one Fallopian tube is blocked, although, of course, you cut your chances of conception in half since you're in effect operating on one cylinder. The doctor will determine if your tubes are blocked with a special test called a hysterosalpingogram (HSG). Tests are discussed in-depth in chapter 9. Also, clear Fallopian tubes are crucial to assisted reproductive technologies such as GIFT and ZIFT. With gamete intrafallopian transfer (GIFT), the egg and sperm are put into the Fallopian tube by the doctor with hopes that fertilization will take place. Zygote intrafallopian transfer (ZIFT) is similar to IVF in that the eggs are fertilized in a petri dish by the doctor, but the resulting embryos are put into your Fallopian tube to continue their journey, rather than your uterus. This Is Your Uterus
Consider this muscular, pear-shaped organ to be the mother ship. The uterus is where it all happens—the final resting spot for the united egg and sperm, now called the fertilized egg. The typical, nonpregnant uterus is about the size of a small pear and hollow, but has the capacity to expand to fit a growing fetus—amazing. The fertilized egg implants itself in the uterine wall, which (hopefully, in a perfect world) has prepared a lush lining, called the endometrium, to nourish it. The uterus then acts as the incubator for the developing embryo and subsequent baby. If the lining is not conducive to support the fertilized egg, or if there is no fertilized egg that month, then this endometrium is discharged during menstruation. This lining is the blood you see each month.This Is Your Cervix
The cervix is the bottom opening of your uterus; the front door to the vagina.If you use tampons and push one in as far as it can go, you may bump into your cervix.This is also what your doctor is looking at during your annual exam, when your feet are in the stirrups, the sheet is over your knees, and the speculum is in place. | en | apollo | train |
Dietary sugars, serum and the biocide chlorhexidine digluconate modify the population and structural dynamics of mixed Candida albicans and Escherichia coli biofilms.
Despite the increasing recognition of the role played by mixed species biofilms in health and disease, the behavior and factors modulating these biofilms remain elusive. We therefore compared the effect of serum, two dietary sugars (sucrose and galactose) and a biocide, chlorhexidine digluconate, on a dual species biofilm (DSB) of Candida albicans and Escherichia coli and, their single species biofilm (SSB) counterparts. Both modes of biofilm growth on polystyrene plastic surfaces were quantified using a viable cell count method and visualized using confocal scanning laser microscopy (CSLM). Present data indicate that co-culture of C. albicans with varying initial concentrations of E. coli leads to a significant inhibition of yeast growth (r=-0.964; p<0.001). Parallel ultrastructural studies using CSLM and a Live/Dead stain confirmed that E. coli growth rendered blastospores and hyphal yeasts non-viable in DSB. SSB of C. albicans showed pronounced growth when its growth surface was pretreated with serum and by sugar supplements in the incubating medium (p<0.05). Intriguingly, C. albicans in DSB was more resistant to the antiseptic effect of chlorhexidine digluconate. Taken together, the current data elucidate some features of the colonization resistance offered by bacteria in mixed bacterial/fungal habitats and how such phenomena may contribute to the development of fungal superinfection during antimicrobial therapy. | en | apollo | train |
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions. In more severe cases, the motions may become harmful to the individual, such as ripping, tearing or chewing at the skin around one's fingernails to the point of bleeding. Psychomotor agitation is a symptom typically found in major depression disorder or OCD, and sometimes the manic phase in bipolar disorder, although it can also be a result of an excess intake of stimulants. The middle aged and the elderly are more at risk to express this condition.
See also: anxiety. | en | apollo | train |
We are a translational research group with a clear mission: to decrease morbidity and mortality of pregnant women and children by developing new knowledge, treatments, diagnostics, and vaccines for infectious diseases.
Pregnancy and early life are times of particular vulnerability to infection. Our goal is to understand the specific mechanisms by which such infections occur and to translate that knowledge into new therapies and prevention strategies. We combine bacterial and host genetics, whole-genome and whole-transcriptome profiling, new animal models of colonization/infection, and human studies in pursuit of that goal. Our recent work has focused on Streptococcus agalactiae (Group B Streptococcus) as a cause of neonatal sepsis, bacterial vaginosis as a driver of preterm birth, and pore-forming toxins as a common bacterial strategy for survival within hosts.
The essential genome of Streptococcus agalactiae.
Hooven TA, Catomeris AJ, Akabas LH, Randis TM, Maskell DJ, Peters SE, Ott S, Santana-Cruz I, Tallon LJ, Tettelin H, Ratner AJ.
BMC Genomics. 2016 May 26;17(1):406. doi: 10.1186/s12864-016-2741-z.
Hyperglycemic Conditions Prime Cells for RIP1-dependent Necroptosis.
LaRocca TJ, Sosunov SA, Shakerley NL, Ten VS, Ratner AJ.
J Biol Chem. 2016 Jun 24;291(26):13753-61. doi: 10.1074/jbc.M116.716027. Epub 2016 Apr 29.
CD59 signaling and membrane pores drive Syk-dependent erythrocyte necroptosis.
LaRocca TJ, Stivison EA, Mal-Sarkar T, Hooven TA, Hod EA, Spitalnik SL, Ratner AJ. Cell Death Dis 2015; 6: e1773.
Group B Streptococcus -hemolysin/cytolysin breaches maternal-fetal barriers to cause preterm birth and intrauterine fetal demise in vivo.
Randis TM, Gelber SE, Hooven TA, Abellar RG, Akabas LH, Lewis EL, Walker LB, Byland LM, Nizet V, Ratner AJ.
J Infect Dis 2014; 210: 265-273.
Human-specific bacterial pore-forming toxins induce programmed necrosis in erythrocytes.
LaRocca TJ, Stivison EA, Hod EA, Spitalnik SL, Cowan PJ, Randis TM, Ratner AJ.
α-Intercalated cells defend the urinary system from bacterial infection.
Paragas N, Kulkarni R, Werth M, Schmidt-Ott K, Forster C, Singer E, Klose AD, Shen TH, Reng R, Francis KP, Ray S, Vijayakumar S, Seward S, Bovino M, Xu K, Takabe Y, Amaral FE, Mohan S, Wax R, Sanna-Cherchi S, Mori K, Johnson L, Nickolas T, D'Agati V, Qiu A, Al-Awqati Q, Ratner AJ‡, Barasch J‡.
J Clin Invest 2014; 124: 2963-2976.
The role of pore-forming toxins in bacterial infectious diseases.
Los FCO, Randis TM, Aroian R, Ratner AJ.
Microbiol Mol Biol Rev 2013; 77: 173-207.
Complete genome sequence of Streptococcus agalactiae CNCTC 10/84, a hypervirulent sequence type 26 strain.
Hooven TA, Randis TM, Daugherty SC, Narechania A, Planet PJ, Tettelin H, Ratner AJ.
Genome Announc 2014; 2: e01338-14.
DNase inhibits Gardnerella vaginalis biofilms in vitro and in vivo.
Hymes SR, Randis TM, Sun TY, Ratner AJ.
J Infect Dis 2013; 207: 1491-1497.
β-Hemolysin/cytolysin of Group B Streptococcus enhances host inflammation but is dispensable for establishment of urinary tract infection.
Kulkarni R, Randis TM, Antala S, Wang A, Amaral FE, Ratner AJ.
PLOS ONE 2013; 8: e59091.
Vaginolysin drives epithelial ultrastructural responses to Gardnerella vaginalis.
Randis TM, Zaklama J, LaRocca TJ, Los FCO, Lewis EL, Desai P, Rampersaud R, Amaral FE, Ratner AJ.
Infect Immun 2013; 81: 4544-4550. | en | apollo | train |
, Coulthard [/bib_ref] [bib_ref] Chronic peritoneal dialysis in infants-preliminary results of a multicenter survey, Jander [/bib_ref] [bib_ref] Peritoneal dialysis in children under two years of age, Laakkonen [/bib_ref] [bib_ref] Outcomes of infants < 28 days old treated with peritoneal dialysis for..., Rheault [/bib_ref] [bib_ref] Long-term outcome of infants with severe chronic kidney disease, Mekahli [/bib_ref] [bib_ref] Renal replacement therapy in infants with chronic renal failure in the first..., Wedekin [/bib_ref]. Neonates have outcomes comparable to those in later infancy [bib_ref] Outcomes of dialysis initiated during the neonatal period for treatment of end-stage..., Carey [/bib_ref] [bib_ref] Outcomes of infants < 28 days old treated with peritoneal dialysis for..., Rheault [/bib_ref]. An important cause of death in this age group is due to non-renal co-morbidities. Prompt recognition of all factors which will have an impact on further survival is a basic issue in the assessment of infants with ESRD.
Due to the relatively small number of infant patients seen at single centers, data from randomised trials are not available and the recommendations presented here are based on literature research (Medline), abstracts presented at international conferences, consensus meetings of the EPDWG and extended e-mail discussion. | en | apollo | train |
beta-Lapachone, an inhibitor of oncornavirus reverse transcriptase and eukaryotic DNA polymerase-alpha. Inhibitory effect, thiol dependence and specificity.
beta-Lapachone is a naturally occuring compound that can be isolated from a number of tropical trees. It is shown to be a potent inhibitor of reverse transcriptase activity from both avian myeloblastosis virus and Rauscher murine leukaemia virus. In addition, it affects eukaryotic DNA-dependent DNA polymerase-alpha activity: 50% inhibition is reached in 60-min incubation time by about 8 micron beta-lapachone. Enzyme activity is inhibited irrespective of the purity of the enzyme used or of the amount or type of template/primer or substrate present. The inhibitory effect of the drug is only observed in the presence of dithiothreitol. The primary site of action of beta-lapachone appears to be the enzyme protein, as is also borne out by the specificity of its action. Eukaryotic DNA-dependent DNA polymerase-beta, prokaryotic DNA-dependent DNA polymerase I, several other nucleic acid polymerases and some completely unrelated enzymes are not affected. Reverse transcriptase and DNA-dependent DNA polymerase-alpha may be in someway related in possessing similarly exposed '--SH structures' in their active sites. beta-lapachone thus affords a novel means of studying such interrelationships and of further characterizing enzymes. | en | apollo | train |
Functional lentiviral vectors for xeroderma pigmentosum gene therapy.
Xeroderma pigmentosum (XP) is a genetic disease characterized by an autosomal-transmitted genodermatosis involving impaired DNA repair activity, where XP patients present severe sensitivity to sunlight (UVB radiation) and are highly victimized by skin cancer. Complementing XP genes by gene therapy is one potential strategy for helping XP patients. However, current viral-based protocols still lack long-term and stable expression, due to limited post-mitotic infection and gene silencing (in the case of retroviruses) or transient expression and activation of immune response (in the case of adenoviruses). Here we demonstrate that the use of third-generation lentiviral vectors can overcome some of these limitations, rescuing the aberrant phenotype in different categories of the disease (XPA, XPC and XPD). Our results show that lentiviruses are efficient tools to transduce XP fibroblasts and correct repair-defective cellular phenotypes by recovering proper gene expression, normal UV survival and unscheduled DNA synthesis after UV radiation. We propose lentiviral vectors as an attractive alternative for gene therapy protocols focusing on DNA repair genetic diseases. | en | apollo | train |
NIRS calibration equations developed in this study could be applied to the rapid analysis of the pinoresinol diglucoside content. | en | apollo | train |
Novel form of fibronectin from zebrafish mediates infectious hematopoietic necrosis virus infection.
The presence of a novel form of zebrafish fibronectin (FN2) on the cell surface increased the cell's susceptibility to infection by infectious hematopoietic necrosis virus (IHNV). Unlike other fibronectins, FN2 possesses a truncated structure and accumulates on the cell surface instead of in the extracellular matrix. Fish embryo cells expressing recombinant FN2 were more susceptible to IHNV infection, with a greater percentage of cells exhibiting cytopathic effect (CPE) compared to nontransfected control cells. Incubation of nontransfected cells with soluble recombinant FN2 increased IHNV infection, as measured by plaque assay. The number of plaques increased in correlation with the amount of protein added and the length of time that cells were incubated with the protein. Incubation of IHNV with soluble FN2 before addition to cells also increased infection. FN2 immobilized on the culture surface inhibited IHNV infection. The results indicate that FN2 present on the cell surface is able to mediate IHNV attachment and cell entry. | en | apollo | train |
Nitroglycerin gel has shown promise as a topical therapy.• Nitroglycerin patches may be helpful, but use is limited by the incidence of severe headache.Oral prostacyclin has not proven useful.• Parenteral iloprost, a prostacyclin, in low doses (0.5 ng/kg/min over 6 hours), has improved ulcerations with severe Raynaud phenomenon when CCBs failed.Follow-Up Tests & Special Considerations
Periodic assessments for a connective tissue disorder
Diagnostic Procedures/Other
Diagnosis is determined by history and physical exam. TREATMENT
Assess using a Raynaud Condition Score. GENERAL MEASURES
• Dress warmly, wear gloves, and avoid cold temperatures. • During attacks, rotate the arms in a windmill pattern or placing the hands under warm water or in a warm body fold to alleviate symptoms. • Tobacco cessation
• Avoid β-blockers, amphetamines, ergot alkaloids, and sumatriptan. • Temperature-related biofeedback may help patients increase hand temperature. 1-year follow-up is no better than control. • Finger guards to protect ulcerated fingertips
MEDICATION
First Line
• Calcium channel blockers (CCBs). Nifedipine is the best studied and most frequently used. • Nifedipine: 30 to 180 mg/day (sustained-release form); seasonal (winter) use is effective with up to 75% of patients experiencing improvement. • Is compatible with breastfeeding
• Contraindications: allergy to drug, pregnancy, CHF
• Precautions: may cause headache, dizziness, lightheadedness, edema, or hypotension
• Significant possible interactions
– Increases serum level of digoxin
Second Line
• Amlodipine (5 to 10 mg/day) and nicardipine are effective and may have fewer adverse effects. • No data exist to support switching CCB if initial drug is ineffective. • Small studies support benefit from losartan and fluoxetine. • Phosphodiesterase type-5 inhibitors (sildenafil, vardenafil) may reduce symptoms without increasing blood flow. • Parenteral iloprost, a prostacyclin, in low doses (0.5 ng/kg/min over 6 hours), has improved ulcerations with severe Raynaud phenomenon when CCBs failed. Oral prostacyclin has not proven useful. • Nitroglycerin patches may be helpful, but use is limited by the incidence of severe headache. Nitroglycerin gel has shown promise as a topical therapy.• ACE inhibitors are no longer recommended.ISSUES FOR REFERRAL
If an underlying disease is suspected, consider rheumatology consultation for evaluation and treatment.ADDITIONAL THERAPIES
• Botulinum toxin has shown some effect in reducing vasospastic episodes, frequency of attacks, rest pain, and helping to promote digital ulcer healing (3)[C]. | en | apollo | train |
Proteomic changes in the hippocampus and motor cortex in a rat model of cerebral palsy: Effects of topical treatment.
Cerebral palsy (CP) is a non-progressive motor-impairment disorder related to brain injury early in development. To gain new insights into the mechanisms of CP and the therapeutic efficacy of Baimai ointment, we used a high-throughput quantitative proteomic approach to evaluate proteomic changes in the hippocampus and motor cortex in a rat model of CP induced by lipopolysaccharide (LPS) combined with hypoxia/ischemia (H/I). More than 2000 proteins were identified in each brain region with high confidence. Quantitative analysis demonstrated profound disturbances in the proteomes of the hippocampus and motor cortex after LPS + H/I, in addition to the disruption of the motor system. In contrast, the topical application of Baimai ointment not only alleviated the motor deficit in the CP model rats, but also restored the proteomes in the brain cortex. Furthermore, astrocytes in the hippocampus were strongly activated in the Baimai-treated CP rat brains, associated with an increase in neurotrophic factors. Proteomic analysis demonstrated that the CP model induced neuroinflammatory responses in the brain which were reversed by the topical application of Baimai ointment. This study highlights the unexpected roles of hippocampus and motor cortex neurons in CP progress and treatment, thus providing potentially novel therapeutic targets for CP. | en | apollo | train |
We do not know why only specific neurons die for each disease or what goes wrong to start the process of neuron degeneration leading to neuron death.All are characterized by sets of neurons, particular to each disease, that degenerate and die.Other common neurodegenerative diseases include Alzheimer disease and Parkinson disease.ALS is one of several neurodegenerative diseases.For example, we know that there are at least two forms of ALS: familial ALS (fALS), where the disease can be passed down in the family, and sporadic ALS (sALS), where there is no family history. Within fALS, different **genes** may be involved, and likely each gene causes different initial changes in motor neurons that lead to their degeneration and death. Furthermore, since ALS begins with symptoms at different regions (bulbar, arm, leg) and with different degrees of involvement of upper motor neurons and lower motor neurons (PLS and PMA), these variations could represent different forms of motor neuron disease (MND). In addition, different time courses of progression are observed among patients, from a very short time (first symptom to death in 1 year) to very long time courses (over 10 years), which could also be due to different mechanisms of nerve cell death. It is important to note that despite differences among patients—fALS or sALS, site of onset, degree of upper and lower motor neuron involvement, and time course—all patients have a recognizable clinical pattern supporting the diagnosis of ALS. Thus it is likely that a number of causative factors (reviewed below) lead to a sequence of pathologic changes in neurons that ultimately leads to a "final common pathway" of degeneration and death of upper and lower motor neurons. ### Why Do Neurons Die in ALS? ALS is one of several neurodegenerative diseases. Other common neurodegenerative diseases include Alzheimer disease and Parkinson disease. All are characterized by sets of neurons, particular to each disease, that degenerate and die. We do not know why only specific neurons die for each disease or what goes wrong to start the process of neuron degeneration leading to neuron death.There are two primary reasons: one is to emphasize that the causes remain unknown for all neurodegenerative diseases, and the other is that because of similarities among neurodegenerative diseases, research on one of these diseases can help in understanding the others. | en | apollo | train |
In cell biology, a bleb is an irregular bulge in the plasma membrane of a cell caused by localized decoupling of the cytoskeleton from the plasma membrane (recently reviewed in ). Blebbing is the term used to describe the formation of blebs. | en | apollo | train |
Modified Interest Checklist, (in occupational therapy) a leisure interest inventory appropriate for adults and adolescents.modified barium swallow, a radiological examination performed while the patient swallows barium-coated substances, done to assess quality of the swallowing mechanisms of the mouth, pharynx, and esophagus.See modifying gene.modification allele.Oversedation or an adverse patient response to sedation may result in life-threatening complications such as hypotension, loss of airway reflexes, inability to maintain a patent airway, hypoventilation, apnea, or agitation and movement at a critical point in the procedure. Anesthetic monitoring during conscious sedation includes at a minimum the monitoring of blood pressure, electrocardiography, and pulse oximetry. Also called conscious sedation. See also anesthesia, awake anesthesia. moderator band /mod″ərā′tər/ [L, moderari, to restrain; AS, bindan, to bind] , a thick bundle of muscle in the central part of the right ventricle of the heart. Missing in some individuals and varying in size in others, it usually contains part of the atrioventricular conduction bundle. Also called trabecula septomarginalis. modesty, propriety of dress, speech, and conduct in relations between patients and health care personnel, including draping and covering of the patient to the greatest extent possible, depending on the type of care or examination. Modicon, an oral contraceptive containing an estrogen and a progestin. Brand name for norethindrone acetate and ethinyl estradiol. modification /mod′ifikā″shən/ , 1. a process whereby a substance is changed from one form to another.2. a change in an organism that is acquired or learned and does not involve inheritance. modification allele. See modifying gene. modified barium swallow, a radiological examination performed while the patient swallows barium-coated substances, done to assess quality of the swallowing mechanisms of the mouth, pharynx, and esophagus. Modified Interest Checklist, (in occupational therapy) a leisure interest inventory appropriate for adults and adolescents.modified jaw thrust /mod″ifīd/ , an upper airway control maneuver to maintain an open airway of an unconscious person in cases of potential spinal injury.In such persons in-line stabilization of the head and neck can be obtained primarily by forward jaw thrust with minimum head extension. | en | apollo | train |
The bronchoscope can be used to sample material not only from the regions that can be directly visualized (i.e., the airways) but also from the more distal pulmonary parenchyma.Although bronchoscopy is now performed almost exclusively with flexible fiberoptic instruments, rigid bronchoscopy, generally performed in an operating room on a patient under general anesthesia, still has a role in selected circumstances, primarily because of a larger suction channel and the fact that the patient can be ventilated through the bronchoscope channel. These situations include the retrieval of a foreign body and the suctioning of a massive hemorrhage, for which the small suction channel of the bronchoscope may be insufficient. #### **FLEXIBLE FIBEROPTIC BRONCHOSCOPY**
This outpatient procedure is usually performed in an awake but sedated patient (conscious sedation). The bronchoscope is passed through either the mouth or the nose, between the vocal cords, and into the trachea. The ability to flex the scope makes it possible to visualize virtually all airways to the level of subsegmental bronchi. The bronchoscopist is able to identify endobronchial pathology, including tumors, granulomas, bronchitis, foreign bodies, and sites of bleeding. Samples from airway lesions can be taken by several methods, including washing, brushing, and biopsy. Washing involves instillation of sterile saline through a channel of the bronchoscope and onto the surface of a lesion. A portion of the liquid is collected by suctioning through the bronchoscope, and the recovered material can be analyzed for cells (cytology) or organisms (by standard stains and cultures). Brushing or biopsy of the surface of the lesion, using a small brush or biopsy forceps at the end of a long cable inserted through a channel of the bronchoscope, allows recovery of cellular material or tissue for analysis by standard cytologic and histopathologic methods. The bronchoscope can be used to sample material not only from the regions that can be directly visualized (i.e., the airways) but also from the more distal pulmonary parenchyma.This procedure, called _bronchoalveolar lavage_ , has been particularly useful for the recovery of organisms such as _P.jiroveci_ in patients with HIV infection.Brushing and biopsy of the distal lung parenchyma can also be performed with the same instruments that are used for endobronchial sampling. | en | apollo | train |
Phospholipid synthesis is decreased in neuronal tissue in a mouse model of Sandhoff disease.
Sandhoff disease is a progressive neurodegenerative disorder caused by mutations in the HEXB gene which encodes for the beta-subunit of beta-hexosaminidase A and B, resulting in ganglioside GM(2) accumulation in the brain. We now demonstrate that phospholipid metabolism is altered in both cultured neurons and in brain tissue from a mouse model of Sandhoff disease, the Hexb-/- mouse. Metabolic labelling using [methyl-(14)C]choline and l-[3-(3)H]serine demonstrated reduced incorporation of [methyl-(14)C]choline into phospholipids in brain tissue but not in liver or spleen. Phospholipid mass was also reduced in brain. The activities of CTP : phosphocholine cytidylyltransferase (CCT) and phosphatidylserine synthase were also reduced in brain tissue from Hexb-/- mice, probably because of post-translational modification as no changes were observed in levels of enzyme expression. The relevance of these findings to Sandhoff disease in human patients is strengthened by observations made over 30 years ago on autopsy tissue of Tay Sachs and Sandhoff disease patients, in which reduced phospholipid levels were observed. We suggest that changes in phospholipid metabolism are not simply because of loss of neuronal tissue as a result of degeneration but rather may cause degeneration, and we discuss the possible effects that changes in phospholipid metabolism could play in the neuropathophysiology of Sandhoff disease. | en | apollo | train |
Lethal sectoring is not the basis for EMS-induced pure mutant clones in Chinese hamster cells.
Treatment of G1-synchronized mammalian cells with mutagenic agents which act on one strand of the DNA at a given site would be expected to produce colonies containing both mutant and wild-type cells (mosaic). We have observed that in addition to mosaic colonies, G1-synchronized Chinese hamster ovary cells which had been treated with the single-strand mutagen ethyl methanesulfonate (EMS), produced colonies in which all the cells lacked glucose-6-phosphate dehydrogenase activity. These completely mutant (pure) colonies could be derived from a potentially mosaic colony by the "death" of the wild-type cell after the first cell division, leaving only the glucose-6-phosphate dehydrogenase (G6PD)-deficient cell to grow into a colony (lethal sectoring). Using time-lapse photography to analyze cell lineages after EMS treatment, we find that cell lysis, cell release, cell migration, or proliferative failure of one lineage at the 2-cell stage accounts for only 20-25% of the pure mutant colonies observed. This result suggests that in the Chinese hamster cell there exists a mutational mechanism which fixes the mutation in both strands of the DNA before the next replication cycle following EMS treatment. | en | apollo | train |
Developing preschool surveillance tools for adaptive functioning: lessons for neuro-oncology.
Advances in neuro-oncology have resulted in dramatic increases in the survival of children with pediatric brain tumors, including those with medulloblastoma, the most common early childhood central nervous system (CNS) malignancy. Because of this increased survival, there is heightened awareness and recognition that an understanding of the impact of treatments and interventions on children's development, learning, and adaptive behaviors is essential for optimization of long-term outcomes. One of the major reasons for studying these outcomes is that the developing nervous system has its unique vulnerabilities with respect to the primary tumor, its complications (hydrocephalus, increased intracranial pressure, hazards of tumor resection), and the late effects of treatments on children's developmental, learning, and adaptive status. In addition, very young children are especially vulnerable to the toxic effects of radiation and other therapies, highlighting the importance of measuring emerging communication, coordination, and social adaptive skills. Lastly, there is increased concern about the long-term consequences of chemotherapy on specific neural populations and neural connectivity that affect memory, learning, and executive function. The purpose of this article is to review ways of conceptualizing CNS adaptive functioning in children diagnosed with brain tumors in early childhood. The international classification of functioning (ICF) model will be used to describe the spectrum of health and developmental outcomes of child neurodisability. An integrated strategy of surveillance for motor, communicative, and adaptive skills that can be linked to neuropsychological assessments will also be highlighted. This health, development, and functional surveillance framework will help us better evaluate how our management impacts on child and family well-being and how our interventions lessen severe multiple motor, communicative, and neurobehavioral morbidities. | en | apollo | train |