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Protective effects of chronic green tea consumption on age-related neurodegeneration.
Dietary antioxidant compounds, due to their pivotal role in the modulation of cellular redox mechanisms, are gaining attention of researchers in the field of brain aging and related degenerative diseases. In this perspective, green tea (GT) can be an excellent resource, as it contains large amounts of brain-accessible polyphenols. Many of these compounds are monomeric catechins, which have been shown to exert antioxidant effects, acting directly as radical scavengers or metal-chelators. In the current article, we review the general properties of GT, the direct antioxidant action of its polyphenols and the fine modulation of signaling systems related to survival and antioxidant defenses in the central nervous system of aging rats. The effects in the glutathione system and the activation of several transcription factors including cyclic AMP response element-binding (CREB) protein, levels of the brain-derived neurotrophic factor (BDNF) and the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) are given in detail. We discuss also the beneficial action of catechins in learning and memory with a particular focus on the hippocampal formation. We conclude that GT polyphenols can have a promising role in the reversal of age-related loss of neuronal plasticity and recovery after neuronal lesions associated with aging. |
WITHDRAWN: Auditory Surprise Model Based on Pattern Retrieval from the Past Observation.
This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the authors. The authors regrets that the reason for withdrawal is due to an disagreement in authorship and in scope of data disclosure. The authors apologize to the readers for this unfortunate error. |
Steroid Receptor RNA Activator bi-faceted genetic system: Heads or Tails?
The Steroid Receptor RNA Activator (SRA) was first identified by Lanz et al. in 1999 as a functional non-coding RNA able to co-activate steroid nuclear receptors. Since this incipient study, our understanding of SRA as a broader co-regulator of nuclear receptors as well as other transcription factors has greatly expanded. Accumulated data has now revealed the diverse roles played by this transcript in both normal biological processes such as myogenesis and adipogenesis, as well as in mechanisms underlying diseases including cardio-myopathies and cancers. Remarkably, as early as 2000, SRA isoforms were identified that were also able to code for a protein now referred to as the Steroid Receptor RNA Activator Protein (SRAP). SRA and SRAP now define a very intriguing bi-faceted genetic system, where both RNA and protein products of the same gene play specific and sometime overlapping roles in cell biology. Due to its initial molecular characterization as an RNA, most reports have in the last ten years focused on the non-coding part of this twosome. As such, only a handful of laboratories have investigated the molecular and biological roles played by SRAP. The scope of this review is to summarize and discuss our current knowledge of the molecular features and functions specifically attributable to the coding nature of the bi-faceted products of the SRA1 gene. |
Gravitational Anderson localization.
We present a higher dimensional model where gravity is bound to a brane due to Anderson localization. The extra dimensions are taken to be a disordered crystal of branes, with randomly distributed tensions of order the fundamental scale. Such geometries bind the graviton and thus allow for arbitrarily large extra dimensions even when the curvature is small. Thus this model is quite distinct from that of Randall and Sundrum where localization is a consequence of curvature effects in the bulk. The hierarchy problem can be solved by having the standard model brane live a distance away from the brane on which the graviton is localized. The statistical properties of the system are worked out and it is shown that the scenario leads to a continuum of four dimensional theories with differing strengths of gravitational interactions. We live on one particular brane whose gravitational constant is G(N). |
[Lipoprotein metabolism in relation to age].
Ageing is associated with a variety of changes of intracellular and extracellular lipid metabolism. Depending upon age the the rapidity of synthesis and metabolism of lipids decreases and partly increased plasma lipoprotein levels are found. Both under basal and under special alimentary conditions the lipoprotein metabolism shows age-dependent changes which may lead to an increased risk for atherosclerosis. These results are important for therapeutic and prophylactic conditions. |
Prolonged activation of the branched-chain alpha-keto acid dehydrogenase complex in muscle of zymosan treated rats.
Whole-body oxidation rates of branched chain amino acids (BCAA) are increased during catabolic diseases. A significant role for muscle in this feature has been suggested and, therefore, activities of the rate limiting enzyme in the degradative pathway of the BCAA in muscle were investigated in a catabolic rat model (intraperitoneal zymosan injection). Both actual and total activities of the branched chain alpha-keto acid dehydrogenase complex zymosan treated rats and compared with values measured in pair fed and ad libitum fed controls. The actual activity and the percentage of the enzyme in the active form were increased 2 and 6 days after the zymosan challenge. Total activity of the BC-complex and the activities of mitochondrial marker enzymes were reduced 2 days after zymosan treatment. We conclude that zymosan treatment leads to (1) a reduction of the mitochondrial content in skeletal muscle and (2) a prolonged activation of the BC-complex in muscle which may explain enhanced oxidation of BCAA during catabolic diseases. |
Antihypertensive effect of salt-free soy sauce, a new fermented seasoning, in spontaneously hypertensive rats.
In this study, we focused on the antihypertensive effect of newly fermented salt-free soy sauce (SFS) in spontaneously hypertensive rats (SHRs). A 13-wk oral administration of SFS was performed daily in 8- to 21-wk-old SHRs with a dose of 200 mg/kg of body weight/d. The systolic (SBP) and diastolic (DBP) blood pressures were measured for each week during the experimental period. As a result, a significant (P < 0.01) BP lowering effect was observed from the 5th d to the end of the experiment in the SFS group compared with the control group (DeltaSBP(21-wk): 27 mmHg, DeltaDBP(21-wk): 20 mmHg). In contrast to such substantial effect by SFS intake, angiotensin I-converting enzyme activities in blood and local organs as well as pharmaceutical parameters such as serum Na(+) or K(+) level did not show any significant difference between in both SFS and control groups. Vasoconstriction experiment using thoracic aorta rings from 21-wk SHRs provided an interesting result that the rings from the SFS group evoked a >2-fold higher increase in the angiotensin II-stimulated constrictive response compared with the rings from the control group (P = 0.012), which suggested that the SFS-intake would be effective in possessing a higher vessel tone. In this study, we investigated the antihypertensive effect of newly fermented SFS in SHRs. As a result of 13-wk SFS-administration, we found a significant antihypertensive effect of the SFS. This finding strongly demonstrates that the developed SFS would be greatly beneficial for health and useful for health-related industries. |
Higenamine inhibits apoptosis and maintains survival of gastric smooth muscle cells in diabetic gastroparesis rat model via activating the β2-AR/PI3K/AKT pathway.
Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus (DM). The numerous clinical symptoms of DGP and the great cost on the treatment of DGP seriously lowered the patients' life quality. However, the pathogenic mechanism of DGP is still elusive till now. In this study, we aimed to explore the effect of higenamine on the proliferation and apoptosis of gastric smooth muscle cells (SMCs) in DGP rat model. The DGP rat model was built by intraperitoneal injection of Streptozotocin (STZ) into male Sprague-Dawley (SD) rats. Compared with the healthy control group, the level of DGP indicator c-kit was strongly suppressed and the level of Gsα was largely elevated in the STZ-induced model group. By contrast, the addition of higenamine obviously counteracted the effect of STZ on the expression of c-kit and Gsα. Besides that, higenamine improved the decreased emptying ability of the stomach. In addition, the number of gastric SMCs was strongly decreased and cell morphology became irregular in STZ-induced model group. The treatment of higenamine weakened the harm of STZ on the number and morphology of gastric SMCs. Beyond that, higenamine promoted gastric SMCs proliferation and inhibited gastric SMCs apoptosis in DGP model. Further research revealed that higenamine regulated cell proliferation and apoptosis via activating the β2-AR/PI3K/AKT pathway. Taken together, our research revealed that higenamine maintained the survival of gastric SMCs in DGP rat model via the β2-AR/PI3K/AKT pathway, providing a new sight for the treatment of DGP. |
Self-Management and Health Care Transition Among Adolescents and Young Adults With Chronic Kidney Disease: Medical and Psychosocial Considerations.
Health care transition (HCT) is a process that requires preparation as a continuum from pediatric- to adult-focused services. For adolescents and young adults with chronic or ESRD, this process can be prolonged due to their physical, psychological, family, or ecological factors. HCT preparation is a matter of patient safety and patient rights as the consequences of poor preparation at the time of transfer to adult-focused services are great, including rejection of organs, disease relapse, or even death. We present a case to illustrate important points of HCT preparation, with suggestions for intervention by the interdisciplinary team members who serve (and will serve) these survivors of pediatric-onset health conditions. To monitor the HCT process, yearly measurements of skill mastery need to take place guide interventions. |
Validation of the beck depression inventory-II in a Jamaican university student cohort.
This project explores the internal consistency reliability and the concurrent and discriminant validity of the Beck Depression Inventory-II (BDI-II) using a wide cross-section of the student population attending the University of the West Indies, Kingston, Jamaica. Students enrolled in UWI Foundation courses during the first and second semesters of the 2005/2006 academic year (n = 690; 77% females, 23% males; mean age = 23.4 +/- 7.4 years) were administered the BDI-II along with the Brief Screen for Depression (BSD), the Centre for Epidemiological Studies--Depression Scale (CES-D) and the UCLA Loneliness Scale--Revised. Overall, the BDI-II was found to have an acceptable degree of reliability (alpha = 0.90). The scale also had reasonably good concurrent validity as evidenced by high correlations with scores on the BSD (r = 0.74) and the CES-D (r = 0.71) and acceptable discriminant validity as demonstrated through moderate correlations with the UCLA Loneliness Scale (r = 0.50). This pattern of scores suggests that the majority of the variance underlying the BDI-II assesses depression (50% to 55%) while a smaller degree of the variability (25%) measures a conceptually similar but distinct concept. The BDI-II is a reliable and valid measure for assessing depression within the Jamaican population. |
Regulation of proliferative response of cardiac fibroblasts by transforming growth factor-beta 1.
Cardiac fibroblasts constitute greater than 90% of the non-myocyte cells in the heart. Previously, it was established that cardiac fibroblasts are predisposed to transformation into a phenotype with muscle-specific features and that transforming growth factor-beta 1 (TGF-beta 1) is a specific inducer of this event. In this study the hypothesis that TGF-beta 1-induced phenotypic modulation of cardiac fibroblasts is associated with their altered proliferative capacity is tested. Therefore the effects of TGF-beta 1 on DNA synthesis in cardiac fibroblasts under normal conditions of cell culture and in response to a potent mitogen, basic fibroblasts growth factor (bFGF) were determined. The results showed that TGF-beta 1 at 15 ng/ml (a concentration that induces fibroblast "transformation") had a regulatory effect on proliferative capacity of cardiac fibroblasts which varied as the function of cell density in culture. In subconfluent and confluent cultures, pre-treatment of cardiac fibroblasts with TGF-beta 1 for 24 h resulted in a dramatic shift in the bFGF-induced stimulation of DNA synthesis. TGF-beta 1-induced inhibition of DNA synthesis in cardiac fibroblasts coincided with their phenotypic modulation as evidenced by the expression of sarcomeric actin mRNA and morphological changes. Cross-linking studies with [125I]-labeled TGF-beta 1 showed the presence of conventional types I, II and III TGF-beta 1 receptor complexes on cardiac fibroblasts and their binding to TGF-beta 1 under the experimental conditions. In summary, these data indicate that the proliferative capacity of cardiac fibroblasts is controlled by TGF-beta 1. They further suggest that the TGF-beta 1-induced phenotypic modulation of cardiac fibroblasts may be extended to include their altered proliferative capacity. |
[Pathological changes and pathogenesis of chronic lung diseases in infants].
Chronic lung disease (CLD) in infants was studied in 50 autopsy cases clinicopathologically. These cases were divided into three groups clinically. Pathological changes in the lung were similar among these three groups. Changes of elastic fibers in the alveolar septum were characteristic; irregular and unevenly distributed elastic fibers were found in the majority of CLD cases. The abnormally distributed elastic fibers could contribute to occurrence of focal emphysema. The lungs from 5 special cases were devoid of elastic fibers in the alveolar septum. In such cases, abnormality of elastin production by fibroblasts or abnormal interaction between protease and anti-protease was hypothesize as the mechanism of occurrence. The relationship to adult lung diseases was also discussed. |
Is colposcopy needed following laser ablation for dysplasia?
To evaluate the effectiveness of cytology and colposcopy in the follow up of women treated by laser CO(2) ablation for cervical intraepithelial neoplasia (CIN). A retrospective analysis of 1784 patients with CIN treated with laser CO(2) ablation from 1998 to 2003 at the Royal Women's Hospital, Melbourne. Data were collected prospectively in a computerised colposcopy database utilised in the Dysplasia Unit. There was equal distribution in the study population treated for low-grade intraepithelial neoplasia (LSIL) and high-grade intraepithelial neoplasia (HSIL), with no significant age difference in both groups (mean 27.6 years). The success rate of treatment of LSIL (94%) was similar to that of HSIL (92%). Fifty-seven per cent of all failures occurred within the first year of treatment. Colposcopy was more sensitive in detecting intraepithelial neoplasia (SIL) than cytology, whereas cytology was more specific. No case of cancer was diagnosed on follow up. CO(2) laser ablation was equally effective in treating different grades of CIN. There is a continuing incidence of recurrent CIN, even up to five years after initial treatment, which suggests that it is necessary for patients to adhere to long-term follow up. The combination of cytology and colposcopic assessment is essential for surveillance of SIL in the initial two years after treatment. |
A call for more dialogue and more details.
Pickering & Garrod (P&G) argue that contemporary models of language use are inadequate. This has resulted largely because of an experimental focus on monologue rather than dialogue. I agree with the need for increased experimentation that focuses on the interplay between production and comprehension. However, I have some concerns about the Interactive Alignment model that the authors propose. |
Isoelectric focusing electrophoresis of lignin.
Isoelectric focusing is introduced as a technique for the analysis of macromolecular lignin. The analysis is performed in a pH gradient from 3.5 to 10. Separated lignin fragments are visualized under uv light or by silver staining. The method can be used to distinguish between differently processed lignin preparations and to identify their components. Even the slight modification resulting from attack by ligninolytic enzymes could be detected. |
Jaw injuries of independence victims from the 1991 War in Croatia.
In the aetiology of maxillofacial injuries, car accidents, violence, sports injuries and lately war injuries are frequently mentioned. The purpose of this study was to exhibit and analyse types of jaw injuries on bodies exhumed from massive and individual graves located in regions temporarily occupied during the War in Croatia that lasted from 1991 to 1995. The sample was the post-mortal documentation of the orofacial region (set of teeth, photographs, radiographic images) of 1068 victims exhumed from massive grave sites in Croatia. The jaw traumatism was analysed on the whole sample as well as on individual graves, whilst the analysis of trauma frequency was performed separately. Descriptive statistics were computed and the value of P < .05 was accepted as statistically significant. Results of this study showed that out of 1068 examined corpses, 332 had midface and lower face fractures, which was 31.1% of the total number. Lower face fractures were more frequent with 28.1%. Age related frequency analysis showed a significant dependency. There were 34.6% of fractures in the under 30 age group, 34.2% in those aged 30-60, while 21.3% of fractures were noted in the over 60 age group. Female bodies had the lowest number of jaw fractures regardless of the osteoporotic changes. The results of this study suggest that younger and middle aged persons were molested more. Jaw fractures suggest ante-mortal molestation. In females, the more likely fracture causes were the falls of the bodies into the graves or body to body hits. |
Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy.
Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising. |
LRF and TRF test during long-term danazol treatment: increase of the LH and FSH responses but decrease of the prolactin and TSH responses.
Seven patients suffering from severe endometriosis were treated with danazol 200 mg X 3 daily for 6 months. Clinical symptoms were alleviated and menses disappeared in response to the treatment. After cessation of the treatment the menstrual bleedings returned in 1-3 months. Blood samples for determination of gonadotrophins, prolactin (Prl), oestradiol (E2), progesterone, thyroid hormones and thyrotrophin in radioimmunoassays were taken and a combined TRF and LRF test carried out in the follicular phase before treatment, at the 6th month of treatment and after reappearance of the first menses. There were no statistically significant changes in the basal levels of serum FSH, LH or TSH during the danazol treatment. Neither was there any change in episodic secretions of FSH, LH or Prl, as determined by the mean coefficients of variation of the hormone levels in seven consecutive samples taken at 20 min intervals. On the other hand, serum E2, Prl and thyroid hormone levels were significantly decreased in the 6th month of treatment. In the TRF-LRF test the responses of serum FSH and LH were significantly higher and those of serum Prl and TSH significantly lower during danazol treatment than before. Prl responses remained lowered after the treatment. It appears that low serum oestrogen levels, induced by the danazol treatment, sensitize the pituitary gonadotrophs to exogenous LRF, but make the sensitivity of thyrotrophs and lactotrophs lower to exogenous TRF. These results thus indicate that danazol does not make the pituitary gonadotrophs insensitive to LRF, but danazol may rather inhibit the secretion of hypothalamic LRF. |
Effect of thawing rate and post-thaw culture on the cryopreserved fetal rat islets: functional and morphological correlation.
The ability of the fetal pancreatic islet cells to multiply rendered them a potential tissue for transplantation studies to cure diabetes. A bank of fetal islets could be created with proper storage in liquid nitrogen. The aim of this study is to evaluate the effect of thawing rate and post-thaw culture on the structural and functional integrity of isolated cryopreserved islets of rat fetuses. Fetal rat islets were isolated by the collagenase digestion, cultured for three days, and then cryopreserved using dimethylsulphoxide as cryoprotectant and the step-rate cooling to -40 degrees C before immersing them in liquid nitrogen. The islets were thawed by the slow or fast warming rates using hyperosmolar sucrose solution and then cultured for 1 or 2 days. Insulin and C-peptide contents of the slow thawed islets were higher than those of the control. In the fast thawed islets the contents were similar to those of the control. Insulin and C-peptide release in response to glucose for the slow thawed islets were lower than those of the control and in the fast thawed islets they were similar to that of the control. Histological examination showed irregular periphery and fragmented central part of the large slowly thawed islets, which showed also variable immunohistochemical reaction to anti-insulin serum, ranging from strongly positive reaction to markedly weak reaction. Fast thawed islets showed mostly regular periphery and their reaction to the anti-insulin serum was slightly weaker than that of the control islets. It was concluded that fast thawing and post-thaw culture is much better than slow thawing, as indicated by nearly normal insulin and C-peptide content and release and intact structural integrity. |
[Educational strategy addressed to nurses in primary care for infertility: an intervention study].
The objective was to assess the impact of an educational strategy approaching infertility assistance; and verify practices introduced into the daily work of the participants after this intervention. Research-action developed with 11 nurses from the Family Health Strategy, in Fortaleza-CE, through the reading of a brochure in a "circle of conversation." Data were collected in August and October 2010, before, immediately after and 60 days after the intervention. An increase in the levels of knowledge was noted immediately after the intervention, when all participants had a "more than good" or "very good" level of knowledge, leaving behind the "little" and "good" levels rated before the intervention; at 60 days, a "good" level of knowledge was noted again, showing a relative decrease in knowledge. There was self-recognition of the ability to introduce practices into the daily work after the intervention, confirming the positive impact thereof |
In vivo and noninvasive three-dimensional patellar tracking induced by individual heads of quadriceps.
Unbalanced actions of the quadriceps components are closely linked to patellar mal-tracking and patellofemoral pain syndrome. However, it is not clear how individual quadriceps components pull and rotate the patella three dimensionally. The purpose of this study was to investigate in vivo and noninvasively patellar tracking induced by individual quadriceps components. Individual quadriceps component was activated selectively through electrical stimulation at the muscle motor point, and the resulting patellar tracking was measured in vivo and noninvasively in 18 knees of 12 subjects. The in vivo and noninvasively patellar tracking was corroborated with in vivo fluoroscopy and in vitro cadaver measurements. Vastus medialis (VM) mainly pulled the patella first in the medial and second in the proximal directions and vastus lateralis (VL) pulled first in the proximal and second in the lateral directions. The oblique portion (VMO) of the VM pulled the patella mainly medially and the longus portion (VML) more proximally. Medial tilt was the major patellar rotation induced by VMO contraction at full knee extension. With the knee at the more flexed positions, the amplitude of patellar movement induced by comparable quadriceps contractions was reduced significantly compared to that at full knee extension, and VMO changed its main action from extending to flexing the patella. The medial and lateral quadriceps components moved the patella in rather different directions, and rotated the patella differently about the mediolateral tilt and mediolateral rotation axes but similarly in extension. The approach can be used to investigate patellar tracking in vivo and noninvasively in both healthy subjects and patients with patellofemoral disorder and patellar malalignment. |
What is a 'return to work' following traumatic brain injury? Analysis of work outcomes 12 months post TBI.
Background: Literature lacks a clear description of return to work following traumatic brain injury (TBI). Aim: to describe work metrics for people with mild and moderate/severe TBI at 3, 6, and 12 months post-injury.Methods: A retrospective cross-sectional analysis of 172 TBI participants measuring work outcomes up to 12-months post-injury. Metrics described vocational status, accommodations, satisfaction, hours, time taken to return, financial status, and responsibilities. Logistic regression identified factors indicative of complete (80% of pre-injury hours) return to work.Results: 59/86 moderate/severely injured (68.6%) and 68/81 mildly injured (84%) people returned to work following TBI. Twenty-eight (16.3%) achieved a complete return by 12 months. The regression model was statistically significant X2 (4) = 51.980, p = <.0005, suggesting that those with high health-related quality of life, anxiety and functional ability were more likely to achieve complete return to work. At 12 months, 41 participants (23.8%) had workplace accommodations. One hundredfifteen (66.9%) were less content with their job and many reported reduced working hours.Discussion: This study highlights the heterogeneity of work post-TBI. Even people with 'mild' TBI fail to make a complete return to work by 12 months.Conclusions: Further longitudinal research is needed to explore the personal and economic legacy of TBI. |
[Mortality and readmission in hospitalized cirrhotic patients in a General Hospital from Lima, Peru].
Liver cirrhosis is a public health problem. In Peru, is the leading cause of death in liver diseases. In addition, patients with chronic liver disease and cirrhosis are at increased risk for readmission. To determine the frequency of mortality and readmission at 3 months, and clinical-epidemiological characteristics of hospitalized cirrhotic patients in a general hospital. Data were collected prospectively of hospitalized cirrhotic patients in the Hospital Nacional Cayetano Heredia,Lima,Peru, from October 2011 to October 2012; telephone follow-up was at 3 months after hospital discharge. The study included 96 patients. The mean age was 59.2 years. The most common etiology of cirrhosis was alcohol (45.8%) and the main reason for hospitalization was upper gastrointestinal bleeding (29.2%). Global mortality was 39.6% (38 patients), from them, 63.2% (24/38) were inpatients, its main cause was septic shock 31.5% (12/38). Forty-four percent of the deceased had infection as complication. Hospital readmission was 42.8% (33/77) and 36.3% of them died. Hospitalized cirrhotic patients showed high mortality at 3 months, these patients at discharge revealed a high readmission within 3 months of follow up. |
A study of the peopling of Greenland using next generation sequencing of complete mitochondrial genomes.
The Greenlandic population history is characterized by a number of migrations of people of various ethnicities. In this work, the analysis of the complete mtDNA genome aimed to contribute to the ongoing debate on the origin of current Greenlanders and, at the same time, to address the migration patterns in the Greenlandic population from a female inheritance demographic perspective. We investigated the maternal genetic variation in the Greenlandic population by sequencing the whole mtDNA genome in 127 Greenlandic individuals using the Illumina MiSeq® platform. All Greenlandic individuals belonged to the Inuit mtDNA lineages A2a, A2b1, and D4b1a2a1. No European haplogroup was found. The mtDNA lineages seem to support the hypothesis that the Inuit in Greenland are descendants from the Thule migration. The results also reinforce the importance of isolation and genetic drift in shaping the genetic diversity in Greenlanders. Based on the mtDNA sequences, the Greenlandic Inuit are phylogenetically close to Siberian groups and Canadian Inuit. |
Recurrent Campylobacter Bacteremia as The First Manifestation of Hypogammaglobulinemia: A Case Report and Literature Review.
A 30-year-old woman with a past medical history of autoimmune hemolytic anemia presented with fever. Blood cultures grew Campylobacter. Her medical history was significant for four prior episodes of Campylobacter gastroenteritis and bacteremia. She received ciprofloxacin for the index presentation, then Meropenem de-escalated to doxycycline 6 months later following recurrence of Campylobacter. This prompted investigation for an immunodeficiency disorder. She was found to have hypogammaglobulinemia. Her Campylobacter infections resolved following the administration of intravenous immunoglobulins every 3 weeks. She did not have recurrence of Campylobacter during 5 years of follow-up. A literature search revealed an additional four case reports of six hypogammaglobulinemic adult individuals presenting with recurrent Campylobacter infections. Two patients were already on IVIG when Campylobacter infection occurred, and two patient achieved clinical cure following therapy with imipenem and IVIG. This case report highlights the importance of suspecting hypogammaglobulinemia in patients with recurrent Campylobacter infections, as this is sometimes the first manifestation of the condition. |
Learning About Conflict and Conflict Management Through Drama in Nursing Education.
In the health care settings in which nurses work, involvement in some form of conflict is inevitable. The ability to manage conflicts is therefore necessary for nursing students to learn during their education. A qualitative analysis of 43 written group assignments was undertaken using a content analysis approach. Three main categories emerged in the analysis-to approach and integrate with the theoretical content, to step back and get an overview, and to concretize and practice-together with the overall theme, to learn by oscillating between closeness and distance. Learning about conflict and conflict management through drama enables nursing students to form new knowledge by oscillating between closeness and distance, to engage in both the fictional world and the real world at the same time. This helps students to form a personal understanding of theoretical concepts and a readiness about how to manage future conflicts. [J Nurs Educ. 2018;57(4):209-216.]. |
Polymorphisms and haplotypes in the XRCC1 gene and the risk of advanced non-small cell lung cancer.
Single-nucleotide polymorphisms (SNPs) and haplotypes in the x-ray repair cross-complementing group 1 (XRCC1) gene, which is one of the base excision repair genes, are thought to be associated with the risk of non-small cell lung cancer (NSCLC). We genotyped three coding (Arg280His, Arg399Gln, and Gln632Gln) SNPs and six haplotype-tagging SNPs (htSNPs) for 140 advanced NSCLC cases and 217 healthy controls (all Koreans) using unconditional logistic regression analysis, and this was adjusted for age, gender, and the smoking status. The haplotypes were reconstructed according to the genotyping data and the linkage disequilibrium status of these nine SNPs. The minor allele heterozygotes of the rs1001581 htSNP showed an increased risk of NSCLC (adjusted odds ratio = 2.118, p = 0.013), and the minor allele homozygotes of the rs2293036 htSNP showed a decreased risk of NSCLC (adjusted odds ratio = 0.363, p = 0.020). Seven possible haplotypes were demonstrated in this study (haplotype frequency >1%). The GGGGGGGGG haplotype, which is composed of nine major alleles, showed a protective effect for developing NSCLC (odds ratio = 0.433, p = 0.002); however, the GGGGGGAGG haplotype that contained the minor allele of the rs1001581 demonstrated an increased risk of NSCLC (odds ratio = 1.597, p = 0.044). The above associations were similarly noted for the never smokers, and so the smoking status might modify the associations between the x-ray repair cross-complementing group 1 (XRCC1) genetic variants and the risk of developing NSCLC. On 10-million permutation testing, only the GGGGGGGGG haplotype was significantly associated with a decreased risk of NSCLC in the total group (p = 0.001). This study presents several novel aspects of the genetic susceptibility to develop NSCLC. Larger studies that will focus on the role of the rs1001581 and rs2293036 htSNPs and haplotypes for developing NSCLC are needed in the future. |
The variation in high sensitive cardiac troponin concentration during haemodialysis treatment is not similar to the biological variation observed in stable end stage renal disease patients.
Cardiovascular mortality is high in end stage renal disease (ESRD). This study aimed to: (1) calculate within-week within- and between-subject biological variation (CVI and CVG) for hs-cTn in ESRD; (2) determine the magnitude of hs-cTn concentration changes during haemodialysis (HD) treatment; and (3) compare the CVI and CVG to the within and between-subject variation of cTn concentration changes during HD treatments (CVDIFF-I and CVDIFF-G). Serum samples were collected from 20 patients before and after 10 consecutive HD treatments. cTn were measured using the hs-cTnT (Roche Diagnostics) and the hs-cTnI (Abbott Diagnostics). The CVA, CVI, CVG, CVDIFF-I and CVDIFF-G, were estimated using nested ANOVA. The within-week data showed hs-cTnT CVA, CVI and CVG of 1.6, 7.3 and 94.4%. Reference change values (RCV) were estimated to -18.7-23.0%. The Index of individuality (II) was 0.08. Corresponding values for hs-cTnI were 5.3, 13.2 and 142.4%, whilst the RCV was -32.5-48.2% and the II was 0.10. The mean concentration of cTn decreased by -6.4% (hs-cTnT) and -7.6% (hs-cTnI) during HD treatment. The CVDIFF-I and CVDIFF-G was 4.2 and 6.3% for hs-cTnT, and 10.7 and 9.4% for hs-cTnI. The RCVDIFF was -18.2-5.4% (hs-cTnT) and -39.0-23.8% (hs-cTnI), respectively, and the IIDIFF-values were 0.7 and 1.3. The CVI and CVG are similar to earlier findings. Mean hs-cTn concentrations decreased during HD. The within-subject hs-cTn variation during HD is similar to the between-subject variation, i.e. determining a cut-off value for hs-cTn changes during HD may be useful. |
Measuring baseline Ca(2+) levels in subcellular compartments using genetically engineered fluorescent indicators.
Intracellular Ca(2+) signaling is involved in a series of physiological and pathological processes. In particular, an intimate crosstalk between bioenergetic metabolism and Ca(2+) homeostasis has been shown to determine cell fate in resting conditions as well as in response to stress. The endoplasmic reticulum and mitochondria represent key hubs of cellular metabolism and Ca(2+) signaling. However, it has been challenging to specifically detect highly localized Ca(2+) fluxes such as those bridging these two organelles. To circumvent this issue, various recombinant Ca(2+) indicators that can be targeted to specific subcellular compartments have been developed over the past two decades. While the use of these probes for measuring agonist-induced Ca(2+) signals in various organelles has been extensively described, the assessment of basal Ca(2+) concentrations within specific organelles is often disregarded, in spite of the fact that this parameter is vital for several metabolic functions, including the enzymatic activity of mitochondrial dehydrogenases of the Krebs cycle and protein folding in the endoplasmic reticulum. Here, we provide an overview on genetically engineered, organelle-targeted fluorescent Ca(2+) probes and outline their evolution. Moreover, we describe recently developed protocols to quantify baseline Ca(2+) concentrations in specific subcellular compartments. Among several applications, this method is suitable for assessing how changes in basal Ca(2+) levels affect the metabolic profile of cancer cells. |
Sarcoptic mange found in wolves in the Rocky Mountains in western United States.
We documented sarcoptic mange caused by mites (Sarcoptes scabiei) in 22 gray wolves (Canis lupus) in the northern Rocky Mountain states of Montana (n=16) and Wyoming (n=6), from 2002 through 2008. To our knowledge, this is the first report of sarcoptic mange in wolves in Montana or Wyoming in recent times. In addition to confirming sarcoptic mange, we recorded field observations of 40 wolves in Montana and 30 wolves in Wyoming displaying clinical signs of mange (i.e., alopecia, hyperkeratosis, and seborrhea). Therefore, we suspect sarcoptic mange may be more prevalent than we were able to confirm. |
Henoch-Schönlein purpura nephritis.
Henoch-Schönlein purpura (HSP) is the one of most common types of systemic vasculitis in childhood. Glomerulonephritis (HSPN) occurs in 30-50 % of HSP patients, mostly in a mild form but a small percentage of patients present with nephrotic syndrome or renal failure. HSPN is caused by the glomerular deposition of immunoglobulin A1 (IgA1)-containing immune complexes in the mesangium, the subepithelial and the subendothelial space. Formation of the IgA1 immune complex is thought to be the consequence of aberrantly glycosylated IgA1 molecules secreted into the circulation and their subsequent recognition by IgG specific for galactose-deficient IgA1. Mesangial proliferation and renal damage are triggered by the deposited immune complexes, which likely require activation of the complement system. Whereas other organ manifestations of HSP are mostly benign and self-limiting, HSPN might lead to chronic renal disease and end stage renal failure, thereby justifying immunosuppressive treatment. Long-term renal outcome correlates to the severity of the initial clinical presentation and the extent of renal biopsy changes, both of which are used to decide upon a possible treatment. As there are no evidence-based treatment options for severe HSPN, a large variety of therapeutic regimens are used. Prospective randomized controlled treatment studies are needed, but the low incidence of severe HSPN renders such studies difficult. |
Properties of alginate fiber spun-dyed with fluorescent pigment dispersion.
Spun-dyed alginate fiber was prepared by the spun-dyeing method with the mixture of fluorescent pigment dispersion and sodium alginate fiber spinning solution, and its properties were characterized by SEM, TGA, DSC, and XRD. The results indicate that fluorescent pigment dispersion prepared with esterified poly (styrene-alt maleic acid) had excellent compatibility with sodium alginate fiber spinning solution, and small amount of fluorescent pigment could reduce the viscosity of spun-dyed spinning solutions. SEM photo of spun-dyed alginate fiber indicated that fewer pigment particles deposited on its surface. TGA, DSC, and XRD results suggested that thermal properties and crystal phase of spun-dyed alginate fibers had slight changes compared to the original alginate fibers. The fluorescence intensity of spun-dyed alginate fiber reached its maximum when the content of fluorescent pigment was 4%. The spun-dyed alginate fiber showed excellent rubbing and washing fastness. |
Qualitative analysis of Coomassie-blue-stained proteins from normal prostate, benign prostatic hypertrophy, or adenocarcinoma of the prostate, separated by two-dimensional protein electrophoresis.
Samples from nine normal prostates (N), ten benign hypertrophic prostates (BPH), and eight adenocarcinomas of the prostate (ACP), obtained from the National Prostatic Cancer Project were analyzed by two-dimensional (2D)-protein electrophoresis. Qualitative analysis of Coomassie-blue-stained acidic proteins between pI 3.5 and 6.8 yielded these results: The total number of enumerated proteins was 136 (N), 107 (BPH), and 147 (ACP). Ninety-two denoted proteins were deemed common to the three kinds of samples, three were considered present in N and BPH, 7 in BPH and ACP, and 28 in N and ACP. Thirteen, five, and 20 proteins were detected only in N, BPH, or ACP. These proteins cannot be considered "unique" to their respective samples, since amounts of protein that do not exceed the minimum sensitivity of the dye may be present in the other samples. The similarity in the patterns of proteins from these three types of prostate samples is consistent with the following hypothesis: The distribution of proteins from histologically ambiguous prostate samples will correlate more closely with these protein profiles than with those associated with cancers originating from other organs. |
Posttraumatic growth experiences and its contextual factors in women with breast cancer: An integrative review.
In this article, we synthesize current research that examines determinants and manifestations of posttraumatic growth (the phenomenon of posttraumatic growth can be embodied in several domains) in women with breast cancer. The findings of the integrative literature review may contribute to facilitating person-centered oncology care by raising health care professionals' awareness and understanding of posttraumatic growth phenomenon among breast cancer survivors. The identification of factors contributing to posttraumatic growth and manifestations of posttraumatic growth are important in increasing the effectiveness of interventions in supporting women during their breast cancer journey. The methods proposed by Whittemore and Knafl ( 2005 ) were adopted to guide this integrative review. Quality assessment was conducted using recognized critical appraisal tools relating to quantitative and qualitative studies. Four main manifestations were synthesized from the literature: new perception of self; relatedness to others; new life philosophy; and spiritual and religious growth. Personal characteristics, illness factors, cognitive processing, coping strategies, social support, religion and spirituality, the body's role and physical activities were identified as influencing posttraumatic growth in women with breast cancer. |
Finite element modelling of a rotating piezoelectric ultrasonic motor.
The evaluation of the performance of ultrasonic motors as a function of input parameters such as the driving frequency, voltage input and pre-load on the rotor is of key importance to their development and is here addressed by means of a finite element three-dimensional model. First the stator is simulated as a fully deformable elastic body and the travelling wave dynamics is accurately reproduced; secondly the interaction through contact between the stator and the rotor is accounted for by assuming that the rotor behaves as a rigid surface. Numerical results for the whole motor are finally compared to available experimental data. |
Non-extensile surgical approaches for two-column acetabular fractures.
We reviewed the outcome, at a mean follow-up of 14 months, of 21 two-column fractures of the acetabulum treated by operation through one or two non-extensile approaches. Eighteen procedures resulted in reduction of the articular surfaces to within 3 mm. The blood loss and operating time when two combined non-extensile approaches were used were similar to those reported for extended acetabular approaches. The incidence of heterotopic ossification which limited joint motion was low, and the average Harris hip score was 81 points. The use of non-extensile approaches for acetabular fractures in which both columns are involved avoids iatrogenic injury to the abductors, and reduces the incidence of complications. |
Is Routine Intraoperative Contrast-Enhanced Ultrasonography Useful During Whole Liver Transplantation?
Vascular complications following liver transplantation (LT) may result from technical deficiencies. Intraoperative diagnosis remains challenging but can prevent serious delayed complications. Intraoperative Doppler ultrasonography (IOUS) represents the gold standard for imaging, although it requires radiological skills. Contrast-enhanced ultrasonography has been reported during postoperative assessments, but never intraoperatively (CE-IOUS). The aim of this study was to assess the feasibility of routine CE-IOUS, to evaluate its impact on surgical strategy and its usefulness. All 553 whole LTs performed in our tertiary centre between 01/2010 and 12/2014 were reviewed. We compared perioperative outcomes and long-term survival in IOUS (n = 370) versus CE-IOUS (n = 103) groups. Secondarily, the seven cases where the two imaging findings conflicted (CE+ Group) were matched 1:2 and compared with an exclusively IOUS procedure (CE- Group, n = 14) to assess the consequences of a specific CE-guided strategy. CE-IOUS assessments were successful in 100% of cases, without any adverse effects. Vascular complications and patient/graft survival rates were identical in the IOUS and CE-IOUS groups (p = 0.65, 0.95 and 0.86, respectively). CE-IOUS confirmed IOUS findings in 93% of cases (n = 96) and led to the realization of an additional procedure (median arcuate ligament lysis) and six conservative strategies despite poor arterial (n = 5) or venous flow (n = 1) under Doppler analysis. The CE+ and CE- groups presented statistically identical perioperative and long-term outcomes. This study demonstrated the feasibility of CE-IOUS during whole LT. However, we failed to demonstrate any advantages of CE-IOUS over IOUS. Therefore, IOUS currently remains the gold-standard imaging technique for the intraoperative assessment of vascular patency. |
Beaconing Sheds Light on the Darkness of Gas Monitor Data.
How can you proactively fix a problem when you don't know where it occurred? |
Infliximab dependency in a national cohort of children with Crohn's disease.
The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohn's disease (CD) treated in Denmark from 1999 to 2003. The National Danish Crohn Colitis Database of infliximab was used to identify all Danish CD patients treated at pediatric departments with infliximab. The clinical outcome was assessed by pattern recognition of the disease course 30 days after the first infliximab infusion and 90 days after intended end of treatment. During a 3 year period, infliximab was given to 24 CD patients (9 male/15 female) aged median 15.4 (range 9.8-18.6) years with a median disease duration of 26 (range 0.7-93) months and a median number of infusions of 6 (range 2-11). Five milligrams of infliximab per kilogram infusions were given intravenously. Immediate response was as follows: 8 (33%) patients achieved complete response (CR), 10 (42%) partial response (PR), and 6 (25%) no response (NR). Long-term response was as follows: 7 (29%) patients achieved prolonged response (PRO), defined as maintenance of CR or PR, 10 (42%) were infliximab dependent (ID), defined as relapse of symptoms requiring reinfusions of infliximab to regain CR or PR, and 6 (25%) had NR. Six (25%) patients needed surgery during or after treatment with infliximab. Side effects were seen in four (17%) patients. No serious events were noted. Seventy-one percent of the children appeared to benefit (PRO or ID) from infliximab treatment with minor side effects when given episodically. Among these patients, two response patterns were recognized: PRO after ending infliximab treatment (29%) or dependency on reinfusions of infliximab (42%). |
[Post-traumatic carpal tunnel syndrome].
In the course of a ten months study on 508 patients with CTS a trauma as a possible causal factor was observed in 22 cases. In none of these cases did the other hand show normal electroneurographic parameters. The mean values of distal motor latency were among 5.5 ms (3.7-9.2 ms) on the injured side and 4.6 (3.5-6.7 ms) on the other. The relatively seldom occurrence of CTS in connection with a trauma requires therefore strict criteria for the evaluation of the casual context. A traumatic etiology can only be recognised if a close temporal relation exists (beginning of the symptomatology during immobilisation or after removal of the cast) or a special tendency to swelling or a dislocation as well as a clear difference in electroneurographic values of the two sides can be observed. Depending on the degree of this difference in latency one can maintain criteria for evaluating the question of causality or of transient or permanent deterioration. Finally in case of CTS the treatment should be given primary importance ahead of reimbursement for the injury. |
How Salmonella became a pathogen.
In many pathogens, virulence can be conferred by a single region of the genome. In contrast, the facultative intracellular lifestyle of Salmonella demands a large number of genes distributed around the chromosome. The evolution of Salmonella has been marked by the acquisition of several 'pathogenicity islands', each contributing to the unique virulence properties of this microorganism. |
Relation Between Memory Impairment and the Fornix Injury in Patients With Mild Traumatic Brain Injury: A Diffusion Tensor Tractography Study.
We investigated the relation between memory impairment and the fornix injury in patients with mild traumatic brain injury, using diffusion tensor tractography. Eighty-six chronic patients with mild traumatic brain injury and 50 normal control subjects were recruited. Fractional anisotropy and fiber volume were measured for each reconstructed fornix. The patients were classified according to the following three types: type A (47 patients), intact integrity of both fornical crura; type B (27 patients), showed a discontinuation in either fornical crus; and type C (12 patients), discontinuations in both fornical crura. The Memory Assessment Scale was used for evaluation of memory function. Fractional anisotropy and fiber volume showed weak positive correlations with global memory of Memory Assessment Scale, respectively (r = 0.303, P = 0.006; r = 0.271, P = 0.014). Significant difference in the global memory of Memory Assessment Scale was observed between type A and B and between type A and C without difference between type B and C (P < 0.05). It seems that the diffusion tensor tractography parameters of the fornix and the integrity of fornical crus can be used as a biomarker for axonal injury of the fornix in patients with mild traumatic brain injury. |
Alterations of vascular alpha 1-adrenergic contractile responses in hypercholesterolemic rabbit common carotid arteries.
In rabbits fed a diet containing 1% cholesterol and 4% lard for 4 or 8 weeks, vascular responses to alpha 1-adrenoceptor agonists, epinephrine (EPI), phenylephrine (PE), norepinephrine (NE), methoxamine (MO), and clonidine (CL) were examined in isolated common carotid arteries by the cannula-insertion method. The high cholesterol diet caused no microscopic evidence of atherosclerosis, and vasodilatory responses to ACh were well maintained, even in the 8-week group. Vasoconstrictions to EPI were augmented and those to NE, MO, and CL were progressively decreased, but that to PE was not influenced in 4- and 8-week-treated groups. These agonist-induced constrictions were readily inhibited by bunazosin and WB 4101, indicating that these result from alpha 1A-adrenoceptor activations. CL- and MO-induced constrictions were much more sensitive to WB 4101. Chlorethylclonidine (CEC) inhibited CL- and MO-induced constrictions, but not PE-induced, at relatively larger doses. We suggest that vasoconstrictivity to alpha-adrenoceptor agonists is altered by hypercholesterolemia without accompanying atherosclerotic changes and endothelial dysfunction, at the early stage of hypercholesterolemia, the sensitivity of alpha 1-adrenoceptors might be decreased at smooth muscle cell levels, and different changes in contractile reactivity to alpha 1-agonists after cholesterol feedings might be due to a decrease in alpha 1A-adrenoceptors. |
In-situ controllable synthesis of Ag nanoparticles: irradiation induced surface segregation of Ag2V4O11 nanobelt.
Ag2V4O11 nanobelt has been synthesized through a hydrothermal process and its surface segregation leading to the in-situ controllable synthesis of Ag nanoparticles under different irradiation conditions is investigated. The resulted materials are characterized by XRD, TEM, HRTEM, and SAED measurements. It is found that well-distributed Ag nanoparticles with a controlled average diameter in the range of 2-50 nm can be formed in-situ and self-loaded on the surface of Ag2V4O11 nanobelt. The segregation mechanism is also discussed in detail. The silver vanadium salt with self-loaded Ag nanoparticles may find application in catalysis and lithium batteries. |
The association of potentially inappropriate medication use on health outcomes and hospital costs in community-dwelling older persons: a longitudinal 12-year study.
To determine (1) whether potentially inappropriate medication (PIM) use defined by the Meds75 + database is associated with fracture-specific hospitalisations and all-cause mortality, and (2) the association between PIM use and all-cause hospitalisation costs in a 12-year follow-up of a nationwide sample of people aged ≥ 65 years in Finland. This is a longitudinal study of 20,666 community-dwelling older persons with no prior purchases of PIMs within a 2-year period preceding the index date (1 Jan 2002), who were followed until the end of 2013. Data were obtained from the Finnish Prescription Register, and it was accompanied by information on inpatient care, causes of deaths and socioeconomic status from other national registers. Propensity score matching (PSM) analysis was used to account for potential selection effect in PIM use. Cox proportional hazards regression was used to identify the time to the first fracture or death by comparing PIM-users (n = 10,333) with non-users (n = 10,333). The association between PIM use and hospital costs was analysed with a fixed effects linear model. PIM use was weakly associated with an increased risk of fractures and death. The association was stronger in the first PIM-use periods. Hospitalised PIM-users had 15% higher hospital costs compared to non-users during the 12-year follow-up. PIM initiation was associated with an increased risk of fracture-specific hospitalisation and mortality and PIM-users had higher hospital costs than non-users. Health care providers should carefully consider these issues when prescribing PIM for older persons. |
Quantification of the interaction forces between metals and graphene by quantum chemical calculations and dynamic force measurements under ambient conditions.
The two-dimensional material graphene has numerous potential applications in nano(opto)electronics, which inevitably involve metal graphene interfaces.Theoretical approaches have been employed to examine metal graphene interfaces, but experimental evidence is currently lacking. Here, we combine atomic force microscopy (AFM) based dynamic force measurements and density functional theory calculations to quantify the interaction between metal-coated AFM tips and graphene under ambient conditions. The results show that copper has the strongest affinity to graphene among the studied metals (Cu, Ag, Au, Pt, Si), which has important implications for the construction of a new generation of electronic devices. Observed differences in the nature of the metal-graphene bonding are well reproduced by the calculations, which included nonlocal Hartree-Fock exchange and van der Waals effects. |
Posttranslational modifications of nuclear proteins in rat cerebral hemispheres during postnatal development.
The processes of acetylation, phosphorylation, and methylation of nuclear proteins in cerebral hemispheres of 10- and 30-day-old rats were investigated. The experiments were carried out in vitro by measuring the incorporation of labeled precursors into histones and nonhistone chromosomal proteins (NHP) extracted from nuclei and separated by polyacrylamide gel electrophoresis. The results obtained indicate that there are age-specific differences in the processes of phosphorylation and methylation of chromosomal proteins, whereas the acetylation process did not change significantly between 10 and 30 days of age. Electrophoretic analysis of histones indicated that the histone H3 was labeled to a greater degree than the other fractions and showed major changes in the processes of phosphorylation and methylation during postnatal development. The electrophoretic analysis of NHP showed considerable changes between 10 and 30 days of age. Certain components of NHP became increasingly evident as the brain developed. The methylation of an as yet unidentified protein with a molecular weight of approximately 118,000 daltons occurred at both ages. |
Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis.
MicroRNA (miRNA)-mediate RNA interference has been identified as a novel mechanism that regulates protein expression. It is recognised that miRNAs play essential roles in the immune system and for correct function in the brain. Moreover, it is now clear that abnormal miRNA expression is a common feature of several diseases involving the immune system including multiple sclerosis (MS). Expression analysis for miR-21, miR-146a and -b, miR-150, miR-155 was carried out in peripheral mononuclear cells (PBMC) from a cohort of 29 MS patients and 19 controls. Subsequently, a case control study for miR-146 rs2910164 variant was performed in an overall population of 346 MS cases and 339 controls. A statistically significant increased expression of miR-21, miR-146a and -b was observed in relapsing remitting (RR)MS patients as compared with controls (1.44±0.13 vs 0.79±0.06, P=0.036; 1.50±0.12 vs 0.84±0.08, P=0.039; 1.54±0.15 vs 0.72±0.08, P=0.001 respectively). On the contrary, no differences were found in the expression levels of both miR-150 and miR-155 in patients as compared with controls (P>0.05). The genetic association study failed to find any differences in the frequencies of rs2910164 between patients and controls. miRNA dysregulation may contribute to the pathogenesis of MS and highlights the possibility to define different disease entities with specific miRNAs profile. |
Serious games for immersive cultural training: creating a living world.
Living worlds offer a nonlinear, unscripted process for experiencing and safely learning the cognitive complexity and nuance of culture through emergent high-fidelity simulation. The 3D Asymmetric Domain Analysis and Training model uses visual, auditory, behavioral, and cultural models for immersive cultural training using the living-world construct. |
Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells.
The 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are widely used and well tolerated cholesterol-lowering drugs. In rare cases, side effects occur in skeletal muscle, including myositis or even rhabdomyolysis. However, the molecular mechanisms are not well understood that lead to these muscle-specific side effects. Here, we show that statins cause apoptosis in differentiated human skeletal muscle cells. The prototypical representative of statins, simvastatin, triggered sustained intracellular Ca(2+) transients, leading to calpain activation. Intracellular chelation of Ca(2+) completely abrogated cell death. Moreover, ryanodine also completely prevented the simvastatin-induced calpain activation. Nevertheless, an activation of the ryanodine receptor by simvastatin could not be observed. Downstream of the calpain activation simvastatin led to a translocation of Bax to mitochondria in a caspase 8-independent manner. Consecutive activation of caspase 9 and 3 execute apoptotic cell death that was in part reversed by the coadministration of mevalonic acid. Conversely, the simvastatin-induced activation of calpain was not prevented by mevalonic acid. These data delineate the signaling cascade that leads to muscle injury caused by statins. Our observations also have implications for improving the safety of this important medication and explain to some extent why physical exercise aggravates skeletal muscle side effects. |
An isoenzyme study in the genus Lotus (Fabaceae) : Segregation of isoenzyme alleles in synthetic allo- and autotetraploids, and in L. corniculatus.
Segregation of the cytosolic Pgi2 locus was studied among progeny of the synthetic allotetraploid (L. japonicus × L. alpinus)(2), the synthetic autotetraploid (L. alpinus)(2), and the cultivated tetraploid species L. corniculatus L. Evidence of an original diploid duplication found within the interspecific hybrid L. japonicus × L. alpinus was also found within the synthetic allotetraploid (quadruplication of loci). Evidence suggesting quadruplication of loci was also found in the tetraploid L. corniculatus, but not in the synthetic autotetraploid (L. alpinus)(2). It is suggested that the original duplication resulted from unequal crossing-over between homoeologues and that it provides evidence that L. corniculatus is a segmental allotetraploid. Quadruplication of loci in L. corniculatus could explain previously reported distorted tetrasomic ratios for segregation of qualitative characters in this species. |
Structure of citrus pectins and viscometric study of their solution properties.
Citrus pectins with degrees of methylation between 30 and 72% were carefully characterized in order to determine their charge density and molecular weight distribution, the content in galacturonic acid and in neutral sugars, the degree of methylation and acetylation. Using enzymic degradation it has been found that pectin molecules consist mainly of long homogalacturonan regions with some regions of neutral sugars as side chains attached on rhamnose residues. The viscometric behaviour of the different samples indicates that 0.1 M NaCl, at 25 degrees C, is a good solvent of sodium pectinates. From the evolution of the Huggins parameter, it appears that pectins with 50% of methylated galacturonic groups exhibit a maximum flexibility. A Mark-Houwink exponent of 0.8 has been found in good agreement with theoretical predictions for flexible polymers in a good solvent. |
Chronic Tubulo-interstitial Nephropathy with Hepatic Involvement in Children.
The clinical, biochemical and histological data are reported in a female infant with rapidly progressive renal failure, hepatosplenomegaly and death at the age of 2 years. This case represents another example of the newly described entity "chronic tubulo-interstitial nephritis with hepatic involvement" and the only reported case of this kind from this part of the world. |
Ischaemic heart disease and low birth weight: a test of the fetal-origins hypothesis from the Swedish Twin Registry.
Twins constitute a population with lower than average birth weight for reasons that are not a consequence of social disadvantage. The hypothesis that ischaemic heart disease (IHD) is linked to low birth weight was tested by analysing whether or not 8174 female and 6612 male Swedish twins had a higher mortality compared to the general Swedish population. The association between adult body height and IHD mortality was also analysed in a nested case-control study among monozygotic and dizygotic twins. Ischaemic heart disease mortality was not higher among twins (women: relative risk [RR] 0.99; 95% confidence limits [CL] 0.89-1.10; men: RR 0.85; CL 0.79-0.92). However, the shorter twin in a twin pair was more likely to die of heart disease than the taller (odds ratio [OR] 1.15, CL 1.03-1.25). We suggest that postnatal influences may well be as important as prenatal influences in producing any effect on ischaemic heart disease mortality and that the type of growth retardation in utero experienced by twins may not constitute a risk for ischaemic heart disease in adulthood. |
Highly tunable Berry phase and ambipolar field effect in topological crystalline insulator Pb(1-x)Sn(x)Se.
Recently, rock-salt IV-VI semiconductors, such as Pb(1-x)Sn(x)Se(Te) and SnTe, have been observed to host topological crystalline insulator (TCI) states. The nontrivial states have long been believed to exhibit ambipolar field effects and possess massive Dirac Fermions in two-dimension (2D) limit due to the surface hybridization. However, these exciting attributes of TCI remain previously inaccessible owing to the complicated control over composition and thickness. Here, we systematically investigate doping and thickness-induced topological phase transitions by electrical transport. We demonstrate the first evidence of the ambipolar properties in Pb(1-x)Sn(x)Se thin films. Surface gap opening is observed in 10 nm TCI originated from the strong finite-size effect. Importantly, magnetoconductance hosts a competition between weak antilocalization and weak localization, suggesting a strikingly tunable Berry phase evolution and strong electron-electron interaction. Our findings serve as a new probe to study electron behavior and pave the way for further exploring and manipulating this novel 2D TCI phase. |
Event-related potentials associated with sound discrimination versus novelty detection in children.
In children, deviant sounds in an oddball paradigm elicit a mismatch negativity (MMN) indexing discrimination of sound change and late difference negativity (LDN) with unknown functional significance. Salient sounds elicit an ERP index if orienting, P3a, and a late negative component, Nc. We compared children's responses elicited by moderate sound changes and novel sounds to examine the relationships between MMN and LDN, and LDN and Nc. Two components of the Nc, the Nc1 and Nc2, were identified. The scalp topography of LDN differed from those of the MMN and Nc1. Children's early P3a appeared mature but late P3a lacked frontal predominance. The findings suggested that LDN is not linked with either the sensory or attentional processing. It might reflect cognitive, albeit preattentive, processing of sound change. The Nc1 appears to reflect cognitive attentive processing of salient stimuli and the Nc2 might reflect reorienting after distraction. |
Familial carcinoma of the ovary. Case report.
A patient was successfully treated by surgery, progestogens and chlorambucil for a poorly differentiated cystadenocarcinoma of the ovary. Four of her relatives had died of ovarian cancer; it was ascertained that two of them also had poorly differentiated cystadenocarcinoma. |
Cell Therapy With Preimmunized Effector Cells Mismatched for Minor Histocompatible Antigens in the Treatment of a Murine Mammary Carcinoma.
SUMMARY: Cell therapy with allogeneic donor cells mismatched for minor histocompatible (MiHC) antigens was applied to a murine mammary carcinoma (4T1) model to test the feasibility of graft versus tumor (GVT) effect against metastatic epithelial tumor cells. BALB/c mice bearing a 4T1 tumor of BALB/c origin were given syngeneic or MiHC-mismatched splenocytes. GVT effects were determined in secondary recipients of adoptively transferred lung cells derived from primary hosts who had previously been inoculated intravenously with 4T1 cells, and injected with one of the following: 1) naive BALB/c splenocytes, 2) naive DBA/2 splenocytes, 3) 4T1-immune DBA/2 splenocytes, or 4) DBA/2 splenocytes immunized with host-derived BABL/c spleen cells. Naive DBA/2 splenocytes inhibited tumor growth only slightly and only slightly prolonged the survival of secondary recipients, in comparison with fully matched tumor/host BALB/c spleen cells. An efficient GVT reaction was demonstrated in vitro and in vivo with MiHC-mismatched DBA/2 splenocytes from mice presensitized by multiple injections of irradiated tumor or BALB/c-derived spleen cells. All 30 mice adoptively inoculated with lung cells from primary hosts that had previously been treated with these presensitized effector cells were tumor free for >250 days. Secondary recipients inoculated with lung cells from mice given naive BALB/c or DBA/2 spleen cells died of metastatic tumors within 33 to 46 days. These results suggest that preimmunized donor cells represent an effective tool against metastatic disease; hence, the next goal should be to control graft-versus-host disease while exploiting the GVT potential. |
Graduating Surgical Residents Lack Competence in Critical Care Ultrasound.
Ultrasound provides accessible imaging for bedside diagnostics and procedural guidance, but may lead to misdiagnosis in untrained users. The main objective of this study was to determine observed and self-perceived competence with critical care ultrasound in graduated general surgery residents. The design of this study was a retrospective review. Ultrasound training program records were reviewed for number of prior ultrasound examinations performed, self-perceived competence, observed competence on faculty examinations, and intended future use of individual critical care ultrasound examinations. This study was undertaken at the R Adams Cowley Shock Trauma Center, which is a tertiary care center in Baltimore, MD. Graduated general surgery residents were identified at the beginning of their surgical critical care fellowship at our institution, and were included if they participated in our critical care ultrasound education program. Fifteen graduated general surgery residents were included. Prior ultrasound experience ranged from 100% for focused assessment of sonography for trauma (FAST) to 13.3% for advanced cardiac assessment. Self-perceived competence ranged from 46.7% with FAST to 0% for advanced cardiac assessment. Observed competence ranged from 20.0% for FAST examinations to 0% for basic cardiac assessment, advanced cardiac assessment, and inferior vena cava (IVC) assessment. All participants intended to use ultrasound in the future for FAST, pneumothorax detection and basic cardiac assessment, and 86.7% for IVC assessment and advanced cardiac assessment. Of participants with self-perceived competence, 28.6% had observed competence with FAST, 0% with IVC assessment, and 100% with pneumothorax detection. Graduated general surgery residents are not competent in multiple critical care ultrasound examinations despite universally planning to use critical care ultrasound in future practice. Current exposure to ultrasound in residency may give a false sense of competency with ultrasound use. A standardized ultrasound curriculum is an urgent need for general surgery training. |
[Laboratory investigation of endocrine function - interpretation of results and pitfalls].
Endocrine disorders are common in internal medicine. Diagnosis of endocrine diseases are usually based on patient history, clinical assessment and laboratory investigations. Thereby, biochemical analyses are used to confirm clinical diagnosis, to assess the need for treatment and to monitor disease progression, in particular to ascertain treatment efficacy. This article will focus on frequently used laboratory investigations for endocrine diseases such as diabetes, thyroid dysfunction, male hypogonadism and adrenal insufficiency. In particular, pre-analytical and analytical variability of biochemical measures as well as its significance in clinical practice will be discussed. |
Autometallographic demonstration of mercury in rat molars.
Male, adult Wistar rats were exposed to 500 micrograms/m3 mercury vapor 6 h per day, 5 days a week for 4 wk. They were subsequently killed by transcardial perfusion. The molars were extracted, demineralized, and embedded in resin before sectioning. Autometallographic development was performed according to the method of Danscher & Möller-Madsen. Mercury deposits were found in small amounts in several areas of the pulp, but with larger accumulations of grains in relation to odontoblasts. Mercury also could be seen in odontoblastic processes in the dentin and predentin. Our conclusion is therefore that systemic uptake of mercury vapor leads to accumulation of mercury in the odontoblasts and that the mercury may be transported into the dentin tubules in the odontoblastic process. |
Changes of somatotype in high school students, V region, Chile: 1985-2010.
To determine the trend of high school students from Valparaíso Chile by means of an anthropometrical somatotype. two samples of students during the years 1984-1985 (86 men and 71 women) and 2009-2010 (77 men and 86 women) between 15 and 18 years of age have been studied. Somatotype was estimated by the Heath-Carter anthropometric method. significant differences were found in all the variables of the somatotype during the periods studied (p < 0.01), except for height (p = 0.176) and humeral breadth in women (p = 0.067). Important distinctions were also found in the endomorphic, mesomorphic and ectomorphic components (p < 0.01). Men measurements registered remarkable differences in all the variables (p < 0.01), with the exception of weight (p = 0.156), calf breadth (p = 0.906) and arm breadth in contraction (p = 0.284). Measurement results of endomorphic (p < 0.01), ectomorphic (p < 0.01) and mesomorfic components (p < 0.05) revealed considerable differences. During the period 1984-1985, men classified as balanced mesomorph 2.7-4.8-3.1 which switched to mesomorph-endomorph 3.8-4.3-2.5 in the period 2009-2010. And the population of women in the 1984-1985 period is classified as mesomorph-endomorph 4.2-4.7-2.1 and changes to a mesomorphic-endomorph biotype 6.6-4.1-1.3 in the 2009-2010. the somatotype of the adolescent population, especially women in Valparaiso, Chile has changed to a predominant endomorphic biotype, and its mesomorphic component has decreased. A high relative adiposity contributes to increase the probability for these people to suffer non-transmissible chronic diseases and cardiovascular issues. |
Effect of UV irradiation on epidermal cell cytokine production.
Within the last decade it has been found that the keratinocyte is not only a mechanical barrier to the outside but is also a fully immunocompetent cell that can release immunomodulating cytokines such as interleukin (IL) 1, IL 3, IL 6 and colony-stimulating factors (CSF). The constitutive production of these mediators by keratinocytes both in vivo and in vitro is very low; however, it can be dramatically enhanced by various stimuli such as tumour promotors or endotoxin. In addition, UV light is one of the most potent inducers of cytokine release. Accordingly, UV exposure results in increased production of IL 1, IL 3, IL 6, tumour necrosis factor and granulocyte/macrophage-CSF by epidermal cells. The secretion of these cytokines causes local immunologic and inflammatory reactions following UV irradiation. These factors, however, may also enter the circulation and thus may be responsible for systemic effects. In addition, UV light causes keratinocytes to release immunosuppressive factors which block contact hypersensitivity reaction and IL 1 activity. The production of such immunoinhibitors may play an essential pathogenic role during systemic UV-induced immunosuppression. This review will focus on the biological effects of epidermal-cell-derived cytokines, whose release is induced by UV light, and their role in immunologic and inflammatory reactions following UV exposure will be discussed. |
The Nationwide Health Information Network: The Case of the Expansion of Health Information Exchanges in the United States.
The Nationwide Health Information Network (NHIN) implemented secure exchange of health records through utilization of the Internet. The NHIN has greatly assisted in achieving the goals of the Health Information Technology for Economic and Clinical Health Act by promoting the adoption of Meaningful Use. Epic introduced a Health Information Exchange platform, Care Everywhere, which has facilitated Health Information Exchange availability. The purpose of this research was to determine the impact of NHIN and Epic Care's Care Everywhere on health care to determine whether their use in the emergency department (ED) has increased. The methodology for this study utilized a literature review. Twenty-eight sources were referenced for this study. With the NHIN implementation, repeated visits were decreased, visit times became faster, and charges were lower. Emergency department reported significant benefits with sharing clinical information. The NHIN implementation throughout the ED has increased the quality of health care; duplicated tests and drug usage were determined, and a reduction of the ED length of stay was also achieved. |
Probing the interactions of O(2) with small gold cluster anions (Au(n)(-), n = 1-7): chemisorption vs physisorption.
Activation of O(2) is the most critical step in catalytic oxidation reactions involving gold and remains poorly understood. Here we report a systematic investigation of the interactions between O(2) and small gold cluster anions Au(n)(-) (n = 1-7) using photoelectron spectroscopy. Higher resolution photoelectron spectra are obtained for the molecularly chemisorbed even-sized Au(n)O(2)(-) (n = 2, 4, 6) complexes. Well-resolved vibrational structures due to O-O stretching are observed and can be readily distinguished from the Au-derived PES bands. The adiabatic detachment energies and O-O vibrational frequencies are measured to be 3.03 +/- 0.04, 3.53 +/- 0.05, and 3.17 +/- 0.05 eV, and 1360 +/- 80, 1360 +/- 80, and 1330 +/- 80 cm(-1) for n = 2, 4, 6, respectively. Physisorbed Au(n)(-)(O(2)) complexes for n = 1, 3, 5, 7 are observed for the first time, providing direct evidence for the inertness of the closed-shell odd-sized Au(n)(-) clusters toward O(2). Neutral even-sized Au(n) clusters are closed-shell and are expected to be inert toward O(2), which is not consistent with the reduced O-O vibrational frequencies observed in the photoelectron spectra relative to free O(2). It is suggested that the photodetachment transitions can only access excited states of the neutral even-sized Au(n)O(2) complexes; a double-well potential is proposed consisting of the ground-state van der Walls well at long Au(n)-O(2) distances and a higher energy deeper well at short Au(n)-O(2) distances derived from singlet O(2) ((1)Delta(g)). The current study provides further insight into O(2) interactions with small gold clusters, as well as accurate experimental data to benchmark theoretical investigations. |
Stakeholders' Views Regarding Their Role as Support System for People with Mental Illness and Their Families in Rural South Africa.
The diverse needs associated with mental illness warrant for the provision of mental health care by various sources. The South African government recognises the involvement of stakeholders as a potential means of narrowing the gaps in mental health service delivery. This study explored the views of different stakeholders about their roles as support systems for people with mental illness and their families at Mashashane, a rural setting in Limpopo Province, South Africa. Seven focus group discussions were conducted with various stakeholders. This qualitative study employed content analysis to allow for comparison of stakeholders' views. Stakeholders understanding of mental illness was based on reaction towards people with mental illness, causes of mental illness and the behaviour displayed by the ill individual. The identified formal and informal systems were seen as ineffective with regards to provision of support. Collaboration was recommended as a mechanism to improve mental health services. The findings contributed in the formulation of guidelines to improve support. |
Validity and reliability of radiographic knee osteoarthritis measures by arthroplasty surgeons.
Most orthopedic surgeons do not routinely use radiographic classification systems to grade the extent of joint space narrowing in patients considered for total knee arthroplasty. The authors compared the validity and reliability of radiographic measures of tibiofemoral osteoarthritis by 2 experienced and 2 inexperienced orthopedic surgeons on individuals who subsequently underwent total knee arthroplasty. The Kellgren-Lawrence and the Osteoarthritis Research Society International classification systems were used by all surgeons to score the radiographs in 116 individuals in the Osteoarthritis Initiative, a federally funded cohort study of individuals with or at risk of knee osteoarthritis. Validity was judged based on comparison with the criterion centrally adjudicated consensus measures obtained by Osteoarthritis Initiative investigators. Weighted kappa, a chance corrected agreement index, was used to describe validity and reliability. Validity and intrarater reliability were substantial to almost perfect for 1 experienced and 1 inexperienced surgeon, with weighted kappas ranging from 0.76 to 0.96 for the surgical knees. The other experienced and inexperienced surgeons demonstrated moderate to substantial validity, with weighted kappas ranging from 0.43 to 0.70 and lower intrarater reliability. Interrater reliability was generally less than intrarater reliability. With minimal training, some surgeons can obtain valid and reliable measurements of knee osteoarthritis status in individuals who eventually undergo total knee arthroplasty. Measurement quality does not appear to be dependent on extent of surgeon experience. Some surgeons require additional training to become proficient in the radiographic classification systems, and future research should examine this issue. |
[Captopril in cardiac insufficiency. Immediate and long-term effects].
Captopril was administered to 23 patients in cardiac failure refractory to digitalo-diuretic therapy. Four patients had a large fall in systolic blood pressure (less than 70 mmHg) with a single dose of 25 mg of captopril. In the other 19 patients a significant fall in mean pulmonary capillary pressure (16,8 +/- 6,1 mmHg vs 27,2 +/- 8,5 mmHg, p less than 0,001), mean pulmonary artery pressure (26,3 +/- 11,3 mmHg vs 38,3 +/- 12,4 mmHg, p less than 0,001), mean right atrial pressure (5 +/- 5 mmHg vs 8 +/- 6 mmHg, p less than 0,01) was observed: there was a moderate fall in mean systemic arterial pressure (13%, p less than 0,001). There was a significant fall in pulmonary resistance (27%, p less than 0,001). The cardiac index increased (2,8 +/- 0,5 l/min/m2, p less than 0,001) and systemic resistance fell by 25% (p less than 0,001). The heart rate decreased by an average of 7 beats/min (p less than 0,02). The treatment was stopped in one patient because of the inefficacy of captopril at 100 mg per dose. The average daily dose in the 18 patients on long-term treatment was 212,5 +/- 106,8 mg. At the second month, the haemodynamic parameters were remeasured before the morning dose of captopril. The effects observed after the single dose were maintained apart from the systemic blood pressure, heart rate and systemic resistances which had returned to the value observed before administration of captopril. The mean pulmonary capillary pressure was significantly lower than before treatment but was higher than after the single dose.(ABSTRACT TRUNCATED AT 250 WORDS) |
Enzymatic cleavage of the epsilon-peptide bond in alpha- and epsilon-substituted glycyl- and phenylalanyl-lysine peptides.
Lysine peptides, X-Lys-OH (Formula: see text) were synthesized, following classic or non-classic routes. Some bacterial and mammalian enzymes, endo- and exo-peptide hydrolases of the enzyme nomenclature type EC 3.4., were tested for their ability to split the epsilon-peptide bond in the above substrates. Kinetic constants (Km,kcat) were evaluated with leucine aminopeptidase from hog kidney and eye lens with aminopeptidase I from yeast. Aminopeptidase M (hog pancreas) and hog intestinal aminopeptidase were additionally examined for their Ki values with the above substrates in comparison to the classic protease substrate leucine p-nitroanilide. Especially the intestinal mucosa hydrolases are shown to be efficient in cleaving epsilon-peptide bonds. |
Airway closure and trapped gas during low volume breathing.
We used a plethysmographic technique to estimate the trapped gas volume (TGV) in seven normal subjects after breathing air or O2 normally at functional residual capacity (FRC-air, FRC-O2) and near residual volume (RV) with small breaths (LVB-air, LVB-O2). If airway closure occurs, lung units subtended by closed airways would tend to collapse as TGV is absorbed; rapidly if the gas is O2 and slowly if it is air. Both inspiratory and expiratory quasi-static and static pressure-volume curves after LVB-O2 for 180 sec demonstrated a shift to the right and increased hysteresis, reduced vital capacity (VC) and significantly increased transpulmonary pressures at 25% and 50% control VC (PL25, PL50) as compared with those of FRC-O2 controls (P less than 0.01-P less than 0.001). Three VC breaths reversed these changes which suggested that they were related to atelectasis. The absolute plethysmographic RV level decreased and was also restored after three VC breaths. We used this reproducible decrease in RV level to represent the absorbed TGV (delta TGV). The delta TGV after LVB-O2 (180 sec) was significantly greater than that after LVB-air (P less than 0.001) or FRC-O2 (P less than 0.001). There was a significant correlation between the increase of delta TGV (DTGV) and the increase of PL25 (delta PL25) (P less than 0.01). The delta TGV after FRC-O2 was 128.6 +/- 50.3 ml (1.61 +/- 0.63% of TLC) and the maximal delta TGV after LVB-O2 (180 sec) averaged 504.3 +/- 40.5 m (7.5 +/- 0.37% TLC). The significant increase in delta TGV near RV during O2 as compared to air breathing is best explained by reversible atelectasis and further supports the concept of dependent airway closure at low lung volumes. |
The relationship of DNA excision repair of ultraviolet-induced lesions to the maximum life span of mammals.
Physical and chemical agents present in the environment can potentially damage mammalian DNA. Such damage is known in some cases to be repaired by the process of DNA excision repair. This process has been extensively studied utilizing the repair of ultraviolet irradiation damage as a model system. In this study we have used this system and the 5-bromodeoxyuridine photolysis assay to measure DNA excision repair in cells derived from 21 mammalian species. We have attempted to relate the DNA repair proficiencies and the average size of the repaired regions seen in the cell cultures with the various maximum life spans of the mammals studied. There was an approximate linear correlation between life span of the mammals and the number of DNA excision repair sites measured 20-22 hours following ultraviolet irradiation of the cell cultures. Several deviations from the linear relationships were observed which remain largely unexplained. The size of the repaired regions was shown not to be related to the maximum life spans of the mammals tested. |
An investigation of visuospatial memory impairment in children with attention deficit hyperactivity disorder (ADHD), combined type.
Memory impairment is not considered a core cognitive feature of attention deficit hyperactivity disorder, combined type (ADHD-CT), although it is associated with impairments in attentional and executive functions. This study investigates visuospatial memory impairment, in particular encoding and retrieval aspects, in children with ADHD-CT who are stimulant-medication naive and medicated with stimulant medication. A cross-sectional study of visuospatial memory in 6- to 12-year-old children with stimulant-medication-naive ADHD-CT (n = 62) and medicated ADHD-CT (n = 58) compared to an age- and gender-matched healthy control group (n = 39) was completed. Both medication-naive and medicated ADHD-CT groups demonstrated subtle yet significant impairment in visuospatial memory. The memory impairment was delay-independent, which, along with other factors, suggest dysfunction of the encoding rather than retrieval phase of visuospatial memory. Careful study of large ADHD-CT samples does detect deficits in a visuospatial memory task, but these reflect attentional deficits rather than being specifically due to dysfunction of the medial temporal lobe explicit memory system. Children with ADHD-CT may benefit from cognitive and behavioural strategies focused on improving encoding of relevant information rather than retrieval strategies. |
Resistin stimulation of 17alpha-hydroxylase activity in ovarian theca cells in vitro: relevance to polycystic ovary syndrome.
A newly discovered hormone resistin has been shown to be increased in women with polycystic ovary syndrome (PCOS). The purpose of this study was to confirm increased resistin concentrations in women with PCOS and to test the direct effect of resistin on human theca cell androgen production. Resistin was measured in fasting serum samples by RIA. To test the direct effects of resistin on ovarian androgen biosynthesis, human theca cells were cultured with resistin for 3 d in the presence and absence of forskolin and insulin. Fasting serum samples were obtained from 45 women with PCOS and 74 regularly cycling premenopausal control women in the follicular phase of their menstrual cycles, and ovarian theca cell cultures were established from two control women. The mean serum resistin concentration was increased (40%) in women with PCOS. Serum resistin concentrations correlated positively with body mass index and testosterone in PCOS women but not in controls. There were no significant correlations between resistin and fasting insulin or indicators of insulin resistance when corrected for body mass index. In cultured human theca cells, basal 17alpha-hydroxylase activity was unchanged by resistin alone, but resistin enhanced 17alpha-hydroxylase activity in the presence of forskolin or a combination of forskolin plus insulin. Resistin (> or =1 ng/ml) augmented forskolin and forskolin plus insulin stimulation of CYP17 mRNA expression in a concentration-dependent manner. These data indicate that abnormal resistin secretion in PCOS may play a role in causing ovarian hyperandrogenism. |
[Synthesis, characterization and fluorescence of Eu3+, Tb3+ complexes with 2-thiophencarboxylic acid and 2,2'-bipyridine].
Two binary complexes of Eu3+ and Tb3+ with 2-thiophene carboxylic acid and two ternary complexes of Eu3+ and Tb3+ with 2-thiophene carboxylic acid(L)-2, 2'-bipyridine were synthesized. By elemental analysis, rare earth coordination titration, and molar conductivities studies, the compositions of the complexes were suggested as REL3 x 2H2O and REL3L' x C2H5OH(RE=Eu, Tb, L = 2-thiophene carboxylic acid, L' = 2, 2'-bipyridine) respectively. The ligands and coordination compounds were studied by means of IR spectra, 1H NMR and fluorescence excitation and emission spectra. IR spectra and 1H NMR studies indicate that 2-thiophene carboxylic acid was bonded with RE(III) through oxygen atoms in the carboxyl group, and 2, 2'-bipyridine ligand was bonded to RE(III) through nitrogen atoms. The fluoresence spectra showed that the fluorescence emission intensity of ternary complexes was stronger than that of the binary complexes. |
Colorectal cancer: have we identified an effective screening strategy?
Three currently used screening methods are aimed at detecting colorectal cancer when it is asymptomatic and curable, and at detecting polyps so that they can be removed before they can progress to cancer. Digital rectal examinations are relatively cheap and easy but can detect only a small fraction of large-bowel cancers. Sigmoidoscopy is more sensitive, but its low acceptability to patients has been only partially mitigated by the introduction of the 35-cm flexible instrument. Fecal occult blood testing has limited sensitivity because blood from cancers and polyps is neither continuously shed nor uniformly distributed in feces; specificity and positive predictive value are also low because of other sources of blood in the stool. Prudent judgment suggests that all of these screening tests may prevent death from colorectal cancer in some patients. However, none has been proven effective in general use by well-controlled studies. Case-control studies can provide timely and valuable new evidence in this regard; the authors' investigations in progress are described. The current lack of strong evidence in support of these screening tests should not be interpreted as evidence against their use. |
Adhesion and Early Colonization of S. Mutans on Lithium Disilicate Reinforced Glass-Ceramics, Monolithic Zirconia and Dual Cure Resin Cement.
Monolithic zirconia and glass ceramics are increasingly used in implant crowns. Limited data is available on bacterial adhesion and early biofilm formation on these materials. Four different materials were investigated: (1) Lithium disilicate glass-ceramics (LDS), (2) Fully stabilized zirconia (FSZ), (3) Partially stabilized zirconia (PSZ), and (4) Dual curing cement (DCC). The materials' surfaces were characterized with spinning disc confocal microscopy and by water contact angle and surface free energy (SFE) measurements. For the adhesion tests the materials were rolled in suspensions of Streptococcus mutans. Early biofilm formation was studied on the materials and allowing the biofilms to form for 24 h. S. mutans cell counts were determined by plate culturing. ANOVA and post-hoc Tukey's tests (p⟨0.05) were used for statistical evaluation. The LDS surfaces were clearly hydrophilic with the highest SFE value (p⟨0.001). For S. mutans adhesion, the ranking of the materials from lowest to highest was: LDS = FSZ ⟨ DCC ⟨ PSZ (p⟨0.05). No significant differences among the materials were noticed in biofilm formation. LDS has lower S.mutans adhesion than other materials examined in this study, but the difference was not reflected in early biofilm formation. |
[Adenosquamous carcinoma of the stomach].
Adenosquamous carcinoma (ASC) of the stomach is a rare tumour. In this report we present a case of adenosquamous carcinoma in the antrum involving the duodenal bulb in a 84 year old woman. Although several theories about the possible origin of this kind of tumours had been proposed, histological and immunohistochemical findings agree with the possibility of a preexisting adenocarcinoma as the most reliable cause. The prognosis of ASC seems worse than that of adenocarcinoma because of the more extensive tumour depth and higher frequency of lymphatic and vascular permeation of the carcinomas cells when it is discovered. |
Autoimmune and gastrointestinal dysfunctions: does a subset of children with autism reveal a broader connection?
A large number of autoimmune disorders have a gastrointestinal (GI) dysfunction component that may interplay with genetic, hormonal, environmental and/or stress factors. This narrarive review investigates possible links between autism, immune system abnormalities and GI symptoms in a subgroup of children with autism. A literature search on Medline (1950 to September 2010) was conducted to identify relevant articles by using the keywords 'autism and gastrointestinal' (71 publications) and 'autism and immune' (237 publications), cross-referencing and general searching to evaluate the available literature on the immunological and GI aspects of autism. Sufficient evidence exists to support that a subgroup of children with autism may suffer from concomitant immune-related GI symptoms. |
Estrogen increases the release of epidermal growth factor from individual pituitary cells in female rats.
Rat mixed anterior pituitary cells from cycling females were microscopically demonstrated to produce epidermal growth factor (EGF), in culture, using a reverse hemolytic plaque assay. Anterior pituitary cells of proestrous female rats secrete more EGF than those of metestrous rats, as evaluated by the mean area and the percentage of EGF plaque-forming cells. Estradiol-17 beta (10 nM) treatment of metestrous culture for 24 h increased significantly the size of EGF plaque-forming cells (from 1290 +/- 58 to 2566 +/- 57 microns 2, P < 0.01) and the percentage of EGF plaque-forming cells (from 20.57 to 28.19%; P < 0.01) to a level as high as observed in proestrous cultures (basal mean area 2171 +/- 157 microns 2, and basal percentage of EGF plaque-forming cells 22.71%). These results suggest that the hormonal status of female rats influences EGF secretion in the anterior pituitary gland and that estradiol is implicated in this phenomenon. |
[Social inequality and health in adolescents].
Previous studies indicate that social disparities in health exist in the Danish population. We examined the relationship between parental socioeconomic status (SES) and a number of indicators of physical and mental health amongst 14-15 year old adolescents from the former Ringkoebing County, now a part of the Central Jutland Region, Denmark. SES was measured in terms of education and income, which, in part, correspond with the concepts of cultural and economic capital. Information concerning parents' level of education and income was obtained from central registers via Statistics Denmark. Health-related data for a total of 3,058 adolescents, corresponding to a response rate of 83%, was gathered via questionnaires. Prevalence proportion ratios (PPR) were calculated and are used in the article as risk estimates. Adolescents with less educated parents had a significantly greater risk of poor self-rated health, high self-perceived stress and being overweight, compared with those with better educated parents. The most substantial difference was seen for self-rated health with a PPR of 3.44. Adolescents with low-income parents had poorer health when compared with higher-income groups on eight out of 11 health indicators. Most noticeable were differences for self-rated health and self-perceived stress with PPRs of 1.86 and 1.54, respectively. The study shows that social disparities in health exist among adolescents from the western part of central Jutland corresponding to the former Ringkoebing County. Both low parental education and income had a negative effect on adolescent health. The study also indicates that education and income affect health in different ways. For this reason it is desirable to use both indicators as measures of SES when studying social disparities in health. |
Role of adenosine in NMDA receptor modulation in the cerebral cortex of an anoxia-tolerant turtle (Chrysemys picta belli).
Accumulation of the neuromodulator adenosine in the anoxia-tolerant turtle brain may play a key role in a protective decrease in excitatory neurotransmission during anoxia. Since excitatory neurotransmission is mediated largely by Ca2+ entry through N-methyl-D-aspartate (NMDA) receptors, we measured the effect of adenosine on NMDA-mediated Ca2+ transients in normoxic and anoxic turtle cerebrocortical sheets. Intracellular [Ca2+] was measured fluorometrically with the Ca2+-sensitive dye Fura-2. Baseline intracellular [Ca2+] and [ATP] were also measured to assess cortical sheet viability and potential toxic effects of NMDA. Baseline [Ca2+] did not change significantly under any condition, ranging from 109 +/- 22 to 187 +/- 26 nmoll-1. Throughout normoxic and 2h anoxic protocols, and after single and multiple NMDA exposures, [ATP] did not change significantly, ranging from 16.0 +/- 1.9 to 25.3 +/- 4.9 nmol ATP mg-1 protein. Adenosine caused a reduction in the normoxic NMDA-mediated increase in [Ca2+] from a control level of 287 +/- 35 to 103 +/- 22 nmoll-1 (64%). This effect is mediated by the A1 receptor since 8-phenyltheophylline (a specific A1 antagonist) effectively blocked the adenosine effect and N6-cyclopentyladenosine (a specific A1 agonist) elicited a similar decrease in the NMDA-mediated response. Cortical sheets exposed to anoxia alone exhibited a 52% decrease in the NMDA-mediated [Ca2+] rise, from 232 +/- 30 to 111 +/- 9 nmoll-1. The addition of adenosine had no further effect and 8-phenyltheophylline did not antagonize the observed decrease. Therefore, the observed down-regulation of NMDA receptor activity during anoxia must involve additional, as yet unknown, mechanisms. |
The novel VIP-like hypothalamic polypeptide PACAP interacts with high affinity receptors in the human neuroblastoma cell line NB-OK.
We investigated the ability of two forms of Pituitary Adenylate Cyclase Activating Polypeptide [PACAP-38, the 38 amino acid peptide isolated from ovine hypothalamus, and PACAP-27, a shorter N-terminal (1-27) amidated version] to interact with specific receptors in membranes from the human neuroblastoma cell line NB-OK. [125I]PACAP-27 bound rapidly and specifically to one class of high affinity sites (Kd 0.5 nM). VIP inhibited [125I]PACAP-27 binding 300- to 1000-fold less potently than PACAP-27 and PACAP-38. One microM PHI prevented tracer binding only partially and secretin, glucagon and GRF(1-29)NH2 were ineffective in this respect. PACAP-27 and PACAP-38 stimulated adenylate cyclase activity dose dependently and with similar efficacy (Kact 0.2-0.3 nM), this activation being compatible with the occupancy of specific high affinity PACAP receptor. VIP was markedly less potent and less efficient on this enzyme than PACAP. Chemical cross-linking of [125I]PACAP-27 followed by SDS-PAGE and autoradiography revealed specific cross-linking with a 68 kDa protein. |
Clinical ethics and the role of clinical ethics committees: proposals for a revival. Commentary.
The issue addressed in the paper published by the Italian National Bioethics Committee (NBC) entitled "Clinical ethics committees", is highly significant for many reasons. One of these is the fact that the ethics committees charged with assessing clinical trials have so much responsibility and such a heavy work-load that they have little time available for other tasks such as engaging directly with patients "at the bedside", as a result of which the role of committees responsible for assessing clinical cases is especially important. According to the NBC, the opinions of clinical ethics committees should be formulated jointly and are non-binding. The NBC offers practical proposals not only for the Italian context. While the Italian National Institute of Health (Istituto Superiore di Sanità - ISS) is not involved directly in treating patients, its role in providing guidance is crucial to the national health service and it has always paid special attention to these issues. |
Interleukin-3-specific modification of cell membrane "fluidity" of haemopoietic cells.
The work reported here clearly demonstrates that a specific growth factor, interleukin-3 (IL-3), which acts on multipotent haemopoietic stem cells as well as on committed myeloid progenitor cells of different lineages (Schrader, 1988; Whetton and Dexter, 1986), specifically induces a modification of the physical state ("fluidity") of the cell membranes of two IL-3-responsive and apparently normal haemopoietic cell lines. Furthermore, in a derived IL-3 independent myeloid leukaemic cell line, no such physical response to IL-3 binding was observed. The rapidity of the "normal" response suggests further that it may be associated with, or even constitute per se a critical early effect elicited by IL-3 in sensitive cells, the necessity for which is abrogated in the malignant derivative. |
Reduction of lethal toxicity of doxorubicin by amrinone.
Administration of amrinone, a new inotropic agent, markedly reduced acute lethal toxicity in normal female Swiss and male BALB/c mice given lethal doses of doxorubicin. Because amrinone abolished the negative inotropic effect of doxorubicin in isolated guinea pig atria, it was suggested that partial protection from acute toxicity of the antitumor antibiotic is directly related to protection of cardiac function. |
Inhaled nitric oxide down-regulates intrapulmonary nitric oxide production in lipopolysaccharide-induced acute lung injury.
To examine whether inhaled nitric oxide (NO) affected the intrapulmonary production of NO, reactive oxygen species, and nuclear factor-kappaB in a lipopolysaccharide (LPS)-induced model of acute lung injury. Prospective, randomized, laboratory study. Experimental laboratory at a biomedical institute. Twenty male rabbits weighing 2.5-3.5 kg. Saline or LPS (5 mg/kg of body weight) was administered intravenously with or without NO inhalation (10 ppm) in each group of five rabbits. LPS increased the lung leak index, the neutrophils and NO levels in bronchoalveolar lavage fluid, and NO levels produced by resting and stimulated alveolar macrophages. Inhaled NO decreased the lung leak index, the neutrophils and NO levels as measured by nitrite levels in the lavage fluid, and NO produced by the resting and stimulated alveolar macrophages. Inhaled NO also blocked the activities of reactive oxygen species and nuclear factor-kappaB binding to DNA in lavage cells and in alveolar macrophages. Inhaled NO attenuates LPS-induced acute lung injury, possibly by decreasing NO production in the lungs. The mechanism of reducing NO production resulting from inhaled NO may involve, in part, the activities of reactive oxygen species and/or nuclear factor-kappaB. |
An assessment of 18 F-FDG PET/CT for thoracic screening and risk stratification of pulmonary nodules in multiple endocrine neoplasia type 1.
Bronchopulmonary neuroendocrine tumours (bpNETs) and thymic carcinoid (ThC) are features of multiple endocrine neoplasia type 1 (MEN 1), and surveillance guidelines recommend periodic thoracic imaging. The optimal thoracic imaging modality and screening frequency remain uncertain as does the prognosis of small lung nodules when identified. To evaluate fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) for identification and prognostic assessment of thoracic lesions in MEN 1. Retrospective observational study. Fifty consecutive MEN 1 patients undergoing screening with 18 F-FDG PET/CT at a tertiary referral hospital between July 2011 and December 2016. 18 F-FDG PET/CT. Pulmonary and thymic lesion prevalence, size, functional characteristics and behaviour. Thirteen patients (26.0%) exhibited pulmonary nodules with multiple nodules identified in nine (18.0%). An asymptomatic 31 mm FDG-avid ThC was identified in one patient (2%). Of the 13 patients with pulmonary nodules, four (8.0%) exhibited 13 FDG-avid nodules (mean size 10.1 ± 9.1 mm), and nine (18.0%) demonstrated 26 FDG nonavid nodules (mean size 6.9 ± 5.8 mm). All FDG-avid lesions increased in size vs 11 (42.3%) FDG nonavid lesions (P = .0004). For FDG-avid and nonavid nodules, the median doubling time was 24.2 months (IQR 11.4-40.7) and 48.6 months (IQR 37.0-72.2), respectively. Nodule resection was undertaken in two patients, typical bronchial carcinoid diagnosed in one (FDG nonavid) and metastatic renal cell carcinoma in the second (FDG avid). Thoracic imaging with 18 F-FDG PET/CT effectively identifies pulmonary nodules and ThC. FDG-avid pulmonary lesions are significantly more likely to progress than nonavid lesions. |
[The biological and electrophysiological parameters in the rat chronically treated with Lobelia inflata L].
In this paper we have studied the rat under chronic treatment with Lobeline sulphate ip. For a three week period we have recorded, once a week, weight, rectal temperature, tail-flick, motor coordination and general activity in a one-arm radial maze and in a Boissier-Simon table. At the end of the third week surface (SEEG) and deep (DEEG) EEG were recorded both from treated and control animals. The findings are: 1) no changes was observed in weight, rectal temperature, tail-flick and motor coordination; 2) the treated rats showed an increased general activity both in a one-arm radial maze and in the Boissier-Simon table; 3) the EEG effects were analyzed and quantified, by means of Fast Fourier transform, as total power and as power in preselected bands of frequency. The lobeline sulphate seems to produce both in SEEG and hippocampus a shift toward low frequencies and in amygdala a drift toward high frequencies. |
Demodectic infestation of the pilosebaceous follicle.
Scanning electron microscopy revealed Demodex folliculorum on the face surface of twenty healthy subjects. The ultrastructural morphology of Demodex and the follicle parasitization process are briefly illustrated. |
Androgen regulation of an antigen expressed in regions of developing brainstem monoaminergic cell groups.
To examine the regulation of brain development by gonadal steroids we are using monoclonal antibodies obtained with neonatal rat brain homogenates as immunogens. One antibody, 3D10, binds selectively in regions of identified monoaminergic neuronal cell groups in the brainstem. Characterization of 3D10 immunoreactivity was carried out using free-floating 50 microns tissue sections from perinatal rats. The strongest reactivity was seen on postnatal day 1 in the locus coeruleus (A6) and in the regions of the A4 (dorsal) and A5 (ventral) noradrenergic cell groups. Immunoreactivity was also seen in the raphe magnus, pallidus and obscuris. Faint immunoreactivity was seen in the more rostral and median raphe nuclei and in the midbrain dopaminergic cell groups of the ventral tegmentum and substantia nigra. The number of 3D10 immunoreactive cells in all groups was greatest perinatally and decreased with age. The number of immunoreactive cells in the A4 region of males decreased at an earlier age than in females. Female offspring treated prenatally with testosterone propionate also had fewer immunoreactive cells in the A4 region at earlier ages, approximating the time course in the male. Thus, changes in the number of 3D10 immunoreactive cells reveal hormonal control of the time course of a developmental process in a selective population of neurons. |
Circadian rhythms in Neurospora crassa: clock gene homologues in fungi.
Computer-based analysis of a total of 17 filamentous fungal and yeasts genomes has shown: (1) homologues of frq, wc-1, wc-2, and vvd, key gene components of the Neurospora crassa clock, are present in Magnaporthe grisea, Gibberella zeae, and Podospora anserina, suggesting an frq-based oscillator in these organisms; (2) some fungal species that are more distantly related to Neurospora, such as Rhizopus oryzae do not appear to have frq homologues; (3) many fungal species that do not appear to contain frq, such as Aspergillus nidulans, do contain wc homologues; (4) of 11 well-described genes classified as clock-controlled genes (ccgs), in Neurospora, all of them were found to have homologues in other fungi; (5) the ccg-8 gene of N. crassa has homologies to opi1p, a transcriptional regulatory gene in Saccharomyces cerevisiae involved in inositol regulation. This suggests the possibilities of rhythmic inositol regulation, and/or a cascade of rhythmic activation of other genes in N. crassa. |
[An epidemiological study on carotid atherosclerosis among veterans in Beijing].
To investigate the prevalence and risk factors of carotid atherosclerosis (CAS) among veterans in Beijing. 820 individuals, aged 60 or above, were randomly selected out from 8202 individuals, 21 military cadre retirement centers in Beijing. Each individual answered a questionnaire and received Doppler ultrasonic examination for an observation of the Internal-Media Thickness and structure of the carotid. A logistic regression analysis was also made to identify possible risk factors and their powers on the prevalence of CAS. The prevalence of carotid atherosclerosis by ultrasonic examinations among the veterans in Beijing was 44.0%, of which males taked 53.8% and females taked 33.5%. The prevalence rised with the increase of age. Among them, the prevalence ratio of CAS for ages of 60-69, 70-79, and 80 or above were 30.4%, 51.8%, 65.27%, respectively. Logistic regression was done to provide the following results: CAS risk factors include the age, sex, obesity, smoking, hypertention and diabetes mellitus. The prevalence of CAS among the veterans in Beijing rises with the increase of age. CAS risk factors include age, sex, obesity, smoking, hypertention and diabetes mellitus. |
Privileged chiral catalysts.
One of the most active current areas of chemical research is centered on how to synthesize handed (chiral) compounds in a selective manner, rather than as mixtures of mirror-image forms (enantiomers) with different three-dimensional structures (stereochemistries). Nature points the way in this endeavor: different enantiomers of a given biomolecule can exhibit dramatically different biological activities, and enzymes have therefore evolved to catalyze reactions with exquisite selectivity for the formation of one enantiomeric form over the other. Drawing inspiration from these natural catalysts, chemists have developed a variety of synthetic small-molecule catalysts that can achieve levels of selectivity approaching, and in some cases matching, those observed in enzymatic reactions. |
Indications of an altered immune balance in preeclampsia: a decrease in in vitro secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil counts compared with normal pregnancy.
It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. This study was designed to examine the systemic immune status at both the innate level and the adaptive level in pregnancies complicated by preeclampsia (n=15) and normal pregnancies (n=15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12, IL-13 and TNF-alpha, in response to paternal blood cells and the vaccination antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT), was detected in cell culture supernatants from blood mononuclear cells by ELISA. Preeclamptic women showed reduced numbers of basophil granulocytes in the blood (p=0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells (p=0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased in preeclampsia compared with normal pregnancy (p=0.012). No further differences between preeclampsia and normal pregnancy were found for any stimuli or cytokines. The present findings of reduced basophil numbers and lower spontaneous in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the decrease in paternal antigen-induced secretion of the immunosuppressive cytokine IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression mediated by blood mononuclear cells. Whether these systemic changes are a cause or a consequence of preeclampsia remains to be elucidated. |
Low-volatility poly-oxygenates in the OH-initiated atmospheric oxidation of alpha-pinene: impact of non-traditional peroxyl radical chemistry.
Following new insights on non-traditional peroxyl radical chemistry, we present an update to our earlier OH-initiated alpha-pinene degradation mechanism (Peeters et al., Phys. Chem. Chem. Phys., 2001, 3, 5489), incorporating ring closure reactions and a fast H-shift isomerization in certain key peroxyl and oxy radical intermediates. These changes, affecting only a single branch of the comprehensive mechanism and based on extensive quantum-chemical and theoretical kinetic calculations, show significant formation, approximately 20% overall, of poly-oxygenated (hydro)peroxides in atmospheric conditions. These low-volatility compounds are expected to have a significant impact on aerosol formation, and are believed to be the high-mass product compounds observed in available experimental work. The proposed changes also affect the predicted acetone yield, matching the experimental data closely. |
Faraday multipass rotator for use in high accuracy polarimetric or ellipsometric devices.
A highly efficient low magnetic field Faraday rotator is presented. A cavity filled with transparent liquid for visible and infrared radiation with a high Verdet coefficient is used. Light travels the cavity several times giving us the advantage of nonreciprocity of the Faraday effect. This cavity is designed in such a way (regarding geometry and the nature of reflecting materials) that it introduces no detectable alteration of the state of polarization of the light, except, under the effect of an applied field, a pure rotation of the polarization plane given by the Faraday law. A rotator using this sort of cavity has potential, in the form of a Faraday modulator, in high precision ellipsometric and polarimetric devices working in the visible and near infrared and using polarization modulation. |
Intra-abdominal adhesion formation is initiated by phospholipase A2.
The etiology of intra-abdominal adhesions is explained by hydrolysis of the peritoneal phospholipid layer caused by phospholipase A2 activity. This view could unify the pre-existing hypotheses that intra-abdominal adhesions are due to ischemia or increased plasminogen activator activity. New therapeutic approaches are suggested. |
Threshold for the effects of ACTH on blood pressure in sheep.
The time of onset and dose threshold for ACTH induced hypertension was examined in conscious sheep. ACTH 1 microgram/kg per day significantly raised blood pressure. The maximum rise occurred at 2 micrograms/kg per day. The rise in pressure was significant after 8 h of ACTH infusion. |
Polyamine regulation of S-adenosylmethionine decarboxylase synthesis through the 5'-untranslated region of its mRNA.
The effect of the 5'-untranslated region (5'-UTR) of S-adenosylmethionine decarboxylase (SAMDC) mRNA and of polyamines on the translation of SAMDC mRNA was studied in a rabbit reticulocyte cell-free system. Using synthetic SAMDC mRNAs possessing different sizes of 5'-UTR, it was shown that nucleotides in the 5'-end of 5'-UTR were responsible for polyamine inhibition at high concentrations. Existence of the 5'-end nucleotides decreased SAMDC synthesis and slightly increased the degree of polyamine stimulation of the synthesis at low concentrations. When poly(A)+ RNA from mouse SAMDC-overproducing cells was used as mRNA, the degree of polyamine inhibition at high concentrations was nearly the same, but that of polyamine stimulation at low concentrations was greater than with synthetic SAMDC mRNAs. The reason for this difference is discussed. |
Novel strategies for the design of new potent and selective human A3 receptor antagonists: an update.
A computer-aided approach has been developed in order to understand the molecular pharmacology of human A3R, and specifically, to lead to the discovery and structural refinement of new, potent and selective human A3R antagonists. This review focuses on our combined target-based and ligand-based drug design strategy, recently applied to provide more accurate information about the recognition mode on human A3R of some pyrazolotriazolopyrimidine and triazoloquinoxalinone analogs. The 3D rhodopsin-based homology model of human A3R has represented the starting point of our approach. A high throughput molecular docking method on the considered antagonists has allowed us to generate a receptor-based pharmacophore model. A novel "Y-shaped" pharmacophore binding motif has been proposed for both pyrazolotriazolopyrimidine and triazoloquinoxalinone derivatives. Moreover, related receptor-based 3D-QSAR analysis has been carried out to provide a suitable tool for prediction of the antagonists binding affinity on human A3R. |