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19023464 | Innovations in optical microfluidic technologies for point-of-care diagnostics. | Despite a growing focus from the munity, the field of microfluidics has yet to produce mercial devices for point-of-care (POC) diagnostics. One of the main reasons for this is the difficulty in producing low-cost, sensitive, and portable optical detection systems. Although electrochemical methods work well for certain applications, optical detection is generally regarded as superior and is the method most widely employed in laboratory clinical chemistry. Conventional optical systems, however, are costly, require careful alignment, and do not translate well to POC devices. Furthermore, many optical detection paradigms such as absorbance and fluorescence suffer at smaller geometries because the optical path length through the sample is shortened. This review examines the innovative techniques which have recently been developed to address these issues. We highlight microfluidic diagnostic systems which demonstrate practical integration of sample preparation, analyte enrichment, and optical detection. We also examine several emerging detection paradigms involving nanoengineered materials which do not suffer from the same miniaturization disadvantages as conventional measurements. |
19023463 | Towards non- and minimally instrumented, microfluidics-based diagnostic devices. | In many health care settings, it is uneconomical, impractical, or unaffordable to maintain and access a fully equipped diagnostics laboratory. Examples include home health care, developing-country health care, and emergency situations in which first responders are dealing with pandemics or biowarfare agent release. In those settings, fully disposable diagnostic devices that require no instrument support, reagent, or significant training are well suited. Although the only such technology to have found widespread adoption so far is the immunochromatographic rapid assay strip test, microfluidics holds promise to expand the range of assay technologies that can be performed in formats similar to that of a strip test. In this paper, we review progress toward development of disposable, low-cost, easy-to-use microfluidics-based diagnostics that require no instrument at all. We also present examples of microfluidic functional elements--including mixers, separators, and detectors--as well plete microfluidic devices that function entirely without any moving parts and external power sources. |
19023465 | Egg beater as centrifuge: isolating human blood plasma from whole blood in resource-poor settings. | This paper demonstrates that a hand-powered egg beater can be modified to serve as a centrifuge for separating plasma from human whole blood. Immunoassays used to diagnose infectious diseases often require plasma from whole blood, and obtaining plasma typically requires electrically-powered centrifuges, which are not widely available in resource-limited settings. Human whole blood was loaded into polyethylene (PE) tubing, and the tubing was attached to the paddle of an egg beater. Spinning the paddle pelleted the blood cells to the distal end of the PE tubing; the plasma remained as the supernatant. A cholesterol assay (run on patterned paper) demonstrated the suitability of this plasma for use in diagnostic assays. The physics of the system was also analyzed as a guide for the selection of other rotating systems for use in centrifugation. Egg beaters, polyethylene tubing, and paper are readily available devices and supplies that can facilitate the use of point-of-care diagnostics at sites far from centralized laboratory facilities. |
19023466 | Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage. | As part of an effort to create a point-of-care diagnostic system for the developing world, we present a microfluidic flow-through membrane immunoassay with on-card dry reagent storage. By preserving reagent function, the storage and reconstitution of anhydrous reagents enables the devices to remain viable in challenging, unregulated environmental conditions. The assay takes place on a disposable laminate card containing both a porous membrane patterned with capture molecules and a fibrous pad containing an anhydrous analyte label. To conduct the assay, the card is placed in an external pumping and imaging instrument capable of delivering sample and rehydrated reagent to the assay membrane at controlled flow rates to generate quantitative results. Using the malarial antigen Plasmodium falciparum histidine-rich protein II (PfHRP2) as a model, we demonstrate selection of dry storage conditions, characterization of reagent rehydration, and execution of an automated on-card assay. Gold-antibody conjugates dried in a variety of sugar matrices were shown to retain 80-96% of their activity after 60 days of storage at elevated temperatures, and the release profile of the reconstituted reagent was characterized under flow in microfluidic channels. The system gave a detection limit in the sub-nanomolar range in under nine minutes, showing the potential to expand into quantitative, multi-analyte analysis of human blood samples. |
19023467 | An integrated microfluidic platform for sensitive and rapid detection of biological toxins. | Towards designing a portable diagnostic device for detecting biological toxins in bodily fluids, we have developed microfluidic chip-based immunoassays that are rapid (< 20 minutes), require minimal sample volume (<10 microL) and have appreciable sensitivity and dynamic range (microM-pM). The microfluidic chip is being integrated with miniaturized electronics, optical elements, ponents, and data acquisition software to develop a portable, self-contained device. The device is intended for rapid, point-of-care (and, in future, point-of-incident) testing in case of an accidental or intentional exposure/intoxication to biotoxins. Detection of toxins and potential host-response markers is performed using microfluidic electrophoretic immunoassays integrated with sample preconcentration and mixing of analytes with fluorescently labeled antibodies. Preconcentration is enabled by photopolymerizing a thin, nanoporous membrane with a MW cut-off of approximately 10 kDa in the sample loading region of the chip. Polymeric gels with larger pores are located adjacent to the size exclusion membrane to perform electrophoretic separation of plex and excess antibody. Measurement of the ratio of bound and unbound plex using sensitive laser-induced fluorescence detection provides quantitation of analyte in the sample. We have demonstrated electrophoretic immunoassays for the biotoxins ricin, Shiga toxin I, and Staphylococcal enterotoxin B (SEB). With off-chip mixing and no sample preconcentration, the limits of detection (LOD) were 300 pM for SEB, 500 pM for Shiga toxin I, and 20 nM for ricin. With a 10 min on-chip preconcentration, the LOD for SEB is <10 pM. The portable device being developed is readily applicable to detection of proteinaceous biomarkers of many other diseases and is intended to represent the next-generation diagnostic devices capable of rapid and quantitative measurements of multiple analytes simultaneously. |
19023468 | Neutrophil migration assay from a drop of blood. | Neutrophil directional migration in response to chemical gradients, also known as chemotaxis, is one of the key phenomena in the immune responses against bacterial infection. To better study neutrophils chemotaxis, several in vitro assays have been developed that replicate chemotactic gradients around neutrophils isolated from whole blood. One drawback for most of these assays is the lengthy processing of blood required for neutrophils isolation, which can alter the responsiveness of pared to the in vivo conditions. To address this limitation, we have designed a microfluidic chip for chemotaxis studies which can use neutrophils isolated on the chip, directly from whole blood. We have tested three different cell adhesion molecules as substrates for neutrophil isolation (P-selectin, E-selectin and fibronectin) and found average capture efficiencies of 20-40 neutrophils/mm2 at optimized concentrations. Subsequent analysis of neutrophil migration in chemoattractant gradients of N-formyl-methyl-leucyl-phenylalanine (fMLP) or Interleukin-8 (IL-8) shows higher average velocities over E-selectin pared to the P-selectin. Our microfluidic assay uses just a drop of whole blood (<10 microL) for neutrophil isolation and provides a robust platform to perform chemotaxis assays in peting environment of different chemokines. |
19023469 | Effect of volume- and time-based constraints on capture of analytes in microfluidic heterogeneous immunoassays. | Despite the prevalence of microfluidic-based heterogeneous immunoassays (where analytes in solution are captured on a solid surface functionalized with a capture molecule), there is plete understanding of how assay parameters influence the amount of captured analytes. This study putational results and corresponding experimental binding assays in which the capture of analytes is studied under variations in both mass transfer and surface binding, constrained by real-world assay conditions of finite sample volume, assay time, and capture area. Our results identify: 1) a "reagent-limited" regime which exists only under the constraints of finite sample volume and assay time; 2) a critical flow rate (e.g. 0.5 microL min(-1) under our assay conditions) to gain the maximum signal with the fastest assay time; 3) an increase in signal by using a short concentrated plug (e.g. 5 microL, 100 nM) rather than a long dilute plug (e.g. 50 microL, 10 nM) of sample; 4) the possibility of spending a considerable fraction of the assay time out of the reaction-limited regime. Overall, an improved understanding of fundamental physical processes may be particularly beneficial for the design of point-of-care assays, where volumes of reagents and available samples are limited, and the desired time-to-result short. |
19023470 | Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics. | We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process. |
19023472 | Development of a digital microfluidic platform for point of care testing. | Point of care testing is playing an increasingly important role in improving the clinical e in health care management. The salient features of a point of care device are rapid results, integrated sample preparation and processing, small sample volumes, portability, multifunctionality and low cost. In this paper, we demonstrate some of these salient features utilizing an electrowetting-based Digital Microfluidic platform. We demonstrate the performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples. Using the same microfluidic cartridge, a 40-cycle real-time polymerase chain reaction was performed within 12 minutes by shuttling a droplet between two thermal zones. We further demonstrate, on the same cartridge, the capability to perform sample preparation for bacterial infectious disease pathogen, methicillin-resistant Staphylococcus aureus and for human genomic DNA using magnetic beads. In addition to rapid results and integrated sample preparation, electrowetting-based digital microfluidic instruments are highly portable because fluid pumping is performed electronically. All the digital microfluidic chips presented here were fabricated on printed circuit boards utilizing mass production techniques that keep the cost of the chip low. Due to the modularity and scalability afforded by digital microfluidics, multifunctional testing capability, such binations within and between immunoassays, DNA amplification, and enzymatic assays, can be brought to the point of care at a relatively low cost because a single chip can be configured in software for different assays required along the path of care. |
19023473 | Photolithographic patterning of organosilane monolayer for generating large area two-dimensional B lymphocyte arrays. | High-density live cell array serves as a valuable tool for the development of high-throughput immunophenotyping systems and cell-based biosensors. In this paper, we have, for the first time, demonstrated a simple fabrication process to form the hexamethyldisilazane (HMDS) and poly(ethylene glycol) (PEG) binary molecular surface which can be used to effectively form high fidelity cell arrays. The HMDS self-assembled monolayer (SAM) on glass substrates was photolithographically patterned and its ability to physically adsorb proteins was characterized by contact angle measurement and fluorescence microscopy respectively. Passivation of the non-HMDS coated background by PEG was verified to have no impact on the pre-patterned HMDS and greatly inhibited the non-specific protein binding. Using the plexation as an intermediate, uniform orientation and high bioactivity were achieved for the immobilized B lymphocyte specific anti-CD19 antibodies and therefore ensured the formation of high resolution B lymphocyte arrays. The cell-ligand interaction specificity was investigated and the anti-CD19 decorated micropatterns presented a much higher cell-capturing rate (88%) than those modified by non-specific ligands (15% for anti-CD5 and 7% for streptavidin). The approach was verified to be patible and the properties of the antibody-modified surface were maintained after 12 h cell culture. The HMDS monolayer formation and patterning processes, and the universal HMDS/biotin-BSA/streptavidin template, provide a very simple and convenient process to generate high resolution micropatterns of cell-adhesive ligands and are extendable to form arrays of other types of cells as well. |
19023471 | Integration of semiconductor quantum dots into nano-bio-chip systems for enumeration of CD4+ T cell counts at the point-of-need. | Recent humanitarian efforts have led to the widespread release of antiretroviral drugs for the treatment of the more than 33 million HIV afflicted people living in resource-scarce settings. Here, the enumeration of CD4+ T lymphocytes is required to establish the level at which the immune system has promised. The gold standard method used in developed countries, based on flow cytometry, though widely accepted and accurate, is precluded from widespread use in resource-scarce settings due to its high expense, high technical requirements, difficulty in operation-maintenance and the lack of portability for these sophisticated laboratory-confined systems. As part of continuing efforts to develop practical diagnostic instrumentation, the integration of semiconductor nanocrystals (quantum dots, QDs) into a portable microfluidic-based lymphocyte capture and detection device pleted. This integrated system is capable of isolating and counting selected lymphocyte sub-populations (CD3+CD4+) from whole blood samples. bining the unique optical properties of the QDs with the sample handling capabilities and cost effectiveness of novel microfluidic systems, a practical, portable lymphocyte measurement modality that correlates nicely with flow cytometry (R2 = 0.97) has been developed. This QD-based system reduces the optical requirements significantly relative to molecular fluorophores and the mini-CD4 counting device is projected to be suitable for use in both point-of-need and resource-scarce settings. |
19023474 | Development of functional lab-on-a-chip on polymer for point-of-care testing of metabolic parameters. | This paper presents the development of an easy-to-handle and disposable clinical diagnostic lab-on-a-chip using fully integrated plastic ponents, which has the sampling/identifying capability to make fast and reliable measurements of metabolic parameters from human whole blood. A smart and functional lab-on-a-chip cartridge, which incorporates a full on-chip auto-calibration function for in the field applications, has been developed, and then fully characterized using a portable analyzer (3 (1/4)''x 5''x 1'') with multi-analyte detection capability. In addition, several new approaches in realizing smart and functional lab-on-a-chips on polymer have been adopted, which include the pinch valve for automatic fluidic sealing, a by-pass channel as the sampling indicator, and a robust connector design for long analyzer lifetimes. Metabolic parameters such as glucose, lactate, and partial oxygen from human whole blood have been successfully measured using the functional polymer lab-on-a-chips and the portable analyzer developed in this work. |
19023476 | Microvortex for focusing, guiding and sorting of particles. | We report a microvortex manipulator (MVM) that is a passive, scalable system with great potential for the manipulation and separation of particulate samples in microfluidic environments. The movement of particles is determined by a bination of helical flow, buoyant, and gravitational forces. Helical flows are induced by topographically patterned microchannel surfaces, which have previously been used for molecular mixing in microfluidic devices. We illustrate the mechanism of MVM and its applications in passive focusing of beads and cells into parallel streams and guiding of particles and cells. We also explore the application of the unique density-selectivity of microvortex focusing and successfully sort a mixture of two bead populations whose density difference is as small as 0.1 g cm(-3). |
19023475 | A polymer lab-on-a-chip for reverse transcription (RT)-PCR based point-of-care clinical diagnostics. | An innovative polymer lab-on-a-chip (LOC) for reverse transcription (RT)-polymerase chain reaction (PCR) has been designed, fabricated, and characterized for point-of-care testing (POCT) clinical diagnostics. In addition, a portable analyzer that consists of a non-contact infrared (IR) based temperature control system for RT-PCR process and an optical detection system for on-chip detection, has also been developed and used to monitor the RT-PCR LOC. The newly developed LOC and analyzer have been interfaced and optimized for performing RT-PCR procedures and chemiluminescence assays in sequence. As a clinical diagnostic application, human immunodeficiency virus (HIV) for the early diagnosis of acquired immune deficiency syndrome (AIDS) has been successfully detected and analyzed using the newly developed LOC and analyzer, where the primer sets for p24 and gp120 were used as the makers for HIV. The developed polymer LOC and analyzer for RT-PCR can be used for POCT for the analysis of HIV with the on-chip RT-PCR and chemiluminescence assays in shorter than one hour with minimized cross-contamination. |
19023478 | FLASH: a rapid method for prototyping paper-based microfluidic devices. | This article describes FLASH (Fast Lithographic Activation of Sheets), a rapid method for laboratory prototyping of microfluidic devices in paper. Paper-based microfluidic devices are emerging as a new technology for applications in diagnostics for the developing world, where low cost and simplicity are essential. FLASH is based on photolithography, but requires only a UV lamp and a hotplate; no clean-room or special facilities are required (FLASH patterning can even be performed in sunlight if a UV lamp and hotplate are unavailable). The method provides channels in paper with dimensions as small as 200 microm in width and 70 microm in height; the height is defined by the thickness of the paper. Photomasks for patterning paper-based microfluidic devices can be printed using an ink-jet printer or photocopier, or drawn by hand using a waterproof black pen. FLASH provides a straightforward method for prototyping paper-based microfluidic devices in regions where the technological support for conventional photolithography is not available. |
19023477 | Microchip DNA electrophoresis with automated whole-gel scanning detection. | Gel electrophoresis continues to play an important role in miniaturized bioanalytical systems, both as a stand alone technique and as a ponent of integrated lab-on-a-chip diagnostics. Most implementations of microchip electrophoresis employ finish-line detection methods whereby fluorescently labeled analytes are observed as they migrate past a fixed detection point near the end of the separation channel. But tradeoffs may exist between the simultaneous goals of maximizing resolution (normally achieved by using longer separation channels) and maximizing the size range of analytes that can be studied (where shorter separation distances reduce the time required for the slowest analytes to reach the detector). Here we show how the miniaturized format can offer new opportunities to employ alternative detection schemes that can help address these issues by introducing an automated whole-gel scanning detection system that enables the progress of microchip-based gel electrophoresis of DNA to be continuously monitored along an entire microchannel. This permits flexibility to selectively observe smaller faster moving fragments during the early stages of the separation before they have experienced significant diffusive broadening, while allowing the larger slower moving fragments to be observed later in the run when they can be better resolved but without the need for them to travel the entire length of the separation channel. Whole-gel scanning also provides a continuous and detailed picture of the electrophoresis process as it unfolds, allowing fundamental physical parameters associated with DNA migration phenomena (e.g., mobility, diffusive broadening) to be rapidly and accurately measured in a single experiment. These capabilities are challenging to implement using finish-line methods, and make it possible to envision a platform capable of enabling separation performance to be rapidly screened in a wide range of gel matrix materials and operating conditions, even allowing separation and matrix characterization steps to be performed simultaneously in a single self-calibrating experiment. |
19023479 | An integrated microfluidic chip for chromosome enumeration using fluorescence in situ hybridization. | Fluorescence in situ hybridization (FISH) is a powerful technique for probing the genetic content of individual cells at the chromosomal scale. Conventional FISH techniques provide a sensitive diagnostic tool for the detection of chromosomal alterations on a cell-by-cell basis; however, the cost-per-test in terms of reagent and highly qualified labour has prevented its wide-spread utilization in clinical settings. Here, we address the inefficient use of labour with the first integrated and automated on-chip FISH implementation, one that requires only minutes of setup time from the technician. Our microfluidic chip has lowered the reagent use by 20-fold, decreased the labour time by 10-fold, and substantially reduced the amount of support equipment needed. We believe this cost-effective platform will make sensitive FISH techniques more accessible for routine clinical usage. |
19023480 | Photoreactive coating for high-contrast spatial patterning of microfluidic device wettability. | For many applications in microfluidics, the wettability of the devices must be spatially controlled. We introduce a photoreactive sol-gel coating that enables high-contrast spatial patterning of microfluidic device wettability. |
19023481 | Surface patterning of (bio)molecules onto the inner wall of fused-silica capillary tubes. | An efficient photochemical method for the site-specific immobilization and patterning of (bio)molecules inside glass capillary tubes is reported. The strategy involves the photodeprotection of reactive aminooxy groups on surfaces and subsequent reaction with aldehyde containing (bio)molecules. |
19023482 | Patterning protein concentration using laser-assisted adsorption by photobleaching, LAPAP. | The study of cellular responses to changes in the spatial distribution of molecules in development, immunology and cancer, requires reliable methods to reproduce in vitro the precise distributions of proteins found in vivo. Here we present a straightforward method for generating substrate-bound protein patterns which has the simplicity required to be implemented in typical life science laboratories. The method exploits photobleaching of fluorescently tagged molecules to generate patterns and concentration gradients of protein with sub-micron spatial resolution. We provide an extensive characterization of the technique and demonstrate, as proof of principle, axon guidance by gradients of substrate-bound laminin peptide generated in vitro using LAPAP. |
19023483 | Sequential enzymatic glycosyltransfer reactions on a microfluidic device: Synthesis of a glycosaminoglycan linkage region tetrasaccharide. | A microfluidic chip carrying three reaction chambers was designed and constructed to examine sequential multiple enzymatic reactions. The synthesis of oligosaccharides in living cells is carried out in the Golgi apparatus where multiple enzymes such as glycosidase and glycosyltransferases act on a variety of substrates to generate glycoconjugates that include glycolipids and glycoproteins. The regulatory mechanism of the process however remains unknown. A microchip-based analysis platform may provide a valuable tool with which to address the issue by mimicking the Golgi function. We thus examined 3 sequential glycosyltransfer reactions on a chip, and succeeded in the synthesis of a tetrasaccharide using immobilized enzymes. Also, the kinetic parameters for a recently identified glycosyltransferase, proteoglycan GalT-I, were obtained for the first time. |
19023485 | Microfluidic polymer multilayer adsorption on liquid crystal droplets for microcapsule synthesis. | Exploiting microfluidic principles, the potential for chip-based multilayer assembly for the synthesis of polymer microcapsules was investigated. We demonstrate that continuous flow microfluidic multilayer synthesis is a fast, efficient, automated alternative to conventional batch synthesis. In this work, we dispersed liquid crystal (LC) molecules (organic phase) as monodisperse droplets in an aqueous continuous phase containing the primary polymer and a suitable surfactant. The primary polymer was coadsorbed with the surfactant at the organic/aqueous interface, stabilizing the LC droplets against coalescence and providing a template for subsequent polymer adsorption. As the droplet templates are transported through the microfluidic channel, the polymer-containing aqueous continuous phase is selectively withdrawn and replaced with rinse solution, and then with an alternative polymer solution. This selective withdrawal and infusion cycle was repeated to assemble polymer multilayers onto the emulsion droplets. The process was followed using fluorescence microscopy of the fluorescently-labelled polymers at the LC interface and of the flowing polymer solutions during the sequential rinse stages. Cross-linking of the multilayers and removal of the dispersed LC phase resulted in polymer capsules retaining the high monodispersity of the droplet templates. This microfluidic approach significantly reduces the multilayer formation time (to <2 min for 3-layer capsules) of well-defined capsules that are envisaged to have benefits in biomedical applications, including drug delivery and encapsulated biochemical reactions. |
19023484 | Live cell lithography: using optical tweezers to create synthetic tissue. | We demonstrate a new method for creating synthetic tissue that has the potential to capture the three-dimensional plexity of a multi-cellular organism with submicron precision. Using multiple laminar fluid flows in a microfluidic network, we convey cells to an assembly area where multiple, time-shared optical tweezers are used to organize them into plex array. The cells are then encapsulated in a 30 microm x 30 microm x 45 microm volume of photopolymerizable hydrogel that mimicks an extra-cellular matrix. To extend the size, shape and constituency of the array without loss of viability, we then step to an adjacent location while maintaining registration with the reference array, and repeat the process. Using this step-and-repeat method, we formed a heterogeneous array of E. coli genetically engineered with a lac switch that is functionally linked to fluorescence reporters. We then induced the array using ligands through a microfluidic network and followed the space-time development of the fluorescence to evaluate viability and metabolic activity. |
19023487 | A microdevice for multiplexed detection of T-cell-secreted cytokines. | Cytokines are produced by immune cells in response to viral or bacterial pathogens and therefore have significant diagnostic value. The goal of the present study was to develop a miniature device for detection of interleukin (IL)-2 and interferon (IFN)-gamma cytokines secreted by a small population of CD4 and CD8 T-cells. Microarrays of T-cell- and cytokine-specific Ab spots were printed onto poly(ethylene glycol) (PEG) hydrogel-coated glass slides and enclosed inside a microfluidic device, creating a miniature ( approximately 3 microL) immunoreaction chamber. Introduction of the red blood cell (RBC) depleted whole human blood into the microfluidic device followed by washing at a pre-defined shear stress resulted in isolation of pure CD4 and CD8 T-cells on their respective Ab spots. Importantly, the cells became localized next to anti-IL-2 and -IFN-gamma Ab spots. Mitogenic activation of the captured T-cells was followed by immunofluorescent staining (all steps carried out inside a microfluidic device), revealing concentration gradients of surface-bound cytokine molecules. A microarray scanner was then used to quantify the concentration of IFN-gamma and IL-2 near CD4 and CD8 T-cells. This study represents one of the first demonstrations of a microdevice for capturing desired T-cell subsets from a small blood volume and determining, on-chip, cytokine profiles of the isolated cells. Such a microdevice is envisioned as an immunology tool for multi-parametric analysis of T-cell function with direct applications in diagnosis/monitoring of HIV and other infectious diseases. |
19023486 | Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform. | A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and position were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776-fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on human insulin and interleukin-6 (IL-6) with a total time to result of 7 min for each assay. |
19023489 | A portable surface-enhanced Raman scattering sensor integrated with a lab-on-a-chip for field analysis. | An integrated real-time sensing system that uses a portable Raman spectrometer and a micropillar array chip has been developed for field analysis. The problem of poor detection sensitivity, caused by miniaturization in the portable Raman spectrometer, was e by using the surface-enhanced Raman scattering (SERS) technique. The problem of poor reproducibility in the SERS detection, caused by different particle sizes and inhomogeneous degrees of aggregation, was also e by using continuous flow and homogeneous mixing between the analytes and nanocolloidal silver in a micropillar array microfluidic chip. Two hazardous materials, dipicolinic acid and malachite green, were quantitatively analysed using our integrated portable Raman sensor system. The observed limit of detection was estimated to be 200 ppb and 500 ppb, respectively. Our proposed analytical method, using a micropillar array PDMS chip and a portable SERS system, offers a rapid and reproducible trace detection capability for hazardous materials in the field. |
19023488 | Tissue reconstruction in 3D-spheroids from rodent retina in a motion-free, bioreactor-based microstructure. | While conventional rotation culture-based retinal spheroids are most useful to study basic processes of retinogenesis and tissue regeneration, they are less appropriate for an easy and inexpensive mass production of histotypic 3-dimensional tissue spheroids, which will be of utmost importance for future bioengineering, e.g. for replacement of animal experimentation. Here pared conventionally reaggregated spheroids derived from dissociated retinal cells from neonatal gerbils (Meriones unguiculatus) with spheroids cultured on a novel microscaffold cell chip (called cf-chip) in a motion-free bioreactor. Reaggregation and developmental processes leading to tissue formation, e.g. proliferation, apoptosis and differentiation were observed during the first 10 days in vitro (div). Remarkably, in each cf-chip micro-chamber, only one spheroid developed. In both culture systems, sphere sizes and proliferation rates were almost identical. However, apoptosis was parably high up to 5 div, but then became negligible in the cf-chip, while it up-rose again in the conventional culture. In both systems, immunohistochemical characterisation revealed the presence of Müller glia cells, of ganglion, amacrine, bipolar and horizontal cells at a parable arrangement. In both systems, photoreceptors were detected only in spheroids from P3 retinae. Benefits of the chip-based 3D cell culture were a reliable sphere production at enhanced viability, the feasibility of single sphere observation during cultivation time, a high reproducibility and easy control of culture conditions. Further development of this approach should allow high-throughput systems not only for retinal but also other types of histotypic spheroids, to e suitable for environmental monitoring and biomedical diagnostics. |
19023490 | High speed clinical data retrieval system with event time sequence feature: with 10 years of clinical data of Hamamatsu University Hospital CPOE. | This paper illustrates a high speed clinical data retrieving system, from 10 years of data of operating hospital information system for the purposes of research, evidence creation, patient safety, etc., even incorporating time sequence of causal relations. |
19023491 | Automatic DPC code selection from electronic medical records: text mining trial of discharge summary. | We extracted index terms related to diseases recorded in hospital discharge summaries and examined the capability of the vector space model to select a suitable diagnosis with these terms. |
19023497 | Comparative analysis of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis - epidemiology and predictive factors. | Extensively drug-resistant tuberculosis (XDR-TB) is defined as a form of multidrug-resistant tuberculosis (MDR-TB) with additional resistance to fluoroquinolones and at least one of the injectable drugs used in tuberculosis treatment: amikacin, kanamycin and capreomycin. It was classified by WHO as a serious threat to tuberculosis (TB) control, with world-wide consequences, taking on the proportions of a real pandemic in some regions. |
19023494 | Correlation between mild hypoxaemia and limb skeletal muscle function in chronic obstructive pulmonary disease - pilot study. | Exercise capacity in COPD patients depends on the degree of airflow obstruction, the severity of the hypoxaemia and skeletal muscle function. Muscle atrophy and weakness are considered systemic consequences of COPD and are associated with reduced exercise capacity. |
19023507 | Reasons for adolescent deliberate self-harm: a cry of pain and/or a cry for help? Findings from the child and adolescent self-harm in Europe (CASE) study. | The present study examines reasons for adolescent deliberate self-harm. A cross-sectional survey using an anonymous self-report questionnaire was carried out in seven countries (Australia, Belgium, England, Hungary, Ireland, the Netherlands and Norway). Data on 30,477 school pupils between the ages of 14-17 were analysed. Past year and lifetime deliberate self-harm were assessed, along with the self-reported reasons for deliberate self-harm. The results showed that 'wanted to get relief from a terrible state of mind' and 'wanted to die' were monly reported. ponent analysis indicated two underlying dimensions in the reasons for deliberate self-harm, i.e. a cry of pain motive and/or a cry for help motive. The majority of self-harmers reported at least one cry of pain motive ('to die', 'to punish myself', and 'to get relief from a terrible state of mind') and an additional cry for help motive ('to show how desperate I was feeling', to frighten someone', 'to get my own back on someone', 'to find out whether someone really loved me', and 'to get some attention'). Females reported more reasons than males. Only females showed an age difference, with girls aged 16-17 more frequently reporting a cry for help motive. There was considerable consistency in choice of motives across countries and genders. Systematic assessment of the reasons for deliberate self-harm can help clinicians to better understand the meaning of self harming behaviour, select appropriate treatment, suggest alternative coping strategies, and hopefully prevent future suicidal behaviour. |
19023506 | Recognition and treatment of depression: a comparison of Australian and Chinese medical students. | Depression is a major public health problem in both China and Australia. To improve services, we need to ensure health professionals have an appropriate understanding of depression and its treatments. This pares the level of awareness of depression between Chinese and Australian medical students. |
19023508 | Psychiatric disorders among infertile and fertile women. | This study was performed in order to determine the prevalence and predisposing factors of psychiatric disorders among infertile and fertile women attending Vali-e-Asr Hospital. A total of 150 fertile women from Vali-e-Asr Reproduction Health Research Center and fertile women from the Gynecology Clinic of Imam Khomeini Hospital were chosen by consecutive sampling. Data included demographic information, SCL-90-R, and a semi-structured questionnaire about stress factors. Results showed that 44% of infertile and 28.7% of fertile women had a psychiatric disorder (P < 0.001). Using the SCL-90-R test, the highest mean scores in infertile women were found to be on the paranoid ideation, depression and interpersonal sensitivity scales, and lowest scores were found on the psychoticism and phobic anxiety scales. The interpersonal sensitivity, depression, phobic anxiety, paranoid ideas and psychoticism scales were significantly different between infertile and fertile women (P < 0.05). Infertile women were at higher risk of developing psychiatric disorders if they were housewives rather than working women (P = 0.001). Considering the high prevalence of psychiatric disorders among infertile women, it seems that gynecologists, psychiatrists and psychologists should be more attentive to identify and treat these disorders. The use of psychotherapy, especially supportive methods, should be considered as part of the general therapeutic framework of infertility. |
19023495 | Foreign bodies in the airway: a quarter of a century's experience. | Foreign body (FB) aspiration in children is mon and potentially dangerous situation that can be associated to significant morbidity. |
19023509 | Copper bioavailability and fractionation in copper-contaminated sandy soils in the wet subtropics (southern Brazil). | We studied the distribution, bioavailability and speciation of copper in subtropical sandy soils exposed to long-term applications of copper-based fungicide. In the surface horizon of the contaminated soils, bioavailable copper surpasses the toxic threshold for plants up to several times. Mobile fractions of copper predominate in top layers, contributing to contamination spreading downward to groundwater. Copper accumulates on the underlying iron hydroxide barrier in parable to total copper concentrations in the surface horizon. Despite the impediment of the geochemical barrier, most applied copper reaches the aquifer, contaminating the groundwater. |
19023496 | An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer. | Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC) versus docetaxel, pemetrexed and best supportive care. |
19023492 | HLA class I and II and TNF-alpha gene polymorphisms in sarcoidosis patients. | Several factors suggest a genetic predisposition to sarcoidosis, namely the recognition of race as a risk factor and the occurrence of familial clustering of cases. Several studies have reported an association of sarcoidosis and HLA class I and especially class II alleles in different populations. |
19023504 | [Congenital lobar emphysema: study of a case]. | Congenital Lobar Emphysema (CLE) is a rare malformation of lung development, which may be the cause of respiratory insufficiency in the suckling child. It is produced by the hyperinsufflation of one or more lung lobs pression of the normal lung parenchyma and contralateral displacement of the mediastinum. Clinical diagnosis is confirmed by simple radiology exams. Lobectomy has better results than clinical treatment and should be chosen. Our purpose is to present one case of this rare illness in a newborn seen in our service with serious respiratory insufficiency and plementary exams, CLE was confirmed. The patient was submitted to a surgical procedure (lobectomy) with an excellent post surgery evolution. Child is asymptomatic in long term follow up. |
19023498 | [Systemic lupus erythematosus association with tuberculosis - critical review]. | The author provides a critical analysis of systemic lupus erythematosus associated with tuberculosis. A brief review of the lupus-tuberculosis association is also given, and stresses that extra-pulmonary TB is the most usual form of TB in these cases. Other issues considered are the heat shock proteins of Mycobacterium tuberculosis HSP70KDa and HSP65KDa families and TLR2, TLR4, TLR9 that can be involved in interaction between bacilli antigen and host tissue causing autoimmune induction by lupus. The author concludes that early diagnosis and appropriate management are mandatory in SLE associated with TB, in areas where TB is endemic. |
19023493 | Prevalence of asthma and rhinitis in 13 year old adolescents in Porto, Portugal. | The prevalence of asthma and rhinitis has been increasing over the past few decades, but the last few years have seen these rates stabilise or even decrease. |
19023503 | Leptospirosis of the lung presenting with crazy-paving pattern: correlation between the high-resolution CT and pathological findings. | The authors present the high-resolution CT findings of a patient with diffuse pulmonary hemorrhage due to leptospirosis. The main finding consisted of extensive ground-glass opacities super imposed on mild interlobular septal thickening, resulting in the appearance termed "crazy- paving". The patient died and the necropsy showed extensive haemorrhage filling the airspace and blood infiltrating the interlobular sep- ta. The correlation between the high-resolution CT and pathological findings is emphasised. |
19023511 | The microvascular anatomy of the metatarsal bones: a plastination study. | The purpose of this study was to categorize and systematize the arterial supply of the metatarsal bones and furthermore the observation of arterial lesions after frequently performed forefoot surgeries. |
19023510 | Increase in vertebral fracture risk in postmenopausal women using omeprazole. | Proton pump inhibitors are taken by millions of patients for prevention and treatment of gastroesophageal diseases. Case-control studies have suggested that use of omeprazole is associated with an increased risk of hip fractures. The aim of this prospective study was to assess the risk of vertebral fractures in postmenopausal women using omeprazole. We studied 1,211 postmenopausal women enrolled in the Osteoporosis and Ultrasound Study from the general population. Information on omeprazole and other risk factors for fractures including prevalent fractures and bone mineral density was obtained at baseline. Vertebral fractures were assessed on X-rays obtained at baseline and at the end of the 6-year follow-up and analyzed centrally. At baseline, 5% of this population was using omeprazole. Age-adjusted rates for vertebral fractures were 1.89 and 0.60 for 100 person-years for omeprazole users and nonusers, respectively (P = 0.009). In the multivariate analysis, omeprazole use was a significant and independent predictor of vertebral fractures (RR = 3.50, 95% CI 1.14-8.44). The other predictors were age higher than 65 years (RR = 2.34, 95% CI 1.02-5.34), prevalent vertebral fractures (RR = 3.62, 95% CI 1.63-8.08), and lumbar spine T score </= -2.5 (RR = 2.38, 95% CI 1.03-5.49). Omeprazole use is associated with an increased risk of vertebral fractures in postmenopausal women. Further studies are required to determine the mechanism of the association between the underlying gastric disease, omeprazole use, and risk of osteoporotic fractures. |
19023500 | [Shouldn't the Achilles' heel be on the foot - regarding a clinical case]. | Clinical suspicion is the bedrock of a thorough clinical work-up, and a review of the clinical files with no definitive diagnosis is a must. Such a review can uncover rare diagnoses, such as Waldenstrom's macroglobulinaemia, a proliferative B-cell disease characterised by medular infiltration and monoclonocal IgM production. 1% of these are biclonal. We present a case of a 74 year old patient diagnosed in October 2004 with acute cholecystitis. Surgical evaluation revealed bilateral pleural effusion with an inconclusive aetiology. Patient underwent a right pleurodesis in May 2005 and the aetiology remained inconclusive. The third evaluation, in July 2005, led to a final diagnosis of Waldenstrom's macroglobulinaemia. |
19023501 | Spinal leptomeningeal metastasis in a patient with squamous cell lung cancer. | Spinal leptomeningeal metastasis occurs rarely in solid tumors, and the prognosis is extremely poor. Adenocarcinomas and small-cell carcinomas are the mon histological type detected among lung tumors. A 58-year-old man with a history of squamous-cell lung carcinoma with mediastinal invasion and brain metastasis was examined because of his low back pain and weakness in both lower limbs. Spinal MRI revealed subpial enhancement in the spinal cord; and innumerable nodules with thickening of the cauda equina fibres. To our knowledge, this is the second reported case of squamous cell lung cancer with spinal leptomeningeal metastasis. |
19023512 | A study of the vascularization of the auricle by dissection and diaphanization. | The vascularization of the auricle is poorly documented, despite the developments in auriculotherapy and reconstructive surgery. The aim of this study was to describe its arterial distribution using two techniques: diaphanization and anatomical dissection. The study was conducted after intravascular injection of eight diaphanized auricles and ten that were dissected. Dissection showed that the auricle is vascularized by an anterior flow arising in the superficial temporal artery and also by a posterior flow arising in the posterior auricular artery in eight cases out of ten, and in the occipital artery in the remaining two. Diaphanization revealed the three-dimensional arterial distribution of preserved specimens. This technique has a didactic use plement to standard anatomical dissection. |
19023513 | Glucose homeostasis abnormalities in cardiac intensive care unit patients. | The aim of this study was to characterize the abnormalities in glucose homeostasis in intensive care unit patients following an acute coronary event. The study population included all non-diabetic patients ages 20-80 years that were admitted to a coronary intensive unit. Glucose, insulin and C-peptide levels during an oral glucose tolerance test (OGTT) were measured during the acute admission. From January to September 2003, 277 patients were admitted to the coronary unit. Of these, 127 patients underwent an OGTT. Of these, only 29 patients (23%) exhibited normal glucose metabolism. The remainder had type 2 diabetes (32%), impaired glucose tolerance (37%) or isolated impaired fasting glucose (8%, 100-125 mg/dl). Based on homeostasis model assessment (HOMA) calculations, diabetic patients had impaired beta-cell function and patients with elevated fasting glucose levels were insulin resistant. Beta-cell dysfunction during the acute stress seems to contribute to the glucose abnormalities. Most patients who experience an acute coronary event demonstrate abnormal glucose metabolism. Post glucose-load abnormalities are mon than abnormal fasting glucose level in this situation. It is postulated that the acute stress of a coronary event may contribute to the dysglycemia. |
19023502 | [Septic pulmonary embolism - case report]. | SPE is a rare syndrome, although a frequent clinical presentation of several disorders, many times misdiagnosed in medical practice. It was described 30 years ago, almost always associated with intravenous drug abuse. Recent reports indicate that the epidemiology of patients with septic pulmonary embolism has changed over the past 30 years. We report a case of septic pulmonary embolism associated with tricuspid valve endocarditis. The patient had a personal history of intravenous drug abuse. The plaints were fever, anorexia and weight loss for 30 days. A chest radiograph revealed multiple pulmonary infiltrates in the lower third of the right lung. Antimicrobial agents were instituted in order to treat pneumonia, with no success. Blood cultures were positive for methicillin -susceptible Staphylococcus aureus. Transthoracic ecocardiography revealed a vegetation in the tricuspid valve. Oriented antimicrobial therapy was introduced, successfully. We have reviewed the literature, suggesting thereafter diagnostic criteria for septic pulmonary embolism. |
19023514 | Refill adherence to oral antihyperglycaemic drugs in Sweden. | Only 49% of the patients with T2D in Sweden that medicate with oral antihyperglycaemic drugs (AHGD) had good blood glucose control (HbA(1C) < 6.0%). The reason can be low medication adherence. The aim of this study was, therefore, to determine the adherence to different oral AHGD. Included were all patients in Sweden, older than 40 years and having at least two expenditures of AHGD between 1 December 2005 and 30 November 2006. After exclusions of inpatients and patients with unspecified daily dosage 171,220 patients (57% men) remained. Medication possession ratio (MPR) was used for estimating adherence and patients were regarded adherent if MPR >or=80%. The overall refill adherence average 90%, with mean MPR (SD) = 107% (30). Eighty-five percent of the patients in their 40s were pared to 91% of the patients in their 80s. About 90.1% of the women were adherent whereas 89.5% of the men were adherent. Patients with an indication for the medicine were more adherent than patients without this information. We conclude that the unsatisfactory blood glucose control showed among many Swedish T2D patients is not the result of non-adherence to prescribed medication. |
19023499 | Intravascular pulmonary lymphoma with good response to treatment. A case report. | Intravascular lymphoma is a very rare form of large B cell non-Hodgkin's lymphoma, characterised by the presence of lymphoma cells in the lumina of small vessels only, particularly in the capillaries. We report a 54 year-old female non-smoker, admitted to hospital for further examination of a four month long clinical condition involving high fever, night sweats, unqualified weight loss and progressive dyspnea. Patient's temperature was 38.5 degrees C, pulse 100/min and respiratory 22 cycles/min. Patient's haemoglobin was 9.4 g/dL, she had leukocytosis, elevated LDH and arterial blood gas analysis with moderate hypoxaemia (FiO2 1l/m: PaO2-63.6 mm Hg). Chest X-ray revealed diffuse interstitial changes. All the possible causes of unknown origin fever were excluded. Diagnosis was made through lung biopsy and treatment bined chemotherapy and rituximab was prescribed leading to a 48 hours clinical remission. We present this case to show how difficult this diagnosis can be and how a good response to therapy is possible. |
19023515 | Minimally invasive spinal surgery using nucleoplasty: a 1-year follow-up study. | Nucleoplasty is a minimally invasive percutaneous intradiscal coblation therapy option in patients with chronic discogenic low back pain. The purpose of this prospective study was to assess the effectiveness of nucleoplasty in our patients up to 1 year after treatment. |
19023516 | Bacterial community composition in thermophilic microbial mats from five hot springs in central Tibet. | Despite detailed study of selected thermophilic taxa, munity diversity of bacteria in thermophilic mats remains relatively poorly understood. A sequence-based survey of munities from several hot spring locations in central Tibet was undertaken. Diversity and frequency of occurrence for 140 unique 16S rRNA gene phylotypes were identified in clone libraries constructed from environmental samples. A lineage-per-time plot revealed that individual locations have evolved to support relatively large numbers of phylogenetically closely related phylotypes. Application of the F ( ST ) statistic and P test munity data was used to demonstrate that phylogenetic divergence between locations was significant, thus emphasizing the status of hot springs as isolated habitats. Among phylotypes, only the Chlorobi were ubiquitous to all mats, other phototrophs (Cyanobacteria and Chloroflexi) occurred in most but not all samples and generally accounted for a large number of recovered phylotypes. Phylogenetic analyses of phototrophic phylotypes revealed support for location-specific lineages. The alpha, beta and gamma proteobacteria were also frequently recovered phyla, suggesting they may be abundant phylotypes in mats, a hitherto unappreciated aspect of thermophilic mat biodiversity. Samples from one location indicated that where phototrophic bacteria were rare or absent due to niche disturbance, the relative frequency of proteobacterial phylotypes increased. |
19023518 | Analysis of OCT4 expression in an extended panel of human tumor cell lines from multiple entities and in human mesenchymal stem cells. | OCT4 is considered a main regulator of embryonic stem cell pluripotency and self renewal capacity. It was shown that relevant OCT4 expression only occurs in cells of embryonic pluripotent nature. However, several recent publications claimed to have demonstrated OCT4 expression in human somatic tumor cells, human adult stem or progenitor cells and differentiated cells.We analysed 42 human tumor cell lines from 13 entities and human bone marrow-derived mesenchymal stem cells (MSC). To validate OCT4 expression we used germ cell tumor (GCT) cell lines, derived xenografts and GCT samples. Analysis by RT-PCR, western blotting, immunocytochemistry and immunohistochemistry was performed. With exception of typical embryonal carcinoma cells, we did not observe reliable OCT4 expression in somatic tumor cell lines and MSC. We suggest that a high level of expression of the OCT4 protein together with its nuclear localization still remains a reliable and definitive feature of cells with embryonic pluripotent nature. |
19023519 | Merkel cell carcinoma. | Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin. More than one-third of MCC patients will die from this cancer, making it twice as lethal as malignant melanoma. Despite the fact that MCC is still a very rare tumor, its incidence is rapidly increasing; the American Cancer Society estimates for 2008 almost 1,500 new cases in the USA. These clinical observations are especially disturbing as the pathogenesis of MCC is not yet fully understood; however, a number of recent reports contribute to a better understanding of its pathogenesis. Here we describe findings regarding the role of Wnt, MAPK and Akt signaling as well as possible aberrations in the p14ARF/p53/RB tumor suppressor network in MCC. Most important, and possibly with high impact on future therapeutic approaches is the demonstration that a polyomavirus has frequently integrated in the genome of the MCC cells prior to tumor development. |
19023520 | Chemotherapy, hormonal therapy, and immunotherapy for recurrent meningiomas. | Meningioma is mon intracranial tumor, originating from the meninges of the skull or spinal canal. Most meningiomas are benign tumors, however atypical or anaplastic tumors can be found in 6% of cases. Patients with asymptomatic small benign meningiomas can be followed without therapy, but in symptomatic plete surgical resection should be performed. For recurrent previously resected tumors re-resection is mended followed by radiotherapy in selected cases. Antiprogesterone treatment can also be considered in recurrent benign meningiomas. Immunotherapy with interferon-alpha and chemotherapy should be reserved for all cases of recurrent meningiomas (benign, atypical, and malignant) when all the standard therapies have failed or contraindicated. |
19023521 | The Factor V Leiden mutation is associated with a higher blood haemoglobin concentration in women below 50 of the Malmö Thrombophilia Study (MATS). | The aim of this study was to investigate a relationship between FVL-mutation and levels of haemoglobin (Hb) in patients with venous thromboembolism (VTE). From March 1998 to December 2005, 927 consecutive patients with objectively diagnosed VTE were registered in the Malmö Thrombophilia Study (MATS). Female patients with FVL-mutation below 50 years of age had significantly higher median-Hb (133 vs. 126 g/l; P < pared to female patients below the age of 50 years without FVL. No significant difference could be found for men or women above 50 years of age or men below 50 years of age. Female patients below the age of 50 years with FVL-mutation and VTE are associated with higher median Hb, and this finding is in accordance with earlier hypothesis that FVL-mutation may have constituted an evolutionary selection advantage. |
19023524 | Enzymatic synthesis of biodiesel via alcoholysis of palm oil. | The enzymatic alcoholysis of crude palm oil with methanol and ethanol was investigated mercial immobilized lipases (Lipozyme RM IM, Lipozyme TL IM). The effect of alcohol (methanol or ethanol), molar ratio of alcohol to crude palm oil, and temperature on biodiesel production was determined. The best ethyl ester yield was about 25 wt.% and was obtained with ethanol/oil molar ratio of 3.0, temperature of 50 degrees C, enzyme concentration of 3.0 wt.%, and stepwise addition of the alcohol after 4 h of reaction. Experiments with 1 and 3 wt.% of KOH and 3 wt.% of MgO were carried out pare their catalytic behavior with the enzymatic transesterification results. mercial immobilized lipase, Lipozyme TL IM, showed the best catalytic performance. |
19023522 | Risk stratification for venous thromboembolism in hospitalized patients in a developing country: a prospective study. | Venous Thrombo-Embolism (VTE) is a plication in hospitalized patients but can be preventable. This prospective study addresses risk factors assessment and the use of heparin in this population. About 2,496 non pediatric patients were admitted to Jordan University Hospital between June 12, 2007 and July 19, 2007. A random sample of 624 patients consisting of every fourth admission was chosen. The stratification of risk factors was assessed using Caprini model and the ACCP score. The mean age of the patients (229 males and 395 females) was 45.34 +/- 18.3 years. More than 80% of the admitted patients were considered at high risk for VTE but heparin was used in only 26% of the patients. The majority of our patients constitute a high-risk population. Implementation of strategies including educational sessions and risk stratification guidelines can reduce the incidence, morbidity, and mortality of VTE especially in developing countries. |
19023523 | Worldwide geographical distribution of ophthalmology publications. | International peer-reviewed publications form the basis of evidence-based medicine and are one of the main indicators of ophthalmology research activity. This paper examines the origins of such articles in relation to geographical location, population demographics and economic research profiles. Publications from five ophthalmology journals over 5 years were analysed using the Medline/Pubmed search engine. Country of origin was ascertained based on the address of the corresponding author. Worldwide ophthalmology research output was analysed in relation to population demographics and research expenditure. In total, 7,754 articles from 67 countries from 2002 to 2006 were analysed. The overall number of articles published increased by over 29% during this period. The United States (US) produced the greatest number of articles. Singapore produced the most publications per 10(6) population. There was a relationship between gross domestic product (GDP) greater than $20,000 and population-adjusted output. The US followed by the United Kingdom and Japan were the greatest gross contributors. Population-adjusted figures revealed that Singapore, Iceland and Australia were the most prolific nations. There was a relationship between GDP and the top-ranked population-adjusted countries. The top 10 most productive population-adjusted countries spend relatively more on research and development than the top 10 gross contributors. |
19023526 | Vesicoureteral reflux: current concepts and management implications. | Long term controlled studies in children with vesicoureteral reflux (VUR) largely conducted in developed societies, challenge the validity of established management principles.The backflow of urine into the upper tracts is not a disease by itself, but part of a clinical spectrum which is heterogeneous and has low risk and high risk categories. Management, medical, endoscopic or surgical have to take into consideration the risk to the child not only from the reflux but also from renal dysplasia and voiding dysfunction which are important risk factors for end stage renal disease (ESRD) and perpetuation of VUR respectively. Social factors, parental choices and access to medical treatment are also important in choosing therapy. |
19023525 | Neonatal surgery: a ten year audit from a university hospital. | Neonatal surgery is the flagship and most ponent of pediatric surgery, which is the youngest subspeciality of surgery. Neonatal surgery carried a survival rate of only 30% three decades ago. In the last decade there has been a significant change in the scenario. Earlier recognition and referral of these anomalies, availability of neonatal intensive care, better preoperative planning, decision, and techniques have lead to the change in the management. This is an audit into the e of neonatal surgery from one of the largest units in India over a ten year period. This audit reveals an across the board survival of 65-70% newborns after surgery on nearly two thousand case over a ten year period. It has an important message that while pediatric surgery units expand, risk stratification of surgical newborns and their treatment in suitable units is mandatory to maintain and improve these figures to match international standards over the next decade. |
19023528 | Corticosteroid physiology and principles of therapy. | The adrenal cortex secretes glucocorticoids (GC), mineralocorticoids (MC) and androgens. GC maintain homeostasis, MC regulate fluid and electrolyte balance and adrenal androgens contribute to development of secondary sexual characteristics. Pharmacologic GC therapy is frequently indicated in the pediatric age group. Besides having many important side effects, prolonged high dose systemic GC therapy has a suppressive effect on endogenous steroid production. Therefore, GC therapy should be withdrawn gradually and stopped based on assessment of hypothalamo-pituitary-adrenal (HPA) axis recovery. Patients with HPA axis suppression require physiological replacement of GC along with enhancement of doses during periods of stress. Due to its immunosuppressive effects, issues about safety and efficacy of live virus vaccines in patients receiving systemic high dose GC therapy must be borne in mind. |
19023530 | Pulse steroid therapy. | Intravenous supra-pharmacological doses of corticosteroids are used in various inflammatory and autoimmune conditions because they are cumulatively less toxic than sustained steroid treatment at lower quantitative dosage. Their action is supposed to be mediated through non-genomic actions within the cell. Common indications for use in children include steroid resistant and steroid dependent nephrotic syndrome, rapidly progressive glomerulonephritis, systemic vasculitis, systemic lupus erythematosus, acute renal allograft rejection, juvenile rheumatoid arthritis, juvenile dermatomyositis, pemphigus, optic neuritis, multiple sclerosis and acute disseminated encephalomyelitis. Methylprednisolone and dexamethasone show similar efficacy in most conditions. Therapy is associated with significant side effects including worsening of hypertension, infections, dyselectrolytemia and behavioral effects. Adequate monitoring is essential during usage. |
19023529 | Pulmonary diseases and corticosteroids. | Steroids (corticosteroids) are anti-inflammatory drugs. Corticosteroids are used in many pulmonary conditions. Corticosteroids have a proven beneficial role in asthma, croup (Laryngotracheobronchitis), decreasing the risk and severity of respiratory distress syndrome (RDS), allergic bronchopulmonary aspergillosis, interstitial lung disease, hemangioma of trachea, Pulmonary eosinophillic disorders. Role of corticosteroids is controversial in many conditions e.g. idiopathic pulmonary hemosiderosis, bronchiolitis, hypersensitivity pneumonitis, hyperplasia of thymus, bronchiolitis, acute respiratory distress syndrome, aspiration syndromes, atypical pneumonias, laryngeal diphtheria, AIDS, SARS, sarcoidosis, meconium aspiration syndrome (MAS), pulmonary haemorrhage, bronchitis, bronchiolitis obliterans with organizing pneumonia in JRA, histiocytosis, alpha-1 antitrypsin deficiency, bordtella pertusis, pulmonary involvement in histiocytosis. However these are used empirically in many of these conditions despite lack of clear evidence in favour. There is concern about their side effects, especially on growth. Systemic steroids are associated with significant adverse effects. Pulmonary conditions have a strategic advantage that inhaled corticosteroids are useful in many of these. Although inhaled preparations of corticosteroids have been developed to maximise effective treatment of lung diseases characterised by inflammation and reduce the frequency of harmful effects, these have not been eliminated. There are situations where only systemic steroids are useful. Clinicians must weigh the benefits against the potential detrimental effects. It is mended that standard protocols for use of steroids available in literature should be followed, always keeping a watch on the potential hazards of prolonged use. |
19023531 | Strategies for minimizing corticosteroid toxicity: a review. | Glucocorticoids (GCs) are monly for the treatment of various pediatric inflammatory and autoimmune diseases. Although potent and generally effective, they are not without risks for producing serious adverse effects, especially when used in high doses for prolonged periods of time. For proper use of systemic glucocortcoids, a basic knowledge of the pharmacology, clinical usage guidelines, and adverse reactions of these agents is imperative. This review article emphasis on monly observed side-effects encountered with GC use in children and their underlying basic pathophysiological mechanisms. The appropriate anticipation of these side-effects with timely implementation of the suggested evidencebased guidelines has the potential significantly to prevent, minimize and mon and plications of glucocortcoid therapy. |
19023533 | Enhancement of the immune responses of mice to Bacillus anthracis protective antigen by CIA07 combined with alum. | Anthrax is an acute zoonotic disease caused by infection with Bacillus anthracis. B. anthracis spores are highly resistant to environmental degradation and are used as a biological weapon. In this study, we investigated the adjuvant activity of CIA07 to anthrax protective antigen (PA). A/J mice were immunized intraperitoneally once, or twice with a 4-week interval, with binant PA alone bined with alum, CpG1826, or CIA07 as adjuvant, and serum anti-PA IgG antibody responses were measured 4 weeks after each immunization. All three adjuvants significantly enhanced anti-PA IgG antibody titer 4 weeks after the priming and boosting immunizations, and alum gave the highest titer. In order to evaluate the adjuvant activity of CIA07 in the presence of alum, Balb/c mice were immunized 3 times at 1-week intervals with PA bination with alum, CIA07 or alum plus CIA07, and the immune responses were assessed 2 weeks after the third immunization. The serum anti-PA IgG antibody titer of the CIA07-treated group was 14-fold higher than the group given PA alone, and the coadministration of CIA07 with alum further increased the titer 3.5-fold (P < 0.05). The toxin neutralizing activity of the sera from the mice given bination of CIA07 and alum was 109-times higher than the animals given PA alone. The mice given CIA07 plus alum also showed a marked increase in the number of IFN-gamma-, IL-2-, and IL-4-producing CD4(+) T cells among their splenocytes. These data suggest the potential of CIA07 bination with alum as an adjuvant for the development of a potent anthrax vaccine. |
19023532 | A new abietane diterpenoid from Isodon inflexus. | A new ent-abietane diterpenoid, 3alpha,6beta-dihydroxy-7,17-dioxo-ent-abieta-15(16)-ene (1), and three known ent-kaurane diterpenids, kamebacetal A (2), kamebakaurin (3), and excisanin A (4), and a known triterpenoid, ursolic acid (5), were isolated from the aerial parts of Isodon inflexus. Their chemical structures were determined by extensive analysis of spectroscopic data including 1D-and 2D-NMR experiments. All isolates (1-5) were evaluated for their potential to inhibit LPS-induced nitric oxide production in RAW264.7 cells. Of pounds 1-4 inhibited the production of NO with IC(50) values ranging from 1.0 to 26.5 microM. |
19023534 | One-pot conversion of trimethylsilyl ethers into urethanes using chlorosulfonyl isocyanate: application to the synthesis of a novel neuromodulator carisbamate. | This paper reports a novel synthetic method for the preparation of various urethanes and the application to the synthesis of carisbamate. The reaction of primary (2a, 2e and 2f) or secondary (2g-2i) trimethylsilyl ethers with chlorosulfonyl isocyanate afforded the corresponding urethanes in good yields without affecting the olefin moiety. However, in the case of secondary benzylic trimethylsilyl ether 2j, the corresponding urethane 3j was obtained in low yield. From the difference in reactivity between the primary and secondary benzylic trimethylsilyl ethers, the one-pot synthesis of carisbamate 1 from bis-trimethylsilyl ether 2l was achieved. |
19023535 | Apoptosis-inducing effect of akebia saponin D from the roots of Dipsacus asper Wall in U937 cells. | Methanol extracts of the root of Dipsacus asper Wall (Dipsacaceae) were found to exhibit apoptosis-inducing activities in U937 (human monocyte-like histiocytic) cells. Investigation of the active n-BuOH fraction led to the isolation of akebia saponin D (ASD). Structure was established by spectroscopic methods. Treatment of U937 cells with ASD induced apoptosis in a dose dependent manner. ASD exerted strong cytotoxicity against human and murine leukemia cells. It is significantly increased the subG1 cell population and expression of p53 and Bax gene. And also ASD enhanced NO production from RAW264.7 macrophage cells. Taken together, these results strongly indicate that ASD may exert apoptosis-inducing activity via induction of apoptosis through activation chiefly via the nitric oxide and apoptosis-related p53 and Bax gene expression. These data provide scientific evidence that Dipsacus asper Wall can be useful as a chemopreventive agent. |
19023537 | Topoisomerase I and II inhibitory constituents from the bark of Tilia amurensis. | Two coumarins (1 and 6), one flavan-3-ol (2), one fatty acid (3), and two lignan glycosides (4 and 5) were isolated from the EtOAc and CH(2)Cl(2) extract of the bark of Tilia amurensis. Their chemical structures were identified paring their physicochemical and spectral data with those of published in literatures. Compounds 4, 5, and 6 were isolated from Tilia genus for the first time. Compounds 2 and 3 showed potent inhibitory activity against both DNA topoisomerase I (IC(50) values; 49 microM and 4 microM, respectively, with 18 microM of positive ptothecin) and DNA topoisomerase II (IC(50) values; 13 microM and 3 microM, respectively, with 50 microM of positive pound, etoposide). However, pounds did not showed cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7), and human liver hepatoblastoma cell line (HepG-2). |
19023536 | Inhibitory activities of the alkaloids from Coptidis Rhizoma against aldose reductase. | As part of our ongoing search of natural sources for therapeutic and preventive agents for plications, the rat lens aldose reductase (RLAR) inhibitory effect of Coptidis Rhizoma (the rhizome of Coptis chinensis Franch) was evaluated. Its extract and fractions exhibited broad and moderate RLAR inhibitory activities of 38.9 approximately 67.5 microg/mL. In an attempt to identify ponents, six quaternary protoberberine-type alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one quaternary aporphine-type alkaloid (magnoflorine) were isolated from the most active n-BuOH fraction, and the chemical structures therein were elucidated on the basis of spectroscopic evidence parison with published data. The plications capacities of seven C. chinensis-derived alkaloids were evaluated via RLAR and human binant AR (HRAR) inhibitory assays. Although berberine and palmatine were previously reported as prime contributors to AR inhibition, these two ponents exhibited no AR inhibitory effects at a higher concentration of 50 microg/ml in the present study. Conversely, epiberberine, coptisine, and groenlandicine exhibited moderate inhibitory effects with IC(50) values of 100.1, 118.4, 140.1 microM for RLAR and 168.1, 187.3, 154.2 microM for HRAR. The results clearly indicated that the presence of the dioxymethylene group in the D ring and the oxidized form of the dioxymethylene group in the A ring were partly responsible for the AR inhibitory activities of protoberberine-type alkaloids. Therefore, Coptidis Rhizoma, and the alkaloids contained therein, would clearly have beneficial uses in the development of therapeutic and preventive agents for plications and diabetes mellitus. |
19023538 | Bavachin and isobavachalcone, acyl-coenzyme A: cholesterol acyltransferase inhibitors from Psoralea corylifolia. | Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays important roles in intestinal absorption of cholesterol, hepatic production of lipoproteins and accumulation of cholesteryl ester within macrophages and smooth muscle cells. Ethanol extract of Psoralea corylifolia showed a significant inhibition of ACAT enzyme. Via bioactivity-guided fractionation of the ethanol extract of Psoralea corylifolia, two prenylated flavonoids were isolated. Their structures were determined as bavachin (1) and isobavachalcone (2) by spectroscopic analysis ((1)H-, (13)C-NMR, 2DNMR, and ESI-MS). The IC(50) values were 86.0 (1) and 48.0 (2) microM in the ACAT assay system using rat liver microsome. Compound 2 also decreased cholesteryl ester formations in HepG2 cells. In addition, pound showed a petitive type of inhibition of ACAT. |
19023539 | In vitro inhibitory potential of decursin and decursinol angelate on the catalytic activity of cytochrome P-450 1A1/2, 2D15, and 3A12 isoforms in canine hepatic microsomes. | Danggui is one of the most popular herbal medicines consumed by patients in different clinical settings in Asian countries. In this study, the two major pounds extracted from the Korean Angelica gigas root decursin (DC) and decursinol angelate (DA) were examined in vitro with regard to their abilities to inhibit hepatic CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities in canine liver microsomes. The ponents were capable of inhibiting CYP1A1/2, CYP2D15, and CYP3A12 catalytic activities, but the potencies varied. DC and DA selectively and petitively inhibited CYP1A1/2 activity, with K ( i ) values of 90.176 and 67.560 microM, respectively. On the other hand, they exhibited slight inhibitory effects on CYP2D15 and CYP3A12 with K ( i ) values of 666.180 and 872.502 microM, 990.500 and 909.120 microM (1'hydroxymidazolam, MDZ1'H), and 802.800 and 853.920 microM (4-hydroxymidazolam, MDZ4H), respectively. Additionally, they showed increased inhibition after preincubation, which suggests the involvement of a mechanism-based inhibition. In sum, this in vitro data should be heeded as a signal of possible in vivo interactions. The use of human liver preparations would considerably strengthen the practical impact of the data generated from this study. |
19023541 | Tectorigenin inhibits IFN-gamma/LPS-induced inflammatory responses in murine macrophage RAW 264.7 cells. | Tectorigenin (Tg) and tectoridin (Td) are the pounds isolated from the rhizomes of iridaceous plant Belamcanda chinensis which is well known as a chinese traditional medicine for the treatment of inflammatory diseases. In this study we investigated whether tectorigenin and tectoridin can be applied to the suppression of interferon-gamma and lipopolysaccharide (IFN-gamma/LPS)-induced inflammatory responses in macrophages. Anti-inflammatory activities of tectorigenin and tectoridin pared with genistein (Ge), well known isoflavonoid as a phytoestrogen and regarded as an emerging anti-inflammatory agent. pounds showed low cytotoxic effect. In Raw 264.7 cells activated with IFN-gamma/LPS, pre-treated tectorigenin was found to inhibit the expression of inducible nitric oxide synthase (iNOS), the production of nitric oxide (NO) and the secretion of interleukin (IL)-1beta dose-dependently. Tectorigenin also decreased the expression of cyclooxigenase (COX)-2 and the production of prostaglandin E(2) (PGE(2)) in dose-dependent manner. These inhibitory effects of tectorigenin were found to be caused by the blocking of nuclear factor kappa-B (NF-kappaB) activation. Compared with genistein and tectoridin, tectorigenin showed significant inhibitory effect for almost anti-inflammatory tests in this study. All these results clearly demonstrated that tectorigenin appears to have the potential to prevent inflammation. |
19023542 | Neuroprotective effects of chronic hesperetin administration in mice. | Flavonoids are considered therapeutic agents in neurodegenerative disease because of their neuroprotective activity. This study investigated the neuroprotective effects of hesperetin in the brains of mice administered hesperetin at 10 or 50 mg/kg body weight (BW) for five weeks. Hesperetin inhibited biomarkers of oxidative stress, such as the level of thiobarbituric acid-reactive substance (TBARS) and carbonyl content, although there was a significant reduction at the higher dose of hesperetin. Moreover, at the higher dose, hesperetin significantly activated the catalase and total superoxide dismutase (SOD) activities. The same patterns were observed in the protein expression, and the expression of CuZn-SOD was more pronounced than that of Mn-SOD. The reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio was increased significantly in a dose-dependent manner, as well as the glutathione peroxidase (GSH-px) and glutathione reductase (GR) activities. Moreover, hesperetin did not induce apoptosis, even at the higher dose, as evidenced by caspase-3 expression and its activity. Based on these results, hesperetin may have a neuroprotective effect via the inhibition of oxidative damage, together with activation of the antioxidant enzyme system. |
19023543 | Cytotoxicity of amphotericin B-incorporated polymeric micelles composed of poly(DL-lactide-co-glycolide)/dextran graft copolymer. | In this study, we prepared amphotericin B (AmpB)-encapsulated polymeric micelle of poly(DL-lactideco-glycolide) (PLGA) grafted-dextran (DexLG) copolymer for the cytotoxicity test. The average particle size of AmpB-encapsulated DexLG polymeric micelles was around 30 approximately 70 nm and their morphology showed spherical shapes. Since aggregation states of AmpB are related to intrinsic cytotoxicity, prevention of AmpB aggregation in aqueous solution will provide low cytotoxicity and increased antimicrobial activity for the infectious disease. At UV/VIS spectrum measurement, polymeric micelle prepared from methanol/water mixture (method B) showed a monomeric state of AmpB while polymeric micelle prepared from DMSO (method A) showed an aggregated state. During the hemolysis activity test, polymeric micelle from method B showed reduced hemolysis pared to AmpB itself and polymeric micelle from method A. These results indicated that AmpB-incorporated polymeric micelle prepared from methanol/water mixture has low cytotoxicity and favorable antimicrobial activity. |
19023540 | Signaling mechanisms of sphingosine 1-phosphate-induced ERK1/2 activation in cultured feline esophageal smooth muscle cells. | Sphingosine 1-phosphate (S1P) is a bioactive lipid, stored and released from activated platelets, macrophages, and other mammalian cells. We previously reported that S1P induces esophageal smooth muscle contraction in freshly isolated intact cells. Here, we measured S1P-induced ERK1/2 activation and upstream signaling in cultured feline esophageal smooth muscle cells. Activation of ERK1/2 by S1P peaked at 5 min, was sustained up to 30 min, and was blocked by PTX. In contrast, S1P did not activate p38 MAPK or JNK. PTX inhibited S1P-induced ERK1/2 activation. We then used phospholipase inhibitors, DEDA for PLA(2), U73122 for PLC, and rhoCMB for PLD, to determine that ERK1/2 activation was downstream of PLC activation. The PKC inhibitors, GF109203X and chelerythrine, also suppressed ERK1/2 activation. Whereas the PTK inhibitor, genistein, partially inhibited ERK1/2 activation, the EGFR tyrosine kinase inhibitor, tyrphostin 51, had no effect. Taken together, S1P-induced ERK1/2 activation in cultured ESMCs requires a PTX-sensitive G protein, stimulation of the PLC pathway, and subsequent activation of the PKC and PTK pathways. |
19023545 | New phenylpropanoid esters of sucrose from Polygonum hydropiper and their antioxidant activity. | By various chromatographic methods, two new phenylpropanoid esters of sucrose named hidropiperosides A (1) and B (2), and three pounds as vanicosides A (3), B (4), and E (5) were isolated from the methanolic extract of the whole plant of Polygonum hydropiper L. (Polygonaceae). Their structures were elucidated by extensive spectroscopic methods including 1D-and 2D-NMR experiments, as well as ESI-MS analysis. All the pounds were tested for their antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay system. Among pounds 2 and 3 showed significant antioxidant activity with their SC(50) values of 23.4 and 26.7 microg/mL, respectively. |
19023547 | Antidiabetic activity of angelan isolated from Angelica gigas Nakai. | Angelan isolated from Angelica gigas Nakai inhibits tumor growth and metastasis by enhancing immune functions of macrophages, dendritic cells, and B cells. Here, we report that angelan can inhibit autoimmunity in non-obese diabetic (NOD) mice. Although 80% of the NOD mice had developed diabetes by 24 weeks of age, none of the angelan-treated NOD mice developed diabetes. The mean glucose levels were 118 mg/dl in angelan-treated mice and 506 mg/dl in control NOD mice. Histological examination of the pancreatic islets revealed that most of the islets isolated from angelan-treated mice were less infiltrated with pared with those of control mice. Spleen cells from diabetic NOD mice could adaptively transfer diabetes into NOD. scid mice, but those from angelan-treated NOD mice did not, suggesting that angelan caused the spleen cells to lose the ability to destroy beta cells. However, angelan did not affect cytokine production of spleen cells. These results suggest that angelan has dual immunomodulatory functions, i.e., immunostimulation in tumor-bearing mice and immunosuppression in autoimmune diabetic mice. |
19023546 | Compound K suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair in human keratinocytes. | Ultraviolet (UV)-induced DNA damage is a crucial molecular trigger for sunburn cell formation and skin cancer. Nucleotide excision repair (NER) is the main mechanism in repairing UVB-induced DNA damage of mammalian cells. The purpose of this study is to investigate the functional role of pound K on HaCaT cells (a keratinocyte-derived permanent cell line) irradiated by UV. Hoechst 33258 staining were performed in analyzing UV-induced apoptosis on keratinocytes which were treated pound K. ImmunoDotBlot assay was used in detecting cyclobutane pyrimidine dimers, the main DNA damage. Western blot analysis was applied for analyzing XPC and ERCC1, two of the NER proteins. Compound K inhibited UV-induced apoptosis of keratinocytes and caused a notable reduction in UV-specific DNA lesions which was due to induction of DNA repair. In agreement with pound K induced the expression of ponents of the plex, such as XPC and ERCC1. Our results demonstrate pound K can protect cells from apoptosis induced by UV radiation by inducing DNA repair. |
19023544 | Expression of thymosin alpha1-thymopentin fusion peptide in Pichia pastoris and its characterization. | Thymopentin plays an important role in improving imbalanced immune systems of patients, however, it has a limited half-life in plasma. To get more stable and active thymopentin analogs, a fusion thymosin alpha1-thymopentin (Talpha1-TP5) gene was synthesized and cloned into vector pGAPZalphaA. Talpha1-TP5 fusion peptide was expressed in pichia pastoris and purified by metal chelating chromatography and gel filtration chromatography. The circular dichroism spectra (CD) indicated that the secondary structure of Talpha1-TP5 fusion peptide is dominated by a-helix and random coil. In vitro analysis showed that the plasma half-life of Talpha1-TP5 fusion peptide is 140 +/- 14 min, which is longer than that of TP5 (5.6+/-0.7 min) and Talpha1 (127+/-11 min). The in vitro activity assay presented that Talpha1-TP5 fusion peptide has greater activity in promoting proliferation of Kunming mouse splenocytes, and in vivo experiment it showed better activity in promoting the phagocytosis of macrophages and secretion of IL-2 than both Talpha1 and TP5. Our findings suggest that Talpha1-TP5 fusion peptide might be a potential therapeutic agent. |
19023549 | Microencapsulation of antibiotic rifampicin in poly(3-hydroxybutyrate-co-3-hydroxyvalerate). | The aim of this study was the preparation of microparticles containing rifampicin using a biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) for oral administration produced by a bacteria. The poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles with and without rifampicin were prepared by the emulsification and solvent evaporation method, in which chloroform and polyvinyl alcohol are used as the solvent and emulsifier, respectively. Microparticles were obtained within a size range of 20-60 microm by changing the initial poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyvinyl alcohol and rifampicin concentrations. An encapsulation efficiency value of 14% was obtained. The optimized total yield of 60% of the poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/ rifampicin was obtained. A load of 0.035 mg/1 mg of PHBV was reached. Almost 90% of the drug loaded in the microparticles was released after 24 h. The size, encapsulation efficiency and ribampicin release of the microparticles varied as a function of the initial poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polyvinyl alcohol and rifampicin concentrations. It was demonstrated that the microencapsulated rifampicin, although was not totally available in the medium, exhibited a similar inhibition value as free rifampicin at 24 h of incubation with S. aureus. Cytotoxicity assays demonstrated a reduction of the toxicity when rifampicin was microencapsulated in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) while maintaining its antibacterial activity. |
19023548 | Enhanced dissolution of ibuprofen using solid dispersion with poloxamer 407. | To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility, and in-vitro ibuprofen release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C(max), and a significant decrease in T(max) over pure ibuprofen. Comparison of the enhanced solubility, dissolution, AUC, and C(max) of ibuprofen from different poloxamers suggested that the preparation of ibuprofen SDs using P 407 as a meltable hydrophilic polymer carrier could be a promising approach to improve its solubility, dissolution and absorption rate. |
19023550 | The effects of ketorolac tromethamine and baicalein on the levels of inflammatory factors in human synoviocytes. | This study examined the effects of ketorolac tromethamine (KT) and baicalein (BE) on the levels of inflammatory factors in human synoviocytes. The fibroblast-like synoviocytes (FLS) cells were used to determine the possible regulatory effects of KT and BE (KTBE) on the levels of inflammatory factors in FLS cells. In addition, the levels of TNF-alpha, IL-6, and IL-1beta mRNA expression in FLS cells induced by a TNF-alpha and IL-1beta co-treatment were largely inhibited by a KTBE treatment. The level of FLS cells proliferation was increased by IL-1beta and TNF-alpha, and strongly inhibited by KTBE treatment. The production of oxygen species (ROS) was inhibited by KTBE in FLS cells. KTBE appears to regulate the levels of mRNA that are important for regulating RA progression. |
19023553 | [Neurological complications of HIV infection]. | After the introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV (human immunodeficiency virus) infection in 1996, plications of this worldwide infectious disease declined in incidence and prevalence. During the following years however, prevalence and finally also incidence, especially of HIV-associated dementia and its precursor stages, rose again. Nowadays neurologists are confronted with HIV-associated neurocognitive disorders, depression, polyneuropathies and muscle disease, opportunistic brain infections (toxoplasmosis, cryptococcosis, cytomegalovirus infection, progressive multifocal leucoencephalopathy), rising rates of neurosyphilis, and the so-called immune reconstitution syndrome which therefore are topics of this review. |
19023551 | [Combined transvaginal and transumbilical approach for cholecystectomy with no visible scarring]. | The use of natural orifices for operations in the abdominal cavity (natural orifice transluminal endoscopic surgery, or NOTES) could be a conclusive development in the field of minimally invasive surgery. Early in the 1990s we had experiences with posterior colpotomy for removal of specimens in laparoscopic surgery. This is why we use the transvaginal approach in NOTES bine it with a trocar hidden in the umbilicus. With this technique we could perform cholecystectomy without a visible scar. The operation could e routine also because of the use of our well-known rigid optics and instruments. From June 2007 until April 2008 we operated on 57 patients using this method. All operations finished successfully, and the mean operation time was 54 min. There was plication. An abscess in the Douglas room had to be evacuated laparoscopically. All other postoperative courses were uneventful. After a minimum follow-up of 3 months, none of the patients had symptoms in the vagina or during sexual intercourse. |
19023554 | [Which antiepileptic drug for men with epilepsy? A critical epileptological and andrological review]. | Choice of antiepileptic drugs (AED) in the treatment of epilepsy is partly based on the assessment of drug-induced sexual dysfunction in men. We examined current knowledge on the effect of AED on reproductive functions in men with epilepsy. |
19023552 | [Prognostic factors for oral squamous cell carcinoma]. | The aim of the present study was to analyze different prognostic factors to calculate the overall survival in oral squamous cell carcinoma (OSCC). Samples retrospectively collected from 99 patients with primary OSCC were analyzed with regard to tumor node metastasis stage, grading, and 5-year survival time and summarized at an SPSS 11.0 databank. Treated were 72 men and 27 women (average age 59 years) due to oral squamous cell carcinoma. A general 5-year survival time of 57.3% was found. Patient survival depended on tumor size and the extent of lymph node metastasis: survival was 80.1% (n=23) for T1 tumors and only 16.2% (n=28) for T4 tumors, 68.7% (n=55) at the N0 stage and 42.8% at >N0 (n=44, chi(2) test P=0.01, Fischer's exact test P=0.014). Highly differentiated carcinomas (n=26) had a survival probability of 78.9% and G2 and G3 tumors of only 48.9% (n=73, chi(2) test P<0.001). Tumor size and lymph node metastases are decisive. |
19023556 | [Pathological changes of the hypopharynx in the focus of imaging]. | The spectrum of pathological changes in anatomical sections of the hypopharynx ranges from benign pathologies to hypopharyngeal carcinoma. Beside the clinical status and the endoscopic evaluation performed by ear, nose and throat specialists, imaging techniques play an important role in pre-therapeutic and post-therapeutic diagnostics and in the follow-up of pharyngeal disease patterns, especially for malignant lesions. A conventional x-ray swallow examination, contrast-enhanced puted tomography (MDCT) and magnetic resonance imaging (MRI), as well as positron emission tomography (PET) and positron emission puted tomography (PET-CT) are applied depending on the medical question and disease. Especially in radiological oncology, it is extremely important in regions which are clinically difficult to assess to determine the exact localization and extent of hypopharyngeal pathologies to plan the optimal therapy for the patient. This article demonstrates the radiological appearance of pathological changes of the hypopharynx and discusses in particular the hypopharynx carcinoma in the focus of pre-therapeutic and post-therapeutic imaging. |