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Various Routes (various + route)
Selected AbstractsApoptosis via the B cell antigen receptor requires Bax translocation and involves mitochondrial depolarization, cytochrome C release, and caspase-9 activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2004Eric Eldering Abstract Various routes to apoptosis can be active during B cell development. In a model system of mature B cells, differences in caspase-3 processing have suggested that antigen receptor (BCR)-mediated apoptosis may involve a zVAD-insensitive initiator protease(s). In search of the events leading to caspase-3 activation, we now establish that both CD95- and BCR-mediated apoptosis depend on Bax activation and cytochrome C (cytC) release. Nevertheless, the timing and caspase-dependence of mitochondrial membrane depolarization differed considerably after CD95- or BCR-triggering. To delineate events subsequent to cytC release, we compared apoptosis induced via BCR triggering and via direct mitochondrial depolarization by CCCP. In both cases, partial processing of caspase-3 was observed in the presence of zVAD. By expression in 293 cells we addressed the potential of candidate initiator caspases to function in the presence of zVAD, and found that caspase-9 efficiently processed caspase-3, while caspase-2 or ,8 were inactive. Finally, retroviral expression of dominant-negative caspase-9 inhibited both CD95- and BCR-mediated apoptosis. In conclusion, we obtained no evidence for involvement of a BCR-specific protease. Instead, our data show for the first time that the BCR-signal causes Bax translocation, followed by mitochondrial depolarization, and cytC release. Subsequent caspase-9 activation can solely account for events further downstream. [source] Aziridines as templates: A general strategy for the stereospecific synthesis of 2-azetidinonesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2006S. D. Sharma Various routes to a variety of azridine-2-carboxylates have been described and the stereochemistry of these compounds has been determined by spectroscopic methods. Further, greater diversity of ,-lactams via ring expansion of these azridines-2-carboxylates were obtained by a general, efficient and direct stereospecific approach. [source] Inventory of shipping emissions in Izmit Gulf, TurkeyENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 2 2010Alper Kiliç Abstract Ships are significant emissions sources in transportation sector. The environmental effects of shipping emissions become more serious because of insufficient international rules and inspections. Especially in inland waters, canals, straits, gulfs, and port areas emissions effects on environment and health are more important. Izmit Gulf is the major industrial, transport, and inland water region which is affected from shipping emissions with 37 ports and industrial plants. In this study, NOx, SO2, CO2, HC, and PM emission amounts from 11,645 ships called to Izmit Gulf in 2005. These emissions are classified according to ships operation modes and ship types. Annual shipping emissions are estimated as 5,356 t yr,1 for NOx, 4,305 t yr,1 for SO2, 254,261 t yr,1 for CO2, 232 t yr,1 for HC and 487 t yr,1 for PM. To determine the most probably effected regions in the gulf, the spatial distribution of NOx emissions within the Gulf region has been prepared in 1 × 1 Nm2 (Nautical miles) grid cells based on ship movement data along the various routes. Ships in Izmit Gulf contribute to urban pollution with sulfur dioxide significantly. © 2009 American Institute of Chemical Engineers Environ Prog, 2010 [source] Permeation of Sumatriptan Through Human Vaginal and Buccal MucosaHEADACHE, Issue 2 2000P. Van Der Bijl DSc Continued interest in the various routes by which sumatriptan may be administered prompted us to investigate its passage through buccal mucosa. Because human buccal mucosa is scarce, we proposed using the relatively abundant vaginal mucosa, which has been shown to have comparable diffusion rates for a number of widely varying molecules, as a model of buccal mucosa. In addition, by comparing these two tissues with respect to their permeability to sumatriptan, the human vaginal/buccal mucosa model could be further evaluated. Clinically healthy human vaginal and buccal mucosa specimens were used in the permeability studies. Permeability to sumatriptan was determined using a continuous flow-through diffusion system in the presence and absence of permeation enhancers. No statistically significant differences in permeability could be demonstrated for both mucosae toward sumatriptan. Flux values obtained in the absence and presence of glycodeoxycholate and lauric acid (1:1 molar ratio) to sumatriptan of buccal and vaginal mucosa, respectively, were not significantly different. The results obtained further support the hypothesis of the vaginal/buccal mucosal in vitro permeability model and suggest that this model may be used in conjunction with various absorption enhancers. Further studies on the buccal route of absorption of sumatriptan are thus warranted. [source] Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injuryJOURNAL OF NEUROCHEMISTRY, Issue 5 2006Barry W. Festoff Abstract Minocycline, a clinically used tetracycline for over 40 years, crosses the blood,brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28 days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase-3 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor-,, as well as caspase-3 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans. [source] Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous routeNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2009S. Sisó Background: It is generally believed that after oral exposure to transmissible spongiform encephalopathy (TSE) agents, neuroinvasion occurs via the enteric nervous system (ENS) and the autonomic nervous system. As a result, the dorsal motor nucleus of the vagus nerve is the initial point of disease-associated prion protein (PrPd) accumulation in the brain. Hypothesis and aim: If direct ENS invasion following oral infection results in an early and specific brain targeting for PrPd accumulation, such topographical distribution could be different when other routes of infection were used, highlighting distinct routes for neuroinvasion. Methods: An immunohistochemical study has been conducted on the brain of 67 preclinically infected sheep exposed to natural scrapie or to experimental TSE infection by various routes. Results: Initial PrPd accumulation consistently occurred in the dorsal motor nucleus of the vagus nerve followed by the hypothalamus, regardless of the breed of sheep, PrP genotype, TSE source and, notably, route of infection; these factors did not appear to affect the topographical progression of PrPd deposition in the brain either. Moreover, the early and consistent appearance of PrPd aggregates in the circumventricular organs, where the blood,brain barrier is absent, suggests that these organs can provide a portal for entry of prions when infectivity is present in blood. Conclusions: The haematogenous route, therefore, can represent a parallel or alternative pathway of neuroinvasion to ascending infection via the ENS/autonomic nervous system. [source] First trimester abortion with mifepristone and three doses of sublingual misoprostol: a pilot studyAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2005Kishor C. SINGH Abstract Objective:, To evaluate the efficacy and safety of a medical abortion regimen with multiple doses of sublingual misoprostol 24 h after mifepristone. Methods:, The regimen was designed on the basis of pharmacokinetics of various routes of administration of misoprostol. Forty women 8 weeks' gestation were given mifepristone 200 mg orally, followed 24 h later by three doses of misoprostol 200 µgm sublingually 6 h apart. They were followed up on day 3 and day 14 with transvaginal ultrasound. Pain and bleeding were assessed using a visual analogue scale and acceptability, by a questionnaire. Results:, Abortion outcome was assessed in terms of onset of pain and vaginal bleeding, time of expulsion of products and duration of vaginal bleeding. Seventy-five per cent of women experienced pain within 2 h after first dose of misoprostol. Bleeding began at a mean of 1.41 h after pain and expulsion at a mean of 6.1 h after first dose of misoprostol. Complete expulsion was confirmed in all women (100%) by ultrasound on day 14. The longest duration of bleeding was 12 days (mean 7.2 days) with 87.5% bleeding for < 10 days. Acceptability was 100% but 70% perceived pain to be moderate and 67.5% bleeding to be light or slightly more than menses. Conclusions:, Medical abortion using three doses of sublingual misoprostol administered 24 h after mifepristone appears to be the most appropriate in terms of pharmacokinetics of the drugs. This pilot study associates the regimen with a short abortion process, which appears to be safe, highly efficacious and acceptable. [source] Systemic toxicity of tacrolimus given by various routes and the response to dose reductionCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 1 2005Laboratory Science Abstract Purpose:,To evaluate the long-term systemic toxicity of tacrolimus (FK-506) administered by various routes, and to assess the effect of dose reduction on toxicity. Methods:,The study animals were 120 experimentally naïve adult female Wistar rats weighing 200,250 g each. The rats were randomly divided into 10 equal groups (n = 12 in each) and treated with tacrolimus administered topically (in drops, 0.3%, q.i.d.), intravitreally (0.5 mg/kg bodyweight/week), intramuscularly (1 mg/kg bodyweight/week), low-dose intravenously (1 mg/kg bodyweight/week) and in high-dose intravenously (2 mg/kg bodyweight/week) for 3 months. The rats in the control groups (one for each different route of administration) were treated with 0.9% NaCl. The blood concentration of tacrolimus, complete blood count and biochemistry parameters were measured each month for the 3-month study period. Results:,The rats in the control groups and experimental groups administered topical and intravitreal tacrolimus did not demonstrate any systemic toxic effects. The rats that developed certain toxic effects (hyperglycaemia, hyperkalaemia and nephrotoxicity) in the groups given low-dose or high-dose i.v. tacrolimus responded well to dose reduction. Following dose reduction, blood glucose concentrations decreased from 247.4 ± 42.3 mg/dL to 189.6 ± 37.9 mg/dL (P < 0.05), and from 237.4 ± 41.1 mg/dL to 182.3 ± 22.7 mg/dL (P < 0.05) in the low- and high-dose i.v. tacrolimus-treated rats, respectively. The rats that developed impaired hepatic function after high-dose tacrolimus did not respond to dose reduction. Baseline cholesterol concentrations for the intramuscular and low- and high-dose i.v. tacrolimus-treated groups, demonstrated decreases, respectively, from 87.4 ± 14.0 mg/dL, 86.4 ± 14.0 mg/dL and 90.4 ± 14.3 mg/dL to 53.6 ± 9.8 mg/dL, 52.1 ± 12.5 mg/dL and 63.5 ± 11.7 mg/dL by the end of the second month. The differences were found to be statistically significant (P < 0.05 for each result). Conclusion:,Topical or intravitreal administration of tacrolimus seems to be systemically safe whereas parenteral administration can cause some systemic haematological changes such as dose-dependent decreased serum cholesterol concentrations. Dose reduction may prevent such adverse effects. [source] | ||||||||||