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排序方式: 共有711条查询结果,搜索用时 15 毫秒
1.
Kamil Kuca Kamil Musilek Daniel Jun Eugenie Nepovimova Ondrej Soukup Jan Korabecny 《Toxin reviews》2020,39(2):157-166
AbstractOxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074. 相似文献
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In order to functionally characterise the muscarinic vasodilator responses, effects of cholinergic agonists were studied on isolated preparations of the rat submandibular artery and vein and carotid and jugular vessels. Tentatively, a cholinergic regulatory mechanism having different effects on the arterial and venous vessels would enhance vascular fluid recruitment for the secretory response. In vitro functional findings were correlated to the expression and cellular location of the different receptors that were assessed by immunohistochemistry. In order to find in vivo correlates to the in vitro findings, the influence of muscarinic receptors on permeability was studied on the vasculature of the submandibular gland in anaesthetised rats. Staining for muscarinic M1 receptors occurred in the endothelium, and muscarinic M5 receptors, and possibly M3 also, were detected in the arterial smooth muscle. In venous endothelium, muscarinic M1 and M4 receptors occurred. In the jugular smooth muscle layer, staining for M1, and possibly also for M3, appeared. Muscarinic agonists caused arteries to relax and veins to contract. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine (L-NNA; 10(-4)M) markedly reduced the cholinergic-evoked relaxation of pre-contracted carotid arterial preparations. In the presence of 4-DAMP (10(-7)M), the relaxation to cholinergic agonists was inhibited. Pirenzepine (10(-5)M) did not only inhibit the relaxatory effects, but even reversed the effects, while it in the jugular vein abolished the cholinergic effects. The arterial nitric oxide-dependent response to muscarinic receptor stimulation consisted of two parts -- one sensitive to pirenzepine and 4-DAMP and the other to 4-DAMP only. Inhibition of the former part only, resulted in cholinergic arterial contraction. Also, the submandibular artery and vein responses to muscarinic receptor stimulation show a resemblance with those of the carotid and jugular vessels, i.e. a pronounced arterial relaxation and a contractile component in the venous response. In vivo examination of submandibular glandular vasculature by studying glandular permeability to Evans blue, confirmed the in vitro observations indicating muscarinic M1 receptors preserving perfusion pressure during the secretory process. 相似文献
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Hanus LO 《Medicinal research reviews》2009,29(2):213-271
Research on the chemistry and pharmacology of cannabinoids and endocannabinoids has reached enormous proportions, with approximately 15,000 articles on Cannabis sativa L. and cannabinoids and over 2,000 articles on endocannabinoids. The present review deals with the history of the Cannabis sativa L. plant, its uses, constituent compounds and their biogeneses, and similarity to compounds from Radula spp. In addition, details of the pharmacology of natural cannabinoids, as well as synthetic agonists and antagonists are presented. Finally, details regarding the pioneering isolation of the endocannabinoid anandamide, as well as the pharmacology and potential therapeutic uses of endocannabinoid congeners are presented. 相似文献
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T Reischig P Hribova P Jindra O Hes M Bouda V Treska O Viklicky 《Journal of the American Society of Nephrology : JASN》2012,23(9):1588-1597
Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival. 相似文献
8.
Trond Rasmussen Lars C. Stene Sven O. Samuelsen Ondrej Cinek Turid Wetlesen Peter A. Torjesen Kjersti S. R?nningen 《Diabetes care》2009,32(10):1904-1906
OBJECTIVE
To assess whether maternal BMI before pregnancy and weight gain during pregnancy predicted the risk of islet autoimmunity in genetically susceptible children.RESEARCH DESIGN AND METHODS
Of 46,939 newborns screened for the high-risk HLA genotype DR4-DQ8/DR3-DQ2, 1,003 were positive and 885 were followed with serial blood samples tested for autoantibodies to insulin, GAD, and insulinoma-associated protein 2 (IA2). The end point was defined as repeated positivity for two or three autoantibodies or the onset of type 1 diabetes (islet autoimmunity).RESULTS
Thirty-six children developed islet autoimmunity, of whom 10 developed type 1 diabetes. Both maternal BMI ≥30 kg/m2 before pregnancy and maternal weight gain ≥15 kg predicted the increased risk of islet autoimmunity (hazard ratio [HR] 2.5, P = 0.023, and HR 2.5, P = 0.015, respectively), independent of maternal diabetes.CONCLUSIONS
Maternal weight may predict risk of islet autoimmunity in offspring with a high genetic susceptibility for type 1 diabetes.Type 1 diabetes is caused by specific autoimmunity against pancreatic β-cells. The incidence of type 1 diabetes is increasing worldwide, and Norway currently has one of the world''s highest incidence rates (1,2). The etiology is multifactorial, determined by a combination of genetic and nongenetic factors. In Norway, 2.1% of newborns carry the HLA genotype DR4-DQ8/DR3-DQ2, which confers a relative risk for type 1 diabetes in excess of 20 and an estimated absolute risk of 7% by age 15 years (3,4). Nongenetic factors have been difficult to identify. Islet autoimmunity may start as early as in the 1st year of life before clinical type 1 diabetes with variable duration or even in utero (5). Studies have suggested that growth and obesity in childhood are associated with risk of type 1 diabetes and islet autoimmunity (6,7), but we are not aware of previous studies investigating the role of maternal BMI or weight gain in pregnancy. 相似文献9.
10.
Jaroslav Juracek Michal Stanik Petra Vesela Lenka Radova Jan Dolezel Marek Svoboda Ondrej Slaby 《Urologic oncology》2019,37(3):184.e1-184.e7