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Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU. 相似文献
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Problems associated with the use of 5-iodo-2-deoxyundine (IDU) in the treatment of herpes simplex keratitis can be attributed largely to the polar nature of IDU resulting in its poor permeability across the lipoidal epithelial layer of the corneal membrane. Five aliphatic 5-esters of IDU were synthesized and evaluated as prodrugs for potential use in the treatment of deep ocular infections such as stromal keratitis, iritis, and even retinitis. A parabolic relationship between in vitro corneal membrane permeability and carbon chain length of prodrugs is evident. For a given prodrug, enzymatic hydrolysis proceeded most readily in iris–ciliary body, followed by cornea and aqueous humor. An increase in carbon chain length made the prodrugs more enzymatically labile but more resistant to chemical hydrolysis at pH 7.4 and 34°C. The 5-butyryl ester of IDU exhibited an approximately fourfold increase in aqueous humor IDU concentration relative to IDU at 25 min following instillation of 25-µl 5 mM solutions. 相似文献
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Various 2-adrenoceptor agonists were assessed for their effects on alcohol abstinence syndrome in rats. In the first experimental model, groups of Wistar rats were made alcohol dependent by feeding alcohol together with sweetened milk for 15 days. The volume of fluid intake was measured every 12 h to determine daily ethanol consumption. Abstinence signs following abrupt alcohol withdrawal were observed in control as well as test groups receiving various 2-adrenoceptor agonists. Clonidine, guanfacine and B-HT 920, in equimolar concentration (0.5 M/kg), effectively attenuated the various abstinence signs, which developed after alcohol withdrawal. In the other experimental model, rats were subjected to cold water immersion to induce wet shakes. The inhibitory action of 2-adrenoceptor agonists was assessed in this test model. Clonidine, guanfacine and B-HT 920 markedly suppressed the cold water immersion-induced wet shakes and pretreatment with yohimbine (0.1 and 2.0 M/kg) reversed this inhibitory effect. The present data reveal the possible therapeutic potential of 2-adrenoceptor agonists in alleviating alcohol abstinence syndrome, and suggest that the resultant reduced noradrenergic activity may be responsible for the beneficial action. 相似文献
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Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the beta-globin locus control region 下载免费PDF全文
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Ronghe MD Foot AB Cornish JM Steward CG Carrington D Goulden N Marks DI Oakhill A 《British journal of haematology》2002,118(4):1124-1127
The impact of transfusion of leucodepleted platelet concentrates (PCs) on cytomegalovirus (CMV) disease was assessed in 215 allogeneic (145 unrelated and 70 related donor) transplants over 3 years. In 43%, both donor and patient were CMV seronegative (CMV-/-). All received CMV-seronegative red cells and random leucodepleted PCs. No CMV disease occurred in any CMV-/- (low risk) transplant. CMV infection occurred in 31 seropositive patients (26%); 13 died and five deaths were attributable to CMV disease. When compared with historical controls, who received CMV-seronegative PCs, we found no difference in transfusion-acquired CMV in the current cohort. 相似文献
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Samant Sanika Naik Milind Parulekar Karishma Charya Lakshangy Vaigankar Divya 《Proceedings of the National Academy of Sciences, India. Section B.》2018,88(2):747-754
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The present study foregrounds the isolation of selenium tolerant bacteria from Mandovi estuary of Goa, India,... 相似文献
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Sharma Gautam Ghati Nirmal Doshi Shrenik Sharma Shruti Sharique Mohd Agarwal Aman Devagourou Velayoudam Hote Milind Padmakar Choudhary Shiv Kumar 《Journal of interventional cardiac electrophysiology》2022,64(3):621-628
Journal of Interventional Cardiac Electrophysiology - Late-onset atrial fibrillation (LOAF) after valve surgery for degenerative mitral valve disease often with underlying mitral valve prolapse is... 相似文献