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71.
Nicoletta Desideri Isabella Sestili Maria Luisa Stein Stefano Manarini Giuseppe Dell'Elba Chiara Cerletti 《Archiv der Pharmazie》1997,330(4):100-106
6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B4 and thromboxane B2 production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors. 相似文献
72.
73.
I. Hilakivi L. Ahtee J. O. Rinne T. Taira L. M. J. Attila P. Marjamäki 《Journal of neural transmission (Vienna, Austria : 1996)》1995,102(2):139-148
Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither3[H]SCH 23390 nor3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus. 相似文献
74.
The role of proteolytic enzymes in the hCG-induced increase in testicular vasopermeability and neutrophil extravasation was studied using protease inhibitors. An intra-testicular injection of hCG together with incubation medium conditioned by polymorphonuclear leucocytes (PMNs) caused a significant increase in vasopermeability and a coincident extravasation of PMN's from the postcapillary venules in the rat testis. When p-aminobenzamidine, a serine protease inhibitor which inhibits urokinase-type plasminogen activator, was administered together with hCG in the incubation medium, both the permeability increase and PMN extravasation were prevented. Aprotinin, another serine protease inhibitor, and Eglin C, a specific neutrophil elastase and cathepsin G inhibitor were, however, without effect. None of these inhibitors caused any non-specific vascular effects in the testis at the concentrations used. These results support the concept that the hCG-induced increase in vasopermeability in the rat testis is related to extravasation of PMNs and suggest that urokinase-type plasminogen activator is involved in migration of these cells through the postcapillary venular walls. 相似文献
75.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
76.
Juraj Sprung MD PhD David Distel CRNA Jeffrey Grass MD Eric L. Bloomfield MD Ian C. Lavery MD 《Journal of clinical anesthesia》1996,8(8):662-665
We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy was discontinued 20 days before surgery with general anesthesia. This patient developed severe perioperative hypotension after administration of 10 mg of bupivacaine through an epidural catheter, which was corrected only after potent vasopressor therapy. We attribute this hemodynamic instability to attenuation of this patient's sympathetic tone based on several mechanisms: (1) residual effect of long-term administration of MAO inhibitor that caused a decrease in the number of β-adrenergic receptors (adrenergic subsensitivity due to receptor down-regulation), (2) recovered MAO activity causing effective degradation of sympathetic amines, and (3) combined attenuating effects of general and epidural anesthesia on sympathetic tone. 相似文献
77.
根除幽门螺杆菌疗效与细胞色素氧化酶P450 2C19基因多态性的关系 总被引:3,自引:0,他引:3
目的 比较雷贝拉唑与奥美拉唑三联疗法根除幽门螺杆菌(Hp)的疗效与细胞色素氧化酶P4502 C19(CYP 2C19)基因多态性的关系。方法 采用随机、对照研究方法,将169例因消化不良症状接受常规胃镜检查确诊为慢性胃炎且Hp阳性的连续患者分人两组:雷贝拉唑三联疗法组(RAC组85例)和奥美拉唑三联疗法组(OAC组84例)。Hp诊断依靠组织病理学检查并参考快速尿素酶试验、血清Hp抗体检测结果。RAC组、OAC组均给予三联治疗:RAC组:雷贝拉唑10mg,OAC组:奥美拉唑20mg,两组均联用羟氨苄青霉素1000mg和克拉霉素500mg,全部药物每日2次,疗程7d。采用聚合酶链式反应结合限制性内切酶技术(PCR-RFLP),进行CYP 2C19基因型分析,治疗结束后第28天用^14C尿素呼气实验检测Hp根除疗效。结果 160例完成治疗方案,RAC组及OAC组的Hp根除率按PP分析及ITT分析均无统计学差异(P〉0.05)。根据CYP 2C19基因型分析,160例中,弱代谢型(PM)、中间代谢型(IM)及强代谢型(EM)的Hp根除率分别为95.5%(21/22)、85.9%(73/85)和67.9%(36/53)。PM型及IM型的Hp根除率均显著高于EM型(P〈0.05),而PM型与IM型间差异无统计学意义(P〉0.05)。RAC组中,各基因型的Hp根除率差异无统计学意义(P〉0.05)。OAC组中。IM型与EM型间(P〈0.01)及EM型与PM型间(P〈0.05)差异均有统计学意义。结论 雷贝拉唑与奥美拉唑两种三联疗法均能有效根除Hp。总疗效差异无统计学意义。雷贝拉唑三联疗法疗效较稳定,个体间差异小。PM型及IM型的Hp根除率均较EM型为高。 相似文献
78.
79.
陈世铭 《军医进修学院学报》1989,(4)
本文应用实验性重症肌无力模型研究了7种新的胆碱酯酶抑制剂对实验性重症肌无力的治疗作用,其中包括6种二甲氨基甲酸烷氧(烷硫)基苯酯及1种中草药提取物,大多数化合物对乙酰胆碱酯酶有较强的抑制作用,并见到有不同程度的治疗效果。二甲氨基甲酸-3-叔丁基-4〔2-(1-哌啶基)乙氧基〕苯酯不仅明显改善肌无力症状,而且毒性小、副作用较新斯的明轻,值得进一步研究。 相似文献
80.
为避免人工心肺机血液泵转速失控现像的发生,特研制人工心肺机监测系统,通过对血泵转速的实时监测,判断系统是否正常,自动进行相应的处理,提高现有系统的安全性。 相似文献