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31.
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
32.
L. Niskanen H. Enlund V. Jormanainen A. Nissinen M. Uusitupa 《European journal of clinical pharmacology》1994,46(2):101-105
The utilisation of antidiabetic drugs reflects both the prevalence of diabetes and the different therapeutic traditions of physicians. A questionnaire survey to study attitudes to the use of oral antidiabetic drugs amongst physicians and possible changes in treatment habits was carried out in a representative sample of Finnish physicians (n=454) in 1992 and the results were compared with those of a similar survey carried out in 1985, and with drug utilisation statistics.The mean fasting blood glucose level at which a physician would start pharmacological treatment was 8.7 mmol·l–1, which was significantly lower than in the 1985 survey. The responses to various case histories suggested a more active approach to pharmacological treatment compared to the 1985 survey. Insulin treatment especially seems to have gained in popularity. This change in attitude was paralled by an increase in the consumption of antidiabetic drugs in Finland during the observation period. The increase in use of oral drugs was steeper in Finland than in Norway and Sweden.Whether this active approach will improve the metabolic control and prognosis of patients with Type 2 diabetes, remains to be demonstrated. 相似文献
33.
B. A. Reikhardt L. M. Belyavtseva O. G. Kulikova 《Bulletin of experimental biology and medicine》1992,113(5):682-684
Academician S. V. Anichkov Department of Pharmacology, Research Institute of Experimental Medicine, Academy of Medical Sciences, St. Petersburg. (Presented by Academician of the Academy of Medical Sciences A. N. Klimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 5, pp. 506–508, May, 1992. 相似文献
34.
[目的 ]观察解毒保肾汤治疗早期糖尿病性肾病的疗效 .[方法 ]将诊断为早期糖尿病性肾病的病人随机分为 2组 ,其中治疗组 4 4例给予解毒保肾汤 ,对照组 2 0例给予阳性对照药络汀新 ,观察治疗前后 2组病人的临床症状、空腹血糖、糖化血红蛋白量及尿蛋白排泄率等的变化 .[结果 ]治疗组总有效率为 80 % ,对照组总有效率为 6 5 % ,治疗组疗效优于对照组 ;治疗组在改善临床症状 ,降低空腹血糖、糖化血红蛋白量及尿蛋白排泄率等方面均优于对照组 .[结论 ]解毒保肾汤能够降低早期糖尿病性肾病患者的血糖、减少尿蛋白的排泄 ,具有一定的保护肾脏功能 ,对早期糖尿病性肾病有治疗作用 . 相似文献
35.
36.
目的探讨原发性高血压(EH)患者微量白蛋白尿(MCA)与血压及左室重塑的关系.方法 84名EH患者按24h尿微量白蛋白值分为微量白蛋白尿组(MCA组)和正常白蛋白尿组(NMCA组),进行动态血压、心脏超声检测,比较两组动态血压值、左室重量指数(LVMI)及左室重塑的特点.结果 MCA组平均收缩压、平均舒张压、脉压、平均动脉压均高于NMCA组(均P<0.01);MCA组LVMI、左室肥厚与向心性肥厚的发生率均高于NMCA组(均P<0.01),正常构型率低于NMCA组(P=0.01).LVMI与尿微量白蛋白值、平均收缩压、平均舒张压均呈显著的正相关(均P<0.05).结论合并有MCA的EH患者血压较高,LVMI较大,左室肥厚与向心性肥厚的发生率较高.MCA与血压及左室重塑密切相关. 相似文献
37.
RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature 总被引:12,自引:0,他引:12
Kai Temming Raymond M. Schiffelers Grietje Molema Robbert J. Kok 《Drug Resistance Updates》2005,8(6):381-402
During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to alphavbeta3-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization of alphavbeta3-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alphavbeta3. We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed. 相似文献
38.
A recent series of randomized prospective clinical trials that compared rate control with rhythm control in patients with atrial fibrillation (AF) found no significant difference in primary outcome between the two strategies. However, these trials lacked clear criteria for defining "successful" rate or rhythm control. Various measures have been used to gauge the success of antiarrhythmic drug therapy, including time to first recurrence of AF, any AF recurrence, AF burden, and a reduction in symptoms. Determining the success of antiarrhythmic therapy can be relatively straightforward by using how patients feel during therapy as a key endpoint. Most patients are satisfied with a major reduction in symptomatic AF episodes and can live comfortably with occasional episodes of AF. For those who are bothered by even infrequent, brief AF episodes, a treatment regimen that eliminates nearly all AF recurrences is required, although often hard to achieve. Catheter ablation may be necessary to achieve a successful outcome in these patients. Suppression of AF in a patient at high risk of stroke does not, however, remove the need for concomitant warfarin therapy. The endpoints of ventricular rate control are not clear, and the recently published rhythm versus rate control trials lacked standard criteria for judging acceptable rate control. One relatively simple method is to try and achieve a 24-hour heart rate that mimics expected normal sinus rhythm. It is important to achieve good rate control to minimize symptoms and the risk of tachycardia-mediated cardiomyopathy. 相似文献
39.
Although non-steroidal anti-inflammatory drug-induced colopathy is well described, colonic perforations complicating non-steroidal anti-inflammatory drug intake are rare. We report a patient with rheumatoid arthritis who was on long-term diclofenac and presented with early colonic stricture formation and a caecal perforation, which to the best of our knowledge, has only been reported once before. It is important to suspect this diagnosis in patients on non-steroidal anti-inflammatory drug therapy who present with an acute abdomen. 相似文献
40.
溃疡散预防消化性溃疡复发临床观察 总被引:4,自引:0,他引:4
冀慧鹏 《河南中医学院学报》2004,19(4):34-35
目的 :观察溃疡散对消化性溃疡的抗复发治疗的临床效果。方法 :随机将 80例患者分成溃疡散治疗组 (4 2例 )和雷尼替丁对照组 (38例 )并同时观察两组患者治疗前后溃疡复发情况。结果 :治疗后治疗组溃疡复发率明显低于对照组 ,P <0 .0 1,两组对比有非常显著性差异。结论 :治疗组能明显的改善患者临床症状和降低消化性溃疡复发率。 相似文献