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41.
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
42.
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
43.
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
44.
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
45.
J. B. Payne R. A. Reinhardt M. P. Masada L. M. DuBois A. C. Allison 《Journal of periodontal research》1993,28(6):451-453
Gingival crevicular fluid (GCF) IL-8 and IL-1,1β levels were determined by sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1β GCF levels, and between these cytokines and patient estrogen status were evaluated. IL-8 and IL-1β were detected more frequently and in higher amounts/30 s GCF sample in estrogen-deficient patients than in estrogensufficient patients. IL-8 and IL-1β GCF levels were significantly correlated. These lindings suggest that GCF IL-8 levels are associated with patient estrogen status and local IL-1β concentrations. 相似文献
46.
47.
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
48.
Antiproliferative Activity Against MCF‐7 Breast Cancer Cells by Diamino‐Triazaspirodiene Antifolates
Xiang Ma Renee Ser‐Peng Woon Paul Chi‐Lui Ho Wai‐Keung Chui 《Chemical biology & drug design》2009,74(3):322-326
Two triazaspirodienes, having similar phenoxy propyloxy side chain, were identified as potent mammalian dihydrofolate reductase inhibitors; one having a 6,5‐spiro bicyclic ring system (IC50 = 2.3 nm ) and the other a 6,6‐spiro bicyclic system (IC50 = 6.9 nm ). They also showed more than 50% antiproliferative activity against the MCF‐7 breast cancer cells at 20 μm . This study demonstrated the potential lead of the diamino‐triazaspirodienes in anticancer chemotherapeutical agents’ discovery. 相似文献
49.
A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. 总被引:2,自引:0,他引:2
P Ken Gillman 《Neuropsychopharmacology》2006,59(11):1046-1051
Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed. 相似文献
50.
p53、nm23蛋白在宫颈鳞癌中的表达及其临床意义 总被引:4,自引:0,他引:4
目的研究p53、nm23基因在宫颈鳞癌中的表达及其临床意义.方法采用免疫组织化学S-P法检测45例宫颈鳞癌组织、10例宫颈上皮内瘤变和10例正常宫颈鳞状上皮中p53、nm23蛋白的表达.结果p53、nm23蛋白在宫颈鳞癌中的阳性表达率分别为64.44%、46.67%;在CIN中阳性表达率分别为0、30.00%;在NE组均无表达.p53蛋白在宫颈鳞癌中阳性表达与在CIN、NE中的不表达差异均有显著性(P<0.01).nm23蛋白在宫颈鳞癌组织中的阳性表达与在NE中的不表达差异有显著性(P<0.05),但与在CIN中的表达差异无显著性(P>0.05);与病理学分级、淋巴结转移均呈负相关(P<0.05,P<0.01).结论p53、nm23基因参与了宫颈鳞癌的发生发展过程.p53蛋白的过表达是宫颈癌组织恶性变的生物学标志;检测nm23蛋白对判断宫颈癌淋巴结转移和预后有重要意义. 相似文献