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101.
Malyshev IY Pshennikova MG Shimkovich MV Malysheva EV 《Bulletin of experimental biology and medicine》2004,138(3):230-232
Caspase inhibitor Z-VAD-FMK potentiated heat shock-induced apoptosis in macrophages. Z-VAD-FMK did not activate HSP70 synthesis, but significantly increased the intensity of this process during heat shock. It cannot be excluded that caspases abolish HSP70 accumulation under these conditions. The HSP70 synthesis inhibitor quercetin potentiated DNA fragmentation in macrophages cocultured with Z-VAD-FMK after heat shock. HSP70 play an important role in the protection of macrophages from caspase-independent apoptosis.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 261–263, September, 2004 相似文献
102.
Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility 总被引:16,自引:0,他引:16
BACKGROUND: Adding clomiphene citrate (CC) to FSH for controlled ovarian stimulation (COS) decreases FSH dose required for optimum stimulation. However, because of its anti-estrogenic effects, CC may be associated with lower pregnancy rates offsetting the FSH-dose reduction benefit. Previously, we reported the success of aromatase inhibition in inducing ovulation without antiestrogenic effects. METHODS: A prospective pilot study that included women with unexplained infertility undergoing COS and intrauterine insemination. Thirty-six women received the aromatase inhibitor letrozole + FSH, 18 women received CC + FSH and 56 women received FSH only. Each woman received one treatment regimen in one treatment cycle. All patients were given recombinant or highly purified FSH (50-150 IU/day) starting on day 3 to 7 until day of hCG. RESULTS: The FSH dose needed was significantly lower in letrozole + FSH and CC + FSH groups compared with FSH-only without a difference in number of follicles >1.8 cm. Pregnancy rate was 19.1% in the letrozole + FSH group, 10.5% in the CC + FSH group and 18.7% in the FSH-only group. Both pregnancy rate and endometrial thickness were significantly lower in CC + FSH group compared with the other two groups. Estradiol (E2) levels were significantly lower in the letrozole + FSH group compared with the other two groups. CONCLUSIONS: Similar to CC, aromatase inhibition with letrozole reduces FSH dose required for COS without the undesirable antiestrogenic effects sometimes seen with CC. 相似文献
103.
Plasminogen activator (PA) is a key enzyme in control of the cascade of extracellular proteolytic activities, proteases that degrade the extracellular components. Mammalian cells produce two molecular forms of PA, the urokinase type (u-PA) and the tissue type (t-PA); the u-PA type enzyme regulates cell migration/invasion and related tissue plasticity events. Thus, these plasticity properties of cells are defined by their PAs' biochemical profiles. The capacity of the differentiating glial cells of the central nervous system (CNS) to express and regulate the two types of PA activities has been examined as a function of cell age in culture. Results of the study suggest that only the immature astrocyte is endowed with these plasticity properties. Differentiating heterogeneous rat glial cells in culture express PA activity. Astroglia were identified as the primary source for the glial PA activity, as no PA activity was detected in the purified oligodendroglia. Cellular PA activity levels of differentiating rat and mouse astroglia are developmentally regulated. The specific activity of PA reached its highest level in rat astroglia at a cell age corresponding to 20-32 postnatal days (P20-P32) and in mouse astroglia at P8-P14; thereafter, this declined (three- to fourfold decrease) within 2 weeks to a low value. At comparable ages (P0-P35), the magnitudes of the PA specific activities of the differentiating rat astroglia and of the developing cerebrum, the tissue from which these cells were purified, were similar. Differentiating rat astroglia produce u-PA and t-PA, the cellular content of both is developmentally regulated, and the u-PA form is only found in the immature cells. u-PA is the predominant form in the immature astrocyte until age P13. Both forms are found in cells at ages P14-P30, and at later stages u-PA disappears while the t-PA type persists as the sole form. After 3 more weeks neither of the PA types was detected. Astroglia express also PA inhibitory activity; the rat astroglial PA inhibitor (PAI) seemed to be identical to PAI-1, one of the known types of PAIs. Stimulation of astroglial proliferation by their subculturing in contrast to Schwann cells did not lead to an increase; rather, beyond a certain cell age (P13) it resulted in a threefold irreversible decline in the PA specific activity of the daughter cells. It has been established that various biochemical properties of CNS mature glia appear on schedule with cell age in culture, thus defining "mature"glia in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
104.
MOTOYOSHI NOMIZU TAKANORI IWAKI TAKEYOSHI YAMASHITA YOSHIMASA INAGAKI KATSUHIKO ASANO MIKI AKAMATSU TOSHIO FUJITA 《Chemical biology & drug design》1993,42(3):216-226
One hundred Suc-X-Y-Ala-pNA peptides (SUC: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, x-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (Km, Kcat and Kcat/Km) were determined. These reaction constants were quantitatively analyzed using the Free–Wilson/Fujita–Ban method. The contribution of amino acid side chains to the reaction constants Km, Kcat and Kcat/Km), expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF3CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the Ki value of the inhibitor was generally correlated to the Km value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation This study may serve as a prototypical approach to unraveling structure–activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance. 相似文献
105.
Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease 总被引:1,自引:0,他引:1
S. Krähenbühl P. Grass A. Surve K. Kutz J. Reichen 《European journal of clinical pharmacology》1993,45(3):247-253
Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16).The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 g·h·l–1, 923 g·h·l–1 and 1300 g·h·l–1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively.Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h–1 in patients vs. 2.00 h–1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls.Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients. 相似文献
106.
“In vitro” and “ex vivo” effects of picotamide,a combined thromboxane A2-synthase inhibitor and -receptor antagonist,on human platelets 总被引:2,自引:0,他引:2
M. Berrettini M. De Cunto P. Parise S. Grasselli G. G. Nenci 《European journal of clinical pharmacology》1990,39(5):495-500
Summary Picotamide (G 137), a new non prostanoid inhibitor of in vitro arachidonic acid induced platelet aggregation, has been further characterized in in vitro and ex vivo studies.When whole blood was activated with collagen in the presence of picotamide 5×10–4 M, thromboxane B2 production was decreased, and 6-keto-PGF1 generation was significantly increased, suggesting a reorientation of platelet endoperoxide metabolism following blockade of thromboxane synthetase. Picotamide also inhibited platelet aggregation and clot retraction induced by the endoperoxide analogue U46619 in human platelets, indicating thromboxane A2-receptor antagonism, possibly of competitive nature.A single oral dose of picotamide 1 g in 24 healthy volunteers produced a significant inhibition of collagen, arachidonic acid and U46619-induced platelet aggregation. Serum levels of thromboxane B2 were also reduced.Chronic administration of picotamide 1.2 g/d to patients with vascular disease resulted in a prompt and persistent fall in their increased plasma levels of -thromboglobulin.The results indicate that picotamide is a combined thromboxane B2-synthetase inhibitor and thromboxane A2-receptor antagonist in human platelets, and that it may prove useful as an antithrombotic agent. 相似文献
107.
Objective To analyse the relationship between age and treatment with captopril after acute myocardial infarction (AMI). Methods In a randomized trial, 822 patients with a first AMI received conventional medic al treatment, including intravenous thrombolytic therapy and oral aspirin or metoprolol, and then were randomly allocated to captopril [dosage fr om the first 6.25 mg to 25 mg/t.i.d, 209 younger patients (≤64 years), 269 elderly patients (65-75 years)] or conventional treatment only (131 younger p atients, 213 elderly). Survival in the four groups was calculated with the Kapl an-Meier method. Multivariate analysis was performed to understand the degree that multi-variables (including age) affect survival in patients taking captopr il in the hospital or during long term follow-up. Results The survival of patients who took captopril correlated significantly with age ( P<0.001). The survival of the elderly patients on captopril treatment did increase (P<0.0001), but not of the younger ones (P>0.05) during hosp italization. During follow-up, the survival of patients who took captopril cor related insignificantly with age (P>0.05), but both the elderly and the you n ger patients have good survival rates (all P<0.01) and lower cardiac events (all P<0.01) when they took captopril.Conclusions Captopril exerts a weak effect on the younger patients but a beneficial effect o n the elderly patients during hospitalization after AMI. However, there is no d ifference between the younger and the elderly in the prognosis, both having good survival and lower cardiac events when they take captopril long term during fol low-up. 相似文献
108.
正、反义组织金属蛋白酶抑制剂1基因转染对肾小球系膜细胞凋亡及相关基因表达的影响 总被引:5,自引:0,他引:5
目的 探讨正、反义组织金属蛋白酶抑制剂1(TIMP-1)对肾小球系膜细胞凋亡的影响。方法 利用前期工作中克隆出的人TIMP-1全长cDNA,分别构建出表达正义及反义TIMP-1的重组真核表达载体pcDNA3-TIMP-1(PTs),pcDNA3-ATIMP-1(PTas),并将上述重组质粒转染至大鼠的肾小球系膜细胞中,Northern杂交检测正、反义TIMP-1的表达。无血清诱导大鼠系膜细胞凋亡,利用DNA缺口末端标记(TUNEL)分析、DNA电泳技术在无血清后的不同时间点检测细胞凋亡,RT-PCR的方法检测凋亡相关基因的表达。结果 转染PTas的大鼠系膜细胞可以高效表达反义TIMP-1,无于血清诱导12h开始发生凋亡;无外源基因转染及空载体转染的大鼠系膜细胞在无血清48h发生凋亡;而转染正义TIMP-1的大鼠系膜细胞可高效表达正义TIMP-1,在无血清4d时才发生凋亡。TIMP-1的高表达或低表达可引起大鼠系膜细胞bax的下调或上调,但并不影响bcl-2的表达。结论 TIMP-1可以抑制无血清诱导的大鼠系膜细胞的凋亡,反义TIMP-1对之则有促进作用。这提示TIMP-1在肾脏除了抑制细胞外基质的作用外还具有新的功能。 相似文献
109.
目的 观察未经治疗的原发性高血压患者的纤维蛋白溶解活性的变化及临床意义。方法 用发色底物法测定42例原发性高血压患者和40例血压正常者的血浆组织型纤维蛋白溶酶原激活物(t-PA)及其抑制剂(PAI-1)的活性和纤维蛋白溶酶原(Plg)活性。结果 原发性高血压患者血浆t-PA活性明显低于血压正常者,PAI-1和Plg活性明显高于血压正常者。结论 研究结果提示原发性高血压患者确实存在内源性纤溶功能低下。 相似文献
110.
目的 研究一氧化氮合酶抑制剂在短暂笥前脑缺血再灌注损伤中的作用。方法 钳夹沙土鼠的双侧颈总动脉制造脑缺血模型,应用尼氏染色观察迟发性神经元坏死的分布与。结果 短暂性前脑缺血导致海马CA1区锥体细胞迟发性神经元坏死,一氧化氮合酶抑制剂左旋硝基精氨酸(L-NNA)明显地减少了迟发性神经元坏死。结论L-NNA可能通过抑制NOS对脑缺血起保护作用。 相似文献