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91.
92.
本文应用雄性小鼠生殖细胞非程序DNA合成(UDS)检测方法研究了“美容牌”染发剂对雄性生殖细胞DNA的损伤作用。发现该染发剂诱发的UDS与药物剂量呈线性正相关。提示此类染发剂对雄性生殖细胞DNA有损伤作用。其遗传毒理效应应引起注意。 相似文献
93.
L. J. Dowie J. E. Smith A. J. MacGilchrist R. Fraser J. W. Honour J. L. Reid C. J. Kenyon 《European journal of clinical pharmacology》1988,35(6):625-629
Summary The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 hydroxysteroid dehydrogenase, 17 hydroxylase or 11 hydroxylation; 21 hydroxylase activity may be marginally attenuated. 相似文献
94.
A. Awad P. Govitrapong Y. Hama M. Hegazy M. Ebadi 《Journal of neural transmission (Vienna, Austria : 1996)》1989,76(2):129-144
Summary The high concentration of zinc in the bovine pineal gland prompted us to investigate the existence of a zinc-binding protein in this organ. In this study, we report that the subcellular distribution of zinc in the bovine pineal gland is nonuniform, with the crude nuclear, mitochondrial, microsomal, and supernatant fractions having 0.264±0.038, 0.160±0.019, 0.130±0.016, and 0.287±0.010 g zinc/mg protein, respectively. Furthermore, gel filtration studies using Sephadex G-75 and a 105,000 g supernatant fraction revealed two zinc binding protein peaks that bind 1.7 and 3.7 g Zn++/mg protein, respectively. Furthermore, purification of the protein peak with an elution volume (ve/vo) of 2.06 on anion exchange chromatography (DEAE-A 25) yielded a single protein peak which binds 10 g zinc/mg protein. The comparative high performance liquid Chromatographic (HPLC) profiles of the zinc-induced hepatic metallothionein isoform I (retention time=17.39 min) and of the bovine pineal metallothionein-like protein isoform I (retention time=17.49 min) are similar. Since zinc is a potent inhibitor of sulfhydryl-containing enzymes and receptor sites, we investigated the effects of zinc and found that it inhibited the binding of [3H]glutamate (IC 50=80 M) and of [3H]spiroperidol (IC 50=0.6 mM) to the pineal membranes. The results of these studies are interpreted to indicate that the bovine pineal gland possesses an active and dynamic zinc homeostatic mechanism, whose precise function(s) remain(s) to be delineated. 相似文献
95.
Alexander Mülsch Eberhard Bassenge Rudi Busse 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(6):767-770
Summary Release of nitric oxide (NO) from endothelial cells critically depends on a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells. Therefore, we studied whether the free cytosolic calcium concentration directly affects the activity of the NO-forming enzyme(s) present in the cytosol from freshly harvested porcine aortic endothelial cells. NO was quantified by activation of a purified soluble guanylate cyclase coincubated with the cytosol. In the presence of 1 mM L-arginine, 0.1 mM NADPH and 0.1 mM EGTA, endothelial cytosol (0.2 mg of cytosolic protein per ml) stimulated the activity of guanylate cyclase 5.0 + 0.5-fold (from 31 + 9 to 153 + 15 nmol cyclic GMP formed per min per mg guanylate cyclase). Calcium chloride increased this stimulation further in a concentration-dependent fashion by up to 136 + 15% (with 2 M free calcium; EC50 0.3 M). The calcium-dependent and -independent activation of guanylate cyclase was enhanced by superoxide dismutase (0.3 M) and was inhibited by the stereospecifically acting inhibitor of L-arginine-dependent NO formation NG-nitro-L-arginine (1 mM) and by LY 83583 (1 M), a generator of superoxide anions. Our findings suggest a calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells.
Send of fprint requests to A. Mülsch, at the above address 相似文献
96.
Cyclic peptide disulfides of the general formula were synthesized from the corresponding peptide derivatives [Boc-Cys(Trt)(Gly)-n-Cys(Trt)-OBut] by oxidation with iodine in methanol and by subsequent removal of the terminal groups with trifluoroacetic acid. Acid ionization constants of the obtained peptides were determined by potentiometric titration in aqueous KCl (0.1 mol/L) medium. All compounds have two dissociable hydrogens, corresponding to carboxyl (pK1= 2.35–2.84) and to terminal amino group (pK2= 5.61–6.93); pK1, values show first an upward and then a downward trend with the increase in ring size; the opposite is true for pK2, values. These trends could be tentatively attributed to the intramolecular salt bridge (-COO——-NH+3-) formation. 相似文献
97.
Lebed'ko OA Timoshin SS Tsygankov VI 《Bulletin of experimental biology and medicine》2002,133(1):26-29
Newborn rats received single intraperitoneal injections of atrial natriuretic peptide (1-28) in a dose of 3.2×10-8 mol/kg on day 6 of life. Autoradiography with 3H-thymidine showed that the peptide inhibited DNA synthesis in smooth muscle cells of the respiratory tract. Pretreatment with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester attenuated, but did not abolish the effect of atrial natriuretic peptide (1-28). Histochemical assay for NADPH diaphorase showed that nitric oxide constitutively produced in the epithelium is involved in the growth-inhibitory effect of atrial natriuretic peptide (1-28) on proliferating smooth muscle cells. 相似文献
98.
目的:观察血小板源生长因子对培养的人血管成纤维细胞DNA及胶原蛋白合成的影响。方法:采用培养的人血管成纤维细胞,应用 [3H]-TdR和 [3H]-脯氨酸掺入的方法,观察血小板源生长因子-BB对人血管成纤维细胞DNA合成以及胶原蛋白合成的影响。结果:血小板源生长因子-BB可促进静止状态的人血管成纤维细胞DNA及胶原蛋白的合成,在 30μg/L浓度时DNA及胶原蛋白的合成达到高峰,DNA及胶原蛋白分别于 2 4h和 36h合成最为显著。结论:血小板源生长因子-BB可明显促进培养的人血管成纤维细胞DNA及胶原蛋白的合成 相似文献
99.
Jutisz M.; Starzec A.; Corbani M.; Counis R. 《Human reproduction (Oxford, England)》1988,3(4):485-489
Regulation of the synthesis of pituitary gonadotrophins LH andFSH has been studied in the rat using either cell-free translationof pituitary mRNAs, or hybridization techniques with syntheticoligodeoxynucleotides or cloned complementary DNAs. Gonadectomygreatly increases and supplementing gonadectomized rats withgonadal steroids diminishes the rate of synthesis of the gonadotrophinsubunits. Hybridization experiments suggest that gonadal steroidsregulate the expression of the genes coding for pituitary gonadotrophinsubunit precursors. Using the incorporation of labelled methionineby pituitary cells in culture, followed by specific immunoprecipitationof LH-related subunits and SDS-poly-acrylamide gel analysisof immunoprecipitated peptides, there was evidence that gonadotrophinreleasing hormone (GnRH) significantly enhances the radioactivityincorporated into both - and LH-subunits. This effect is specific,it is not a secondary effect due to the release of LH. A cyclicAMP (cAMP) analogue, 8-Br-cAMP, as well as forskolin and choleragen,which are cAMP generators and a diacylglycerol analogue, tetradecanoylphorbolacetate (TPA), mimic the stimulatory action of GnRH on the synthesisof the polypeptide chains of LH. However, no evidence has beenobtained that either cAMP or diacylglycerols mediate this GnRHeffect. These results suggest that the synthesis of pituitarygonadotrophins is under a double control of gonadal steroidsand GnRH which exert opposite effects, inhibitory for steroidsand stimulatory for GnRH. The negative control by steroids occursat the genomic level, while the positive effect of GnRH proceedsvia different mechanisms which remain to be elucidated. 相似文献
100.
Endothelin-1 (ET-1) is known to act via G-protein coupled receptors. It has therefore been suggested that any mitogenic activity it may possess, is due to activation of phospholipase C and protein kinase C (PKC). We have therefore examined both the ability of ET-1 to act as a mitogen and its ability to activate PKC. We found that ET-1 significantly increased thymidine incorporation and enhanced platelet-derived growth factor-induced DNA synthesis, as well as causing a prolonged translocation of PKC to the cell membrane. ET-1 significantly increased PKC dependent phosphorylation of two specific substrates. The phosphorylation of MBP4–14 (from myelin basic protein) was partially dependent on extracellular Ca2+, implicating activation of PKC-α, whereas phosphorylation of the so called ε-peptide was Ca2+-independent and prolonged. This could be due either to the δ or ζ isoform of PKC, known to be present in these cells. However, ET-1 induced little proliferation or PKC activity in a transformed smooth muscle cell line, DDT1 MF-2, which lacks expression of the PKC-αisoform, but expresses the ζ-isoform. Thus, it would appear that ET-1-induced mitogenicity in smooth muscle cells may be related to the sustained, Ca2+-independent activation of PKC-δ. 相似文献