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71.
72.
5-氟尿嘧啶加奥曲肽对乳腺癌细胞凋亡的影响 总被引:7,自引:0,他引:7
目的 探讨5-氟尿嘧啶(5-FU)加奥曲肽(善得定)对乳腺癌细胞凋亡的影响。方法取手术切除的16例乳腺癌标本,制备癌单细胞悬液。每例癌细胞均分成4组:5-FU组(加入5-FU10μg/ml)、善得定组(加入善得定0.1μg/ml)、5-FU加善得定组(加入5-FU10μg/ml、善和定01μg/ml)及对照组(不加任何药物)。用DNA断端标记法(TDT法)检测乳腺癌细胞癌细胞凋亡率。结果 16例标 相似文献
73.
肉毒碱治疗TPN大鼠肝脂肪变性的研究 总被引:4,自引:1,他引:3
目的 探讨在全胃肠外营养(TPN)中补充肉毒碱减轻肝脂肪变性的作用。方法 18只正常Wistar大鼠和19只肝硬化Wistar大鼠分别随机分为6组,A1组、A2组,自由进食和进水(各6只);B1组、B2组,TPN(分别6只、7只);C1组、 ,TPN加肉毒碱(各6只)。各组实验结束后测肝功能,肝脂肪及行肝脏的组织学检查。结果 TPN组肝内脂肪显著2,TPN+肉毒碱组肝内脂肪明显减少。结论 在TPN 相似文献
74.
水泥厂立窑烟气适宜除尘方法研究 总被引:1,自引:0,他引:1
目的 提出小水泥厂立窑烟气应选用的适宜除尘方法。方法 根据GB/T16157-1996固定污染源排气中颗粒物的测定和气态污染物的采样方法,并使用WY-1型烟道用7级冲击式尘粒分级仪等测定了立窑烟气的温度、露点温度、粉尘浓度、粉尘粒径分级组成等特性;测定了沉降室、旋风、冲击水浴、冲击-喷雾除尘器的粒径分级除尘效率等特性。结果 在上述基础上,将除尘器与尘源进行合理匹配,提出了排放达标的几种除尘器选型组 相似文献
75.
应用铈细胞化学方法镉诱发氧自由基对肾脏的损伤 总被引:3,自引:1,他引:2
目的 研究镉及其诱发的氧自由基对肾脏的急性损伤。方法 应用民镜细胞化学及能量色散谱分析技术。结果 镉离子可进入到肾近曲小管上皮细胞内,肾组织内有氧自由基的过量 产生,基 于血管内皮细胞,肾近曲小管上皮细胞的线粒体,微绒毛及其底膜等部位。肾近曲小管上皮细胞及细粒体可发生肿胀及内皮细胞脱落等病变。结论 镉离可导致氧自由基的大量形成,从面对肾脏造损伤。 相似文献
76.
1. 12,14-dichlorodehydroabietic acid (12,14-Cl2DHA) reduced GABA-stimulated uptake of 36Cl- into mouse brain synaptoneurosomes suggesting inhibition of mammalian GABA(A) receptor function. 2. 12,14-Cl2DHA did not affect the binding of [3H]-muscimol to brain membranes but displaced specifically bound [3H]-EBOB. The inhibitory effect on [3H]-EBOB binding was not reversible. 12,14-Cl2DHA reduced the availability of [3H]-EBOB binding sites (Bmax) without changing the KD of the radioligand for remaining sites. 12,14-Cl2DHA did not affect the rate of association of [3H]-EBOB with its chloride channel receptor, but increased the initial rate of [3H]-EBOB dissociation. 3. 12,14-Cl2DHA enhanced the incidence of EPSCs when rapidly applied to cultured rat cortical neurones. Longer exposures produced block of IPSCs with marked increases in the frequency of EPSCs and min EPSCs. 12,14-Cl2DHA also irreversibly suppressed chloride currents evoked by pulses of exogenous GABA in these cells. 4. Ultimately, 12,14-Cl2DHA inhibited all synaptic traffic and action currents in current clamped cells indicating that, in contrast to picrotoxinin (which causes paroxysmal bursting), it is not fully selective for the GABA(A) receptor-chloride channel complex. 5. The depolarizing block seen with 12,14-Cl2DHA in amphotericin-perforated preparations implicates loss of Ca2+ buffering in the polarity change and this may account for inhibition of spontaneous action potentials. 6. Our investigation demonstrates that 12,14-Cl2DHA blocks GABA-dependent chloride entry in mammalian brain and operates as a non-competitive insurmountable GABA(A) antagonist. The mechanism likely involves either irreversible binding of 12,14-Cl2DHA to the trioxabicyclooctane recognition site or a site that is allosterically coupled to it. We cannot exclude, however, the possibility that 12,14-Cl2DHA causes localized proteolysis or more extensive conformational change within a critical subunit of the chloride channel. 相似文献
77.
Our earlier studies have identified oligomycin sensitivity-conferring protein (OSCP), a subunit of proton F0F1-ATPase/ATP synthase in the mitochondrial inner membranes, as a new estradiol binding protein. This finding suggests that mitochondrial ATPase/ATP synthase could be a potential target for estradiol or compounds with similar structures. Here, we report that estradiol and several other compounds inhibited F0F1-ATPase activity of detergent-solubilized rat brain mitochondrial preparations in a following decreasing order: diethylstilbestrol (half-inhibition concentration, IC50 of 10-25 microM) > alpha-zearalenol, 4-hydroxyestradiol (1C50 of 55 microM) >2-hydroxyestradiol (IC50 of 110 microM), 17beta-estradiol, 17alpha-estradiol > beta-zearalanol > estriol, testosterone, 16alpha-hydroxyestrone > corticosterone, progesterone, dehydroepiandrosterone, dehydroepiandrosterone 3-sulfate, cholesterol (less than 10% inhibition at 140 microM). On the other hand, Na+, K+ -ATPase of porcine cortex showed different sensitivity to the compounds tested above. At 70 microM, the rank of inhibitory potency in decreasing order was as follows: 2-hydroxyestradiol (IC50 of 70 microM) > diethylstilbestrol> 4-hydroxyestradiol > progesterone > alpha-zearalenol, while other compounds had little effect (less than 5%). The data indicate that the ubiquitous mitochondrial F0F1-ATPase is a specific target site for estradiol and related estrogenic compounds; however, under this in vitro condition, the effect seems to require pharmacological concentrations. 相似文献
78.
Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein 总被引:9,自引:0,他引:9
Seabrook GR Smith DW Bowery BJ Easter A Reynolds T Fitzjohn SM Morton RA Zheng H Dawson GR Sirinathsinghji DJ Davies CH Collingridge GL Hill RG 《Neuropharmacology》1999,38(3):349-359
Abnormal processing of amyloid precursor protein (APP), in particular the generation of beta-amyloid (Abeta) peptides, has been implicated in the pathogenesis of Alzheimer's disease. This study examined the consequences of deleting the APP gene on hippocampal synaptic plasticity, and upon the biophysical properties of morphologically identified neurones in APP-null mice. The hippocampus of APP-null mice had a characteristic increase in gliosis throughout the CA1 region and a disruption of staining for the dendritic marker MAP2 and the presynaptic marker synaptophysin. The disruption of MAP2 staining was associated with a significant reduction in overall dendritic length and projection depth of biocytin labeled CA1 neurones. In two groups of APP-null mice that were examined at 8-12 months, and 20-24 months of age, there was an impairment in the formation of long-term potentiation (LTP) in the CA1 region compared to isogenic age matched controls. This LTP deficit was not associated with an alteration in the amplitude of EPSPs at low stimulus frequencies (0.033 Hz) or facilitation during a 100 Hz stimulus train, but was associated with a reduction in post-tetanic potentiation. Paired-pulse depression of GABA-mediated inhibitory post-synaptic currents was also attenuated in APP-null mice. These data demonstrate that the impaired synaptic plasticity in APP deficient mice is associated with abnormal neuronal morphology and synaptic function within the hippocampus. 相似文献
79.
Yang ZW Zheng T Wang J Zhang A Altura BT Altura BM 《Naunyn-Schmiedeberg's archives of pharmacology》1999,360(6):646-653
The effects of hydrogen peroxide (H2O2) on isolated canine basilar arteries, and single smooth muscle cells isolated from these arteries, were investigated in the present study. Exposure of isolated endothelium-intact and denuded arterial rings to H2O2, at concentrations of 2.2x10(-5) M to 4.4x10(-3) M, produced concentration-dependent contractile responses. Removal of the endothelium attenuated, but did not eliminate the contractions. H2O2-induced contractions were inhibited, to different degrees, by preincubation of the vessels with low concentrations of staurosporine or bisindolylmaleimide I HCl [antagonists of protein kinase C (PKC)], G?6976 (a PKCalpha and PKCbeta1 selective antagonist), genistein (an antagonist of protein tyrosine kinase), PD-98059 (an antagonist of mitogen-activated protein kinase), wortmannin [an antagonist of phosphatidylinositol 3 (PI3)-kinases], and LY-294002 (an antagonist of PI3-kinases). These agents were also found to relax arteries precontracted by H2O2. Removal of extracellular Ca2+ or pretreatment of the vessels with 5.0 microM verapamil markedly attenuated the contractions. Complete inhibition of the contractile response was obtained after buffering intracellular Ca2+ with BAPTA-AM. A variety of specific pharmacological antagonists of several known vasoconstrictors neither inhibited nor attenuated the H2O2-induced contractions. Exposure of smooth muscle cells to H2O2 (4.4x10(-6) M to 4.4x10(-4) M) significantly raised intracellular Ca2+ ([Ca2+]i) within 20 s. This was abolished in the absence of extracellular Ca2+ or after application of 5.0 microM verapamil. Pretreatment of the cells with low concentrations of staurosporine, bisindolylmaleimide I, G?6976, genistein, PD-98059, wortmannin, and LY-294002 markedly suppressed the H2O2-mediated [Ca2+]i elevation. The present findings suggest that hydrogen peroxide, in vitro, produces endothelium-dependent and independent contractions of canine basilar arteries, which are clearly Ca2+-dependent and are not associated with release of endogenous vasoconstrictors. Several intracellular signal transduction systems, such as PKC (both Ca2+-dependent and Ca2+-independent), protein tyrosine phosphorylation, IP3, mitogen-activated protein kinase and PI3 kinase appear to play a role in the H2O2-induced contractions in cerebral arterial muscle. 相似文献
80.
Bazinet M Karakiewicz PI Aprikian AG Trudel C Aronson S Péloquin F Dessureault J Goyal MS Zheng W Bégin LR Elhilali MM 《Urologic oncology》1996,2(2):65-69
The main objectives of this study were to reassess complications associated with transrectal ultrasound-guided biopsies (TRUSBx) of the peripheral zone (PZ) and to compare morbidity of exclusive PZ biopsy to morbidity associated with two additional transition zone (TZ) biopsies. We distributed a self-administered questionnaire assessing TRUSBx complications to 883 consecutive patients who underwent two systematic TZ TRUSBx in addition to systematic sextant PZ TRUSBx, and to 383 consecutive patients who underwent exclusive PZ TRUSBx. Of 316 (35.8%) patients subjects to TZ and PZ TRUSBx, 71% experienced hematuria, 63% hematospermia, 39% rectal bleeding, and 2.2% temperature elevation greater than 38°C. Of 137 (35.8%) patients who exclusively underwent PZ TRUSBx, 57%, 62%, 36%, and 1.4% reported these complications, respectively. Symptom duration and severity were similar in both groups. Although we report a substantially higher incidence of biopsy complications than previously published, these complications are self limited and require no intervention. Furthermore there appears to be no significant difference between complication rates associated with exclusive PZ biopsy compared with those associated with two additional biopsies of the TZ. 相似文献