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991.
Effect of erythromycin on contractile response of uterine smooth muscle strips in non-pregnant rats 总被引:2,自引:0,他引:2
OBJECTIVE: Erythromycin stimulates stomach smooth muscle contraction via action on motilin receptors, but the effects of erythromycin on non-pregnant uterine smooth muscle are unknown. The purpose of this study was to assess the effect of erythromycin on non-pregnant uterine smooth muscle and to examine the possible mechanism of its action. STUDY DESIGN: Uterine smooth muscle strips from rats were suspended in organ baths containing Krebs solution, and then isometric tension was measured. The response to erythromycin and the effect of hexamethonium, indomethacin, phentolamine, diphenhydramine, atropine, metoclopramide and verapamil on erythromycin-induced contraction were also assessed. RESULTS: The present study showed for the first time that erythromycin dose-dependently increased contractile frequency, and at a dose of 1.55 x 10(-3) mol/l it also increased contractile tension in non-pregnant uterine smooth muscle strips in rats. These actions were not affected by pretreatment with hexamethonium, indomethacin, phentolamine, atropine and metoclopramide, but histamine H1 receptor blocker diphenhydramine and calcium channel blocker verapamil inhibited both responses induced by erythromycin. CONCLUSION: Our results suggest that erythromycin could increase contractile frequency and tension of non-pregnant uterine smooth muscle via histamine H1 receptor and calcium channel. 相似文献
992.
Wong BR Parlati F Qu K Demo S Pray T Huang J Payan DG Bennett MK 《Drug discovery today》2003,8(16):746-754
The ubiquitin system has been implicated in the pathogenesis of numerous disease states, including oncogenesis, inflammation, viral infection, CNS disorders and metabolic dysfunction. Ubiquitin conjugation and deconjugation to substrate proteins is carried out by multiple families of proteins, each with a defined role in the enzymatic cascade. This conjugation-deconjugation system parallels the kinase-phosphatase system in that both alter protein function by the addition and removal of post-translational modifiers. Our understanding of ubiquitin biology and strategies to interfere pharmacologically with the ubiquitin regulatory machinery is progressing rapidly. In light of increased interest in ubiquitin pathways as drug targets, we review the ubiquitin enzymatic cascades, highlighting therapeutic opportunities and enzymatic mechanisms. We also discuss the challenges of targeting this class of enzymes with small molecules, as well as current approaches and progress in drug discovery. 相似文献
993.
人晶状体上皮细胞系内肌醇1,4,5-三磷酸受体和兰尼碱受体的表达和作用 总被引:11,自引:2,他引:9
目的 确定人晶状体上皮细胞 (HLEC)系LEC B3细胞内两种钙池调控系统肌醇1,4,5 三磷酸 (IP3 )受体和兰尼碱受体的表达 ,并鉴定其亚型 ,初步探讨两系统对HLEC内Ca2 + 的调控作用。方法 传代培养HLEC系LEC B3细胞 ,选用第 3代融合状态良好的细胞 ,提取细胞总RNA ,反转录获取cDNA ,分别用IP3 受体的Ⅰ、Ⅱ、Ⅲ亚型和兰尼碱受体的Ⅰ、Ⅱ、Ⅲ亚型特异引物进行逆转录聚合酶链反应 ,判定分析mRNA的表达。并在激光扫描共聚焦显微镜下分别采用一定浓度的乙酰胆碱、阿托品、咖啡因、兰尼碱及普鲁卡因作用于细胞外液含Ca2 + 、Mg2 + 和不含Ca2 + 、Mg2 +的同代细胞 ,观察分析Ca2 + 信号的变化。结果 HLEC系LEC B3细胞中分别表达IP3 受体和兰尼碱受体的Ⅰ和Ⅲ型mRNA ,且均Ⅲ型表达强于Ⅰ型 (P <0 0 5 )。10 μmol/L乙酰胆碱、10mmol/L咖啡因及 5 0 μmol/L兰尼碱均可使细胞内Ca2 + 浓度增高 ,而波动的开始时间、幅度及持续时间因细胞外液成分和药物不同而异 ;1μmol/L阿托品可阻断乙酰胆碱的作用 ,5 0 μmol/L普鲁卡因可抑制兰尼碱的作用。结论 HLEC系LEC B3细胞内同时存在IP3 受体和兰尼碱受体基因的转录 ,且存在亚型特异性。两种受体的激动剂和抑制剂均可引起细胞内Ca2 + 浓度的变化 ,提示IP3 受体和兰尼碱受 相似文献
994.
Effects of the nerve growth factor on the survival and wound healing in mice with combined radiation and wound injury 总被引:4,自引:0,他引:4
High dose of ionizing radiation could cause bone-marrow aplasia and delay wound healing. Nerve growth factor (NGF) has been demonstrated to play roles in wound healing and to affect the functional activities of mature immune and hematopoietic cells. In this study, we investigated the effects of NGF on survival and wound healing in mice with combined radiation and wound injury. Immunohistochemical analysis indicated that the expression of NGF decreased significantly at postwounding days 3, 5, 7, 10 and 14 in wounded tissues combined with total body irradiation of 5 Gy. NGF significantly increased the survival and migration of skin fibroblasts with the irradiation of 15 Gy in in vitro experiments. Intraperitoneal and topical applications of NGF increased the survival rate, peripheral white blood cells and bone-marrow nucleated cells; they also promoted wound healing and increased the cell number of fibroblasts and blood capillaries in granulation tissues. These results showed evidence that NGF could increase wound healing and promote survival in irradiated animals. This dual effect of NGF may provide a new tool for the treatment of radiation-combined injuries. 相似文献
995.
The coat protein (CP) gene of cucumber mosaic virus (CMV) was cloned from a Chinese CMV isolate, the CaMV promoter and NOS terminator added and the gene construct was transformed into both sweet pepper and tomato plants to confer resistance to CMV. Safety assessments of these genetically modified (GM) plants were conducted. It was found that these two GM products showed no genotoxicity either in vitro or in vivo by the micronucleus test, sperm aberration test and Ames test. Animal feeding studies showed no significant differences in growth, body weight gain, food consumption, hematology, blood biochemical indices, organ weights and histopathology between rats or mice of either sex fed with either GM sweet pepper or tomato diets compared with those with non-GM diets. These results demonstrate that the CMV-resistant sweet pepper and tomato are comparable to the non-GM counterparts in terms of food safety. 相似文献
996.
In this ex vivo study, the inhibitory activity of hypocrellin A (HA), a perylene quinonoid pigment isolated from the Chinese medicinal fungus Hypocrella bambuase, on protein kinase C (PKC) enzyme activity in insulin target tissues of obese Zucker rats was assessed. Pre-incubation with HA for 30 minutes significantly inhibited the activity of partially purified PKC enzyme from liver and soleus skeletal muscle in a dose-dependent manner (IC50 = 0.07 and 0.26 microg/ml, respectively). HA produced a greater inhibitory effect in enzyme prepared from the liver than enzyme prepared from soleus muscle. Since total PKC activity in these two insulin target tissues is the net result of several different isoforms of PKC, and PKC-theta is a major isoform expressed in the soleus skeletal muscle, the present data suggest that the naturally occurring compound, HA, may selectively inhibit certain PKC isoforms other than PKC-theta. Further investigations are required to determine which PKC isoforms are most susceptible to HA and whether changes in PKC signaling during treatment with HA can reverse abnormalities of glucose and lipid metabolism in insulin resistant and diabetic states. 相似文献
997.
Barrero AF Quílez del Moral JF Lucas R Payá M Akssira M Akaad S Mellouki F 《Journal of natural products》2003,66(6):844-850
Ten new compounds, eight of them pimarane derivatives (1-8), together with a menthane dimer (9) and a totarane diterpenoid (10), were isolated from the leaves and wood of Tetraclinis articulata. The structures of 1-10 were established by using spectroscopic techniques, including 2D NMR spectra. Pimaranes 1-5 were found to possess an unusual cis interannular union of the B and C rings, which, from a biogenetic perspective, could be derived from the hydration of a carbocation at C-8. Compounds 4-6 and a mixture of 7 and 11 modulated different human leukocyte functions at a concentration of 10 microM, mainly the degranulation process measured as myeloperoxidase release and, to a lesser extent, the superoxide production measured by chemiluminescence. 相似文献
998.
"木香-槟榔"制剂对大鼠胃肠运动的影响 总被引:5,自引:0,他引:5
目的 观察木香、槟榔单独及配伍使用对大鼠胃肠运动的影响。方法 采用胃饲树脂小球并计数的方法计算胃排空率及采用高灵敏度应片传感器记录在体胃和离体十二指肠运动在用药(木香、槟榔、木香—槟榔)前后的改变。结果 单味木香制剂不能加快大鼠胃排空;使用单味槟榔和木香—槟榔制剂后胃排空率均快于对照组(P<0.05,P<0.001),但前者作用弱于后者(P<0.05)。木香、按榔、木香—槟榔制剂均使胃运动加快,木香、槟榔的作用较木香—核榔制剂小(P<0.001)。木香使离体十二指肠运动减弱,槟榔和木香—槟榔制剂则增强十二指肠运动,前者的作用较后者弱。结论 木香—槟榔配伍使用能增强胃肠运动,效果好于单独用药。 相似文献
999.
Recent data indicate that intravascular betaa-irradiation from centrally located sources at the time of balloon angioplasty or stenting reduces proliferation of smooth muscle cells, neointima formation, and restenosis. In an effort to simplify radiation delivery, a novel beta-radiation source was developed based on the adsorption of 32P (phosphoric acid) by pH-sensitive chitosan hydrogel on a poly(ethylene terephthalate) balloon surface. To prevent the 32P-isotope desorption in the patient's blood, the adsorbed phosphoric acid was precipitated as CaHPO4 on the surface by a saturated Ca(OH)2/5% CaCl2 solution. Various polyurethanes were applied to seal the radioactive surface by the dip-coating method. The isotope off-rate results were determined. Optimal results were obtained by serially coating with two polyurethane solutions. This approach holds promise for simplifying and improving the safety, and minimizing the cost of intravascular brachytherapy. 相似文献
1000.
Objective To investigate the effects of thoracic epidural blockade (TEB) on plasma fibrinogen (FIB) levels.Methods Thirty cases of dilated cardiomyopathy (DCM) were selected randomly into a TEB group and a control group. TEB patients were subjected to a persistent TEB (T1-5), and injected with 0.5% lidocaine 3-5 ml every two or four hours for four weeks in addition to routine medicine, while patients in the control group were given routine medicine only. Plasma concentrations of FIB were measured using the micro-capillary assay. Doppler echocardiography was performed before and after the treatment. Results Plasma concentrations of FIB in two groups were greater than the normal value before the treatment. There was a significant decrease of plasma concentrations of FIB in the TEB group after the treatment (4.2±1.3 g/L vs 3.6±0.9 g/L, P<0.05), but there was no significant change in the control group (4.2±1.2 g/L vs 4.3±1.9 g/L, P>0.05). After four weeks of treatment, the left ventricular end diastolic diameters (LVEDD) of TEB patients were reduced (72±10 mm vs 69±10 mm, P<0.05) and the left ventricular ejection fraction (LVEF) of TEB patients increased significantly (33%±13% vs 44%±14%, P<0.05). In contrast, LVEDD (73±11 mm vs 73±12 mm, P>0.05) and LVEF (32%±14% vs 33%±12%, P>0.05) did not change significantly in the control group. Conclusions The results suggest that plasma FIB levels in patients with DCM were decreased by performing a TEB, in addition to a reduction of the enlarged cardiac cavity and an improvement in cardiac systolic dysfunction. TEB might contribute to lowering the occurrence of thrombus and thromboembolism in patients with DCM. TEB might be a promising therapeutic method to improve the prognosis of DCM patients. 相似文献