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41.
Effects of 4-Nonylphenol on Sex Differentiation and Puberty in Mosquitofish (Gambusia holbrooki) 总被引:1,自引:0,他引:1
Vincent Drèze Gilles Monod Jean-Pierre Cravedi Sylvie Biagianti-Risbourg Florence Le Gac 《Ecotoxicology (London, England)》2000,9(1-2):93-103
Three days post-parturition mosquitofish were exposed to different concentrations of 4-NP following a semi-static protocol. Exposure lasted up to the development of male anal fin in male individuals of the control group. Exposure to 50 g/L 4-NP resulted in 100% females considering secondary sexual characters, while external sex-ratio did not statistically differed from unity in control group. In group exposed to 0.5 and 5.0 g/L sex-ratio did not differ from unity but incompletely developed gonopodium was observed in several individuals. Individuals exposed to 50 g/L 4-NP exhibited female or undeveloped gonads, while gonadal sex-ratio did not statistically differ from unity in control group. Percentage of undeveloped gonads increased with 4-NP concentration. Additional observations demonstrated hepatic histopathology in fish exposed to the highest concentration and growth reduction dependent on 4-NP concentration. In a complementary experiment, extensive metabolism of [3H]4-n-NP was characterized following in vivo exposure of juvenile mosquitofish suggesting that metabolism could modulate 4-NP toxicity. This study suggests susceptibility of early life stages of mosquitofish to endocrine modulators with regard to development of reproductive capabilities. 相似文献
42.
Rationale l-Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS) and mediates its actions via activation of both ionotropic and metabotropic receptor families. The development of selective ligands, including competitive agonists and antagonists and positive and negative allosteric modulators, has enabled investigation of the functional roles of glutamate receptor family members.Objective In this review we describe the subunit structure and composition of the ionotropic and metabotropic glutamate receptors and discuss their pharmacology, particularly with respect to selective tools useful for investigation of their function in the CNS.Results A large number of ligands are now available that are selective either for glutamate receptor subfamilies or for particular receptor subtypes. Such ligands have enabled considerable advances in the elucidation of the physiological and pathophysiological roles of receptor family members. Furthermore, efficacy in animal models of neurological and psychiatric disorders has supported the progression of several glutamatergic ligands into clinical studies. These include ionotropic glutamate receptor antagonists, which have entered clinical trials for disorders including epilepsy and ischaemic stroke, -amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor positive allosteric modulators which are under evaluation as cognitive enhancers, and metabotropic glutamate receptor 2 (mGluR2) agonists which are undergoing clinical evaluation as anxiolytics. Furthermore, preclinical studies have illustrated therapeutic potential for ligands selective for other receptor subtypes in various disorders. These include mGluR1 antagonists in pain, mGluR5 antagonists in anxiety, pain and drug abuse and mGluR5 positive allosteric modulators in schizophrenia.Conclusions Selective pharmacological tools have enabled the study of glutamate receptors. However, pharmacological coverage of the family is incomplete and considerable scope remains for the development of novel ligands, particularly those with in vivo utility, and for the their use together with existing tools for the further investigation of the roles of receptor family members in CNS function and as potentially novel therapeutics. 相似文献
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44.
Purpose Multidrug resistance (MDR) is known as a problem limiting the success of therapy in patients treated long term with chemotherapeutic drugs. The drug resistance is mainly due to the overexpression of the 170 kDa P-glycoprotein (Pgp), which causes a reduction in drug accumulation in the cancer cells. In this study, novel chemical modulator(s) from bitter melon (Momordica charantia L.) extracts obtained from leaves, fruits and tendrils were tested for their abilities to modulate the function of Pgp and the MDR phenotype in the multidrug-resistant human cervical carcinoma KB-V1 cells (high Pgp expression) in comparison with wildtype drug-sensitive KB-3-1 cells (lacking Pgp).Methods The KB-V1 and KB-3-1 cells were exposed to bitter melon extracts in the presence of various concentrations of vinblastine, and cytotoxicity was assessed by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Relative resistance was calculated as the ratio of the IC50 value of the KB-V1 cells to the IC50 value of the KB-3-1 cells. Accumulation and efflux of vinblastine in KB-V1 and KB-3-1 cells were measured using a [3H]-vinblastine incorporation assay.Results The leaf extracts increased the intracellular accumulation of [3H]-vinblastine in KB-V1 cells in a dose-dependent manner, but extracts from the fruits and tendrils had no effect. By modulating Pgp-mediated vinblastine efflux, the leaf extracts decreased the [3H]-vinblastine efflux in KB-V1 cells in a dose-dependent manner, but not in KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with bitter melon leaf extracts increased their sensitivity to vinblastine, but similar treatment of KB-3-1 cells showed no modulating effect. The fruit and tendril extracts did not affect the MDR phenotype in either cell line.Conclusion The leaf extracts from bitter melon were able to reverse the MDR phenotype, which is consistent with an increase in intracellular accumulation of the drug. The exact nature of the active components of bitter melon leaf extracts remains to be identified. 相似文献
45.
微生态制剂对抗生素相关性腹泻预防作用的研究 总被引:13,自引:2,他引:13
目的 探讨微生态制剂培菲康、整肠生对抗生素相关性腹泻(AAD)的预防作用。方法 调查患有严重肺和(或)腹腔感染,静脉应用〉2种抗菌药物连续治疗〉5d,排除慢性胃肠道疾病的出院成年患者344例作为对照组;按≤59岁及≥60岁分为两组,了解AAD发生情况;再选择符合上述条件的住院患者141例,随机分为两组,在抗感染治疗的同时,分别加用双歧杆菌/嗜酸乳杆菌/粪肠球菌制剂(培菲康)或地衣芽胞杆菌胶囊制剂(整肠生),比较分析各组≤59岁及≥60岁患者AAD的发生情况。结果 对照组≥60岁患者AAD发生率(22.31%)明显高于≤59岁患者(8.88%P〈0.01);在抗菌治疗同时口服培菲康或整肠生两组≥60岁患者AAD发生率均明显低于对照组。结论 应用抗菌药物治疗同时,口服微生态制剂培菲康或整肠生均能有效预防AAD的发生。 相似文献
46.
目的 评价Ⅱ类新生物制品绿脓杆菌菌毛株菌苗(PAMSHA菌苗)作为免疫调节剂的有效性和安全性。方法 采用非盲法随机对照试验。试验组纳入肺癌患者44例,对照组45例。两组采用同样的化疗方案,试验组加用PAMSHA菌苗。治疗结束后评价疗效和感染率,并在治疗前、中、后分别检测患者免疫功能。结果 在临床疗效评价中,试验组有效率(CR+PR)为59.09%,对照组为42.23%(P<0.01);试验组感染率为15.91%,对照组为40%(P<0.05)。试验组治疗后C3、C4、CD4/CD8比值、NK细胞活性和IL2水平均高于对照组(P<0.05)。试验组中3例患者出现不良反应,仅1例给予特殊处理,其余自行缓解。结论 作为一类新的免疫调节剂,PAMSHA菌苗能明显提高肺癌患者的免疫功能,与化疗药物合用可提高疗效,并有预防感染作用。临床应用安全有效 相似文献
47.
《Expert opinion on pharmacotherapy》2013,14(7):949-956
Management of the menopause is a rapidly growing concern due to the ageing human population. The overall female lifespan has increased over the last century and up to a third of a woman’s life is now spent in menopause. To that end, significant attention has been placed on maximising the quantity and quality of life in the menopausal years. The optimal management strategies are ones that are highly flexible and sensitive to an individual’s expectations and concerns. Thus, while traditional oestrogen replacement therapy has been in place for > 20 years, there is now a greater interest in alternatives to this modality for those women who cannot or will not use it. This article reviews some of the alternative therapies that are being incorporated both in the allopathic and complementary medicine arenas. 相似文献
48.
《Expert opinion on drug discovery》2013,8(6):691-708
Introduction: Cystic fibrosis (CF) is the most prevalent, recessively inherited, disease in the western world. It is characterized by gene mutations in CF transmembrane conductance regulator (CFTR), a transmembrane ion channel that is responsible for chloride secretion in the airway passages. Although much is known about the defects in CFTR and the consequences of these mutations, CF therapy currently focuses on the secondary outcomes and symptoms of the disease. However, developments in CFTR modulators may bring about new therapeutic options. Areas covered: The authors discuss CFTR defects, as a molecular basis, before presenting and discussing CFTR modulators including correctors and potentiators. Specifically, the authors review promising CFTR modulators currently in preclinical and clinical development along with their medicinal chemistry and structure–activity relationships (SARs) and their in vitro and in vivo pharmacology. Expert opinion: Although the development of CFTR-targeting agents has little access to structural information from crystal structures, several promising compounds have been discovered so far. Advanced virtual models of CFTR and high-throughput assays have helped the developmental programs. While Ivacaftor, the first of the CFTR potentiators, has now reached clinical use, CFTR corrector development has not been successful thus far. However, intense research of the mutation F508del, the mutation considered the most frequent in CF, could provide new causal treatment options in the future. Furthermore, the eventual synergy with multiple correctors may bring further success. CFTR modulators provide a new personalized therapeutic option where CF therapy is based on the mutations patients carry rather than by simply their symptoms. 相似文献
49.
急性重症胰腺炎继发感染的大黄复方免疫疗法的临床实验研究 总被引:1,自引:0,他引:1
目的:初步探讨大黄复方综合免疫疗法对ASP继发感染的治疗作用。方法:肠道菌群检测和免疫组化,放射免疫分析法研究了ANP模型肠道菌群变化和肠道局部免疫的变化,在此基础上进一步对严格按标准选入的ASP病人,采用中药大黄复方及微生态制剂综合疗法分别在临床表现,生化及血清内毒素,肠道局部免疫与细菌易位等方面进行对比研究。结果:ANP肠道膜菌群生物屏障受到破坏,G^-肠杆菌是急性重症胰腺炎内源性感染的主要原因菌,综合免疫疗法治疗后1周及2周的生化指标及血清内毒素水平降低均优于常规组,结论:初步表明综合疗法能减轻或消除ANP继发感染临床表现,缩短感染持续时间。 相似文献
50.
A heat-stable trichloracetic acid-stable protein fraction stimulates protein kinase activity in chick brain cytosol. This protein kinase (tentatively referred to as protein kinase S) can be partially purified by chromatography on DEAE-cellulose and Sepharose G-100. The partially purified protein kinase has an absolute requirement for magnesium and the heat-stable protein for the phosphotransferase activity and is not influenced by cyclic nucleotides, calcium or ethylenediaminetetraacetic acid. The substrate specificity of protein kinase S indicates that it is not a casein kinase and prefers histones over the substrates tested. The specific activity of this protein kinase changes with chick brain development and the activity increased by two-fold by the second post-hatch week, suggesting a role of this protein kinase in chick brain development. 相似文献