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目的 研究脂质过氧化代谢产物4-羟基壬烯醛(HNE)在糖尿病性白内障中的代谢过程以及发病中的作用.方法 实验研究.采用两因素析因设计:处理因素为两水平(正常对照组和糖尿病组),时间因素为三水平(30、45、70 d).对于不同时期的正常与糖尿病大鼠晶状体采用下列方法进行处理:(1)使用一定晕的带有放射活性的HNE与这些晶状体一起培养,测定HNE在晶状体的代谢;(2)分光光度计法测定醛脱氢酶(ALDH)活性;(3)免疫印迹法检测ALDH和HNE-蛋白质加合物的表达.采用两因素析因设计定量资料方差分析对资料进行统计学处理.结果 HNE在正常对照组的晶状体的代谢主要是与谷胱甘肽(GSH)结合形成GS-HNE(约45%),其次为经ALDH氧化成HNA(约9.1%);但糖尿病组晶状体的HNE与GSH结合径路受到抑制,GS-HNE形成减少,与正常组相比30 d时减少约64%(F=49.59,P<0.001);而糖尿病组晶状体的ALDH氧化径路代偿增强,HNA形成增多,70 d比30 d增多约1.7倍(F=11.51,P=0.0442).糖尿病组的晶状体ALDH活性增高,免疫印迹法显示ALDH较正常对照组增多,HNE-蛋白质加合物较对照组减少.结论糖尿病性白内障中HNE与GSH的结合径路受到抑制,而氧化径路代偿性增强,揭示了结合径路的损伤可能与白内障发生有密切关系,氧化径路的代偿增强可能对防止糖尿病性白内障的发生有一定的意义.(中华眼科杂志,2009,45:248-253) 相似文献
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Sheikh Rayees Rohit Sharma Gurdarshan Singh Ishtiyaq Ahmad Najar Amarinder Singh Dastagir Basheer Ahamad Subash Chander Sharma Manoj Kumar Tikoo Vijay Kumar Gupta Payare Lal Sangwan Surjeet Singh Surinder Koul Rakesh Kamal Johri 《Environmental toxicology and pharmacology》2013,35(2):347-359
An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h. 相似文献
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Ibrahim A. Aljuffali Mohd. Abul Kalam Yasmin Sultana Ahamad Imran Aws Alshamsan 《Saudi Pharmaceutical Journal》2015,23(1):85-94
Quantitative determination of gatifloxacin in tablets, solid lipid nanoparticles (SLNs) and eye-drops using a very simple and rapid chromatographic technique was validated and developed. Formulations were analyzed using a reverse phase SUPELCO® 516 C-18-DB, 50306-U, HPLC column (250 mm × 4.6 mm, 5 μm) and a mobile phase consisting of disodium hydrogen phosphate buffer:acetonitrile (75:25, v/v) and with orthophosphoric acid pH was adjusted to 3.3 The flow rate was 1.0 mL/min and analyte concentrations were measured using a UV-detector at 293 nm. The analyses were performed at room temperature (25 ± 2 °C). Gatifloxacin was separated in all the formulations within 2.767 min. There were linear calibration curves over a concentration range of 4.0–40 μg.mL−1 and correlation coefficients of 0.9998 with an average recovery above 99.91%. Detection of analyte from different dosage forms at the same Rt indicates the specificity and stability of the developed method. 相似文献
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Gap Junction Mediated Intercellular Metabolite Transfer in the Cochlea Is Compromised in Connexin30 Null Mice
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Connexin26 (Cx26) and connexin30 (Cx30) are two major protein subunits that co-assemble to form gap junctions (GJs) in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG) among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a novel pathogenesis process in the cochlea for Cx-mutation-linked deafness. 相似文献
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Delazar A Byres M Gibbons S Kumarasamy Y Modarresi M Nahar L Shoeb M Sarker SD 《Journal of natural products》2004,67(9):1584-1587
Reversed-phase preparative HPLC of a methanol extract of the rhizomes of Eremostachys glabra yielded three new iridoid glycosides, namely, 6,9-epi-8-O-acetylshanziside methyl ester, 5,9-epi-penstemoside, and 5,9-epi-7,8-didehydropenstemoside. Their structures were elucidated on the basis of spectroscopic data interpretation. The free-radical scavenging activity of these compounds was assessed using the DPPH assay. 相似文献