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1.
《Drug metabolism and pharmacokinetics》2019,34(1):87-94
The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CLR (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CLR of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates. 相似文献
2.
目的总结利用骨外固定器行胫骨迁移治疗血栓闭塞性脉管炎的护理经验.方法对35例血栓闭塞性脉管炎37条患肢应用骨外固定器迁移胫骨治疗.术前积极处理患肢、有效的心理护理,术后严密观察,做好骨外固定器迁移胫骨的护理.结果 32例间歇性跛行距离增加;27例夜间静息痛均得到缓解;7例足趾缺血坏死中除3例术后患肢缺血加重截肢外,余4例患肢供血改善,坏死区域结痂愈合;总有效率91.9%.结论全面、准确地评估患者,完善术前准备及术后正确迁移指导可提高骨外固定器行胫骨迁移治疗血栓闭塞性脉管炎的有效性. 相似文献
3.
Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of
galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated
insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect
of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin
lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80
pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas
arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets
was dose-dependently suppressed by galanin (10-6-10-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower
dose levels, the peptide also inhibits basal glucagon release. 相似文献
4.
T B Vree Y A Hekster M W Tijhuis E F Termond J F Nouws 《Biopharmaceutics & drug disposition》1986,7(3):239-252
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes. 相似文献
5.
杨黛仙 《中国民族民间医药杂志》2010,19(17):68-69
目的:探讨生活方式治疗在血脂异常人群中的作用,观察其效果。方法:100例在体检中发现的血脂异常者,随机分为实验组和对照组,对实验组进行生活方式治疗,对照组未进行生活方式治疗,两组均未使用药物降脂,随访6—9个月,平均7.6个月,复查血脂,以检测血脂结果是否达到目标值进行对比。结果:经统计学处理,两组血脂在达到目标值方面存在显著性差异(p〈0.01)。结论:生活方式治疗对血脂异常人群具有明显的防治作用。 相似文献
6.
7.
目的:比较二维超声心动图(2DE)和心电图(ECG)对心肌梗塞(MI)定位诊断的异同、优劣。方法:对59例 MI 患者进行了2DE 和 ECG 检查。在2DE 上将左室分为16个节段而分别确定与 ECG 各导联的对应关系,分别计数2DE 上室壁运动异常(WMA)节段数和 ECG 上有异常 Q 波导联所对应节段数,对比分析两种方法检查结果的一致性。结果:2DE 和 ECG 分别检出338和311个节段阳性,两种方法阳性一致率57.9%,两种方法阳性一致率在各壁的高低依次为下壁、前壁、后壁、前间隔、侧壁;两种方法检测结果的差别有显著性(P<0.05);两种方法检测结果的相关系数 r=0.595(P=0.0000)。结论:两种方法的检查结果有较好的一致性,2DE 优于 ECG。 相似文献
8.
目的探讨儿童行为问题与社交能力之间的的关孔方法使用Achenbach’s儿童行为量表对1051名儿童进行筛查,检出98名行为异常者,计数统计其社交项目与总体儿童社交项目人数比较之,x2统计分析。结果在活动的技巧水平上,在家庭关系中,在校学习对知识的理解、掌握程度、心情舒畅程度等方面,异常儿不如总体(P<0.05),但在活动的时间、对外社交及学习成绩方面二者无明显差异(P>0.05)。结论儿童行为问题与社交能力的关系。并不是单一的正、负相关所能概括的,应该具体问题具体分析,审视其全面。 相似文献
9.
KYOSUKE YAMAMOTO NOBUHIRO FUKUDA LEI ZHANG TAKAHIRO SAKAI 《Pharmacological research》1996,33(6):337-342
The aim of this study was to examine the effects of dietary fenofibrate (0.05% in the diet) on ketone body production and lipid secretion in isolated perfused rat liver. Feeding with fenofibrate for 7–9 days caused an increased liver weight. Ketone body production was significantly greater in the livers perfused with oleic acid than in those perfused without fatty acid, with the elevation of the ratio ofβ-hydroxybutyrate:acetoacetate indicating an increased redox potential in mitochondrial compartments by exogenous fatty acid. On the other hand, fenofibrate feeding caused a further stimulation of ketone body production from both endogenous and exogenous fatty acid substrates, respectively, with a decreased ratio ofβ-hydroxybutyrate:acetoacetate as compared to respective control livers, indicating a decreased redox potential. Hepatic secretion of triglyceride, but not of cholesterol, was decreased markedly in the fenofibrate-fed rats, especially when oleate was provided, suggesting an inverse relationship between rates of ketogenesis and triglyceride secretion. These results suggest that the altered hepatic metabolism of long-chain fatty acids between oxidation and esterification caused by fenofibrate may thus be a factor responsible for the decreased secretion of triglyceride, hence leading to hypotriglyceridaemiain vivo. 相似文献
10.
天蚕素A-蛙皮肽杂合肽基因的表达及产物抗菌活性测定 总被引:5,自引:0,他引:5
目的 研究天蚕素A-蛙皮肽杂合肽基因[CA(1-8)-MA(1-12)]抗菌肽的抗菌活性。方法 将天蚕素A-蛙皮肽杂合肽基因抗菌肽的人工基因克隆到具有自切割功能的表达载体pTYB12上,并在大肠杆菌(E.coli)BL21(DE3)中进行表达,表达产物用几丁质树脂进行了亲和吸附,自切割后洗脱得到抗菌肽,进行透析以去除盐类物质,最后用大肠杆菌与金黄色葡萄球菌进行活性检测。结果 天蚕素A-蛙皮肽杂合肽[CA(1-8)-MA(1-12)]对大肠杆菌与金黄色葡萄球菌均有一定的抗菌活性。结论 天蚕素A-蛙皮肽杂合肽具有抗菌活性。其抑瘤活性的研究还有待于进一步研究。 相似文献