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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.
教学与德育有机融会贯通,是当前教育领域的共识。医学本科生秉承"以德载医"的精神,肩负"治病救人"的重任,因此德育教育在整个医学教学中占有重要的地位。《医用有机化学》教材中含有丰富的德育内容,高校教师传授专业知识的同时,在教学过程中巧妙的穿插辩证唯物主义、爱国主义和社会责任感的思政教育,可以帮助学生们树立正确的世界观和人生观。文章以医用有机化学课程为例,主要从教师的自身道德素养、德育在教学过程中的具体实践和德育实施过程中需要注意的问题三方面进行阐述,充分将新时代新理念融入大纲、教案和课堂中,化"知识"为"智慧",变"文化"为"品格",充分发挥医用有机化学课程的德育功能。 相似文献
3.
建立了顶空毛细管GC法测定吉非罗齐中甲酸乙酯、THF和甲基环己烷3种有机溶剂的残留量。采用HP-1毛细管柱,溶剂DMA,内标乙酸乙酯。平均同收率分别为99.8%、100.3%、100.0%,RSD分别为0.71%、1.51%和1.76%。 相似文献
4.
T Kyrklund 《American journal of industrial medicine》1992,21(1):15-24
The nervous system differs from many other body organs by its central control of vital functions and its low regeneration capacity. Organic solvents have, as a group, been suspected to have neurotoxic effects. Because of their similar physical properties and the fact that in industrial uses, they are often present in various mixtures, organic solvents have also been regarded, unfortunately, to induce common neurotoxic effects. However, it is evident from experimental studies using specified exposure conditions that different organic solvents have very diverse neurotoxic effects and also that the toxic mechanism may differ between acute and chronic exposure. No specific method used to describe a neurotoxic effect or single toxic response can be used for the overall occupational risk assessment of all organic solvents. Each solvent has to be considered as having its own unique toxic effects. 相似文献
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6.
L. F. Trevillian A.-L. Ponsonby† T. Dwyer† L. L.-Y. Lim A. Kemp§ J. Cochrane† A. Carmichael‡ 《Clinical and experimental allergy》2003,33(4):483-489
BACKGROUND: Higher house dust mite (HDM) allergen exposure during infancy has been associated with increased HDM sensitization. Infant bedding has been associated with the accumulation of varying levels of HDM. Prospective data on the relationship between infant bedding and the development of HDM sensitization has not been previously examined. OBJECTIVES: To determine if particular types of bedding used in infancy are associated with increased risk of house dust mite sensitization in childhood. METHODS: A population-based sample (n = 498) of children born in 1988 or 1989, and who were resident in Northern Tasmania in 1997, participated in this study. These children were part of a birth cohort study (1988-95), the Tasmanian Infant Health Survey. Data on infant underbedding and mattresses was available on 460 and 457 children, respectively. The main outcome measure was HDM sensitization defined as a skin prick test (SPT) reaction of 3 mm or more to the allergens of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. RESULTS: The use of either sheepskin underbedding or plastic mattress covers in infancy was associated with an increased risk of sensitization to HDM allergens at age 8 years. The adjusted risk ratio (RR) for sensitization to HDM with sheepskin in infancy was 2.27 (95% CI: 1.14, 4.55), P = 0.020. The adjusted RR for sensitization to HDM with the use of plastic mattress covers in infancy was 2.06 (95% CI: 1.22, 3.51), P = 0.007. The use of a foam mattress in infancy was not related to subsequent HDM sensitization. CONCLUSION: Infant's bedding plays a role in the development of HDM sensitization in childhood. Intervention studies to examine mite allergen levels and the role of underbedding on the development of HDM sensitization are required. 相似文献
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9.
目的 研究巢湖水有机提取物致突变性。方法 单细胞凝胶电泳技术测定鱼红细胞DNA损伤效应。结果 巢湖源水引起慧星细胞的百分率最高 (5 7.2 5 % ) ,滤前水最低 (2 7.6 3% ) ,出厂水经过二次加氯后慧星细胞的百分率有所上升 (4 4 .0 0 % )。结论 巢湖源水具有潜在致突变性 ,经混凝、活性炭吸附及沉淀处理后其DNA损伤作用有所下降 ,但氯化消毒可增加水中有机提取物的DNA损伤作用。 相似文献
10.
Alexandra H. Heussner Evelyn O'Brien Daniel R. Dietrich 《Experimental and toxicologic pathology》2002,54(2):151-159
The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs. 相似文献