Hypocholesterolaemic mechanism of bitter melon aqueous extracts via inhibition of pancreatic cholesterol esterase and reduction of cholesterol micellar solubility

This study investigated the hypocholesterolaemic effects of bitter melon aqueous extracts (BMAE) in vitro, the inhibitory effects of BMAE on pancreatic cholesterol esterase (CEase) and incorporation of cholesterol into micelles were investigated. BMAE decreased the in vitro micellar solubility of cholesterol in a dose-dependent manner. The conformation of CEase was investigated by means of circular dichroism (CD) and fluorescence. The result revealed the decrease of α-helix contents, increase of β-sheet and exposure of aromatic amino acid residuals. The incorporation of cholesterol into micelles was inhibited by BMAE. A complex was observed by transmission electron microscopy (TEM), which indicated interaction between cholesterol and BMAE. The result revealed that BMAE can play a role in decreased intestinal cholesterol absorption via inhibition of CEase, and of micelle formation.     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

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 K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m 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 (CL_R) 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 CL_R (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 CL_R 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.     

刺五加水提物对人精子体外运动活力的影响

目的研究刺五加水提物对正常男性精子体外运动活力的影响，探讨其可能的作用机制。方法将20例正常男性的精子通过上游优化法处理后，一组精子加入10 mg·mL^-1的刺五加水提物，另一组加入等量的Ham’s F10培养液作对照。应用计算机辅助的精子分析系统，分别测定孵育0.5，1，2，3，4，5 h后人精子各运动参数。结果随着时间的延长，加入Ham’s F10培养液的精子活动能力有不同程度的下降；加入10 mg·mL^-1的刺五加水提物后，不同时段精子的运动能力均较对照组明显提高，精子存活率、前向运动精子百分率、曲线运动速度、直线运动速度和平均路径速度与对照组比较，均明显改善(均P＜0.05)。 结论刺五加水提物能明显提高正常男性精子的体外存活率和运动能力。     

有机锗对环磷酸胺抗移植肝癌作用的影响

用有机锗（Ge－132）试验治疗荷移植肝癌小鼠。结果：De－132高剂量（12．5mg/次）治疗组的抑癌率为用31．0％，移植肝癌白细胞（WBC）浸润（＋＋＋）占72．7％、血清超氧化物歧化酶（SOD）活性为121Nu／ml，而生理盐水对照治疗组相应的后两项指标分别为用36．4％及81Nu／ml，两组比较有显著性差异（P＜0．05）；环磷酰胺（CTX）治疗组的抑癌率为37.0％，癌体WBC浸润（＋＋＋）为27.3％，血清SOD活性为102Nu／ml；ge-132高剂量与CTX2联合治疗组的抑癌率为45．0％，癌体WBC浸润（＋＋＋）为54．5％，血清SOD活性为142Nu/ml，两组比较，后二项指标有显著性差异（P＜0．05）。由此提示Ge-132高剂量能明显增强荷移植肝癌小鼠的细胞免疫及血清SOD活性，并有一定的抗移植肝癌作用。     

Occupational hydrocarbon exposure and chronic nephropathy

This review aims at discussing the questions raised by the hydrocarbon-related chronic nephropathy and its possible consequence, the hydrocarbon-related chronic renal failure. It has been attempted to adopt the point of view of the clinician. Therefore, the most important part of the review is devoted to a presentation and an analysis of the available data on humans. The main features of the available studies on human subjects are presented, their conclusions discussed in the light of the possible methodological flaws, and practical conclusions drawn. After a discussion of the main difficulties encountered for selecting the suitable exposure indicator, the studies are discussed in order of decreasing quality of the study design (cohort, case-control, cross-sectional studies, and the case reports). It is concluded that a great deal of controversies about chronic hydrocarbon-related nephropathy is explained by differences in the study design and that hydrocarbon-induced nephropathy is probably more than a mere hypothesis, although a causal relationship has not yet been proven. Finally, some practical consequences for dealing with a hydrocarbon-exposed patient diagnosed with a kidney disease and the need for further research are discussed.     

饮水有机浓集物致突变活性影响因素的研究

本文探讨饮水有机物浓集流速及加氯量对致突变活性的影响。试验表明，饮水有机物浓集流速控制在每分钟２倍树脂柱床体积时，可获得最佳致突变效果。当加氯量≥２０ｍｇ／Ｌ时，对ＴＡ９８±Ｓ９和ＴＡ１００—Ｓ９菌株有致突变活性，≤２ｍｇ／Ｌ时对ＴＡ９８±Ｓ９和ＴＡ１００±Ｓ９菌株无致突变活性。为最大限度减少致突变效应，在净水过程中保证流行病学安全前提下，减少加氯量和加氯次数是十分必要的。     

白洋淀上游蓄污工程沿岸地下水污染状况及对居民健康影响的调查

白洋淀污染一直是国家和河北省所关注的问题，对白洋淀上游蓄污工程沿岸小环境调查表明；饮用深层地下水受到城市工业废水的污染，主要污染物为有机物。污染区儿童贫血率、白细胞计数、舒张压高于非污染区，白细胞吞噬率低于非污染区，居民恶性肿瘤标化死亡比高于非污染区，肝癌标化死亡比明显上升。     

蜂胶提取物对小鼠胸腺肽合成的影响

目的：研究蜂胶乙醇提取物黄酮（EEP）对小白鼠衰老过程中胸腺肽合成量的影响。方法：垂直板电泳法。结果：EEP可增加小鼠胸腺肽的合成量。结论：EEP可增强小鼠的免疫力。具有抗衰老作用。     

做好病理组织切片的方法

<正>病理技术是病理学的重要组成部分,并广泛应用于临床和科研工作中。病理制片的质量直接影响着病理诊断的准确性,为保证病理医师的诊断准确,结合20余年实际工作经验,谈谈做好病理组织切片的体会。