Pharmacokinetics of 1 -(2-Deoxy-2-fluoro-β-L-arabino-furanosyl)-5-methyluracil (L-FMAU) in Rats

Purpose. The objective of this study was to characterize the pharmacokinetics of 1 -(2-deoxy-2-fluoro--L-arabinofuranosyl)-5-methyluracil (L-FMAU), a nucleoside analogue with potent activity against the hepatitis B virus and the Epstein-Barr virus, in rats. Methods. Three doses of L-FMAU were administered intravenously (10, 25, and 50 mg/kg) to rats, and L-FMAU concentrations in plasma and urine were measured by HPLC. Pharmacokinetic parameters were generated by using area-moment analysis. Results. There were no significant differences in the pharmacokinetic parameters between the three doses ( < 0.05). Thus, the disposition of L-FMAU was linear over the dosage of 10 to 50 mg/kg. Plasma concentrations of L-FMAU declined rapidly with a terminal phase half-life of 1.33 ± 0.45 h (mean ± SD). Total clearance of L-FMAU was moderate, averaging 1.15 ± 0.28 L/h/kg. The fraction of compound excreted unchanged in urine was 0.59 ± 0.13. No glucuronide metabolite was found in the urine. The steady-state volume of distribution was 1.12 ± 0.26 L/kg indicating intracellular distribution of the compound. The fraction of L-FMAU bound to plasma proteins was approximately 15% and was independent of nucleoside concentration. Conclusions. The pharmacokinetics of L-FMAU in rats were independent of dose over the dosage range of 10 to 50 mg/kg.     

Modelling and monitoring organochlorine and heavy metal accumulation in soils,earthworms, and shrews in Rhine-delta floodplains

In the Rhine-delta, accumulation of microcontaminants in floodplain foodwebs has received little attention in comparison with aquatic communities. To investigate organochlorine and metal concentrations in a terrestrial foodchain, samples of soil, earthworms (Lumbricus rubellus), and shrew (Crocidura russula, Sorex araneus) livers and kidneys were taken from two moderately to heavily polluted floodplains.Chlorobiphenyl residues in earthworm fat were 0.10 to 3.5 times the concentrations in soil organic matter, whereas ratios for other organochlorines varied between 0.87 and 8.8. These ratios are one order of magnitude lower than expected from laboratory experiments with earthworms, and laboratory and field studies on aquatic invertebrates. Bioconcentration ratios for heavy metals are in accordance with literature values for other locations, confirming the high potential for cadmium accumulation in Lumbricidae.Concentrations of organochlorines in shrew liver lipids were 1.0 to 13 times the residues in earthworm fat. These values are higher than lipid-corrected biomagnification ratios for laboratory rodents, but equal to those measured for benthivorous birds in the Rhine-delta. On a dry weight basis, kidney-earthworm ratios for cadmium were about one order of magnitude lower than previously reported values for insectivores.Soil concentrations of many compounds in both floodplains did not meet Dutch quality standards. Yet, hexachlorobenzene, chlorobiphenyl 153 (PCB153), -hexachlorocyclohexane, DDT, and dieldrin residues in earthworms and shrews did not exceed diet levels expected to be safe for endothermic species. An exception was noted for cadmium in worms and shrew kidneys.Heavy metal pollution in soil was close to levels that are critical to earthworms in laboratory studies. Cadmium concentrations in shrew kidneys were below levels suggested to be safe for Sorex araneus, but above those that were critical to the rat.     

Growth hormone secretion in children and adolescents with familial tall stature

Sixty-five patients (22 boys and 43 girls) presenting with familial tall stature were investigated with regard to growth hormone (GH) secretion, both physiological and after stimulation with thyrotropin releasing hormone (TRH) and growth hormone relasing hormone (GHRH). Plasma insulin-like growth factor-I (IGF-I) was also measured. Two groups of patients were distinguished according to their physiological secretion of GH: a high secretory group (n=49) with a mean 24 h integrated concentration of GH (IC-GH) of 5.4±2.3 g/l per minute and a large number of peaks (5.1±1.6 in 24 h), and a low secretory group (n=16) with a mean 24 h IC-GH of 2.1±0.5 g/l per minute and few peaks (3.3±1.3 in 24h). Plasma IGF-I levels and GH peak values after the TRH test were significantly higher in the high secretory group. These results indicate that familial tall stature is the consequence either of hypersecretion of GH or of hypersensivity to this hormone (IGF-I levels being normal in spite of low GH levels).     

肌源性耳鸣的声导抗测试特征（附3例报告）

本文报道了１１例病例,并以３例典型病例就肌源性耳鸣的声导抗测试的基本方法和特征作了探讨。腭肌阵挛的幅度较大,在鼓室导抗图和声反射曲线上均可出现锯齿状波。镫骨肌阵挛在表情肌运动时可诱发,为持续性,镫骨肌声反射对其无影响或可掩盖之。鼓膜张肌阵挛与面部三叉神经受刺激有关,易疲劳,表现为一短暂的声顺变化波形。     

职业人群不健康行为生活方式与高尿酸血症的关系及高血压、血脂异常的效应修饰作用

目的 探索不健康行为生活方式与高尿酸血症的关系,以及高血压、血脂异常的效应修饰作用,为预防高尿酸血症提供理论依据。方法 采用横断面调查研究设计,基于2021年10-12月来自四川省、贵州省28个地级市和重庆市33个区（县）中国铁路成都局集团有限公司的西南职业人群队列基线数据,通过问卷调查、体格测量及实验室生化检测收集研究对象的人口学特征、行为生活方式、慢性非传染性疾病患病情况。不健康行为生活方式得分根据吸烟、饮酒、膳食模式、体力活动和低体重/超重状况进行评分,分值越高不健康行为生活方式越多。采用多因素logistic回归模型分析不健康行为生活方式评分、吸烟状况、饮酒状况等与高尿酸血症的关系,采用分层分析探索高血压等疾病对不健康行为生活方式与高尿酸血症之间关系的修饰效应。结果 共纳入11 748名研究对象,高尿酸血症患病率为34.4%。多因素logistic回归分析显示,现在吸/既往吸烟、现在饮/既往饮酒及BMI异常是高尿酸血症患病的危险因素,不健康行为生活方式对高尿酸血症患病风险呈现累积效应,随着得分的升高,高尿酸血症患病风险升高,OR值由1.64（95%CI：1.34~2.00）上升至2.89（95%CI：2.39~3.50）。分层分析结果显示,在高血压及血脂异常人群中,不健康行为生活方式对高尿酸血症患病风险影响更大。结论 多种不健康行为生活方式的共存会升高高尿酸血症患病风险,这一效应在高血压、血脂异常人群中更明显。及时纠正不健康行为生活方式,并控制高血压和血脂异常,降低患高尿酸血症的风险。     

急性有机磷农药中毒致大鼠肌无力的实验研究

目的探讨急性有机磷中毒致肌无力的机制。方法以乐果作为受试物,建立染毒后肌无力大鼠模型,测定血液、脑组织、肌肉组织胆碱酯酶（ＡＣｈＥ）活力。结果腹腔注射乐果后,大鼠全血、红细胞、血浆ＡＣｈＥ活力持续下降,至２４小时时,这三部分血液成分的ＡＣｈＥ活力分别由染毒前的（２３．４±４．６）μｍｏｌ／Ｌ、（１８．７±３．４）μｍｏｌ／Ｌ、（６．０±１．１）μｍｏｌ／Ｌ降至（２．１±１．６）μｍｏｌ／Ｌ、（１．５±１．１）μｍｏｌ／Ｌ、（０．８±０．５）μｍｏｌ／Ｌ。大鼠肌无力表现与血液ＡＣｈＥ活力变化不平行,二者相关程度较低（ｒ＝０．６４,Ｐ＞０．０５）。大鼠发生肌无力时,中枢及外周组织ＡＣｈＥ活力亦显著下降,但不同组织中ＡＣｈＥ活力下降的程度及趋势各不相同。肌肉组织与血液ＡＣｈＥ活力变化趋势较为一致。结论ＡＣｈＥ持续抑制可能不是肌无力的主要原因,其在肌无力发病中的意义需进一步研究。     

吸烟与动脉硬化性脑梗塞关系的研究

目的：探讨吸烟与动脉硬化性脑硬塞（ＡＳＣＩ）的关系。方法：对１０２例ＡＳＣＩ患者及１０８例正常人血清载脂蛋白（Ａｐｏ－Ｂ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、总胆固醇（ＴＣ）进行测定及对比分析。结果：ＡＳＣＩ组Ａｐｏ－Ｂ比对照组显著升高（Ｐ＜０．０１）,ＨＤＬ－Ｃ比对照组显著降低（Ｐ＜０．０１）,而ＴＣ两组间无明显差异（Ｐ＞０．０５）。在对照组及ＡＳ－ＣＩ组吸烟者Ａｐｏ－Ｂ均高于非吸烟者（Ｐ＜０．０１,Ｐ＜０．０５）,而ＨＤＬ－Ｃ吸烟者明显低于非吸烟者（Ｐ＜０．０１）。结论：吸烟能促使血清Ａｐｏ－Ｂ增高及ＨＤＬ－Ｃ下降,可以认为吸烟是ＡＳＣＩ的危险因素之一。     

一氧化氮,抗氧化剂,抗氧化酶与矽肺关系的研究

目的 探讨一氧化氮、抗氧化剂、抗氧化酶与矽肺的关系。方法 检测７３例矽肺患者和６０例健康对照者的血浆一氧化氮（Ｐ－ＮＯ）、维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素（Ｐ－β－ＣＡＲ）含量及红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）、过氧化氢酶（Ｅ－ＣＡＴ）、谷胱甘肽过氧化物酶（Ｅ－ＧＳＨ－Ｐｘ）活性。结果 与对照组比较,患者组的Ｐ－ＮＯ平均值显著升高（Ｐ〈０．００１）,Ｐ－ＶＣ、Ｐ－ＶＥ、Ｐ     

磁处理黄酒对实验性高脂血症大鼠血脂水平的影响

目的　研究磁处理黄酒对大鼠血脂水平影响,探索食物控制血脂新途径。方法　采用卫生部《保健食品功能学评价程序和检验方法》中调节血脂作用检验方法高血脂模型法进行本次研究。结果　高剂量组（７５０ｍ ｌ／ｋｇ）受试物能显著降低高脂血症大鼠血清胆固醇（ Ｔ Ｃ）和血清甘油三酯（ Ｔ Ｇ）的含量。结论　磁处理黄酒具有调节血脂作用,适量饮用对防止心血管疾病可能具有良好的保健作用。