Disposition of tacrolimus in isolated perfused rat liver: influence of troleandomycin, cyclosporine, and gg918.

The disposition of tacrolimus and the influence of cyclosporine, troleandomycin, and GF120918 (GG918, or N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine) on its hepatic disposition were examined in the isolated perfused rat liver. Livers from groups of rats were perfused in a recirculatory manner following a bolus dose of tacrolimus (100 microg), a substrate for P-glycoprotein (P-gp) and CYP3A, or with felodipine (200 microg), a substrate only for CYP3A. Perfusions of each substrate were also examined in groups of rats in the presence of the inhibitors: troleandomycin (20 microM, CYP3A inhibitor), GG918 (1 microM, P-gp inhibitor), or cyclosporine (10 microM, CYP3A and P-gp inhibitor). In all experiments, perfusate and bile were collected for 60 min. Tacrolimus, felodipine, and their primary metabolites were determined in perfusate and bile by liquid chromatography/tandem mass spectrometry. The area under the curve (AUC) from 0 to 30 min was determined. For the dual CYP3A and P-gp substrate, tacrolimus, AUC +/- S.D. was decreased from control (2,260 +/- 430 ng. min/ml) by GG918 (1,730 +/- 270 ng. min/ml, P < 0.05) and was increased by troleandomycin (5,200 +/- 2,470 ng. min/ml, P < 0.05) and cyclosporine (4,390 +/- 2,080 ng. min/ml, P < 0.05). For the exclusive CYP3A substrate, felodipine, AUC was unchanged from control by GG918 but increased by troleandomycin and cyclosporine. It is concluded that GG918 increased the hepatic exposure of tacrolimus by inhibiting the canalicular P-gp transport, whereas GG918 has no effect on hepatic disposition of felodipine. These results support our hypothesis that the hepatic metabolic clearance of a dual substrate will be increased by inhibiting the efflux transporter.     

2001年与2004年抗菌药物应用情况比较

目的　了解抗菌药物应用的基本情况。方法　将 2 0 0 1年 3月 14 3 0例住院患者病历与 2 0 0 4年 3月的 2 0 66例住院患者病历进行回顾性调查和对比分析。结果　 2 0 0 1年的 14 3 0例中有 948(66 3 % )例 ,和 2 0 0 4年的 2 0 66例有 10 60例 (5 1.3 % ) ,应用了抗菌药物。结论　定期检查考评 ,严格掌握用药指征 ,是加强抗菌药物应用管理的关键。     

20例胃平滑肌肿瘤的病理-X线分析

为了提高对胃平滑肌肿瘤的认识,作者回顾性分析了20例经手术、病理证实的胃平滑肌肿瘤的钡餐造影所见。结果表明,胃底与胃体上部是胃平滑肌肿瘤的病变高发区。本病具有典型胃粘膜下肿瘤的X线特征,腔内型者可见胃内边缘光滑的充盈缺损或软组织肿块,粘膜展平或推移;腔外型者可见突出胃外肿块或/和胃与邻近脏器受压;腔内外型者具有上述双重特征,肿瘤较大者多有溃疡形成,甚至囊变,根据肿瘤的大小、形态、生长类型及溃疡表现可作良恶性鉴别。本病的术前诊断主要依靠X线钡餐检查,但无胃肠压迫的腔外型肿瘤,钡餐则难以发现,CT或选择性血管造影可助诊断。     

浙江医科大学附二院门诊处方中精神药物使用调查

本文对浙江医科大学附属二院１９９３年７月间３１３７８张合格处方进行统计分析，并用限定日剂量（ＤＤＤ）和药物使用指数（ＤＵＩ）为指标，分析镇静催眠药物使用情况。结果表明苯二氮　类药方２０６７张，占总处方量的６．５９％，巴比妥类药方４９张，占０．１６％，麻醉药方１１１张；占０．３５％。苯二氮　类药方中．女性处方量１２０２张，男性处方量８６５张，男、女组间比较有显著性差异。苯二氮　类药方多分布在神经内科，常用的药有舒乐安定和阿普唑仑。九种常用的苯二氮　类药和麻醉性镇痛药的ＤＵＩ均小于１。提示药物滥用现象少见，该院对这类药物的管理比较严格。麻醉性镇痛药中二氢埃托啡处方占６７．５７％。     

AN-132 block of cardiac sodium channels: A gate-related receptor analysis

Summary Based on the gate-related receptor hypothesis, an analysis of kinetics of AN-132, a new antiarrhythmic agent, blockade of cardiac sodium channels and the gate-related receptor which is bound by the drug was performed by computer simulation. Model-predicted apparent rates of onset of AN-132 (30 μmol/L) blocking were 0.051, 0.038, and 0.034 AF⁻¹ at stimulation frequencies of 1.0, 2.0 and 3.0 Hz, respectively. The time constant of recovery from block by AN-132 at resting potential -90 mV was 39.5 s. These findings are in agreement with those experimental data documented. The analysis of gate-related receptor shows that AN-132 binds the inactivation gate-related receptor, and the binding and unbinding are modulated by the inactivation process.     

Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ

Lung function, smoking, age and mortality data in 158 adult severe alpha₁-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV₁ value was significantly associated with increased mortality (p < 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV₁ values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV₁ values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV₁ levels (p = 0.008) and higher mortality (p < 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV₁ level were not statistically significant (p = 0.9 and p>0.25, respectively). Cross-sectional analysis of the initial FEV₁ values indicated a significant decline (p < 0.005) of FEV₁ with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV₁ rates of decline in 80 cases with follow-up FEV₁ measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.     

山谷型垃圾填埋场渗滤液场内收集管网系统的设计计算方法研究

以苏州七子山垃圾填埋场为背景，采用理论分析的方法，探讨山谷型垃圾填埋场合理的渗滤液收集系统的形式和定量计算方法。     

Data Bank and Consulting System for Medical Management of Patiens with Acute Radiation Sickness

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Physiological pharmacokinetics of solutes in the isolated perfused rat hindlimb: Characterization of the physiology with changing perfusate flow,protein content,and temperature using statistical moment analysis

Distribution of Evans Blue (EB), sucrose, and water into the isolated perfused rat hindlimb was studied under various conditions using the multiple indicator dilution (MID) technique. Statistical moment analyses of the outflow profiles for the EB, sucrose, and water were used to define the vascular, extravascular, and total water spaces, respectively. The varied perfusion conditions included albumin content (2, 4.7, and 7%), temperature (25, 37, and 42 C), perfusate flow rate (2, 4, 8, and 12 ml/min) and the presence/absence of red blood cells. The range of studies undertaken were chosen to represent the variety of conditions used in the preparation of both isolated animal and human limbs, the latter being particularly important in cytotoxic therapy for recurrent malignant melanoma. The distribution volumes of EB, sucrose, and water were dependent on the flow rate and the albumin content of perfusate. The normalized variances (CV ² ) of the markers were of the following order: sucrose (2.18) > water (1.58) > EB (0.68), indicating that some disequilibrium occurs during the capillary exchange of water and sucrose. It is suggested that a Krebs-Henseleit buffer containing 2% BSA is a suitable perfusate for most studies of the isolated rat hindlimb perfusion. The effect of albumin concentration manifests itself only at higher flows.We acknowledge the support of the National Heart Foundation (Queensland) and the Mayne Bequest Foundation. This study was conducted while the investigator (Z.Y. Wu) was in receipt of a WHO Research Training Grant. Professor M. S. Roberts also acknowledges the support of the Queensland and Northern New South Wales Lions Kidney & Medical Research Foundation.     

阻断大脑中动脉建立大鼠局灶性脑梗塞模型的观察

通过经颅阻断大鼠大脑中动脉制成局灶性脑缺血动物模型。大脑中动脉阻塞后大鼠均出现各种神经病学征象。氯化三苯基四氮唑染色发现梗塞区位于皮质及基底节。光镜和电镜观察大脑中动脉阻塞后脑组织的病理改变,发现梗塞区不同程度的细胞和间质变性坏死。结果表明该模型是比较理想的局灶性脑缺血模型.