The influence of liver dysfunction on cyclosporine pharmacokinetics —A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs—

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. This research was performed in the Department of Surgery, University of Pittsburgh Health Center, University of Pittsburgh, USA     

Plasma volume estimation using indocyanine green with biexponential regression analysis of the decay curves

We studied seven analytical methods of estimating the plasma volume from the decay curves of indocyanine green. Fifteen volunteers received 1.0 mgkg⁻¹ of the dye by intravenous injection and the plasma concentration was measured continuously using spectrophotometry. Plasma volumes were calculated using three single-regression methods (1-a, 1-b, 1-c) and four biexponential regression methods (2-a, 2-b, 2-c, 2-d). The means (SD) of 1-a, 1-b and 1-c were 39 (5.0), 44 (5.7) and 54 (11.5) mlkg⁻¹, respectively, and these were significantly different from each other (p < 0.05). The values for methods 2-b, 2-c and 2-d were similar to each other: 39 (4.6), 40 (4.1) and 40 (4.0) mlkg⁻¹, respectively. These required more than 3 min circulation or mixing time. When the time allowed for mixing was less than 3 min (method 2-a) the plasma volume was underestimated. We conclude that plasma volume estimation using indocyanine green and spectrophotometry is most accurate when the mixing time is adequate (3–5 min) and the decay curves are analysed using biexponential regression.     

HBcAg显性失活突变体质粒的构建及体外表达

目的：探讨HBcAg显性失活突变体质粒pCDNA4-C-GFP的构建及体外表达。方法：选择编码乙肝核心抗原C基因片段及绿色荧光蛋白（green fluorescent protein,GFP)基因片段，利用基因重组技术构建成DNA质粒pCDNA4-C-GFP,并将该质粒转染肝癌细胞株HepG2。结果：通过RT－PCR检测到其RNA的表达，Confocal观察到GFP绿色荧光。结论：HBcAg显性失活突变体质粒pCDNA4-C-GFP的构建成功可以进行对HBV作用的研究。     

离子对提取比色法测定复方制剂中氨基比林的含量

复方制剂中氨基比林与溴甲酚绿形成稳定的离于对，用氯仿萃取后在４１６．８ｎｍ处测定吸收度．回收率为９９．８０％，相对标准偏差为０．９２％（ｎ＝５）。方法简便快速，结果准确可靠。     

EVALUATION OF INDOCYANINE GREEN RETENTION AND AMINOPYRINE BREATH TESTS IN PATIENTS WITH MALIGNANT BILIARY OBSTRUCTION

Impaired hepatic function is a major contributory factor to the high incidence of postoperative morbidity and mortality in patients with malignant biliary obstruction. Dynamic hepatic function tests such as indocyanine green (ICG) retention and aminopyrine breath tests were evaluated in such patients to define whether they were clinically useful for prediction of postoperative morbidity and mortality. Forty-four patients with malignant biliary obstruction undergoing surgery for relief of obstructive jaundice were recruited into the study. Indocyanine green retention and aminopyrine breath tests were carried out in all patients pre-operatively and repeated in 36 patients postoperatively. The ICG retention was abnormal in all patients before surgery and there was significant improvement 2 weeks after surgery (32.8 ± 2.5%vs 18.3 ± 2.8%, P= 0.001). The change in ICG retention levels correlated with the serum bilirubin levels but the pre-operative ICG retention value could not predict postoperative morbidity and mortality. The aminopyrine breath test was abnormal in all but one patient. It correlated with pre-operative prothrombin time of the patients before surgery but it did not improve significantly after surgery and was not predictive of postoperative outcome. It is concluded that both ICG retention and aminopyrine breath tests have limited clinical value in the pre-operative evaluation of patients with malignant biliary obstruction.     

绿茶对交链孢霉代谢物致突变性的抑制作用

观察绿茶对交链孢酚单甲醚(AME)和B_(2-a6)提取物诱导人胚肺2BS细胞SCE的影响。结果表明:不同浓度的绿茶,均不能增加SCE的频率,但在绿茶存在的情况下,由AME(10μg/ml)和B_(2-a6)(0.1mg/ml)所诱导的SCE频率比没有绿茶时低(P<0.01),并呈剂量—效应关系。结果提示:绿茶对某些霉菌毒素的致突变性有抑制作用。     

A prospective evaluation of changes in neuropsychological and liver function tests following transjugular intrahepatic portosystemic stent-shunt

Background/Aims: This study was designed to assess changes in: (a) neuropsychological tests, measures of memory, quality of life and scores for anxiety and depression; (b) liver function tests; and (c) the relationship between these following transjugular intrahepatic portosystemic stent-shunt.Methods: Twenty-nine patients undergoing transjugular intrahepatic portosystemic stent-shunt for recurrent variceal haemorrhage, 12 matched patients with cirrhosis and variceal haemorrhage manage with variceal band ligation and 16 normal controls were studied. Patients in any of the groups who were clinically encephalopathic were excluded from the study. Serial changes in the conventional liver function tests and Indocyanine green clearance, and psychometric function (Hospital Anxiety Depression Scale, Rivermead Behavioral Memory Test, Quality of Life and the memory and reaction sub-tests of the Cambridge Automated Neuropsychological Test Assessment Battery) were measured prior to and 1, 3, 9 and 15 months following transjugular intrahepatic portosystemic stent-shunt.Results: Over a mean follow up of 9.1 months in the transjugular intrahepatic portosystemic stent-shunt group (range 3–28), one patient (3%) developed clinically detectable encephalopathy. Sixty-seven percent of patients with cirrhosis showed evidence of subclinical encephalopathy as compared with the control population. Significant deterioration occurred in the reaction sub-tests of the Cambridge Automated neuropsychological Test Assessment Battery in patients, both in the transjugular intrahepatic portosystemic stent-shunt group and the controls with cirrhosis, during follow up. Transjugular intrahepatic portosystemic stent-shunt was followed by significant deterioration in levels of anxiety and psychological component of the quality of life. The Rivermead Behavioural Memory Test and the memory sub-test of the Cambridge Automated Neurpsychological Test Assessment Battery did, however, improve significantly at 1 and 15 months after transjugular intrahepatic portosystemic stent-shunt, respectively. Serum alanine aminotransferase, bilirubin and indocyanine green clearance deteriorated significantly following transjugular intrahepatic portosystemic stent-shunt (p<0.001, p<0.001 and p<0.0001, respectively). Significant correlation was observed between changes in the indocyanine green clearance and changes in the complex and simple reaction time subtests of the Cambridge Automated Neuropsychological Test Assessment Battery (r=0.6 and r=0.66, respectively).Conclusions: The results of this study showed that about 67% of patients with cirrhosis were subclinically encephalopathic and that temporary deterioration occurred in the Cambridge Automated Neuropsychological Test Assessment Battery during follow up, both in patients having transjugular intrahepatic portosystemic stent-shunt and in the controls with cirrhosis. These parallel the changes in the liver function tests and indocyanine green clearance. Temporary deterioration was also observed in the Quality of Life and Hospital Anxiety Depression Scale in the transjugular intrahepatic portosystemic stent-shunt group, although the measures of memory improved. Further studies should address the biochemical mechanisms of these changes and the role of prophylactic measures.     

苏乐康等抑制细胞转化能力及其机制的探讨

研究了苏乐康、绿茶提取物对~(60)钴γ射线和雌性激素联合诱发叙利亚金黄地鼠胚胎细胞恶性转化的抑制能力,并用脉冲辐解技术,对其抑制机制进行初步探讨。实验结果表明,苏乐康、绿茶提取物对γ射线和雌性激素联合诱发的金黄地鼠胚胎细胞恶性转化的抑制率分别为70.15％(P<0.05)和81.59％(P<0.05),它们的这种抑制能力与其清除超氧阴离子的能力有关,     

Ziehl-Neelsen-维多利亚蓝-碘绿复合染色法显示抗酸杆菌

目的 :探讨显示皮肤活检组织中抗酸麻风杆菌、弹力纤维和细胞等组织成分的复合染色法。方法 :运用Ziehl Neelsen(Z N)苯酚复红染色液、维多利亚蓝 (Victoriablue ,VB)染色液、碘绿 (iodinegreen ,IG)和马汀氏黄 (Mar tiusyellow ,MY)染色液对皮肤活检组织进行复合染色。结果 :组织内结核样结节中麻风杆菌显示为红色 ,细胞核呈淡绿色 ,细胞浆无色 ,结节周围的弹性纤维呈蓝色 ,基质呈淡黄色。结论 :Z N原法染色单一 ,对比效果差 ,应用碘绿、马汀氏黄和维多利亚蓝复合的改造染色液 ,能更好显示组织中的麻风杆菌 ,以及包绕于结核样结节周围的弹力纤维等成分 ,该方法是一种对比清晰 ,可靠的复合染色法     

荧光分析法测定血清中微量硒

为测定血清中微量硒,较低温度消化后,用2,3-二氨基萘为试剂,以荧光法测定,取得了满意的结果。方法简便快速,结果稳定准确。血清中加入标准硒,8次测定的回收率为96.6％～102.4％,平均值±标准差为99.6±1.8％。