Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemiareperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirtyone HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16)， 1×105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P＜0.05). On the first postoperative day, the plasma CRP concentration in the UTI group was significantly lower than that in the control group(P＜0.01). The plasma cortisol level in the control group markedly increased compared with the level before operation(P=0.046). However, there was no significant difference in the UTI group between before and after operation. Conclusion Ulinastatin can effectively protect liver from ischemia/reperfusion injury in HCC patients undergoing hepatectomy performed after hepatic inflow occlusion. Also, it can relieve the surgical stress for patients.
Objective To study the distribution and concentration of meropenem in rabbit bile. Methods The rabbits were cannulated with a silicone tube in the common bile duct and the blank bile was collected. The rabbits were then administered intravenously with meropenem. Multiple bile samples (1.5 ml) were collected at different phases after the administrations. According to requirement of the high performance liquid chromatography (HPLC), the specificity test was undertook. The blank bile was then mixed with meropenem and mobile phase, respectively, in order to obtain a series of bile samples at different concentrations ranging from 0.5 to 500 μg/ml. The samples were analyzed with HPLC and the chromatographic peak area of meropenem contents were quantitated through external reference method. The linear regression equation was used to analyzed the relationship between the drug concentrations and the chromatographic peak areas. The bile samples that were collected after drug administrations were pretreated and the chromatographic peak areas were assayed by the liquid chromatograph. The bile concentrations were then calculated according to the regression equation, and the concentration-time distribution of meropenem in the bile was obtained ultimately. Results The specificity test indicated the bile dopant peak and the meropenem chromatographic peak were well-separated under chromatographic condition of the mobile phase. The standard curve regression equation was S=2 209.10C-1 251.34, r=0.999 9, and minimum quantitation limit of meropenem was 0.5 μg/ml. After a single i.v. administration of 75 mg/kg of meropenem in each rabbit, drug concentrations reached (38.36±14.17) μg/ml immediately in bile， which significantly exceeded the minimum inhibitory concentrations (MIC90) for most gram negatives, which range from 0.031 to 2 μg/ml. The bile concentration of meropenem decreased quickly over time, and meropenem was eliminated completely in rabbit bile 3 hours after intravenous injection. Conclusion Meropenem could achieve adequate bile concentration for the treatment of biliary tract infection due to susceptible bacteria. However, because of its rapid biliary elimination, meropenem should be used in shorter interval time.
Objective To study the effect and feasibility of gradual oral diethylnitrosamine (DENA) induced liver cirrhotic model in rats under avoirdupois monitoring. Methods Fifty Wistar rats (6 weeks old) were divided into 3 groups: normal control group （n=10）, traditional DENA induction group (receiving traditional oral DENA treatment, n=20）, gradual DENA induction group (receiving gradual oral DENA treatment under avoirdupois monitoring, n=20). The weight, mortality and liver cirrhosis formation were observed. Results After 4 weeks of inducing cirrhosis, the weight of traditional DENA induction group 〔(234.9±27.1) g〕 was significantly lower than that of normal control group 〔(264.8±33.7) g, P＜0.05〕. After 8 weeks of inducing cirrhosis, the weight of traditional DENA induction group 〔(251.5±34.3) g〕 was significantly lower than that of normal control group 〔(303.2±49.4) g， P＜0.01〕 and gradual DENA induction group 〔(277.5±27.6) g， P＜0.05〕. However, the difference between normal control group and gradual DENA induction group was not remarkable (P＞0.05). The mortality in traditional DENA induction group (35%) was significantly higher than that in normal control group (0) and gradual DENA induction group (0)， P＜0.05. But the rate of cirrhosis formation both in traditional DENA induction group and gradual DENA induction group was 100%. Conclusion Oral DENA induced cirrhotic model in rats is a simple, reproducible and reliable technique. Gradual oral technique, in which DENA is given under avoirdupois monitoring, can improve rat’s security and reduce mortality.