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Background and Aims: Host genetic factors may affect clinical outcomes of hepatitis C virus (HCV) infection; however, the possible mechanisms remain largely unknown. The role of immunopathogenesis in chronic hepatitis C leads to extensive exploration of host immunity including inflammatory cytokines., Methods: We examined interleukin 10 (IL-10) promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site and studied their association with response to 24 weeks of pegylated interferon plus ribavirin treatment in 143 chronic hepatitis C patients, of whom 97 (67.8%) achieved a sustained virologic response (SVR). In addition, 134 healthy adults were used as controls., Results: Of chronic hepatitis C patients, 111 (77.6%) were genotype 1 infection, 32 (22.4%) were genotype 2 infection. Patients with sustained virologic response were younger and had higher pretreatment ALT levels than those without. No statistical difference was found between chronic hepatitis C patients who achieved SVR or not in terms of gender, HCV genotype, pretreatment HCV RNA levels, and severity of liver disease. The serum IL-10 levels were comparable between healthy controls and chronic hepatitis C patients as well as between HCV patients with and without SVR. The distribution of IL-10 promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site was comparable between HCV patients and healthy controls as well as HCV patients with and without SVR. A high frequency of ATA haplotype of common IL-10 promoter gene SNPs was found in both chronic hepatitis C patients (70.3%) and healthy controls (69.8%). However, ATA haplotype was not associated with SVR in chronic hepatitis C patients., Conclusions: Our data fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the response to combination therapy in Taiwanese chronic hepatitis C patients. The impact of genetic variations in IL-10 haplotype on the response to anti-HCV treatment among different ethnic populations deserves further examination.

N-acetyltransferases (NATs) are recognized to play a key role in the primary step of arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow acetylators, which are being thought to involve cancer risk related to environmental exposure. Berberine has been shown to induce apoptosis and affect NAT activity in human leukemia cells. The purpose of this study is to examine whether or not berberine could affect arylamine NAT activity and gene expression (NAT mRNA) and the levels of NAT protein in mouse leukemia cells (L 1210). N-acetylated and non-N-acetylated AF were determined and quantited by using high performance liquid chromatography. NAT mRNA was determined and quantited by using RT-PCR. The levels of NAT protein were examined by western blotting and determined by using flow cytometry. Berberine displayed a dose-dependent inhibition to cytosolic NAT activity and intact mice leukemia cells. Time-course experiments indicated that N-acetylation of AF measured from intact mice leukemia cells were inhibited by berberine for up to 24 h. The NAT1 mRNA and NAT proteins in mouse leukemia cells were also inhibited by berberine. This report is the first demonstration, which showed berberine affect mice leukemia cells NAT activity, gene expression (NAT1 mRNA) and levels of NAT protein.

The effect of flumazenil, a benzodiazepine antagonist, was assessed in a random, double-blind clinical study in which each of the four groups of surgical outpatients comprising 20 in each was given either ketamine 100 mg (K), etomidate 20 mg (E), thiopental 300 mg (T) or flunitrazepam 4 mg (F) for induction of anesthesia. On emergence, patients in each group were randomly given 2cc of either 2 coded solutions, one of which contained 0.2 mg flumazenil and the other of which was normal saline. Following injection of coded solution, all patients were assessed at 0, 5, 15, 30, 60 and 120 min for wakefulness. All 10 patients of group F who received flumazenil were alert and able to recall at 5 min, whereas in group T this was noted from 15 to 30 min. Patients of group E and K responded alike in a manner as of those who received normal saline placebo with onset of wakefulness at 30 and 60 min respectively. These results confirm that flumazenil antagonizes flunitrazepam (within 5 min) and also indicate that the antagonizing effect occurs 30 min following injection for thiopental, suggestive of some cross-reactivity between these two drugs.

Two hundred patients were given peridural anaesthesia with 16 ml of 0.975% plain bupivacaine in connection with operations on the lower extremities, and the lower abdomen or perineum. More than 92% of these had a good anaesthesia and a pronounced motor block. The frequency of serious complications was low but when they existed they were usually due to the spread of the anaesthesia which led to circulatory and respiratory insufficiency. It is therefore essential to be able to recognize such complications early and treat them rapidly.