Background. Hepatic fibrosis due to chronic hepatitis B virus (HBV) infection has an enormous socio-economic impact. Besides strategies aiming at virus elimination, prevention or reversal of liver fibrosis is amenible. Given the antifibrotic activity of IFN-γ, a randomized open-labeled multicenter trial was initiated to test IFN-γ in HBV infection. Methods. HBs-antigen positive patients with biopsy proven hepatic fibrosis (n=99, stages 2–4 according to Scheuer criterion) were treated with diammone glycyrrhizinate and potassium magnesium aspartate.Treatment with 50g IFN-γ i.m. on a daily basis for three months and on alternate days the subsequent six months was performed in 66 randomly assigned patients. Efficacy was evaluated by liver biopsy and serologic markers. Results. 54 patients in the IFN-γ group and 29 patients in the control group completed the study protocol. The hepatic fibrosis score was significantly reduced in 63 percent of IFN-γ treated patients compared to 24.1 percent in the control group as assessed by a semiquantitative scoring system evaluating both liver architecture and fibrotic deposits. Mean values for total fibrosis score decreased from 13.8±5.8 to 10.1±5.1 in the IFN-γ group, whereas they were unchanged in controls (13.2±6.8 versus 12.6±4.8 after 9 months). The Scheuer fibrosis scoring system revealed 12 out of 54 patients improved 1 stage(s) in the IFN-γ compared to 1/29 in the control group. Antifibrotic activity may be attributed to decreased TGF-β signaling via phospho-Smad2 and reduced number of activated, α smooth muscle actin positive hepatic stellate cells. Conclusions. Prolonged IFN-γ treatment over 9 months significantly improves the fibrosis score in patients with chronic HBV infection most likely by antagonizing profibrogenic TGF-β effects.

OBJECTIVETo evaluate the effect of lamivudine on the loss of serum hepatitis B virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance compared with placebo.METHODSFour hundred and twenty-nine patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty-two patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 9-month open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters.RESULTSDuring the 12-week treatment period, 92.2% of lamivudine treated patients became HBV DNA negative (below 1.6 pg/ml) compared with only 14.1% of those receiving placebo (P < 0.01). At the end of 12 week, the sustained negative rate for HBV DNA in the lamivudine treated group was 78.5% compared with the placebo group (11.1%; P < 0.01). There was a trend to a high proportion of patients treated with lamivudine to lose HBeAg (8.1%) and develop antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this difference was not statistically significant. Patients with elevated ALT levels at baseline became normal in 60. 3% of the lamivudine treated group compared with the placebo group where only 27.5% were normal (P < 0.01). Lamivudine was well tolerated in a dose of (100 mg daily) and the overall incidence of adverse events was similar to that of the placebo.CONCLUSIONSLamivudine (100 mg daily) is very effective in the inhibition of HBV replication, indicated by the rapid loss of serum HBV DNA, and often accompanied by a decrease of serum ALT levels. Lamivudine is well tolerated without severe adverse events during treatment.

There are suggestions that duodenal ulcer protects individuals from gastric cancer and that rice is ulcerogenic while wheat is gastro‐protective. We aimed to examine the relationship of gastric cancer, duodenal and gastric ulcers in different geographical regions in China and identified dietary risk factors for duodenal ulcer and gastric cancer. The prevalence of peptic ulcer and gastric cancer among symptomatic patients in eight major cities, four each from the north and the south representing all the six defined regions of China were studied. Endoscopy and case records over a 10 year period were reviewed and cases of confirmed duodenal and gastric ulcer and gastric cancer, together with the total number of endoscopies performed per year, were recorded. Rates were expressed as cases/1000 endoscopies. Results were compared to another epidemiological study on diet and mortality in the same regions in China conducted at the same time. Duodenal ulcer rates were 2.4‐fold higher in southern China than northern China, whereas gastric cancer rates were 1.6‐fold higher in the north than in the south. Correlation studies showed for the first time an inverse linear relationship between the gastric cancer rates and the duodenal ulcer rates (r=‐0.8076, P=0.015), as well as the duodenal ulcer: gastric ulcer ratios (r=‐0.9133, P=0.002). Gastric ulcer rates were higher in southern China but did not correlate with the gastric cancer rates (r=0.1455, P=0.731). Duodenal ulcer rates were found to be related to daily rice intake (r=0.8554, P=0.029) and inversely related to daily wheat flour intake (r=‐0.8472, P=0.033). Gastric cancer rates were not related to any dietary risk factors tested. We concluded there was an inverse relationship between gastric cancer rates and duodenal ulcer rates. Although duodenal ulceration and gastric cancer are both linked to Helicobacter pylori infection, the findings of this study indicate independent additional aetiological factors for the pathogenesis of these conditions. Dietary factors such as rice or wheat intake may play a role.

Purpose: To investigate the time course of nitric oxide synthase (NOS) mRNA alterations during kainic acid (KA)-induced epilepsy in rat hippocampus. Methods: Using Northern blot, hippocampal NOS mRNA contents were measured before administration and at 1, 4, 6, 12, 24 hour respectively after onset of epileptic activity evoked by KA (12 mg/kg). Results: 1 hour after initiating epilepsy, the hippocampal NOS mRNA levels increased to 300% of the control, and stayed at this high level during the rest of 24 hours. Conclusions: KA-induced epilepsy may be related to the changes of hippocampal NOS mRNA level.

Immunocytochemical technics were used to evaluate the influence of penicillin-induced seizure and electroacupuncture treatment on dynorphin1-8 and leu-enkephalin immunoreactivity in hippocampus. It was found that 3 h after beginning of seizure there started a dramatic decrease in dynorphin1-8 in hilus, mossy fiber of hippocampus but an increase in hilus, mossy fiber of hippocampus but an increase in leu-enkephalin in subiculum, CA1 area of hippocampus and some other limbic structures. Electroacupuncture treatment decreased the leu-enkephalin immunoreactivity in the nuclei mentioned above and increased dynorphin1-8 immunoreactivity in hippocampus. The results show that epileptiform activity and electroacupuncture inhibitory effect on seizure may be related to the alteration of dynorphin1-8 and leu-enkephalin in the brain.

Our previous studies have shown that seizure induced by injecting penicillin (0.24 mg/2 microliters) into hippocampus could be inhibited by electroacupuncture (EA) probably via decreasing enkephalin content in hippocampus. To determine whether this change reflected the peptide synthesis, preproenkephalin (PPE) mRNA was detected in hippocampus and some other limbic structures during seizure and after EA treatment by in situ hybridization. Four hours after injecting penicillin into hippocampus, PPE mRNA levels were significantly increased by 10 folds in entorhinal cortex, subiculum, CA1 area of hippocampus, amygdaloid nucleus and piriform cortex, whereas EA treatment apparently attenuated the seizure-induced increase of PPE mRNA in the areas mentioned above. The results indicated that EA may regulate the biosynthesis of PPE in hippocampus during seizure by an alteration in gene transcription.

C-fos proteins were visualized immunohistochemically in the brain of rats after seizures induced by injecting penicillin into hippocampus and by penicillin+electroacupuncture treatment. Three hours following seizures there was an evident expression of c-fos proteins in the hippocampus (CA1 area), dentate gyrus, piriform cortex, dorsal part of entorhinal cortex, and amygdaloid nucleus, and there was a dramatic increase of c-fos proteins in CA3 area and the areas mentioned above except the CA1 area where c-fos proteins apparently decreased after electroacupuncture treatment. The results showed that seizures can induce c-fos proteins in some nuclei related with seizure and that electroacupuncture can also regulates the c-fos expression after seizure.

The effect of schisandrin B (Sin B) on oxygen free radicals--induced lipoperoxidative damage to plasma membrane of rat hepatocytes was investigated. When the plasma membrane of rat hepatocytes was incubated with iron/cysteine or Vit C/NADPH, the production of malondialdehyde (MDA) and consumption of NADPH increased, while the membrane fluidity reduced. Addition of Sin B (3-25 micrograms.ml-1) to the incubation mixture inhibited all these alterations of the plasma membrane induced by iron/cysteine and Vit C/NADPH. The results indicated that Sin B could maintain membrane stability of rat hepatocytes under oxidative stress.

The effects of seven phenolic compounds isolated from Salvia miltiorrhiza on peroxidative damage to liver microsomes, hepatocytes and erythrocytes of rats were studied. The results show that the seven compounds inhibited lipid peroxidation of rat liver microsomes induced by iron/cysteine and Vitamin C/NADPH. The hemolysis of rat erythrocytes induced by hydrogen peroxide was also inhibited. The degree of inhibition varied with different compounds. Among the seven compounds, the action of salvianolic acid A (Sai A) was the most potent. Therefore, the protective action of Sai A against peroxidative damage to isolated rat hepatocytes and their plasma membranes was evaluated further. Malondialdehyde (MDA) production and bleb of the surfaces of rat hepatocytes induced by iron/ cysteine were prevented by Sai A. The production of MDA and the consumption of NADPH of the plasma membrane during lipid peroxidation initiated by iron/cysteine and Vitamin C/NADPH were also inhibited. The results strongly suggest that several phenolic compounds like Sai A have a protective action against peroxidative damage to biomembranes.

The action of schizandrin B (Sin B) was observed in freshly isolated hepatocytes damaged by FeSO4/cysteine and CCl4. Two types of free radicals, .OH and .CCl3, generated from FeSO4/cysteine and CCl4, respectively, induced lipid peroxidation in hepatocytes. It was found that the speed of lipid peroxidation (MDA production) and the degree of alteration in hepatocyte morphology were closely related to the type of free radicals. MDA production and membrane protrusion of hepatocytes injuries by FeSO4/cysteine were faster and more severe than those observed with CCl4. Sin B was shown to decrease the production of MDA and the release of GPT and LDH, and to increase hepatocyte viability as well as maintaining the integrity of the hepatocyte membrane surface. These actions of Sin B were stronger than vitamin E at the same concentration. It was observed that no inhibitory effect of phenobarbital, a typical inducer of cytochrome P-450, as Sin B induced liver cytochrome P-450, on MDA production in hepatocytes damaged by FeSO4/cysteine. The results suggest that Sin B possesses antioxidant activity.