Journal of Gastroenterology and Hepatology (Australia)

During the prereplicative period of liver regeneration the changes in the levels of mRNA for tumour necrosis factor‐α (TNF‐α) and its receptors were nearly synchronous. The mRNA levels reached their maximum 1 – 3 h after operation and exceeded the values for intact animals about tenfold. Lipopolysaccharide stimulation induced an increase in TNF‐α and TNF receptor production comparable with that occurring during regeneration.

Nitric oxide (NO) production in the regenerating liver was determined by electron paramagnetic resonance (EPR) spectroscopy. The first increase in NO production occurred approximately 1 h after partial hepatectomy (PHE). The second and more pronounced peak of NO production was observed about 6 h after PHE when the hepatocytes entered the first cell cycle; it originated mainly from these cells. The consequent minimum of NO synthesis coincided with the maximal rate of DNA synthesis. The third gradual rise of NO production was seen at the transit from the first to the second cell cycle of the hepatocytes and the entrance of the non‐parenchymal cells into proliferation.

Hepatocytes, Kupffer and endothelial cells were isolated from livers after PHE. They were found to start their main NO production in the described sequence at the times corresponding to their respective entrance into the cell cycle. The maxima of NO synthesis were inversely correlated to the DNA‐synthesizing activity of the individual cell type.

Epstein‐Barr virus (EBV) is part of the herpesvirus family that infects up to 90% of the population. Initial infection is often subclincal in children but will generally result in symptomatic infectious mononucleosis in adolescents and adults. Ganciclovir has been utilized in immunocompromised patients with EBV encephalitis and post‐liver transplant for EBV fulminant hepatitis. Herein, the successful use of ganciclovir in two immunocompetent patients with severe EBV hepatitis is reported.

Quiescent hepatic stellate cells (HSCs) in healthy liver store 80% of total liver retinols and release them depending on the extracellular retinol status. However, HSCs activated by liver injury lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Emerging evidence suggests that retinols and their metabolites such as retinoic acids (RAs) contribute to liver regeneration, fibrosis and tumor. However, it is not clear yet why HSCs lose retinol, which enzymes are involved in the retinol metabolism of HSCs and what function of retinol metabolites on HSCs upon liver injury. Recently, our group and collaborators have demonstrated that during activation, HSCs not only lose retinols but also metabolize them into RAs by alcohol dehydrogenases and retinaldehyde dehydrogenases. As transcriptional factors, metabolized RAs induce retinoic acid early inducible‐1 and suppressor of cytokine signaling 1 in HSCs, which plays an important role in the interaction between HSCs and natural killer cells. In addition, RAs released from HSCs may induce hepatic cannabinoid receptor 1 expression in alcoholic liver steatosis or regulate immune responses upon liver inflammation. The present review summarizes the role of endogenous metabolized RAs on HSCs themselves and on other liver cells including hepatocytes and immune cells. Moreover, the effects of exogenous retinol and RA treatments on HSCs and liver disease are discussed.

Background : Mongolian gerbils have been reported to be a suitable model for Helicobacter pylori‐associated gastric mucosal injury, including gastric cancer. Although ethanol is known to be one of the harmful substances in the gastric mucosa, the relationship between ethanol and H. pylori infection remains unknown. The aim of the present study is to investigate the effect of ethanol treatment prior to H. pylori inoculation on associated gastric mucosal injury.

Methods : Male Mongolian gerbils were used for the study. Helicobacter pylori was orally inoculated after 15 h fasting (Hp group). Thirty minutes prior to H. pylori inoculation, a group of gerbils was orally treated with 40% ethanol (20 mL/kg; E + Hp group). Another group of animals was treated either with H. pylori culture media alone (controls) or with 40% ethanol plus culture media (E group). Gerbils were killed 2, 4 or 12 weeks after H. pylori inoculation. Helicobacter pylori infection was confirmed by both histological examination and serological tests. Mucosal damage was evaluated histologically according to the modified Sydney system.

Results : Although in the controls and E group no significant change to the gastric mucose was observed, persistent H. pylori infection was seen in the mucosa and mucosal leucocyte infiltration and severe epithelial damage was observed in the Hp and E + Hp groups after 4 weeks. The histological scores for polymorphonuclear cell infiltration and myeloperoxidase activity were higher in the E + Hp group at 4 weeks than in the Hp group (P < 0.05).

Conclusions : Ethanol intake preceding H. pylori inoculation could promote the progression of gastric mucosal inflammation in Mongolian gerbils.

© 1999 Blackwell Science Asia Pty Ltd

It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia‐reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, N^G‐nitro‐L‐arginine or N^G‐monomethyl‐L‐arginine. Gastric mucosal integrity was continuously monitored by measuring the blood‐to‐lumen clearance of [⁵¹chromium]‐labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [⁵¹Cr]‐EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L‐arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia‐reperfusion stress in rat gastric mucosa.