Slc26a3 deficiency is associated with loss of colonic HCO3 (-) secretion, absence of a firm mucus layer and barrier impairment in mice.

AIM: Downregulated in adenoma (DRA, Slc26a3) is a member of the solute carrier family 26 (SLC26), family of anion transporters, which is mutated in familial chloride-losing diarrhoea (CLD). Besides Cl(-) -rich diarrhoea, CLD patients also have a higher-than-average incidence of intestinal inflammation. In a search for potential explanations for this clinical finding, we investigated colonic electrolyte transport, the mucus layer and susceptibility against dextran sodium sulphate (DSS)-induced colitis in Slc26a3(-/-) mice. METHODS: HCO3 (-) secretory (JHCO3 (-) ) and fluid absorptive rates were measured by single-pass perfusion in vivo and in isolated mid-distal colonic mucosa in Ussing chambers in vitro. Colonocyte intracellular pH (pHi ) was assessed fluorometrically, the mucus layer by immunohistochemistry and colitis susceptibility by the addition of DSS to the drinking water. RESULTS: HCO3 (-) secretory (JHCO3- ) and fluid absorptive rates were strongly reduced in Slc26a3(-/-) mice compared to wild-type (WT) littermates. Despite an increase in sodium/hydrogen exchanger 3 (NHE3) mRNA and protein expression, and intact acid-activation of NHE3, the high colonocyte pH in Slc26a3(-/-) mice prevented Na(+) /H(+) exchange-mediated fluid absorption in vivo. Mucin 2 (MUC2) immunohistochemistry revealed the absence of a firm mucus layer, implying that alkaline secretion and/or an absorptive flux may be necessary for optimal mucus gel formation. Slc26a3(-/-) mice were highly susceptible to DSS damage. CONCLUSIONS: Deletion of DRA results in severely reduced colonic HCO3 (-) secretory rate, a loss of colonic fluid absorption, a lack of a firmly adherent mucus layer and a severely reduced colonic mucosal resistance to DSS damage. These data provide potential pathophysiological explanations for the increased susceptibility of CLD patients to intestinal inflammation.

Role of monokine induced by interferon-γ in liver injury induced by hepatitis B virus in mice.

The chemokine monokine induced by interferon-γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)-κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome-containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad-HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF-κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo-jetPEI-Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF-κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3-kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.

[Synthesis of glycoproteins by mucosa of gastric antrum in chronic gastritis B]. / Die Glykoproteinsynthese antraler Magenschleimhaut beichronischer Gastritis Typ B.

The tissue culture and autoradiography techniques were used to study the effect of infiltration by inflammatory cells and of HP infection on the synthesis of glycoproteins by the gastric antrum. The results showed that in active phase of gastritis, the synthesis of glycoprotein was increased but no correlation between HP infection and synthesis of glycoprotein was noted. The mechanism of increased synthesis in chronic gastritis was discussed. It is suggested that the inflammatory cells and media released by them may play important role.

[Effect of pituitrin or phentolamine alone or in combination on WHVP and systemic hemodynamics in patients with liver cirrhosis]. / Wirkung von Pituitrin und Phentolamin allein oder in Kombination auf WHVP und die systemische Hämodynamik bei Patienten mit Leberzirrhose.

We observed the effect of pituitrin and phentolamine alone or in combination on wedged hepatic venous pressure (WHVP) and systemic hemodynamics in 28 patients with cirrhosis. The results showed that either of these drugs used separately could lead to reduction in WHVP, each of them could also cause by-effects on systemic hemodynamics. When pituitrin in combination with phentolamine was administered, no change could be found in inferior vena cava pressure, mean arterial pressure, pulse rate and cardiac index. This suggested that pituitrin in combination with phentolamine could not only efficaciously decrease WHVP, but also counteract side effects on systemic hemodynamics of each other and improve hepatic microcirculation. Our study provided evidence for the usefulness of the combination of the two drugs in controlling bleeding from esophagus varices.