Árpád Kiss

Hepatic regeneration induces transient acute phase reaction: systemic elevation of acute phase reactants and soluble cytokine receptors.

The growth factors present during liver regeneration partially overlap with the regulators of the hepatic acute phase response. We analysed the acute phase reaction and changes in soluble cytokine receptors after partial hepatectomy, when tissue injury inducing acute phase reaction and major reduction of liver mass occur simultaneously. Three acute phase proteins and mRNAs were determined by ELISA and northern blot hybridisation in rats. Serum levels of IL‐6 and three soluble cytokine receptors (sTNF‐αR I and II, sIL‐6R) were detected by ELIBA or dot‐blot assay. Time‐course profiles of fibrinogen, α2‐macroglobulin and haptoglobin proteins and mRNA are presented. Elevation of IL‐6, soluble TNF‐α receptors and soluble IL‐6 receptor levels were also detected. The time‐course of changes in haptoglobin concentration and elevation of soluble cytokine receptors is described by this in vivo experimental system. The results show good correlation with (post)transcriptional activation of immediate and delayed early gene products. These data suggest the involvement of both acute phase proteins and soluble cytokine receptors in the regulation of liver regeneration.

Synthesis of 8-substituted 7-azarutaecarpines

Abstract The synthesis of 8-substituted 7-azarutaecarpines 2 is described. These compounds were prepared by Fischer indolization of 3-amino-2-(1-phenylhydrazonoethyl)-4(3H)-quinazolinone 5, followed by cyclocondensation with a series of aliphatic, araliphatic or aromatic aldehydes and formic acid or a Vilsmeier–Haack reagent. The stereochemistry of compounds 2 was investigated by 1H NMR spectroscopy. It was found that the 8-substituents assume a quasi-axial position on the flattened boat conformation of ring C of 2, with the exception of ortho substituted phenyl groups, which occupy quasi-equatorial positions. Semi-empirical MO calculations support these conformational preferences.

Elevated hepatic glucocorticoid receptor expression during liver regeneration in rats

In rats within the first week of partial hepatectomy reconstruction of the normal histological structure of the liver already starts. To approach the possible role of endogenous glucocorticoids in the process of regeneration we measured the changes in the expression of steroid glucocorticoid receptor gene after various regeneration intervals. After partial hepatectomy, between 0.5–168 hours from the surgery, the gene expression (mRNA) of glucocorticoid receptor was determined by reverse transcription followed by PCR and normalized to that of glycerolphoshate dehydrogenase. Two peaks of glucocorticoid receptor mRNA were detected first, bet ween 3 and 6 hours (first peak) and a second between 24 and 36 hours. Immunoreactive glucocorticoid receptor was detected by immunohistochemistry using monoclonal anti-glucocorticoid receptor. Three days after the surgery immunohistochemical studies showed substantially more immunoreactive GcR protein in the regenerated liver than in the controls. These semiquantitative data provide evidence suggesting elevation of glucocorticoid receptor expression during regeneration of liver at mRNA and protein levels.