Effect of glutamine on intestinal mucosal barrier function in rats with acute hepatic injury / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the role of glutamine in LPS and D-Gal induced acute hepatic injury.</p><p><b>METHODS</b>A total of 61 Wistar rats were randomly divided into three groups: control group, model group and GLN pretreated group. The animal model was established by LPS and D-Gal intraperitoneal injection. GLN at dose of 1 g/kg was intragastrically administrated for 7 d before intraperitoneal injection. To evaluate the hepatic injury, the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBiL) were detected by automatic biochemistry analysator. The liver and bowel tissue was observed by lightmicroscope and transmission electron microscope (TEM). The apoptosis of hepatocyte was detected by TUNEL. HPLC-PED was used in the study of intestinal permeability.</p><p><b>RESULTS</b>No significant differences were noted between ALT, AST, TBIL level, death rate and intestinal permeability (L/M) between model group and GLN pretreated group; In microscope, the confused structure of hepatic injury and inflammatory infiltration were similar between model group and GLN pretreated group. The injury of bowel was not obviously. Compared with the model group, there was better trend in liver and bowel in GLN pretreated group by transmission electron microscope (TEM). The apoptosis index in GLN pretreated group were lower than those in model group.</p><p><b>CONCLUSION</b>LPS can induce acute liver injury in D-Gal-sensitized rats.Glutamine has't the trend of protecting liver function and intestinal barrier function,decreasing death rates.</p>

Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment.</p><p><b>METHODS</b>Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.</p><p><b>RESULTS</b>Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure.</p><p><b>CONCLUSION</b>We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.</p>

Detection of hepatic progenitor cells in patients with severe hepatitis and their distribution / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To identify hepatic progenitor cells (HPCs) in patients with severe hepatitis (SH) by detecting their markers and investigate the features of their distribution and location.</p><p><b>METHODS</b>Liver tissues taken from 59 SH patients were tested for the receptor of stem cell factor (c-kit), pi-class glutathione S-transferase (GST-pi), cluster of differentiation 34 (CD34), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and alpha fetoprotein (AFP) by immunohistochemistry (IHC). Meanwhile, 58 patients with acute or chronic hepatitis were also detected to act as controls.</p><p><b>RESULTS</b>Hepatic progenitor cells could be seen in SH patients. Most of them existed as ductular cells that had been called "typical ductular proliferation (ADP)" or "typical ductular reaction" in previous research. These ductular cells were mainly located at the portal areas, fibro septa, periportal parenchyma and the border of the pseudolobuli and inflammatory foci. Further, c-kit, GST-pi, CK19 and CK18, but not CD34 and AFP could be detected in these cells. Another kind of HPC was the small hepatocyte-like cell (SHLC), which could express c-kit, GST-pi, and CK18, but not CK19, CD34 and AFP. The semi-quantitative analysis showed that the scope of ADP in SH patients was significantly larger than that in acute and chronic hepatitis patients (chi2= 63.62, P<0.05), and the scope of ADP in subacute severe hepatitis and chronic severe hepatitis patients was also significantly larger than that in acute severe hepatitis patients.</p><p><b>CONCLUSION</b>In the course of regeneration of viral hepatitis, different types of pathology have different features. In acute and chronic hepatitis (G1-2), the regeneration is mainly owing to the proliferation of mature hepatocytes, and in chronic hepatitis (G3-4), there is the participation of HPCs, although they are limited. In severe hepatitis, however, since the replicative capacity of normal hepatocytes is impaired or prohibited, liver regenerates and restores mainly by the means of hepatic stem cells activation and proliferation. But the hepatic stem cells don't differentiate into their mature functional compartments directly at all. There are several intermediary or transition populations. In human severe hepatitis, they are mainly ductular cells, and parts of them are small hepatocyte-like cells.</p>

A clinicopathological study on 3 cases of severe acute respiratory syndrome / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation.</p><p><b>METHODS</b>Tissue specimens from 3 autopsy cases of diagnosed SARS were studied under microscopy and the clinical data were reviewed.</p><p><b>RESULTS</b>The typical pathological changes of lungs were diffuse hemorrhage on surface. A mixture features of serous, fibrinous and hemorrhagic inflammation were seen in most pulmonary alveoli with engorgement of capillary and there were microthrombosis in some capillary. Pulmonary alveoli became thick with interstitial mononuclear inflammatory infiltration, diffused alveoli damage, desquamation of pneumocytes and hyaline-membrane formation. Fibrinoid materials and erythrocytes could be found in alveolar spaces. There were thrombo-embolisms in some bronchial artery. Meanwhile, haemorrhagic necrosis was showed in lymph nodes and spleen with attenuation of lymphocytes. Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and some lesions observed in liver, heart, kidney, pancreas may have existed before the hospitalization.</p><p><b>CONCLUSION</b>Severe damages of pulmonary and immunological system damage are responsible for clinical features of SARS and may lead to death of patients.</p>

A clinicopathological study on nonalcoholic steatohepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the pathological and clinical characters of nonalcoholic steatohepatitis (NASH).</p><p><b>METHODS</b>Liver biopsy tissues taken from 97 patients negative for common viral detection with serological test and immunohistochemistry as well as in situ hybridization, were observed by routine light microscopic examination. And the clinical data of patients with NASH was analyzed.</p><p><b>RESULTS</b>Among the chronic hepatitis patients with unknown etiology, the detection rate of NASH was 15.5% (15/97). The characteristic lesions in NASH patients included macrovesicular steatosis in zone 3 of lobules, hepatocytes ballooning degeneration, lobules diffused with acute and chronic inflammation, and perisinusoidal fibrosis. Grading and staging according to Brunt's method, histological lesions could be accounted for G1S1 in 7 patients, G2S2 in 3 patients, G3S1 in 4 patients and G3S2 in 1 patient. There were 14 patients with mild to moderate elevation of transaminase, 10 with hyperlipemia, 8 with diabetes and 9 with fatty liver by ultrasonography.</p><p><b>CONCLUSION</b>Nonalcoholic steatohepatitis is a common form of unknown etiology chronic liver disease with certain clinic-pathological features.</p>