Proteases and antiproteases related to the coagulation system in plasma and ascites — An approach to differentiate between malignant and cirrhotic ascites

Summary The concentrations of several proteases and antiproteases known to be present in ascites were tested in plasma and ascitic fluid with regard to their ability to separate ascites according to malignant or nonmalignant disease. Seventeen patients with proven malignant ascites and 37 with ascites due to liver cirrhosis were included. Activities of plasminogen, ₂-antiplasmin, antithrombin-III, and factor V, and the concentration of ₁-protease inhibitor were significantly higher in the plasma of patients with malignant ascites than in cirrhotic patients. Fibronectin, plasminogen, ₂-macroglobulin, ₁-protease inhibitor, antithrombin-III, and albumin revealed higher concentrations or activities in malignant ascites than in cirrhotic ascites. Due to a wide variation of most parameters, only fibronectin, antithrombin III, and ₁-protease inhibitor in ascites had a sensitivity and specificity higher than 90% for malignant ascites. When the specific protein/albumin ratio was used, only the accuracy of fibronectin was increased reaching a sensitivity and specificity of 100%. The plasma/ascites gradients of the proteins assessed differed significantly, that of fibronectin being much higher (22±7) than that of all other proteins. In malignant ascites fibronectin concentration was only correlated with ₁-protease inhibitor concentration but not with the concentration or activity of all other proteins, while in cirrhotic ascites most proteins revealed a positive correlation.The determination of the fibronectin concentration or the fibronectin/albumin ratio in ascites can differentiate malignant and nonmalignant ascites. All other proteases and antiproteases assessed are of lesser value for this purpose, although most are significantly increased in ascites and plasma of patients with malignant disorders.Abbreviations ₂AP ₂-Antiplasmin - ₁PI ₁-Protease inhibitor - AT III Antithrombin III - FDP Fibrin(ogen) degradation products - FM Fibrin monomers - ₂MG ₂-Macroglobulin - PTT Partial thromboplastin time - RT Reptilase time     

Hepatitis C virus (HCV) genotype 1 NS5A resistance-associated variants are associated with advanced liver fibrosis independently of HCV-transmission clusters

Objectives

The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis.

Scanning and transmission electron microscopy of venous sphincters in the rat lung

The rat pulmonary microvasculature was studied using scanning and transmission electron microscopy of vascular corrosion casts and tissue sections. Special emphasis was placed on small pulmonary venous vessels. The shape of vascular casts was analyzed and interpreted concerning the wall composition of corresponding vessels studied in tissue sections. On the casts of pulmonary venules and small pulmonary veins, narrow or wider annular constrictions were regularly observed. Within these constrictions, marks of circularly running grooves were seen as an additional structural detail, which obviously mimic impressions of single or grouped smooth muscle cells. The depth of the constrictions varies; it may be more or less pronounced, occasionally narrowing down the luminal diameter to approximately 50%. These constrictions are caused by muscular sphincters. In tissue sections of small pulmonary veins, sphincter regions were identified as abruptly appearing single or grouped true smooth muscle cells. Smooth muscle cells may be arranged side by side in a group or bundle or even staked in two or three layers. Between the sphincter regions, the venous wall consists merely of endothelium and an accompanying connective tissue layer. The smooth muscle cells of a sphincter are regularly positioned between endothelial layer and elastic lamina. The smooth muscle cells next to the endothelium form myoendothelial junctions. Autonomic nerves near the sphincters were never seen. The venous sphincters described are suggested to be effective devices involved in blood flow regulation. Blood-borne substances or local tissue hormones might govern sphincter function. © 1992 Wiley-Liss, Inc.     

血清谷氨酰转肽酶含量测定在慢性乙型肝炎中的临床意义

目的探讨血清谷氨酰转肽酶（GGT）含量变化在慢性乙型肝炎（CHB）不同程度肝脏病理损害中的变化规律及临床意义。方法测定70例CHB患者血清ALT、AST、GGT水平，同时行肝活体组织检查，对肝脏进行炎症分级和纤维分期。分析ALT、AST、GGT与CHB之间的关系。结果（1）ALT、AST、GGT随炎症程度和纤维化程度的上升而上升，但到G4和s4后则下降。GGT随ALT、AST的升高而升高，ALT、AST和GGT的相关系数分别为：0．322、0．328（P〈0．05）。在保肝治疗后，ALT较快降至正常且GGT保持在一个较低水平的为轻度CHB，而随着ALT下降，GGT仍持续在一个较高水平的为中度及重度CHB，其中重度CHB的GGT水平有所波动。结论血清GGT比ALT、AST更准确的反映肝脏的炎症程度，GGT的活动度给临床判断慢乙肝的炎症提供了重要的判断依据。     

Effect of different types of high carbohydrate diets on glycogen metabolism in liver and skeletal muscle of endurance-trained rats

Male Wistar rats were fed ad libitum four different diets containing fructose, sucrose, maltodextrins or starch as the source of carbohydrate (CH). One group was subjected to moderate physical training on a motor-driven treadmill for 10 weeks (trained rats). A second group received no training and acted as a control (sedentary rats). Glycogen metabolism was studied in the liver and skeletal muscle of these animals. In the sedentary rats, liver glycogen concentrations increased by 60%–90% with the administration of simple CH diets compared with complex CH diets, whereas skeletal muscle glycogen stores were not significantly affected by the diet. Physical training induced a marked decrease in the glycogen content in liver (20%–30% of the sedentary rats) and skeletal muscle (50%–80% of the sedentary rats) in animals fed simple (but not complex) CH diets. In liver this was accompanied by a two-fold increase of triacylglycerol concentrations. Compared with simple CH diets, complex CH feeding increased by 50%–150% glycogen synthase (GS) activity in liver, whereas only a slight increase in GS activity was observed in skeletal muscle. In all the animal groups, a direct relationship existed between tissue glucose 6-phosphate concentration and glycogen content (r = 0.9911 in liver, r = 0.7177 in skeletal muscle). In contrast, no relationship was evident between glycogen concentrations and either glycogen phosphorylase activity or adenosine 5-monophosphate tissue concentration. The results from this study thus suggest that for trained rats diets containing complex CH (compared with diets containing simple CH) improve the glycogenic capacity of liver and skeletal muscle, thus enabling the adequate regeneration of glycogen stores in these two tissues.     

Ramification of the portal vein at the porta hepatis in humans

The ramification of the portal vein at the porta hepatis was studied by anatomic dissection performed in 32 formalin fixed human livers. In all the specimens there were branches which ran towards the caudate lobe, arising from the portal vein and either from the left or the right portal branches. Tri-and quadrifurcation of the portal vein was observed. In 5 cases (16%) there were branches arising from left portal branch or portal vein and directed anteriorly to the quadrate lobe or to the region of the gall-bladder sulcus. These branches ranged from 1.0 to 6.0 mm in diameter. The portal caudate branches were divided into 3 groups.Group 1: Branches to the papillary process; 1 or 2 branches in 26 cases (82%), 3 or 5 branches in 3 cases (9%) and no branches in 3 cases (9%);     

The influence of uric acid treatments on liver glutathione system prevent oxidative damages in experimental autoimmune encephalomyelitis mice

Recently we reported that antioxidant system in brain and spinal cord in experimental autoimmune encephalomyelitis (EAE) mice is mainly affected at early stages of the disease [M. Zargari, A. Allameh, M.H. Sanati, T. Tiraihi, S.H. Lavasani, O. Emadyan, Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice, Neurosci. Lett. 412 (2007), 24–28]. The aim of the present study was to investigate the role of uric acid (UA) on antioxidant system in liver and plasma of EAE mice. EAE was induced in C57/BL6 mice (n = 60), followed by i.p. administration of UA (10 mg/kg BW) in 30 mice at three distinct clinical stages (A: prior to onset, B: after onset, C: after development of EAE). Livers were removed and processed for measurement of lipid peroxidation products, reduced glutathione (GSH), and glutathione S-transferase (GST) and total antioxidant capacity of plasma (FRAP). The results showed that lipid peroxidation products in liver of EAE mice was increased significantly (∼85%) as compared to normal. UA administration to EAE mice caused a significant suppression of liver lipid peroxidation products (∼45%) at early stages (A and B). There was an inverse relationship between lipid peroxidation and cellular GSH in liver. GSH was significantly depleted in mice liver during the EAE progression, but it was recovered (∼29%) when UA was injected before the onset of the disease (groups A and B). Plasma total antioxidant capacity was significantly decreased during the development of EAE, however it was subsided in mice treated with UA as compared to the corresponding controls (21%) in groups A and B. Elevated liver GST as a result of EAE induction was reversed in mice treated with UA particularly in groups A and B. These results indicate that hepatic glutathione system, particularly GST plays a major role in modulation of oxidative damages to central nervous system (CNS) during EAE induction. The positive response of antioxidant system to UA administration in EAE mice was corroborated with improvement of clinical manifestation of the animals.     

Mathematical model to analyse urea synthesis following alanine infusion in control subjects and in patients with liver cirrhosis

A three-compartment model was used to analyse the urea response to an alanine infusion in control subjects and patients with liver cirrhosis. Discriminant analysis showed a good separation between model coefficients of the two groups. A single parameter was derived, able to quantify the liver functional capacity. The method provides a useful diagnostic tool in patients with liver disease.     

The innate immune response under the control of the LXR pathway

Macrophages play essential roles in infection and resolution of inflammation. This review summarizes recent findings that suggest a relevant role for the nuclear receptor liver X receptor (LXR) in the evolution of immune responses. By exerting both positive and negative regulation of specific macrophage gene expression networks, LXRs display anti-inflammatory activities and promote macrophage survival in bacterial infection settings. Agonists that activate the LXR pathway may be used to enhance innate immunity to highly virulent pathogens that otherwise induce macrophage apoptosis as a means to subvert host immune defense.     

Effects of Alkyl Alcohols and Related Chemicals on Rat Liver Structure and Function: III. Physicochemical Properties of Ethanol-, Propanol- and Butanol-treated Rat Liver Mitochondrial Membranes

The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calo-rimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsatu-rated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (δ H ) was revealed by differential scanning calo-rimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6 diphenyl 1, 3, 5 hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol induced hepatic megamitochondria is discussed on the basis of these results. Acta Pathol Jpn 42: 549–557, 1992.