Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured blood platelet count and plasma beta-thromboglobulin concentration in 67 patients with acute or chronic liver diseases. Plasma TXB2 and 6-keto-PGF1a concentration were also measured in these patients. The results showed that blood platelet count of less than 100 x 10(9)/L was found in 14% of the patients with acute hepatitis, 23% with chronic hepatitis, 67% with hepatic cirrhosis but without splenectomy and 40% with primary liver carcinoma. Platelet count is lowest in patients with hepatic cirrhosis without splenectomy but normal in patients with hepatic cirrhosis after splenectomy. Plasma beta-TG concentration increased in patients with acute or chronic liver diseases. A negative correlation was found between beta-TG concentration and platelet count in chronic liver diseases. It is suggested that platelet is in activated state in vivo and this may be one of the important reasons for both decrease of platelet count and impairment of platelet function. Plasma TXB2 concentration increased in chronic liver diseases, while plasma 6-keto-PGF1a concentration decreased. The balance between TXA2 and PGI2 is upset; this may be an important mechanism for activation of platelets in vivo.
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PMID:[Studies on plasma beta-thromboglobulin, thromboxane A2, prostaglandin I2 concentration and platelet count in liver diseases]. 139 19

This paper reports on investigations of the formation of PGI2 and TXA2 using their stabile products 6-keto-PGF1 alpha and TXB2 (RIA) in liver biopsy specimens of 46 patients suffering from fatty liver (n = 19), chronic hepatitis B (n = 11), liver cirrhosis (n = 13), and miscellaneous diseases (n = 3). The measured formation rates in chronic liver disease were evaluated in comparison to a reference group (n = 19) consisting of minimal liver lesions. The 6-keto-PGF1 alpha formation correlating to the degree of the portal inflammation in the liver (morphometric evaluation). The same trend existed in relation to the intralobular inflammation. The results presented suggest in respect of analogous data in animal experiments that PGI2 is predominantly generated in mesenchymal cells of the liver and, presumably influences the course of liver diseases.
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PMID:[Prostacyclin and thromboxane synthesis in liver tissue in chronic liver diseases]. 228 9

Urinary excretion rates of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane (TX) B2 were evaluated in three groups of cirrhotic patients [without ascites (group 1, 13 cases), with ascites and normal renal function (group 2, 15 cases), and with ascites and renal failure (group 3, 5 cases)] and in 14 healthy controls. All urinary arachidonate metabolites were significantly increased in group 2 patients. Patients with renal failure showed lower PGE2, PGF2 alpha, and TXB2 values than those from group 2; PGF2 alpha values were also lower than controls. Platelet TXA2 production during whole blood clotting was significantly reduced in all groups of patients. Administration of low-dose aspirin and sulindac, two cyclooxygenase inhibitors selectively sparing renal cyclooxygenase activity, effectively inhibited platelet TXA2 production without affecting urinary TXB2 excretion, thus ruling out platelets as a possible source of urinary TXB2. We conclude that patients with ascites and normal renal function show an overall activation of the renal PG system. Renal production of vasodilating PGE2 and PGI2 may be involved in supporting renal function in these patients. A reduced platelet synthesis of proaggregatory TXA2 also occurs in cirrhotic patients. This may play a role in the bleeding tendency of cirrhosis.
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PMID:Altered renal and platelet arachidonic acid metabolism in cirrhosis. 307 16

Chronic propranolol administration is followed by some haemodynamic alterations, which may impair renal function. It has also been suggested that it may reduce platelet production of proaggregatory thromboxane (TX) A2. We therefore evaluated cardiac index (CI), systemic vascular resistance (SVR), creatinine clearance, daily sodium excretion under controlled sodium intake, platelet aggregation and platelet TXA2 production during whole blood clotting in eight patients with cirrhosis, portal hypertension and no ascites, before and after 3 months of propranolol administration. Liver function was also assessed by evaluating the galactose elimination capacity (GEC) and galactose clearance (Cgal). The expected, significant reduction of CI and increase of SVR was observed. Creatinine clearance and sodium balance were unchanged throughout the study. Furthermore, the renal prostaglandin system, as reflected by urinary prostaglandin E2 and TXB2 excretion, was also unaffected by the drug. No modification of platelet aggregation, platelet TXA2 production during whole blood clotting, GEC and Cgal was observed. We conclude that chronic propranolol administration is followed by alterations of CI and SVR, but it does not impair renal function and platelet aggregation in patients with cirrhosis, portal hypertension and no ascites. The maintenance of renal function during beta-adrenergic blockade is not due to an increased renal production of vasodilating prostaglandins.
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PMID:Systemic haemodynamics, renal and platelet function during chronic propranolol administration in patients with compensated cirrhosis. 347 23

Glucagon secretion has been tested in 12 cirrhotic patients and the results have been compared with those obtained in 10 normal subjects. Two antisera reputed to be specific for glucagon (antiserum 30-K and antiserum RCS5) were used. The patients with cirrhosis exhibited significantly higher levels of plasma immunoreactivity for glucagon, suggesting hyperglucagonemia when using antiserum 30-K but not when using antiserum RCS 5. A positive correlation (r = 0.527, p less than 0.001) was found between plasma immunoreactive glucagon measured by antiserum 30-K and IgG. With antiserum RCS 5 there was no such correlation. These data suggest that hyperglucagonemia may be wrongly suspected when glucagon is measured with antiserum 30-K, due to cross-reaction with IgG. Cirrhotic patients exhibit only a slight increase of glucagon.
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PMID:[Plasma glucagon in alcoholic cirrhosis: cross reaction with IgG]. 740 20

The aim of this study is to investigate the role of prostaglandins (PGI2 and TXA2) in relation with the hemodynamic alterations occuring after graft reperfusion in patients undergoing OLT. A total of 40 patients with liver cirrhosis were studied. Systemic 6-keto-PGF1 alpha and TXB2, stable metabolites of PGI2 and TXA2 respectively, were determined at the radial artery, at four different surgical stages: basal, hepatectomy, anhepatic, and 10 minutes after graft reperfusion. Overall results showed that 6-keto-PGF1 alpha levels were significantly elevated during hepatectomy (1143 +/- 204) when compared to values in the basal stage (p = 0.007). During hepatectomy, 6-keto-PGF1 alpha levels did not correlate to systemic vascular resistance index (SVRI), neither with the cardiac index (IC) nor with the medial arterial pressure (MAP) in the same stage. During the anhepatic stage, only IRVS was inversely correlated with 6-keto-PGF1 alpha levels (p = 0.004): there was no relation with MAP and CI. During reperfusion no correlations were observed between 6-keto-PGF1 alpha levels and MAP, CI or SVRI. We conclude that systemic PGI2 levels are very high in cirrhotic patients undergoing OLT. The absence of correlation between the magnitude of changes in hemodynamic parameters and 6-keto-PGF1 alpha levels during reperfusion of the new liver suggests that other factors must play a role in these hemodynamic changes.
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PMID:[Relation of the levels of systemic prostaglandins and hemodynamic changes present during orthotopic transplant of the liver]. 907 53

An augmented systemic production of thromboxane (TX) A2, as assessed by urinary excretion of the thromboxane metabolites, has been described in severe liver cirrhosis. However, the significance of this finding remains unclear since in liver cirrhosis a number of phenomena i.e. altered hepatic TXA2 metabolism, increased intrasplenic platelet destruction, may affect TXA2 entry into systemic circulation as well as its metabolism. In order to further clarify this, we measured both major enzymatic metabolites of TXB2 in the urine of 44 patients affected by liver cirrhosis, subdivided in three classes on the basis of Child-Pugh criteria. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were assayed with previously validated RIA techniques. The urinary excretion rate of 11-dehydro-TXB2 was significantly (p = 0.0001) increased in the cirrhotic patients (673.5 pg/mg cr, median) in comparison with the controls (275 pg/mg cr, median) but no significant difference could be demonstrated among the excretion rates of the three patient subgroups. The excretion rate of 2,3 dinor-TXB2 was also significantly (p = 0.0001) increased in the patients (824 pg/mg cr, median) in comparison with controls (175 pg/mg cr, median), with a significant (p < 0.05) increase from class A (381 pg/mg cr) to class C (1337 pg/mg cr). The sum of the two enzymatic metabolites was significantly (p = 0.0001 ) increased in the cirrhotic patients in comparison to controls, with a progressive increase from class A (1003 pg/mg cr, median) to class C (2240 pg/mg cr, median). The urinary excretion of 2,3 dinor-TXB2 was significantly (p = 0.008) related to plasma prothrombin fragment 1+2 (F1+2). This study provides further evidence of increased thromboxane biosynthesis in liver cirrhosis. Moreover, we demonstrate intraliver shift of thromboxane metabolic disposition, due to progressive liver decompensation, because only the fraction undergoing beta-oxidation to 2,3-dinor-TXB2 was progressively increased with the degree of liver failure. We, also, find a significant correlation between urinary excretion of 2,3-dinor-TXB2 and plasma F1+2, suggesting that clotting activation could partly account for in vivo platelet activation.
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PMID:Increased thromboxane metabolites excretion in liver cirrhosis. 956 86

Liver cirrhosis is characterized by increased IHR (intrahepatic resistance) and lipid peroxidation, and decreased antioxidative defence. The present study investigates the effects of administration for 1 month of the antioxidant UDCA (ursodeoxycholic acid) in BDL (bile-duct-ligated) cirrhotic rats. Splanchnic haemodynamics, IHR, hepatic levels of TBARS (thiobarbituric acid-reacting substances), GSH (glutathione), SOD (superoxide dismutase) activity, nitrite, PIIINP (N-terminal propeptide of type III procollagen) and collagen deposition, histological examination of liver, mRNA expression of PIIIP-alpha1 (type III procollagen) and TGF-beta1 (transforming growth factor-beta1), protein expression of TXS (thromboxane synthase) and iNOS (inducible NO synthase), and TXA2 (thromboxane A2) production in liver perfusates were measured. The results showed that portal pressure and IHR, hepatic levels of PIIINP, hepatic collagen deposition, mRNA expression of PIIIP-alpha1 and TGF-beta1, protein expression of iNOS and TXS, and production of TXA2 in liver perfusates were significantly decreased in UDCA-treated BDL rats. The increased levels of hepatic GSH and SOD activity and decreased levels of TBARS and nitrite were also observed in UDCA-treated BDL rats. In UDCA-treated BDL rats, the reduction in portal pressure resulted from a decrease in IHR, which mostly acted through the suppression of hepatic TXA2 production and lipid peroxidation, and an increase in antioxidative defence, leading to the prevention of hepatic fibrosis.
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PMID:Chronic administration of ursodeoxycholic acid decreases portal pressure in rats with biliary cirrhosis. 1847 49

Our present study examines, in mesenteric resistance arteries, possible vasodilation alterations, and the role of NO and COX (cyclo-oxygenase) derivatives, in cirrhosis. The vasodilator response to acetylcholine was analysed in segments from control and cirrhotic rats. The effects of the non-specific COX inhibitor indomethacin, the specific COX-1 inhibitor SC-560 and the specific COX-2 inhibitor NS-398 were analysed in segments from both groups of rats. NO release was measured, and eNOS [endothelial NOS (NO synthase)], phospho-eNOS, iNOS (inducible NOS), COX-1 and COX-2 protein expression was also analysed. The effects of the TP receptor [TXA2 (thromboxane A(2)) receptor] antagonist SQ 29548, the TXA(2) synthesis inhibitor furegrelate, the PGI(2) (prostaglandin I(2)) synthesis inhibitor TCP (tranylcypromine) or TCP+furegrelate were only determined in segments from cirrhotic rats. The vasodilator response to acetylcholine was higher in segments from cirrhotic rats. Indomethacin, SC-560 and NS-398 did not modify the vasodilator response in control rats; however, indomethacin, NS-398 and TCP+furegrelate increased, whereas SC-560 did not modify and SQ 29548, furegrelate or TCP decreased, the vasodilator response to acetylcholine in cirrhotic rats. NO release was higher in cirrhotic rats. Furegrelate decreased, whereas TCP+furegrelate increased, the NO release in segments from cirrhotic rats. eNOS and COX-1 protein expression was not modified, whereas phosho-eNOS, iNOS and COX-2 protein expression was higher in cirrhotic rats. Therefore the increase in iNOS expression and eNOS activity may mediate increases in endothelial NO release. The COX-2 derivatives TXA(2) and PGI(2) may act simultaneously, producing a compensatory effect that reduces NO release and may limit the hyperdynamic circulation.
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PMID:Simultaneous inhibition of TXA(2) and PGI(2) synthesis increases NO release in mesenteric resistance arteries from cirrhotic rats. 2045 96