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)

Although prostaglandins are thought to be involved in the hyperdynamic circulation of portal hypertension, the role of this substance has not been elucidated. Dose-response curves, the hemodynamic effects of prostacyclin (20 micrograms/kg) and its inhibitor indomethacin and measurements of plasma and urinary levels of 6-keto-prostaglandin F1 alpha were compared in three groups of six rats each: normal, with portal vein stenosis and with secondary biliary cirrhosis. Plasma and urinary levels of 6-keto-prostaglandin F1 alpha were higher in rats with portal vein stenosis and cirrhotic rats than in normal rats. Dose-response curves showed similar maximal decreases in arterial pressure in the three groups, whereas the maximal increase in portal pressure was less marked in cirrhotic rats than in normal rats and rats with portal vein stenosis. In normal rats, prostacyclin increased cardiac output by 21% and portal pressure by 41%. Similar increases were observed in rats with portal vein stenosis. In contrast, prostacyclin did not affect cardiac output and portal pressure in cirrhotic rats. Indomethacin induced a more marked vasoconstrictive effect in normal rats than in cirrhotic rats. This study shows that prostacyclin plays a role in the hemodynamic alterations in portal hypertension. Moreover, the hyporeactivity observed in cirrhotic rats suggests that prostacyclin plays a major role in the circulatory changes of portal hypertension due to chronic liver disease.
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PMID:Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension. 835 3

The paper summarizes the results of in-depth study of the prostaglandin system in healthy individuals and in patients with chronic hepatic diseases. Radioimmunological, gas chromatographic, enzyme immunoassays, and other biochemical studies have first provided evidence for the relationship between the impaired endogenous biological synthesis of prostaglandins (PG) E, F2 alpha, I2, thromboxane A2, the development of metabolic and hormonal disorders and the severity of hepatic failure in chronic hepatitis and cirrhosis of varying etiology, which leads to the conclusion that PGs play an important role in the regulation of liver function and in the pathogenesis of chronic damages. Previously unknown biochemical mechanisms of decreased PGE, PGF2 alpha, and PGI2 in this diseased organ have been revealed, which trigger the deficiency of their precursors (essential fatty acids), the impairment of lipid metabolism and the activity decline of prostaglandin synthetase and adenylate cyclase, etc. A concept on the multiplicity of the biochemical mechanisms responsible for systemic PG action, whose impairments are essential in the pathogenesis of chronic hepatic diseases has been forwarded. The findings are discussed by comparing recent data published in the literature on this problem.
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PMID:[Prostaglandins in chronic liver diseases]. 866

Plasma levels of PGI2 were measured by radioimmunoassay in 20 consecutively admitted cirrhotic patients with portal hypertension from Aug. 1993 to Aug. 1994. It was found that cirrhotic patients with portal hypertension had much higher portal venous PGI2 levels than controls (528.25 +/- 205.48ng/L vs. 235.73 +/- 49.36ng/L, P < 0.001). Portal venous PGI2 levels in patients with cirrhosis and portal hypertension correlated significantly with portal venous pressure (r = 0.60, P < 0.05). The results indicate that increased portal venous PGI2 levels may have a role in maintenance of established portal hypertensive state in cirrhotic patients with portal hypertension.
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PMID:[Plasma prostacyclin (PGI2) levels in peripheral venous, arterial and portal venous blood in cirrhotic patients with portal hypertension and their clinical implication]. 873 81

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

Prostaglandins (PGs) are arachidonic acid (AA) derivatives via the PG endoperoxyde H synthase (PGHS) complex. Two PGHS isoforms have been recognized, constitutive (PGHS-1) and inducible (PGHS-2), respectively. Within the kidney, vascular endothelium mainly produces PGI2; the whole glomerulus synthesizes several prostanoids, the predominant AA metabolite in humans being PGI2; tubules and medullary interstitial cells produce mainly PGE2. Renal PGs modulates the action of other hormones and autacoids involved in the regulation of renal hemodynamics, glomerular filtration and the renal handling of sodium and water. Renal PGs are, at least in part, excreted into urine. Measurement of urinary PGs or their metabolites has been found to provide a reliable estimation of basal as well as stimulated PG synthesis. Patients with cirrhosis of the liver show an increased renal synthesis of vasodilating PGs, as indicated by the high urinary excretion of PGs and/or their metabolites. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to these patients causes a profound reduction in renal blood flow and glomerular filtration rate, a reduction in sodium excretion, and an impairment of free water clearance. These data clearly indicate that the increased renal synthesis of vasodilating PGs has a relevant role in maintaining renal hemodynamics, sodium and water excretion in a clinical setting characterized by a reduction of effective plasma volume and a striking activation of the major vasoconstricting systems, namely the renin-angiotensin-aldosterone, the sympathetic nervous system, and vasopressin. Patients with hepato-renal syndrome have a reduced renal synthesis of vasodilating PGE2 in the setting of a striking activation of endogenous vasoconstrictors and a maintained or increased renal production of thromboxane A2. Therefore, an imbalance between vasoconstricting systems and the renal vasodilator PGE2 was proposed to explain the renal failure observed in this condition. The urinary excretion of 2-3-dinor 6-keto-PGF1 alpha, an index of systemic PGI2 synthesis, is increased in patients with cirrhosis and hyperdynamic circulation, thus raising the possibility that systemic synthesis of PGI2 may contribute to the arterial vasodilatation of these patients. Finally, administration of exogenous prostanoids to patients with cirrhosis is not effective either in ameliorating renal function or in preventing the deleterious effect of NSAIDs.
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PMID:Arachidonic acid derivatives and renal function in liver cirrhosis. 935 64

Topics of this review are the bronchopulmonary manifestations of gastroesophageal reflux disease, cirrhosis of the liver and chronic inflammatory bowel diseases. About 20% of patients with chronic obstructive airway disease show evidence of gastroesophageal reflux disease. Reflux bronchoconstriction seems to be of greater importance than microaspiration. First studies show the positive effects of acid inhibition by proton pump inhibitors on pulmonary symptoms. Hepatorenal syndrome is characterized by arterial hypoxemia with PaO2-values < 70 mm Hg. Different mediators (endotoxins, amines, polypeptides or allergens) are discussed. Furthermore, elevated levels of prostacycline, atrial natriuretic factor and platelet activating factor have been described. Recently published studies focused on the role of nitric oxide (NO). Patients with cirrhosis of the liver show a higher rate of a pathologically elevated airway resistance which might be induced by a reduced histamine clearance. Ascites leads to reversible restrictive airway disease. Bronchopulmonary manifestations in chronic inflammatory bowel diseases include obstructive and restrictive airway diseases, vascular or serosal changes and show low clinical evidence. In contrast, pathological changes of the common function tests were found in 30 to 50%. These findings may be induced by circulating immune complexes, vasculitis, increased permeability or a combined immune reaction of both, the bronchial and intestinal mucosa. Undesired effects of salicylates should be taken into account. This review shows that bronchopulmonary manifestations in diseases of the Gl-tract or the liver are more common than usually known and should be taken into clinical consideration.
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PMID:[Bronchopulmonary manifestations of gastroenterologic and hepatic diseases]. 948 15

Splanchnic and systemic arteriolar vasodilation plays an important role in ascites formation in cirrhosis. Octreotide produces splanchnic vasoconstriction, but the effects on systemic hemodynamics and renal function are controversial. This study evaluated the effect of subcutaneous octreotide administration on systemic hemodynamics, endogenous vasoactive systems, and renal function in cirrhotic patients with ascites. Twenty patients were included: 10 received octreotide 250 microg/12 hr subcutaneously (for five days), and 10 did not. No statistically significant changes were found in mean arterial pressure and cardiac rate. Octreotide induced a statistically significant decrease in plasma renin activity (P < 0.01), plasma aldosterone (P = 0.01) and plasma glucagon (P < 0.05). No significant variations were observed in other systemic vasoactive substances (nitric oxide and prostacyclin). Renal function was not modified in either group. In conclusion, in cirrhotic patients with ascites, subcutaneous octreotide administration decreases plasma glucagon, renin activity, and aldosterone without changing in systemic hemodynamics or renal function.
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PMID:Effect of subcutaneous administration of octreotide on endogenous vasoactive systems and renal function in cirrhotic patients with ascites. 979 Apr 52

Variceal bleeding is a life-threatening complication of cirrhosis. Potential risk factors include clinical, endoscopic, and haemodynamic factors, but why bleeding occurs unpredictably in individual patients is not known. We postulate that bacterial infections in patients with variceal haemorrhage may be the critical factor that triggers bleeding. In patients with large varices and a high wall tension, the release of endotoxin into the systemic circulation during episodes of bacterial infection results in a further increase in portal pressure through the induction of endothelin and possibly vasoconstrictive cyclo-oxygenase products. The subsequent contraction of hepatic stellate cells causes a rise in intrahepatic vascular resistance. Furthermore, endotoxin-induced nitric oxide and prostacyclin, and prostacyclin induced by endothelin could inhibit platelet aggregation, which may result in a further deterioration of primary haemostasis at the level of varix. We propose that the combination of these two effects leads to the onset of variceal haemorrhage.
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PMID:Bacterial infection in the pathogenesis of variceal bleeding. 1019 80

Prostacyclin is a powerful vasodilator and inhibits platelet adhesion and cell growth. We hypothesized that a decrease in expression of the critical enzyme PGI2 synthase (PGI2-S) in the lung may represent an important manifestation of pulmonary endothelial dysfunction in severe pulmonary hypertension (PH). Immunohistochemistry and Western blot analysis were used to assess lung PGI2-S protein expression, and in situ hybridization was used to assess PGI2-S mRNA expression. In the normal pulmonary circulation (n = 7), PGI2-S was expressed in 48% of small, 67% of medium, and 76% of large pulmonary arteries as assessed by immunohistochemistry. PPH (n = 12), cirrhosis-associated (n = 4) and HIV-associated PH (n = 2) lungs exhibited a marked reduction in PGI2-S expression, involving all size ranges of pulmonary arteries. Vessels with concentric lesions showed complete lack of PGI2-S expression. Congenital heart (n = 4) and CREST (n = 2) cases exhibited a more variable immunohistological pattern of PGI2-S expression. These results were complemented by in situ hybridization and Western blots of representative lung samples. We conclude that the different sizes of the pulmonary arteries express PGI2-S differently and that the loss of expression of PGI2-S represents one of the phenotypic alterations present in the pulmonary endothelial cells in severe PH.
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PMID:Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. 1035 41

Pulmonary hypertension (PH) may develop because of a spectrum of insults to the lungs; in some patients, there seems to be no cause. Noninvasive tests, such as standard chest radiography, electrocardiography, and transthoracic Doppler echocardiography, provide effective screening if PH is suspected. This synopsis focuses on these screening studies and the more common clinical problems, including primary cardiac abnormalities, obstructive sleep apnea, chronic pulmonary embolism, pulmonary parenchymal problems, connective tissue disorders, cirrhosis with portal hypertension, and use of appetite suppressants, that should be considered when PH exists. Treatment options for PH, including intravenous prostacyclin (epoprostenol), and investigational agents such as subcutaneous or oral prostacyclin analogues and oral endothelin receptor antagonists are described.
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PMID:Pulmonary hypertension: diagnostics and therapeutics. 1085 24


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