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)

Density-defined macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 (LTB4, 16%) and 5-hydroxy-eicosatetraenoic acid (5-HETE, 24%) and the cyclooxygenase products 12-hydroxyheptadecatrienoic acid (HHT, 22%) and thromboxane B2 (TXB2, 18%). The synthesis of eicosanoids was linear with the maturity of the macrophage subpopulations, suggesting that eicosanoid production is increased in in-vivo activated macrophages.
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PMID:Eicosanoid production by density-defined human peritoneal macrophages during inflammation. 133 54

We investigated lipopolysaccharide-induced tumor necrosis factor production in vitro by peripheral blood monocytes from patients with various liver diseases. Tumor necrosis factor production was found to be significantly reduced in patients with chronic hepatitis B (n = 17; 135 +/- 30 pg tumor necrosis factor/ml; mean +/- S.E.M.) and patients with chronic non-A, non-B hepatitis (n = 15; 212 +/- 22 pg tumor necrosis factor/ml) compared with healthy control individuals (n = 47; 411 +/- 40 pg tumor necrosis factor/ml; p less than 0.0005 and p less than 0.01, respectively). This reduced tumor necrosis factor production was not only seen with an optimal stimulating concentration of lipopolysaccharide (100 ng/ml) but also with suboptimal concentrations (0.1 ng/ml). In contrast to patients with chronic viral hepatitis, monocytes from patients with alcohol-induced cirrhosis (n = 26; 444 +/- 49 pg tumor necrosis factor/ml), primary biliary cirrhosis (n = 7; 412 +/- 81 pg tumor necrosis factor/ml) and alcohol-induced fatty liver changes (n = 5; 401 +/- 62 pg tumor necrosis factor/ml) produced normal amounts of tumor necrosis factor when stimulated with an optimal concentration of lipopolysaccharide. Lipopolysaccharide (0.1 ng lipopolysaccharide/ml)-stimulated peripheral blood monocytes of patients with chronic hepatitis B (n = 15; 102 +/- 32 pg/ml) or non-A, non-B hepatitis (n = 13; 97+/- 16 pg/ml) could not be induced to produce more tumor necrosis factor either when prestimulated with gamma-interferon (170 +/- 45 pg/ml and 149 +/- 32 pg/ml, respectively), a lymphokine known to activate monocytes, or with the cyclooxygenase inhibitor indomethacin to reduce the suppressive effect of prostaglandin E2 (148 +/- 40 pg/ml and 153 +/- 45 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired lipopolysaccharide-inducible tumor necrosis factor production in vitro by peripheral blood monocytes of patients with viral hepatitis. 212 37

Macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 and 5-monohydroxyeicosatetraenoic acid. The cyclooxygenase products 6-keto-PGF1 alpha and thromboxane B2 were the most important prostaglandin-like substances. Malotilate, an anti-fibrotic substance, selectively inhibited the 5-lipoxygenase, whereas both the 12- and the 15-lipoxygenase pathways were stimulated. The effects of malotilate on eicosanoid production differ from those of known lipoxygenase inhibitors. Such differential effects have not been reported previously.
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PMID:Differential effects of malotilate on 5-, 12- and 15-lipoxygenase in human ascites cells. 253 38

Nonsteroidal antiinflammatory drugs impair renal function in susceptible patients with cirrhosis and ascites. A new antiinflammatory drug, sulindac, is reported not to affect renal function. To evaluate its renal-sparing mechanism, sulindac was administered for 5 days and ibuprofen for 1 day to 10 patients and paraaminohippurate and inulin clearances, serum and urine eicosanoids, and serum and urine sulindac metabolites were monitored. Ibuprofen reduced renal clearances in the 5 subjects with greatest sodium retention, whereas sulindac had no effect. Plasma concentration of the active sulfide metabolite was markedly increased in liver patients, and this concentration correlated with the inhibition of serum thromboxane (r = 0.75, p = 0.01). The percent inhibition of serum thromboxane with sulindac administration correlated with the inhibition of urinary eicosanoids (r = 0.68-0.81, all p less than 0.02). Ibuprofen was generally a more potent inhibitor of serum and urine eicosanoids. Thus, a major factor in the renal-sparing effect of sulindac appears to be its less potent inhibition of renal and extrarenal cyclooxygenase systems.
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PMID:Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac. 307 94

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

Recent evidence suggests that renal prostaglandins play a major role in the control of renal hemodynamics and function in patients with advanced liver disease. The available data suggest that alterations in renal prostaglandin metabolism participate in the pathogenesis of at least three prominent renal complications of liver disease: sodium retention, impaired renal diluting ability, and the hepatorenal syndrome. Nonsteroidal anti-inflammatory agents that inhibit cyclooxygenase activity favor sodium retention and diminish renal plasma flow and glomerular filtration rate in patients with decompensated cirrhosis. The clinical caveat emerging from these observations is that nonsteroidal anti-inflammatory agents, which inhibit cyclooxygenase activity, should not be prescribed for sodium-retaining patients with decompensated liver disease.
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PMID:Renal prostaglandins and the control of renal function in liver disease. 351 84

Arterial and hepatovenous concentrations of circulating prostaglandin E2 and prostaglandin F2 alpha, the stable metabolites of prostacyclin and thromboxane A2 were measured in patients with chronic liver disease and compared with those in control patients with coronary artery disease but without hepatic dysfunction. Specific radioimmunoassays were used after extraction on octadecyl C 18-silica gel columns and thin-layer chromatography. While low levels of all cyclooxygenase products were found in hepatic arterial blood in patients with proven cirrhosis (n = 10) and fibrosis (n = 8), significantly higher concentrations were detected in the hepatic vein. A similar concentration profile was observed in controls (n = 4). Thus, there is a marked but comparable release of prostanoids from the normal as well as the diseased liver. Hepatovenous prostaglandin E2 was 11.6-fold, prostaglandin F2 alpha was 7.5-fold, prostacyclin was 12.2.-fold and thromboxane B2 was 3.9-fold above the level in the artery in both groups of patients. The hepatovenous concentrations of all arachinodate metabolites were unrelated to changes of liver morphology, biochemical abnormalities or the presence of ascites. No correlation could be demonstrated between hepatic venous pressure gradient and the concentration of prostanoids in the hepatic vein with the exception of thromboxane B2 (r = 0.55, p less than 0.05). The occurrence of esophageal varices was not associated with a specific pattern of circulating prostanoids in the posthepatic vasculature. Moreover, the portal-venous concentrations of all prostanoids (five patients: two with fibrosis, three with cirrhosis) exceeded the level in the hepatic vein substantially.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of prostanoids into the portal and hepatic vein in patients with chronic liver disease. 353 Sep 46

We have studied platelet function in 10 patients with severe liver cirrhosis, compared to healthy subjects. Using washed platelets, we have investigated the molecular mechanism underlying the defect in platelet aggregation frequently observed in these patients. We have found that platelets from cirrhotic patients have a reduced responsiveness to thrombin and collagen in terms of aggregation, and receptor-dependent activation of phospholipase C, A2 and cyclooxygenase/thromboxane synthetase. We thus suggest that this impairment in transmembrane signalling is responsible for the defective platelet function observed in cirrhosis.
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PMID:Molecular mechanism underlying impaired platelet responsiveness in liver cirrhosis. 360 14

Prostaglandin E2 (PGE2) is the major renal cyclooxygenase metabolite of arachidonic acid. Urinary excretion of PGE2 is increased by dietary salt restriction, as well in cirrhosis and congestive heart failure. To determine whether urinary PGE2 affects transport along the nephron, the actions of luminal PGE2 were studied in the isolated perfused rabbit cortical collecting duct (CCD). Luminal PGE2 transiently hyperpolarized transepithelial voltage (Vt) in a dose-dependent manner (half-maximal effect approximately 10(-8) M) in contrast to a sustained depolarization of Vt produced by basolateral PGE2. Luminal PGE2 (0.1 microM) also significantly stimulated osmotic water permeability in the CCD. In CCDs cultured on semipermeable supports, apical PGE2 stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production, suggesting the effects of luminal PGE2 are mediated by adenylyl cyclase-stimulating EP2 or EP4 receptors. Sulprostone, a PGE2 analogue selective for EP1 and EP3 receptors, affected Vt only when applied from the basolateral but not the luminal surface. Luminal application of the EP2 receptor agonist butaprost was also without effect. These results suggest that luminal PGE2 affects Vt via a butaprost-insensitive EP4 receptor. The Vt effect of luminal PGE2 was not blocked by pertussis toxin, also arguing against an EP3-mediated Gi-coupled effect. Finally, 1 microM luminal PGE2 only slightly increased CCD intracellular calcium concentration ([Ca2+]i), in contrast to the marked increase in [Ca2+]i produced by basolateral PGE2 (0.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal prostaglandin E receptors regulate salt and water transport in rabbit cortical collecting duct. 765

Impaired vascular responsiveness to angiotensin II is a common feature in human cirrhosis with ascites. The aim of this study was to investigate whether vascular reactivity to angiotensin II is also decreased in rats with carbon tetrachloride-induced cirrhosis and ascites and to assess the role of endogenous nitric oxide in this abnormality. Increasing doses of angiotensin II (from 31 to 500 ng.kg-1.min-1) induced significantly smaller increases in total peripheral resistance in conscious cirrhotic rats with ascites (n = 8) than in control animals (n = 9) at each dose tested. A reduced response to angiotensin II was also observed in vitro in aortic rings of rats with cirrhosis and ascites compared with that in control aortic rings (maximal response: 104 +/- 16 mg vs. 204 +/- 18 mg; p < 0.001). This in vitro hyporesponsiveness to angiotensin II in aortic rings of cirrhotic rats with ascites was reversed on endothelium denudation or nitric oxide synthesis inhibition with N omega-nitro-L-arginine but was not influenced by cyclooxygenase inhibition with indomethacin. In conclusion, this study shows reduced vascular reactivity to angiotensin II in carbon tetrachloride-induced cirrhosis with ascites and indicates that this abnormality is mediated by nitric oxide.
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PMID:Impaired responsiveness to angiotensin II in experimental cirrhosis: role of nitric oxide. 802 Sep


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