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)

The effect of serum from patients with cirrhosis and hepatocellular carcinoma on the release of prostaglandin E2 by the human histiocytic lymphoma cell line U937 was investigated to explain the mechanism underlying the immunoregulatory dysfunction of monocytes in cirrhosis and hepatocellular carcinoma. Prostaglandin E2 production by U937 cells cultured with serum from cirrhosis patients (5.9 +/- 2.7 ng/ml, p less than 0.01) and hepatocellular carcinoma patients (5.4 +/- 2.6 ng/ml, p less than 0.01) was significantly higher than that of control cultures (2.0 +/- 1.0 ng/ml). This activity was decreased after heating and after freezing and thawing. By size exclusion fast protein liquid chromatography, the probable factor was eluted in the fraction with a molecular weight of 150 kD. By anion exchange chromatography with a stepwise increase of the NaCl concentration, the peak activity augmenting prostaglandin E2 production by U937 cells was eluted in the 0.05 to 0.1 mol/L NaCl fraction. The high level of this factor (monocyte-regulating factor) in patient serum might be one cause of abnormal monocyte immunoregulatory function in cirrhosis and hepatocellular carcinoma.
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PMID:Serum factor from patients with cirrhosis and hepatocellular carcinoma enhances production of prostaglandin E2 by U937 cells. 166 19

Prostaglandins and leukotrienes are ubiquitous mediators of a wide variety of physiologic and immunologic effects in liver function and disease. Although the biochemical, synthetic and catabolic pathways of these compounds from arachidonic acid are well known, their cellular mechanisms of action are less well understood. Numerous studies have demonstrated the role for leukotrienes in the pathogenesis and the protective action of PG in experimental animal models of liver injury. These have included models of liver cell damage due to ischemia, galactosamine, carbon tetrachloride, and lipopolysaccharide. More importantly, the results of these studies have led to the demonstration of protective properties of 16, 16 dimethyl PGE2 (dm PGE2) in a mouse model of viral hepatitis. These results have led to the use of IV PGE1 in the treatment of patients with fulminant viral hepatitis, where 71% overall survival was observed as well as in the setting of primary non function and recurrent hepatitis B following liver transplantation. While the mechanisms of prostaglandin hepatic protection are not well understood, it has been demonstrated that dm PGE2 abrogates the induction of tumour necrosis factor, leukotriene B4 (LTB4) and procoagulant activity by macrophages as well as attenuating the expression of major histocompatibility class antigens on the surface of hepatocytes, and may inhibit viral replication. Finally, prostaglandins are known to play a role in the renal dysfunction associated with cirrhosis and fulminant hepatic failure, and therefore further studies of these agents in the pathophysiology and treatment of liver diseases and their complications are warranted.
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PMID:Eicosanoids and the liver. 213 47

Plasma levels of glucagon, secretin, norepinephrine, arginine-vasopressin, and prostaglandin biosynthesis in the gastric mucosa were determined in cirrhotic patients with gastric vascular ectasia associated with hypoacidity, in cirrhotics without this lesion, and in healthy controls. Plasma concentrations of glucagon, secretin, and norepinephrine were similar in cirrhotics with gastric vascular ectasia and cirrhotics without this lesion, these concentrations being significantly higher (p less than 0.05) than in healthy controls. However, there was no significant difference between plasma levels of arginine-vasopressin in patients with cirrhosis (with or without gastric vascular ectasia) and those in healthy controls. The biosynthesis of prostaglandin E2 in the antrum of the gastric mucosa was significantly higher in cirrhotics with gastric vascular ectasia than in cirrhotics without this lesion (p less than 0.05) and healthy controls (p less than 0.005). Prostaglandin E2 in the corpus was significantly higher (p less than 0.05) in cirrhotics with gastric vascular ectasia than in healthy controls. The biosynthesis of 6-keto PGF1 alpha (a stable metabolite of prostacyclin) and PGF2 alpha in the corpus and antrum of gastric mucosa was not significantly different in cirrhotics with gastric vascular ectasia, cirrhotics without this lesion and healthy controls. Since prostaglandin E2 has a vasodilator and acid-inhibitory effect, we speculate that high content of this prostanoid in the gastric mucosa may play a role in the pathogenesis of ectatic capillaries and acid inhibition present in some cirrhotic patients.
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PMID:Increased gastric PGE2 biosynthesis in cirrhotic patients with gastric vascular ectasia. 230 36

Alcohol inhibits phospholipase (PL) activity in a number of animal models. We have therefore measured prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), liberated by stimulated peripheral blood mononuclear cells (PBMC) and neutrophils respectively in chronic alcoholics and in control subjects. Peripheral blood mononuclear cells from alcoholics produced less PGE2 (p less than 0.01) and neutrophils produced less LTB4 (p less than 0.025). Reduced PGE2 production by PBMC of alcoholics was corrected by the addition of exogenous arachidonic acid (p less than 0.005) whilst neutrophil LTB4 production remained lower in the alcoholics (p less than 0.01). Percutaneous liver biopsies were undertaken in the 20 alcoholics having abnormal liver function tests. Prostaglandin E2 biosynthesis was lower in PBMC from patients with alcoholic hepatitis than with alcoholic cirrhosis (p less than 0.05). Analysis of PBMC fatty acid composition demonstrated that endogenous arachidonate and linoleate contents were not significantly different in alcoholics and controls. Cells from controls and alcoholics were incubated with 0, 50 and 150 mmol/l ethanol for two hours but there was no alteration in PGE2 or LTB4 biosynthesis. In summary, we found reduced eicosanoid production by peripheral leucocytes in alcoholics, supporting the hypothesis that chronic alcohol consumption either inhibits membrane bound phospholipase activity or enhances, alternatively, catabolism of eicosanoids. This phenomenon is more marked in alcoholic patients with hepatitis than in those with cirrhosis alone.
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PMID:Prostaglandin E2 and leukotriene B4 synthesis by peripheral leucocytes in alcoholics. 255 53

Daily urine levels of PGE2 and PGF2 alpha as well as water-electrolyte exchange were measured in 72 patients with chronic active hepatitis (CAH) and hepatic cirrhosis (HC) in comparison with healthy controls. Furosemide treatment was performed in 26 HC patients. It was established that in CAH and compensated HC daily excretion of PGE2 and PGF2 alpha as well as 22Na elimination were within the range registered in the control. In association of HC with nonrefractory ascites the above excretion was elevated, with refractory one daily excretion of PGE2 was low, the urine ratio PGF2 alpha/PGE2 rose. Daily urine excretion of prostaglandins and PGF2 alpha/PGE2 value may be of prognostic significance in evaluating efficacy of diuretic therapy in HC patients with ascites.
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PMID:[Effect of furosemide on the renal prostaglandin system in liver cirrhosis with ascites]. 261 14

1. A cross-sectional study (protocol A) was performed in 19 rats with cirrhosis, induced by carbon tetrachloride (CCl4), and ascites and in 10 control animals to assess renal prostaglandin (PG) excretion in experimental cirrhosis. In an additional group of animals, including nine rats chronically exposed to CCl4 (CCl4 rats) and six control rats, a longitudinal study (protocol B) was performed to investigate the temporal relationship between changes in renal PG excretion, the renin--aldosterone system and renal function. 2. Urinary PG excretion was assessed by specific radioimmunoassay of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX) B2 after extraction with octadecyl silica cartridges and h.p.l.c. purification. Recoveries for each prostanoid (61 +/- 8% for PGE2, 64 +/- 12% for PGF2 alpha, 65 +/- 11% for 6-keto-PGF1 alpha and 66 +/- 17% for TXB2) were determined in every sample by adding tritiated standards, and the final values were corrected according to the individual recoveries. 3. Cirrhotic rats with ascites in protocol A showed a significantly higher plasma renin and aldosterone concentrations and urinary excretion of 6-keto-PGF1 alpha and TXB2 than did control animals. Urinary excretion of PGE2 and PGF2 alpha, however, was significantly reduced in cirrhotic animals as compared with controls. 4. In CCl4 rats included in protocol B, there was a close chronological relationship between the activation of the renin-aldosterone system, as estimated by urinary aldosterone excretion, the onset of sodium retention and the increase in urinary excretion of 6-keto-PGF1 alpha and TXB2. The urinary excretion of PGE2 and PGF2 alpha in CCl4 rats was reduced throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Longitudinal study of renal prostaglandin excretion in cirrhotic rats: relationship with the renin-aldosterone system. 304 23

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

The effects of polyunsaturated fatty acids (phosphatidylcholine) on renal function in healthy subjects and in patients with chronic renal failure, with liver cirrhosis, and with heart failure were studied. The drug was administered at 3.5 mg/kg i.v. (Linoleic acid 1.24 mg/kg). In all cases, the administration of the drug caused an increased excretion of sodium and especially of water with a reduction in basal urinary hypertonicity. The polyuria was caused by the higher glomerular filtration rate not being counterbalanced by an increase in tubular water reabsorption. The water reabsorption was mostly anisosmotic. The presence of urinary hypertonicity excluded an inhibition of ADH secretion by this drug. The sodium excretion was probably caused by an increase of the glomerular filtration rate whereas no significant changes in the tubular reabsorption of sodium were seen. We found a significant (p 0.05) increase in PGE2 urinary excretion after phosphatidylcholine administration. Lysine - acetylsalicylate injection after phosphatidylcholine, in other trials in the same patients, prevented the effects previously reported. Therefore we suggest that the effects of this drug are mediated by an increased availability of renal prostaglandins.
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PMID:Effects of polyunsaturated fatty acids and prostaglandin synthesis on renal function. 308 1

Prostaglandin (PG) synthesis in the kidney is localised to specific sites and is not uniformly present throughout the nephron. It is generally accepted that the regional heterogeneity of PGs, as well as the lack of vascular communications between the medulla and cortex, dictate that PGs [primarily prostacyclin (PGI2)] synthesised in the cortex (glomeruli and vasculature) regulate cortical function, while PGs (primarily PGE2) synthesised in the medulla (collecting tubule and medullary interstitial cells) regulate medullary function. Measurement of urinary unmetabolised PGs, or their stable hydration products, provides the best clinical assessment of the state of renal PG production. Under physiological circumstances, renal function is not critically dependent upon the integrity of PG synthesis, possibly because other regulatory mechanisms can compensate for PG synthesis inhibition. However, when renal PG synthesis is activated in response to altered haemodynamics (e.g. cirrhosis with ascites) or is pathologically reduced (e.g. chronic glomerular disease) then the consequences of pharmacological inhibition can become clinically apparent and measurable. In these circumstances, drugs that inhibit renal cyclo-oxygenase activity can acutely reduce glomerular filtration rate and renal blood flow by 30 to 50%. These functional changes are usually reversible upon discontinuing the drug. The long term consequences of renal PG synthesis inhibition are more difficult to assess. Theoretically, chronic inhibition of renal PG synthesis might be responsible for medullary ischaemia, possibly contributing to the picture of so-called analgesic nephropathy. Selective sparing of renal cyclo-oxygenase activity can be obtained by at least 3 mechanisms: differential 'sensitivity' of the glomerular cyclo-oxygenase; selective intra-renal inactivation of an active metabolite of the drug; differential rate of recovery of glomerular cyclo-oxygenase following irreversible acetylation by aspirin. The recent demonstration of a functional correlate of such biochemical selectivity suggests novel strategies for reducing the chronic renal toxicity of cyclo-oxygenase inhibitors.
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PMID:The role of prostaglandin synthesis inhibition in the renal syndromes associated with non-narcotic analgesics. 310 92

1. Functional renal failure (FRF) in cirrhosis with ascites could be related to an inappropriately low renal prostaglandin (PG) production. To investigate whether the impaired renal PG synthesis in these patients is related to a PG precursor fatty acid deficiency, serum levels of linoleic and arachidonic acids and the urinary excretion of PGE2, 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured in 10 normal subjects, 17 non-azotaemic cirrhotic patients with ascites and 10 cirrhotic patients with ascites and FRF. 2. Serum linoleic acid levels were similar in the three groups studied. Both groups of cirrhotic patients showed lower arachidonic acid levels than normal subjects; however, non-azotaemic cirrhotic patients and patients with FRF did not differ in relation to serum arachidonic acid. 3. Non-azotaemic cirrhotic patients had higher urinary PGE2, 6-keto-PGF1 alpha and TxB2 excretion than normal subjects and cirrhotic patients with FRF. Patients with FRF showed similar urinary PGE2 and TxB2 and lower urinary 6-keto-PGF1 alpha than normal subjects. In all cirrhotic patients no significant correlation was found between serum linoleic and arachidonic acid levels and urinary PGs. 4. In seven patients with FRF an acute intravenous infusion of linoleic acid induced a marked increase in serum levels of this fatty acid. However, no increase in serum arachidonic acid levels and urinary PG excretion and no improvement in renal function was observed. 5. This study suggests that an arachidonic acid deficiency is present in cirrhotic patients with ascites but that this abnormality is not a major determinant of renal function and PG production in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandin precursor fatty acids in cirrhosis with ascites: effect of linoleic acid infusion in functional renal failure. 313 42


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