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

Ascites was collected from six patients with liver cirrhosis and the cells isolated. These cells, mainly macrophages, were labelled with 14C-arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by HPLC. The main substances formed by the ascites cells were leukotriene B4, 5-hydroxy-6,8,11,14 eicosatetraenoic acid and leukotriene C4. Smaller amounts of thromboxane B2, 12-hydroxy-5,8,10 heptodecatrienoic acid and 6-keto-prostaglandin F1 alpha were isolated. Human peritoneal macrophages are therefore capable of producing leukotrienes and prostaglandins. Production of these substances might play a role in some of the complications of patients with liver cirrhosis and ascites.
 ...
PMID:Production of leukotrienes and prostaglandins by human ascites cells. 300 58

To investigate whether paracentesis could be an alternative therapy for ascites, 117 cirrhotics with tense ascites were randomly allocated into two groups. Fifty-eight patients (group 1) were treated with paracentesis (4-6 L/day until disappearance of ascites) and intravenous albumin infusion (40 g after each tap). Fifty-nine patients (group 2) were treated with spironolactone (200-400 mg/day) plus furosemide (40-240 mg/day). Patients from group 2 not responding to diuretics were treated with a LeVeen shunt. After disappearance of ascites, patients from both groups were discharged from hospital and were instructed to take diuretics. Patients developing tense ascites during follow-up were readmitted to hospital and treated according to their initial schedule. Paracentesis was effective in eliminating the ascites in 56 patients from group 1 (96.5%) and did not induce significant changes in renal and hepatic function, plasma volume, cardiac index, peripheral resistance, plasma renin activity, plasma norepinephrine and antidiuretic hormone concentration, and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1 alpha. Diuretics were effective in eliminating the ascites in 43 patients from group 2 (72.8%) (p less than 0.05). Ten patients in group 1 and 36 in group 2 developed complications during their first hospital stay (p less than 0.001). This difference was due to the significantly higher incidence of hepatic encephalopathy, renal impairment, and electrolyte disturbances occurring in patients treated with diuretics. The duration of hospital stay was 11.7 +/- 1.5 days for patients from group 1 and 31 +/- 2.8 days for patients from group 2 (p less than 0.001). The two groups did not differ significantly with respect to the probability of requiring readmission to hospital during follow-up, reasons for readmission, survival probability after entry into the study, and causes of death. These results indicate that paracentesis associated with intravenous albumin infusion is a fast, effective, and safe therapy for ascites in patients with cirrhosis.
 ...
PMID:Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. 329 7

To assess the possible role of increased renal thromboxane A2 (TXA2) synthesis in nonazotemic patients with cirrhosis and ascites and to establish the potential beneficial effect of inhibitors of renal TXA2 production in this clinical setting, we administered OKY 046, a selective TXA2 synthase inhibitor, 200 mg t.i.d. for 5 days, to 9 nonazotemic cirrhotic patients with ascites and avid sodium retention. OKY 046 inhibited platelet TXA2 production, as expressed by serum thromboxane B2 (TXB2) concentration, by approximately 85% (p less than 0.001 vs. baseline values) and reduced urinary TXB2 excretion by 72% (p less than 0.01). A significant increase of approximately 19% in inulin clearance was observed during the treatment (from 61.0 +/- 8.42 to 72.7 +/- 7.45 ml/min, p less than 0.05), whereas renal blood flow was unchanged (from 408.50 +/- 19.97 to 424.50 +/- 30.84 ml/min). Drug administration did not affect positive sodium balance [sodium excretion was 4.67 +/- 1.22 mEq/day before drug administration and 6.26 +/- 1.05 mEq/day during drug administration (on day 7)], plasma renin activity, plasma aldosterone concentration, or the urinary excretion of prostaglandin E2, 6-keto prostaglandin F1 alpha, or prostaglandin F2 alpha. These results suggest that renal TXA2 synthesis contributes to the regulation of renal hemodynamics in nonazotemic cirrhotic patients with ascites and avid sodium retention, but it does not seem to affect sodium balance.
 ...
PMID:Effects of OKY 046, a thromboxane-synthase inhibitor, on renal function in nonazotemic cirrhotic patients with ascites. 336 Feb 68

Urinary excretion of two prostacyclin metabolites was investigated in 48 subjects: 8 controls and 40 cirrhotics (9 without ascites, 22 with ascites and preserved renal function, and 9 with functional renal failure). Urinary 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), believed to reflect renal prostacyclin production, was significantly increased in patients without ascites and in ascitic patients with preserved renal function, but cirrhotics with renal failure showed rates similar to controls. Excretion of 2,3-dinor-6-keto-PGF1 alpha (PGI-M), the major urinary metabolite of systemic prostacyclin, was increased in all groups of patients, including those with renal failure. A single dose of sulindac, a renal-sparing prostaglandin synthesis inhibitor, reduced PGI-M but not 6-keto-PGF1 alpha in 5 cirrhotic patients. This would be consistent with the predicted renal origin of the latter and the systemic origin of the former. Ascitic patients with high urinary excretion of PGI-M (above the median value) showed significantly lower mean arterial pressure and higher plasma renin activity and aldosterone than patients with excretion below the median. Urinary 6-keto-PGF1 alpha was higher in patients with low PGI-M. Finally, creatinine clearance corrected excretion of PGI-M, as an estimation of relative plasma levels correlates both with plasma renin activity and plasma aldosterone in the 31 subjects who presented with ascites. It is suggested that enhanced synthesis of systemic prostacyclin may influence hemodynamic changes in patients with liver cirrhosis. Overproduction of systemic prostacyclin in the absence of increased renal prostacyclin synthesis appears to be characteristic of patients with functional renal failure.
 ...
PMID:Increased synthesis of systemic prostacyclin in cirrhotic patients. 351 Sep 38

In 5 patients with cirrhosis and ascites the glomerular filtration rate (GFR), free water clearance (CH2O) and urinary excretion of prostaglandin E2(PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured before and after a 3-day treatment with sulindac (400 mg/day). The administration of sulindac induced a marked fall of urinary excretion of PGE2 (from 24.2 +/- 5.5 to 3.8 +/- 1.1 ng/h; p less than 0.05), 6-keto-PGF1 alpha (from 19.9 +/- 2.9 to 5.6 +/- 1.1 ng/h; p less than 0.02) GFR (from 111 +/- 15 to 67 +/- 10 ml/min; p less than 0.01) and CH2O (from 7 +/- 1.5 to 3.7 +/- 1.3 ml/min; p less than 0.02) in all patients studied. The plasma concentration of the active metabolite sulindac sulfide in cirrhotics was 400% of that found in 6 healthy volunteers (9.6 +/- 1.7 vs. 2.4 +/- 0.6 ng/ml). Our results indicate that sulindac, at a dose of 400 mg/day, inhibits the renal synthesis of prostaglandins and impairs renal function in cirrhotics with ascites. These effects are probably related to the marked alteration of sulindac kinetics that occurs in these patients.
 ...
PMID:Sulindac reduces the urinary excretion of prostaglandins and impairs renal function in cirrhosis with ascites. 351 19

The object of this study was to investigate clinical conditions in which increased production of prostacyclin (PGI2) has been reported. 6-Oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) is the stable hydrolysis product of PGI2 and was measured in plasma from patients undergoing hepatic or cardiac surgery and in unoperated patients with vascular and hepatic disease, using gas chromatography/mass spectrometry. Blood obtained simultaneously from portal and peripheral veins, during emergency surgery for bleeding oesophageal varices in six patients with cirrhosis of the liver, contained very high concentrations of 6-oxo-PGF1 alpha (range 99-11,485 pg/ml of plasma). 6-Oxo-PGF1 alpha was higher in portal than in peripheral blood in five out of six patients. Six unoperated patients with cirrhosis and oesophageal varices which were not bleeding all had normal peripheral plasma concentrations of 6-oxo-PGF1 alpha less than 2 pg/ml (normal up to 5 pg/ml). Seventeen patients with severe vascular disease had normal basal plasma 6-oxo-PGF1 alpha concentrations (less than 2 pg/ml). Eighteen subjects with atheromatous coronary artery disease underwent aorta-coronary artery grafting, and plasma concentrations of 6-oxo-PGF1 alpha were markedly elevated during surgery (range 55-1207 pg/ml). We conclude that surgery stimulates PGI2 production substantially, and argue that the function of PGI2 may be to limit intravascular extension of thrombus from sites of haemostasis. Inappropriate PGI2 synthesis may contribute to the massive haemorrhage characteristic of oesophageal variceal bleeding.
 ...
PMID:Prostacyclin in the circulation of patients with vascular disorders undergoing surgery. 353 59

Imidazole-salicylate is a non-steroidal anti-inflammatory drug with limited inhibitory effects on prostaglandin synthesis. The renal effects of this drug were investigated by a double-blind cross-over study in 10 patients with cirrhosis and ascites. Two therapeutic doses of imidazole-salicylate (750 mg each) were given at midnight and 08:00 h and 80 mg of furosemide were injected intravenously at 09:00 h. The same procedure was followed on another day but a placebo replaced imidazole-salicylate. Renal function (creatinine clearance, free water and electrolyte excretions) and urinary excretion of prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were evaluated for 8 h after the first dose of the drug and for 2 h after furosemide injection. Platelet thromboxane production was also determined 9 h after the first administration of drug or placebo. Imidazole-salicylate did not affect renal function or inhibit kidney prostanoid production either under basal conditions or after the stimulating effect of furosemide. On the contrary, imidazole-salicylate significantly inhibited platelet thromboxane production (45.8 +/- 9 vs. 69.4 +/- 7.5 ng/ml, P < 0.05). These results suggest that imidazole-salicylate is an anti-inflammatory drug that can be given to patients with decompensated cirrhosis without risk of inhibiting kidney prostaglandin synthesis or the renal response to furosemide.
 ...
PMID:Effects of imidazole-salicylate on renal function and the diuretic action of furosemide in cirrhotic patients with ascites. 830 Oct 62

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.
 ...
PMID:Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension. 835 3