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 urinary excretion of aldosterone, kallikrein and prostaglandin E2 (PGE2) was studied in sodium-retaining (RC) and nonretaining (NRC), nonascitic cirrhotic rats, under basal conditions and after an oral sodium load (5 mmol). The glomerular synthesis of PGE2 was measured in RC rats under the same conditions. Both groups of cirrhotic animals showed a decreased urinary excretion of PGE2. Isolated glomeruli of RC rats produced less PGE2 than those of the control animals, both under basal conditions and after the sodium load. The NRC group was the only one able to increase the urinary excretion of kallikrein in response to the sodium load. These findings could contribute to explain the early physiopathological events of hepatic cirrhosis.
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PMID:Urinary excretion and glomerular synthesis of prostaglandin E2 and prostaglandin F2 alpha in cirrhotic, non-ascitic rats: the effects of sodium overload. 316 14

Urinary kallikrein excretion was found as compared with 22 normal subjects (0.88 +/- 0.05 mumol/min/day) to be significantly reduced in 15 cirrhotics without ascites (0.42 +/- 0.04; p less than 0.01) and in 23 cirrhotics with ascites (0.15 +/- 0.02; p less than 0.01), and further, showed a significant difference between the two groups (p less than 0.01), but did not significantly change in 14 patients with chronic active hepatitis. Urinary kallikrein excretion in cirrhotics showed a positive correlation with serum albumin, indocyanine green disappearance rate, cholinesterase, and prothrombin, and an inverse correlation with bilirubin. After indomethacin administration to 13 cirrhotics with ascites, not only plasma renin activity and plasma aldosterone decreased significantly (p less than 0.01), but urinary kallikrein excretion also showed a small but statistically significant decrease (p less than 0.05). These results suggest that urinary kallikrein excretion decreases almost parallel to the severity of liver damage and is mediated via prostaglandins or the renin-angiotensin-aldosterone system, which may be involved in the reduction of renal blood flow in patients with liver cirrhosis.
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PMID:Urinary kallikrein excretion in chronic liver disease and effect of indomethacin. 351 May 29

A study of 93 patients with liver cirrhosis showed that the most important blood coagulation disorder in this pathology resulting in hypocoagulation, was not decreased synthesis and deficit of the prothrombin complex factors but disturbance of the final stage determined by afibrinogenemia. Considerable depression of XIIa-kallikrein-dependent fibrinolysis and marked increment of an antiplasmin level in the plasma were noted. Positive paracoagulation tests were revealed in 57% of the patients, and as other signs typical of the lingering DIC-syndrome were absent, they were interpreted as the "hypercoagulation syndrome" or "pre-DIC syndrome". The problem of possible relationship of development of both thromboses and hemorrhages with acquired afibrinogenemia in liver cirrhosis was discussed.
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PMID:[Role of dysfibrinogenemia and disorders of fibrinolysis in the pathogenesis of hemostatic pathology in liver cirrhosis]. 357 61

Increased renal production of prostaglandins are thought to be important for the maintenance of kidney blood flow in advanced cirrhosis. In alert, unanesthetized dogs with chronic cirrhosis and ascites, produced by bile duct ligation, we measured inulin and p-aminohippurate (PAH) clearance before and after the intravenous administration of 2 mg/kg indomethacin, an inhibitor of prostaglandin production. Inulin and PAH clearance declined by 42 and 43%, respectively. This decline in renal perfusion was not associated with changes in blood pressure or cardiac output. If portal hypertension was prevented by creating an end-side portacaval anastomosis at the time of bile duct ligation, indomethacin was without effect on renal perfusion whether or not the dog had ascites. If ascites was completely mobilized in cirrhotic dogs with portal venous hypertension with the aid of a LeVeen valve, indomethacin depressed inulin and PAH clearance as usual during the steady-state period once all ascites had been removed. An attempt was made to determine some of the factors mediating the apparent increase in renal prostaglandin synthesis by administering various pharmacological antagonists. The inhibition of angiotensin effect with saralasin and the inhibition of kallikrein with aprotinin prevented the usual indomethacin effect. It is concluded that portal hypertension, but not a "sick liver per se, in cirrhosis activates the renin-angiotensin system to both produce renal vasoconstriction and stimulate prostaglandin synthesis, thereby normalizing renal perfusion. Renal kallikrein also appears to play a role, probably by augmenting renin release.
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PMID:Renal perfusion in dogs with experimental hepatic cirrhosis: role of prostaglandins. 635 40

The behaviour of prekallikrein (PKK), factor XII, high molecular weight kininogen (HMWK) and kallikrein-inhibitor (KK-I) in 367 patients with various diseases is described. Malignancies lead to elevation of factor XII and KK-I, and reduction of PKK. The effect is more pronounced in patients with metastases. In renal diseases also one or more of the above mentioned parameters are abnormal. Defects requiring dialysis treatment significantly impair the contact factors. In this group low levels of PKK, Factor XII and HMWK and increased KK-I are common. In chronic renal disease patients, only F XII and KK-I are elevated, whereas PKK and HMWK are normal. Kidney transplantation leads to a rise in KK-I and reduction of PKK and HMWK. The values almost normalize few days after the operation. Factor XII, slightly increased immediately after transplantation, remains high in long term transplant recipients, whereas HMWK falls below normal. In liver disease patients, acute and chronic hepatitis, cirrhosis of the liver and coma, PKK is reduced. In cases with acute hepatitis PKK raises with recovery. Cirrhosis and coma lead to low HMWK and factor XII concentrations. KK-I is mostly affected during acute hepatitis, and is then highly increased. Our results clearly demonstrate that the biologic activity of one or more of contact factors is affected in many diseases.
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PMID:Prekallikrein, HMW-kininogen and factor XII in various disease states. 635 59

To investigate if the renal kallikrein-kinin system may be involved in the homeostasis of renal perfusion in cirrhosis, urinary kallikrein activity was measured in 11 normal subjects, 31 cirrhotics with ascites and preserved renal plasma flow (548.2 +/- 32.2 ml per min) and glomerular filtration rate (85.8 +/- 3.4 ml per min), and 18 cirrhotics with functional renal failure (renal plasma flow: 229.9 +/- 23.4 ml per min; glomerular filtration rate: 34.9 +/- 3.3 ml per min). Plasma renin activity, plasma norepinephrine concentration and the urinary excretion of prostaglandin E2 were also measured in these subjects. Cirrhotics without renal failure showed a significantly higher renin (4.9 +/- 1.1 ng per ml per hr), norepinephrine (458.2 +/- 50.4 pg per ml), urinary kallikrein (15.4 +/- 1.8 pkat per min) and urinary prostaglandin E2 (0.52 +/- 0.08 ng per min) than did normal subjects (1.08 +/- 0.1 ng per ml per hr, 218.1 +/- 18.2 pg per ml; 8.4 +/- 1.4 pkat per min and 0.24 +/- 0.02 ng per min, respectively). Cirrhotics with renal failure showed a significantly higher renin (16.1 +/- 3.4 ng per ml per hr) and norepinephrine (739.4 +/- 79.2 pg per ml), and a significantly lower urinary kallikrein (5.2 +/- 0.6 pkat per min) and urinary prostaglandin E2 (0.15 +/- 0.02 ng per min) than did normal subjects and cirrhotics without renal failure. Glomerular filtration rate correlated (p less than 0.001) with urinary kallikrein (r = 0.53), urinary prostaglandin E2 (r = 0.55), plasma renin (r = -0.41) and norepinephrine (r = -0.44).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal kallikrein excretion in cirrhotics with ascites: relationship to renal hemodynamics. 636 54

The renal kallikrein-kinin system is involved in the regulation of intrarenal blood flow and natriuresis. To study whether deranged sodium and water excretion in terminal cirrhosis is associated with an altered renal kallikrein-kinin system, urinary kallikrein excretion (UkalV) was measured. Low UkalV excretion was found in cirrhosis. In particular, nine cirrhotics with ascites showed a significantly lowered ratio of UkalV to urinary aldosterone excretion when compared with eight cirrhotics without ascites. Continuous infusion in cirrhosis and ascites of prostaglandin E1 (0.1 ng/kg/min) for 3 days resulted in marked increases in both daily urine volume and urinary sodium excretion; this was associated with a significant elevation of UkalV. These results suggest that in cirrhosis the impairment in renal sodium and water excretion may be attributed, at least in part, to deficient activation of the renal kallikrein-kinin system.
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PMID:Role of renal kallikrein in the derangement of sodium and water excretion in cirrhotic patients. 639 17

Twenty cirrhotic patients with ascites, divided into two groups of 10 each, according to their daily urinary sodium excretion (sodium retainers and sodium excretors) and given a diet of 75 mEq of sodium daily, underwent acute plasma volume expansion with 1,000 ml of 10% dextran in saline, infused through a catheter located in the right atrium. Even if a significant increase in sodium excretion was observed in both groups (p less than 0.001 in sodium excretors and p less than 0.05 in sodium retainers), plasma expansion did not reverse sodium retention in sodium retainers. A significant increase in creatinine clearance was found only in sodium retainers (p less than 0.02). Basal plasma renin activity and plasma aldosterone were elevated only in a few patients of both groups. The renin-angiotensin-aldosterone system was highly responsive to plasma expansion. Sodium retainers, who showed an ineffective natriuretic response after expansion, were able to suppress both plasma renin activity and plasma aldosterone in an analogous manner to the sodium-excreting group. This result lends strong support to the concept that the elevated aldosterone level in cirrhosis is not the major determinant of sodium retention. The kallikrein-kinin system was responsive to volume stimulus, since a decrease in kallikrein excretion was noted. It was significant in sodium retainers (p less than 0.05). Plasma PGE1,2 levels were significantly higher in sodium retainers than in controls. This may suggest that there is an activation of the intrarenal prostaglandin system, which could play a protective role against renal ischaemia. After volume expansion, PGE1,2 increased, but not significantly. Octopamine appeared unrelated to sodium excretion and unresponsive to volume stimulus. Endotoxins did not seem to be involved in renal sodium handling. Plasma volume expansion seemed effective in inducing a reduction of vasoconstrictor and sodium-retaining factors, such as the renin-angiotensin-aldosterone system. It is possible to suggest that volume expansion could increase PGE1,2. Plasma volume expansion produced different rates of sodium excretion in the two groups of patients and this suggests that impaired sodium handling in cirrhosis could, to some extent, be independent of effective plasma volume.
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PMID:Vasoactive factors in the mechanism of renal sodium handling in cirrhotics: the effect of acute plasma expansion. 643 53

1. Previous studies have documented activation of protease enzymes, such as the plasma kallikrein-kinin system, in hepatic cirrhosis. Increased plasma kinin generation could contribute to pathological systemic vasodilatation in cirrhosis, and reduced systemic vascular resistance has been suggested as a trigger to renal sodium retention in this disease. We investigated the effect of aprotinin, a protease inhibitor which binds to plasma kallikrein, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites. 2. Aprotinin was infused intravenously in high dosage (2 x 10(6) kallikrein inhibitory units loading, 1 x 10(6) kallikrein inhibitory units/h). 3. Of 13 patients, 10 had a low systemic vascular resistance (< 1200 dyn s cm-5) at baseline. In this group, eight showed an increase in systemic vascular resistance during aprotinin infusion. Overall, the increase in systemic vascular resistance was significant, and there was a small but significant increase in mean arterial pressure. In all patients, there were increases in renal plasma flow, glomerular filtration rate, and absolute and fractional urinary sodium excretion during aprotinin infusion. 4. Plasma renin activity, plasma angiotensin II and plasma aldosterone fell significantly during aprotinin infusion. Plasma prekallikrein, plasma noradrenaline and plasma atrial natriuretic peptide did not change. Plasma aprotinin concentration was 209 +/- 11 kallikrein inhibitory units/ml at the end of the infusion. 5. Before and during the infusion, there was a significant negative correlation between systematic vascular resistance and plasma renin activity. There was a positive correlation between the change in systemic vascular resistance and the change in renal plasma flow during aprotinin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the serine protease inhibitor, aprotinin, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites. 752 42

The vasoactive peptide bradykinin may be involved in the pathogenesis of vasodilation, which has been considered the initiating event of ascites formation in cirrhotic patents. Since bradykinin is generated through the cleavage of high molecular weight kininogen (HK) by kallikrein, we looked for the cleavage of HK by an immunoblotting technique in plasma and ascitic fluid of 28 patients with cirrhosis of different etiology. The majority of patients showed massive cleavage of HK in ascitic fluid (median 50% of total HK; range 23-100%). Patients with severe ascites had more cleaved HK in plasma (29%; range 8-38%) than normal subjects (22%; range 11-32) (P = 0.02). Patients with high levels of plasma renin activity (5-60 ng/ml/hour), which is considered a consequence of peripheral vasodilation, had more plasma cleaved HK (31%; range 18-38)(p = 0.0097) than normals. Thus, our data support the view that cleavage of HK could play a role in the pathogenesis of vasodilation and ascites formation in patients with decompensated cirrhosis.
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PMID:Cleavage of high molecular weight kininogen in ascites and plasma of patients with cirrhosis. 763 8


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