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)

Interruption of hepatic blood supply for 60 min deteriorated liver mitochondrial respiratory functional indices--that is, respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2). Recovery of ischemia-induced decreases in these functional indices in a saline-administered cirrhotic liver group was retarded compared with that in a normal liver group, and significantly low RCI and ST III O2 persisted 15 min after reperfusion. Prostaglandin E1 (PGE1) did not improve ischemia-induced decreases in RCI and ST III O2 but accelerated the recovery of mitochondrial respiratory function after reperfusion. Adenosine triphosphate (ATP) levels were markedly decreased during ischemia, and retardation of ATP recovery was also observed in rats with cirrhosis. PGE1 improved the recovery of ATP level in rats with cirrhosis. Liver blood flow in the cirrhotic liver was significantly lower than that of the normal liver. PGE1 enhanced liver blood flow. These results indicate that retardation of the recovery of RCI and ST III O2 in the cirrhotic liver might be based on the decrease in tissue blood flow and that agents increasing tissue blood flow might contribute to the acceleration of the recovery of mitochondrial respiratory function.
 ...
PMID:Effects of prostaglandin E1 on the recovery of ischemia-induced liver mitochondrial dysfunction in rats with cirrhosis. 185 49

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.
 ...
PMID:Eicosanoids and the liver. 213 47

An animal model of liver fibrosis was produced by means of albumin immunization. Human serum albumin was given subcutaneously to immunize the rats with a dose of 4 mg, for 4 times. Then a booster dose was given through the caudal vein of rats in which albumin antibodies had been produced. Liver fibrosis and cirrhosis was formed in 85.5% of the animals. The increase of collagen content in liver tissue was parallel with the pathological grading of fibrosis. Reabsorption of fibrous tissue in this model occurred much later than in CC14 model. Subcutaneous administration of PGE1 could effectively protect the rats from anaphylactoid shock due to bigger booster dose. In regard to the mechanism of fibrosis, study with electronic microscopy, immunofluorescence histology, detection of serum C1q and C3 suggested that liver fibrosis results from proliferation of lipocytes, which was promoted by the formation of albumin and immune complex, and excessive secretion of collagen.
 ...
PMID:[Animals with liver fibrosis induced by albumin immunization]. 263 26

To evaluate the sensitivity of the renin-angiotensin-aldosterone system in patients with liver cirrhosis, prostaglandin E1 was intravenously administered at the rate of 50 micrograms/hour for two hours to the 11 control subjects and 11 patients with liver cirrhosis (6 compensated and 5 decompensated). Basal plasma renin activity (PRA) in decompensated patients was significantly higher than those in control and compensated cirrhotics (P less than 0.01). Basal plasma aldosterone was also higher in decompensated than in control and compensated patients, but without significance. PGE1 had no virtual effect on PRA in control, but stimulated PRA in liver cirrhotics, in which statistical significance was only observed in decompensated (basal vs. one hour after PGE1: 2.4 +/- 0.9 ng/ml/min (mean +/- SE) vs. 6.9 +/- 2.1: P less than 0.025). The rate of renin release was significantly higher in compensated than in decompensated (327 +/- 50% vs. 143 +/- 26: P less than 0.05). Though PGE1 also increased plasma aldosterone in liver cirrhotics, statistical change was not seen. Fractional excretion of urinary sodium after PGE1 increased significantly in control (P less than 0.025), but not in liver cirrhotics. These results indicate that the renin-angiotensin-aldosterone system is easily activated by PGE1 in patients with liver cirrhosis and further suggest that the sensitivity of this system in compensated is more augmented than in decompensated patients.
 ...
PMID:Increased renin release by exogenous prostaglandin E1 in liver cirrhosis with and without ascites. 304 80

Prostaglandin E1 (PGE1, Prostin VR) in doses of 30 ng/kg . min was studied in two series of severely ill surgical patients with adult respiratory distress syndrome (ARDS). First the drug was administered in an initial trial in six patients; then a prospective, randomized, blinded trial was conducted in 10 studies on nine patients. PGE1 markedly decreased pulmonary artery pressure, pulmonary and systemic vascular resistance indexed, and venous pressures, while increasing cardiac output, arterial PO2 (PaO2), oxygen delivery, and oxygen consumption when compared with the baseline preinfusion control values and with the response of the placebo-treated control series. The PGE1 responses were greater in patients whose ARDS was primarily attributed to the postoperative state with or without sepsis and least in patients with cirrhosis. The data are consistent with the concept that the drug reduces vasoconstriction primarily in the pulmonary circulation but also in the systemic circulation; improved PaO2 usually follows the hemodynamic effect. We conclude that PGE1 may be a useful adjunctive therapy for ARDS.
 ...
PMID:Effects of prostaglandin E1 in adult respiratory distress syndrome. 351 57

In the fasting state the mean portal blood flow demonstrated by the pulsed Doppler system with the Octoson in liver cirrhosis (LC) patients (velocity (PV), 10.2 +/- 3.5 (mean +/- SD) cm/sec, 7.0 +/- 2.6 cm/sec/m2; flow (PF), 579 +/- 262 ml/min, 383 +/- 184 ml/min/m2 (n = 40)) was significantly lower than that in control subjects (PV, 21.2 +/- 5.2 cm/sec, 14.7 +/- 3.9 cm/sec/m2; PF, 966 +/- 344 ml/min, 667 +/- 220 ml/min/m2 (n = 40)). Food intake increased PV by 15% and PF by 15% in LC (n = 8) and increased PV by 56%, PF by 125% in controls (n = 8). Glucagon increased PV by 30% and PF by 52% in LC (n = 10) and increased PV by 50% and PF by 120% in controls (n = 8). Secretin increased PV by 44% and PF by 75% in LC (n = 9) and increased PV by 66% and PF by 142% in controls (n = 8). Vasopressin decreased PV by 42% and PF by 54% in LC (n = 9) and decreased PV by 48% and PF by 62% in controls (n = 8). Insulin, gastrin, and prostaglandin E1 had no effect in either group.
 ...
PMID:Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson. 354 85

This study was undertaken to compare the in vitro responses of the portal vascular bed of normal and cirrhotic rat livers to a variety of vasodilator agents. Using carbon tetrachloride-induced cirrhosis in the rat as a model, isolated liver preparations were perfused via the portal vein with a synthetic medium (2.5% bovine serum albumin in Krebs-Henseleit buffer) to eliminate extrahepatic neural and humoral influences. Under these experimental conditions the mean perfusion resistance of the cirrhotic livers was approximately 117% higher than in controls (P less than 0.001). The vascular tone of the normal liver was minimal as assessed by the response to a variety of vasodilator agents, including sodium nitroprusside (3.0 X 10(-3) M), magnesium sulphate (6.0 X 10(-2) M), papaverine hydrochloride (6.4 X 10(-4) M), and cytochalasin B (6.3 X 10(-5) M). In contrast, these agents reduced the perfusion resistance of the cirrhotic livers by approximately 15%. Prostaglandin E1 (3.0 X 10(-6) M) and isoprenaline hydrochloride (2.4 X 10(-6) M) produced a lesser fall in resistance which nevertheless was greater in cirrhotic livers than controls. Cirrhotic livers, unlike the controls, were found to contain large numbers of myofibroblasts in perivenous and perisinusoidal locations. Previous studies have shown that myofibroblasts are capable of sustaining a high level of intrinsic tone and relax in response to vasodilator agents. It is concluded that part of the increased resistance to flow through the portal vascular bed of the cirrhotic rat liver in vitro is due to an increase in intrinsic vascular tone, possibly mediated via myofibroblasts, and can be reversed by pharmacological agents.
 ...
PMID:Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators. 1515 26

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.
 ...
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.
 ...
PMID:Vasoactive factors in the mechanism of renal sodium handling in cirrhotics: the effect of acute plasma expansion. 643 53

83 patients with chronic active hepatitis (CAH), 38 of them with cirrhosis, were studied and compared with 10 control subjects suffering from chronic persistent hepatitis (CPH). Tubular acidosis frequently was found in our cases. Renal plasma flow and glomerular filtration rate were significantly decreased in CAH when compared with CPH. Selective renal arteriography showed evident decrease of arterial flow in the outer cortex. Selective renal scan with 99mTc microspheres of human albumin showed a frequent escape of the tracer from the kidney to the lung. PGE1 and PGE2 levels appeared higher in the renal artery than in the vein and were significantly more elevated in 9 cases with cirrhosis vs. 13 controls. These results suggest the frequent functional impairment of the kidney also in the early stages of CAH, with an increase of PGE levels and an opening of intrarenal shunts.
 ...
PMID:Functional renal alterations in chronic liver diseases. 698 60


1 2 3 Next >>