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)

To test further the competence of the cirrhotic liver to metabolize xenobiotics, hepatocytes were isolated from control and CCl4-induced cirrhotic male or female rats. Histologically micronodular cirrhosis was present in all CCl4-treated rats, while control rats had normal livers. Portal perfusion pressure and intrahepatic collagen content were also significantly increased by CCl4 administration. In male rats, no significant differences in levels of circulating transaminases nor in alkaline phosphatase was observed between cirrhotic and control rats, while CCl4-treated females had slightly higher than normal serum transaminase levels at the time of the studies. Hepatocytic cytochrome P-450 and basal xenobiotic biotransformation were unaffected by micronodular cirrhosis in both genders; calculation of the aminopyrine and 7-ethoxycoumarin intrinsic clearances (Cli) revealed, however, a slightly decreased transformation potential in hepatocytes obtained from cirrhotic females, a phenomenon not observed in cirrhotic male rats. It is speculated that the observed reduction in Cli may have been independent of cirrhosis per se, owing to the perduring cytotoxic effect of CCl4 as evidenced by the higher than normal level of transaminases in female rats. Finally, male rats were subjected to in vivo administration of phenobarbital or 3-methylcholanthrene; both compounds led to significant induction of the mixed-function oxidase system, which was similar in magnitude and in selectivity in control and cirrhotic rats as illustrated by calculation of the Michaelis-Menten kinetic parameters for aniline p-hydroxylation, aminopyrine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and p-nitrophenol UDP-glucuronyl transferase. We conclude that in well-established but compensated and hepatolysis-free micronodular cirrhosis, hepatocytes are fully able to transform xenobiotics and to respond normally and selectively to inducers of drug metabolism.
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PMID:Unimpaired induction of drug-metabolizing enzymes in hepatocytes isolated from rats with micronodular cirrhosis. 205 6

Ammonia is generated from a large number of metabolically important reactions. Despite its central importance in whole body nitrogen homeostasis excess ammonia is neurotoxic and its concentration must be kept low. Ammonia generated in most extrahepatic tissues is detoxified by incorporation into glutamine (amide). This glutamine may be used in a number of biosynthetic reactions (e.g. in pyrimidine synthesis). Alternatively, as a means of maintaining nitrogen balance, glutamine may be released to the blood. Resting skeletal muscle is particularly important 1) as a "sink" for removal of blood ammonia, and 2) as a major source of circulating glutamine. However, during vigorous exercise skeletal muscle may become a net contributor of ammonia to the blood. A few tissues and cell types (e.g. lymphocytes, macrophages, enterocytes, colonocytes, thymocytes, fibroblasts, bone) and tumors exhibit marked rates of glutamine utilization. In the kidney, glutamine is an important source of urinary ammonia. Ammonia generated from 1) the breakdown of nitrogenous substances in the gut, and 2) from the use of glutamine as a metabolic fuel in the small intestine, is taken up by the liver wherein it is detoxified by conversion to urea and to a lesser extent, glutamine. Some portal vein glutamine acts as a source of urea nitrogen. Ultimately, however, most excess ammonia nitrogen is detoxified indirectly (via glutamine (blood)----glutamine (small intestine)----ammonia (portal vein) or directly in the liver as urea. Portal-systemic shunting of blood, as occurs in chronic cirrhosis of the liver or following the surgical construction of a portacaval shunt results in portal blood bypassing the normal ammonia detoxification machinery of the liver. Under this condition blood ammonia levels rise markedly, increasing the burden on extrahepatic tissues, such as skeletal muscle, brain, and kidney, in maintaining ammonia homeostasis. The most commonly employed animal model of human liver disease is the rat in which an end-to-side portacaval shunt (PCS) has been surgically constructed. Brain glutamine synthetase activity is not increased in PCS rats and in some areas of the brain there may even be a decrease in activity. The brain glutamine synthetase appears to be working at near maximal capacity. Thus, the PCS rats exhibit profound neurological dysfunction when administered ammonium salts in amounts easily tolerated by normal animals. Because of the limited capacity of brain to remove excess ammonia, a rational approach to the treatment of patients with liver disease should include a regimen directed toward lowering the associated hyperammonemia.
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PMID:Ammonia metabolism in normal and portacaval-shunted rats. 210 90

Portal vein haemodynamics as demonstrated by the pulsed Doppler system were studied in 37 patients with cirrhosis who had been classified in three groups (A, B, and C) in accordance with the degree of liver failure. Maximal inner diameter of the portal vein was significantly lower in patients who were considered to be in good condition (group A) than in patients with moderate and severe liver failure (group B and group C) (p less than 0.001). A significant difference was also found between group A and group B and between group A and group C with regard to the portal blood velocity and portal blood flow (p less than 0.001). In accordance with the presence and size of the oesophageal varices, in patients with large varices the portal blood velocity and portal blood flow were significantly lower than in patients without varices (p less than 0.001), whereas maximal inner portal vein diameter was significantly higher (p less than 0.001). This study demonstrated that in patients with cirrhosis circulatory alterations in the portal vascular bed may be, at least in part, an indicator of the stage of liver disease.
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PMID:Influence of the degree of liver failure on portal blood flow in patients with liver cirrhosis. 218 74

We investigated portal hemodynamic changes in 86 patients with hepatic tumors who underwent partial hepatectomy. Portal blood flow was measured using a sector type Doppler ultrasound system before, during and after operation. In the intraoperative studies, the portal flow in patients who underwent massive liver resection decreased significantly. On the other hand, the portal flow in patients with minor liver resection tended to increase, but not significantly. Overall, portal flow per unit of cardiac out put decreased significantly; it also decreased significantly in patients who underwent massive or major liver resection, in patients with liver cirrhosis, and in patients whose post operative clinical course was satisfactory. In the post-operative studies (10-12 days after surgery), the portal blood flow decreased significantly in patients who manifested a severe post-operative clinical course; it showed no significant change in other patients. It is thus essential to monitor the portal hemodynamics of partial-hepatectomy patients. This is most readily realized using Doppler ultrasound.
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PMID:[Portal hemodynamic changes from partial hepatectomy--quantitative analysis of portal flow before, during and after hepatectomy, using an Doppler ultrasound system]. 219 61

Dopamine may be used in cirrhotic patients with renal or circulatory failure, but this drug can also increase the degree of portal hypertension. Hence, the systemic and splanchnic hemodynamic effects of dopamine have been studied in portal hypertensive rats with secondary biliary cirrhosis. The dose-response curves showed that dopamine significantly increased portal pressure at the same dose (80 micrograms min-1 kg-1 body wt.) in normal and biliary cirrhotic rats. Arterial pressure only increased with higher doses of dopamine in rats with biliary cirrhosis (160 micrograms min-1 kg-1 body wt.) while in normal animals it increased (80 micrograms min-1 kg-1 body wt.). Dopamine (160 micrograms min-1 kg-1 body wt.) significantly increased mean arterial pressure in normal and biliary cirrhotic rats. It significantly increased cardiac output in biliary cirrhotic rats from 134 +/- 6 to 153 +/- 7 ml/min but not in normals. Accordingly, systemic vascular resistance increased significantly in normal rats but not in cirrhotics. Portal pressure increased significantly in normal rats from 8.0 +/- 0.3 to 12.1 +/- 0.6 mmHg and in rats with biliary cirrhosis from 15.9 +/- 1.0 to 19.0 +/- 1.3 mmHg. Portal tributary blood flow increased significantly in normal and biliary cirrhotic rats (14.1 +/- 1 to 20.9 +/- 2.3 ml/min and 18.0 +/- 0.9 to 25.5 +/- 1.8 ml/min, respectively). This study shows that an elevated dose of dopamine increases the hyperkinetic syndrome in rats with secondary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic effects of dopamine in conscious rats with secondary biliary cirrhosis. 225 34

The effect of metoclopramide on portal blood flow, the maximal diameter of the portal vein, and some cardiovascular haemodynamic variables was studied in 10 patients with cirrhosis of the liver and portal hypertension. Portal vein haemodynamics were studied by the pulsed Doppler system. Within 15 min of intravenous administration of 20 mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 11.2 +/- 1.1 to 10.8 +/- 1.2 cm/sec and from 769.0 +/- 87.7 to 707.9 +/- 84.2 ml/min, respectively (p less than 0.001). Within about 30 min portal blood velocity and portal blood flow returned to basal values (p greater than 0.05). The maximal diameter of the portal vein, systolic and diastolic blood pressure, and heart rate remained unchanged. These results support the hypothesis that metoclopramide, which raises lower oesophageal sphincter pressure and reduces intravariceal blood flow, significantly decreases the portal blood flow in cirrhotic patients with portal hypertension.
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PMID:Effect of metoclopramide on portal blood flow in patients with liver cirrhosis, measured by the pulsed Doppler system. 226 72

The present study was intended to assess the incidence and the nature of gastric red spots (GRS) in patients with liver cirrhosis. Endoscopically, GRS was more frequently observed in patients with cirrhosis (n = 146) than those without cirrhosis (n = 103) (43.2% vs. 4.8%; P less than 0.001). There was no relationship between the incidence of GRS and the severity of cirrhosis or the size of varices. Portal venous pressure was higher in cirrhotics with GRS (n = 21) than those without GRS (n = 25) (33.7 +/- 6.0 mmHg vs. 28.2 +/- 4.8 mmHg; P less than 0.001). Morphometric analysis using the biopsied specimens was made in 16 cirrhotics with GRS, 12 cirrhotics without GRS, and 15 non-cirrhotics. The capillary bed occupation ratio (vascular area/mucosal area) was higher in cirrhotics with GRS (9.3 +/- 4.0%) than those without GRS 84.1 +/- 1.1%) or the non-cirrhotics (3.4 +/- 9.8%) (P less than 0.005, P less than 0.005), while there was no significant differences in the number of capillaries per unit area. Infiltrating inflammatory cell count was similar among the three groups. Extravascular red blood cell count per unit area was higher in cirrhotics with GRS (29.7 +/- 31.4) than those without GRS (5.4 +/- 5.1) or non-cirrhotics (5.4 +/- 6.3) (P less than 0.05, P less than 0.01). Furthermore, extravasation of red blood cells through defective portion of the endothelium and interposition of red blood cells in interepithelial spaces were observed electron microscopically in cirrhotics with GRS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastric red spots in patients with cirrhosis: subclinical condition of gastric mucosal hemorrhage? 227 29

Portal circulation in patients with chronic liver disease was evaluated by per-rectal portal scintigraphy, and per-rectal portal shunt indices were calculated to estimate the extent of the portosystemic shunt. The purpose was to identify patients with cirrhosis at special risk of developing esophageal varices. The cumulative incidence of varices in 3 years of the study in patients whose shunt index was originally 20% or over, was significantly higher than that in patients whose shunt index was originally under 20%. The cumulative survival rate in 7 years of the study in patients whose shunt index was originally under 70% was significantly higher than that in patients whose shunt index was originally 70% or over. The information obtained by calculating the shunt index could be used by physicians in out-patient clinics when deciding the schedule with which to monitor patients using barium esophagogram or endoscopy, and choosing the examination method.
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PMID:Prediction of esophageal varices in cirrhosis by per-rectal portal scintigraphy. 228 65

The pathogenesis of variceal hemorrhage is not well understood. Portal pressure and gastroesophageal collateral (azygous) blood flow are similar in patients with cirrhosis with or without a history of variceal bleeding. However, acute increases in these parameters in individual patients might predispose them to variceal rupture. Fifteen patients with alcoholic cirrhosis and portal hypertension were evaluated to test the hypothesis that ethanol intake acutely increases portal pressure or gastroesophageal blood flow and is a possible risk factor in variceal hemorrhage. A 10% solution of ethanol in 5% dextrose in water was infused intravenously at a rate sufficient to raise the blood-alcohol level to 100 mg/dl over 30 min. Eight patients received ethanol 5% dextrose in water; seven patients received a placebo (5% dextrose in water alone). Ethanol did not produce a significant change in wedged hepatic-vein pressure, free hepatic-vein pressure, azygous blood flow, mean arterial pressure or heart rate compared with the effects of 5% dextrose in water alone. Acute administration of ethanol does not increase portal pressure or gastroesophageal blood flow. It is unlikely that acute ethanol ingestion is a risk factor for variceal hemorrhage.
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PMID:The effects of ethanol administration on portal pressure and gastroesophageal collateral blood flow in patients with alcoholic cirrhosis. 232 59

We report the first detailed study of hepatic morphology in 28 biopsies from 16 Greenland Eskimo children with fatal familial cholestatic syndrome. The changes were categorized as early, intermediate and late. In the early stage, until 5 months of age, changes were restricted to zone 3, consisting of cholestasis and rosette formation without fibrosis. In the intermediate stage, from 5 to 14 months, cholestasis persisted and rosette formation increased, both with further extension into zone 2. Perisinusoidal fibrosis developed, first in zone 3 and later in zone 1. The late stage, from 17 to 60 months, showed a further increase in cholestasis and rosette formation, and fibrosis of zones 3 and 1 in nearly all biopsies. Portal to portal and portal to central fibrosis was evident with resulting cirrhosis in 2 of 7 patients. The morphological features can be summarized as pure cholestasis with prominent rosette formation followed by zone 3 fibrosis, zone 1 fibrosis, and, cirrhosis. Other characteristics are the virtual absence of inflammation and the lack of anatomical abnormalities such as paucity of bile ducts. The changes and their progression resemble those of Byler disease. Clinical and biochemical features are also largely similar, except for the presence of thrombocytosis in many of the Eskimo patients.
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PMID:Fatal familial cholestatic syndrome in Greenland Eskimo children. A histomorphological analysis of 16 cases. 250 28


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