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)

Torasemide (torsemide) is a high-ceiling loop diuretic which acts on the thick ascending limb of the loop of Henle to promote rapid and marked excretion of water, sodium and chloride. Like furosemide (frusemide), its major site of action is from the luminal side of the cell. Torasemide is at least twice as potent as furosemide on a weight-for-weight basis, produces equivalent diuresis and natriuresis at lower urinary concentrations and has a longer duration of action, allowing once-daily administration without the paradoxical antidiuresis seen with furosemide. Torasemide also appears to promote excretion of potassium and calcium to a lesser extent than furosemide. In trials of up to 48 weeks' duration in patients with mild to moderate essential hypertension, torasemide, administered as a single daily dose, has been shown to achieve adequate blood pressure control reaching steady-state within 8 to 12 weeks. Those patients not responding initially have generally responded to a doubling of the dose. Comparative trials of up to 6 months show torasemide is as effective as indapamide, hydrochlorothiazide or a combination of triamterene/hydrochlorothiazide in maintaining control of blood pressure. Torasemide has also been used successfully to treat oedematous states associated with chronic congestive heart failure, renal disease and hepatic cirrhosis. In short term trials control of blood pressure, bodyweight and residual oedema has been sustained. Torasemide appears to be a useful alternative to furosemide in these patients, providing potent and long-lasting diuresis while being relatively potassium and calcium sparing. In clinical trials to date torasemide has been well tolerated with adverse effects of a mild, transient nature reported by only small numbers of patients. Changes in biochemical parameters have been common, including decreases in plasma sodium and potassium levels and increases in plasma creatinine and uric acid levels. These changes are typical of loop diuretics. No changes were clinically significant nor were clinically relevant changes noted in glucose metabolism, cholesterol or triglyceride levels or in haematological values. Thus, torasemide is an interesting new loop diuretic with potential use in the treatment of mild to moderate essential hypertension and of oedematous states in which diuretic therapy is warranted. Preliminary studies suggest it to be as efficacious as other diuretics in common use and to have some advantage over furosemide in duration of action and in effects on potassium and calcium. However, further long term trials in larger groups of patients are needed to delineate the place of torasemide in therapy fully, both as a single agent and in combination with other currently accepted drug regimens.
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PMID:Torasemide. A review of its pharmacological properties and therapeutic potential. 170 90

Insulin action was studied in rats with CCl4/phenobarbital-induced cirrhosis of the liver using the euglycemic hyperinsulinemic clamp technique coupled with isotopic measurement of individual tissue glucose uptake, glycogen formation, and lipogenesis. In cirrhotic rats, dose response curves showed a reduction of insulin-stimulated total body glucose disposal of about 30%. Insulin action on tissue glucose uptake and initial phosphorylation (assessed with [3H]2-deoxyglucose) were unchanged; however, incorporation of [14C]glucose into lipids and particularly into glycogen was reduced substantially (being most pronounced in skeletal muscle and diaphragm) at maximally as well as half-maximally effective serum insulin concentrations during euglycemic clamping. At identical IV insulin infusion rates, steady-state serum insulin concentrations were elevated up to fourfold in cirrhotic animals. Antilipolytic action of insulin was unaltered. These data suggest that the principal metabolic pathway affected in insulin resistance of rats with experimental cirrhosis appeared to be insulin-stimulated glycogen formation in muscle tissues.
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PMID:Mechanism of insulin resistance in CCl4-induced cirrhosis of rats. 172 57

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: a multicenter sequential trial. 172 3

The role of plasma glucose as a major regulator of glucagon secretion is well established. However, this feedback regulation appears to break down in several states in which a closer relationship is apparently evident between plasma glucagon and hepatic glycogen content. Therefore, we assessed plasma glucagon as well as glucose response (delta glucose) to intravenous (IV) bolus administration of 1 mg glucagon after an overnight fast (a reliable and accurate estimate of the magnitude of hepatic glycogen content) in a population of normal subjects and subjects with hepatic cirrhosis and hyperthyroidism, both of which are disorders characterized by hepatic glycogen depletion. Plasma glucose concentrations were not significantly different in either group. However, plasma glucagon and insulin concentrations were significantly increased and delta glucose significantly decreased in both cirrhotic patients and hyperthyroid patients as compared with normal subjects. Furthermore, a significant relationship (r = -.55, P less than .0001) was noted between delta glucose and plasma glucagon, but not plasma insulin. Therefore, we believe that pancreatic alpha-cell function may be dependent on hepatic glycogen content. Moreover, the primary action of glucagon may be to induce gluconeogenesis in the absence of hepatic glycogen stores due to declining insulin concentrations or insulin resistance.
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PMID:Is hepatic glycogen content a regulator of glucagon secretion? 173 31

In the post-absorptive stage L-alanine is the main source of alpha-amino-nitrogen reaching the liver as glucose precursor. This aminoacid has been used as a measure of urea synthesis capacity in several pathologic conditions, but it has not been employed sistematically in patients with liver cirrhosis. We tried to address this issue by evaluating: a) L-alanine plasma levels, b) urea extraformation (UE), and c) ammoniogenesis after oral L-alanine (0.25 and 0.50 g/kg b wt) in healthy control subjects and in patients with nonalcoholic compensated (Child-Pugh's A class) and decompensated (Child-Pugh's B and C) liver cirrhosis. L-alanine plasma levels after oral load were higher and lasted longer in cirrhotics as compared to controls. Furthermore, after L-alanine oral load, significantly higher ammonia plasma levels were observed in cirrhotics than in controls. Changes in the urea extraformation were comparable in cirrhotics and controls. Both delayed L-alanine elimination from plasma and L-alanine-induced hyperammoniemia were more evident in decompensated cirrhotics and related to L-alanine dose.
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PMID:L-alanine plasma levels after oral loads in non-alcoholic liver cirrhosis: relationship with urea extraformation and ammoniogenesis. 174 21

The in vivo dose response curve to insulin were studied, using an euglycemic insulin clamp technique, in 13 cirrhotic patients [8 with "hepatocellular" (HC) (nonalcoholics) and 5 with "cholestatic" (CHOL) cirrhosis] and 12 healthy controls (N). Subjects were studied in the basal state and during infusion of insulin at 3 different rates - 1, 3, 10 mU kg-1 min-1. Insulin responsiveness was similar in N and in HC, but it was 23% greater in CHOL (p less than 0.001). Insulin sensitivity was decreased in cirrhotics as compared with N but this difference was only significant (p less than 0.001) in HC. (ED50:62 + 5, 88 + 13 and 136 + 16 muu ml-1 in N, CHOL and HC respectively). Insulin clearance rate (ICR) was significantly (p less than 0.005) decreased in HC (1060 +/- 80, 996 +/- 95 and 776 +/- 128 ml sq m-1 ml-1 in N, CHOL and HC respectively. Basal hepatic glucose production (BHGP) was 39% lower in HC (p less than 0.005) and 24% lower in CHOL (p less than 0.05) than in N. Erythrocyte cholesterol phospholipid ratio was significantly elevated (p less than 0.001) in both groups of cirrhotic patients but was not correlated to specific metabolic changes described. In summary: i) intervariations in insulin dependent glucose metabolism were described in different cirrhotic groups; ii) basal hepatic glucose production and insulin clearance rate impaired in the different groups of cirrhotics; iii) the role of decreased cholesterol/phospholipid ratio on tissues glucose metabolism in cirrhotic patients should be further studied.
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PMID:In vivo insulin action in hepatocellular and cholestatic liver cirrhosis. 176 7

Patients with cirrhosis of liver are more prone to have accompanying diabetes mellitus. The present study was conducted to investigate various biochemical parameters in patients with hepatic cirrhosis without diabetes. In these patients blood pyruvate, total bilirubin and globulin levels were elevated as compared to normal individuals. In contrast serum albumin level declined significantly whereas no significant change was observed in the concentrations of blood glucose, total proteins, total lipids, urea and serum cholesterol. These studies confirm the previous reports that carbohydrate metabolism is deranged in hepatic cirrhosis which may lead to diabetes mellitus.
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PMID:Carbohydrate metabolism in liver cirrhosis. 177 May 58

Forty-four patients aged between 12 and 64 years comprising 16 hepatitis (group 1); 12 cirrhosis (group 2); 16 primary liver cell carcinoma (group 3) and 18 normal controls were studied. In hepatitis, plasma total cholesterol and total cholesterol/phospholipid ratio were significantly reduced, while the changes in red cell cholesterol and phospholipid and plasma phospholipid were not. The blood glucose was significantly reduced. The plasma total cholesterol/phospholipid ratio was positively correlated with the plasma total bilirubin. In cirrhosis patients, red cell total cholesterol and ratio to phospholipid were significantly increased and the plasma cholesterol reduced with no significant changes in red cell and plasma phospholipids. The plasma total cholesterol/phospholipid ratio was reduced while the corresponding ratio in red cells was increased. Both total cholesterol and the ratio to phospholipid in red cells were negatively correlated with albumin and positively correlated with the plasma total bilirubin. In primary liver cell carcinoma, the plasma and red cholesterol and their ratio in the red cell were significantly increased while the ratio in plasma was not. The serum albumin levels were reduced while the liver enzymes and total bilirubin were raised in all patient groups. Our results suggest a possible relationship between liver function and cholesterol deposition in red cells in liver disease.
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PMID:Erythrocyte and plasma lipids in liver diseases. 184 97

Insulin secretion and insulin sensitivity were evaluated in eight clinically stable cirrhotic patients and in 12 controls. OGTT was normal in cirrhotics but plasma insulin response was increased approximately twofold compared with controls. Subjects received a three-step (0.1, 0.5, 1.0 mU/kg.min) euglycemic insulin clamp with indirect calorimetry, [6-3H]-glucose, and [1-14C]-palmitate. During the two highest insulin infusion steps glucose uptake was impaired (3.33 +/- 0.31 vs. 5.06 +/- 0.40 mg/kg.min, P less than 0.01, and 6.09 +/- 0.50 vs. 7.95 +/- 0.52 mg/kg.min, P less than 0.01). Stimulation of glucose oxidation by insulin was normal; in contrast, nonoxidative glucose disposal (i.e., glycogen synthesis) was markedly reduced. Fasting (r = -0.553, P less than 0.01) and glucose-stimulated (r = -0.592, P less than 0.01) plasma insulin concentration correlated inversely with the severity of insulin resistance. Basal hepatic glucose production was normal in cirrhotics and suppressed normally with insulin. In postabsorptive state, plasma FFA conc (933 +/- 42 vs. 711 +/- 44 mumol/liter, P less than 0.01) and FFA turnover (9.08 +/- 1.20 vs. 6.03 +/- 0.53 mumol/kg.min, P less than 0.01) were elevated in cirrhotics despite basal hyperinsulinemia; basal FFA oxidation was similar in cirrhotic and control subjects. With low-dose insulin infusion, plasma FFA oxidation and turnover failed to suppress normally in cirrhotics. During the two higher insulin infusion steps, all parameters of FFA metabolism suppressed normally. In summary, stable cirrhotic patients with normal glucose tolerance exhibit marked insulin resistance secondary to the impaired nonoxidative glucose disposal. Our results suggest that chronic hyperinsulinism may be responsible for the insulin resistance observed in cirrhosis.
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PMID:Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. 186 66

Clinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with 14C-leucine and indirect calorimetry. In the first study insulin alone was infused, and the plasma amino acid concentration was allowed to decline. During the second study a balanced amino acid solution was infused with insulin to increase the total plasma amino acid concentration approximately twofold. Insulin-mediated glucose disposal (4.68 vs. 6.45 mg/kg-min, p less than 0.01) was significantly impaired by 30% in cirrhotic patients during both insulin clamp studies. In the postabsorptive state, cirrhotic patients manifested low plasma leucine (76 vs. 102 mumol/L) and alpha-ketoisocaproate (19 vs. 30 mumol/L) concentrations, but all parameters of leucine turnover were normal. When insulin alone was infused, the endogenous leucine flux (an index of protein degradation) declined similarly in cirrhotic patients (30.8 mumol/m2-min) and control (26.9) subjects, and this was accompanied by a similar decrease in plasma leucine concentration (31% vs. 33%). The decline in circulating leucine concentration was accompanied by a parallel decline in leucine oxidation (5.1 vs. 4.6 mumol/m2-min) and nonoxidative (28.9 vs. 26.0 mumol/m2-min) leucine disposal, which were of similar magnitude in cirrhotic patients and control subjects, respectively. In both cirrhotic patients and control subjects, combined hyperinsulinemia/hyperaminoacidemia elicited a similar stimulation of nonoxidative leucine disposal (an index of protein synthesis) and leucine oxidation while causing a greater suppression of endogenous leucine flux than observed with insulin alone. Thus the suppressive effect of insulin on protein degradation and the stimulatory effect of insulin/amino acid infusion on protein synthesis are not impaired in cirrhotic patients, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism.
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PMID:Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis. 187 88


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