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)

Atrial natriuretic factor (ANF) is a humoral agent isolated in recent years from cardiac atrial tissue, and produced by atrial cardiocytes as a peptide precursor containing 152 amino acids. In secretory atrial granules, it is stored in reserve form as a prohormone and released into circulation as a 28-amino acid peptide from the C-terminal portion of the peptide precursor representing the active circulating hormone. ANF possesses potent natriuretic, myorelaxant, vasodilatory and blood pressure-lowering properties. Besides, it inhibits renin, aldosterone and vasopressin secretion. It is present also in the CNS and its function is closely related to the sympathetics nerves. By its direct renal and vascular effect, renin-angiotensin-aldosterone system and vasopressin inhibition and, by its neuromodulatory action on the central and sympathetic nerves, ANF plays an important role in electrolyte, volume and pressure homeostasis. The development of a radioimmunoassay for ANF determination in the plasma of rats and man enabled us to follow up its changes under various experimental conditions (water deprivation, increased or decreased salt intake, effect of anaesthetics, ontogenetic changes in ANF concentration during development of hypertension in the spontaneously hypertensive rat) and in clinical studies (effect of ECV expansion in controls, arterial hypertension, liver cirrhosis as well as ANF changes in congestive heart failure or chronic renal failure). These findings of ours have supported the concept that ANF represents an important adaptive and corrective mechanism mobilized during intravascular volume and blood pressure changes in an effort to normalize these. ANF is expected to find use also in the treatment of oedema, arterial hypertension and acute renal failure.
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PMID:Atrial natriuretic factor and its role in the regulation of electrolyte, volume and pressure homeostasis. 252 70

The renal response to atrial natriuretic factor (ANF) (175 ng.kg-1.min-1) was tested in nine dogs during a control period and again after the appearance of experimental cirrhosis, ascites, and avid sodium retention. During the cirrhotic phase, plasma volume had increased by 28.4% (P less than 0.05), renal perfusion and glomerular filtration rate (GFR) were unchanged from control values, and plasma immunoreactive ANF (iANF) had declined from 71.6 +/- 9.5 to 34.7 +/- 5.4 pg/ml (P less than 0.05). During the control phase, change of urinary sodium excretion rate (delta UNaV) increased by 132 +/- 22 mu eq/min but was attenuated in the cirrhotic phase (delta UNaV = 29 +/- 12.5 mu eq/min). Of these nine cirrhotic dogs, five responded with a delta UNaV ranging from 20 to 114 mueq/min (mean delta UNaV = 59.6 +/- 10.6 mu eq/min), whereas 4 were nonresponders (delta UNaV = 1.3 +/- 0.6 mu eq/min). In neither group could delta UNaV be correlated to changes in GFR, clearance of p-aminohippurate, or filtration fraction. In an additional 10 dogs studied only during cirrhosis, 5 were natriuretic responders and 5 were nonresponders. Atrial content of ANF, half time of infused ANF, and plasma levels of iANF did not differentiate the two groups. We conclude that, like chronic caval dogs with ascites, salt-retaining cirrhotic dogs show heterogeneity of natriuretic response to infused ANF, which is unexplained by differences in renal perfusion.
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PMID:Heterogeneous renal responses to atrial natriuretic factor. II. Cirrhotic dogs. 253 53

Malignant ascites is often refractory to therapy and rapidly deteriorating the nutritional and physical state of the cancer patient. Nevertheless, ascites does not always implicate preterminal state of the cancer process (e.g. ovarian carcinoma). A short review is made of the pathophysiology of ascites in cirrhosis and in malignancy, and different modes of treatment are discussed. The results of medical therapy of malignant ascites (salt and water restriction, diuretics, intraperitoneal cytostatics or radiocolloids) are not convincing. The immunotherapy with OK-432, as worked out by Katano (16-46) has to prove its value. The best and most hopeful results in cases of massive previously resistant ascites, are obtained with a peritoneojugular shunt, improving immediately the nutritional status and life condition, providing excellent palliation. The superiority of the Denver shunt versus the Le Veen shunt has been assessed recently, especially for malignant ascites. Some technical and perioperative details merit more attention, to limit the high risk ratio. Control of the intrathoracic position of the catheter tip, the maintenance of the bloodflow in the jugular vein, the intramuscular tunnelisation of the peritoneal catheter, the discard of 3 or 5 liters ascitic fluid and the substitution of part of it by physiological fluid, perioperative prophylactic antibiotics and heparinisation, flow-rate control in the postoperative period by changing patients position, respiratory exercises, daily flushing, all those measures limit the risk of fibrinolysis (DIC), shunt occlusion, fluid overload and infection. The fear of metastasis by shunt is unfounded, since the survival of the primary tumor is mostly too short (41). The postoperative follow up in an intensive care unit is necessary during 24-72 hours.
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PMID:[The Denver shunt in malignant ascites]. 258 Apr 8

1. In cirrhosis the kidney tends to retain salt and water abnormally. Two theories have been proposed to account for this: the 'underfilling' theory, in which sodium retention is thought to occur secondary to perceived underfilling of the circulation, and the 'overflow' theory, in which sodium retention is considered to be due to a primary renal defect. 2. Using the model of cirrhosis produced by carbon tetrachloride administration in the rat, the ability of the kidney to excrete sodium has been examined in vivo and during isolated perfusion. 3. Cirrhotic animals demonstrated a reduced ability to excrete an acute sodium load: 6 h after 2 mmol of sodium was given by gavage, 27.5 +/- 10.5% had been excreted by the cirrhotic rats and 62.5 +/- 7.0% by control rats (P less than 0.025). 4. In contrast, during isolated perfusion, kidneys from cirrhotic animals excreted the same amount of sodium as control animals over a range of perfusion pressures from 90 to 150 mmHg (12 to 20 kPa). 5. The data are consistent with the view that in cirrhosis the kidney retains sodium in response to immediate external factors.
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PMID:Sodium handling in the isolated perfused kidney of the cirrhotic rat. 260 69

This study was conducted to investigate the relationship between life style factors and adult disease for Chinese living in Japan. The mortalities of major cancers and other major diseases of Chinese in Japan were compared with those of Japanese by calculating Standardized Mortality Ratios (SMR) for the Chinese using death rates in the Japanese population the standard. The life style data on smoking, drinking and dietary habits for Chinese in Japan were collected by self-administered questionnaire surveys, and age-adjusted proportions were calculated with the truncated world population as the standard. Then the corrected indexes on life style for Chinese in Japan were compared with those of Japanese. The results are summarized as follows: 1. The mortality rates of heart disease, diabetes mellitus, hypertensive disease, liver cirrhosis, rectum cancer, liver cancer (both sexes), lung cancer (females), breast cancer and cerebrovascular disease (females) for Chinese in Japan were higher than those for Japanese, but the rates of stomach cancer, pancreas cancer (both sexes), uterus cancer (females) and cerebrovascular disease (males) were lower than those for Japanese. 2. The prevalence of current smokers for Chinese males in Japan was lower than that of Japanese, and that of females was higher than that of Japanese. The prevalence of non-smokers for Chinese males was higher than that of Japanese, and that of females was lower than that of Japanese. 3. Although the prevalence of regular drinkers for Chinese of both sexes in Japan were lower than that of Japanese, the prevalence of heavy drinkers who drank over 80 ml of ethanol every day for Chinese males was higher than that of Japanese males. 4. Significant differences were not found in the prevalences of frequent consumers of meat, milk, eggs, fish, other vegetables and food using oil between cooks and non-cooks of Chinese of both sexes in Japan. 5. The age-adjusted prevalences of frequent meat and milk consumers for Chinese in Japan were higher than those of Japanese in both sexes, but those of frequent pickled vegetable and MISO soup consumers were lower than those of Japanese. The dietary pattern of Chinese in Japan was different from that of Japanese with intakes of much fat and less salt. 6. It is assumed that the mortalities due to adult disease for Chinese in Japan are related to their heavy drinking and to their dietary habits.
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PMID:[A socio-medical study of adult diseases related to the life style of Chinese in Japan]. 263 81

The effect of chronic alcoholism (with or without associated moderate cirrhosis) on the disposition of the antidepressant tianeptine, which is devoid of substantial first-pass metabolism, was examined in 21 patients and 11 age-matched controls. Pharmacokinetic parameters for tianeptine and its C5 acid analogue metabolite (MC5 metabolite) were estimated by non-compartmental analysis. The area under the curve (AUC) for tianeptine, following a 12.5mg single oral dose, was decreased by 31% in chronic alcoholics and increased by only 14% in cirrhotics, compared to controls. These changes did not attain statistical significance. The trend of changes in the AUC for the MC5 metabolite was similar to that observed for the parent drug. No statistical difference was found in the terminal half-life for both tianeptine and its MC5 metabolite between patients and controls. On the basis of this study, it appears unnecessary to modify the proposed dosage regimen used in clinical trials (tianeptine sodium salt 12.5mg 3 times daily) in chronic alcoholics with or without associated moderate cirrhosis.
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PMID:Tianeptine and its main metabolite pharmacokinetics in chronic alcoholism and cirrhosis. 272 Oct 88

To investigate whether the hypercholeresis seen in cirrhotic humans and animals is due to ductular proliferation or altered inactivation of secretin, or both, we studied the response of bile flow and biliary erythritol clearance to synthetic porcine secretin in rats rendered cirrhotic by chronic exposure to phenobarbital/carbon tetrachloride (n = 11) and untreated control rats (n = 5). Bile duct mass was determined morphometrically. Furthermore, plasma disappearance of secretin was measured by radioimmunoassay. Basal bile flow did not differ between the two groups. Whereas secretin had no effect in the control group, it stimulated bile flow by 49% +/- 33% in the cirrhotic group (p less than 0.001). Erythritol bile-to-plasma ratio was lower and biliary bicarbonate concentration higher in the cirrhotic rats, suggesting some ductular contribution to bile flow even in the absence of secretin. Biliary bicarbonate concentration did not increase further during secretin administration, whereas bile salt concentration decreased from 27 +/- 6 to 18 +/- 4 mM. The elimination half-life of secretin was not affected by cirrhosis, averaging 5 +/- 2 min in both groups. Bile duct volume was increased in cirrhotics (2.9% +/- 1.4% vs. 0.2% +/- 0.1%; p less than 0.01) and showed an excellent correlation with the maximal secretin-induced increment of bile flow. Our results suggest that the proliferating ductules contribute to bile flow and that increased secretin responsiveness is not due to altered pharmacokinetics in cirrhotic rat liver.
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PMID:Effect of secretin on bile formation in rats with cirrhosis of the liver: structure-function relationship. 232 32

Hypertransaminasemia is a frequent side effect during chenodeoxycholic administration for gallstone dissolution. Evidence suggests that this effect is not mediated by lithocholic acid, the intestinal metabolite of chenodeoxycholic acid, but that toxicity is due to the chenodeoxycholic acid itself. In vitro cytotoxicity of bile salts is positively proportional to their detergent effect, which is, on the other hand, related to their hydrophobic-hydrophilic balance. We hypothesize that in vivo also liver injury can occur when the liver is perfused by an high proportion of strongly detergent bile salts. The more detergent bile salts are unconjugated or glycine conjugated, while the lesser are taurine conjugated and sulfated. Within each class the following order of decreasing detergent power can be indicated: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. Besides chronic exogenous administration of chenodeoxycholic or deoxycholic acids, conditions in which the liver is perfused by an high mass of highly detergent bile salts are those characterized by an enhanced intestinal biodegradation of bile salts. These conditions, which are common features of some chronic inflammatory bowel diseases, are frequently associated with liver damage. On the other hand, a normally detergent bile salt pool can become hepatotoxic for liver cells which have already been injured. In this respect, as already reported for increased sulfation, the increased proportion of taurine conjugates and the reduced formation of deoxycholic acid in liver cirrhosis can be regarded as protective mechanisms. Liver toxicity induced by bile salts' detergent action can be prevented by favouring tauroconjugation or reducing the intestinal degradation of bile salts or by administering poorly detergent bile salts.
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PMID:Bile acid-induced liver toxicity: relation to the hydrophobic-hydrophilic balance of bile acids. 287 79

The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. All patients received 1 mg bumethanide intravenously and were randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1,133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly greater during recumbency: mean sodium 96 v 45 mmol (mEq)/6 h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and the heart rate 76 and 83 beats/min (p less than 0.05) in the supine and upright positions, respectively. Plasma concentrations of noradrenaline, renin, and aldosterone rose significantly during the upright position. The results suggest that the attenuated response to intravenous bumethanide in the upright position and during normal daily activity may be due to the activation of several, homoeostatic mechanisms which may reduce the excretion of water and salt.
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PMID:[Effect of posture on the diuretic treatment of decompensated cirrhosis and heart failure]. 291 77

Renal sodium and potassium handling, plasma aldosterone and cortisol concentrations, and urine free norepinephrine excretion were determined every 4 h for 24 h in 15 cirrhotics (7 without ascites, group 1; 8 with ascites, group 2) and 7 healthy controls during controlled salt intake and recumbency. Renal sodium excretion was significantly reduced in group 2, whereas it exceeded threefold the salt intake in group 1. Its circadian rhythm was disrupted in both groups of patients. Significant inverse correlations with plasma aldosterone were found erratically in controls, never in group 1, and at every 4-h interval in group 2. In the latter, the indexes of tubular activity and effectiveness of aldosterone were also significantly increased. Urine norepinephrine excretion was never related to sodium excretion in either controls or patients; in group 2 it was directly correlated with glomerular filtration rate in many instances. The cortisol-related circadian rhythm of kaliuresis was retained only in group 1. The 24-h renal potassium excretion of controls and patients was comparable, in spite of the striking hyperaldosteronism, and the more than doubled contribution of aldosterone to kaliuresis shown in group 2. The influence of aldosterone on potassium excretion was also witnessed by the direct correlation between these variables found in group 1 and, when kaliuresis was corrected by the distal sodium delivery, group 2. Renal sodium handling in cirrhosis is altered even before ascites formation and compensated patients can undergo "spontaneous natriuresis." Aldosterone is the main cause of sodium retention in nonazotemic ascitic patients, while sympathoadrenergic hyperactivity may contribute to preserve renal perfusion. The influence of aldosterone on kaliuresis is enhanced, but renal potassium wasting in patients with ascites and hyperaldosteronism is prevented by reduced distal tubular availability of sodium.
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PMID:Circadian variation in renal sodium and potassium handling in cirrhosis. The role of aldosterone, cortisol, sympathoadrenergic tone, and intratubular factors. 292 63


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