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)

In most regimens proposed for the depletive management of cirrhosis of the liver, spirolactone is associated with other diuretics. Treatment of 28 patients with uncompensated forms by means of spirolactone only, using high, protracted doses determined essentially in accordance with the depletion obtained, is described. The disappearance of signs of water retention was gradual and unattended by difficulties. Normalisation of the urinary Na/K ratio preceded the diuretic response; Increased diuresis led to a slight increase in urinary potassium/day. Higher doses were used in patients with lower urinary Na/K ratios. Here a critical diuretic response was only obtained around the 5th day. Transient low blood sodium and chlorine and high blood potassium were noted; the last parameter was not related to the drug dose, nor to changes in Bun; No marked changes in blood uric acid, calcium, ammonium, bilirubin or sugar were observed.
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PMID:[Depletive treatment of uncompensated liver cirrhosis with high doses of spirolactone only]. 32 May 4

Twenty uncomplicated cases of cirrhosis of liver, proved by liver biopsy, and free from other systemic diseases were studied. Glucose (pre- and postprandial) and electrolytes (Na+, K+, Cl-) values were compared to those of systemic and portal venous blood. Chloride level in ascitic fluid was found to be significantly high in cirrhosis, as compared to portal and systemic venous blood. Sodium and glucose levels were similar in ascitic fluid and portal venous blood except in two cases complicated with tuberculous peritonitis, where pre- and postprandial glucose levels were considerably low. In 55% cases, there was impaired glucose tolerance, as measured by pre- and postprandial glucose levels in systemic venous blood.
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PMID:Study of ascitic fluid in relation to systemic and portal venous blood in hepatic cirrhosis. 194 Apr 16

The pathogenetic role of ADH in determining hyponatremia in patients with liver cirrhosis is still much debated. Osmotic stimuli are not able to inhibit secretion of ADH in refractory ascites and under such conditions the reduction in effective plasma volume has been put forward as the main cause. Twenty patients with liver cirrhosis and refractory ascites were studied before and during extraction-concentration-reinfusion (ECR) of ascitic fluid by means of Rhodiascit. ADH, renin, aldosterone, blood and urine osmolarity, plasma and urinary concentration of sodium, potassium, chlorine, and the clearance of free water were evaluated. All patients presented high renin values (15.4 +/- 11.7 ng/ml), aldosterone (341 +/- 172 ng/ml), ADH (6.3 +/- 5.2 pg/ml). During ECR, a significant drop was observed in renin (p less than 0.001), aldosterone (p less than 0.001) urinary osmolarity (p less than 0.001) and an equality significant increase in diuresis (p less than 0.001), natriuria (p less than 0.005), kaliuria (p less than 0.001) while ADH presented an irregular course: in 11 cases it remained unchanged, in 3 it fell and in 6 it presented a constant increase. To conclude, data suggest that the diminished filtrate reaching the distal tubule constitutes the greatest cause of the inability to dilute urine in many patients with cirrhosis and that ADH is a permissive rather than a primary factor.
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PMID:[Changes in antidiuretic hormone (ADH) in liver cirrhosis with resistant ascites]. 268 81

Cause-specific mortality was surveyed among 23,180 male (580,000 person-years) and 3,860 female (86,898 person-years) employees with 1 or more years of service from 1940 through 1989 at a large chemical plant. Vital status was ascertained for 99.1% of the males (n = 5,658 deaths) and 98.6% of the females (n = 355 deaths). Comparisons of observed mortality with expected levels based on any of three population comparisons (United States, Texas, or five local counties) showed lower mortality for all causes of death, diseases of the circulatory system, diabetes mellitus, and cirrhosis of the liver. There was an increased risk for lung cancer mortality among male operations employees when compared to the U.S. and Texas populations but not to the local five-county region. Additional evidence suggests this increase was primarily attributable to cigarette smoking. Male operations employees also had an elevated, although not statistically significant, risk for kidney cancer. Prior research had shown an association with work in the cell maintenance area of chlorine production. As a result of a high prevalence of deaths certified by justices of the peace, a mortality excess was observed of cancer of other and unspecified sites and symptoms, senility, and ill-defined conditions. Although specific chemical exposures were not studied, the generally favorable mortality experience suggests that major hazards are unlikely.
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PMID:Half-century of cause-specific mortality experience of chemical manufacturing employees. 797 96

Chloride-bicarbonate anion exchanger 2 (AE2) is expressed in a variety of tissues, including the liver and salivary glands, where it may participate in the generation of hydroionic fluxes into secretions. We have previously reported decreased hepatic levels of AE2 messenger RNA in patients with primary biliary cirrhosis (PBC), a cholestatic condition frequently associated with pluriglandular exocrine failure. Here we investigated the expression of AE2 protein in the liver of PBC patients. Using a monoclonal antibody against an AE2 peptide, immunohistochemistry was performed on liver biopsy specimens from subjects with normal liver (n = 7), patients with PBC (n = 13), and patients with cirrhosis or cholestasis other than PBC (n = 17 and 11, respectively). Immunostaining was graded from 0 to 7, according to its intensity and distribution. AE2 immunoreactivity was observed in normal livers, as previously reported, and in many pathological liver biopsy specimens, being mainly restricted to canaliculi and the luminal membrane of terminal and interlobular bile ducts. Canalicular and ductular scores were significantly reduced in the PBC group compared with each control group (normal liver and cirrhosis or cholestasis other than PBC), whereas no differences in immunoreactivity scores were observed among control groups. When four patients with primary sclerosing cholangitis (PSC) were analyzed, they also differed from those with PBC. These results suggest that PBC is characterized by diminished expression of AE2 in the liver. Reduced levels of this transporter protein might be involved in the pathogenesis of cholestasis in PBC.
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PMID:Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis. 898 58

Chronic hepatitis C virus infection represents a serious global public health problem, typically resulting in fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Based on our previous discovery of lead compound 2 (Liu et al. J Med Chem 54:5747-5768, 2011), 35 new quinoxalinone derivatives were explored in this study. Outline of the structure-activity relationships (SARs) revealed that compound BH6870 (36) showed high anti-HCV potency ([Formula: see text]) and a good cell safety index (SI [Formula: see text]). SARs analysis indicated that quinoxalin-2(1H)-one containing a 4-aryl-substituted thiazol-2-amine moiety was optimal for antiviral activity. Introducing a hydrogen-bond acceptor (such as ester or amide group) at the C-3 position of quinoxalin-2(1H)-one was beneficial for the antiviral potency, and especially, N,N-disubstituted amide was far superior to N-monosubstituted amide. Incorporation of more than one halogen (fluorine or chlorine atom) or a strong electron-withdrawing group on the benzene ring of the thiazole-phenyl moiety might reduce electron atmosphere density further and resulted in a dramatical loss of activity. The NH-group of the lactam moiety was clearly required for anti-HCV activity. Design and synthesis of quinoxalin-2(1H)-one derivatives as new non-nucleoside small-molecule HCV inhibitors. BH6870 (36), showing higher antiviral potency and a good cell safety index, was identified.
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PMID:Structure-activity relationship studies on quinoxalin-2(1H)-one derivatives containing thiazol-2-amine against hepatitis C virus leading to the discovery of BH6870. 2620 8