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 order to elucidate the mechanisms by which beta-adrenoceptor blockade leads to a reduction in portal pressure, we have measured portal pressure, heart rate and cardiac index in 17 patients with cirrhosis and portal hypertension following the oral administration of the selective beta 2-adrenoceptor blocking agent, ICI 118551, in the two dosage ranges 10-20 mg and 50-100 mg. There was a fall in portal pressure in 14 of the 17 patients from a median of 17 mm Hg to a median of 15 mm Hg, P less than 0.01, that occurred only at 60 min following administration of the drug. Although there were early systemic haemodynamic changes, with a significant fall in heart rate and cardiac index from before to 30 min after the ingestion of ICI 118551 (median heart rates 86 and 80 beats/min respectively, P less than 0.01, median cardiac indices 3.5 and 3.31 min-1 m-2, P less than 0.05), these occurred before the fall in portal pressure and were unrelated to changes in portal pressure. This reduction in portal pressure independent of systemic haemodynamic changes is consistent with beta 2-adrenoceptor blockade within the splanchnic and hepatic arterial circulations; subsequent increases in splanchnic and hepatic arterial resistances with a concomitant fall in portal blood flow and hepatic portal resistance may lead to the reduction in portal pressure.
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PMID:Reductions in portal pressure by selective beta 2-adrenoceptor blockade in patients with cirrhosis and portal hypertension. 614 30

This study examined the hemodynamic effects of selective beta 2-adrenergic blockade (ICI 118,551, 100 micrograms/kg intravenous (i.v.)), selective beta 1-blockade (atenolol, 2 mg i.v.) and nonselective beta-blockade (propranolol, 2 mg i.v.) in conscious rats with cirrhosis. Pressure and blood flow measurements (radioactive microsphere method) were performed before and following drug administration. ICI 118,551 significantly decreased portal tributary blood flow (21%), portal pressure (4%) and cardiac index (12%). Portal tributary blood flow decreases were significantly more marked than changes in cardiac index. Atenolol significantly decreased portal tributary blood flow (27%), portal pressure (15%), cardiac index (17%) and arterial pressure (7%). Propranolol significantly decreased portal tributary blood flow (37%), portal pressure (17%), cardiac index (30%), and arterial pressure (9%). Portal tributary blood flow decreases due to ICI 118,551, but not those due to atenolol, were significantly less marked than the decreases caused by propranolol. ICI 118,551- and atenolol-induced cardiac index decreases were significantly less marked than propranolol-induced decreases. In conclusion, in rats with cirrhosis, selective beta 2-blockade reduces portal pressure and portal tributary blood flow mainly by a direct effect on splanchnic vessels. This portal hypotensive action, however, was slight. Propranolol decreases portal tributary blood flow by the combination, but not the summation, of its beta 1- and beta 2-blocking effects.
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PMID:Hemodynamic responses to selective blockade of beta 2- and beta 1-adrenoceptors in conscious rats with cirrhosis. 789 Aug 94

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administered orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group, liver damage was established. In the combined group, liver injury was more frequent and more severe compared to the aflatoxin B1 group and biliary copper excretion was diminished compared with the copper group. Histologically, only the livers of this group exhibited degeneration, atrophy and steatosis of liver cells, inflammatory processes and a more or less prominent fibrosis. For childhood cirrhosis (ICC and ICT) a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.
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PMID:Experimental induction of liver fibrosis in young guinea pigs by combined application of copper sulphate and aflatoxin B1. 933 26

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administrated orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group liver damage was established. In the combined group liver injury was more frequent and more severe compared to the aflatoxin B1 group. Compared with the copper group biliary copper excretion was diminished and the kidney copper content was elevated in the Afl. B1 + Cu group. While copper concentrations in bile and kidney correlated with other parameters, notably the pathological lesions of the liver, no such correlation was found for liver copper. Therefore in this experiment the degree of Cu accumulation was not decisive for the liver lesions. The livers' capacity for excreting Cu by bile seems to be a much more important factor. Histologically only the livers of the combined group exhibited degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.
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PMID:Liver fibrosis in guinea pigs experimentally induced by combined copper and aflatoxin application. 978 33

In a multicentric retrospective clinical study with 16 pediatric centres we identified 103 cases of histologically confirmed early childhood cirrhosis (ECC) in Germany for the years 1984-1994. The most prominent diagnoses were congenital bile duct anomalies (47.5%), inborn metabolic disorders (17.5%) and unclear etiologies (17.5%). Chronic and excessive intake of copper might be discussed as an etiological factor in 8 other cases. 5 of these were proven to have coincided with very high hepatic copper contents and copper plumbing/acid well water. Their connection with copper exposure must be considered as probable, whereas 3 others were only suspected copper cases, mainly due to reliable exclusion of other etiologies. High corrosivity (base capacity) values and copper levels in the water for infants formula of 9-26.4 mg/L were determined in those probable cases for which exposure conditions could be exactly reproduced. Additional reports on copper associated ECC, either Indian Childhood Cirrhosis (ICC) from outside India or so-called Idiopathic Copper Toxicosis ( ICT ), originate from Austria, Australia, Germany, Ireland, USA.
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PMID:Early childhood cirrhoses (ECC) in Germany between 1982 and 1994 with special consideration of copper etiology. 1052 17

The clinical outcomes of patients infected with hepatitis C virus (HCV) range from acute resolving hepatitis to chronic liver diseases such as liver cirrhosis or hepatocellular carcinoma. Identification of the infecting virus genotype is indispensable for the exploration of many aspects of HCV infection, including epidemiology, pathogenesis, and response to antiviral therapy. 1419 individuals were screened for anti-HCV in this study, of which 166 (11.7%) were found reactive by ICT (Immunochromatographic test). These 166 anti-HCV positive and 26 normal individuals were further analyzed. RNA was extracted from serum and reverse-transcribed to cDNA and the core region of HCV genome was targeted and amplified by multiplex PCR. HCV RNA was detected in 121 individuals, of which 87 were male and 34 were female. Genotype 3a was the most prevalent among all the genotypes observed followed by 3b. Genotypes 1a, 2a, and 2b were found in 10.89%, 13.22%, and 6.61% patients, respectively. 25.41% of the HCV RNA positive samples were not typed. 6.05% of patients were found having mixed genotypes. These findings will not only help the physicians to prescribe more appropriate treatment for the HCV infection but will also draw the attention of health-related policy makers to devise strategies to curb the disease more effectively.
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PMID:Genotyping of HCV RNA reveals that 3a is the most prevalent genotype in mardan, pakistan. 2471 2

Hepatitis C is an ailment of liver caused by hepatitis C virus (HCV) infection. About 3% of the world population is infected by this virus. HCV infection is a leading reason for liver cirrhosis and therefore a major source of hepatocellular carcinoma. The study focused on the incidence of active HCV infection in blood donors of Mardan district of KPK, Pakistan. A total of 5318 blood donors were inspected for the presence of anti-HCV antibodies and HCV-RNA using ICT (immune-chromatographic test), ELISA and RT-PCR at Mardan Medical Complex (MMC), Mardan. Out of these, 157 (2.95%) were positive by ICT, 60 (1.12%) by ELISA and 56 (1.05%) for HCV-RNA. The frequency of active HCV infectivity amongst the blood donors from district Mardan, KPK Pakistan was 1.05 %. Application of strict measures during blood donor selection and use of proper screening assays such as ELISA in place of ICT devices can give a more accurate picture so that the incidence of this viral infection in HCV negative blood recipients can be reduced.
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PMID:Incidence of Active HCV infection amongst Blood Donors of Mardan District, Pakistan. 2683 16