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)

Colchicine, which has been used for hundreds of years in the treatment of gout, has found a new use in the treatment of cirrhosis. In the experimental animal, and in vitro, colchicine decreases inflammation, inhibits collagen synthesis and also increases collagen degradation by activating collagenase. Many of the putative beneficial actions of the drug in cirrhosis, as well as its toxic side effects, are due to the fact that it binds to tubulin and thereby disrupts microtubules; however, it is unclear which of these actions, mostly demonstrated in the experimental animal, are present in the doses currently used in man. There have been 4 controlled trials of colchicine in various forms of cirrhosis, three of which have concerned primary biliary cirrhosis. Data are currently available on 146 colchicine-treated patients, of which 92 had primary biliary cirrhosis. Colchicine improves the conventional liver function tests in primary biliary cirrhosis and also reverses the basic defect in hepatic excretory capacity characteristic of this disease. The drug appears to have no significant effect on symptoms, clinical features or liver histology, but in 2 of the 3 primary biliary cirrhosis trials, as in the Mexican study of alcoholic and post-hepatitic cirrhosis, colchicine treatment was associated with improved survival.
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PMID:Colchicine in primary biliary cirrhosis. 177 43

The effect of D-penicillamine (Pe) on liver fibrosis-cirrhosis induced by chronic CCl4 and phenobarbital (Pb) administration in Fischer 344 male rats was studied. Morphometric analysis did not reveal a decrease in the amount of connective tissue fibers after Pe-treatment. Compared to the CCl4 and Pb-treated control groups, Pe had no significant effect on the concentrations of hydroxyproline, a parameter of collagen degradation, either; however, it increased the glycosaminoglycan concentrations. Lymphocyte stimulation by Con-A in the Pe-treated groups did not differ from that of the CCl4 and Pb-treated ones. According to our studies, Pe-treatment was ineffective in rats with liver fibrosis-cirrhosis induced by CCl4 and Pb administration. It seems that Pe can be effective only in the cirrhosis types accompanied by a considerable copper accumulation due to suppression of the toxic effects of copper.
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PMID:The effect of D-penicillamine on CCl4-induced experimental liver cirrhosis. 178 39

We have previously reported that monocyte aryl hydrocarbon hydroxylase (AHH) activity is depressed in patients with liver disease and is decreased more in cirrhosis than in early stage liver disease. To determine if monocyte AHH activity reflects liver AHH activity, we studied an animal model of cirrhosis, i.e., yellow phosphorus induced cirrhosis in the pig. AHH activity was detectable in monocytes isolated from peripheral blood of normal pigs (0.32 +/- 0.13 nmol.mg-1 P.h-1, n = 11) and was comparable to the level of AHH activity in hepatic Kupffer cells isolated from wedge or needle biopsies of livers of normal pigs (0.38 +/- 0.21, n = 7). The AHH level in pig Kupffer cells was approximately 10% of the AHH level in hepatocytes and microsomes. To induce liver disease, pigs were administered yellow phosphorus (0.6 mg/kg) 5 days per week for 16 weeks. At 4 weeks of treatment, monocyte AHH activity was not different from control and liver histology was normal. Depression of monocyte AHH activity was evident at 8 weeks of treatment when liver fibrosis was seen histologically. At 12 weeks of treatment when histology revealed extensive liver fibrosis and collagen levels were elevated, the level of monocyte AHH activity was decreased 67% compared with controls. Similar changes were observed at 12 weeks in Kupffer cell AHH activity (86% decrease) and hepatocyte AHH activity (70% decrease) compared with controls. These results suggest that monocyte AHH activity reflects liver AHH activity and may be a good indicator of change in liver enzyme function in liver disease in the pig model of cirrhosis.
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PMID:Monocyte aryl hydrocarbon hydroxylase (AHH) activity mimics Kupffer cell and hepatocyte AHH activity in an animal model of liver disease. 180 52

Alcoholic hepatitis is associated with progressive hepatic fibrosis and the development of cirrhosis. The increased fibrosis is principally the result of increased collagen synthesis which exceeds lesser increases in collagen degradation. No proven therapy exists for progressive hepatic fibrosis in alcoholic liver disease. Sobriety increases long-term survival, but there is no evidence that it affects the process of fibrogenesis once initiated. Corticosteroids increase hospital survival in severe alcoholic hepatitis, while long-term propylthiouracil therapy increased survival in moderately severe alcoholic hepatitis. However, neither therapy was found to decrease hepatic fibrosis. By contrast, long-term therapy with colchicine improved survival and decreased hepatic fibrosis in a few patients with cirrhosis. Potential new therapies which have been shown to decrease fibrosis in animals or by cells in vitro include prostaglandin E2, gamma interferon, and inhibitors of proline hydroxylation.
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PMID:Approaches to treatment of fibrogenesis in alcoholic liver disease. 184 64

The expression of blood group antigens (A, B, H, Lewis(a) and Lewis(b)), Ulex europaeus agglutinin I (UEA-I), factor VIII-related antigen, and type IV collagen on the sinusoids was examined immunohistochemically in 15 cases of hepatocellular carcinomas (HCC), 11 cases of cirrhosis, 12 cases of chronic active hepatitis, and in a control sample of 16 normal livers. Sinusoidal endothelial cells of HCC characteristically showed a diffuse and strong immunoreactivity to ABH blood group antigens in the specimen with a comparable ABO blood group. The sinusoidal endothelial cells were also diffusely and strongly positive for UEA-I receptors. In contrast, in cirrhosis and chronic active hepatitis a few sinusoidal endothelial cells were positive for ABH blood group antigens and UEA-I receptors. In normal livers, only a few sinusoidal endothelial cells were positive for ABH blood group antigens and UEA-1 receptors. Tests for factor VIII-related antigen and Lewis blood group antigens were almost negative on sinusoidal endothelial cells. Although type IV collagen was distributed diffusely in the space of Disse in these four groups, its expression was strongest in HCC. Blood vessels of portal tracts and fibrous septa were positive for ABH blood group antigens, UEA-1 receptors, factor VIII-related antigen, and type IV collagen, but negative for Lewis blood group antigens. These findings suggest that some sinusoidal endothelial cells undergo "capillarization" in cirrhosis and chronic active hepatitis, and that the majority of sinusoidal endothelial cells of HCC have phenotypic characteristics of capillaries.
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PMID:Expression of ABH blood group antigens, Ulex europaeus agglutinin I, and type IV collagen in the sinusoids of hepatocellular carcinoma. 184 86

To test further the competence of the cirrhotic liver to metabolize vitamin D3 at C-25, hepatocytes were isolated from controls and from CCl4-induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D3 into 25-hydroxyvitamin D3 was studied in the presence of 10(7) hepatocytes at D3 concentrations of 20 nmol/L to 15.4 mumol/L. Histologically, micronodular cirrhosis was present in all CCl4-treated rats, whereas controls had normal livers; portal venous pressure (p less than 0.008) and intrahepatic collagen content (p less than 0.0001) were significantly increased in CCl4-treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P-450 was 0.27 +/- 0.02 and 0.25 +/- 0.02 nmol/10(6) hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3-methylcholanthrene administration (p less than 0.0001). 25-Hydroxyvitamin D3 formation was best described by power law equations and varied between 0.02 +/- 0.0004 and 29.57 +/- 2.8 in controls, and 0.024 +/- 0.0004 and 32.0 +/- 7.0 pmol.hr-1.10(6) hepatocytes-1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25-hydroxyvitamin D3 formation, but the y-axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p less than 0.005). Inducers of the mixed function oxidases significantly increased 25-hydroxyvitamin D3 formation in controls as well as in cirrhotic rats (p less than 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D3. Furthermore, the cell sequestration of D3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well-compensated micronodular cirrhosis, the C-25 hydroxylation of D3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity.
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PMID:In micronodular cirrhosis, hepatocytes retain a normal C-25 hydroxylation capacity toward vitamin D3: a study using the rat carbon tetrachloride-induced cirrhotic model. 184 94

We examined the reaction of cell-mediated immunity with wound healing in liver cirrhosis. Cirrhosis was induced in male Wistar rats with a basal diet supplemented with 0.06% dimethylaminoazobenzene (DAB) over a four week period. Rats fed with a basal diet were served as control. Midline laparotomy of 2cm was performed. We determined the number of lymphocyte, the collagen content and the bursting pressure of the abdominal wound. In addition, the delayed hypersensitivity response was measured using dinitrofluorobenzene (DNFB) applied to the ears. The rats with cirrhosis showed significant decrease in the number of lymphocytes, the collagen content and the bursting pressure of the wound in comparison with the control rats. Also the rats with cirrhosis had depressed DNFB response. The response of infiltrating lymphocytes in the ear was similar to the response of lymphocytes in the wound. There was a positive correlation between the lymphocyte number and the collagen content in the wound. Moreover, the bursting pressure had a significant correlation with the number of lymphocyte in the wound. The data strongly suggest that depressed cell-mediated immunity impairs wound healing in liver cirrhosis.
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PMID:[The effect of immunological response on wound healing in rat with liver cirrhosis]. 190 31

The case survey of drug-induced hematologic disorders in Shikoku District (Ehime Prefecture) disclosed 21 patients. Cases were 12 rheumatoid arthritis patients, 2 brain tumor, one epilepsy, 2 liver cirrhosis, one neuralgia, one arthralgia, one hyperthyroidism, and one IBL-like T-lymphoma. Causative drugs for aplastic anemia were Metalcaptase, Shiosol, Voltaren and Emeside. Drug-induced aplastic anemia was so severe that 4 out of 5 patients had died of bone marrow dysfunction. Neutropenia was caused by drugs as Rimatil, Cefobit, Sepatren, Mercazole, Sulpyrin, Aleviatin, Cefamedin and Metalcaptase. The real causes of these drug-induced hematologic disorders have not been clear. Remarkably high incidence among rheumatoid arthritis patients is suggestive several reasons as unique reactivity associated with HLA, suppression on hematologic stem cells by abnormal metabolites, and immunologic dysfunction commonly seen in collagen diseases. Further studies of more accurate incidence of drug-induced hematologic disorders are needed in investigating real causes of unhappy side-effects.
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PMID:[Drug-induced hematologic disorders in Shikoku district]. 192 Aug 31

It is suggested that during active phases of acute and chronic pancreatitis (aP and cP) a major breakdown of extracellular matrix occurs. Since our group previously established that serum levels of the precollagen-III-peptide (P-III-P) are good markers for changes in the extracellular matrix in liver disease (e.g. fibrosis and cirrhosis), we investigated whether this would also serve as a possible marker for pancreatitis. A total of 52 patients with pancreatitis were studied (aP = 17; cP = 35) and compared to 194 controls. Diagnosis of pancreatitis was done on the basis of established classifications. Concomitant diseases, e.g. of the liver, were excluded. Serum levels of P-III-P (three assays with polyclonal and monoclonal antibodies and Fab-Fragments), hyaluronic acid (HA) and laminin (LAM) were measured by RIA or IRMA. Patients with pancreatitis displayed elevated levels in all groups, when compared with the controls. Since the P-III-P-Fab RIA measures the Col1-fragment by 50%, which is considered to be a degradation product of P-III-P, this could mean that neogenesis of collagen is paralleled by degradation during the initial course of an acute episode of pancreatitis. The ratio (quotient) of P-III-P-Fab and P-III-PMoAb (nl = 127.3 +/- 27) is changed in patients with pancreatitis towards P-III-P-Fab (aP: 115.4 +/- 84.7*, cP: 94.9 +/- 21.8*, cP-I: 89.3 +/- 9.2*; * = p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Parameters of connective tissue metabolism as markers in acute and chronic pancreatitis. A retrospective study with a cohort of normal subjects]. 195 31

The authors examined the aminoterminal type III procollagen peptide level of serums and killer-cell activity peripheric blood lymphocytes with 75 patients suffering from ethanol originated liver diseases as well as control samples from 40 healthy volunteers. Determination of type III procollagen peptide (Fab) took place by the RIA method. The cytotoxic activity of killer-cells was tested against human red blood cells. Both in fatty liver and chronic alcoholic hepatitis the level of type III procollagen peptide increased, while in liver cirrhosis the same level reached a value three times of the normal. At the same time in cirrhosis hepatitis an increased killer-cell activity could be observed. Type III procollagen peptide values were also analysed in view of the cytotoxic capacity of killer-cells. At first ill, then healthy control individuals were divided into three groups according killer-cell activity values. Results have shown that in the group with a high level killer-cell activity average type III procollagen peptide values were significantly greater as compared to those of the medium or low level activity groups. These results might indicate a relation between a conditional antibody-dependent cellular cytotoxicity reaction and increasing collagen synthesis.
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PMID:[Serum aminoterminal type III procollagen peptide level and killer cell activity in patients with alcoholic liver diseases]. 195 78


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