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)

Among the patients with liver cirrhosis (LC) who undergo the operation, the postoperative complications are not infrequent and sometimes prove fatal. The impaired hepatic function, especially the impaired reticuloendothelial system (RES) function, has been claimed to be a possible pathogenic factor for these complications. The present experimental and clinical studies were undertaken to investigate the RES function and the effect of preoperative OK-432 administration as an RES potentiator in LC. The results are as follows: 1) CCl4-induced LC rats were evaluated for RES global phagocytic function, Kupffer cell phagocytic function, plasma opsonic activity and plasma opsonic substances such as fibronectin, C3 and IgG. All parameters except IgG showed significant depression compared to those values in normal rats. However, the administration of OK-432 (0.1 KE/rat, ip) improved all these depressed parameters. The OK-432 administration also significantly improved the survival following panperitonitis in LC rats. 2) Among 18 LC patients with hepatocellular carcinoma undergoing partial hepatectomy, the RES global phagocytic function, plasma opsonic activity and plasma opsonic substances were evaluated. Same as the experimental study, all parameters except IgG were significantly depressed among the LC patients compared to those values in the patients with normal liver. However, the preoperative OK-432 administration (5 KE/day sc for 4 days) significantly improved these parameters and consequently decreased the postoperative complications. These results indicate that the preoperative RES activation by the OK-432 was effective and useful for the prevention of the postoperative complications in the LC patients.
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PMID:[Experimental and clinical studies on the effect of reticuloendothelial system (RES) potentiator in the depressed RES function in cirrhotics]. 362 94

Acute and chronic alcohol intoxication may lead to various types of corpuscular hemolytic anemias, irrespective of other coexisting organ damage such as liver cirrhosis. It also suppresses hemopoiesis in the bone marrow, leading to hyporegenerative anemia and to a pathogenetically unclear red cell macrocytosis, which in turn represents a sensitive and valuable index for occult alcoholism. Alcohol also suppresses platelet production. Acute intoxication may, furthermore, lead to reversible thrombocytopenia due to platelet sequestration. Platelet function is affected by alcohol both in vitro and in vivo, the defect being similar to that provoked by aspirin. The impaired host defense in chronic alcoholism is not yet adequately explained. It appears to be based on depression of bone marrow granulocyte reserve, granulocyte mobilization and granulocyte function, and also on impressive functional abnormalities of the lympho-plasmocellular system. The clinical relevance of alcohol-mediated hematological changes has not yet been sufficiently defined. It is certainly underestimated.
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PMID:[Alcohol and the blood]. 391 82

Both cimetidine therapy and cirrhosis individually interfere with normal elimination of various drugs. Cimetidine is often prescribed in patients with cirrhosis but there is incomplete data on its effect on drug elimination in cirrhotics. The purpose of this study was to address this issue. Eight stable cirrhotics were studied prior to and following 7 days of cimetidine administration, (300 mg orally q.i.d.). Chlordiazepoxide (Librium), which is eliminated by the liver after demethylation, and indocyanine green, which is removed by the liver without biotransformation, were used as probes. Consistent with the concept that cimetidine interferes with drug metabolism by inhibiting microsomal oxidation, chlordiazepoxide clearance in the cirrhotics was inhibited by cimetidine (p less than 0.05), but indocyanine green clearance was unaffected. As shown by us previously (Roberts, R. K. et al., Gastroenterology 1978; 75:479-485), untreated cirrhotics had substantially lower chlordiazepoxide clearance than did controls. The inhibitory effect of cimetidine on chlordiazepoxide clearance was less in cirrhotics than in controls (p less than 0.05). In all subjects, there was excellent correlation between initial clearance and magnitude of depression in clearance after cimetidine, i.e., the larger the initial clearance, the larger the change (r = 0.97, p less than 0.0001). Forty-eight hours after stopping cimetidine, chlordiazepoxide clearance returned to baseline in cirrhotics and controls. Our data demonstrate that cimetidine and cirrhosis may act additively to impair drug metabolism. This effect of cimetidine on chlordiazepoxide clearance is smaller in cirrhotics than in controls, but, because of impaired initial drug elimination in cirrhosis, it may result in adverse clinical effects.
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PMID:The effect of cimetidine on hepatic drug elimination in cirrhosis. 397 62

Human polynuclear neutrophilic function was studied to determine the role of alcohol in the increased susceptibility to infection of chronic alcoholics: in vitro studies investigated the effects of different concentrations of ethanol; in vivo studies included comparison with healthy subjects after alcohol intake, with excessive drinkers without liver disease and with chronic alcoholics with confirmed cirrhosis. In vitro depression of polynuclear neutrophilic function was observed only with significantly higher concentrations of ethanol than encountered clinically. In social and excessive drinkers, phagocytosis was decreased but there was no change in bactericidal activity. On the other hand, in cirrhotic alcoholics chemotaxis, phagocytosis and bactericidal activity were all significantly reduced. A direct action of alcohol alone on polynuclear function would not seem to be the cause of the increased risk of bacterial infection of chronic alcoholics.
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PMID:[Effect of ethanol on human polynuclear neutrophils. In vitro and in vivo study]. 402 7

Patients with cirrhosis were found to be extremely sensitive to tranylcypromine, and the use of this drug for the treatment of depression in such patients is contraindicated. Amitriptyline has a wider margin of safety in such patients, but caution is necessary when the higher therapeutic doses are prescribed.
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PMID:Antidepressants and liver disease. 463 4

Serum C(3) (beta(1C)/beta(1A)) has been measured in normal individuals and the range found is in agreement with findings of other authors (85-370 mg/100 ml). In 18 patients with acute hepatitis and massive necrosis serum C(3) was consistently reduced to below 50% of normal. In other patients with acute hepatitis the serum C(3) concentration was normal. In the majority of the 150 patients with chronic liver disease serum C(3) concentration was normal. However, 10 patients (six with active chronic hepatitis, four with cryptogenic cirrhosis) had hypocomplementaemia. The reason for the depression is not clear but could reflect either decreased synthesis or increased consumption, or a combination of the two.
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PMID:The serum concentration of the third component of complement beta-1C-beta-1A in liver disease. 499 91

We experienced a 68 years-old male who had frequent hypoglycemic attacks. The diagnosis of a giant hepatoma associated with hypoglycemia was established by oral glucose tolerance test (O-GTT), angiography and computed tomography. The cavography demonstrated the invasion or depression of the tumor. It was ascertained by an operative exploration that the tumor occupied most of the right trisegments of the liver and infiltrated into a part of the left lateral segment. The right hepatic trisegmentectomy along 1.5cm left side line apart from the falciform ligament was performed. Resected tumor showed 11 X 13 X 10cm in size and 1200g in weight. Microscopic findings demonstrated hepatocellular carcinoma as Edmondson's Type II. After the operation, this patient became free from the hypoglycemic attack. A fasting blood sugar became within normal limits and O-GTT demonstrated a normal blood sugar level and insulin response. No concentration of immuno-reactive insulin was found in the resected tumor, however, the blood sugar in rats which received the intravenous injection of the tumor extracts was remarkably decreased in 20 minutes. From these observation, hypoglycemia in this patient seemed to depend mainly on the factor of insulin-like activity of the tumor. In the literature, the hepatocellular carcinoma associated with paraneoplastic phenomenon, e.g. hypoglycemia, has rarely been resected because of accompanied liver cirrhosis or giant size of the tumor. This is the second patient in our country in whom the tumor was fortunately resected and the paraneoplastic syndrome disappeared postoperatively.
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PMID:[Successful resection of giant hepatocellular carcinoma with hypoglycemic attack]. 609 7

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74

The aim of the study was to establish whether and how circadian rhythms alter the bioavailability of, and response of circulatory and ventilatory functions to 80 mg of propranolol given at four different test times. Both Cmax and AUC were lowest at 2:00 pm as compared with other test times in healthy group (N = 6), lower in cirrhosis (N = 6), but none in portacaval shunt (N = 3). Thus, at 2:00 pm, liver extraction seems to be the best in healthy subjects, worse in cirrhotics and negligible in PC shunt. The mean AUC value in PC shunt patients was three times as high as in healthy subjects and cirrhotics. This seems to be due to the reduced first-pass extraction phenomenon in the liver in PC cases. All subjects exhibited a prompt and significant depression of radial pulse and systolic BP; this effect on radial pulse was lasting longer at 2:00 am than at other test times. The initial values of PEF were lowest at 2:00 am and no depressing effect of propranolol was observed in comparison with other test times. From the practical point of view, the changeable bioavailability of propranolol given at different times of the day has no direct consequences in regards to the temporal response to the drug in healthy subjects and cirrhotics, since it is likely that both propranolol and its metabolites (4-OHP) are active as beta-blockers. Twenty-four hour oscillations of the responses to propranolol seem to exist both in healthy and cirrhotic patients.
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PMID:Circadian bioavailability and some effects of propranolol in healthy subjects and in liver cirrhosis. 652 40

The chronic ingestion of ethanol results in liver-cell damage, and characteristic features of this injury are the marked alterations in both the functions and morphology of the mitochondria. Morphologically, the changes observed in human alcoholics and experimental animals appear similar. Bizarrely shaped mitochondria and megamitochondria are detected at the fatty liver stage and persist as the disease progresses. As yet, however, no correlation has been found between the severity of these morphological changes and the development of cirrhosis. Analysis of the mitochondrial membranes indicates that ethanol consumption produces changes in both the protein and lipid composition of the membrane. Profound decreases in the components of the respiratory chain have been detected, and these changes are associated with marked depressions in the activity of NAD+-linked dehydrogenases, cytochrome oxidase, and the ATP synthetase complex. On the other hand, no consistent pattern has emerged as to the effect of chronic ethanol consumption on the composition of the membrane phospholipids. Many of the changes appear to be dependent on the sex of the animal, the dietary status, and the duration of ethanol intake, and are suggestive of changes in fatty acid desaturase activity. Mitochondria isolated from ethanol-fed rats displayed impaired respiration and a lowered steady-state rate of ATP synthesis. Whether or not these functional changes are directly related to alterations in the physical properties of the membranes remains to be resolved. This marked depression of respiratory functions in isolated mitochondria was not reflected by a significant decrease in O2 consumption by the livers of ethanol-fed animals.
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PMID:Alcohol-induced mitochondrial changes in the liver. 672 59


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