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)

Isopropyl-2-(1,3-dithietane-2-ylidene)-2[N-(4-methyl-2-thiazol+ ++-2-yl) carbamoyl]acetate (YH439) was synthesized as a hepatoprotective drug for the treatment of chronic hepatitis and liver cirrhosis. In the present investigation, we have tested YH439 for its chemoprotective activity against the carcinogen benzo[a]pyrene. The drug exhibited dose-dependent protection against bacterial mutagenesis induced by benzo[a]pyrene its covalent binding to DNA in vitro mediated by rat hepatic postmitochondrial supernatant enriched with NADPH. The direct mutagenicity of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide, the ultimate electrophilic and carcinogenic metabolite of benzo[a]pyrene, was also ameliorated by YH439 in a dose-dependent manner. The results of this study suggest that YH439 has a potential as a chemopreventive agent.
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PMID:Inhibition of covalent DNA binding and mutagenicity of benzo[a]pyrene by isopropyl-2-(1,3-dithietane-2-ylidene)-2-[N-(4-methylthiazol-2-yl) carbamoyl]acetate (YH439), a novel hepatoprotective agent. 862 28

The authors describe a case of giant benign cystadenoma of the ovary in a 55 year old woman. The patient came to their observation complaining of severe abdominal pain which started right after she was treated with a paracentesis, because of the suspicion of cirrhosis with ascites. The authors briefly outline the two goals of the diagnostic strategy: the diagnosis of the disease and the diagnosis of the nature of the disease. They stress the utmost importance of ultrasound and computerized tomography scans in the diagnosis of disease. For the diagnosis of the nature of the disease the authors counted on Ca 125, CEA, LDH levels and on Ca 19.9 and ACE levels as well. The surgical management of abdominal mass, which is the only possible treatment, led to the removal of a 60 cm in diameter and 30 kg mucinous cystadenoma. After the viscera of the higher abdomen (liver and stomach) had been repositioned, a plastic closure of the enormously expanded anterior abdominal walls was performed.
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PMID:[Benign giant ovarian cystadenoma. Description of a clinical case]. 878 69

Zone electrophoresis of serum proteins is still widely performed as a routine procedure in clinical laboratories. It is used in the diagnosis and management of many disorders, e.g. monoclonal gammopathies, cirrhosis, nephrotic syndrome, acute-phase reaction, immunoglobulin deficiency and others. The aim of this work is to evaluate the analytical performance of zone electrophoresis of serum proteins carried out in the Helena Laboratories Rapid Electrophoresis analyser (REP) comparing the results with those obtained in the Olympus Hite System 200 (HS-200). The REP system employs agarose gel as support medium, the HS-200 system employs cellulose acetate and it is the routine method in our laboratory. To date, we have not found any paper that deals with the assessment of a system for performing zone electrophoresis of serum proteins in terms of comparison with another.
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PMID:Evaluation of zone electrophoresis of serum proteins performed on the Helena Laboratories rapid electrophoresis analyser. 890 43

Lactulose exerts a beneficial effect on hepatic encephalopathy by decreasing toxic short-chain (iC4-nC6) fatty acid (isobutyrate, butyrate, isovalerate, valerate, isocaproate and caproate) production. However, the precise mechanism by which lactulose exerts this effect remains uncertain. This study investigated the effect of lactulose on faecal flora, particularly Clostridium difficile, which produces mostly iC4-nC6 fatty acids. An in-vitro faecal incubation system was used to estimate how lactulose influences production of short-chain (C2-nC6) fatty acids and lactate. Faecal specimens were collected from patients with liver cirrhosis, who carried C. difficile in the colon. Supplementation of lactulose along with blood in faecal specimens decreased iC4-nC6 fatty acids production and increased acetate and lactate production, resulting in increased faecal acidity. These changes were statistically significant when compared with supplementation by blood alone. Quantitative faecal culture demonstrated that lactulose supplementation suppressed the growth of C. difficile and Bacteroides spp. (B. fragilis group), iC4-nC6 fatty acids-producing organisms. These results suggest that decreased faecal levels of iC4-nC6 fatty acids after lactulose supplementation may be related to suppression of iC4-nC6 fatty acids-producing faecal organisms, especially C. difficile.
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PMID:Effect of lactulose on short-chain fatty acids and lactate production and on the growth of faecal flora, with special reference to Clostridium difficile. 900 50

Thus far, a large number of hypothesis have been proposed to explain how ethanol causes liver diseases including fatty liver, hepatitis, hepatic fibrosis, cirrhosis, as well as hepatocellular carcinoma. Although it still remains obscure, recent progress of science enables us to understand the mechanisms more deeply. We reviewed the latest aspects of mechanisms of alcoholic liver diseases, including alteration of redox state, effects of acetaldehyde and acetate, changes of metabolisms of lipid and protein, production of free radicals, alteration of hepatic micro circulation, change of hepatic membrane composition followed by changes of intracellular signal transduction, and effects of endotoxin. Moreover, we discussed the recent progress of studies on enzyme systems which participate in ethanol metabolism.
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PMID:[Recent progression in research on alcoholic liver disease]. 904 44

In an open trial, the pharmacokinetics of the angiotensin converting enzyme inhibitor ramipril and its active metabolite ramiprilat were studied in 12 patients with liver cirrhosis. After a single oral dose of 5 mg ramipril plasma levels of the parent compound reached peak concentrations of 48.6 +/- 39.8 ng/ml after 0.7 +/- 0.5 h and declined rapidly to 0.7 +/- 1.2 ng/ml after 8 h. Plasma levels of ramiprilat reached peak concentrations of 3.8 +/- 2.9 ng/ml after 3.0 +/- 2.2 h, thereafter declined slowly and could be detected up to 240 h. The total recovery of ramipril and metabolites in urine within 96 h was on average 46.0 +/- 10.9% of the administered dose. Major fractions were due to diketopiperazines and glucuronides of ramipril and ramiprilat. The overall ACE inhibition was still 92.0 +/- 8.6%. In conclusion, patients with liver cirrhosis had enough capacity to metabolize and excrete the parent compound ramipril, but had not enough capacity to form ramiprilat, although enough ramiprilat was formed for sufficient ACE inhibition of about 90%. This indicates that titration of the dose should start with 5 mg or even lower doses in patients with markedly impaired liver function.
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PMID:Angiotensin-converting enzyme inhibition in cirrhotic patients--pharmacokinetics of ramipril. 915 Aug 5

Cirrhosis encompasses a range of pathophysiological changes that may alter drug disposition. Drugs that are dependent primarily on the liver for their systemic clearance are more likely to be subject to reduced elimination and subsequent accumulation. Drug accumulation may lead to excessive plasma drug concentrations and adverse effects, if the adverse effects of the drug are concentration-dependent. The effects of hepatic insufficiency on the pharmacokinetics of drugs are not consistent or predictable. Furthermore, the influence of hepatic disease on the disposition of various drugs can vary, even though those drugs may share the same apparent metabolic pathway. Problems in forecasting drug kinetic behaviour are further enhanced by the additional impairment of kidney function (frequently encountered in patients with advanced liver disease) and by the unpredictability of the glomerular filtration rate using customary methods in patients with cirrhosis. Accordingly, dosages are generally adapted empirically, with the help of serum drug concentrations, when applicable. However, drugs eliminated predominantly by hepatic metabolism are not among those most commonly inducing adverse drug reactions or causing severe complications in patients with cirrhosis. Electrolyte disturbances and the hepatorenal syndrome produced by furosemide (frusemide)-the disposition of which is not substantially modified in liver disease-appear to be the most frequent adverse drug reactions in patients with liver disease. Furthermore, clinically significant alterations in the action of medications at concentrations generally considered to be in the normal therapeutic range are not uncommon. Tissue responsiveness to the pharmacological action of some drugs may be modified, as evidenced by the increased susceptibility of the brain in patients with cirrhosis to the action of many psychoactive agents. Another example is the greater susceptibility of such patients to the nephrotoxic potential of aminogly-cosides, which should not be used in this patient group. Drugs may also interfere with adaptive physiological processes induced by liver disease. ACE inhibitors and nonsteroidal anti-inflammatory drugs counteract the enhanced activity of the renin-angiotensin system in advanced liver disease, thereby generating a high risk of excessive hypotension or acute renal failure, respectively. These drugs are best avoided in patients with cirrhosis. Finally, there may be pharmacological effects that overlap with some pathophysiological modifications related to the process of liver disease, such as increased portal pressure produced by some calcium antagonists, or hypoprothrombinaemia related to the inhibition of synthesis of vitamin K-dependent clotting factors by some beta-lactam antibacterials (especially moxalactam and cefamandole). Accordingly, the use of these drugs should be avoided in advanced liver disease. It is noteworthy that reduced drug metabolism in patients with liver disease does not seem to have a significant impact on the frequency of hepatotoxicity. Special caution should be exercised, however, in patients with alcoholic liver disease because excessive alcohol intake may potentiate the hepatotoxic effect of paracetamol (acetaminophen).
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PMID:Drug administration in chronic liver disease. 925 30

Many, but not all, previous epidemiological studies indicated a greater risk of hepatocellular cancer (HCC) in women who have used combined oral contraceptives for a long period of time, but no one has analyzed this risk based upon use of different formulations. It was decided to analyze specifically the risk of OC containing cyproterone acetate (CPA) after toxicological experiments in animals found hints for a potential genotoxicity. This report describes the risk associated with ever having used combined oral contraceptives (OC) among 317 cases of primary hepatocellular cancer (HCC) in women under age 65, compared with 1060 age-matched hospital and 719 population controls in a case-control study, which was conducted in six European countries. The adjusted odds ratio (unconditional logistic regression) for ever having used any OC was found to be 0.75 (0.54 to 1.03) when all cases were compared with all controls, and compared to hospital and population controls separately: 1.13 (0.86 to 1.48) and 0.78 (0.59 to 1.03), respectively. The adjusted odds ratios for OC containing all progestins of the CPA group were 0.89 (0.49 to 1.61); and 0.89 (0.37 to 2.18) for OC containing only CPA. There was no increase in risk for HCC with increasing duration of OC use among the different groups of OCs in the total group of cases with pooled controls. The risk estimates were not related to time since first or last use of any of the types of OCs considered. The most important risk factors for HCC were confirmed as a prior history of hepatitis B and C (adjusted odds ratio 3.1 (2.2; 4.3) and 37.9 (20.2; 70.9) for HBV and HCV, respectively). In the small subgroup of HCC cases without liver cirrhosis and with negative serology for HBV and HCV, there was evidence of an association with duration of OC use. No such trend was observed for the CPA group of OCs. Altogether, there is no evidence for an increased risk of HCC associated with CPA or CPA-like OCs. Oral contraceptives in the aggregate may enhance the risk of liver carcinomas not associated with HBV or HCV infection, but if so, this is an extremely rare adverse effect of their use.
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PMID:Oral contraceptives and liver cancer. Results of the Multicentre International Liver Tumor Study (MILTS). 943 55

The therapy of portal hypertension depends to a significant extent on its clinical manifestation. In cases of acute haemorrhage from oesophageal varices in patients with portal hypertension, the objective of the therapy is to stop the haemorrhage (endoscopically, or by compression by means of a balloon probe) and to decrease the pressure and the reflux within the portal vascular bed. Urgent sclerotisation under the simultanous pharmacologic decrease of portal hypertension is successful in 93-95%. There is an alternative procedure residing in introducing a balloon probe for several hours and subsequent repeated sclerotisation until a complete eradication of varices is achieved regarding the prevention of haemorrhage exacerbation. Urgent surgical solution is on the basis of the results of various investigated studies reserved for patients in whom endoscopic sclerotisation was not successful. Indication of surgical therapy must be also deliberated in candidates for liver transplantation, regarding the possible consequent technical problems after some types of interventions. Endoscopic sclerotisation of oesophageal varices is also an appropriate preparation for transplantation of the liver in patients with liver cirrhosis included into the transplantation programme. TIPS is a perspective new method in the therapy of portal hypertension of both, non-bleeding varices, as well as in other indications. It is also a certain intermediating link in therapy in some patients with liver cirrhosis on the waiting list of candidates for liver transplantation. Pharmacotherapy is a significant part of the portal hypertension therapy. It is appropriate to combine the endoscopic treatment with pharmacotherapy of portal hypertension in both, cases of acute haemorrhage, as well as in the prevention of haemorrhage exacerbation. In cases of acute haemorrhage, the combination of glypressin with nitroglycerin is justified, as well as the therapy by somatostatin. The prevention of haemorrhage exacerbations uses a whole series of vasoactive substances, especially nitrates, beta-blockers and ACE inhibitors. The prevention of the first bleeding includes the prophylactic therapy (endoscopic, pharmacologic, or surgical) recommended only in a selected group of patients under high risk of bleeding. The possible perspective option will reside especially in the combined pharmacological therapy, the fact of which will have to be proven in the future. (Fig. 1, Ref. 25.)
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PMID:[Treatment of portal hypertension]. 958 83

Recent studies have shown that serum activity of angiotensin-converting enzyme (ACE; EC 3.4.15.1) significantly decreases in patients with carcinoma of different localizations. There is no information in literature about measuring this enzyme in primary liver carcinoma patients. The serum activity of ACE has been examined on 15 primary liver carcinoma patients, 10 patients with cirrhosis, and 26 healthy subjects. Serum activity has been determined by spectrophotometric method using synthetic substrate Hip-His-Leu. The results were given in units which correspond to one nmol of hippuric acid released by enzymatic hydrolyze of Hip-His-Leu substrate in one minute on serum milliliter. The results have shown that serum activity of ACE increased in patients with cirrhosis (37.06 +/- 2.9; X +/- SEM; p < 0.05), and decreased in primary liver carcinoma patients (23.44 +/- 1.87; p < 0.01), what was statistically significant in comparison with the activity of the same enzyme in healthy subjects (29.90 +/- 2.72). These results point out the possibility of clinical application of measuring serum ACE activity as one of primary liver carcinoma marker in differential diagnosis of the disease.
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PMID:[Serum angiotensin converting enzyme in patients with primary liver carcinoma]. 1038 37


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