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)

Sera from 54 children (mean age 5.8 years) with chronic hepatitis B virus (HBV) infection were investigated for the presence of immune complexes containing HBV proteins. Clinical diagnosis was established by histology and biochemical markers and included chronic persistent (36 cases) or chronic aggressive (seven) hepatitis, liver cirrhosis (six) and HBV-mediated membranous glomerulonephritis (five). Circulating immune complexes were precipitated with 2.5% polyethylene glycol and analysed by immune blot using monoclonal antibodies against S, pre-S2 glycopeptide, pre-S1 and HBe/c epitopes. All sera, including those from 11 healthy HBV-negative blood donors contained PEG-precipitable substances, but the amount of precipitate did not correlate with the presence or amount of HBV proteins. The great majority (36 out of 40) of HBeAg-positive patients contained HBs proteins in immune complexes, but no detectable HBe protein. The immune complexes usually contained more pre-S1 than the free HBsAg particles from the same patient. The precipitates of anti-HBe-positive patients rarely contained HBV proteins (two out of 14) and, if so, in low amounts. During follow up of six patients we found that high levels of HBs-containing immune complexes may be correlated with subsequent elimination of HBV. This elimination is possibly initiated by binding of anti-pre-S1 antibodies to HBV and HBs particles.
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PMID:Analysis of viral proteins in circulating immune complexes from chronic carriers of hepatitis B virus. 204 31

The effects of pretreatment with the hepatotoxin, thioacetamide, on the pharmacokinetics of praziquantel, a broad spectrum schistosomicidal agent with a high hepatic clearance, were studied in male Wistar rats. Animals were pretreated with either thioacetamide (25 mg in 100 ml of drinking water, n = 5) for 24 weeks or received plain drinking water (n = 5) over the same period. After the treatment period, praziquantel was administered orally (25 mg/kg as a 20 mg/ml solution in PEG 200) as a single dose. Blood samples (0.3 ml) were collected from the clipped tail at various times up to 4 h post administration. Plasma was analysed for praziquantel using an HPLC method. Mean peak plasma praziquantel concentrations were approximately 1.0 mg/l for both groups. The time to reach peak concentrations, and post-peak elimination half-life, were approximately 0.7 h and 1.0 h, respectively, for both groups. Similarly, mean AUC was approximately 2.0 mg.h/l for both groups. Statistical comparisons indicated that there were no significant differences in the pharmacokinetic parameters estimated in the two groups of animals. It was concluded that thioacetamide-induced hepatic cirrhosis has no effect on the pharmacokinetics of orally administered praziquantel in the rat, at the dose level studied.
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PMID:Effect of experimentally-induced hepatic cirrhosis on the pharmacokinetics of orally administered praziquantel in the rat. 225 49

The composition of immune complexes (IC) found in 28 patients with HBsAg positive and negative acute and chronic hepatitis was analysed. Components were defined in PEG-precipitated material isolated by preparative ultracentrifugation on linear sucrose density gradients and analysed by the Ouchterlony plate technique and by the radioimmunoassay of hepatitis B virus markers. Sedimentation rate ranged from 8 to 19s in the serum of patients with chronic hepatitis, whereas heavier IC (greater than 19s) were present in the active phase of the disease. The participation of hepatitis B virus in acute hepatitis was shown by the presence of its antigens. In contrast, a low incidence of vital components was seen in IC of chronic active hepatitis and liver cirrhosis. Thus, other causes must contribute to the formation of IC in chronic liver disease.
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PMID:Characterization of the circulating immune complexes in acute and chronic liver diseases. 686 64

Both the PEG-N technique and the PACIA were applied to determine ICLM in sera from patients with liver cirrhosis and gram-negative septicemia, that have been shown to yield positive reactions for endotoxemia with the LAL test. The precision of the PEG precipitation technique, with a stabilized fraction of human HAG of known molecular size used as a calibrator, was satisfactory. In liver cirrhosis, the detectable ICLM was mainly composed of IgG and C3, whereas in gram-negative septicemia IgM, IgG, and C3 were found. PACIA also measured significantly elevated levels of ICLM with rheumatoid factor-binding activity in both patient groups, although the two assay systems did not correlate. PEG precipitates from both patient groups analyzed by gel-chromatography and passive hemolysis test contained large immune aggregates and various amounts of immunoglobulins with specificity directed toward lipid A, the least variable portion of endotoxin. These compositional differences of detected substances may imply the presence of different types of ICLM in patients with liver cirrhosis and gram-negative septicemia.
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PMID:The polyethylene glycol precipitation technique and the particle-counting immunoassay for detection of circulating immune complex-like material in liver cirrhosis and septicemia. 707 26

A new one-step ELISA using two monoclonal antibodies specific for distinct epitopes of the free form of protein S (ELISA-m) has been developed for the direct measurement of free protein S in untreated plasma. This assay has been compared with the classic method using polyclonal antibodies to protein S (ELISA-p). The latter method has the drawback of requiring PEG precipitation of plasma which is time-consuming, difficult to perform with accuracy and therefore poorly reproducible in most laboratories. Results of both ELISAs were compared with those of a functional assay. In 30 normal subjects, there was an excellent correlation between ELISA-m and ELISA-p (r = 0.95) as well as between ELISA-m and the functional assay (r = 0.96). In twelve patients with a congenital deficiency, the levels of free protein S antigen were similarly decreased with ELISA-m and ELISA-p and in good agreement with those of protein S activity. In 20 patients with miscellaneous inflammatory diseases, the levels of free proteins S were normal with good correlation between both ELISAs and PS activity, despite high levels of C4bBP-protein S complexes. As expected, in 15 dicoumarol-treated patients, there was a significant and parallel decrease of free protein S antigen with both ELISAs, with even lower levels of protein S activity. In 14 patients with liver cirrhosis, the mean values for free protein S antigen were normal using both assays, but with wide extreme values, whereas protein S activity was significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical applications of a direct assay of free protein S antigen using monoclonal antibodies. A study of 59 cases. 751 89

Laparoscopic gastrostomy was performed on 70 patients with contraindications to PEG. All procedures were performed successfully, even in patients with gastric resections, after gallbladder surgery, and in patients with liver cirrhosis and ascites. Long-term results comprise a low complication rate of 0.12 in 100 application days. Laparoscopic gastrostomy is a highly effective procedure with low morbidity and good long-term results in patients with contraindications to PEG requiring enteral feeding.
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PMID:[Laparoscopic gastrostomy--advantages in comparison with percutaneous endoscopic gastrostomy (PEG)]. 957 70

NATURAL HISTORY OF HEPATITIS C-INFECTION AND VIRAL CHARACTERISTICS: Hepatitis C-virus (HCV) infection is a major cause of non-A, non-B-hepatitis and, additionally, is associated with liver cirrhosis and hepato-cellular carcinoma. The high degree of chronificity of HCV-infection is reasonable due to antigenic variability of neutralizing epitopes leading to incomplete immunoresponse with subsequent virus persistence. Besides genetic variants of HCV within a virus population (quasispecies nature of HCV), different genotypes are classified being genetically and phenotypically distinct, and geographically restricted in part. Genotyping of HCV is not only important for phylogenetic and epidemiological studies, but also a predictive marker for pathogenesis and therapy. VIRAL PREDICTORS OF HCV THERAPY: In a meta-analysis of 18 therapeutical studies of chronical HCV infections, genotype 1 and high levels of viremia determined markedly the response to interferon therapy. In this context, clinical trials have proven the effect of a combined therapy with interferon and ribavirin. Especially patients with HCV genotype 1 or high levels of viremia had a real benefit from combined antiviral therapy in comparison to monotherapy with interferon. CONCLUSION AND FUTURE CONCEPTS: Besides recent concepts improving the therapeutical response to HCV infection, further effort is necessary to develop more successful strategies for eradication of hepatitis C virus. In this context, variations of interferon therapy should be evaluated (e.g. higher and daily doses, longer duration of interferon therapy, "retarded" interferon (PEG-IFN). In addition, new therapeutical concepts should be performed including a combination of interferon with other known antiviral agents (amantadine), a combination with immunomodulators (GM-CSF, thymosin alpha 1), the development of new antiviral agents (inhibitors of viral proteases, helicases and polymerases) and the exploration of anti-viral, molecular strategies (specific ribozymes, antisense oligonucleotides and DNA-vaccination). Nevertheless, the development of an effective vaccination should be the most important challenge for the future.
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PMID:[Characteristics of the hepatitis C virus and viral predictors of therapeutic response]. 1060 34

Hepatitis C is one of the world's leading infectious diseases. The interferon-ribavirin combination therapy is the new standard for the treatment of hepatitis C in naive and relapse patients. Virological sustained response rates can be more than doubled by the IFN-ribavirin combination therapy compared to IFN-monotherapy and treatment duration can be reduced to six months in many cases. The IFN-ribavirin combination therapy has a high relative benefit in patients with unfavorable predictive parameters like high viral load, HCV genotype-1 infection and compensated liver cirrhosis. Anemia is the most important side effect of the guanosin analogue ribavirin. There are no official therapeutic recommendations for non-responder patients at present. These patients should be treated within controlled clinical trials. Monotherapy with PEG(pegylated)-interferons and combination therapies with PEG-interferons and ribavirin are the most promising future therapeutic options.
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PMID:[Antiviral therapy of hepatitis C]. 1076 50

Interferon(IFN) is an essential component of the treatment of chronic HCV infection and at present, it is the most important to improve its efficacy, not only for HCV chronic liver diseases, but also for the prevention of HCV-associated hepatocellular carcinoma. Two long-acting IFN preparations(PEG-IFN alpha 2a and 2b) have been used at present and clinical studies have shown that sustained virologic, biochemical and histological responder rates are significantly higher in PEG-IFN-treated patients with HCV associated chronic hepatitis and cirrhosis comparing with ones treated with conventional IFN. In addition, PEG-IFN treatment in combination with ribavirin seems to be the best for HCV-associated chronic liver diseases.
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PMID:[Present status of clinical trials on long-acting IFNs preparations (PEG-IFN alpha 2a, alpha 2b, IFN alpha-minipellet)]. 1149 53

Pegylated IFN-alpha(2a) (PEG-IFN-alpha(2a) [40 kDa]; Pegasys, Hoffmann-La Roche) is a new subcutaneous formulation of IFN-alpha(2a), produced by its attachment to a 40 kDa branched polyethylene glycol moiety by a stable amide bond. PEG-IFN-alpha(2a) 180 micro g once-weekly has enhanced pharmacokinetic and pharmacodynamic properties which translate into significantly improved efficacy and similar safety and tolerability compared with IFN-alpha in patients with chronic hepatitis C even with underlying cirrhosis. The combination of PEG-IFN-alpha(2a) (40 kDa) plus ribavirin produces significantly better sustained virological responses than the combination of IFN-alpha(2b) and ribavirin, while it is accompanied by a similar or even lower incidence of adverse events and better quality of life. PEG-IFN-alpha(2a) (40 kDa) is the first pegylated IFN-alpha for which evidence-based recommendations can be made on optimum therapy duration and ribavirin dose according to HCV genotype. PEG-IFN-alpha(2a) (40 kDa) is expected to improve the efficacy and tolerability of treatment for chronic hepatitis C.
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PMID:Peginterferon-alpha2a (40 kDa) for chronic hepatitis C. 1266 17


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