Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential effects of cytokines on hepatocellular transport functions remain undefined. Interleukin-6 (IL-6) is a cytokine that is produced in sepsis, hepatitis, and other inflammatory conditions often associated with cholestasis. Using cultured rat hepatocytes, we have investigated the effects of IL-6 on hepatocellular bile salt uptake. Because hepatocyte Na(+)-K(+)-adenosinetriphosphatase (ATPase) produces the electrochemical gradient that drives sodium-dependent bile salt contransport, we also examined the effects of IL-6 on Na(+)-K(+)-ATPase activity. Hepatocytes cultured for 20 h in media containing IL-6 exhibited a dose-dependent noncompetitive inhibition of [3H]taurocholate uptake, which was maximal at an IL-6 dose of 100 U/ml. IL-6 treatment had no effect on hepatocyte sodium-independent taurocholate uptake. Northern blotting of RNA from cultured hepatocytes revealed that IL-6 had no effect on steady-state RNA levels of the Na(+)-taurocholate transporter (Ntcp). Hepatocytes incubated with IL-6 for 20 h, however, exhibited a 55% decrease in hepatocyte Na(+)-K(+)-ATPase activity. This effect also was dose dependent, with maximal inhibition occurring at an IL-6 dose of 100 U/ml. Similar treatment with IL-6 did not influence hepatocyte Mg(2+)-ATPase activity. The inhibition of Na(+)-K(+)-ATPase activity induced by IL-6 provides a putative mechanism for the observed inhibition of sodium-dependent taurocholate uptake. Since modulation of bile salt transport and Na(+)-K(+)-ATPase activity occurred at IL-6 concentrations comparable to the serum levels observed in patients with severe inflammatory states, these findings have potential pathophysiological relevance for the cholestasis of sepsis and other inflammatory disorders.
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PMID:Interleukin-6 inhibits hepatocyte taurocholate uptake and sodium-potassium-adenosinetriphosphatase activity. 781 Jun 56

Fasting serum conjugated bile salt concentrations were measured in a group of 20 patients with moderate post-hepatitis cirrhosis. Twenty healthy volunteers were used as controls. The individual conjugated bile acids were analyzed by a specific and sensitive method which couples reversed-phase high-performance liquid chromatography with mass spectrometry. Significantly elevated levels of the total and individual conjugated bile acids were found in cirrhotic patients. The predominant serum bile acids were conjugates of chenodeoxycholic acid. The conjugates of lithocholic acid were also increased; in subjects with normal liver function, on the contrary, they were found only in traces.
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PMID:Serum bile acid concentrations in mild liver cirrhosis. 814 35

Self-cleaving sequences or ribozymes from the hepatitis delta virus (HDV) genomic RNA and its complement form similar secondary structures that suggest a core region and potential active site composed of "single-stranded" sequences. However, there is little data on tertiary interactions in these ribozymes, therefore structural features were investigated using cross-linking and hydroxyl radical cleavage. Cross-links in cis and trans forms of the antigenomic RNA were generated using the photoactivatable azidophenacyl group tethered to the cleavage site phosphate. Specific cross-links formed to J4/2, and to the 3' sides of P3 and L3. Different sites were cross-linked in low salt or monovalent cations versus divalent cations, suggesting a metal ion-dependent conformational change near the cleavage site. The solvent-inaccessible regions of both the genomic and antigenomic ribozymes were revealed by cleavage in Fe(II)-EDTA. In Mg2+, backbone segments most strongly protected from solvent-based hydroxyl radicals were mapped to J4/2 and parts of L3. Similar patterns of protection were seen in trans-acting ribozymes bound to a product oligonucleotide. These data provide evidence for a common tertiary structure for the HDV ribozymes. They would be consistent with a model in which the end of P1, including the cleavage site phosphate and the nucleotide 5' to the cleavage site, is positioned in an active site pocket or cleft formed by the three single-stranded regions, L3, J4/2, and J1/4.
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PMID:Hepatitis delta virus ribozymes fold to generate a solvent-inaccessible core with essential nucleotides near the cleavage site phosphate. 878 96

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

Intravenous immunoglobulins (IVIg) purified by cold ethanol fractionation have a very good safety record with regard to the transmission of many viruses. However, a few cases of non-A-non-B hepatitis have been described after intravenous injection of some immunoglobulin preparations. To ensure even higher safety for our IVIg, an additional virus inactivation step, based on pasteurization, was developed. The heating of aqueous IVIg was performed without stabilizer, and at a very low salt concentration (< 1 mM) at acidic pH. No generation of polymer was detected after pasteurization and a significant decrease in the proportion of dimers was observed. Analysis of the secondary structure by circular dichroism showed a very slight change in the secondary structure. The biological properties of the Fc region as well as the Fab region were not affected by the pasteurization. Our method has several advantages: (1) improvement of viral safety; (2) there is no need to add stabilizer which may stabilize viral particles, and (3) the absence of any hypotensive effect and low anticomplementary activity indicates a good clinical tolerance of IgG preparation.
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PMID:Liquid pasteurization of an immunoglobulin preparation without stabilizer: effects on its biological and biochemical properties. 922 20

In order to investigate the aetiological factors of Primary Liver Cancer (PLC) in Shunde City of Guangdong province, 96 clinically diagnosed PLC patients and 144 matched hospital controls were interviewed and their blood samples were examined for HBV, HCV and other seven indices. Monofactorial and multifactorial analyses were fitted by using Non-conditional Logistic Regression model. The findings confirmed the strong association between HBV infection and PLC. Histories of hepatitis and histories of eating raw fish, shrimp or salt fish were also noticed. The history of alcohol intake might have associated with PLC. The present study did not find associations between PLC and drinking water, histories of blood transfusion and injection- or exposure to insecticides. Antibody of HBV surface antigen seemed to be a protective factor with a relative risk of 0.3064 (0.1647-0.5701). The results showed that the combined effects of HBsAg infection and HCV infection were worthy for further study.
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PMID:[An epidemiologic study on the aetiological factors of primary liver cancer in Shunde City of Guangdong province]. 920 9

Biotechnological techniques of cross-linking and microencapsulation of hemoglobin result in blood substitutes that can replace red blood cells. Unlike red blood cells they can be sterilized by pasteurization, ultrafiltration and chemical means. This removes microorganisms responsible for AIDS, hepatitis, etc. Since they are free of red blood cell blood group antigens, there is no need for cross-matching or typing. This saves time and facilities and allows on-the-spot transfusion such as the infusion of salt solution. Furthermore, they can be stored for a long time. Hemoglobin for modification can be extracted from human red blood cells. Other sources of hemoglobin include bovine hemoglobin and recombinant human hemoglobin. Clinical trials are ongoing testing the possible uses of cross-linked hemoglobin in cardiac, orthopedic, trauma and other types of surgery. It is also being tested for the replacement of lost blood in severe bleeding due to trauma or other causes. Cross-linked hemoglobins are first generation blood substitutes that only fulfil some of the functions of red blood cells. New generations of more complete red blood cell substitutes are being developed. These include cross-linked hemoglobin-catalase-superoxide dismutase and microencapsulated hemoglobin-enzyme systems.
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PMID:Modified hemoglobin blood substitutes: present status and future perspectives. 989 Jan 39

Protective influence of a new phospholipid preparation "Phospholiv" was studied using a model of chronic hepatitis. Animals were treated 45 days intraperitoneay with CCl4 with parallel intragastral administration of Phospholiv or--(for comparison)--the of other phospholipid hepatoprotector, Essential. Morphologic changes of liver, as well as protein and RNA biosynthesis were evaluated in the end of experiment--by means of measuring C14-leucine and C14-orotic acid incorporation into hepatocyte subcellular fractions. Both phospholipid preparations attenuated dystrophic liver changes, Phospholiv effect being more pronounced. They both prevented CCl4 induced inhibition of label incorporation into subcellular fraction proteins, but only Phospholiv, promoted the maintaining normal level of radioactivity incorporation into cytosol proteins and hepatocyte RNA. The results, confirming certain protective effect of Essential, show more pronounced hepatoprotective action of the new preparation Phospholiv (developed on the basis of polyunsaturated phosphatidylcholine and glycyrrhizinic acid salt). Data show also on possible fit hepatitis treatment.
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PMID:[Use of a novel hepato-protective preparation "phospholiv" for inhibition of development of chronic hepatitis in rats]. 1059 39

Patients with acute viral hepatitis B, A and mixed hepatitis B + C were treated in two independent clinics with phosphogliv--a new hepatoprotective drug based on polyunsaturated phosphatidylcholine and glycyrrhizic acid salt. Phosphogliv removed some symptoms of intoxication (nausea, weakness, jaundice, etc.) quicker than basic therapy. Among biochemical hepatitis markers, serum bilirubin level was most responsive to phosphogliv. Standard therapy decreases bilirubin by 30% on the average for 5 days, phosphogliv reduces bilirubin for one more week to half those values observed in control patients. At that point low aminotransferase activities were seen in phosphogliv treated patients. No side effects were seen. The new hepatoprotector phosphogliv which repairs biomembranes represents drugs of new generation compared to phospholipid drug essential.
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PMID:[New domestic phospholipid preparation "Fosfogliv" as an effective treatment for patients with acute viral hepatitis]. 1088 9

Hepatitis delta virus (HDV) encodes a single polypeptide called hepatitis delta antigen (DAg). Dimerization of DAg is required for viral replication. The structure of the dimerization region, residues 12 to 60, consists of an anti-parallel coiled coil [Zuccola et al., Structure, 6(1998)821]. Multiple Copy Simultaneous Searches (MCSS) of the hydrophobic core region formed by the bend in the helix of one monomer of this structure were carried out for many diverse functional groups. Six critical interaction sites were identified. The Protein Data Bank was searched for backbone templates to use in the subsequent design process by matching to these sites. A 14 residue helix expected to bind to the D-isomer of the target structure was selected as the template. Over 200,000 mutant sequences of this peptide were generated based on the MCSS results. A secondary structure prediction algorithm was used to screen all sequences. and in general only those that were predicted to be highly helical were retained. Approximately 100 of these 14-mers were model built as D-peptides and docked with the L-isomer of the target monomer. Based on calculated interaction energies, predicted helicity, and intrahelical salt bridge patterns, a small number of peptides were selected as the most promising candidates. The ligand design approach presented here is the computational analogue of mirror image phage display. The results have been used to characterize the interactions responsible for formation of this model anti-parallel coiled coil and to suggest potential ligands to disrupt it.
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PMID:Computational design of D-peptide inhibitors of hepatitis delta antigen dimerization. 1113 65


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