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)

This report describes the development, characterization and preclinical efficacy evaluation of water soluble glucan sulfate. Glucan sulfate was derived from insoluble beta-1,3-D-glucan isolated from Saccharomyces cerevisiae. The proposed repeating unit empirical formula of glucan sulfate is [(C6H10O5)5.3H2SO4]n. Two polymer peaks were resolved by aqueous high-performance size exclusion chromatography (HPSEC) with on-line multi-angle laser light scattering (MALLS) photometry and differential viscometry. Peak 1 (MW = 1219697 Da) represents approximately 1% of the total polymers, while peak 2 (MW = 8884 Da) accounts for approximately 99% of polymers. 13C-NMR spectroscopy suggests that glucan sulfate polymer strands may be partially cross-linked. Glucan sulfate (250 mg/kg, i.v.) increased (P less than 0.01) macrophage vascular clearance of 131I-reticuloendothelial emulsion by 42% (P less than 0.01) and in vitro bone marrow proliferation by 46% (P less than 0.05). Glucan sulfate (250 mg/kg, i.v.) increased (P less than 0.05) median survival time of C57B1/6J mice with syngeneic melanoma B16 or sarcoma M5076. In addition, glucan sulfate immunoprophylaxis increased resistance of mice to challenge with Escherichia coli, Candida albicans or Mouse Hepatitis Virus strain A-59. We concluded that: (1) insoluble beta-1,3-D-glucan can be converted to a water soluble sulfated form; (2) glucan sulfate activates macrophages and stimulates bone marrow; (3) glucan sulfate exerts antitumor therapeutic activity, and (4) glucan sulfate immunoprophylaxis will modify the course of experimental infectious disease.
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PMID:Development, physicochemical characterization and preclinical efficacy evaluation of a water soluble glucan sulfate derived from Saccharomyces cerevisiae. 177 55

Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for ozone-depleting chlorofluorocarbons (CFCs); because widespread human exposure to HCFCs may be expected, it is important to evaluate their toxicities thoroughly. Here we report studies on the bioactivation of the CFC substitute 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) to an electrophilic intermediate that reacts covalently with liver proteins. HCFC-123 and its analog halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were studied in rats by 19F NMR spectroscopy, and we found that a trifluoroacetylated lysine adduct was formed with liver proteins. Also, the pattern of proteins immunoreactive with hapten-specific anti-trifluoroacetylprotein antibodies was identical in livers of HCFC-123- and halothane-exposed rats. Because halothane causes an idiosyncratic, and sometimes fatal, hepatitis that is associated with an immune response against several trifluoroacetylated liver proteins, the present findings raise the possibility that humans exposed to HCFC-123 or structurally related HCFCs may be at risk of developing an immunologically mediated hepatitis.
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PMID:Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane. 199 42

A conjugate consisting of the antiviral nucleotide analogue adenine arabinoside 5'-monophosphate (araAMP, vidarabine monophosphate) and the naturally occurring polysaccharide arabinogalactan was synthesized. The conjugate consisted of 7.9 araAMP residues per molecule of arabinogalactan. The proposed structure of the conjugate was consistent with 13C NMR spectroscopic studies. Daily injections of the conjugate, at a dose of 3 mg of araAMP/kg, into woodchuck carriers of woodchuck hepatitis virus (WHV) decreased serum levels of WHV DNA. A dose of 3 mg/kg of unconjugated araAMP was ineffective, while a higher dose of araAMP (15 mg/kg, 14 days) produced a drop in WHV DNA. After cessation of dosing with the conjugate, serum viral DNA levels remained depressed for 42 days. In contrast, after cessation of dosing with araAMP, WHV DNA rapidly returned to original levels.
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PMID:Conjugation of adenine arabinoside 5'-monophosphate to arabinogalactan: synthesis, characterization, and antiviral activity. 754 Dec 49

The survival rate for acute hepatic failure induced by Propionibacterium acnes and lipopolysaccharide (LPS) was increased when a hot water extract from the flowers of Inula britannica L. subsp. japonica Kitam. was injected into the experimental hepatitis mice, and anti-hepatitis substances could be extracted with CHCl3. The CHCl3 extract from I.britannica was fractionated and anti-hepatitis fractions IB-3-2 and IB-3-3 were obtained. IB-3-3 had the most potent anti-hepatitis activity among the fractions but further purification of the active compound was not achieved because of the low yield. IB-3-2 contained only one substance which was identified to be taraxasteryl acetate by 1H- and 13C-NMR and MS. Taraxasteryl acetate showed potent preventive activity against acute hepatic failure induced by P.acnes and LPS in a dose-dependent manner, however deacetylation and modification of the olefinic bonds significantly decreased the anti-hepatitis activity of taraxasteryl acetate. Taraxasteryl acetate also inhibited the increment of plasma transaminase on acute hepatic failure induced by carbon tetrachloride (CCl4) or D-galactosamine. From a histological study it appeared that degeneration and necrosis, which were observed in the liver from CCl4 mice, were not found in the liver cells from taraxasteryl acetate treated mice. These results indicates that taraxasteryl acetate shows preventive effects on experimental hepatitis caused by either immunologically induced injuries or hepatotoxic chemicals.
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PMID:Preventive effect of taraxasteryl acetate from Inula britannica subsp. japonica on experimental hepatitis in vivo. 1725 90

To evaluate the changes in hepatocellular phospholipid metabolism during hepatitis virus infection, 26 patients with acute viral hepatitis A were studied by means of phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. The spectroscopy of liver showed six signal components in all patients as well as in the normal volunteers. During the early phase of illness, the phosphomonoester (PME)-phosphodiester (PDE) ratios in the patients became markedly greater than the ratios in the controls (P < 0.001). Within six weeks after the onset, the PME/PDE ratios returned to the level of controls. The time course analysis indicated an inverse correlation between the PME/PDE ratio and the period of time after onset (r = 0.738, P < 0.001). The spectral changes of human liver observed in acute viral hepatitis A are similar to those in the regenerating rat liver, indicating that 31P-NMR spectroscopy allows a noninvasive study of cell turnover in human liver disease associated with acute virus infection.
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PMID:Phosphorus-31 nuclear magnetic resonance in vivo spectroscopy of human liver during hepatitis A virus infection. 828 64

We have obtained and analyzed the 600 MHz proton NMR spectra of a 74-mer RNA derived from the catalytic domain of hepatitis delta virus genomic RNA (HDV RNA) to determine its secondary structure. Deconvolution of the NMR spectrum obtained at 32 degrees C indicates that part of the 74-mer RNA molecule may exist in multiple conformations in equilibrium. The major conformer contains two A-U base pairs and 14 +/- 2 G-C base pairs. It appears to contain no standard G-U base pairs. Our NMR melting study suggests that this conformer has at least two stem-loop regions. One of the regions has been identified to be a tetra-loop. We have assigned five imino proton resonances of the tetra-loop stem. Our data is consistent with the pseudoknot model of Perrotta and Been.
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PMID:The catalytic domain of human hepatitis delta virus RNA. A proton nuclear magnetic resonance study. 840 69

Post ESWL haemorragic complications are frequent and most patients experience temporary haematuria and focal intrarenal bleeding or perirenal haematoma are detected by NMR or US imaging. By tradition coagulation troubles have been a contraindication for ESWL but literature describes cases of coagulopathic patients treated with ESWL. From January 1992 to July 1993, 4 of our patients with severe haemostatis troubles (severe haemophilia A in two cases, acquired deficit of coagulation factors and mild thrombocytopenia secondary to post-necrotic hepatitis in 1 case and Glanzmann's thrombasthenia in 1 case) underwent ESWL using Dornier HM3 mod. or MPL 9000. An extensive haematological and clinical evaluation pre and post-ESWL with an adequate haematological prophylaxis (transfusion of blood derivatives) has been performed depending on the coagulation disorder. In our patients we did not observe any haemorragic complication and we propose a reappraisal of the contraindications of ESWL in subjects with coagulation disorders: careful evaluation of haemorragic risk factors, by suitable correction measures and close clinical and instrumental monitoring, allows a reduction of the risk of haemorragic complications in coagulopathic patients who undergo ESWL treatment.
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PMID:[Extracorporeal lithotripsy in patients with acquired or congenital coagulopathies]. 858 Sep 83

The biotransformation of the aerosol propellant 1,1,1,2,3,3,3-heptafluoropropane (HFA-227) was investigated in rats in vivo and in rat and human liver microsomes. In the urine of rats exposed to 5000 ppm HFA-227 for 6 hr, very small amounts of hexafluoroacetone trihydrate were identified as an HFA-227 metabolite by 19F-NMR. Fluoride concentrations in the urine samples (0-48 hr after the end of the exposure) from exposed animals were not significantly different from those found in samples from nonexposed rats. In rat and human liver microsomes, fluoride and hexafluoroacetone trihydrate formation from HFA-227 was detected in very low levels only in liver microsomes from pyridine-treated rats and in two of eight human liver microsome samples, which exhibited the highest cytochrome P4502E1 activities. Because some aldehydes may covalently bind to proteins and the formation of fluorinated protein adducts has been implicated in immune-mediated hepatitis induced by halothane, the binding of hexafluoroacetone trihydrate to proteins was also investigated. Hexafluoroacetone trihydrate also gave only a very small resonance in fluorine NMR experiments when binding to human serum albumin was studied in comparison with the acylating agent S-ethyltrifluoroacetate. Moreover, no fluorine-containing products were formed by the reaction of hexafluoroacetone trihydrate with N alpha-acetyl-L-lysine, and hexafluoroacetone trihydrate was not metabolized to fluorine-containing metabolites or inorganic fluoride in rats. Comparative studies in human liver microsomes demonstrated that a halothane metabolite may covalently bind to proteins; in contrast, metabolism and covalent binding of HFA-227 could not be demonstrated. In summary, these data indicate that HFA-227 is biotransformed at very low rates to hexafluoroacetone trihydrate but irreversible binding of hexafluoroacetone trihydrate cannot be demonstrated, even with the application of very sensitive methods, and is considered unlikely, based on the combination of the results obtained.
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PMID:Biotransformation of the aerosol propellant 1,1,1,2,3,3,3-heptafluoropropane (HFA-227): lack of protein binding of the metabolite hexafluoroacetone. 886 27

The Hepatitis Delta Virus (HDV) ribozyme self-cleaving activity in 20 M formamide solutions is unique. Does this catalytic activity result from the conservation of its tertiary structure in 20 M formamide? We followed the ribozyme structure in formamide solutions by monitoring the amount of bound Ethidium Bromide (EB). We were able to measure the quantity of dye bound using time-resolved fluorescence spectroscopy, as an estimate of the ribozyme double helical content. This method, calibrated by using oligonucleotides with defined tertiary structure and denaturing solvents, parallels NMR and UV measurements as a function of temperature. Measurements with the HDV ribozyme lead to three conclusions: (a) both the precursor and product RNAs are structured to 24 M (95% w/w) formamide or 4 M H2O solutions which is equivalent to 4 M H2O; (b) the HDV ribozyme is the only RNA sequence investigated in this study that retains so much structure in formamide; and (c) DNA analogs of formamide resistant HDV ribozyme sequences lose their structure at less than 15 M formamide. Thus, the structural integrity of the HDV ribozyme is an intrinsic property of the RNA molecule and its sequence.
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PMID:Secondary structure content of the HDV ribozyme in 95% formamide. 891 91

The structure of an RNA hairpin containing a seven-nucleotide loop that is present in the self-cleaving sequence of hepatitis delta virus antigenomic RNA was determined by high resolution NMR spectroscopy. The loop, which is composed of only one purine and six pyrimidines, has a suprisingly stable structure, mainly supported by sugar hydroxyl hydrogen bonds and base-base and base-phosphate stacking interactions. Compared with the structurally well-determined, seven-membered anticodon loop in tRNA, the sharp turn which affects the required 180 degrees change in direction of the sugar-phosphate backbone in the loop is shifted one nucleotide in the 3' direction. This change in direction can be characterized as a reversed U-turn. It is expected that the reversed U-turn may be found frequently in other molecules as well. There is evidence for a new non-Watson-Crick UC base pair formed between the first and the last residue in the loop, while most of the other bases in the loop are pointing outwards making them accessible to solvent. From chemical modification, mutational and photocrosslinking studies, a similar picture develops for the structure of the hairpin in the active ribozyme indicating that the loop structure in the isolated hairpin and in the ribozyme is very similar.
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PMID:The structure of the isolated, central hairpin of the HDV antigenomic ribozyme: novel structural features and similarity of the loop in the ribozyme and free in solution. 921 9


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