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)

Studies of virus sterilization of coagulation factor concentrates using marker viruses, AIDS, hepatitis B (HBV) and non-A, non-B hepatitis (NANBHV) viruses indicate the following: Strategies adopted to stabilize coagulation factors to heat denaturation, including addition of high concentrations of solutes or lyophilization, stabilize virus. At 60 degrees C, heating in the liquid state provides more rapid virus kill than heating in the lyophilized state with 2% residual moisture. To achieve the same virucidal potency as achieved on heating albumin at 60 degrees C for 10 hours, stabilized coagulation factor concentrates would require a substantial increase in the dose of heat. The rate of inactivation by either thermal or solvent/detergent methods slows with time. Improved virus kill is attained more easily by increasing the temperature than by extending the duration of exposure. Viruses vary widely in their sensitivity to thermal denaturation or solvent/detergent action. Because studies on the rate of inactivation of HBV and NANBHV are not feasible, assessment of their sensitivity is at best approximate. Sensitivity to thermal inactivation appears to follow the order HTLV-III greater than VSV, EMC greater than NANBHV?, Sindbis much greater than HBV. Sensitivity to organic solvent/detergent mixtures appears to follow the order HTLV-III greater than Sindbis, Sendai, HBV?, NANBHV? greater than VSV much much greater than EMC. Protein enveloped forms of NANBHV must occur rarely or not at all. Use of marker viruses to compare virucidal potency of methods that inactivate by different mechanisms may lead to erroneous conclusions; however, marker virus data probably provide useful comparisons of related sterilization methods or of a single method applied to different protein mixtures. If virus sterilization processes are to be validated in a manner which enables a meaningful comparison between laboratory and clinical results, higher titers of virus will be required.
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PMID:Laboratory and preclinical evaluation of the virus safety of coagulation factor concentrates. 360 83

Use of the organic solvent, tri(n-butyl)phosphate (TNBP), and detergents for the inactivation of viruses in labile blood derivatives was evaluated by addition of marker viruses (VSV, Sindbis, Sendai, EMC) to anti-hemophilic factor (AHF) concentrates. The rate of virus inactivation obtained with TNBP plus Tween 80 was superior to that observed with ethyl ether plus Tween 80, a condition previously shown to inactivate greater than or equal to 10(6.9) CID50 of hepatitis B and greater than or equal to 10(4) CID50 of Hutchinson strain non-A, non-B hepatitis. The AHF recovery after TNBP/Tween treatment was greater than or equal to 90 percent. Following the reaction, TNBP could be removed from the protein by gel exclusion chromatography on Sephadex G25; however, because of its large micelle size, Tween 80 could not be removed from protein by this method. Attempts to remove Tween 80 by differential precipitation of protein were only partially successful. An alternate detergent, sodium cholate, when combined with TNBP, resulted in almost as efficient virus inactivation and an 80 percent recovery of AHF. Because sodium cholate forms small micelles, it could be removed by Sephadex G25 chromatography. Electrophoretic examination of TNBP/cholate-treated AHF concentrates revealed few, if any, changes in protein mobility, except for plasma lipoprotein(s).
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PMID:Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri(n-butyl)phosphate detergent combinations. 393 1

Under most circumstances, hepatitis B virus (HBV) is noncytopathic. However, hepatocellular regeneration that accompanies each bout of hepatitis appears to be associated with increased integration of HBV DNA fragments expressing the virus encoded hepatitis B x antigen (HBxAg). Intrahepatic HBxAg staining correlates with the intensity and progression of chronic liver disease (CLD), and additional work has shown that HBxAg blocks immune mediated killing by Fas and by tumor necrosis factor alpha (TNFalpha). This is not only associated with the blockage of caspase activities by HBxAg, but also by the constitutive stimulation of hepatoprotective pathways, such as nuclear factor kappa B (NF-kappaB), phosphoinositol 3-kinase (PI3K), and beta-catenin (beta-catenin). HBxAg also appears to promote fibrogenesis, by stimulating the production of fibronectin. HBxAg also stimulates the production and activity of transforming growth factor beta1 (TGFbeta1) by several mechanisms, thereby promoting the profibrogenic and tumorigenic properties of this important cytokine. In addition, HBxAg appears to remodel the extracellular matrix (ECM) by altering the expression of several matrix metalloproteinases (MMPs), which may promote tumor metastasis. Hence, HBxAg appears to promote chronic infection by preventing immune mediated apoptosis of infected hepatocytes, by promoting the establishment and persistence of fibrosis and cirrhosis preceding the development of HCC, and by promoting the remodeling of EMC during tumor progression.
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PMID:Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease. 1920 Oct 80