Browsing by Subject "Hepatitis"
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Item Calpain and lipopolysaccharide mediated hepatitis(2009-06-02) Rose, Robert EdwardThis study tested the role of the calcium dependent cytosolic protein calpain in neutrophilic hepatitis. We hypothesized that inhibition of calpain would protect against LPS-induced neutrophilic liver damage. To test our hypothesis, a reliable LPS-mediated hepatitis model to investigate the mechanisms of hepatic neutrophil infiltration following LPS administration was developed by repeat intravenous injection of LPS at a dose of 10 mg/kg to rats. Blood was collected for hematologic and biochemical analysis and multiple organs including liver were collected for evaluation of histopathologic changes. Flow cytometry was employed to investigate L-selectin (CD 62L) and MAC-1 (CD11b/18) expression on neutrophils both in vivo and in vitro. Significant hematologic changes included neutrophilia, elevation in neutrophil to lymphocyte ratio with toxic changes and left shift. Biochemical changes were observed in several liver (AST, GGT) and kidney (BUN) parameters generally at the earliest time points. Histopathology revealed a time-dependent neutrophil and mononuclear infiltration around the periportal areas in the single dose study and mid-zonal inflammation with multifocal coagulative necrosis in the repeated dose study. CD 11b was up-regulated both in vitro and in vivo. After development of a suitable model, the first goal was to investigate the role of the intracellular enzyme calpain in the development of neutrophilic hepatitis and midzonal necrosis. A second goal was to compare the observed protective effects of calpain inhibition with a relatively selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine and an inhibitor of coagulation, heparin. When compared to rats administered LPS alone, administration of calpain 1 inhibitor prior to LPS significantly reduced hepatic iNOS expression, hepatic neutrophil infiltration and attenuated midzonal hepatic necrosis. Administration of heparin and aminoguanidine prior to LPS also decreased liver iNOS expression, hepatic neutrophil infiltration and liver pathology comparable to calpain inhibition. Blood neutrophil activation, as measured by the neutrophil adhesion molecule CD11b integrin, was upregulated in all the LPS treated groups regardless of inhibitor administration. We conclude that amelioration of liver pathology via calpain inhibition is likely dependent on the down-regulation of iNOS expression in the rat model of LPS mediated hepatitis.Item Intraindividual construct validity of anxiety, depression, fatigue, and irritability in chronic hepatitis C: A daily process study(2005-12) Mooney, Scott R.; Mumma, Gregory; Cohen, Lee M.; Borrego, Joaquin P.; Epkins, Catherine C.Anxiety, depression, fatigue, and irritability are common symptoms in patients who are chronically infected with the hepatitis C virus (HCV). Review of the recent empirical literature suggests that these symptoms are highly inter-correlated in HCV patients, but are not related to level of liver enzymes or amount of liver scaring. Given evidence that psychological distress may be related to poorer antiviral treatment outcome in HCV patients because of poor treatment compliance and dose reduction or cessation, closer examination of the functional relationships between these symptoms in HCV patients is needed in order to improve the potential benefits from HCV treatment, and to assist in psychological and pharmacological treatment planning for anxiety, depression, fatigue and irritability. Using a multivariate replicated single-subject repeated measures design, this study examined the intraindividual, over-time construct validity of anxiety, depression, fatigue, and irritability in two adult patients who were chronically infected with HCV and who were experiencing clinically significant depression and/or anxiety. Daily ratings completed over 87 and 90 days were analyzed with confirmatory dynamic factor analysis (CDFA), confirmatory P-technique factor analysis (CPTFA), and dynamic time series regression (DTSR). For both cases, CDFA and CPTFA analyses indicated the intraindividual, over time daily- and phase-state trajectory (over time trend) dimensional structures of anxiety, depression, fatigue, and irritability were empirically distinct. However, DTSR analyses provided mixed support for the predicted relationships between certain types of stressful events and cognitions within the four types of psychological distress. Findings from the present study have implications for the clinical assessment and treatment of these symptoms and compliance with antiviral medical treatment in HCV patients.Item Intraindividual construct validity of anxiety, depression, fatigue, and irritability in chronic hepatitis C: a daily process study(Texas Tech University, 2005-12) Mooney, Scott R.; Mumma, Gregory; Cohen, Lee M.; Borrego, Joaquin P.; Epkins, Catherine C.Anxiety, depression, fatigue, and irritability are common symptoms in patients who are chronically infected with the hepatitis C virus (HCV). Review of the recent empirical literature suggests that these symptoms are highly inter-correlated in HCV patients, but are not related to level of liver enzymes or amount of liver scaring. Given evidence that psychological distress may be related to poorer antiviral treatment outcome in HCV patients because of poor treatment compliance and dose reduction or cessation, closer examination of the functional relationships between these symptoms in HCV patients is needed in order to improve the potential benefits from HCV treatment, and to assist in psychological and pharmacological treatment planning for anxiety, depression, fatigue and irritability. Using a multivariate replicated single-subject repeated measures design, this study examined the intraindividual, over-time construct validity of anxiety, depression, fatigue, and irritability in two adult patients who were chronically infected with HCV and who were experiencing clinically significant depression and/or anxiety. Daily ratings completed over 87 and 90 days were analyzed with confirmatory dynamic factor analysis (CDFA), confirmatory P-technique factor analysis (CPTFA), and dynamic time series regression (DTSR). For both cases, CDFA and CPTFA analyses indicated the intraindividual, over time daily- and phase-state trajectory (over time trend) dimensional structures of anxiety, depression, fatigue, and irritability were empirically distinct. However, DTSR analyses provided mixed support for the predicted relationships between certain types of stressful events and cognitions within the four types of psychological distress. Findings from the present study have implications for the clinical assessment and treatment of these symptoms and compliance with antiviral medical treatment in HCV patients.