RESUMO
The natural history of HIV infection has been dramatically changed by the highly active antiretroviral therapies, reducing complications, morbidity and mortality of the disease. Approximately 25% of persons infected with HIV are co-infected with hepatitis C, and some high risk populations have a prevalence of HCV of more than 75%. Liver disease has become one of the principal causes of morbidity and mortality in this population. Co-infection increases viremia of hepatitis C, with increase in fibrosis progression, cirrhosis and death related to hepatitis C. The permanent state of chronic immune activation related to the persistent hepatitis C virus favors transcription of HIV in infected cells and causes a more rapid destruction of T4 and absolute lymphocytes. In addition, the immunologic response after the start of highly active antiretroviral therapy for HIV is less than in mono-infected patients. The role of liver biopsy in the management of co-infected patients is controversial. Many of these patients, even with normal transaminases, show fibrosis in liver biopsy. Predictive factors for advanced fibrosis include male sex, alcohol consumption in excess of 50 grams per day, age over 35, and HIV infection of more than 15 years with CD4 lymphocytes less than 400/ mm3. The treatment of hepatitis C is limited and sustained viral response is less than 30% for genotypes 1 and 4. This response is even less in the more advanced stages of HIV and hepatitis C. The determination of when to start treatment and the increased toxicity when combining pegylated interferon plus ribavirin and antiretroviral medications makes the management of these patients more difficult. The development of more potent, safe and tolerated medications is required. Management strategies for patients unresponsive to conventional therapy are geared towards improving liver histology and delaying progression to cirrhosis, hepatocellular cancer and liver transplantation.
Assuntos
Humanos , Hepatite C/complicações , Hepatite C/terapia , Infecções por HIV/complicações , Infecções por HIV/terapia , Biópsia , Hepatite C/patologiaRESUMO
OBJECTIVE: To determine whether cell cycle changes can be detected in myosin II-deficient cells using flow cytometry techniques. BACKGROUND: Although the primary role of myosin II (Myo1p) in the yeast Saccharomyces cerevisiae is in cytokinesis we have reported that this conventional myosin also appears to influence the regulation of cell wall metabolism as indicated by increases in the expression of chitin metabolizing enzymes in a null mutant of the MYO1 gene. The expression of these enzymes is known to be regulated in the cell cycle suggesting that cell cycle changes may alter their expression. METHODS: Flow cytometry was employed to assess the nuclear DNA content of logarithmic yeast cell cultures as a means of determining changes in the cell cycle of Myo1p-deficient cells. RESULTS: Significant changes were observed in the Myo1p-deficient strain suggesting that these cells are arrested in G2/M-phase of the cell cycle. CONCLUSIONS: Based on the results of this preliminary study, we propose a model in which the increased activity of chitin metabolizing enzymes may be explained by a mitotic arrest in these cells.
Assuntos
Cadeias Pesadas de Miosina/metabolismo , Leveduras/citologia , Leveduras/metabolismo , Técnicas de Cultura de Células , Ciclo Celular , Divisão Celular , Parede Celular/metabolismo , Quitina/metabolismo , Quitina Sintase/genética , Quitina Sintase/metabolismo , Citometria de Fluxo , Expressão Gênica , Haploidia , Mitose , Cadeias Pesadas de Miosina/deficiência , Cadeias Pesadas de Miosina/genética , RNA Mensageiro/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Leveduras/genéticaRESUMO
Serum from patients which tested positive for hepatitis C virus (HCV) by Enzyme Linked Immunosorbent Assay (ELISA) were analyzed for the presence of HCV RNA by nested Polymerase Chain Reaction (PCR) and for anti-HCV antibodies by Recombinant Immunoblot Assay (RIBA II). Total RNA was extracted from whole blood by a new procedure and subjected to reverse transcription of HCV RNA employing primers to the conserved 5' non-coding region of the HCV genome. PCR performed on these samples uncovered several false positive ELISAs. Reciprocal confirmation between PCR and RIBA II results was observed. These results substantiate this variation of the HCV PCR assay as a reliable alternative for routine confirmation of HCV serological tests.