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1.
Artigo em Russo | MEDLINE | ID: mdl-24000602

RESUMO

Various macroorganism factors influence spontaneous and therapy induced elimination of hepatitis C virus. Standard therapy is application of a combination of pegylated interfernos and ribavirin. However such tactics results in attainment of a resistant virological response in approximately half the cases during infection by genotype 1 virus. The future of viral hepatitis C therapy lies most probably in the sphere of application of specific antiviral preparations such as protease and/or polymerase inhibitors as an addition to standard therapy. The aim of this review was to describe mechanisms of resistance to therapy in light of reaction of innate and adaptive immune response as well as an attempt to determine factors capable of prognosing response to therapy


Assuntos
Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Interações Hospedeiro-Patógeno , Imunidade Adaptativa/genética , Antivirais/uso terapêutico , Terapia Combinada , Gerenciamento Clínico , Farmacorresistência Viral/efeitos dos fármacos , Hepatite C Crônica/terapia , Hepatite C Crônica/virologia , Humanos , Imunidade Inata/genética , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
2.
Artigo em Russo | MEDLINE | ID: mdl-24000592

RESUMO

AIM: Evaluation of CD3+ and CD3-/CD56+ proliferative response on hepatitis C virus antigens in healthy medical workers. MATERIALS AND METHODS: The study included 15 medical workers with length of service of 2 and more years without common risk factors (blood and blood products transfusion, abdominal operations, invasive procedures, use of intravenous drugs). Control group consisted of 9 healthy individuals without risk factors. Peripheral mononuclears were isolated from blood and then incubated 72 hours in the presence of mitogen/PHA, Core+NS4 1b genotype HCV, NS4 HCV2a+3a genotypes or medium. Proliferative activity was registered by the presence of cell division marker ki67 by using FACS. RESULTS: The initial immunogram of medical workers differed from the control group by a significantly lower quantity of CD3+ lymphocytes, in particular CD3+/CD8+ population. Incubation with PHAresulted in a decrease of quantity of CD3+/ ki67+, CD4+/ki67+ and CD3-/CD56+/ki67+ in the medical workers group. Cultivation with HCV antigens resulted in a significant decrease of Treg (CD3+/CD25high/FoxP3+) and activated T-lymphocytes population in the case of stimulation by Core and NS4 1b genotype antigens. Analysis of cell response on virus antigens based on proliferative activity index detected significant differences only for CD8+/ki67+. Stimulation by Core and NS4 1b genotype antigens resulted in an increase of quantity of these cells whereas in the case of NS4 2a+3a genotypes their decrease was observed. CONCLUSION: The described changes may reflect exhaustion of cell reactivity due to extra antigen load in the group of medical workers, while differentiated immunologic shifts on hepatitis C viruses of various genotypes are noted.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Pessoal de Saúde , Hepacivirus/química , Antígenos da Hepatite C/farmacologia , Exposição Ocupacional , Subpopulações de Linfócitos T/efeitos dos fármacos , Antígenos CD/imunologia , Biomarcadores/análise , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Antígenos da Hepatite C/isolamento & purificação , Humanos , Imunofenotipagem , Antígeno Ki-67/análise , Ativação Linfocitária/efeitos dos fármacos , Contagem de Linfócitos , Fito-Hemaglutininas/farmacologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia
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