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Resultados del tratamiento con peginterferón alfa-2a y ribavirina en pacientes con hepatitis crónica C
Pizarro,Carolina; Venegas,Mauricio; Hola,Karen; Smok,Gladys; Brahm,Javier;
Revista médica de Chile , 2011, DOI: 10.4067/S0034-98872011000600002
Abstract: background: the current treatment recommendation for chronic hepatitis c virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. the aim of the therapy is to obtain a sustained virological response. aim: to report our experience in the treatment of chronic hepatitis c. material and methods: analysis of 52 patients treated between september 2000 and june 2009. patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg /day. results: viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. age was the only variable that infl uenced the response to treatment. conclusions: approximately half of the patients with chronic hepatitis c, achieve a sustained viral response with peginterferon and ribavirin.
Resultados del tratamiento con peginterferón alfa-2a y ribavirina en pacientes con hepatitis crónica C Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C
Carolina Pizarro,Mauricio Venegas,Karen Hola,Gladys Smok
Revista médica de Chile , 2011,
Abstract: Background: The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. Aim: To report our experience in the treatment of chronic hepatitis C. Material and Methods: Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg /day. Results: Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. Twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that infl uenced the response to treatment. Conclusions: Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.
Use of the viral 2A peptide for bicistronic expression in transgenic mice
Georgios Trichas, Jo Begbie, Shankar Srinivas
BMC Biology , 2008, DOI: 10.1186/1741-7007-6-40
Abstract: To test 2A function in transgenic mice and uncover any possible toxicity of widespread expression of the 2A peptide, we made a bicistronic reporter construct containing the coding sequence for a membrane localised red fluorescent protein (Myr-TdTomato) and a nuclear localised green fluorescent protein (H2B-GFP), separated by a 2A sequence. When this reporter is transfected into HeLa cells, the two fluorescent proteins correctly localise to mutually exclusive cellular compartments, demonstrating that the bicistronic construct is a reliable readout of 2A function. The two fluorescent proteins also correctly localise when the reporter is electroporated into chick neural tube cells. We made two independent transgenic mouse lines that express the bicistronic reporter ubiquitously. For both lines, transgenic mice are born in Mendelian frequencies and are found to be healthy and fertile. Myr-TdTomato and H2B-GFP segregate to mutually exclusive cellular compartments in all tissues examined from a broad range of developmental stages, ranging from embryo to adult. One transgenic line shows X-linked inheritance of the transgene and mosaic expression in females but uniform expression in males, indicating that the transgene has integrated into the X chromosome in this line.The 2A peptide efficiently mediates co-translational cleavage in transgenic mice in which it has been inherited through the germ-line. Mice expressing it ubiquitously throughout development and into adulthood appear normal. It is therefore a viable tool for use in genetically engineered mice and represents a superior alternative to the widely used internal ribosomal entry site.Transgenic animals play a central part in biomedical research and biotechnology. The ability to genetically modify mice, either through random genomic integration by pronuclear injection or through targeted modification by homologous recombination in embryonic stem cells, has transformed the field of mouse molecular genetics, making it n
Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept Talidomida, peginterferón alfa-2b y ribavirina en el tratamiento de pacientes no respondedores con hepatitis crónica C genotipo 1: estudio piloto  [cached]
Benjamín Pardo-Yules,Rocío Gallego-Durán,Mohammed Eslam,Carlos García-Collado
Revista Espa?ola de Enfermedades Digestivas , 2011,
Abstract: Background: fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients. Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV). Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia a adiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en el ensayo consiguió respuesta viral completa en la semana 12 ni respuesta viral sostenida. La dinámica viral en las 12 primeras semanas de tratamiento no difirió de la dinámica viral durante el primer curso de tratamiento. La triple terapia fue bien tolerada y solo un paciente desarrolló neuropatía bilateral autolimitada. Conclusiones: a adir talidomida al tratamiento estándar fue bien tolerado pero no incrementó la tasa de respuesta viral sostenida en pacientes con hepatitis C genotipo 1 no respondedores previos.
Hepatite D
Fonseca José Carlos Ferraz da
Revista da Sociedade Brasileira de Medicina Tropical , 2002,
Abstract: O vírus da hepatite D (VHD), também chamado de vírus delta, é um pequeno vírus contendo RNA circular. O VHD causa infec o, quando há coinfec o com o vírus da hepatite B (VHB) em indivíduos normais ou superinfec o em portadores cr nicos do VHB. Três genótipos já foram clonados e seqüenciados. A infec o apresenta distribui o mundial, sendo a regi o ocidental da Amaz nia brasileira considerada área de alta endemicidade. Estima-se que 18 milh es de pessoas encontram-se infectadas pelo vírus entre os 350 milh es de portadores cr nicos do VHB no mundo. As vias de transmiss o do VHD e os fatores de risco mostram-se similares aos da infec o pelo VHB. O diagnóstico se faz pela identifica o imuno-histológica do HDAg no fígado e pelo encontro das fra es IgM e IgG anti-HD no soro por radioimunoensaio ou ELISA. O curso clínico da infec o pelo VHD mostra-se variável. Os pacientes podem apresentar formas fulminantes de hepatite. As formas cr nicas associam-se a achados histopatológicos graves no fígado, com curso rápido e progressivo, evoluindo para cirrose, insuficiência hepática e morte. O interferon alfa constitui a única op o terapêutica com algum efeito benéfico no tratamento da hepatite. O transplante hepático encontra indica o nos casos terminais de cirrose. A profilaxia indireta da infec o pelo VHD tornou-se possível com o advento da vacina contra o vírus da hepatite B.
A importancia do perfil clínico-laboratorial no diagnóstico diferencial entre malária e hepatite aguda viral  [cached]
Amaral Cacyane Naiff do,Albuquerque Yael Duarte de,Pinto Ana Yecê das Neves,Souza José Maria de
Jornal de Pediatria , 2003,
Abstract: OBJETIVOS: Destacar o perfil clínico-laboratorial de malária e hepatite aguda viral em dois grupos de crian as, ressaltando semelhan as e diferen as entre os dois quadros; subsidiar o aumento da sensibilidade clínica de presun o diagnóstica precoce de malária na infancia. MéTODOS: Foram estudados dois grupos de 30 crian as, de dois a dez anos de idade, portadoras de primo infec o malárica ou hepatite viral aguda, confirmados pela pesquisa de plasmódio e pesquisa de marcadores virais de hepatite A e B. As crian as foram submetidas às seguintes avalia es no primeiro dia de atendimento: hemograma, contagem de plaquetas, dosagem de enzimas hepáticas, uréia, creatinina e bilirrubinas. Os achados clínicos e laboratoriais foram descritos e comparados entre os dois grupos. Propor es de indivíduos com exames físicos alterados foram comparadas nos dois grupos, pelo teste exato de Fisher. RESULTADOS: A apresenta o clínica inicial da doen a foi semelhante em todos os pacientes: febre, cefaléia, sintomas digestivos e colúria. Metade dos portadores de malária n o apresentou a tríade clássica, apesar de todos terem apresentado febre moderada ou alta, ao contrário dos portadores de hepatite. Na avalia o laboratorial, os portadores de malária apresentaram mais anemia e plaquetopenia quando comparados aos portadores de hepatite. Foram marcantes, nos portadores de hepatite, as eleva es de bilirrubinas e enzimas hepáticas. CONCLUS ES: A propedêutica detalhada e a avalia o criteriosa dos exames laboratoriais inespecíficos constituem pe as fundamentais para a diferencia o clínica entre os dois diagnósticos, refor ando a identifica o precoce do parasita e, conseqüentemente, o tratamento rápido de malária em crian as.
Expression of Multiple Transgenes from a Single Construct Using Viral 2A Peptides in Drosophila  [PDF]
Richard W. Daniels, Adam J. Rossano, Gregory T. Macleod, Barry Ganetzky
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100637
Abstract: Expression of multiple reporter or effector transgenes in the same cell from a single construct is increasingly necessary in various experimental paradigms. The discovery of short, virus-derived peptide sequences that mediate a ribosome-skipping event enables generation of multiple separate peptide products from one mRNA. Here we describe methods and vectors to facilitate easy production of polycistronic-like sequences utilizing these 2A peptides tailored for expression in Drosophila both in vitro and in vivo. We tested the separation efficiency of different viral 2A peptides in cultured Drosophila cells and in vivo and found that the 2A peptides from porcine teschovirus-1 (P2A) and Thosea asigna virus (T2A) worked best. To demonstrate the utility of this approach, we used the P2A peptide to co-express the red fluorescent protein tdTomato and the genetically-encoded calcium indicator GCaMP5G in larval motorneurons. This technique enabled ratiometric calcium imaging with motion correction allowing us to record synaptic activity at the neuromuscular junction in an intact larval preparation through the cuticle. The tools presented here should greatly facilitate the generation of 2A peptide-mediated expression of multiple transgenes in Drosophila.
The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil  [cached]
Artico Simara,Amaral Karine Medeiros,Gon?alves Candice Beatriz Treter,Picon Paulo Dornelles
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-377
Abstract: Background More than 50% of patients infected with chronic hepatitis C virus (HCV) do not respond to treatment with conventional interferon (IFN) combined with ribavirin (RBV). The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b) concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR). Methods From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg) per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR). Virological Response (VR) within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. Results The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031). As predictive factors that contribute to improve SVR, were identified the age (p = 0.005), to be relapsers to previous treatment (p = 0.023) and present liver biopsy examination Metavir F0-F2 (p = 0.004). In assessing the safety profile, 51 patients (23.6%) discontinued treatment prematurely. Conclusions This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.
Dupla hepatite aguda por vírus da hepatite C  [cached]
A. Cruz,S. C. Lima,J. Cotter
Jornal Português de Gastrenterologia , 2006,
Abstract: Apresenta-se o caso clínico de um doente toxicómano, com diagnóstico de hepatite aguda por vírus da hepatite C (genótipo 3a). Após iniciar tratamento com interfer o alfa 2b e se assistir a uma boa resposta terapêutica, às 12 semanas de tratamento verificou-se um súbito agravamento, cuja investiga o mostrou tratar-se de nova hepatite aguda por vírus C (genótipo 1a). O doente tinha mantido consumo de drogas intravenosas. A continua o da terapêutica anteriormente iniciada levou à recupera o clínica e analítica. Aos 6 meses de tratamento, teve aquela de ser interrompida devido a depress o grave. Apesar disto, na avalia o trinta e seis meses após suspens o da terapêutica, o doente mantinha-se assintomático, com aminotransferases normais e determina o negativa do RNA do vírus da hepatite C. Os autores destacam a raridade do caso, nomeadamente a dupla infec o aguda sequencial por diferentes genótipos do vírus da hepatite C e o facto da segunda infec o ocorrer em pleno período de tratamento com interfer o, salientando-se mais uma vez a reconhecida importancia da abstinência de consumo de drogas. The authors report a case of an intravenous drug user diagnosed with acute hepatitis C virus (genotype 3a). After initial improvement when treatment was begun, sudden decompensation occurred, compatible with the onset of a new acute hepatitis C virus (genotype 1a). The patient had continued using intravenous drugs. Clinical recovery and normalisation of laboratory values were achieved with continuation of the initial therapy. Six months later, treatment had to be discontinued because of the patient’s severe depression. Nevertheless, thirty-six months after treatment was stopped, serum HCV RNA levels were undetectable, ALT levels were normal and the patient was symptom free. This case shows a rare clinical course, namely double acute sequential infection by different genotypes of hepatitis C virus with the second infection occurring during treatment with interferon. This once again highlights the importance of drug abstinence.
Results from TOTEM and ALFA  [cached]
Eggert Karsten
EPJ Web of Conferences , 2012, DOI: 10.1051/epjconf/20122802002
Abstract: Results from TOTEM and ALFA
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