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1.
Braz. j. med. biol. res ; 50(3): e5796, 2017. tab
Artigo em Inglês | LILACS | ID: biblio-839267

RESUMO

We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Nucleosídeos/uso terapêutico , Linfócitos T Reguladores , Resistência a Medicamentos , Genótipo , Guanina/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Resposta Viral Sustentada , Linfócitos T Reguladores/imunologia , Fatores de Tempo
2.
Mem. Inst. Oswaldo Cruz ; 111(4): 252-257, Apr. 2016. tab
Artigo em Inglês | LILACS | ID: lil-778998

RESUMO

There are about 350 million hepatitis B virus (HBV) carriers worldwide and chronic HBV is considered a major public health problem. The objective of the present study was to assess the effectiveness of the nucleos(t)ide analogues tenofovir (TDF) and entecavir (ETV) in the treatment of chronic HBV. A cross-sectional study was carried out from March-December 2013, including all patients with chronic HBV, over 18 years of age, undergoing therapy through the public health system in southern Brazil. Only the data relating to the first treatments performed with TDF or ETV were considered. Retreatment, co-infection, transplanted or immunosuppressed patients were excluded. Six hundred and forty patients were evaluated, of which 336 (52.5%) received TDF and 165 (25.8%) ETV. The other 139 (21.7%) used various combinations of nucleos(t)ide analogues and were excluded. The negativation of viral load was observed in 87.3% and 78.8% and the negativation of hepatitis B e antigen was achieved in 79% and 72% of those treated with ETV or TDF, respectively. Negativation of hepatitis B surface antigen was not observed. There was no occurrence of adverse effects. This is a real-life study demonstrating that long-term treatment with ETV and TDF is both safe and effective.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Estudos Transversais , DNA Viral , Guanina/uso terapêutico , Antígenos E da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Saúde Pública , Resultado do Tratamento , Carga Viral
3.
Braz. j. infect. dis ; 19(3): 291-295, May-Jun/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-751886

RESUMO

Background: Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. Objective: To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. Methods: HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing. Results: Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either ade-fovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay. Conclusion: The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus. .


Assuntos
Adulto , Feminino , Humanos , Masculino , Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Mutação , Grupo com Ancestrais do Continente Asiático , Adenina/administração & dosagem , Adenina/análogos & derivados , DNA Viral/genética , Genótipo , Guanina/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Análise em Microsséries , Organofosfonatos/administração & dosagem , Prognóstico , Análise de Sequência de DNA , Timidina/administração & dosagem , Timidina/análogos & derivados
5.
Hist. ciênc. saúde-Manguinhos ; 21(4): 1093-1112, Oct-Dec/2014.
Artigo em Português | LILACS | ID: lil-732505

RESUMO

O objetivo deste trabalho é analisar o discurso do excesso sexual produzido pelo pensamento social brasileiro das décadas de 1920 e 1930 na sua interlocução com o discurso médico da época. De inspiração foucaultiana, o texto inscreve-se no campo da história dos saberes e está subsidiado por documentos sociológicos e médicos do período de referência. No quadro da recodificação vintecentista sobre o imaginário da brasilidade, o tema do excesso sexual foi revisitado pelo pensamento sociológico local, forjando-o ora como um perturbador do projeto civilizatório nacional, ora como um traço que deveria ser positivado por ter sido a condição de possibilidade da hibridização cultural de suas matrizes identitárias.


The objective of this article is to analyze the discourse of sexual excess produced by Brazilian social thinking in the 1920s and 1930s and its dialog with the medical discourse at the time. Inspired by Foucault, it is within the field of the history of knowledge and is supported by sociology and medical documents from the period in question.Within the framework of the twentieth century re-codification of the imagery of Brazilianness, the topic of sexual excess was revisited by local thinkers in the field of sociology and seen either as disturbing the national civilizing project, or as a trait that should be seen in a positive light because it permitted the cultural hybridization of its sources of identity.


Assuntos
Animais , Bovinos , Adenina/metabolismo , Adutos de DNA/metabolismo , Compostos de Epóxi/metabolismo , Guanina/metabolismo , Mutagênicos/metabolismo , Adutos de DNA/química , Adutos de DNA/isolamento & purificação , Compostos de Epóxi/química , Compostos de Epóxi/isolamento & purificação , Guanosina/metabolismo , Mutagênicos/química , Mutagênicos/isolamento & purificação
7.
Rev. saúde pública ; 47(4): 769-780, ago. 2013. tab, graf
Artigo em Português | LILACS | ID: lil-695415

RESUMO

OBJETIVO Avaliar o custo-efetividade de diferentes tratamentos medicamentosos para hepatite B crônica entre pacientes adultos. MÉTODOS Utilizando modelo de Markov, construiu-se coorte hipotética de 40 anos para pacientes HBeAg-positivo ou HBeAg-negativo. Foram comparados os usos de adefovir, entecavir, tenofovir e lamivudina (com terapia de resgate em caso de resistência viral) para tratamento de pacientes adultos com hepatite B crônica, virgens de tratamento, com elevados níveis de alanina aminotransferase, sem evidência de cirrose e sem coinfecção por HIV. Valores para custo e efeito foram obtidos da literatura. A medida do efeito foi expressa em anos de vida ganhos (AVG). Taxa de desconto de 5% foi aplicada. Análise de sensibilidade univariada foi conduzida para avaliar incertezas do modelo. RESULTADOS O tratamento inicial com entecavir ou tenofovir apresentou melhores resultados clínicos. As menores razões custo-efetividade foram de entecavir para pacientes HBeAg-positivo (R$ 4.010,84/AVG) e lamivudina para pacientes HBeAg-negativo (R$ 6.205,08/AVG). Para pacientes HBeAg-negativo, a razão custo-efetividade incremental de entecavir (R$ 14.101,05/AVG) está abaixo do limiar recomendado pela Organização Mundial da Saúde. Análise de sensibilidade mostrou que variação nos custos dos medicamentos pode tornar tenofovir alternativa custo-efetiva tanto para pacientes HBeAg-positivo quanto para HBeAg-negativo. CONCLUSÕES Entecavir é alternativa recomendada para iniciar o tratamento de pacientes com hepatite B crônica no Brasil. Contudo, se houver redução no custo de tenofovir, esta pode se tornar alternativa mais custo-efetiva. .


OBJETIVO Evaluar el costo-efectividad de diferentes tratamientos medicamentosos para hepatitis B crónica entre pacientes adultos. MÉTODOS Utilizando el modelo de Markov, se construyó cohorte hipotética de 40 años para pacientes HBeAg-positivo o HBeAg-negativo. Se compararon los usos de adefovir, entecavir, tenofovir y lamivudina (con terapia de rescate en caso de resistencia viral) para tratamiento de pacientes adultos con hepatitis B crónica, vírgenes de tratamiento, con elevados niveles de alanina aminotransferasa, sin evidencia de cirrosis y sin coinfección por VIH. Valores para costo y efecto fueron obtenidos de la literatura y efecto en años de vida ganados (AVG). Tasa de descuento de 5% fue aplicada. Análisis de sensibilidad univariado fue conducido para evaluar incertidumbres del modelo. RESULTADOS El tratamiento inicial con entecavir o tenofovir presentó mejores resultados clínicos. Los menores cocientes costo-efectividad fueron de entecavir para pacientes HBeAg-positivo (R.010,84/AVG) y lamivudina para pacientes HBeAg-negativo (R.205,08/AVG).Para pacientes HBeAg-negativo, el cociente costo-efectividad incrementado de entecavir (R.101,05/AVG) está por debajo del límite recomendado por la Organización Mundial de la Salud. El análisis de sensibilidad mostró que la variación en los costos de los medicamentos puede tornar tenofovir una alternativa costo-efectiva tanto para pacientes HBeAg-positivo como para los HBeAg-negativo. CONCLUSIONES Entecavir es una alternativa recomendada para iniciar el tratamiento de pacientes con hepatitis B crónica en Brasil. Sin embargo, al haber reducción en el costo de tenofovir, éste puede convertirse en una alternativa más costo-efectiva. .


OBJECTIVE To evaluate the cost-effectiveness of different drug therapies for chronic hepatitis B in adult patients. METHODS Using a Markov model, a hypothetical cohort of 40 years for HBeAg-positive or HBeAg-negative patients was constructed. Adefovir, entecavir, tenofovir and lamivudine (with rescue therapy in cases of viral resistance) were compared for treating adult patients with chronic hepatitis B undergoing treatment for the first time, with high levels of alanine aminotransferase, no evidence of cirrhosis and without HIV co-infection. Values for cost and effect were obtained from the literature, and expressed in effect on life years (LY). A discount rate of 5% was applied. Univariate sensitivity analysis was conducted to assess model uncertainties. RESULTS Initial treatment with entecavir or tenofovir showed better clinical outcomes. The lowest cost-effectiveness ratio was for entecavir in HBeAg-positive patients (R$ 4,010.84/LY) and lamivudine for HBeAg-negative patients (R$ 6,205.08/LY). For HBeAg-negative patients, the incremental cost-effectiveness ratio of entecavir (R$ 14,101.05/LY) is below the threshold recommended by the World Health Organization. Sensitivity analysis showed that variation in the cost of drugs may make tenofovir a cost-effective alternative for both HBeAg-positive and HBeAg-negative patients. CONCLUSIONS Entecavir is the recommended alternative to start treating patients with chronic hepatitis B in Brazil. However, if there is a reduction in the cost of tenofovir, it can become a cost-effective alternative. .


Assuntos
Adulto , Humanos , Antivirais/economia , Hepatite B Crônica/tratamento farmacológico , Análise de Variância , Adenina/análogos & derivados , Adenina/economia , Adenina/uso terapêutico , Antivirais/classificação , Antivirais/uso terapêutico , Brasil , Análise Custo-Benefício , Progressão da Doença , Guanina/análogos & derivados , Guanina/economia , Guanina/uso terapêutico , Vírus da Hepatite B , Lamivudina/economia , Lamivudina/uso terapêutico , Cadeias de Markov , Organofosfonatos/economia , Organofosfonatos/uso terapêutico , Resultado do Tratamento
8.
Braz. j. infect. dis ; 17(4): 418-426, July-Aug. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-683128

RESUMO

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.


Assuntos
Feminino , Humanos , Masculino , Antivirais/economia , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Adenina/análogos & derivados , Adenina/economia , Adenina/uso terapêutico , Antivirais/uso terapêutico , Brasil , Análise Custo-Benefício , Quimioterapia Combinada/economia , Guanina/análogos & derivados , Guanina/economia , Guanina/uso terapêutico , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Lamivudina/economia , Lamivudina/uso terapêutico , Cadeias de Markov , Organofosfonatos/economia , Organofosfonatos/uso terapêutico , Polietilenoglicóis/economia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêutico
9.
Rev. saúde pública ; 46(6): 942-949, Dez. 2012. ilus, graf, tab
Artigo em Português | LILACS | ID: lil-667604

RESUMO

.


OBJECTIVE: To conduct a cost-effectiveness analysis of drug alternatives with rescue therapy in case of relapse due to viral resistance for the treatment of patients with chronic hepatitis B (CHB). METHODS: Hypothetical cohort of patients with CHB, HBeAg-negative, without clinical or histological evidence of cirrhosis, detectable HBV DNA, histological diagnosis of the disease, positive serum HBsAg for longer than six months, high levels of alanine aminotransferase (ALT) (twice as high as the upper limit of normality) and mean age of 40 years. A Markov model was developed for chronic hepatitis B (HBeAg- negative) with a 40-year time horizon. Costs and benefits were discounted at 5%. Annual rates of disease progression, costs due to complications and the efficacy of medicines were obtained from the literature. One-way and probabilistic sensitivity analysis evaluated uncertainties. RESULTS: Initiation of treatments with entecavir resulted in an increase of 0.35 discounted life-years gained compared to lamivudine. The incremental cost-effectiveness ratio was R$16,416.08 per life-years gained. In the sensitivity analysis, the incremental cost-effectiveness ratio was more sensitive to variation in the probability of transition from chronic hepatitis B to compensated cirrhosis, discount rate and medicine prices (± 10%). In the probabilistic sensitivity analysis, the acceptability curve showed that beginning treatment with entecavir was the most cost-effective alternative in comparison with the use of lamivudine. CONCLUSIONS: The availability of entecavir is economically attractive as part of early treatment for patients with chronic hepatitis B without HIV co-infection.


.


Assuntos
Humanos , Antivirais/economia , Farmacorresistência Viral , Hepatite B Crônica/tratamento farmacológico , Adenina/análogos & derivados , Adenina/economia , Adenina/uso terapêutico , Antivirais/uso terapêutico , Análise Custo-Benefício , Quimioterapia Combinada , Guanina/análogos & derivados , Guanina/economia , Guanina/uso terapêutico , Hepatite B Crônica/economia , Cadeias de Markov , Modelos Teóricos , Organofosfonatos/economia , Organofosfonatos/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida
10.
Rev. gastroenterol. Perú ; 32(4): 400-404, oct.-dic. 2012. ilus, tab
Artigo em Espanhol | LILACS, LIPECS | ID: lil-692409

RESUMO

Paciente varón de 45 años natural de Lima, casado con antecedentes de , múltiples parejas sexuales y operado de fimosis, que debuta con eritema nodoso y diagnosticado de hepatitis B crónica en Agosto del 2008, en controles por consultorio se realiza diagnóstico de cirrosis hepática child A y hepatocarcinoma. Inicia tratamiento para la hepatitis B con Entecavir 0,5mg y luego se realiza hepatectomía del segmento V, En Febrero 2009 en controles de imágenes se evidencia recidiva de hepatocarcinoma en el segmento VI (lesión de 14mm) con AFP de 68 ng/dl, se realiza etanolización, con evolución final favorable. Durante el seguimiento no se observa evidencia de recidiva de HCC, continua con Entecavir 0,5 mg /d y en abril 2010, luego de 72 semanas de tratamiento con adecuada adherencia al tratamiento presenta rebrote virológico (carga viral positiva de 646 UI/dl), y se decide agregar a la terapia Tenofovir. Actualmente paciente con buena evolución con última carga viral de Abril del 2012 negativa recibiendo terapia doble para VHB. Reportamos el caso por ser uno de los primeros en nuestro país de resistencia probable a Entecavir y donde se pone de manifiesto la necesidad de examenes complementarios que confirmen dicha sospecha.


A 45 year- old - married man, with several sexual partners, initiated symptoms with nodosum erythema and in August 2008, is diagnosed of chronic hepatitis due to hepatitis B virus (HBV). Later he was diagnosed of Child A cirrhosis and hepatocarcinoma. He began HBV treatment with Entecavir 0,5 mg; then he underwent a V segment hepatectomy. In February 2009 he presented a relapse with a tumor of 14 mm on VI segment with AFP values of 68 ng/dl, so he underwent an ethanolization with good evolution. During the follow up, he has not presented evidence of relapse of hepatocarcinoma and continued with Entecavir 0,5 mg/d. In April 2010, after 72 weeks of therapy with good compliance, the patient presented a virological breakthrough (viral load 646 UI/dl) and Tenofovir was added to his therapy. Nowadays the patient is receiving double therapy for HBV and his last viral load, April 2012, was negative. This could be the first case in our country of a probable resistance to Entecavir; complementary tests are needed in order to rule out this suspicion.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Farmacorresistência Viral , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Guanina/uso terapêutico , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia
11.
Braz. j. infect. dis ; 16(4): 366-372, July-Aug. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-645427

RESUMO

The results of several new clinical trials that compared the effectiveness of entecavir (ETV) treatment with that of adefovir (ADV) treatment in patients with chronic hepatitis B (CHB) were published in recent years. However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion as to whether ETV is more effective than ADV. Therefore, a new meta-analysis was needed to compare ETV with ADV for the treatment of CHB. A search of the Cochrane Central Register of Controlled Trials (CCTR), MEDLINE, the Science Citation Index, Embase, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database for relevant studies published between 1966 and 2010 was performed. Trials comparing the use of ETV and ADV for the treatment of CHB were assessed. Of the 2,358 studies screened, 13 randomized controlled clinical trials comprising 1,230 patients (ETV therapy, 621; ADV therapy, 609) were analyzed. The serum hepatitis B virus (HBV) DNA clearance rate obtained in patients treated with ETV was significantly higher than that in patients treated with ADV at the 24th and 48th weeks of treatment (24 weeks: 59.6% vs. 31.8%, relative risk [RR], 1.82, 95% CI: 1.49-2.23; 48 weeks: 78.3% vs. 50.4%, RR, 1.61, 95% CI: 1.32-1.96). The serum HBeAg clearance rate, the HBeAg seroconversion rate, and the ALT normalization rate obtained for patients treated with ETV were also higher than the corresponding values for patients treated with ADV at the 48th week of treatment. The safety profiles were similar between patients treated with ETV and those treated with ADV. The evidence reviewed in this meta-analysis suggests that patients with hepatitis B have a greater likelihood of achieving a viral response and a biomedical response when treated with ETV than when treated with ADV.


Assuntos
Humanos , Adenina/análogos & derivados , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Guanina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Mem. Inst. Oswaldo Cruz ; 107(3): 317-325, May 2012. graf, tab
Artigo em Inglês | LILACS | ID: lil-624012

RESUMO

The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).


Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Mutação/efeitos dos fármacos , Adenina/administração & dosagem , Adenina/análogos & derivados , Estudos Transversais , DNA Viral/análise , Quimioterapia Combinada/métodos , Genótipo , Guanina/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Mutação/genética , Organofosfonatos/administração & dosagem , Carga Viral
13.
J. bras. pneumol ; 37(4): 556-559, jul.-ago. 2011. ilus
Artigo em Português | LILACS | ID: lil-597207

RESUMO

Relatamos o caso de um paciente do sexo masculino de 58 anos de idade, que foi encaminhado para a consulta de oncologia por apresentar uma massa epigástrica de crescimento rápido em três meses de evolução. A investigação diagnóstica revelou tratar-se de um adenocarcinoma pulmonar metastático estádio IV. Recebeu cinco ciclos de cisplatina e gemcitabina como tratamento de primeira linha, que foi interrompido devido a efeitos adversos. Houve estabilidade da doença pulmonar e progressão cutânea. Recebeu pemetrexed como tratamento de segunda linha e radioterapia externa concomitante, com boa tolerância e regressão completa da massa epigástrica. Entretanto, o paciente faleceu três meses após o tratamento. Destacamos aqui importância da multidisciplinaridade e do seu papel na individualização do tratamento.


We report the case of a 58-year-old male patient who was referred for oncology consultation due to an epigastric mass that had been growing rapidly for three months. Diagnostic investigation revealed that the mass was a metastasis of stage IV lung adenocarcinoma. The patient received five cycles of chemotherapy with cisplatin and gemcitabine as a first-line treatment, which was interrupted due to major adverse events. Although the pulmonary disease stabilized, the cutaneous disease progressed. The patient then received pemetrexed as a second-line chemotherapy, together with concurrent external radiotherapy, which was well tolerated. There was complete remission of the epigastric mass. However, the patient died three months after the treatment. Here, we emphasize the importance of a multidisciplinary approach and of its role in individualizing the treatment.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/secundário , Neoplasias Pulmonares/patologia , Neoplasias Cutâneas/secundário , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Biópsia , Evolução Fatal , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Guanina/uso terapêutico , Estadiamento de Neoplasias , Neoplasias Cutâneas/tratamento farmacológico
14.
Rio de Janeiro; s.n; 2011. 138 p. ilus.
Tese em Português | LILACS | ID: lil-691530

RESUMO

Didaticamente, podemos dividir o espectro da radiação ultravioleta (UV) em três faixas: UVA (400 a 320 nm), UVB (320 a 290 nm) e UVC (290 a 100 nm). Apesar do UVC ou UV-curto ser eficientemente filtrado pela camada de ozônio da Terra e sua atmosfera, este é uma das faixas do espectro de UV mais usadas para explorar as consequências de danos causados ao DNA, já que a letalidade induzida por este agente está relacionada aos danos diretos no genoma celular, como as lesões dímero de pirimidina, que são letais se não reparadas. Contudo, demonstrou-se que a radiação UVC pode gerar espécies reativas de oxigênio (ERO), como o oxigênio singleto (1O2). Embora, o radical hidroxil (•OH) cause modificações oxidativas nas bases de DNA, alguns trabalhos indicam que o 1O2 também está envolvido nos danos oxidativos no DNA. Esta ERO é produzida por vários sistemas biológicos e reações fotossensibilização, quando cromóforos são expostos à luz visível ou são excitados pela luz UV, permitindo que essa energia possa ser transferida para o oxigênio sendo convertido em 1O2, que é conhecido por modificar resíduos de guanina, gerando 8-oxoG, que caso não seja reparada pode gerar uma transversão GC-TA. O objetivo deste trabalho foi o de elucidar a participação de ERO nos efeitos genotóxicos e mutagênicos gerados pela radiação UVC, assim como as enzimas envolvidas no processo de reparação destas lesões em células de Escherichia coli. Nos ensaios as culturas foram irradiadas com o UVC (254 nm; 15W General Electric G15T8 germicidal lamp, USA). Nossos resultados mostram que o uso de quelantes de ferro não alterou a letalidade induzida pelo UVC. A azida sódica, um captador de 1O2, protegeu as cepas contra os danos genotóxicos gerados pelo UVC e também diminuiu a frequência de mutações induzidas no teste com rifampicina. A reversão específica GC-TA foi induzida mais de 2,5 vezes no ensaio de mutagênese. A cepa deficiente na proteína de reparo Fpg, enzima que corrige a lesão 8-oxoG...


Didactically, we can divide the ultraviolet radiation (UV) spectrum into three bands: UVA (400 to 320 nm), UVB (320-290 nm) and UVC (290-100 nm). Despite the UVC or far-UV be efficiently filtered by Earth´s ozone layer and its atmosphere, this is one of bands of UV spectrum used to explore the consequences of DNA damages, since the UVC-induced lethality is related to direct damage in genome cells, such as pyrimidine dimers, which are lethal if not repaired. However, it was shown that UVC radiation can generate reactive oxygen species (ROS) such as singlet oxygen (1O2). Although hydroxyl radical (•OH) cause oxidative modifications in DNA bases, some works suggests that 1O2 is also involved in oxidative DNA damage. This ROS is produced by several biological systems and photosensitivity reactions when chromophores are exposed to visible light or excited by UV light, allowing that energy can be transferred to the oxygen being converted to 1O2, which is known to modify guanine residues, generating 8-oxoG, if not repaired can lead to a GC-TA transversion. The objective of this work was to elucidate the ROS involvement in the genotoxic and mutagenic effects generated by UVC radiation, as well as the enzymes involved in the repair process of these lesions in Escherichia coli cells. In the assays, cultures were irradiated with UVC (254 nm, 15 W General Electric germicidal lamp G15T8, USA). Our results show that the use of iron chelators did not affect the UVC-induced lethality. The sodium azide, a 1O2 quencher, protected strains against the genotoxic damage produced by UVC and also decreased the frequency of mutations induced in rifampicin assay. Reversal specific GC-TA was induced more than 2.5 fold in the mutagenesis assay. The deficient strain in the repair protein Fpg, an enzyme that corrects 8-oxoG lesions, had less DNA breakage than the wild strain in electrophoresis alkaline assay. The UVC-induced lethality was increased in mutants transformed with the pFPG...


Assuntos
Reparo do DNA , Dano ao DNA/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Enzimas Reparadoras do DNA , Escherichia coli/genética , Escherichia coli/metabolismo , Espécies Reativas de Oxigênio/efeitos da radiação , Guanina/análogos & derivados , Oxigênio Singlete , Dímeros de Pirimidina , Azida Sódica
15.
Rev. Soc. Bras. Med. Trop ; 43(4): 440-451, jul.-ago. 2010. ilus, tab
Artigo em Português | LILACS | ID: lil-556013

RESUMO

INTRODUÇÃO: A hepatite crônica B é uma das doenças infecciosas mais frequentes no mundo e constitui um grave problema de saúde pública MÉTODOS: Para avaliar a eficácia dos análogos de núcleosídeo/nucletídeo utilizados no seu tratamento (adefovir dipivoxil, entecavir e telbivudina) foi conduzida uma revisão sistemática de ensaios clínicos randomizados. Foram consultadas, dentre outras, as bases de dados PubMed e LILACS RESULTADOS: Foram selecionados 29 artigos entre os publicados de janeiro/1970 até dezembro/2009 CONCLUSÕES: Todos os análogos de núcleosídeo/nucletídeo apresentam eficácia superior ou similar à lamivudina. O entecavir pode ser indicado para o tratamento da hepatite B crônica como alternativa à lamivudina em pacientes HBeAg positivo e negativo virgens de tratamento, considerando seu baixo potencial de resistência viral. A adição de adefovir à lamivudina apresentou bons resultados em pacientes resistentes à lamivudina. O uso de entecavir e telbivudina nesses pacientes apresenta risco de resistência cruzada. Telbivudina é um dos mais recentes antivirais disponíveis, mas resistência antiviral já documentada representa limitação ao seu uso como opção terapêutica à lamivudina. Eventos adversos aos análogos de núcleosídeo/nucletídeo foram similares em características, gravidade e incidência quando comparados à lamivudina e placebo.


INTRODUCTION: Chronic hepatitis B is one of the most frequent infectious disease in the world and represents a serious problem of public health METHODS: A systematic review of randomized clinical trials was conducted to evaluate the efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and telbivudine) used for the treatment of chronic hepatitis B. The databases PubMed and LILACS were consulted, among others RESULTS: Twenty nine articles published between January/1970 to December/2009 were selected CONCLUSIONS: All nucleoside/nucleotide analogues demonstrate upper or similar efficacy to lamivudine. The entecavir can be appropriate for patients with chronic hepatitis B, HBeAg positive and negative treatment-naive as alternative to lamivudine, considering its low potential of viral resistance. The addition of adefovir to lamivudine presented good results in lamivudine resistant patients. The use of entecavir and telbivudine in those patients presents risk of crossed resistance. TBV is one of the most recent antivirals available, but antiviral resistance already documented represents limitation to its use as therapeutic option to LAM. Adverse events of nucleoside/nucleotide analogues were similar in characteristics, gravity and incidence when compared to the lamivudina and placebo.


Assuntos
Humanos , Adenina/análogos & derivados , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Ácidos Fosforosos , Pirimidinonas/uso terapêutico , Adenina/uso terapêutico , Guanina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
16.
Braz. j. infect. dis ; 12(5): 368-373, Oct. 2008. tab
Artigo em Inglês | LILACS | ID: lil-505348

RESUMO

Hepatitis B virus infection is an important public-health issue. Chronic patients have a higher risk of death due to complications, which increases health-care expenses in. Cost-effectiveness analysis of entecavir (ETV) versus lamivudine (LVD) for treatment of chronic hepatitis B, in e antigen (AgHBe)-positive and negative patients, based on two phase 3, controlled and randomized studies. A decision analysis model was developed, using the following endpoints: cost per patient with undetectable viral load and cost per quality life year (QALY) gained. Risks for complications (compensated or decompensated cirrhosis and hepatocellular carcinoma) were based on the cohort study REVEAL, published in 2006. The REVEAL parameters were applied to the results of the viral load levels obtained from the clinical assay data. The complication costs were based on a study of the disease cost conducted in Brazil, in 2005. The cost data were obtained predominantly from Sistema Único de Saúde [SUS - Brazilian public health system] payment tables and drug price lists. The utility data were obtained from literature and life expectancy information was based on IBGE data. The analysis perspective was that of SUS. A discount rate of 3 percent per year was used. For the horizon of time of 10 years, the ETV had an incremental cost of approximately two million Brazilian Reais (R$) compared to LVD. Reducing the number of complications, ETV treatment reduced costs by around 3 million, reducing final costs by 1 million, for AgHBe-positive patients. ETV also reduced the incremental cost per QALY gained. ETV was found to be the most cost-effective alternative for AgHBe-positive and negative patients.


Assuntos
Humanos , Antivirais/economia , Guanina/análogos & derivados , Hepatite B Crônica/virologia , Lamivudina/economia , Replicação Viral/efeitos dos fármacos , Antivirais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Guanina/economia , Guanina/uso terapêutico , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/economia , Lamivudina/uso terapêutico , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Carga Viral
17.
Genet. mol. res. (Online) ; 7(1): 133-139, Jan. 2008. ilus, tab
Artigo em Inglês | LILACS | ID: lil-553780

RESUMO

Heat stress is one of the main problems in modern aviculture, since it affects birds especially in the final phase of rearing, causing bird mortality and economic losses to the aviculturist. The quail, as most birds, has difficulties in dissipating heat. However, little is known about the mechanism that controls the responses of the organism to stressor agents. Therefore, the study of heat shock proteins (HSPs) in these birds is important. A 960-bp portion of HSP70 was amplified using oligonucleotide primers specific for chickens. The fragment was sequenced, since it was the same protein, although some modifications have been observed. It showed 98% homology with HSP70 stress protein in Gallus gallus and 99% homology with Numida meleageris.


Assuntos
Animais , Coturnix/genética , /genética , Sequência de Aminoácidos , Sequência de Bases , DNA , Guanina/metabolismo , Dados de Sequência Molecular , Peso Molecular , Técnicas de Amplificação de Ácido Nucleico , Mutação Puntual , Reação em Cadeia da Polimerase , Primers do DNA/química , /química , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico
19.
Braz. j. infect. dis ; 9(4): 330-335, Aug. 2005. tab
Artigo em Inglês | LILACS | ID: lil-415688

RESUMO

The reactivation of Herpes Simplex virus (HSV) occurs in 70 percent to 80 percent of patients submitted to autologous stem cell transplantation (ASCT); it increases the severity of chemotherapy-induced mucositis. Therefore, the use of acyclovir in ASCT patients is considered standard practice. However, the minimum dose needed to prevent reactivation is a matter of debate. We compared two doses of acyclovir in a non-randomized fashion in 59 patients submitted to ASCT: 32 patients received a dose of 125 mg/m² IV every six hours and the subsequent 27 patients received a dose of 60 mg/m² IV every six hours. Viral excretion was evaluated through weekly viral culture of oral swabs. Grade 4 mucositis was more frequent in Group 1 (p= 0.03). The reactivation rates in Groups 1 and 2 were 9 percent and 4 percent, respectively (p= 0.62, 95 percent confidence interval -7 - 18). Prophylaxis with reduced doses of intravenous acyclovir seems to be as effective as a higher dose in inhibiting HSV reactivation, with a significant reduction in cost. Prospective randomized studies are needed to confirm our conclusions.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Antivirais/administração & dosagem , Guanina/administração & dosagem , Herpes Simples/prevenção & controle , Transplante de Células-Tronco , Estomatite/prevenção & controle , Transplante Autólogo
20.
RBCF, Rev. bras. ciênc. farm. (Impr.) ; 40(3): 411-420, jul.-set. 2004. tab, graf
Artigo em Espanhol | LILACS | ID: lil-420690

RESUMO

Se determinó el coeficiente de reparto octanol/agua y la solubilidad de acetaminofén (paracetamol) en octanol, agua y los solventes mutuamente saturados a 25.0, 30.0, 35.0 y 40.0 °C. Mediante el análisis termodinámico de Gibbs y van't Hoff se observa que el proceso de transferencia del fármaco desde el agua hasta el octanol es espontáneo y de conducción principalmente entálpica. Se encuentra que la saturación mutua de las fases juega un papel importante en el reparto y la solubilidad de este fármaco, lo cual se ha demonstrado para otras sustancias semipolares tales como algunos derivados de la guanina y algunas sulfonamidas


Assuntos
Acetaminofen , Termodinâmica , Guanina , Preparações Farmacêuticas
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