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1.
Int. j. morphol ; 39(2)abr. 2021. 659^c666
Artigo em Inglês | LILACS | ID: biblio-1385365

RESUMO

SUMMARY: The aim of this study was to determine the relationship of autophagy-enhancing rapamycin (RAPA) and autophagy- inhibitor 3-methyladenine (3-MA) with Nitric oxide synthases (NOS) in Cisplatin (CIS)-induced neurotoxicity in rats. Rats were divided into 4 groups (n=10): Control was applied saline, CIS (a single dose of 8mg/kg intraperitoneal (i.p.) on 7th day of experiment), RAPA+CIS (2 mg/kg/i.p. RAPA per day and 8 mg/kg/i.p. CIS on 7th day), 3-MA+CIS (15 mg/kg/i.p. 3-MA per day and 8 mg/kg/i.p. CIS on 7th day). Rats were sacrificed under anesthesia. Brain tissues were evaluated histopathologically. eNOS, Inos, nNOS and MAP 2 immunostaining were performed to determine the expression levels of these proteins among groups. Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) and Interleukin IL-6 levels in brain tissue and serum nitric oxide (NO) level were measured by ELISA assay. In histopathological evaluation, neurodegeneration was seen in the CIS group. There was an increase in eNOS, iNOS and nNOS immunostaining in CIS group. While MAP2 immunostaining of the CIS group decreased. There was a decrease in SOD and CAT levels of brain tissue in CIS group. However, there was an increase in MDA, IL-6 and NO levels of brain tissue in CIS group. We found that antioxidant capacity increase while, inflammation and nitric oxide levels decreased in the RAPA-treated group. 3-MA does not have a significant effect. We suggest that CIS-induced neurotoxicity is more effective than Rapa 3-MA and may also be linked to NOS enzymes.


RESUMEN: El objetivo de este estudio fue determinar la relación de la rapamicina potenciadora de la autofagia (RAPA) y el inhibidor de la autofagia 3-metiladenina (3-MA) con óxido nítrico sintasas (NOS) en la neurotoxicidad inducida por cisplatino (CIS) en ratas. Las ratas se dividieron en 4 grupos (n = 10): grupo control se aplicó solución salina, CIS (una dosis única de 8 mg / kg intraperitoneal (ip) el día 7 del experimento), RAPA + CIS (2 mg / kg / ipRAPA por día y 8 mg / kg / ip CIS el día 7), 3-MA + CIS (15 mg / kg / ip 3-MA por día y 8 mg / kg / ip CIS el día 7). Las ratas se sacrificaron bajo anestesia y los tejidos cerebrales fueron analizados histopatológicamente. Se realizaron inmunotinciones con eNOS, Inos, nNOS y MAP 2 para determinar los niveles de expre- sión de estas proteínas entre los grupos. Se midieron los niveles de superóxido dismutasa (SOD), catalasa (CAT), malondialdehído (MDA) e interleucina IL-6 en el tejido cerebral y el nivel de óxido nítrico (NO) en suero mediante ensayo ELISA. En la evaluación histopatológica, se observó neurodegeneración en el grupo CIS. Hubo un aumento en la inmunotinción de eNOS, iNOS y nNOS en el grupo CIS. Mientras que la inmunotinción de MAP2 del grupo CIS disminuyó. Hubo una disminución en los niveles de SOD y CAT del tejido cerebral en el grupo CIS, sin embargo, hubo un aumento en los niveles de MDA, IL-6 y NO en el tejido cerebral en el grupo CIS. Observamos que la capacidad antioxidante aumentó, mientras que la inflamación y los niveles de óxido nítrico disminuyeron en el grupo tratado con RAPA. 3-MA no tiene un efecto significativo. Sugerimos que la neurotoxicidad inducida por CIS es más eficaz que Rapa 3-MA y también puede estar relacio- nada con las enzimas NOS.


Assuntos
Animais , Masculino , Ratos , Adenina/análogos & derivados , Cisplatino/toxicidade , Óxido Nítrico Sintase/efeitos dos fármacos , Sirolimo/farmacologia , Síndromes Neurotóxicas , Superóxido Dismutase , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Adenina/farmacologia , Catalase , Interleucina-6 , Ratos Wistar , Malondialdeído , Antineoplásicos/toxicidade
2.
Braz. j. med. biol. res ; 54(8): e10850, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1249328

RESUMO

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2′-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.


Assuntos
Humanos , Adenosina Desaminase , Dipeptidil Peptidase 4 , Leucócitos Mononucleares , Adenina , Linfócitos
3.
Int. j. morphol ; 38(3): 530-535, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098283

RESUMO

Dysregulated autophagy, whether excessive or downregulated, has been thought to be associated with neurodegenerative disorders including Parkinson's disease. Accordingly, the present study was carried out to investigate whether 3-methyladenine, an autophagy inhibitor, can modulate the effects of rotenone on dopaminergic neurons in primary mesencephalic cell culture. Cultures were prepared from embryonic mouse mesencephala at gestation day 14. Four groups of cultures were treated on the 10th DIV for 48 h as follows: the first was kept as an untreated control, the second was treated with 3-methyladenine alone (1, 10, 100, 200 mM), the third was treated with 20 nM rotenone and the fourth was co-treated with 20 nM rotenone and 3-methyladenine (1, 10, 100, 200 mM). On the 12th DIV, cultured cells were stained immunohistochemically against tyrosine hydroxylase and culture media were used to measure the levels of lactate dehydrogenase. 3methyladenine had no effects on both the survival of dopaminergic neurons and the release of lactate dehydrogenase. Rotenone significantly decreased the number of dopaminergic neurons and increased the levels of lactate dehydrogenase in the culture media. When cultures concomitantly treated with 3-methyladenine and rotenone, 3-methyladenine had no effect against rotenone-induced dopaminergic cell damage and lactate dehydrogenase release into the culture medium. In conclusion, the autophagy inhibitor 3-methyladenine could not modulate rotenone-induced dopaminergic cell damage in primary mesencephalic cell culture.


Se estima que la autofagia desregulada, ya sea excesiva o con baja regulación, está asociada con trastornos neurodegenerativos, incluyendo la enfermedad de Parkinson. En consecuencia, el se realizó este estudio para investigar si la 3metiladenina, un inhibidor de la autofagia,puede modular los efectos de la rotenona en las neuronas dopaminérgicas en el cultivo primario de células mesencefálicas. Los cultivos se prepararon a partir de mesencéfalo de ratón embrionario el día 14 de gestación. Cuatro grupos de cultivos se trataron en el 10º DIV durante 48 h de la siguiente manera: el primer grupo se mantuvo como un control no tratado, el segundo se trató con 3-metiladenina sola (1, 10, 100, 200 mM), el tercer grupo se trató con rotenona 20 nM y el cuarto se trató conjuntamente con rotenona 20 nM y 3-metiladenina (1, 10, 100, 200 mM). En el 12º DIV; las células cultivadas fueron tratadas mediante tinción inmunohistoquímica en tirosina hidroxilasa y se usaron medios de cultivo para medir los niveles de lactato deshidrogenasa. La 3-metiladenina no tuvo efectos tanto en la supervivencia de las neuronas dopaminérgicas como en la liberación de lactato deshidrogenasa. La rotenona disminuyó significativamente el número de neuronas dopaminérgicas y se observó un aumento de los niveles de lactato deshidrogenasa en los medios de cultivo. Cuando los cultivos tratados concomitantemente con 3-metiladenina y rotenona, la 3metiladenina no tuvo efecto contra el daño celular dopaminérgico inducido por la rotenona y la liberación de lactato deshidrogenasa en el medio de cultivo. En conclusión, el inhibidor de la autofagia 3-metiladenina no moduló el daño celular dopaminérgico inducido por la rotenona en el cultivo celular mesencefálico primario.


Assuntos
Animais , Camundongos , Doença de Parkinson , Rotenona/toxicidade , Adenina/análogos & derivados , Autofagia , Mesencéfalo , Adenina/farmacologia , Células Cultivadas , Morte Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , L-Lactato Desidrogenase/análise
4.
J. coloproctol. (Rio J., Impr.) ; 40(2): 135-142, Apr.-Jun. 2020. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1134976

RESUMO

ABSTRACT Colorectal cancer is one of the most important malignancies in the classification of gastrointestinal cancers. One of the predisposing factors at molecular level for this cancer is via WNT signaling which is associated with the vast numbers of different genes. Thus, in this study, we aimed to investigate whether Adenomatous Polyposis Coli gene (APC) mutation of rs41115in two locations such as 132.002 and 131.989 acts as a trigger or cause of colorectal cancer. Relatively, 30 blood samples of colorectal cancer patients and 30 normal blood samples as control group after colonoscopy and also confirmation of pathology report at Rohani Hospital in Babol (Iran) were investigated. The primers were designed in order to be included the rs41115 to identify the particular polymorphisms of gene. The polymerase chain reaction (PCR direct sequencing method) was used. Conclusively, deletion of adenine in two specific locations such as 131.989 and 132.002 has been identified, but there was no relationship between rs41115 polymorphisms located in adenomatous polyposis coli gene and colorectal cancer.


RESUMO O câncer colorretal é uma das neoplasias malignas mais importantes na classificação dos cânceres gastrointestinais. Um dos fatores predisponentes no âmbito molecular para esse câncer é através da via de sinalização WNT, que está associada a um grande número de genes diferentes. Portanto, neste estudo, objetivamos investigar se a mutação rs41115 do gene da polipose adenomatosa do cólon (Adenomatous Polyposis Coli - APC) em dois locais como 132.002 e 131.989 atua como gatilho ou como causa do câncer colorretal. Relativamente, 30 amostras de sangue de pacientes com câncer colorretal e 30 amostras de sangue normal (grupo controle) foram analisadas após a colonoscopia, bem como a confirmação do laudo da patologia no Rohani Hospital em Babol (Irã). Os primers foram projetados de modo a incluir o rs41115 para identificar os polimorfismos particulares do gene. A reação em cadeia da polimerase (método de sequenciamento direto por PCR) foi utilizada. Conclusivamente, a deleção de adenina em dois locais específicos, como 131.989 e 132.002, foi identificada, mas não houve relação entre o polimorfismo rs41115 localizado no gene da polipose adenomatosa do cólon e o câncer colorretal.


Assuntos
Humanos , Masculino , Feminino , Polimorfismo Genético , Neoplasias Colorretais/patologia , Genes APC , Adenina , Transdução de Sinais/genética , Reação em Cadeia da Polimerase , Colonoscopia , Polipose Adenomatosa do Colo/patologia
5.
J. bras. nefrol ; 42(1): 8-17, Jan.-Mar. 2020. tab, graf
Artigo em Inglês, Português | LILACS | ID: biblio-1098345

RESUMO

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.


RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.


Assuntos
Animais , Masculino , Ratos , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Uremia/complicações , Intensificação de Imagem Radiográfica/métodos , Densidade Óssea , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Uremia/induzido quimicamente , Uremia/sangue , Adenina/efeitos adversos , Biomarcadores/sangue , Remodelação Óssea , Ratos Wistar , Modelos Animais de Doenças , Fosfatase Alcalina/sangue , Insuficiência Renal Crônica/sangue
6.
Int. braz. j. urol ; 46(1): 70-80, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056356

RESUMO

ABSTRACT Objective: To analyze the compositions of upper urinary tract stones and investigate their distributions in different gender and age groups. Materials and Methods: Patients diagnosed with upper urinary tract stone disease between December 2014 and March 2018 were retrospectively reviewed. Patient's age, gender, BMI, comorbidities, stone event characteristics, and compositions were collected, and proportions of stone components in different gender and age groups were analyzed. Results: A total of 1532 stone analyses were performed (992 from males and 540 from females). The mean age was younger in males (p <0.001). Males included more cases with larger BMI, hyperuricemia, and obesity, while females had more urinary tract infections. Multiple components were present in 61.8% of stones. Calcium oxalate (CaOx) (67.0%) was the most common component, followed by uric acid (UA) (11.8%), infection stone (11.4%), calcium phosphate (CaP) (8.0%), cystine (1.1%), brushite (0.4%), and 2, 8-dihydroxyadenine (0.2%). Men contributed with more CaOx stones than women at age 30-49 years (all p <0.01) and more UA stones at 30-59 years (all p <0.05). Women contributed with more infection stones than men in age groups 30-49 and 60-69 years (all p <0.05), and more CaP stones at 30-49 years. The prevalence peak was 50-59 years in men and 60-69 years in women. Both genders had the lowest prevalence in adolescence. Prevalence of UA stones increased while that of infection stones decreased with aging in both genders. Conclusions: Age and sex had a strong association with distribution of stone compositions in this Chinese cohort.


Assuntos
Humanos , Masculino , Feminino , Adulto , Cálculos Urinários/epidemiologia , Cálculos Urinários/química , Fatores de Risco , Ácido Úrico/análise , Oxalato de Cálcio/análise , Fosfatos de Cálcio/análise , Adenina/análise , Adenina/análogos & derivados , Cálculos Urinários/etiologia , Modelos Logísticos , China/epidemiologia , Fatores Sexuais , Prevalência , Estudos Retrospectivos , Fatores Etários , Distribuição por Sexo , Distribuição por Idade , Pessoa de Meia-Idade
7.
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 , Povo 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
8.
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
10.
Braz. j. med. biol. res ; 47(4): 287-298, 8/4/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-705764

RESUMO

The compounds 6-dimethylaminopurine and cycloheximide promote the successful production of cloned mammals and have been used in the development of embryos produced by somatic cell nuclear transfer. This study investigated the effects of 6-dimethylaminopurine and cycloheximide in vitro, using the thiazolyl blue tetrazolium bromide colorimetric assay to assess cytotoxicity, the trypan blue exclusion assay to assess cell viability, the comet assay to assess genotoxicity, and the micronucleus test with cytokinesis block to test mutagenicity. In addition, the comet assay and the micronucleus test were also performed on peripheral blood cells of 54 male Swiss mice, 35 g each, to assess the effects of the compounds in vivo. The results indicated that both 6-dimethylaminopurine and cycloheximide, at the concentrations and doses tested, were cytotoxic in vitro and genotoxic and mutagenic in vitro and in vivo, altered the nuclear division index in vitro, but did not diminish cell viability in vitro. Considering that alterations in DNA play important roles in mutagenesis, carcinogenesis, and morphofunctional teratogenesis and reduce embryonic viability, this study indicated that 6-dimethylaminopurine and cycloheximide utilized in the process of mammalian cloning may be responsible for the low embryo viability commonly seen in nuclear transfer after implantation in utero.


Assuntos
Animais , Humanos , Masculino , Camundongos , Adenina/análogos & derivados , Ensaio Cometa , Clonagem de Organismos/métodos , Cicloeximida/toxicidade , Mutagênicos/toxicidade , Adenina/toxicidade , Técnicas de Cultura de Células , Corantes , Sobrevivência Celular/efeitos dos fármacos , Citocinese/efeitos dos fármacos , /efeitos dos fármacos , Mamíferos , Testes para Micronúcleos , Testes de Mutagenicidade , Técnicas de Transferência Nuclear , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologia , Azul Tripano/farmacologia
11.
Full dent. sci ; 4(16): 621-625, out. 2013.
Artigo em Português | LILACS, BBO - Odontologia | ID: lil-695737

RESUMO

Esforços têm sido concentrados na busca de um fármaco que tenha eficácia clínica no processo de cicatrização de feridas odontológicas. O complexo B pode ser importante no processo de cicatrização e reparação porque é constituído por nutrientes necessários às funções fisiológicas normais ou às reações metabólicas específicas. Além disso, a terapia com laser de baixa intensidade modula vários processos biológicos em modelos animais e em humanos, estimulando a síntese de colágeno, promovendo o processo de regeneração do músculo esquelético após injúria, diminuindo a resposta inflamatória, elevando a neoformação de vasos sanguíneos e auxiliando no processo de cicatrização. Desta maneira, é relevante o estudo da influência do complexo B e do laser de baixa intensidade na tentativa de melhorar o processo de cicatrização de feridas odontológicas, aumentando a eficácia clínica. Essa revisão bibliográfica sugere que tanto o laser de baixa intensidade como o complexo B podem aumentar o processo de cicatrização em feridas e procedimentos odontológicos.


Currently, efforts have been concentrated in the search for a drug clinically efficient on healing dental wounds. The B complex may be important in wound healing process since it is composed of nutrients necessary for normal physiological functions or for specific metabolic reactions. The low intensity laser therapy modulates various biological processes in both animals and humans stimulating collagen synthesis, promoting the regeneration process of skeletal muscle injury after injury In addition it reduces the inflammatory response, increasing the formation of new blood vessels and aiding the healing process. Therefore it is important to study the influence of B complex and of low intensity laser aiming to improve the healing process of dental wounds, increasing clinical efficacy. This literature review suggests that both B complex and low intensity laser therapy can improve the healing process of dental wounds and dental procedures.


Assuntos
Ácido Pantotênico/farmacologia , Adenina/farmacologia , Cicatrização , Niacinamida/farmacologia , Riboflavina/farmacologia , Terapia com Luz de Baixa Intensidade/métodos , Terapia com Luz de Baixa Intensidade , Tiamina/farmacologia , /farmacologia , /farmacologia
12.
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 , Adenina/análogos & derivados , Adenina/economia , Adenina/uso terapêutico , Análise de Variância , 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
13.
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
14.
Braz. j. med. biol. res ; 46(7): 580-588, ago. 2013. graf
Artigo em Inglês | LILACS | ID: lil-682394

RESUMO

Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.


Assuntos
Animais , Masculino , Ratos , Apoptose/fisiologia , Autofagia/fisiologia , Isquemia Encefálica/fisiopatologia , Precondicionamento Isquêmico/métodos , Degeneração Neural/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Isquemia Encefálica/prevenção & controle , /metabolismo , Cérebro/lesões , Marcação In Situ das Extremidades Cortadas , Imunossupressores/farmacologia , Ratos Sprague-Dawley , Sirolimo/farmacologia , Fatores de Tempo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Supressoras de Tumor/metabolismo
15.
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
16.
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
17.
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
18.
Braz. j. infect. dis ; 15(6): 560-566, Nov.-Dec. 2011. ilus, tab
Artigo em Inglês | LILACS | ID: lil-610527

RESUMO

OBJECTIVES: Detection of mutations associated to nucleos(t)ide analogs and hepatitis B virus (HBV) genotyping are essential for monitoring treatment of HBV infection. We developed a multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) assay for the rapid detection of HBV genotypes and mutations associated with lamivudine, adefovir, and telbivudine resistance in HBV-infected patients. METHODS: HBV templates were amplified by PCR, followed by LDR and electrophoresis on a sequencer. The assay was evaluated using plasmids that contained wild-type or mutant HBV sequences and 216 clinical samples. RESULTS: The PCR-LDR assay and sequencing gave comparable results for 158 of the 216 samples (73.1 percent) with respect to mutation detection and genotyping. Complete agreement between the two methods was observed for all the samples (100 percent) at codon 180 and codon 204. Concordant results were observed for 99.4 percent of the 158 samples at codon 181 and 98.7 percent at codon 236. The genotyping results were completely concordant between the PCR-LDR assay and sequencing. The PCR-LDR assay could detect a proportion of 1 percent mutant plasmid in a background of wild-type plasmid. CONCLUSION: The PCR-LDR assay is sensitive and specific for detection of HBV genotypes and drug resistance mutations, and could be helpful for decision making in the treatment of HBV infection.


Assuntos
Humanos , Adenina/análogos & derivados , Antivirais/farmacologia , Farmacorresistência Viral Múltipla/genética , Vírus da Hepatite B/efeitos dos fármacos , Lamivudina/farmacologia , Mutação/genética , Nucleosídeos/farmacologia , Ácidos Fosforosos , Pirimidinonas/farmacologia , Adenina/farmacologia , DNA Viral/genética , Genótipo , Vírus da Hepatite B/genética , Hepatite B/virologia , Reação em Cadeia da Ligase , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase Multiplex
19.
Electron. j. biotechnol ; 13(6): 3-4, Nov. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-591907

RESUMO

An efficient, highly reproducible protocol for multiple shoot induction and plant regeneration of Pongamia pinnata has been successfully developed using cotyledonary node explants. This study also demonstrates that preconditioning of explant stimulates production of multiple shoots from cotyledonary nodes of P. pinnata. The highest direct shoot regeneration (90 percent) with an average of 18.4 +/- 3.1 shoots/explant were obtained when cotyledonary node explants were excised from seedlings germinated on Murashige and Skoog (MS) media supplemented with benzyladenine (BA) 1 mg l-1, and subsequently cultured on MS media with 1 mgl-1 thidiazuron (TDZ). Scanning electron microscope observations of cotyledonary node (CN) explants excised from pre-conditioned and normal seedlings, revealed larger buds with rapid development in BA-preconditioned CN explants. The addition of adenine sulphate significantly increased the average number of shoots per explant. The highest direct shoot regeneration (93 percent) with an average of 32.2 +/- 0.93 shoots/explant was obtained from BA-preconditioned CN when cultured on MS media supplemented with 1 mg l-1 TDZ and 200 mg l-1 adenine sulphate (ADS). Repeated shoot proliferation was observed from BA preconditioned CN explants up to 3 cycles with an average of 15 shoots/explant/cycle when cultured on MS media supplemented with 1 mg l-1 TDZ and 150 mg l-1 L-glutamine, thus producing 45 shoots/CN explant. Shoots were elongated on hormone free MS media and rooted on 1/2 MS media supplemented with 1 mg l-1 of IBA. Rooted shoots were successfully acclimatized and established in soil with 80 percent success. The highly regenerative system developed in this investigation for this important tree could be a useful tool for genetic transformation.


Assuntos
Adenina/farmacologia , Brotos de Planta/fisiologia , Compostos de Fenilureia/farmacologia , Cotilédone/fisiologia , Pongamia/fisiologia , Tiadiazóis/farmacologia , Adenina/análogos & derivados , Brotos de Planta , Cotilédone/ultraestrutura , Germinação , Cinetina , Microscopia Eletrônica de Varredura , Pongamia , Regeneração , Reguladores de Crescimento de Plantas/farmacologia , Sementes
20.
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
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