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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
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Carcinoma Hepatocelular , Gastroenterologia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Brasil , Sociedades MédicasRESUMO
ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.
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OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.
Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Hepacivirus , Humanos , Neoplasias Hepáticas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Hepatitis A virus (HAV) infection has been considered one of the leading causes of acute hepatitis. The aim of the present study was to estimate the prevalence of HAV among children and adolescents in a population-based study in the capitals of the States of the North, Southeast and South of Brazil and identify predictive factors for the infection. A multi-stage sampling was used to select subjects aged between 5-9 and 10-19 years. Individual and household levels aside from the level of variables in the areas were collected. The outcome was the total IgG antibodies to HAV levels detected using a commercial Enzyme Immuno Assay (EIA). The associations between HAV and the independent variables were assessed using the odds ratio. A multilevel analysis was performed by GLLAMM using the Stata software. The prevalence of HAV infection in the 5-9 and 10-19 age groups was 28.7% and 67.5%, respectively for the North, 20.6% and 37.7%, for the Southeast and 18.9% and 34.5% for the South Region. The prevalence of HAV increased according to age in all sites. Variables related to education at the individual level (North and South), family and area level (South and Southeast) and family income level (Southeast and South) were independently associated with HAV infection. This emphasizes the need for individualized strategies to prevent the infection.
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Hepatite A , Adolescente , Brasil/epidemiologia , Criança , Hepatite A/diagnóstico , Hepatite A/epidemiologia , Anticorpos Anti-Hepatite A , Humanos , Prevalência , Fatores de Risco , Estudos SoroepidemiológicosRESUMO
OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.
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Humanos , Hepatite C , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Estudos de Casos e Controles , Hepacivirus , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Fator A de Crescimento do Endotélio Vascular/genética , GenótipoRESUMO
The aim of this study was to develop an assay to analyze the serum profile of Mannose-binding lectin (MBL) through a simple and "in-house" method (called "dot-N-man"). Furthermore, the study attempted to associate molecular masses of MBL to the profile of MBL gene polymorphisms in patients with hepatitis C. Heterogeneity in molecular masses of MBL is due to the impairment of oligomers formation, which is linked to genetic polymorphisms in the MBL gene. Individuals with AA genotype (wild-type) produce high-molecular-mass proteins, whereas AO and OO individuals produce intermediate and low-molecular-mass proteins, respectively. Sera of thirty patients carrying the hepatitis C virus (HCV) were investigated using MBL binding assay with mannan-coated nitrocellulose (dot-N-man). Purified MBL was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Dot-N-Man assay yielded MBL with molecular masses ranging between 55 and 320â¯kDa, comparable to low and high molecular mass forms of MBL. Nonreducing SDS-PAGE showed high molecular mass bands in all AA individuals while bands of 270 and 205â¯kDa were observed in sera for a number of patients with AO and OO genotypes, respectively. Immunoblotting confirmed the MBL samples obtained from the dot-N-man. These results provide new insights to understand the MBL molecular forms profile in patients infected with HCV- which could be useful in future investigations on the influence of the MBL structure/genotype on both the progression of infection and the response to hepatitis C therapy.
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Hepacivirus/imunologia , Hepatite C , Immunoblotting/métodos , Lectina de Ligação a Manose , Polimorfismo Genético , Colódio/química , Feminino , Hepatite C/genética , Hepatite C/imunologia , Humanos , Masculino , Mananas/química , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/imunologiaRESUMO
The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0-F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV.
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Catalase/genética , Glutationa Peroxidase/genética , Hepatite C Crônica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Carcinoma Hepatocelular/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Glutationa Peroxidase GPX1RESUMO
A population-based hepatitis survey was carried out to estimate the prevalence of hepatitis B virus (HBV) infection and its predictive factors for the state capitals from the north, south, and southeast regions of Brazil. A multistage cluster sampling was used to select, successively, census tracts, blocks, households, and residents in the age group 10-69 years in each state capital. The prevalence of hepatitis B surface antigen (HBsAg) was lower than 1% in the north, southeast, and south regions. Socioeconomic condition was associated with HBV infection in north and south regions. Variables related to the blood route transmission were associated with HBV infection only in the south whereas those related to sexual behavior were associated with HBV infection in the north and south regions. Drug use was associated in all regions, but the type of drug differed. The findings presented herein highlight the diversity of the potential transmission routes for hepatitis B transmission in Brazil. In one hand, it reinforces the importance of national control strategies of large impact already in course (immunization of infants, adolescents, and adults up to 49 years of age and blood supply screening). On the other hand, it shows that there is still room for further control measures targeted to different groups within each region.
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Vacinas contra Hepatite B/uso terapêutico , Hepatite B/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Criança , Feminino , Inquéritos Epidemiológicos , Hepatite B/etiologia , Hepatite B/prevenção & controle , Hepatite B/transmissão , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Fatores Socioeconômicos , Abuso de Substâncias por Via Intravenosa/complicações , Adulto JovemRESUMO
BACKGROUND: Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. METHODS: The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case-control approach. RESULTS: The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%-1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. CONCLUSIONS: The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.
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Hepacivirus , Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Estudos Transversais , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/história , Anticorpos Anti-Hepatite C/sangue , Anticorpos Anti-Hepatite C/imunologia , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , População Urbana , Adulto JovemRESUMO
BACKGROUND/AIM: Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T (Ala222Val) polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC) from Northeast of Brazil. METHOD: One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy) levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week. RESULTS: Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01). Nevertheless, association was found between the MTHFR genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p < 0.05). A significant difference was found on plasma Hcy levels in patients with steatosis regardless of HCV genotype (p = 0.03). CONCLUSION: Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.
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Hepatite C Crônica/genética , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Brasil/epidemiologia , Estudos Transversais , Feminino , Genótipo , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/patologia , Humanos , Hiper-Homocisteinemia/genética , Hiper-Homocisteinemia/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Patients with hepatitis B virus (HBV) infection may develop severe chronic liver disease. Carriers of HBV have an increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Worldwide an estimated 350 million people are infected with HBV, and 15-40% will develop serious sequelae in their lifetime. In our study we investigated the association of single nucleotide polymorphisms (SNPs) in the first exon and promoter region of the mannose-binding lectin gene 2 (MBL2) situated on chromosome 10, with susceptibility to HBV infection. One-hundred and two patients infected with HBV were included in this study, and 232 uninfected individuals were used as healthy controls. Genotyping of the first exon (alleles A/O) was performed using a melting temperature assay. Genotyping of the promoter region (-550 H/L; -221 Y/X) was performed using the Taqman PCR technique. In the HBV-infected group we found a significantly increased frequency of haplotypes associated with low serum MBL. Our findings may indicate that MBL has a protective role against HBV infection in the studied population.
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Predisposição Genética para Doença , Hepatite B/genética , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Alelos , Brasil , Éxons/genética , Feminino , Frequência do Gene , Haplótipos , Hepatite B/imunologia , Humanos , Imunidade Inata , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genéticaRESUMO
Combination of citric acid dipping (5 g/L) and cassava starch coating (10 g/L), with and without glycerol (10 g/L), was studied to verify the effectiveness of these treatments to inhibit enzymatic browning, to reduce respiration rate, and to preserve quality parameters of "Tommy Atkins" fresh-cut mangoes during storage at 5 degrees C. Color characteristics (L and C), mechanical properties (stress at failure), weight loss, beta-carotene content, sensory acceptance, and microbial growth of fruits were evaluated during 15 d. The respiration rate of fruit subjected to the treatments was also analyzed. Nontreated fresh-cut mango was used as a control sample. Cassava starch edible coatings and citric acid dipping promoted a decrease in respiration rate of mango slices, with values up to 41% lower than the control fruit. This treatment also promoted better preservation of texture and color characteristics of mangoes and delayed carotenoid formation and browning reactions during storage. Moreover, the treated fruit showed great sensory acceptance by consumers throughout the whole storage period. However, the use of glycerol in the coating formulation was not efficient in the maintenance of quality parameters of fresh-cut mangoes, promoting a higher weight loss of samples, impairing fruit texture characteristics, increasing carotenogenesis, and favoring microbial growth during storage.
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Antioxidantes/farmacologia , Ácido Cítrico/farmacologia , Conservação de Alimentos/métodos , Frutas/metabolismo , Mangifera/metabolismo , Manihot , Contagem de Colônia Microbiana , Manipulação de Alimentos/métodos , Frutas/química , Humanos , Reação de Maillard , Mangifera/química , Odorantes , Pigmentação , Controle de Qualidade , Resistência ao Cisalhamento , Paladar , beta Caroteno/análiseRESUMO
The effect of calcium lactate on osmodehydrated guavas in sucrose and maltose solutions was monitored during storage under passive modified atmosphere for 24 d at 5 °C. Sample texture and color characteristics, microbial spoilage, sensory acceptance, structural changes, and gas composition inside the packages were periodically evaluated. Calcium lactate inhibited microbial growth on guavas, with yeast and mold counts in the order of 10(2) CFU/g throughout storage. The calcium salt reduced respiration rate of guava products, showing O(2) and CO(2) concentrations around 18% and 3% inside the packages. A firming effect on fruit texture, with up to 5 and 2 times higher stress and strain at failure values and tissue structure preservation could also be attributed to calcium lactate use. However, fruits treated with calcium lactate, osmodehydrated in maltose and sucrose solutions, showed sensory acceptance scores below the acceptability limit (4.5) after 13 and 17 d of storage, respectively.
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Anti-Infecciosos/farmacologia , Compostos de Cálcio/farmacologia , Microbiologia de Alimentos , Conservação de Alimentos , Frutas/efeitos dos fármacos , Lactatos/farmacologia , Psidium/efeitos dos fármacos , Dióxido de Carbono/análise , Contagem de Colônia Microbiana , Contaminação de Alimentos/análise , Embalagem de Alimentos , Frutas/microbiologia , Concentração de Íons de Hidrogênio , Oxigênio/análise , Pigmentação/efeitos dos fármacos , Psidium/microbiologia , Salmonella/crescimento & desenvolvimento , Salmonella/patogenicidadeRESUMO
This multicentric population-based study in Brazil is the first national effort to estimate the prevalence of hepatitis B (HBV) and risk factors in the capital cities of the Northeast, Central-West, and Federal Districts (2004-2005). Random multistage cluster sampling was used to select persons 13-69 years of age. Markers for HBV were tested by enzyme-linked immunosorbent assay. The HBV genotypes were determined by sequencing hepatitis B surface antigen (HBsAg). Multivariate analyses and simple catalytic model were performed. Overall, 7,881 persons were included; < 70% were not vaccinated. Positivity for HBsAg was less than 1% among non-vaccinated persons and genotypes A, D, and F co-circulated. The incidence of infection increased with age with similar force of infection in all regions. Males and persons having initiated sexual activity were associated with HBV infection in the two settings; healthcare jobs and prior hospitalization were risk factors in the Federal District. Our survey classified these regions as areas with HBV endemicity and highlighted the risk factors differences among the settings.
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Hepatite B/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Estudos Transversais , Feminino , Anticorpos Anti-Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Caracteres Sexuais , Fatores Socioeconômicos , Adulto JovemRESUMO
Angiotensin-converting enzyme inhibitors reduce the blood pressure (BP) and inhibit the generation of the angiotensin II from the inactive angiotensin I. Ten 28-week-old spontaneously hypertensive rats (SHRs) had their ovaries bilaterally removed and five rats were left intact and studied for 7 additional weeks: intact group, ovariectomized group (ovx SHRs) and ovariectomized + enalapril group (ovx + en). BP was higher in ovx SHRs and lower in treated ovx SHRs. Left ventricular (LV) mass index was greater in untreated ovx SHRs and smaller in ovx + en group. The LV cardiomyocyte (cmy) mean cross-sectional area, measured by stereology, was greater in ovx SHRs and smaller in both intact and ovx + en SHRs. Ovx significantly decreased the density of intramyocardial blood vessels (ive), but administration of enalapril was able to restore the density of the ive to that seen in intact group. The worst ive:cmy ratio was found in untreated ovx SHRs, the intact group showed a 90% greater ratio, and the treated ovx group showed a 150% greater ratio than the untreated ovx group. In conclusion, ovariectomy, in SHRs, causes cardiac hypertrophy and an unfavourable myocardial remodelling. Of the spectrum of changes seen, the major effect of enalapril appears to be mediated via an increase in the density of ive.
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Inibidores da Enzima Conversora de Angiotensina/farmacologia , Enalapril/farmacologia , Coração/efeitos dos fármacos , Animais , Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Cardiomegalia/fisiopatologia , Estradiol/sangue , Feminino , Coração/fisiopatologia , Ventrículos do Coração/fisiopatologia , Hipertensão/fisiopatologia , Miócitos Cardíacos/fisiologia , Ovariectomia , Ratos , Ratos Endogâmicos SHRRESUMO
Twenty mature male Wistar rats were maintained alive for 40 days, separated in four groups of five rats each: control, L-NAME (LN), L-NAME + Enalapril (LN + E), L-NAME + Verapamil (LN + V). Blood pressure (BP), left ventricular (LV) mass index, and aortic wall parameters were analyzed: aortic wall thickness, tunica media sectional area, surface density of lamellae (Sv[lamellae]), and smooth muscle cell nuclear profiles per section (SMC). At the end of the experiment, the LN group showed high BP and a high LV mass index (cardiac hypertrophy). The control group and the other groups showed significant differences in aortic wall thickness, tunica media sectional area, Sv[lamellae], and SMC. When comparing the LN group with both the LN + E group and the LN + V group, aortic thickness was not different. Tunica media sectional area and SMC differed between the LN group and the LN + E group. There were also differences between the LN group and the LN + V group in SMC. The Sv[lamellae] decreased in the following sequence: control group > LN group = LN + E group > LN + V group. In conclusion, treatment with enalapril and verapamil shows partial efficiency in preventing or treating aortic wall tunica media hypertrophy, suggesting that these alterations are due to a mechanism other than blood pressure control, where nitric oxide synthesis inhibition could be involved.
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Inibidores da Enzima Conversora de Angiotensina/farmacologia , Aorta Torácica/patologia , Bloqueadores dos Canais de Cálcio/farmacologia , Enalapril/farmacologia , Óxido Nítrico/deficiência , Verapamil/farmacologia , Animais , Aorta Torácica/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos WistarRESUMO
Stereological structural alterations of the heart and kidney were studied in four groups (n=5) of spontaneously hypertensive rats (SHRs) treated for 30 days: (i) control, (ii) NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthesis inhibitor] alone, (iii) enalapril alone and (iv) L-NAME plus enalapril. Blood pressure (BP) was elevated significantly in NO-deficient SHRs (rats receiving L-NAME) or significantly lower in enalapril-treated SHRs. Co-administration of L-NAME and enalapril caused a 20% decrease in BP compared with untreated SHRs. NO-deficient SHRs had a decrease in body mass, but this loss of body mass was prevented efficiently in the enalapril-treated group. Enalapril treatment decreased the left ventricular (LV) mass index in SHRs, even in animals with NO synthesis blocked. NO deficiency in SHRs caused a larger decrease in the number of LV cardiomyocyte nuclei, which had a negative correlation with both LV mass index and BP. The volume-weighted glomerular volume (VWGV) separated the SHRs into two groupings: (i) control and NO-deficient SHRs, and (ii) enalapril- and L-NAME plus enalapril-treated SHRs. There was a significant difference between these two groupings, with VWGV being more than 15% smaller in the latter compared with the former grouping. The present findings reinforce the evidence that enalapril efficiently treats genetic hypertension, and demonstrate that this effect is observed even when NO synthesis is inhibited. Enalapril administration also decreases cardiac and renal structural damage caused by genetic hypertension, as well as by the interaction between genetic hypertension and NO deficiency.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Hipertensão/tratamento farmacológico , Glomérulos Renais/patologia , Miócitos Cardíacos/patologia , Óxido Nítrico/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Contagem de Células , Hipertensão/metabolismo , Hipertensão/patologia , Masculino , NG-Nitroarginina Metil Éster/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos Endogâmicos SHRRESUMO
In order to assess the potential risk of anti-HBc-positive blood donors for post-transfusional hepatitis and to investigate whether other HBV serological markers are capable of identifying the presence of the virus, 1000 first-time blood donors were enrolled between June and July 1997. These donors were screened using routine Brazilian blood center tests (HIV 1 and 2, HTLV 1 and 2, Chagas disease, Syphilis, HCV, HBsAg, anti-HBc and ALT ). The 120 (12%) found to be anti-HBc-positive underwent further tests: HBe, anti-HBe, anti-HBs and HBV-DNA by PCR. Ten cases were HBsAg positive and all were HBV-DNA positive by PCR. Three HBsAg-negative donors were HBV-DNA-positive. Two HBV-DNA-positive donors were also anti-HBs-positive. All the HBV-positive donors had at least one HBV marker other than anti-HBc. Anti-HBc is an important cause of blood rejection. Testing for HBsAg alone is not fully protective and anti-HBc remains necessary as a screening test. The presence of anti-HBs is not always indicative of absence of the virus. The addition of other HBV serological markers could represent an alternative in predicting the presence of the virus when compared with PCR. It is recommended that other studies should be carried out to confirm this finding.
Assuntos
Doadores de Sangue , DNA Viral/sangue , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Biomarcadores/sangue , Estudos Transversais , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B/prevenção & controle , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Anticorpos Anti-Hepatite C/sangue , Humanos , Medições Luminescentes , Masculino , Reação em Cadeia da PolimeraseRESUMO
In order to assess the potential risk of anti-HBc-positive blood donors for post-transfusional hepatitis and to investigate whether other HBV serological markers are capable of identifying the presence of the virus, 1000 first-time blood donors were enrolled between June and July 1997. These donors were screened using routine Brazilian blood center tests (HIV 1 and 2, HTLV 1 and 2, Chagas disease, Syphilis, HCV, HBsAg, anti-HBc and ALT ). The 120 (12 percent) found to be anti-HBc-positive underwent further tests: HBe, anti-HBe, anti-HBs and HBV-DNA by PCR. Ten cases were HBsAg positive and all were HBV-DNA positive by PCR. Three HBsAg-negative donors were HBV-DNA-positive. Two HBV-DNA-positive donors were also anti-HBs-positive. All the HBV-positive donors had at least one HBV marker other than anti-HBc. Anti-HBc is an important cause of blood rejection. Testing for HBsAg alone is not fully protective and anti-HBc remains necessary as a screening test. The presence of anti-HBs is not always indicative of absence of the virus. The addition of other HBV serological markers could represent an alternative in predicting the presence of the virus when compared with PCR. It is recommended that other studies should be carried out to confirm this finding
Assuntos
Humanos , Biomarcadores , Doadores de Sangue , DNA Viral , Dopagem Esportivo , Anticorpos Anti-Hepatite B , Vírus da Hepatite B , Estudos Transversais , DNA Viral , Ensaio de Imunoadsorção Enzimática , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Anticorpos Anti-Hepatite C , Reação em Cadeia da PolimeraseRESUMO
The distributions of the different genotypes of the hepatitis C virus (HCV) and GBV-C virus (GBV-C/HGV) vary geographically and information worldwide is still incomplete. In particular, there are few data on the distribution of genotypes (and their relationship to the severity of liver disease) in South America. Findings are described in 114 consecutive patients from Northeast Brazil (median age 52 years, range 18-72 years) who had abnormal levels of serum aminotransferases and seropositivity for HCV RNA. The patients were recruited from an outpatient clinic between November 1997 and April 1998. Quantitative HCV RNA and GBV-C/HGV RNA estimations were carried out by double-nested polymerase chain reaction (PCR) using primers from the 5'-untranslated regions (UTRs) of the genomes. HCV genotypes were determined by restriction fragment length polymorphism (RFLP) analysis with 5'-UTR primers and by PCR with type-specific 5'-UTR primers. GBV-C/HGV-RNA genotypes were determined by RFLP with specific 5'-UTR primers and phylogenetic trees were constructed using the Neighbour-Joining and Drawtree programs. Histological features were graded and staged according to international criteria. Of the 114 patients, 35 (30.7%) patients had cirrhosis and 22 (27.8%) had mild, 51 (64.6%) had moderate, and 6 (7.6%) had severe chronic hepatitis. Median HCV viral load was 10(6) genome equivalents per millilitre (range 10(4)-10(9)/ml). Frequencies of genotypes were 5.3% type 1a, 44.7% type 1b, 3.5% type 2, 41.2% type 3, and 5.3% mixed types. GBV-C/HGV-RNA was detected in the sera of 12 (10.5%) patients and was distributed among three phylogenetic groups. There were no significant differences between patients with the predominant HCV genotypes (1b and 3) with respect to gender, age group, viral load, severity of liver disease, or coinfection with GBV-C/HGV.