RESUMEN
The influence of hepatitis B virus (HBV) genotypes in the natural history of the disease and its response to antiviral treatment have been addressed in many studies. In Brazil, studies on HBV genotype circulation have been restricted to specific population groups and states. Here, we have conducted a nationwide multicentre study with an unprecedented sample size representing all Brazilian regions in an effort to better understand the viral variants of HBV circulating among chronic carriers. Seven HBV genotypes were found circulating in Brazil. Overall, HBV/A was the most prevalent, identified in 589 (58.7â%) samples, followed by HBV/D (23.4â%) and HBV/F (11.3â%). Genotypes E, G, C and B were found in a minor proportion. The distribution of the genotypes differed markedly from the north to the south of the country. While HBV/A was the most prevalent in the North (71.6â%) and Northeast (65.0â%) regions, HBV/D was found in 78.9â% of the specimens analysed in the South region. HBV/F was the second most prevalent genotype in the Northeast region (23.5â%). It was detected in low proportions (7 to 10â%) in the North, Central-West and Southeast regions, and in only one sample in the South region. HBV/E was detected in all regions except in the South, while monoinfection with HBV/G was found countrywide, with the exception of Central-West states. Our sampling covered 24 of the 26 Brazilian states and the Federal District and is the first report of genotype distribution in seven states. This nationwide study provides the most complete overview of HBV genotype distribution in Brazil to date and reflects the origin and plurality of the Brazilian population.
Asunto(s)
Genotipo , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis B/virología , Filogeografía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Femenino , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) polymorphisms seem to be linked to higher angiogenic phenotype than the remaining alleles and may act on breast cancer (BC) origin. We investigated the influence of the VEGF C936T and G634C polymorphisms on the occurrence and clinicopathologic characteristics of sporadic breast cancer (SBC) in 235 patients and 235 controls. Peripheral blood samples of all individuals were analysed by the polymerase chain reaction for identification of genotypes and by enzyme-linked immunosorbent assay (ELISA) for quantification of serum VEGF levels. The variant 634CC genotype isolated (16.2% versus 10.7%, P = 0.01) and in combination with the wild 936CC genotype (10.6% versus 5.5%, P = 0.01) were more common in patients than in controls. The carriers of the respective genotypes were under a 2.20-fold and a 3.08-fold increased risks for the disease. Additionally, the frequency of the wild 936CC genotype was higher in patients with tumours of histological grade III compared to those with tumours of I+II histological grades (84.0% versus 64.7%, P = 0.004) and in patients with positive oestrogen receptor tumours compared to those with tumours lacking oestrogen receptor expression (84.7% versus 73.9%, P = 0.02). Similar serum values of VEGF were seen in patients and controls with the distinct genotypes of the VEGF. The data suggest that the VEGF wild 936CC and the variant 634CC genotypes constitute inherited determinants of SBC and SBC aggressiveness in Brazil, but are not significant predictors of circulating VEGF levels.
Asunto(s)
Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Polimorfismo Genético/genética , Regiones no Traducidas/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Neoplasias de la Mama/etnología , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/etnología , Carcinoma Ductal de Mama/metabolismo , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Persona de Mediana Edad , Receptores de Estrógenos/metabolismo , Factores de Riesgo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: More than 50% of hepatitis C viruses (HCV)-infected patients do not respond to the classical Interferon (IFN)/Ribavirin (RBV) combination therapy. The aim of this study was to evaluate the efficacy of retreatment with Peg-Interferon alpha-2b (PEG-IFN alpha-2b) plus RBV, in patients with HCV, genotypes 1 or 3, who were non-responders to the previous standard treatment with IFN/RBV. METHODS: In the period 2005-2007, a total of 238 HCV chronic patients were non-responders to previous treatment with IFN plus RBV. Of these 130 agreed to be retreated with PEG-IFN alpha-2b and participated in this evaluation (90 with genotype 1 HCV and 40 with genotype 3 HCV). Patients were retreated at assisted IFN application hubs in compliance with the country's public health system rules. They received subcutaneous PEG-IFN alpha-2b, 1.5 microg, once weekly, associated with RBV, through the oral route, with doses determined according to weight (1,000 mg if weight
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Interferones/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Quimioterapia Combinada/métodos , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteínas Recombinantes , Retratamiento/métodos , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil) and to correlate results with clinical and histopathological data. METHODS: One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 +/- 14.5 years; range 7-80 years; 84% Caucasian) and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche). RESULTS: HBV genotype A was the most prevalent (55%), while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76) were African descendents and, among the patients infected by genotype D, 11.3% (6/53) were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7) genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F). The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8) was significantly higher than the mean stage of fibrosis in genotype D patients (2.0) (P = 0.0179). CONCLUSION: The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status predominated, possibly due to the length of time of infection. The viral load in HBeAg-positive patients was higher than in HBeAg-negative individuals. The fibrosis grade in genotype A-infected patients was more advanced than genotype D-infected patients.
Asunto(s)
Antígenos e de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Hepatitis B/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Femenino , Genotipo , Hepatitis B/epidemiología , Virus de la Hepatitis B/clasificación , Humanos , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
BACKGROUND: The progression of liver disease in patients with chronic hepatitis C virus (HCV) infection is influenced by host and viral factors. Distinct clinical outcomes in patients infected with different HCV genotypes have been described in the literature. However, the association between specific HCV genotype and clinical outcome remains unclear. We set out to study the natural history of HCV genotype 1 and 3 infections in Campinas, São Paulo state, Brazil, focusing on epidemiological, clinical, biochemical, and histological characteristics. METHODS: Patients with HCV infection referred for treatment between January 2003 and December 2006 were included in this study. We collected epidemiological, clinical, and laboratorial data using standard forms. RESULTS: A total of 283 patients were included; genotype 1 was identified in 163 (57.6%) patients, genotype 3 in 112 (39.6%), genotype 2 in 7 (2.5%), and genotype 4 in 1 (0.35%). Patients with genotype 2 and 4 were excluded from analysis. Multivariate analysis showed that intravenous energetic drug, positive cryoglobulin, and cirrhosis were independently and significantly associated with HCV genotype 3 (p < 0.05). CONCLUSION: Genotype 3 currently seems to be associated with intravenous energetic drug, high frequency of cryoglobulinemia, and advanced liver disease in our region. Understanding the distribution of the different HCV genotypes can elucidate transmission of HCV and support optimal prevention strategies.
Asunto(s)
Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Anciano , Brasil/epidemiología , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Blood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patients METHODS: In order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil. RESULTS: The study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10-2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 +/- 26.46 and 23.99 +/- 30.58 respectively; P = 0.75, Mann-Whitney test). CONCLUSION: Multiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions.
Asunto(s)
Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/transmisión , Exámenes Obligatorios , Reacción a la Transfusión , Adolescente , Adulto , Animales , Brasil/epidemiología , Enfermedad de Chagas/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios SeroepidemiológicosRESUMEN
We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin, on the occurrence of sporadic breast cancer in 181 patients and 448 controls. The homozygous 104NN polymorphism was found in five patients but was absent in controls (2.8% vs 0.0%; P = 0.002). Individuals with this genotype had a significantly increased risk for disease. Our results suggest, for the first time, that the homozygous 104NN polymorphism, even at low frequency, constitutes an important inherited determinant of the disease.
Asunto(s)
Neoplasias de la Mama/genética , Endostatinas/genética , Regulación Neoplásica de la Expresión Génica , Polimorfismo Genético , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Persona de Mediana Edad , Medición de Riesgo , Factores de RiesgoRESUMEN
Transgene elimination is a poorly studied phenomenon in plants. We made genetic and molecular studies of a transgenic dry bean line immune to bean golden mosaic geminivirus and a soybean line. In both lines, the transgenes were stable during the vegetative phase but were eliminated during meiosis. Due to its potential biotechnological value, this transgenic line was micropropagated by grafting and the vegetative copies were studied for more than two years. More than 300 plants of progeny were obtained during this period, demonstrating that the phenomenon of elimination was consistently repeated and offering an opportunity for detailed study of transgene elimination, including the characterization of the integration sites. Cloning and sequencing of the transgenic loci, reciprocal crosses to untransformed plants, genomic DNA blots, and GUS assays were performed in the transgenic lines. Based on the molecular and genetic characterization, possible mechanisms involved in transgene elimination include intrachromosomal recombination, genetic instability resulting from the tissue culture manipulations, and co-elimination of transgenes, triggered by a process of genome defense.
Asunto(s)
Glycine max/genética , Phaseolus/genética , Plantas Modificadas Genéticamente/genética , Transgenes/genética , Virus del Mosaico , ADN de Plantas , Eliminación de Gen , Glycine max/virología , Phaseolus/virología , Reacción en Cadena de la Polimerasa , Vectores Genéticos/genéticaRESUMEN
We identified a transgenic line exhibiting albinism during our work to introduce genes through genetic engineering in dry bean (Phaseolus vulgaris). The transgenic mother plant (R0) presented a normal phenotype and generated albino and normal green plants in the first generation (R1). The segregation ratio of the albino character in the R1 and R2 generations fitted the expected ratio for a character controlled by a single recessive gene linked to a foreign gus gene, suggesting that albinism could be a consequence of insertional mutation caused by introduction of the exogenous gene. Analysis by electron microscope revealed that the albino cells possessed no chloroplasts and a greater number of mitochondria when compared to normal green plants. This transgenic bean line may be used in understanding the genetic control of chloroplast genesis, for acquiring additional knowledge of genomic structure or in physiological studies. This is the first described transgene-associated mutant bean plant.
Asunto(s)
Cloroplastos/genética , Genes Recesivos/fisiología , Phaseolus/genética , Plantas Modificadas Genéticamente/genética , Transgenes/fisiología , Cloroplastos/fisiología , Color , Expresión Génica , Mitocondrias/genética , Mitocondrias/fisiología , Mutación , Phaseolus/fisiología , Phaseolus/ultraestructura , Fenotipo , Plantas Modificadas Genéticamente/fisiología , Plantas Modificadas Genéticamente/ultraestructuraRESUMEN
BACKGROUND: Transfusion-transmitted infections (TTI) continue to be a problem in many parts of the world, and multi-transfused patients (MTP) are at a particularly increased risk of TTI. OBJECTIVES: to estimate the prevalence of TTI among multi-transfused patients in Brazil, and to understand the epidemiological characteristics of TTI among these patients. STUDY DESIGN: cross-sectional study of 353 MTP, who were interviewed using a structured questionnaire and tested for serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infection. RESULTS: the overall prevalence of HCV, HIV, HBV and co-infection among MTP were 16.7%, 1.7%, 0.8% and 1.7% respectively. A dose-effect relationship could be detected between the number of units transfused and HCV infection. Other non-transfusion related (NTR) risk factors for HCV did not confer any excess risk of HCV infection to MTP. CONCLUSIONS: HCV infection was the most prevalent TTI among MTP, and remains a major health problem for these patients. A dose-effect relationship could be detected between HCV and the number of units transfused. The implementation of measures such as donor education programs, standards for donor selection criteria, and of improved serological screening protocols, paralleled the decline in the prevalence of TTI, specially of HCV, observed in MTP, underscoring the importance of such measures for the reduction of the residual risk of TTI.
Asunto(s)
Anticuerpos Anti-VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/etiología , Anticuerpos contra la Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis B/etiología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Hepatitis C/etiología , Reacción a la Transfusión , Adulto , Brasil/epidemiología , Comorbilidad , Estudios Transversales , Transmisión de Enfermedad Infecciosa , Femenino , Infecciones por VIH/transmisión , Hepatitis B/transmisión , Hepatitis C/transmisión , Hospitales Universitarios , Humanos , Masculino , Estudios Seroepidemiológicos , Encuestas y CuestionariosRESUMEN
Screening blood donations for anti-HCV antibodies and alanine aminotransferase (ALT) serum levels generally prevents the transmission of hepatitis C virus (HCV) by transfusion. The aim of the present study was to evaluate the efficiency of the enzyme immunoassay (EIA) screening policy in identifying potentially infectious blood donors capable to transmit hepatitis C through blood transfusion. We have used a reverse transcriptase (RT)-nested polymerase chain reaction (PCR) to investigate the presence of HCV-RNA in blood donors. The prevalence of HCV-RNA positive individuals was compared with the recombinant immunoblot assay (RIBA-2) results in order to assess the usefulness of both tests as confirmatory assays. Both tests results were also compared with the EIA-2 OD/C ratio (optical densities of the samples divided by the cut off value). ALT results were expressed as the ALT quotient (qALT), calculated dividing the ALT value of the samples by the maximum normal value (53UI/l) for the method. Donors (n=178) were divided into five groups according to their EIA anti-HCV status and qALT: group A (EIA > or = 3, ALT<1), group B (EIA > or = 3, ALT>1), group C (1<=EIA<3, ALT<1), group D (1<=EIA<3, ALT>1) and group E (EIA<=0.7). HCV sequences were detected by RT-nested PCR, using primers for the most conserved region of viral genome. RIBA-2 was applied to the same samples. In group A (n=6), all samples were positive by RT-nested PCR and RIBA-2. Among 124 samples in group B, 120 (96.8 percent) were RIBA-2 positive and 4 (3.2 percent) were RIBA-2 indeterminate but were seropositive for antigen c22.3. In group B, 109 (87.9 percent) of the RIBA-2 positive samples were also RT-nested PCR positive, as well as were all RIBA-2 indeterminate samples. In group C, all samples (n=9) were RT-nested PCR negative: 4 (44.4 percent) were also RIBA-2 negative, 4 (44.4 percent) were RIBA-2 positive and 1 (11.1 percent) was RIBA-2 indeterminate. HCV-RNA was detected by RT-nested PCR in 3 (37.5 percent) out of 8 samples in group D. Only one of them was also RIBA-2 positive, all the others were RIBA-2 indeterminate. All of the group E samples (controls) were RT- nested PCR and RIBA-2 negative. Our study suggests a strong relation between anti-HCV EIA-2 ratio > or = 3 and detectable HCV-RNA by RT-nested PCR. We have also noted that blood donors with RIBA-2 indeterminate presented a high degree of detectable HCV-RNA using RT-nested PCR...
Asunto(s)
Humanos , Alanina Transaminasa/sangre , Hepatitis C/diagnóstico , Immunoblotting , Técnicas para Inmunoenzimas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Hepacivirus/inmunología , Hepatitis D , Prevalencia , Proteínas Recombinantes , ARN Viral/análisisRESUMEN
Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6 percent were repeatedly EIA-2 reagent, 94 percent were symptomless and denied any hepatitis history, with only 2 percent mentioning previous jaundice. In 47 percent of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8 percent). Blood transfusion was the second factor for HCV transmission (27.2 percent). Hepatomegaly was detected in 54 percent of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65 percent of the subjects, being the steatosis the most frequent (50 percent). In 83.5 percent of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89 percent) with mild or moderate grade in most of the cases (99.5 percent). The histopathological exam of the liver was normal in 1.5 percent of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75 percent of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82 percent of the RIBA-2 positive subjects, in 37.5 percent of the indeterminate RIBA-2 donors and in 9 percent of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50 percent of the histopathological exams of the anti-HCV EIA-2 reagent donors which were indeterminate RIBA-2...
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Donantes de Sangre , Anticuerpos contra la Hepatitis C/aislamiento & purificación , Hepatitis C/diagnóstico , Hepatitis C/sangre , Hepatitis C/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Factores de RiesgoRESUMEN
A case of a pregnant patient with chronic hepatitis C who gave birth to monozygotic twins that were infected with HCV is reported. One of the newborns was positive for HCV-RNA in blood sample collected 12 hours after delivery. The other newborn was negative for HCV-RNA at birth, but was detected HCV viremia at three months of age. The results have led to the conclusion that one of the twins was probably contaminated in the intrauterine period, while the other acquired the infection in the perinatal period. Both were negative for HCV-RNA and for anti-HCV in the serum samples collected at nine months of age. The report describes the changes in the laboratory tests conducted in mother and twins until 29 months after delivery.
Asunto(s)
Humanos , Femenino , Embarazo , Recién Nacido , Lactante , Adulto , Hepacivirus/aislamiento & purificación , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Gemelos Monocigóticos , Enfermedad Crónica , Estudios de SeguimientoRESUMEN
TTV e um virus DNA recentemente descoberto no Japao a partir de um paciente portador de hepatite pos-transfusional de origem desconhecida. Neste estudo, avaliamos a presenca deste virus em pacientes com hepatopatias cronicas dos estados de Sao Paulo e do Para, representando duas regioes geograficamente diferentes. O DNA do TTV foi encontrado em 21/105 (20 por cento) e 9/20 (45 por cento) dos casos de Sao Paulo e do Para, respectivamente. O sequenciamento do DNA amplificado confirmou a presenca dos genotipos 1a e 2a, bem como de outros genotipos ainda nao descritos ate o momento. Em conclusao, TTV esta presente em casos de hepatopatias cronicas do Sudeste e do Norte do Brasil. por outro lado, maiores estudos ainda sao necessarios antes de se estabelecer relacao causal entre o TTV e a hepatite em seres humanos