RESUMO
BACKGROUND: An association between class I and II alleles of the major histocompatibility complex and idiopathic chronic urticaria has previously been observed in different populations, but there are still no studies on Brazilian populations in this regard. OBJECTIVE: The involvement of the major histocompatibility complex classes I and II (loci A, B and DR) in Brazilian patients with idiopathic chronic urticaria and a positive autologous serum skin test was investigated and compared with a healthy population group. METHODS: DNA was extracted from the blood of 42 patients with idiopathic chronic urticaria and major histocompatibility complex classes I and II alleles were determined using the polymerase chain reaction and a laboratory test for oligonucleotide hybridization using a single-filament probe. The frequencies of these alleles in patients with chronic urticaria were compared with the frequencies in 1000 genetically unrelated voluntary blood donors from the same region of Brazil. The diagnosis of idiopathic chronic urticaria was based on the patients' clinical history and routine laboratory tests. Only the patients with positive autologous serum skin test were selected. The allele distribution resulted from the patient and control groups were analyzed using odds ratios and 95% confidence intervals. RESULTS: No statistically significant differences were found between the positive autologous serum skin test patients with chronic urticaria and the control group. CONCLUSIONS: We found that in this population group, there was no specific association between the HLA alleles studied and chronic urticaria. We believe that further population studies are needed in order to investigate the possible existence of this association.
Assuntos
Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe I/análise , Urticária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Doença Crônica , Feminino , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Testes Cutâneos , Urticária/imunologia , Adulto JovemRESUMO
BACKGROUND: An association between class I and II alleles of the major histocompatibility complex and idiopathic chronic urticaria has previously been observed in different populations, but there are still no studies on Brazilian populations in this regard. OBJECTIVE: The involvement of the major histocompatibility complex classes I and II (loci A, B and DR) in Brazilian patients with idiopathic chronic urticaria and a positive autologous serum skin test was investigated and compared with a healthy population group. METHODS: DNA was extracted from the blood of 42 patients with idiopathic chronic urticaria and major histocompatibility complex classes I and II alleles were determined using the polymerase chain reaction and a laboratory test for oligonucleotide hybridization using a single-filament probe. The frequencies of these alleles in patients with chronic urticaria were compared with the frequencies in 1000 genetically unrelated voluntary blood donors from the same region of Brazil. The diagnosis of idiopathic chronic urticaria was based on the patients' clinical history and routine laboratory tests. Only the patients with positive autologous serum skin test were selected. The allele distribution resulted from the patient and control groups were analyzed using odds ratios and 95% confidence intervals. RESULTS: No statistically significant differences were found between the positive autologous serum skin test patients with chronic urticaria and the control group. CONCLUSIONS: We found that in this population group, there was no specific association between the HLA alleles studied and chronic urticaria. We believe that further population studies are needed in order to investigate the possible existence of this association.
FUNDAMENTOS: A associação entre os alelos do MHC classe I e II e a urticária crônica idiopática tem sido previamente constatada em diferentes populações, sendo que na população brasileira ainda não existem estudos a este respeito. OBJETIVOS: Foi estudado o envolvimento do MHC classe I e II (locci A, B e DR) em pacientes brasileiros com urticária crônica idiopática e teste cutâneo do soro autólogo positivo, comparando-se com um grupo populacional saudável. MÉTODOS: O DNA foi extraído do sangue de 42 pacientes com urticária crônica idiopática e o MHC classe I e II determinado por reação em cadeia da polimerase e teste laboratorial de hibridização de oligonucleotídeo com sonda de filamento único. A freqüência destes alelos em pacientes com urticária crônica idiopática foi comparada com a de 1000 doadores de sangue voluntários e geneticamente não relacionados, da mesma região do Brasil. O diagnóstico de urticária crônica idiopática foi baseado na história clínica do paciente e exames laboratoriais de rotina; foram selecionados apenas os pacientes com teste cutâneo do soro autólogo positivo. O resultado da distribuição alélica entre o grupo de pacientes e o grupo controle foi analisado através do odds rate com o cálculo do intervalo de confiança de 95% (95% IC). RESULTADOS: Não foram encontradas diferenças com significância estatística entre os pacientes com urticária crônica teste cutâneo do soro autólogo positivos e o grupo controle. CONCLUSÕES: Verificamos que neste grupo populacional estudado não houve associação específica entre os alelos HLA estudados e a urticária crônica; acreditamos na necessidade de outros estudos populacionais, para podermos verificar a possível existência desta associação.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe II/análise , Urticária/genética , Alelos , Estudos de Casos e Controles , Doença Crônica , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Reação em Cadeia da Polimerase , Testes Cutâneos , Urticária/imunologiaRESUMO
Leptospirosis is an important global human and veterinary health problem. Humans can be infected by exposure to chronically infected animals and their environment. An important focus of the current leptospiral research is the identification of outer membrane proteins (OMPs). Due to their location, leptospiral OMPs are likely to be relevant in host-pathogen interactions, hence their potential ability to stimulate heterologous immunity. The existing whole-genome sequence of Leptospira interrogans serovar Copenhageni offers a unique opportunity to search for cell surface proteins. Predicted genes encoding potential surface proteins were amplified from genomic DNA by PCR methodology and cloned into an Escherichia coli expression system. The partially purified recombinant proteins were probed by Western blotting with sera from human patients diagnosed with leptospirosis. Sixteen proteins, out of a hundred tested, were recognized by antibodies present in human sera. Four of these proteins were conserved among eight serovars of L. interrogans and absent in the non-pathogenic Leptospira biflexa. These proteins might be useful for the diagnosis of the disease as well as potential vaccine candidates.
Assuntos
Proteínas da Membrana Bacteriana Externa/análise , Leptospira interrogans/genética , Leptospirose/imunologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/metabolismo , Western Blotting , DNA Bacteriano/análise , Genoma Bacteriano , Humanos , Leptospira interrogans/química , Leptospira interrogans/imunologia , Leptospirose/prevenção & controle , Proteínas Recombinantes/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologiaRESUMO
Existem diversos derivados de hidrazina com atividade farmacológica, todos apresentando propriedades carcinogênicas em animais experimentais. Muitos derivados mono e dissubstituídos produzem radicais alquila quando da oxidaçäo por sistemas biológicos. Nossos resultados demonstraram que neutrófilos ativados säo capazes de metabolizar derivados de hidrazina mono e dissubstituídos a radicais alquila, detectados por ressonância paramagnética electrônica/captaçäo de spin, sendo caracterizado o papel de mieloperoxidase e de espécies reativas de oxigênio. Na investigaçäo dos mecanismos de toxicidade dos DH, nossos resultados estabeleceram uma correlaçäo entre a citotoxicidade sobre os fibroblastos de camundongo (medida pela inibiçäo da incorporaçäo de [nH]-dT) e a formaçäo de radicais alquila...
Assuntos
Animais , Ratos , Carcinógenos , Linhagem Celular , Fibroblastos , Hidrazinas/toxicidade , Neutrófilos , Proto-Oncogenes , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
There are several hydrazine derivatives with pharmacological activity, all of which have carcinogenic properties in experimental animals. Several mono- and disubstituted derivatives have been shown to produce carbon-centered radicals upon oxidation by enzymatic systems such as HbO2' Cytochrome P-450, monoamine oxidases, horseradish peroxidase and myeloperoxidase. Proposed mechanisms of hydrazine metabolism leading to alkylating species are discussed. The in vitro induction of DNA alterations by carbon-centered radicals generated in hydrazine metabolism ascertains the possibility of its occurrence in vivo. Our results, discussed herein, established the induction of cytotoxicity, proliferation and transformation of cultured mouse fibroblasts by systems in which hydrazine-derived alkyl radicals are formed. These studies represent another step towards distinguishing the possible involvement of metabolism-generated carbon-centered radicals in the onset of carcinogenic processes, which reinforces the importance of additional experimental approaches in order to consolidate this hypothesis.
