RESUMO
Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithelial cells. Here, we show that upon H. pylori infection, abasic (AP) sites accumulate and lead to increased levels of double-stranded DNA breaks (DSBs). In contrast, downregulation of the OGG1 DNA glycosylase decreases the levels of both AP sites and DSBs during H. pylori infection. Processing of AP sites during different phases of the cell cycle leads to an elevation in the levels of DSBs. Therefore, the induction of oxidative DNA damage by H. pylori and subsequent processing by BER in normal gastric epithelial cells has the potential to lead to genomic instability that may have a role in the development of gastric cancer. Our results are consistent with the interpretation that precise coordination of BER processing of DNA damage is critical for the maintenance of genomic stability.
RESUMO
OBJECTIVES: To study the occurrence of female genital tuberculosis (FGTB) in Ethiopia and to compare the different methods available for its diagnosis. METHODS: Biopsy or curettage samples from 25 clinically suspected cases of FGTB were investigated with histopathology, smear microscopy, TB culture and PCR for mycobacteria. HIV status was determined by ELISA. CD4:CD8 ratio was evaluated by flow cytometry. RESULTS: Among the 25 clinically suspected patients investigated, only one was AFB smear positive, three were culture positive, seven were histology positive and 12 were positive by PCR (a total of 16 positives). Samples taken from the fallopian tube were more frequently positive than those from the endometrium. CONCLUSIONS: The results showed that FGTB is a significant clinical problem in Ethiopia. A combination of PCR with the other available methods was found to be the best alternative to achieve sufficient sensitivity and specificity for the diagnosis of FGTB in this setting.
Assuntos
Tuberculose dos Genitais Femininos/epidemiologia , Adolescente , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias , Etiópia/epidemiologia , Feminino , Citometria de Fluxo , Soropositividade para HIV/epidemiologia , Humanos , Reação em Cadeia da Polimerase , Tuberculose dos Genitais Femininos/diagnósticoRESUMO
UNLABELLED: To study the occurrence of female genital tuberculosis (FGTB) in Ethiopia and to compare the different methods available for its diagnosis. METHODS: Biopsy or curettage samples from twenty-five clinically suspected cases of FGTB were investigated with histopathology, smear microscopy, TB culture and PCR for mycobacteria. HIV status was determined by ELISA. CD4:CD8 ratio was evaluated by flow cytometry. RESULTS: Among the 25 clinically suspected patients investigated, only one was AFB smear positive, three were culture positive, seven were histology positive and 12 were positive by PCR (a total of 16 positives). Samples taken from the fallopian tube were more frequently positive than those from the endometrium. CONCLUSIONS: The results showed that FGTB is a significant clinical problem in Ethiopia. A combination of PCR with the other available methods was found to be the best alternative to achieve sufficient sensitivity and specificity for the diagnosis of FGTB in this setting.
Assuntos
Tuberculose dos Genitais Femininos/epidemiologia , Adolescente , Adulto , Antígenos de Bactérias , Proteínas de Bactérias , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Etiópia/epidemiologia , Feminino , Citometria de Fluxo , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Reação em Cadeia da Polimerase , Estatísticas não Paramétricas , Tuberculose dos Genitais Femininos/diagnósticoRESUMO
The number of registered leprosy patients world-wide has decreased dramatically after extensive application of WHO recommended Multiple Drug Therapy (MDT). The annual number of new cases has, however, been almost unchanged in several populations, indicating that the infection is still present at community level. Nasal carriage of Mycobacterium leprae DNA was studied in Lega Robi village in Ethiopia. MDT had been applied for more than ten years, and 718 residents over 5 years old were eligible for the study. During the first survey nasal swab samples were collected from 664 (92.5%) individuals. The results of a Peptide Nucleic Acid-ELISA test for M. leprae DNA interpreted by stringent statistical criteria were available for 589 (88.7%) subjects. Thirty-five (5.9%) individuals without clinical signs of leprosy were positive for M. leprae DNA. Seven PCR positive individuals lived in a household where one or two other members were also positive for M. leprae DNA. During a second survey 8 (46%) of 175 interpretable PNA-ELISA tests were positive. Of 137 individuals tested twice, only two were positive on both occasions whereas 10 were PCR positive only once. The study confirms the widespread distribution of M. leprae DNA in healthy individuals. The feasibility of curbing possible transmission of subclinical infection needs further consideration.
Assuntos
Portador Sadio/epidemiologia , DNA Bacteriano/análise , Hanseníase/epidemiologia , Mycobacterium leprae/isolamento & purificação , Nariz/microbiologia , Adolescente , Adulto , Idoso , Portador Sadio/microbiologia , Criança , Ensaio de Imunoadsorção Enzimática , Etiópia/epidemiologia , Feminino , Humanos , Hanseníase/transmissão , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
The number of registered leprosy patients world-wide has decreased dramatically after extensive application of WHO recommended Multiple Drug Therapy (MDT). The annual number of new cases has, however, been almost unchanged in several populations, indicating that the infection is still present at community level. Nasal carriage of Mycobacterium leprae DNA was studied in Lega Robi village in Ethiopia. MDT had been applied for more than ten years, and 718 residents over 5 years old were eligible for the study. During the first survey nasal swab samples were collected from 664 (92.5%) individuals. The results of a Peptide Nucleic Acid-ELISA test for M. leprae DNA interpreted by stringent statistical criteria were available for 589 (88.7%) subjects. Thirty-five (5.9%) individuals without clinical signs of leprosy were positive for M. leprae DNA. Seven PCR positive individuals lived in a household where one or two other members were also positive for M. leprae DNA. During a second survey 8 (46%) of 175 interpretable PNA-ELISA tests were positive. Of 137 individuals tested twice, only two were positive on both occasions whereas 10 were PCR positive only once. The study confirms the widespread distribution of M. leprae DNA in healthy individuals. The feasibility of curbing possible transmission of subclinical infection needs further consideration.