HELICOBACTER PYLORI INFECTION AND GASTRIC CANCER PRECURSOR LESIONS: PREVALENCE AND ASSOCIATED FACTORS IN A REFERENCE LABORATORY IN SOUTHEASTERN BRAZIL.

BACKGROUND: Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. OBJECTIVE: To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. METHODS: A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. RESULTS: Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. CONCLUSION: The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.

Infecção por Helicobacter pylori e lesões precursoras de câncer gástrico: prevalência e fatores associados em um laboratório de referência no Sudeste do Brasil / Helicobacter pylori infection and gastric cancer precursor lesions: prevalence and associated factors in a reference laboratory in southeastern brazil

ABSTRACT BACKGROUND: Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. OBJECTIVE: To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. METHODS: A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. RESULTS: Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. CONCLUSION: The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.

RESUMO CONTEXTO: A infecção por Helicobacter pylori é o fator de risco mais importante para atrofia gástrica e metaplasia intestinal, ambas consideradas lesões precursoras do câncer gástrico. Portanto, a investigação da ocorrência de infecção por H. pylori, das lesões precursoras e dos fatores associados orienta a adoção de estratégias específicas para o controle deste tipo de câncer. OBJETIVO: Avaliar a prevalência de infecção por H. pylori em pacientes submetidos à endoscopia digestiva alta, bem como a prevalência de metaplasia intestinal, atrofia e inflamação crônica e a associação destas com a infecção por H. pylori. MÉTODOS: Foi realizado um estudo retrospectivo com base em laudos de biópsias endoscópicas gástricas realizadas em laboratório privado afiliado ao Sistema Único de Saúde (SUS). Os pacientes foram avaliados quanto à idade, sexo e tipo de serviço de saúde. As amostras foram avaliadas quanto à presença de H. pylori e também de inflamação crônica, metaplasia intestinal e atrofia glandular. RESULTADOS: Do total de 4.604 pacientes (idade média de 51±16,6), 63,9% eram do sexo feminino e 63,1% provenientes de serviços de saúde privado. A prevalência de infecção por H. pylori foi de 31,7% (n=1.459) e o percentual de infecção foi significativamente maior nos pacientes do serviço público de saúde (42,0%) em relação aos pacientes do serviço privado de saúde (25,6%). Entre os pacientes com H. pylori (+), foi observado maior percentual de metaplasia intestinal (17,7% vs 13,3%) e atrofia glandular (17,6% vs 6,9%) quando comparados aos H. pylori (-) (P<0,01). Dos pacientes H. pylori (+) com pelo menos um tipo de lesão precursora (n=418), 161 (38,5%) apresentaram metaplasia e inflamação crônica, 160 (38,3%) apresentaram atrofia e inflamação crônica e, finalmente, 97 (23,2%) apresentaram metaplasia, atrofia e inflamação crônica simultaneamente. CONCLUSÃO: O presente estudo reforça a associação da infecção por H. pylori com lesões precursoras de câncer gástrico em uma população brasileira, enfatizando a importância de medidas de prevenção de infecção, bem como o tratamento de pacientes infectados, principalmente em regiões com níveis socioeconômicos mais baixos que apresentam maior prevalência de infecção por H. pylori.

Challenging Mycobacterium tuberculosi s dormancy mechanisms and their immunodiagnostic potential

ABSTRACT Mycobacterium tuberculosis is the etiologic agent of tuberculosis, one of the world's greatest cause of morbidity and mortality due to infectious disease. Many evolutionary mechanisms have contributed to its high level of adaptation as a host pathogen. Prior to become dormant, a group of about 50 genes related to metabolic changes are transcribed by the DosR regulon, one of the most complex and important systems of host-pathogen interaction. This genetic mechanism allows the mycobacteria to persist during long time periods, establishing the so-called latent infection. Even in the presence of a competent immune response, the host cannot eliminate the pathogen, only managing to keep it surrounded by an unfavorable microenvironment for its growth. However, conditions such as immunosuppression may reestablish optimal conditions for bacterial growth, culminating in the onset of active disease. The interactions between the pathogen and its host are still not completely elucidated. Nonetheless, many studies are being carried out in order to clarify this complex relationship, thus creating new possibilities for patient approach and laboratory screening.

Challenging Mycobacterium tuberculosis dormancy mechanisms and their immunodiagnostic potential.

Mycobacterium tuberculosis is the etiologic agent of tuberculosis, one of the world's greatest cause of morbidity and mortality due to infectious disease. Many evolutionary mechanisms have contributed to its high level of adaptation as a host pathogen. Prior to become dormant, a group of about 50 genes related to metabolic changes are transcribed by the DosR regulon, one of the most complex and important systems of host-pathogen interaction. This genetic mechanism allows the mycobacteria to persist during long time periods, establishing the so-called latent infection. Even in the presence of a competent immune response, the host cannot eliminate the pathogen, only managing to keep it surrounded by an unfavorable microenvironment for its growth. However, conditions such as immunosuppression may reestablish optimal conditions for bacterial growth, culminating in the onset of active disease. The interactions between the pathogen and its host are still not completely elucidated. Nonetheless, many studies are being carried out in order to clarify this complex relationship, thus creating new possibilities for patient approach and laboratory screening.

Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis.

The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.

Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis

The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.

Effects of aqueous extract of Echinodorus grandiflorus on the immune response in ovalbumin-induced pulmonary allergy.

BACKGROUND: Asthma is a disease characterized by intermittent obstruction of the airways and chronic inflammation that affects approximately 300 million people worldwide. The immune response in asthma is predominantly T(H)2, with high levels of total and allergen-specific IgE and bronchial eosinophilia. Asthma treatment is aimed at controlling the disease, and the drugs used currently have systemic adverse effects and generally are not effective in difficult-to-control cases. OBJECTIVE: To investigate the effect of aqueous extract of Echinodorus grandiflorus, a plant used in folk medicine for its diuretic and anti-inflammatory properties, in a model of pulmonary allergy. METHODS: BALB/c mice were intraperitoneally sensitized and nasally challenged with ovalbumin. Aqueous extract and dexamethasone treatments (0.1 mL/d per mouse) were initiated on day 32 and concluded on day 40. Eight hours after the last challenge evaluations, of serum, bronchoalveolar lavage, and lung tissue were performed. RESULTS: Oral treatment with the extract markedly reduced the number of total cells and eosinophils in bronchoalveolar lavage. The eosinophil peroxidase activity in lung tissue, the levels of ovalbumin-specific IgE in serum, the levels of CCL11, and the gene expression of interleukin 4 and interleukin 13 in lung tissue were also lower after treatment. CONCLUSIONS: These results suggest that the aqueous extract of E grandiflorus is able to modulate allergic pulmonary inflammation and may be useful as a potential therapeutic agent for asthma.

Expressão de marcadores de proliferação celular e apoptose em carcinoma basocelular / Markers expression of cell proliferation and apoptosis in basal cell carcinoma

Fundamentos: O carcinoma basocelular é o câncer mais comum em humanos. Estudos que utilizam recursos da biologia molecular e genética, associados à histomorfologia, permitem a identificação de fatores de risco no desenvolvimento de lesões mais recorrentes e agressivas. Objetivo: Correlacionar a expressão dos marcadores de apoptose (p53 e Bcl-2) e proliferação celular (Ki-67 e PCNA) com os indicadores histológicos de gravidade do tumor. Métodos: Estudaram-se cinco amostras das formas nodular, morfeiforme e superficial, respectivamente, e um grupo-controle com três pacientes livres de lesão. Empregou-se o teste de Mann-Whitney na comparação da expressão desses marcadores com a forma de apresentação do carcinoma basocelular. Resultados: Verificou-se que a marcação do Bcl-2 foi expressiva nos CBCs ditos agressivos (variantes morfeiforme e nodular). Dos tumores estudados, 66,7 por cento (n = 10) indicaram fortemente o p53. Nossos resultados mostram maior expressão do Ki-67 no carcinoma basocelular nodular e superficial, sem expressão nos controles. O PCNA mostrou forte marcação em todos os tipos de tumores e nos controles. Conclusão: Os achados nos permitem concluir que o Bcl-2 e o p53 apresentam tendência para diagnosticar gravidade do carcinoma basocelular e o Ki-67, por seu comportamento variável, não pode ser considerado como marcador de gravidade, assim como o PCNA, que não foi um bom marcador de proliferação celular.

Background: - Basal cell carcinoma is the most common form of human cancer. Studies employing molecular and genetic biology techniques, associated with histomorphology, lead to the identification of risk factors in the development of more recurring and aggressive lesions. Objetive - To correlate markers expression of apoptosis (p53 and bcl-2) and cell proliferation (Ki-67 and PCNA) with histological indicators of tumor severity. Methods - Five samples of the nodular, morpheaform and superficial types of carcinoma were studied, espectively.One control group with three lesion-free patients was also included in the study. The Mann-Whitney test was used to compare these markers expression with the manifestation form of basal cell carcinoma. Results - Bcl-2 expression was significant in basal cell carcinomas said to be aggressive (morpheaform and nodular types). Of the studied tumors, 66.7 percent (n =10) strongly expressed p53.Our results show a greater expression of Ki-67 in nodular and superficial basal cell carcinoma, with no expression in the controls. PCNA showed a strong expression in all types of tumors and in the controls. Conclusion - The findings allow us to conclude that Bcl-2 and p53 show a tendency to indicate the severity of basal cell carcinoma. In contrast, Ki-67, due to its variable behavior, cannot be considered a marker of severity. Also, PCNA was not a good marker of cell proliferation.

Expressão de marcadores de proliferação celular e apoptose no carcinoma espinocelular de pele e ceratose actínica / Expression of cell proliferation and apoptosis biomarkers in skin spinocellular carcinoma and actinic keratose

FUNDAMENTOS: O câncer de pele é o mais frequente tipo de câncer humano e mostra aumento de sua incidência. Em muitos casos, antes do surgimento do carcinoma, instala-se uma lesão precursora, ceratose actínica, podendo evoluir para carcinoma espinocelular. Estudos buscam determinar os parâmetros com significado prognóstico na predição daqueles tumores que terão comportamento mais agressivo. OBJETIVO: Avaliar a expressão dos marcadores de proliferação celular (PCNA, Ki-67) e apoptose (p53, Bcl-2), em portadores de carcinoma espinocelular e ceratose actínica. MÉTODO: Foram estudadas amostras de 30 pacientes: sendo dez portadores do carcinoma espinocelular; dez de ceratose actínica e dez indivíduos livres de lesões submetidos à blefaroplastia. RESULTADOS: A proteína p53 foi expressa em todos os casos estudados, embora apresentassem padrões quantitativos diferentes. O Bcl-2 foi expresso em baixa intensidade. Em seis casos de ceratose actínica, nas peles de blefaroplastia, e negativo nos casos de carcinoma espinocelular. O PCNA exibiu expressão intensa, em todas as amostras. O Ki-67 apresentou expressão variável, nos casos de carcinoma e de ceratose, e negativo na pele de pálpebra. CONCLUSÃO: A expressão do Ki-67 e a não-expressão de Bcl-2, no grupo CEC, indica intensificação da atividade proliferativa. Ao passo que, a maior expressão de p53 e Bcl-2, no grupo CA, sugere imortalização celular.

BACKGROUND: Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion - actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to etermine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. OBJECTIVE: To evaluate the expression of markers of cell proliferation (PCNA, Ki-67) and apoptosis (p53,Bcl-2) in patients with squamous cell carcinoma and actinic keratosis. METHOD: We studied samples from 30 patients, ten patients of squamous cell carcinoma, ten with actinic keratosis and ten lesion-free samples from blepharoplasty. RESULTS: p53 protein was expressed in all cases with different quantitative patterns. Bcl-2 was expressed at low intensity in six cases of actinic keratosis in the skin from blepharoplasty and negative in cases of squamous cell carcinoma. PCNA showed intense expression in all samples. Ki-67 showed variable expression in cases of keratosis and carcinoma and negative in the skin from the eyelid. CONCLUSION: The high expression of Ki-67 associated with low expression of Bcl-2 indicates proliferation in the carcinoma group. Thus, expression of p53 and Bcl-2 in patients with actinic keratosis indicates cell immortalization.

[Markers expression of cell proliferation and apoptosis in basal cell carcinoma]. / Expressão de marcadores de proliferação celular e apoptose em carcinoma basocelular.

BACKGROUND: - Basal cell carcinoma is the most common form of human cancer. Studies employing molecular and genetic biology techniques, associated with histomorphology, lead to the identification of risk factors in the development of more recurring and aggressive lesions. OBJECTIVE - To correlate markers expression of apoptosis (p53 and bcl-2) and cell proliferation (Ki-67 and PCNA) with histological indicators of tumor severity. METHODS - Five samples of the nodular, morpheaform and superficial types of carcinoma were studied, respectively.One control group with three lesion-free patients was also included in the study. The Mann-Whitney test was used to compare these markers expression with the manifestation form of basal cell carcinoma. RESULTS - Bcl-2 expression was significant in basal cell carcinomas said to be aggressive (morpheaform and nodular types). Of the studied tumors, 66.7% (n =10) strongly expressed p53.Our results show a greater expression of Ki-67 in nodular and superficial basal cell carcinoma, with no expression in the controls. PCNA showed a strong expression in all types of tumors and in the controls. CONCLUSION - The findings allow us to conclude that Bcl-2 and p53 show a tendency to indicate the severity of basal cell carcinoma. In contrast, Ki-67, due to its variable behavior, cannot be considered a marker of severity. Also, PCNA was not a good marker of cell proliferation.

[Expression of cell proliferation and apoptosis biomarkers in skin spinocellular carcinoma and actinic keratosis]. / Expressão de marcadores de proliferação celular e apoptose no carcinoma espinocelular de pele e ceratose actínica.

BACKGROUND: Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion--actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to determine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. OBJECTIVE: To evaluate the expression of markers of cell proliferation (PCNA, Ki-67) and apoptosis (p53,Bcl-2) in patients with squamous cell carcinoma and actinic keratosis. METHOD: We studied samples from 30 patients, ten patients of squamous cell carcinoma, ten with actinic keratosis and ten lesion-free samples from blepharoplasty. RESULTS: p53 protein was expressed in all cases with different quantitative patterns. Bcl-2 was expressed at low intensity in six cases of actinic keratosis in the skin from blepharoplasty and negative in cases of squamous cell carcinoma. PCNA showed intense expression in all samples. Ki-67 showed variable expression in cases of keratosis and carcinoma and negative in the skin from the eyelid. CONCLUSION: The high expression of Ki-67 associated with low expression of Bcl-2 indicates proliferation in the carcinoma group. Thus, expression of p53 and Bcl-2 in patients with actinic keratosis indicates cell immortalization.