Influência da amoxicilina na virulência do Helicobacter pylori

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Achados histopatológicos gástricos em crianças e adolescentes brasileiros com dispepsia e infecção por Helicobacter pylori

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desenvolvimento de compostos potencialmente ativos contra Helicobacter Pylori

Pós-graduação em Ciências Farmacêuticas - FCFAR

Determination of strains of Helicobacter pylori and of polymorphism in the interleukin-8 gene in patients with stomach cancer

CONTEXTO: A neoplasia gástrica é a segunda causa mais comum de morte por câncer no mundo e o H. pylori é classificado como carcinógeno humano tipo I pela Organização Mundial de Saúde. Entretanto, apesar da elevada prevalência da infecção pelo H. pylori em todo mundo, menos de 3% de indivíduos portadores dessa bactéria desenvolvem neoplasias gástricas. Tal fato indica que a evolução para malignização possa estar associada a fatores bacterianos, do hospedeiro e do ambiente. OBJETIVOS: Investigou-se a associação do polimorfismo da região promotora do gene IL-8 (-251) e do genótipo do H. pylori, baseado nos alelos vacA e na presença do gene cagA, com a clínica e os dados histopatológicos. MÉTODOS: Em estudo prospectivo, 102 pacientes com câncer gástrico e 103 voluntários saudáveis foram analisados. O polimorfismo da IL-8 (-251) foi determinado pela reação de PCR-RFLP e sequenciamento. Para genotipagem dos alelos vacA e do gene cagA das cepas bacterianas foi utilizada a PCR. As biopsias gástricas foram avaliadas histologicamente. RESULTADOS: A sorologia para o H. pylori foi positiva em 101 (99%) de todos os pacientes analisados, e 98 (97%) deles foram colonizados por apenas uma cepa bacteriana. Em pacientes com monoinfecção, 82 (84%) das cepas bacterianas observadas apresentavam o genótipo s1b/m1. O gene cagA foi detectado em 74 (73%) dos pacientes infectados pelo H. pylori. A presença do gene cagA demonstrou estar associada com a presença do genótipo s1b/m1 do gene vacA (P = 0,002). Quanto ao polimorfismo do gene da IL-8 (-251), observou-se que os genótipos AA (P = 0,026) e AT (P = 0,005) foram mais frequentes no grupo de pacientes com adenocarcinoma gástrico. Comparando os diferentes tipos de cepas bacterianas isoladas, com o polimorfismo do gene da IL-8-251 e dados histopatológicos, observou-se que, portadores do alelo A (AT e AA) infectados por cepas virulentas (m1s1 cagA+), demonstraram risco aumentado de apresentar maior grau de inflamação (OR = 24,75 IC 95% 2,29-267,20 P = 0,004) e aumento da atividade neutrofílica (OR = 28,71 IC 95% 2.62-314 P = 0,002) na mucosa gástrica. CONCLUSÃO: Os resultados demonstram que a interação entre o polimorfismo do gene da IL-8, particularmente em portadores do alelo A, e o tipo de cepa infectante do H. pylori (s1m1 cagA positiva) desempenha importante função no desenvolvimento do câncer gástrico.

Detection of Helicobacter pylori in gastric cancer

Background and Objectives — Considering the high prevalence of stomach cancer in the northern region of Brazil and the recognized relationship between chronic gastric inflammation caused by Helicobacter pylori, and its carcinogenic potential, the objective we had with this study was to investigate the presence of the microorganism in macro and microscopic presentations of neoplasm in different regions of the stomach, and in non-malignant lesions concomitant to the adenocarcinoma in patients originating from the metropolitan area of Belém (State of Pará, Brazil). Methods - Examinations were made on 172 patients divided into two groups: group I, formed by 75 patients with gastric carcinoma, and group II, formed by 97 patients with mild enanthematic gastritis, considered control group. The diagnosis was obtained during endoscopic examination and the respective biopsy. Gastric neoplasms were classified macroscopically in accordance with Borrmann's classification, and microscopically in accordance with Laurén's classification. In group I, 54 patients were male and 21 female while in group II, 22 patients were male and 75 female. The average age in group I was 61.2 years (range 27 to 86 years), while in group II it was 37.5 years (range 16 to 69 years). Thin sections were prepared and stained using the hematoxylin-eosin method. In the Helicobacter pylori research, the modified Gram stain was utilized. Statistical analysis was done by utilizing the chi-squared (c 2) test, Mann-Whitney test (U), and Fisher's exact test. Results - The results showed the detection of Helicobacter pylori were significantly greater in patients with mild enanthematic gastritis than in patients with gastric carcinoma. The presence of Helicobacter pylori in patients with gastric carcinoma and mild enanthematic gastritis was significantly greater in the antral region than in other gastric regions. Helicobacter pylori detection in patients with gastric carcinoma did not present a significant difference in relation to the macroscopic aspect of the tumor either intestinal or diffuse histological types. Conclusions - These data suggest the presence of the bacteria is predominant in the antral region and it does not show relation with the macroscopic types or histological intestinal or diffuse types of gastric carcinoma.

Sugarcane tolerance to ratoon eradication with glyphosate determined by physiological responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Alkyl Caffeates as Anti-Helicobacter Pylori and Scavenger of Oxidants Produced by Neutrophils

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dor abdominal crônica, dispepsia não ulcerosa e infecção pelo Helicobacter pylori em crianças e adolescentes

Pós-graduação em Patologia - FMB

Interleukin-6 polymorphism and Helicobacter pylori infection in Brazilian adult patients with chronic gastritis

Helicobacter pylori is recognised as the most common cause of chronic active gastritis and this bacterium is also an important pathogenic factor in peptic ulcer disease. The biological factors that influence clinical outcome in H. pylori infection have been extensively studied. In addition to immunological factors in the host, bacterial virulence determinants in H. pylori strains are likely to play a crucial role in gastric cancer development. Single-nucleotide polymorphisms at the 5' flanking region of the interleukin (IL)-6 gene promoter (G or C at -174 base) have been identified and individuals with the G allele at position -174 have been shown to produce higher levels of IL-6 than those with the C/C genotype. The mucosal levels of IL-6 were reported to be increased in H. pylori-associated gastritis. The present study was conducted to examine any relationship between inflammatory cytokine polymorphisms and the inflammatory process in mucosa infected by H. pylori. In our study we did not find any association between the C and G alleles in adult patients with chronic gastritis and inflammatory process in gastric mucosa.

Antimicrobial activity of natural products against Helicobacter pylori: a review

Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection.

Valor de corte para teste respiratório com isótopos estáveis (Carbono 13) no diagnóstico do Helicobacter pylori utilizando IRMS para análise do sopro

After the isolation of Helicobacter pylori from an injury at the stomach mucosa by Marshall and Wareen, work that was recognized with the Nobel Prize of Medicine or Physiology in 2005, many other works showed the relationship between the presence of H. pylori and diseases at the digestive system, such as gastritis, gastric, duodenal and peptic ulcer, and stomach cancer. The 13C-Urea Breath Test - 13C-UBT is a non-invasive diagnostic method that utilizes the breath of a patient to determine the presence of H. pylori through stable isotopes. This work aimed to find an ideal 13C-UBT Isotopic Ratio Mass Spectroscopy cut-off value (a threshold between positive and negative) to diagnose H. pylori infection at Brazilian population. Patients were selected at the UNESP-Botucatu Clinical Hospital Endoscopy Section. With these results it was possible to indicate that the best cut-off value is between 2.5 to 6 ‰ of Delta Over Baseline (DOB)

Helibacter pylori: preaparação de Lapdesf-IUNI e ensaio de inibição de urease (IC50) de derivados de tiouréia e guanidínicos

O presente trabalho de conclusão de curso visou à otimização e preparação da síntese de Lapdesf-IUNI e avaliação do potencial de inibição de urease de três compostos previamente sintetizados, direcionados especificamente para o tratamento de infecções por Helicobacter pylori, bactéria mundialmente reconhecida como uma das principais causadoras de infecções no mundo, responsável pelos casos de infecções gástricas, como gastrites crônicas, úlceras (gástricas e duodenais) e carcinomas. Lapdesf-IUNI é um composto derivado de metronidazol, com atividade potencialmente inibidora de urease, enzima presente neste microrganismo e essencial a sua sobrevivência no ambiente gástrico. O produto foi obtido, porém com baixo rendimento, por isso sua metodologia ainda necessita ser aperfeiçoada, para que, em seguida este composto possa ser testado. Outros três compostos, um derivado de tiouréia e dois derivados guanidínicos, com potencial atividade inibidora de urease, T-6, R-17 e R-21, sintetizados pela equipe do Prof. Eduardo Perez, foram avaliados com relação a sua atividade inibidora frente à enzima urease e IC50, apresentando bons resultados, que permitem a continuidade dos estudos, comparando inclusive com fármacos utilizados nos protocolos de tratamento padrões para o tratamento das infecções causadas por H. pylori

Influência do SNP T3801C CYP1A1 sobre os níveis de danos oxidativos no DNA de células da mucosa gástrica de pacientes infectados pelo H. Pylori

Helicobacter pylori (H. pylori) is a common gastric pathogen that has infected more than 50% of the population of the world and it has been associated with chronic gastritis, gastric ulcers, duodenal ulcer, and gastric cancer. Although, almost all infected people develop gastritis, there is a variety of clinical outcomes, and only a minority (<1%) of infected individuals develop gastric cancer. There are evidences which suggest that the chronic inflammatory reaction caused by the bacterial infection may be involved in the production of reactive oxygen species or reactive nitrogen species. It may lead to DNA damage, which together with the cellular response could lead to gene mutations, chromosomal aberrations characterizing genomic instability that may represent the early step in gastric carcinogenesis. The extent and severity of gastric mucosal inflammation, as well as the clinical outcome of the infection, depend on a number of factors, including the host genetic susceptibility such SNP T3801 CYP1A1, immune response, age at which the infection was acquired, environmental factors, especially dietary and bacterial virulence factors. Due to the risk of developing gastric cancer in humans infected by H. pylori, we used the Comet Assay to investigate the influence of the SNP T3801C CYP1A1 on levels of oxidative DNA damage in gastric epithelial cells. The study was conducted with biopsies from the gastric antrum and corpus of 103 H. pylori-infected patients and 24 uninfected control patients. Genotype of SNP T3801C CYP1A1 was determined by PCR-RFLP and DNA damage levels were measured in gastric mucosal cells from antrum and corpus by the Comet assay. Levels of DNA damage in gastric mucosa cells from antrum and corpus of H. pylori-infected patients with mild, moderate, severe gastritis, and gastric cancer were significantly higher compared to uninfected normal mucosa cells. However, levels... (Complete abstract click electronic access below)

Atividade anti-Helicobacter pylori de extratos hidroetanólicos de caule e folhas de Astronium fraxinifolium e Astronium graveolens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)