Orientadores: Nelci Fenalti Hoehr, Alessandra Gambero / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T07:18:18Z (GMT). No. of bitstreams: 1 Marostica_MartaContieri_M.pdf: 4600757 bytes, checksum: 4c8d07137661d1c9c63647c1959bc5bf (MD5) Previous issue date: 2007 / Resumo: O mecanismo pelo qual o H. pylori provoca a inflamação gástrica inclui a secreção de substâncias pró-inflamatórias pela bactéria e a estimulação da liberação de citocinas induzida pelo contato direto entre a bactéria e as células epiteliais gástricas. A resposta inicial à infecção por H. pylori é predominantemente neutrofílica e estes, liberam mediadores inflamatórios e enzimas proteolíticas que induzem o dano gástrico. Estresse oxidativo ocorre em pacientes infectados com H. pylori onde a expressão de enzimas como a óxido nítrico sintase induzida (iNOS), superóxido dismutase e catalase encontram-se aumentadas. A iNOS participa da resposta inflamatória e promove a apoptose de células na mucosa gástrica. Durante a infecção por H. pylori, observa-se níveis reduzidos da expressão de Bcl-2 e o aumento da expressão de Bax na mucosa gástrica, sugerindo que uma tendência pró-apoptótica na infecção. A erradicação pode ser alcançada pela combinação de antibióticos associada a uma droga anti-ácida. As duas maiores classes de inibidores de secreção ácida são: os inibidores de bomba protônica, como o omeprazol, e os antagonistas de receptor de histamina H2, como a ranitidina. Várias evidências experimentais têm mostrado que o omeprazol apresenta efeitos anti-ulcerogênicos adicionais. Deste modo, o objetivo deste trabalho foi avaliar o efeito do tratamento com omeprazol e ranitidina em um modelo animal de infecção por H. pylori, enfocando possíveis propriedades adicionais destes fármacos Para este estudo foram utilizados camundongos machos C57BL/6 com 4 semanas de idade. Os camundongos receberam por via oro-gástrica suspensão de H. pylori. Na 11ª semana de inóculo, os animais foram tratados (i.p.) com omeprazol (100 mg/kg), ranitidina (100 mg/kg) ou veículo (PBS) durante 7 dias sempre no mesmo horário. As duas drogas inibiram a produção de ácido gástrico no tratamento agudo, porém no tratamento por uma semana, apenas o omeprazol inibiu a secreção ácida. Os animais tratados com omeprazol apresentaram um aumento significativo nos níveis de colonização gástrica e elevado nível de MPO. Ambas as drogas diminuíram as lesões da mucosa provocada pela infecção. O tratamento com omeprazol restaurou a produção de Bcl-2 na mucosa gástrica e não alterou a produção de Bax. O omeprazol não protegeu a mucosa gástrica contra o dano ao DNA gerado pela infecção e o tratamento com ranitidina aumentou os níveis de dano oxidativo ao DNA. Não observamos a presença de propriedades anti-neutrofílicas, atribuídas ao omeprazol, após uma semana de tratamento, sugerindo que essas propriedades são restrita a ensaios in vitro. Entretanto, o omeprazol restaurou a produção de Bcl-2 na mucosa gástrica, sugerindo uma atividade anti-apoptótica dessa droga / Abstract: H. pylori induces gastric inflammation characterized by secretion of pro-inflammatory substances by bacteria and the stimulation of cytokine release by the gastric epithelial cells. The initial response to the H. pylori infection is predominantly by neutrophils and these cells liberate inflammatory mediators and enzymes that induce the gastric damage. Oxidative stress also occurs in infected patients where induced nitric oxide sintase (iNOS), superoxide dismutase and catalase expression were increased. Nitric oxide participates in the inflammatory response and promotes apoptosis of gastric mucosa cells. Eradication therapy can be achieved with antibacterial agents in association with anti-acid drugs. There are two major classes of gastric acid inhibitors: the proton pump inhibitors, such as omeprazole, and the histamine H2 receptor antagonists, such as ranitidine. Some experimental evidence demonstrates that omeprazole has additional pharmacological properties. Thus, the aim of this study was to evaluate the effect of omeprazole and ranitidine treatment on H. pylori-infected mice, focusing on possible additional pharmacological properties. For this study, male C57BL/6 mice that received H. pylori suspension were used. After the 11th week, the mice were treated intraperitoneally (i.p.) with omeprazole (100 mg/kg), ranitidine (100 mg/kg) or vehicle (PBS) for 7 days. Both drugs inhibited the gastric acid production after acute administration; however after one week of treatment just omeprazole inhibited gastric acid secretion. Omeprazole-treated mice presented an increase in H. pylori and MPO levels in gastric mucosa. Both drugs reduced the mucosa damage provoked by H. pylori infection. Omeprazole treatment restored the Bcl-2 production in the gastric mucosa and did not modify Bax production. Omeprazole did not reduce the DNA damage in the gastric mucosa while ranitidine treatment increased it. We conclude that some additional omeprazole-related properties, such as antineutrophil properties, were not observed in H. pylori-infected mice after one week of treatment. However, the antiapoptotic activity of omeprazole could be attributed to an ability to modify the protein expression of Bcl-2, decreased by H. pylori infection / Mestrado / Patologia Clinica / Mestre em Ciências Médicas

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No. of bitstreams: 4 1-CapaFinal_1.pdf: 90775 bytes, checksum: c4f6f2534fe59c39e7eb14147ce16e9a (MD5) 2-ficha.pdf: 6030 bytes, checksum: b4b337f5058b8d68854f98d82a614d6c (MD5) 3-SumarioFinal_1.pdf: 188058 bytes, checksum: 96e5c8a96c05703663265eb75c5d68ce (MD5) 4-TeseCorrigida_1.pdf: 2150184 bytes, checksum: 94512b258a1bcccdeaa694a3d19716f2 (MD5) Previous issue date: 2012-07-23 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / The Amazonian riverine communities seem to have all of the conditions of sanitation and socioeconomic suspicions for the conditioning to the infection for Helicobacter pylori, bacterium associated to the etiopatogenia of several diseases gastrointestinais. In Brazil, they are registered on average, fifteen thousand cases of cancer of the digestive system a year, with a percentile adult in the north area. Once the H. pylori is considered one of the etiological agents of this malignitude, the objective of this study was to determine the prevalence of the infection for H. pylori and to accomplish the rising of epidemic variables and of susceptibility related to the bacterial infection in riverine communities, and to validate a rehearsal copromolecular for diagnosis of the infection. The accomplished study was of the type traverse, contemporary, analytical and observacional, understanding a sample of 200 individuals, of which they were collected blood, saliva and feces, besides the application of a questionnaire epidemic employee, with subjects driven to his/her identification, obtaining data on the conditions socioeconomic, hygienic, sanitary and symptoms. For detection sorologic of antibodies of the type IgG anti-H. pylori were used plasma samples that were tested for systemic antibodies of the type IgG anti-H. pylori through a rehearsal immunological, using the Kit Ridascreen Helicobacter IgG (RBiopharm AG, Germany); for detection it activates of the H. pylori, it was used the samples of feces that were tested through the Kit MKBIO H. pylori (MK BIO GMBH, DIMA, Germany). Besides the detection of antibodies and antigens for H. pylori, they were also applied techniques of molecular biology, in the fecal samples, to confirm the diagnosis of the infection, for direct detection of bacterial DNA, using the primers RNAr16S that amplify a fragment gene of 1200bp of the gender Helicobacter and the primers p1 and p2, which amplify a fragment gênico of 298 pb that codifies a protein antigenic of 26kDa species specify of the H. pylori. This research had about central point to the infection for the bacterium H. pylori, that was detected through three diagnosis methods: The sorologia, fecal antigen and PCR. The sorologia went to the chosen technique to relate with the epidemic aspects regarding the study, and the obtained results revealed a frequency of soropositive of 83,5% (167/200). The analysis of the epidemic variables related to the bacterial infection demonstrated a larger frequency of infected individuals female, in the age group from 0 to 17 years, in addition 97,4% of the population that ingested water without treatment were positive the infection. The comparison of the prevalence of the infection, obtained through the three different detection methods, they were high, however the detection copromolecular was what detected a smaller number of positive individuals (113/200), although it presents the largest indexes of sensibility 79% and specificities 100%. The detection copromolecular demonstrated to be an important tool in the detection of the bacterial infection, making possible in these populations the application of a test high sensibility and specificity, could be applied in the precocious detection of the patogen. / e sócio-econômicas suspeitas para o condicionamento à infecção por Helicobacter pylori, bactéria associada à etiopatogenia de várias doenças gastrointestinais. No Brasil, são registrados em média, quinze mil casos de câncer do aparelho digestivo por ano, com um maior percentual na região norte. Uma vez que o H. pylori é considerada um dos agentes etiológicos desta malignitude, o objetivo deste estudo foi determinar a prevalência da infecção por H. pylori e realizar o levantamento de variáveis epidemiológicas e de suscetibilidade relacionados à infecção bacteriana em comunidades ribeirinhas, e validar um ensaio copromolecular para diagnóstico da infecção. O estudo realizado foi do tipo transversal, contemporâneo, analítico e observacional, compreendendo uma amostra de 200 indivíduos, dos quais foram coletados sangue, saliva e fezes, além da aplicação de um questionário epidemiológico empregado, com questões dirigidas à sua identificação, obtendo dados sobre as condições socioeconômicas, higiênicas, sanitárias e sintomatologia apresentada. Para detecção sorológica de anticorpos do tipo IgG anti-H. pylori específicos foram utilizados amostras de plasma que foram testadas para anticorpos sistêmicos do tipo IgG anti-H. pylori através de um ensaio imunoenzimático, usando o Kit Ridascreen Helicobacter IgG (R-Biopharm AG, Alemanha); para detecção ativa do H. pylori, foi utilizado as amostras de fezes que foram testadas através do Kit MKBIO H. pylori (MK BIO GMBH, DIMA, Alemanha). Além da detecção de anticorpos e antígenos para H. pylori, também foram aplicadas técnicas de biologia molecular, nas amostras fecais, para confirmar o diagnóstico da infecção, por detecção direta do DNA bacteriano, utilizando os primers RNAr16S que amplificam um fragmento gênico de 1200bp do gênero Helicobacter e os primers P1 e P2, os quais amplificam um fragmento gênico de 298 pb que codifica uma proteína antigênica de 26kDa espécie especifica da H. pylori. Esta pesquisa teve como ponto central à infecção pela bactéria H. pylori, que foi detectada através de três métodos de diagnóstico: A sorologia, o antígeno fecal e PCR. A sorologia foi à técnica escolhida para relacionar com os aspectos epidemiológicos referentes ao estudo, sendo que os resultados obtidos revelaram uma frequência de soropositividade de 83,5% (167/200). A análise das variáveis epidemiológicas relacionadas à infecção bacteriana demonstrou uma maior frequência de indivíduos infectados do sexo feminino, na faixa etária de 0 a 17 anos, além do que 97,4% da população que ingeriam água sem tratamento foram positivos a infecção. A comparação da prevalência da infecção, obtidas através dos três diferentes métodos de detecção, foram elevadas, no entanto a detecção copromolecular foi o que detectou um menor número de indivíduos positivos (113/200), embora apresente os maiores índices de sensibilidade 79% e especificidades 100%. A detecção copromolecular demonstrou ser uma ferramenta importante na detecção da infecção bacteriana, possibilitando nestas populações a aplicação de um teste de elevada sensibilidade e especificidade, podendo ser aplicada na detecção precoce do patógeno.

Introdução: A reinfecção pelo Helicobacter pylori em países em desenvolvimento parece ser maior do que nos países desenvolvidos. O retratamento da bactéria e o controle periódico de cura são necessários, quando elevadas taxas de reinfecção são verificadas. O objetivo do trabalho foi determinar a taxa anual de reinfecção, em pacientes brasileiros com úlcera péptica, num seguimento de cinco anos. Métodos: Pacientes com úlcera péptica, diagnosticada por endoscopia digestiva alta e infecção pelo Helicobacter pylori documentada por histologia, teste da urease, reação em cadeia da polimerase e teste respiratório, foram tratados para erradicação da bactéria. A cura da infecção foi verificada com os mesmos exames, três meses após o término do tratamento. Avaliação clínica e teste respiratório foram realizados aos seis e nove meses. Com um ano de seguimento, endoscopia, exame histológico, teste da urease, reação em cadeia da polimerase e teste respiratório foram novamente realizados. Até o quinto ano de seguimento, foram feitas consultas semestrais e testes respiratórios anuais. Na inclusão dos pacientes e nos reinfectados foram estudados 15 diferentes genes da bactéria. Resultados; Cento e quarenta e sete pacientes foram seguidos: 19 por um ano, oito por dois anos, quatro por três anos, cinco por quatro anos e 98 por cinco anos, num total de 557 pacientes/ano. Não ocorreu reinfecção no primeiro ano. No segundo ano, dois pacientes se reinfectaram, no terceiro quatro pacientes, no quarto três pacientes e no quinto um paciente, num total de 10 reinfecções. A taxa anual de reinfecção por pacientes/ano foi de 1,8%. Conclusão: O Brasil, um país em desenvolvimento com alta prevalência da infecção pelo Helicobacter pylori, apresenta uma taxa de reinfecção semelhante à dos países desenvolvidos / Introduction: The Helicobacter pylori reinfection rate seems to be higher in developing countries, than in developed ones. If a high reinfection rate is verified, periodical exams and bacterial retreatment would be necessary. The objective of this study was to determine the annual reinfection rate of Helicobacter pylori, in Brazilian patients with peptic ulcer disease, in a five year follow-up. Methods: Patients, with peptic ulcer disease diagnosed by upper digestive endoscopy and Helicobacter pylori infection verified by histological examination, rapid urease test, polymerase chain reaction and urea breath test, were treated for bacterial eradication. The infection cure was determined by the same proceedings, three months after the treatments end. Clinical evaluation and urea breath test were performed at sixth and ninth months of the follow-up. At one year of the follow-up, upper digestive endoscopy, histological examination, rapid urea test, polymerase chain reaction and urea breath test were repeated. Up to the fifth year of follow-up semester clinical evaluation and annual urea breath test were performed. All the patients included in the study and all the reinfected patients were tested for fifteen different genes of the Helicobacter pylori. Results: One hundred and forty-seven patients were followed: nineteen patients for one year, eight patients for two years, four patients for three years, five patients for four years and ninety-eight patients for five years. The total of patients/years follow-up was 557. Reinfection did not occur in the first year of the follow-up. In the second year, two patients became reinfected; in the third year, four patients; in the fourth, three and in the fifth, one patient. The total of reinfected patients was 10. The annual reinfection rate was 1,8%. Conclusion: Brazil, a developing country, presents a high prevalence of Helicobacter pylori infection. Nonetheless, the reinfection rate is similar to the developed countries.

Orientador : Nelson Adami Andreollo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-01T06:39:22Z (GMT). No. of bitstreams: 1 CoelhoNeto_JoaodeSouza_M.pdf: 7373210 bytes, checksum: 6d9e611e766b06494974bc46984c317a (MD5) Previous issue date: 2002 / Resumo: A descoberta e a associação do Helicobacter pylori (HP) com as úlceras pépticas em 1983 trouxe mudanças sobre a fisiopatologia, etiologia e o tratamento desta doença. Alguns anos se passaram para que a comunidade médica e científica aceitassem amplamente que a úlcera péptica pudesse ter uma causa infecciosa. O conceito de que sem ácido não há úlcera norteou por muito tempo a tática terapêutica que passou pelas cirurgias como as gastrectomias e as vagotomias até chegar aos dias de hoje com o uso de potentes inibidores da bomba de prótons e associações antibióticas. O objetivo deste trabalho foi avaliar tardiamente os doentes submetidos à gastrectomia parcial como tratamento da úlcera péptica em época em que o HP ainda não era erradicado de forma intencional. A avaliação incluiu o estudo dos sintomas do pós-operatório em comparação com os pré-operatórios, tabagismo e etilismo, e a incidência de síndromes pós-gastrectomias; avaliação endoscópica incluindo, o tipo de cirurgia realizada e os achados macroscópicos da mucosa do coto gástrico, duodeno ou jejuno dependendo do tipo de reconstrução; avaliação histopatológica, incluindo a pesquisa de HP por dois métodos: histológico e teste de urease; e a possível associação do HP presente no estômago remanescente com as avaliações clínica, endoscópica e histopatológica pós-operatórias. Cinqüenta e nove doentes gastrectomizados por úlcera péptica entre os anos de 1985 e 1993 na UNICAMP foram convocados a comparecer no GASTROCENTRO, 44 (74,6%) eram do sexo masculino e tinham idade média de 55 anos com variação de 31 a 77 anos, passaram por entrevista clínica e por exame endoscópico, onde foram colhidos fragmentos de biópsia para teste de urease e para análise histopatológica, incluindo a pesquisa do HP. Além disto, foi pesquisada a presença do HP nas peças cirúrgicas ressecadas para constatação da presença ou não da bactéria no pré-operatório. Na avaliação clínica os resultados mostraram que 96% dos doentes apresentaram boa (Visick II) ou ótima (Visick I) evolução clínica pós-operatória tardia. Os sintomas pós-operatórios mais comuns foram dispepsias leves e independentes da presença ou não do HP. Algumas síndromes pós-gastrectomia como diarréia, anemia e dumping ocorreram em respectivamente em 11 (18,6%), dois (3,4%) e dois (3,4%) casos. A reconstrução tipo BI trouxe melhores resultados clínicos tardios com significância estatística (p<0.05) quando comparado com as reconstruções tipo BII e Y de Roux. Na avaliação endoscópica, a maioria dos doentes (52,5%) apresentou exame normal, enquanto os demais apresentaram gastrites enantematosa (37,3%), erosiva (8,5%). Recidiva da úlcera foi diagnosticada em dois doentes (3,4%). Na análise histopatológica foi observado uma incidência elevada de gastrite crônica (98,3%). A presença de HP ocorreu em 86% nos doentes antes da cirurgia e em 89,8% no pós-operatório tardio. As conclusões mostraram que os doentes gastrectomizados, apresentaram boa evolução clínica pós-operatória tardia. A gastrectomia parcial com reconstrução tipo BI foi a que trouxe melhores resultados clínicos a longo prazo. O HP apesar de estar presente no coto gástrico em 89,8% dos doentes não influenciou de forma negativa nos resultados clínicos, endoscópicos ou histopatológicos no pós-operatório tardio / Abstract: After the discovery of Helicobacter pylori (HP) and this relationship with the etiology and physiopathology of peptic ulcer in 1983, a lot has changed about the treatment of the duodenal and gastric ulcers. Many years have passed until the medical and scientific community accepted that peptic ulcer could have an infectious cause. That saying: no acid, no ulcer; guided the treatment for many years and these peptic ulcers were treated by surgery only, like antrectomy or hemigastrectomy plus vagotomy, that can eliminate the gastric acid production. Vagotomy with drainage procedures (without resection), have followed. Later, other physiological procedures were employed, like high selective vagotomy, where the ulcer recurrence is still high. The antacids and histamine receptor blocks were the first drugs used with good results. Later, the protons inhibitors pumps were introduced, which were stronger than the others. The objectives of this research were to evaluate later on those patients who underwent partial gastrectomy as a treatment for peptic ulcer, at that time when their did not use any antibiotic therapy to eradicate the Helicobacter pylori. The clinical evaluation included the late postoperative symptoms and comparing to the preoperative period, post gastrectomy syndromes like dumping, diarrhea, alkaline gastritis and nutritional aspects, smoking and alcoholism; endoscopic evaluation included surgery reconstruction and gastric stump, duodenum and jejunum mucosa aspects, histopathological evaluation included looking for Helicobacter pylori by using two different methods: histology and urease test. Fifty-nine patients, 44 (74,6%) male, median age 55,5 year old (range from 31 to 77 year old), who underwent a clinical interview and a high digestive endoscopy, where biopsies were collected from the gastric stump for urease test and histological analysis. Paraffin blocks from the surgical specimen were reanalyzed in order to find out if the patients did have or did not have Helicobacter pylori before surgery. The final results show that most of the patients had good and very good clinical evolution (Visick I e II) in 96%. The most common symptoms on late post operative are mild dyspepsia with or without HP, and an acceptable number of patients presented post gastrectomy syndromes like diarrhea, anemia and dumping. The Billroth I reconstruction had the best clinical results on statistical rate. On endoscopic view, 52,5% showed normal results and the other showed endoscopic enanthema gastritis, reflux alkaline gastritis or erosive gastritis. Ulcer recurrences were diagnosed in two patients (3,4%), and both had positive HP. In the histological analysis, a large number of chronic gastritis was found (98,3%). Most of the patients had HP (86%) before surgery and also in the postoperative time (89,9%). The conclusions showed that the patients had a very good clinical evolution. The Billroth I reconstruction had the best clinical results. The HP is still present on gastric stump in late postoperative time, and we believe that it does not bring any negative influence to surgical results / Mestrado / Cirurgia / Mestre em Cirurgia

Orientador: Jose Murilo Robilotta Zeitune / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-03T19:54:13Z (GMT). No. of bitstreams: 1 Parente_JoseMiguelLuz_M.pdf: 780772 bytes, checksum: e0c5b9ba3b5e0866ef4ebb5cdea5ead2 (MD5) Previous issue date: 2003 / Resumo: O Helicobacter pylori (H. pylori) é uma bactéria com características de bacilo Gram negativo, de forma espiralada ou curvada, possuindo até cinco flagelos unipolares, e que desencadeia um processo inflamatório crônico ativo da mucosa gástrica, levando, como conseqüência, ao desenvolvimento de inúmeras doenças gastro-duodenais, principalmente a doença ulcerosa péptica, o carcinoma gástrico e o linfoma tipo MALT. Foi conduzido um estudo epidemiológico do tipo observacional de corte transversal com o objetivo de detectar a prevalência da infecção pelo H. pylori em crianças até 12 anos de idade, residentes em bairros de uma mesma área urbana da cidade de Teresina, contudo pertencentes a dois grupos populacionais distintos do ponto de vista de renda familiar e disponibilidade de infra-estrutura básica domiciliar, caracterizando dois grupos, um de baixa renda e precárias situações sócio-econômicas e de infra-estrutura sanitária, e outro de alta renda e boas condições sanitárias, denominados grupo I e grupo II, respectivamente. Nesta pesquisa, foram estudados os seguintes aspectos em relação à infecção ativa pelo H. pylori: a prevalência em função da faixa etária, a distribuição da prevalência de acordo com o gênero, a sua relação com renda familiar e com diferentes condições de disponibilidade de infra-estrutura sanitária. O universo populacional que participou do estudo foi formado por 303 crianças, sendo 169 do grupo I e 134 do grupo II. Em relação ao gênero, 163 eram do sexo masculino e 140 do sexo feminino. Como método diagnóstico, foi utilizado um teste não invasivo, que pesquisou a presença de um antígeno específico do H. pylori presente nas fezes dos indivíduos infectados, denominado HpSA, através da técnica de ELISA. Os resultados deste estudo indicaram que a prevalência global da infecção pelo H. pylori foi de 38,0%, tendo sido muito elevada no grupo I, qual seja, 55,0%, enquanto no grupo II foi muito baixa, atingindo apenas 16,4%. Os resultados obtidos isoladamente nos dois grupos foram semelhantes aos dados observados nos países subdesenvolvidos e industrializados, respectivamente, indicando que nesta população existiam condições que favoreceram a aquisição da infecção nas populações com baixa renda familiar e precárias condições higiênico-sanitárias. As demais análises da pesquisa também indicaram que a infecção ocorreu precocemente na infância, em ambos as populações, já nos primeiros anos de vida, havendo aumento progressivo com a idade, nos anos seguintes durante a infância. Em relação ao gênero, o resultado global do estudo demonstrou que a infecção pelo H. pylori ocorreu igualmente em ambos os sexos. Os fatores de risco associados à infecção pelo H. pylori, determinados neste estudo, foram baixa renda familiar e aqueles associados a precárias condições de infra-estrutura domiciliar, quais sejam, ausência de pavimentação da rua, moradias construídas precariamente, ausência ou precariedade de pisos nas residências, ausência ou deficiência de esgotamento sanitário e ausência de coleta do lixo domiciliar / Abstract: Helicobacter pylori (H. pylori) is a small curved and S-shaped Gram negative bacilli, with up to five sheathed flagelae arising from one end. The bacteria has been associated to some histological changes and gastroduodenal diseases, among which active chronic gastritis, duodenal ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. A cross-sectional study was conducted in the urban area of Teresina, a city situated in the Northeast of Brazil, the poorest region of the country. The aims of this study were to determine (a) the prevalence of active H. pylori infection in asymptomatic children, in 0.5¿12-year-olds, (b) the age-distribuition pattern during childhood, and (c) the relationships with factors such as SES (including family income, housing and sanitary conditions) and gender. Data collect was carried out in a community base, by sampling, at random, in a zone of the city inhabited by population groups with different SES and available sanitary infrastructure, though they have lived in adjacent areas. This zone includes concentrated areas of high and middle classes families along with powerty areas in shantytowns with mud wallet dwellings for the very low income families. The global population that participated in this study was constituted of 303 children, divided in two groups: group I, composed of 169 children from low income families, and group II composed of 134 from families with higher incomes and standards of living. Of the eligible study population, 163 (53,8%) were males and 140 (46,2%) females. The diagnostic method used in this study was a noninvasive enzyme linked imuneassay (ELISA) that detects H. pylori specific antigen (HpSA) in selected faeces samples, employing anti-HpSA policlonal antibody absorbed in microwells. Overall 303 stool samples analysed, 115 (38.0%) were HpSA positive. Low income population (group I) presented greater prevalence rates, equivalent to 55.0%, while in high income population (group II) the prevalence was only 16.4%. In both groups, it was very clear that H. pylori infection occurs early in childhood since a very young ages and increases gradually with age. It was found that the prevalence rates, in accordance with gender, was not considered statistically significant. This study has shown that low family income, precarious conditions of living, housing and sanitary infrastructure can play an important role in H. pylori infection acquisition. On the other hand, there was a clear relationship between low H. pylori prevalence with high standards of living. In fact, the low prevalence observed in high SES group, similar to the rates showed in developed countries, may be linked to improvements in hygiene pratices and standards of living / Mestrado / Medicina Interna / Mestre em Ciências Médicas

Submitted in partial fulfillment of the requirement for the Degree of Master of Technology: Biological Sciences, ML Sultan Technikon, 1999. / Today, the number one income-generating drugs are remedies prescribed for gastric disorders, in particular dyspepsia. These clinical conditions have a multi-faceted aetiology and pathology of dysfunction. One likely causal factor is the entero-pathogen Helicobacter pylori. It has been shown to be more than just a commensal related to gastric diseases like dyspepsia (80-90% incidence) and duodenal ulcer sufferers (100% incidence), with a total estimated world-wide population infection of 50%. The current therapy offered to dyspepsia sufferers is a triple regimen of an anti-bacterial, an Ir proton-pump inhibitor, and bismuth colloidal salts. / M

Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative motile curved rod that inhabits the gastric mucosa of the human stomach. The organism chronically infects billions of people worldwide and is one of the most genetically diverse of bacterial species. Infection with the organism potentially induces chronic gastritis and peptic ulcer disease. In addition, H. pylori plays a role in the etiology of gastric cancer and gastric MALT lymphoma. The risk of infection is increased in those living in the developing world, which has been ascribed to precarious hygiene standards, crowded households, and deficient sanitation common in this part of the world. Thus, the aim of this study was to identify the risk factors in the transmission of H. pylori in our environment, i.e. in Nkonkobe Municipality in the Eastern Cape Province, South Africa. Faecal samples were collected from 356 apparently healthy subjects, consisting of 168 males and 188 females aged from 3 months to 60 years (Mean = 31 years). A standardized questionnaire was applied, it described demographic characteristics including age, sex, household hygiene, socioeconomic status, area of residence, duration of stay in the area, sharing bath water, sharing tooth brush, habit of sucking thumb, medication currently being taken or medication taken within the past three months, source of water, type of toilet used, education and occupation. A sandwich-type enzyme immunoassay amplification technology (Amplified IDEIA TM Hp StAR TM , Oxoid, UK) was used to analyze the faecal samples for the detection of H. pylori antigens using monoclonal antibodies specific for H. pylori antigens. To assess the possibility of faecal oral route with tap water as an intermediary link, PCR targeting the ureC (glmM), a highly conserved gene in H. pylori ii was carried out to detect H. pylori DNA in faecal samples of already positive samples by HpSA test as well as in direct tap water used by the H. pylori positive subjects. QIAamp DNA stool mini kit was used to extract DNA from faecal samples. Tap water samples were then obtained using sterile bottles from areas inhabited by H. pylori positive subjects as determined by HpSA test and PCR. DNA extraction from water samples was done using UltraCleanTM Water DNA Isolation Kit (0.22μm) according to the manufacturer’s instructions. PCR with primers specific for H. pylori glmM gene was carried out with both positive and negative controls incorporated. Fisher’s exact test was used to assess the univariate association between H. pylori infection and the possible risk factors. Odds ratio (OR) and the corresponding 95 percent confidence interval (CI) were calculated to measure the strength of association using EPI INFO 3.41 package. P values of < .05 were required for significance. The precision rate of the diagnostic tests used was also determined. H. pylori antigen was detected in 316 of the 356 subjects giving an overall prevalence of 88.8 percent. Prevalence increased with age from 75.9 percent in children < 12 years age to 100 percent in the age group from 13 years to 24 years, also 100 percent prevalence of H. pylori was recorded in young adults aged 25-47 years and subjects aged 60 years (P < .05). H. pylori prevalence was higher in females than in males. Of 188 females who participated in the study, H. pylori antigen was detected in 172 (91.5 percent) versus 144 (85.7 percent) of 168 males (P > .05). Interestingly, H pylori antigen was detected more often (100 percent) in the high socioeconomic group than in those of low socioeconomic group (85.9 percent). Sixteen (66.7 percent) of twenty four faecal samples that had previously tested positive for the organism by HpSA test were confirmed positive by PCR. However none of the treated tap water samples tested positive for the organism by PCR. The present iii study revealed a high prevalence of H. pylori in faecal samples of asymptomatic individuals in the Nkonkobe Municipality, an indication of active infection. The obtained results also revealed that direct treated tap water might not be playing a crucial role in the oral transmission of H. pylori in the studied population.

Orientador: A. Frederico N. de Magalhães / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-31T17:07:32Z (GMT). No. of bitstreams: 1 Reis_MaisaPrandodeMoura_M.pdf: 25147226 bytes, checksum: 894a70c9e21976c037bd3a83a1c37cc9 (MD5) Previous issue date: 2001 / Resumo: A dispepsia funcional é definida como dor abdominal ou desconforto, persistente ou recorrente, situado no abdome superior sem causas orgânicas ou bioquímicas que expliquem os sintomas. O objetivo desse estudo prospectivo, randomizado, duplo-cego, controlado com um ano de seguimento, foi determinar se a erradicação do Hp me1hora os sintomas dispépticos e os índices de ansiedade e depressão em pacientes com dispepsia funcional. Cinqüenta e três pacientes Hp-positivos com dispepsia funcional dos tipos "dismotilidade", "úlcera" e "refluxo" foram incluídos nesse estudo e receberam tratamento. Eram 11 homens e 42 mulheres,com idade média de 40.24, variando entre 18 e 65 anos. A infecção pelo Hp foi avaliada pelo teste da urease, da histologia e da cultura. Os pacientes foram distribuídos aleatoriamente em dois grupos de acordo com o tratamento: tetraciclina 500mg - 1 cápsula,4 vezes/dia,furazolidona200mg- 1 cápsula, 2 vezes/dia e subcitrato de bismuto 240mg - 1 cápsula, 3 vezes/dia (grupo droga-ativa) ou subcitrato de bismuto associado a placebos (grupo controle), ambos por 7 dias. A pesquisa do Hp foi realizada um mês e 12 meses após o término do tratamento, por meio do exame endoscópico, com co1heitade biópsias. A intensidade dos sintomas foi medida pela escala de Likert com variação de 1/5, onde 1 corresponde a sem problema e 5 corresponde a problema intenso. Os índices de ansiedade e depressão foram avaliados pela escala (HAD) na primeira avaliação e após 12 meses. Vinte e um pacientes apresentaram índices de ansiedade e depressão (39,6%). Vinte e oito pacientes (52,8%) integraram o grupo droga-ativa e 25 (47,2%) o grupo controle. A taxa de erradicação após um mês foi de 75% no grupo droga-ativa e de 0% no grupo controle. A melhora dos sintomas após um ano ocorreu em 14 (77,8%) pacientes erradicados e em 27 (77,1%) não erradicados. Os Índices de ansiedade e de depressão reduziram-se em 9 pacientes (36%), não apresentando relação com a erradicação do Hp. Concluúnos que, na dispepsia funcional, não há relação aparente entre a infecção pelo Hp e a intensidade dos sintomas dispépticos ou os Índices de ansiedade ou depressão / Abstract: Functional dyspepsia (FD) is defined as persistent or recurrent abdominal pain or discornfort centered in the upper abdomen in patients who have no detinite structural or biochemical explanation for their symptoms (e.g., peptic ulcer disease, gastroesophageal reflux, ma1ignancyor pancreaticobiliarydisease). The discovery of Helicobacter pylori has resulted in important advances in the management of dyspepsia.The role of Hp in functional dyspepsia is still controversial. Several studies have evaluated the effect of eradicating Hp infection on dyspeptic symptoms in patients with functional dyspepsia, but conflicting results and design flaws have been found. There is abundant evidence that psychological factors can be identified in most patients with functional diseases, inc1udingdyspepsia. This study aimed to determine whether Hp eradication therapy improves dyspeptic symptomsand anxiety/depressionrates. Fifty-three Hp-positive patients with functional dyspepsia were inc1uded and treated: 11 male and 42 female, mean age 40.24, between 18-65 years. The Hp infection was assessed by urease, histological and culture. Patients were randomly allocated to a 7- day treatment of tetracyclin 500mgx4, furazolidone 20mgx2 and bismuth subcitrate 240mgx3 (active-treatment group) or placebo associated to subcitrate bismuth 24Omgx3 (control group). Presence of Hp was assessed at one month after completion oftherapy and 12 months by endoscopic biopsies. Symptoms severity was measured using Likert scale ITom1= no problem to 5= very severe. Anxiety and depression were evaluated trough (HAD) scale at the first and at 12 months. Chi-square test, t Student's test and Fisher's exact test were used to compare the values of variables. The two groups were comparable. Anxiety and depression rates were positive in 21 patients (39,6 percent). Twenty-eight patients (52,8 percent) received the anti-Hp therapy and 25 (47,2 percent) received on1ybismuth . Helicobacterpylori eradicationrates at one month were 75 percent in active-treatment group and zero percent in control group. At 12 months, symptoms improvement was identified in 14 (77,8 percent) Hpnegative patients and in 27 (77,1 percent) Hp-positive patients. Anxiety and depression rates improved in 9 patients (36 percent), showing no relation with Hp eradication. We conclude that there is no evidence that curing Hp infection in patients with functional dyspepsia leads to relief of symtoms or anxiety and depression features / Mestrado / Clinica Medica / Mestre em Clinica Medica

Tesis para optar al Grado de Magíster en Ciencias Animales y Veterinarias mención en Patología Animal / RESUMEN Introducción: El síndrome ulceroso gástrico en equinos FSC se asocia principalmente a factores de manejo y alimentación, sin embargo al igual que en otras especies se ha postulado el eventual rol que pudiese jugar la presencia de Helícobacter pylorí en el desarrollo de esta enfermedad. El objetivo de este trabajo es evaluar en caballos que presenten la enfermedad la presencia de la bacteria y así contribuir al conocimiento de la etiopatogenia del cuadro. Material y Métodos: En 45 equinos con diagnóstico gastroscópico de úlcera gástrica se obtuvo una muestra de la lesión por biopsia, la cual fue sometida a test rápido de ureasa HE-PY Test (BIOS Chile), se seleccionaron aquellas muestras positivas con mayor carga bacteriana, en total 13, las cuales se analizaron mediante técnica de PCR, con un par de partidores HP01 y HP02 de secuencias conocidas. Los resultados se expresaron mediante distribución de frecuencias de los valores cualitativos. En las muestras al test de ureasa se usó prueba de hipótesis para muestras asociadas mediante distribución de X2 . En el caso de los elementos coincidentes se determinó la correlación de Spearman. Resultados y discusión: Las lesiones de la mucosa gástrica se clasificaron en cuatro grados: 25, 1 % grado1, 45%, 13,3% y 16,6% grados 2, 3 y 4 respectivamente. Los test de ureasa se clasificaron según tiempo que demoró en virar el color asociándolo a la carga bacteriana; 25% con ausencia de carga bacteriana, 38.3% carga bacteriana baja, 25 % moderada y 11 ,6% alta carga bacteriana. Aquellas muestras con alta carga bacteriana y el 50% de muestras con carga moderada fueron sometidas a PCR para H. pylorí, lo que arrojó como resultado un 14,3% de muestras positivas a H. pylorí, demostrando así una alta sensibilidad del test de ureasa, sin embargo una baja especificidad en el equino, debido al alto porcentaje de falsos positivos (85,7%). Conclusiones: Existe presencia de H. pylorí en el equino fina sangre de carrera asociado a lesión de mucosa gástrica. Un 48.8% de las muestras viraron antes de 24 hrs. lo que indica una moderada a alta carga bacteriana, asociada a grados 2, 3 y 4 de lesión en la mucosa gástrica. / SUMMARY lntroduction: The equine gastric ulcer syndrome is mainly associated with feeding and management factors, however, as in other species has been postulated the possible role that could play the presence of Helícobacter pylorí in the development of this disease. The aim of this study is to assess horses presenting disease the presence of bacteria and thus contribute to the understanding the pathogenesis. Material and Methods: In 45 horses with gastroscopic diagnosis of gastric ulcer was sampled by biopsy of the lesion, which underwent rapid urease test HE-PY Test (BIOS Chile), those positive samples were selected more bacteria! load, a total of 13, which was analyzed by PCR with a pair of primers HP01 and HP02 known sequences. The results were expressed as frequency distribution of qualitative values. In samples with urease test was used far hypothesis testing samples associated with X2 distribution. In the case of the matching elements are determined Spearman correlation. Results and discussion: The mucosal gastric lesions were classified into four grades: grade 1 25.1 %, 45%, 13.3% and 16.6% grade 2, 3 and 4 respectively. The urease test were classified as in turn delayed while associating color to bacteria! load, 25% with no bacteria!, low bacteria! presence 38.3%, 25% moderate and 11.6% high bacteria! presence. Those samples with high bacteria! presence and 50% samples with moderate bacteria! presence were subjected to PCR to H. pylorí, showing results in 14.3% of samples positive far H. pylorí, demonstrating high sensitivity of urease test, but low specificity in the horse, due to the high percentage of false positives (85.7%). Conclusions: The presence of H. pylorí in thoroughbred race horses associated with gastric mucosal lesion. A 48.8% of the samples within 24 hrs tacked. indicating a moderate to high bacteria! counts associated with degrees 2, 3 and 4 of gastric mucosal injury

Bacterial small non-coding RNAs (sRNAs) play fundamental roles in controlling and finetuning gene expression in a wide variety of cellular processes, including stress responses, environmental signaling and virulence in pathogens. Despite the identification of hundreds of sRNA candidates in diverse bacteria by genomics approaches, the mechanisms and regulatory capabilities of these posttranscriptional regulators have most intensively been studied in Gram-negative Gammaproteobacteria such as Escherichia coli and Salmonella. So far, almost nothing is known about sRNA-mediated regulation (riboregulation) in Epsilonproteobacteria, including the major human pathogen Helicobacter pylori. H. pylori was even thought to be deficient for riboregulation as none of the sRNAs known from enterobacteria are conserved in Helicobacter and since it lacks the major RNA chaperone Hfq, which is crucial for sRNA function as well as stability in many bacteria. Nonetheless, more than 60 cis- and trans-acting sRNA candidates were recently identified in H. pylori by a global RNA sequencing approach, indicating that this pathogen, in principle, has the capability to use riboregulation for its gene expression control. However, the functions and underlying mechanisms of H. pylori sRNAs remained unclear. This thesis focused on the first functional characterization and target gene identification of a trans-acting sRNA, RepG (Regulator of polymeric G-repeats), in H. pylori. Using in-vitro and in-vivo approaches, RepG was shown to directly base-pair with its C/Urich terminator loop to a variable homopolymeric G-repeat in the 5’ untranslated region (UTR) of the tlpB mRNA, thereby regulating expression of the chemotaxis receptor TlpB. While the RepG sRNA is highly conserved, the length of the G-repeat in the tlpB mRNA leader varies among different H. pylori isolates, resulting in a strain-specific tlpB regulation. The modification of the number of guanines within the G-stretch in H. pylori strain 26695 demonstrated that the length of the homopolymeric G-repeat determines the outcome of posttranscriptional control (repression or activation) of tlpB by RepG. This lengthdependent targeting of a simple sequence repeat by a trans-acting sRNA represents a new twist in sRNA-mediated regulation and a novel mechanism of gene expression control, since it uniquely links phase variation by simple sequence repeats to posttranscriptional regulation. In almost all sequenced H. pylori strains, tlpB is encoded in a two gene operon upstream of HP0102, a gene of previously unknown function. This study provided evidence that HP0102 encodes a glycosyltransferase involved in LPS O-chain and Lewis x antigen production. Accordingly, this glycosyltransferase was shown to be essential for mice colonization by H. pylori. The coordinated posttranscriptional regulation of the tlpB-HP0102 operon by antisense base-pairing of RepG to the phase-variable G-repeat in the 5’ UTR of the tlpB mRNA allows for a gradual, rather than ON/OFF, control of HP0102 expression, thereby affecting LPS biosynthesis in H. pylori. This fine-tuning of O-chain and Lewis x antigen expression modulates H. pylori antibiotics sensitivity and thus, might be advantageous for Helicobacter colonization and persistence. Whole transcriptome analysis based on microarray and RNA sequencing was used to identify additional RepG target mRNAs and uncover the physiological role of this riboregulator in H. pylori. Altogether, repG deletion affected expression of more than 40 target gene candidates involved various cellular processes, including membrane transport and adhesion, LPS modification, amino acid metabolism, oxidative and nitrosative stress, and nucleic acid modification. The presence of homopolymeric G-repeats/G-rich sequences in almost all target mRNA candidates indicated that RepG hijacks a conserved motif to recognize and regulate multiple target mRNAs in H. pylori. Overall, this study demonstrates that H. pylori employs riboregulation in stress response and virulence control. In addition, this thesis has successfully established Helicobacter as a new model organism for investigating general concepts of gene expression control by Hfq-independent sRNAs and sRNAs in bacterial pathogens. / Bakterielle kleine, nicht-kodierende RNAs (sRNAs, engl. für small RNAs) spielen eine fundamentale Rolle in der Kontrolle und Feinabstimmung der Genexpression in Bakterien. Sie sind an einer Vielzahl von zellulären Prozessen, einschließlich der Adaption an unterschiedliche Stress- sowie Umweltbedingungen und der Virulenz von bakteriellen Pathogenen, beteiligt. Trotz der Identifizierung von Hunderten von sRNA-Kandidaten in diversen Bakterien durch genomweite Untersuchungsmethoden, wurden die regulatorischen Eigenschaften und Mechanismen dieser posttranskriptionellen Regulatoren bisher hauptsächlich in Gram-negativen Gammaproteobakterien wie Escherichia coli und Salmonella untersucht. Bislang ist nur wenig über sRNA-basierte Regulation (Riboregulation) in Epsilonproteobakterien, einschließlich dem weitverbreiteten Humanpathogen Helicobacter pylori, bekannt. Es wurde sogar angenommen, dass H. pylori über keine Art der Riboregulation verfügt, da keine der enterobakteriellen sRNAs in Helicobacter konserviert sind. Zudem konnte in diesem Erreger kein Homolog für das RNAChaperon Hfq, welches in vielen Bakterien essentiell für die Funktion und Stabilität von sRNAs ist, identifiziert werden. Nichtsdestotrotz wurden mit Hilfe einer globalen RNASequenzierungsstudie,die auf der Sequenzierung primärer Transkripte in einem Hochdurchsatzverfahren basiert, kürzlich mehr als 60 in cis- und in trans-agierende sRNAKandidaten in H. pylori identifiziert. Diese Transkriptomanalyse deutet darauf hin, dass H. pylori prinzipiell die Fähigkeit hat Riboregulation zur Kontrolle seiner Genexression zu nutzen. Die Funktionen und Mechanismen von sRNAs in H. pylori sind jedoch immer noch unklar. In der vorgelegten Arbeit wurde erstmals eine in trans-agierende sRNA, RepG (Regulator of polymeric G-repeats), in Helicobacter charakterisiert sowie dessen zelluläre Zielgene identifiziert. Mit Hilfe diverser in-vitro und in-vivo Analysen konnte gezeigt werden, dass der C/U-reiche Transkriptionsterminatorloop von RepG direkt an eine variable, repetitive G-Sequenz in der 5‘ untranslatierten Region (UTR) der tlpB mRNA bindet. Durch diese direkte sRNA-mRNA Interaktion wird die Expression des Chemotaxis Rezeptors TlpB reguliert. Im Gegensatz zu einer hohen Konservierung der Sequenz der RepG sRNA, variiert die Länge des G-Stretches im 5‘ UTR der tlpB mRNA zwischen unterschiedlichen H. pylori Isolaten. Diese Längenvariation resultiert in einer Stamm-spezifischen Regulation der TlpB Expression. Die Modifikation der Anzahl der Guanin-Basen im G-Stretch des H. pylori Stammes 26695 demonstrierte, dass die Länge der repetitiven G-Sequenz das Ergebnis der posttranskriptionellen Regulation (Repression oder Aktivierung) von tlpB durch RepG beeinflusst. Die hier beschriebene Längen-abhängige Interaktion zwischen einer in transagierenden sRNA und einer einfachen, repetitiven Sequenz repräsentiert nicht nur ein neues Konzept für die Genregulation durch sRNAs, sondern stellt auch einen neuen Mechanismus der Genexpressionskontrolle dar. Darüber hinaus, veranschaulicht die hier beschriebene sRNA-mRNA Interaktion eine bislang einzigartige Verknüpfung von Phasenvariation durch hochvariabel, repetitive Sequenzen mit Genregulation durch sRNAs. In nahezu allen sequenzierten H. pylori Stämmen ist das tlpB Gen in einem Operon zusammen mit einem Gen mit bisher unbekannter Funktion, HP0102, kodiert. In dieser Arbeit konnte gezeigt werden, dass HP0102 für eine Glykosyltransferase kodiert, die an der Synthese der O-Seitenketten des LPS und des Lewis x Antigens in H. pylori beteiligt ist. Darüber hinaus konnte demonstriert werden, dass diese Glykosyltransferase für die Kolonisierung des murinen Magens durch H. pylori essentiell ist. Die koordinierte, posttranskriptionelle Regulation des tlpB-HP0102 Operons, welche durch antisense Basenpaarung zwischen RepG und der phasen-variablen, repetitiven G-Sequenz im 5‘ UTR der tlpB mRNA vermittelt wird, ermöglicht eine graduelle Kontrolle der Genexpression von HP0102, und somit Einflussnahme auf die LPS Biosynthese in H. pylori. Diese Feinabstimmung der LPS O-Seitenketten und Lewis x Antigen Expression beeinflusst die Resistenz von H. pylori gegen diverse Antibiotika und könnte somit sowohl für die Kolonisierung als auch für die persistente Infektion des Wirts durch H. pylori vorteilhaft sein. Um Einblicke in die physiologische Funktion von RepG zu gewinnen, wurden in einer genom-weiten Transkriptomanalyse mittels Microarray und RNA-Sequenzierung weitere Zielgene von RepG bestimmt. Insgesamt beeinflusste die Deletion von repG die Expression von mehr als 40 potentiellen Zielgenen, welche an diversen zellulären Prozessen beteiligt sind, wie z.B. Membrantransport und Adhäsion, Aminosäure- und Nukleinsäure-Metabolismus, oxidative und nitrosative Stressantwort sowie LPS Modifizierung. Die Identifizierung von homopolymeren G-Stretchen bzw. G-reichen Sequenzen in allen ZielmRNAs deutet darauf hin, dass RepG ein konserviertes Motiv bindet, um mehrere Zielgene in H. pylori zu erkennen und zu regulieren. Zusammenfassend zeigt diese Arbeit, dass H. pylori Riboregulation basierend auf sRNAs nutzt, um seine Genexpression in unterschiedlichen Stress- und Virulenzbedingungen zu regulieren. Darüber hinaus hat diese Studie Helicobacter als neuen Modelorganismus für die Untersuchung genereller Wirkungsweisen Hfq-unabhängiger sRNAs und sRNAs in bakteriellen Pathogenen etabliert.