Die weltweit steigenden Antibiotikaresistenzen sind zu einer globalen Herausforderung geworden. Von dieser Entwicklung betroffen ist auch das Bakterium Helicobacter Pylori (H.p), welches in Ländern des afrikanischen Kontinents besonders hohe Prävalenzraten aufweist. In ressourcenschwachen Ländern wie Tansania ist aufgrund der begrenzten Verfügbarkeit diagnostischer Testverfahren die Identifizierung und Therapie von H.p. infizierten Personen oft unzureichend. Tansania weist im internationalen Vergleich bislang nur wenige Studien zur H.p.-Prävalenz und Antibiotikaresistenzlage auf. Um die Datenlage für Tansania zu verbessern wurden im Rahmen dieser Arbeit potentielle Risikofaktoren für sowie die Prävalenz und aktuelle Resistenzlage von H.p.-Infektionen bei Patientinnen und Patienten mit epigastrischen Beschwerden in Tansania untersucht. Darüber hinaus wurden diagnostische Schnelltestverfahren für H.p.-Infektionen im Hinblick auf ihre Testgenauigkeit und Anwendbarkeit in Tansania geprüft. Zur Identifizierung mögliche infektionsassoziierte Faktoren wurden mittels Fragebögen soziodemographische und klinische Merkmale sowie Aspekte der Lebensgewohnheiten und Lebensumstände der Probanden erhoben und statistisch ausgewertet. Die Prävalenzbestimmung des untersuchten Studienkollektivs erfolgte anhand der auf dem 23S-rDNA Gen basierten qRT-PCR, welche für diese Arbeit als Referenzverfahren definiert wurde. Die resistenzcodierenden DNA-Abschnitte wurden auf bekannte Resistenzmutationen gegen Clarithromycin- und Fluorchinolon-Antibiotika hin untersucht. Die Ergebnisse dieser Studie deuten auf eine weite Verbreitung von H.p.-Infektionen bei Patientinnen und Patienten mit epigastrischen Beschwerden in Tansania hin. Die darüber hinaus festgestellte hohe Anzahl molekulargenetisch nachgewiesener Resistenzraten von H.p.-Stämmen gegenüber Antibiotika verdeutlichen die Wichtigkeit einer sicheren Diagnostik und resistogrammgerechten Therapie im Klinikalltag. Die in dieser Arbeit untersuchten Schnelltestmethoden scheinen aufgrund der geringen Sensitivitäts- und NPW-Werte als Standardverfahren hierfür nicht geeignet. Die Etablierung einer routinemäßig durchgeführten prätherapeutischen Antibiogrammerstellung und eine daran angepasste Therapie wären wünschenswert. / Increasing antimicrobial resistance to commonly used antibiotics have become a global challenge. This development also affects the bacterium Helicobacter Pylori (H.p.), which shows high prevalence rates in African countries. The identification and therapy of H.p. infected people in resource-limited countries such as Tanzania is often insufficient due to the limited availability of diagnostic tests. By international comparison, there are only a few studies on the prevalence of antibiotic resistance rates of H.p. for Tanzania. In order to improve the data situation for Tanzania, this study investigates potential risk factors as well as the prevalence and current resistance situation of H.p. infections in Tanzanian patients with dyspeptic symptoms. In addition, rapid diagnostic test methods for H.p. infections were tested to identify their accuracy and applicability in Tanzania. Data about the patients’ sociodemographic situation, symptoms and aspects of lifestyle habits and living conditions were collected and statistically examined in order to identify possible risk factors for infection. The prevalence of H.p. is based on the results of the 23S-rDNA gene-based qRT-PCR. The resistance-encoding DNA segments: the 23S rDNA gene region and the gyrA gene were sequenced and evaluated for known resistance mutations to clarithromycin and fluoroquinolone antibiotics. The results of this study indicate that H.p. infections are widespread in patients with dyspeptic symptoms in Tanzania and that the resistance rates of H.p. strains to antibiotics are relatively high. This underlines the importance of reliable diagnostic tests and resistogram-based therapy in clinical practice. The establishment of a routine pretherapeutic antibiogram and an accordingly adapted therapy are desirable.

Helicobacter pylori is a unique bacterial pathogen which colonises the human stomach. Infection with H. pylori has been linked to several disease outcomes including gastric and duodenal ulcer, gastric cancer and MALT lymphoma. Considering the harsh environment in which it resides and the lack of competition from other bacteria, this host/pathogen relationship is particularly interesting. Microarray analysis is a new and powerful technique which can be used to investigate various aspects of these complex interactions. Expression profiling of bacteria using microarrays remains in its infancy and thus appropriate methods were developed herein for investigating the transcriptional responses of H. pylori to various environments in vitro. Studies showed the tight relationship between growth phase dependent expression of iron homeostasis, motility and virulence genes in H. pylori for the first time. Consequently, the late exponential phase of growth was implicated as the most virulent growth phase of this bacterium in vitro. In response to mammalian cell co-culture, induced expression of H. pylori metabolism/respiration genes, genes of unknown function and genes encoding the 2-component regulators, HP1021 and HP0166, were detected. These represent a set of genes likely to be important specifically in the context of infection. To investigate the host response to infection a new mouse colonising strain of H. pylori, the Sydney Strain 2000 (SS2000), was isolated for use in comparative studies with the established strain, Sydney Strain 1 (SS1). Both host and strain specific effects were studied in a 15 month colonisation experiment using C57BL/6 and BALB/c mice. Genomic typing was used to investigate dynamic changes that occurred in the mouse-adapted strains during colonisation. In these animals reponses relating to the severity of inflammation and to the infecting H. pylori isolate were revealed by gene expression profiling. Previously unrealised cellular responses were uncovered. These included the significant down-regulation of both ferritin and haemoglobin expression. This perhaps suggests a mechanism for H. pylori induced iron deficiency anaemia. Physiological connections between colonisation, acid secretion and expression of the endocrine hormones were also implicated. These experiments have shown the utility of microarray analysis in the investigation of pathogenesis and have highlighted many directions for further investigation.

Helicobacter pylori (H. pylori) is a gram-negative pathogenic bacterium that infects half of the world’s population. It resides in the human stomach, where it survives extremely acidic conditions. Efficient colonization by H. pylori requires urease and hydrogenase enzymes, both of which utilize nickel as a cofactor. The intracellular level of nickel in H. pylori is strictly maintained by a nickel-responsive transcription factor, HpNikR, which acts as a master regulator to control both activation of the urease genes and repression of a variety of other genes including its own. In addition to its role in nickel homeostasis, HpNikR has been implicated in the adaptive response of H. pylori to acidic environmental conditions. In this work, two representative genes, ureA and nikR, are confirmed to be regulated by HpNikR directly in response to changes in nickel concentration, with HpNikR binding to the promoter region of each gene. The binding sequences on the two promoters are distinct from each other and no consensus sequence could be identified from them. The binding affinity of HpNikR to the ureA promoter is much tighter than to the nikR promoter. Another signal that can activate the DNA-binding activity of HpNikR is a change in pH. Once HpNikR is activated by proton binding, it binds to the ureA promoter independently of nickel concentration, but still binds to the nikR promoter in a nickel-dependent manner. Several amino acids at the N-terminus of HpNikR, including Asp7, Asp8 and Lys6, are critical for the specific response of HpNikR to pH changes. In addition, the binding of HpNikR to distinct DNA sequences induces different degrees of DNA bending, which provides another possible means of gene regulation by HpNikR. The ability of HpNikR to differentially regulate distinct genes in response to several signals allows a graduated level of control of gene expression by HpNikR. In vivo studies to evaluate the physiological relevance of the above in vitro results have been initiated. Given the relatively low abundance of transcription factors in H. pylori, information about the effects of nickel and pH on HpNikR in vivo is important for understanding the multifaceted roles of HpNikR in fine-tuning the physiology of this organism. Ultimately this study may provide us with a better idea of how to control H. pylori-caused diseases.

Helicobacter pylori (H. pylori) is a gram-negative pathogenic bacterium that infects half of the world’s population. It resides in the human stomach, where it survives extremely acidic conditions. Efficient colonization by H. pylori requires urease and hydrogenase enzymes, both of which utilize nickel as a cofactor. The intracellular level of nickel in H. pylori is strictly maintained by a nickel-responsive transcription factor, HpNikR, which acts as a master regulator to control both activation of the urease genes and repression of a variety of other genes including its own. In addition to its role in nickel homeostasis, HpNikR has been implicated in the adaptive response of H. pylori to acidic environmental conditions. In this work, two representative genes, ureA and nikR, are confirmed to be regulated by HpNikR directly in response to changes in nickel concentration, with HpNikR binding to the promoter region of each gene. The binding sequences on the two promoters are distinct from each other and no consensus sequence could be identified from them. The binding affinity of HpNikR to the ureA promoter is much tighter than to the nikR promoter. Another signal that can activate the DNA-binding activity of HpNikR is a change in pH. Once HpNikR is activated by proton binding, it binds to the ureA promoter independently of nickel concentration, but still binds to the nikR promoter in a nickel-dependent manner. Several amino acids at the N-terminus of HpNikR, including Asp7, Asp8 and Lys6, are critical for the specific response of HpNikR to pH changes. In addition, the binding of HpNikR to distinct DNA sequences induces different degrees of DNA bending, which provides another possible means of gene regulation by HpNikR. The ability of HpNikR to differentially regulate distinct genes in response to several signals allows a graduated level of control of gene expression by HpNikR. In vivo studies to evaluate the physiological relevance of the above in vitro results have been initiated. Given the relatively low abundance of transcription factors in H. pylori, information about the effects of nickel and pH on HpNikR in vivo is important for understanding the multifaceted roles of HpNikR in fine-tuning the physiology of this organism. Ultimately this study may provide us with a better idea of how to control H. pylori-caused diseases.

La tesis se ha planteado en dos partes, en la primera se incluyen dos estudios terapéuticos sobre la cicatrización de la úlcera duodenal asociada a la infección por H. pylori.1. IMPACT OF COLLOIDAL BISMUTH SUBCITRATE (SBC) IN THE ERADICATION RATES OF Helicobacter pylori INFECTION-ASSOCIATED DUODENAL ULCER USING A SHORT TREATMENT REGIMEN WITH OMEPRAZOLE AND CLARITHROMYCIN: A RANDOMIZED STUDY. Am J Gastroenterol 1995; 90:718-21.2. RANDOMIZED CLINICAL TRIAL COMPARING TWO ONE-WEEK TRIPLE-THERAPY REGIMENS FOR THE ERADICATION OF Helicobacter pylori INFECTION AND DUODENAL ULCER HEALING. Am J Gastroenterol 1998; 93:35-38En la segunda parte de la tesis se presenta el tercer estudio en el que se ha valorado objetivos sobre la eficacia de los métodos diagnósticos en la infección y en el control de la erradicación de la infección por H. pylori.3. ACCURACY OF AN ENZYME IMMUNOASSAY FOR THE DETECTION OF Helicobacter pylori IN STOOL SPECIMENS IN THE DIAGNOSIS OF INFECTION AND POSTTREATMENT CHECK-UP. Am J Gastroenterol 2000; 95:2200-5Conclusiones: 1. La cicatrización de la úlcera duodenal asociada a infección por H. pylori obtenida con pautas de tratamiento erradicador de 7 días es similar a la obtenida con omeprazol durante 4 semanas y superior a la obtenida cuando se administra el antisecretor durante 15 días. 2. La pauta de tratamiento con omeprazol 40 mg/d x 8 días, SBC 120 mg cuatro veces al día y claritromicina 500mg cada 12 horas durante 7 días, o omeprazol 40 mg / 12h, claritromicina 500 mg / 12 horas con amoxicilina 1 gr / 12h o SBC 120 mg / 6h, son muy eficaces en la erradicación de H. pylori y en la cicatrización de la úlcera duodenal. Su cumplimiento es muy bueno y los efectos secundarios mínimos. 3. El SBC aumenta la acción del omeprazol y de la claritromicina en la erradicación de H. pylori. 4. La dosis de omeprazol, cuando se utilizan estas combinaciones terapéuticas, no parece que juegue un papel importante en la erradicación de H. pylori. 5. Los pacientes que erradican la infección de la mucosa gástrica presentan una mejoría del índice de gastritis. 6. El test HpSA, utilizando el punto de corte de 0,130, puede ser útil en el diagnóstico primario de la infección por H. pylori, con una sensibilidad similar a la obtenida por la histología, el test de la ureasa rápida y el TAU, aunque con menor especificidad. 7. El test HpSA no es útil en el control de la erradicación de la infección a las 24 horas después de finalizar el tratamiento. 8. El test HpSA es ineficaz en el control de la erradicación a las 6 semanas de finalizar el tratamiento por su menor precisión en comparación con el test del aliento con urea-C13. / The thesis has been planed in two parts. 1. Included two therapeutics studies about duodenal ulcer healing associated with Hp infection. 2. The assessment of efficacy of the diagnosis methods in the diagnosis of infection and posttreatment check-up.IMPACT OF COLLOIDAL BISMUTH SUBCITRATE (CBS) IN THE ERADICATION RATES OF Helicobacter pylori (Hp) INFECTION-ASSOCIATED DUODENAL ULCER (DU) USING A SHORT TREATMENT REGIMEN WITH OMEPRAZOLE AND CLARITHROMYCIN: A RANDOMIZED STUDY. Am J Gastroenterol 1995; 90:718-21.Objectives: To evaluate the efficacy of a short treatment regimen in Hp eradication UD healing and to asses the impact of colloidal bismuth subcitrate (CBS) in Hp eradication and ulcer healing. Conclusions: The addition of CBS to the double therapy with omeprazole and clarithromycin improves the eradication rate of Hp .This short therapy is a safe, well tolerated combination that achieves a 80,6% eradication rate of Hp and DU healing rates as good as hose achieved by omeprazole 20mg/d when given for 4 wk. RANDOMIZED CLINICAL TRIAL COMPARING TWO ONE-WEEK TRIPLE THERAPY REGIMENS FOR THE ERADICATION OF HELICOBACTER PYLORI INFECTION AND DUODENAL ULCER HEALING. Am J Gastroenterol 1998; 93:35-38Objectives: To evaluate if higher doses of omeprazole improve the efficacy of two one-week triple therapy regimens in Hp eradication and DU healing. Conclusions: High rates of both Hp eradication and DU healing were obtained with both short-treatment regimens, which were safe and well-tolerated. CBS seems to be a good alternative to amoxicillin in the triple therapy combining they with omeprazole and clarithromycin. The omeprazole dose does not seem to play a major role in Hp eradication in these therapeutic combinations.ACCURACY OF AN ENZYME IMMUNOASSAY FOR THE DETECTION OF Helicobacter pylori IN STOOL SPECIMENS IN THE DIAGNOSIS OF INFECTION AND POSTTREATMENT CHECK-UP. Am J Gastroenterol 2000; 95:2200-5Objectives: To assess the reliability of a newly developed EIA assay for Hp specific antigen detection in stools (HpSA) compared to histology (H), rapid urease test (RUT) and 13C-urea breath test (UBT) to diagnose Hp infection and to evaluate its usefulness to determine Hp status after treatment. Methods: One hundred and eighty eight patients were included. Hp infection was confirmed in all patients by HpSA test in stools, RUT, UBT and H. Patients were defined as positive for Hp if RUT and UBT or H were positive. One hundred and forty two symptomatic patients received eradication treatment and were reassessed 6 weeks after therapy; in 70 of these patient stool samples were also collected at 24 hours and 6 months after finishing eradication treatment. In the post-treatment follow-up UBT was used as gold standard. Conclusions: 1.-The HpSA stools test using a cut-off value of 0.130 may be useful for the primary diagnosis of H. pylori infection, with sensitivity similar to that obtained with other standard tests, but with less specificity. 2.- HpSA test is not useful for early monitoring of treatment efficacy; and 3.- At 6 weeks and at 6 months post-treatment, HpSA test lacks accuracy as compared to UBT to evaluate the outcome of the eradication treatment.

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To elucidate the correlation between host susceptible genes and the carcinogenesis of gastric cancer and duodenal ulcer, myeloperoxidase (MPO) -463 G/A polymorphism was detected by PCR-RFLP and nucleotide autosequencing, respectively. On the other hand, E-cadherin (CDH1) -160 C/A polymorphism was analyzed by nucleotide autosequencing. No positive correlation among MPO genotype distributions, gastric cancer (p=0.26,

Abstract The members of interleukin-1 (IL-1) gene family, interleukin-1£] (IL-1b) and Interleukin -1 receptor antagonist (IL-l RN) are cytokines that play a key role in modulating the inflammatory response in the gastrointestinal mucosa. IL-1£]

No description available.

El estudio se realizó en 50 pacientes del servicio de Gastroenterología del Hospital Central PNP Luis N. Saenz, con el objetivo de establecer la relación de la prueba de urea en muestras de placa dental y la de biopsia gástrica para la determinación de la presencia del Helicobacter pylori. Se tomaron simultáneamente muestras de placa dental y de biopsias gástricas en el servicio de Gastroenterología a quienes se les indicó endoscopias por el médico tratante obteniéndose muestras del estómago mediante sacabocado y colocadas en caldo urea las que fueron llevadas al laboratorio del hospital. Las muestras de placa dental fueron colocadas directamente en el caldo urea y llevados al laboratorio del la Facultad de Odontología para su incubación a 37 ºC, los resultados fueron leídos a las 24, 48 y 72 horas y registrados en una base de datos. Los resultados de las biopsias gástricas fueron obtenidos del laboratorio de histopatología del Hospital. El análisis de los resultados obtenidos corrobora la hipótesis que existe relación entre la determinación de la prueba de urea positiva en muestras de placa dental con las obtenidas en biopsias gástricas ya que se obtiene un 68% de concordancias de valores tanto positivos como negativos para ambos.