[Show abstract][Hide abstract] ABSTRACT: The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood.
[Show abstract][Hide abstract] ABSTRACT: Until now, it has been unclear how proton pump inhibitors (PPIs) support Helicobacter pylori therapy. We tested whether the PPI omeprazole acts on the spatial orientation of H. pylori in the gastric mucus of infected Mongolian gerbils. Following repetitive PPI administration once daily but not following single doses or administration every 8 h, the bacterial spatial distribution changed, indicating a loss of orientation. Therefore, the therapeutic scheme of PPI administration may affect efficiency of treatment.
Antimicrobial Agents and Chemotherapy 07/2009; 53(8):3511-4. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eustachian tube dysfunction plays a pivotal role in the pathogenesis of otitis media with effusion. Besides the lack of sufficient animal models to investigate the role of gastroesophageal reflux on Eustachian tube function, there is no reliable test that clinically allows the quantification of Eustachian tube function. Therefore, we established a Mongolian gerbil model to trace gastroesophageal reflux into the middle ear. In gerbils with traceable reflux, the refluxate reached the both middle ears through the Eustachian tubes in most cases.
Clinical studies were performed to analyze the reproducibility of measuring the accuracy of modified tube manometry in healthy Caucasians.
Tube manometry was found to be a reliable and reproducible tool for measuring Eustachian tube function.
Both our animal model and the clinical application of tube manometry are likely to be useful for further experimental and clinical studies.
[Show abstract][Hide abstract] ABSTRACT: HintergrundBei der Pathogenese chronisch-rezivierender Mittelohrentzündungen spielt die Physiologie der Tuba Eustachii eine wesentliche
Rolle. Wir haben ein Tiermodell etabliert, mit dem der Einfluss des extraösophagealen Reflux (EÖR) auf die Tubenfunktion untersucht
werden kann. Wir konnten zeigen, dass EÖR über die Tube in das Mittelohr gelangen kann. Daher könnte EÖR ein pathogenetischer
Faktor für eine gestörte Tubenfunktion sein. Neben bislang fehlenden Tiermodellen zum möglichen Einfluss eines EÖR auf die
Tubenfunktion konnte bisher auch keine quantifizierende Untersuchungsmethode für die klinische Tubenfunktionsprüfung beim
Menschen etabliert werden.
MethodenZur Analyse der Reproduzierbarkeit und Messgenauigkeit erfolgte die Testung der modifizierten Tubenmanometrie an Probanden
mit regelrechter Tubenfunktion.
ErgebnisseDie Tubenmanometrie liefert untersucherunabhängige, reproduzierbare Ergebnisse zu unterschiedlichen Untersuchungszeitpunkten.
SchlussfolgerungenMit der modifizierten Tubenmanometrie steht ein valides klinisches Verfahren zur Verfügung, welches eine Quantifizierung der
Tubenfunktion ermöglicht. Der Einsatz dieses Verfahrens eignet sich in der klinischen Routine zur reproduzierbaren Abklärungen
der Tubenfunktion. Das vorgestellte Tiermodell eignet sich zu weiterführenden Untersuchungen des EÖR auf die Tubenfunktion.
BackgroundEustachian tube dysfunction plays a pivotal role in the pathogenesis of otitis media with effusion. Besides the lack of sufficient
animal models to investigate the role of gastroesophageal reflux on Eustachian tube function, there is no reliable test that
clinically allows the quantification of Eustachian tube function. Therefore, we established a Mongolian gerbil model to trace
gastroesophageal reflux into the middle ear. In gerbils with traceable reflux, the refluxate reached the both middle ears
through the Eustachian tubes in most cases.
MethodsClinical studies were performed to analyze the reproducibility of measuring the accuracy of modified tube manometry in healthy
ResultsTube manometry was found to be a reliable and reproducible tool for measuring Eustachian tube function.
ConclusionsBoth our animal model and the clinical application of tube manometry are likely to be useful for further experimental and
[Show abstract][Hide abstract] ABSTRACT: As more than 40% of adults experience symptoms of the gastroesophageal reflux (GER) and 26% are affected by the extraesophageal reflux (EER), the aim of this article was to review the literature concerning pathophysiological mechanisms contributing to these common diseases. Reflux symptoms are ascribable for nearly one-third of otolaryngeal disorders. In contrast to patients solely affected by GERD, patients with otolaryngeal disorders attributable to extraesophageal reflux have a relatively good esophageal acid clearance but for unknown reasons increased amounts of laryngeal reflux. Transient upper esophageal sphincter relaxations are discussed as the pathophysiological mechanism, as the resting tone of the upper esophageal sphincter is not affected. When exposed to gastroduodenal contents, the ciliated epithelium of otolaryngeal structures is more susceptible to damage, and thereby even a few reflux episodes are suggested to cause extraesophageal reflux disease (EERD). Particularly active pepsin contributes to laryngeal lesions and eustachian tube dysfunction. Despite the importance of EER in laryngeal diseases, the causative role in other otolaryngeal disorders like sinusitis and otitis media with effusion remains unresolved.
Archives of Oto-Rhino-Laryngology 09/2008; 266(1):17-24. · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The gastric H(+)/K(+)-ATPase is located within an infolding (secretory canaliculus) of the apical plasma membrane of gastric parietal cells. Our aim was to measure the pH values in the cytosol and canaliculus of the acid-secreting parietal cell and the adjacent gland lumen in situ. We used ultrafine double-barreled tip-sealed microelectrodes at high acceleration rates for intracellular and canalicular measurements. Immunohistochemical staining of the parietal cells was used to identify the track of the electrode and to estimate the position of the electrode tip at the time of the last intracellular measurement. En route to the deepest regions of the mucosa, where the average gland lumen pH was approximately 3, and on advancing in steps of 2 mum, the electrode entered the cytosol of the parietal cells, where the pH value was 7.4. Advancing the electrode further resulted, in several instances, in a sharp decrease in pH to an average value of 1.7 +/- 0.2, which we interpreted as the measurement within the canaliculus. When the electrode was advanced even further, the pH reading returned to the cytosolic value. From the difference in pH between the secreting canaliculus and the adjacent gland lumen, we concluded that the released acid was immediately buffered. Thus, the only cellular structure directly exposed to the highly acidic canalicular content is the apical membrane forming the canaliculus in the parietal cell.
Cell and Tissue Research 09/2007; 329(2):313-20. · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The human pathogen Helicobacter pylori has infected more than half of the world's population. Nevertheless, the first step of infection, the acute colonization of the gastric mucus, is poorly understood. For successful colonization, H. pylori must retain active motility in the gastric lumen until it reaches the safety of the mucus layer. To identify the factors determining the acute colonization, we inserted bacteria into the stomach of anesthetized Mongolian gerbils. We adjusted the gastric juice to defined pH values of between 2.0 and 6.0 by using an autotitrator. Despite the fact that Helicobacter spp. are known to survive low pH values for a certain time in vitro, the length of time that H. pylori persisted under the assay conditions within the gastric juice in vivo was remarkably shorter. In the anesthetized animal we found H. pylori to be irreversibly immotile in less than 1 min at lumen pH values of 2 and 3. At pH 4 motility was lost after 2 min. However, the period of motility increased to more than 15 min at pH 6. Blocking pepsins in the gastric lumen in vivo by using pepstatin significantly increased the period of motility. It was possible to simulate the rapid in vivo immotilization in vitro by adding pepsins. We conclude that pepsin limits the persistence of H. pylori in the gastric chymus to only a few minutes by rapidly inhibiting active motility. It is therefore likely that this short period of resistance in the gastric lumen is one of the most critical phases of Helicobacter infection.
Infection and Immunity 04/2005; 73(3):1584-9. · 4.07 Impact Factor