Abstract. We report a simple novel rat model that combines prolonged esophagitis and parallel sphincters failure. The anti-ulcer gastric pentadecapeptide BPC 157, which was found to be stable in gastric juice, and is being evaluated in inflammatory bowel disease trials, is an antiesophagitis therapy that recovers failed sphincters. Twelve or twenty months after the initial challenge (tubes sutured into sphincters for one week and then spontaneously removed by peristalsis), rats exhibit prolonged esophagitis (confluent hemorrhagic and yellowish lesions, thinner epithelium and superficial corneal layer, with stratification derangement); constantly lowered pressure of both sphincters (assessed by using a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through esophageal or duodenal incision); and both lower esophageal and pyloric sphincter failure. Throughout the esophagitis experiment, BPC 157 was given at either 10 µg / kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 µg/ ml (12 ml / rat). This treatment recovers i) esophagitis (macroscopically and microscopically, at either region or investigated time period) and ii) pressure in both sphincters (cmH 2 O). In addition, BPC 157 (10 µg / kg) or saline (1 ml / rat, 5 ml / kg) was specifically given directly into the stomach; pressure assessment was performed at 5 min thereafter. The effect of BPC 157 is specific because in normal rats, it increases lower esophageal sphincter-pressure, but decreases pyloric sphincter-pressure. Ranitidine, given as the standard drug using the same protocol (50 mg / kg, i.p., once daily; 0.83 mg / ml in drinking water; or 50 mg / kg directly into the stomach) had no effect.
Abstract. Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 µg / kg, 10 ng / kg, last application 24 h before assessment), or continuously in drinking water at 0.16 µg / ml, 0.16 ng / ml (12 ml / rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH 2 O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg / kg, intraperitoneally, once daily; 0.83 mg / ml in drinking water; 50 mg / kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.
The impact of bacterial colonization on the severity and pattern of chronic inflammation in rhinosinusitis is not clear. In this study, it was hypothesized that bacterial colonization of the sinus mucosa would have a greater impact on inflammatory response modulation in asthmatic patients than in non-asthmatic patients with chronic rhinosinusitis. In order to test this hypothesis, granulocyte activation was measured and related to bacteria identified in the sinus lavage. Lavages from the maxillary sinuses of 21 asthmatic and 19 non-asthmatic patients with chronic rhinosinusitis (CRS) were microbiologically examined for aerobic and anaerobic growth. Eosinophil cationic protein (ECP), an eosinophil activation marker, and myeloperoxidase (MPO), a neutrophil activation marker, were measured in the sinus lavages. Bacteria were recovered in 20/32 samples from the asthmatics and in 21/33 samples from the non-asthmatics. Gram-positive aerobes and anaerobes were slightly more common than Gram-negative bacteria. A different bacterial profile was found when comparing Gram-negatives between the groups. Concentrations of MPO were significantly higher in samples with bacterial recovery from asthmatic patients, compared to sterile samples of both groups. Concentrations of ECP in the samples from asthmatic patients were significantly higher than in the controls, with no significant difference related to bacterial colonization. Bacterial colonization in chronically inflamed sinuses may have an impact on neutrophil granulocyte activation in patients with bronchial asthma, which was not confirmed for patients with CRS without asthma.
The aim of the study was to show the difference in the pattern of inflammation, and Th1/Th2 polarization between asthmatic and non-asthmatic patients with CRS, specifically eosinophil activation, local IgE levels in the sinus fluid and tissue, and the severity of inflammation were measured. The maxillary sinus lavages, mucosal biopsies and bacteriological swabs were taken in 17 asthmatic and 36 non-asthmatic adult patients with CRS. The concentrations of IgE, eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase were analyzed and IgE+ cells, eosinophils, lymphocytes and plasma cells were counted. The granulocyte activation markers and IgE in sinus lavages, and the inflammatory and IgE+ cells counts were significantly higher in the asthmatics with the greatest difference in ECP and IgE concentrations. The tryptase concentrations did not differ, but only in the asthmatics they correlated significantly with the IgE concentrations and IgE+ cells count. Asthmatic patients present a distinct subgroup among the patients with chronic rhinosinusitis (CRS). The levels of the cellular markers and IgE in the sinus fluid differ from those of non-asthmatic patients with CRS. The activation of granulocytes (especially eosinophils), local IgE concentrations and the inflammatory cells infiltration are significantly higher in the asthmatics.
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