RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.
Introduction: There are no published data on the prevalence of common gastrointestinal disorders such as dyspepsia, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), constipation and bloating in the Polish population. Aim: The aim of this study was to determine the prevalence of these most common abdominal symptoms. Material and methods: The study involved a population sample aged 21 years or older from a medium-sized city. A total of 850 people (age range: 21-76 years) were interviewed. Demographic and anthropometric data, symptoms specific to dyspepsia, GERD, constipation, diarrhoea, bloating, IBS, as well as nutritional habits, alcohol and tobacco use, and presence of concomitant diseases were studied in a face-to-face interview.Results: Approximately 23% of participants suffered from dyspepsia, 36% had GERD, constipation was present in 13% of participants, and bloating in 31%. Only 7 participants reported chronic diarrhoea and 13% of participants had IBS symptoms. All the above-mentioned complaints were slightly more common in diabetic patients, but the difference was not significant. Conclusions: The prevalence of gastrointestinal symptoms in the Polish population is high, and similar to the rates reported by investigators from other countries.
A significantly higher incidence of IGM appears to occur in CRC patients than in the healthy population. This phenomenon is not dependent on age and body-weight, which may suggest that it is cancer that predisposes to diabetes rather than the other way round. The neoplastic process in the colon is not associated with hyperinsulinaemia or insulin resistance, but in CRC patients, pancreatic B-cell dysfunction typical of the early stages of diabetes is seen.
IntroductionMany clinicians consider chronic gastritis to be equivalent to Helicobacter pylori infection. However, it is known that there are numerous other causes of the condition.AimDetermination of the incidence of gastritis in patients with dyspepsia referred for diagnostic endoscopy of the upper part of the digestive tract, identification of the parts of the stomach most frequently affected by the inflammation, as well as the impact of an insufficient number of collected samples on the correct diagnosis.Material and methodsUpper gastrointestinal endoscopy due to dyspepsia was performed in 110 patients. In the course of gastroscopy two biopsy specimens were collected for histopathological examination and towards H. pylori infection from the lesser and greater curvature in the antrum 3 cm from the pyloric sphincter, in the body – 4 cm proximally to the stomach angular incisure on the lesser curvature, and in the middle of the greater curvature, as well as in the subcardiac region on the side of the lesser and greater curvature.ResultsIn patients with dyspepsia H. pylori-negative chronic gastritis is more common than gastritis with accompanying H. pylori infection. Collection of too small a number of biopsy specimens results in failure to detect inflammatory changes and/or H. pylori infection, which may be limited to one part of the stomach. Biopsy specimens of gastric mucosa should be collected in compliance with the assumptions of the Sydney System. Helicobacter pylori infection in people with dyspepsia is now being reported more rarely than in the past (36%).ConclusionsIn patients with dyspepsia chronic H. pylori-negative gastritis is more common than gastritis with an accompanying H. pylori infection. Helicobacter pylori infection is not always equivalent to the presence of chronic gastritis.
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