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Bei der Aufnahme von Arzneimitteln in Zellen spielen Transportprozesse eine große Rolle. Das ATP-abhängige Transportprotein P-Glykoprotein vermittelt häufig Resistenzen gegenüber Arzneimitteln. Zunächst wurde dieser Effekt in P-Glykoprotein-überexprimierenden Tumoren entdeckt. Auch viele gesunde Gewebe enthalten P-Glykoprotein. Einige der Substanzen, die von P-Glykoprotein transportiert werden, sind vielverwendete Medikamente bei der Therapie von Herzerkrankungen. Die individuelle Expressionhöhe von P-Glykoprotein im Herzen könnte für das unterschiedliche Ansprechen von Patienten auf von P-Glykoprotein transportierte Medikamente verantwortlich sein. Im Rahmen dieser Arbeit wurde die Expression von P-Glykoprotein an 15 humanen Herzgewebeproben untersucht. Verwendet wurde die Methode der RT-PCR und die immunhistochemische Darstellung des Proteins. Die Expression von P-Glykoprotein in humanem Herzmuskelgewebe konnte an allen Proben gezeigt werden. Immunhistochemisch ist P-Glykoprotein in den Endothelzellen der Arteriolen und Kapillaren lokalisiert worden. Hinsichtlich der Expression bei verschiedenen Krankheiten konnte bei Patienten mit einer dilatativen Kardiomyopathie eine signifikante Verminderung (p = 0,05) beobachtet werden. Die gewonnenen Ergebnisse zeigen eine Beteiligung des Herzens an Transportprozessen. Intrakardiale Konzentrationen vieler Substanzen können abhängig von der individuellen P-Glykoprotein-Expression beeinflusst werden
Periodontitis is one of the most prevalent oral diseases worldwide and is caused by multifactorial interactions between host and oral bacteria. Altered cellular metabolism of host and microbes releases a number of intermediary end products known as metabolites. There is an increasing interest in identifying metabolites from oral fluids such as saliva to widen the understanding of the complex pathogenesis of periodontitis. It is believed that some metabolites might serve as indicators toward early detection and screening of periodontitis and perhaps even for monitoring its prognosis in the future. Because contemporary periodontal screening methods are deficient, there is an urgent need for novel approaches in periodontal screening procedures. To this end, we associated oral parameters (clinical attachment level, periodontal probing depth, supragingival plaque, supragingival calculus, number of missing teeth, and removable denture) with a large set of salivary metabolites (n = 284) obtained by mass spectrometry among a subsample (n = 909) of nondiabetic participants from the Study of Health in Pomerania (SHIP-Trend-0). Linear regression analyses were performed in age-stratified groups and adjusted for potential confounders. A multifaceted image of associated metabolites (n = 107) was revealed with considerable differences according to age groups. In the young (20 to 39 y) and middle-aged (40 to 59 y) groups, metabolites were predominantly associated with periodontal variables, whereas among the older subjects (≥60 y), tooth loss was strongly associated with metabolite levels. Metabolites associated with periodontal variables were clearly linked to tissue destruction, host defense mechanisms, and bacterial metabolism. Across all age groups, the bacterial metabolite phenylacetate was significantly associated with periodontal variables. Our results revealed alterations of the salivary metabolome in association with age and oral health status. Among our comprehensive panel of metabolites, periodontitis was significantly associated with the bacterial metabolite phenylacetate, a promising substance for further biomarker research.