Personalized medicine is commonly regarded as an extension of genomic medicine. However, a personalized treatment should not [corrected] be based solely on the presence or absence of genetic factors. Complex imaging methods supplement the diagnostic picture of an individual patient. Comprehensive imaging in population-based settings provides information on reference intervals, the predictive value of subclinical findings, and the complex interrelationships among risk factors, subclinical imaging phenotypes, and diseases.

No abstract

No abstract

One of the clinical characteristics associated with septic shock is heart failure. Several lines of evidence indicate that functional consequences of heart failure in septic shock are linked to the activated NO-cyclic guanosine monophosphate (NO-cGMP) pathway. We have previously shown that the high-affinity cGMP export transporter, multidrug resistance protein 5 (MRP5), is expressed in the heart, which modulates intracellular concentrations and, hence, the effects of cGMP. Thus, modified expression of cardiac MRP5 in septic shock can alter cGMP concentrations and contribute to the development of heart failure. We therefore investigated MRP5 expression in the heart using two established murine models of septic shock (intraperitoneal LPS injection and surgical implantation of a stent into the ascending colon, resulting in a multibacterial peritonitis [CASP, colon ascendens stent peritonitis] in C57BL/6N mice, respectively; n = 38). Cardiac MRP5 was assessed by quantitative polymerase chain reaction and immunofluorescence. The protein was localized in the endothelial wall, smooth muscle, and cardiac myocytes. MRP5 mRNA expression was significantly reduced compared with controls both in the LPS (31.9 +/- 16.8 x 10(-4) vs. 54.1 +/- 14.8 x 10(-4), P = 0.025) and CASP model (18.3 +/- 9.4 x 10(-4) vs. 42.8 +/- 12.1 x 10(-4), P = 0.009; MRP5/glyceraldehyde 3-phosphate dehydrogenase copy numbers, respectively). In parallel, IL-6 plasma levels were significantly increased in both models. Incubation of cultured murine cardiomyocytes (HL1) with 5 ng/mL IL-6 resulted in decreased expression of MRP5 (54% of control), as did incubation of the cells with serum from septic mice (LPS serum, 22% of control; CASP serum, 11% of control). In conclusion, cardiac expression of the cGMP export transporter MRP5 is decreased in two murine models of septic shock, most likely by a transcriptional mechanism. Reduced cGMP export as a consequence of decreased MRP5 expression can attenuate heart failure in sepsis.

Das MDR1-Genprodukt P-Glykoprotein ist nicht nur Ursache der "multidrug resistance", sondern erfüllt auch eine wichtige physiologische Funk-tion, da es in zahlreichen Gewebe-und Organschranken sowie in Zellen mit Ausscheidungsfunktion vorkommt. Es behindert die Absorption und Verteilung einer Vielzahl von Arzneistoffen und fördert ihre Elimination. Die Variabilität der Expression und Funktion von P-Glykoprotein kann sich auf die Sicherheit der Arzneimitteltherapie auswirken. Faktoren, die zu klinisch bedeutsamen Verände-rungen führen können, sind