Search

Background: Off-label use is frequent in paediatrics but that does not necessarily mean that the risk-benefit ratio is negative. Nevertheless, evidence-based data is essential for safe drug therapy. In Germany, there is no publicly available compendium providing transparent, evidence-based information for paediatric pharmacotherapy to date. This work describes the development of a web-based paediatric drug information system (PDIS) for Germany and its evaluation by health care professionals (HCP). Methods: Since 2012, a PDIS is being developed by the authors and is supported by the Federal Ministry of Health since 2016. Dosing recommendations were established based on systematic literature reviews and subsequent evaluation by clinical experts. The prototype was evaluated by HCP. Based on the results, the further development was concluded. Results: 92% of HCP believed that the PDIS could improve the quality of prescribing, as currently available information is deficient. Besides the license and formulations, dosing recommendations were the most relevant modules. A dosage calculator was the most wanted improvement. To facilitate sustainability of future development, a collaboration with the Dutch Kinderformularium was established. As of 2021, the database will be available to German HCP. Conclusion: The fundamentals for a German PDIS were established, and vital steps were taken towards successful continuation.

Anatomical and metabolic parameters of mice without a deletion in Apoe (Apoe +/+ Itga8 +/+ or Apoe ++ Itga8 â /â ). (DOCX 22 kb)

Atherosclerotic plaque formation in mice without a deficiency of Apoe. Exemplary en face preparations of aortae of male and female Apoe +/+ Itga8 +/+ or Apoe +/+ Itga8 −/− mice, stained with Sudan IV (left) or unstained (right). One en face preparation of the aorta of an Apoe-deficient (Apoe −/− Itga8 +/+) female mouse was stained for Sudan IV as a positive control. (PDF 257 kb)

Primer pairs used in the study. (DOCX 24 kb)

Results from two-way ANOVA of markers of vascular and renal injury. (DOCX 19 kb)

Osteopontin in the brachiocephalic trunk. Exemplary osteopontin-stained cross sections of the brachiocephalic trunk of male and female mice with a deficiency of Apoe. (PDF 303 kb)

Suppl_Material_Table_2 for Expression and Regulation of Retinoic Acid Receptor Responders in the Human Placenta by Hanna Huebner, Andrea Hartner, Wolfgang Rascher, Reiner R. Strick, Sven Kehl, Felix Heindl, David L. Wachter, Matthias W. Beckmann, MD, Fabian B. Fahlbusch, and Matthias Ruebner in Reproductive Sciences

Vascular and renal changes in 7- and 9-month-old mice. (DOCX 25 kb)

Osteopontin in the kidney. Exemplary photomicrographs of osteopontin-stained renal sections of male and female Apoe −/− Itga8 +/+ or Apoe −/− Itga8 −/− mice. (PDF 548 kb)

Suppl_Material_Table_1 for Expression and Regulation of Retinoic Acid Receptor Responders in the Human Placenta by Hanna Huebner, Andrea Hartner, Wolfgang Rascher, Reiner R. Strick, Sven Kehl, Felix Heindl, David L. Wachter, Matthias W. Beckmann, MD, Fabian B. Fahlbusch, and Matthias Ruebner in Reproductive Sciences

Background The placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR) is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas. Methods We aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR. Results CRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h. Conclusion The relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction.