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RBM3, a cold-inducible neuronal survival factor

Principal Investigator: Prof. Dr. Christoph Bührer

Induced hypothermia has become the first evidence-based treatment to reduce long-term neuronal damage after birth asphyxia. While the clinical effectiveness of this new therapeutic modality has been shown by several large randomized controlled trials, the underlying mechanisms are still poorly understood. Expression of the RNA-binding protein RBM3 is upregulated in response to low temperature (32-34°C) or moderate hypoxia (8% O2), in contrast to most other proteins. After having demonstrated that RBM3 increases resistance of cultured cell against serum deprivation, we now investigate its role in mediating hypothermia-induced protection against acute hypoxia
Study Investigators: Stefanie Endesfelder, Ruth Herrmann, Rodica Altmann
Cooperation: Dr S Wellmann, Neonatologie Unispital Zürich; A Zelmer, Universitätskinderspital beider Basel; Dr M Truss, Molekulare Pädiatrie Charité Universitätsmedizin Berlin

Neonatal Haematopoiesis

Principal Investigator: Dr. Malte Cremer

Almost every premature infant admitted to a neonatal intensive care unit is affected by anaemia and/or thrombocytopenia. Analysing innovative parameters of the full blood count by fully-automated analysers is helpful to evaluate neonatal thrombocytopenia. We could demonstrate that the immature platelet fraction (IPF) is useful parameter in predicting the course of neonatal thrombocytopenia. This parameter is now under investigation in a prospective trial in combination with other megakaryopoietic parameters in premature infants. On the other hand, regulation of haematopoiesis by cytokines and growth factor is complex. The therapy of the anaemia of prematurity with erythropoietin results in a marginal effect erythropoiesis and only the minority of premature infants profit from such therapy. We are investigating with other factors may contribute to anaemia of prematurity. Similar questions are answered in animal models of congenital thrombocytopenia.

Cooperation: PD Dr. rer. nat. Harald Schulze, Padiatric Molecular Biology, Charité, Dr. Med. Dipl. biochem. Andreas Weimann, Institute for Laboratory Medicine and Pathobiochemistry, Charité

Co-workers: Philipp Deindl, Sebastian Hartenstein, Oliver Winter, David Szekessy

Evaluation of new echocardiographic parameters and urinary NT-proBNP in preterm infants < 1500 g

Principal Investigator: Dr. med. C. Czernik

Patent ductus arteriosus (PDA) is frequent in preterm infants who weigh less than 1500 g at birth. Clinical and echocardiographic signs (LA/Ao-ratio and ductal diameter) define hemodynamic significance of PDA, but do not reveal the need for PDA intervention in the first days of life. Plasma levels of NT-proBNP correlated positively with a hemodynamically significant PDA and proved to be a good predictor for ductus intervention. Because NT-proBNP clearance occurs only in the kidney, we investigated the urine concentration in our study. Additionally, we evaluated the accuracy of conventional and new echocardiographic measurements (Tissue Doppler, 2D Speckle Tracking) in preterm infants. The aim of this study was to validate speckle tracking and tissue dopler imaging echocardiography and the biological marker NT-proBNP in NICUs to predict the need for subsequent PDA treatment. Patient recruitment completed between 1 August 2008 and 31 December 2009.

Study Investigators: PD Dr med. Lothar Schmitz, Stefanie Rohde

Sponsor: Roche Diagnostics, GE

Protection of the immature brain against high oxygen-mediated damage

Principal Investigator: Dr. Stefanie Endesfelder

The growing understanding of molecular mechanisms involved in the increased sensitivity of the developing brain towards various conditions such as high oxygen, anti-epileptic drugs or mediators of inflammation provides opportunities to specifically search for potentially protective medications. Experiments carried out in vivo (employing newborn rats) and in vitro (employing cultured fetal or neonatal brain cells) complement each other to elucidate signal transduction pathways and characterize the interaction of neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells.

Study Investigators: Felix Brehmer, Ulrike Weichelt, Monika Berns, Ruth Herrmann, Rodica Altmann, Max Lehmann, Maria Breiler, Greta Freundt, Christoph Bührer

Cooperation: Prof U Felderhoff-Müser, Universitätskinderklinik Essen

Nutritional intervention in very low birth weight infants and term infants

Principal Investigator: Andrea Loui, MD

Very immature infants have higher nutritional needs than term infants because of immaturity, rapid growth and postnatal diseases which may occur after birth. Our group performed nutritional balance studies on trace elements and minerals in infants with a birth weight below 1500g to investigate their special nutritional requirements. As a result of these studies the nutritional guidelines were changed and human breast milk was fortified with higher amounts of trace elements and minerals. By using a bone ultrasound devise in two different studies we investigate bone growth in preterm infants and in children with phenylketonuria. Human milk also contains hormones, e.g. leptin. In a study we analyse the concentration of leptin and other hormones in human milk of mothers given birth to preterm and term infants. Vitamin A plays an important role in the maturation of lungs and kidneys. Preterm infants have low plasma vitamin A levels. In a study we included 100 very low birth weight infants with or without parenteral vitamin A supplementation and investigate the levels of retinol, retinol binding protein 4 and transthyretin in serum and urine. One aim is to test the possibility of a monitoring system for the vitamin A supplementation via urine levels.

Coworkers: Ann-Carolin Hoyer, MD; Silke Brodkorb, MD; Juliane Wauer, MD; Elisabeth Eilers MD (Dpt. of Perinatal Medicine Neukölln)

Pain assessment and therapy in newborns

Principal Investigator: Lars Garten, MD

Aside from being exposed to stress resulting from their illnesses, newborns on the intensive care unit often experience pain. Despite a significant increase in our knowledge of neonatal pain in recent years, many questions remain unanswered. Our clinical research focuses on different fields of neonatal pain research, e.g. new methods for pain assessment in premature and full-term infants or differences in the use of opioids during palliative care in neonatal and paediatric intensive care units.

Collaborators: Annette Münch, Anke Wendt, Philipp Deindl, Steffen Dähmlow, Tobias Reindl

Cooperation: Klinik für Allgemeine Pädiatrie und Klinik für Pädiatrie mit Schwerpunkt Onkologie/Hämatologie der Charité (Clinic for General Paediatrics and Clinic for Paediatrics, Focus on Oncology/Haematology of the Charité)

Sponsorship: "Förderverein für frühgeborene Kinder an der Charité e.V."