The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. We studied the effect of EPO on dermal regeneration using intravital microscopy in a model of full dermal thickness wounds in the skin-fold chamber of hairless mice. Animals received repetitive low doses or high doses of EPO (RLD-EPO or RHD-EPO) or a single high dose of EPO (SHD-EPO). SHD-EPO accelerated wound epithelialization, reduced wound cellularity, and induced maturation of newly formed microvascular networks. In contrast, RHD-EPO impaired the healing process, as indicated by delayed epithelialization, high wound cellularity, and lack of maturation of microvascular networks. Also, RHD-EPO caused an excessive erythrocyte mass and rheological malfunction, further deteriorating vessel and tissue maturation. Moreover, RHD-EPO altered fibroblast and keratinocyte migration in vitro, while both cell types exposed to RLD-EPO, and, in particular, to SHD-EPO showed accelerated wound scratch closure. In summary, our data show that a single application of a high dose of EPO accelerates and improves skin wound healing.

No abstract

The liver responds to elevated plasma concentrations of free fatty acids (FFAs) with an enhanced uptake of FFAs and their esterification to triacylglycerol (TAG). On the long term, this may result in massive hepatic TAG accumulation called steatosis hepatitis. In hepatocytes, the poor water-soluble TAG is packed in specialized organelles: Lipid droplets (LDs) serving as transient cellular deposit and lipoproteins (LPs) transporting TAG and cholesterol esters to extra-hepatic tissues. The dynamics of these organelles is controlled by a variety of regulatory surface proteins (RSPs). Assembly and export of VLDLs are mainly regulated by the microsomal transfer protein (MTP) and apoprotein B100. Formation and lipolysis of LDs are regulated by several RSPs. The best studied regulators belong to the PAT (Perilipin/Adipophilin/TIP47) and CIDE families. Knockdown or overexpression of SRPs may significantly affect the total number and size distribution of LDs. Intriguingly, a large cell-to-cell heterogeneity with respect to the number and size of LDs has been found in various cell types including hepatocytes. These findings suggest that the extent of cellular lipid accumulation is determined not only by the imbalance between lipid supply and utilization but also by variations in the expression of RSPs and metabolic enzymes. To better understand the relative regulatory impact of individual processes involved in the cellular TAG turnover, we developed a comprehensive kinetic model encompassing the pathways of the fatty acid and triglyceride metabolism and the main molecular processes governing the dynamics of LDs. The model was parametrized such that a large number of experimental in vitro and in vivo findings are correctly recapitulated. A control analysis of the model revealed that variations in the activity of FFA uptake, diacylglycerol acyltransferase (DGAT) 2, and adipose triglyceride lipase (ATGL) have the strongest influence on the cellular TAG level. We used the model to simulate LD size distributions in human hepatoma cells and hepatocytes exposed to a challenge with FFAs. A random fold change by a factor of about two in the activity of RSPs was sufficient to reproduce the large diversity of droplet size distributions observed in individual cells. Under the premise that the same extent of variability of RSPs holds for the intact organ, our model predicts variations in the TAG content of individual hepatocytes by a factor of about 3-6 depending on the nutritional regime. Taken together, our modeling approach integrates numerous experimental findings on individual processes in the cellular TAG metabolism and LD dynamics metabolism to a consistent state-of-the-art dynamic network model that can be used to study how changes in the external conditions or systemic parameters will affect the TAG content of hepatocytes.

Individual fit-testing of earplugs is an exciting new trend in hearing conservation. This article reviews how this technology is being used to protect noise-exposed workers. Earplug fit-testing systems are becoming more commercially available and more feasible for field use. Individual fit-testing is no longer used only for research investigations but is being incorporated in Hearing Conservation Programs (HCP) to improve training, document protection and evaluate the effectiveness of the hearing protector element of an effective HCP.

Zusammenfassung Hintergrund Seit der Erstbeschreibung einer lokoregionären Lappenplastik zur Nasenrekonstruktion im 6. Jahrhundert v. Chr. durch den indischen Arzt Sushruta Samhita sind diese ein fester Bestandteil in der Wiederherstellungschirurgie geworden. Neben der konsequenten Weiterentwicklung chirurgischer Operationsmethoden wurden die zu Grunde liegenden physikalischen Messmethoden des Lappenmonitoring in den letzten Dekaden stetig weiterentwickelt. Das Hyperspektralimaging (HSI) stellt eine neue quantitative Messmethode zur Beurteilung der Gewebeperfusion dar. Ziel Das Ziel dieser Arbeit ist die Evaluation des HSI als Monitoringverfahren nach lokoregionärer Defektdeckung. Patienten und Methode Bei insgesamt 16 Patienten wurde nach gefäßgestieltem Gewebetransfer die Sauerstoffsättigung, der Hämoglobingehalt sowie der Wassergehalt von Haut, Monitorinsel und nekrotischen Lappenarealen am 1. bis 7. postoperativen Tag gemessen. Die erhobenen Daten wurden statistisch deskriptiv ausgewertet und grafisch ausgearbeitet. Ergebnisse Das HSI zeigte einen erhöhten Hämoglobingehalt, eine Abnahme der Sauerstoffsättigung sowie des Wassergehaltes in den nekrotischen Lappenarealen im Vergleich zur vitalen Monitorinsel und zur gesunden Haut. Monitorinsel und vitale Hautareale wiesen eine nahezu identische Werteverteilung auf. Schlussfolgerung HSI erlaubt die sichere, kontaktfreie und sofortige Bestimmung der Gewebeperfusion von transferierten Gewebearealen bei Patienten nach lokoregionärer Defektdeckung. Daher erscheint die Verwendung von HSI im Rahmen des postoperativen Lappenmonitorings sinnvoll.