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Preissner S.C.,Charite - Medical University of Berlin | Hoffmann M.F.,Charite - Medical University of Berlin | Preissner R.,Charite - Medical University of Berlin | Dunkel M.,Charite - Medical University of Berlin | And 2 more authors.
PLoS ONE | Year: 2013

The cytochrome P450 (CYP) enzymes are major players in drug metabolism. More than 2,000 mutations have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity. Therefore, CYPs play an important role in inter-individual drug response and their genetic variability should be factored into personalized medicine. To identify the most relevant polymorphisms in human CYPs, a text mining approach was used. We investigated their frequencies in different ethnic groups, the number of drugs that are metabolized by each CYP, the impact of CYP SNPs, as well as CYP expression patterns in different tissues. The most important polymorphic CYPs were found to be 1A2, 2D6, 2C9 and 2C19. Thirty-four common allele variants in Caucasians led to altered enzyme activity. To compare the relevant Caucasian SNPs with those of other ethnicities a search in 1,000 individual genomes was undertaken. We found 199 non-synonymous SNPs with frequencies over one percent in the 1,000 genomes, many of them not described so far. With knowledge of frequent mutations and their impact on CYP activities, it may be possible to predict patient response to certain drugs, as well as adverse side effects. With improved availability of genotyping, our data may provide a resource for an understanding of the effects of specific SNPs in CYPs, enabling the selection of a more personalized treatment regimen. © 2013 Preissner et al.

Balancing the partly different needs and expectations of stakeholders is one of the most fundamental tasks of a manager. Therefore, successful managing means identifying and prioritizing the relevant stakeholders, balancing out their needs and interests, and achieving outstanding results. Professional methods have to be used to overcome these challenging tasks. The extensive results of the working group " Laboratory Management " are presented in short. The article focusses on topics such as outcome measures, benchmarking, cost accounting, and business excellence that have been well-known subjects in other sectors for a long time. © 2013 Walter de Gruyter GmbH.

Muller D.-P.,Klinikum Augsburg | Hoffmann R.,Institute for Laboratory Medicine | Welzel J.,Klinikum Augsburg
JDDG - Journal of the German Society of Dermatology | Year: 2014

Background There has been a steady increase of the incidence of erysipelas in Germany in the recent past. Affected patients also often show defects in the cutaneous barrier caused by microorganisms. The aim of this non-interventional case-control study was to investigate a possible interrelationship between interdigital tinea pedis and bacterial toe web (interdigital space) infections and erysipelas of the leg, as well as a potential interaction among the microorganisms themselves. Material and methods The patient population contained 150 people equally distributed among three groups, one retrospective and one prospective erysipelas group (EG = rEG + pEG) plus one control group (KG). Results 51 % of the patients with erysipelas and 32 % of the control group suffered from interdigital tinea pedis. There was a significant association between interdigital tinea pedis and the recurrence rate of erysipelas, but not with erysipelas itself. Staphylococcus aureus (EG: 30.34 %; KG: 3.23 %) and non-pathogenic aerobic bacteria were significantly associated with erysipelas in each statistical analysis. Staphylococcus aureus showed a positive, the non-pathogenic aerobic germs (EG: 28,09 %; KG: 80,65 %) a negative association. Conclusions This study demonstrates an association between the microorganisms of the toe web and erysipelas of the leg. Erysipelas itself is influenced to a great extent by the bacterial flora, while its recurrence relates more to interdigital tinea pedis. © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Minder E.I.,Institute for Laboratory Medicine
Expert Opinion on Orphan Drugs | Year: 2013

Introduction: Erythropoietic protoporphyria (EPP) is characterized by incapacitating pain in the sunlight-exposed skin areas due to accumulation of the metabolite protoporphyrin. Until now, no effective prevention of phototoxicity has been available. Afamelanotide, an α-melanocyte-stimulating hormone (α-MSH) analogue and first-in-class drug, induces melanin formation. The skin tan diminishes activation of protoporphyrin by reducing the sunlight penetration into the dermis. For continuous photoprotection, afamelanotide is applied every second month as a 16-mg controlled release implant. Areas covered: In two Phase II and two Phase III trials in Europe, Australia and the US afamelanotide significantly reduced EPP-related phototoxic pain when tested in > 250 patients. To date, safety including compassionate use programs for up to 6 years appears to be excellent, including only nausea and flushing for a brief time after administration. No immunogenicity was observed. Approval for EPP treatment is pending at the European Medicines Agency. Expert opinion: The authors assume that afamelanotide, being the first effective treatment of EPP, will be a broadly applied treatment of EPP in Europe, North America, Australia and likely also in other countries such as Japan, South Africa and South America within 5 years. © 2013 Informa UK, Ltd.

Liu K.,Institute for Laboratory Medicine | Lin B.,Institute for Laboratory Medicine | Zhao M.,Institute for Laboratory Medicine | Yang X.,Institute for Laboratory Medicine | And 5 more authors.
Cellular Signalling | Year: 2013

The Sry-containing protein Sox2 initially was known to regulate the self-renewal of the mouse and human embryonic stem cells (ESCs). It is also important for the maintenance of stem cells in multiple adult tissues including the brain and trachea, and it is one of the key transcription factors for establishing induced pluripotent stem cells. Recently, overexpression and gene amplification of Sox2 have been associated with the development of squamous cell carcinoma in multiple tissues such as the lung and esophagus. These different roles for Sox2 involve a complicated regulatory networks consisting of microRNAs, kinases and signaling molecules. While the levels of Sox2 are modulated transcriptionally and translationally, post-translational modification is also important for the various functions of Sox2. In clinics, high levels of Sox2 are correlated with poor prognosis and increased proliferation of cancer stem cells. Therefore targeting Sox2 can be potentially explored for a new therapeutic avenue to treat cancers. This review will focus on the different roles for Sox2 in stem cell maintenance and its oncogenic roles in the context of signal transcription and microRNA regulation. We will also review the main upstream and downstream targets of Sox2, which can be potentially used as therapeutic measures to treat cancer with abnormal levels of Sox2. © 2012 Elsevier Inc.

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