Institute for Laboratory Medicine

Leipzig, Germany

Institute for Laboratory Medicine

Leipzig, Germany
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Dreimuller N.,Johannes Gutenberg University Mainz | Schlicht K.F.,Johannes Gutenberg University Mainz | Wagner S.,Johannes Gutenberg University Mainz | Peetz D.,Institute for Laboratory Medicine | And 5 more authors.
Neuropharmacology | Year: 2012

In Major Depressive Disorder, a growing data base suggests that the onset of antidepressants' action can be detected by improvement of depressive symptoms in the first 10-14 days of treatment. Previous studies showed that the mean concentration of the brain-derived neurotrophic factor (BDNF) in blood increases during antidepressant treatment and positively correlates with amelioration of MDD symptoms. We previously showed an association between very early changes of the serum BDNF concentration and treatment outcome (Tadić et al., 2011. Prog Neuropsychopharmacol Biol Psychiatry 35, 415-420). However, no study has yet investigated whether BDNF concentration in plasma increases in the early course of treatment and enables the prediction of final treatment outcome. The goal of this study was to investigate in MDD patients, whether the change of pBDNF in the early course of treatment is a specific and sensitive marker for final treatment outcome. For this purpose, we performed a naturalistic pilot study with 39 inpatients with MDD according to DSM-IV. Depression severity and pBDNF were measured in weekly intervals from baseline (EP) to endpoint (EP, max. week six) with the 21-item Hamilton Depression Rating Scale (HAMD-21) and enzyme-linked immunosorbent assay (ELISA), respectively. According to ROC-analysis, the best cut-off value for the prediction of response at EP is an increase of 338 pg/ml or 126%, respectively, of pBDNF between BL and day 7. The single markers pBDNF change and HAMD-21 improvement from BL-d7 predicted later treatment outcome with moderate to high sensitivity and specificity (pBDNF: 42% and 96%, resp.; HAMD improvement: 83% and 65%, resp.). The combined marker early pBDNF change plus HAMD-21 improvement at day 7 increased the specificity for response to 100%. Our data provide first preliminary evidence that an early change of pBDNF in conjunction with early improvement might be a peripheral marker predictive for treatment outcome in patients with MDD. This has to be confirmed in further investigations. This article is part of a Special Issue entitled 'Anxiety and Depression'. © 2011 Elsevier Ltd. All rights reserved.

PubMed | Ruhr University Bochum, University Hospital Frankfurt, Berufsgenossenschaftliche Unfallklinik, Institute for Laboratory Medicine and Hessian State Health Office
Type: | Journal: GMS hygiene and infection control | Year: 2016

Multidrug-resistant Gram-negative bacteria (MRGN) and the infections they cause are a serious threat and a challenge to the healthcare system. This particularly applies to carbapenem-resistant Gram-negative bacteria (CRGN). Currently, the introduction of a nationwide mandatory notification system for CRGN in Germany is under consideration. Against this background, this paper presents an analysis of the mandatory reporting system for CRGN in effect since November 2011 in the federal state of Hesse (Germany).All carbapenem-resistant Gram-negative bacteria and the detected carbapenemases reported to the public health department of the city of Frankfurt am Main, Hesse, Germany, on the basis of the mandatory notification system were analyzed.827 CRGN cases were reported to the public health department of Frankfurt/Main between April 2012 and December 2015. The following bacterial species were reported: Pseudomonas spp. (n=268), Acinetobacter spp. (n=183), Klebsiella spp. (n=195), Enterobacter spp. (n=77), Escherichia coli (n=75) and others (n=29). Between 2012 and 2015, a reduction of the CRGN reports was noticed, mainly due to changes in the reporting of Pseudomonas spp. Between 2012 and 2015, the total number of notifications decreased slightly, although the number of reported CRGN in screening samples increased, thus giving no indication of a decreased testing frequency. For 10.5% of the patients, the place of residence was not Germany, 18.0% of the patients had previously stayed in hospitals abroad, often in countries with a high CRGN prevalence. CRGN bacteria were reported from all of Frankfurts hospitals, and 3.9% were reported from out-patient care facilities. Carbapenemases were detected and reported in 251 CRGN bacteria, including 73 OXA-48, 76 OXA-23, 56 NDM subtypes, and 21 KPC subtypes. There have been no major epidemiological signs of outbreak scenarios.CRGN bacteria are already widespread in patients from hospitals and out-patient care facilities. Clearly, infection control measurements should therefore not only include hospital patients but also those receiving out-patient care. Screening strategies focused on patients from foreign countries with high MRGN prevalence is not sufficient, as only 10.5% of MRGN patients resided in those countries, and only 18% of the patients had been previously treated in a foreign hospital. In a public health context, infection control measures should therefore encompass broader screening strategies.

News Article | December 21, 2016

Diet-related diseases like non-alcoholic fatty liver disease (NAFLD) are known to have a major inflammatory component. However, the molecular pathways linking diet-induced changes with inflammation remained elusive. In a new study, scientists at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Medical University of Vienna identified crucial inflammatory processes in NAFLD. Moreover, the study published in Hepatology shows that malondialdehyde (MDA), a biomarker for oxidative stress, plays a key role in the development of NAFLD and can be neutralized by specific natural antibodies - a novel approach towards a potential therapy for the prevalent disease. The combination of a nutrient rich, western diet and a lack of exercise is a lifestyle which can lead to serious health issues: Worldwide, the incidences of obesity, hypertension or insulin resistance are alarmingly high. As a consequence, risk of developing inflammation-associated diseases like type 2 diabetes, NAFLD and cardiovascular disease increased accordingly. However, the exact pathways that link the eating habits with the ensuing inflammation were so far not well understood. The team of Christoph Binder, Professor of Atherosclerosis Research at the Medical University of Vienna and Principal Investigator at CeMM, in collaboration with Ronit Shiri-Sverdlov at the Maastricht University, Christoph Reinhardt at the University Medical Center of the Johannes Gutenberg University Mainz and the German Center for Cardiovascular Research Mainz was not only able to shed light on the biological processes that lead to the development of chronic inflammation upon a nutrient rich diet in mice. Moreover, the scientists found MDA to be a key player in hepatic inflammation which can be neutralized with natural antibodies. Their results were published in Hepatology (DOI: 10.1002/hep.28970). The highly reactive molecule malondialdehyde, a product from lipid decomposition and biomarker for oxidative stress, accumulates on the surface of dying cells in the liver. Chemically bound to membrane proteins or phospholipids, they form so called MDA epitopes - Binder's research group showed that those MDA epitopes induce cytokine secretion as well as leukocyte recruitment and thereby propagate existing inflammation and render it chronic. "We were able to show in cell culture as well as in model organisms that those MDA epitopes play a major role in diet-induced hepatic inflammation," says Clara Jana-Lui Busch, one of the co-first authors of the study and PhD student at CeMM and the Medical University of Vienna. This was not the only insight of the study: "With intravenous injection of a specific MDA antibody which binds MDA epitopes selectively, we could ameliorate the inflammation in mice" Tim Hendrikx, the other co-first author and PostDoc in the group of Christoph Binder adds. This study shows how the close collaboration of CeMM and the Medical University of Vienna fosters the development of a future precision medicine, says senior author Christoph Binder. "With cutting edge RNA sequencing methods and bioinformatic analyses of transcriptome data, we discovered key mechanisms in some of the most prevalent diseases and we confirmed those findings in mice models." Binder explains, and adds: "Above that, the administration of specific antibodies for MDA epitopes provide a promising new approach for the development of therapeutic strategies." The study "Malondialdehyde epitopes are sterile mediators of hepatic inflammation in hypercholesterolemic mice" was published in Hepatology online in advance on December 16 2016. DOI: 10.1002/hep.28970 The study was funded by The Austrian Science Fund (FWF, SFB Lipotox F30), Boehringer Ingelheim (PhD Fellowship), Austrian Academy of Sciences (Doc Fellowship), EMBO (Short Term Fellowships), The Netherlands Organisation for Scientific Research (NWO), German Center for Cardiovascular Research (DZHK), German Federal Ministry of Education and Research, and the German Research Foundation (DFG). Christoph Binder obtained his MD degree at the University of Vienna in 1997 and received his Ph.D. in Molecular Pathology at the University of California San Diego (UCSD) in 2002. Following a postdoctoral training period at UCSD, he joined the Institute for Laboratory Medicine of the Medical University of Vienna and became Principal Investigator at CeMM in 2006. In 2009 he was appointed Professor of Atherosclerosis Research at the Medical University of Vienna. Christoph Binder is dually affiliated with CeMM and the Medical University of Vienna. http://cemm. The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is an interdisciplinary research institute committed to advancing the understanding of human diseases through basic and biomedical research. Located at the center of the Medical University of Vienna's campus, CeMM fosters a highly collaborative and interactive research mindset. Focusing on medically relevant questions, CeMM researchers concentrate on human biology and diseases like cancer and inflammation/immune disorders. In support of scientific pursuits and medical needs, CeMM provides access to cutting-edge technologies and has established a strategic interest in personalized medicine. Since 2005, Giulio Superti-Furga is the Scientific Director of CeMM. http://www. The Medical University of Vienna is one of the most traditional medical education establishments with nearly 8,000 students and approximately 5,500 staff members, and one of the most important top-level biomedical research institutions in Europe. Its international outlook is one of its most important pillars and the research focus is centered on immunology, cancer research, imaging, brain research and cardiovascular diseases. https:/ For further information please contact CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria Phone +43-1/40160-70 057 Fax +43-1/40160-970 000 http://www.

Preissner S.C.,Charité - Medical University of Berlin | Hoffmann M.F.,Charité - Medical University of Berlin | Preissner R.,Charité - Medical University of Berlin | Dunkel M.,Charité - 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.

Hoermann R.,Klinikum Luedenscheid | Midgley J.E.M.,North Lakes Clinical | Giacobino A.,Klinikum Luedenscheid | Eckl W.A.,Klinikum Luedenscheid | And 3 more authors.
Clinical Endocrinology | Year: 2014

Objective We examined the interrelationships of pituitary thyrotropin (TSH) with circulating thyroid hormones to determine whether they were expressed either invariably or conditionally and distinctively related to influences such as levothyroxine (L-T4) treatment. Design and methods This prospective study employing 1912 consecutive patients analyses the interacting equilibria of TSH and free triiodothyronine (FT3) and free thyroxine (FT4) in the circulation. Results The complex interrelations between FT3, FT4 and TSH were modulated by age, body mass, thyroid volume, antibody status and L-T4 treatment. By group comparison and confirmation by more individual TSH-related regression, FT3 levels were significantly lower in L-T4-treated vs untreated nonhypothyroid autoimmune thyroiditis (median 4·6 vs 4·9 pm, P < 0·001), despite lower TSH (1·49 vs 2·93 mU/l, P < 0·001) and higher FT4 levels (16·8 vs 13·8 pm, P < 0·001) in the treated group. Compared with disease-free controls, the FT3-TSH relationship was significantly displaced in treated patients with carcinoma, with median TSH of 0·21 vs 1·63 (P < 0·001) at a comparable FT3 of 5·0 pm in the groups. Disparities were reflected by calculated deiodinase activity and remained significant even after accounting for confounding influences in a multivariable model. Conclusions TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization. © 2014 John Wiley & Sons Ltd.

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.

Spichty R.,Institute for Laboratory Medicine | Balimann M.,Institute for Laboratory Medicine | Barman J.,Institute for Laboratory Medicine | Barman J.,University of Zürich | Minder E.I.,Institute for Laboratory Medicine
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

The tridecapeptide afamelanotide (Scenesse®) is a congener of α-melanocyte stimulating hormone (α-MSH). Upon binding to the melanocortin 1 receptor (MC1R) on the surface of pigment cells of the skin, the melanocytes, α-MSH or afamelanotide trigger the synthesis of cAMP, which stimulates the synthesis of melanin and therefore induces skin tanning. In a recent trial, afamelanotide administered as controlled release implants protected erythropoietic protoporphyria (EPP) patients from sunlight induced phototoxic skin reactions. Administration of biological therapeutic peptides may elicit unwanted immunogenic responses in recipients of these products. Although in a previous study using ELISA technique we excluded any newly developed immunogenicity during prolonged exposure to afamelanotide, we confirmed the previously published existence of low titers of antibodies against α-MSH in drug-naïve individuals that cross-reacted with afamelanotide. In order to investigate whether such antibodies are neutralizing, i.e. could block the biological effect of afamelanotide, we developed a cell culture-based bioassay. The basis of our assay was the measurement of afamelanotide-induced cAMP formation in a strain of the B16 mouse melanoma cell line, G4F-7, expressing the transfected human MC1R. Average half-effective concentrations of the natural hormone α-MSH and its congener afamelanotide were 38.8±10.6 and 10.9±7.17nM (n=5), respectively. Neutralizing antibodies would reduce the cAMP formation. Two neutralizing anti-α-MSH antibodies served as positive controls. cAMP formation in the G4F-7 cells after addition of sera of drug-naïve (n=6) and of drug-exposed EPP patients (n=17) was significantly lower than after that from healthy volunteers (n=13). There was no difference between drug-naïve and drug-exposed patients. Using forskolin as a hormone-independent stimulator of cAMP formation, we excluded an unspecific interference of EPP sera with cAMP formation.We conclude that afamelanotide even after prolonged application to EPP patients did not elicit neutralizing antibodies. Further, the low titer immunoreactivity observed in sera of some drug-naïve individuals had no effect on the biological activity of afamelanotide. © 2012 Elsevier B.V.

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.

Ceglarek U.,Institute for Laboratory Medicine | Werner M.,Institute for Laboratory Medicine | Kortz L.,Institute for Laboratory Medicine | Korner A.,University of Leipzig | And 3 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2010

Preclinical challenges in the analysis of steroid hormones are primarily determined by biological factors involved in the physiology and pathophysiology of hormone secretion. Major biologically influencing factors like age, sex, pubertal stage, pregnancy, phase of the menstruation, and diurnal rhythm have to be considered in the definition of reference ranges for steroids and their clinical interpretation. Hitherto, in clinical routine laboratories steroids were mainly determined by direct immunoassays applied on automated platforms, which are simple, rapid and cheap if a high number of samples are measured. However, technical factors like cross-reactivity of related steroid metabolites or limited analytical ranges have to be taken in account and may impair accuracy and precision of these direct methods. The actual development of mass spectrometry based analytical platforms for the determination of single steroid or steroid patterns seems to be an alternative analytical approach combining multi-parametric analysis, high sensitivity and specificity as well simple sample pre-treatment, robustness and low running costs for steroid analysis.This short review will give an overview about biological influencing factors and technical disturbing factors of routinely used immunoassay for the analysis of steroids. The application of LC-MS/MS as an alternative routine high-throughput platform for steroid analysis and its perspective role in the standardization and harmonisation of steroid measurements in clinical routine application will be discussed. © 2010 Elsevier Ltd.

Jambor C.,Ludwig Maximilians University of Munich | Von Pape K.-W.,Institute for Laboratory Medicine | Spannagl M.,Ludwig Maximilians University of Munich | Dietrich W.,Ludwig Maximilians University of Munich | And 2 more authors.
Anesthesia and Analgesia | Year: 2011

Background: Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin. Methods: Consecutive patients scheduled for surgery were prospectively enrolled in this study. The patients last aspirin ingestion had occurred within the previous 48 hours before blood sampling in the "full aspirin effect" group, between 48 and 96 hours before in the "variable aspirin effect" group, and >96 hours before in the "recovered aspirin effect" group. The control group had not taken any aspirin. Multiple electrode aggregometry, platelet function analyzer (PFA)-100, and in vivo BT were performed to assess the effects of aspirin. One-way analysis of variance on ranks with a post hoc multiple-comparison procedure (Dunn) was used to detect differences among the groups. Categorical data were compared using the z test. Receiver operating characteristic (ROC) curves were created to determine the diagnostic accuracy of the platelet function assays investigated. The area under the ROC curve (AUC), sensitivity, and specificity of the assays were calculated. The level of statistical significance was set at P < 0.05. Results: Three hundred ninety-four patients were included in the analysis (133 control and 261 aspirin-treated patients). All 3 methods were able to detect the antiplatelet effect of aspirin in the full aspirin effect group. Furthermore, no difference in the measurement values between the recovered aspirin effect and control group was found, irrespective of the assay performed. Measurement values in the variable aspirin effect group were different from those of the control group in the ASPItest using multiple electrode aggregometry and COL-EPI using PFA-100 but not in BT. ROC analysis showed the highest diagnostic accuracy in excluding the residual aspirin effect in the ASPItest (AUC 0.81, P < 0.001), followed by COL-EPI (AUC 0.78, P < 0.001) and BT (AUC 0.56, P = 0.05). The cutoff value of 53 U in the ASPItest excluded the effect of aspirin with a sensitivity of 88% and specificity of 71%. Conclusions: The full therapeutic antiplatelet effects of aspirin can be expected within 48 hours of the patients last aspirin ingestion. Platelet function recovered in our study if aspirin cessation occurred >96 hours (4 days) before; thus, in these patients, preoperative platelet function testing is not useful. To quantify any residual aspirin effect in patients who ceased their intake of aspirin between 48 and 96 hours before surgery, the ASPItest might have the highest diagnostic accuracy. © 2011 International Anesthesia Research Society.

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