Garmisch-Partenkirchen, Germany
Garmisch-Partenkirchen, Germany

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Diederich S.,Diabetes and Nutrition | Diederich S.,Center for Endocrine and Metabolism Diseases | Quinkler M.,Center for Internal Medicine | Mai K.,Diabetes and Nutrition | And 5 more authors.
Hormone and Metabolic Research | Year: 2011

The 11β-Hydroxysteroid dehydrogenases (11β-HSDs) play a pivotal role in glucocorticoid (GC) action. 11β-HSD1 is a predominant reductase, activating GCs from inert metabolites, whereas 11β-HSD2 is a potent dehydrogenase inactivating GCs. Knowing the metabolic effects of GCs, a selective inhibition of 11β-HSD1 represents a potential target for therapy of impaired glucose tolerance, insulin insensitivity and central obesity. In vitro, 11β-HSD1 is selectively inhibited by chenodesoxycholic acid (CDCA) and upregulated under GC exposure. Therefore, we aimed to investigate the effects of CDCA and prednisolone on hepatic 11β-HSD1 activity in vivo by measuring 11-reduction of orally given cortisone (E) acetate to cortisol (F). CDCA or placebo was given to 5 male healthy volunteers within a randomised cross-over trial before and after oral administration of 12.5 mg E acetate at 8:00 h. For measurement of in vivo effects of GCs on 11β-HSD1 activity, hepatic reduction of 25 mg E acetate before and after treatment with prednisolone (30 mg for 6 days) was determined in 7 healthy males. Serum GC levels were determined using a fully automated liquid chromatographic system. CDCA had no effect on the activity of 11β-HSD1 in vivo. Prednisolone therapy leads to a marked rise in serum F concentrations and an elevated F/E serum ratio. This proves GC-induced activation of hepatic 11β-HSD1, which could not be extinguished by a parallel increase of IGF-1 under prednisolone. CDCA does not affect in vivo activity of 11β-HSD1 when given in therapeutic dosages. During GC treatment, increased hepatic activation of E to F may aggravate metabolic side effects of GCs such as seen in the metabolic syndrome. © Georg Thieme Verlag KG, Stuttgart - New York.


Seifert W.,Charité - Medical University of Berlin | Kuhnisch J.,Charité - Medical University of Berlin | Kuhnisch J.,Max Planck Institute for Molecular Genetics | Tuysuz B.,Istanbul University | And 3 more authors.
Human Mutation | Year: 2012

Digital clubbing is usually secondary to different acquired diseases. Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder with variable digital clubbing as the most prominent feature, subperiosteal new bone formation, and arthropathy. Recently, mutations in the 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) encoding gene HPGD were found to cause PHO. Here, we identified three unrelated families with different mutations in the prostaglandin transporter (PGT) encoding gene SLCO2A1 which presumably result in reduced metabolic clearance by 15-PGDH due to diminished cellular uptake of prostaglandin E 2 (PGE 2) by mutant PGT. In two consanguineous families, homozygous mutations, an intragenic deletion that results in frameshift and a missense mutation, are associated with a severe PHO phenotype. In a third family, a heterozygous carrier of a stop mutation presents with isolated digital clubbing. Thus, our study further supports the importance of PGE 2 metabolism in the pathogenesis of digital clubbing and PHO. © 2012 Wiley Periodicals, Inc.


Elseviers M.M.,University of Antwerp | Arias-Guillen M.,Hospital Clinic Barcelona | Gorke A.,Center for Internal Medicine | Arens H.-J.,Fresenius Medical Care Deutschland GmbH
Journal of Renal Care | Year: 2014

Background: Sharps injuries and the related risk of infections such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) represent one of the major occupational health risks for healthcare workers (HCWs). Literature Review: An overview of available data on the incidence of sharps injuries and the related HBV, HCV and HIV infections and ensuing costs is provided. Results: Literature reported incidence rates of sharps injuries ranging from 1.4 to 9.5 per 100 HCWs, resulting in a weighted mean of 3.7/100 HCWs per year. Sharps injuries were associated with infective disease transmissions from patients to HCWs resulting in 0.42 HBV infections, 0.05-1.30 HCV infections and 0.04-0.32 HIV infections per 100 sharps injuries per year. The related societal costs had a mean of €272, amounting to a mean of €1,966 if the source patient was HIV positive with HBV and HCV co-infections. Conclusion: Sharps injuries remain a frequent threat amongst HCWs. The follow-up and treatment of sharps injuries and the deriving consequences represent a significant cost factor. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.


De Beer I.H.,PharmAccess Foundation Namibia | Gelderblom H.C.,New York University | Gelderblom H.C.,University of KwaZulu - Natal | Gelderblom H.C.,Emory University | And 9 more authors.
Journal of the International AIDS Society | Year: 2012

Background: With an overall adult HIV prevalence of 15.3%, Namibia is facing one of the largest HIV epidemics in Africa. Young people aged 20 to 34 years constitute one of the groups at highest risk of HIV infection in Namibia. However, little is known about the impact of HIV on this group and its access to healthcare. The purpose of this study was to estimate HIV prevalence, to assess the knowledge of and attitudes towards HIV/AIDS, and to assess access to healthcare among university students in Namibia. Methods. We assessed HIV/AIDS knowledge and attitudes, HIV prevalence and access to healthcare among students at the Polytechnic of Namibia and the University of Namibia. HIV prevalence was tested through anonymous oral fluid-based tests. Results: Half (n = 2790/5568) of the university students and 45% (n = 2807/6302) of the Polytechnic students participated in the knowledge and attitudes surveys. HIV/AIDS knowledge was reasonable, except for misperceptions about transmission. Awareness of one's own HIV status and risks was low. In all, 55% (n = 3055/5568) of university students and 58% (n = 3680/6302) of Polytechnic students participated in the HIV prevalence survey; 54 (1.8%) university students and 103 (2.8%) Polytechnic students tested HIV positive. Campus clinics were not the major providers of healthcare to the students. Conclusions: Meaningful strategies addressing the gap between knowledge, attitude and young people's perception of risk of HIV acquisition should be implemented. HIV prevalence among Namibian university students appears relatively low. Voluntary counselling and testing should be stimulated. Efforts should be made to increase access to healthcare through the campus clinics. © 2012 De Beer et al; licensee BioMed Central Ltd.


Tiede A.,Hannover Medical School | Klamroth R.,Center for Internal Medicine | Oldenburg J.,University of Bonn
Hamostaseologie | Year: 2015

Turoctocog alfa (NovoEight®) is a new recombinant factor VIII (rFVIII) with a truncated B domain and a high degree of tyrosine sulphation, similar to plasma-derived FVIII products. The manufacturing process includes double nanofiltration with a 20-nm pore size and immunoaffinity chromatography with monoclonal F25 anti-FVIII antibodies. Treatment with turoctocog alfa can be monitored with both one-stage and chromogenic substrate assays without a product-specific laboratory standard. In total, 213 previouslytreated patients with severe haemophilia A participated in the pivotal part of the clinical trial programme guardian™. The median annualised bleeding rate during turoctocog alfa prophylaxis was 3.7 and 3.0 in adolescents/adults and children, respectively, with marked differences between participating countries. The success rate for the treatment of breakthrough bleeds was 85% (adults/adolescents) and 94% (children). A total of 41 surgical procedures (15 major, 26 minor) were performed in 33 patients, with a successful haemostatic response reported in all cases. No patient developed confirmed inhibitors in any of the trials. © Schattauer 2015.


Sibaev A.,Ludwig Maximilians University of Munich | Yuece B.,Ludwig Maximilians University of Munich | Allescher H.D.,Center for Internal Medicine | Saur D.,TU Munich | And 2 more authors.
Pharmacological Reports | Year: 2014

Background: Endocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are involved in the regulation of motility in the gastrointestinal (GI) tract. However, the underlying physiological mechanisms are not completely resolved. The purpose of this work was to study the physiological influence of the endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and of the CB1 receptor on ascending peristaltic activity and to identify the involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms. Methods: The effects of anandamide and the CB1 receptor antagonist SR141716A were investigated on contractions of the circular smooth muscle of rat ileum and in longitudinal rat ileumsegments where the ascending myenteric part of the peristaltic reflex was studied in a newly designed organ bath. Additionally intracellular recordings were performed in ileum and colon. Results: Anandamide significantly reduced cholinergic twitch contractions of ileum smooth muscle whereas SR141716A caused an increase. Anandamide reduced the ascending peristaltic contraction by affecting neuro-neuronal and neuro-muscular neurotransmission. SR141716A showed opposite effects and all anandamide effects were antagonized by SR141716A (1 μM). Anandamide reduced excitatory junction potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal slow waves were not affected. Conclusions: CB1 receptors regulate force and timing of the intestinal peristaltic reflex and these actions involve interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates these effects by activation of CB1 receptors. The endogenous cannabinoid system is permanently active, suggesting the CB1 receptor being a possible target for the treatment of motility related disorders. © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.


Fois G.,University of Ulm | Weimer M.,University of Ulm | Busch T.,Center for Internal Medicine | Felder E.T.,University of Ulm | And 5 more authors.
FASEB Journal | Year: 2013

Keratin filaments impart resilience against mechanical extension of the cell. Despite the pathophysiological relevance of this function, very little is known about the mechanical properties of intermediate filaments in living cells and how these properties are modulated. We used keratin mutants that mimic or abrogate phosphorylation of keratin 8-serine431 and keratin 18-serine52 and investigated their effect on keratin tortuousness after cell stretch release in squamous cell carcinoma cells. Cells transfected with the wild-type keratins were used as controls. We can show that keratin dephosphorylation alters the stretch response of keratin in living cells since keratin tortuousness was abolished when phosphorylation of keratin18- serine52 was abrogated. Additional experiments demonstrate that keratin tortuousness is not simply caused by a plastic overextension of keratin filaments because tortuousness is reversible and requires an intact actinmyosin system. The role of actin in this process remains unclear, but we suggest anchorage of keratin filaments to actin during stretch that leads to buckling on stretch release. Dephosphorylated keratin18-serine52 might strengthen the recoil force of keratin filaments and hence explain the abolished buckling. The almost exclusive immunolabeling for phosphorylated keratin18- serine 52 in the cell periphery points at a particular role of the peripheral keratin network in this regard.-Fois, G., Weimer, M., Busch, T., Felder, E. T., Oswald, F., von Wichert, G., Seufferlein, T., Dietl, P., Felder, E. Effects of keratin phosphorylation on the mechanical properties of keratin filaments in living cells. FASEB J. 27, 1322-1329 (2013). www.fasebj.org.


Doerr R.,Praxisklinik Herz und Gefaesse | Hoffmann U.,Praxisklinik Herz und Gefaesse | Otter W.,Center for Internal Medicine | Heinemann L.,Profil Institute | And 11 more authors.
Diabetologia | Year: 2011

Aims/hypothesis: The primary aim of this study was to compare the results of HbA1c measurements with those of an OGTT for early diagnosis of silent diabetes in patients with coronary artery disease (CAD) undergoing angiography without prediagnosed diabetes. A secondary aim was to investigate the correlation between the extent of CAD and the glycaemic status of the patient. Methods: Data from 1,015 patients admitted for acute (n = 149) or elective (n = 866) coronary angiography were analysed. Patients with known diabetes were excluded from the study. Using the OGTT results, patients were classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. According to the results of the HbA1c measurements, patients were classified into three groups: normal (HbA1c <5.7% [<39 mmol/mol]), borderline (HbA 1c 5.7-6.4% [39-47 mmol/mol]) and diabetes (HbA1c ≥6.5% [≥48 mmol/mol]). Results: Based on the OGTT, 513 patients (51%) were classified with NGT, 10 (1%) with IFG, 349 (34%) with IGT and 149 (14%) were diagnosed with diabetes. According to HbA1c measurements, 588 patients (58%) were classified as normal, 385 (38%) as borderline and 42 (4%) were diagnosed with diabetes. The proportion of patients with IGT and diabetes increased with the extent of CAD (IGT ρ = 0.14, p < 0.001, diabetes ρ = 0.09, p = 0.01). No differences in HbA1c were seen among the groups with different extents of CAD (p = 0.652). Conclusions/interpretation: An OGTT should be performed routinely for diagnosis of diabetes in patients with CAD undergoing coronary angiography, since HbA1c measurement alone appears to miss a substantial proportion of patients with silent diabetes. A limitation of the study is that the OGTT was not performed before the angiography. © 2011 Springer-Verlag.


PubMed | Ludwig Maximilians University of Munich, TU Munich, Center for Internal Medicine and Abdomen Endooffice
Type: Journal Article | Journal: Pharmacological reports : PR | Year: 2014

Endocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are involved in the regulation of motility in the gastrointestinal (GI) tract. However, the underlying physiological mechanisms are not completely resolved. The purpose of this work was to study the physiological influence of the endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and of the CB1 receptor on ascending peristaltic activity and to identify the involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms.The effects of anandamide and the CB1 receptor antagonist SR141716A were investigated on contractions of the circular smooth muscle of rat ileum and in longitudinal rat ileum segments where the ascending myenteric part of the peristaltic reflex was studied in a newly designed organ bath. Additionally intracellular recordings were performed in ileum and colon.Anandamide significantly reduced cholinergic twitch contractions of ileum smooth muscle whereas SR141716A caused an increase. Anandamide reduced the ascending peristaltic contraction by affecting neuro-neuronal and neuro-muscular neurotransmission. SR141716A showed opposite effects and all anandamide effects were antagonized by SR141716A (1 M). Anandamide reduced excitatory junction potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal slow waves were not affected.CB1 receptors regulate force and timing of the intestinal peristaltic reflex and these actions involve interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates these effects by activation of CB1 receptors. The endogenous cannabinoid system is permanently active, suggesting the CB1 receptor being a possible target for the treatment of motility related disorders.

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