Medizinische Klinik und Poliklinik IV

München, Germany

Medizinische Klinik und Poliklinik IV

München, Germany
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Nakazawa D.,Medizinische Klinik Und Poliklinik IV | Kumar S.V.,Medizinische Klinik Und Poliklinik IV | Marschner J.,Medizinische Klinik Und Poliklinik IV | Desai J.,Medizinische Klinik Und Poliklinik IV | And 9 more authors.
Journal of the American Society of Nephrology | Year: 2017

Severe AKI is often associated with multiorgan dysfunction, but the mechanisms of this remote tissue injury are unknown. We hypothesized that renal necroinflammation releases cytotoxic molecules that may cause remote organdamage. In hypoxia-inducedtubular epithelial cell necrosis in vitro, histone secretion fromischemic tubular cells primed neutrophils to form neutrophil extracellular traps. These traps induced tubular epithelial cell death and stimulated neutrophil extracellular trap formation in fresh neutrophils. In vivo, ischemia-reperfusion injury in themouse kidney induced tubular necrosis,which preceded the expansion of localized and circulating neutrophil extracellular traps and the increased expression of inflammatory and injury-related genes. Pretreatment with inhibitors of neutrophil extracellular trap formation reduced kidney injury. Dual inhibition of neutrophil trap formation and tubular cell necrosis had an additive protective effect. Moreover, pretreatment with antihistone IgG suppressed ischemia-induced neutrophil extracellular trap formation and renal injury. Renal ischemic injury also increased the levels of circulating histones, andwe detected neutrophil infiltration and TUNEL-positive cells in the lungs, liver, brain, and heart along with neutrophil extracellular trap accumulation in the lungs. Inhibition of neutrophil extracellular trap formation or of circulating histones reduced these effects as well. These data suggest that tubular necrosis and neutrophil extracellular trap formation accelerate kidney damage and remote organ dysfunction through cytokine and histone release and identify novel molecular targets to limit renal necroinflammation and multiorgan failure. © 2017 by the American Society of Nephrology.

Nonnenmann J.,Medizinische Klinik und Poliklinik IV | Stirner R.,Medizinische Klinik und Poliklinik IV | Roider J.,Medizinische Klinik und Poliklinik IV | Jung M.C.,Leberzentrum Prof. Dr. Jung und Dr. Fischer | And 3 more authors.
Journal of Virology | Year: 2014

Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive function. Compared to the level in healthy controls (HC), no elevation of MDSC in chronic hepatitis C (cHEP-C) patients was found, and there was no difference in MDSC based on genotype or viral load (P>0.25). Moreover, MDSC of cHEP-C patients inhibited CD8 T cell function as efficiently as MDSC of HC did. Since we detected neither quantitative nor qualitative differences in MDSC of cHEP-C patients relative to those of HC, we postulate that MDSC in peripheral blood are most likely not significant regarding immune dysfunction in cHEP-C. © 2014, American Society for Microbiology.

Vollbrecht T.,Medizinische Klinik und Poliklinik IV | Stirner R.,Medizinische Klinik und Poliklinik IV | Tufman A.,Medizinische Klinik und Poliklinik V | Roider J.,Medizinische Klinik und Poliklinik IV | And 6 more authors.
AIDS | Year: 2012

Objectives: Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell functions in many tumor models. However, MDSC in HIV-1 infection have not been studied to date. As impaired T-cell function is a hallmark of chronic progressive HIV-1 infection, we hypothesized that MDSC also play a role here. Methods: Surface staining and flow cytometry analysis were performed on freshly isolated peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and compared to healthy controls and individuals with lung carcinoma. MDSC of late-stage HIV-infected individuals were isolated using magnetic beads and cocultured with the respective CD8 T cells for evaluation of proliferative capacity. Results: We found that chronically HIV-infected HAART-naive individuals had significantly higher CD11b+CD14 -CD33+CD15+ MDSC levels than healthy controls (P=0.01). MDSC frequencies showed a positive correlation with viral load (r=0.24, P=0.0002) and a negative correlation with CD4 cell count (r 2=0.29, P<0.0001). Initiation of HAART led to a rapid drop in MDSC levels. MDSC from HIV-infected progressors restricted the proliferative capacity of CD8 T cells from healthy donors and of Gag/Nef-specific CD8 T cells from HIV-controllers in vitro. Furthermore, CD11b+CD14 -CD33+CD15+ MDSC induced the expansion of CD4CD25FoxP3 regulatory T cells when coincubated with PBMC from controllers in vitro. Conclusion: We conclude that chronic uncontrolled HIV-infection is associated with elevated levels of MDSC, which potentially contribute to the impaired T-cell responses characteristic for the progressive disease stage. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

PubMed | Ludwig Maximilians University of Munich, Medizinische Klinik und Poliklinik IV and Ruhr University Bochum
Type: Journal Article | Journal: Der Unfallchirurg | Year: 2015

Osteoporosis-associated fractures represent a growing challenge in the treatment of orthopedic patients. In November 2014 a new revision of the guidelines on osteoporosis by the German Osteology Society (Dachverband Osteologie DVO) was adopted, in which additional risk factors for fractures and further treatment options have been included. On the one hand the existing model used to diagnose osteoporosis and estimate a high fracture risk as a guidance for the use of specific anti-osteoporotic therapy in patients without a fragility fracture was maintained and further refined. On the other hand the guideline includes the option to initiate a specific osteoporosis therapy without a prior bone densitometry in patients with typical radiographs of a proximal femur fracture and higher grade vertebral fractures, suspicious for osteoporosis, depending on the overall clinical context. This may reduce the treatment gap of osteoporosis in Germany. In this paper the changes in the DVO guidelines 2014 on osteoporosis are summarized, focusing on the most important changes with practical relevance for orthopedic surgeons.

Pircher J.,Medizinische Klinik und Poliklinik IV | Pircher J.,Ludwig Maximilians University of Munich | Fochler F.,Ludwig Maximilians University of Munich | Czermak T.,Ludwig Maximilians University of Munich | And 7 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

OBJECTIVE-: Hydrogen sulfide (H2S)-releasing NSAIDs exert potent anti-inflammatory effects beyond classical cyclooxygenase inhibition. Here, we compared the platelet inhibitory effects of the H2S-releasing aspirin derivative ACS14 with its mother compound aspirin to analyze additional effects on platelets. METHODS AND RESULTS-: In platelets of mice fed with ACS14 for 6 days (50 mg/kg per day), not only arachidonic acid-induced platelet aggregation but also ADP-dependent aggregation was decreased, an effect that was not observed with an equimolar dose of aspirin (23 mg/kg per day). ACS14 led to a significantly longer arterial occlusion time after light-dye-induced endothelial injury as well as decreased thrombus formation after ferric chloride-induced injury in the carotid artery. Bleeding time was not prolonged compared with animals treated with equimolar doses of aspirin. In vitro, in human whole blood, ACS14 (25-500 μmol/L) inhibited arachidonic acid-induced platelet aggregation, but compared with aspirin additionally reduced thrombin receptor-activating peptide-, ADP-, and collagen-dependent aggregation. In washed human platelets, ACS14 (500 μmol/L) attenuated αIIbβ3 integrin activation and fibrinogen binding and increased intracellular cAMP levels and cAMP-dependent vasodilator-stimulated phosphoprotein (VASP) phosphorylation. CONCLUSION-: The H2S-releasing aspirin derivative ACS14 exerts strong antiaggregatory effects by impairing the activation of the fibrinogen receptor by mechanisms involving increased intracellular cyclic nucleotides. These additional antithrombotic properties result in a more efficient inhibition of thrombus formation in vivo as achieved with aspirin alone. © 2012 American Heart Association, Inc.

Linkermann A.,University of Kiel | Stockwell B.R.,Howard Hughes Medical Institute | Krautwald S.,University of Kiel | Anders H.-J.,Medizinische Klinik und Poliklinik IV
Nature Reviews Immunology | Year: 2014

Regulated cell death (RCD) is either immunologically silent or immunogenic. RCD in parenchymal cells may lead to the release of damage-associated molecular patterns that drive both tissue inflammation and the activation of further pathways of RCD. Following an initial event of regulated necrosis, RCD and inflammation can induce each other and drive a local auto-amplification loop that leads to exaggerated cell death and inflammation. In this Opinion article, we propose that such crosstalk between pro-inflammatory and RCD pathways has pathophysiological relevance in solid organ failure, transplantation and cancer. In our opinion, clinicians should not only prescribe immunosuppressive treatments to disrupt this circuit, but also implement the neglected therapeutic option of adding compounds that interfere with RCD. © 2014 Macmillan Publishers Limited. All rights reserved.

PubMed | Ludwig Maximilians University of Munich and Medizinische Klinik und Poliklinik IV
Type: Journal Article | Journal: Der Unfallchirurg | Year: 2016

Osteoporosis-associated fractures are of increasing importance in trauma surgery. The implementation of systematic diagnostics and treatment of osteoporosis during hospitalization, however, remains insufficient; therefore, a specific algorithm for the diagnosis and treatment of osteoporosis in trauma surgery patients was developed based on the German Osteology Society (Dachverband Osteologie, DVO) guidelines for osteoporosis from 2014. In a first step, the individual patient age and risk profile for osteoporosis are identified considering specific fractures indicative of osteoporosis. For these patients a questionnaire is completed which detects specific risk factors. In addition, the physical activity, risk of falls, dietary habits and the individual medication are collated as these can have a decisive influence on the subsequent therapy decisions. Prior to a specific treatment, laboratory osteoporosis tests, bone densitometry by dual energy X-ray absorptiometry (DXA) and if needed X-rays of the spine are carried out. For proximal femoral fractures the treatment of osteoporosis could already be indicated. With pre-existing glucocorticoid therapy, a history of previous fractures or other risk factors according to the risk questionnaire, the threshold of treatment has to be adjusted according to the table of T-scores detected by DXA. The treatment algorithm for diagnostics and treatment of osteoporosis in hospitalized trauma surgery patients can systematically and efficiently improve the identification of patients at risk. Thus, further fractures associated with osteoporosis or failure of internal fixation could be reduced in future. A prospective validation of the algorithm has already be initiated.

Vogt A.,Medizinische Klinik und Poliklinik IV
Application of Clinical Genetics | Year: 2015

Familial hypercholesterolemia (FH) results in very high levels of atherogenic low-density lipoprotein (LDL) cholesterol from the time of birth. Mutations of the genes encoding for the LDL receptor, apolipoprotein B and proprotein convertase subtilisin/kexin type 9, are causes for this autosomal dominant inherited condition. Heterozygous FH is very common, while homozygous FH is rare. Affected individuals can experience premature cardiovascular disease; most homozygous patients experience this before the age of 20 years. Since effective LDL cholesterol lowering therapies are available, morbidity and mortality are decreased. The use of statins is the first choice in therapy; combining other lipid-lowering medications is recommended to lower LDL cholesterol sufficiently. In some cases, lipoprotein apheresis is necessary. In heterozygous FH, these measures are effective to lower LDL cholesterol, but in severe cases and in homozygous FH there remains an unmet need. Emerging therapies, such as the recently approved microsomal triglyceride transfer protein inhibitor and the apolipopro-tein B antisense oligonucleotide, might offer further options for these patients with very high cardiovascular risk. Early diagnosis and early treatment are important to reduce cardiovascular events and premature death. © 2015 Vogt.

Czihal M.,Medizinische Klinik und Poliklinik IV | Hoffmann U.,Medizinische Klinik und Poliklinik IV
Zeitschrift fur Gefassmedizin | Year: 2014

Autoimmune and infectious inflammatory diseases of the aorta are summarized under the umbrella term "aortitis". Clinical presentation is highly variable, ranging from asymptomatic incidental findings to acute symptoms of aortic dissection or rupture. Diagnostic imaging techniques are essential in the diagnostic workup. The treatment approach varies depending on the underlying disease and on the extent of the vessel wall damage secondary to mural inflammation. © 2014, Krause und Pachernegg GmbH. All rights reserved.

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