Zentrum fur Innere Medizin

Garmisch-Partenkirchen, Germany

Zentrum fur Innere Medizin

Garmisch-Partenkirchen, Germany
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Aslam M.,Justus Liebig University | Pfeil U.,Justus Liebig University | Gunduz D.,Zentrum fur Innere Medizin | Rafiq A.,Justus Liebig University | And 3 more authors.
British Journal of Pharmacology | Year: 2012

BACKGROUND AND PURPOSE Intermedin is a member of the calcitonin gene-related-peptide (CGRP) family expressed in endothelial cells and acts via calcitonin receptor-like receptors (CLRs). Here we have analysed the receptors for intermedin and its effect on the endothelial barrier in monolayers of human umbilical vein endothelial cells (HUVECs). EXPERIMENTAL APPROACH We analysed the effect of intermedin on albumin permeability, contractile machinery, actin cytoskeleton and VE-cadherin in cultured HUVECs. KEY RESULTS Intermedin concentration-dependently reduced basal endothelial permeability to albumin and antagonized thrombin-induced hyperpermeability. Intermedin was less potent (EC 50 1.29 ± 0.12 nM) than adrenomedullin (EC 50 0.24 ± 0.07 nM) in reducing endothelial permeability. These intermedin effects were inhibited by AM 22-52 and higher concentrations of αCGRP 8-37, with pA 2 values of αCGRP 8-37 of 6.4 for both intermedin and adrenomedullin. PCR data showed that HUVEC expressed only the CLR/RAMP2 receptor complex. Intermedin activated cAMP/PKA and cAMP/Epac signalling pathways. Intermedin's effect on permeability was blocked by inhibition of PKA but not of eNOS. Intermedin antagonized thrombin-induced contractile activation, RhoA activation and stress fibre formation. It also induced Rac1 activation, enhanced cell-cell adhesion and antagonized thrombin-induced loss of cell-cell adhesion. Treatment with a specific inhibitor of Rac1 prevented intermedin-mediated barrier stabilization. CONCLUSION AND IMPLICATIONS Intermedin stabilized endothelial barriers in HUVEC monolayers via CLR/RAMP2 receptors. These effects were mediated via cAMP-mediated inactivation of contractility and strengthening of cell-cell adhesion. These findings identify intermedin as a barrier stabilizing agent and suggest intermedin as a potential treatment for vascular leakage in inflammatory conditions. © 2011 The British Pharmacological Society.

Wastl D.,Zentrum fur Innere Medizin | Helwig K.,Medizinische Klinik III | Dietrich C.F.,Zentrum fur Innere Medizin
Medizinische Klinik - Intensivmedizin und Notfallmedizin | Year: 2015

As a point-of-care tool, emergency sonography has the potential to rule out or to confirm a diagnosis in the context to the leading symptom of critically ill persons. Extended focused assessment with sonography for trauma (E-FAST) and focused echo entry level (FEEL) are examples of algorithms that have been developed for this purpose. Echoscopy is another form of point-of-care sonography that is used at the bedside. It helps to answer simple questions (yes/no) and allows follow-up examinations to be made with little effort. Point-of-care sonography does not compete with normal standardized sonography because it is not able to answer medical questions in a sophisticated manner. © 2015, Springer-Verlag Berlin Heidelberg.

The detection of autoantibodies has become an essential part of the rheumatological routine diagnostic evaluation of collagenosis and vasculitis. This is especially true for antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA). However, as these antibody specificities are also found in gastroenterological diseases, misinterpretations are entirely possible. For example, if antibody findings are incorrectly attributed to a rheumatological disease in the context of viral hepatitis, this may lead to administration of immunosuppressants with unfavourable effects regarding the underlying gastroenterological disease. Avoiding such risks requires precise knowledge of the differential diagnostic evaluation of ANA and ANCA findings in rheumatology and gastroenterology. Copyright ©, Georg Thieme Verlag KG. All rights reserved.

In the course of several gastroenterological diseases rheumatological symptoms can occur which in some cases are even the main symptoms. Important examples are Crohn's disease, ulcerative colitis, Whipple's disease and gluten-sensitive enteropathy. Arthralgia and also arthritis with or without joint destruction are possible in the context of chronic inflammatory bowel diseases. Pathogenetically, the bowels are of central importance. The interrelation of hepatological and rheumatological diseases is also complex. Viral hepatitis can present a clinical picture resembling classical rheumatoid arthritis but also show symptoms of collagenosis and vasculitis. In addition to the differential diagnostic demarcation, in most cases therapy of the underlying gastroenterological disease is the determining factor regarding the development of rheumatological symptoms. © 2011 Springer-Verlag.

The increase in prevalence of diabetes mellitus and in life expectancy cause the growing number of diabetic patients with peripheral artery disease (PAD). Patients with long standing diabetes suffer frequently (about 70%) from peripheral sensory neuropathy. Therefore these patients miss the symptoms of claudication. Patients with silent ischemia will be classified to Stadium I (Fontaine) instead to stadium II or III or their diagnosis will be missed at all. The clinical investigation of the food pulses should be done at least once per year in all patients with diabetes mellitus. When one or more pulses are not detectable the further diagnostic procedures should start with the measurement of the ABI (Ancle Brachial Index). In patients with mediasclerosis the measurement will give false high numbers. After early diagnosis conventional treatment may be effective. With late diagnosis in the stadium IV (Fontaine) always and especially before any amputation revascularisation should be done. Guidelines give the right choise of katheter-based or open vascular-surgical procedures. © Springer-Verlag 2011.

Paraneoplastic syndromes, as syndromes associated with malignancy, can present unrelated to tumor invasion or metastases. They can occur with varying clinical appearance and are often indistinguishable from idiopathic rheumatic symptoms. Some musculoskeletal disorders are more associated with malignancies. The therapy of rheumatic syndromes can itself have an effect on the tumorigenic process. The clinical severity of paraneoplastic rheumatic symptoms can in many cases aid in the assessment of tumor activity and the response to therapy. While generally an extensive search for occult malignancies in every older rheumatoid patient in cases with no indications of malignancy is not advisable, knowledge of rheumatic symptoms associated with malignancies aids in the important early detection of tumors, while avoiding unnecessary examinations. © Springer-Verlag 2011.

Hartmann B.,Zentrum fur Innere Medizin
Clinica Chimica Acta | Year: 2012

Inhibitors of the mammalian target of rapamycin (mTOR) are administered as immunosuppressant as well as antineoplastic agents. Because of the narrow therapeutic index of mTOR inhibitors, drug monitoring is required, and this is usually done by measuring blood drug levels. Increasing knowledge of the signaling pathways of the mTOR protein kinase provides an opportunity for pharmacodynamic drug monitoring.With the different laboratory methods it is becoming possible to measure new biomarkers to control the influence of mTOR activity. One of these biomarkers is phospho-S6 kinase, with its isoform p70S6K. © 2012.

Allescher H.D.,Zentrum fur Innere Medizin
Gastroenterologe | Year: 2012

Aging causes typical changes in several regions of the human body which lead to altered function. These changes can also be observed in the gastrointestinal tract, despite the fact that food and fluid intake is a well preserved function of the human body and changes are less prominent than those in the skeletal regions. In general a clear distinction has to be made between primary "physiological" aging changes of the laryngo-pharynx, esophagus or stomach and changes of swallowing function which are due to secondary effects of other diseases which have an increased incidence with rising age. The latter include cerebro-vascular and neurodegenerative disorders and malignant disease of the oropharynx, esophagus and cardia. © Springer-Verlag 2012.

During laboratory monitoring of patients with rheumatic diseases it is not uncommon to notice elevated liver transaminase levels. From a rheumatological perspective there are multiple causes for this. Liver dysfunction can be the result of certain rheumatological diseases, such as systemic lupus erythematosus. Primary biliary cirrhosis and primary sclerosing cholangitis are associated with rheumatic diseases. On the other hand, hepatological diseases, such as hepatitis C and autoimmune hepatitis show rheumatological symptoms. The most common cause of elevation of liver transaminase levels in rheumatic patients is without doubt the anti-rheumatic therapy. © 2015, Springer-Verlag Berlin Heidelberg.

Oesophageal motility disorders are associated with typical changes in bolus transport, with dysphagia and retrosternal pain. Depending on the underlying pathophysiology, disorders with hyper- and hypomotility can be distinguished. Hypermotile and spastic motility can be reduced with nitrates, calcium antagonists, antimuscarinic agents, phosphodiesterase inhibitors and other spasmolytics like peppermint oil; however, the clinical symptomatic effect is sparse or lacking. Using intramuscular injection of botulinum toxin, which causes selective inhibition of acetylcholine release, a targeted reduction or blockade of striated and smooth oesophageal muscle can be achieved and used for clinical treatment, e.g. for classical achalasia and diffuse oesophageal spasm. Besides pneumatic dilatation of the cardia, peroral endoscopic myotomy (POEM) offers a new interventional endoscopic therapy, which can be successfully applied in patients with achalasia and spastic oesophageal motility disorders. As some disorders are linked to altered pain perception, modification of hypersensitive states in the oesophagus with tricyclic antidepressants and selective serotonin reuptake inhibitors offer new therapeutic possibilities. In contrast to the hypermotile disorders, treatment alternatives for hypomotile disorders are limited. Systemic direct and indirect muscarinic agents show limited efficacy and the use of prokinetics is hampered by side effects and interactions. © 2016, Springer-Verlag Berlin Heidelberg.

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