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Eppendorf, Germany

Spahn V.,Charite - Medical University of Berlin | Stein C.,Charite - Medical University of Berlin | Zollner C.,Charite - Medical University of Berlin | Zollner C.,Universitatsklinikum Hamburg
Molecular Pharmacology | Year: 2014

Transient receptor potential vanilloid 1 (TRPV1) is a nonselective ligand-gated cation channel responding to noxious heat, protons, and chemicals such as capsaicin. TRPV1 is expressed in sensory neurons and plays a critical role in pain associated with tissue injury, inflammation, and nerve lesions. Transient receptor potential ankyrin 1 (TRPA1) is coexpressed with TRPV1. It is activated by compounds that cause a burning sensation (e.g., mustard oil) and, indirectly, by components of the inflammatory milieu eliciting nociceptor excitation and pain hypersensitivity. Previous studies indicate an interaction of TRPV1 and TRPA1 signaling pathways. Here we sought to examine the molecular mechanisms underlying such interactions in nociceptive neurons. We first excluded physical interactions of both channels using radioligand binding studies. By microfluorimetry, electrophysiological experiments, cAMP measurements, and site-directed mutagenesis we found a sensitization of TRPV1 after TRPA1 stimulation with mustard oil in a calciumand cAMP/protein kinase A (PKA)-dependentmanner. TRPA1 stimulation enhanced TRPV1 phosphorylation via the putative PKA phosphorylation site serine 116. We also detected calcium-sensitive increased TRPV1 activity after TRPA1 activation in dorsal root ganglion neurons. The inhibition of TRPA1 by HC-030031 (1,2,3,6-tetrahydro-1,3- dimethyl-N-[4-(1-methylethyl)phenyl]-2,6-dioxo-7H-purine-7- acetamide, 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7Hpurin- 7-yl)-N-(4- isopropylphenyl)acetamide) after its initial stimulation (and the calcium-insensitive TRPA1 mutant D477A) still showed increased capsaicin-induced TRPV1 activity. This excludes a calcium-induced additive TRPA1 current after TRPV1 stimulation. Our study shows sensitization of TRPV1 via activation of TRPA1, which involves adenylyl cyclase, increased cAMP, subsequent translocation and activation of PKA, and phosphorylation of TRPV1 at PKA phosphorylation residues. This suggests that cross-sensitization of TRP channels contributes to enhanced pain sensitivity in inflamed tissues. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Aberle J.,Universitatsklinikum Hamburg Eppendorf | Reining F.,Universitatsklinikum Hamburg Eppendorf | Dannheim V.,Universitatsklinikum Hamburg Eppendorf | Flitsch J.,Universitatsklinikum Hamburg Eppendorf | And 2 more authors.
Experimental and Clinical Endocrinology and Diabetes | Year: 2012

Metformin is the oral drug of first choice in type 2 diabetes. Therefore a large number of patients undergoing bariatric surgery will be on Metformin treatment. However, use of Metformin has been associated with lactate acidosis. Weight loss following bariatric surgery is most pronounced during the first weeks after the operation and this creates a phase of negative energy balance with ketone body formation. To shed more light on this situation we measured ketone bodies in 90 patients 5 days-18 months after bariatric surgery. Ketone bodies were markedly elevated during the first 3-4 months. Metformin use should therefore be critically reconsidered after bariatric operations. © 2012 Georg Thieme Verlag KG Stuttgart New York.

Anders J.,University of Hamburg | Heinemann A.,Universitatsklinikum Hamburg | Leffmann C.,Fortbildungsakademie der Arztekammer | Leutenegger M.,University of Hamburg | And 2 more authors.
Deutsches Arzteblatt | Year: 2010

Background: Pressure sores are a serious complication of multimorbidity and lack of mobility. Decubitus ulcers have become rarer among bedridden patients because of the conscientious use of pressure-reducing measures and increased mobilization. Nonetheless, not all decubitus ulcers can be considered preventable or potentially curable, because poor circulation makes some patients more susceptible to them, and because cognitive impairment can make prophylactic measures difficult to apply. Methods: A systematic literature search was performed in 2004 and 2005 in the setting of a health technology assessment, and a selective literature search was performed in 2009 for papers on the prevention of decubitus ulcers. Results: Elderly, multimorbid patients with the immobility syndrome are at high risk for the development of decubitus ulcers, as are paraplegic patients. The most beneficial way to prevent decubitus ulcers, and to treat them once they are present, is to avoid excessive pressure by encouraging movement. At the same time, the risk factors that promote the development of decubitus ulcers should be minimized as far as possible. Conclusions: Malnutrition, poor circulation (hypoperfusion), and underlying diseases that impair mobility should be recognized if present and then treated, and accompanying manifestations, such as pain, should be treated symptomatically. Over the patient's further course, the feasibility, implementation, and efficacy of ulcer-preventing measures should be repeatedly re-assessed and documented, so that any necessary changes can be made. Risk factors for the development of decubitus ulcers should be assessed at the time of the physician's first contact with an immobile patient, or as soon as the patient's condition deteriorates; this is a prerequisite for timely prevention. Once the risks have been assessed, therapeutic measures should be undertaken on the basis of the patient's individual risk profile, with an emphasis on active encouragement of movement and passive relief of pressure through frequent changes of position.

Anders M.,Universitatsklinikum Hamburg
Gastroenterologe | Year: 2013

Barrett's esophagus (BE), the acquired replacement of squamous epithelium lining the distal esophagus by columnar epithelium containing goblet cells, is a consequence of chronic gastroesophageal reflux disease. Endoscopic surveillance aims at the timely recognition and treatment of patients developing neoplastic BE. Recently, several new modalities for the diagnosis and treatment of neoplastic BE have been introduced, e.g. virtual chromoendoscopy and radiofrequency ablation. In this article current knowledge on the clinical impact of these techniques will be discussed. Furthermore, this article gives an overview of recent findings concerning the development of BE and the malignant transformation. © 2013 Springer-Verlag Berlin Heidelberg.

Mehnert A.,Universitatsklinikum Hamburg Eppendorf | Veers S.,Universitatsklinikum Hamburg Eppendorf | Howaldt D.,Universitatsklinikum Hamburg Eppendorf | Braumann K.-M.,University of Hamburg | And 3 more authors.
Onkologie | Year: 2011

Background: Since physical exercise programs have the potential to help cancer patients regain physical fitness and may exert a range of positive consequences for recovery and psychological well-being, the impact of a physical exercise program was investigated in this prospective study. Patients and Methods: Women with primary nonmetastatic breast cancer after a minimum 4-week period post chemotherapy and/or radiotherapy completion were randomly assigned to one of 2 groups: intervention group (IG) (n = 30) and waiting group (WG) (n = 28). The 10-week twice weekly exercise group program consisted of gymnastics, movement games, relaxation, walking, and jogging. Anxiety, depression, body image, and quality of life were measured using standardized questionnaires. Maximal oxygen uptake (VO2max/kg) was assessed as a measure of physical fitness. Results: Patients in the IG improved significantly over time with regard to anxiety (p = 0.03, d = 0.45), depression (p = 0.05, d = 0.43), individual body image (p = 0.006, d = 0.44), and VO2max/kg (p < 0.001, d = 0.50), whereas no improvements were observed in the WG. However, this randomized controlled trial failed to demonstrate significant intervention effects in quality of life and social body image. Conclusions: This prospective study provided evidence for the effectiveness of a 10-week physical exercise intervention to significantly improve psychosocial wellbeing, individual body image, and physical fitness. © 2011 S. Karger GmbH, Freiburg.

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