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Articles by W Hoffmann
Total Records ( 2 ) for W Hoffmann
  S Pinkert , D Westermann , X Wang , K Klingel , A Dorner , K Savvatis , T Grossl , S Krohn , C Tschope , H Zeichhardt , K Kotsch , K Weitmann , W Hoffmann , H. P Schultheiss , O. B Spiller , W Poller and H. Fechner
 

Background— Group B coxsackieviruses (CVBs) are the prototypical agents of acute myocarditis and chronic dilated cardiomyopathy, but an effective targeted therapy is still not available. Here, we analyze the therapeutic potential of a soluble (s) virus receptor molecule against CVB3 myocarditis using a gene therapy approach.

Methods and Results— We generated an inducible adenoviral vector (AdG12) for strict drug-dependent delivery of sCAR-Fc, a fusion protein composed of the coxsackievirus-adenovirus receptor (CAR) extracellular domains and the carboxyl terminus of human IgG1-Fc. Decoy receptor expression was strictly doxycycline dependent, with no expression in the absence of an inducer. CVB3 infection of HeLa cells was efficiently blocked by supernatant from AdG12-transduced cells, but only in the presence of doxycycline. After liver-specific transfer, AdG12 (plus doxycycline) significantly improved cardiac contractility and diastolic relaxation compared with a control vector in CVB3-infected mice if sCAR-Fc was induced before infection (left ventricular pressure 59±3.8 versus 45.4±2.7 mm Hg, median 59 versus 45.8 mm Hg, P<0.01; dP/dtmax 3645.1±443.6 versus 2057.9±490.2 mm Hg/s, median 3526.6 versus 2072 mm Hg/s, P<0.01; and dP/dtmin –2125.5±330.5 versus –1310.2±330.3 mm Hg/s, median –2083.7 versus –1295.9 mm Hg/s, P<0.01) and improved contractility if induced concomitantly with infection (left ventricular pressure 76.4±19.2 versus 56.8±10.3 mm Hg, median 74.8 versus 54.4 mm Hg, P<0.05; dP/dtmax 5214.2±1786.2 versus 3011.6±918.3 mm Hg/s, median 5182.1 versus 3106.6 mm Hg/s, P<0.05), respectively. Importantly, hemodynamics of animals treated with AdG12 (plus doxycycline) were similar to uninfected controls. Preinfection induction of sCAR-Fc completely blocked and concomitant induction strongly reduced cardiac CVB3 infection, myocardial injury, and inflammation.

Conclusion— AdG12-mediated sCAR-Fc delivery prevents cardiac dysfunction in CVB3 myocarditis under prophylactic and therapeutic conditions.

  C. O Schmidt , R. A Fahland , M Franze , C Splieth , J. R Thyrian , S Plachta Danielzik , W Hoffmann and T. Kohlmann
 

Enhancing health literacy is a keystone in health promotion. Yet, most studies on health literacy are limited to functional literacy levels. Furthermore, little evidence is available from children. Based on Nutbeam's outcome model for health promotion, this study aims (i) to elaborate a set of short scales to measure important health literacy domains in children and (ii) to analyse their associations among each other, with health behaviour as an intermediate health outcome, subjective health, social status and gender. The sample comprised 852 school children in fifth grade, aged 9–13 years, in Western Pomerania, Germany. Items were taken from the child's questionnaire to form short scales for health-related knowledge, attitudes, communication and behaviour. The internal consistencies of the communication and attitude scales were 0.73 and 0.57, respectively. Unidimensional scalability of the knowledge and behaviour scales was supported by item response models. Associations between health scales were modest. In regression analyses, social status and gender predicted only health knowledge and communication but not health behaviours, attitudes and self-efficacy. Health knowledge was not associated with any other scale. Our results suggest that targeting one specific component of health literacy in children is likely to exert only small effects on health status and health behaviour.

 
 
 
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