26 research outputs found

    Gene-therapeutic approach for the expression of heterologous receptors in the heart

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    Vorliegende Arbeit untersucht die Grundlagen und die Durchführbarkeit für einen neuen, möglichen Ansatz zur Therapie der Herzinsuffizienz auf molekularer Ebene. Hierzu wurde der im Herzen heterologe, G-Protein-gekoppelte, PTH/PTHrP1-Rezeptor in Kardiomyoblasten und Kardiomyozyten zur Expression gebracht. Da in der Herzinsuffizienz im Myokard dehnungsabhängig PTHrP ausgeschüttet wird, könnte so über die Expression des heterologen Rezeptors und cAMP-Bildung über das Gs-Adenylatzyklase-System ein parakriner Loop geschlossen und damit eine Steigerung der Kontraktilität rezeptorbesetzter Zellen, d.h. ein positiv inotroper Effekt erreicht werden. Als Gen-Vektoren untersuchten wir zum einen Adenoviren, zum anderen Adeno-assoziierte Viren, die beide mittels Markergenen auf ihre Effektivität, Fremd-DNA in Herzzellen einzuschleusen, getestet wurden. Alle Virus-Proplasmide, in die das Gen für den PTH/PTHrP1-Rezeptor einkloniert worden war, wurden funktionell gemessen. Die Arbeit zeigt, daß es prinzipiell möglich ist, fremde Gene, insbesondere das Gen für den PTH/PTHrP1-Rezeptor, mit guter Effizienz sowohl in vitro in Kardiomyoblasten und in isolierten Kardiomyozyten als auch in vivo im Myokard zur Expression zu bringen. Alle Gene behielten nach Umklonierung und heterologer Expression in den verschiedenen Zellen ihre Funktion.The present study investigates the feasibility of a novel, molecular approach to therapy congestive heart failure. For this, we overexpressed the heterologous, G-Protein-coupled, PTH/PTHrP1-Receptor in cardiomyoblasts and cardiomyocytes. Because PTHrP is released in a stretch-responsive manner from the myocard in congestive heart failure, overexpression of the heterologous receptor and cAMP formation via the Gs/adenylyl cyclase system could result in a positive inotropic paracrine loop through an increased contractility of PTH/PTHrP1-expressing cells. As gene-vectors we investigated on the one hand adenoviruses, on the other hand adeno-associated viruses. Both were tested with reportergenes for their ability to transfer foreign DNA into heartcells. All virus-proplasmides, encoding the PTH/PTHrP1-receptor, were functionally tested. The investigations show, that it is possible to express with a good efficiency heterologous genes, especially the PTH/PTHrP1-gene, as well in vitro in cardiomyoblasts and in cardiomyocytes as in vivo in the myocard. All genes maintained after cloning and heterologous expression in the different cells their function

    Epidemiological and clinical outcome comparison of indirect (strain) versus direct (contusion) anterior and posterior thigh muscle injuries in male elite football players: UEFA Elite League study of 2287 thigh injuries (2001-2013)

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    Background Data regarding direct athletic muscle injuries (caused by a direct blunt or sharp external force) compared to indirect ones (without the influence of a direct external trauma) are missing in the current literature-this distinction has clinical implications. Aim To compare incidence, duration of absence and characteristics of indirect and direct anterior (quadriceps) and posterior thigh (hamstring) muscle injuries. Methods 30 football teams and 1981 players were followed prospectively from 2001 until 2013. The team medical staff recorded individual player exposure and time-loss injuries. Muscle injuries were defined as indirect or direct according to their injury mechanism. Results In total, 2287 thigh muscle injuries were found, representing 25% of all injuries. Two thousand and three were valid for further analysis, of which 88% were indirect and 12% direct. The incidence was eight times higher for indirect injuries (1.48/1000 h) compared to direct muscle injuries (0.19/1000 h) (p&amp;lt;0.01). Indirect muscle injuries caused 19% of total absence, and direct injuries 1%. The mean lay-off time for indirect injuries amounted to 18.5 days and differed significantly from direct injuries which accounted for 7 days (p&amp;lt;0.001). 60% of indirect injuries and 76% of direct injuries occurred in match situations. Foul play was involved in 7% of all thigh muscle injuries, as well as in 2% of indirect injuries and 42% of direct injuries. Summary Muscle anterior and posterior thigh injuries in elite football are more frequent than have been previously described. Direct injuries causing time loss are less frequent than indirect ones, and players can usually return to full activity in under half the average time for an indirect injury. Foul play is involved in 7.5% of all thigh muscle injuries.</p

    Fußball

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    Suture anchor repair of proximal rectus femoris avulsions in elite football players.

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    To report the results of suture anchor repair of proximal rectus femoris avulsions in elite football players.Four professional football players (first-team regulars of European first division football clubs) underwent suture anchor repair of complete proximal rectus femoris avulsions with significant tendon retraction. The following parameters were analysed: demographic data, mechanism of injury, type of injury, classification according to the Munich consensus statement, time between injury and surgery, time between surgery and full participation in training and availability for match and/or competition selection (return to play/RTP), and time between surgery and the comeback to the first official league match (return to competition/RTC). Radiographic evaluation was performed by magnetic resonance imaging (MRI) obtained pre-operatively and at 6 and 12 weeks post-operatively. All players were followed for at least 24 months after return to play to exclude recurrence.Mean age at surgery was 30 ± 2 years. All injuries occurred while kicking a ball, with the dominant leg affected in all patients. The injury was considered acute in three cases and chronic in one case. According to the Munich classification, all injures were type 4. Mean time to surgery was 60 ± 88 days (range, 8-191), mean time to RTP was 111 ± 15 days (range, 100-134), and mean time to RTC was 140 ± 23 days (range, 114-166). Follow-up MRIs demonstrated anatomically reinserted tendons with decreasing signal intensity over time in all cases. After a mean follow-up of 35 ± 6 months, all players were still competing at the same level as before the injury without re-injury.Suture anchor repair of proximal rectus femoris avulsions allows unrestricted return to play in professional elite football players. Return to play can be expected at approximately 16 weeks post-operatively
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