Die Biologie der Heilung der Rotatorenmanschettenläsion: Welche Rolle spielen Wachstumsfaktoren heutzutage?

Zusammenfassung: Die Rotatorenmanschettenläsion ist eine häufige Diagnose in der orthopädischen Sprechstunde. Die Rerupturrate ist trotz Weiterentwicklung der Nahtmaterialien und -techniken im offenen und arthroskopischen Bereich nach wie vor hoch. In den letzten Jahren wurden den physiologischen Vorgängen der natürlichen Insertion wie auch den biologischen Eigenschaften der Rotatorenmanschettenheilung in der Forschung vermehrt Aufmerksamkeit geschenkt. Es hat sich gezeigt, dass die Heilung der Sehnen-Knochen-Insertion der Rotatorenmanschette ein komplexes Zusammenspiel von lokalen Zellen, Stammvorläuferzellen, extrazellulärer Matrix sowie von Wachstumsfaktoren und anderen Zytokinen ist. Dementsprechend wurden verschiedene biologische In-vitro- und In-vivo-Therapieverfahren zur potenziellen Verbesserung der Reinsertion entwickelt. Ziel dieses Artikels ist es, einen Überblick über die heutige Evidenz der Augmentation der Rotatorenmanschettenrekonstruktion mit Wachstumsfaktoren zu geben. Weiterhin werden mögliche zukünftige Therapieansätze diskutier

Expression of Atrophy mRNA Relates to Tendon Tear Size in Supraspinatus Muscle

Skeletal muscle atrophy and fatty infiltration develop after tendon tearing. The extent of atrophy serves as one prognostic factor for the outcome of surgical repair of rotator cuff tendon tears. We asked whether mRNA of genes involved in regulation of degradative processes leading to muscle atrophy, ie, FOXOs, MSTN, calpains, cathepsins, and transcripts of the ubiquitin-proteasome pathway, are overexpressed in the supraspinatus muscle in patients with and without rotator cuff tears. We evaluated biopsy specimens collected during surgery of 53 consecutive patients with different sizes of rotator cuff tendon tears and six without tears. The levels of corresponding gene transcripts in total RNA extracts were assessed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Supraspinatus muscle atrophy was assessed by MRI. The area of muscle tissue (or atrophy), decreased (increased) with increasing tendon tear size. The transcripts of CAPN1, UBE2B, and UBE3A were upregulated more than twofold in massive rotator cuff tears as opposed to smaller tears or patients without tears. These atrophy gene products may be involved in cellular processes that impair functional recovery of affected muscles after surgical rotator cuff repair. However, the damaging effects of gene products in their respective proteolytic processes on muscle structures and proteins remains to be investigate

Development of an effective outsourcing strategy for toxicological studies in the chemical industry

The chemical industry has been put under considerable time pressure by the European Community Regulation REACH (Registration, Evaluation, and Authorization of Chemicals). The work outlined here has been developed at the BASF SE’s Experimental Toxicology and Ecology Unit with the objective of promoting a faster reaction to the testing demand generated by the new legislation. A considerable increase in forecasted demand for tests has created the necessity to increase the Toxicology Unit’s outsourcing activities. The first goal was to optimize the selection and management process of Contract Research Organizations (CROs), so that toxicological studies can be performed with minimal risk while maximizing quality and cost advantage. A second objective was to develop performance measurement system in form of a balanced scorecard to evaluate contracting efficiency by monitoring major drivers in the outsourcing process to ensure the alignment between strategic objectives and actual performance.<br

Antibody-mediated PCSK9 neutralization worsens outcome after bare-metal stent implantation in mice

AIMS Despite advances in pharmacotherapy and device innovation, in-stent restenosis (ISR) and stent thrombosis (ST) remain serious complications following percutaneous coronary intervention (PCI) procedure with stent implantation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved in plasma cholesterol homeostasis and recently emerged as a therapeutic target for hypercholesterolemia. Antibody-based PCSK9 inhibition is increasingly used in different subsets of patients, including those undergoing PCI. However, whether PCSK9 inhibition affects outcome after stent implantation remains unknown. METHODS AND RESULTS 12 to 14 weeks old C57Bl/6 mice underwent carotid artery bare-metal stent implantation. Compared to sham intervention, stent implantation was associated with increased expression of several inflammatory mediators, including PCSK9. The increase in PCSK9 protein expression was confirmed in the stented vascular tissue, but not in plasma. To inhibit PCSK9, alirocumab was administered weekly to mice before stent implantation. After 6 weeks, histological examination revealed increased intimal hyperplasia in the stented segment of alirocumab-treated animals compared to controls. In vitro, alirocumab promoted migration and inhibited the onset of senescence in primary human vascular smooth muscle cells (VSMC). Conversely, it blunted the migration and increased the senescence of endothelial cells (EC). CONCLUSION Antibody-based PCSK9 inhibition promotes in-stent intimal hyperplasia and blunts vascular healing by increasing VSMC migration, while reducing that of EC. This effect is likely mediated, at least in part, by a differential effect on VSMC and EC senescence. The herein-reported data warrant additional investigations concerning the use of PCSK9 inhibitors in patients undergoing PCI with stent implantation

Offene Latarjet-Patte-Operation nach Walch : Tipps, Tricks und Komplikationsvermeidung

Walch hat die Latarjet-Patte-Operation in offener Technik unter Anwendung eines Subskapularis-Splits in den 1980er-Jahren modifiziert, standardisiert und über Jahrzehnte mit großem Erfolg bei über 3500 Patienten angewandt. In Langzeitnachuntersuchungen wurden Rezidivraten von 1–5 % bei hoher Patientenzufriedenheit im Subjective Shoulder Value (SSV > 90 %) dokumentiert [1, 2]. Diese Ergebnisse konnten in Zürich durch Gerber reproduziert werden [3]. Die Methode hat in mehreren Langzeitstudien den Beweis des Erreichens dauerhafter Stabilität (Langzeitstabilität nach mehr als 6 bis 10 Jahren) bei Risikopatienten erbracht [2, 3], besonders für Wettkampfsportler [4,5,6], junge Patienten [7, 8] und Patienten mit glenoidalem Knochenverlust [1, 9]. Bei korrekter Operationstechnik entsteht kein klinisch relevanter Beweglichkeitsverlust, und es besteht kein Zusammenhang mit der Entstehung oder Progression einer Instabilitätsarthrose [10]. In einer randomisierten kontrollierten Studie (RCT) zeigte sich eine signifikant niedrigere Reluxationsrate für die Latarjet-Stabilisierung bei jungen Männern unter 25 Jahren im Vergleich zur arthroskopischen Bankart-Operation [8]

Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

BACKGROUND Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. METHODS PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. RESULTS The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. DISCUSSION Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks