Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study.

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Pharmacoproteomics: advancing the efficacy and safety of regenerative therapeutics.

Proteomic analyses encompass a suite of high-throughput technologies for large-scale separation and identification of proteins responsible for execution of physiological processes. As such, proteomics is ideally suited to dissecting developmental complexity and dynamics, an understanding of which is vital to the realization of regenerative therapeutic medicine. Pharmacoproteomics is increasingly targeting characterization of regenerative therapeutic strategies. A perspective on the application of proteomics to further our understanding of cardiac regenerative medicine, in concert with guided cardiogenic programming, is delineated herein.

[Dislocation of the peroneal tendons]. / Peronealsehnenluxation.

Dislocations of the peroneal tendons are more common than they are diagnosed. Probable reasons for misinterpretation of the injury are the hidden position of the peroneal tendons behind the malleolus lateralis and the tendency to self-reduction of the peroneal tendons. Insufficient treatment leads to a chronic recurrent peroneal tendon dislocation which is not necessarily accompanied by pain. However, if the instability of the peroneal tendons is painful, surgical treatment is advised. Various surgical methods are described in the literature. Nearly all report good postoperative results. In case of chronic recurrent peroneal tendon dislocation, we prefer the surgical management described by Viernstein, namely, mobilisation of connective tissue of the region, leading it over the peroneal tendons and suturing it in a bone pouch of the malleolus lateralis. The advantages of this surgical method are that it does not damage important anatomical structures of the region and that no second operation to extract implants is necessary. We treated 13 patients by the method described by Viernstein. 12 of 13 patients have resumed sports activities. We have not seen any redislocation of the peroneal tendons.

[Arthroscopy of the pediatric knee joint]. / Arthroskopie des kindlichen Kniegelenkes.

From April 1981 to April 1984 arthroscopy was performed on the knee joints of 33 children at the orthopedic clinic of Hanover Medical University. At the time of examination the children were aged between 5 and 14. It was found that the knee joints could be classified in two categories: Category 1: knee joints in which clinical findings were unclear and in which arthroscopy contributed to diagnosis. Category 2: knee joints in which the diagnosis had already been established, and in which arthroscopy was a help in deciding subsequent therapy. On the basis of the findings obtained in these investigations it can be stated that even in children, arthroscopy of the knee joint is a valuable diagnostic and therapeutic aid.