The ability of tendons to withstand stress generally decreases with age, often resulting in increased tissue degeneration and decreased regeneration capacity. However, the underlying molecular and cellular mechanisms of tendon senescence remain poorly characterized. Therefore, the aim of the current study was to identify genes showing an age-dependent altered expression profile in tendons. A suppression-subtractive-hybridization (SSH) screen comparing cDNA libraries generated from Achilles tendons of mature-adult (3 months) and old (18 months) female C57BL/6 mice was conducted. Subsequently, the differential expression of the identified genes was validated by RT-qPCR and selected genes were then further analysed by immunohistochemistry and Western blot. To investigate age-related structural alterations in the collagenous extracellular matrix we applied SHG-microscopy and TEM. In vitro experiments with young and old tendon derived stem/progenitor cells (TDSCs) involved wounding assays, tendon-like constructs as well as collagen gel contraction assays.Introduction
Materials and Methods
Tranexamic acid is a potent antifibrinolytic which has shown efficacy in reducing blood loss in total knee arthroplasty when administered intravenously. We performed a randomised controlled trial of oral tranexamic acid in total knee arthroplasty in order to assess the blood sparing effect of this preparation. We investigated the effects of oral tranexamic acid on blood loss in 50 patients (25 treatment arm and 25 placebo) undergoing unilateral total knee replacement in a two year period starting January 2007. The treatment arm received 1500 mg of encapsulated oral tranexamic acid TDS pre-operatively, with the third dose occurring within two hours of surgery, and a fourth dose six hours post surgery. The control arm received an identically encapsulated non-active formulation at the same dosing intervals. Baseline pre-operative haemoglobin and heamatocrit measures were collected. Outcome measures were post-operative haemoglobin and haematocrit taken 12 to 24 hours post operatively and total blood loss in wound drains at 24 hours. Results showed a non-clinically significant trend towards decreased blood loss and transfusion rates in the treatment arm when compared to placebo. No significant adverse events occurred in relation to the use of oral Tranexamic acid in this study. The perioperative use of oral tranexamic acid in conjuntion with elective total knee arthroplasty appears safe; however, its efficacy as a blood sparing medication is less than that which has been recorded with intravenous dosing. The study supports further consideration of the availability of intravenous tranexamic acid for decreasing blood loss in orthopaedic arthroplasty.
