Hydrogen peroxide induced tendinopathic changes in a rat model of patellar tendon injury.

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 µM H2 O2 (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 µM but not 500 µM H2 O2 group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 µM H2 O2 group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 µM H2 O2 group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H2 O2 impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H2 O2 -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3268-3274, 2018.

Dapagliflozin and Empagliflozin Ameliorate Hepatic Dysfunction Among Chinese Subjects with Diabetes in Part Through Glycemic Improvement: A Single-Center, Retrospective, Observational Study.

INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic dysfunction, although studies focusing on their underlying mechanisms are lacking, especially ones on dapagliflozin and empagliflozin. Here, we investigated the relationship between amelioration of hepatic dysfunction and improvement in various metabolic parameters among Chinese subjects with type 2 diabetes (T2DM). METHODS: This was a single-center, retrospective, observational study that involved 115 Chinese participants with T2DM treated with either dapagliflozin or empagliflozin for at least 6 months between July 2016 and February 2017. RESULTS: Of the 115 participants included in this study, 69 received dapagliflozin and 46 received empagliflozin. After 6 months of treatment, all patients showed significant improvements in body weight (BW), systolic blood pressure (SBP) and fasting glucose (FG) and glycated hemoglobin (HbA1c) levels. All participants also showed a significant reduction in serum alanine aminotransferase (ALT) levels, from 40.3 ± 28.0 to 29.0 ± 14.1 U/L (p < 0.001). Pearson's correlation analysis revealed a positive correlation between the reduction in ALT levels after treatment with the respective SGLT2i and changes in FG (p = 0.014) and HbA1c (p = 0.043) levels over 6 months, but not with changes in BW and SBP. Multiple linear regression analysis revealed that the reduction in serum ALT levels was independently associated with changes in both HbA1c and FG but not with the changes in the other clinical variables, including BW. CONCLUSIONS: Dapagliflozin and empagliflozin improved both metabolic and hepatic dysfunction as a class effect. The amelioration of hepatic dysfunction was mediated partly through an alleviation of hyperglycemia and possibly through an improvement in insulin resistance, independent of BW.

Effects of Redox Modulation on Cell Proliferation, Viability, and Migration in Cultured Rat and Human Tendon Progenitor Cells.

Tendon healing is slow and usually results in inferior fibrotic tissue formation. Recently, application of tendon derived stem cells (TDSCs) improved tendon healing in animal studies. In a chicken model, local injection of antioxidants reduced tendon adhesion after tendon injury. An in vitro study demonstrated that supplementation of H2O2 reduced tenogenic marker expression in TDSCs. These findings suggested that the possibility of TDSCs is involved in tendon healing and the cellular activities of TDSCs might be affected by oxidative stress of the local environment. After tendon injury, oxidative stress is increased. Redox modulation might affect healing outcomes via affecting cellular activities in TDSCs. To study the effect of oxidative stress on TDSCs, the cellular activities of rat/human TDSCs were measured under different dosages of vitamin C or H2O2 in this study. Lower dose of vitamin C increased cell proliferation, viability and migration; H2O2 affected colony formation and suppressed cell migration, cell viability, apoptosis, and proliferation. Consistent with previous studies, oxidative stresses (H2O2) affect both recruitment and survival of TDSCs, while the antioxidant vitamin C may exert beneficial effects at low doses. In conclusion, redox modulation affected cellular activities of TDSCs and might be a potential strategy for tendon healing treatment.

Motion Task Selection for Kinematic Evaluation After Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To examine the different motion tasks and the protocols used to objectively quantify dynamic stability in terms of knee kinematics at different stages of anterior cruciate ligament reconstruction (ACLR) recovery. METHODS: A systematic search was done using OVID in Embase, Cochrane Central Register of Controlled Trials, Medline, PsychINFO, and AMED. A combination of the following keywords and their variations were used: anterior cruciate ligament, motion tasks (e.g., jump, hop, gait), and stability. The inclusion criteria were as follows: (1) ACLR subjects were recruited, (2) at least 1 motion task was performed and kinematics data were recorded, and (3) uninjured subjects or the contralateral uninjured limbs were included as a control group. Exclusion criteria were as follows: (1) non-English language publications, (2) retrospective studies and review articles, (3) animal studies, and (4) cadaveric studies. RESULTS: The search returned 2,195 studies, and 56 were included in this review according to the criteria. A total of 1,086 ACLR subjects were included. Pivoting, landing, walking, running, stair negotiation, and squats were assessed using optoelectronic motion capture, electrogoniometry, or video-radiography. CONCLUSIONS: The appropriate selection of motion tasks is an integral factor in dynamic stability testing as it evokes different kinematic outcomes in relation to the different stages of ACLR recovery. Stair negotiation and landing tasks are best performed during the early stages of recovery, and landing and pivoting are recommended 6 months after ACLR surgery. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

Use of a portable motion analysis system for knee dynamic stability assessment in anterior cruciate ligament deficiency during single-legged hop landing.

BACKGROUND/OBJECTIVE: Anterior cruciate ligament (ACL) rupture results in knee instability, and patients are often unable to return to their previous level of activity. Current assessments rely on passive laxity tests, which do not correlate with function. Dynamic stability may be a better indicator for return to sport. However, equipment for measuring dynamic stability is ill suited for clinical use. The purpose of this study is to evaluate knee kinematics in ACL-deficient patients with a single-legged hop task using a portable motion analysis system. We hypothesize that the assessment task is able to differentiate ACL-deficient knees from healthy knees. METHODS: Ten ACL-deficient patients and 10 healthy controls were recruited. Participants were instructed to perform a single-legged hop, while kinematics was measured using a portable motion capture system (Opti-Knee; Shanghai Innomotion Inc., Shanghai, China). Kinematic changes after initial contact were examined. Repeatability of the results was examined by calculating the coefficient of variations of the pooled standard deviation of the tibiofemoral displacements. Side-to-side differences were calculated and compared between the two groups. RESULTS: One patient could not perform the task. Intraindividual variability was small after initial contact; the coefficient of variation in this region was 13-26%. ACL-deficient knees demonstrated lower flexion range of motion (p = 0.008) and increased internal/external rotation range of motion after landing (p = 0.038), while no significant differences were detected in the healthy group. Only the side-to-side difference in flexion was significantly different between the two groups (p = 0.002). CONCLUSION: The altered knee kinematics in ACL-deficient patients can be revealed by a portable motion capture system, which may enable the clinical application of kinematic assessment in the evaluation of ACL deficiency.