Efficacy of autologous mesenchymal stromal cell treatment for chronic degenerative musculoskeletal conditions in dogs: A retrospective study.

Introduction: The objective of this study was to retrospectively analyze clinical data from a referral regenerative medicine practice, to investigate the efficacy of autologous mesenchymal stromal cells (MSC) in 245 dogs deemed unresponsive to conventional treatment by their referring vet. Methods: Diagnostic imaging [radiology and musculoskeletal ultrasound (MSK-US)] identified musculoskeletal pathology holistically. MSCs, produced according to current guidelines, were initially administered with PRP by targeted injection to joints and/or tendons, with a second MSC monotherapy administered 12 weeks later to dogs with severe pathology and/or previous elbow arthroscopic interventions. Dogs with lumbosacral disease received epidural MSCs with additional intravenous MSCs administered to dogs with spondylosis of the cervical, thoracic and lumbar spine. All dogs received laser therapy at 10 J/cm2 at the time of treatment and for 5 sessions thereafter. Objective outcome measures (stance analysis, range of joint motion, pressure algometry) and validated subjective outcome measures (owner reported VetMetrica HRQL™ and veterinary pain and quality of life impact scores) were used to investigate short and long-term (6-104 weeks) efficacy. Outcome data were collected at predetermined time windows (0-6, 7-12, 13-18, 19-24, 25-48, 49-78, 79-104) weeks after initial treatment. Results: There were statistically significant improvements in post compared with pre-treatment measures at all time windows in stance analysis, shoulder and hip range of motion, lumbosacral pressure algometry, and to 49-78 weeks in carpus and elbow range of motion. Improvements in 4 domains of quality of life as measured by VetMetricaTM were statistically significant, as were scores in vet-assessed pain and quality of life impact. In dogs receiving one initial treatment the mean time before a second treatment was required to maintain improvements in objective measures was 451 days. Diagnostic imaging confirmed the regenerative effects of MSCs in tendinopathies by demonstrating resolution of abnormal mineralization and restoration of normal fiber patterns. Discussion: This represents the first study using "real-world" data to show that cell-based therapies, injected into multiple areas of musculoskeletal pathology in a targeted holistic approach, resulted in rapid and profound positive effects on the patient's pain state and quality of life which was maintained with repeat treatment for up to 2 years.

ɑ-Lactalbumin Improves Sleep and Recovery after Simulated Evening Competition in Female Athletes.

PURPOSE: This study aimed to determine the efficacy of α-lactalbumin (A-LAC) supplementation for improving sleep and performance recovery after simulated evening competition in female athletes. METHODS: Sixteen trained women (mean ± SD: age, 27 ± 7 yr; mass, 62 ± 10 kg; stature, 167 ± 8 cm) participated in this randomized double-blind three-arm crossover study. Participants completed a simulated evening competition before consuming either an A-LAC whey protein, whey protein placebo (PLA), or water control (CON) beverage. Sleep was monitored via polysomnography, and participants completed a series of physical, cognitive, and perceptual assessments before, and 14 and 24 h after simulated competition. RESULTS: Non-rapid eye movement stage 2 sleep increased after competition in A-LAC (pre, 199 ± 44 min; post, 212 ± 37 min) but decreased in CON (pre, 228 ± 43 min; post, 195 ± 40 min) and PLA (pre, 224 ± 25 min; post, 211 ± 35 min; P = 0.012). In addition, Yo-Yo Intermittent Recovery Test Level 1 distance improved over time in A-LAC (baseline, 664 ± 332 m; 14 h post, 667 ± 326 m; 24 h post, 781 ± 427 m) compared with CON (baseline, 741 ± 366 m; 14 h post, 648 ± 351 m; 24 h post, 720 ± 407 m) and PLA (baseline, 763 ± 394 m; 14 h post, 636 ± 366 m; 24 h post, 720 ± 396 m; P < 0.001). CONCLUSIONS: The findings indicate that A-LAC supplementation may be useful for retaining some sleep characteristics after evening competition, leading to improved physical performance in female athletes.

Influence of body composition on physiological responses to post-exercise hydrotherapy.

This study examined the influence of body composition on temperature and blood flow responses to post-exercise cold water immersion (CWI), hot water immersion (HWI) and control (CON). Twenty-seven male participants were stratified into three groups: 1) low mass and low fat (LM-LF); 2) high mass and low fat (HM-LF); or 3) high mass and high fat (HM-HF). Experimental trials involved a standardised bout of cycling, maintained until core temperature reached 38.5°C. Participants subsequently completed one of three 15-min recovery interventions (CWI, HWI, or CON). Core, skin and muscle temperatures, and limb blood flow were recorded at baseline, post-exercise, and every 30 min following recovery for 240 min. During CON and HWI there were no differences in core or muscle temperature between body composition groups. The rate of fall in core temperature following CWI was greater in the LM-LF (0.03 ± 0.01°C/min) group compared to the HM-HF (0.01 ± 0.001°C/min) group (P = 0.002). Muscle temperature decreased to a greater extent during CWI in the LM-LF and HM-LF groups (8.6 ± 3.0°C) compared with HM-HF (5.1 ± 2.0°C, P < 0.05). Blood flow responses did not differ between groups. Differences in body composition alter the thermal response to post-exercise CWI, which may explain some of the variance in the responses to CWI recovery.

Iminosugars: Promising therapeutics for influenza infection.

Influenza virus causes three to five million severe respiratory infections per year in seasonal epidemics, and sporadic pandemics, three of which occurred in the twentieth century and are a continuing global threat. Currently licensed antivirals exclusively target the viral neuraminidase or M2 ion channel, and emerging drug resistance necessitates the development of novel therapeutics. It is believed that a host-targeted strategy may combat the development of antiviral drug resistance. To this end, a class of molecules known as iminosugars, hydroxylated carbohydrate mimics with the endocyclic oxygen atom replaced by a nitrogen atom, are being investigated for their broad-spectrum antiviral potential. The influenza virus glycoproteins, hemagglutinin and neuraminidase, are susceptible to inhibition of endoplasmic reticulum α-glucosidases by certain iminosugars, leading to reduced virion production or infectivity, demonstrated by in vitro and in vivo studies. In some experiments, viral strain-specific effects are observed. Iminosugars may also inhibit other host and virus targets with antiviral consequences. While investigations of anti-influenza iminosugar activities have been conducted since the 1980s, recent successes of nojirimycin derivatives have re-invigorated investigation of the therapeutic potential of iminosugars as orally available, low cytotoxicity, effective anti-influenza drugs.

Liposome-mediated delivery of iminosugars enhances efficacy against dengue virus in vivo.

A key challenge faced by promising antiviral drugs, such as iminosugars, is in vivo delivery to achieve effective levels of drug without toxicity. Four iminosugars, all deoxynojirimycin (DNJ) derivatives-N-butyl DNJ (NB-DNJ), N-nonyl DNJ, N-(9-methoxynonyl) DNJ, and N-(6'-[4″-azido-2″-nitrophenylamino]hexyl)-1-DNJ (NAP-DNJ)-potently inhibited both the percentage of cells infected with dengue virus and release of infectious virus from primary human monocyte-derived macrophages, demonstrating their efficacy in primary cells. In a lethal antibody-dependent enhancement mouse model of dengue pathogenesis, free NB-DNJ significantly enhanced survival and lowered viral load in organs and serum. Liposome-mediated delivery of NB-DNJ, in comparison with free NB-DNJ, resulted in a 3-log(10) reduction in the dose of drug sufficient to enhance animal survival. The optimizing of the effective dose in this way could liberate the therapeutic potential of many cytotoxic antivirals against both dengue virus and a wide array of other viruses.