Integrative Philosophy: Case Management.

This article serves as an introduction into integrative case management as it applies to the horse's mental health, pain management, and tissue healing. The integrative philosophy pertains to the combination of conventional Western medicine and complementary and alternative therapies to provide the best patient care possible using currently available evidence. The goal is to improve the health of the patient in a more holistic manner.

Temporal metabolic profiling of bone healing in a caprine tibia segmental defect model.

Bone tissue engineering is an emerging field of regenerative medicine, with a wide array of biomaterial technologies and therapeutics employed. However, it is difficult to objectively compare these various treatments during various stages of tissue response. Metabolomics is rapidly emerging as a powerful analytical tool to establish broad-spectrum metabolic signatures for a target biological system. Developing an effective biomarker panel for bone repair from small molecule data would provide an objective metric to readily assess the efficacy of novel therapeutics in relation to natural healing mechanisms. In this study we utilized a large segmental bone defect in goats to reflect trauma resulting in substantial volumetric bone loss. Characterization of the native repair capacity was then conducted over a period of 12 months through the combination of standard (radiography, computed tomography, histology, biomechanics) data and ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolic profiling. Standard metrics demonstrated that samples formed soft callus structures that later mineralized. Small molecule profiles showed distinct temporal patterns associated with the bone tissue repair process. Specifically, increased lactate and amino acid levels at early time points indicated an environment conducive to osteoblast differentiation and extracellular matrix formation. Citrate and pyruvate abundances increased at later time points indicating increasing mineral content within the defect region. Taurine, shikimate, and pantothenate distribution profiles appeared to represent a shift toward a more homeostatic remodeling environment with the differentiation and activity of osteoclasts offsetting the earlier deposition phases of bone repair. The generation of a comprehensive metabolic reference portfolio offers a potent mechanism for examining novel biomaterials and can serve as guide for the development of new targeted therapeutics to improve the rate, magnitude, and quality of bone regeneration.

The Effect of Ground Poles and Elastic Resistance Bands on Longissimus Dorsi and Rectus Abdominus Muscle Activity During Equine Walk and Trot.

Core strengthening and postural stability are desired outcomes of certain therapeutic exercises performed in horses. This study aimed to quantify changes in muscle activation at a walk and trot in horses traveling over eight consecutive ground poles evenly spaced (at 30 inches for walk and 48 inches for trot) in parallel fashion in a straight line, and with hindquarter and abdominal elastic resistance bands applied at 25% stretch. Surface electromyography (sEMG) data were collected for the longissimus dorsi and rectus abdominus muscles in six horses. A 2 × 2 repeated measures ANOVA was performed for each muscle to test for significant differences in differences in normalized average rectified values and maximum low pass signals. Within subject effects were reported, followed by post-hoc pairwise comparisons to evaluate differences between the conditions of with or without ground poles or elastic resistance bands. The use of ground poles at a walk resulted in a significant (p < .05) increase in the maximum low pass value bilaterally in the longissimus dorsi and rectus abdominus muscles, with an increase in the average rectified value bilaterally in the rectus abdominus muscles and right longissimus dorsi muscle. The use of ground poles at a trot resulted in a significant increase in the maximum low pass value bilaterally in the rectus abdominus muscles. The hindquarter and abdominal elastic resistance bands resulted in a respective 27% and 27.2% increase in the mean average rectified value of the left and right RA muscles; however this only reached statistical significance in the left RA (p < .05). These findings provide support regarding changes in muscle activation when using ground poles to increase core and epaxial muscle engagement. While a significant effect on core muscle activation was identified with the elastic resistance bands at a trot, further research is needed in this area to further characterize their effects on muscle activation.

Effects of Normal Synovial Fluid and Interferon Gamma on Chondrogenic Capability and Immunomodulatory Potential Respectively on Equine Mesenchymal Stem Cells.

Synovial fluid contains cytokines, growth factors and resident mesenchymal stem cells (MSCs). The present study aimed to (1) determine the effects of autologous and allogeneic synovial fluid on viability, proliferation and chondrogenesis of equine bone marrow MSCs (BMMSCs) and (2) compare the immunomodulatory properties of equine synovial fluid MSCs (SFMSCs) and BMMSCs after stimulation with interferon gamma (INF-γ). To meet the first aim of the study, the proliferation and viability of MSCs were evaluated by MTS and calcein AM staining assays. To induce chondrogenesis, MSCs were cultured in a medium containing TGF-ß1 or different concentrations of synovial fluid. To meet the second aim, SFMSCs and BMMSCs were stimulated with IFN-γ. The concentration of indoleamine-2,3-dioxygenase (IDO) and nitric oxide (NO) were examined. Our results show that MSCs cultured in autologous or allogeneic synovial fluid could maintain proliferation and viability activities. Synovial fluid affected chondrocyte differentiation significantly, as indicated by increased glycosaminoglycan contents, compared to the chondrogenic medium containing 5 ng/mL TGF-ß1. After culturing with IFN-γ, the conditioned media of both BMMSCs and SFMSCs showed increased concentrations of IDO, but not NO. Stimulating MSCs with synovial fluid or IFN-γ could enhance chondrogenesis and anti-inflammatory activity, respectively, suggesting that the joint environment is suitable for chondrogenesis.

Concepts and challenges in the use of mesenchymal stem cells as a treatment for cartilage damage in the horse.

Osteoarthritis (OA), the most common form of joint disease affecting humans and horses, is characterized by the advance and decline of cartilage and loss of function of the affected joint. The progression of OA is steadily accompanied with biochemical events, which interfere with the cytokines and proteolytic enzymes responsible for progress of the disease. Recently, regenerative therapies have been used with an assumption that mesenchymal stem cells (MSCs) possess the potential to prevent the advancement of cartilage damage and potentially regenerate the injured tissue with an ultimate goal of preventing OA. We believe that despite various challenges, the use of allogenic versus autologous MSCs in cartilage regeneration, is a major issue which can directly or indirectly affect the other factors including, the timing of implantation, dose or cell numbers for implantation, and the source of MSCs. Current knowledge reporting some of these challenges that the clinicians might face in the treatment of cartilage damage in horses are presented. In this regard we conducted two independent studies. In the first study we compared donor matched bone marrow and synovial fluid - derived equine MSCs in vitro, and showed that the SFMSCs were similar to the BMMSCs in their proliferation, expression of CD29, CD44 and CD90, but, exhibited a significantly different chondrogenesis. Additionally, 3.2-21% of all SFMSCs were positive for MHC II, whereas, BMMSCs were negative. In the second study we observed that injection of both the autologous and allogenic SFMSCs into the tarsocrural joint resulted in elevated levels of total protein and total nucleated cell counts. Further experiments to evaluate the in vivo acute or chronic response to allogenic or autologous MSCs are imperative.