Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model.

Calpain activation has been implicated in various pathologies, including neurodegeneration. Thus, calpain inhibition could effectively prevent spinal cord injury (SCI) associated with neurodegeneration. In the current study, a dog SCI model was used to evaluate the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) as an anti-inflammatory drug. SCI was experimentally induced in sixteen mongrel dogs through an epidural balloon compression technique. The dogs were allocated randomly into four groups: control, MPSS, PD150606, and MPSS+PD150606. Clinical evaluation, serum biochemical, somatosensory evoked potentials, histopathological, and immunoblotting analyses were performed to assess treated dogs during the study. The current findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group and to a lesser extent in MPSS or PD150606 treatment alone. Interestingly, the combined treatment effectively inhibited the calpain-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

Reconstruction of a partial esophageal defect using tunica vaginalis and buccal mucosa autograft: an experimental study in mongrel dogs.

In veterinary clinics, esophageal reconstruction is essential in many clinical situations. In this study, two autografts, the tunica vaginalis (TV) and the buccal mucosa (BM), were proposed to reconstruct a semi-circumferential cervical esophageal defect in dogs. This study aimed to verify whether these two grafts could successfully patch esophageal defects. Twelve male mongrel dogs were divided into two groups. Following cervical esophagoplasty, the defective area was patched with either a TV or a BM graft. Comprehensive clinical, serum biochemical, and histological analyses were performed to evaluate the two grafts. Throughout the study (120 days), the dogs survived the procedure well with minor complications. The lumen of the patched areas was covered with mucosa, with slight scar retraction. Compared with that of the natural esophagus, the average relative luminal diameter was not significantly decreased. Importantly, the measured cortisol and inflammatory marker levels returned to the preoperative levels after 14 days. Although histological examination revealed that both grafts repaired the esophageal defect with complete re-epithelialization, the BM graft showed a histological structure similar to that of the natural esophagus. Both grafts effectively repaired the esophageal defect with minor complications; therefore, both are recommended as promising low-cost clinical alternatives for cervical esophagoplasty in dogs.

Enhancement of chronic wound healing with maltodextrin/ascorbic acid gel: a clinical evaluation of distal limb wounds in horses.

Delayed healing associated with distal limb wounds is highly challenging in equine clinical practice. This study aimed to evaluate healing rates between chronic non-granulating wounds of horse distal limbs that were treated with maltodextrin/ascorbic acid gel alone or in combination with povidone-iodine 1% solution and those treated with povidone-iodine 1% only throughout the study period (35 days) in clinical settings. The study was conducted on 18 adult horses (3-15 years old). Based on the treatment regimen utilized, the horses were divided into three groups (n = 6), with each group having a similar mean wound area. The percentages of wound contraction, epithelialization, and overall wound healing were determined weekly for each wound. By the end of the study, the total wound healing percentage was significantly increased between the study groups (p < 0.05). The use of maltodextrin/ascorbic acid gel resulted in considerable wound contraction, rapid epithelialization, and complication-free wound healing. Based on the findings of this study, maltodextrin/ascorbic acid gel, independently or in combination with a 1% povidone-iodine solution, might be applied as a safe and effective wound healing promoting agent in horses with chronic non-granulating wounds.

Effect of exercise on serum concentration of cartilage oligomeric matrix protein in Thoroughbreds.

OBJECTIVE: To evaluate changes in serum cartilage oligomeric matrix protein (COMP) concentrations in response to exercise in horses. ANIMALS: 15 horses in experiment 1 and 27 horses in experiment 2. PROCEDURES: In experiment 1, 15 Thoroughbreds free of orthopedic disease underwent a standardized exercise protocol. Running velocity and heart rate (HR) were recorded, and blood samples were collected immediately before (baseline) and 1, 5, and 24 hours after a single episode of exercise. In experiment 2, 27 horses underwent 9 stages of a training program in which each stage consisted of 4 to 8 consecutive daily workouts followed by a rest day. Blood samples were collected immediately before the first and final daily workouts in each stage. Serum COMP concentrations were measured via inhibition ELISA with a monoclonal antibody (14G4) against equine COMP. RESULTS: In experiment 1, mean serum COMP concentration was significantly higher than baseline 1 and 5 hours after exercise and returned to baseline concentrations 24 hours after exercise. Mean serum baseline COMP concentration increased as the velocity of running at maximum HR and at an HR of 200 beats/min increased, being significantly higher during the third and fourth exercise tests than during the first. In experiment 2, mean baseline COMP concentration at the final workout of each stage was significantly higher than that at the first workout, beginning with stage 3. CONCLUSIONS AND CLINICAL RELEVANCE: Serum COMP concentrations changed significantly in response to exercise. Exercise may enhance movement of COMP into the circulation as well as change the basal turnover rate of COMP.