Heterogeneous distribution of viscosupplements in vivo is correlated to ex vivo frictional properties of equine cartilage.

Intra-articular injections of hyaluronic acid (HA) are the cornerstone of osteoarthritis (OA) treatments. However, the mechanism of action and efficacy of HA viscosupplementation are debated. As such, there has been recent interest in developing synthetic viscosupplements. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively lubricate and bind to the surface of cartilage in vitro. However, its ability to localize to cartilage and alter the tribological properties of the tissue in a live articulating large animal joint is not known. The goal of this study was to quantify the distribution and extent of localization of pAAm in the equine metacarpophalangeal or metatarsophalangeal joint (fetlock joint), and determine whether preferential localization of pAAm influences the tribological properties of the tissue. An established planar fluorescence imaging technique was used to visualize and quantify the distribution of fluorescently labeled pAAm within the joint. While the pAAm hydrogel was present on all surfaces, it was not uniformly distributed, with more material present near the site of the injection. The lubricating ability of the cartilage in the joint was then assessed using a custom tribometer across two orders of magnitude of sliding speed in healthy synovial fluid. Cartilage regions with a greater coverage of pAAm, that is, higher fluorescent intensities, exhibited friction coefficients nearly 2-fold lower than regions with lesser pAAm (Rrm = -0.59, p < 0.001). Collectively, the findings from this study indicate that intra-articular viscosupplement injections are not evenly distributed inside a joint, and the tribological outcomes of these materials is strongly determined by the ability of the material to localize to the articulating surfaces in the joint.

Serial injections of 4% polyacrylamide hydrogel have no detrimental effects in equine joints following clinical, histologic, and synovial biomarker evaluation.

OBJECTIVE: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS: 8 healthy horses. METHODS: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.

Polyacrylamide hydrogel lubricates cartilage after biochemical degradation and mechanical injury.

Intra-articular injections of hyaluronic acid have been a mainstay of osteoarthritis treatment for decades. However, controversy surrounds the mechanism of action and efficacy of this therapy. As such, there has been recent interest in developing synthetic lubricants that lubricate cartilage. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively decrease lameness in horses. However, its mechanism of action and ability to lubricate cartilage is unknown. The goal of this study was to characterize the lubricating ability of this hydrogel and determine its efficacy for healthy and degraded cartilage. The study utilized previously established IL-1ß-induced biochemical degradation and mechanical impact injury models to degrade cartilage. The lubricating ability of the hydrogel was then characterized using a custom-built tribometer using a glass counterface and friction was evaluated using the Stribeck framework for articular cartilage. pAAm hydrogel was shown to significantly lower the friction coefficient of cartilage explants from both degradation models (30%-40% reduction in friction relative to controls). A striking finding from this study was the aggregation of the pAAm hydrogel at the articulating surface. The surface aggregation was observed in the histological sections of explants from all treatment groups after tribological evaluation. Using the Stribeck framework, the hydrogel was mapped to higher Sommerfeld numbers and was characterized as a viscous lubricant predominantly in the minimum friction mode. In summary, this study revealed that pAAm hydrogel lubricates native and degraded cartilage explants effectively and may have an affinity for the articulating surface of the cartilage.

Equine shock wave therapy - where are we now?

Over the past three decades, electrohydraulic extracorporeal shock wave therapy (ESWT) as a treatment modality for equine orthopaedic disorders has sparked exponential interest among practitioners, but its clinical applications are quickly evolving and a current review highlighting modernised equine clinical use is lacking. The objective of this review is to summarise the most current ESWT technology, evidence for its use, proposed mechanisms of action and clinical applications in horses while also highlighting the areas requiring further investigation. The three ways to generate a shock wave are through electrohydraulic, electromagnetic or piezoelectric mechanisms, but over the last decade, electrohydraulic systems have predominated due to the ability to focus and control a therapeutic waveform. Shock waves' primary physical effect is believed to be via mechanotransduction leading to cellular activation and downstream signalling. Experimentally, ESWT's effects on osseous, connective tissue and wound healing via various mechanisms of action have been reported both in the human and veterinary literature. Clinical trials have investigated ESWT's orthopaedic application including osteoarthritis, thoracolumbar pain, navicular syndrome, tendinopathy and proximal suspensory desmopathy, with its concomitant use with biologics representing an area of active research. Direct ESWT protocol comparisons in terms of long-term efficacy with variables of energy, depth and exposed tissue types are still lacking with evidence-based recommendations being largely anecdotal. Technical advancements to facilitate the safe and judicious use of ESWT include human and equine hearing protection, light sedation and/or patient restraint. Efforts to ensure the safe and judicious use of ESWT and its analgesic effects are ongoing.

Effect of cold compression therapy on postoperative pain, swelling, range of motion, and lameness after tibial plateau leveling osteotomy in dogs.

OBJECTIVE: To evaluate the effect of cold compression therapy (CCT) on postoperative pain, lameness, range of motion of the stifle joint, and swelling following tibial plateau leveling osteotomy (TPLO) in dogs. DESIGN: Randomized, blinded, placebo-controlled clinical trial. ANIMALS: 34 client-owned dogs with unilateral deficiency of a cranial cruciate ligament undergoing TPLO. PROCEDURES: Dogs were assigned to 2 groups. Group 1 (n = 17 dogs) received CCT in the 24-hour period following TPLO. Group 2 (n = 17 dogs) received no CCT. Degree of lameness, range of motion, and circumference of the stifle joint were measured before surgery and 1,14, and 28 days after surgery. A modified composite Glasgow pain scale, visual analogue scale, and pain threshold score were used to evaluate signs of pain before surgery and 1,14, and 28 days after surgery. Logistic regression and linear regression analysis were used to compare the measured variables. RESULTS: No complications were observed, and all dogs tolerated CCT. Use of CCT resulted in lower values for the visual analogue scale and Glasgow pain scale and lower pain threshold scores; lower lameness scores; less swelling; and an increased range of motion 24 hours after surgery. At 14 days after surgery, there were no significant differences between groups. At 28 days after surgery, too few data sets were available for comparison. CONCLUSIONS AND CLINICAL RELEVANCE: CCT decreased signs of pain, swelling, and lameness and increased stifle joint range of motion in dogs during the first 24 hours after TPLO.

Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses.

OBJECTIVE: To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. ANIMALS: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. PROCEDURES: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed. RESULTS: Mean +/- SD clearance and steady-state volume of distribution of firocoxib were 40.5 +/- 14.7 mL/h/kg and 2.3 +/- 0.7 L/kg, respectively. Mean half-life was 44.2 +/- 21.6 hours and 36.5 +/- 9.5 hours for IV and oral administration, respectively. The urine concentration- time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 +/- 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance. CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.

Acoustic field of a ballistic shock wave therapy device.

Shock wave therapy (SWT) refers to the use of focused shock waves for treatment of musculoskeletal indications including plantar fascitis and dystrophic mineralization of tendons and joint capsules. Measurements were made of a SWT device that uses a ballistic source. The ballistic source consists of a handpiece within which compressed air (1-4 bar) is used to fire a projectile that strikes a metal applicator placed on the skin. The projectile generates stress waves in the applicator that transmit as pressure waves into tissue. The acoustic fields from two applicators were measured: one applicator was 15 mm in diameter and the surface slightly convex and the second was 12 mm in diameter the surface was concave. Measurements were made in a water tank and both applicators generated a similar pressure pulse consisting of a rectangular positive phase (4 micros duration and up to 8 MPa peak pressure) followed by a predominantly negative tail (duration of 20 micros and peak negative pressure of -6 MPa), with many oscillations. The rise times of the waveforms were around 1 micros and were shown to be too long for the pulses to be considered shock waves. Measurements of the field indicated that region of high pressure was restricted to the near-field (20-40 mm) of the source and was consistent with the Rayleigh distance. The measured acoustic field did not display focusing supported by calculations, which demonstrated that the radius of curvature of the concave surface was too large to effect a focusing gain. Other SWT devices use electrohydraulic, electromagnetic and piezoelectric sources that do result in focused shock waves. This difference in the acoustic fields means there is potentially a significant mechanistic difference between a ballistic source and other SWT devices.

Immunohistochemical evaluation of substance P and calcitonin gene-related peptide in skin and periosteum after extracorporeal shock wave therapy and radial pressure wave therapy in sheep.

OBJECTIVE: To evaluate the effect of focused extracorporeal shock wave therapy (ESWT) and radial pressure wave therapy (RPWT) on immunohistochemical staining for substance P and calcitonin gene-related peptide (CGRP) in the skin and periosteum of sheep. ANIMALS: 36 sheep. PROCEDURES: All 4 limbs of 36 sheep were treated with ESWT, RPWT, or a sham treatment. For 14 days after treatment, at least 2 sheep were euthanized daily and tissue was harvested for histologic evaluation of nerves via staining for substance P and CGRP in the skin and periosteum. RESULTS: No effects of ESWT or RPWT were observed on the number of nerves with stain uptake for substance P or CGRP in the skin or periosteum. CONCLUSIONS AND CLINICAL RELEVANCE: Substance P- and CGRP-containing nerve fibers are not disrupted by EWST or RPWT. Further studies are needed to identify the mechanism of analgesia observed in association with these treatment modalities.

Effects of short-term light to heavy exercise on gastric ulcer development in horses and efficacy of omeprazole paste in preventing gastric ulceration.

OBJECTIVE: To determine the effects of 8 days of light to heavy exercise on gastric ulcer development in horses and determine the efficacy of omeprazole paste in preventing gastric ulceration. DESIGN: Randomized, controlled, multicenter clinical trial. ANIMALS: 102 horses with normal-appearing gastric mucosa on endoscopic examination that were in light to heavy training. PROCEDURES: Horses at 4 trial locations were allocated into replicates and sham dosed orally (empty syringe) or treated with a paste formulation of omeprazole (1 mg/kg [0.45 mg/ lb], PO) once daily for 8 days. Training regimens varied among locations and included early training for western performance events; walking, trotting, and cantering in a mechanical exerciser; and race training (2 locations). Prevalences of gastric ulceration at the completion of the 8-day treatment period were compared between groups. RESULTS: At the end of the 8-day treatment period, the proportion of omeprazole-treated horses free from gastric ulceration (88%) was significantly higher than the proportion of sham-dosed horses free from gastric ulceration (27%). CONCLUSIONS AND CLINICAL RELEVANCE: Results showed that horses in light to heavy training for as short as 8 days were at risk of developing gastric ulcers and that administration of omeprazole paste decreased the incidence of gastric ulcers.

Evaluation of transfixation casting for treatment of third metacarpal, third metatarsal, and phalangeal fractures in horses: 37 cases (1994-2004).

OBJECTIVE: To evaluate clinical findings, complications, and outcome of horses and foals with third metacarpal, third metatarsal, or phalangeal fractures that were treated with transfixation casting. DESIGN: Retrospective case series. Animals-29 adult horses and 8 foals with fractures of the third metacarpal or metatarsal bone or the proximal or middle phalanx. PROCEDURES: Medical records were reviewed, and follow-up information was obtained. Data were analyzed by use of logistic regression models for survival, fracture healing, return to intended use, pin loosening, pin hole lysis, and complications associated with pins. RESULTS: In 27 of 35 (77%) horses, the fracture healed and the horse survived, including 10 of 15 third metacarpal or metatarsal bone fractures, 11 of 12 proximal phalanx fractures, and 6 of 8 middle phalanx fractures. Four adult horses sustained a fracture through a pin hole. One horse sustained a pathologic unicortical fracture secondary to a pin hole infec-tion. Increasing body weight, fracture involving 2 joints, nondiaphyseal fracture location, and increasing duration until radiographic union were associated with horses not returning to their intended use. After adjusting for body weight, pin loosening was associated with di-aphyseal pin location, pin hole lysis was associated with number of days with a transfixation cast, and pin complications were associated with hand insertion of pins. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that transfixation casting can be successful in managing fractures distal to the carpus or tarsus in horses. This technique is most suitable for comminuted fractures of the proximal phalanx but can be used for third metacarpal, third metatarsal, or middle phalanx fractures, with or without internal fixation.

Force platform evaluation of lameness severity following extracorporeal shock wave therapy in horses with unilateral forelimb lameness.

OBJECTIVE: To measure alterations in lameness severity that occur following use of extracorporeal shock wave therapy (ESWT) in horses with naturally occurring unilateral forelimb lameness. DESIGN: Nonrandomized clinical trial. ANIMALS: 9 horses with unilateral forelimb lameness. PROCEDURES: Force platform gait analysis was performed prior to administration of any treatments (baseline) and after use of local anesthesia to eliminate the lameness. Extracorporeal shock wave therapy was then administered, and gait analysis was repeated 8 hours later and then daily for 7 days. RESULTS: Compared with the baseline value, peak vertical force was significantly increased 8 hours and 2 days after ESWT, and peak vertical force on day 2 was not significantly different from force measured after use of local anesthesia to eliminate the lameness. Similarly, vertical impulse was significantly increased, compared with the baseline value, 8 hours and 2 days after ESWT, but at all times, it was significantly lower than vertical impulse measured after use of local anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in horses with naturally occurring lameness, use of ESWT results in a period of acute improvement in lameness severity that typically persists for 2 days. Thus, in horses undergoing ESWT, exercise should be controlled for a minimum of 2 days after treatment to prevent further injury.

Effect of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus equi in experimentally infected foals.

This study evaluated the prophylactic effectiveness of hyperimmune plasma (HIP) as an aid in the prevention of pneumonia caused by experimental infection with Rhodococcus equi. Thirty neonatal foals were administered R. equi HIP or saline at 2 days of age and were infected with virulent R. equi at 7 days. All foals developed signs or symptoms of respiratory disease. Radiographic scores on day 28 and neutrophil concentrations on day 49 were significantly greater in control foals, and time to respiratory effort score of 2 or higher was significantly shorter for control foals. Three foals, all in the principal group, died or were euthanized before the end of the study, but there was no significant difference in mortality between groups. VapA titers were significantly greater in principal foals. Administration of R. equi HIP decreased the severity of radiographic lesions and prolonged time to increased respiratory effort due to R. equi-induced pneumonia.

Evaluation of adipose-derived stromal vascular fraction from the lateral tailhead, inguinal region, and mesentery of horses.

Use of mesenchymal stem cells (MSCs) found in the stromal vascular fraction (SVF) of equine adipose tissue has promising applications for regenerative therapies. The most commonly used source of equine adipose tissue is the subcutaneous tailhead. The objective of this study was to compare 3 adipose depot sites in horses and determine the viability and cellular yield, capillary density, gene expression for selected markers, and colony-forming unit fibroblasts (CFU-Fs) in adipose tissue taken from these sites. Adipose tissue was excised from the area lateral to the tailhead, the inguinal region, and the small colon mesentery of 6 horses. Lipoaspirate was also collected from the area lateral to the tailhead. Stromal vascular fraction (SVF) was prepared in duplicate from the 3 different adipose tissue depots. The total nucleated and dead cell counts was determined manually using a hemocytometer and percent viability was calculated. Mass and volume of adipose were determined in order to calculate density and factor-VIII immunohistochemical staining was used to determine vascular density in the excisional adipose tissue samples from each horse. Quantitative polymerase chain reaction (qPCR) was used to quantify gene expression for selected cellular markers from each site. There were significant differences in viability, yield of nucleated cells/gram of adipose tissue, vascular density, gene expression, and CFU-Fs among adipose depots. Adipose from the mesentery yielded the highest number of nucleated cells/gram of tissue and the highest vascular density and percentage of CFU-Fs. In the horse, both the anatomical site of collection and the method of tissue collection significantly impact the yield and composition of cells in the SVF. Further study is needed to assess whether one adipose source is superior for harvesting mesenchymal stem cells (MSCs) and whether the differences among sources are clinically relevant for in-vivo treatment of musculoskeletal injuries in horses.

L'utilisation de cellules souches mésenchymateuses (CSMs) retrouvées dans la fraction du stroma vasculaire (FSV) du tissu adipeux équin a des applications prometteuses pour les thérapies régénératrices. La source la plus fréquemment utilisée de tissu adipeux équin est le tissu sous-cutané de la base de la queue. L'objectif de la présente étude était de comparer trois sites de dépôts adipeux chez le cheval et de déterminer la viabilité et la récolte cellulaire, la densité capillaire, l'expression génique de marqueurs sélectionnés, et le nombre de fibroblastes formateur des colonies (FFC) dans le tissu adipeux prélevés de ces sites. Le tissu adipeux a été excisé de la région latérale à la base de la queue, de la région inguinale, et du mésentère du petit colon de six chevaux. Des aspirations de lipide ont également été prélevées de la région latérale de la base de la queue. La FSV a été préparée en duplicata à partir de chacun des trois dépôts différents de tissu adipeux. Les dénombrements totaux des cellules nucléées et mortes ont été déterminés manuellement à l'aide d'un hémocytomètre et le pourcentage de viabilité calculé. La masse et le volume de tissu adipeux ont été déterminés afin de calculer la densité et la coloration par immunohistochimie du facteur VIII a été utilisée afin de déterminer la densité vasculaire dans les échantillons de tissu adipeux excisé de chaque cheval. Une réaction d'amplification en chaine par la polymérase quantitative (ACPq) a été utilisée pour quantifier l'expression génique pour des marqueurs cellulaires sélectionnés de chaque site. Il y avait des différences significatives dans la viabilité, le rendement de cellules nucléées/gramme de tissu adipeux, la densité vasculaire, l'expression génique, et les FFCs entre les dépôts adipeux. Le tissu adipeux provenant du mésentère a généré le plus grand nombre de cellules nucléées/gramme de tissu et la plus haute densité vasculaire et pourcentage de FFCs. Chez le cheval, le site anatomique de prélèvement et la méthode de prélèvement du tissu ont un impact significatif sur le rendement et la composition cellulaire dans la FSV. Des études additionnelles sont requises pour évaluer si une source de tissu adipeux est supérieure pour récolter des cellules souches mésenchymateuses et si les différences entre les sources sont cliniquement pertinentes pour le traitement in vivo de blessures morpho-squelettiques chez les chevaux.(Traduit par Docteur Serge Messier).

Evaluation of analgesia resulting from extracorporeal shock wave therapy and radial pressure wave therapy in the limbs of horses and sheep.

OBJECTIVE: To identify the duration and potential mechanisms of analgesia following extracorporeal shock wave therapy (ESWT) and radial pressure wave therapy (RPWT) in limbs of horses and sheep. ANIMALS: 6 horses and 30 sheep. PROCEDURE: An electrical stimulus was used to identify the nociceptive threshold for each horse daily for 3 days before treatment (baseline) with ESWT or RPWT, 8 hours after treatment, and at 24-hour intervals for 7 days after treatment. Testing was conducted for the treatment field (midmetacarpus or midmetatarsus) and nerve field (medial and lateral forelimb heel bulbs) distal to a treatment site that included the nerve on the abaxial surface of the proximal sesamoid bone. All 4 limbs of 30 sheep were treated with ESWT, RPWT, or a sham treatment. Two sheep were euthanatized daily and tissue harvested for histologic evaluation of nerves, and concentrations of substance P and calcitonin gene-related peptide were measured in the skin and periosteum. RESULTS: Values did not differ significantly between baseline and after treatment for the treatment field or nerve field sensation. There was a large difference in the slope when data for horses were plotted for the first 3 days after treatment, compared with the slope for days 4 to 7 after treatment. No differences were found in neuropeptide concentrations after treatment of the sheep, but there was an inflammatory response in the treated nerves. CONCLUSIONS AND CLINICAL RELEVANCE: A small cutaneous analgesic effect may exist at the treatment site for approximately 3 days after ESWT or RPWT in horses.

Gastric ulcer development in horses in a simulated show or training environment.

OBJECTIVE: To determine whether conditions representing activities that are typical in the recreational use of horses, including transport to and from show grounds, stall confinement in unfamiliar surroundings, and light exercise, are associated with increased incidence of gastric ulcers in horses. DESIGN: Randomized controlled study. ANIMALS: 20 client-owned horses. PROCEDURE: Horses had no gastric ulcers as determined by endoscopic examination on study day -1. Ten control horses were maintained on-site with no changes in management variables. Ten horses were transported via trailer for 4 hours on day 0 to another site, placed in individual stalls, fed twice daily, and exercised twice daily for 3 days. On day 4, they were transported back to the original site via trailer for 4 hours. On day 5, endoscopic examinations were performed on all horses to assess gastric mucosa status. RESULTS: Horses that were transported and housed off-site had a significantly higher incidence of hyperkeratosis and reddening of the gastric mucosa than control horses. Two control horses and 7 transported horses developed gastric ulcers by day 5. Ulcer scores of transported horses increased significantly from day -1, whereas ulcer scores in control horses did not change significantly from day -1. CONCLUSIONS AND CLINICAL RELEVANCE: Activities that are typical in recreational use of horses were ulcerogenic, and ulcers in the gastric squamous mucosa can develop under these conditions within 6 days.

Efficacy of omeprazole paste for prevention of gastric ulcers in horses in race training.

OBJECTIVE: To determine the minimal effective dosage of omeprazole oral paste for the prevention of naturally occurring ulcers in horses starting race training. DESIGN: Prospective study. ANIMALS: 175 horses. PROCEDURE: Horses in the dose selection portion of the study were sham dose treated or received 1 mg (0.45 mg/lb) or 2 mg (0.9 mg/lb) of omeprazole/kg, PO, every 24 hours for 28 days or 4 mg of omeprazole/kg (1.8 mg/lb; loading dose), PO, every 24 hours for 4 days, then 1 or 2 mg of omeprazole/kg, PO, every 24 hours for 24 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for 28 days. Gastric ulcer scores at the beginning and end of the study were compared. RESULTS: Sham-dose-treated horses had significantly higher ulcer scores than did horses treated with any of the omeprazole dosages evaluated. Among horses treated with omeprazole, there was no significant interaction of dose (1 or 2 mg/kg) and loading dose; therefore, the lowest effective dose (1 mg/kg) was evaluated in the dose confirmation portion of the study. In the dose confirmation study, 4 of 39 (10%) sham-dose-treated horses remained ulcer free, which was significantly different from the proportion of horses (31/38 [82%]) receiving 1 mg of omeprazole/kg that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE; Results indicated that omeprazole administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of gastric ulcers in horses starting race training.

Efficacy of omeprazole paste for prevention of recurrence of gastric ulcers in horses in race training.

OBJECTIVE: To determine whether omeprazole oral paste administered at a dosage of 0.5 or 1 mg/kg (0.23 or 0.45 mg/lb), PO, every 24 hours would effectively prevent the recurrence of gastric ulcers in horses in race training. DESIGN: Prospective study. ANIMALS: 135 horses. PROCEDURES: Horses with gastric ulcers were treated with omeprazole at a dosage of 4 mg/kg (1.8 mg/lb), PO, every 24 hours for 28 days. Horses in the dose selection portion of the study were sham dose treated or received 0.5 or 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Gastric ulcers were scored before and after the preventive phase of the study (day 28 to day 56) via gastroscopy, and ulcer scores were compared. RESULTS: Sham-dose-treated horses and horses receiving 0.5 mg of omeprazole/kg had significantly higher ulcer scores than did horses receiving 1 mg of omeprazole/kg. There was a significant difference between the proportion of horses receiving 1 mg of omeprazole/kg (38/48 179%]) that remained ulcer free and the proportion of sham-dose-treated horses (7/44 [16%]) that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE: Omeprazole oral paste administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of recurrence of gastric ulcers in horses in race training.

A randomized controlled field trial of a novel trimethoprim-sulfadiazine oral suspension for treatment of Streptococcus equi subsp zooepidemicus infection of the lower respiratory tract in horses.

OBJECTIVE: To evaluate the effectiveness of a novel trimethoprim-sulfadiazine oral suspension for the treatment of naturally acquired Streptococcus equi subsp zooepidemicus infection in horses. DESIGN: Randomized, controlled field trial. ANIMALS: 180 horses with S equi subsp zooepidemicus infection. PROCEDURES: Horses with lower respiratory tract infections caused by S equi subsp zooepidemicus were treated with a new formulation of combined trimethoprim-sulfadiazine oral suspension at a dosage of 24 mg/kg (10.9 mg/lb) twice daily for 10 days (treatment group) or with an equivalent volume of saline (0.9% NaCl) solution (placebo group). Response to treatment, including clinical signs and fecal consistency scores, was assessed twice daily. Any adverse effects were recorded. The primary outcome variable was clinical response; the secondary outcome variable was eradication of S equi subsp zooepidemicus on study day 17 as determined by bacteriologic culture of repeated transtracheal-wash specimens. RESULTS: Of the 119 horses allocated to the treatment group, 69 (58%) had a positive clinical response. A significantly smaller proportion of horses in the placebo group (9/61 [15%]) had a positive clinical response. By day 5, 25 of 61 (41%) placebo horses had been withdrawn from the study because of negative clinical response, compared with only 10 of 119 (8.4%) treated horses. By day 10, 28 of 61 (46%) placebo horses had been withdrawn because of negative clinical response, compared with only 13 of 119 (11%) treated horses. There were few adverse events associated with the trimethoprim-sulfadiazine suspension. There were no significant differences in fecal consistency scores between treatment and placebo groups. CONCLUSIONS AND CLINICAL RELEVANCE: The new oral suspension administered at 24 mg/kg twice daily effectively treated the clinical signs of S equi subsp zooepidemicus lower respiratory infection in horses and eliminated the organism from the respiratory tract. Adverse effects were minimal.

High yield recovery of equine mesenchymal stem cells from umbilical cord matrix/Wharton's jelly using a semi-automated process.

Umbilical cord is an abundant source of perinatal, plastic adherent mesenchymal stem cells (UC-MSCs). UC-MSCs exhibit robust stemness and strong immunosuppressive and regenerative effects in vivo. This protocol describes enzymatic and mechanical dissociation of umbilical cord matrix (Wharton's jelly) that results in efficient isolation of large numbers of fresh nucleated umbilical cord regenerative cells (UC-RCs) that, when cultured on plastic, exhibit similar characteristics of UC-MSCs. This protocol potentially alleviates the need for culture expansion to obtain large numbers of cells required for clinical application. Dissociation is achieved with a blend of collagenase and neutral proteases with agitation at 37 °C in a semi-automatic system. Average expected yield is 1.65 × 10(6) cells/g tissue with 93 % viability. This protocol has been successfully used to isolate an uncultured nucleated regenerative cell population (also referred to as stromal vascular fraction or SVF) from surgically debrided skin and from human, equine, and canine adipose tissue. The procedure requires less than 30 min for tissue dissection and less than 100 min for cell extraction. Quickly obtaining a large number of UC-RCs that have pluripotent differentiation capacity without the complexity and risks of culture expansion could simplify and expand the use of UC-RCs in clinical as well as research applications.

Effects of extracorporeal shock wave therapy and radial pressure wave therapy on elasticity and microstructure of equine cortical bone.

OBJECTIVE: To measure changes in the modulus of elasticity (E) and describe histologic findings after extracorporeal shock wave therapy and radial pressure wave therapy on equine cortical bone specimens. SAMPLE POPULATION: 16 bone specimens from the proximodorsal cortex of an equine third metacarpal or metatarsal bone. PROCEDURE: Baseline E was determined by the density (p) and unidirectional ultrasound transmission velocity (C) of each specimen according to the equation E = pC2. Eight specimens were treated with 500 pulses of 0.15 mJ/mm2 of extracorporeal shock wave therapy, and 8 specimens were treated with 500 pulses of 0.16 mJ/mm2of radial pressure wave therapy. After treatment, C was determined again. Four treatment sessions resulted in 2,000 pulses and 5 C measurements. The p of each sample was measured again. Mean post-treatment E was calculated for each group. Nondecalcified sections of all specimens were stained with toluidine blue or basic fuchsin for histologic evaluation. RESULTS: Overall treatment group effect was not significant for C or E. Final E was not different from baseline values for extracorporeal shock wave therapy and radial pressure wave therapy. No histologic changes could be attributed to either treatment modality. CONCLUSIONS AND CLINICAL RELEVANCE: Extracorporeal shock wave therapy and radial pressure wave therapy did not affect the material properties of equine bone at the energy and pulse values used in this study.