Osteoarthritis is a ubiquitous disease affecting many horses. The disease causes chronic pain and decreased performance for patients and great cost to owners for diagnosis and treatment. The most common treatments include systemic nonsteroidal anti-inflammatory drugs and intraarticular injection of corticosteroids. There is excellent support for the palliative pain relief these treatments provide, however they do not arrest progression and may in some instances hasten advancement of disease. Orthobiologic treatments have been investigated as potential osteoarthritis treatments that may not only ameliorate pain but also prevent or reverse pathologic articular tissue changes. Clinical protocols for intraarticular use of such treatments have not been optimized; the high cost of in vivo research and concerns over humane use of research animals may be preventing discovery. The objective of this study was to evaluate a novel in vitro articular coculture system for future use in osteoarthritis treatment research. Concentrations and fold increases in various markers of inflammation (prostaglandin E2 and tumor necrosis factor-alpha), degradative enzyme activity (matrix metalloproteinase-13 [MMP-13]), cartilage and bone metabolism (bone alkaline phosphatase and dimethyl-methylene blue), and cell death (lactate dehydrogenase) were compared between IL-1-stimulated equine articular cartilage explant cultures and co-cultures comprised of osteochondral and synovial explants (OCS). Results suggested that there are differences in responses of culture systems to inflammatory stimulation. In particular, the IL-1-induced fold changes in MMP-13 concentration were significantly different between OCS and cartilage explant culture systems after 96 hours. These differences may be relevant to responses of joints to inflammation in vivo and could be important to the biological relevance of in vitro research findings.

OBJECTIVE To compare the effects of 3 equimolar concentrations of methylprednisolone acetate (MPA), triamcinolone acetonide (TA), and isoflupredone acetate (IPA) on equine articular tissue cocultures in an inflammatory environment. SAMPLE Synovial and osteochondral explants from the femoropatellar joints of 6 equine cadavers (age, 2 to 11 years) without evidence of musculoskeletal disease. PROCEDURES From each cadaver, synovial and osteochondral explants were harvested from 1 femoropatellar joint to create cocultures. Cocultures were incubated for 96 hours with (positive control) or without (negative control) interleukin (IL)-1β (10 ng/mL) or with IL-1β and MPA, TA, or IPA at a concentration of 10⁻⁴, 10⁻⁷, or 10⁻¹⁰M. Culture medium samples were collected from each coculture after 48 and 96 hours of incubation. Concentrations of prostaglandin E₂, matrix metalloproteinase-13, lactate dehydrogenase, and glycosaminoglycan were determined and compared among treatments at each time. RESULTS In general, low concentrations (10⁻⁷ and 10⁻¹⁰M) of MPA, TA, and IPA mitigated the inflammatory and catabolic (as determined by prostaglandin E₂ and matrix metalloproteinase-13 quantification, respectively) effects of IL-1β in cocultures to a greater extent than the high (10⁻⁴M) concentration. Mean culture medium lactate dehydrogenase concentration for the 10⁻⁴M IPA treatment was significantly greater than that for the positive control at both times, which was suggestive of cytotoxicosis. Mean culture medium glycosaminoglycan concentration did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the in vitro effects of IPA and MPA were similar to those of TA at clinically relevant concentrations (10⁻⁷ and 10⁻¹⁰M).

Irreversible electroporation is a proven ablation modality for local ablation of soft tissue tumors in animals and humans. However, the strong muscle contractions associated with the electrical impulses (duration, 50–100 μs) requires the use of general anesthesia and, in most situations, application of neuromuscular blockade. As such, this technology is not used in an outpatient setting for ablating common cutaneous tumors (e.g., squamous cell carcinoma or melanoma) in humans or animals. Recently, high-frequency irreversible electroporation (H-FIRE) technology has been developed to enable electroporation of tumors without stimulation of nearby skeletal muscle. H-FIRE administers bursts of electrical pulses (duration, 0.5–2 μs) through bipolar electrodes placed in tumor parenchyma. We hypothesized that H-FIRE could be used to safely ablate superficial tumors in standing, awake horses without the need for general anesthesia. Here, we describe the treatment of superficial tumors in five horses using this novel ablation therapy without the need for general anesthesia. In each case, H-FIRE therapy predictably ablated tumor volume. All patients tolerated the procedure, no complications developed, and veterinary personnel safety was maintained. The H-FIRE treatment may be useful for treatment in veterinary and human patients in an outpatient setting without the need for hospitalization, general anesthesia, and advanced monitoring techniques.

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.

Ileus is a common life-threatening problem in horses, and currently available treatments may be ineffective. The purpose of this study was to determine whether bit chewing, a form of sham feeding, decreases the gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) in clinically normal horses in a prospective crossover study. Nine healthy horses were acclimated and fed a standardized diet. Following 24 h of fasting, self-contained video endoscopy capsules and acetaminophen were administered into the stomach via a nasogastric tube. Each horse underwent experimental (bit chewing for 20 min every 6 h) or control (no bit chewing) conditions, with a 3-week minimum washout period between conditions. The horses were enrolled in either part of the study until all video capsules were retrieved and/or 30 days lapsed. The video capsules were recovered from manure, and GET, SITT, and OCTT were determined from a video analysis. Bit chewing significantly decreased OCTT (p = 0.015) compared to the control conditions. Bit chewing decreased GET and SITT, but the differences were not significant. The mean (median) times determined via the video capsule analysis for the bit-chewing conditions were as follows: GET, 2.34 h (2.86 h); SITT, 3.22 h (3.65 h); and OCTT, 5.13 h (6.15 h), and for the control conditions, they were as follows: GET, 3.93 h (5 h); SITT, 3.79 h (4.4 h); and OCTT, 8.02 h (9.92 h). Bit chewing decreased OCTT in healthy horses. Because this segment of the gastrointestinal tract is frequently affected by ileus, bit chewing may be a safe and inexpensive intervention for that condition in horses. Further investigation in clinical patients with ileus is warranted.