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Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro-inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well-established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000-fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = -0.6 to -0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E 2 (PGE 2 ), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA., (© 2024 Orthopaedic Research Society.)

Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells. Changes in glycocalyx thickness of approximately 10 nm can alter the susceptibility to immune cell attack. Enhanced stimulation of natural killer and T cells through equipment with chimeric antigen receptors can improve the cytotoxicity against mucin-bearing target cells. Alternatively, cytotoxicity can be enhanced through engineering effector cells to display glycocalyx-editing enzymes, including mucinases and sialidases. Together, our results motivate the development of immunoengineering strategies that overcome the glycocalyx armour of cancer cells., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Plantar osteochondral fragments (POF) are common but their effect on joint health of young Standardbreds in race training is largely unknown., Objectives: Evaluate the inflammatory effects of POF in metatarsophalangeal joints of young Standardbreds as a step towards developing evidence-based recommendations for surgical removal., Study Design: Cohort study., Methods: Forty-nine Standardbred horses (age 11-33 months) presented for surgical removal of POF from 56 metatarsophalangeal joints. Synovial tissue collected at arthroscopy was subjected to histopathology. IL-1β, TNF-α, and PGE-2 were measured in synovial fluid using ELISA. Digital arthroscopy images were scored for inflammation. Racing performance data were retrieved from a public database., Results: Median time in race training prior to surgery was 8 weeks (IQR 4-12; range 0-40). There was minimal evidence of synovial inflammation as assessed by histopathology (median total score 2/20, IQR 0-2, range 0-5) or arthroscopy (median average total score 2.67/15, IQR 1.79-4, range 0-8.83). IL-1β was not detected in any sample. TNF-α (median 0 pg/mL, IQR 0-0) and PGE-2 (median 56.6 pg/mL, IRQ 40.5-99.8) were measured at low levels. Weeks in training prior to surgery was associated with the number of starts in the season after surgery (incidence rate ratio 1.02, 95% CI 1.00, 1.04, P = .03)., Main Limitations: Small sample size from a single breed with a relatively short training time prior to surgery., Conclusions: There was minimal evidence of synovial inflammation in the metatarsophalangeal joints in this population of young Standardbred horses with POF. It is possible that POF may result in a different inflammatory response than other fragments because they are generally well-embedded in situ. These findings suggest that, in Standardbreds, race training can commence several weeks prior to surgical removal of POF with minimal detrimental effects on joint health, although further investigation of long-term effects of POF on joint health is warranted., (© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Objective: Osteoarthritis is a painful, chronic joint disease affecting man and animals with no known curative therapies. Palliative nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but they cause adverse side effects prompting the search for safer alternatives. To address this need, we evaluated the anti-inflammatory activity of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS) with or without the NSAID carprofen., Design: Canine chondrocytes were propagated in microcarrier spinner culture and incubated with (1) control medium, (2) ASU (8.3 µg/mL) + GLU (11 µg/mL) + CS (20 µg/mL) combination for 24 hours; and/or carprofen (40 ng/mL). Cultures were next incubated with control medium alone or IL-1β (10 ng/mL) for another 24 hours. Production of PGE 2 , IL-6, IL-8, and MCP-1 (also known as CCL-2) were measured by ELISA., Results: Chondrocytes proliferated in microcarrier spinner culture and produced type II collagen and aggrecan. Stimulation with IL-1β induced significant increases in PGE 2 , IL-6, IL-8, and MCP-1 production. The increases in production were suppressed by carprofen as well as [ASU+GLU+CS]. The combination of carprofen and [ASU+GLU+CS] reduced PGE 2 production significantly more than either preparation alone. The inhibitory effect of carprofen on IL-6, IL-8, and MCP-1 production was significantly less than that of [ASU+GLU+CS], whereas the combination did not reduce the production of these molecules significantly more than [ASU+GLU+CS] alone., Conclusions: The potentiating effect of [ASU+GLU+CS] on low-dose carprofen was identified in chondrocyte microcarrier spinner cultures. Our results suggest that the combination of low-dose NSAIDs like carprofen with [ASU+GLU+CS] could offer a safe, effective management for joint pain.

Objective: To report our experience with partial arytenoidectomy in sedated standing horses., Study Design: Retrospective study., Animals: Fourteen client-owned adult horses., Methods: The medical records (2013-2017) of horses treated with unilateral partial arytenoidectomy while standing and sedated were reviewed. Demographics, endoscopic findings, previous treatments, and outcome after surgery were investigated and recorded., Results: Thirteen horses had unilateral left-sided recurrent laryngeal neuropathy (RLN) and 1 horse had bilateral RLN. Five horses had a previous failed prosthetic laryngoplasty. Left-sided partial arytenoidectomy without mucosal closure was successfully completed in all horses under sedation and local anesthesia. Report of long-term outcome was obtained via telephone conversations for 12 horses, of which 9 also had an endoscopic reevaluation performed; 3 horses had granulomas at the surgical site, of which 2 eventually required a permanent tracheostomy. Nine horses returned to athletic use without respiratory noise, 2 horses returned to athletic use with noise during exercise that was reduced compared with preoperative levels, and 1 horse continued to be used as a broodmare., Conclusion: Partial arytenoidectomy in standing horses was achieved with adequate sedation and local anesthesia., Clinical Significance: Partial arytenoidectomy on standing sedated horses could be considered as an alternative to eliminate the risks associated with general anesthesia., (© 2019 The American College of Veterinary Surgeons.)

Objective: To determine the influence of tissue preparation and long-term storage methods on structural integrity and risk of bacterial contamination of equine amnion., Study Design: Prospective experimental investigation SAMPLE POPULATION: Amniotic membranes from 8 healthy mares (n = 440 tested samples)., Methods: Samples for baseline bacteriology and histology were taken after removal of debris. The remaining tissue was divided and processed with 0.05% chlorhexidine or 2% iodine/0.25% acetic acid. Processed amnion samples were assigned to 1 of 9 combinations of storage media (saline, chlorhexidine, acetic acid) and temperature (4 °C, -20 °C, -80 °C). Samples were submitted for quantitative bacteriology and histopathology at 1 week, 4 weeks, and 3, 6, 9, and 12 months., Results: Baseline bacterial levels ranged from <200 to > 150 000 colony-forming units (cfu)/mL. None of the potentially pathogenic bacteria in baseline samples were subsequently cultured throughout the study. Nonpathogenic bacteria (median 20 cfu/mL), most commonly Bacillus sp, were cultured sporadically across storage conditions. Tissue architecture was minimally affected histologically by processing protocol, storage temperature, or storage duration., Conclusion: The 2 processing protocols tested here resulted in minimal bacterial contamination or loss of structural integrity of equine amnion stored for up to 12 months at 4 °C, -20 °C, or -80 °C., Clinical Significance: Amnion collected during the foaling season may be stored for up to 12 months without significant bacterial contamination or structural alterations., (© 2018 The American College of Veterinary Surgeons.)

OBJECTIVE To report complication rates following elective arthroscopy in horses and determine whether postoperative complication rates are higher for outpatient procedures, compared with inpatient procedures. DESIGN Retrospective cohort study. ANIMALS 357 client-owned horses that had undergone 366 elective arthroscopic procedures between January 2008 and February 2015. PROCEDURES Medical records were retrospectively reviewed. Data collected included signalment, travel time to the hospital, clinical signs, joints treated, lesions diagnosed, medications administered, anesthesia and surgery times, details of the procedure (including closure method and surgeons involved), and hospitalization status (inpatient or outpatient). Inpatients were horses that remained hospitalized overnight, and outpatients were horses that were discharged in the afternoon of the day of surgery. The collected data were analyzed along with follow-up information to identify factors associated with postoperative complications and potentially associated with hospitalization status. RESULTS Data were collected on 366 elective arthroscopic procedures (outpatient, n = 168 [46%]; inpatient, 198 [54%]). Complications that occurred included bandage sores, catheter problems, colic, diarrhea, postoperative discomfort, esophageal impaction, fever, incisional drainage, postanesthetic myopathy, persistent synovitis, persistent lameness, septic arthritis, and osteochondral fragments not removed during the original surgery. None of these complications were associated with hospitalization status (outpatient vs inpatient). However, Standardbreds were overrepresented in the outpatient group, and anesthesia and surgery times were longer for the inpatient group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that outpatient elective arthroscopy in healthy horses could be performed safely and without a higher risk of complications, com pared with similar procedures performed on an inpatient basis.

OBJECTIVE To biomechanically compare modified and standard laryngoplasty constructs in monotonic load to failure and cyclic loading. SAMPLES 41 equine cadaveric larynges. PROCEDURES Laryngoplasty constructs were created by use of a standard technique on one side and a modified technique (with a toggle to anchor suture to the arytenoid cartilage) on the other side. For monotonic loading, laryngoplasty constructs were prepared and suture ends attached to a load frame; constructs then were loaded until mechanical failure. Mean load at failure and failure modes were compared between constructs. For cyclic loading, arytenoid cartilages were maximally abducted and constructs were circumferentially loaded for 10,000 cycles. Loss of arytenoid abduction was evaluated every 500 cycles with a subjective grading scale and objective change in rima glottidis cross-sectional area. RESULTS In monotonic loading, modified laryngoplasty constructs failed at a significantly higher mean ± SD load (191 ± 29 N) than did standard laryngoplasty constructs (91 ± 44 N). None of the modified laryngoplasty constructs failed by suture pull-through of the muscular process of the arytenoid cartilage, whereas most of the standard laryngoplasty constructs failed in that manner. In cyclic testing, 11 of 20 standard laryngoplasty constructs failed or achieved Dixon grade 3 abduction, whereas 0 of 20 modified laryngoplasty constructs failed. Modified laryngoplasty constructs lost significantly less rima glottidis cross-sectional area in circumferential testing, compared with loss for standard laryngoplasty constructs. CONCLUSIONS AND CLINICAL RELEVANCE The modified laryngoplasty technique was biomechanically superior to the standard laryngoplasty technique in this ex vivo study.

Fell Pony syndrome (FPS) is a fatal immunodeficiency that occurs in foals of the Fell Pony breed. Affected foals present with severe anemia, B cell lymphopenia, and opportunistic infections. Our objective was to conduct a prospective study of potential FPS-affected Fell Pony foals to establish clinical, immunological, and molecular parameters at birth and in the first few weeks of life. Complete blood counts, peripheral blood lymphocyte phenotyping, and serum immunoglobulin concentrations were determined for 3 FPS-affected foals, 49 unaffected foals, and 6 adult horses. In addition, cytology of bone marrow aspirates was performed sequentially in a subset of foals. At birth, the FPS-affected foals were not noticeably ill and had hematocrit and circulating B cell counts comparable to those of unaffected foals; however, over 6 weeks, values for both parameters steadily declined. A bone marrow aspirate from a 3-week-old FPS-affected foal revealed erythroid hyperplasia and concurrent erythroid and myeloid dysplasia, which progressed to a severe erythroid hypoplasia at 5 weeks of life. Immunohistochemical staining confirmed the paucity of B cells in primary and secondary lymphoid tissues. The mRNA expression of genes involved in B cell development, signaling, and maturation was investigated using qualitative and quantitative reverse transcriptase PCR (RT-PCR). Several genes, including CREB1, EP300, MYB, PAX5, and SPI1/PU.1, were sequenced from FPS-affected and unaffected foals. Our study presents evidence of fetal erythrocyte and B cell hematopoiesis with rapid postnatal development of anemia and B lymphopenia in FPS-affected foals. The transition between fetal/neonatal and adult-like hematopoiesis may be an important aspect of the pathogenesis of FPS.

This study aimed to determine whether TNF-α is transferred to equine neonates via colostrum and the relationship between TNF-α and IgG concentrations in the equine neonate. Colostrum, presuckle and postsuckle foal serum samples were collected from healthy mares and their foals. Equine TNF-α ELISA and IgG SRID kits were used to determine the concentrations of TNF-α and IgG, respectively. Statistical analysis was performed using the Spearman rank correlation. TNF-α concentrations in all presuckle foal serum were below the limit of detection in 15/16 foals and increased in postsuckle foal serum to a mean concentration of 7.7 x 10(4) pg/ml. TNF-α concentrations in postsuckle foal serum and colostrum showed significant correlation (rho=0.668; P=0.005). However, TNF-α and IgG concentrations in colostrum or postsuckle foal serum did not correlate (rho<-0.016; P>0.05). Ratios of TNF-α/IgG in colostrum or postsuckle foal serum showed significant correlation (rho=0.750; P=0.0008). These results indicate that TNF-α is transferred to the foal via colostrum absorption and may play a role in early immunity.