Objective. To explore the involvement of proteaseactivated receptor 1 (PAR-1) and PAR-2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR-1 or PAR-2 in mice.Methods. OA was induced in the joints of wildtype (WT), PAR-1 ؉/؉ , PAR-1 ؊/؊ , and PAR-2 ؊/؊ mice by destabilization of the medial meniscus (DMM), and scores of histologic features (cartilage aggrecan loss and erosion, subchondral bone sclerosis, osteophytes, and synovitis) were compared at 1, 4, and 8 weeks post-DMM. The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression/ activity were studied in cultures of mouse femoral head tissue with or without interleukin-1␣ (IL-1␣). At 1 week post-DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription-polymerase chain reaction, and populations of inflammatory cells were quantified by flow cytometry.Results. Deletion of PAR-2, but not that of PAR-1, in mice significantly delayed the progression of cartilage damage and inhibited subchondral bone sclerosis following DMM. There was no inhibitory effect of PAR-1 or PAR-2 ablation on IL-1␣-induced cartilage degradation or chondrocyte metalloproteinase expression/activation. A low but significant level of synovitis persisted in mice subjected to DMM compared to that in control mice subjected to sham surgery, but no differences between the genotypes were seen 4 or 8 weeks post-DMM. One week after DMM, increased synovial expression of proinflammatory cytokines and metalloproteinase genes, along with increased levels of CD4؉ T cells, inflammatory monocytes, and activated macrophages, were seen in all genotypes. However, there was a significant reduction in the percentage of activated macrophages in PAR-2 ؊/؊ mice compared to PAR-1 ؊/؊ and WT mice.Conclusion. Deletion of PAR-2, but not that of PAR-1, results in a significant decrease in DMMinduced cartilage damage. The chondroprotection in PAR-2 ؊/؊ mice appears to occur indirectly through modulation of extracartilaginous events such as subchondral bone remodeling and synovial macrophage activation, rather than through alteration of chondrocyte catabolic responses.The synovial joint is an "organ" with communication and interdependence between the component tissues and cells necessary for maintenance of normal articular function (1). Osteoarthritis (OA) is the most common arthropathy, and although progressive loss of articular cartilage is pathognomonic, there are varying
The available data indicates that the molecular mechanisms of both joint structural damage and pain may be distinct in animal models of OA induced or initiated by different means. This suggests the need to continue using multiple OA animal models but that the subsequent interpretation of the data and its extrapolation to the human condition must be more precise.
Alfaxan-CD is an effective anaesthetic agent in young healthy cats, providing a smooth induction and rapid recovery. Cats that were premedicated with acepromazine and butorphanol prior to induction with Alfaxan-CD had better recovery scores than those that were not premedicated.
Resilience is a dynamic and multifaceted process in which individuals draw on personal and contextual resources. In difficult situations, resilient people use specific strategies to learn from the situation without being overcome by it. As stressors are inherent to veterinary work, including long work hours, ethical dilemmas, and challenging interactions with clients, resilience is an important component of professional quality of life. However, while resilience in other health professionals has received attention, it has received little in the veterinary field. In this cross-sectional study, veterinary students from six veterinary schools in Australia completed an online survey, with 193 responses (23%). Very few veterinary students (6%) reached the threshold to be considered highly resilient using the Brief Resilience Scale, and approximately one third classified as having low levels of resilience. In the final linear multiple regression model, predictors of resilience included nonjudgmental and nonreactive mindfulness (Five Facet Mindfulness Questionnaire) and self-compassion (Neff Self-Compassion Scale). Students with higher nonjudgmental and nonreactive mindfulness and self-compassion had higher resilience scores. These findings indicate that fostering these qualities of mindfulness and self-compassion may be aligned with strengthening veterinary student resilience. Importantly, if the factors that help veterinary students develop a capacity for resilience can be identified, intervention programs can be targeted to educate future veterinary professionals with a high quality of life, both professional and personal.
Background: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA. Methods: Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/ macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR). Results: MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages. Conclusions: This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.
Peritoneopericardial diaphragmatic hernia is a common incidental finding in cats and is rarely symptomatic. The case report described herein presented with dyspnoea secondary to incarceration of hepatic cysts within the pericardial space of a cat with a peritoneopericardial diaphragmatic hernia.
A 10-year-old spayed domestic shorthaired cat was presented for behavioural changes, signs suggestive of visual deficits and aimless circling. Neuro-ophthalmological examination suggested the cat had central blindness. CT scans following administration of iohexol demonstrated a contrast-enhancing mass in the vicinity of the third ventricle resulting in obstructive hydrocephalus. Following rostral tentorial craniotomy and incision through the cerebral cortex, the third ventricle was approached via the dilated left lateral ventricle. An ependymoma was seen through a dorsocaudolateral incision into the third ventricle, and removed by gentle manipulation and suction. The cat recovered unremarkably, regaining normal vision and behaviour.
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