Clinical, morphological and immunohistochemical features of cutaneous lymphocytosis, an uncommon disease histologically resembling well-differentiated malignant lymphoma, were characterized in 23 cats. Clinical outcome was correlated with histomorphology and immunophenotype in an attempt to predict benign vs. malignant behaviour. The disease mainly affected older cats. Lesions were solitary in 61% of cats and often characterized by alopecia (73.9%), as well as erythema, scaling and ulceration. The lateral thorax was most commonly affected (43.5%). Pruritus was frequent (65.2%). Systemic signs included anorexia and weight loss. Morphologically, lesions were characterized by dermal infiltrations of well-differentiated CD3+ T-cells (100%) and aggregates of CD79+ B-cells (64.3%). Cutaneous lymphocytosis is slowly progressive and relatively benign, although in some cats systemic signs led to euthanasia. Four of 12 euthanized cats and one live cat also had lymphoid infiltrates in internal organs. Unfortunately, we were unable to predict clinical outcome by histological and immunohistochemical evaluations of skin lesions.
Clonal chondroprogenitors from immature articular cartilage provide a useful tool to understand progenitor cell biology from the perspective of cartilage repair. Comparisons with more mature progenitor populations may lead to greater understanding in optimising repair strategies.
ObjectivesSynovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA).MethodsGluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined.ResultsAMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (p<0.001, days 1–21), gait abnormalities (days 1–2), end-stage joint destruction (p<0.001), synovial inflammation (p<0.001), and messenger RNA expression of meniscal IL-6 (p<0.05) and whole joint cathepsin K (p<0.01). X-ray and MRI revealed fewer cartilage and bone erosions, and less inflammation after NBQX treatment. NBQX reduced HOB number and prevented mineralisation.ConclusionsAMPA/KA GluRs are expressed in human OA and RA, and in AIA, where a single intra-articular injection of NBQX reduced swelling by 33%, and inflammation and degeneration scores by 34% and 27%, respectively, exceeding the efficacy of approved drugs in the same model. AMPA/KA GluR antagonists represent a potential treatment for arthritis.
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