Cathy J Fuller

The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse.

OBJECTIVE Equine models of osteoarthritis (OA) have been used to investigate pathogenic pathways of OA and evaluate therapeutic candidates for naturally occurring equine OA which is a significant clinical disease in the horse. This review focuses on the macroscopic and microscopic criteria for assessing naturally occurring OA in the equine metacarpophalangeal joint as well as the osteochondral fragment-exercise model of OA in the equine middle carpal joint. METHODS A review was conducted of all published OA studies using horses and the most common macroscopic and microscopic scoring systems were summarized. Recommendations regarding methods of OA assessment in the horse have been made based on published studies. RESULTS A modified Mankin scoring system is recommended for semi-quantitative histological assessment of OA in horses due to its already widespread use and similarity to other scoring systems. Recommendations are also provided for histological scoring of synovitis and macroscopic lesions of OA as well as changes in the calcified cartilage and subchondral bone of naturally occurring OA. CONCLUSIONS The proposed system for assessment of equine articular tissues provides a useful method to quantify OA change. It is believed that addition of quantitative tracing onto plastic and macroscopic measurement as recently described would be an improvement for overall assessment of articular cartilage change.

Chondrocyte death by apoptosis is associated with the initiation and severity of articular cartilage degradation

Aim:  To investigate the role of chondrocyte apoptosis in the initiation and severity of articular cartilage (AC) damage.

Ultrasonography of the medial palmar intercarpal ligament in the Thoroughbred: technique and normal appearance

REASONS FOR PERFORMING STUDY Tearing of the medial palmar intercarpal ligament (MPICL) has been recognised as a cause of lameness in the Thoroughbred, but diagnosis is difficult due to the nonspecific clinical signs, and can be achieved only by performing arthroscopy on the mid carpal joint (MCJ). It would be beneficial to be able to image the MPICL using ultrasonography to determine whether pathology is present in the ligament in order to aid diagnosis and prognosis. OBJECTIVES To determine whether the MPICL could be imaged using ultrasound from the dorsal aspect of the MCJ, and to describe the technique and normal ultrasonographic appearance of the ligament. METHODS A pilot study was performed using 2 cadaver carpi. Each carpus in turn had the MPICL imaged simultaneously using arthroscopy and ultrasound, with a metallic probe positioned on the dorsal aspect of the ligament to highlight the position of the MPICL. Six further pairs of carpi had the MPICL imaged ultrasonographically followed by dissection of the carpus to evaluate the ligament and relate its anatomy to the ultrasound images. Finally, 15 Thoroughbreds with no history of lameness isolated to the carpus had their MPICLs assessed and measured ultrasonographically. RESULTS The MPICL could be imaged via the dorsal aspect of the MCJ using standard ultrasound equipment. The body and division into medial and lateral branches could be seen as a distinct, moderately dense granular echogenic structure in the palmar aspect of the joint, with clearly defined margins. CONCLUSIONS The normal MPICL can be imaged reliably using ultrasound in the Thoroughbred from the dorsal aspect of the MCJ. There is a wide range in the normal width of the lateral aspect of the MPICL, but there is good symmetry between contralateral limbs. POTENTIAL RELEVANCE This report of the normal ultrasonographic appearance of the ligament will be beneficial in acting as a reference for the detection of pathology using ultrasound.

Variations in cartilage catabolism in different equine joints in response to interleukin-1 in vitro

An explant system was used to investigate the hypothesis that cartilage from different equine joints might respond differently to challenge with interleukin-1 α (L-1 α). Pairs of normal cartilage samples were taken from the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints of six horses. One of each pair was stimulated with 10 ng/ml human recombinant IL-1 α for three days, and the supernatants and remaining cartilage explants were analysed for their total content of glycosaminoglycans. A significantly higher percentage of glycosaminoglycans was released from the cartilage of the proximal and distal interphalangeal joints than from the metacarpophalangeal joint.

Experimental Jetlag Disrupts Circadian Clock Genes But Improves Performance in Racehorses After Light-Dependent Rapid Resetting of Neuroendocrine Systems and the Rest–Activity Cycle

Abrupt alterations in the 24‐h light : dark cycle, such as those resulting from transmeridian air travel, disrupt circadian biological rhythms in humans with detrimental consequences on cognitive and physical performance. In the present study, a jetlag‐simulated phase shift in photoperiod temporally impaired circadian peaks of peripheral clock gene expression in racehorses but acutely enhanced athletic performance without causing stress. Indices of aerobic and anaerobic capacities were significantly increased by a phase‐advance, enabling prolonged physical activity before fatigue occurred. This was accompanied by rapid re‐entrainment of the molecular clockwork and the circadian pattern of melatonin, with no disturbance of the adrenal cortical axis, but a timely rise in prolactin, which is a hormone known to target organs critical for physical performance. Subsequent studies showed that, unlike the circadian pattern of melatonin, and in contrast to other species, the daily rhythm of locomotor activity was completely eliminated under constant darkness, but it was restored immediately upon the reintroduction of a light : dark cycle. Resetting of the rhythm of locomotion was remarkably fast, revealing a rapid mechanism of adaptation and a species dependency on light exposure for the expression of daily diurnal activity. These results show that horses are exquisitely sensitive to sudden changes in photoperiod and that, unlike humans, can benefit from them; this appears to arise from powerful effects of light underlying a fast and advantageous process of adjustment to the phase shift.

Plasma and synovial fluid concentrations of calcium pentosan polysulphate achieved in the horse following intramuscular injection.

Results from in vitro studies have indicated that calcium pentosan polysulphate (CaPPS) may be of therapeutic value in osteoarthritis (OA) in the horse. However, no controlled clinical trials using this drug in equine OA have yet been reported. If CaPPS is to be developed for such use, the relationship between the proposed i.m. dose of CaPPS to be used and the concentrations of drug attained in plasma and synovial fluid of the target joint should first be established. An investigation was undertaken to determine these concentrations after a single 2 mg/kg i.m. injection of CaPPS. Blood and synovial fluid samples were taken from 6 healthy, sound horses following i.m. CaPPS administration. Concentrations of CaPPS measured in the synovial fluid were, on the basis of published studies, sufficient to elicit a potential therapeutic effect on synoviocyte metabolism, and possibly also to stimulate proteoglycan synthesis and reduce matrix metalloproteinase activities in articular cartilage. It would therefore seem justified to investigate further the therapeutic effect of CaPPS in OA in the horse.

Microscopic change in macroscopically normal equine cartilage from osteoarthritic joints

The objective of this study was to assess whether macroscopically normal articular cartilage taken from joints containing focal osteoarthritic lesions is histologically similar to articular cartilage taken from macroscopically normal joints. Metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were obtained from 10 horses following euthanasia. Gross articular cartilage damage was scored and the cartilage assigned to one of two groups: (1) macroscopically normal cartilage from normal joints (control) and (2) macroscopically normal cartilage from diseased joints in which there were focal osteoarthritic lesions. Chondrocytes expressing specific cytokines and cytokine receptors were identified by immunohistochemistry. The total number of chondrocytes, and percentage of chondrocytes positive for these cytokines and receptors, was recorded in the superficial, middle, and deep cartilage zones. There was a significant increase in the expression of interleukin-1β in the superficial and middle zones and interleukin-18 receptor in the superficial zone in Group 2 compared with Group 1 control samples. A significant positive correlation also was found between the grade of osteoarthritis and the percentage of chondrocytes positive for interleukin-1β in the superficial and middle zones, and for interleukin-18 and interleukin-18R in the superficial zone. There was a significant increase in histology score for glycosaminoglycan loss in Group 2 compared with that in Group 1. In joints with focal osteoarthritis lesions, all the articular cartilage, even if macroscopically apparently normal, may have microscopic changes associated with osteoarthritis.