Effects of thromboxane synthetase inhibition on immune complex glomerulonephritis.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histological changes associated with immune complex glomerulonephritis.     

Metabolic and mitogenic activities of insulin-like growth factor-1 in interleukin-1-conditioned equine cartilage

OBJECTIVE: To determine response of interleukin-1alpha (IL-1alpha)-conditioned equine articular cartilage explants to insulin-like growth factor-1 (IGF-1). Sample Population-Cartilage from the trochlea and condyles of the femur of a clinically normal 4-year-old horse. PROCEDURE: Effects of IGF-1 (0 to 500 ng/ml) after addition of IL-1alpha were evaluated by assessing matrix responses, using a sulfated glycosaminoglycan (GAG) assay, matrix 35SO4 GAG incorporation, and release of GAG. Mitogenic response was assessed by 3H-thymidine incorporation into DNA and fluorometric assay of total DNA concentration. RESULTS: Human recombinant IL-1alpha (40 ng/ml) increased the amount of labeled GAG released and decreased labeled and total GAG remaining in explants, and IL-1alpha decreased mitogenic response. Addition of IGF-1 counteracted effects seen with IL-1alpha alone. In general, IGF-1 decreased total and labeled GAG released into the medium, compared with IL-1alpha-treated explants (positive-control sample). Values for these variables did not differ significantly from those for negative-control explants. A significant increase in total and newly synthesized GAG in the explants at termination of the experiment was observed with 500 ng of IGF-1/ml. Labeled GAG remaining in explants was greater with treatment at 50 ng of IGF-1/ml, compared with treatment with IL-1alpha alone. Concentrations of 200 ng of IGF-1/ml abolished actions of IL-1alpha and restored DNA synthesis to values similar to those of negative-control explants. CONCLUSIONS AND CLINICAL RELEVANCE: IGF-1 at 500 ng/ml was best at overcoming detrimental effects associated with IL-1alpha in in vitro explants. These beneficial effects may be useful in horses with osteoarthritis.     

Spontaneous production of nitric oxide (NO), prostaglandin (PGE2) and neutral metalloproteinases (NMPs) in media of explant cultures of equine synovial membrane and articular cartilage from normal and osteoarthritic joints

Nitric oxide (NO), prostaglandin E2 (PGE2), and the activity of neutral metalloproteinases (NMPs) were measured in conditioned media of equine synovial membrane and articular cartilage explant cultures from horses with normal joints (n = 7) and from horses affected with moderate (n = 7) or severe osteoarthritis (n = 14) as judged by macroscopic appearance. Normal articular cartilage appeared glossy and bluish-white, was of normal thickness and showed no evidence of discolouration, fibrillation or other cartilage discontinuity. Slight discolouration and fibrillation or minor clefts of the cartilage were considered as moderate OA, whereas erosions of articular cartilage down to the subchondral bone were considered as cases of severe OA. Explant cultures of equine synovial membrane and articular cartilage released the local mediators, NO and PGE2, as well as detectable levels of NMP activity into culture media. Concentrations of NO were higher in articular cartilage explants compared to synovial membrane explants, whereas concentrations of PGE2 were higher in synovial membrane explants. The NMPs with collagenolytic activities were similar in both explant cultures, whereas gelatinolytic activities were higher in synovial membrane explant cultures and caseinolytic activities were generally higher in articular cartilage explant cultures. Furthermore it was shown that concentrations or enzyme activities increased according to the severity of disease of the joints. Concentrations for NO, collagenolytic and gelatinolytic NMPs were relatively stable, whereas PGE2 and caseinolytic NMP concentrations increased over time in culture.     

Treatment of rupture of suspensory ligament and superficial flexor tendon in a bull

Rupture of the suspensory ligament at the insertions on the proximal sesamoid bones, and of the superficial flexor tendon of the left fore limb, occurred in an adult Angus bull as a result of fighting. There was severe hyperextension of the metacarpophalangeal (MCP) joint with the dewclaws almost touching the ground. Radiographs revealed severe hyper-extension of the MCP joint with the sesamoid bones aligned directly distal to the metacarpus. Initially, a full length fiberglass cast was applied with the limb partially flexed within the cast and the heels elevated. The cast was replaced twice. The cast was removed after 136 days and the bull was bearing full weight on the limb. Prolonged immobilisation of the limb produced new bone in the area (a normal response in cattle) to cause ankylosis of the traumatized MCP joint and partial ankylosis of the carpus. The bull was being used for pasture breeding one year after the injury.     

Mechanical comparison of materials used for extra-capsular stabilisation of the stifle joint in dogs

Objective The mechanical properties of three materials (No. 2 polypropylene, No. 5 polybutilate-coated multifilament polyester and 18, 27 and 36 kg test monofilament nylon leader material) commonly used for extra-capsular stabilisation of the stifle in dogs with cranial cruciate ligament insufficiency were determined. The ability of No. 5 polybutilate-coated multifilament polyester and 36 kg test monofilament nylon leader material, when placed as extra-capsular sutures, to mitigate cranial drawer was evaluated in hindlimbs of cadavers. Design An in vitro mechanical study. Animals Seven pairs of hindlimbs harvested from adult greyhound dogs recently euthanased for other reasons. Procedure Samples of each material, including samples of 27 kg test leader material that had been sterilised by one of three methods (ethylene oxide, one or five cycles in an autoclave), were loaded to determine tensile and stress relaxation properties. The effect of cyclic loading on a No. 5 polybutilate-coated multifilament polyester and 36 kg test leader material was also determined. Using the harvested hindlimbs, cranial drawer was measured before and after transection of the cranial cruciate ligament and on the first and twelfth cycle following extra-capsular stabilisation with either No. 5 polybu-tilate-coated multifilament suture or 36 kg test leader material. Results Leader material was found to have the most suitable mechanical characteristics for use as extracapsular stabilisation of the cranial cruciate ligament deficient stifle. Of the sterilisation methods, ethylene oxide was found to have the least detrimental effects on the handling and material characteristics of the leader material. Stifles stabilised with 36 kg test leader material had significantly less drawer than those stabilised with No. 5 polybutilate-coated multifilament polyester suture. Clinical implications Monofilament nylon leader material would appear to have suitable mechanical properties for extra-capsular stabilisation of the cranial cruciate ligament deficient stifle. If possible the material should be sterilised using ethylene oxide.     

Gene therapy: future therapies in osteoarthritis.

The field of equine veterinary practice is in an ever-evolving state, requiring current technologies to be constantly evaluated for new applications. The specific use of gene therapy in the horse is a novel application. The authors want to help familiarize the equine practitioner with the concept of gene therapy, and introduce its use and potential future benefits for the equine industry in the treatment of osteoarthritis.     

Electrical resistance of long conjugated molecular wires

The charge transport mechanism of a wire can be revealed by how its electrical resistance varies with length. We have measured the resistance and current-voltage characteristics of conjugated molecular wires ranging in length from 1 to 7 nanometers, connected between metal electrodes. We observe the theoretically predicted change in direct-current transport from tunneling to hopping as a function of systematically controlled wire length. We also demonstrate that site-specific disruption of conjugation in the wires greatly increases resistance in the hopping regime but has only a small effect in the tunneling regime. These nanoscale transport measurements elucidate the role of molecular length and bond architecture on molecular conductivity and open opportunities for greater understanding of electrical transport in conjugated polymer films.