Objective: To develop an in vitro model of cartilage injury in full-thickness equine cartilage specimens that can be used to simulate in vivo disease and evaluate treatment efficacy. Sample: 15 full-thickness cartilage explants from the trochlear ridges of the distal aspect of the femur from each of 6 adult horses that had died from reasons unrelated to the musculoskeletal system. Procedures: To simulate injury, cartilage explants were subjected to single-impact uniaxial compression to 50%, 60%, 70%, or 80% strain at a rate of 100% strain/s. Other explants were left uninjured (control specimens). All specimens underwent a culture process for 28 days and were subsequently evaluated histologically for characteristics of injury and early stages of osteoarthritis, including articular surface damage, chondrocyte cell death, focal cell loss, chondrocyte cluster formation, and loss of the extracellular matrix molecules aggrecan and types I and II collagen. Results: Compression to all degrees of strain induced some amount of pathological change typical of clinical osteoarthritis in horses; however, only compression to 60% strain induced significant changes morphologically and biochemically in the extracellular matrix. Conclusions and Clinical Relevance: The threshold strain necessary to model injury in full-thickness cartilage specimens from the trochlear ridges of the distal femur of adult horses was 60% strain at a rate of 100% strain/s. This in vitro model should facilitate study of pathophysiologic changes and therapeutic interventions for osteoarthritis.

Apoptosis, also known as programmed cell death, has become a target for treating many diseases, especially cancer. Many factors are influential in the cell's pathway to apoptosis. The defects in these pathways may transform the cell to become malignant, and the organism may face a lethal outcome such as cancer. Understanding apoptosis will provide clues in guiding the pathogenesis of diseases. Two main pathways leading to apoptosis, intrinsic and extrinsic, take an active role. The granzyme B pathway is also considered an apoptotic pathway, and this pathway is activated by enzymes secreted by immune cells such as T and NK. Many caspase molecules have initiator and enforcer roles and are active at critical points in the cell's apoptosis process. In cancer treatments, activating molecules in these pathways and repairing disrupted pathways are among the target approaches. This review discusses target strategies for inhibiting apoptotic pathways and molecules in cancer cells and activating these apoptotic pathways.

Objective-To evaluate the effects of various concentrations of l-lysine on in vitro replication of feline herpesvirus 1 (FHV-1). Sample- Cultures of Crandell-Rees feline kidney (CRFK) cells. Procedures- CRFK cells were inoculated with FHV-1 and maintained in media with 20 combinations of l-arginine and l-lysine concentrations. Changes in cell viability were monitored by continuous measurement of electrical impedance of cultured cells and by observation of viral cytopathic effects. Viral load was determined by use of quantitative PCR assay in supernatants obtained from infected cultures at specified time points. Results- Increases in l-lysine concentration had no effect on the kinetics of cell death in FHV-1-infected cultures. There was also no significant effect (r2 < 0.1) on viral DNA load for l-arginine concentrations ≥ 12 μg/mL There was a significant effect of increases in l-lysine concentration on viral DNA load in media supplemented with 6 μg of l-arginine/mL (mean ± SD slope, −4,641 ± 1,626 units; adjusted r2 = 0.45). However, the difference between the lowest (1 × 10(6.28) copies/μL) and highest (1 × 10(6.86) copies/μL) FHV-1 DNA load in these media was < 1 logarithm. Conclusions and Clinical Relevance-The difference in FHV-1 DNA load was unlikely to be biologically important. Various l-lysine concentrations did not inhibit in vitro replication of FHV-1 at l-arginine concentrations sufficient to maintain cell growth. This conclusion was consistent with results of other studies in which investigators have not detected a consistently beneficial effect when l-lysine is administered to FHV-1-infected cats.

Addition of alanine and taurine blocked killing of lymphocytes caused by culture at 45 C. The optimal concentration for thermoprotection was achieved at 12.5 mM for L-alanine and 5 mM for taurine. Both D and L forms of alanine provided thermoprotection. The effect of these agents was not simply to increase osmolarity of the culture medium, because NaCl did not provide thermoprotection at comparable concentrations. Alanine and taurine were each tested at concentration of 50 mM for ability to block heat shock-induced killing and developmental retardation of 8- to 16-cell mouse embryos. Both agents enhanced embryo development after exposure to high temperature, though development remained less than that for embryos not exposed to high temperature. In one experiment, for example, 81% of embryos cultured at 38 C advanced in development during culture vs 0% at 42 C, 15% at 42 C with alanine, and 32% at 42 C with taurine. The beneficial effect of alanine at high temperature may have been partly attributable to effects independent of thermoprotection, because development of embryos cultured at 38 C was also improved by alanine.