Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

OBJECTIVE: The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). METHODS: Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. RESULTS: PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. CONCLUSION: Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage.

Digigait quantitation of gait dynamics in rat rheumatoid arthritis model.

INTRODUCTION: Rheumatoid arthritis (RA) is characterized by joint pain, allodynia and hyperalgesia. The rat carrageenan model utilizes inflammation-associated pain following injection of the knee joint to model RA. Traditional assessment of pain in these models utilizes behavioral scoring or manual measurements, methods that are labor intensive and prone to subjective interpretation. This study utilizes the Digigait system to objectively quantify movement and gait dynamics in a monoarthritic rat model. MATERIAL AND METHODS: A pilot study in rats selected "natural" runners using Digigait, and also measured inter and intraday variability as well as effects of anesthesia on gait dynamics. In the main study, 12 female rats were tested at baseline, divided in two groups of 6 rats, briefly anesthetized with isoflurane and injected with 60 microl of 2% lambda carrageenan or vehicle; Digigait testing was repeated 2 and 4 hours post injection and data analyzed. RESULTS: Selection of "natural" runners significantly contributed to accuracy and reproducibility of gait parameters obtained by the Digigait system. There was minimal intra and inter day variation between individual rats and 4 minutes of isoflurane anesthesia had no effect on gait dynamic at 2 and 4 hours post administration. In the main study a highly reproducible gait signature in the injected limb, and well coordinated adaptation of gait during locomotion in the non-affected limbs were noted as short-term changes following carrageenan injection. CONCLUSION: Digigait system was found to be an objective and reliable method for quantification of early behavioral changes consistent with allodynia and hyperalgesia in an inflammatory pain model.

Fluvastatin in combination with rad significantly reduces graft vascular disease in rat cardiac allografts.

BACKGROUND: RAD is a potent immunosuppressive agent that has been shown to be effective in preventing acute and chronic allograft rejection in animal models. The HMGCoA reductase inhibitors have been found to reduce the incidence of graft vascular disease (GVD) in heart transplant patients and in animal models. This study was designed to investigate the effects of fluvastatin or pravastatin in a rodent model of GVD produced using low doses of RAD to prevent acute rejection. METHODS: Hearts from Fisher 344 rats were heterotopically transplanted to Lewis rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14 and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection but allow for the development of GVD. Pravastatin (20 mg/kg per day) or fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of a 100-day treatment period, the hearts were harvested for morphometric and histopathologic examinations. RESULTS: Rats treated with fluvastatin, at either dose, had a significant (P< or =0.0239) decrease in coronary arterial intimal thickening (GVD) of approximately 43%. Rats treated with pravastatin had a 22% reduction in GVD that did not reach statistical significance. Treatment with fluvastatin, but not pravastatin, decreased the degree of endomyocardial mononuclear cell infiltration seen with RAD administered alone. CONCLUSIONS: Fluvastatin significantly decreased GVD in a rat model produced using low-dose RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this model. These data lend further support for the study of fluvastatin, pravastatin, and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac transplant patients.

Enhanced nitric oxide production induced by the administration of L-arginine does not inhibit arterial neointimal formation after overwhelming alloimmune injury.

BACKGROUND: Nitric oxide suppresses proliferation and function of T cells and inhibits proliferation of smooth muscle cells in vitro and in vivo. The purpose of this study was to determine whether nitric oxide, stimulated by means of the oral administration of L-arginine, would reduce the degree of intimal thickening produced by immune injury in rat arterial allografts. METHODS: Orthotopic femoral artery transplantation was done with Brown Norway donors and Lewis recipients. Seven days before operation, and for 39 additional days, one group received 2.25% L-arginine and one group received 0.01% N-omega-nitro-L-arginine in tap water; one group received tap water only. Forty days after operation, all arterial segments were excised and examined by histopathologic, morphometric, and immunohistochemical assays. RESULTS: There was no difference in the rejection response or degree of intimal thickening among the three groups. There were no qualitative differences in numbers of T cells, macrophages, or smooth muscle cells in the neointima, media, or adventitia among the untreated and treated groups. Induced nitric oxide synthase was present in the media and adventitia of the allograft vessels, but not in native rat arteries. CONCLUSIONS: Enhanced production of nitric oxide, via the administration of L-arginine, has been shown to reduce tissue pathologic changes in models of mechanical or dietary injury. Enhanced nitric oxide production did not suppress rejection or inhibit intimal thickening in this model of immune-mediated injury.

Effects of xylazine hydrochloride during isoflurane-induced anesthesia in horses.

OBJECTIVE: To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose concentrations, and urinary output also were measured during the anesthetic studies. RESULTS: Isoflurane MAC (mean +/- SEM) was reduced by 24.8 +/- 0.5 and 34.2 +/- 1.9% at 42 +/- 7 and 67 +/- 10 minutes, respectively, after administration of XYL at 0.5 and 1 mg/kg. Amount of MAC reduction by XYL was dose- and time-dependent. Overall, cardiovascular and respiratory values varied little among treatments. Administration of XYL increased blood glucose concentration; the magnitude of change was dose- and time-dependent. Urine volume increased but not significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of XYL reduced the anesthetic requirement for isoflurane in horses. The magnitude of the decrease is dose- and time-dependent. Administration of XYL increases blood glucose concentration in anesthetized horses in a dose-related manner.