Standardized study of atorvastatin possible osteoarthritis disease-modifying effect in a rat model of osteoarthritis.

We studied the osteoarthritis (OA)-modifying effects of atorvastatin in an experimental OA rat model and possible underlining mechanisms. We used 62 adult male Sprague-Dawley rats (250-300 g): 32 rats were used to assess the effects of atorvastatin on surgically induced OA in the knee, and 30 rats were used to assess the potential inflammatory effects of carrageenan-induced paw edema. In the OA model, joint stiffness was assessed by measuring the knee extension angle, and pathological changes in the OA knee joint were determined by histological examination and the measurement of serum biochemical markers, including interleukin-1ß (IL-1ß), matrix metalloproteinase-13 (MMP-13), and reduced glutathione (GSH). In the carrageenan-induced paw edema model, both paw thickness and pain threshold were assessed in different groups. Atorvastatin significantly improved joint stiffness, pathological changes, a significant mitigation of the higher MMP-13 and IL-1ß, and a significant increase of reduced GSH in OA rats. Additionally, atorvastatin significantly improved both paw thickness and pain threshold in animals. Atorvastatin is a potential OA-modifying drug that warrants further clinical investigation.

Chitosan and chitosan nanoparticles as adjuvant in local Rift Valley Fever inactivated vaccine.

The present study aimed to improve the potency of inactivated Rift Valley Fever Virus (RVFV) vaccine using chitosan (CS) or chitosan nanoparticles (CNP) as adjuvants. Chitosan nanoparticles were prepared by ionic gelation method. Rift Valley Fever Virus (RVFV) inactivated antigen was loaded on CS and CNP to form two vaccine formulations, RVFV-chitosan nanoparticles based vaccine (RVFV-CNP) and RVFV chitosan based vaccine (RVFV-CS). Five groups of mice were used in this study, each group was injected with one of the following: phosphate buffer saline (group1 G1), RVFV-CNP (G2), (RVF-CS) (G3), RVFV-Alum based vaccine (RVFV-Alum) (G4) and adjuvant free RVFV inactivated antigen (RVFV-Ag) (G5). The immunization was performed twice with 2 weeks interval. The results showed that, RVFV-CNP vaccine enhanced strongly the phagocytic activity of peritoneal macrophage (PM), neutralization antibodies titer against RVFV and IgG values against RVFV nucleoprotein than other vaccine formulations did. In addition, the RVFV-CNP and RVF-CS vaccines upregulate the gene expression of IL-2, IFN-γ (which promote cell mediated immunity) and IL-4 (which promote humeral immunity), while RVFV-Alum vaccine upregulate the gene expression of IL-4 only. These findings indicated that CS and CNP were comparable to the alum as adjuvant in efficacy but superior to it in inducing cell-mediated immune response and might be a candidate adjuvant for inactivated RVFV vaccine.