Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis.

Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue target sites at optimal doses for clinical efficacy. The dense, negatively charged matrix of cartilage poses a major hindrance to the transport of potential therapeutics. In this work, electrostatic interactions were utilised to overcome this challenge and enable higher uptake, full-thickness penetration and enhanced retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished by using the positively charged glycoprotein avidin as nanocarrier, conjugated to Dex by releasable linkers. Therapeutic effects of a single intra-articular injection of low dose avidin-Dex (0.5 mg Dex) were evaluated in rabbits 3 weeks after anterior cruciate ligament transection (ACLT). Immunostaining confirmed that avidin penetrated the full cartilage thickness and was retained for at least 3 weeks. Avidin-Dex suppressed injury-induced joint swelling and catabolic gene expression to a greater extent than free Dex. It also significantly improved the histological score of cell infiltration and morphogenesis within the periarticular synovium. Micro-computed tomography confirmed the reduced incidence and volume of osteophytes following avidin-Dex treatment. However, neither treatment restored the loss of cartilage stiffness following ACLT, suggesting the need for a combinational therapy with a pro-anabolic factor for enhancing matrix biosynthesis. The avidin dose used caused significant glycosaminoglycan (GAG) loss, suggesting the use of higher Dex : avidin ratios in future formulations, such that the delivered avidin dose could be much less than that shown to affect GAGs. This charge-based delivery system converted cartilage into a drug depot that could also be employed for delivery to nearby synovium, menisci and ligaments, enabling clinical translation of a variety of DMOADs.

MALT lymphomas -Treated with chemotherapy or radiotherapy: Clinical Features, Prognostic factors and Survival.

OBJECTIVE: MALT lymphomas are a group of extranodal indolent lymphomas that usually present as stage IE. To clarify clinical features, treatment alternatives and outcomes, we evaluated 38 patients treated with chemotherapy or radiotherapy between 2000 and 2011. PATIENTS AND METHODS: MALT lymphoma patients identified according to WHO classification and treated at KCCC between 2000 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A p value < 0.05 was considered significant. RESULTS: The median age of the patients was 49 years and the male to female ratio was 2:1. Gastric MALT accounted for 63% of all patients and the most common presenting symptom was abdomen pain and dyspepsia. The common extra gastric sites were salivary glands, lung and orbit. 90% of the patients presented with early stage disease. Two patients had history of pre-existing autoimmune disease. Even among patients who had failed prior antibiotic therapy for Helicobacter pylori, treatment with chemotherapy achieved good results with 5 year survival of 80%. CONCLUSION: MALT lymphomas are indolent neoplasm's with excellent long term outcome. There is no significant difference in survival between gastric and extra-gastric MALT lymphoma. KEYWORDS: MALT lymphoma, Gastric Neoplasm, H. pylori.