Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA)

Objective: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients. Method: This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32mg delivered dose, N=63) or TAcs (1 mL, 40mg, N=18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week1, Week6, Week12, Week16 or Week20; TAcs: Week6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means), pharmacokinetics (non-compartmental analysis models), and adverse events (AEs) were assessed. Results: SF TA concentrations following FX006 were quantifiable through Week12 (pg/mL: 231,328.9 at Week1; 3590.0 at Week6; 290.6 at Week12); post-TAcs, only 2 of 8 patients had quantifiable SF TA at Week6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 hours and slowly declined to <110 pg/mL over Weeks12-20; following TAcs, plasma TA peaked at 4 hours (9,628.8 pg/mL), decreased to 4,991.1 pg/mL at 24 hours, and was 149.4 pg/mL at Week6, the last post-treatment time point assessed. AEs were similar between groups. Conclusion: In knee OA patients, microsphere-based TA delivery via a single IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs

Resposta da produtividade de grãos e outras características agronômicas do trigo EMBRAPA-22 irrigado ao nitrogênio em cobertura

As doses e a época de aplicação do nitrogênio (N) podem influenciar as características agronômicas do trigo (Triticum aestivum L.) irrigado e, conseqüentemente, a produtividade de grãos. Neste sentido, foram instalados dois experimentos na Estação Experimental da Universidade Federal de Viçosa, localizada em Coimbra (MG), em 1995 e 1996. Os tratamentos foram constituídos pela combinação de quatro doses de N (30, 60, 90 e 120 kg ha-1), quatro formas de parcelamento (dose total aos 20 dias da emergência (DAE); ½ aos 20 + ½ aos 40 DAE; 1/3 aos 20 + 2/3 aos 40 DAE e 2/3 aos 20 + 1/3 aos 40 DAE) e uma testemunha (sem N em cobertura), dispostos em esquema fatorial 4 x 4 + 1, no delineamento em blocos casualizados com quatro repetições. A altura e o acamamento das plantas, a biomassa seca, o índice de colheita, a massa de mil grãos, o peso hectolítrico e a produtividade de grãos foram influenciados pelas doses de N. Em 1996, o número de espigas por metro quadrado e o número de perfilhos férteis por planta diminuíram, em conseqüência do acamamento precoce das plantas, enquanto o número de grãos por espiga e o número de grãos por metro quadrado aumentaram com o incremento nas doses de N. As formas de parcelamento influenciaram somente o acamamento das plantas

Metabolic risk factors and renal disease

Accumulating evidence supports that components of the metabolic syndrome coexist with both albuminuria and chronic kidney disease (CKD). The article by Tomaszewski et al. indicates that this interrelation exists in young obese men before overt renal or cardiovascular disease and also suggests that early treatment of hypertension is especially compelling to prevent the evolution of renal hyperfiltration to CKD