Objective. Scientific evidence is lacking for the antiarthritic efficacy of turmeric dietary supplements that are being promoted for arthritis treatment. Therefore, we undertook studies to determine the antiarthritic efficacy and mechanism of action of a well-characterized turmeric extract using an animal model of rheumatoid arthritis (RA).Methods. The composition of commercial turmeric dietary supplements was determined by highperformance liquid chromatography. A curcuminoidcontaining turmeric extract similar in composition to these supplements was isolated and administered intraperitoneally to female Lewis rats prior to or after the onset of streptococcal cell wall-induced arthritis. Efficacy in preventing joint swelling and destruction was determined clinically, histologically, and by measurement of bone mineral density. Mechanism of action was elucidated by analysis of turmeric's effect on articular transcription factor activation, microarray analysis of articular gene expression, and verification of the physiologic effects of alterations in gene expression. Results.A turmeric fraction depleted of essential oils profoundly inhibited joint inflammation and periarticular joint destruction in a dose-dependent manner. In vivo treatment prevented local activation of NF-B and the subsequent expression of NF-B-regulated genes mediating joint inflammation and destruction, including chemokines, cyclooxygenase 2, and RANKL. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E 2 , and periarticular osteoclast formation were inhibited by turmeric extract treatment.Conclusion. These translational studies demonstrate in vivo efficacy and identify a mechanism of action for a well-characterized turmeric extract that supports further clinical evaluation of turmeric dietary supplements in the treatment of RA.The use of botanical remedies for arthritis treatment is promoted in the US by the lay press and high-profile medical practitioners (1,2). Interest in the use of nonpharmaceutical arthritis treatments has grown with the withdrawal of Food and Drug Administrationapproved antiinflammatory drugs (3). However, scientific data are almost uniformly lacking concerning the antiarthritic efficacy and mechanism of action of popular botanical remedies (4,5). The rational medicinal use of botanical dietary supplements is further complicated by the fact that the composition of over-the-counter botanical dietary supplements is not strictly regulated (4,5). Unfortunately, in the medical literature, the chemical composition and biologic activity of botanicals that are tested for antiarthritic efficacy are frequently also not well characterized (6-9). Therefore, benchmarks are lacking for assessing the potential suitability of commercially available botanical supplements or phytomedicines. 3452Turmeric is one such botanical supplement whose use against arthritis, supported almost exclusively by its traditional, centuries-old use as an antiinflammatory agent in Ayurvedic medicine, has been heavily prom...
One hundred and twenty‐four patients underwent aortic valve replacement with a nonviable 4°C refrigerated aortic allograft valve. One hundred and eighty‐four patients underwent aortic valve replacement with a viable cryopreserved aortic allograft valve in a later era. The longest follow‐up was 16 years for the group with the nonviable valve and 11 years for the group with the viable valves. Within this time frame, reoperation was required in 23 patients with nonviable valves for leaflet perloration or rupture whereas no patients in the group with viable valves developed this complication (p < 0.0001). The prevalence of endocarditis and thromboembolism was very low in both groups. Viability of leaflet tissue is associated with an important improvement in durability over nonviable allograft valves. Consequently, long‐term follow‐up results of allograft valves might be best expressed in terms of viability. The current evidence suggests that the viable cells are donor in origin. The viable cryopreserved aortic allograft valve offers significant advantages over current nonviable allograft valves, mechanical valves, and bioprostheses.
Objective. To determine whether parathyroid hormone-related protein (PTHrP), an interleukin-1-inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA.Methods. PTHrP expression and the effect of PTHrP 1-34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW)-induced arthritis, an animal model of RA.Results. As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone. Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor-positive neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was stimulated by PTHrP 1-34.Conclusion. These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA. Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders.
Background-Little information exists regarding mid-term and long-term patency of radial artery grafts. Methods and Results-We performed restudy coronary angiography at 5.2Ϯ0.4 years after surgery on 50 asymptomatic patients who had undergone coronary artery bypass graft surgery, using at least 1 radial artery graft, to determine both graft patency and presence of narrowing. We examined preoperative clinical or angiographic variables that might predict graft occlusion. Radial artery graft patency was 89%, with 91% of grafts free of narrowing. Preoperative New York Heart Association anginal class Յ2, target vessel proximal stenosis Յ70%, and small target vessel supply territory were predictive of graft occlusion. Conclusion-At
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