Vascular endothelial growth factor (VEGF) and its receptors have recently reported to be expressed in human osteoarthritis (OA), suggesting that VEGF could be implicated in the pathogenesis of this disease. In the present study, expression of VEGF in the articular cartilage was determined in three different OA models: medial meniscectomy and monoiodoacetate (MIA) injection in rats and age-associated spontaneous joint cartilage destruction in guinea pigs. VEGF was detected by immunohistochemical analysis in the regenerative and hypertrophic chondrocytes, perichondrium and osteophyte areas and chondrocyte clones. Stain intensity of VEGF immunoreactivity increased simultaneously with the degree of cartilage destruction and reparation. These results suggest that VEGF is a key factor in the articular cartilage in human OA and animal OA models.
Abstract. Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyperfiltration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb̸Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction. IntroductionChronic kidney disease (CKD) is a major public health concern worldwide because of the increasing prevalence of end-stage renal failure requiring dialysis or kidney transplantation and the increased risk of morbidity and mortality due to cardiovascular diseases (1-6). Aging leads to renal structural changes and functional decline. Imai et al (7) and Coresh et al (8) suggested that the prevalence of CKD increases with age. Moreover, a significantly higher prevalence of CKD was reported in hypertensive patients compared to normotensive subjects (8,9). High systemic blood pressure leads to pressure elevation in the glomerular capillaries, which is associated with renal vascular dysfunction. Elevated pressure in the glomerular capillaries results in glomerular sclerosis, increased albuminuria and decreased glomerular filtration rate (10). Furthermore, glomerular hyperfiltration is often observed during the early stages of diabetes and may contribute to the development of diabetic nephropathy (11,12). Thus, the progression of CKD is affected by various risk factors such as aging, hypertension and hyperfiltration. However, the interrelationship of individual risk factors during the course of renal dysfunction has not been fully elucidated.Tsukuba hypertensive mice (THM) are transgenic mice carrying both human renin and angiotensino...
Introduction: The combination of methotrexate (MTX) with biological disease-modifying antirheumatic drugs (bDMARDs) is a recommended treatment option for rheumatoid arthritis (RA) patients showing an inadequate response to MTX monotherapy. However, the adequate dose of MTX, especially in long-term treatment with bDMARDs/MTX combination therapy, remains under-addressed. Since RA patients require long-term treatment, we examined the effects of using golimumab (GLM) in the long run as well as its persistency and associated factors. Methods: We used the Japan Medical Data Center Inc. (JMDC) administrative claims data of 489 patients receiving GLM therapy for calculating the persistency in patients with constant, reduced, or escalated MTX dosing. The factors associated with GLM persistency were assessed using Cox proportional hazard modeling, controlling for the dose adjustment of concomitant MTX, age, sex, RA disease period, and the initial dose of GLM or concomitant MTX during GLM/MTX combination therapy. Results: During GLM/MTX combination therapy, up to 52% of patients were reported to experience dose adjustments of concomitant MTX treatment (i.e., dose reduction and escalation in 34% and 18% of patients, respectively). Persistency was similar in the MTX dosereduction patients and the MTX dose-constant patients. In the Cox proportional hazard model, no significant differences were observed in association with GLM persistency, including with respect to MTX dose adjustment. Conclusions: GLM prescription was continued in 80% or more (1 year) and 50% or more (3 years) of RA patients receiving reduced concomitant MTX dosing, suggesting that MTX Digital Features To view digital features for this article go to
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