Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.
AimsWe aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination.Methods and ResultsThe Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5 years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p < 0.0001; IgM 0.83[0.75,0.93], p = 0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p < 0.0001, IgM OR 0.81 (0.71,0.93); p = 0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index.ConclusionHigh total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.
Background: A paradigm shift from such toxic ‘nonspecific’ therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. Design: To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. Results: In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. Conclusion: For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.
Objective-The renin-angiotensin-aldosterone system (RAS) plays a central role in atherosclerosis. To investigate the effects of a direct renin inhibitor aliskiren on vascular inflammation, we conducted leukocyte adhesion assays in vivo and in vitro using a novel real-time imaging system. Methods and Results-Aliskiren (10 mg/kg/d) or PBS was administered to C57BL/6 mice (6 -7 weeks of age; Oriental Yeast, Tokyo, Japan) for 2 weeks via an osmotic pump. Blood pressure was not significantly changed in the 2 groups throughout the experimental period. A perivascular cuff injury was then introduced to the femoral artery and real-time intravital microscopic observation was conducted 24 hours after injury. The number of adherent leukocytes was elevated in the injured mice without aliskiren (43.8Ϯ9.3/10 Ϫ2 mm 2 ), whereas that was significantly reduced in the mice with aliskiren (18. 4Ϯ4.4, PϽ0.05). Treatment of human umbilical vein endothelial cells (HUVECs) with aliskiren significantly reduced the adhesion of THP-1 cells to TNF-␣-activated HUVECs (PϽ0.05). Interestingly, TNF-␣-induced renin activity and angiotensin II production in HUVECs were also blunted by aliskiren. Furthermore, exogenous renin and angiotensin II abrogated the aliskiren-mediated reduction of THP-1 cell adhesion to HUVECs. Key Words: atherosclerosis Ⅲ renin-angiotensin-aldosterone system Ⅲ renin inhibition Ⅲ endothelium T he renin-angiotensin-aldosterone system (RAS) has been recognized as one of the key mechanisms involved in various vascular diseases including atherosclerosis. [1][2][3] Recent reports have also demonstrated that production of RAS in extrarenal tissues exerts critical biological effects, 4 -7 whereas regulation of local RAS contributes to the pathophysiological condition of endothelial cells and smooth muscle cells. 8,9 Therefore, modulation of local as well as systemic RAS has emerged as a therapeutic concept for cardiovascular diseases. Conclusions-OurAngiotensin (Ang) II, a potent vasoconstrictive peptide, plays a crucial role in atherosclerosis via local activation of mitogen-activated protein kinases (MAPK). In addition, we previously found that Ang II-related oxidative stress in leukocytes induces leukocyte recruitment in vivo. 10 However, the continued presence of other bioactive angiotensin-related peptides has made it difficult to elucidate the contributions of Ang II in these processes.Renin, a rate-limiting enzyme for Ang II formation, exerts various inflammatory reactions, including activation of thrombogenic molecules 11 and intracellular signaling proteins independent of local Ang II, 12 which are mediated via the recently characterized renin receptor (RR). 13 Recently aliskiren, a direct renin inhibitor, has been shown to modulate vascular diseases such as hypertension, 14 experimental atherosclerosis, 15 and diabetic nephropathy 16 via RAS dependent or independent pathway. Although local RAS are important in those processes, the importance of renin inhibition in vascular inflammation has not been elucidated.In the ...
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