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Glomerular Injury (glomerular + injury)
Selected AbstractsSulphated Polysaccharides: New Insight in the Prevention of Cyclosporine A-Induced Glomerular InjuryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2007Anthony Josephine Nephrotoxicity induced by cyclosporine A continues to be a major problem despite its potent immunosuppressive action. Adult male albino rats of Wistar strain were categorized into four groups. Two groups (II and IV) were administered cyclosporine A (25 mg/kg body weight, orally) for 21 days, in which Group IV rats were also treated simultaneously with sulphated polysaccharides (5 mg/kg body weight, subcutaneously) for the same period. A significant loss in body weight was noted in the cyclosporine A-induced rats. Renal damage was assessed in terms of decreased creatinine clearance and increased activity of lysosomal enzymes. The levels of glycoproteins were found to be decreased in the renal tissue, and a noticeable rise in glycosaminoglycanuria coupled with marked proteinuria was more prominent in the cyclosporine A-induced animals. Furthermore, the extent of kidney damage was assessed by histopathological findings. Toxic manifestations were also confirmed by transmission electron microscopic studies. These morphological abnormalities and other alterations in the renal tissue were significantly offset by sulphated polysaccharides supplementation. These findings underline that restoration of normal cells accredits sulphated polysaccharides, from Sargassum wightii, with nephroprotective role, against cyclosporine A-induced renal injury. [source] HISTOPATHOLOGICAL AND SCINTIGRAPHIC COMPARISONS OF THE PROTECTIVE EFFECTS OF l -CARNITINE AND AMIFOSTINE AGAINST RADIATION-INDUCED LATE RENAL TOXICITY IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2009Murat Caloglu SUMMARY 1The aim of the present study was to compare the protective effects of l -carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., l -carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., l -carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (Tmax) and time from peak count to half count (T˝) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T˝ of the right kidney was 8 ± 2 and 21 ± 2 min, respectively. The Tmax values for the AMI + RAD and LC + RAD groups (2.8 ± 0.2 and 3.2 ± 0.2 min, respectively) were similar to those in the control group (2.5 ± 0.3 min). 4Based on the results of the present study, l -carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity. [source] Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS productionIMMUNOLOGY, Issue 2 2008Edilberto Postól Summary The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology. [source] Formation of lipid raft redox signalling platforms in glomerular endothelial cells: an early event of homocysteine-induced glomerular injuryJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Fan Yi Abstract The present study tested the hypothesis that homocysteine (Hcys)-induced ceramide production stimulates lipid rafts (LRs) clustering on the membrane of glomerular endothelial cells (GECs) to form redox signalling platforms by aggregation and activation of NADPH oxidase subunits and thereby enhances superoxide (O2.,) production, leading to glomerular endothelial dysfunction and ultimate injury or sclerosis. Using confocal microscopy, we first demonstrated a co-localization of LR clusters with NADPH oxidase subunits, gp91phox and p47phox in the GECs membrane upon Hcys stimulation. Immunoblot analysis of floated detergent-resistant membrane fractions found that in LR fractions NADPH oxidase subunits gp91phox and p47phox are enriched and that the activity of this enzyme dramatically increased. We also examined the effect of elevated Hcys on the cell monolayer permeability in GECs. It was found that Hcys significantly increased GEC permeability, which was blocked by inhibition of LR redox signalling platform formation. Finally, we found that Hcys-induced enhancement of GEC permeability is associated with the regulation of microtubule stability through these LR-redox platforms. It is concluded that the early injurious effect of Hcys on the glomerular endothelium is associated with the formation of redox signalling platforms via LR clustering, which may lead to increases in glomerular permeability by disruption of microtubule network in GECs. [source] IgA nephropathy and mesangial cell proliferation: shared global gene expression profilesNEPHROLOGY, Issue 2002Hideto SAKAI SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. the expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [,- 33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. the radioactive hybridization signals were analysed by phosphorimager. Approximately 8212±530 different gene transcripts were detected per target. Close to 5% (386±90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN. [source] Mid-term effects of steroid therapy on childhood-onset IgA nephropathyNEPHROLOGY, Issue 2001S Watanabe Purpose: IgA nephropathy (IgAN) is considered the most common glomerular disease in the world. Although treatment of children with severe IgAN with predonisolone (PSL) has been reported, the mid-term prognosis of paediatric patients treated with PSL is unclear. In the present study we examined the mid-term effects of PSL therapy. Method: Thirty-seven paediatric patients with IgAN (18 males, 19 females), whose biopsy findings showed acute segmental lesions including cellular crescent and adhesion in more than 10% of glomeruli examined, were prospectively treated with PSL plus heparin-warfarin and dipyridamole (Tx) for 1.5 years and followed up over 1 years after Tx end. Fifteen age and histological grade-matched children with IgAN (six males, nine females), who had never been treated with PSL, were also evaluated as a historical control. The mean observation period was 5.0 ± 1.8 years (range, 2.5,8.6 years). The histological grade (acute lesion) and stage (chronic lesion) were scored semiquantitatively based on the Shigematsu's grade-stage system.1 Result: Proteinuria decreased 1.48 g/day/1.73 m2 at the start of Tx to 0.32 g/day/1.73 m2 at the end of Tx. Eighteen patients (48.6%) achieved complete remission (CR). No patient developed chronic renal failure in Tx group, while two of the controls deteriorated renal function in the last observation. The pattern of responsiveness to Tx were divided into three groups according to the levels of proteinuria: CR, rebound (> 0.5 g/day/1.73 m2) and incomplete remission (< 0.5 g/day/1.73 m2). The rebound of proteinuria is usually accompanied with PSL reduction. The grade of glomerular pathology was improved with Tx (Gg: 0.8,0.3), while the stage of tubulo-interstitial change progressed (Sint: 0.7,1.2). Conclusions: The present study shows that Tx to children with IgAN showing acute lesions for 1.5 years is effective to subside acute glomerular injury. However, because clinical courses of treated patients vary in each patient, dosage and duration of PSL administration should be modified in their clinical setting. [source] Development and fate of crescentic and granulomatous lesions in rat Masugi nephritisPATHOLOGY INTERNATIONAL, Issue 2 2001Tetsuro Horio It has been observed that with Masugi nephritis in Wistar rats the initiation of endocapillary proliferative changes with macrophage accumulation is usually followed by glomerular sclerosis without extracapillary extension. In the present study, the provocation of an extracapillary lesion was attempted using accelerated Masugi nephritis in Wistar,Kyoto rats. In order to accelerate the accumulation of monocyte/macrophages, the administration of methylcellulose was added in an additional group. The development and fate of extracapillary lesions were analyzed histopathologically and immunohistochemically. As a result, the formation of extracapillary proliferation of granulomatous lesions could be initiated in this model. Granulomatous lesions were composed of CD4+ T cells and CD8+ T cells and monocyte/macrophages including multinucleated giant cells. These inflammatory cells had seemingly escaped from the capillary lumen through the injured glomerular basement membrane and formed cellular and granulomatous crescents. In addition, tenascin was strongly expressed in cellular crescents and was a unique extracellular matrix at this cellular stage. The cellular crescents then progressed to sclerosis with the formation of increased collagenous extracellular matrix. These results suggest that a delayed-type hypersensitivity plays a role in granulomatous crescent formation, even though the initial glomerular injury was evoked by a humoral antibody. [source] Glomerular dysfunction, independent of tubular dysfunction, induced by antineoplastic chemotherapy in childrenPEDIATRICS INTERNATIONAL, Issue 5 2004Yukie Ikarashi AbstractBackground:,For the purpose of studying renal side-effects induced by antineoplastic agents, the authors examined glomerular injury as well as tubular injury of patients with chemotherapy. Methods:,Thirteen patients underwent a combined total of 64 courses of chemotherapy. Urinary albumin, ,2-microglobulin (,2-MG), N-acetyl-,-glucosaminidase (NAG) and urinary protein were measured before and serially after chemotherapy. Results:,The values of albumin/creatinine (albumin/cre) ratio and ,2-MG/creatinine (,2-MG/cre) ratio after chemotherapy were higher than those before chemotherapy (P < 0.01). NAG/creatinine (NAG/cre) ratio and creatinine clearance (Ccr) were not different. These were also examined before the next course of chemotherapy and were compared with those of control children. Albumin/cre ratio was significantly different (P < 0.01). ,2-MG/cre ratio and NAG/cre were not different. Furthermore, in patients with normal ,2-MG/cre, the albumin/cre ratio was significantly higher than in control children. Conclusions:,These results indicate that antineoplastic agents can not only induce tubular dysfunction but also glomerular dysfunction, which is persistent and independent of tubular dysfunction. [source] Lessons from studies on focal segmental glomerulosclerosis: an important role for parietal epithelial cells?THE JOURNAL OF PATHOLOGY, Issue 3 2006B Smeets Abstract Glomerular diseases are caused by multiple mechanisms. Progressive glomerular injury is characterized by the development of segmental or global glomerulosclerosis independent of the nature of the underlying renal disease. Most studies on glomerular disease focus on the constituents of the filtration barrier (podocytes, glomerular basement membrane (GBM), endothelial cells) or the mesangial cells. Little attention is given to the epithelial cells lining Bowman's capsule, the so called parietal epithelial cells (PECs). This ,lack of attention' is partly explained by the presumed ,passive' function of PECs, which are large, flattened cells that cover Bowman's capsule in a single cell layer and form a barrier between the ultrafiltrate and the periglomerular interstitium, in normal glomerular physiology. A more important reason has been the lack of an established primary role for the parietal epithelium in glomerular diseases. However, in recent years, several studies have demonstrated that PECs are involved in extracapillary proliferation. In addition, PECs can become highly active, proliferating cells, expressing many growth factors, chemokines, cytokines, and their receptors. It was recently demonstrated that PECs also play a part in the development of focal segmental glomerulosclerosis (FSGS). This review summarises current knowledge of the PEC, with emphasis on the role of PECs in the development of FSGS. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Glomerulonephritis, Th1 and Th2: what's new?CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2005P. G. Tipping Summary Glomerulonephritis (GN), the major worldwide cause of chronic renal disease and renal failure, shows a wide spectrum of histological patterns, severity of injury and clinical outcomes that may be related to the nature of the nephritogenic immune response. In the majority of cases, there is evidence of a central role for cognate immunity in the initiation of human GN and contributions of both humoral and cellular effector mechanisms have been demonstrated in both humans and in animal models. T helper cell subsets are known to activate different immune effector mechanisms which influence disease outcomes in infectious and autoimmune diseases and evidence is now accumulating that Th1 and Th2 subsets direct diverging effector pathways that lead to different patterns and severity of glomerular injury in GN. Th1-predominant responses appear to be associated strongly with proliferative and crescentic forms of GN that result in severe renal injury, while Th2 responses are associated with membranous patterns of injury. The challenge remains to understand fully the relevance of T helper cell subset responses to the spectrum of human GN and to apply this new knowledge to the development of more potent and selective therapeutic strategies. [source] Cardiac diastolic dysfunction in renal-transplant recipients is associated with increased circulating AdrenomedullinCLINICAL TRANSPLANTATION, Issue 3 2006Bernard Geny Abstract:, Background:, Renal transplantation is an excellent therapeutic alternative for end-stage renal diseases. Nevertheless, the cardiac function is often impaired in renal-transplant patients (RTR) and importantly determines their prognosis. Adrenomedullin (ADM), a peptide involved in cardiovascular homeostasis, is believed to protect both cardiac and renal functions , by increasing local blood flows, attenuating the progression of vascular damage and remodelling and by reducing glomerular injury , and might be involved in renal-transplantation physiopathology. This work was performed to investigate whether an increase in circulating ADM might be related to RTR cardiac function. Methods:, Twenty-nine subjects, 19 RTR and 10 healthy subjects, participated in the study. After 15 min rest in supine position, heart rate and systemic blood pressure were measured together with cyclosporine through levels, creatinine and ADM. Systolic and diastolic cardiac functions were assessed, using Doppler echocardiography. Results:, Subjects were similar concerning age, weight, heart rate and blood pressure. Creatinine and ADM (53.8±6.9 vs. 27.2±4.1 pmol/L, p = 0.02) were significantly increased in RTR (73±10 months after transplantation). Cardiac systolic function was normal, but a reduced mitral E:A ratio was observed in RTR (0.90±0.06 vs. 1.38±0.10, p<0.001), reflecting their impaired left ventricular relaxation. Such a ratio was negatively correlated with ADM (r = ,0.55, p = 0.002). Conclusions:, RTR present with an increased ADM is likely related to cardiac diastolic dysfunction. In view of its protective effect on the cardiovascular system, these data support further studies to better define the role and the therapeutic potential of ADM after renal transplantation. [source] | |||||||||||||||||||