摘要:

The immunosuppressant mycophenolate mofetil (MMF) inhibits the enzyme inosine-5′ monophosphate dehydrogenase and thus interferes with cellular GTP synthesis. MMF suppresses the cellular and humoral immune response and has antiproliferative effects on vascular smooth muscle and mesangial cellsin vitroandin vivo. In large multicenter trials with almost 1500 patients MMF has been proven highly efficacious for transplant rejection prophylaxis with the main side-effects of gastrointestinal disorders and a slightly increased incidence of viral infections. Recent investigations suggest MMF as an alternative immunosuppressant in cyclosporin A nephrotoxicity. Preliminary observations show promising results for MMF in the treatment of autoimmune-mediated renal disease. The rationale for its use in this patient group and evidence from experimental studies are discussed. As current therapy of this disease entity is still unsatisfactory, future clinical trials are necessary to investigate the efficacy and safety of MMF for this new indication.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Integrins represent a superfamily of cell surface molecules that are important mediators of cell-extracellular matrix interactions. Of the many known integrin subunit combinations, only a few (alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, alpha 8 beta 1 and alpha v beta 3) appear to play significant roles in renal development and function. The current understanding of these roles is reviewed. Potential therapeutic benefits from the alteration of integrin function by arginine-glycine-aspartic acid peptides in renal ischemic injury have been suggested. Reduced tubular obstruction is a potential mechanism, however other mechanisms remain to be explored. Finally, recent studies suggest a mechanism whereby abnormal interactions between integrins and non-specifically glycosylated glomerular basement membrane components could be involved in the pathogenesis of diabetic nephropathy. The elucidation of other potential pathophysiological roles for integrins in renal disease has just begun.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Acute renal failure continues to have an unacceptably high mortality rate. Ischemic renal injury is the most common cause of acute renal failure. Understanding the molecular mechanisms of cell death and regeneration is important for designing future therapeutic strategies. Recent interest in our laboratory has focused on molecular response after ischemic renal injury and, in particular, genes that are important in cell death and repair after ischemia. The identification of genes that are differentially expressed after ischemia has led to new information regarding the identity of possible mediators of cell death and regeneration in renal tubular epithelial cells.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Transforming growth factor beta is a multifunctional polypeptide growth factor implicated in a variety of renal diseases. The expression of transforming growth factor beta is enhanced in renal diseases and available evidence suggests that its activity in promoting the synthesis of extracellular matrix plays a crucial role in fibrotic deposition and the decline in renal function. Transforming growth factor beta is, however, also expressed in response to renal injury and may play an important role in normal repair processes. It appears that renal diseases may result from the inappropriate regulation of transforming growth factor beta expression. The determination of the factors that mediate transforming growth factor beta activity will be of primary importance in elucidating the mechanisms leading to renal disease or repair after injury. Both in-vitro and in-vivo studies have demonstrated that proteolytic activity, thrombospondin-1, elevated glucose, angiotensin II, oxidant stress and hemodynamic forces regulate transforming growth factor beta activity through both transcriptional and post-transcriptional mechanisms. In some cases, therapies that may partly disrupt renal transforming growth factor beta activity have shown promise in slowing the progression to end-stage renal disease.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The expression and function of ion co-transporters/exchangers/channels in the distal nephron have recently been defined. The role of cation-chloride co-transporters and proteins implicated in aldosterone target cell function are reported in the adult and during ontogeny. Volume disorders can currently be related to identified gene products acting in defined nephron sites.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Vitamin A closely modulates nephron endowment at birth. It is also required for the development of renal vasculature. Fetal vitamin A status may thus be responsible for most of the variations in nephron number found in the general population, and may play a major role in the intrauterine programming of chronic renal disease and hypertension.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Aldosterone plays a major role in the regulation of renal sodium reabsorption, of extracellular fluid volume and blood pressure. Such specific mineralocorticoid physiological adaptations occur despite the large prevalence of glucocorticoid hormones over aldosterone in the plasma. Indeed both classes of hormones bind with the same affinity to the mineralocorticoid receptor, but several mechanisms allow selective and tissue-specific aldosterone effects. They represent a series of mutually interacting selectivity filters, which have not yet been fully documented. The main determinants of aldosterone selective effects include an enzymatic protection of the mineralocorticoid receptor, the intrinsic properties of the mineralocorticoid receptor towards different ligands, and numerous possibilities of interaction between corticosteroid receptors (forming different homo or heterodimers) and other transcription factors.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Nitric oxide production by the Ca2+/calmodulin-dependent enzyme endothelial nitric oxide synthase primarily reflects changes in intracellular [Ca2+], increasing as Ca2+rises and decreasing as Ca2+falls. This simplistic bimodal mechanism of regulation has recently been refined by the finding that the binding of Ca2+/calmodulin to endothelial nitric oxide synthase involves the disruption of the association of endothelial nitric oxide synthase from the scaffolding protein caveolin and the subsequent translocation of the enzyme from plasmalemmal caveolae. Moreover, other endothelial nitric oxide synthase-associated proteins could account for a delayed Ca2+-independent activation of nitric oxide production, and may be involved with caveolin in the reversible trafficking of a large endothelial nitric oxide synthase-containing heterocomplex between the caveolae and cytosolic cell structures.

ISSN:1062-4821    

出版商:OVID    

年代:1999

数据来源: OVID