The enzyme 11-beta hydroxysteroid dehydrogenase type 2 plays a major role in blood pressure regulation. It metabolizes glucocorticoid hormones into derivatives with low affinity for the mineralocorticoid receptor, preventing its permanent occupancy by circulating cortisol, which is 100- to 1000-fold more abundant than aldosterone in the plasma. Inactivating mutations of the enzyme result in severe hypertension, as seen in children with apparent mineralocorticoid excess syndrome.
View Article and Find Full Text PDFObjectives: Study the renal consequences of lithium therapy and find out whether lithium-induced chronic renal toxicity can provoke a progressive nephropathy, leading to advanced renal failure, requiring periodical dialysis.
Methods: Fifty-three patients treated with long-term lithium salts were included in the study. They had developed chronic renal failure (creatinine clearance inferior to 80 ml/min) not due to any other cause.
We report a single case documenting substantial improvement in the course of human immunodeficiency virus (HIV)-associated, biopsy-proven nephropathy after introduction of highly active antiretroviral therapy. Our case report joins several others recording improvement or stabilization in the course of nephropathy following better control of HIV replication.
View Article and Find Full Text PDFThe results of MR angiography at 1.0 T with digital intraarterial angiography in the screening of patients with suspected renal hypertension were compared. In this first phase of the study, 10 volunteers underwent examination with both two-dimensional (2D) with traveling saturation time-of-flight (TOF) magnetic resonance angiography (MRA) with various parameters to develop a protocol for evaluation of the renal arteries.
View Article and Find Full Text PDFEnzymatic properties of the enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD), which confers mineralocorticoid selectivity, have been explored in the aldosterone-sensitive collecting duct (CCD) and the aldosterone-insensitive Pars Recta (PR) of the rat kidney. After incubation of freshly isolated tubular segments with [3H]corticosterone (3H-B) or [3H]dehydrocorticosterone (3H-A), the rate of transformation of 3H-B into 3H-A (dehydrogenase activity), or the reverse reaction (reductase activity) were measured by HPLC, Vmax for dehydrogenase activity was found to be 8- to 10-fold higher in CCD than PR. The enzyme functions over a very wide range (0.
View Article and Find Full Text PDFThe expression of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid dehydrogenase (11HSD) activity has been investigated in the epidermis and appendages of the human skin. Aldosterone binds to MR and regulates sodium transport in tight epithelia. Mineralocorticoid selectivity is achieved through coexpression of MR and 11HSD, which prevents permanent MR occupancy by glucocorticoids.
View Article and Find Full Text PDFTo investigate the mechanisms involved in the in vivo aldosterone selectivity of the mineralocorticoid receptor (MR), we studied the respective contribution of the receptor and the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD), which converts glucocorticoids into inactive metabolites. Using a cotransfection assay in CV-1 cells, aldosterone activated mouse mammary tumor virus promoter through human MR (hMR) with an ED50 of 0.01 nM.
View Article and Find Full Text PDFThe enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) plays a major role in the protection of the mineralocorticoid receptor (MR). This cellular mechanism of aldosterone selectivity relies on the coexpression of MR and 11 beta-OHSD in the same cells. Localization of renal 11 beta-OHSD along the nephron is reviewed; comparison of data contained in different species is made; and original data is presented to show that the catalytic activity of the enzyme in tubules from human kidney is the highest in the mineralocorticoid-sensitive distal nephron.
View Article and Find Full Text PDFThe mineralocorticoid receptor displays equal affinity for aldosterone and corticosterone. It has been proposed that aldosterone selectivity in vivo is achieved by the conversion of corticosterone into its inactive metabolite 11-dehydrocorticosterone by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). To test this hypothesis, we transfected rat liver 11 beta HSD cDNA into TBM cells, a sodium-transporting cell line.
View Article and Find Full Text PDFThe enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examined whether 11 beta-OHSD is similarly located along the nephron of other mammals.
View Article and Find Full Text PDFEleven-beta-hydroxysteroid dehydrogenase (11 beta OHSD) protects the aldosterone receptor (MR) against its occupancy by glucocorticoid hormones. We examined the intrarenal distribution of 11 beta OHSD, as compared to that of MR. MR were localized in histological sections from rabbit kidney, using immunohistochemical methods with an anti-MR monoclonal antibody.
View Article and Find Full Text PDFTwo patients with AIDS-related complex who presented with renal failure and microscopic hematuria were found to have mesangial deposits of IgA at renal biopsy. Though such glomerular deposits have not yet been reported in patients with HIV infection, their occurrence is most likely not coincidental. Indeed, there are striking similar abnormalities in patients with primary IgA nephropathy and in those infected with HIV.
View Article and Find Full Text PDFAnn Med Interne (Paris)
September 1989
A 17 year old female presented with an acute interstitial nephritis and anterior uveitis. She had constitutional symptoms, a biological inflammatory syndrome, circulating immune complexes and a negative tuberculin reaction. None of the usual causes of acute interstitial nephritis and/or uveitis was found; the infectious diseases work-up was negative and the diagnosis of Behcet's syndrome and sarcoidosis were excluded.
View Article and Find Full Text PDFPharmacokinetics of pyrazinamide and its major metabolite, pyrazinoic acid, were assessed in 10 chronic uremic patients treated by maintenance hemodialysis in comparison with 10 normal subjects. All subjects ingested a single dose of 1 g of pyrazinamide, the patients receiving the drug immediately after the end of a dialysis session. Bioavailability of pyrazinamide was only slightly increased in patients, its dialysis extraction coefficient being 55.
View Article and Find Full Text PDFInterstitial lesions which are frequent in systemic diseases such as systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis and Dobrin's syndrome (acute interstitial nephritis with uveitis) are described as well as their clinical expression. The immune reactions which are recognized to be responsible for these lesions are discussed in respect to each of these diseases.
View Article and Find Full Text PDFAs erythromycin ototoxicity appears to be favored by renal insufficiency, its pharmacokinetics were assessed in chronic uremic patients treated by maintenance hemodialysis in comparison with normal subjects. Two groups of 8 patients each were studied, the first one on an interdialytic day, the second immediately after the end of an hemodialysis session. All subjects ingested a single dose of 1 gram of erythromycin ethylsuccinate.
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