Biomedical subjects

A O Amor

Publications and source records attributed to A O Amor.

4 recordsLinked to original sources

PubMed1990

Urinary proteins and red blood cell membrane negative charges in diabetes mellitus.

The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low (beta 2-microglobin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of beta 2-microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin (r = -0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass (r between - 0.5 and - 0.2) but presented no relation with urinary beta 2-microglobulin or retinol-binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transferrin excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria (r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy.

Adult↗

PubMed1988

Potentiation of cadmium nephrotoxicity by acetaminophen.

The possible interactions between acetaminophen and cadmium (Cd) on the kidney were investigated in female Sprague-Dawley rats. Acetaminophen was administered in the food at an average dose of 900 mg/kg and Cd in drinking water at the concentration of 200 ppm. The treatment with acetaminophen and Cd lasted 2 and 10 months, respectively. No interaction between Cd and acetaminophen was observed during the period of their concomitant administration: the increase in albuminuria caused by Cd and acetaminophen was additive, while the tubular impairment caused by acetaminophen (increased beta 2-microglobulinuria and decreased kidney concentrating ability) was not exacerbated by Cd. None of these treatments affected the glomerular filtration rate. Four months after the end of acetaminophen treatment, the renal changes had almost completely disappeared in the rats which had received the analgesic alone. Those continuously exposed to Cd had developed slight tubular damage, as evidenced by an increased urinary excretion of beta 2-microglobulin and beta-N-acetylglucosaminidase. By contrast, rats pretreated with acetaminophen for 2 months and exposed to Cd showed a marked increase in urinary excretion of albumin and beta 2-microglobulin, suggesting an interaction between both treatments. At the end of the study, only the interaction with beta 2-microglobulin excretion was still evident; that with the urinary excretion of beta-N-acetylglucosaminidase and albumin having been masked by the chronic progressive nephrosis affecting most animals at that stage. As acetaminophen had no effect on the renal accumulation of Cd, it may be concluded that pretreatment with this analgesic at a dose causing slight tubular dysfunction renders rat kidney more sensitive to the nephrotoxic action of Cd. This observation may be of clinical relevance for population groups occupationally or environmentally exposed to Cd.

Acetaminophen↗

PubMed1988

The renal uptake of proteins: a nonselective process in conscious rats.

The selectivity of the renal reabsorption of proteins has been investigated by competition experiments in conscious rats. The animals were intravenously injected with increasing doses of proteins over a wide range of net charge and size, including lysozyme, cytochrome C, metallothionein, beta 2-microglobulin, retinol-binding protein, albumin and IgG. The urinary excretion of exogenous proteins injected concomitantly (human beta 2-microglobulin, retinol-binding protein, albumin and/or egg white lysozyme depending on the experiment) and of rat beta 2-microglobulin, albumin and IgG was determined with specific immunoassays. The results show that low molecular weight cationic proteins and low or high molecular weight anionic proteins can increase each other's urinary excretion. Several observations strongly suggest that these effects result from a competitive inhibition of renal uptake. The phenomenon is dose-related in most cases and, as evidenced by cytochrome C injection, transient, reproducible and saturable. In addition, the injected proteins induce a tubular type proteinuria irrespective of their net charge and size. In the case of cationic proteins, this finding excludes the possibility of an enhanced glomerular permeability due to a partial neutralization of the glomerular polyanion which, as demonstrated with protamine sulfate, entails a glomerular type proteinuria. These quantitative data on the mutual inhibition of renal uptake of a wide spectrum of specific proteins lead us to challenge the concept of charge- and size-selective tubular reabsorption of proteins, and to postulate that proteins filtered through the glomeruli are taken up by common tubular endocytotic sites irrespectively of their physicochemical features. As demonstrated by the ability of beta 2-microglobulin and IgG to inhibit the uptake of lysozyme, the affinity of a protein for reabsorption sites is not simply related to its size and net positive charge. Evidence is also presented that proteins, when administered intravenously at high doses, induce a lysosomal enzymuria most likely reflecting a stimulated exocytosis.

Absorption↗

PubMed1988

Decrease of erythrocyte and glomerular membrane negative charges in chronic cadmium poisoning.

Negative charges on red blood cell membranes were measured by the alcian blue binding test in 11 workers with high exposure to cadmium. Compared with 12 age matched control subjects, cadmium workers showed a significant decrease in red blood cell charge, which on average paralleled both the cadmium body burden and protein excretion. Animal data confirm these observations and also show that the loss of red blood cell charge caused by chronic cadmium poisoning is irreversible and associated with a loss of glomerular negative charges. The present study suggests thus that cadmium can increase the urinary excretion of anionic macromolecules such as albumin by reducing the glomerular polyanion charge.

Adult↗