Biomedical subjects
A Cardenas
Publications and source records attributed to A Cardenas.
Health risk assessment of long term exposure to chemicals: application to cadmium and manganese.
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Monitoring of early nephrotoxic effects of industrial chemicals.
Long-term exposure to certain industrial chemicals (e.g. heavy metals, some halogenated hydrocarbons) may cause progressive degenerative changes in the kidney, possibly leading to renal insufficiency. The screening tests most widely used to assess the integrity of the kidney (i.e. serum creatinine or BUN and the quantitative or semi-quantitative measurement of total proteinuria) lack sensitivity; they do not permit the detection of renal disturbances at a stage when removal from exposure may prevent progression of the disease process and are not suitable to determine the no-effect levels of potentially nephrotoxic chemicals. During the last decades new markers have been proposed for the early detection of structural and/or functional changes at various sites of the renal parenchyma. Some tests mainly attempt to assess the integrity of the glomerulus (e.g. high Mr proteinuria such as transferrinuria and albuminuria; increased excretion of some components of the glomerular basement membrane or the mesangium matrix, increased plasma concentration of low Mr proteins such as beta 2-microglobulin and free retinol binding protein), the proximal tubule (e.g. urinary excretion of several low Mr plasma proteins, tubular enzymes and antigens), the loop of Henle and distal tubule (e.g. excretion of various prostanoids). Currently, the majority of these tests are of limited value at the individual level because their health significance, even when they are persistently abnormal, has not yet been sufficiently studied. In workers exposed to Cd, however, it has been shown that a persistent low Mr proteinuria is predictive of an exacerbation of the age-related decline of the GFR; this biological change should be considered as an adverse effect. Currently, the principal application of these tests lies in the framework of epidemiologic studies designed to assess permissible exposure levels to nephrotoxic pollutants. The study of dose-effects/response relationships based on a large battery of renal markers has allowed the better determination of the internal dose of Cd, which is not associated with significant renal risk.
Cadmium and health: the Belgian experience.
Studies in the 1970s on chronic cadmium poisoning in man in Belgium showed that the earliest effect was renal dysfunction with proteinuria. Subsequent studies were focused on the characterization of cadmium proteinuria, the diagnosis and prognosis of cadmium nephropathy and the assessment of the concentrations in urine and renal cortex leading to its occurrence. Chronic exposure to cadmium in industry gives rise to a proteinuria which may be tubular, glomerular or mixed in character. This proteinuria may be accompanied or preceded by a variety of other renal effects. In active male workers, three main groups of thresholds for urinary cadmium have been identified for the induction of these effects with corresponding thresholds in the renal cortex. However, these estimates probably cannot be extrapolated to the general population exposed to cadmium mainly by the oral route. The results of a large-scale cross-sectional study (Cadmibel) suggest that subclinical changes in tubular function may occur in the general population above a threshold of urinary cadmium as low as 2 micrograms/24h.
Disturbance of sialic acid metabolism by chronic cadmium exposure and its relation to proteinuria.
In workers exposed to Cd (8 years on the average), we have found a significant decrease of sialic acid in erythrocyte membranes (22.61 +/- 1.84 vs 25.80 +/- 3.01 micrograms/mg of protein in controls, p less than 0.05) and an increase of sialic acid concentration in both urine (276.7 +/- 132.3 vs 174.5 +/- 70.9 micrograms/g of creatinine, p less than 0.05) and plasma (761.8 +/- 83.5 vs 640.4 +/- 70.7 micrograms/ml, p less than 0.01). In rats exposed to Cd (100 ppm in drinking water for 5.5 months), we have observed a reduction of the sialic acid level in erythrocyte membranes (31.4 +/- 1.2 vs 33.4 +/- 1.1 micrograms/mg of protein, p less than 0.01) and glomeruli (12.5 +/- 1.3 vs 13.9 +/- 1.6 micrograms/mg of protein, p less than 0.05). These effects in Cd treated rats were accompanied by a loss of the glomerular barrier selectively as reflected by an increased urinary output of albumin and transferrin. After 10 months of Cd exposure, the albuminuria and transferrinuria were negatively correlated with the sialic acid content of glomerular membranes (r = -0.47 and -0.51, p less than 0.05), which suggests that the depletion of sialic acid is involved in the loss of glomerular barrier function induced by long term Cd exposure. In Cd-treated rats, sialidase activity was enhanced in kidney cortex and in serum but not in glomeruli.
Effects of pneumotoxic trialkylphosphorothioates on the pentose phosphate pathway in rat lung slices.
The extent of glucose oxidation via the pentose phosphate pathway (PPP), a possible indicator of oxidative stress, was assessed in rat lung slices by measuring the production of 14CO2 on incubation with either [6-14C]glucose or [1-14C]glucose. Incubation in the presence of the pneumotoxins O,S,S-trimethyl phosphorodithioate (OSSMe, 10(-5) -10(-3) M), O,O,S-triethyl phosphorothioate (10(-4) -10(-2) M) or S,S,S-trimethyl phosphorotrithioate (10(-4) -10(-2) M) resulted in a significant, but small stimulation of PPP (max. 276%), compared to that found in the presence of the model oxidant, paraquat (1089%, 10(-5) M). Following in vivo treatment with an LD50 dose of OSSMe, PPP was unchanged (after 6 h) or decreased (after 24 h) compared to saline-treated rats. PPP was also decreased in slices which had been preincubated with OSSMe (10(-3) M) and then transferred to fresh medium. Following treatment with phorone (250 mg/kg i.p.) pulmonary levels of non-protein sulfhydryls were first reduced (20% of control at 3 h) and then increased (288% of control at 24 h), but at neither time was lung slice PPP activity affected, thus suggesting that in the rat lung PPP activity does not directly depend on pulmonary glutathione content.
Potentiation of diabetic glomerulopathy in uninephrectomized rats subchronically exposed to cadmium.
The renal effects of diabetes mellitus and cadmium (Cd), separately or in combination, were investigated in unilaterally nephrectomized female Sprague-Dawley rats. Diabetes was induced by injection of streptozotocin and Cd was administered in drinking water at a concentration of 100 p.p.m. for 2.5 months. Cd did not affect the reduction in glomerular filtration rate or the rise in beta 2-microglobulinuria caused by diabetes. By contrast, the effect of diabetes on the urinary excretion of albumin, transferrin or IgG was greatly enhanced by concomitant exposure to Cd. This interaction occurred at Cd levels in the renal cortex which are very similar to those found in the general population of industrialized countries. These observations, in agreement with the results of a recent epidemiological study, suggest that Cd polluting the environment might potentiate the development of diabetic nephropathy.
Inorganic arsenic methylation by rat tissue slices.
Rat liver, kidney and lung slices methylate trivalent inorganic arsenic (AsIII) to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA); the liver has the greatest methylating capacity. AsIII enters the liver cells by a diffusion process followed by extensive binding to intracellular components which favors its extensive accumulation inside the cells. Reduced glutathione regulates AsIII metabolism through several mechanisms: facilitation of AsIII diffusion into the cells, stimulation of the first methylation reaction and increase of DMA excretion by the cells. An excess of AsIII inhibits DMA production by liver cells but this inhibition is reversible; mercuric ions inhibit both MMA and DMA production probably by decreasing inorganic arsenic (Asi) uptake and the second methylation reaction. DMA can be produced from MMA by rat liver slices and this methylation step is stimulated by GSH. In contrast to AsIII, AsV is not extensively taken up by the hepatocyte and is thus poorly methylated.
Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.
Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.
Validity of the alcian blue binding test as an indicator of red blood cell and glomerular membrane negative charges.
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The effects of heparin and low molecular weight dextran on survival after fibrinopurulent peritonitis.
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[Changeable aspects in the epidemiology of Parkinson disease (analysis of 262 cases during a period of 9 years].
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Hilus cell tumor of the ovary and endometrial carcinoma.
A case of hilus cell tumour of the ovary was found in a patient with adenocarcinoma of the endometrium, the sixth such case reported in the literature. Serum levels of estradiol-17beta, progesterone, and testosterone were measured before and after surgical removal of the tumor and after dexamethasone suppression in the postoperative period. Only testosterone appeared to be related to the presence of the hilus cell tumor; its levels decreased after removal of the tumor.
Endoscopy of the thoracic duct (lymphoscopy) via the external jugular vein in dogs.
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A comparative analysis of the mesocaval H graft versus the distal splenorenal shunt.
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