Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapour

A significant reduction of kallikrein activity in urine (assayed by its amidolytic activity) was found in 64 normotensive workers who had been exposed to cadmium for 11 years on average and whose cadmium concentrations in urine ranged from 2.2 to 33.1 micrograms/g creatinine. The mean (geometric) urinary kallikrein activity (in U/g creatinine) amounted to 0.52 (range 0.11-1.90) in the control group (n = 193) against 0.39 (range 0.10-1.03) in the cadmium group, and the prevalence of abnormally low activity levels (less than or equal to 0.20 U/g creatinine) amounted to 17.2% in the cadmium group against 5.2% in the control group. A reduction of aldosterone release (aldosterone in urine) associated with an increased natriuresis was also observed. This might constitute a compensatory mechanism maintaining blood pressure in the normal range. These biological effects of cadmium were not reversible after removal from exposure. This study indicates that cadmium can induce an irreversible toxic effect in the distal nephron. It also suggests that an excessive cadmium body burden alone may not be sufficient to induce hypertension, but in individuals whose blood pressure regulation may be impaired by other factors cadmium could stimulate the development of hypertension. This study also supports the recommendation to prevent hypertensive subjects from being exposed to cadmium. There was no indication that moderate exposure to mercury vapour (n = 53; mercury in urine, range 11-224 micrograms/g creatinine; average duration of exposure: six years) or to inorganic lead (n = 23; lead in blood, range 40-67 micrograms/100 ml; average duration of exposure: eight years) was associated with a reduction of kallikrein production by the kidney.     

Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study.

This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden.     

Polarizing inclusions in some organs of children with congenital peroxisomal diseases (Zellweger's,Refsum's,chondrodysplasia punctata (rhizomelic form), X-linked adrenoleukodystrophy)

Summary Polarizing material has been reported in the liver of children with infantile Refsum's disease (IRD) and was absent in two patients with the cerebro-hepato-renal syndrome of Zellweger (CHRS). We examined in polarized light 15 liver biopsy and autopsy samples from six other patients with the cerebro-hepato-renal syndrome of Zellweger, two with the rhizomelic form of chondrodysplasia punctata (rCDP) and two with X-linked adrenoleukodystrophy (ALD), all conditions with deficient peroxisomes. Two types of birefringent inclusions were found in CHRS only: the first is transparent in bright field, the second appears as brown granules or rods, similar to lipofuscins. As in IRD large PAS-positive macrophage-like cells contain the transparent type. Electron microscopical investigation of these cells shows trilaminar structures within membrane-bound organelles. The two types were also seen in kidney and brown adipose tissue, the first type in pancreas, the second type in adrenal gland; no such was observed in myocardium or in thyroid gland (CHRS). No birefringent inclusions were present in rCDP and ALD. The nature of the inclusions is still unclear. An accumulation of the transparent polarizing material with increasing age of the patients is most likely.     

Sensitivity and specificity of human immunodeficiency virus rapid serologic assays and testing algorithms in an antenatal clinic in Abidjan, Ivory Coast

To evaluate serologic testing algorithms for human immunodeficiency virus (HIV) based on a combination of rapid assays among persons with HIV-1 (non-B subtypes) infection, HIV-2 infection, and HIV-1-HIV-2 dual infections in Abidjan, Ivory Coast, a total of 1,216 sera with known HIV serologic status were used to evaluate the sensitivity and specificity of four rapid assays: Determine HIV-1/2, Capillus HIV-1/HIV-2, HIV-SPOT, and Genie II HIV-1/HIV-2. Two serum panels obtained from patients recently infected with HIV-1 subtypes B and non-B were also included. Based on sensitivity and specificity, three of the four rapid assays were evaluated prospectively in parallel (serum samples tested by two simultaneous rapid assays) and serial (serum samples tested by two consecutive rapid assays) testing algorithms. All assays were 100% sensitive, and specificities ranged from 99.4 to 100%. In the prospective evaluation, both the parallel and serial algorithms were 100% sensitive and specific. Our results suggest that rapid assays have high sensitivity and specificity and, when used in parallel or serial testing algorithms, yield results similar to those of enzyme-linked immunosorbent assay-based testing strategies. HIV serodiagnosis based on rapid assays may be a valuable alternative in implementing HIV prevention and surveillance programs in areas where sophisticated laboratories are difficult to establish.     

Cyclic changes of the canine endometrial surface: an electron-microscopic study

The endometrial surface morphology of 38 dogs during different stages of the estrous cycle was investigated with scanning electron microscopy. The cell surface altered from convex in proestrus and estrus to very variable in early metestrus, flattened in late metestrus and became completely plane in anestrus. Microvilli were numerous and long in proestrus and in estrus, became short and variable in number in early metestrus, decreased further in length in late metestrus and became very short and rare in anestrus. The variable appearance in early metestrus was not influenced by changing the osmolarity of the fixative and might be a physiological process. The number of glandular openings showed little variability throughout the estrous cycle. Ciliated cells were rare but present in all cycle stages except in late metestrus. However, in the latter cycle stage and in anestrus rare single strands were noted. Transmission electron microscopy was used to determine the inner structure of these strands. Microtubuli were detected in transversal and longitudinal sections but without the 9 + 2 arrangement which is characteristic for cilia. The nature and function of these structures remain unclear.     

Peroxisomal localization of the immunoreactiveβ-oxidation enzymes in a neonate with aβ-oxidation defect

Summary A boy born to healthy, unrelated parents, presented at birth with hypotonia and seizures. Very long chain fatty acids in the plasma were strongly elevated; bile acid intermediates and plasmalogen biosynthesis were normal. Acyl-CoA oxidase activity was normal. The patient died at the age of 3 months. The cerebellum and medulla oblongata showed neuronal migration defects. The specific biochemical basis for the impaired peroxisomal-oxidation has not been found. The three immunoreactive peroxisomal- oxidation enzymes and catalase were localized in the hepatocellular peroxisomes. Aberrant features of the peroxisomes included: a subpopulation of organelles larger than 1 m, an amorphous nucleoid in many organelles, and invaginations of the peroxisomal membrane into the matrix. Peroxisomes in the proximal renal tubules also contained the three immunoreactive-oxidation enzymes. Regularly spaced trilamellar inclusions were seen in hepatic macrophages; they were much more abundant in adrenocortical macrophages. The inclusions were birefringent and resistant to acetone extraction. Distinct hepatic fibrosis had developed over a period of 2.5 months. We speculate that the impaired-oxidation is due to a defect at the level of the peroxisomal carnitine octanoyl or -acetyl transferase, responsible for the export of-oxidation products.     

Hepatic peroxisomes are deficient in infantile refsum disease: a cytochemical study of 4 cases

We examined liver biopsies from 4 patients with the infantile form of Refsum disease. No peroxisomes were visualized by light microscopy after cytochemical staining for catalase, a marker enzyme for this organelle. Absence of peroxisomes was confirmed by electron microscopy in 3 patients; in the 4th patient we observed organelles of peculiar size and structure and with minimal catalase activity. Light microscopy also showed birefringent macrophages containing P.A.S.-positive material; they were abundant in the 3 older children, and rare in the youngest (8 months). Peroxisomes and birefringent macrophages were absent in 2 patients with the cerebrohepatorenal syndrome of Zellweger. The simultaneous presence of these unique light microscopical characteristics may be of diagnostic value.     

Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity.

A successful prevention of renal diseases induced by occupational or environmental exposure to toxic metals such as mercury (Hg), lead (Pb), or cadmium (Cd) largely relies on the capability to detect nephrotoxic effects at a stage when they are still reversible or at least not yet compromising renal function. The knowledge of dose-effect/response relations has been useful to control nephrotoxic effects of these metals through a "biological monitoring of exposure approach". Chronic occupational exposure to inorganic mercury (mainly mercury vapor) may result in renal alterations affecting both tubules and glomeruli. Most of the structural or functional renal changes become significant when urinary mercury (HgU) exceeds 50 micrograms Hg/g creatinine. However, a marked reduction of the urinary excretion of prostaglandin E2 was found at a HgU of 35 micrograms Hg/g creatinine. As renal changes evidenced in moderately exposed workers were not related to the duration of Hg exposure, it is believed that those changes are reversible and mainly the consequence of recently absorbed mercury. Thus, monitoring HgU is useful for controlling the nephrotoxic risk of overexposure to inorganic mercury; HgU should not exceed 50 micrograms Hg/g creatinine in order to prevent cytotoxic and functional renal effects. Several studies on Pb workers with blood lead concentrations (PbB) usually below 70 micrograms Pb/dl have disclosed either no renal effects or subclinical changes of marginal or unknown health significance. Changes in urinary excretion+ of eicosanoids was not associated with deleterious consequences on either the glomerular filtration rate (GFR)--estimated from the creatinine clearance (C(Cr))--or renal hemodynamics if the workers' PbB was kept below 70 micrograms Pb/dL. The health significance of a slight renal hyperfiltration state in Pb workers is yet unknown. In terms of Pb body burden, a mean tibia Pb concentration of about 60 micrograms Pb/g bone mineral (that is 5 to 10 times the average "normal" concentration corresponding to a cumulative PbB index of 900 micrograms Pb/dL x year) did not affect the GFR in male workers. This conclusion may not necessarily be extrapolated to the general population, as recent studies have disclosed inverse associations between PbB and GFR at low-level environmental Pb exposure. A 10-fold increase in PbB (e.g., from 4 to 40 micrograms Pb/dL) was associated with a reduction of 10-13 mL/min in the C(Cr) and the odds ratio of having impaired renal function (viz. C(Cr) < 5th percentile: 52 and 43 mL/min in men and women, respectively) was 3.8 (CI 1.4-10.4; p = 0.01). However, the causal implication of Pb in this association remains to be clarified. The Cd concentration in urine (CdU) has been proposed as an indirect biological indicator for Cd accumulation in the kidney. Several biomarkers for detecting nephrotoxic effects of Cd at different renal sites were studied in relation to CdU. In occupationally exposed males, the CdU thresholds for significant alterations of renal markers ranged, according to the marker, from 2.4 to 11.5 micrograms Cd/g creatinine. A threshold of 10 micrograms Cd/g creatinine (corresponding to 200 micrograms Cd/g renal cortex: the critical Cd concentration in the kidney) is confirmed for the occurrence of low-molecular-mass proteinuria (functional effect) and subsequent loss of renal filtration reserve capacity. In workers, microproteinuria was found reversible when reduction or cessation of exposure occurred timely when tubular damage was still mild (beta(2)-microglobulinuria < 1500 micrograms/g creatinine) and CdU had never exceeded 20 micrograms Cd/g creatinine. As the predictive significance of other renal changes (biochemical or cytotoxic) is still unknown, it seems prudent to recommend that occupational exposure to Cd should not allow that CdU exceeds 5 micrograms Cd/g creatinine.(ABSTRACT TRUNCATED)     

Placental transfer of lead,mercury and cadmium in women living in a rural area

Summary The influence of the lead content of drinking water on the transplacental transfer of lead was investigated in 70 pregnant women living in a rural area of Belgium. The mothers were divided into 2 groups: group A: morning water lead below 50 g/liter; group B: morning water lead above this value. In group A, the mean lead content of water was 11.8 g/liter and in group B it amounted to 247.4 g/liter.The difference in the mean lead concentration between the two groups were for maternal blood: 3.2 g/100 ml, for umbilical cord blood: 3.3 g/100 ml, and for placenta: 3.6 g/100 g. These differences are statistically significant.There were significant correlations between water lead and lead concentration in blood (mother, newborn) or placenta. An increment of water lead concentration from 50 to 500 g/liter increases blood lead concentration in mother and in newborn by about 3 g/100 ml and in placenta by about 2.5 g/100 g (wet weight).     

Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite,monomethylarsonate, or dimethylarsinate in man

Summary The urinary elimination of the metabolites of arsenic has been followed up as a function of time in volunteers who ingested a single oral dose of arsenic (500 g As) either as sodium arsenite (As_i), monomethylarsonate (MMA), or cacodylate (DMA). The excretion rate increased in the order As_i < DMA < MMA. After 4 days, the amount of arsenic excreted in urine represents 46, 78, and 75% of the ingested dose in the case of As_i, MMA and DMA, respectively. With regard to the in vivo biotransformations, it is concluded that DMA is excreted unchanged; MMA is slightly (13%) methylated into DMA while roughly 75% of the arsenic excreted after ingestion of As_i is methylated arsenic (about 1/3 as MMA and about 2/3 as DMA).This study was supported by a grant from the Commission of the European Communities