[Diagnostic definition of urine albumin isolated by determining tubular antigen excretion using monoclonal antibodies].
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Adult↗
Biomedical subjects
I Franchini
Publications and source records attributed to I Franchini.
Urinary excretion of brush-border antigen revealed by monoclonal antibody: early indicator of toxic nephropathy.
Mouse monoclonal antibodies against brush-border antigens of the proximal tubule of human kidney were produced by the hybridisation technique. The urinary excretion of a brush-border protein with an apparent molecular weight of 50 000 (BB-50) was measured by a sandwich enzyme-linked immunosorbent assay with a mouse IgG1 against BB-50 and a polyclonal rabbit antiserum against human kidney as coating and second antibodies. The urinary excretion of BB-50 was fifty times higher in patients treated with cisplatin than in a matched control group and twice as high in workers occupationally exposed to water-soluble chromium(VI) compounds as in their matched controls. These findings suggest that the urinary excretion of kidney antigens revealed by monoclonal antibodies is a very sensitive and specific test for the assessment of toxic nephropathies.
Adolescent↗
Styrene metabolism and striatal dopamine depletion in rabbits.
The striatal concentration of dopamine (DA), norepinephrine (NE), and homovanillic acid (HVA) was assessed in adult male rabbits exposed to styrene vapours or dosed with mandelic acid (MA), phenylglyoxylic acid (PGA) and phenylglycine (PG). Styrene exposure produced a marked and dose-dependent decrease in striatal DA, concomitant with a consistent increase in HVA. The same effects were caused by i.p. administration of PGA and PG, but not of MA. The increased catabolism of DA was concomitant with a normal turnover time after inhibition of tyrosine hydroxylase by the administration of methyl-p-tyrosine. The amination of PGA to PG with a subsequent competition of the latter with DA for the vesicular storage capacity is suggested as the possible mechanism for styrene-induced brain dysfunction.
Animals↗
Exposure-effect and exposure-response relationships between occupational exposure to styrene and neuropsychological functions.
A neuropsychological test battery was administered to 50 workers exposed to styrene and to 50 sex-, intelligence-, and age-matched controls. The main styrene metabolites, ie, mandelic acid (MA) and phenylglyoxylic acid (PGA), were measured as exposure indices in the urine collected on Saturday mornings, just before neuropsychological testing. Exposure-response and exposure-effect relationships were found between the intensity of the exposure (as reflected by the sum of MA and PGA) and the scores of the neuropsychological tests. Verbal learning skills were significantly impaired in workers with a sum of MA and PGA higher than 150 mmole/mole creatinine, corresponding to styrene airborne concentrations higher than 25 ppm (mean daily exposure). Logical memory and visuo-constructive abilities were shown to be significantly affected in workers with MA and PGA higher than 300 mmole/mole creatinine, corresponding to exposure levels of more than 50 ppm of styrene in air.
Adult↗
Regional alterations of brain catecholamines by styrene exposure in rabbits.
The regional distribution of dopamine, norepinephrine and homovanillic acid was assessed in adult male rabbits exposed to styrene vapours. The turnover of dopamine and norepinephrine was also measured in several brain regions by the decay in endogenous catecholamines after inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine. Styrene exposure produced a marked and dose-dependent decrease in striatal and tuberoinfundibular dopamine, associated with a consistent increase in homovanillic acid content in the same regions. Norepinephrine levels were unaffected by styrene exposure. The observed increase in catabolism of dopamine cannot be explained by the turnover time, which was not significantly different in the exposed as compared to the control rabbits. Competition of a styrene metabolite with dopamine for the vesicular storage capacity or a selective destruction of dopaminergic terminals are suggested as the possible mechanisms for styrene neurotoxicity.
Animals↗
Biological monitoring of occupational exposure to different chromium compounds at various valency states.
Chromium concentrations in the air were measured in seven different workroom environments, where exposure to water soluble hexavalent or trivalent compounds was expected. Urinary excretion of chromium was measured before and after the same arbitrarily chosen working day. End-of-shift urinary chromium and its increase above pre-exposure levels were closely related to the concentration of water soluble chromium (VI) in the air. The values corresponding to 50 micrograms m-3 in the air, which is the current threshold limit value in most countries, were 29.8 and 12.2 micrograms g-1 of creatinine, respectively. Urinary chromium in workers exposed to water insoluble chromates or to water soluble chromic (III) sulphate was definitely higher than that observed in subjects not occupationally exposed to chromium compounds, but it cannot be recommended as short-term exposure test for evaluation of the job-related hazard.
Absorption↗
n-Hexane metabolism in occupationally exposed workers.
Lung uptake and excretion of n-hexane were studied in ten workers in a shoe factory. Simultaneous samples of inhaled and alveolar air were collected with the aid of a Rhan-Otis valve, personal samplers, and charcoal tubes. Alveolar excretion was monitored during a six hour postexposure period. Uptake was calculated from lung ventilation, the retention coefficient, and environmental concentrations. The amount of exhaled n-hexane was calculated from the decay curve. According to the experimental data, alveolar retention was about 25% of the inhaled n-hexane, corresponding to a lung uptake of about 17%. The postexposure alveolar excretion was about 10% of the total uptake. The main metabolites of n-hexane were identified and measured by capillary GC/MS in spot urine samples collected before, at the end, and 15 hours after the same working shift. Urinary concentrations were low, though related to n-hexane in the air. 2,5-Hexanedione in the end of shift samples gave the best estimate of overall exposure. About 3 mg/g creatinine of 2,5-hexanedione would correspond to about 50 ppm of n-hexane in the air (mean daily exposure).
Absorption↗
Neuroendocrine effects of styrene on occupationally exposed workers.
The serum levels of prolactin (PRL), human growth hormone (HGH), thyroid-stimulating hormone (TSH), and the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in 30 females exposed to about 130 (range 65-300) ppm of styrene in the air and in 30 age-matched referents to show whether styrene exposure influences the dopaminergic tuberoinfundibular system (TIDA). The exposed subjects' serum levels of PRL were more than double the reference values and were significantly related to the urinary excretion of styrene metabolites, ie, to the sum of mandelic acid (MA) and phenylglyoxylic acid (PGA) in the "next-morning" urine spot sample. Such a relationship still proved to be statistically significant after the removal of the effects of age and duration of exposure with the method of partial correlation. The serum concentrations of HGH in the exposed workers were also higher than in the reference group. Though within the reference levels, the TSH values of the exposed subjects were significantly related to the urinary excretion of MA and PGA. These results are consistent with the dose-dependent depletion in tuberoinfundibular dopamine after experimental styrene exposure of rabbits.
Adult↗
Enzyme-linked immunosorbent assay of retinol-binding protein in serum and urine.
This highly sensitive method for determining retinol-binding protein in human serum and urine is based on a double-antibody "sandwich"-type enzyme-linked immunosorbent assay. The assayable concentration range is 0.8-48 micrograms/L, the detection limit 0.2 micrograms/L. Within-assay coefficients of variation for 10 determinations at two different concentrations were 5.5 and 5.8%. The corresponding between-assay CVs were 7.9 and 9.2%. We saw no interference from any components of urine or serum. The mean urinary excretion by 30 healthy subjects, as determined by this method, was 101 micrograms/g of creatinine (SD 38.8). The concentration in serum averaged 43 mg/L (SD 12.1).
Adult↗
Early indicators of renal damage in workers exposed to organic solvents.
In order to investigate the renal function, a cross-sectional study was carried out on four groups of workers significantly exposed to a mixture of alicyclic and aliphatic C5-C7 hydrocarbons, to styrene, to a mixture mostly composed of toluene and xylenes and to chlorinated hydrocarbons, respectively. The study involved 438 workers. Exposure was characterized by means of urinary metabolites, or by means of environmental measures, when biological indicators were not available. The renal function impairment indicators included total proteinuria, albuminuria and urinary excretion of muramidase (E.C. 3.2.1.17) and beta-glucuronidase (E.C. 3.2.1.31). The trend of these parameters provides some evidence of renal damage due to occupational exposure to organic solvents and suggests that the lesions are mild and tubular rather than glomerular.
Adult↗
Mortality experience among chromeplating workers. Initial findings.
A retrospective cohort study was conducted in nine chromeplating plants to examine the mortality of workers employed for at least one year during the period January 1951-December 1981. The study group totaled 178 individuals, 116 of whom were from "hard" and 62 from "bright" chromeplating plants. Vital status ascertainment was 97% complete. The total number of deaths was fairly close to the expected figure (15 observed, 15.2 expected), whereas deaths from tumors exceeded the expected number (8 observed, 4.2 expected). Individuals were distinguished into two subcohorts depending on the exposure intensity, which was much higher in hard than in bright chromeplating. Most deaths from cancer occurred among hard chromium platers, the excess against the expected rate being statistically significant (7 observed, 2.7 expected, p = 0.02). All deaths from lung cancer occurred in this subcohort (3 observed, 0.7 expected, p = 0.03). The increased mortality from cancer among chromium platers seems to be related to exposure intensity and strongly suggests the need for further studies on larger cohorts to confirm the carcinogenicity of chromic acid in man.
Chromium↗
Mandelic acid and phenylglyoxylic acid excretion in workers exposed to styrene under model conditions.
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Adolescent↗
Neurophysiological effects of long-term exposure to hydrocarbon mixtures.
Motor nerve conduction velocity (MCV) was measured on median, ulnar and peroneal nerves in a reference group of 52 workers and a group of 95 workers exposed to hydrocarbon mixtures in a shoe factory. Exposure-related changes were found in motor action potential (MAP) amplitudes of the three nerves and in median and peroneal MCVs. Electroneurographic abnormalities were also present in a subgroup of workers exposed to air concentrations near the current ACGIH (1979) recommended threshold limit value (TLV) for the mixture. Our results suggest the need for lowering the TLV for the main components n-hexane and cyclohexane. A synergistic effect of the two hexacarbon solvent might also be considered in the hygienic evaluation of the workplace.
Action Potentials↗
n-Hexane-induced changes in nerve conduction velocities and somatosensory evoked potentials.
Fifteen women from a shoe factory were examined clinically and their cerebral evoked responses to 256 electrical stimulations of the median nerve were averaged. Neurophysiological investigations included maximal motor (MCV) and distal sensory (dSCV) nerve conduction velocity measurement on ulnar, median, and peroneal nerves. A referent group was composed of 15 age-matched women without exposure to neurotoxic chemicals. MCVs and dSCVs of the exposed workers were significantly reduced vs referents, while P15 and N20 components of the somatosensory evoked potentials (SEP) showed an increased latency. A negative linear relationship was found between dSCV and P15 latency. However, two subjects with an abnormally low dSCV showed normal SEP latency, and two other subjects displayed abnormal SEP latency, while their dSCV was in the normal range. Therefore, SEP investigation may give additional information on nervous system function, even in subjects with peripheral neuropathy. The later SEP components were much flatter in the exposed than in the referent group, suggesting some neurotoxic effects of n-hexane on the central nervous system too.
Adult↗
Neurophysiological changes in workers exposed to organic solvents in a shoe factory.
Motor conduction velocity (MCV) was measured in the median, ulnar, and peroneal nerves of 52 referents and 95 workers from a shoe factory, in a search for dose-effect and dose-response relationships between exposure to organic solvents and subclinical impairment of the peripheral nervous system (PNS). According to the environmental concentrations, the exposure was expressed as the sum of the products between the median hygienic effect (ranging from 0.08 to 2.89) and worktime (from 1 to 29 a) in every job. The motor action potential (MAP) amplitudes, durations and shapes of the exposed workers were significantly affected even if to a different extent and significance level when compared to those of the MCVs of the referents. The MCVs of the median (t = 3.17, p less than 0.01) and peroneal (t = 2.11, p less than 0.05) nerves were reduced as compared to reference values. In the exposed group, the MCV of the median nerve was negatively correlated with exposure score (r = 0.45, p less than 0.01) but not with age. No relationship was found between MVCs of the ulnar and peroneal nerves and exposure. The MCV of the median nerve was particularly slow in a subgroup of workers with an exposure score of greater than 20 (t = 2.30, p less than 0.05 vs the other exposed workers; t = 5.56, p less than 0.01 vs the referents). This exposure score represents only 50% of the maximum allowable score for a worktime of 40 a. Even if none of the examined workers showed clinical signs of polyneuropathy, evidence of subclinical effects on the PNS were found among subjects with long-term exposure to hexacarbon mixtures. Therefore, our results suggest the need for a lowering of current threshold limit values at least for n-hexane.
Adolescent↗
Absorption and alveolar excretion of cyclohexane in workers in a shoe factory.
The lung uptake and excretion of cyclohexane were studied in five workers and three volunteers in a shoe factory. Air samples were collected from the breathing zones with personal samplers, and simultaneous samples of inhaled and alveolar air were collected with the aid of a Rhan-Otis valve. Cyclohexane was absorbed on activated NIOSH approved charcoal tubes. The uptake was calculated from the pulmonary ventilation, the retention coefficient and environmental concentration. Alveolar excretion was monitored during a 6 h post-exposure period. The amount of exhaled cyclohexane was calculated from the decay curve. According to experimental data, the alveolar retention of cyclohexane is about 34% of the inhaled dose. This corresponds to a lung uptake of 23%. The post-exposure alveolar excretion does not exceed 10% of the total uptake. The difference between respiratory uptake and excretion indicates that the amount metabolized may be very large. Nevertheless, the urinary excretion of the main metabolites, cyclohexanol and cyclohexanone, was only about 1% of the absorbed dose.
Absorption↗
Organic solvents and chronic glomerulonephritis: a cross-sectional study with negative findings for aliphatic and alicyclic C5-C7 hydrocarbons.
Proteinuria, albuminuria, urinary beta-glucuronidase and serum creatinine were estimated in 182 workers exposed to organic solvents in four shoe factories, as well as 30 workers with past exposure and 80 control subjects. Ambient air concentrations at each workplace were also measured. In most of these samples, the concentration of organic solvents exceeded the ACGIH recommended threshold limit value for the mixture. Total protein excretion was significantly elevated in exposed workers, although none of the workers had abnormal albuminuria or serum creatinine. Four had increased lysozymuria. There was also a simultaneous elevation of beta-glucuronidase. These findings suggest that a mild and presumably reversible tubular lesion, but not glomerular damage, may occur in workers occupationally exposed to C5-C7 hydrocarbon mixtures.
Adult↗
Behaviour of indicators of exposure and effect after cessation of occupational exposure to lead.
The behaviour of blood lead (PbB) and of some indicators of effect (erythrocyte protoporphyrin IX (EP), delta-aminolaevulinic acid dehydratase activity of erythrocytes (ALAD), and urinary delta-aminolaevulinic acid (ALAU)) were studied in subjects who had ceased working with inorganic lead for at least one year. Relations between these indices and chelatable lead (PbU-EDTA (lead in urine after injection of CaNa2 EDTA 1 g intravenously)), a test that is used to evaluate the lead deposits in the body, were also analysed. As a comparison, a group of subjects currently exposed was studied. In the workers with past exposure the PbB values were significantly lower, at the same PbU-EDTA levels, than those found in subjects at work. The relation between EP and PbU-EDTA shows that, corresponding levels of chelatable lead, the values of the erythrocyte metabolite are identical in the two groups. Considering the EP-PbB relation, however, at the same PbB levels the protoporphyrin values appear distinctly more altered in the subjects with past exposure. Similar results were obtained from a study of the relations between ALAD and PbU-EDTA and between ALAD and PbB. The relation between ALAU and PbU-EDTA, however, shows that, at the same PbU-EDTA levels the urinary metabolic in past-exposed subjects is distinctly lower than in subjects at work, while the relation between ALAU and PbB shows that, for similar blood lead values, the ALAU levels are identical. On the basis of the results obtained it is concluded that in subjects with past exposure, EP and ALAD can be used in establishing the persistence and extent of an "active deposit" of lead in the organism, while PbB is of very limited use.
Adult↗