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Biomedical subjects

A Mutti

Publications and source records attributed to A Mutti.

At least 91 records · Page 5Linked to original sources
PubMed1989

[The nephrotoxicity of ionic and nonionic contrast media in urography. An evaluation with immunoenzyme technics and monoclonal antibodies].

The nephrotoxicity of ionic and nonionic contrast media (cm) was evaluated in 52 patients undergoing pyelography. The contrast media were i.v. injected in 30'. Urine samples were collected before, 2 and 48 hours after the injection. Urinary albumin (alb) and retinol binding protein (RBP) excretion was evaluated by immunoenzymatic methods; alb and RBP were considered as indicators of glomerular permeability and of tubular reabsorption, respectively. The urinary excretion of brush-border antigen of proximal tubule (BBA) was also measured, as an indicator of microtissue damage, by a sensitive double-antibody ELISA with monoclonal antibodies. The results demonstrate ionic cm to have greater functional effects than nonionic ones, as suggested by the increased urinary excretion of both alb and RBP. However, tubular damage seemed to be more severe with nonionic agents, as suggested by BBA excretion. Although toxic damage had little significance for the patients' health, long-term effects are not to be excluded.

Adult↗
PubMed1988

Hydrophobic interaction of alcian blue with soluble and erythrocyte membrane proteins.

Alcian Blue (AB), a cationic dye widely employed for monitoring negative surface charge variations on red blood cell (RBC), platelet and glomerular membranes of patients with nephrotic syndromes, was found in fact to aggregate with itself and precipitate in the pH range 7.0-7.8, i.e., at the physiological pH values used for performing the binding assay between the dye and cell surfaces. This aggregation appears to be essentially hydrophobic as it is insensitive to urea but fully prevented in presence of 2% zwitterionic detergent. In addition, AB binds to most RBC membrane proteins solubilized by urea-detergent extraction, again suggesting hydrophobic interaction. AB also interacts with freely soluble proteins such as haemoglobin and myoglobin; such binding is disrupted by ethylurea and/or 2% zwitterionic detergent, typical inhibitors of hydrophobic liaisons. AB also strongly binds to myoglobin with all the negative charges blocked by esterification of the carboxyl groups, again ruling out direct interaction via surface negative charges. It is concluded that AB binding to the RBC surface can hardly monitor variations in surface charge due to sialic acid residues but, at best, variations in surface hydrophobicity.

Adult↗
PubMed1988

Selected toxicological aspects of chromium(VI) compounds.

Chromium(III) is thought to be an essential element in mammals, its toxicity being very low. On the contrary, chromium (VI) is highly toxic to man, even if its effects are generally local, involving the respiratory tract and the skin. Once absorbed, chromium(VI) is quickly reduced to the trivalent form which accounts for all of this element present in the blood stream or taken up by tissues. As a result, any differences in systemic toxicity can only be attributed to differential solubilities and absorption rates. The kidney should be regarded as the critical organ, although tubular damage following occupational exposure is mostly due to acute absorption and transient in nature. Sensitive immunochemical techniques for the measurement of specific proteins in the urine have been used for the early detection of kidney damage, a possible threshold having been indicated at exposure levels yielding 15 micrograms/g creatinine in urine. Such a threshold has been confirmed by using monoclonal antibodies to reveal antigens from the brush-border of proximal tubules. Two main features of kidney damage were, however, apparent. The first one is the lack of dose-effect/response relationships, i.e. the lack of any progression toward more severe impairments when the exposure intensity increases. The second one is that the recent absorption rate more than the cumulated dose is responsible for the observed nephrotoxic effects.

Albuminuria↗
PubMed1988

Effects derived from long-term low-level chromium exposure in ferro-alloy metallurgy. Study of absorption and renal function in workers.

Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepted that chromium in this form is not able to cross biological barriers. However, the data on the toxic and carcinogenic effects of hexavalent chromium in man are now firmly established. Some studies have questioned these data, calling for a clarification as to whether exposure to trivalent chromium can also produce human effects, perhaps with different latency time. A study was carried out on the exposure conditions (type and degree) in a ferro-chromium foundry that had been in operation since 1972. The absorption levels in the working population of the foundry, and the possible toxic effects on the kidney have been investigated. A total of 236 workers (142 employed in production departments, 33 office workers and 61 sub-contractor employees) were examined with measurement of the indicators of dose (urinary-chromium) and of effect on the kidney (albumin, retinol binding protein, and renal tubular epithelium antigens in the urine). Environmental hygiene measurements showed relatively low values of total chromium in the air (always less than 0.160 mg/m3). Hexavalent chromium was absent or, if present, at levels below the sensitivity of the analytical method used (0.001 mg/m3). The values of urinary chromium measured at the beginning and at the end of the working day and at the end of the work shift were always less than 5 micrograms/g creatinine, which has been proposed as a biological limit in chromium exposure. However, differences were observed between groups of subjects employed on different jobs, which is indicative of an absorption process varying according to the degree of exposure. The indicators of effect did not reveal any renal impairment, even early, that could be attributed to the toxic action of chromium.

Adult↗
PubMed1988

Brain dopamine as a target for solvent toxicity: effects of some monocyclic aromatic hydrocarbons.

Adult male rabbits were exposed to toluene, xylene, styrene, ethylbenzene, vinyltoluene or were dosed with hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tubero-infundibular dopamine. Such an effect was also caused by treatment with mandelic and phenylglyoxylic acids. These results indicate that dopamine is a target for some solvents of their metabolites, the presence of a lateral vinyl- or ethyl-chain which may be biotransformed into alpha-keto acids being crucial for the effect. Experiments in vitro suggest that dopamine condenses non-enzymatically with reactive carbonylic groups of such and other alpha-keto acids, thus becoming ineffective as neurotransmitter. This mechanism might account for the neurobehavioral and neuroendocrine changes which have been reported in workers occupationally exposed to styrene and to some solvent mixtures.

Animals↗
PubMed1987

A cross-sectional survey of kidney function in refinery employees.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

Adult↗
PubMed1986

Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits.

Adult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3-methylstyrene), and 7-methyl-styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7-methyl-mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl- or ethyl-chain being crucial for the structure/activity relationship of such compounds.

Animals↗
PubMed1986

Neuropsychological deficits in arterial hypertension.

Sixty subjects with uncomplicated essential hypertension and 60 matched normal subjects were submitted to neuropsychological tests in order to establish whether some impairment of cognitive functions can be evidenced even in those hypertensive subjects that are in this respect asymptomatic on standard examination and interview. The hypertensive subjects obtained significantly poorer results than normotensive subjects on memory, visuo-motor and performance tests. In the control group, the classic negative correlation pattern between age and scores was observed, while in the patient group this correlation could be confirmed only in a few tests. Subgrouping of patients according to hypertension duration and treatment showed that the impairment of cognitive functions manifested itself very early and did not tend to progress within 6-10 years of hypertension duration.

Adolescent↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗