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Biomedical subjects

M Maroni

Publications and source records attributed to M Maroni.

At least 55 records · Page 3Linked to original sources

Low-pH method for the enzymatic assay of D-glucaric acid in urine.

The enzymatic methods for measuring D-glucaric acid in urine are based on the conversion of D-glucaric acid into its 1,4-lactone and measurement of inhibition of 1,4-lactone against beta-glucuronidase at pH 5.0. All the enzymatic methods described suffer from the disadvantage of a procedure that is complicated and inherently inaccurate, because the nature of glucaric acid/1,4-lactone equilibrium has not been properly considered in the development of such methods. After elucidating the factors influencing glucaric acid/1,4 lactone equilibrium in more detail, a low-pH enzymatic method has been developed in which the 1,4-lactone is formed in the urine sample by acid boiling at pH 3.8 and assayed at the same pH using beta-glucuronidase from Limpets. This procedure allows the acid/lactone equilibrium to remain stable during both the lactonization step and the enzymatic assay. The coefficient of variation for the proposed method (within-run and between-day precision) was from 4.2 to 8.7. The analytical recovery varied from 92-108%.

Glucaric Acid↗

Influence of sex, age, and smoking habits on the urinary excretion of D-glucaric acid.

Reference values for urinary D-glucaric acid and the influence of sex, age and smoking habits were evaluated with a low-pH enzymatic method. D-Glucaric acid measured on spot urine samples from 573 healthy subjects gave mean concentrations (mumol/1) and D-glucaric acid/creatinine ratios (mmol/mol creatinine) of 56.1 (+/- 22.9) and 3.05 (+/- 0.99) for males and 53.3 (+/- 20.9) and 3.35 (+/- 0.95) for females. No difference between morning and evening was observed for urinary D-glucaric acid/1 values, but D-glucaric acid/creatinine was higher in the evening samples for both sexes. There was a negative correlation between D-glucaric acid/1 values and age in males but not in females: the decrease of D-glucaric acid concentration was, however, quantitatively very small. Smoking produced a significant increase in D-glucaric acid concentration and in the D-glucaric acid/creatinine ratio for males and also partially for females.

Adolescent↗

Liquid chromatography of urinary porphyrins for the biological monitoring of occupational exposure to porphyrinogenic substances.

Very sensitive and precise analytical methods for measuring total porphyrin excretion and the relative amounts of different porphyrins in urine are required in order to monitor the biological effects of porphyrinogenic substances in workers and the general population. Many analytical steps of a HPLC method for measuring porphyrins as methyl esters in urine have been perfected. Sensitivity is 0.1 microgram/1 for each type of porphyrin, and average recovery is 92% in the range of 50-450 micrograms/liter porphyrins. The coefficient of variation is 3.4% within a series and 12.5% between series. Chemical oxidation before analysis and appropriate storing of the samples are the key points in achieving high quality results. The urinary excretion of porphyrins in healthy male workers varies within the range 21 to 161 micrograms/liter (95% limits of a group of 78 subjects). Concomitant factors, like drug use or liver disorders, were found to alter urinary porphyrin excretion. The proposed method permits the detection of extremely small alterations in porphyrin excretion resulting from occupational exposure to industrial chemicals such as, for example, mild coproporphyrinuria or early stages of chemical porphyria induced by polyhalogenated arylhydrocarbons.

Adult↗

Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environmental and blood polychlorinated biphenyls concentrations.

Industrial exposure to polychlorinated biphenyls (PCBs) and internal dose were investigated in 80 worker exposed for many years to PCB mixtures with a 42% chlorine content (Pyralene 3010 and Apirolio). PCBs were determined by liquid gas chromatography on samples taken from workroom air, workroom surfaces and tools, the palms of the hand, and the blood of the workers. In the workroom air samples, PCB concentrations ranged from 48 to 275 micrograms/m3. All tested surfaces and tools were heavily contaminated, with a range from 0.2 to 159 micrograms PCBs per cm2 of surface. Considerable amounts of PCBs were detected on the palms of the hands of the workers (2-28 microgram/cm2 of skin surface). In blood, total PCB concentrations from 88 to 1319 micrograms/kg were observed: comparing the blood concentrations of low and high chlorine content biphenyls, a significant difference was found for the low-chlorinated biphenyl concentrations between workers currently exposed and workers exposed only in the past. In groups of workers who were homogeneous as regards work area and job, the PCB concentrations in the blood were closely correlated with the length of actual occupational exposure to these compounds. These findings led to the conclusion that absorption of PCBs in these workers had occurred mainly through the skin, therefore industrial preventive surveillance must take this route of exposure into account. Since blood PCB concentrations appear to be correlated with the length of exposure, PCB determination on whole blood may be used to monitor industrial and environmental exposure to PCBs.

Adult↗

Occupational exposure to polychlorinated biphenyls in electrical workers. II. Health effects.

Health conditions were evaluated in 80 electrical workers exposed for many years to polychlorinated biphenyl (PCB) mixtures with a 42% mean chlorine content, who had blood PCB concentrations from 41 to 1319 micrograms/kg. The clinical study was based on personal history data, physical examination, and laboratory tests (red cell and leukocyte count; determination of haemoglobin, packed cell volume, bilirubin, serum protein electrophoretic fractions, pseudocholinesterase, AST, ALT, GGT, and OCT). Fifteen workers were found to have skin diseases--chloracne (4), folliculitis (4), oil dermatitis (1), juvenile acne (1), and dermatitis due to irritative or allergic agents (5). Sixteen workers showed more or less pronounced hepatic involvement, consisting most often of hepatomegaly with an increase in serum GGT, AST, ALT, and OCT values. In two workers bleeding cavernous haemangiomas were discovered, in one case associated with chronic myelocytic leukaemia. All the workers with chloracne were employed on electric capacitor impregnation with PCBs, and no definite association was found between chloracne and blood PCB concentrations. Conversely, a significant positive association was found between the abnormal liver findings and blood PCB concentrations, particularly trichlorobiphenyl blood concentrations. The abnormal hepatic findings observed are similar to those reported in experimental animals given PCBs, and in some workers such findings should probably be considered as clinical signs of hepatic microsomal enzyme induction.

Adult↗

Carbon disulfide neuropathy in rats. A morphological and ultrastructural study of degeneration and regeneration.

The aim of this study was to elucidate the site and detailed nature of peripheral nerve damage induced in the rat by chronic CS2 inhalation exposure in the light of the relationship between pathological and neurophysiological data. Adult male rats were exposed to 700 ppm of CS2 2 h/d, 5 d/week for 12 weeks and then followed-up for 18 weeks. The first alteration observed was a decrease in the nerve conduction velocity, discovered after only 3 weeks of exposure. Pathological lesions were first observed in the 10th week and consisted of a typical "giant axon" axonopathy. Obvious pathological lesions of the myelin sheaths were revealed much later, in the 3rd week after the end of exposure, when some nerve fibers were dying back. Recovery took place with the regeneration of new fibers which started in the 8th week after the end of exposure and was nearly complete in the 18th week. These findings demonstrate that CS2-induced polyneuropathy is an axonopathy very similar to that caused by other occupational neurotoxic agents like MnBK, n-hexane, and acrylamide. The timing of the pathological events within the nerve fibers suggests that the pathogenesis of the nerve lesions should probably be attributed to a primary energy failure of the axonal membrane induced by CS2.

Animals↗

Effects of ganglioside therapy on experimental CS2 neuropathy.

Both in animals and in man the inhalation of CS2 vapor induces a chronic polyneuropathy with primary lesions in the axons of peripheral nerves. Since it was reported in several studies that the administration of gangliosides improves nerve regeneration and the functional recovery of nerves damaged by section as well as cryodegeneration, a study was undertaken to evaluate the effects of bovine-brain gangliosides administration on the experimental CS2 neuropathy in the rat. One hundred and fifty male rats were intoxicated with CS2 by a discontinuous inhalation exposure to 700 ppm for 12 weeks until a clear neuropathy developed. Thereafter the animals were subdivided at random into five groups and treated in different ways: 10 mg/kg BW gangliosides, 0.5 mg/kg gangliosides, 0.5 mg/kg vitamin B1, and 1 mg/kg vitamin B6, physiological solution, and controls without any treatment. The recovery from neuropathy was controlled for 18 weeks of treatment and assessed periodically by means of clinical, electromyographic, and morphological examination. The results of morphological studies showed more pronounced regeneration activity in the rats treated with the high dose of gangliosides than in all others, while no differences among the groups could be observed as far as clinical and neurophysiological parameters are concerned. The mechanism supporting this ganglioside-induced effect has so far not been ascertained, and further studies on this subject are in progress.

Animals↗

A clinical, neurophysiological and behavioral study of female workers exposed to 1,1,1-trichloroethane.

Twenty-two female subjects working in a factory in which 1,1,1-trichloroethane was the only solvent used were investigated by means of clinical, neurophysiological and psychometric methods so that the neurotoxicity of the solvent could be evaluated. On the basis of the ambient air concentrations of 1,1,1-trichloroethane ranging from 110 to 990 ppm, the workers were divided into three risk groups and compared with a reference group. No significant difference was observed between the exposed and unexposed females with respect to clinical features, maximal motor conduction velocity, conduction velocity of slow fibers, and psychometric data. The most frequent complaints of the workers were of the "neurotic" type with a slightly higher, but not significant, difference in the exposed group. The results obtained favor the absence of a manifest neurotoxic effect of 1,1,1-trichloroethane under the specific work conditions of the investigation; generally unfavorable work conditions seem to have played a prominent role in the genesis of the neurotic complaints. The importance of a global methodological approach in the study of work-related risks, particularly in neurological and psychological surveys, is stressed.

Adult↗

Biological monitoring of human exposure to acephate.

Acephate is a water-soluble organophosphate insecticide whose action on insects has been related to its conversion to methamidophos, a very potent anticholinesterase agent which has caused delayed neuropathy in man. Inhalation and skin exposure to acephate was evaluated in four workers engaged in 8-day campaigns with the formulation of the 97%-pure technical product. Before, during, and after exposure, the workers were monitored for the urine content of acephate and methamidophos, and for erythrocyte (AChE) and plasma (PChE) cholinesterase levels. Median air concentrations (8-hr TWA) ranged from 0.278 to 2.170 mg/m3; median total-body skin deposition ranged from 26.1 to 41.9 mg/day. Based on these values, daily workers' absorption of acephate was estimated to be in the order of 10-20 mg. Urinary excretion of unchanged acephate followed a pattern consistent with exposure, showing peak values of excretion during the workshift or in the eight hr after the end of the workshift. The urine levels of unchanged acephate were found to vary from 1 to 10 mg/L. Methamidophos was not detected in any urine sample (detection limit: 30 micrograms/L). High correlation (r = 0.78) was found between skin exposure level and urine acephate elimination. No changes in AChE or PChE were observed for the workers whose urinary concentrations of acephate were 1 or 2 mg/L. One subject who had urinary acephate excretion between 3 and 8 mg/L, showed slightly decreased values of PChE during exposure and of AChE after exposure.

Agricultural Workers' Diseases↗

Biological indicators of neurotoxicity in central and peripheral toxic neuropathies.

This article reviews the biological indicators available for monitoring human neurotoxicity by exogenous chemicals with reference to the phases in which the neurotoxic process takes place, namely delivery, receptor-linkage, and toxicodynamic phase. Among the delivery phase tests, indicators are available for metals (lead, mercury) and some organic substances (CS2, n-hexane, DDT, etc.), but a correlation between neurotoxic effects and these indices is rather loose or not yet proved. The receptor-phase tests comprise well known enzymes, such as cholinesterase, less known but promising indicators, such as neuropathy target esterase (NTE), and new tools under study, such as acrylamide-hemoglobin adducts or 2,5-hexanedione-protein adducts. The toxicodynamic phase tests, which mainly consist of measuring substances released from the nervous system, have provided so far rather poor results, but more specific techniques of measurement (monoclonal antibodies) could offer new possibilities in the future.

Animals↗

Toxicological and immune findings in workers exposed to pentachlorophenol (PCP).

Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls. PCP concentrations were determined in plasma and urine of all subjects. Lymphocyte subsets of CD3-, CD4-, and CD8-positive cells were evaluated, and the proliferative response of peripheral blood mononuclear cells (PBM) to mitogens was assessed. The results suggested the absence of major laboratory and clinical signs of PCP-dependent immune deficiency. A weak effect of long-term exposure to PCP on the functional immune response could not be ruled out because of the finding of a decreased response to 5% PHA in the high-exposure group. A weak effect against hepatocyte membrane was evidenced by the finding of raised serum concentration of glycocholic, taurodeoxycholic, and glycochenodeoxycholic acids in subjects directly exposed to PCP for more than 10 y.

Adolescent↗

Immunomodulatory effects of occupational exposure to mancozeb.

The effects of occupational exposure to ethylene-bis-dithiocarbamate of manganese and zinc on the immune system were evaluated in a group of mancozeb-exposed manufacturers and controls. The immune system tests revealed the following: (a) lymphocyte proliferative responses triggered by different activators and mitogen-induced IL-2 production were higher in exposed subjects than in controls; (b) production of monocyte/macrophage-derived IL-1 and polyclonal IgG and IgM, by beta-lymphocytes, did not differ between exposed subjects and controls; (c) percentages and absolute numbers of total T-cells, T-helper cells, T-suppressor/cytotoxic cells, activated T-cells, total beta-cells, and natural killer cells were similar in exposed subjects and controls; (d) serum immunoglobulin classes and complement fractions were within the range of normality; and (e) rheumatoid factor and non-organ-specific serum autoantibodies were absent in exposed and control subjects. An increase in T-cell functional response was found in the exposed group, suggesting a slight immunomodulator effect of mancozeb in conditions of low-level, prolonged occupational exposure.

Air Pollutants, Occupational↗