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Biomedical subjects

L Alessio

Publications and source records attributed to L Alessio.

At least 37 records · Page 2Linked to original sources

Manganese effects on the human neuroblastoma cell line SK-ER3.

SK-ER3 cells were recently demonstrated to represent a valuable model for the study of estrogen-inducible differentiation of neural cells in culture. This system may constitute an important tool also for the analysis of the effects of neurotoxic drugs. The present study demonstrates that short term exposure to Mn causes increased proliferation rate of SK-ER3 cells regardless of their differentiation. Long term treatment causes cell death in undifferentiated cells at concentrations of the metal as low as 100 nM. When the cells are differentiated with estrogens, death is observed only with a Mn concentration two orders of magnitude higher. Measurement of neurite extension and quantitation of tyrosine hydroxylase content after long-term exposure to the metal allow the conclusion that Mn does not alter the state of differentiation of SK-ER3 cells induced by the treatment with the hormone. The study underlines the importance of studying the effect of Mn in proliferating neural cells and demonstrates the toxic role of micromolar concentrations of the metal in fully differentiated neural cells. Since other authors produced evidence of effects of the metal on cell death and proliferation only at millimolar concentrations, and none described its proliferative activity, the model utilized in the present study seems to be of particular interest.

Cell Differentiation↗

Neurotoxicity in operating room personnel working with gaseous and nongaseous anesthesia.

Occupational exposure to high concentrations of anesthetic gases (more than 500 ppm of nitrous oxide and more than 15 ppm of halothane and enflurane) can cause neurobehavioral effects in operating room personnel. Factors such as stress and work organization play an additional role in reducing performance capacities. It is still unclear whether these conditions may become the predominant factor in behavioral impairment when exposure to anesthetic gases is reduced; in addition, we wished to ascertain the extent of neurobehavioral and neuroendocrine effects at relatively low levels of exposure to such gases. Therefore the same group of 30 operating room personnel was examined with neurobehavioral tests during gaseous and nongaseous anesthesia. In this way, the neuropsychological performance was examined under the same stress conditions, but with different exposure levels to anesthetic gases. Serum cortisol was measured as an additional "biological stress indicator." Prolactin secretion was examined to study possible interference of anesthetic gases with the dopaminergic system. The results were compared with those in a control group of 20 hospital workers from other departments, with similar characteristics in respect of age, sex, and education. During work with gaseous anesthesia, average airborne concentrations (geometric mean) of nitrous oxide were 50.9 ppm (SD 20.8) on the first day of the working week, and 54.2 ppm (SD 22.1) on the last day of the working week, whereas average urinary nitrous oxide (geometric mean) were 21.54 micrograms/l on the first day of the working week and 25.67 micrograms/l on the last day of the working week. The operating room workers showed slower reaction times at the end of the week with gaseous anesthesia, compared with workers using nongaseous anesthesia and the control group. At the same time they also showed increased secretion of prolactin, whereas cortisol remained unchanged. Therefore, it can be concluded that lower levels of exposure to anesthetic gases (and not only high exposure levels) cause an impairment of neurobehavioral performance, with the action of stress being less relevant. The mechanism of anesthetics' neurotoxic action seems to be related to interference with the dopaminergic system.

Adult↗

Immune infiltrates and cytokines in gliomas.

Frozen sections of 21 gliomas were analysed to characterize inflammatory infiltrating cells, HLA-DR antigen expression and cytokine secretion. Mononuclear cells infiltrating the tumours were mostly macrophages, which were detected in 100% of cases, and expressed HLA-DR antigens. Lymphocytes were less frequently seen and expressed the CD8 phenotype. Interleukin-1 beta (IL-1 beta) and Interleukin-6 (IL-6), two cytokines mainly produced by activated cells of the macrophage lineage, were demonstrated especially in neoplastic astrocytes. IL-1 beta immunoreactivity was detected in all tumours, and was prevalent in more anaplastic gliomas; IL-6 was found in anaplastic gliomas and in glioblastomas. IL-1 receptors were expressed by both infiltrating macrophages and neoplastic astrocytes in the gliomas analysed. These findings suggest that cytokine production in gliomas seems not related to immune reactions against the tumour and their synthesis by anaplastic astrocytes could follow an unregulated activation of many metabolic processes after neoplastic transformation.

Astrocytes↗

The use of chelating agents in occupational lead poisoning.

Chelating agents have long been used in the pharmacological treatment of lead poisoning, whose management is still a problem, particularly in developing countries. This article reviews the pharmacological properties of dimercaprole, peniclliamine. CaNa2EDTA and dimercaprosuccinic acid, examines their indications, contraindications and side effects and discusses the possible use of each drug in occupational Pb poisoning. Proposals are also presented for the treatment and follow-up of subjects with signs and symptoms of poisoning and of subjects with low-moderate Pb absorption. CaNa2EDTA seems to be the most reliable and safer chelating agent nowadays available and with a wider spectrum of action. DMSA seems to be promising in the treatment of occupational Pb poisoning. Even though there is no doubt that chelation therapy has significantly contributed to reduce mortality and morbidity from occupational Pb poisoning, the efficacy of this treatment in subjects with subtle neurological or renal damage has not yet been studied properly.

Body Burden↗

Bladder cancer and occupation: a case-control study in northern Italy.

OBJECTIVES: A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer. METHODS: The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence. RESULTS: A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found. CONCLUSIONS: Occupational exposures seem to contribute to bladder cancer risk in the area under study.

Adult↗

Interferences of urinary tract infection in the measurement of urinary nitrous oxide.

OBJECTIVES: To investigate the effective role of micro-organisms in producing N2O. METHODS: The N2O in either urine samples inoculated with 24 microbial strains or urine samples from patients with urinary tract infections were measured. RESULTS: Gram negative bacilli generally produced high amounts of nitrous oxide (N2O), whereas Gram positive cocci and yeasts did not. The production of N2O depends on the incubation time and follows exponential kinetics, reaching a plateau at 48 hours. Furthermore, the results of urinocultures agreed well with N2O concentrations found in urine samples: samples negative for bacteria were found to contain very low concentrations of N2O whereas those positive--for example, for Enterobacteriaceae--gave highest N2O values. CONCLUSION: The urinary tract infections caused by Gram negative bacilli are important confounding factors in biological monitoring practices of exposure to inhalation anaesthetics. The current methods adopted to avoid these factors (urine acidification, storage of samples at 4 degrees C) are not good enough because of the relative acid tolerance of some strains and the production of N2O directly into the bladder.

Anesthetics, Inhalation↗

Influence of individual factors and personal habits on the levels of biological indicators of exposure.

The progressive improvement of hygienic conditions in the workplace has increased the importance of obtaining detailed information on extra-occupational factors that might influence the levels of the biological indicators. This information is indispensable both when subjects belonging to the general population are selected for establishing 'reference values' and when subjects occupationally exposed to specific chemical substances are studied. In non-occupationally exposed subjects the biological indicator levels may be influenced by circumstances which enhance absorption of the substance in question. Examples of interference factors considered for biological indicators of main metals are: gender, age, smoking habits, alcohol consumption and dietary habits. In occupationally exposed subjects the levels of the biological indicators can be influenced by factors that interfere with the metabolism of the substances absorbed in the workplace. In particular, factors such as alcohol, drugs and tobacco appear to play an important role in modifying the biological indicator levels in the occupationally exposed. Ethanol can inhibit as well as induce the metabolism of solvents. Inhibition occurs after excessive ingestion of ethanol, whereas induction occurs in subjects who regularly consume alcohol. There are several examples of inhibition of the metabolism of solvents by alcohol in man, occurring at levels of exposure frequently encountered in the workplace, also within the 'occupational exposure limits', (OEL). Conversely, there are very few studies on the effects of induction, which presumably occur only when the exposure levels greatly exceed OEL. Among drugs, analgesics seem to play a particular role in interfering with the metabolism of solvents. Since cigarette smoking is frequently associated with alcohol ingestion at present it is difficult to extrapolate the isolated effect of smoking on the metabolism of solvents. In order to facilitate interpretation of the results of biological monitoring, we propose to prepare informative sheets for the main substances which will contain information on factors that can influence the levels of the indicators.

Biomarkers↗

Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure.

OBJECTIVES: The goal of this study was to assess long-term neurobehavioral effects associated with low airborne concentrations of manganese in a ferroalloy plant. METHODS: During a period of forced cessation of work (1 to 42 d) neurobehavioral performance on tests of simple reaction time, finger tapping, digit span, additions, symbol digit, and shapes comparison was evaluated for 58 workers exposed from 1 to 28 (mean 13, SD 7) years to manganese. Airborne manganese concentrations in total dust had been reduced in the last 10 years from 70-159 micrograms x m-3 (geometric means in different areas) to 27-270 micrograms x m-3. For each worker, manganese concentrations in blood and urine were measured, and a cumulative exposure index was also calculated. RESULTS: Blood manganese and urinary manganese ranged from 4 to 18 micrograms x 1-1 (0.07 to 0.03 mumol x 1-1) and from 0.7 to 7 micrograms x 1-1 (0.01 to 0.13 mumol x 1-1) respectively. Significant relationships were found between the blood manganese and urinary manganese levels and between these biological measures and the cumulative exposure index. Correlations were also found between the blood manganese level, the urinary manganese level, and the cumulative exposure index and the following tests: finger tapping, symbol digit, digit span, and additions. The correlation coefficients increased as the latency time after the cessation of exposure and work seniority increased. CONCLUSIONS: The results support the hypothesis that the neurobehavioral effects observed at exposure levels well below current occupational standards are related to manganese body burden, which is better reflected by the blood manganese level after the cessation of exposure.

Adult↗

Estimation of pooled reference values for cadmium in blood using meta-analysis and TRACY criteria.

Reference values for blood-cadmium levels (B-Cd) are available for only a limited number of geographical areas and for particular population strata (sex, age, smoking habits). This paper, in agreement with the TRACY guidelines, describes and discusses the criteria used to rank published papers on reference values for cadmium retrieved by Medline and Toxline between 1976 and 1991. The TRACY criteria deal with the grading of published papers in terms of their suitability for calculating provisional reference values. Only four out of 18 papers were considered suitable for the TRACY project. The four articles were finally used via meta-analysis to provide provisional reference values for smokers and non-smokers. The comparison of results obtained using published statistics and individual data is used to discuss the appropriateness of meta-analysis in the case of cadmium. Due to the availability of large enough studies and to the clear differences across countries, the suitability of a compound upper reference limit to B-Cd levels seems limited.

Adult↗

Urinary cobalt excretion in short time occupational exposure to cobalt powders.

In order to evaluate the urinary excretion of cobalt, a study was carried out in two plants producing diamond segments and sintered wires for stone cutting. In both plants, the highest Co exposures were found during mixing and granulation of Co powders, generally performed 1-2 times per week for 1-2 h in the first plant and 3-4 h in the other. Environmental hygiene conditions were good in the first plant and poor in the other with environmental Co concentrations around the ACGIH TLV (50 micrograms/m3) in the first and many times higher (up to 8000 micrograms/m3) in the second. In two workers employed in the above mentioned jobs. Cobalt in urine (CoU) was determined in samples collected during the first day, before shift and about 2, 4, 7 and 10 h after the beginning of exposure; samples were also collected on the 2nd, 3rd and 4th day, before and at the end of the shift. The study showed that Co in urine rapidly increased in the hours following the cessation of exposure, with a peak of elimination about 2-4 h after exposure, and a subsequent decrease (more rapid for the first 24 h) in the following days. Such a pattern was apparently independent of the degree of exposure, since it was detected in both plants and confirmed also in an industrial hygienist with lower Co exposure. The data indicate that for a correct evaluation of Co exposure through CoU determination, variables such as type and characteristics of the job and most importantly, the times at which biological samples are collected should be carefully considered.

Cobalt↗

The utility of health education among lead workers: the experience of one program.

Health education represents a fundamental tool in the prevention of occupational diseases. For lead-exposed workers, work practices, personal hygiene, and life habits are certainly influences in the amount of the metal absorbed in the body. This study evaluated the effectiveness of a health education program in 50 workers exposed to inorganic lead employed in seven small factories. The study was performed in 3 phases over one year. Before the program, blood lead levels were measured, and a questionnaire was administered in order to evaluate the baseline knowledge of the workers about lead poisoning and its prevention. After the health education program, the blood lead levels decreased (from 38.2 to 32.3 micrograms/dl) and the questionnaire scores improved in a highly significant manner (p < 0.001). These results were obtained both in the short (4 months) and in the medium term (1 year). The reduction of blood lead concentrations seemed to be due to changes in hygienic behaviors and life habits, such as alcohol consumption or cigarette smoking, probably induced by an increase in specific knowledge about the prevention of lead damages.

Adult↗

Increases in polycyclic aromatic hydrocarbon content and mutagenicity in a cutting fluid as a consequence of its use.

The aim of this study was to evaluate the relationships between the length of time a cutting fluid was used, its content in polycyclic aromatic hydrocarbons (PAHs) and its mutagenic potential. The PAH concentrations were determined by means of a high-resolution gas chromatograph-mass spectrometer in samples of new cutting fluid and in samples used for 3, 6 and 9 months. The following PAHs were measured: phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene+triphenylene, benzo[e]pyrene, benzo[a]pyrene and perylene. Mutagenicity assays were carried out on the aforementioned samples using the Ames test. Salmonella typhimurium TA98 was used as an indicator to show up mutagens capable of inducing frame-shift genetic changes, and Escherichia coli WP2 uvrA was used as an indicator to detect mutagens capable of inducing base pair genetic changes. The mutagenic tests were carried out with and without microsomal activation, using 1:1, 1:10, 1:20 and 1:50 dilutions of cutting fluid samples. An increase in the concentrations of total PAHs over time was observed in the samples of cutting fluid used for 3, 6 and 9 months. The highest percentage increase in PAH concentrations was observed in the 6-month-old sample (10 times the initial concentration, from 45 to 411.8 micrograms of oil). None of the samples were mutagenic to S. typhimurium without metabolic activation or to E. coli with and without metabolic activation. All samples except for the 1:1 diluted sample showed moderate but significant mutagenic activity in the S. typhimurium test with metabolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Industrial Oils↗

Reference values for the study of low doses of metals.

The role of biological monitoring (BM) in the prevention of exposure to toxic metals has currently acquired considerable importance. However, in the near future the usefulness of BM in occupational medicine could be reduced by the fact that exposure to toxic substances will progressively decrease and consequently problems of comprehension will occur. BM can maintain its importance in the prevention field if sensitivity and specificity of the biological indicators (BI) are increased and if this activity is specifically directed towards groups of subjects. To achieve this last goal, one of the problems which must be solved is the identification of "reference values" (RV) which define the BI levels in the general population not occupationally or environmentally exposed to the toxic substance under study. It is necessary to "refer" to these values in order to compare the data obtained in a population which is presumed to be exposed. In this presentation, the example of blood cadmium is used in order to discuss the criteria required to identify RV. Herein the data of a personal case list are reported, particularly the variables which must be considered when selecting subjects to form "reference groups". Conversely, the possibility of obtaining RV through meta-analysis studies, pooling the results published in international literature, are evaluated.

Adult↗

International project for producing reference values for concentrations of trace elements in human blood and urine--TRACY.

In assessing the concentrations of toxic metals, such as cadmium, chromium, and mercury, in human blood and urine samples to determine whether they are abnormal or not, reliable reference values are needed from populations of nonoccupationally exposed subjects. Numerous publications present concentrations claimed to be typical for the study populations, but they can differ by up to an order of magnitude for a particular element. This is the consequence of general problems that are related to the definition of the reference groups, and the sampling and analytical procedures used, and that make it difficult to define typical and unbiased values. An international group of experts now establishes criteria and procedures to evaluate publications containing information on the concentrations of metals in tissues and body fluids for reference populations. These evaluations have been compiled in a data base (TRACY).

Hazardous Substances↗

Biological monitoring of cadmium exposure--an Italian experience.

Studies carried out over the last 12 years in northern Italy on a case list of 105 cadmium (Cd) workers showed that blood levels (B-Cd) were influenced not only by current exposure but also by body burden, while urinary levels (U-Cd) were influenced predominantly by body burden. Moreover, no advantages were gained by adjusting U-Cd for creatinine or specific gravity. The urinary beta 2-microglobulin levels were within the reference values when B-Cd and U-Cd were below the current threshold values. However, some indicators of early renal effect appeared to be altered. An increase in chromosome-type aberrations in lymphocytes occurred in workers with a heavy cadmium burden. Studies carried out on more than 600 subjects from the general population showed higher B-Cd levels in smokers than in nonsmokers. B-Cd levels were higher in men and in higher age groups. Identifying reference values for B-Cd through meta-analysis studies seems useful.

Cadmium↗

Reference values for the study of low doses.

At present, the quantitative differences between environmental exposure and occupational exposure to toxic metals are steadily decreasing, it becomes important to establish reference values of the tests used for biological monitoring. However, the word 'reference values' is often used inappropriately and in particular its significance is often confused with that of 'limit values' or 'normal values'. The term reference values defines the levels of the biological indicators in the general population which are not occupationally exposed. It is necessary to refer to these values in order to compare the data obtained through biological monitoring programmes in workers and in groups of the general population which are presumed to be exposed. The most essential aspects for identifying reference values for toxic metals, using a rigorous methodology, are taken into consideration and in particular, the requisites needed for identifying the subjects which must be included in the reference groups are also examined. The modalities for using reference values for individual subjects as well as for groups are then discussed and the main points of research which must be faced in the near future regarding reference values are highlighted.

Environmental Monitoring↗

Ten-year follow-up of biological monitoring of cadmium-exposed workers.

In this study, 105 workers exposed to cadmium for over 10 years were subjected periodically to environmental monitoring, biological monitoring and medical surveillance. They were divided into subgroups, one in which Cd-B and Cd-U exceeded 10 micrograms/l and 10 micrograms/g creatinine respectively and the other in which they were below these proposed biological exposure indices. Urinary beta 2-microglobulin was used as an indicator of tubular damage. Over the past 3 years 12 workers had raised urinary beta 2-microglobulin values (above 250 micrograms/l). Among workers with Cd-B and Cd-U levels always below the above limits, less than 3% had increased urinary excretion of beta 2-microglobulin, a percentage comparable with that of the reference population. When Cd-B exceeds 10 micrograms/l and Cd-U 10 micrograms/g creatinine on one or more occasions (although the median value still remains below this level), the frequency of tubular damage seems to be considerably higher (8.4 and 7.5% respectively). Thus the Cd-B and Cd-U limits proposed appear to be quite safe if strictly respected. However, median values appear too high to rule out the possibility of an increased incidence of tubular alterations.

Adult↗