Exposure to toxic metals remains a widespread occupational and environmental problem in world. There have been a number of reports in the recent past suggesting an incidence of childhood lead poisoning and chronic arsenic poisoning due to contaminated drinking water in many areas of West Bengal in India and Bangladesh has become a national calamity. Low level metal exposure in humans is caused by air, food and water intake. Lead and arsenic generally interferes with a number of body functions such as the central nervous system (CNS), the haematopoietic system, liver and kidneys. Over the past few decades there has been growing awareness and concern that the toxic biochemical and functional effects are occurring at a lower level of metal exposure than those that produce overt clinical and pathological signs and symptoms. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Medical treatment of acute and chronic lead and arsenic toxicity is furnished by chelating agents. Chelating agents are organic compounds capable of linking together metal ions to form complex ring-like structures called chelates. They have been used clinically as antidotes for acute and chronic poisoning. 2, 3-dimercaprol (BAL) has long been the mainstay of chelation therapy for lead or arsenic poisoning. Meso 2, 3, -dimercaptosuccinic acid (DMSA) has been tried successfully in animals as well as in a few cases of human lead and arsenic poisoning. DMSA could be a safe and effective method for treating lead or arsenic poisoning, but one of the major disadvantages of chelation with DMSA has been its inability to remove lead from the intracellular sites because of its lipophobic nature. Further, it does not provide protection in terms of clinical/ biochemical recovery. A new trend in chelation therapy is to use combined treatment. This includes the use of structurally different chelators or a combination of an adjuvant and a chelator to provide better clinical/biochemical recovery in addition to lead mobilization. The present review article attempts to provide update information about the current strategies being adopted for a safe, effective and specific treatment for two major toxic metals or metalloid.
The concept of biological monitoring (BM) has gained the special interest of individual scientists and international organizations. Today, when analytical problems have almost ceased due to new laboratory techniques and quality assurance systems, the methods for interpretation of results have become the most important issue. There are important discrepancies regarding the role of biological monitoring of occupational exposure between Europe and the United States. BM has been an important tool of medical health surveillance in the European countries. In the United States it belongs rather to the field of occupational hygiene. It seems that both the approaches can be accepted. More attention should be paid to the development of the truly health-based biomarkers of exposure based on the dose-effect and dose-response relationships. New areas of application of BM of occupational exposure include determination of DNA and protein adducts, unchanged volatile organic compounds in urine, monitoring of exposure to pesticides, antineoplastic drugs, hard metals, and polycyclic aromatic hydrocarbons. In the general environment BM is the most valuable tool for acquiring knowledge of current levels of internal exposure to xenobiotics, identifying the hot spots and developments in trends of exposure. BM can provide policy makers with more accurate information on the control measures undertaken. At present, the main areas include heavy metals, persistent organic pollutants and pesticides. BM of chemical exposure has become increasingly important in the assessment of the health risk in occupational and environmental medicine. Therefore it would be worthwhile to include BM in the curricula for the training of occupational hygienists.
To elucidate the effect of maternal styrene exposure, which is due to various postnatal changes in the development and behavior of offspring, we investigated pregnancy-induced changes in the metabolism of styrene in rat liver in relation to the regulation of cytochrome P450 enzymes. We also examined age and sex-induced changes in the metabolism of styrene. Pregnancy appeared to exert a negative effect on cytochrome P450 content at the late stage, whereas microsomal protein content showed little change during pregnancy. Pregnancy significantly decreased the rate of formation of styrene glycol at the late stage. The percentage of remaining activity in microsomes exposed to anti-CYP2E1 was lower than that exposed to anti-CYP2C11/6 in pregnant and non-pregnant female rats and immature male rats, indicating that CYP2E1 contributes to the metabolism of styrene more than CYP2C11/6 in these rats. Although pregnancy seemed to decrease styrene metabolism, the contribution of CYP2E1 seemed to be slightly increasing. In conclusion, pregnancy clearly influences the metabolism of styrene as well as other characteristic factors such as age and sex. It is very important to elucidate the changes in specific P450 isozyme composition related to their characteristic modification and in their affinity for chemicals.
The most sensitive method used in monitoring the blood lead-level is atomic absorption spectrophotometry. Its limitation due to its high cost has made delta-aminolaevulinic acid dehydratase (δ-ALAD) inhibition more popular. This work demonstrates that ceruloplasmin (Cp), the blue-colored copper containing alpha-2 globulin (α2 globulin) glycoprotein in serum, can serve as a high-potential biomarker for lead exposure. Sephadex G-200 column chromatography demonstrated that lead-intoxicated patient serum transferrin and ceruloplasmin are bound to lead. The ceruloplasmin's oxidase and δ-ALAD activities are reduced when the blood-lead level increases (thresholds of 10.0 and 12.5 μg/100 mL respectively), with a correlation coefficient of -0.8643 and -0.6785 which accurately estimate a blood lead level of 74.7% and 46.0%, respectively. When the blood-lead level was less than 20 μg/100 mL, correlation coefficients of -0.5785 and -0.6963 suggested that Cp may serve as a good biomarker. Other advantages in using Cp in monitoring the blood-lead level were its stability: the enzyme was more stable at -20°C, for more than 2 wk, and its practical and rapid determination procedure.
We reported previously the autoantibodies directed to caspase-8 among patients with silicosis, systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) , and in healthy individuals. In this study, we analyzed the correlation between anti-caspase-8 autoantibody responses and HLA class II alleles in silicosis patients. The frequencies of HLA-DRB1*0406 were significantly higher in antibody positive patients (16.67%) than in control individuals (3.03%, p=0.0006). The lysine (K) at position 71 as in DRB1*0406 has been reported to be associated with rheumatoid arthritis (RA) and insulin dependent diabetes mellitus (IDDM). The haplotype HLA-DR4; DQB1*0302 was detected in 4 of 12 antibody positive patients. RA, IDDM, or pemphygus vulgaris link to the haplotype. The frequencies of DQB1*0401 were significantly lower in antibody positive patients (0%) than that in controls (13.33%, p=0.0390). The aspartic acid at position 57 in the DQB1 molecule as in DQB1*0401 is reported to play a role in the resistance to IDDM. The frequency of DPB1*0601 in antibody positive patients (5.88%) was significantly higher than that in controls (0.56%, p=0.0003). DPB1*0601 is reported to be a risk factor among RA patients, and glutamate at position 69 of the DPB1 molecule may be involved. Repeated and continuous screening of autoantibodies seems to be necessary among workers in contact with Si-related substances for the detection of immunological disorders in the early stage.
We examined whole blood (MnB), red blood cell (MnRBC), plasma (MnP) and urinary Mn (MnU) concentrations in 22 liver cirrhotics and 10 healthy controls to evaluate Mn concentration in which a fraction of biological samples best reflects pallidal signal intensities (pallidal index; PI) on T1-weighted magnetic resonance images (MRI) in liver cirrhotics. Increased signal intensity in the globus pallidus was observed in 18 (81.8%) of the 22 patients with liver cirrhosis. In a transplanted patient, increased pallidal signals also resolved as his liver function tests normalized after liver transplantation. There were significant correlations between MnB/MnRBC and PI (ρ=0.529, ρ=0.573, respectively) in liver cirrhotics, although no significant correlation was observed between MnP/MnU and PI. According to a multiple linear regression, MnB and MnRBC reflected the signal intensities of T1-weighted MRI better than MnP or MnU.
Workers in the salt industry are exposed to direct sunlight, salt dust and contact with brine. To assess their awareness, attitude and practices related to occupational health problems, 205 salt workers were interviewed about health hazards and problems related to their working conditions, usage of protective measures and suggestions for their improvisation. The brine workers had a fair knowledge of their occupational health problems (98.7%), protective measures (100.0%) and their benefits (100.0%) as compared to non brine workers for whom these figures were 89.0%, 85.8% and 78.7% respectively. The brine workers (29.5%) and non brine workers (31.5%) used unconventional measures to prevent contact with salty water, salt dust, raw salt and glare. There was a huge gap between their knowledge and practice with protective devices, though they suggested improvements in protective devices to increase their acceptability.