Attention deficit hyperactivity disorder and environmental toxic metal exposure in the United Arab Emirates.

No systematic studies have been carried out on the effects of toxic metals on childhood behavior in the Gulf Region including the UAE. The relationship between blood levels of heavy metals and Attention Deficit Hyperactivity disorder (ADHD) were explored in school-aged children of UAE and it was found that increased blood concentrations of lead (Pb), manganese (Mn) and zinc (Zn) were significantly associated with ADHD. The findings suggest that monitoring for exposure to heavy metal levels and education on potential child health hazards related to them are indicated.

Quantitative analysis of toxic and essential elements in human hair. Clinical validity of results.

Over the last three decades, there has been an increasing awareness of environmental and occupational exposures to toxic or potentially toxic trace elements. The evolution of biological monitoring includes knowledge of kinetics of toxic and/or essential elements and adverse health effects related to their exposure. The debate whether a hair is a valid sample for biomonitoring or not is still attracting the attention of analysts, health care professionals, and environmentalists. Although researchers have found many correlations of essential elements to diseases, metabolic disorders, environmental exposures, and nutritional status, opponents of the concept of hair analysis object that hair samples are unreliable due to the influence of external factors. This review discusses validity of hair as a sample for biomonitoring of essential and toxic elements, with emphasis on pre-analytical, analytical, and post-analytical factors influencing results.

Influence of urbanization of the western coast of the United Arab Emirates on trace metal content in muscle and liver of wild Red-spot emperor (Lethrinus lentjan).

We hypothesized that increased ambient concentrations of metals, as a consequence of escalating urbanization and industrialization of the Gulf region will respond in increased contamination of edible fish species. In this study, we report concentrations of chromium, manganese, cobalt, copper, zinc, arsenic, cadmium, mercury and lead in meat and liver of wild Red-spot emperor (Lethrinus lentjan) from three sampling points at the UAE coast. Analysis was performed by the ICP-MS/microwave digestion. Our study has shown that meat and liver metal content was significantly higher in areas with higher industrial activity, although metal values did not exceed permitted levels of fish for human consumption.

The association of exposure to cadmium through cigarette smoke with pregnancy-induced hypertension in a selenium deficient population.

Oxidative stress has been postulated as major contributor to endothelial dysfunction and pregnancy-induced hypertension. We have examined the association of exposure to cadmium through cigarette smoke with hypertension disorders during pregnancy in the selenium deficient population. Markers of lipid peroxidation and antioxidative defense were measured and correlated with cadmium blood concentration in normotensive and hypertensive pregnant smokers and nonsmokers. We have observed significantly higher blood Cd in hypertensive smokers and significant differences in all other parameters. Se concentrations were lower in smokers, both in normotensive and hypertensive group as well as values of nonenzymatic (Zn, Cu, and glutathione) and enzymatic (superoxide dismutase, glutathione peroxidase, and glutathione reductase) parameters of antioxidative defense. Results of the study indicate that exposure to cadmium through cigarette smoke in pregnant women, living in Se deficient areas is associated with significantly higher cadmium concentrations and lower levels of enzymatic and nonenzymatic antioxidants and that it can be considered as a risk factor for pregnancy-induced hypertension. Selenium supplementation should be considered for recommendation in such condition.

Organophosphate induced delayed polyneuropathy.

This review discusses the current understanding of organophosphate induced delayed polyneuropathy (OPIDP) with emphasis on molecular mechanisms, pathogenesis and possibilities for prevention/therapy. OPIDP is a rare toxicity caused by certain organophosphorus compounds (OP) characterized by degeneration of some long axons in the central and peripheral nervous system that appear about 2-3 weeks after exposure. The molecular target for OPIDP is considered to be an enzyme in the nervous system known as neuropathy target esterase (NTE). NTE can be inhibited by two types of inhibitors: a) phosphates, phosphonates, and phosphoramidates, which cause OPIDP when >70% of the enzyme is inhibited, and b) phosphinates, carbamates, and sulfonyl halides which inhibit NTE and cause either protection from, or promotion, of OPIDP when given before or after a neuropathic OP, respectively. The ability of a NTE inhibitor to cause OPIDP, besides its affinity for the enzyme, is related to its chemical structure and the residue left attached to the NTE. If such residues undergo the aging reaction i.e. the loss of an alkyl group bound to the enzyme, those OPs usually have a high likelihood of causing OPIDP. Protection from neuropathic doses of OP inhibitors is obtained when NTE is inhibited with nonageable inhibitors. Promotion of OPIDP involves another site besides NTE because it can occur when all NTE is affected. It is now known that this other site is similar to NTE in that it is also sensitive to mipafox but at much higher concentrations. Promotion affects either the progression or expression of OPIDP after the initial biochemical effect on NTE. Some recent observations suggest that development of OPIDP in hens can be influenced by atropine, oximes and methylprednisolone when they are given before or soon after neuropathic OPs.

Maternal and fetal cadmium and selenium status in normotensive and hypertensive pregnancy.

Cadmium and selenium concentrations in maternal and umbilical cord blood and amniotic fluid were determined in 37 normotensive and 23 hypertensive women during the last trimester of pregnancy in relation to their smoking status. Thiocyanate concentration in plasma was used as the index of smoking status. Cadmium and selenium were determined with atomic absorption spectrometry (graphite furnace and mercury hydride system). In the group of normotensive and hypertensive women, significantly higher cadmium and lower selenium concentrations in blood in smokers were observed than in nonsmokers. Umbilical cord blood selenium concentrations in both normotensive and hypertensive smokers were significantly lower than in nonsmokers as well. In the group of normotensive women, significant differences in selenium concentrations in amniotic fluid were observed between smokers and non-smokers. In conclusion, the results of this study show that hypertension in pregnant women smokers is related to significantly higher blood cadmium concentrations, which indicates that cadmium may be considered as an independent factor involved in hypertension.

Oxidative damage and inflammation in obese diabetic Emirati subjects.

Visceral obesity is more common in the Arab population and more closely related to morbidity, including diabetes and related cardiovascular diseases (CVD). Possible mechanisms that link visceral fat/obesity to diabetes and CVD complications include inflammation and increased oxidative stress; however, few data are available from the Arab population. Our aim was to determine whether increased adiposity in obese diabetic United Arab Emirates citizens is associated with sub-clinical inflammation and/or increased oxidative stress. A hundred diabetic patients who were part of a randomized controlled trial of nutritional supplements had their baseline characteristics assessed from anthropometric and clinical data following informed written consent. We used WHO figures to classify general and central obesity. Fasting blood samples were collected for the measurement of antioxidants and markers of oxidative damage and inflammation. We found that increased adiposity measured by both body mass index and waist circumference was associated with increased C-reactive protein (CRP) and decreased vitamin C after adjusting for age, duration and treatment of diabetes (p < 0.05). Although there is a clear trend of increased inflammatory markers, notably CRP, and decreased antioxidants with increased BMI and waist circumference in both men and women, the results are statistically significant for women only. CRP were also inversely associated with HDL. Overall, we found that BMI underestimates the rates of obesity compared to waist circumference and that increased adiposity is associated with increased inflammation and decreased HDL and antioxidant status.

Learning disorder and blood concentration of heavy metals in the United Arab Emirates.

Children are frequently exposed to toxic metals in the environment, and their developing central nervous system is particularly vulnerable to their effects. This study examined the blood level of heavy metals in children with learning disorder (LD) as compared to children without LD in the United Arab Emirates (UAE). Significantly high blood concentrations of seven heavy metals were found in children with LD. Further analysis using forward stepwise logistic regression showed that molybdenum levels and family history of developmental problems were the best predictors of LD. Our findings suggest the need for monitoring for toxic metals in the environment.

Organophosphate induced delayed polyneuropathy in man: an overview.

About 80 years have passed since the first cases of organophosphate induced delayed polyneuropathy (OPIDP), as the consequence of human poisoning with certain organophosphorus compounds, were described in the literature. OPIDP is a relatively rare neurodegenerative disorder in humans characterized by loss of function, ataxia and paralysis of distal parts of sensory and motor axons in peripheral nerves and ascending and descending tracts of spinal cord appearing 2-3 weeks after exposure or later. The molecular target for OPIDP is considered to be an enzyme in the nervous system known as neuropathy target esterase (NTE). This review discusses OPIDP in man with emphasis on clinical presentation, pathogenesis, molecular mechanisms, and possibilities for prevention/therapy.

Neurotoxic effects in patients poisoned with organophosphorus pesticides.

In this paper we review neurotoxic disorders appearing in patients poisoned with organophosphorus pesticides. These compounds cause four important neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP) and chronic organophosphate-induced neuropsychiatric disorder (COPIND). Compared to the cholinergic syndrome, that causes millions of cases of poisoning each year, other disorders involve much smaller numbers of patients. The review is focused on the neurotoxic effects appearing after acute and chronic exposure to organophosphates with emphasis on clinical presentation, pathogenesis, molecular mechanisms, and possibilities for prevention/therapy.

Trace element composition of plasma and breast milk of well-nourished women.

A wide variation in the composition of breast milk has been reported from various countries. This study was undertaken to determine the trace element content of breast milk and plasma in lactating women. Mothers of children 4 weeks to 80 weeks in age, were studied. Blood and breast milk from the mothers were analysed for trace element content. Prepared samples were analysed using ICP-MS. 209 women agreed to take part in the study, 68 of whom were from the UAE and 124 were other nationalities (17 did not fill the this part of the questionnaire). Ninety-seven infants were male. The concentration of different trace elements in blood and breast milk were little different between women from the UAE and those from outside the UAE. Molybenum, chromium and arsenic significantly increased with increasing age of the infant, while manganese, copper and zinc significantly decreased with increasing age of the infant. The trace element concentrations of breast milk and maternal blood were comparable to published values. Normal values for plasma and breast milk trace metal concentrations have been obtained for UAE women.

Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses.

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.

Metoclopramide protection of cholinesterase from paraoxon inhibition.

This study evaluated the protective effect of the benzamide compound metoclopramide (MCP) against inhibition by paraoxon (POX) as assessed by red blood cell acetylcholinesterase (RBC-AChE) activity. Three groups of 6 rats each were used. All substances were applied ip daily for 5 d, followed by a 2-d rest. The 7-d cycle was repeated 6 times. Group 1 received 100 nM POX, Group 2 received 50 microM MCP. Group 3 received 100 nM POX + 50 microM MCP. Red blood cell acetylcholinesterase measurements were performed at base line and then after each 7-d cycle. Enzyme activities were compared using the Mann-Whitney rank order test. Metoclopramide conferred significant in vivo protection from inhibition of RBC-AChE by POX.

In vitro protection of red blood cell acetylcholinesterase by metoclopramide from inhibition by organophosphates (paraoxon and mipafox).

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition, MCP is a reversible inhibitor of cholinesterases from the human central nervous system and blood, and may have a red blood cell (RBC) acetylcholinesterase (AChE) protective effect against inhibition by organophosphates. The purpose of the study was to quantify 'in vitro', by means of the IC50 shift, the extent of MCP conferred protection, by using paraoxon (POX) and mipafox (MPFX) as inhibitors. Paraoxon is a widely used non-neuropathic organophospate responsible for a large number of accidental or suicidal exposures. Mipafox is a neuropathic organophospate. Red blood cell AChE activities in human plasma were measured photometrically in the presence of different POX, MPFX and MCP concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the IC50 shift induced by the presence of MCP increases with the MCP concentration in a linear manner. The protective effect of MCP on cholinesterases could be of practical relevance in the treatment of POX and MPFX poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.