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ENVIRONMENTAL ~dEnvironmental ~tUse of nanoparticles for degradation of water contaminants in oxidative and reductive reactions ~w2010-05-14 Nanomaterials have received extensive attention recently as the next generators of scientific revolution. As such, nanomaterials are expected to be implemented in a wide range of applications. In the environmental field, nanomaterials hold promise for providing elegant solutions to numerous problems, from implementation of green chemistry processes for industrial and agrochemical uses, to production of novel materials for treatment of various contaminants. In this context the elimination of hazardous materials from the water environment is a major challenge facing environmental scientists today. In this chapter we present some results of our recent studies towards degradation of water contaminants. We exemplify both oxidative and reductive pathways for water remediation. In both cases we show the transformation of persistent contaminants through the use of nanomaterials as catalysts under ambient conditions. Authors: Dror, Ishai; Ben Moshe, Tal; Berkowitz, Brian Full Source: ACS Symposium Series 2009, 1027(Environmental Applications of Nanoscale and Microscale Reactive Metal Particles), 23-37 (English) ~dEnvironmental ~tFish from an artificial lake: n-3 PUFA content and chemical-physical and ecological features of the lake ~w2010-05-14 The beneficial health effects of n-3 polyunsaturated fatty acids (PUFAs) from marine fish are widely recognized. However, concern exists about the safety of fish intake, since the water in which they live is often highly contaminated. In the present work we analysed the n-3 PUFA and R- and ç-tocopherol composition of 12 fish species from an artificial lake located in an Italian region far from metropolitan and industrial sites, to evaluate whether the n-3 PUFA content could be comparable to that of marine fish, and whether the levels of the antioxidant tocopherols were enough to ensure a correct preservation of the fish after being caught. Moreover, we studied the chemical and physical features of the lake water and the levels of chemical pollutants present. The benthic macro invertebrates representing the main food source for freshwater fish were also analysed. The good chemical-physical quality of the water, as well as the n-3 PUFA and tocopherol levels in the fish, would constitute the basis for advising the dietary usage of these fish to increase intakes of these important nutrients. Pregnant or lactating women, and infants after weaning, in particular, could benefit from eating them, since safe and adequate n-3 PUFA dietary supplementation is required to guarantee the correct pre- and post-natal development of cerebral tissues in children. Authors: Serini, Simona; Piccioni, Elisabetta; Rinaldi, Cristina; Mostra, Daniela; Damiani, Giovanni; Calviello, Gabriella Full Source: Journal of Food Composition and Analysis 2010, 23(2), 133- 141 (English) MEDICAL ~dMedical ~tLead inhibits in vitro creatine kinase and pyruvate kinase activity in brain cortex of rats ~w2010-05-14 Lead intoxication is a serious occupational disease that constitutes a major public health problem. Lead, a heavy metal, has been used by humans for many technological purposes, which is the main reason for its widespread distribution. The toxic mechanisms of lead on the molecular machinery of living organisms include metal transport, energy metabolism, diverse enzymic processes, genetic regulation, and membrane ionic channels and signalling molecules. Since lead is able to cross the blood-brain barrier it may cause neurotoxicity. Creatine kinase and pyruvate kinase are two thiol-containing enzymes that exert a key role for cellular energy homeostasis in brain. Our main objective was to investigate the in vitro effect of lead on pyruvate kinase and creatine kinase activities of extracts and subcellular fractions from the brain cortex of rats in the presence or not of thiol-protecting substances such as glutathione and cysteamine. The results showed that lead inhibited the two enzyme activities and the thiol-protecting substances prevented their inhibition. These results suggest that lead inhibits creatine kinase and pyruvate kinase activity by interaction with their thiol groups. Therefore, lead may disrupt energy homeostasis and this effect may contribute to the neurological dysfunction found in lead exposed individuals. Authors: Lepper, Tatiana Wannmacher; Oliveira, Evandro; Koch, Gustavo Duarte Waltereith; Berlese, Daiane Bolzan; Feksa, Luciane Rosa Full Source: Toxicology in Vitro 2010, 24(3), 1045-1051 (English) ~dMedical ~tUsing biologic agents in paediatric rheumatologic diseases ~w2010-05-14 Juvenile Idiopathic Arthritis (JIA) is an "umbrella" term which is used to cover Juvenile Rheumatoid Arthritis (JRA) and Juvenile Chronic Arthritis (JCA). Biologic agents are needed when others like NSAIDs (Non-steroidal anti-inflammatory agents), DMARDs (Disease modifying antirheumatic drugs) cannot provide or maintain clinical remission, and patients are mainly bound on steroids, which are potential anti-inflammatory drugs with serious well-known side effects to the growing child. TNF-R antagonists are the first anticytokine agents introduced in the last decade. However, there are important subtypes, such as systemic JIA which are resistant to these drugs, because IL-1 â (Interleukin 1 â) activation is shown to be the main pathway. One of the most frequently asked questions about biologics, particularly ETN (Etanercept), is the duration of the treatment, regarding both the safety and efficacy. Regarding the current literature, ETN seems to be effective and safe in treating the children with JIA. The high dose regimen (6 mg/kg) of infliximab, a TNF monoclonal antibody, has achieved better results on JIA and is now used in paediatric rheumatology practice. Adalimumab, another TNF inhibitor and abatacept (CTLA-4) were also shown to be effective and safe in JIA. Anakinra, canakinumab, and tocilizumab are the ones recently studied, and they are shown to be effective particularly for systemic arthritis. Author: Unsal, Erbil Full Source: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2010, 9(1), 41-45 (Eng) ~dMedical ~tNaltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics ~w2010-05-14 Naltrexone is an opioid receptor antagonist with established efficacy, albeit moderate, for the treatment of alcohol dependence. This manuscript provides a critical review of the literature on naltrexone as a pharmacotherapy for alcoholism by covering the following areas: (a) clinical findings from treatment studies; (b) pharmacokinetics and safety data; (c) medication compliance and persistence; and (d) neurobiological and biobehavioural mechanisms of action of naltrexone for the indication of alcohol dependence. This review will then focus on the emerging literature on naltrexone pharmacogenetics, which has the potential to identify responders on the basis of genetic variation and to use genetic tools to individualize the use of this medication. Limitations and future directions in the research and practice of naltrexone for alcoholism are also outlined. Authors: Ray, Lara A.; Chin, Pauline F.; Miotto, Karen Full Source: CNS & Neurological Disorders: Drug Targets 2010, 9(1), 13-22 (Eng) ~dMedical ~tCapture Compound Mass Spectrometry Sheds Light on the Molecular Mechanisms of Liver Toxicity of Two Parkinson Drugs ~w2010-05-14 Capture compound mass spectrometry (CCMS) is a novel technology that helps understand the molecular mechanism of the mode of action of small molecules. The Capture Compounds are trifunctional probes: A selectivity function (the drug) interacts with the proteins in a biological sample, a reactivity function (phenylazide) irreversibly forms a covalent bond, and a sorting function (biotin) allows the captured protein(s) to be isolated for mass spectrometric analysis. Tolcapone and entacapone are potent inhibitors of catechol-O-methyltransferase (COMT) for the treatment of Parkinson's disease. We aimed to understand the molecular basis of the difference of both drugs with respect to side effects. Using Capture Compounds with these drugs as selectivity functions, we were able to unambiguously and reproducibly isolate and identify their known target COMT. Tolcapone Capture Compounds captured five times more proteins than entacapone Capture Compounds. Moreover, tolcapone Capture Compounds isolated mitochondrial and peroxisomal proteins. The major tolcapone-protein interactions occurred with components of the respiratory chain and of the fatty acid β -oxidation. Previously reported symptoms in tolcapone-treated rats suggested that tolcapone might act as decoupling reagent of the respiratory chain. Our results demonstrate that CCMS is an effective tool for the identification of a drug's potential off targets. It fills a gap in currently used in vitro screens for drug profiling that do not contain all the toxicologically relevant proteins. Thereby, CCMS has the potential to fill a technological need in drug safety assessment and helps reengineer or to reject drugs at an early preclinical stage. Authors: Fischer, Jenny J.; Michaelis, Simon; Schrey, Anna K.; Graebner nee Baessler, Olivia; Glinski, Mirko; Dreger, Mathias; Kroll, Friedrich; Koester, Hubert Full Source: Toxicological Sciences 2010, 113(1), 243-253 (Eng) ~dMedical ~tDiscovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach ~w2010-05-14 In order to develop a safety biomarker for atorvastatin, this drug was orally administered to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg-1 day-1 or 250 mg kg-1 day-1 for a period of 7 days (n ) 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatograohy/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers. Authors: Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa Full Source: Analytica Chimica Acta 2010, 661(1), 47-59 (Eng) OCCUPATIONAL ~dOccupational ~tThe New Zealand Workforce Survey I: Self-Reported Occupational Exposures ~w2010-05-26 This study examines the prevalence of a range of occupational risk factors reported by a random sample of the New Zealand working population. Men and women aged 20-64 were selected from the New Zealand Electoral Roll and invited to take part in a telephone interview, which collected information on lifetime work history, current workplace exposures and organisational factors, and various health conditions. The prevalence of occupational risk factors in each occupational and industry group are reported. Three thousand and three interviews were completed (37% of the eligible sample and 55% of those that could be contacted). Trades workers reported the highest exposure to dust (75%) and oils and solvents (59%). Agriculture and fishery workers reported the highest exposure to pesticides (63%) and acids or alkalis (25%). Plant and machine operators and assemblers reported the highest exposure to smoke/fume/gas (43%), working night shift in the previous 4 wk (18%), and working irregular hours (33%). In the high exposure occupational and industry groups, males reported a higher exposure than females. Lifting, exposure to loud noise, and the use of personal protective equipment were reported by >50% of the manual occupational groups. The authors concluded that the findings from this study indicate that occupational exposure to risk factors for work-related disease and injury remains common in the New Zealand working population. While these occupational exposures are disproportionately experienced by workers in certain industries, they also occur in occupational groups not traditionally associated with hazardous exposures or occupational disease. Authors: Eng, Amanda; 't Mannetje, Andrea; Cheng, Soo; Douwes, Jeroen; Ellison-Loschmann, Lis; McLean, Dave; Gander, Philippa; Laird, Ian; Legg, Stephen; Pearce, Neil Full Source: Annals of Occupational Hygiene 2010, 54(2), 144-153 (English) ~dOccupational ~tElemental Bio-imaging of Thorium, Uranium, and Plutonium in Tissues from Occupationally Exposed Former Nuclear Workers ~w2010-05-26 This study examines the application of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantifying and visualising the mass distribution of uranium and thorium isotopes from both occupational and natural background exposure in human respiratory tissues and, for the first time, extends this application to the direct imaging of plutonium isotopes. Sections of lymphatic and lung tissues taken from deceased former nuclear workers with a known history of occupational exposure to specific actinide elements (uranium, plutonium, or americium) were analysed by LA-ICPMS. Using a previously developed LA-ICPMS protocol for elemental bio-imaging of trace elements in human tissue and a new software tool, the authors generated images of thorium (232Th), uranium (235U and 238U), and plutonium (239Pu and 240Pu) mass distributions in sections of tissue. A laboratory-produced matrix-matched standard was used to quantify the 232Th, 235U, and 238U concentrations. The plutonium isotopes 239Pu and 240Pu were detected by LA-ICPMS in 65 ím diameter localised regions of both a paratracheal lymph node and a sample of lung tissue from a person who was occupationally exposed to refractory plutonium (plutonium dioxide). The average (overall) 239Pu concentration in the lymph node was 39.2 ng/g measured by high purity germanium (HPGe) ç-spectrometry. Localised mass concentrations of thorium (232Th) and uranium (238U) in lymph node tissue from a person not occupationally exposed to these elements (chronic natural background inhalation exposure) ranged up to 400 and 375 ng/g, respectively. In lung samples of occupationally nonexposed to thorium and uranium workers, 232Th and 238U concentrations ranged up to 200 and 170 ng/g, respectively. In a person occupationally exposed to air-oxidised uranium metal, the maximum 235U and 238U isotopic mass concentrations in a lymph node, measured at higher resolution (with a 30 ím laser spot diameter), were 70 and 8500 ng/g, respectively. The ratio of these simultaneously measured mass concentrations signifies natural uranium. The authors concluded that the current technique was not sufficiently sensitive, even with a 65 ím laser spot diameter, to detect 241Am (at an overall tissue concentration of 0.024 ng/g, i.e., 3 Bq/g). Authors: Hare, Dominic; Tolmachev, Sergei; James, Anthony; Bishop, David; Austin, Christine; Fryer, Fred; Doble, Philip Full Source: Analytical Chemistry (Washington, DC, United States) 2010, ACS ASAP (English) ~dOccupational ~tHealth hazard and intervention measures of benzene-exposed workers in jewellery processing enterprises in Shenzhen city ~w2010-05-26 This study investigated the health hazards associated with exposure to benzene from jewellery processing. In addition, the intervention methods were examined. The benzene series concentration in the working environment air was detected, occupational health examinations of the workers were carried out and intervention measures were performed. The qualified rate of the benzene series concentration in the working environment air was 20% and 100% before and after intervention respectively. Following the intervention measures, the subjective symptoms and signs of workers (headache, dizziness, insomnia, poor appetite, skin lesions and hemorrhagic tendency) improved in different degree. The abnormal menstruation of female workers (menostaxis, menorrhagia and irregular menstrual periods) improved after intervention as well. In terms of blood routine examination, the incidences of the WBC, Hb and PLT decreases before intervention were higher than those after intervention. The difference in examination results between before and after intervention was significant. The authors concluded that the findings from this study demonstrate that after the intervention measures were implemented in the jewellery processing enterprises, the benzene series concentration decreased into the allowable range, and the health conditions of workers improved greatly. Authors: Lin, Yijia; Fang, Shaobo; Huang, Lijing; Zhang, Fenglei Full Source: Zhiye Yu Jiankang 2009, 25(22), 2381-2383 (Chinese) ~dOccupational ~tFluoride analysis and fluoride related health problems in clinical, experimental, occupational and environmental aspects: a narrative review ~w2010-05-26 Fluoride's compounds are extraordinary high strategic chemicals with unique physico-chemical properties that make them indispensable in recent high technological industries. Thus, fluoride related health problems appear in various situations of our clinical, nutritional, industrial and environmental activities. In the past 15 years, the authors analysed fluoride concentrations of fluid samples obtained from healthy adults, patients undergoing hemodialysis, fluoride-exposed animal models, workers suffered hydrofluoric acid exposure, common bottled mineral water and groundwater by means of a fluoride ion selective electrode. This literature describes urinary fluoride reference value, insufficient fluoride removal during dialysis session, fluoride induced renal toxicity, occupational fluoride exposure, fluoride content in common bottled water and endemic dental fluorosis in India including recent work from the first author's lab. In addition, the article discusses the potential health risk of fluoride, particularly in industrial workers, young children and elderly people. Authors: Usuda, Kan; Kono, Koichi; Dote, Tomotaro; Watanabe, Misuzu; Shimizu, Hiroyasu; Tanimoto, Yoshimi; Yamadori, Emi; Yoshida, Yasuhisa Full Source: Biomedical Research on Trace Elements 2009, 20(4), 274-283 (English) ~dOccupational ~tDetermination of benzene, toluene and n-hexane in urine and blood by headspace solid-phase microextraction/gas-chromatography for the biomonitoring of occupational exposure ~w2010-05-26 The analysis of unchanged toluene, benzene, and n-hexane in human blood and urine can be useful to evaluate occupational exposure to these solvents. A simple method was developed using headspace-solid phase microextraction (HS-SPME) for simultaneous gas-chromatography analysis of toluene, benzene, and n-hexane in urine and blood; with purpose of biological monitoring of occupational exposure. Carboxen/polydimethylsiloxane fibre (CAR-PDMS) and PDMS fibre coating were employed in this study. Blood and urine samples were collected from handling glue workers. The results demonstrated the presence of toluene in all blood samples collected from workers handling glue in shoe repair shops, when using CARPDMS fibres (16.0-55.2 íg L-1, n ) 7). n-Hexane was only detected in 2 blood samples (33.0 and 41.3 íg L-1) and benzene was not detected in anyone. The authors concluded that no solvent could be quantified in urine samples. Authors: de Lima Gomes, Paulo C. F.; D'Andrea, Everton D.; Mendes, Camila B.; de Siqueira, Maria Elisa P. B. Full Source: Journal of the Brazilian Chemical Society 2010, 21(1), 119-126 (Eng) PUBLIC HEALTH ~dPublic Health ~tDental caries and content of hair microelement among children in nonferrous metal industrial area ~w2010-05-26 In this study the authors investigated the relationship between microelements in children's hair and their caries in nonferrous metal industrial area in Gansu Province. Two hundreds 12-yr-old children in nonferrous metal industrial area and the same number of children in a control area were randomly sampled. The examination included the condition of dental caries, dental fluorosis and the contents of Zn, Cd, Fe, Mg and Cu in the children's hair. The prevalence and DMF index of children in the nonferrous metal industrial area were markedly higher than those of children in control area and the fluorosis index was on the edge of prevail. The contents of microelement (Zn, Cd, Pb, Fe, Mg and Cu) were higher in the metal industrial area than in control area, esp. for Cd and Pb. The authors concluded that the nonferrous metal microelement pollution caused by the industrial activity may be contributed to children dental caries in nonferrous metal industrial area. Authors: Zhao, Wanghong; Zhang, Jing; Zhang, Ke; Su, Shaochen Full Source: Zhongguo Gonggong Weisheng 2008, 24(11), 1320-1321 (Ch) ~dPublic Health ~tEndometriosis and organochlorinated environmental pollutants: a case-control study on Italian women of reproductive age ~w2010-05-26 Endometriosis is a common gynaecological disease characterised by the ectopic growth of endometrial tissue. In industrialised countries, it affects approximately 10% of women of reproductive age. Its aetiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesised to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. During this study, the authors explored the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. A case-control study was conducted in Rome involving 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1- dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p'-DDE), and hexachlorobenzene (HCB) were detected by ion-trap mass spectrometry. DRCALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equiv. (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. The results demonstrated an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) ) 3.79; 95% confidence interval (CI), 1.61-8.91], NDL-PCB-138 (OR ) 3.78; 95% CI, 1.60-8.94), NDL-PCB-153 (OR ) 4.88; 95% CI, 2.01-11.0), NDL-PCB-170 (OR ) 3.52; 95% CI, 1.41-8.79), and the sum of DL-PCBs and NDLPCBs (OR ) 5.63; 95% CI, 2.25-14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DLPCBs given as total TEQs. The authors concluded that the results of this study showed that an association exists between increased PCB and p,p'-DDE serum concentrations and the risk of endometriosis. Authors: Porpora, Maria Grazia; Medda, Emanuela; Abballe, Annalisa; Bolli, Simone; De Angelis, Isabella; di Domenico, Alessandro; Ferro, Annamaria; Ingelido, Anna Maria; Maggi, Antonella; Panici, Pierluigi Benedetti; De Felip, Elena Full Source: Environmental Health Perspectives 2009, 117(7), 1070-1075 (Eng) ~dPublic Health ~tExposure to concentrated coarse air pollution particles causes mild cardiopulmonary effects in healthy young adults ~w2010-05-26 While there is lots of evidence supporting that exposure to fine particulate matter (PM) air pollution [aerodynamic diameter e 2.5 ím (PM2.5)], which derives primarily from combustion processes, can result in increased mortality and morbidity. Less information is available regarding the contribution of coarse PM (PM2.5-10), which derives from crustal materials and from mech. processes, to mortality and morbidity. This study investigated the effects of coarse PM causes cardiopulmonary effects. Fourteen healthy young volunteers were exposed to coarse concentrated ambient particles (CAPs) and filtered air. Coarse PM concentration averaged 89.0 íg/m3 (range, 23.7-159.6 íg/m3). Volunteers were exposed to coarse CAPs and filtered air for 2 h while they underwent intermittent exercise in a singleblind, crossover study. Pulmonary, cardiac, and haematological end points before exposure, immediately after exposure, and again 20 h after exposure, were measured. The results showed that compared with filtered air exposure, coarse CAP exposure produced a small increase in polymorphonuclear neutrophils in the bronchoalveolar lavage fluid 20 h postexposure, indicating mild pulmonary inflammation. No changes in pulmonary function were observed. Blood tissue plasminogen activator, which is involved in fibrinolysis, was decreased 20 h after exposure. The standard deviation of normal-to-normal intervals (SDNN), a measure of overall heart rate variability, also decreased 20 h after exposure to CAPs. The authors concluded that coarse CAP exposure produces a mild physiological response in healthy young volunteers approximately 20 h postexposure. The authors concluded that these changes are similar in scope and magnitude to changes previously reported for volunteers exposed to fine CAPs, suggesting that both size fractions are comparable at inducing cardiopulmonary changes in acute exposure settings. Authors: Graff, Donald W.; Cascio, Wayne E.; Rappold, Ana; Zhou, Haibo; Huang, Yuh-Chin T.; Devlin, Robert B. Full Source: Environmental Health Perspectives 2009, 117(7), 1089-1094 (Eng) ~dPublic Health ~tGender specific differences in neurodevelopmental effects of prenatal exposure to very low-lead levels: The prospective cohort study in three-year olds ~w2010-05-26 The study assessed the relationship between very low-level of prenatal lead exposure measured in the cord blood (< 5 íg/dL) and possible gender specific cognitive deficits in the course of the first three years of life. The accumulated lead dose in infants over the pregnancy period was measured by the cord blood lead level (BLL) and cognitive deficits were assessed by the Bayley Mental Development Index (MDI). The study sample consisted of 457 children born to non-smoking women living in the inner city and the outlying residential areas of Krakow. The relationship between prenatal lead exposure and MDI scores measured at 12, 24 and 36 mo of age and adjusted to a set of important covariates (gender of child, maternal education, parity, breastfeeding, prenatal and postnatal environmental tobacco smoke) was evaluated with linear multivariate regression, and the Generalised Estimating Equations (GEE) longitudinal panel model. The median of lead level in cord blood was 1.21 íg/dL with the range of values from 0.44 to 4.60 íg/dL. Neither prenatal BLL (dichotomised by median) nor other covariates affected MDI score at 12 months of age. Subsequent testing of children at 24 months of age showed a borderline significant inverse association of lead exposure and mental function (beta coefficient) - 2.42, 95%CI: - 4.90 to 0.03), but the interaction term (BLL male gender) was not significant. At 36 months, prenatal lead exposure was inversely and significantly associated with cognitive function in boys (Spearman correlation coefficient) - 0.239, p ) 0.0007) but not girls (r ) - 0.058, p) 0.432) and the interaction between BLL and male gender was significant (beta coefficient) - 4.46; 95%CI: - 8.28 to - 0.63). Adjusted estimates of MDI deficit in boys at 36 months confirmed very strong negative impact of prenatal lead exposure (BLL > 1.67 íg/dL) compared with the lowest quartile of exposure (beta coefficient) - 6.2, p ) 0.002), but the effect in girls was insignificant (beta coefficient) - 0.74, p ) 0.720). The average deficit of cognitive function in the total sample over the first three years of life (GEE model) associated with higher prenatal lead exposure was also significant (beta coefficient) - 3.00; 95%CI: - 5.22 to - 0.70). Beside prenatal lead exposure, presence of older siblings at home and prenatal environmental tobacco smoke had a negative impact on MDI score. Better maternal education showed a strong beneficial effect on the cognitive development of children. The authors concluded that the findings suggest that there might be no threshold for lead toxicity in children and provides evidence that 3-yr old boys are more susceptible than girls to prenatal very low lead exposure. The results of the study should persuade policy makers to consider gender-related susceptibility to lead and possibly to other toxic hazards in setting environmental protection guidelines. To determine whether the cognitive deficit documented in this study persists to older ages, the follow-up of the children over the next several years is to be carried out. Authors: Jedrychowski, Wieslaw; Perera, Frederica; Jankowski, Jeffery; Mrozek-Budzyn, Dorota; Mroz, Elzbieta; Flak, Elzbieta; Edwards, Susan; Skarupa, Anita; Lisowska-Miszczyk, Ilona Full Source: Early Human Development 2009, 85(8), 503-510 (Eng) ~dPublic Health ~tMechanism for quinolinic acid cytotoxicity in human astrocytes and neurons ~w2010-05-26 There is growing evidence implicating the kynurenine pathway (KP) and particularly one of its metabolites, quinolinic acid (QUIN), as important contributors to neuroinflammation in several brain diseases. While QUIN has been shown to induce neuronal and astrocytic apoptosis, the exact mechanisms leading to cell death remain unclear. In this study, the authors determined the mechanism of QUIN-mediated excitotoxicity in human brain cells by measuring intracellular levels of NAD (NAD+) and poly(ADP-ribose) polymerase (PARP) and extracellular lactate dehydrogenase (LDH) activities, in primary cultures of human neurons and astrocytes treated with QUIN. The results showed that QUIN acts as a substrate for NAD+ synthesis at very low concentrations (<50 nM) in both neurons and astrocytes, but is cytotoxic at subphysiological concentrations (>150 nM) in both the cell types. The authors demonstrated that the NMDA ion channel blockers, MK801 and memantine, and the nitric oxide synthase (NOS) inhibitor, L-NAME, significantly attenuate QUIN-mediated PARP activation, NAD+ depletion, and LDH release in both neurons and astrocytes. An increased mRNA and protein expression of the inducible (iNOS) and neuronal (nNOS) forms of nitric oxide synthase was also observed following exposure of both cell types to QUIN. The authors concluded that when taken together, these results suggests that QUIN-induced cytotoxic effects on neurons and astrocytes are likely to be mediated by an over activation of an NMDA-like receptor with subsequent induction of NOS and excessive nitric oxide (NOá)-mediated free radical damage. These results contribute significantly to the authors understanding of the pathophysiological mechanisms involved in QUIN neuro- and gliotoxicity and are relevant for the development of therapies for neuroinflammatory diseases. Authors: Braidy, Nady; Grant, Ross; Adams, Seray; Brew, Bruce J.; Guillemin, Gilles J. Full Source: Neurotoxicity Research 2009, 16(1), 77-86 (Eng) SAFETY ~dSafety ~tThe disaster accident simulation system based on VR technology ~w2010-05-14 Based on the actual construction experience, a disaster simulation system is designed using virtual reality technology. The system can simulate the occurrence and development of disasters in the chemical system, and it is an effective platform used for research and exercises in disaster simulation. Virtual reality technology used in petrochemical disaster system simulation belongs to the exploring of new areas. The introduction of the models of leakage, diffusion, explosion accidents to show the dynamic development process of the accidents, reflects the characteristics of chemical disasters. How to combine the use of virtual reality technology with the disaster simulation mechanism models achieves a useful idea exploration for simulation realization. This achievement can offer the basis platform for the research, establishment, and exercise of Safety Emergency Plan based on disaster simulation. This paper has the prospects of applications to accident analysis, disaster prevention formulation and emergent training. This simulation system designed by Beijing HuaKangDa Computer Application Technol. CO., LTD, can preferably simulate the occurrence and development progress of accidents of disasters in chemical enterprises. It was applied in largescale oil and petrochemical enterprises, and has obtained good simulation results. Authors: Yi, Tao; Li, Yuanyuan; Su, Yang Full Source: Jisuanji Yu Yingyong Huaxue 2009, 26(8), 966-970 (Ch) ~dSafety ~tNumerical study of the effect of water addition on gas explosion ~w2010-05-14 Through amending the SENKIN code of CHEMKIN III chemical kinetics package, a computational model of gas explosion in a constant volume bomb was built, and the detailed reaction mechanism (GRIMech 3.0) was adopted. The mole fraction profiles of reactants, some selected free radicals and catastrophic gases in the process of gas explosion were analysed by this model. Through the sensitivity analysis of the reaction mechanism of gas explosion, the dominant reactions that affect gas explosion and the formation of catastrophic gases were found out. At the same time, the inhibition mechanisms of water on gas explosion and the formation of catastrophic gases were analysed. The results show that the induced explosion time is prolonged, and the mole fractions of reactant species such as CH4, O and catastrophic gases such as CO, CO2 and NO are decreased as water is added to the mixed gas. With the water fraction in the mixed gas increasing, the sensitivities of the dominant reactions contributing to CH4, CO2 are decreased and the sensitivity coefficients of CH4, CO and NO mole fractions are also decreased. The inhibition of gas explosion with water addition can be ascribed to the significant decrease of H, O and OH in the process of gas explosion due to the water presence. Authors: Liang, Yuntao; Zeng, Wen Full Source: Journal of Hazardous Materials 2010, 174(1-3), 386-392 (Eng) ~dSafety ~tCalculated flame temperature (CFT) modelling of fuel mixture lower flammability limits ~w2010-05-14 Heat loss can affect experimental flammability limits, and it becomes indispensable to quantify flammability limits when app. quenching effect becomes significant. The lower flammability limits of binary hydrocarbon mixtures are predicted using calculated flame temperature (CFT) modelling, which is based on the principle of energy conservation. Specifically, the hydrocarbon mixtures lower flammability limit is quantitatively correlated to its final flame temperature at non-adiabatic conditions. The modelling predictions are compared with experimental observations to verify the validity of CFT modelling, and the minor deviations between them indicated that CFT modelling can represent experimental measurements very well. The CFT modelling results and Le Chatelier's Law predictions are also compared, and the agreement between them indicates that CFT modelling provides a theoretical justification for the Le Chatelier's Law. Authors: Zhao, Fuman; Rogers, William J.; Mannan, M. Sam Full Source: Journal of Hazardous Materials 2010, 174(1-3), 416-423 (Eng)