Parkinson* & (metal*, manganese, iron, aluminum, cadmium, copper, zinc, mercury, copper) for year 2000-present Song W, Su H, Song S, Paudel HK, Schipper HM . 2006 Mar. Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia. J Cell Physiol 206(3):655-63. Abstract: Glial heme oxygenase-1 is over-expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up-regulation of HO-1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO-1 induction promotes mitochondrial oxidative stress, assays for 8-epiPGF(2alpha) (ELISA), protein carbonyls (ELISA) and 8-OHdG (HPLC-EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole-cell compartments derived from cultured rat astroglia engineered to over- express human (h) HO-1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [(3)H] thymidine incorporation and total cell counts. In rat astrocytes, hHO-1 over-expression (x3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 microM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up-regulation of HO-1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme- derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO-1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. (c) 2005 Wiley-Liss, Inc. Fored CM, Fryzek JP, Brandt L, Nise G, Sjogren B, McLaughlin JK, Blot WJ, Ekbom A. 2006 Feb. Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders. Occup Environ Med 63(2):135-40. Abstract: INTRODUCTION: Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. METHODS: The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD-10, G20-26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49,488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489,572). RESULTS: The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). CONCLUSION: This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders. Bates MN. 2006 Jan 27. Mercury amalgam dental fillings: An epidemiologic assessment. Int J Hyg Environ Health . Abstract: Dental amalgam fillings containing approximately 50% mercury have been used for almost 200 years and have been controversial for almost the same time. Allegations of effects caused by amalgams have involved many diseases. Recent evidence that small amounts of mercury are continuously released from amalgam fillings has fuelled the controversy. This is a comprehensive review of the epidemiologic evidence for the safety of dental amalgam fillings, with an emphasis on methodological issues and identifying gaps in the literature. Studies show little evidence of effects on general chronic disease incidence or mortality. Limited evidence exists for an association with multiple sclerosis, but few studies on either Alzheimer's or Parkinson's diseases. The preponderance of evidence suggests no renal effects and that ill-defined symptom complexes, including chronic fatigue syndrome, are not caused by amalgams. There is little direct evidence that can be used to assess reproductive hazards. Overall, few relevant epidemiologic studies are available. Most prior assessments of possible amalgam health effects have been based on comparisons of dental mercury exposures with occupational exposures causing harm. However, the amalgam-exposed population contains a broader, possibly more susceptible, spectrum of people. Common limitations of population-based studies of dental amalgam effects include inadequate longitudinal exposure assessment and negative confounding by better access to dental care in higher socioeconomic groups. Better designed studies are needed, particularly for investigation of neurodegenerative diseases and effects on infants and children. Charles LE, Burchfiel CM, Fekedulegn D, Kashon ML, Ross GW, Petrovitch H, Sanderson WT. 2006 Jan 26. Occupational Exposures and Movement Abnormalities among Japanese-American Men: The Honolulu-Asia Aging Study. Neuroepidemiology 26(3):130-139. Abstract: Objective: The authors analyzed data on 1,049 men aged 71-93 years (excluding those with prevalent Parkinson's disease and stroke) from the Honolulu Heart Program (1965-1968) and the Honolulu-Asia Aging Study (1991-1999) to determine whether occupational exposures to pesticides, solvents, metals, manganese, and mercury during middle age were associated with 14 movement abnormalities 25 years later. Methods: Analyses of variance and multivariate logistic regression were used to assess associations of interest. Results: After adjustment for age, BMI, cognitive functioning, smoking, alcohol drinking, education, and physical activity, there was a positive association between abnormal 'facial expression' and the highest exposure to metals [odds ratio (OR) = 2.62; 95% confidence interval (CI) = 1.35-5.11; trend, p = 0.02], and the highest exposure to mercury (OR = 1.91; 95% CI = 1.04-3.49; trend, p = 0.03). Age was positively associated with all movement abnormalities, and cognitive function, body mass index and physical activity were inversely associated with most movement abnormalities. Conclusion: Higher exposure to any metal, and specifically mercury, was associated with abnormal facial expression. Copyright (c) 2006 S. Karger AG, Basel. Fasano M, Bergamasco B, Lopiano L. 2006 Jan 17. Modifications of the iron- neuromelanin system in Parkinson's disease. J Neurochem . Abstract: Parkinson's disease is a common neurodegenerative disorder with a mainly sporadic aetiology, although a number of monogenic familiar forms are known. Most of the motor symptoms are due to selective depletion of dopaminergic, neuromelanin-containing neurones of the substantia nigra pars compacta. Neuromelanin is the dark insoluble macromolecule that confers the black (substantia nigra) or grey (locus coeruleus) colour to monoaminergic basal ganglia. In particular, nigral neurones are pigmented because of the accumulation of by-products of oxidative metabolism of the neurotransmitter dopamine. The occurrence of dopamine (and all the enzymatic machinery required for dopamine synthesis, re-uptake and disposal) and neuromelanin, and a large amount of iron ions that interact with them, makes dopaminergic nigral neurones peculiarly susceptible to oxidative stress conditions that, in turn, may become amplified by the iron-neuromelanin system itself. In this mini- review we describe biophysical evidence for iron-neuromelanin modifications that support this hypothesis. Furthermore, we discuss the formation of the covalent linkage between alpha-synuclein and neuromelanin from the early stages of the disease. Bae JH, Jang BC, Suh SI, Ha E, Baik HH, Kim SS, Lee MY, Shin DH. 2006 Jan 14. Manganese induces inducible nitric oxide synthase (iNOS) expression via activation of both MAP kinase and PI3K/Akt pathways in BV2 microglial cells. Neurosci Lett . Abstract: It is well documented that manganese neurotoxicity induces clinical symptoms similar to those of idiopathic Parkinson's disease. Although microglial cytotoxic mediator-induced neurotoxicity is suggested, the mechanism by which manganese up-regulates cytotoxic mediator, such as nitric oxide (NO), remains poorly understood. Therefore, in this study, we investigated the mechanism of manganese on induction of iNOS in microglial cells. iNOS promoter/luciferase assay revealed that manganese (500(M) regulated the iNOS expression at the transcriptional level. Immunoblot analysis also revealed that phosphorylation levels