91 research outputs found
Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S-Transferase Omega Genes
BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility
toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through
sequential reduction and oxidative methylation being mediated by the following genes: purine
nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), glutathione S-transferase
omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates
inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites.
Alteration in functions of these gene products may lead to arsenic-specific disease manifestations.
OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide
polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the
exons in those genes in an arsenic-exposed population.
METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we
screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals
without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated
water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated
individuals (229 cases and 199 controls) for association study.
RESULTS: Among four candidate genes, PNP, As3MT, GSTO1, and GSTO2, we found that distribution
of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated
with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case
group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08–2.66] for His20His; OR = 1.66
[95% CI, 1.04–2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05–2.66] for Pro57Pro.
CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible
toward developing arsenic-induced skin lesions.
KEY WORDS: arsenic, As3MT, GSTO1, GSTO2, PNP, skin lesion, susceptibility. Environ Health
Perspect 116:501–505 (2008). doi:10.1289/ehp.10581 available via http://dx.doi.org/ [Online
14 January 2008
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Material Parameters and ESEM Characterization of Functional ENT Prostheses During Ongoing Degradation
The normally available voice prostheses of the Provox® and ESKA-Herrmann types are made of silicone rubber. Further details of the materials are not available. For comparison, samples of the Halle voice prostheses, which are produced from polyurethane [5], were examined. The surfaces were investigated with light microscopy and with conventional and environmental scanning electron microscopy. The plastic hardness was measured with the Fischerscope H100 test device, which measures micro-hardness. For measurement of the pressure/flow characteristics, an aerodynamic measuring device was used [6]
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