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The proteolipid protein 1 (PLP1) gene encodes the two major proteins of the central nervous system (CNS) myelin: PLP and DM20. PLP1 gene mutations are associated with a large spectrum of X-linked dysmyelinating disorders ranging from hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease (PMD), to spastic paraplegia (SPG2) according to the nature of the mutation. Genetic heterogeneity exists and mutations in the gap-junction alpha 12 (GJA12) gene have been related to PMD. About 20% of patients with the PMD phenotype remain without mutation in these two genes and are classified as affected by Pelizaeus-Merzbacher-like disease (PMLD). To study PLP1 splicing abnormalities, we analyzed PLP/DM20 transcripts from nerves and/or skin cultured fibroblasts of 14 PMD/SPG2 patients carrying different PLP1 mutations and 20 PMLD patients. We found that various types of PLP1 mutations result in missplicing, including one considered as a missense in exon 2 and a nucleotide substitution in intron 3 outside the classical donor and acceptor splicing sites. Moreover, we demonstrated for two patients that the fibroblast transcript pattern was in accordance with the one observed in the corresponding CNS/peripheral nervous system (PNS) tissues. Finally, we observed no abnormal splicing in fibroblasts of 20 PMLD patients tested; suggesting that PLP1 gene splicing abnormalities, potentially caused by undetected intronic mutations, are either not involved or are very rarely implicated in the PMLD phenotype. These results confirm that fibroblasts are reliable, accessible cells useful in detecting PLP1 transcript abnormalities, better characterizing the functional consequences of PLP1 mutations for genotype-phenotype correlation, characterizing new PLP1 splicing regulatory elements, and identifying PLP1 mutations undetected by conventional PLP1 screening.

Ethnic groups from the Atacama Desert (known as Atacameños) have been exposed to natural arsenic pollution for over 5000 years. This work presents an integral study that characterizes arsenic species in water used for human consumption. It also describes the metabolism and arsenic elimination through urine in a chronically exposed population in northern Chile. In this region, water contained total arsenic concentrations up to 1250 μg L(-1), which was almost exclusively As(V). It is also important that this water was ingested directly from natural water sources without any treatment. The ingested arsenic was extensively methylated. In urine 93% of the arsenic was found as methylated arsenic species, such as monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. The original ingested inorganic species [As(V)], represent less than 1% of the total urinary arsenic. Methylation activity among individuals can be assessed by measuring primary [inorganic As/methylated As] and secondary methylation [MMA/DMA] indexes. Both methylation indexes were 0.06, indicating a high biological converting capability of As(V) into MMA and then MMA into DMA, compared with the control population and other arsenic exposed populations previously reported.

This article presents experimental results on 47 μmol L(-1) sulfathiazole (STZ) degradation by Fenton and photo-Fenton reactions using multivariate analysis. The optimal experimental conditions for reactions were obtained by Response Surface Methodology (RSM). In the case of the Fenton reactions there were 192 μmol L(-1) ferrous ions (Fe(II)) and 1856 μmol L(-1) hydrogen peroxide (H2O2), as compared with 157 μmol L(-1) (Fe(II)) and 1219 μmol L(-1) (H2O2) for photo-Fenton reactions. Under these conditions, around 90% of STZ degradation were achieved after 8 minutes treatment by Fenton and photo-Fenton reactions, respectively. Moreover, a marked difference was observed in the total organic carbon (TOC) removal after 60-min treatment, achieving 30% and 75% for the Fenton and photo-Fenton reactions, respectively. Acetic, maleic, succinic and oxamic acids could be identified as main Fenton oxidation intermediates. A similar pattern was found in the case of photo-Fenton reaction, including the presence of oxalic acid and ammonia at short periods of irradiation with UV-A. The calculated values of Average Oxidation State (AOS) corroborate the formation of oxidized products from the initial steps of the reaction.

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