ABSTRACT
Epidemiological studies demonstrate an association between chronic consumption of arsenic contaminated water and cognitive deficits, especially when the exposure takes place during childhood. This study documents structural changes and nitrergic deficits in the striatum of adult female Wistar rats exposed to arsenic in drinking water (3 ppm, approximately 0.4 mg/kg per day) from gestation, throughout lactation and development until the age of 4 months. Kainic acid injected animals (10mg/kg, i.p.) were also analyzed as positive controls of neural cell damage. Morphological characteristics of cells, fiber tracts and axons were analyzed by means of light microscopy as well as immunoreactivity to neuronal nitric oxide synthase (nNOS). As nitrergic markers, nitrite/nitrate concentrations, nNOS levels and expression of nNOS-mRNA were quantified in striatal tissue. Reactive oxygen species (ROS) and lipid peroxidation (LPx) were determined as oxidative stress markers. Arsenic exposure resulted in moderate to severe alterations of thickness, organization, surrounding space and shape of fiber tracts and axons, while cell bodies remained healthy. These anomalies were not accompanied by ROS and/or LPx increases. By contrast, except the expression of nNOS-mRNA, all nitrergic markers including striatal nNOS immunoreactivity presented a significant decrease. These results indicate that arsenic targets the central nitrergic system and disturbs brain structural organization at low exposure levels.
Subject(s)
Arsenites/toxicity , Corpus Striatum/drug effects , Nitrergic Neurons/drug effects , Nitric Oxide/metabolism , Prenatal Exposure Delayed Effects , Sodium Compounds/toxicity , Water Pollutants, Chemical/toxicity , Animals , Corpus Striatum/enzymology , Corpus Striatum/pathology , Excitatory Amino Acid Agonists/toxicity , Female , Gestational Age , Kainic Acid/toxicity , Lactation , Lipid Peroxidation/drug effects , Nitrates/metabolism , Nitrergic Neurons/enzymology , Nitrergic Neurons/pathology , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type I , Nitrites/metabolism , Pregnancy , RNA, Messenger/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species/metabolismABSTRACT
Second-order, Møller-Plesset (MP2)-unrestricted Hartree-Fock calculations with full geometry optimization in the 6-31G(d, p) basis set were carried out to study the initial atmospheric oxidation reactions of alkanes. All structures in the initial hydrogen abstraction reaction by an OH radical and the subsequent addition of molecular oxygen to the alkyl radical were characterized for alkanes with three and four carbon atoms. The reaction paths for the formation of the peroxyl radicals were obtained and discussed in the light of similarities along series involving primary, secondary, and tertiary hydrogens. A 0.999 correlation was found between the height of our barriers for the OH abstraction of a primary hydrogen atom from alkanes containing one to four carbon atoms and the optimally estimated activation energies for this reaction recently presented. From the slope and the intersection at zero activation energy an equation was obtained that yields scaled values of the activation energies to account for the tunnel effect and for the error due to the basis set and the method employed. We present new results for the abstraction of the less favored primary hydrogens in propane, butane, and isobutane, which should be important at high temperatures. Negative net activation energies were obtained for the addition of molecular oxygen to all the alkyl radicals formed in the first reaction. The structure of the peroxyl radicals is discussed; and very good correlations are observed for similar compounds, regardless of the length of the carbon chain. A revision of some experimental values is suggested. Single point density functional calculations at the MP2 geometries were also performed with the B3LYP functional for comparison. The observed trends are exactly the same for the two methods. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 845-856, 1999.
ABSTRACT
A controlled clinical trial, corresponding to stage 2, was conducted in a population of sound adult males aged 18-23 to evaluate the immunogenicity of 5 schedules of Cuban vaccine against hepatitis B (Heberbiovac-HB [correction of Cheberbiovac-HB]). 5 groups were studied: I (control group 0, 1 and 6 months), II (0 and 2 months), III (0 and 4 months), IV (0 and 6 months), and V (0 and 8 months). The results showed no significant differences as regards the percentage of seroprotection of any of the groups of 2 doses compared with the control of 3 doses. It is concluded that between the first and the second dose there may be a period of time from 2 to 6 months with no need to reinitiate the schedule. This information will serve as a basis for a population based study to determine which schedule is the best to be used.
Subject(s)
Hepatitis B Vaccines/administration & dosage , Vaccines, DNA/administration & dosage , Adolescent , Adult , Cuba , Dose-Response Relationship, Immunologic , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/immunology , Humans , Immunization Schedule , Male , Time Factors , Vaccines, DNA/immunologyABSTRACT
Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone.