Perfluoroalkyl chemicals in neurological health and disease: Human concerns and animal models.

Perfluoroalkyl acids (PFAAs) are man-made organic pollutants that are found ubiquitously in the environment and may impact human health. Here, we review the published literature concerning PFAA impacts on neurobiological, neuroendocrine, and neurobehavioral outcomes. We find that there are many mechanisms through which PFAAs may enter the brain and interact with biochemical endpoints to impact neurological function. These results are supported by epidemiological evidence in humans and experimental evidence in animals that demonstrate numerous and varied PFAA impacts on the nervous system. However, the methods commonly used in animal models of PFAA exposure result in durations of exposure and serum PFAA concentrations in blood that may not appropriately mimic human absorption, distribution, metabolism, and excretion. If animal models lack validity, confidence in mechanistic inferences regarding PFAA exposure and brain function is reduced, limiting these studies' utility. Finally, we end by suggesting some potential impacts of PFAA exposure in human neurological health and disease states whose associations may not readily present themselves in the epidemiological literature.

Determination of Energy-Transfer Distributions in Ionizing Ion-Molecule Collisions.

The ionization and fragmentation of the nucleoside thymidine in the gas phase has been investigated by combining ion collision with state-selected photoionization experiments and quantum chemistry calculations. The comparison between the mass spectra measured in both types of experiments allows us to accurately determine the distribution of the energy deposited in the ionized molecule as a result of the collision. The relation of two experimental techniques and theory shows a strong correlation between the excited states of the ionized molecule with the computed dissociation pathways, as well as with charge localization or delocalization.

Study of the mode of action of some nitrodiphenyl ethers.

Nitrosoderivatives of the nitrodiphenyl ether herbicides (nitrofen, bifenox) have been studied. UV irradiation in different organic solvents gives degradation products. In buffered aqueous media, in the presence of chloroplasts and spin traps such as DMPO, hydroxy and peroxy radicals have been characterized. In organic media and in the presence of spin traps such as DMPO, PBN, 4-POBN, solvent radicals (.CHCl2, .CCl3, .CH2 [symbol: see text]) have been formed. Nitro-derivatives have been studied under UV irradiation and in the presence of tetramethylethylene (TME), alkenylhydroxylamines are formed which autoxidize in nitroxide radicals. The formation of the stable nitroxide radical occurs in the dark process after continuous irradiation. The intensity of the signal decreases strongly when a new irradiation is applied. Radical species, with analogous ESR spectral characteristics are formed on reaction with nitrodiphenyl ethers and fatty acids. The reactivity of these herbicides in micellar media (SDS, Brij 35, and CTAB) has been investigated. The kinetics of formation of the ESR signal corresponding to the photoreduction of the nitrodiphenyl ether in the presence of TME behave differently in a micellar environment as compared to solution. The intensity of the formation of the nitroxide increases under irradiation and decreases in the dark; the rotational correlation time tau c has been determined for each type of micelle. Synthetic nitrosodiphenyl ether made by the reduction of nitrodiphenyl ether using hydrogen gas and PtO2 as a catalyst gives the corresponding amine, which is oxidized with meta-chloroperbenzoic acid (m.CPBA). The nitrosodiphenyl ether in the presence of soja azolectin liposome containing a fluorescent probe has been analysed.(ABSTRACT TRUNCATED AT 250 WORDS)

The association and embryogenesis of tracheo-oesophageal and anorectal anomalies.

Thirty-one patients with combined oesophageal and anorectal anomalies were studied. They comprised 10% of 328 consecutive foregut malformations and 246 anorectal deformities. Twenty-three of this series also exhibited at least 3 of the VATER defects. There was a very high incidence particularly of associated vertebral, urological and musculoskeletal anomalies. This high incidence of addditional lesions is presumably a reflection of generalized early damage to the mesenchymal tissues at the fourth week of gestation. Similar embryological mechanisms may take place and be affected similarly in both foregut and hindgut systems. The concept of a two-component septum dividing the foregut and hindgut is proposed to explain the formation and malformations in these regions. Disturbances of alignment, direction and extent of these component septa induced by hyperflexion of the foregut and hindgut, and intrinsic septal defects presumably account for most of the malformations. Hyperflexion may also account for malformations of other systems and for the high incidence of associated anomalies in the 31 patients with oesophagorectal deformities.