Effects of Glutaraldehyde Exposure on Human Health: Tomoko TAKIGAWA, et

SummaryThe urinary concentrations of 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity Creactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.

Organophosphate esters are used as additives in flame retardants and plasticizers, and they are ubiquitous in the indoor environment. Phosphorus flame retardants (PFRs) are present in residential dust, but few epidemiological studies have assessed their impact on human health. We measured the levels of 11 PFRs in indoor floor dust and multi-surface dust in 182 single-family dwellings in Japan. We evaluated their correlations with asthma and allergies of the inhabitants. Tris(2-butoxyethyl) phosphate was detected in all samples (median value: 580 μg/g in floor dust, 111 μg/g in multi-surface dust). Tris(2-chloro-iso-propyl) phosphate (TCIPP) was detected at 8.69 μg/g in floor dust and 25.8 μg/g in multi-surface dust. After adjustment for potential confounders, significant associations were found between the prevalence of atopic dermatitis and the presence of TCIPP and tris(1,3-dichloro-2-propyl) phosphate in floor dust [per log10 -unit, odds ratio (OR): 2.43 and 1.84, respectively]. Tributyl phosphate was significantly associated with the prevalence of asthma (OR: 2.85 in floor dust, 5.34 in multi-surface dust) and allergic rhinitis (OR: 2.55 in multi-surface dust). PFR levels in Japan were high compared with values reported previously for Europe, Asia-Pacific, and the USA. Higher levels of PFRs in house dust were related to the inhabitants' health status.

High titers of anti-GM1 ganglioside antibodies (anti-GM1 antibodies) may be implicated in lower motor neuron disease. We studied the pathogenic role of anti-GM1 antibody using the petroleum jelly-gap voltage clamp technique on isolated single myelinated rat nerve fibers. Anti-GM1 antisera were obtained from rabbits immunized with GM1 ganglioside. Extracellularly applied anti-GM1 antisera without complement activity increased both the rate of rise and the amplitude of the K+ current elicited by step depolarization, with little effect on Na+ current. In the presence of active complement, however, anti-GM1 antibodies decreased the Na+ current, and caused a progressive increase of nonspecific leakage current. Neither complement alone nor complement-supplemented antisera from which anti-GM1 antibodies were depleted by affinity chromatography had any effect on ionic current. These observations indicate that anti-GM1 antibodies themselves can uncover K+ channels in the paranodal region, while anti-GM1 antibodies bound to the nodal membrane in the presence of complement may form antibody-complement complexes that block Na+ channels and disrupt the membrane at the node of Ranvier.

Several neuromodulators including adenosine (via A1 receptors), serotonin (via 5-HT1A receptors) and GABA (via GABAB receptors) target G protein-activated inwardly rectifying K¤ (GIRK) currents to influence the excitability of CNS neurons (Nicoll et al. 1990;Yamada et al. 1998). GIRK current activation occurs in a direct, membranedelimited fashion, with the Gâã-subunit serving as the major gating particle (Dascal, 1997). It has long been disputed whether GIRK currents serve as effectors of G protein-coupled receptors on both the presynaptic and the postsynaptic side, leading to inhibition of transmitter release and hyperpolarization of the postsynaptic neuron, respectively. This issue was resolved only recently by combining transgenic mice technology with electrophysiology: recordings from brain slices of normal and transgenic mice lacking a subunit essential for functional GIRK channels demonstrated that GIRK currents of pyramidal cells are confined to the postsynaptic side, and play no role in the inhibition of transmitter release (L uscher et al. 1997). One important, but still missing piece of information to further elucidate the function of GIRK currents in the postsynaptic neuron is their relative density along the somatodendritic axis. Recordings from different types of CNS neurons in brain slices and after acute isolation have provided ample evidence that various G protein-coupled receptors are capable of evoking GIRK currents in cell somata (e.g. G ahwiler & Brown, 1985;Andrade et al. 1986;Alzheimer & ten Bruggencate, 1991;Misgeld et al. 1995;Sodickson & Bean 1998). In contrast, evidence for dendritic GIRK currents is scarce and indirect, based mainly on intracellular recordings from pyramidal neurons in vitro, where local application of baclofen to apical dendrites was found to induce hyperpolarization of the (somatically recorded) membrane potential (Newberry & Nicoll, 1985;Luhmann & Prince, 1991). Given the functional significance attributed to dendritic ion channels, information on the density of ion currents in somatic vs. dendritic compartments is essential for understanding their