Sequential analysis of hair mercury levels in relation to fish diet of an Amazonian population, Brazil

Several studies in the Amazonian Basin have shown that riverine populations are exposed to methylmercury through fish consumption. It has been suggested that seasonal variations in hair mercury observed through sequential analyses may be related to the changes in fish species ingested by the local communities. The aim of the present study was to investigate the relationship between fish-eating practices and seasonal variation in mercury exposure. A group of 36 women from a village located on the banks of the Tapajós River, a major tributary of the Amazon, comprised the present study population. An interview-administered questionnaire was used to gather information on socio-demographic characteristics, fish-eating practices and other relevant information. The women also provided hair samples of at least 24 cm in length for mercury analysis. Hair total and inorganic mercury concentration was measured using a cold vapor atomic absorption analytical method. Trigonometric regression analysis was done to assess the seasonal variation of total mercury levels. Variations in inorganic mercury were examined by repeated measures analysis of variance, and analysis of contrast variable with a polynomial transformation. The results showed that hair mercury levels varied with the season. Higher levels were observed in months corresponding to the dry season, with lower levels in the rainy season. Herbivorous fish predominated the diet for 47.2% of the women during the dry season, but this rose to 72.2% during the rainy season. Those who reported eating fish daily had higher mercury levels in hair compared to those who only ate fish a few times per week. Retrospective mercury analyses, evaluated by the quantity of mercury present in each centimeter of hair, indicate that mean mercury level of the population decreased over the 2 years prior to the study. The percentage of inorganic mercury over the total mercury in hair increased towards the extremities of the hair strand. Higher percentages of inorganic mercury were found for the group who ate more fish (on a daily consumption basis). These results support the assumption that there are seasonal variations in methylmercury exposure and also a relationship between type of fish species consumed and the resulting hair mercury levels.     

Velocardiofacial manifestations and microdeletions in schizophrenic inpatients

Sigma receptors are found in motor and limbic areas in the brains of humans, non-human primates, and rodents. The most extensive pharmacological studies of ligand binding to sigma receptors have utilized brain tissue from guinea pigs, where two subtypes of sigma receptor, designated sigma1 and sigma2, have been identified. Few functional roles for sigma receptors have been described. Their location in guinea pig striatum, a terminal field of dopaminergic projections arising from the substantia nigra, suggested that this tissue would be a logical choice in which to examine physiological properties of sigma receptor activation. We found that sigma1 receptor agonists inhibited N-methyl-D-aspartate-stimulated [3H]dopamine release from guinea pig striatal slices in a concentration-dependent manner. The inhibition by sigma1 receptor agonists was reversed by a selective sigma1 receptor antagonist, as well as by a non-subtype-selective sigma receptor antagonist. The ability of agonists working through sigma1 receptors, but not through sigma2 receptors, to inhibit the stimulated release of catecholamines appears to be a unique characteristic of guinea pig striatum. We have previously reported that in rat striatum and hippocampus, as well as in guinea pig nucleus accumbens, prefrontal cortex, and hippocampus, activation of either sigma receptor subtype inhibits such release. Stimulated release of [3H]dopamine from guinea pig striatum was also inhibited by the phencyclidine receptor agonist dizocilpine, but this inhibition was not reversed by the sigma receptor antagonists. Therefore, the inhibition produced by sigma receptor agonists was not mediated via the phencyclidine binding site within the N-methyl-D-aspartate-operated cation channel. Our findings support the hypothesis that sigma receptor activation provides a mechanism of modulating dopamine release from striatum, and that striatal tissue from guinea pigs appears to be an appropriate model for characterizing sigma1 receptor-mediated effects.     

Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R

Human serum paraoxonase (PON 1) exists in 2 major polymorphic forms (Q and R), which differ in the amino acid at position 191 (glutamine and arginine, respectively). These PON allozymes hydrolyze organophosphates and aromatic esters, and both also protect LDL from copper ion-induced oxidation. We have compared purified serum PONs of both forms and evaluated their effects on LDL oxidation, in respect to their arylesterase/paraoxonase activities. Copper ion-induced LDL oxidation, measured by the production of peroxides and aldehydes after 4 hours of incubation, were reduced up to 61% and 58%, respectively, by PON Q, but only up to 46% and 38%, respectively, by an equivalent concentration of PON R. These phenomena were PON-concentration dependent. Recombinant PON Q and PON R demonstrated similar patterns to that shown for the purified serum allozymes. PON Q and PON R differences in protection of LDL against oxidation were further evaluated in the presence of glutathione peroxidase (GPx). GPx (0.1 U/mL) alone reduced copper ion-induced LDL oxidation by 20% after 4 hours of incubation. The addition of PON R to the above system resulted in an additive inhibitory effect on LDL oxidation, whereas PON Q had no such additive effect. The 2 PON allozymes also differed by their ability to inhibit initiation, as well as propagation, of LDL oxidation. PON Q was more efficient in blocking LDL oxidation if added when oxidation was initiated, whereas PON R was more potent when added 1 hour after the initiation of LDL oxidation. These data suggest that the 2 allozymes act on different substrates. Both PON allozymes were also able to reduce the oxidation of phospholipids and cholesteryl ester. PON Q arylesterase activity was reduced after 4 hours of LDL oxidation by only 28%, whereas the arylesterase activity of PON R was reduced by up to 55%. Inactivation of the calcium-dependent PON arylesterase activity by using the metal chelator EDTA, or by calcium ion removal on a Chelex column, did not alter PON's ability to inhibit LDL oxidation. However, blockage of the PON free sulfhydryl group at position 283 with p-hydroxymercuribenzoate inhibited both its arylesterase activity and its protection of LDL from oxidation. Recombinant PON mutants in which the PON free sulfhydryl group was replaced by either alanine or serine were no longer able to protect against LDL oxidation, even though they retained paraoxonase and arylesterase activities. Overall, these studies demonstrate that PON's arylesterase/paraoxonase activities and the protection against LDL oxidation do not involve the active site on the enzyme in exactly the same way, and PON's ability to protect LDL from oxidation requires the cysteine residue at position 283.     

Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation

The effect of consuming red wine, or its major polyphenol constituents catechin or quercetin, on the development of atherosclerotic lesions, in relation to the susceptibility of plasma LDL to oxidation and to aggregation, was studied in atherosclerotic apolipoprotein E deficient (E degree) mice. Forty E degree mice at the age of 4 weeks were divided into four groups, 10 mice in each group, and were supplemented for up to 6 weeks in their drinking water with placebo (1.1% alcohol); catechin or quercetin (50 micrograms/d per mouse), or red wine (0.5 mL/d per mouse). Consumption of catechin, quercetin, or red wine had no effect on plasma LDL or HDL cholesterol levels. The atherosclerotic lesion area was smaller in the treated mice by 39%, 46%, and 48%, respectively, in comparison with E degree mice that were treated with placebo. In accordance with these findings, cellular uptake of LDL derived after catechin, quercetin, or red wine consumption was found to be reduced by 31%, 40%, and 52%, respectively. These results were associated with reduced susceptibility to oxidation (induced by different modes such as copper ions, free radical generator, or macrophages) of LDL isolated after red wine or quercetin and, to a lesser extent after catechin consumption, in comparison with LDL isolated from the placebo group. Similar results were obtained when LDL was preincubated in vitro with red wine or with the polyphenols prior to its oxidation. Even in the basal oxidative state (not induced oxidation), LDL isolated from E degree mice that consumed catechin, quercetin, or red wine for 2 weeks was found to be less oxidized in comparison with LDL isolated from E degree mice that received placebo, as evidenced by 39%, 48%, and 49% reduced content of LDL-associated lipid peroxides, respectively. This effect could be related to enhanced serum paraoxonase activity in the polyphenol-treated mice. LDL oxidation was previously shown to lead to its aggregation. The present study demonstrated that the susceptibility of LDL to aggregation was reduced in comparison with placebo-treated mice, by 63%, 48%, or 50% by catechin, quercetin, and red wine consumption, respectively, and this effect could be shown also in vitro. The inhibition of LDL oxidation by polyphenols could be related, at least in part, to a direct effect of the polyphenols on the LDL, since both quercetin and catechin were found to bind to the LDL particle via the formation of an ether bond. We thus conclude that dietary consumption by E degree mice of red wine or its polyphenolic flavonoids quercetin and, to a lesser extent, catechin leads to attenuation in the development of the atherosclerotic lesion, and this effect is associated with reduced susceptibility of their LDL to oxidation and aggregation.     

Shell-dependent correlation functions for solid3He

Ground-state energy of solid ³ He was computed by a Monte Carlo procedure in which the correlation parameter for nearest neighbor pairs was assigned different values from that for more distant pairs. This results in a ground-state energy which is lower by about 0.5 K than the value obtained with a single correlation parameter.     

Altered regulation of L-type channels by protein kinase C and protein tyrosine kinases as a pathophysiologic effect in retinal degeneration

The effect of protein tyrosine kinases (PTK) on L-type calcium channels in cultured retinal pigmented epithelium (RPE) from rats with retinal dystrophy was investigated. Barium currents through Bay K 8644 (10(-6) M) sensitive L-type channels were measured using the patch-clamp technique. The current density of L-type currents is twice as high and the inactivation time constants are much slower than in cells from nondystrophic control rats. Application of the PTK blockers genistein, lavendustin A, and herbimycin A (all 5 x 10(-6) M) led to an increase of L-type currents. Intracellular application of pp60c-src (30 U/ml) via the patch pipette led to a transient decrease of L-type currents. The protein kinase A (PKA) and PKG blocker H9 (10(-6) M) showed no effect on L-type currents. However, the protein kinase C blocker chelerythrine (10(-5) M) reduced these currents. Up-regulation of PKC by 10(-6) M 4beta-phorbol-12 myristate-13 acetate (PMA) led to a decrease of L-type currents. Additional application of genistein led to a further decrease of these currents. However, intracellular application of pp60(c-src) in PMA-treated cells led to a transient increase of L-type currents. Investigating the calcium response to bFGF application showed that RPE cells from RCS rats used different pathways than control RPE cells to increase cytosolic free calcium. This different pathway does not involve the activation of L-type channels. The present study with RPE cells from rats with retinal dystrophy shows a changed integration of PTK and PKC in channel regulation. Considering the altered response to bFGF in RCS-RPE cells, this disturbed regulation of L-type channels by tyrosine kinases is involved in the etiology of retinal degeneration in RCS rats.     

Consumption of polyphenolic-rich beverages (mostly pomegranate and black currant juices) by healthy subjects for a short term increased serum antioxidant status, and the serum's ability to attenuate macrophage cholesterol accumulation

The present study analyzed the antioxidative effects of various beverages, in vitro, and also the effect of short term consumption of beverages richest in polyphenols by healthy subjects on serum anti-atherogenic properties. Healthy subjects consumed 250 mL of the selected beverages for 2 h, or daily, for up to 1 week.We hypothesized that differences in the anti-atherogenic properties of the studied beverages could be related, not only to the quantity of polyphenols, but also to their quality. Furthermore, we hypothesized that consumption of these juices by healthy subjects for just a short-term, will increase their serum anti-atherogenic properties, as was demonstrated previously in long-term consumption studies.Of 35 beverages studied, both 100% Wonderful-variety pomegranate and 100% black currant juices were the most potent antioxidants in vitro, as they inhibited copper ion-induced LDL oxidation by up to 94% and AAPH-induced serum lipid peroxidation by up to 38%. Furthermore, they increased in vitro serum paraoxonase 1 (PON1) lactonase activity by up to 51%. Consumption of five selected polyphenol rich beverages by healthy subjects increased serum sulfhydryl group (SH) levels and serum PON1 activities after 2 h, and more so after 1 week of drinking these beverages. These effects were most pronounced after the consumption of 100% Wonderful-variety pomegranate and 100% black currant juices. In conclusion, polyphenolic-rich juices with impressive in vitro antioxidant properties, also demonstrate antioxidant effects in vivo when analyzed for short term consumption. In this respect, 100% Wonderful-variety pomegranate and 100% black currant juices were most the potent.