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Objective: To quantify marine food product consumption and EPA + DHA intake among Quebecers, and to compare the results with the most recent recommendations., Design: Data were obtained from a representative cross-sectional telephone survey (June 2006). Intakes of marine food product species and EPA + DHA were estimated from a validated FFQ on the consumption of marine food products during the previous month. Prevalence of fish oil consumption in the last 6 months was also assessed., Setting: Province of Quebec (Canada)., Subjects: A representative sample (n 1001) of adults in the province of Quebec. Of these, eight were excluded from the present analysis (n 993)., Results: Mean and median EPA + DHA intakes for all participants were estimated to be 291 mg/d (sem 11) and 207 mg/d, respectively. 85.0 % (95 % CI 82.7, 87.3) of Quebecers had an EPA + DHA intake lower than 500 mg/d, which is the amount internationally recommended for the prevention of CVD. Mean and median DHA intakes among women of childbearing age (n 128, 18-34 years) were estimated to be 169 mg/d (sem 17) and 126 mg/d, respectively. Of these women, 27.7 % had a daily intake >200 mg DHA and 15.9 % had an intake >300 mg DHA. We noted that 13 % of Quebecers take >or=1 capsule of fish oil/d., Conclusions: Consumption of marine food products and EPA + DHA among Quebecers clearly appears to be lower than international recommendations. Since EPA + DHA confer health benefits and may reduce health costs, strategies to increase their consumption should be implemented to improve public health in Quebec.

Objectives: The Inuit of Nunavik in northern Quebec have a lower risk for ischemic heart disease (IHD) compared to Caucasian populations. Acylation stimulating protein (ASP), which is involved in the storage of dietary fat, may play a role. The objective of the study was to determine plasma concentration of ASP in an Inuit and a southern Quebec Caucasian population., Study Design: This is a cross-sectional study evaluating the relationship between ASP and dietary factors, such as retinol, whose intake is higher in the Inuit. As well, concentrations of ASP were evaluated in relationship to components of the metabolic syndrome., Methods: Medical history was collected via a questionnaire and anthropometric measurements and blood samples were collected., Results: ASP was significantly higher in both the Inuit men and women compared to Caucasian men (66.1 +/- 4.1 nM vs 27.5 +/- 2.5 nM, p < 0.0001) and women (71.8 +/- 3.8 nM vs 29.4 +/- 1.3 nM, p < 0.0001). In addition, ASP significantly correlated with total retinol (r = 0.17, p = 0.02) and free retinol (r = 0.15, p = 0.04) in Inuit men but not with other distinctive dietary markers such as omega-3 fatty acids., Conclusions: Inuit men and women have higher ASP which was unrelated to the number of risk factors for IHD that were present.

Objective: To examine the relationship between psychological distress (PD) and plasma n-3 long-chain (LC) PUFA, i.e. EPA, docosapentaenoic acid (DPAn-3) and DHA., Design: Population-based, cross-sectional Santé-Québec Health Survey (1991). Participants were categorized as high-level PD if they scored over the 80th percentile of the PD Index in the Santé-Québec Survey; non-distressed subjects were those who scored less than this cut-off. Associations between tertiles of n-3 fatty acids (FA) and the risk of high-level PD were expressed as odds ratios, with the lowest tertile as the reference group., Setting: Québec, Canada., Subjects: Data were analysed from a representative sample of 852 James Bay Cree Indian adults aged 18 years and over., Results: Proportions of n-3 FA were statistically significantly lower in the PD than in the non-distressed group. After adjustment for confounders, EPA was the only individual n-3 FA significantly associated with the risk of high-level PD. Combinations of EPA + DHA or EPA + DPAn-3 + DHA or the sum of n-3 were also associated with the risk of high-level PD. Compared with the lowest tertile of EPA + DHA, the OR for high-level PD was 0.89 (95 % CI 0.59, 1.36) for the second and 0.56 (95 % CI 0.32, 0.98) for the third tertile, after controlling for confounders., Conclusions: In the present retrospective, cross-sectional study, we found that proportions of n-3 LC PUFA in plasma phospholipids, markers of n-3 LC PUFA consumption from fish, were inversely associated with PD.

Epidemiological evidence suggests a negative impact of methylmercury on the cardiovascular system, but findings regarding the effect on blood pressure (BP) are not consistent. We aimed to study the impact of mercury levels on BP among Nunavik Inuit adults. The health survey Qanuippitaa? was conducted in Nunavik (northern Quebec, Canada), and data were obtained from 732 Inuit > or = 18 years of age. Anthropometric blood samples, as well as systolic BP and diastolic BP, were assessed. Pulse pressure (systolic BP-diastolic BP) was calculated. Mercury blood concentration was used as a biomarker of recent exposure. Simple relations between mercury and BP parameters were studied by using the Pearson correlation, whereas multiple regressions were performed to control for confounders. Mean age of the participants was 34.3 years (95% CI: 33.6 to 34.9 years). Systolic BP, diastolic BP, and pulse pressure means were 117 mm Hg (95% CI: 116 to 118 mm Hg), 73 mm Hg (95% CI: 72 to 74 mm Hg), and 43 mm Hg (95% CI: 42 to 44 mm Hg), respectively. Mercury mean was 50.2 nmol/L. In multivariable analyses, mercury was associated with systolic BP (beta=2.14; P=0.0004), whereas the association with diastolic BP was near the significance level (beta=0.96; P=0.069). In conclusion, mercury is associated with increasing BP and pulse pressure among Nunavik Inuit adults after considering the effect of fish nutrients (n-3 fatty acids and selenium) and other confounders.

The event-related potential (ERP) P3b, a cognitive electrophysiological measure that has been linked to working memory processing in many experimental paradigms, was measured in Inuit children from Nunavik (Arctic Québec, Canada) to assess lead (Pb) neurotoxicity. Visual and auditory oddball paradigms were administered at 5 (N=27) and 11 (N=110) years of age, respectively, to elicit this ERP component. Pearson correlations and multiple regression analyses were performed to examine the associations between Pb levels and P3b parameters (peak latency and amplitude). Greater prenatal Pb exposure was related to a decrease in P3b amplitude at 5 years of age, and early childhood Pb exposure was associated with delayed P3b latency at 5 years. No significant association was observed at 11 years. These results, in line with those from previous neurobehavioral studies, suggest that Pb exposure affects cognitive processing in children even though the Pb levels measured in a large majority of our sample were below the threshold value for public health intervention used by federal agencies. This study strengthens the arguments for reducing sources of Pb exposure in Nunavik and for lowering the blood Pb concentrations considered "acceptable" in governmental policies.

Background: During androgen ablation prostate cancer cells' growth and survival become independent of normal regulatory mechanisms. These androgen-independent cells acquire the remarkable ability to adapt to the surrounding microenvironment whose factors, such as neurotransmitters, influence their survival. Although findings are becoming evident about the expression of alpha(1A)-adrenoceptors in prostate cancer epithelial cells, their exact functional role in androgen-independent cells has yet to be established. Previous work has demonstrated that membrane lipid rafts associated with key signalling proteins mediate growth and survival signalling pathways in prostate cancer cells., Methodology/principal Findings: In order to analyze the membrane topology of the alpha(1A)-adrenoceptor we explored its presence by a biochemical approach in purified detergent resistant membrane fractions of the androgen-independent prostate cancer cell line DU145. Electron microscopy observations demonstrated the colocalization of the alpha(1A)-adrenoceptor with caveolin-1, the major protein component of caveolae. In addition, we showed that agonist stimulation of the alpha(1A)-adrenoceptor induced resistance to thapsigargin-induced apoptosis and that caveolin-1 was necessary for this process. Further, immunohistofluorescence revealed the relation between high levels of alpha(1A)-adrenoceptor and caveolin-1 expression with advanced stage prostate cancer. We also show by immunoblotting that the TG-induced apoptosis resistance described in DU145 cells is mediated by extracellular signal-regulated kinases (ERK)., Conclusions/significance: In conclusion, we propose that alpha(1A)-adrenoceptor stimulation in androgen-independent prostate cancer cells via caveolae constitutes one of the mechanisms contributing to their protection from TG-induced apoptosis.

Background: Several ubiquitous polyhalogenated compounds (PHCs) have been shown to alter thyroid function in animal and in vitro studies. So far, epidemiologic studies have focused on the potential effect of a small number of them, namely, polychlorinated biphenyls (PCBs) and some organochlorines (OCs), without paying attention to other important PHCs., Objectives: We investigated the relationship between exposure to several PHCs and thyroid hormone homeostasis in Inuit adults from Nunavik., Methods: We measured thyroid parameters [thyroid-stimulating-hormone (TSH), free thyroxine (fT(4)), total triiodothyronine (tT(3)), and thyroxine-binding globulin (TBG)] and concentrations of 41 contaminants, including PCBs and their metabolites, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), perfluorooctanesulfonate (PFOS), and a measure of dioxin-like compounds, detected in plasma samples from Inuit adults (n = 623)., Results: We found negative associations between tT(3) concentrations and levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites of PCBs (MeSO(2)-PCBs), and 2 OCPs. Moreover, we found negative associations between fT(4) levels and hexachlorobenzene concentrations. TBG concentrations were inversely related to 8 PCBs, 5 HO-PCBs, and 3 OCPs. Exposure to BDE-47 was positively related to tT (3), whereas PFOS concentrations were negatively associated with TSH, tT(3,) and TBG and positively with fT(4) concentrations., Conclusion: Exposure to several PHCs was associated with modifications of the thyroid parameters in adult Inuit, mainly by reducing tT(3) and TBG circulating concentrations. The effects of PFOS and BDE-47 on thyroid homeostasis require further investigation because other human populations display similar or higher concentrations of these chemicals.

Dietary exposure to trans-fatty acids (TFA) is likely to be high among Canadian Inuit; yet no data are available on the physiological effects of TFA in this population. The purpose of the present study was to assess the association between TFA and plasma lipid profiles in Inuit men and women living in Nunavik (Québec, Canada). In a cross-sectional, population-based survey, a total of 795 Nunavik Inuit eligible participants gave a blood sample. Exposure to TFA was assessed by their relative proportion in erythrocyte membrane. We performed multiple regression analysis using plasma lipids or their linear combinations as the dependent variables and TFA as the main predictor, adjusting for potential confounders. The associations varied markedly between the sexes and according to age. In men (n 357, aged 36.3 (sd 14.3) years, TFA 1.24 (sd 0.54) %), TFA tended to be negatively associated with HDL-cholesterol (HDL-C), apoA1 and LDL particle size, and positively associated with non-HDL-C, LDL-cholesterol (LDL-C), apoB100, the apoB100:apoA1 ratio and the ratios of total cholesterol (TC), LDL-C and TAG to HDL-C. No such trends were observed in women (n 438, aged 37.0 (sd 14.1) years, TFA 1.16 (sd 0.54) %), except for HDL-C and apoA1 in women aged 50 years and more. These results suggest that TFA could raise the risk of CHD in Inuit men at least through their physiological effects on plasma lipids. The differential associations reported in pre- and postmenopausal women need to be reproduced in other populations and in experimental studies addressing the influence of sex hormones in response to dietary fats.

Perfluorooctanesulfonate (PFOS) and brominated organic compounds (BOCs) have been found in biota and humans worldwide with levels of BOCs being the highest in North America. PFOS and BOC exposure of remote populations that consume species of a marine food web for their subsistence has seldom been investigated. In 2004, we determined the concentrations of these contaminants in 883 Nunavik Inuit adults from the Canadian Arctic and investigated the demographic and dietary factors associated with them. Demographic and dietary information were collected by questionnaires. Multiple linear regressions were conducted to investigate predictors of exposure to those contaminants. Polychlorinated biphenyl (PCB) congener 153 concentrations are presented for comparative purposes. PFOS and PCB 153 were detected in all samples, with plasma concentrations several times higher than BOCs. The consumption of fish and marine mammals appears to be an important contributor to PFOS exposure among Nunavik Inuit. While PBDE 153 also appears as a persistent PBDE congener, exposure to PBDE 47 seems to be more recent in this population. Adoption of a westernized lifestyle seems to be related to an increased exposure to PBDE 47, but specific sources remain to be elucidated. In conclusion, we found that the remote geographical location and traditional lifestyle of the Nunavik Inuit population do not protect them against exposure to emerging POPs, particularly PFOS.

Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against dementia, although epidemiologic studies have yielded inconclusive results. Fish is the main dietary source of n-3 PUFAs and is sometimes contaminated with mercury. This neurotoxicant may modify the association with dementia., Objective: We evaluated the association of erythrocyte membrane total n-3 PUFAs, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and blood mercury with the incidence of dementia and Alzheimer disease (AD) in the Canadian Study of Health and Aging (CSHA) with adjustment for confounders including apolipoprotein E epsilon4 (APOE epsilon4) status., Design: The CSHA is a cohort study of a representative sample of persons aged > or =65 y, conducted from 1991 to 2002. A subsample of 663 nondemented CSHA subjects with a complete clinical examination, blood samples, and follow-up information was eligible for prospective analyses on laboratory measurements. Of these, 149 were incident cases of dementia, including 105 with AD., Results: In adjusted Cox regression models with age as the time scale, there were no associations between total n-3 PUFAs, DHA, or EPA and dementia or AD. In contrast, a mercury concentration in the highest quartile was associated with a reduced risk of dementia (hazard ratio: 0.53; 95% CI: 0.33, 0.88). However, significant risk reductions were limited to subjects with concentrations of both n-3 PUFAs and mercury that were above the median. There was no modification of risk by APOE epsilon4 status., Conclusions: No associations between n-3 PUFAs and dementia or AD were found. The results regarding mercury may indicate a spurious association.

Background: An increasing number of studies have shown that several ubiquitous environmental contaminants possess thyroid hormone-disrupting capacities. Prenatal exposure to some of them, such as polychlorinated biphenyls (PCBs), has also been associated with adverse neurodevelopmental effects in infants., Objectives: In this study we examined the relationship between exposure to potential thyroid hormone-disrupting toxicants and thyroid hormone status in pregnant Inuit women from Nunavik and their infants within the first year of life., Methods: We measured thyroid hormone parameters [thyroid stimulating hormone (TSH), free thyroxine (fT(4)), total triiodothyronine (T(3)), thyroxine-binding globulin (TBG)] and concentrations of several contaminants [PCB-153, hydroxylated metabolites of PCBs (HO-PCBs), pentachlorophenol (PCP) and hexachlorobenzene (HCB)] in maternal plasma at delivery (n = 120), in umbilical cord plasma (n = 95), and in infant plasma at 7 months postpartum (n = 130)., Results: In pregnant women, we found a positive association between HO-PCBs and T(3) concentrations (beta = 0.57, p = 0.02). In umbilical cord blood, PCB-153 concentrations were negatively associated with TBG levels (beta = -0.26, p = 0.01). In a subsample analysis, a negative relationship was also found between maternal PCP levels and cord fT(4) concentrations in neonates (beta = -0.59, p = 0.02). No association was observed between contaminants and thyroid hormones at 7 months of age., Conclusion: Overall, there is little evidence that the environmental contaminants analyzed in this study affect thyroid hormone status in Inuit mothers and their infants. The possibility that PCP may decrease thyroxine levels in neonates requires further investigation.

Marine omega-3 (n-3) fatty acid eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have been associated with beneficial effects in mental health. Cultural and social changes have been related to a decline in mental health of the Inuit, but the role of diet has received scant attention. We examined the relationship between psychological distress (PD) and plasma n-3 among 368 Nunavik Inuit aged 18-74 years who took part in a survey in 1992. Participants were categorized as high-level PD if they scored over the 80th percentile of the PD Index Santé-Québec Survey (PDISQS-14), and non-distressed subjects were those who scored less than this cutoff. Compared with the non-distressed group, n-3 concentrations in the PD group were significantly lower in women but not in men. Compared with the lowest tertile of EPA + DHA, the odds ratios for high-level PD among women were 0.32 (95% CI: 0.13-0.82) for the second, and 0.30 (95% CI: 0.10-0.90) for the third tertile, after controlling for confounders. In males, there were no significant associations between EPA+DHA and PDISQS-14 scores. Our findings suggest that marine n-3 may play a role in PD among Inuit women. The gender difference observed in our analysis must be examined more carefully in future studies.

As a result of their intimate contact with the land and their nutritional habits, the Inuit of Nunavik are considered to be at risk from zoonotic infections. To better understand the risk factors for Toxoplasma gondii infection, a serosurvey was conducted in Nunavik, Québec, in September 2004. A representative sample of the Inuit adult population of Nunavik participated in this cross-sectional study (n = 917). Antibodies (IgG) against T. gondii were detected by immunoassay. Information on sociodemographic characteristics, traditional activities, domestic environment and nutrition was gathered by questionnaire and explored as variables explanatory of seropositive results. Associations found to be statistically significant in univariate analyses were assessed by multivariable logistic regression to control for confounding factors. Almost two thirds (59.8%) of the Inuit of Nunavik were found to be seropositive for T. gondii. In multivariate analyses, risk factors for seropositivity were: increasing age, gender (women > men), lower level of education, consumption of potentially contaminated water (determined by an index of risk from waterborne infections), frequent cleaning of water reservoirs, and consumption of seal meat and feathered game. There was some variation in seroprevalence between the Ungava Bay coast (52.3%) and the Hudson Bay coast (65.6%), the two main regions of Nunavik, but this variation was not significant in the multivariable logistic regression model. This cross-sectional study demonstrated high T. gondii seroprevalence in the Inuit population and revealed that age, gender, schooling and community of residence all influence serostatus in this population. Variables related to drinking water and food choices may also influence the risk of infection. These results raise important questions about T. gondii transmission in Nunavik including possible links between terrestrial and marine cycles.

Objective: We evaluated the prevalence of type 2 diabetes, obesity and metabolic syndrome according to International Diabetes Federation criteria in the First Nations Cree community of Mistissini, Quebec., Methods: A cross-sectional study of 172 adults was performed as part of a broader regional environmental study., Results: Type 2 diabetes, hyperinsulinemia and abdominal obesity were documented in 20%, 70% and 91% of participants, respectively. The prevalence of metabolic syndrome was 54%, with the main profile including abnormal plasma glucose levels (60%) associated with high triacylglycerol (40%). Women displayed the highest prevalence of abdominal obesity (99%). In both sexes, waist circumference was clearly associated with other metabolic parameters, such as blood glucose and lipid profile (p<0.0001). However, a significant proportion of the population (13%), especially women, showed high waist circumference with no metabolic disturbances., Conclusion: Among the Cree population of Mistissini, the results suggest that the high prevalence of abdominal obesity occurs most frequently in women, and earlier in women than in men. Subsequent metabolic disturbances associated with metabolic syndrome develop with age, supporting the core role of abdominal obesity in the cascade of events leading to diabetes and cardiovascular disease., (Copyright © 2009 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two vitamin D receptor (VDR) gene single nucleotide polymorphisms restriction enzyme detecting SNP of VDR (FokI and BsmI) with breast cancer risk in two independent case-control studies carried out in the same population. The modifying effect of family history of breast cancer on this relationship was also evaluated. The first and second studies included respectively 718 (255 cases/463 controls) and 1596 (622 cases/974 controls) women recruited in Quebec City, Canada. FokI and BsmI genotypes were assessed. Relative risks of breast cancer were estimated by multivariate logistic regression. Compared with homozygotes for the common F allele (FF genotype), FokI ff homozygotes had a higher breast cancer risk (study 1: odds ratio (OR)=1.22, 95% confidence interval (CI)=0.76-1.95; study 2: OR=1.44, 95% CI=1.05-1.99; and combined studies: OR=1.33, 95% CI=1.03-1.73). Significant interactions were observed between FokI and family history of breast cancer in the two studies as well as in the combined analysis (P interaction=0.031, 0.050 and 0.0059 respectively). Among women without family history, odds ratios were 1.00, 1.27 (95% CI=1.02-1.58) and 1.57 (95% CI=1.18-2.10) respectively for FF, Ff and ff carriers (P(trend)=0.0013). BsmI Bb+bb genotypes were associated with a weak non-significant increased risk in the two studies (combined OR=1.22, 95% CI=0.95-1.57) without interaction with family history. Results support the idea that vitamin D, through its signalling pathway, can affect breast cancer risk. They also suggest that variability in observed associations between VDR FokI and breast cancer from different studies may partly be explained by the proportion of study subjects with a family history of breast cancer.

Fish consumption today is widely recognized as highly beneficial since it constitutes a good source of several essential nutrients, such as selenium and polyunsaturated fatty acids (n-3 PUFA). However, fish can also contain contaminants such as mercury, which make the consumer, especially pregnant women, confused about the risk-benefit balance associated with fish consumption. This is particularly true for tropical fish species for which little information is available. We have previously reported that some Bermudian neonates had elevated mercury in their umbilical blood compared with international guidelines. The objective of this study was to give precise and balanced information on the content of mercury, selenium and PUFA in the most consumed fish species in Bermuda. In 2003 and 2006, a total of 307 fish were collected from 43 fish species and 351 samples were analysed (305 flesh samples, 44 liver samples, one roe and one fat sample) by inductively coupled plasma-mass spectrometry (ICP-MS) (metals) and high-resolution gas chromatography (HRGC) (fatty acids). Results show that mercury varies among species from 0.03 to 3.3 microg g(-1) and that it is possible for at-risk groups such as pregnant women to make informed choices concerning fish consumption, e.g. maximizing fish species rich in nutrients and low in mercury.

Background: Several prospective studies have revealed that prenatal exposure to polychlorinated biphenyls (PCBs) and other organochlorine compounds (OCs) affect neurodevelopment during infancy. One of the mechanisms by which PCBs might interfere with neurodevelopment is a deficit in thyroid hormone (TH) concentrations., Objectives: We investigated the potential impact of transplacental exposure to PCBs and hexachlorobenzene (HCB) on TH concentrations in neonates from two remote coastal populations exposed to OCs through the consumption of seafood products., Methods: Blood samples were collected at birth from the umbilical cord of neonates from Nunavik (n=410) and the Lower North Shore of the St. Lawrence River (n=260) (Québec, Canada) for thyroid parameters [thyroid-stimulating hormone (TSH), free T4 (fT4), total T3 (tT3), and thyroxine-binding globuline (TBG)] and contaminants analyses., Results: In multivariate models, umbilical cord plasma concentrations of PCB 153, the predominant PCB congener, were not associated with TH and TSH levels in both populations. Prenatal exposure to HCB was positively associated with fT4 levels at birth in both populations (Nunavik, beta=0.12, p=0.04; St. Lawrence, beta=0.19, p<0.01), whereas TBG concentrations were negatively associated with PCB 153 concentrations (beta=-0.13, p=0.05) in the St. Lawrence cohort., Conclusion: OCs levels were not associated to a reduction in THs in neonates from our two populations. Essential nutrients derived from seafood such as iodine may have prevented the negative effects of OCs on the thyroid economy during fetal development.

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities in which visceral obesity is a prominent feature. Although a matter of debate, the MetS essentially represents "at risk obesity." The purpose of this study was to compare the various definitions of MetS, with a special focus on abdominal obesity, and to explore sex and ethnic differences in the prevalence and nature of this syndrome in 3 ethnic groups residing in the Canadian province of Québec. The study population included adult participants of 3 cross-sectional health surveys conducted in southern Québec, James Bay, and Nunavik between 1990 and 1992. A total of 2613 adults (18-74 years old) were included: 1417 Quebecers, 817 Indian Crees, and 379 Inuit. The prevalence of MetS varied by definitions, and the highest agreement was observed between the National Cholesterol Education Program-Adult Treatment Panel III and the International Diabetes Federation (79%). Most women (25%), regardless of ethnic origin, presented with a "triad" profile characterized by high waist circumference, elevated triglycerides, and low high-density lipoprotein, whereas 20% of men had the "deadly quartet" of high blood pressure with the triad mentioned above. Furthermore, our results highlight an obvious difference in the impact of the increased abdominal obesity on metabolic parameters such as insulin resistance measured by the homeostasis model assessment according to ethnic origin (P < .001). These 3 unique population-based samples suggest that abdominal obesity does not have a similar deleterious impact according to ethnicity, suggesting the need for an ethnic-based MetS definition.

The Inuit are heavily exposed to potentially prooxidant contaminants such as methylmercury (MeHg) and polychlorinated biphenyls (PCB) through their traditional diet. This diet is also an abundant source of n-3 polyunsaturated fatty acids (n-3 PUFA), selenium, and antioxidants, which might reduce cardiovascular risk. Although Inuit from Nunavik have low concentrations of plasma oxidized low-density lipoprotein (OxLDL) and elevated glutathione-related antioxidant defenses, the variance in OxLDL was predicted by PCB and blood glutathione, leaving the issue of contaminant-associated oxidative stress unresolved. The objective of the study was to assess oxidative stress in these Inuit by measuring the plasma concentrations and redox states of alpha-tocopherol and coenzyme Q10 (CoQ10), 2 sensitive biomarkers of oxidative stress, in relation to exposure. Plasma lipophilic antioxidants were determined by high-performance liquid chromatography-coupled electrochemical detection; and their relations to PCB, MeHg, n-3 PUFA, selenium, and OxLDL were assessed by multivariate analyses. Ubiquinol-10, ubiquinone-10, and ubiquinone-10 to CoQ10(total) ratio were elevated as compared with white populations but showed no associations with PCB, MeHg, or n-3 PUFA. Ubiquinol-10 (beta = .23, P = .007) and CoQ10(total) (beta = .27, P = .009) were predicted by blood selenium; and alpha-tocopherol, by PCB (beta = 4.12, P = .0002), n-3 PUFA (beta = 9.16, P = .02), and OxLDL (beta = 3.04, P = .05). Unexpectedly, the alpha-tocopheryl quinone to alpha-tocopherol ratio, in the reference range, was negatively predicted by PCB (beta = -0.41, P = .02). Using sensitive biomarkers of redox alterations, we found no evidence for MeHg- or PCB-associated oxidative stress in these Inuit. However, despite robust blood antioxidant defenses, the unusually elevated ubiquinone-10 to CoQ10(total) ratio (0.21 +/- 0.11) suggests some form of oxidative stress of unknown origin.

Background: Mercury is a contaminant that reaches high levels in Nunavik (North of Quebec). It is transformed into methylmercury (MeHg) and accumulated in marine mammals and predator fish, an important part of the traditional Inuit diet. MeHg has been suggested to affect BP in adults and children while the influence on HRV has only been studied in children. We aimed to assess the impact of MeHg levels on HRV and BP in Inuit adults from Nunavik., Methods: In the fall of 2004, the <> Health Survey was conducted in Nunavik (Quebec, Canada) and information on HRV was collected among 280 adults aged 40 years and older. Indicators of the time and frequency domains of HRV were derived from a 2-hour Holter recording. BP was measured according to the Canadian Coalition for High Blood Pressure technique. Pulse pressure (PP) was the difference between systolic (SBP) and diastolic blood pressure (DBP). Blood mercury concentration was used as exposure biomarker. Statistical analysis was conducted through linear regression and multivariable linear regression was used to control for confounders., Results: Mercury was negatively correlated with low frequency (LF) (r = -0.18; p = 0.02), the standard deviation of RR intervals (SDNN) (r = -0.14; p = 0.047) and the coefficient of variation of RR intervals (CVRR) (r = -0.18; p = 0.011) while correlations with other HRV parameters did not reach statistical significance. After adjusting for confounders, the association with LF (beta = -0.006; p = 0.93) became non significant. However, the association with SDANN became statistically significant (beta = -0.086; p = 0.026) and CVRR tended to decrease with blood mercury concentrations (beta = -0.057; p = 0.056). Mercury was positively correlated with SBP (r = 0.25; p < 0.0001) and PP (r = 0.33; p < 0.0001). After adjusting for confounders, these associations remained statistically significant (beta SBP = 4.77; p = 0.01 and beta PP = 3.40; p = 0.0036). Moreover, most of the HRV parameters correlated well with BP although SBP the best before adjustment for mercury exposure., Conclusion: The results of this study suggest a deleterious impact of mercury on BP and HRV in adults. SBP and PP increased with blood mercury concentrations while SDANN decreased with blood mercury concentrations.

Bermuda residents collect rainwater from rooftops to fulfil their freshwater needs. The objective of this study was to assess the microbiological quality of drinking water in household tanks throughout Bermuda. The tanks surveyed were selected randomly from the electoral register. Governmental officers visited the selected household (n = 102) to collect water samples and administer a short questionnaire about the tank characteristics, the residents' habits in terms of water use, and general information on the water collecting system and its maintenance. At the same time, water samples were collected for analysis and total coliforms and Escherichia coli were determined by 2 methods (membrane filtration and culture on chromogenic media, Colilert kit). Results from the 2 methods were highly correlated and showed that approximately 90% of the samples analysed were contaminated with total coliforms in concentrations exceeding 10 CFU/100 mL, and approximately 66% of samples showed contamination with E. coli. Tank cleaning in the year prior to sampling seems to protect against water contamination. If rainwater collection from roofs is the most efficient mean for providing freshwater to Bermudians, it must not be considered a source of high quality drinking water because of the high levels of microbial contamination.

The effects of a moderate seasonal exposure to methylmercury on plasma low-density lipoprotein (LDL) oxidation and cardiovascular risk indices are not known. The objective of the study was to assess the effects of a seasonal exposure to mercury at similar dose reported to increase cardiovascular risk through fish consumption. Effects on lipoprotein cholesterol and fatty acid profiles, LDL oxidation, and blood oxidant-antioxidant balance were to be assessed in sport fishermen presenting normal blood selenium and omega-3 fatty acid contents. Thirty-one healthy James Bay sport fishermen were assessed for within-subject longitudinal seasonal variations in hair and blood mercury, plasma oxidized LDL, lipophilic antioxidants, homocysteine, blood selenium, and glutathione peroxidase and reductase activities determined before and after the fishing season and compared by matched-pair tests. Hair mercury doubled during the fishing season (2.8+/-0.4 microg/g, P<.0001). Baseline blood selenium, homocysteine, and erythrocyte fatty acid profiles did not change. Plasma high-density lipoprotein cholesterol increased (+5%, P=.05), whereas very low-density lipoprotein cholesterol and oxidized LDL decreased (-8%, P=.05; -18%, P=.008). Blood glutathione peroxidase (+9.7%, P=.001), glutathione reductase (+7.2%, P<.0001), and total glutathione (+45% P<.0001) increased during the fishing season. Plasma total coenzyme Q10 (+13%, P=.02), ubiquinone-10 (+67%, P=.03), and beta-carotene (+46%, P=.01) also increased, whereas vitamin E status was unaffected. Pairwise correlations revealed no association between mercury exposure and any of the biomarkers investigated. In contrast, strong predictors of cardiovascular risk such as high-density lipoprotein cholesterol, oxidized LDL, and glutathione peroxidase improved during the fishing season despite elevated methylmercury exposure. The beneficial effects of seasonal fishing activity and fish consumption on cardiovascular health may suppress detrimental effects of concomitant moderate methylmercury exposure.

Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgen-independent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.

Objective: To assess if vitamin A concentration in umbilical cord blood is associated with incidence and severity of respiratory infections in preschool Inuit children from Nunavik (Québec, Canada)., Method: The medical charts of 305 children were reviewed from 0 to 5 years of age. The association between vitamin A concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and hospitalization rates for LRTIs was evaluated using Poisson regression., Results: Compared to children with vitamin A concentration > or =20 microg/dl, adjusted rate ratios (RR) for children below 20 microg/dl ranged between 1.06-1.62 for AOM, 1.12-1.34 for LRTIs, and 1.09-1.43 for hospitalization for LRTIs. Most RRs were statistically significant for AOM and LRTIs, but not for hospitalization for LRTIs., Conclusion: Neonatal vitamin A deficiency appears to be a significant risk factor for AOM and LRTIs in this population.

Objectives: To examine the relation of cord plasma docosahexaenoic acid (DHA) concentration to gestation length, birth size, growth, and infant visual acuity, cognitive, and motor development and the effects on growth and development associated with DHA intake from breast-feeding., Study Design: DHA, other polyunsaturated fatty acids, and 3 environmental contaminants (polychlorinated biphenyls, mercury, and lead) were assessed in cord plasma and maternal plasma and milk in 109 Inuit infants in Arctic Quebec. Multiple regression was used to examine the relation of cord DHA and DHA from breast-feeding on growth and development at 6 and 11 months, after controlling for contaminant exposure and other potential confounders., Results: Higher cord DHA concentration was associated with longer gestation, better visual acuity and novelty preference on the Fagan Test at 6 months, and better Bayley Scale mental and psychomotor performance at 11 months. By contrast, DHA from breast-feeding was not related to any indicator of cognitive or motor development in this full-term sample., Conclusions: The association of higher cord DHA concentration with more optimal visual, cognitive, and motor development is consistent with the need for substantial increases in this critically important fatty acid during the third trimester spurt of synaptogenesis in brain and photoreceptor development.

French Polynesians consume high quantities of fish and are therefore exposed to seafood-related contaminants such as mercury (Hg) or lead (Pb) and nutrients such as iodine, selenium and long chain polyunsaturated fatty acids (LC-PUFAs). As the developing foetus is sensitive to contaminants and nutrients, a cross-sectional study was conducted in French Polynesia in 2005-2006 to assess prenatal exposure to contaminants and nutrients through fish consumption. Two hundred and forty one (241) delivering women originating from all islands of French Polynesia were recruited and agreed to answer questions on fish consumption and gave permission to collect umbilical cord blood for metals and nutrients analyses. All parameters were found in high concentrations in cord blood samples except for lead. Mercury concentrations averaged 64.6 nmol/L (or 13 microg/L) with values ranging from 0.25 to 240 nmol/L. Of the sample, 82.5% had Hg concentrations above the US-EPA blood guide-line of 5.8 microg/L. Tuna was the fish species which contributed the most to Hg exposure. High selenium and LC-PUFAs may counterbalance the potential risk of prenatal exposure to Hg in French Polynesia. Due to the high fish consumption of mothers, Polynesian newborns are prenatally exposed to high doses of mercury. Although selenium and omega-3 fatty acids may counteract mercury toxicity, informing pregnant women on both the mercury and nutrient content of local fish species is important.

French Polynesians, like other remote maritime populations are intimately connected to the ocean which nourishes their daily life and culture. Their reliance on fish raises the issue of potential exposure to harmful natural and anthropogenic contaminants as well as providing essential nutrients. The purpose of this study was to assess the risks and benefits of fish consumption in French Polynesia. This cross-sectional study included 195 adults aged 18 years old and over from the Tahiti and Moorea islands. Fatty acids, selenium (Se) and mercury (Hg) blood concentrations were measured in participants and were all very high. Blood concentrations indicate that Hg, Se and omega-3 fatty acids have a common origin, i.e. fish consumption. In comparing the Polynesian group with northern populations, we found that the Polynesian group had levels of Hg similar to those observed in Inuit populations (geometric mean (range): 90.3 (15-420) nmol/L vs. Inuit: m(r): 79.6 (4-560) nmol/L). Similar results were observed with Se blood concentrations. The fatty acid concentration was also similar to that of the Inuit population even though the specific profile of fatty acids differed. For the first time, we report very high blood concentrations of mercury, selenium and omega-3 fatty acids in a fishing population from the South Pacific, comparable to those reported among fishing populations from the Northern hemisphere. Further work is ongoing to better substantiate public health nutritional policies.

Ciguatoxins exert their effect on the voltage-sensitive sodium channels of the cellular membranes of all excitable tissues. This effect confers to ciguatera disease (CD) its neurologic hallmarks. A prospective study among French Polynesian adults over a two-month period was conducted to characterize and determine the persistence of neurologic symptoms of CD. We compared 47 patients with CD with 125 controls. In the acute phase of the disease, patients had mainly sensory disturbances as detected by an hypoesthesia on the palm of the hand and poorer sway performance compared with controls. Follow-up two months showed improvement of sway performance that eventually reaching control levels. However, for light-touch threshold, even if we observed a decrease threshold towards normal values, more than 50% of patients did not reach normal values 60 days after disease onset. Our results support the existence of neurologic impairments of CD and suggest their persistence for at least two months after onset.

Cree trappers and hunters are at risk for contracting infectious diseases conveyed by wildlife. We performed a study in a Cree community (Canada) to determine the seroprevalence of 8 zoonotic infections among hunters and trappers for evidence of exposure to Trichinella sp., Toxoplasma gondii, Toxocara canis, Echinococcus granulosus, Leptospira sp., Coxiella burnetii, Francisella tularensis, and Sin Nombre virus. A total of 50 participants (28 women and 22 men) were included in this study. Results indicate no or infrequent exposure to the Sin Nombre virus (0%) and 3 of the 4 parasites investigated (0-4%). Exposure to T. gondii (10%) and some bacteria appeared to be more prevalent (range, 4-18%). Overall, seropositivity was related to fishing, hunting, and trapping activities. Physicians should be aware of these infections in this population, particularly Q fever, tularemia, and leptospirosis.

Ciguatera is a tropical disease caused by seafood poisoning, for which the duration of symptoms remains to be determined. The objectives of this prospective study were to determine the prevalence of symptoms at different time points and to identify factors associated with chronic symptoms observed in adults suffering from this disease. At the time of onset, we observed a dose-response relationship including a strong association between the delay of appearance of symptoms and a severity index (P < 0.001). Our results confirmed the key role of fish organs in the risk of contracting a more severe form of ciguatera. In the chronic stage, only the severity score based on information recorded in the acute phase is related to the persistence of symptoms (P < 0.001). Our findings suggest that several symptoms observed in the acute phase of the disease are still experienced 15 days after onset. This supports previous observations based on isolated case reports.

The aim of this study was to investigate the association between prenatal exposure to lead (Pb) and several aspects of behavioral function during infancy through examiner ratings and behavioral coding of video recordings. The sample consisted of 169 11-month-old Inuit infants from Arctic Quebec. Umbilical cord and maternal blood samples were used to document prenatal exposure to Pb. Average blood Pb levels were 4.6 mug/dL and 5.9 mug/dL in cord and maternal samples respectively. The Behavior Rating Scales (BRS) from the Bayley Scales of Infant Development (BSID-II) were used to assess behavior. Attention was assessed through the BRS and behavioral coding of video recordings taken during the administration of the BSID-II. Whereas the examiner ratings of behaviors detected very few associations with prenatal Pb exposure, cord blood Pb concentrations were significantly related to the direct observational measures of infant attention, after adjustment for confounding variables. These data provide evidence that increasing the specificity and the precision of the behavioral assessment has considerable potential for improving our ability to detect low-to-moderate associations between neurotoxicants, such Pb and infant behavior.

Recent reports on the presence of persistent organic chemicals in wild and farmed salmon have left consumers and health professionals confused regarding the safety of regular fish consumption. The objectives of this study were (1) to compare concentrations of key contaminants and the essential nutrients omega-3 fatty acids between farmed and wild salmon and trout, and (2) to balance risks and benefits from regularly consuming these species. Concentrations of mercury, polychlorinated biphenyls, dioxins and furans as well as omega-3 fatty acids were determined in fillets from farmed salmon and trout bought in various markets located in Quebec, Canada, as well as in fillets from wild salmonids obtained from fishermen and various Canadian agencies. While differences were observed between market (farmed) and wild fish with regard to the concentrations of mercury and polychlorinated biphenyls, overall the concentrations of contaminants were low, such that the regular consumption of these fish would not cause tolerable daily intakes to be exceeded. Our results indicate that salmon and trout sold in Quebec markets, which as in markets located elsewhere in North America originate for the most part from Chilean farms, can be consumed regularly to achieve optimal nutritional benefits from omega-3 fatty acids, without incurring significant contaminant related health risks.

Objectives: We investigated the prevalence of obesity and the metabolic correlates of different levels of body mass index (BMI) and waist circumference among the Inuit in 3 countries., Methods: Data from 4 surveys of Inuit in Canada, Greenland, and Alaska conducted during 1990-2001 were pooled, with a total sample size of 2545 participants. These data were compared with data from a Canadian population of predominantly European origin., Results: Using the World Health Organization criteria for overweight and obesity, we found that the crude prevalence of overweight among Inuit men and women was 36.6% and 32.5%, respectively, and obesity was 15.8% and 25.5%, respectively. Inuit prevalences were similar to those of the highly developed countries of Europe and North America. As levels of obesity increased, as measured by BMI or waist circumference, the mean values of various metabolic indicators-lipid, glucose, and insulin levels and blood pressure-also increased. However, at each level of BMI or waist circumference, the Inuit had lower blood pressure and lipid levels than did Euro-Canadians., Conclusions: Our data indicate that universal criteria for obesity may not reflect the same degree of metabolic risk for populations such as the Inuit and suggest that ethnic-specific criteria are needed.

Objectives: The purpose of this study was to report the temporal trends of the incidence of ciguatera poisoning from 1992 to 2001 in French Polynesia., Methods: This retrospective study analysed 7842 cases of ciguatera disease recorded over a period of 10 years., Results: The annual incidence varied from 26.3 to 41.9 per 10,000 person-years. An analysis of cases grouped by archipelago revealed differences in incidences (P < 0.0001) with the most remote archipelagos having the highest incidences. A detailed analysis on a sub-sample of recorded cases for which clinical information was available (n = 1824) confirmed the neurological and gastrointestinal nature of this seafood poisoning., Conclusion: The incidence of ciguatera poisoning appeared relatively stable during the 10 years of the study period. However, the gradient of remoteness observed suggests an adaptation of management of ciguatera disease to each archipelago.

Prolactin (PRL) has been shown to be involved in the differentiation and proliferation of numerous tissues, including the prostate gland. Moreover, variations in [Ca2+]ER (calcium concentration within the endoplasmic reticulum) may play a role in cell growth. However, few studies have focused on the regulation of calcium homoeostasis by prolactin. The present study evaluates the regulation of calcium pools as well as the possible role of [Ca2+]ER variations as a signal for growth modulation by PRL. We show that PRL stimulates the proliferation of normal SV40 immortalized epithelial prostate (PNT1A) cells with a maximum effect at a dose of 100 ng/ml. We also show that 100 ng/ml PRL increases the [Ca2+]ER when measured either by indirect quantification with Fura-2AM after application of 1 mM thapsigargin or by direct quantification with Mag-Fura-2AM within the endoplas-mic reticulum. Western blot analysis shows that the SERCA 2b (sarcoendoplasmic calcium ATPase 2b) is over-expressed in PNT1A cells treated with 100 ng/ml PRL for 24 h. A small inter-fering RNA SERCA 2a/b, used to down-regulate endogenous SERCA 2b expression, reduced both PNT1A cell proliferation and [Ca2+]ER. We thus identify [Ca2+]ER and SERCA 2b as protagonists in PRL-induced proliferation.

Background: Inuit women are highly exposed through their traditional seafood based diet to organochlorine compounds, some of them displaying endocrine disrupting properties. We hypothesized that this exposure might be related to bone characteristics that are altered in osteoporosis, because hormone deficiency is a known risk factor for the disease., Methods: We measured quantitative ultrasound parameters (QUS) at the right calcaneum of 153 peri- and postmenopausal Inuit women (49-64 year old) from Nuuk, Greenland, and investigated the relation between these parameters and plasma organochlorine concentrations. We used high-resolution gas chromatography with electron capture detection to analyze plasma samples for 14 polychlorinated biphenyls (PCB) congeners and 11 chlorinated pesticides and metabolites. We analysed morning urine samples for cadmium, a potential confounder, by atomic absorption spectrometry. We used a validated questionnaire to document dietary and lifestyle habits as well as reproductive and medical histories., Results: Concentrations of PCB 153, a surrogate of exposure to most organochlorines present in plasma samples, were inversely correlated to QUS parameters in univariate analyses (p < 0.001). However, PCB 153 concentrations were not associated with QUS values in multivariate analyses that comprised potential confounding factors such as age, body weight, former oral contraceptive use and current hormone replacement therapy (HRT) use, which were all significant predictors of bone stiffness (total R2 = 0.39; p < 0.001)., Conclusion: Overall we found little evidence that organochlorines exposure is related to osteoporosis in Greenlandic Inuit women, but the hypothesis that exposure to dioxin-like compounds might be linked to decreased bone quality and osteoporosis deserves further attention.

Objective: Inuit children from around the world are burdened by a high rate of infectious diseases. The objective of this study was to evaluate the incidence rate of infections in Inuit preschool children from Nunavik (Northern Québec)., Methods: The medical chart of 354 children from a previously recruited cohort was reviewed for the first five years of life. All outpatient visits that led to a diagnosis of acute infection and all admissions for acute infections were recorded., Results: Rates of outpatient visits for acute otitis media (AOM) were 2314, 2300, and 732 events/1000 child-years for children 0-11 months, 12-23 months, and 2-4 years, respectively. Rates of outpatient visits for lower respiratory tract infections (LRTI) were 1385, 930, and 328 events/1000 child-years, respectively. Rates of hospitalization for pneumonia were 198, 119, and 31 events/1000 child-years, respectively., Conclusion: Inuit children from Nunavik have high rates of AOM and LRTI. Such rates were higher than that of other non-native North-American populations previously published. Admission for LRTI is up to 10 times more frequent in Nunavik compared to other Canadian populations.

Objective: We set out to assess whether environmental prenatal exposure to polychlorinated biphenyls (PCBs) is associated with incidence of acute respiratory infections in preschool Inuit children., Study Design: We reviewed the medical charts of 343 children from 0 to 5 years of age and evaluated the associations between PCB-153 concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM) and of upper and lower respiratory tract infections (URTIs and LRTIs, respectively)., Results: The incidence rates of AOM and LRTIs were positively associated with prenatal exposure to PCBs. Compared with children in the first quartile of exposure (least exposed), children in fourth quartile (most exposed) had rate ratios of 1.25 (p<0.001) and 1.40 (p<0.001) for AOM and LRTIs, respectively. There was no association between prenatal PCB exposure and incidence rate of URTIs or hospitalization., Conclusion: Prenatal exposure to PCBs could be responsible for a significant portion of respiratory infections in children of this population.

The aim of the present study was to investigate the potential deleterious effects of dietary contaminants such as polychlorinated biphenyls (PCBs) and methylmercury (MeHg) on different molecules sensitive to oxidative stress, namely, plasma oxidized low-density lipoproteins (OxLDLs), plasma homocysteine (Hcy), blood glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). We also planned to assess the potential beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) and selenium (Se) that are also present in the traditional Inuit diet. A total of 99 participants were studied. Plasma levels of PCBs, blood levels of Se and MeHg, plasma lipids (triacylglycerols, total, LDL-, and high-density lipoprotein cholesterol [LDL-C and HDL-C, respectively], apolipoprotein B-LDL), erythrocyte n-3 PUFAs, OxLDL, Hcy, blood GPx, GSH, and GR have been determined. Mean concentrations of MeHg, Se, and PCBs were respectively 10- to 14-fold, 8- to 15-fold, and 16- to 18-fold higher than reported in white population consuming little or no fish. Multivariate analyses show that variance in plasma OxLDL concentrations was predicted by LDL-C (P = .007), HDL-C (P = .005), and PCBs (P = .006). The level of LDL oxidation, represented as the ratio OxLDL/apolipoprotein B-LDL, was predicted by LDL-C (P = .0002), HDL-C (P = .002), and GSH (P = .005). Concentration of plasma Hcy was positively predicted by age (P = .02) but negatively by body mass index (P = .04) and Se (P = .005). Glutathione was predicted by the smoking status (P = .004) and the level of LDL oxidation (P = .005), whereas GR was only predicted by the smoking status (P = .0009). The variance of GPx was not predicted by any contaminant or other physiological parameter. Dietary MeHg showed no association with the examined oxidative biomarkers, whereas PCB level was a predictor of the plasma concentration of OxLDL, although this concentration remained very low. The level of GPx activity in Inuit was higher than levels previously reported to be protective in whites. Homocysteine was negatively predicted by Se, suggesting a possible beneficial effect of Se. Moreover, n-3 PUFAs were highly correlated with dietary contaminants, but had no relationships with oxidative biomarkers. This study suggests that, in adult Inuit, contaminated traditional diet seems to have no direct oxidative effects on molecules involved in oxidative stress.

The aim of the present study was to assess the impact of chronic exposure to polychlorinated biphenyls (PCBs) and methylmercury on visual brain processing in Inuit children from Nunavik (Northern Québec, Canada). Concentrations of total mercury in blood and PCB 153 in plasma had been measured at birth and they were again measured at the time of testing in 102 preschool aged children. Relationships between contaminants and pattern-reversal visual evoked potentials (VEPs) were assessed by multivariate regression analyses, taking into account several potential confounding variables. The possible protective effects of selenium and omega-3 polyunsaturated fatty acids against methylmercury and PCB toxicity were also investigated. Results indicate that exposure to methylmercury and PCBs resulting from fish and sea mammal consumption were associated with alterations of VEP responses, especially for the latency of the N75 and of the P100 components. In contrast, the concomitant intake of omega-3 polyunsaturated fatty acids was associated with a shorter latency of the P100. However, no significant interactions between nutrients and contaminants were found, contradicting the notion that these nutrients could afford protection against environmental neurotoxicants. Interestingly, significant associations were found with concentrations of neurotoxicants in blood samples collected at the time of testing, i.e. at the preschool age. Our findings suggest that VEP can be used as a valuable tool to assess the developmental neurotoxicity of environmental contaminants in fish-eating populations.

In response to mounting concerns about the endocrine-disrupting influence of environmental chemicals on human health, this epidemiological study was initiated to test the hypothesis that nonoccupational exposure to the estrogenic pesticide 1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane (DDT) affects male reproductive parameters. One hundred and sixteen men aged 27 years (SD = 8.2) living in malaria endemic-areas in Chiapas (Mexico), where DDT was sprayed until 2000, participated in a cross-sectional study. Semen analyses were conducted according to World Health Organization methods and a quality control program was followed. DDT exposure was defined as the level of blood plasma p,p'-dichlorodiphenyl dichloroethylene (DDE), the major metabolite of DDT. The p,p'-DDE concentration adjusted for total lipids was 100 times higher than that reported for nonexposed populations at 45 plus or minus 32 mug/g (mean +/- SD). Crude regression analysis showed that several sperm motion parameters, including the percentage of motile sperm, decreased with higher p,p'-DDE concentrations (beta = -8.38; P = .05 for squared motility), and the percentage of sperm with morphological tail defects increased with higher plasma p,p'-DDE concentration (beta = 0.003; P = .017). Insufficient sperm chromatin condensation was observed in 46.6% of participants, and the most severe category of incomplete DNA condensation was also positively correlated with p,p'-DDE concentration (r = .223; P = .044). Therefore, nonoccupational exposure to DDT, as assessed by plasma p,p'-DDE concentrations, is associated with poorer semen parameters in men, indicating adverse effects on testicular function and/or the regulation of reproductive hormones. Previously, a causal role of environmental toxicants in human male infertility has been lacking because observed effects have been the result of unusually high exposures, either occupationally or as a result of industrial accidents, resulting in unprecedented controversy (reviewed by Cheek & McLachlan, Environmental hormones and the male reproductive system. J Androl. 1998;19:5). This is the first epidemiological study demonstrating effects after nonoccupational exposures to DDT. Based on these findings, the effect of DDT on male reproductive health should not be ignored.

There has been an increasing recognition of the inter-relationship between human health and the oceans. Traditionally, the focus of research and concern has been on the impact of human activities on the oceans, particularly through anthropogenic pollution and the exploitation of marine resources. More recently, there has been recognition of the potential direct impact of the oceans on human health, both detrimental and beneficial. Areas identified include: global change, harmful algal blooms (HABs), microbial and chemical contamination of marine waters and seafood, and marine models and natural products from the seas. It is hoped that through the recognition of the inter-dependence of the health of both humans and the oceans, efforts will be made to restore and preserve the oceans.

The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs). We measured biomarkers indicative of liver enzyme induction and investigated the relationship with organochlorine body burden in adult volunteers from this population. We determined plasma concentrations of PCBs and chlorinated pesticides by high-resolution gas chromatography (HRGC) with electron capture detection. DLC concentrations were measured by the dioxin-receptor chemically activated luciferase expression (DR-CALUX) assay and in a subset of participants, by HRGC/high-resolution mass spectrometry. We measured cotinine, d-glucaric acid, and porphyrins in morning urine samples and determined liver CYP1A2 activity in vivo using the caffeine breath test. Neither DLC concentrations as measured by the DR-CALUX nor PCB-153 concentrations, the latter representing total PCB exposure, were correlated with biomarkers of effects. Smoking (morning urinary cotinine concentration) was positively related to CYP1A2 activity as measured by the caffeine breath test (p < 0.01). Liver CYP1A2 activity was in turn negatively correlated with PCB-105:PCB-153 and PCB-118:PCB-153 congener ratios (p < 0.05). Hence, despite the relatively high body burden of PCBs and DLCs in this population, only smoking had a significant correlation with biomarkers of hepatic enzyme induction. Our data are consistent with smoking-induced liver CYP1A2 activity altering heme metabolism and increasing the biotransformation of mono-ortho PCB congeners.

Prostate smooth muscle cells predominantly express alpha1-adrenoceptors (alpha1-AR). alpha1-AR antagonists induce prostate smooth muscle relaxation and therefore they are useful therapeutic compounds for the treatment of benign prostatic hyperplasia symptoms. However, the Ca(2+) entry pathways associated with the activation of alpha1-AR in the prostate have yet to be elucidated. In many cell types, mammalian homologues of transient receptor potential (TRP) genes, first identified in Drosophila, encode TRPC (canonical TRP) proteins. They function as receptor-operated channels (ROCs) which are involved in various physiological processes such as contraction, proliferation, apoptosis, and differentiation. To date, the expression and function of TRPC channels have not been studied in prostate smooth muscle. In fura-2 loaded PS1 (a prostate smooth muscle cell line) which express endogenous alpha1A-ARs, alpha-agonists epinephrine (EPI), and phenylephrine (PHE) induced Ca(2+) influx which depended on the extracellular Ca(2+) and PLC activation but was independent of PKC activation. Thus, we have tested two membrane-permeable analogues of diacylglycerol (DAG), oleoyl-acyl-sn-glycerol (OAG) and 1,2-dioctanoyl-sn-glycerol (DOG). They initiated Ca(2+) influx whose properties were similar to those induced by the alpha-agonists. Sensitivity to 2-aminoethyl diphenylborate (2-APB), SKF-96365 and flufenamate implies that Ca(2+)-permeable channels mediated both alpha-agonist- and OAG-evoked Ca(2+) influx. Following the sarcoplasmic reticulum (SR) Ca(2+) store depletion by thapsigargin (Tg), a SERCA inhibitor, OAG and PHE were both still able to activate Ca(2+) influx. However, OAG failed to enhance Ca(2+) influx when added in the presence of an alpha-agonist. RT-PCR and Western blotting performed on PS1 cells revealed the presence of mRNAs and the corresponding TRPC3 and TRPC6 proteins. Experiments using an antisense strategy showed that both alpha-agonist- and OAG-induced Ca(2+) influx required TRPC3 and TRPC6, whereas the Tg-activated ("capacitative") Ca(2+) entry involved only TRPC3 encoded protein. It may be thus concluded that PS1 cells express TRPC3 and TRPC6 proteins which function as receptor- and store-operated Ca(2+) entry pathways., ((c) 2004 Wiley-Liss, Inc.)

The goal of this study was to examine the FA composition of wild and farmed Atlantic salmon (AS) and rainbow trout (RT). FA profiles were obtained by GC/FID. Results showed that lipid and n-3 highly unsaturated FA contents of farmed and wild AS were similar. Total n-3 and n-6 PUFA were significantly higher in farmed AS than in wild AS. Farmed RT contained more fat and less n-3 PUFA than wild RT. Our results show that farmed salmonids provide high levels of n-3 HUFA to consumers.

The aim of this study was to examine the effects of prenatal and postnatal chronic exposure to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb) on the neuromotor development of preschool children. The study population consisted of 110 preschool Inuit children from Nunavik (Canada). Blood Hg, PCBs and Pb concentrations were measured at birth (cord blood) and at the time of testing. Gross motor functions were evaluated and a neurological examination was performed. Fine neuromotor performance was assessed using quantitative measures of postural hand tremor, reaction time, sway oscillations, as well as alternating and pointing movements. Potential covariates were documented including demographic and familial characteristics, other prenatal neurotoxicants (alcohol, tobacco) and nutrients (selenium (Se), Omega-3 polyunsaturated fatty acids (n-3 PUFA)). Hierarchical multivariate regression analyses were performed, controlling for significant covariates. Gross motor development was not linked to prenatal exposures. However, significant associations were observed between blood Pb concentration at testing time and changes in reaction time, sway oscillations, alternating arm movements and action tremor. For some of these outcomes, neuromotor effects of Pb exposure are observed at blood concentrations below 10 microg/dl. Negative effects of PCBs on neuromotor development were not clearly observed, neither were the potential beneficial effects of n-3 PUFA and selenium. Tremor amplitude was related to blood Hg concentrations at testing time, which corroborate an effect already reported among adults.

Hyperinsulinemia has been suggested to be involved in the etiology of obesity-associated hypertension. The objective of the present study was to quantify, in a population-based study, the respective contributions of excess adiposity (body mass index [BMI]), waist circumference (WC), fasting insulin levels, and insulin sensitivity to the variation of resting blood pressure. The Quebec Health Survey was used to obtain fasting plasma insulin and glucose levels and resting blood pressure as well as anthropometric measurements in a representative sample of 907 men and 937 women. When the sample was divided into tertiles of BMI and further stratified on the basis of the 50th percentile of WC (88 cm in men), nonobese men in the first BMI tertile (<23.2 kg/m2) but with abdominal obesity were characterized by an increased systolic blood pressure (SBP) compared with nonobese men with low WC (130+/-18 versus 120+/-11 mm Hg; mean+/-SD; P=0.075). The SBP was comparable to SBP values measured among men in the top BMI tertile (129+/-14 mm Hg for BMI > or =26.6 kg/m2). When subjects were classified into tertiles of fasting insulin and WC, no association between insulin levels and blood pressure was noted, once the variation in WC was considered. Insulin sensitivity (estimated with homeostasis model assessment [HOMA]) did not explain variation in blood pressure in men, whereas the contribution of HOMA in women was of marginal clinical significance (R2 of <1.3%; P<0.0001). These results suggest that the documented association between obesity, fasting insulin, insulin sensitivity, and blood pressure is largely explained by concomitant variation in WC.

The authors investigated the effect of residues from copper- and gold-mining on the Cree population of Oujé-Bougoumou, located 560 km north of Quebec City, Canada. Subjects (225) from Oujé-Bougoumou and a control population (100) completed a questionnaire on lifestyle and dietary habits and provided blood and urine samples for analysis. Geometric means of arsenic, lead, cadmium, and copper concentrations were not significantly different for subjects or controls 15 yr and older or children (8-14 yr old). However, blood zinc was higher and selenium was lower in Oujé-Bougoumou samples. Mean blood lead level was higher in children from Oujé-Bougoumou, but lower in adults aged 40 yr and older. For adults (15 yr and older) blood lead level increased with age and was higher in men, those who hunted, and consumed wild meat (R2 = 0.43). Blood cadmium increased with age and smoking (R2 = 0.61). No influence of mine residues was observed among residents of Oujé-Bougoumou, but lifestyle exposure associations were noted for both communities.

Variations in calcium concentration within the endoplasmic reticulum ([Ca(2+)](ER)) may play a role in cell growth. This study evaluates the regulation of calcium pools by growth modulators of prostate cancer (PC) cells, the insulin growth factor (IGF), and the tumor necrosis growth factor-alpha (TNFalpha) as well as evaluating the possible role of [Ca(2+)](ER) variations as signals for growth modulation. We show that IGF (5 ng/ml), which increases cell growth, induces an increase in [Ca(2+)](ER) whereas TNFalpha (1 ng/ml) which reduces cell proliferation and induces apoptosis, reduces [Ca(2+)](ER). IGF-induced [Ca(2+)](ER) increase is correlated to an overexpression of the sarcoendoplasmic calcium-ATPase 2B (SERCA2b), whereas TNFalpha-induced [Ca(2+)](ER) decrease is associated to a reduction in SERCA2b expression. Pretreatment with epidermal growth factors (EGF) or IGF does not prevent TNFalpha from affecting the induction of apoptosis, [Ca(2+)](ER) reduction and SERCA2b downregulation. Reduction in [Ca(2+)](ER) induced by thapsigargin (TG) (from 1 pM to 1 microM, 48 h) reduces LNCaP growth in a dose dependent manner and induces apoptosis when cells are treated with 1 microM TG. We also show that a transient TG application (1 pM, 1 nM, 1 microM 15 min) is insufficient to induce a long lasting decrease in [Ca(2+)](ER), since [Ca(2+)](ER) remains identical to the control for 48 h following TG application. These treatments (1 pM and 1 nM, 15 min) do not modify cell growth. However, TG (1 microM, 15 min) induces apoptosis. We thus identify [Ca(2+)](ER) and SERCA2b as a central targets for causing LNCaP PC cell life or death induced by growth modulators. Furthermore our results indicate that calcium pool contents can regulate cell growth., (Copyright 2004 Wiley-Liss, Inc.)