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Biomedical subjects

E Dewailly

Publications and source records attributed to E Dewailly.

At least 19 recordsLinked to original sources

Oceans and human health: Emerging public health risks in the marine environment.

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.

Animals↗

Receptor-operated Ca2+ entry mediated by TRPC3/TRPC6 proteins in rat prostate smooth muscle (PS1) cell line.

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.

Adrenergic alpha-Agonists↗

Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds.

During the past 20 years a number of studies have found neurological and immunological effects in the developing fetus and infants exposed to background or only slightly elevated levels of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). To address concerns arising from possible increased human exposure in the Arctic and possible effects of POPs, all circumpolar countries agreed in 1994 to monitoring of specific human tissues for contaminants in the Arctic under the Arctic Monitoring and Assessment Program (AMAP). Mothers in eight circumpolar countries contributed blood samples that were analysed at a single laboratory for 14 PCB congeners (IUPAC No. 28, 52, 99, 105, 118, 128, 138, 153, 156, 170, 180, 183, 187) and 13 organochlorine pesticides (aldrin, beta-hexachlorocyclohexane (beta-HCH), dichlordiphenyltrichloroethane (p,p'-DDT), diphenyldichloroethylene (p,p'-DDE), dieldrin, heptachlorepoxide, hexachlorobenzene (HCB), mirex, and the chlordane derivatives alpha-chlordane, gamma-chlordane, cis-nonachlor, oxychlordane and trans-nonachlor). Inuit mothers from Greenland and Canada have significantly higher levels of oxychlordane, transnonachlor and mirex than mothers from Norway, Sweden, Iceland and Russia. Inuit mothers from Greenland also have significantly higher levels of these contaminants than Inuit mothers from Canada and Alaska. These differences among Inuit groups may represent regional dietary preferences or different contaminant deposition patterns across the Arctic. Levels of PCBs are also elevated among some arctic populations due to their consumption of marine mammals and are in the range where subtle effects on learning and the immune system have been reported. The Russian mothers who consume mainly food imported from southern Russia have elevated levels of DDT, DDE, beta-HCH and a higher proportion of lower chlorinated PCB congeners. This study has allowed an assessment of the variation of contaminants such as PCBs and various organochlorine pesticides (DDT, chlordane, etc.) in human populations around the circumpolar north.

Adult↗

Very high concentrations of n-3 fatty acids in peri- and postmenopausal Inuit women from Greenland.

OBJECTIVES: The objectives of this study were to examine the profile of relative concentrations in plasma phospholipids of n-3 fatty acids among peri- and postmenopausal Inuit women living in Greenland and to verify their relationships with ischemic heart disease risk factors and more particularly, with concentrations of plasma triacylglycerols. STUDY DESIGN: This study was part of a survey conducted in 2000, which aimed to assess the prevalence of osteoporosis and the associated risk factors among peri- and postmenopausal Greenland Inuit women. METHODS: The study population consisted of 153 women aged 49-69 years (mean +/- SD: 55.3 +/- 4.4 y) randomly selected. Data were obtained through an interview (questionnaire on lifestyle habits, medical history etc) and a clinical session (physiologic and anthropologic measurements). Plasma samples were used to measure the fatty acid composition of plasma phospholipids. RESULTS: The mean body mass index of women was 27.9 +/- 6.1. Seventy-five percent were smokers and 9% were currently on hormone replacement therapy. Relative concentrations of total n-3 fatty acids were very high (13.8%, 95% CI: 13.1-14.6), with docosahexanoic and eicosapentanoic acids accounting for 4.7% and 7.2%, respectively. The ratio of n-3:n-6 fatty acids was 0.67. n-3 fatty acids were inversely correlated to triacylglycerols. CONCLUSION: These data show that peri- and post-menopausal Greenland Inuit women have very high plasma concentrations of n-3 fatty acids that protect them from ischemic heart disease.

Aged↗

Monitoring of umbilical cord blood lead levels and sources assessment among the Inuit.

Analyses completed on samples collected between 1993 and 1996 showed that about 7% of 475 Inuit newborns from northern Quebec (Canada) had a cord blood lead concentration equal to or greater than 0.48 micromol/l, an intervention level adopted by many governmental agencies. A comparison between the cord blood lead isotope ratios of Inuit and southern Quebec newborns showed that lead sources for these populations were different. Our investigation suggests that lead shots used for game hunting were an important source of lead exposure in the Inuit population. A cohort study conducted in three Inuit communities shows a significant decrease of cord blood lead concentrations after a public health intervention to reduce the use of lead shot. Lead shot ammunition can be a major and preventable source of human exposure to lead.

Cohort Studies↗

Increase in plasma pollutant levels in response to weight loss is associated with the reduction of fasting insulin levels in men but not in women.

Environmental pollutants can act as endocrine modulators. In this study, we examined whether weight loss-induced changes in plasma organochlorine compounds (OC) were associated with those in plasma insulin levels. Fasting insulin and the area under the curve (AUC) of insulin after a 75-g oral glucose load, plasma levels of 1 commercial polychlorinated biphenyl (PCB) mixture (Aroclor 1260), 1 PCB congener (PCB 153), and 3 pesticides (2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB)) were measured before and after a 15-week weight loss program induced by a caloric restriction in a sample of obese men and women. Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean +/- SD 9.4 +/- 4.1 v 5.9 +/- 5 kg, respectively, P <.05). Fasting insulin and AUC of insulin significantly decreased in men and women after the treatment. In response to weight loss, a significant increase in OC was observed in both genders, and this effect was more pronounced in men. The greater the increase in plasma OC levels, the greater the reduction in fasting insulin was in response to weight loss in men (-.49 < r < -.59, P <.05), but not in women (-.22 < r <.01, not significant [NS]). In both genders, no relationship was observed between changes in plasma OC levels and changes in AUC of insulin (-.41 < r < -.08, NS). In men, relationships between changes in plasma HCB, Aroclor 1260, and PCB-153 concentrations and those in fasting insulin levels in response to weight loss remained significantly correlated after correction for fat mass loss (-.46 < partial r < -.51, P values ranging from.05 to.07). These results suggest that weight loss-induced increase in plasma pollutant levels tends to be independently associated with the reduction of fasting insulin levels in men, but not in women. Further studies are needed to verify whether these findings are causally related.

Adipose Tissue↗

Ca2+ pools and cell growth. Evidence for sarcoendoplasmic Ca2+-ATPases 2B involvement in human prostate cancer cell growth control.

The present study demonstrates for the first time that intracellular calcium-ATPases and calcium pool content are closely associated with prostate cancer LNCaP cell growth. Cell growth was modulated by changing the amount of epidermal growth factor, serum, and androgene in culture media. Using the microspectrofluorimetric method with Fura-2 and Mag Fura-2 as probes, we show that in these cells, the growth rate is correlated with intracellular calcium pool content. Indeed, an increased growth rate is correlated with an increase in the calcium pool filling state, whereas growth-inhibited cells show a reduced calcium pool load. Using Western blotting and immunocytochemistry, we show that endoplasmic reticulum calcium pump expression is closely linked to LNCaP cell growth, and are a common target of physiological stimuli that control cell growth. Moreover, we clearly demonstrate that inhibition of these pumps, using thapsigargin, inhibits LNCaP cell growth and prevents growth factor from stimulating cell proliferation. Our results thus provide evidence for the essential role of functional endoplasmic reticulum calcium pumps and calcium pool in control of prostate cancer LNCaP cell growth, raising the prospect of new targets for the treatment of prostate cancer.

Blotting, Western↗

Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population.

We studied the association of breast cancer with the polymorphic polyglutamine repeat of the androgen receptor (AR) in 255 incident cases of breast cancer and 461 matched controls from the Quebec City metropolitan area. Women for whom the sum of both of the AR (CAG)n-repeats alleles is 39 or less (short-allele AR genotypes) have one-half the risk of breast cancer compared with women for whom the sum of AR (CAG)n-repeats is 40 or more [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3-0.83; P = 0.007]. This association is stronger in postmenopausal women (180 cases, 297 controls; OR, 0.36; 95% CI, 0.19-0.7; P = 0.003). We also observed an interaction between the type of menopause (natural versus surgical) and the AR genotype on breast cancer risk. Alternately, when subjects were grouped according to their (CAG)n-repeat genotype [homozygous for short alleles (CAG)n < or = 20; other genotypes ("long allele")], results were similar (OR. 0.5; 95% CI, 0.27-0.82; P = 0.007). Thus, women with short-alleles AR genotypes appear to be protected against breast cancer. Short-alleles AR genotypes were observed in 16% of the general population as represented by the control group. Short polyglutamine repeats in the AR protein have been reported to be associated with an increase in the capacity of the receptor to activate transcription of reporter genes in vitro. Furthermore, androgens have been previously shown to inhibit in vitro the growth of breast cancer cell lines. This suggests that differences in the number of polyglutamines in the AR protein may influence individual risk of breast cancer, especially in postmenopausal women, and that this apparent protection could be the consequence of an increased response/sensitivity to androgens.

Breast Neoplasms↗

Exposure of Inuit in Greenland to organochlorines through the marine diet.

High organochlorine concentrations have been found among the Inuit in eastern Canada and in Greenland. The present study was undertaken to assess the exposure to organochlorines in relation to age, sex, and diet in a general population sample of Inuit from Greenland. Survey data and plasma concentrations of 14 polychlorinated biphenyl (PCB) congeners and 16 pesticides, including 5 toxaphene congeners, were recorded in a random population survey of 408 adult indigenous Greenlanders. In a two-stage design, the survey response rate was 66%, and 90% of those randomly selected for blood testing participated. This was equivalent to an overall response rate of 59%. The median plasma concentration of the sum of PCB congeners was 13.3 microg/L; the lipid-adjusted value was 2109 microg/kg. The PCB concentration was twice as high as among the Inuit of Nunavik, Canada, 25 times higher than in a control group from southern Canada, and several times higher than the values found in European studies. Concentrations were similarly elevated for all PCB congeners and pesticides. The PCB congener pattern was similar to previous observations from the eastern Canadian Arctic and Greenland. Concentrations showed statistically significant positive associations with age, marine diet, and male sex in multiple linear regression analyses. The exceptionally high plasma concentrations of several organochlorines among the Inuit of Greenland are attributed to a lifelong high intake of seafood, in particular marine mammals. Concentrations of PCB adjusted for the consumption of marine food increased until approximately 40 yr of age, which is equivalent to the birth cohorts of the early 1950s. The age pattern indicates that bioaccumulation of PCB started in the 1950s, which is a likely date for the introduction of the compounds into the Arctic environment.

Adolescent↗

Increase in plasma pollutant levels in response to weight loss in humans is related to in vitro subcutaneous adipocyte basal lipolysis.

OBJECTIVE: To examine whether weight loss-induced changes in in vitro basal lipolysis of subcutaneous abdominal and femoral fat cells were related to those in plasma organochlorine levels. DESIGN: A 15 week weight loss program induced by a moderate caloric restriction. SUBJECTS: Seventeen men and 20 women (age 36-50 y, body fat 25-50%). MEASUREMENTS: In vitro basal lipolysis of subcutaneous abdominal and femoral adipocytes and plasma levels of five polychlorinated biphenyl congeners (Aroclor 1260, PCBs 118, 138, 153 and 180) and three chlorinated pesticides (dichlorodiphenyl dichloroethene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH) and hexachlorobenzene (HCB)) were measured before and after the weight reducing program. RESULTS: Both genders showed a similar reduction in body weight (approximately 11 kg) in response to treatment, although men lost significantly more fat mass than women (mean+/-s.d., 9.4+/-4.1 vs 5.9+/-5 kg, respectively, P<0.05). Mean basal fat cell lipolysis did not vary before and after weight reduction, regardless of depots and genders. In response to weight loss, significant increases of all organochlorines investigated were observed in men, whereas only p,p'-DDE, Aroclor 1260, PCBs 153 and 180 significantly rose in women. In men, higher the increase in basal lipolysis of subcutaneous abdominal or femoral adipocytes, greater the rise in plasma levels of most pollutants (HCB, Aroclor 1260, PCBs 118, 138 and 153) was in response to weight loss (0.51<r<0.70, P<0.05). Similar positive correlations were also observed in women but only a few reached statistical significance (p,p'-DDE, PCBs 118 and 180). CONCLUSION: The weight loss-induced increase in plasma pollutant levels is related to the rise in subcutaneous abdominal and femoral adipocyte basal lipolysis, especially in men.

Abdomen↗

n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik.

BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.

Adult↗

Effects of hyperprolactinemia on rat prostate growth: evidence of androgeno-dependence.

The effects of the polypeptide hormone prolactin (PRL) in the development and regulation of benign prostate hyperplasia (BPH) and also in prostate cancer are not very well characterized. This study examines the action of PRL, either alone or in association with androgens [testosterone (T) or dihydrotestosterone (DHT)], in the rat prostate gland. The effects of PRL and androgens were investigated after 30 and 60 days in control, castrated, castrated with a substitutive implant of T or DHT, and sham-operated Wistar rats. To enhance PRL release, we induced hyperprolactinemia by administering chronic injections of sulpiride (40 mg. kg(-1). day(-1)). Chronic hyperprolactinemia induces enlargement and inflammation of the lateral rat prostate without any histological changes on ventral and dorsal lobes. We also demonstrate that hyperprolactinemia induces Bcl-2 overexpression in the lateral rat prostate and that this could inhibit the level of apoptosis. The in vivo model established here is a useful in vivo approach for studying the hormonal regulation of normal and pathological prostate development.

Animals↗

KV1.1 K(+) channels identification in human breast carcinoma cells: involvement in cell proliferation.

Electrophysiological, immunocytochemical, and RT-PCR methods were used to identify a K(+) conductance not yet described in MCF-7 human breast cancer cells. A voltage-dependent and TEA-sensitive K(+) current was the most commonly observed in these cells. The noninactivating K(+) current (I(K)) was insensitive to iberiotoxin (100 nM) and charybdotoxin (100 nM) but reduced by alpha-dendrotoxin (alpha-DTX). Perfusion of alpha-DTX reduced a fraction of I(K) amplitude in a dose-dependent manner (IC(50) = 0.6 +/- 0.3 nM). This DTX sensitive I(K) exhibited a voltage threshold at -20 mV and was not inactivated. The time constant of activation was 5.3 +/- 2.2 ms measured at +60 mV. The averaged half-activation potential and slope factor values were 14 +/- 1.6 mV and 10 +/- 1.4, respectively. Immunocytochemical analysis demonstrated that plasma membrane was labeled by anti-Kv1.1 but not by anti-Kv1.2 nor anti-Kv1.3 antibodies. Furthermore, only Kv1.1 mRNA was detected in MCF-7 cells. Incubation in 1 and 10 nM alpha-DTX reduced cell proliferation by 20 and 30%, respectively. These data provide the first evidence of Kv1.1 K(+) channels expression in MCF-7 cells and indicate that these channels are implicated in cell proliferation.

Breast Neoplasms↗

Evaluation of the health risk associated with exposure to chloroform in indoor swimming pools.

The exposure of swimmers to chloroform (CHCl3) was investigated in indoor swimming pools of the Quebec City region along with the associated carcinogenic risk. Six training sessions involving 52 competition swimmers (11 to 20 yr old) were conducted in 3 different pools, while 12 adult leisure swimmers attended 5 sessions, each held in a different pool. For each session, water and ambient air CHCl3 concentrations were measured and CHCl3 levels in alveolar air samples (CHCl3 ALV) collected from swimmers prior to entering the swimming pool premises and after 15, 35, and 60 min of swimming. Mean water concentrations varied from 18 microg/L to 80 microg/L, while those in air ranged from 78 microg/m3 to 329 microg/m3. Multiple linear regression analyses revealed that CHCl3 ALV values in competition swimmers were strongly correlated to ambient air and water levels, and to a lesser degree to the intensity of training. Only ambient air concentration was positively correlated to CHCl3 ALV in the leisure group. Concentrations of CHCl3 metabolites bound to hepatic and renal macromolecules, estimated using a physiologically based pharmacokinetic (PBPK) model, were 1.6 and 1.9 times higher for the competition swimmers than for the leisure swimmers, respectively. The highest hepatic concentration predicted in competition swimmers, 0.22 microg CHCl3 equivalents/kg of tissue, was at least 10,000 times lower than the smallest no observed effect level for liver tumors in animals. Data indicate that the safety margin is therefore very large, for competitive swimmers as well as for leisure swimmers.

Adolescent↗

Breast cancer, lactation history, and serum organochlorines.

The authors analyzed the relation between lactation history, organochlorine serum levels-in particular, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE)-and the risk of breast cancer within a subsampe from a larger breast cancer case-control study conducted among women living in Mexico City, Mexico, between 1990 and 1995. From the original study, they selected a random sample of 260 subjects (1:1 case/control ratio). Analysis was restricted to 120 cases and 126 controls who had given birth to at least one child and had complete information on all key variables. Serum DDE levels were higher among cases (mean = 3.84 microg/g lipids, standard deviation = 5.98) than among controls (mean = 2.51 microg/g lipids, standard deviation = 1.97). After adjustment for age, age at menarche, duration of lactation, Quetelet index, and serum DDT levels, serum DDE levels were positively related to the risk of breast cancer (adjusted odds ratio (OR)Q1-Q2 = 1.24, 95% confidence interval (CI): 0.50, 3.06; ORQ1-Q3 = 2.31, 95% CI: 0.92, 5.86; ORQ1-Q4 = 3.81, 95% CI: 1.14, 12.80; test of trend, p = 0.02). The increased risk associated with higher serum DDE levels was more apparent among postmenopausal women (ORQ1-Q4 = 5.26, 95% CI: 0.80, 34.30; test of trend p = 0.03). A longer period of lactation was associated with a slightly decreased risk of breast cancer independently of serum DDE levels (OR = 0.91, 95% CI: 0.85, 0.99 change in risk per 10 months of lactation). Serum DDT level was not related to the risk of breast cancer. The data suggest that high levels of exposure to DDE may increase women's risk of breast cancer, particularly among postmenopausal women.

Adult↗

Body weight loss increases plasma and adipose tissue concentrations of potentially toxic pollutants in obese individuals.

BACKGROUND: While there appears to be a consensus among scientists and clinicians that body weight loss reduces the risk of several chronic diseases, these apparently favourable effects should be balanced against any potentially harmful side effect of weight loss. In this regard, weight loss has been shown to produce an increase in blood concentration of potentially toxic organochlorine pollutants in animals that can cause prejudice to health, but human data are lacking. METHODS: Thirty-nine obese individuals were subjected to a hypocaloric diet during 15 weeks. Blood and subcutaneous adipose tissue samples were analysed before and after treatment for 26 organochlorine compounds. A control group consisting of 57 women of similar mean age was also formed in order to compare plasma concentrations. RESULTS: Organochlorine pollutants were found in every subject and all 19 compounds detected had their plasma concentration increased following treatment (mean body weight loss 9.5 kg), 15 of which were statistically significant. When compared with a control group, five compounds increased significantly. These observations persisted after an 18 week low-fat diet/exercise program follow-up. Increases were correlated with body weight loss (-0.3 > or = r > or = -0.6, P<0.05) and adipose tissue analyses yielded similar results, as their concentration of organochlorine compounds increased following treatment. CONCLUSION: Body weight loss increases plasma and subcutaneous adipose tissue concentrations of organochlorine pesticides and PCBs in obese subjects. These results raise concerns about an undesired and potentially harmful side effect of weight loss in some obese patients who seem to be at greater risk of health problems than leaner subjects since they show higher organochlorine body burden.

Adipose Tissue↗