Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals

Vitamin E (α-tocopherol, α-TOH) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance (NMR) with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-hour urine quantified by LC/MS-MS. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) with vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (45% men) with mean (SD) age of 55.7 (6.0) years. Out of 147 metabolomic measures, 106 were associated (p < 1.34E-3) with serum α-TOH [median beta (IQR): 0.416 (0.383, 0.466)], predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC are with similar directions as those with α-TOH, but effect sizes were smaller and non-significant [median beta (IQR):0.065 (0.047, 0.084)]. However, associations of metabolomic measures with urinary α-TLHQ were markedly different from the associations of metabolomic measures with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most VLDL and amino acids. Therefore, our results highlight the differences of the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not to antioxidative function of vitamin E

Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells

Contains fulltext : 76028.pdf (publisher's version ) (Open Access)8 p

Drug resistance in cancer

Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There was a special focus on leukaemia, breast and ovarian cancer, and the potential use of positron-emission tomography to study anticancer-drug resistance. The progress made in translating these findings to the clinic, like Gefitinib, P-glycoprotein phenotyping, or genome-wide analysis technology, was also discussed

Protein kinase Cδ expression in breast cancer as measured by real-time PCR, western blotting and ELISA

The protein kinase C (PKC) family of genes encode serine/threonine kinases that regulate proliferation, apoptosis, cell survival and migration. Multiple isoforms of PKC have been described, one of which is PKCδ. Currently, it is unclear whether PKCδ is involved in promoting or inhibiting cancer formation/progression. The aim of this study was therefore to investigate the expression of PKCδ in human breast cancer and relate its levels to multiple parameters of tumour progression. Protein kinase Cδ expression at the mRNA level was measured using real-time PCR (n=208) and at protein level by both immunoblotting (n=94) and ELISA (n=98). Following immunoblotting, two proteins were identified, migrating with molecular masses of 78 and 160 kDa. The 78 kDa protein is likely to be the mature form of PKCδ but the identity of the 160 kDa form is unknown. Levels of both these proteins correlated weakly but significantly with PKCδ concentrations determined by ELISA (for the 78 kDa form, r=0.444, P<0.005, n=91 and for the 160 kDa form, r=0.237, P=0.023, n=91) and with PKCδ mRNA levels (for the 78 kDa form, r=0.351, P=0.001, n=94 and for the 160 kDa form, r=0.216, P=0.037, n=94). Protein kinase Cδ mRNA expression was significantly higher in oestrogen receptor (ER)-positive compared with ER-negative tumours (P=0.007, Mann–Whitney U-test). Increasing concentrations of PKCδ mRNA were associated with reduced overall patient survival (P=0.004). Our results are consistent with a role for PKCδ in breast cancer progression

Naphthoquinones and Anthraquinones from Scent Glands of a Dyspnoid Harvestman, Paranemastoma quadripunctatum

Extracts of Paranemastoma quadripunctatum (Opiliones, Dyspnoi, Nemastomatidae) contained seven components, all of which likely originated from the secretion of well-developed prosomal scent glands. The two main components (together accounting for more than 90% of the secretion) were identified as 1,4-naphthoquinone and 6-methyl-1,4-naphthoquinone. The minor components were 1,4-naphthalenediol, two methoxy-naphthoquinones (2-methoxy-1,4-naphthoquinone, and 2-methoxy-6-methyl-1,4-naphthoquinone) and two anthraquinones (2-methyl-9,10-anthraquinone and a dimethyl-9,10-anthraquinone). While some chemical data on scent gland secretions of the other suborders of Opiliones (Cyphophthalmi, palpatorean Eupnoi, and Laniatores) already exist, this is the first report on the scent gland chemistry in the Dyspnoi. Naphthoquinones are known scent gland exudates of Cyphophthalmi and certain Eupnoi, methoxy-naphthoquinones and anthraquinones are new for opilionid scent gland secretions

Acculturation and use of health care services by Turkish and Moroccan migrants: a cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>There is insufficient empirical evidence which shows if and how there is an interrelation between acculturation and health care utilisation. The present study seeks to establish this evidence within first generation Turkish and Moroccan migrants, two of the largest migrant groups in present-day Western Europe.</p> <p>Methods</p> <p>Data were derived from the Amsterdam Health Monitor 2004, and were complete for 358 Turkish and 288 Moroccan foreign-born migrants. Use of health services (general practitioner, outpatient specialist and health care for mental health problems) was measured by means of self-report. Acculturation was measured by a structured questionnaire grading (i) ethnic self-identification, (ii) social interaction with ethnic Dutch, (iii) communication in Dutch within one's private social network, (iv) emancipation, and (v) cultural orientation towards the public domain.</p> <p>Results</p> <p>Acculturation was hardly associated with the use of general practitioner care. However, in case of higher adaptation to the host culture there was less uptake of outpatient specialist care among Turkish respondents (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.82-0.99) and Moroccan male respondents (OR = 0.81, 95% CI = 0.71-0.93). Conversely, there was a higher uptake of mental health care among Turkish men (OR = 0.81, 95% CI = 0.71-0.93) and women (OR = 0.81, 95% CI = 0.71-0.93). Uptake of mental health care among Moroccan respondents again appeared lower (OR = 0.74, 95% CI = 0.55-0.99). Language ability appeared to play a central role in the uptake of health care.</p> <p>Conclusion</p> <p>Some results were in accordance with the popular view that an increased participation in the host society is concomitant to an increased use of health services. However, there was heterogeneity across ethnic and gender groups, and across the domains of acculturation. Language ability appeared to play a central role. Further research needs to explore this heterogeneity into more detail. Also, other cultural and/or contextual aspects that influence the use of health services require further identification.</p

Estrogen-like activity of seafood related to environmental chemical contaminants

BACKGROUND: A wide variety of environmental pollutants occur in surface waters, including estuarine and marine waters. Many of these contaminants are recognised as endocrine disrupting chemicals (EDCs) which can adversely affect the male and female reproductive system by binding the estrogen receptor and exhibiting hormone-like activities. In this study the estrogenic activity of extracts of edible marine organisms for human consumption from the Mediterranean Sea was assayed. METHODS: Marine organisms were collected in two different areas of the Mediterranean Sea. The estrogenic activity of tissues was assessed using an in vitro yeast reporter gene assay (S. cerevisiae RMY 326 ER-ERE). Concentrations of polychlorinated biphenyls (PCBs) (congeners 28, 52, 101, 118, 138, 153, 180) in fish tissue was also evaluated. RESULTS: Thirty-eight percent of extracts showed a hormone-like activity higher than 10% of the activity elicited by 10 nM 17b-estradiol (E2) used as control. Total PCB concentrations ranged from 0.002 up to 1.785 ng/g wet weight. Chemical analyses detected different levels of contamination among the species collected in the two areas, with the ones collected in the Adriatic Sea showing concentrations significantly higher than those collected in the Tyrrhenian Sea (p < 0.01). CONCLUSION: The more frequent combination of chemicals in the samples that showed higher estrogenic activity was PCB 28, PCB 101, PCB 153, PCB 180. The content of PCBs and estrogenic activity did not reveal any significant correlation

Clinical significance of the nuclear receptor co-regulator DC-SCRIPT in breast cancer: an independent retrospective validation study

Contains fulltext : 88921.pdf (publisher's version ) (Open Access

Social and cultural factors underlying generational differences in overweight: a cross-sectional study among ethnic minorities in the Netherlands

<p>Abstract</p> <p>Background</p> <p>The prevalence of overweight appears to vary in people of first and second generation ethnic minority groups. Insight into the factors that underlie these weight differences might help in understanding the health transition that is taking place across generations following migration. We studied the role of social and cultural factors associated with generational differences in overweight among young Turkish and Moroccan men and women in the Netherlands.</p> <p>Methods</p> <p>Cross-sectional data were derived from the LASER-study in which information on health-related behaviour and socio-demographic factors, level of education, occupational status, acculturation (cultural orientation and social contacts), religious and migration-related factors was gathered among Turkish and Moroccan men (n = 334) and women (n = 339) aged 15-30 years. Participants were interviewed during a home visit. Overweight was defined as a Body Mass Index ≥ 25 kg/m². Using logistic regression analyses, we tested whether the measured social and cultural factors could explain differences in overweight between first and second generation ethnic groups.</p> <p>Results</p> <p>Second generation women were less often overweight than first generation women (21.8% and 45.0% respectively), but this association was no longer significant when adjusting for the socioeconomic position (i.e. higher level of education) of second generation women (Odds Ratio (OR) = 0.77, 95%, Confidence Interval (CI) 0.40-1.46). In men, we observed a reversed pattern: second generation men were more often overweight than first generation men (32.7% and 27.8%). This association (OR = 1.89, 95% CI 1.09-3.24) could not be explained by the social and cultural factors because none of these factors were associated with overweight among men.</p> <p>Conclusions</p> <p>The higher socio-economic position of second generation Turkish and Moroccan women may partly account for the lower prevalence of overweight in this group compared to first generation women. Further research is necessary to elucidate whether any postulated socio-biological or other processes are relevant to the opposite pattern of overweight among men.</p