Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial.

BACKGROUND: In sepsis, neutrophil respiratory bursts participate in endothelium damage, the first step to multiple organ failure. In plasma two antioxidant selenoenzymes, which protect the endothelium, decrease: selenoprotein-P, and to a lesser extent glutathione peroxidase (GPX3). Sodium selenite (Na2SeO3) is a Se donor, but also an oxidant chemotherapy drug depending on its concentration. In a previous published study, Na2SeO3 continuous infusion in septic shock patients at a pharmacological dose of 4 mg1 Se/day on day-1, followed by a high nutritional dose of 1 mg Se/day during 9 days, showed no beneficial effect on weaning of catecholamine nor on survival. In this ancillary study, we report clinical and biological effects of such continuous infusion of Na2SeO3. METHODS: This was a multicenter, placebo-controlled, double-blind study on 60 patients. Na2SeO3 or placebo in continuous infusion as described above. Evolution with time of plasma Se, selenoprotein-P, GPX3, Organ dysfunction (sequential organ failure assessment SOFA scores, including PaO2/FiO2, for respiratory failure, and plasma lactate) and quality of life at 6 months (by SF36 scores) were analyzed using two-way (time, treatment) non-parametric repeated-measures analysis of variance (Friedman test). MAIN RESULTS: At baseline, plasma Se was about a quarter of reference values. From baseline to day-4 plasma Se, selenoprotein-P and GPX3 significantly increased by 3.9, 2.7 and 1.8 respectively in the Na2SeO3 group as compared with placebo and remained elevated by 2.3, 2.7 and 2.1 at day-14 respectively (p < 0.001). Na2SeO3 did not affect global and organ by organ SOFA Scores and plasma lactate concentration at day-1 and later up to day-14. The evolution of PaO2/FiO2 until day-14 was similar in the two groups. Quality of life in the surviving patients at 6 months was similar between the two groups. CONCLUSION: Continuous infusion of Na2SeO3 at 4 mg Se at day-1 seems to have neither beneficial nor toxic effect at day-1 or later and induces a late increase of selenoprotein-P at day-4. Preclinical studies are required to confirm the use of Na2SeO3 as a cytotoxic drug against neutrophils and protection of the endothelium by selenoprotein-P.

Association of allelic combinations in selenoprotein and redox related genes with markers of lipid metabolism and oxidative stress - multimarkers analysis in a cross-sectional study.

BACKGROUND: Selenium (Se) and selenoproteins have been shown to be involved in lipid metabolism mainly due to their ability to modulate redox homeostasis in adipose tissue. The underlying mechanisms are yet to be evaluated. In the light of few data related to the association between polymorphic variants of selenoprotein encoding genes and metabolic syndrome or obesity in humans, the role of selenoprotein polymorphisms in lipid metabolism remains unclear. The aim of this study was to investigate the impact of allelic combination within selenoprotein and redox related genes on the markers of lipid metabolism and oxidative stress. METHODS: The study comprised 441 healthy individuals from Poland, in the 18-74 year age group. Allelic combinations were investigated within the polymorphic variants of four selenoprotein encoding genes (GPX1 rs1050450, GPX4 rs713041, SELENOP rs3877899 and SELENOF rs5859) and the redox related gene (SOD2 rs4880). The impact of the most common allelic GPX1-GPX4-SELENOP-SELENOF-SOD2 combinations was assessed on the following markers: triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glutathione peroxidase activities (GPX1, GPX3), lipid peroxidation (as TBARS), ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1). RESULTS: Multivariable analysis revealed significant associations between three allelic combinations and markers of lipid metabolism, including HDL-C and TC/HDL-C ratio (AAAAa), LDL-C (aaAaa), and triglycerides (aaaaA), whereas two allelic combinations (aAaAA, aaaAA) were associated with GPX3 activity. CONCLUSION: This study confirms the possible implication of selenoproteins in lipid metabolism and warrants further research on specific allele combinations within selenoprotein and redox related genes in order to identify functional genetic combinations linked to metabolic phenotype.

Determinants of the Essential Elements and Vitamins Intake and Status during Pregnancy: A Descriptive Study in Polish Mother and Child Cohort.

The study objective was to identify determinants of essential elements and vitamins intake, and microelements and vitamins concentration in blood among pregnant women from Poland. Based on the data from food frequency questionnaires and information about supplements taken (n = 1252), daily supply of six elements (calcium, magnesium, iron, zinc, copper, selenium) and nine vitamins (folate, vitamins A, E, C, B1, B2, B3, B6, B12) was calculated. Zinc, copper, selenium (n = 340), vitamin A and E (n = 358) concentration was determined in blood collected during pregnancy. Most of the women did not meet the demand for essential elements and vitamins with a diet. About 94% of the respondents declared supplements use. The women with higher education, indicating leisure-time, physical activity and multiparity had a higher chance of meeting the average demand for the majority of the analyzed nutrients. On the other hand, factors such as BMI < 18.5kg/m2, a higher level of stress, and late first medical-care visit were associated with a lower chance of meeting the recommendations. Higher socio-economic status was a determinant of a higher selenium concentration in plasma (ß = 3.1; 95%CI: 0.2-5.9), whereas BMI ≥ 25 kg/m2, and multiparity of a higher copper concentration in plasma (ß = 0.2; 95%CI: 0.03-0.4; ß = 0.2; 95%CI: 0.1-0.4). Higher plasma concentration of vitamin E was noted among women older than 30 years of age comparing to those who were 30 or younger (ß = 1.5; 95%CI: 0.6-2.4). Although more studies are required, especially such based on laboratory measures, our results indicate target groups for dietary interventions during pregnancy for children's optimal health and development.

Changes in Oxidative Stress, Inflammation, and Muscle Damage Markers Following Diet and Beetroot Juice Supplementation in Elite Fencers.

The aim of this study was to assess the impact of diet and active substances in beetroot juice on the parameters of oxidative stress, inflammation, and muscle damage as well as on the maximum rate of oxygen uptake (VO2max) in elite fencers (10 women, 10 men). Athletes during four weeks realized dietary recommendations (ID) and, after that, diet with freeze-dried beetroot juice supplementation (ID&BEET). At baseline and after each stage, fasting antioxidants, biomarkers of oxidative stress, inflammation, and skeletal muscle damage were measured, and a VO2max test was performed. Only after ID&BEET was a significant increase of VO2max observed, and changes of this parameter were negatively related with changes of serum lactate dehydrogenase (∆LDH) activity, as well as with serum ∆ß-carotene and malondialdehyde concentration (∆MDA). Additionally, positive relationships were observed between ∆ß-carotene versus changes of the serum concentration of advanced oxidation protein products (∆AOPP), changes of serum glutathione peroxidase activity (∆GPx3) versus both changes of physical activity level and ∆LDH, as well as erythrocyte glutathione peroxidase activity (∆GPx1) versus ∆LDH. To summarize, we showed that long-term beetroot juice supplementation increases lipid peroxidation, and improvement of VO2max after ID&BEET seems to be dependent on LDH activity, as well as on the serum concentration of MDA and ß-carotene.

The role of antioxidants and 25-hydroxyvitamin D during pregnancy in the development of allergic diseases in early school-age children - Polish Mother and Child Cohort Study.

Purpose: Based on the available data, alterations of the antioxidant defense as well as the vitamin status in mothers may affect the prenatal process of lung and immune system development as a pathophysiological background of increased prevalence of allergic diseases. The primary aim of the current study was to assess the associations among cord blood concentrations of zinc (Zn); copper (Cu); selenium (Se); ß-carotene; and vitamin A, E, and D, and the occurrence of atopic dermatitis, food allergy, allergic rhinitis, and asthma in early school-age children. Methods: We evaluated 211 children, 7-9 years old, from the Polish Mother and Child Cohort Study. the women were interviewed during pregnancy to collect demographic and socioeconomic data, and the medical and reproductive history. At delivery, umbilical cord blood plasma was sampled. Seven to nine years after the birth, the child's exposure and health status (including skin-prick test and spirometry for allergy assessment and urine sample for cotinine level) were examined. In the analyses, a multivariable model was applied. Results: Statistically significant relationships were found among Zn; Cu; Se; and vitamin A, E, and D concentrations in cord blood; and the prevalence of food allergy, allergic rhinitis, atopic dermatitis, and asthma in children ages 7-9 years after adjustment for several confounders. Conclusion: We showed an imbalance in the antioxidant defense system in cord blood, which may lead to the occurrence of allergic diseases later in life. The maternal diet may have substantial potential to modify immune tolerance and, consequently, the development of allergic disease in the offspring.Clinical trial NCT01861548, www.clinicaltrials.gov.

Health risk in transport workers. Part II. Dietary compounds as modulators of occupational exposure to chemicals.

Professional drivers are exposed to a number of factors that have a negative influence on their health status. These include vibrations, noise, the lack of fresh air in the car cabin, shift work (frequently at night), monotony resulting from permanent repetition of certain actions, static loads due to immobilization in a sitting position, stress resulting from the need to ensure safety in heavy traffic, as well as air pollution (dust, volatile organic substances, nitrogen and sulfur oxides, polycyclic aromatic hydrocarbons, heavy metals, dioxins, furans and others). Factors associated with the specificity of the profession of a driver, including exposure to chemical substances, result in an increased risk of the development of many diseases, i.e., obesity, diabetes, heart disease, hypertension, extensive genitourinary pathology experienced by taxi drivers, lung cancer and other forms of cancer. In the case of drivers, especially those covering long distances, there are also actual difficulties related to ensuring a proper diet. Although attempts at interventional research that would change the principles of nutrition, as well as ensure physical activity and weight reduction, have been made, their results have not been satisfactory. The paper focuses on the discussion on the role of a diet and dietary phytochemicals in the prevention of adverse health effects of such chemicals as a mix of chemicals in the polluted air, benzo(a)pyrene, benzene and metals (lead, cadmium, chromium, nickel), which are the main sources of exposure in the case of transport workers. Int J Occup Med Environ Health. 2019;32(4):441-64.

Environmental mercury exposure and selenium-associated biomarkers of antioxidant status at molecular and biochemical level. A short-term intervention study.

Mercury (Hg) is a potent toxicant. In the field of public health a chronic-low-level environmental Hg exposure resulting from fish consumption in general population is still being discussed. The objective of the study was to assess the influence of real Hg exposure on biomarkers of selenium (Se) status and selected biomarkers of pro-oxidant/anti-oxidant effects in healthy men (n = 67) who participated in the short-term intervention study consisting in daily fish consumption for two weeks. The analysis included Se level, Se-associated antioxidants at molecular (profile of 7 genes encoding selected proteins related to antioxidant defense) and biochemical levels (Se-dependent glutathione peroxidases activities and plasma selenoprotein P concentration). A pro-oxidant/anti-oxidant balance was explored using a biomarker of plasma lipid peroxidation and total antioxidant activity. The study revealed significant correlations (p < 0.05) between the biomarkers of exposure to Hg, Se level and Se-dependent antioxidants. Even though the risk of adverse effects of Hg for volunteers was substantially low, biomarkers of Hg altered levels of circulation selenoproteins and their genes expression. Changes in genes expression during study differed between the main enzymes involved in two systems: downregulation of thioredoxin reductase1 and upregulation of glutathione peroxidases. Hg exposure caused imbalance between the biomarkers of pro-oxidant/anti-oxidant effects.

Biomarkers of selenium status and antioxidant effect in workers occupationally exposed to mercury.

The present observation based research was designed to evaluate the influence of occupational human exposure to metallic mercury (Hg°) vapor on the biomarkers of selenium status involved in the antioxidant defense system. For this purpose we determined Hg and selenium (Se) concentrations in body fluids, the markers of antioxidant effect measured as an activity of Se-dependent enzymes (red blood cell and plasma glutathione peroxidase: GPx1-RBC and GPx3-P), concentration of selenoprotein P in the plasma (SeP-P) and total antioxidant activity in the plasma (TAA-P) in 131 male workers from a chloralkali plant exposed to Hg° and 67 non-exposed males (control group). The mRNA expression levels of glutathione peroxidases (GPX1, GPX3), selenoprotein P (SEPP1), thioredoxin reductase 1 (TRXR1), thioredoxin 1 (TRX1), peroxiredoxins (PRDX1, PRDX2) were also examined in the leukocytes of peripheral blood. Hg concentration in the blood (Hg-B) and urine (Hg-U) samples was determined using the thermal decomposition amalgamation/atomic absorption spectrometry (TDA-AAS) method and Se concentrations in plasma (Se-P) and urine (Se-U) using the inductively coupled plasma mass spectrometry (ICP-MS) method. Activities of GPx1-RBC, GPx3-P and TAA-P were determined using the kinetic and spectrophotometric method, respectively. Gene expression analysis was performed using the quantitative Real-Time PCR. The results showed significant higher Hg levels among the Hg°-exposed workers in comparison to control group (12-times higher median for Hg-B and almost 74-times higher median for Hg-U concentration in chloralkali workers). Se-P was also significantly higher (Me (median): 82.85 µg/L (IQR (interquartile range) 72.03-90.28 µg/L) for chloralkali workers vs. Me: 72.74 µg/L (IQR 66.25-80.14 µg/L) for control group; p = 0.0001) but interestingly correlated inversely with Hg-U in chloralkali workers suggesting depletion of the Se protection among the workers with the highest Hg-U concentration. The mRNA level for GPX1, PRXD1 were markedly but significantly higher in the workers compared to the control group. Moreover, concentrations of Hg-B and Hg-U among the workers were significantly positively correlated with the levels of selenoprotein P at both the mRNA and selenoprotein levels. In the multivariate model, after adjusting to cofounders (dental amalgam fillings, age, BMI, job seniority time, smoking), we confirmed that Hg-U concentration was inversely correlated with genes expression of TRXR1. This is the first comprehensive assessment of the impact of occupational exposure of workers to Hg° at both the mRNA and selenoprotein levels, with investigation of fish intake obtained by means of a questionnaire. These findings suggest that exposure to Hg° alters gene expression of the antioxidant enzymes and the level of Se-containing selenoproteins.

Micronutrients during pregnancy and child psychomotor development: Opposite effects of Zinc and Selenium.

Studies on the impact of micronutrient levels during different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the association between maternal plasma concentrations of selected micronutrients, such as: copper (Cu), zinc (Zn), selenium (Se), and child neuropsychological development. The study population consisted of 539 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). The micronutrient levels were measured in each trimester of pregnancy, at delivery and in the cord blood. Psychomotor development was assessed in children at the age of 1 and 2 years using the Bayley Scales of Infant and Toddler Development. The mean plasma Zn, Cu and Se concentrations in the 1st trimester of pregnancy were 0.91±0.27mg/l, 1.98±0.57mg/l and 48.35±10.54µg/l, respectively. There were no statistically significant associations between Cu levels and any of the analyzed domains of child development. A positive association was observed between Se level in the 1st trimester of pregnancy and child language and motor skills (ß=0.18, p=0.03 and ß=0.25, p=0.005, respectively) at one year of age. Motor score among one-year-old children decreased along with increasing Zn levels in the 1st trimester of pregnancy and in the cord blood (ß=-12.07, p=0.003 and ß=-6.51, p=0.03, respectively). A similar pattern was observed for the association between Zn level in the 1st trimester of pregnancy and language abilities at one year of age (ß=-7.37, p=0.05). Prenatal Zn and Se status was associated with lower and higher child psychomotor abilities, respectively, within the first year of life. Further epidemiological and preclinical studies are necessary to confirm the associations between micronutrient levels and child development as well as to elucidate the underlying mechanisms of their effects.

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism.

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

OBJECTIVES: The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. METHODS: A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. RESULTS: Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (P<0.05 when compared to night work duration <5 years). Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. CONCLUSIONS: The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

Selenium status during pregnancy and child psychomotor development-Polish Mother and Child Cohort study.

BACKGROUND: The studies on the impact of selenium (Se) levels in different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the impact of prenatal Se on child neurodevelopment. METHODS: The study population consisted of 410 mother-child pairs from Polish Mother and Child Cohort. Se levels were measured in each trimester of pregnancy, at delivery, and in cord blood by graphite furnace atomic absorption spectrometry. Psychomotor development was assessed in children at the age of 1 and 2 y using the Bayley Scales of Infant and Toddler Development. RESULTS: Plasma Se levels decreased through pregnancy (from 48.3 ± 10.6 µg/l in the first trimester to 38.4 ± 11.8 µg/l at delivery; P < 0.05). A statistically significant positive association between Se levels in the first trimester of pregnancy and motor development (ß = 0.2, P = 0.002) at 1 y of age, and language development (ß = 0.2, P = 0.03) at 2 y of age was observed. The positive effect of Se levels on cognitive score at 2 y of age was of borderline significance (ß = 0.2, P = 0.05). CONCLUSION: Prenatal selenium status was associated with child psychomotor abilities within the first years of life. Further epidemiological and preclinical studies are needed to confirm the association and elucidate the underlying mechanisms of these effects.

Parabens. From environmental studies to human health.

Parabens are a group of substances commonly employed as preservatives, mainly in personal care products, pharmaceuticals and food. Scientific reports concerning their endocrine disrupting potential and the possible link with breast cancer raised wide discussion about parabens' impact and safety. This paper provides holistic overview of paraben usage, occurrence in the environment, methods of their degradation and removal from aqueous solution, as well as hazards related to their endocrine disrupting potential and possible involvement in carcinogenesis.

Relationship between intensity of night shift work and antioxidant status in blood of nurses.

PURPOSE: Light-at-night exposure can disrupt the human circadian rhythm via clock gene expressions. The circadian rhythm influences antioxidant enzymes' activity and cellular mRNA levels of these enzymes. The employees working based on a shift system adjust to the changes occurring both on the cell level and on the level of the whole organism. Therefore, a question should be answered whether shift work disturbs oxidant-antioxidant balance and/or generates oxidative stress. METHODS: A cross-sectional study was conducted among nurses selected from the Local Registry of the Chamber of Nurses and Midwives in Lodz: 359 nurses worked daily only and 349 working rotating night shifts. These two groups differed significantly in respect of age (p < 0.0001), menopausal status (p < 0.0001), and current smoking habit (p = 0.02). The average total work duration was significantly shorter (12.4 years) in nurses working currently rotating night shifts who worked significantly longer on night shifts than day-workers (26.6 years). RESULTS: We found statistically significant higher red blood cell glutathione peroxidase in nurses working on night shifts (21.0 ± 4.6 vs. 20.0 ± 5.0 U/g Hb, p < 0.009) after adjusting for age, oral contraceptive hormone use, smoking, and drinking alcohol during last 24 h. Statistically significant lower vitamin A and E levels were found in the premenopausal women working in rotating system (0.690 ± 0.238 vs. 0.786 ± 0.262 µg/ml, p < 0.0001 for vitamin A and 10.93 ± 4.15 vs. 12.78 ± 4.75 µg/ml, p < 0.0001 for vitamin E). The marker of lipid peroxidation (TBARS concentration) was significantly lower in the premenopausal nurses than postmenopausal ones working day shifts only (2.06 ± 0.76 vs. 2.21 ± 0.80 nmol/ml, p < 0.038). We observed that erythrocyte GSH-Px activity rose statistically significant in nurses working more night shifts per month (p < 0.01). CONCLUSIONS: The results quoted above seem to support the existence of an association between light-at-night exposure and blood glutathione peroxidase activity in female shift workers. Nevertheless, in order to explain the mechanisms of this association, we need more studies.

SeP, ApoER2 and megalin as necessary factors to maintain Se homeostasis in mammals.

Selenoprotein P (SeP) is an extracellular protein containing ten selenium atoms in the form of selenocysteine, secreted mainly from the liver. About 60% of the whole plasma selenium level is present in SeP, which makes it a useful biomarker of selenium nutritional status. The main functions of SeP are transport and storage of selenium in plasma. It is especially an important protein for the brain, testes and kidneys where the supplementation of the proper amount of Se ensures the synthesis of selenoenzymes with antioxidant properties.Recently, it has been found that SeP uptake in kidneys, testes and brain depends on the apolipoprotein receptor 2 (ApoER2) and lipoprotein megalin receptor (Lrp2). Megalin receptor represents a physiological SeP receptor in kidneys, mediating the re-uptake of secreted SeP from the primary urine. The absence of a functional megalin receptor causes a significant reduction of plasma selenium and the SeP levels as a result of Se excretion. ApoER2 is a SeP receptor in the brain and testes which uptakes Se from the extracellular fluid. Deletion of ApoER2 in mice leads to a lowered selenium level in the brain and testes, neurological dysfunction, production of abnormal spermatozoa, infertility and even death when the subjects are fed a low-selenium diet.

Rotating night shift work and mammographic density.

BACKGROUND: An increased risk of breast cancer has been observed in night shift workers. Exposure to artificial light at night and disruption of the endogenous circadian rhythm with suppression of the melatonin synthesis have been suggested mechanisms. We investigated the hypothesis that rotating night shift work is associated with mammographic density. METHODS: We conducted a cross-sectional study on the association between rotating night shift work characteristics, 6-sulfatoxymelatonin (MT6s) creatinine adjusted in a spot morning urine sample, and a computer-assisted measure of mammographic density in 640 nurses and midwives ages 40 to 60 years. The associations were evaluated using regression models adjusted for age, body mass index, menopausal status, age at menopause, age at menarche, smoking, and the calendar season of the year when mammography was conducted. RESULTS: The adjusted means of percentage of mammographic density and absolute density were slightly higher among women working rotating night shifts but not statistically significant [percentage of mammographic density = 23.6%, 95% confidence interval (CI), 21.9%-25.4% vs. 22.5%, 95% CI, 20.8%-24.3%; absolute density = 23.9 cm(2), 95% CI, 21.4-26.4 cm(2) vs. 21.8 cm(2), 95% CI, 19.4-24.3 cm(2) in rotating night shift and day shift nurses, respectively). There were no significant associations between the current or cumulative rotating night shift work exposure metrics and mammographic density. No association was observed between morning MT6s and mammographic density. CONCLUSIONS: The hypothesis on the link between rotating night shift work, melatonin synthesis disruption, and mammographic density is not supported by the results of the present study. IMPACT: It is unlikely that the development of breast cancer in nurses working rotating night shifts is mediated by an increase in mammographic density.

Night shift work characteristics and 6-sulfatoxymelatonin (MT6s) in rotating night shift nurses and midwives.

OBJECTIVES: Synthesis of melatonin follows a circadian cycle, with high melatonin levels during the night and low levels during the day. Light exposure at night has been hypothesised as one of potential mechanisms of breast carcinogenesis in the night shift workers through inhibition of melatonin synthesis. The aim of the study was to examine a number of determinants for night shift work in relation to 6-sulfatoxymelatonin (MT6s), primary melatonin metabolite. METHODS: The cross-sectional study included 354 nurses and midwives (aged 40-60 years) currently working on rotating night shifts and 370 working days only. Data from questionnaires and 1-week diaries were used to characterise current job and total occupational history. Associations between rotating night shift work characteristics and MT6s (creatinine adjusted) in spot morning urine were tested in multiple linear regression models. RESULTS: No significant differences were found for MT6s concentrations between women currently working on rotating night shifts and those working only day shifts (means 47.2 vs 45.7 ng/mg Cr, respectively). The adjusted means among rotating night shift nurses and midwives varied depending on the department of employment, from 35.1 ng/mg Cr in neonatology to 68.2 ng/mg Cr in the orthopaedics department. Women working eight or more night shifts per month had significantly lower MT6s levels than those having fewer night shifts per month (37.9 vs 47.4 ng/mg Cr, respectively). Total night shift work history was not associated with MT6s. CONCLUSIONS: The results of this study indicate that working eight or more night shifts per month may disrupt the synthesis of melatonin.

The effect of selenium supplementation in the prevention of DNA damage in white blood cells of hemodialyzed patients: a pilot study.

Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis (HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients were supplemented with 200 µg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA.

Carcinogenic effect of arsenate in C57BL/6J/Han mice and its modulation by different dietary selenium status.

In this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice exposed in drinking water to 50, 200 or 500microgAs/L for 24 months were investigated. All animals were fed low-selenium diet, however half of them were supplemented with sodium selenite in drinking water (200microgSe/L) to ensure the normal dietary level of selenium. Glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma after 3, 6, 12 and 18 months in satellite groups showed considerable decrease in animals from non-selenium supplemented groups in comparison to supplemented groups. A clear arsenic concentration-dependent increase in the number of malignant lymphoma associated with increase in the risk of death was observed (hazard ratio=0.91, 1.46, and 2.24, for 50, 200 and 500microgAs/L, respectively). No significant influence of selenium dietary status on arsenic carcinogenicity was shown. A significant association between selenium supplementation status and increased risk of death of the animals from causes other than malignant tumors was found (HR=1.79, p=0.04).