There is an urgent need to adopt a pull-flow logic for the supply of RBCs to meet patients' needs: A single center study.

BACKGROUND: Despite major demographic changes, several decisions and initiatives, among which Patient Blood Management, have led to a significant reduction in the transfusion of packed red blood cells (RBCs) in Belgium, as it has been observed in many countries. Unfortunately, not all blood groups were proportionately impacted and shortage in O D-negative RBCs is regularly or chronically observed. The goal of this study was to examine how to optimize the use and the supply of O D-negative blood in our academic hospital. METHODOLOGY: All blood transfusions performed at Cliniques universitaires Saint-Luc between January 1, 2019 and December 31, 2021 were reviewed. The blood group of the patients was compared with the blood group of the RBCs actually supplied and transfused. RESULTS: 49.823 RBCs transfusions were analyzed. The patients' needs didn't reflect those of a Caucasian population, with an increase of O (47.9%) and B (10.3%) for the ABO blood group, and a quite high proportion of R0r (8.6%) for the Rh blood group. Only two thirds of O D-negative RBCs were transfused to O rr or R0r patients. CONCLUSION: The application of PBM and the ethnic imbalance between blood donor and patient populations are two important risk factors for chronic shortages of O D-negative blood. To adapt blood component resources, it is essential to have a complete picture of the real needs of patients according to their blood group profile. Blood donor centers must adapt to the evolving needs of hospitals in order to plan future supplies in a "pull-flow" approach.

Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

BACKGROUND: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. METHODS: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7-9, n-3 and n-6 FAs (patterns ω7-9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. RESULTS: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). CONCLUSIONS: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent.

Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.

Anticancer properties of sodium selenite in human glioblastoma cell cluster spheroids.

Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared. SS impacts on proliferation, cell death, and invasiveness were evaluated as well as epigenetic modifications by focusing on histone deacetylase (HDAC) activity and dimethyl-histone-3-lysine-9 methylation (H3K9m2), after 24h to 72h SS exposition. SS was absorbed by spheroids and was more cytotoxic than TMZ (i.e., for LN229, the IC50 was 38 fold-more elevated for TMZ than SS, at 72h). SS induced a cell cycle arrest in the S phase and apoptosis via caspase-3. SS decreased carbonic anhydrase-9 (CA9) expression, invasion on a Matrigel matrix and modulated E- and N-Cadherin transcript expressions. SS decreased HDAC activity and modulated H3K9m2 levels. 3D model provides a relevant strategy to screen new drugs and SS is a promising drug against GBM that should now be tested in GBM animal models.

Rye polyphenols and the metabolism of n-3 fatty acids in rats: a dose dependent fatty fish-like effect.

As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers' health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.

Whole Rye Consumption Improves Blood and Liver n-3 Fatty Acid Profile and Gut Microbiota Composition in Rats.

BACKGROUND: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition. METHODS: For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs. RESULTS: The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats. INTERPRETATION: This study shows for the first time that WR consumption results in major biological modifications-increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity-known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the interactions between whole rye (fiber and polyphenols) and gut microbiota and also the mechanisms of action responsible for stimulating n-3 fatty acid metabolism.

Correlations between Fruit, Vegetables, Fish, Vitamins, and Fatty Acids Estimated by Web-Based Nonconsecutive Dietary Records and Respective Biomarkers of Nutritional Status.

BACKGROUND: It is of major importance to measure the validity of self-reported dietary intake using web-based instruments before applying them in large-scale studies. OBJECTIVE: This study aimed to validate self-reported intake of fish, fruit and vegetables, and selected micronutrient intakes assessed by a web-based self-administered dietary record tool used in the NutriNet-Santé prospective cohort study, against the following concentration biomarkers: plasma beta carotene, vitamin C, and n-3 polyunsaturated fatty acids. PARTICIPANTS/SETTING: One hundred ninety-eight adult volunteers (103 men and 95 women, mean age=50.5 years) were included in the protocol: they completed 3 nonconsecutive-day dietary records and two blood samples were drawn 3 weeks apart. The study was conducted in the area of Paris, France, between October 2012 and May 2013. MAIN OUTCOME MEASURES: Reported fish, fruit and vegetables, and selected micronutrient intakes and plasma beta carotene, vitamin C, and n-3 polyunsaturated fatty acid levels were compared. STATISTICAL ANALYSES: Simple and adjusted Spearman's rank correlation coefficients were estimated after de-attenuation for intra-individual variation. RESULTS: Regarding food groups in men, adjusted correlations ranged from 0.20 for vegetables and plasma vitamin C to 0.49 for fruits and plasma vitamin C, and from 0.40 for fish and plasma c20:5 n-3 (eicosapentaenoic acid [EPA]) to 0.55 for fish and plasma c22:6 n-3 (docosahexaenoic acid). In women, correlations ranged from 0.13 (nonsignificant) for vegetables and plasma vitamin C to 0.41 for fruits and vegetables and plasma beta carotene, and from 0.27 for fatty fish and EPA to 0.54 for fish and EPA+docosahexaenoic acid. Regarding micronutrients, adjusted correlations ranged from 0.36 (EPA) to 0.58 (vitamin C) in men and from 0.32 (vitamin C) to 0.38 (EPA) in women. CONCLUSIONS: The findings suggest that three nonconsecutive web-based dietary records provide reasonable estimates of true intake of fruits, vegetables, fish, beta carotene, vitamin C, and n-3 fatty acids. Along with other validation studies, this study shows acceptable validity of using such diet-assessment methods in large epidemiologic surveys and broadens new perspectives for epidemiology.

Sodium Selenite Decreased HDAC Activity, Cell Proliferation and Induced Apoptosis in Three Human Glioblastoma Cells.

AIMS: Selenium (Se) is an essential trace element for human health which also has antitumor properties. Little is known about its effects on brain tumor cells (BTC). The aim of this study was to investigate the anticancer effects of sodium selenite (SS) including histone deacetylase (HDAC) activity in three human glioblastoma (GBM) cell lines (LN229, T98G and U87). MATERIALS & METHODS: LN229, T98G and U87 GBM cell lines were treated with variable doses of SS for time varying from 24 to 72h. HDAC activity, cell proliferation, toxicity, cell death process, caspase-3 and MMP2 activities and Se absorption were evaluated. RESULTS: SS modulated all the parameters tested in a dose- and time-dependent manner. We found that SS decreased HDAC activity, blocked cell proliferation and cell cycle at the G2 phase, triggered an apoptotic cell death process caspase-3-dependent and reduced MMP2 activities. All these effects were performed whereas SS was weakly absorbed (<2%). CONCLUSIONS: SS decreasing HDAC activity exhibited interesting antitumor properties in GBM cells which may be taken into account in the novel strategies for achieving tumor growth inhibition and cytotoxicity. Epigenetic modifications induced by SS should be evaluated in further studies.

Wheat aleurone fractions and plasma n-3 fatty acids in rats.

The main aim of this study was to compare the effects of two wheat aleurone (WA) fractions on circulating n-3 fatty acids in rats. We demonstrated that only the fraction able to induce the highest urinary excretion of polyphenol metabolites (>1µmol) resulted in a significant increase in plasma level of Eicosapentanoic acid (+22%, p < 0.05). While other constituents of whole wheat can be involved in this response, our data suggest that cereals containing high levels of phenolic compounds can increase blood n-3 without affecting n-6 fatty acids. Further studies are required to confirm this hypothesis and explore the underlying biological mechanisms.

Validation of a Web-based, self-administered, non-consecutive-day dietary record tool against urinary biomarkers.

New technologies are promising for the use of short-term instruments for dietary data collection; however, innovative tools should be validated against objective biomarkers. The aim of the present study was to investigate the validity of a Web-based, self-administered dietary record (DR) tool using protein, K and Na intakes against 24 h urinary biomarkers (24 h U). Of the total participants, 199 adult volunteers (104 men and 95 women, mean age 50·5 (23-83 years)) of the NutriNet-Santé Study were included in the protocol. They completed three non-consecutive-day DR and two 24 h U on the first and third DR days. Relative differences between reported (DR) and measured (24 h U) intakes were calculated from the log ratio (DR/24 h U) for protein, K and Na intakes: -14·4,+2·6 and -2·1 % for men; and -13·9, -3·7 and -8·3 % for women, respectively. The correlations between reported and true intakes were 0·61, 0·78 and 0·47 for men and 0·64, 0·42 and 0·37 for women for protein, K and Na, respectively. Attenuation factors, that represent attenuation of the true diet-disease relationship due to measurement error (a value closer to 1 indicating lower attenuation), ranged from 0·23 (Na, women) to 0·60 (K, men). We showed that the Web-based DR tool used in the NutriNet-Santé cohort study performs well in estimating protein and K intakes and fairly well in estimating Na intake. Furthermore, three non-consecutive-day DR appear to be valid for estimating usual intakes of protein and K, although caution is advised regarding the generalisability of these findings to other nutrients and general population.

Wheat aleurone polyphenols increase plasma eicosapentaenoic acid in rats.

METHODS: These studies were designed to assess whether wheat polyphenols (mainly ferulic acid [FA]) increased the very-long-chain omega-3 fatty acids (VLC n-3) [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in rats. Wheat aleurone (WA) was used as a dietary source of wheat polyphenols. Two experiments were performed; in the first one, the rats were fed WA or control pellets (CP) in presence of linseed oil (LO) to provide alpha-linolenic acid (ALA), the precursor of VLC n-3. In the second one, the rats were fed WA or CP in presence of control oil (CO) without ALA. The concentrations of phenolic acid metabolites in urine were also investigated. RESULTS: The urinary concentration of conjugated FA increased with WA ingestion (p<0.05). Plasma EPA increased by 25% (p<0.05) with WA in the CO group but not in the LO group. In contrast, there was no effect of WA on plasma DHA and omega-6 fatty acids (n-6). Finally, both n-3 and n-6 in the liver remained unchanged by the WA. CONCLUSION: These results suggest that WA consumption has a significant effect on EPA in plasma without affecting n-6. Subsequent studies are required to examine whether these effects may explain partly the health benefits associated with whole wheat consumption.

Six-day selenium supplementation led to either UVA-photoprotection or toxic effects in human fibroblasts depending on the chemical form and dose of Se.

Selenium (Se) is an essential trace element with a narrow safety zone and unclear effects on skin photoageing. The aim of this work was to investigate the photoageing properties of sodium selenite or selenomethionine (SeMet) after a long term (6 days) Se supplementation in normal human skin fibroblasts (NHSF) subjected to ultraviolet-A (UVA) irradiation inducing 30% cell death. The uptake, toxicity and antioxidant effects of sodium selenite and SeMet were compared to better understand their photoageing properties. SeMet uptake was better than sodium selenite and their uptake by fibroblasts was not via an actively transport process. Sodium selenite induced a higher toxicity than SeMet. At 5 µM, sodium selenite inhibited cell proliferation associated with a blockage in the G2 phase and induced DNA fragmentation leading to caspase-3-dependent apoptosis cell death. At low doses (<1 µM), SeMet and sodium selenite induced glutathione peroxidase-1 (GPX1) activity and selenoproteinW1 (SEPW1) transcript expression but metalloproteinase (MMP)-1 was only induced by sodium selenite. SeMet and sodium selenite did not protect NHSFs from UVA-induced cell death. However, SeMet decreased malondialdehyde (MDA) and protected NHSFs from UVA-induced MMP1 and MMP3. We then observed a large difference in terms of photoprotection according to selenium forms. SeMet may be a potential agent for the prevention and treatment of skin photoageing.

Elements of margin of safety, toxicity and action of sodium selenite in a lipopolysaccharide rat model.

PROJECT: Both septic shock and sodium selenite (Na2SeO3) lead to multiple organ failure through oxidation. Na2SeO3 has direct oxidant effects above the nutritional level and indirect anti-oxidant properties. In a lipopolysaccharide (LPS) rat model we assessed margin of safety, toxicity and beneficial effect of pentahydrate Na2SeO3 (5H2O·Na2SeO3) at oxidant doses. PROCEDURE: In a three-step study on 204 rats we: (i) observed toxic effects of Na2SeO3 injected intraperitoneously (IP) and determined its Minimum Dose Without Toxic effect (MDWT) 0.25-0.35 mg/kg selenium (Se) content; (ii) injected IP LPS at 70% lethal dose (LD) followed, or not, one hour later by IP Na2SeO3 at MDWT and (iii) by doses>MDWT. At 48 h, in survivors, we measured plasma creatinine, lactate, aspartate and alanine aminotransferase (AST, ALT), nitric oxide (NO) and Se concentrations. RESULTS: (i) Na2SeO3 alone did not increase NO and lactate. Encephalopathy appeared at 1mg Se/kg. Creatinine increased at 1-1.75 mg Se/kg, AST, ALT at 3-4.5 mg Se/kg, and the minimum LD was 3 mg Se/kg. (ii) Mortality after LPS was 37/50 (74%, [62-86%]) vs. 20/30 (67%, [50-84%]) when followed by Na2SeO3 at MDWT (p=0.483) with a decreased in NO (-31%, p=0.038) a trend for lactate decrease (-19%, p=0.068) and an increased Se in plasma of survivals. (iii) All rats died at doses ≥0.6 mg/kg (p<0.001). CONCLUSION: Mechanisms of LPS and Na2SeO3 toxicity differ (i.e. NO, lactate). In septic shock 5H2O·Na2SeO3 toxicity increased, margin of safety decrease, but IP administration of dose considered as oxidant of 5H2O·Na2SeO3 showed beneficial effects.

Baseline plasma fatty acids profile and incident cardiovascular events in the SU.FOL.OM3 trial: the evidence revisited.

OBJECTIVE: We aimed to investigate the association between baseline plasma fatty acids profile and the risk of future major cardiovascular events in patients with a history of ischaemic heart disease or ischemic stroke. METHODS: Baseline plasma fatty acids as well as established cardiovascular risk factors were measured in 2,263 patients enrolled in the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids randomized controlled trial. Incident major cardiovascular, cardiac and cerebrovascular events were ascertained during the 4.7 years of follow up. Hazard ratios were obtained from Cox proportional hazards models after adjustment for cardiovascular risk factors. RESULTS: During the follow-up, 154, 379 and 84 patients had major cardiovascular, cardiac and cerebrovascular events respectively. Upon adjustment for gender, initial event, baseline age and BMI, the risk of developing a major cardiovascular event decreased significantly in successive quartiles of arachidonic acid (P trend<0.002), total omega 3 polyunsaturated fatty acids (P trend<0.03), docosapentaenoic acid (P trend<0.019), docosahexaenoic acid (P trend<0.004), eicosapentaenoic acid + docosahexaenoic acid (P trend<0.03) and eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid (P trend<0.02). This inverse association was borderline significant with increased quartiles of stearidonic acid (P trend<0.06). In the full model, only stearidonic acid remained inversely associated with the risk of developing a major cardiovascular event (P trend<0.035), a cardiac event (P trend<0.016) or a cerebrovascular event (P trend<0.014), while arachidonic acid was inversely associated with the risk a cerebrovascular event (P trend<0.033). CONCLUSION: The inverse association of long chain omega 3 polyunsaturated fatty acids with recurrence of Cardiovascular diseases was mainly driven by well-known cardiovascular risk factors. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN41926726.

Prospective associations between plasma saturated, monounsaturated and polyunsaturated fatty acids and overall and breast cancer risk - modulation by antioxidants: a nested case-control study.

BACKGROUND: Mechanistic data suggest that different types of fatty acids play a role in carcinogenesis and that antioxidants may modulate this relationship but epidemiologic evidence is lacking. Our aim was to investigate the association between plasma saturated, monounsaturated and polyunsaturated fatty acids (SFAs, MUFAs and PUFAs) and overall and breast cancer risk and to evaluate the potential modulatory effect of an antioxidant supplementation on these relationships. METHODS: A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX study between 1994 and 2002 (n=250 cases, one matched control/case). Participants to the SU.VI.MAX randomized controlled trial received either vitamin/mineral antioxidants or placebo during this intervention period. Baseline fatty acid composition of plasma total lipids was measured by gas chromatography. Conditional logistic regression was performed overall and stratified by intervention group. RESULTS: Dihomo-γ-linolenic acid (Ptrend=0.002), the dihomo-γ-linolenic/linoleic acids ratio (Ptrend=0.001), mead acid (Ptrend=0.0004), and palmitoleic acid (Ptrend=0.02) were inversely associated with overall cancer risk. The arachidonic/dihomo-γ-linolenic acids ratio (Ptrend=0.02) and linoleic acid (Ptrend=0.02) were directly associated with overall cancer risk. Similar results were observed for breast cancer specifically. In stratified analyses, associations were only observed in the placebo group. Notably, total PUFAs were directly associated with overall (Ptrend=0.02) and breast cancer risk in the placebo group only. CONCLUSION: Specific SFAs, MUFAs and PUFAs were prospectively differentially associated with cancer risk. In addition, this study suggests that antioxidants may modulate these associations by counteracting the potential effects of these fatty acids on carcinogenesis.

Cellular and molecular mechanisms activating the cell death processes by chalcones: Critical structural effects.

Chalcones are naturally occurring compounds with diverse pharmacological activities. Chalcones derive from the common structure: 1,3-diphenylpropenone. The present study aims to better understand the mechanistic pathways triggering chalcones anticancer effects and providing evidences that minor structural difference could lead to important difference in mechanistic effect. We selected two recently investigated chalcones (A and B) and investigated them on glioblastoma cell lines. It was found that chalcone A induced an apoptotic process (type I PCD), via the activation of caspase-3, -8 and -9. Chalcone A also increased CDK1/cyclin B ratios and decreased the mitochondrial transmembrane potential (ΔΨm). Chalcone B induced an autophagic cell death process (type II PCD), ROS-related but independent of both caspases and protein synthesis. Both chalcones increased Bax/Bcl2 ratios and decreased Ki67 and CD71 antigen expressions. The present investigation reveals that despite the close structure of chalcones A and B, significant differences in mechanism of effect were found.

Long-term selenium supplementation in HaCaT cells: importance of chemical form for antagonist (protective versus toxic) activities.

The beneficial effect of selenium (Se) on cancer is known to depend on the chemical form, the dose and the duration of the supplementation. The aim of this work was to explore long term antagonist (antioxidant versus toxic) effects of an inorganic (sodium selenite, Na2SeO3) and an organic (seleno-L-methionine, SeMet) forms in human immortalized keratinocytes HaCaT cells. HaCaT cells were supplemented with Na2SeO3 or SeMet at micromolar concentrations for 144 h, followed or not by UVA radiation. Se absorption, effects of UVA radiation, cell morphology, antioxidant profile, cell cycle processing, DNA fragmentation, cell death triggered and caspase-3 activity were determined. At non-toxic doses (10 µM SeMet and 1 µM Na2SeO3), SeMet was better absorbed than Na2SeO3. The protection of HaCaT from UVA-induced cell death was observed only with SeMet despite both forms increased glutathione peroxidase-1 (GPX1) activities and selenoprotein-1 (SEPW1) transcript expression. After UVA irradiation, malondialdehyde (MDA) and SH groups were not modulated whatever Se chemical form. At toxic doses (100 µM SeMet and 5 µM Na2SeO3), Na2SeO3 and SeMet inhibited cell proliferation associated with S-G2 blockage and DNA fragmentation leading to apoptosis caspase-3 dependant. SeMet only led to hydrogen peroxide production and to a decrease in mitochondrial transmembrane potential. Our study of the effects of selenium on HaCaT cells reaffirm the necessity to take into account the chemical form in experimental and intervention studies.

Trace element status and fatty acids metabolism during healthy ageing: an example of a population from the Tunisian eastern coast.

Micronutrients as well as essential fatty acids are indispensable for the correct functioning of the organism. The risk of disturbance in the associated nutrition and metabolism is expected to increase during ageing. In addition, it seems that trace elements are involved in the fatty acids metabolism. The aim of the present study was then to assess age-related changes in trace elements status and in plasma essential fatty acids composition with an emphasis on the desaturase activity estimation. Two hundred healthy Tunisian subjects (30-85 years old) were recruited and separated into two subgroups: elderly (65-85 years old) and middle-aged (30-60 years old). The findings revealed that plasma zinc and calcium concentrations significantly decreased according to age. The prevalence of zinc deficiency was therefore shown to increase in old age (over 60% of elderly subjects were deficient or at risk of deficiency). No age-related changes were obtained for copper or magnesium status. The Δ6 desaturase, involved in the EFAs conversion, was shown to decrease according to age and to be associated with the plasma zinc level. Since elderly subjects were at risk of nutritional imbalance, it would be interesting to set optimal dietary proportion. This will help to prevent age-associated alterations and diseases for a better and healthy ageing.

Atherogenic lipid profile in Behçet's disease: evidence of alteration of HDL subclasses.

BACKGROUND AND AIMS: Behçet's disease (BD) is an inflammatory vasculitis, most common in the Mediterranean area and Asia. Evidence for accelerated atherosclerosis in BD has been observed. The relationship between cardiovascular risk factors and accelerated atherosclerosis in patients with BD is still controversial. The aim of this study was to evaluate the lipid profile and to investigate the low-density lipoprotein (LDL) size and the distribution of high-density lipoprotein (HDL) subpopulations in BD patients. METHODS: Thirty six BD patients were compared to 36 healthy controls. Total cholesterol (TC), triglycerides (TG) and HDL-cholesterol (HDL-C) levels were measured using standard techniques. HDL subclasses and LDL-C size were estimated using polyacrylamide linear gradient gel electrophoresis. The LDL-C/HDL-C ratio was also calculated. High-sensitive C-reactive protein (hsCRP) level was measured by a turbidimetric method. Homocysteine (Hcy) level was determined using a liquid chromatography tandem mass spectrometry (LC/MS/MS). RESULTS: In BD patients, HDL-C levels as well as its subfraction levels were decreased (respectively, p <10(-6) and p <10(-3)). Percentage of HDL2 subpopulation was also decreased (p=0.02). HDL3 subfraction was significantly higher (p=0.02). The LDL-C/HDL-C ratio and CRP level were increased (respectively, p=10(-4) and p=0.003). TC was correlated with CRP. HDL-C and its subfractions were correlated with CRP and TG levels. HDL subparticle percentages were also correlated with age. CONCLUSIONS: Our findings of a reduction of HDL-C and HDL2 subpopulation and an increase HDL3 subclass and a higher LDL-C/HDL-C ratio may be considered as important predictors of cardiovascular events in BD patients.