Hugo Neels

Lowered ω3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients

Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4omega6/C20:5omega3 ratio and decreases in omega3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5omega3 proportions and increased C20:4omega6/C20:5omega3 and C22:5omega6/C22:6omega3 ratios; lower C22:4omega6, C20:5omega3 and C22:5omega3 fractions in phospholipids; lower C18:3omega3, C20:5omega3 and total (sigma)omega3 FAs, and higher C20:4omega6/C20:5omega3 and sigmaomega6/sigmaomega3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5omega3 and C22:6omega3 fractions in phospholipids; and significant inverse correlations between serum Zn and the sigmaomega6/sigmaomega3, C20:4omega6/C20:5omega3, and C22:5omega6/C22:6omega3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of omega3 PUFAs and a compensatory increase in MUFAs and C22:5omega6 in phospholipids. The results suggest that: (i) there is an abnormal metabolism of omega3 PUFAs in depression; (ii) the FA alterations in depression are related to the inflammatory response in that illness; and (iii) the disorders may persist despite successful antidepressant treatment.

Illicit drug consumption estimations derived from wastewater analysis: A critical review ☆

The consumption of illicit drugs causes indisputable societal and economic damage. Therefore it is necessary to know their usage levels and trends for undertaking targeted actions to reduce their use. Recently, a new approach (namely sewage epidemiology) was developed for the estimation of illicit drug use based on measurements of urinary excreted illicit drugs and their metabolites in untreated wastewater. This review aims at critically evaluating the published literature and identifying research gaps of sewage epidemiology. Firstly, the existing analytical procedures for the determination of the four most used classes of illicit drugs worldwide (cannabis, cocaine, opiates and amphetamine-like stimulants) and their metabolites in wastewater are summarized and discussed. The focus lies on the sample preparation and on the analysis with chromatographic techniques coupled to mass spectrometry. Secondly, back-calculations used to transform measured concentrations in wastewater (in ng/L) into an amount of used illicit drug (in g/day per 1000 inhabitants or doses/day per 1000 inhabitants) are discussed in detail for the four groups of illicit drugs. Sewage epidemiology data from Spain, Belgium, UK, Italy, Switzerland and USA are summarized and compared with data from international organisations, such as the European Monitoring Centre for Drug and Drug Addiction (EMCDDA) and the United Nations Office on Drugs and Crime (UNODC). The results derived from wastewater analysis show in general good agreement with existing prevalence data (percentage of a population that uses illicit drugs at a given time) and demonstrate the potential of sewage epidemiology. However, this review confirms that future work should focus on further optimisation and standardisation of various important parameters (e.g. sample collection and back-calculations). In the future, sewage epidemiology could be used in routine drug monitoring campaigns as a valuable tool in addition to the classical socio-epidemiological studies for the determination of local, national and international illicit drug use.

Analytical developments and preliminary assessment of human exposure to organophosphate flame retardants from indoor dust

A new and efficient analytical method was developed and validated for the analysis of organophosphorus flame retardants (OPFRs) in indoor dust samples. This method involves an extraction step by ultrasonication and vortex, followed by extract clean-up with Florisil solid-phase extraction cartridges and analysis of the purified extracts by gas chromatography-mass spectrometry (GC-MS). Method recoveries ranged between 76 and 127%, except for volatile OPFRs, such as triethyl phosphate (TEP) and tri-(n-propyl) phosphate (TnPP), which were partially lost during evaporation steps. The between day precision on spiked dust samples was <14% for individual OPFRs, except for TEP, tri-iso-butyl phosphate (TiBP) and tri (2-butoxyethyl) phosphate (TBEP). Method limit of quantifications (LOQ) ranged between 0.02 μg/g (TnPP and tris(1-chloro-2-propyl phosphate (TCPP)) and 0.50 μg/g (TiBP). The method was further applied for the analysis of indoor dust samples taken from Flemish homes and stores. TiBP, TBEP and TCPP were most abundant OPFR with median concentrations of 2.99, 2.03 and 1.38 μg/g in house dust and of 1.04, 3.61, and 2.94 μg/g in store dust, respectively. The concentration of all OPFRs was at least 20 to 30 times higher compared to polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs). Estimated exposure to OPFRs from dust ingestion ranged for individual OPFRs between <1 and 50 ng/kg body weight for adults and toddlers, respectively. The estimated body burdens were 1000 to 100 times below reference dose (RfD) values, except for the scenario with high dust ingestion and high concentrations of TBEP in toddlers, where intake was only 5 times below RfD. Exposure of non-working and working adults to OPFRs appeared to be similar, but in specific work environments, exposure to some OPFRs (e.g. TDCPP) was increased by a factor >5.

Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness

The aims of the present study were to examine i) serum zinc (Zn) and copper (Cu) in treatment resistant depression (TRD); ii) the effects of subchronic antidepressant therapy on these trace elements; and iii) the relationships between serum Zn and Cu and immune/inflammatory markers. Serum Zn was significantly lower in TRD than in normal controls. There was a significant inverse correlation between baseline serum Zn and staging of depression based on severity of prior treatment resistance. There were no significant effects of antidepressive treatment on serum Zn, whereas serum Cu was significantly reduced. There were highly significant correlations between serum Zn and the CD4+/CD8+ T-cell ratio (negative), and total serum protein, serum albumin, and transferrin (all positive). The results suggest that lower serum Zn is a marker of TRD and of the immune/inflammatory response in depression. It is suggested that treatment resistance may bear a relationship with the immune/inflammatory alterations in major depression.

Lower serum vitamin E concentrations in major depression Another marker of lowered antioxidant defenses in that illness

OBJECTIVE Major depression is associated with defective antioxidant defenses. Vitamin E is the major fat soluble antioxidant in the body. The aim of the present study is to examine serum vitamin E concentrations in major depressed patients versus normal volunteers. METHOD Serum vitamin E concentrations were measured in 26 healthy volunteers and 42 major depressed patients by means of HPLC. Since vitamin E is a fat soluble vitamin, and serum vitamin E concentrations are strongly related to these of low-density-lipoprotein cholesterol (LDL-C) and triglycerides, we have adjusted the results for possible differences in these lipids. The numbers of peripheral blood leukocytes were measured. RESULTS Patients with major depression had significantly lower serum vitamin E concentrations than healthy controls. The area under the ROC (receiver operating characteristics) curve was 83%. There were significant and negative correlations between serum vitamin E and number of total leukocytes and neutrophils. CONCLUSIONS Major depression is accompanied by significantly lower serum vitamin E concentrations, suggesting lower antioxidant defenses against lipid peroxidation. The results could, in part, explain previous findings, which suggest increased lipid peroxidation in major depression.

Lower serum high‐density lipoprotein cholesterol (HDL‐C) in major depression and in depressed men with serious suicidal attempts: relationship with immune‐inflammatory markers

Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune‐inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high‐density lipoprotein cholesterol (HDL‐C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL‐C or by abnormal levels of serum total cholesterol, triglycerides, low‐density lipoprotein‐C (LDL‐C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL‐C and (iii) there are significant associations between serum HDL‐C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T‐helper/T‐suppressor (CD4+/ CD8+) T‐cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL‐C and total cholesterol, as well as the HDL‐C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL‐C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL‐C or other lipid variables. Serum HDL‐C levels were significantly and negatively correlated with the (CD4+/CD8+) T‐cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL‐C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL‐C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.

Occurrence of alternative flame retardants in indoor dust from New Zealand: Indoor sources and human exposure assessment

Due to worldwide restrictions on polybrominated diphenyl ethers (PBDEs), the demand for alternative flame retardants (AFRs), such as organophosphate flame retardants (OPFRs), novel brominated FRs (NBFRs) and hexabromocyclododecanes (HBCDs), has recently increased. Little is known about human exposure to NBFRs and OPFRs and that their levels in dust have been scarcely evaluated worldwide. To increase the knowledge regarding these chemicals, we measured concentrations of five major NBFRs, ten OPFRs and three HBCD isomers in indoor dust from New Zealand homes. Dust samples were taken from living room floors (n=34) and from mattresses of the same houses (n=16). Concentrations (ngg(-1)) of NBFRs were: 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) (<2-175), decabromodiphenyl ethane (DBDPE) (<5-1430), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) (<2-2285) and bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH) (<2-640). For OPFRs, concentrations (ngg(-1)) ranged between: tri-ethyl-phosphate (TEP) (<10-235), tri-n-butyl-phosphate (TnBP) (<20-7545), tris-(2-chloroethyl)-phosphate (TCEP) (<20-7605), tris-(1-chloro-2-propyl) phosphate (TCPP) (20-7615), tri-(2-butoxyethyl)-phosphate (TBEP) (50-27325), tris-(2,3-dichloropropyl)-phosphate (TDCPP) (20-16560), tri-phenyl-phosphate (TPhP) (20-35190), and tri-cresyl-phosphate (TCP) (<50-3760). HBCD concentrations fell in the range <2-4100ngg(-1). BTBPE, DBDPE, TBPH, TBEP, and TnBP showed significant positive correlation (p<0.05) between their concentrations in mattresses and the corresponding floor dust (n=16). These data were used to derive a range of plausible exposure scenarios. Although the estimated exposure is well below the corresponding reference doses (RfDs), caution is needed given the likely future increase in use of these FRs and the currently unknown contribution to human exposure by other pathways such as inhalation and diet.

Assessment of human exposure to Bisphenol-A, Triclosan and Tetrabromobisphenol-A through indoor dust intake in Belgium.

Bisphenol-A (BPA), Triclosan (TCS) and Tetrabromobisphenol-A (TBBPA) are phenolic organic contaminants used in a variety of household applications. Through manufacture and usage, these contaminants can leach into the environment and can be detected in indoor dust. In this study, we determined the concentrations of BPA, TCS and TBBPA in indoor dust samples from 18 houses and 2 offices in Flanders, Belgium. The analysis was performed using solid-liquid extraction, clean-up and measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Median concentrations of the 18 domestic dust samples were 1460, 220 and 10 ng g(-1) dust for BPA, TCS and TBBPA, respectively. Concentrations in offices were almost 5-10 times higher for BPA and TBBPA, while TCS concentrations were comparable at both locations. An assessment of the daily intake of these contaminants through dust was made and the contribution of dust to the total human exposure was calculated. For all three contaminants, dust seems to be a minor contributor (<10% of total exposure) to the total daily exposure. Food intake appears to be the major source of human exposure to BPA and TBBPA as dermal uptake through personal care products seems to be the major contributor for TCS.

Obesity and persistent organic pollutants : possible obesogenic effect of organochlorine pesticides and polychlorinated biphenyls

Persistent organic pollutants (POPs) are endocrine‐disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross‐sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro‐diphenyl‐dichloroethylene (pp‐DDE), and β‐hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMAIR). βHCH correlated significantly positively with HOMAIR. A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMAIR, whereas serum PCB levels were inversely correlated with BMI and HOMAIR. Combined, these results suggest that the diabetogenic effect of low‐dose exposure to POPs might be more complicated than a simple obesogenic effect.

Exposure to Hexabromocyclododecanes (HBCDs) via Dust Ingestion, but Not Diet, Correlates with Concentrations in Human Serum: Preliminary Results

Background Hexabromocyclododecane (HBCD) is a high-production-volume chemical used as flame retardant in polystyrene insulation and textiles. Because it is not chemically bound to the polymer, HBCD can migrate into the environment, contaminating indoor dust and foodstuff. Objectives We examined for the first time the relationship between combined exposure to three HBCD isomers (∑HBCDs) via ingestion of food (duplicate diets) and indoor dust and HBCD concentrations in serum for 16 Belgian adults (20–25 years of age). We also determined the chiral signatures of HBCDs to advance understanding of source-to-human enantioselective degradation and/or metabolism. Methods Concentrations and chiral signatures of α-, β-, and γ-HBCD in duplicate diets, dust, and serum were measured by liquid chromatography/tandem mass spectrometry. Results Dietary intakes of ∑HBCDs were 1.2–20 ng/day (average, 7.2 ng/day), whereas those estimated under average (20 mg dust/day) and high (50 mg dust/day) dust ingestion scenarios were 1.1–15 ng/day (average intake, 3.2 ng/day) and 2.8–38 ng/day (average intake, 8.0 ng/day), respectively. Concentrations of ∑HBCDs measured in blood serum were < 0.5 to 11 ng/g lipid weight (lw) (average, 2.9 ng/g lw). γ-HBCD dominated in food, whereas α-HBCD dominated in dust and was the sole isomer in serum. Although exposure via dust ingestion correlated significantly (p < 0.01) with concentrations in serum, no such correlation was evident with dietary exposure (p > 0.1). Although no enantioselective enrichment was detected in either dust or diet, substantial enrichment of (−)α-HBCD was observed in serum. Conclusions Serum concentrations of HBCDs were correlated with the exposure via dust, but not via dietary ingestion. The enrichment of the (−)α-HBCD enantiomer in humans appears to be due to in vivo enantioselective metabolism/excretion rather than ingestion of dust or diet.