DNA Damage Estimation after Chronic and Combined Exposure to Endocrine Disruptors: An In Vivo Real-Life Risk Simulation Approach.

Exposure to chemical substances has always been a matter of concern for the scientific community. During the last few years, researchers have been focusing on studying the effects resulting from combined exposure to different substances. In this study, we aimed to determine the DNA damage caused after chronic and combined exposure to substances characterized as endocrine disruptors using comet and micronuclei assays, specifically glyphosate (pure and commercial form), bisphenol A, parabens (methyl-, propyl- and butylparaben), triclosan and bis (2-ethylhexyl) phthalate. The highest mean tail intensity was observed in the group exposed to a high-dose (10 × ADI) mixture of substances (Group 3), with a mean value of 11.97 (11.26-13.90), while statistically significant differences were noticed between the groups exposed to low-dose (1 × ADI) (Group 2) and high-dose (10 × ADI) (Group 3) mixtures of substances (p = 0.003), and between Group 3 and both groups exposed to high doses (10 × ADI) of the pure and commercial forms of glyphosate (Groups 4 (p = 0.014) and 5 (p = 0.007)). The micronuclei assay results were moderately correlated with the exposure period. Group 5 was the most impacted exposure group at all sampling times, with mean MN counts ranging between 28.75 ± 1.71 and 60.75 ± 1.71, followed by Group 3 (18.25 ± 1.50-45.75 ± 1.71), showing that commercial forms of glyphosate additives as well as mixtures of endocrine disruptors can enhance MN formation. All exposure groups showed statistically significant differences in micronuclei counts with an increasing time trend.

Biomonitoring of bisphenol A, triclosan and perfluorooctanoic acid in hair samples of children and adults.

Bisphenol A (BPA), triclosan (TCS) and perfluorooctanoic acid (PFOA) are endocrine disruptors linked with negative health effects such as developmental, reproductive and cardiovascular toxicity. The aim of this study was to determine simultaneously the concentration of BPA, TCS and PFOA in hair from children and adults and examine possible associations between biomonitoring data and age, gender, dietary habits and body mass index. Methanolic extraction was applied and the compounds were determined by liquid chromatography-mass spectrometry. Low levels of exposure to PFOA were detected for children and adults at concentrations below limit of quantification. The mean concentration of BPA in children and adults was 20.6 and 16.6 pg mg-1 , while for TCS 275.2 and 687.0 pg mg-1 , respectively. Children were highly exposed to BPA relative to adults (P = .011) although adults had greater exposure to TCS (P = .003). Hair from girls had a greater burden of BPA (P = .06) compared to boys. Moreover, higher TCS levels were depicted for females in both examined groups (children P = .200 and adults P = .213) compared to males, but no statistical differences were observed. Significant differences were also observed between age groups (P = .0007) for TCS. No correlations were found between BPA or TCS levels and body mass index or dietary habits for both children and adults. Children have a greater exposure to BPA compared to adults, whereas exposure of adults to TCS seems to be higher than that in children and elderly people. Exposure to BPA occurs mainly via ingestion whereas exposure to TCS mainly via dermal absorption.

Long lasting effects of chronic heavy cannabis abuse.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the extent of short-term memory impairment and schizophrenia-like symptoms in heavy and systematic cannabis users and the association between the severity of abuse and the longevity of its persistent symptoms after refraining from such use. METHODS: A complete psychiatric examination and a psychometric evaluation were performed in 48 solely cannabis users. Additionally, head hair samples were analyzed and the detected cannabinoids levels were correlated with the psychometric findings. RESULTS: A total of 33.3% (n = 16) of the total examined cannabis users were currently imprisoned. The years of abuse ranged from 1 to 35 years and the median daily dose was 5.84.4 gr and 4.84.0 gr for prisoners (n = 16) and non prisoners (n = 32), respectively. A total of 39.6% of the users experienced hallucinations (mostly auditory), 54.2% experienced delusions (mostly ideas of reference and persecution), 85.4% had organic brain dysfunction in a test addressing visual-motor functioning and visual perception skills, and all users (100%) were found to have organic brain dysfunction in a test of visual memory immediate recall. The cannabinoid metabolite levels in the hair samples were consistent with the reported history of substance abuse and total grams of consumption for the participants below 35 years old (p < .001). Statistically elevated cannabinoids levels were observed in users with auditory hallucinations compared to users without any hallucinations (p = .019). CONCLUSIONS: The existence of hallucinations, delusions, and organic brain dysfunction in heavy cannabis users seems to be associated with cannabinoid levels in hair. The continuation of persistent symptoms 3 months after the discontinuation of cannabis abuse, was a remarkable finding. SCIENTIFIC SIGNIFICANCE: We provide evidence that chronic and heavy cannabis abuse results in long-lasting brain dysfunction in all users and in long-lasting schizophrenia-like psychotic symptoms in more than half of all users. These findings suggest a reevaluation of the current classification of cannabis as a "soft narcotic" which erroneously, therefore, is typically considered harmless. (Am J Addict 2017;26:335-342).

Amphiphilic poly-N-vinylpyrrolidone nanoparticles as carriers for non-steroidal, anti-inflammatory drugs: In vitro cytotoxicity and in vivo acute toxicity study.

Polymeric nanoparticles were prepared from self-assembled amphiphilic N-vinylpyrrolidone polymers in aqueous media and evaluated as novel carriers of indomethacin, a non-steroidal, anti-inflammatory drug. It was determined that these nanoparticles could be created in spherical morphologies with sizes less than 100nm, narrow size distributions and high indomethacin contents(up to 35%) combined with high drug loading efficiencies(up to 95%). In cytotoxicity tests using the human embryonic stem cell derived fibroblasts (EBF-H9) and hepatocellular carcinoma cells (HepG2), the indomethacin-loaded polymeric nanoparticles showed higher cell viability compared to that of free indomethacin at the same concentration. The median LD50 values, determined by the Litchfield-Wilcoxon method, were 55-70mg/kg body weight depending on the polymer molecular design in both mice and rats. Based on the acquired results, these novel amphiphilic poly-N-vinylpyrrolidone nanoparticles can be considered as potential carriers for new, highly efficient, injectable drug delivery systems for hydrophobic drugs such as indomethacin.

The relationship between cotinine concentrations and inflammatory markers among highly secondhand smoke exposed non-smoking adolescents.

BACKGROUND: Secondhand smoke (SHS) exposure is a risk factor of respiratory, cardiovascular and inflammatory diseases, however its association with inflammatory markers among highly SHS exposed adolescents has not yet been explored. METHODS: Participants included in this study were a subset of 68 non-smoking adolescents, aged 12.5-17.5 from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, recruited from Crete Greece. Smoking and SHS exposure was assessed via serum cotinine concentrations. Cytokines (Interleukin-1ß, 2, 4, 5 and 6, tumor necrosis factor-α, interferon-γ, tumor growth factor-ß1), immunoglobulins IgG, IgA, IgM, complement factors C3, C4, high sensitivity C-reactive protein, and endothelial inflammatory markers [soluble E-selectin, soluble L-selectin, soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecules-1 (sVCAM-1)] were assessed. Inflammatory markers in the lower 25th percentile and upper 75th percentile groups of cotinine levels were compared and multivariate linear regression analysis was performed controlling for age, sex and BMI. RESULTS: Cotinine concentrations were notably elevated (geometric mean 0.82ng/ml, 95%CI 0.62-1.07) in this study population. A significant decrease in IL-4 (130.09 vs. 25.77pg/ml, p=0.014) and IL-6 (19.52 vs. 5.52pg/ml, p=0.008) concentrations between the upper 75th percentile cotinine level group and lower 25th percentile cotinine level group was observed. In a multivariate linear regression analysis, cotinine concentrations had a weak inverse association with IL-4 and IL-6 (p=0.028 and p=0.06) which was not statistically significant when adjusted for multiple comparisons (modified Bonferroni, p>0.016). No differences in the other variables was noted. CONCLUSIONS: Among highly SHS exposed adolescents, cotinine levels had weak inverse association with IL-4 and IL-6, which did not achieve statistical significance. However, our results potentially indicate an immunosuppressive role of SHS. Further research is warranted to explore this hypothesis.

Biomonitoring of dialkylphosphate metabolites (DAPs) in urine and hair samples of sprayers and rural residents of Crete, Greece.

PURPOSE: The aim of this study was to evaluate the exposure of rural residents (control group) and occupational exposed population group of sprayers to organophosphorus pesticides (OPs) by measuring their non-specific dialkylphosphate metabolites (DAPs) in hair and in urine samples. All subjects (n=120) were residents of the municipality of Ierapetra, an area of intensive cultivation in Crete, Greece. METHODS: The determined OPs metabolites were DMP, DEP, DETP and DEDTP. Two different approaches were used for the analysis of the collected samples; solid-liquid extraction with sonication for hair and liquid-liquid extraction for urine. Gas chromatography-mass spectrometry (GC-MS) analysis was performed after derivatization of the isolated analytes. RESULTS AND DISCUSSION: The detection rates of DMP, DEP and DETP for both control and sprayers groups were high in both matrices, ranging from 91% to 100%. DEDTP was detected only in 9% of sprayers hair samples, while its detection rates in urine samples ranged from 83% to 90% for both population groups. Data analysis revealed significantly higher sumDAPs levels in urine of sprayers than in the urine of control group (p<0.001) and this is justified since sampling occurred during spraying periods. SumDAPs levels in hair samples of the sprayers were also significantly higher than in the hair of control group (p<0.001), confirming the long-term exposure to OPs. SumDAPs found levels in urine and hair samples of subjects were significantly correlated (Spearman׳s rho=0.728, p<0.001). Our study confirmed the elevated levels of DAPs in hair and urine samples in occupationally exposed group of sprayers in comparison to control group, even detected levels were similar in logarithmic scale.

Exposure to secondhand smoke promotes sympathetic activity and cardiac muscle cachexia.

Recent trials demonstrated that a single brief exposure to secondhand smoke (SHS) generates acute adverse health effects. We evaluated the acute (immediately after exposure) and short-term (0.5, 1, 2, 3 and 4 h after exposure) effects of SHS on cardiac autonomic control and myocardial integrity. Nineteen adult healthy never-smokers underwent a 1 h exposure to SHS at bar/restaurant levels and a 1 h control exposure. Heart rate variability (HRV), serum cotinine, and six cardiac protein markers were assessed before, during, and up to four hours following each exposure. SHS reduced the standard deviation of normal-to-normal intervals and increased cotinine levels, creatine kinase (CK)-MB, and myoglobin (p < 0.05). We conclude that acute exposure to SHS suppresses HRV and augments CK-MB and myoglobin. The SHS-induced elevations in CK-MB and myoglobin may reflect a generalized lytic state, especially of the cardiac muscle, which is apparent for at least 2 h following the SHS exposure.

Acute effects of second-hand smoke on complete blood count.

We assessed the acute effects of a 1-h exposure to second-hand smoke (SHS) on complete blood count (CBC) markers in a controlled simulated bar/restaurant environment. Nineteen adult never-smokers completed a 1-h .exposure to SHS at bar/restaurant levels, and a 1-h exposure to normal room air. Blood samples were collected at the baseline at 30 min during each exposure, and at 0, 0.5, 1, 2, 3, and 4 h after each exposure. The values of white blood cells (WBC) at 1 h (p = 0.010), 3 h (p = 0.040), and 4 h (p = 0.008) following SHS were significantly increased compared with the baseline values. Also, there was a positive association between the WBC and cotinine levels (r = 0.28, p = 0.007). A 1-h exposure to SHS at bar/restaurant levels significantly increased the WBC for at least 4 h following the exposure time. This effect of SHS on WBC has dose-response characteristics and should be considered to prescribing CBC.

Benefits of Quercetin on Glycated Hemoglobin, Blood Pressure, PiKo-6 Readings, Night-Time Sleep, Anxiety, and Quality of Life in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

Background: Diabetes is a rapidly growing global morbidity issue with high prevalence, and the associated dysglycemia leads to complications. Patients with type 2 diabetes mellitus (T2DM) often experience elevated anxiety levels, affecting their quality of life and diabetes management. This study investigated quercetin, a nutraceutical and potential senolytic with antioxidant activity, to detect its possible positive effect on the bio-clinical measurements and routine health of patients with T2DM. Methods: This prospective randomized controlled trial (RCT) investigated the clinical usefulness of quercetin in patients with T2DM receiving non-insulin medications. One hundred participants were stratified by age and sex (1:1) and randomized to control (n = 50) or intervention (n = 50) groups. The control received standard care only, while the intervention received 500 mg quercetin daily for 12 weeks, followed by an 8-week washout and a final consecutive 12-week supplementation period (total: 32 weeks), as adjunct to their usual care. Comprehensive health assessments, including blood analyses, were conducted at baseline and study termination. Quality of life and anxiety were assessed using the 36-item Short Form Health Survey (SF-36) and Short Anxiety Screening Test (SAST-10). Results: Eighty-eight patients with T2DM concluded the trial. Compared with the control, glycated hemoglobin (HbA1c) levels showed a significant decrease (Δ%-change: -4.0% vs. 0.1%, p = 0.011). Quercetin also significantly improved PiKo-6 readings (FEV1: 5.6% vs. -1.5%, p = 0.002), systolic blood pressure (-5.0% vs. -0.2%, p = 0.029), night-time sleep (11.6% vs. -7.3%, p < 0.001), anxiety levels (SAST-10) (-26.2% vs. 3.3%, p < 0.001), and quality of life (SF-36) (both physical and mental components, p < 0.001). Conclusions: Based on the current open-label study, quercetin appears to be a promising supplement for T2DM, providing lifestyle and care support. Further research is warranted to shift this potential from clinical usefulness and feasibility to multidisciplinary evidence.

The Impact of the Mediterranean Diet on Telomere Biology: Implications for Disease Management-A Narrative Review.

INTRODUCTION: Telomeres are nucleoprotein complexes at the ends of chromosomes that are under the control of genetic and environmental triggers. Accelerated telomere shortening is causally implicated in the increasing incidence of diseases. The Mediterranean diet has recently been identified as one that confers protection against diseases. This review aimed to identify the effect of each component of the Mediterranean diet on telomere length dynamics, highlighting the underlying molecular mechanisms. METHODS: PubMed was searched to identify relevant studies to extract data for conducting a narrative review. RESULTS: The Mediterranean diet alleviates clinical manifestations in many diseases. Focusing on autoimmune diseases, the Mediterranean diet can be protective by preventing inflammation, mitochondrial malfunction, and abnormal telomerase activity. Also, each Mediterranean diet constituent seems to attenuate aging through the sustenance or elongation of telomere length, providing insights into the underlying molecular mechanisms. Polyphenols, vitamins, minerals, and fatty acids seem to be essential in telomere homeostasis, since they inhibit inflammatory responses, DNA damage, oxidative stress, mitochondrial malfunction, and cell death and induce telomerase activation. CONCLUSIONS: The Mediterranean diet is beneficial for maintaining telomere dynamics and alleviating age-related illnesses. This review provides a comprehensive overview of cross-sectional, observational, and randomized controlled trials regarding the beneficial impact of every constituent in the Mediterranean diet on telomere length and chronic disease management.

Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function.

CONTEXT: Electronic cigarettes (e-cigarettes) are becoming increasingly popular yet their effects on health remain unknown. OBJECTIVE: To conduct the first comprehensive and standardized assessment of the acute impact of active and passive e-cigarette smoking on serum cotinine and lung function, as compared to active and passive tobacco cigarette smoking. MATERIALS AND METHODS: Fifteen smokers (≥15 cigarettes/day; seven females; eight males) and 15 never-smokers (seven females; eight males) completed this repeated-measures controlled study. Smokers underwent a control session, an active tobacco cigarette (their favorite brand) smoking session and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session and a passive e-cigarette smoking session. Serum cotinine, lung function, exhaled carbon monoxide and nitric oxide were assessed. The level of significance was set at p ≤ 0.001 to adjust for multiple comparisons. RESULTS: e-Cigarettes and tobacco cigarettes generated similar (p > 0.001) effects on serum cotinine levels after active (60.6 ± 34.3 versus 61.3 ± 36.6 ng/ml) and passive (2.4 ± 0.9 versus 2.6 ± 0.6 ng/ml) smoking. Neither a brief session of active e-cigarette smoking (indicative: 3% reduction in FEV1/FVC) nor a 1 h passive e-cigarette smoking (indicative: 2.3% reduction in FEV1/FVC) significantly affected the lung function (p > 0.001). In contrast, active (indicative: 7.2% reduction in FEV1/FVC; p < 0.001) but not passive (indicative: 3.4% reduction in FEV1/FVC; p = 0.005) tobacco cigarette smoking undermined lung function. CONCLUSION: Regarding short-term usage, the studied e-cigarettes generate smaller changes in lung function but similar nicotinergic impact to tobacco cigarettes. Future research should target the health effects of long-term e-cigarette usage, including the effects of nicotine dosage.

Chemical Warfare in Ancient Greek Ionia: Mass Intoxication With Hecate's Deleterium.

The rich land of Erythrae in the coast of Asia Minor attracted the attention of the Ionian king Codrus. An oracle demanded the presence of the murky deity Hecate for him to conquer the city. Priestess Chrysame was sent by Thessalians to set the strategy of the clash. The young sorceress poisoned a sacred bull who turned mad, later to be released toward the camp of Erythraeans. The beast was captured and sacrificed. In the feast that followed, all ate a piece of his flesh and went crazy, stimulated by the poison, an easy prey for the army of Codrus. The deleterium used by Chrysame is unknown, but her strategy shaped the origin of biowarfare.

Endocrine-Disrupting Chemicals and Persistent Organic Pollutants in Infant Formulas and Baby Food: Legislation and Risk Assessments.

Human milk is the healthiest option for newborns, although, under specific circumstances, infant formula is a precious alternative for feeding the baby. Except for the nutritional content, infant formulas and baby food must be pollutant-free. Thus, their composition is controlled by continuous monitoring and regulated by establishing upper limits and guideline values for safe exposure. Legislation differs worldwide, although there are standard policies and strategies for protecting vulnerable infants. This work presents current regulations and directives for restricting endocrine-disrupting chemicals and persistent organic pollutants in infant formulas. Risk assessment studies, which are limited, are necessary to depict exposure variations and assess the health risks for infants from dietary exposure to pollutants.

Telomere length as a predictive biomarker in osteoporosis (Review).

Telomeres are the ends of chromosomes that protect them from DNA damage. There is evidence to suggest that telomere shortening appears with advanced age. Since aging is a significant risk factor for developing age-related complications, it is plausible that telomere shortening may be involved in the development of osteoporosis. The present review summarizes the potential of telomere shortening as a biomarker for detecting the onset of osteoporosis. For the purposes of the present review, the following scientific databases were searched for relevant articles: PubMed/NCBI, Cochrane Library of Systematic Reviews, Scopus, Embase and Google Scholar. The present review includes randomized and non-randomized controlled studies and case series involving humans, irrespective of the time of their publication. In six out of the 11 included studies providing data on humans, there was at least a weak association between telomere length and osteoporosis, with the remaining studies exhibiting no such association. As a result, telomere shortening may be used as a biomarker or as part of a panel of biomarkers for tracking the onset and progression of osteoporosis.

Effect of Mediterranean diet on lipid peroxidation marker TBARS in obese patients with OSAHS under CPAP treatment: a randomised trial.

PURPOSE: The aim of our study was to examine the possible effect of the Mediterranean diet on thiobarbituric acid reacting substances (TBARS) in obese patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) who are under continuous positive airway pressure treatment. METHODS: Nine hundred patients were evaluated during a 1-year period (November 2008-October 2009), and 21 obese patients who met the inclusion criteria, with moderate to severe OSAHS based on overnight attended polysomnography, were included in the study. After randomisation, 11 followed the Mediterranean diet and 10 a prudent diet for a 6-month period. TBARS were measured in serum. RESULTS: TBARS levels decreased notably in both groups (p < 0.05), but no difference was observed between them (p > 0.05). There were significant differences in other characteristics. The Mediterranean diet group showed a greater reduction in weight (-10.8 ± 3.8), body mass index (-3.9 ± 1.6), waist circumference (-9.9 ± 3.0) and percentage of body fat (-4.7 ± 2.3) compared with the other group (-6.9 ± 3.1, -2.5 ± 1.0, -5.3 ± 2.6 and -2.2 ± 1.5, respectively; p < 0.05). CONCLUSIONS: Our results showed that the Mediterranean diet did not reduce the TBARS more than the prudent diet.

Antibiotics in Raw Meat Samples: Estimation of Dietary Exposure and Risk Assessment.

The extensive use of antibiotics in livestock farming poses increased concerns for human health as residues of these substances are present in edible tissues. The aim of this study was the determination of the levels of four groups of antibiotics (sulfonamides-SAs, tetracyclines-TCs, streptomycines-STr and quinolones-QNLs) in meat samples (muscles, livers and kidneys from beef, chicken and pork) and the estimation of the dietary exposure to antibiotics from meat consumption and the potential hazard for human health. Fifty-four samples of raw meat were randomly collected in 2018 from the Cretan market, Greece and analyzed both with an enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-mass spectrometry (LC-MS). According to the results derived from the ELISA method, only 2% of the meat samples were free from antibiotics, 2% were detected with 4 antibiotics and the great majority of the samples (87%) were detected with 2 to 3 antibiotics. SAs presented the highest detection frequencies for all samples whereas TCs were not detected in any bovine sample. The highest median concentration was detected for STr in bovine muscles (182.10 µg/kg) followed by QNLs (93.36 µg/kg) in pork kidneys whereas the chicken samples had higher burdens of QNLs compared to the other meat samples. LC-MS analysis showed that oxytetracycline (OTC) was the most common antibiotic in all samples. The highest median concentration of all antibiotics was detected for doxycycline (DOX) (181.73 µg/kg in pork kidney) followed by OTC in bovine liver (74.46 µg/kg). Risk characterization was applied for each of the two methods; The hazard quotients (HQ) did not exceed 0.059 for the ELISA method and 0.113 for the LC-MS method for any group of antibiotics, whereas the total hazard indexes (HI) were 0.078 and 0.021, respectively. The results showed the presence of different groups of antibiotics in meat from the Cretan market and that the health risk to antibiotics is low. A risk assessment analysis conducted for meat consumption and corrected for the aggregated exposure revealed no risk for the consumers.

In Vivo Estimation of the Biological Effects of Endocrine Disruptors in Rabbits after Combined and Long-Term Exposure: Study Protocol.

Recently, an increasing number of chemical compounds are being characterized as endocrine disruptors since they have been proven to interact with the endocrine system, which plays a crucial role in the maintenance of homeostasis. Glyphosate is the active substance of the herbicide Roundup®, bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) are used as plasticizers, while triclosan (TCS), methyl (MePB), propyl (PrPB), and butyl (BuPB) parabens are used as antimicrobial agents and preservatives mainly in personal care products. Studies indicate that exposure to these substances can affect humans causing developmental problems and problems in the endocrine, reproductive, nervous, immune, and respiratory systems. Although there are copious studies related to these substances, there are few in vivo studies related to combined exposure to these endocrine disruptors. The aim of the present pilot study is the investigation and assessment of the above substances' toxicity in rabbits after twelve months of exposure to glyphosate (both pure and commercial form) and to a mixture of all the above substances at subtoxic levels. The lack of data from the literature concerning rabbits' exposure to these substances and the restrictions of the 3Rs Principle will result in a limited number of animals available for use (four animals per group, twenty animals in total).

A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood.

Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD+opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 µg/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs.

Design and study protocol of the maternal smoking cessation during pregnancy study, (M-SCOPE).

BACKGROUND: Maternal smoking is the most significant cause of preventable complications during pregnancy, with smoking cessation during pregnancy shown to increase birth weight and reduce preterm birth among pregnant women who quit smoking. Taking into account the fact that the number of women who smoke in Greece has increased steadily throughout the previous decade and that the prevalence of smoking among Greek females is one of the highest in the world, smoking cessation should be a top priority among Greek health care professionals. METHODS/DESIGN: The Maternal Smoking Cessation during Pregnancy Study (M-SCOPE), is a Randomized Control Trial (RCT) that aims to test whether offering Greek pregnant smokers a high intensity intervention increases smoking cessation during the third trimester of pregnancy, when compared to a low intensity intervention. Prospective participants will be pregnant smokers of more than 5 cigarettes per week, recruited up to the second trimester of pregnancy. Urine samples for biomarker analysis of cotinine will be collected at three time points: at baseline, at around the 32nd week of gestation and at six months post partum. The control group/low intensity intervention will include: brief advice for 5 minutes and a short leaflet, while the experimental group/intensive intervention will include: 30 minutes of individualized cognitive-behavioural intervention provided by a trained health professional and a self-help manual especially tailored for smoking cessation during pregnancy, while counselling will be based on the ''5 As.'' After childbirth, the infants' birth weight, gestational age and any other health related complications during pregnancy will be recorded. A six months post-partum a follow up will be performed in order to re-assess the quitters smoking status. DISCUSSION: If offering pregnant smokers a high intensity intervention for smoking cessation increases the rate of smoking cessation in comparison to a usual care low intensity intervention in Greek pregnant smokers, such a scheme if beneficial could be implemented successfully within clinical practice in Greece. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01210118.

Quantification of BNN27, a novel neuroprotective 17-spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administration.

BNN27 is a novel 17-spiroepoxy derivative of the neurosteroid Dehydroepiandrosterone with neuroprotective properties. The purpose of this study was the detection and quantification of BNN27 after single intraperitoneal administration, in the serum and retina of normal rodents. Forty-two C57BL/6 mice and 48 Sprague-Dawley rats were used for the quantification of BNN27 in the blood serum and retina, respectively. BNN27 was injected intraperitoneally (i.p.) at concentrations of 100 and 30 mg/kg of body weight (b.w.), respectively. The blood was collected with retro-orbital bleeding and the retina was isolated after enucleation at various time points. The molecule concentrations were measured with Liquid chromatography-mass spectrometry (LC-MS). Non-compartmental analysis was used to determine pharmacokinetic parameters. BNN27 was found to have an elimination constant kel  = 0.465 h-1 and mean residence time (MRT) 2.154 h in the mouse serum. The maximum concentration (Cmax ) in the retina was detected at 2 h ( tCmax ) after intraperitoneal administration and was equal to 1100 ng/g. BNN27 is rapidly eliminated from both blood and retina. In the retina specifically, it is undetectable 6 h after injection. BNN27 shows a rapid systemic elimination as anticipated by its small size and lipophilicity. It is measurable in small peripheral tissues such as the rat retina, after one single i.p. injection, using a simple method such as LC-MS. Its detection in the retina corroborates the existing biological data that the molecule crosses the blood-retinal barrier, highlighting it as a potential neuroprotective agent for retinal disease.