Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a behavioral disorder affecting 3-5% of children. Although ADHD is highly heritable, environmental factors like exposure during early development to various toxic substances like polychlorinated biphenyls (PCBs) may contribute to the prevalence. PCBs are a group of chemical industrial compounds with adverse effects on neurobiological and cognitive functioning, and may produce behavioral impairments that share significant similarities with ADHD. The present study examined the relation between exposure to PCB 153 and changes in ADHD-like behavior in an animal model of ADHD, the spontaneously hypertensive rats (SHR/NCrl), and in Wistar Kyoto (WKY/NHsd) controls. Methods SHR/NCrl and WKY/NHsd, males and females, were orally given PCB 153 dissolved in corn oil at around postnatal day (PND) 8, 14, and 20 at a dosage of 1, 3 or 6 mg/kg bodyweight at each exposure. The control groups were orally administered corn oil only. The animals were behaviorally tested for exposure effects from PND 37 to 64 using an operant procedure. Results Exposure to PCB 153 was associated with pronounced and long-lasting behavioral changes in SHR/NCrl. Exposure effects in the SHR/NCrl depended on dose, where 1 mg/kg tended to reduce ADHD-like behaviors and produce opposite behavioral effects compared to 3 mg/kg and 6 mg/kg, especially in the females. In the WKY/NHsd controls and for the three doses tested, PCB 153 exposure produced a few specific behavioral changes only in males. The data suggest that PCB 153 exposure interacts with strain and sex, and also indicate a non-linear dose–response relation for the behaviors observed. Conclusions Exposure to PCB 153 seems to interact with several variables including strain, sex, dose, and time of testing. To the extent that the present findings can be generalized to humans, exposure effects of PCB 153 on ADHD behavior depends on amount of exposure, where high doses may aggravate ADHD symptoms in genetically vulnerable individuals. In normal controls, exposure may not constitute an environmental risk factor for developing the full range of ADHD symptoms, but can produce specific behavioral changes

Collection and sharing of medical information and medical intelligence (M2I) in NATO: a transversal survey.

International audienceINTRODUCTION:There is a requirement for adequate medical expertise to be available throughout the range of potential future operations involving members of the North Atlantic Treaty Organization (NATO). The aim of this study was to assess the collection and sharing of medical intelligence and medical information (M2I) by NATO Nations, Partner Nations and NATO Command Structure and NATO Force Structure Headquarters (NCS/NFS HQs).MATERIALS AND METHODS:A transversal survey was conducted between December 2014 and March 2015 using a survey form on M2I sent to NATO Nations and Partnership for Peace (PfP) Nations as well as NCS/NFS HQs.RESULTS:Correctly completed responses were received from 15/40 (37.5%) of the possible NATO and PfP Nations (37.5%) and 7/8 (87.5%) of the NCS/NFS HQs (100.0%). Deficiencies in the collection of M2I data were found due to lack of specific doctrines, networks, tools, structures and organisation.CONCLUSIONS:The survey provided an indication even though the participation rate was low for Nations. Part of the problem is thought to be that medical information and medical intelligence often lie in different chains of command. Future directions for this research could include studying the possibilities of a new specific information technology (IT) system to collect and to share M2I. Collection and sharing of M2I within the NATO/PfP community requires facilitation in order to strengthen the basis for decision-making and force health protection. The development of a dedicated NATO IT system may be a precondition for the implementation of an efficient M2I network

Postnatal exposure to PCB 153 and PCB 180, but not to PCB 52, produces changes in activity level and stimulus control in outbred male Wistar Kyoto rats

Abstract Background Polychlorinated biphenyls (PCBs) are a class of organic compounds that bioaccumulate due to their chemical stability and lipophilic properties. Humans are prenatally exposed via trans-placental transfer, through breast milk as infants, and through fish, seafood and fatty foods as adolescents and adults. Exposure has several reported effects ranging from developmental abnormalities to cognitive and motor deficiencies. In the present study, three experimental groups of rats were orally exposed to PCBs typically found in human breast milk and then behaviorally tested for changes in measures of stimulus control (percentage lever-presses on the reinforcer-producing lever), activity level (responses with IRTs > 0.67 s), and responses with short IRTs ( Methods Male offspring from Wistar Kyoto (WKY/NTac) dams purchased pregnant from Taconic Farms (Germantown, NY) were orally given PCB at around postnatal day 8, 14, and 20 at a dose of 10 mg/kg body weight at each exposure. Three experimental groups were exposed either to PCB 52, PCB 153, or PCB 180. A fourth group fed corn oil only served as controls. From postnatal day 25, for 33 days, the animals were tested for behavioral changes using an operant procedure. Results PCB exposure did not produce behavioral changes during training when responding was frequently reinforced using a variable interval 3 s schedule. When correct responses were reinforced on a variable interval 180 s schedule, animals exposed to PCB 153 or PCB 180 were less active than controls and animals exposed to PCB 52. Stimulus control was better in animals exposed to PCB 180 than in controls and in the PCB 52 group. Also, the PCB 153 and PCB 180 groups had fewer responses with short IRTs than the PCB 52 group. No effects of exposure to PCB 52 were found when compared to controls. Conclusions Exposure to PCBs 153 and 180 produced hypoactivity that continued at least five weeks after the last exposure. No effects of exposure to PCB 52 were observed.</p

MOF thin films with bi-aromatic linkers grown by molecular layer deposition

Thin films of metal–organic frameworks (MOFs) are promising for a wide range of applications including membranes for separations and sensor materials in microelectronics. Growth of such thin films using atomic/molecular layer deposition (ALD/MLD) has recently been demonstrated; however, the range of examples is still narrow. Here, we expand the repertory of gas-phase MOF thin film synthesis by ALD/MLD to include 2,6-naphthalenedicarboxylate (2,6-NDC) and biphenyl-4,4′-dicarboxylate (BP-4,4′-DC) as organic linkers. The films, which were deposited using ZrCl4 and either H2–2,6-NDC or H2–BP-4,4′-DC, were amorphous and formed crystalline MOF-structures when treated with acetic acid vapour at 160 °C. The film growth was investigated using in situ quartz crystal microbalance (QCM) measurements, and was in addition characterized using spectroscopic ellipsometry (SE), photoluminescence (PL), scanning electron microscopy (SEM), grazing incidence X-ray diffraction (GIXRD) and X-ray reflectivity (XRR). We further performed introductory investigations into a selection of possible future applications of these films, due to their porosity, luminescent and antibacterial properties. Expanding the repertory of MOF synthesis by ALD/MLD to include longer linkers such as 2,6-NDC and BP-4,4′-DC enables synthesis of thin films with a larger range of pore sizes

Postnatal exposure to PCB 153 and PCB 180, but not to PCB 52, produces changes in measures of attention, activity level and impulsivity in outbred male Wistar Kyoto rats

Background: Polychlorinated biphenyls (PCBs) are a class of organic compounds that bioaccumulate due to their chemical stability and lipophilic properties. Humans are prenatally exposed via trans-placental transfer, through breast milk as infants, and through fish, seafood and fatty foods as adolescents and adults. Exposure has several reported effects ranging from developmental abnormalities to cognitive and motor deficiencies. In the present study, three experimental groups of rats were orally exposed to PCBs typically found in human breast milk and then behaviorally tested for changes in measures of stimulus control (percentage lever-presses on the reinforcer- producing lever), activity level (responses with IRTs > 0.67 s), and responses with short IRTs (< 0.67 s). Methods: Male offspring from Wistar Kyoto (WKY/NTac) dams purchased pregnant from Taconic Farms (Germantown, NY) were orally given PCB at around postnatal day 8, 14, and 20 at a dose of 10 mg/kg body weight at each exposure. Three experimental groups were exposed either to PCB 52, PCB 153, or PCB 180. A fourth group fed corn oil only served as controls. From postnatal day 25, for 33 days, the animals were tested for behavioral changes using an operant procedure. Results: PCB exposure did not produce behavioral changes during training when responding was frequently reinforced using a variable interval 3 s schedule. When correct responses were reinforced on a variable interval 180 s schedule, animals exposed to PCB 153 or PCB 180 were less active than controls and animals exposed to PCB 52. Stimulus control was better in animals exposed to PCB 180 than in controls and in the PCB 52 group. Also, the PCB 153 and PCB 180 groups had fewer responses with short IRTs than the PCB 52 group. No effects of exposure to PCB 52 were found when compared to controls. Conclusions: Exposure to PCBs 153 and 180 produced hypoactivity that continued at least five weeks after the last exposure. No effects of exposure to PCB 52 were observed

Postnatal exposure to PCB 153 and PCB 180, but not to PCB 52, produces changes in measures of attention, activity level and impulsivity in outbred male Wistar Kyoto rats

Background: Polychlorinated biphenyls (PCBs) are a class of organic compounds that bioaccumulate due to their chemical stability and lipophilic properties. Humans are prenatally exposed via trans-placental transfer, through breast milk as infants, and through fish, seafood and fatty foods as adolescents and adults. Exposure has several reported effects ranging from developmental abnormalities to cognitive and motor deficiencies. In the present study, three experimental groups of rats were orally exposed to PCBs typically found in human breast milk and then behaviorally tested for changes in measures of stimulus control (percentage lever-presses on the reinforcer-producing lever), activity level (responses with IRTs > 0.67 s), and responses with short IRTs (< 0.67 s). Methods: Male offspring from Wistar Kyoto (WKY/NTac) dams purchased pregnant from Taconic Farms (Germantown, NY) were orally given PCB at around postnatal day 8, 14, and 20 at a dose of 10 mg/kg body weight at each exposure. Three experimental groups were exposed either to PCB 52, PCB 153, or PCB 180. A fourth group fed corn oil only served as controls. From postnatal day 25, for 33 days, the animals were tested for behavioral changes using an operant procedure. Results: PCB exposure did not produce behavioral changes during training when responding was frequently reinforced using a variable interval 3 s schedule. When correct responses were reinforced on a variable interval 180 s schedule, animals exposed to PCB 153 or PCB 180 were less active than controls and animals exposed to PCB 52. Stimulus control was better in animals exposed to PCB 180 than in controls and in the PCB 52 group. Also, the PCB 153 and PCB 180 groups had fewer responses with short IRTs than the PCB 52 group. No effects of exposure to PCB 52 were found when compared to controls. Conclusions: Exposure to PCBs 153 and 180 produced hypoactivity that continued at least five weeks after the last exposure. No effects of exposure to PCB 52 were observed

Short-term treatment with a peroxisome proliferator-activated receptor α agonist influences plasma one-carbon metabolites and B-vitamin status in rats

Introduction: Peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of one-carbon metabolism. Previously we have reported effects on plasma concentrations of metabolites along these pathways as well as markers of B-vitamin status in rats following treatment with a pan-PPAR agonist. Here we aimed to investigate the effect on these metabolites after specific activation of the PPARα and PPARγ subtypes. Methods: For a period of 12 days, Male Wistar rats (n = 20) were randomly allocated to receive treatment with the PPARα agonist WY-14.643 (n = 6), the PPARγ agonist rosiglitazone (n = 6) or placebo (n = 8). The animals were sacrificed under fasting conditions, and plasma concentration of metabolites were determined. Group differences were assessed by one-way ANOVA, and planned comparisons were performed for both active treatment groups towards the control group. Results: Treatment with a PPARα agonist was associated with increased plasma concentrations of most biomarkers, with the most pronounced differences observed for betaine, dimethylglycine, glycine, nicotinamide, methylnicotinamide, pyridoxal and methylmalonic acid. Lower levels were observed for flavin mononucleotide. Fewer associations were observed after treatment with a PPARγ agonist, and the most notable was increased plasma serine. Conclusion: Treatment with a PPARα agonist influenced plasma concentration of one-carbon metabolites and markers of B-vitamin status. This confirms previous findings, suggesting specific involvement of PPARα in the regulation of these metabolic pathways as well as the status of closely related B-vitamins

Short-term treatment with a peroxisome proliferator-activated receptor α agonist influences plasma one-carbon metabolites and B-vitamin status in rats

Introduction: Peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of one-carbon metabolism. Previously we have reported effects on plasma concentrations of metabolites along these pathways as well as markers of B-vitamin status in rats following treatment with a pan-PPAR agonist. Here we aimed to investigate the effect on these metabolites after specific activation of the PPARα and PPARγ subtypes. Methods: For a period of 12 days, Male Wistar rats (n = 20) were randomly allocated to receive treatment with the PPARα agonist WY-14.643 (n = 6), the PPARγ agonist rosiglitazone (n = 6) or placebo (n = 8). The animals were sacrificed under fasting conditions, and plasma concentration of metabolites were determined. Group differences were assessed by one-way ANOVA, and planned comparisons were performed for both active treatment groups towards the control group. Results: Treatment with a PPARα agonist was associated with increased plasma concentrations of most biomarkers, with the most pronounced differences observed for betaine, dimethylglycine, glycine, nicotinamide, methylnicotinamide, pyridoxal and methylmalonic acid. Lower levels were observed for flavin mononucleotide. Fewer associations were observed after treatment with a PPARγ agonist, and the most notable was increased plasma serine. Conclusion: Treatment with a PPARα agonist influenced plasma concentration of one-carbon metabolites and markers of B-vitamin status. This confirms previous findings, suggesting specific involvement of PPARα in the regulation of these metabolic pathways as well as the status of closely related B-vitamins