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Sample records for adverse neurobehavioral effects

  1. Neurobehavioral effects of developmental methylmercury exposure

    SciTech Connect

    Gilbert, S.G.; Grant-Webster, K.S.

    1995-09-01

    Methylmercury (MeHg) is a global environmental problem and is listed by the International Program of Chemical Safety as one of the six most dangerous chemicals in the world`s environment. Human exposure to MeHg primarily occurs through the consumption of contaminated food such as fish, although catastrophic exposures due to industrial pollution have occurred. The fetus is particularly sensitive to MeHg exposure and adverse effects on infant development have been associated with levels of exposure that result in few, if any, signs of maternal clinical illness or toxicity. High levels of prenatal exposure in humans result in neurobehavioral effects such as cerebral palsy and severe mental retardation. Prenatal exposure to MeHg in communities with chronic low-level exposure is related to decreased birthweight and early sensorimotor dysfunction such as delayed onset of walking. Neurobehavioral alterations have also been documented in studies with non human primates and rodents. Available information on the developmental neurotoxic effects of MeHg, particularly the neurobehavioral effects, indicates that the fetus and infant are more sensitive to adverse effects of MEHg. It is therefore recommended that pregnant women and women of childbearing age be strongly advised to limit their exposure to potential sources of MeHg. Based on results from human and animal studies on the developmental neurotoxic effects of methylmercury, the accepted reference dose should be lowered to 0.025 to 0.06 MeHg {mu}g/kg/day. Continued research on the neurotoxic effects associated with low level developmental exposure is needed. 107 refs., 3 tabs.

  2. Neurobehavioral effects of aspartame consumption.

    PubMed

    Lindseth, Glenda N; Coolahan, Sonya E; Petros, Thomas V; Lindseth, Paul D

    2014-06-01

    Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40-50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health.

  3. Neurobehavioral effects of environmental tobacco smoke

    SciTech Connect

    Benignus, V.A.

    1987-05-01

    In order to try to predict effects of environmental tobacco smoke, neurobehavioral effects of mainstream smoke were reviewed and, in conjunction with what is known about body uptake of components of environmental tobacco smoke, conjectures were made about the probable effect of environmental tobacco smoke. Effects of mainstream smoke differ in smokers and nonsmokers. Mainstream smoke has a beneficial effect on vigilance in habitual smokers. The effect in nonsmokers is less clear and may be disruptive. In both smokers and nonsmokers mainstream smoke produces increased tremor and reduced fine motor skills. The neurobehaviorally active substances in mainstream smoke appear to be nicotine and carbon monoxide. It appears that COHb is the more important consequence of environmental tobacco smoke for neurobehavioral effects, since nicotine levels in nonsmokers only reach a small fraction of those in smokers.

  4. Examining the Relationships Between Prenatal Methamphetamine Exposure, Early Adversity, and Child Neurobehavioral Disinhibition

    PubMed Central

    Abar, Beau; LaGasse, Linda L.; Newman, Elana; Smith, Lynne M; Huestis, Marilyn; Neal, Charles; DeRauf, Chris; Shah, Rizwan; Arria, Amelia; Grotta, Sheri Della; Dansereau, Lynne M.; Lester, Barry M.

    2013-01-01

    Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother–infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed. PMID:23067308

  5. Examining the relationships between prenatal methamphetamine exposure, early adversity, and child neurobehavioral disinhibition.

    PubMed

    Abar, Beau; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Smith, Lynne M; Arria, Amelia; Huestis, Marilyn; Della Grotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

    2013-09-01

    Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother-infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed. PMID:23067308

  6. Modification of neurobehavioral effects of mercury by genetic polymorphisms of metallothionein in children.

    PubMed

    Woods, James S; Heyer, Nicholas J; Russo, Joan E; Martin, Michael D; Pillai, Pradeep B; Farin, Federico M

    2013-01-01

    Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that genetic variants of metallothionein (MT) that are reported to affect Hg toxicokinetics in adults would modify the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary Hg levels. Following the completion of the clinical trial, we performed genotyping assays for variants of MT isoforms MT1M (rs2270837) and MT2A (rs10636) on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between allelic status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant interactions or independent main effects for Hg exposure and either of the MT gene variants were observed. In contrast, among boys, numerous significant interaction effects between variants of MT1M and MT2A, alone and combined, with Hg exposure were observed spanning multiple domains of neurobehavioral function. All dose-response associations between Hg exposure and test performance were restricted to boys and were in the direction of impaired performance. These findings suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children with relatively common genetic variants of MT, and may have important public health implications for future strategies aimed at protecting children and adolescents from the potential health risks associated with Hg exposure. We note that because urinary Hg reflects a composite exposure index that cannot be attributed to a specific

  7. [Effects of electromagnetic radiation from handsets of cellular telephone on neurobehavioral function].

    PubMed

    Cao, Z; Liu, J; Li, S; Zhao, X

    2000-03-30

    In order to study the effects of electromagnetic radiation from handsets of cellular telephone on neurobehavioral function, 81 staff with handsets of cellular telephone and 63 staff without handsets of cellular telephone from corporations were selected as the subjects. The subjects were investigated by questionnaire on their general health, lifestyle habit, suppress of spirit, handset using of cellular telephone, environmental exposure, morbidity, and the neurobehavioral core test battery(NCTB). The data was analyzed by chi-square, stepwise regression analysis and covariance statistics. The results showed that the average reaction time in user's group was longer than that in control group (P < 0.01). The time of using handset was negatively associated with corrected reaction number (P < 0.01). The fast reaction time and the slowest reaction time were positively associated with the length of handset using (P < 0.01, P < 0.05). The results suggested that the handset using could cause adverse health effects in neurobehavioral function.

  8. Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior

    PubMed Central

    Levoe, S. Nikki; Flannery, Brenna M.; Brignolo, Laurie; Imai, Denise M.; Koehne, Amanda; Austin, Adam T.; Bruun, Donald A.; Tancredi, Daniel J.; Lein, Pamela J.

    2015-01-01

    Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory. PMID:25705100

  9. Neurobehavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6.

    PubMed

    Liu, W F; Shih, J H

    1990-01-01

    A series of neurobehavioral testing procedures was used to evaluate the behavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6 in male Sprague-Dawley rats. These procedures were fixed-ratio (FR) responding, shuttle-box conditioned avoidance response (CAR), conditioned taste aversion (CTA), drinking behavior, open-field exploratory behavior, negative geotaxis, and wire suspension time. Dose-response studies of HI-6 at dose-levels of 25, 50 and 100 mg/kg, or saline (IP) were evaluated. HI-6 disrupted FR responding in a dose-dependent fashion, with significant effects occurring at doses of 50 and 100 mg/kg. The pattern of disruption was characterized by extended periods of nonresponding having an abrupt onset and offset. HI-6 produced CTA in a dose-related manner, with significant effects at doses equal to those that disrupted FR performance. HI-6 did not alter CAR, drinking motivation, exploratory behavior, negative geotaxis, or wire suspension time. These data suggest that there may be a commonality in the underlying mechanism(s) for the disruption in FR performance and the induction of the CTA. This mechanism may relate to the presumed drug-induced adverse internal state inducing the CTA.

  10. NEUROBEHAVIORAL EFFECTS OF EXPOSURE TO ENVIRONMENTAL POLLUTANTS IN CZECH CHILDREN

    EPA Science Inventory

    Ambient levels of SO2, NOx, PAHs and heavy metals are elevated in Northern Bohemia as a result of intensive mining and combustion of brown coal. To assess the neurotoxicological effects of exposure to these chemicals, tests from the Neurobehavioral Evaluation System (NES2) we...

  11. Effects of methanol vapor on human neurobehavioral measures.

    PubMed

    Cook, M R; Bergman, F J; Cohen, H D; Gerkovich, M M; Graham, C; Harris, R K; Siemann, L G

    1991-08-01

    Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three-choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand

  12. Mindfulness Training among Individuals with Parkinson's Disease: Neurobehavioral Effects.

    PubMed

    Pickut, Barbara; Vanneste, Sven; Hirsch, Mark A; Van Hecke, Wim; Kerckhofs, Eric; Mariën, Peter; Parizel, Paul M; Crosiers, David; Cras, Patrick

    2015-01-01

    Objective. To investigate possible neurobehavioral changes secondary to a mindfulness based intervention (MBI) training for individuals living with Parkinson's disease (PD). Background. In the context of complementary medicine, MBIs are increasingly being used for stress reduction and in patient populations coping with chronic illness. The use of alternative and complementary medicine may be higher in patients with chronic conditions such as PD. However, behavioral effects of mindfulness training in PD have not yet been reported in the literature and this points to an unmet need and warrants further examination. Methods. A total of 27 out of 30 PD patients completed a randomized controlled longitudinal trial. Questionnaires and the UPDRS I-IV were obtained at baseline and 8-week follow-up. Results. Significant changes after the MBI were found including a 5.5 point decrease on the UPDRS motor score, an increase of 0.79 points on Parkinson's disease questionnaire (PDQ-39) pain item, and a 3.15 point increase in the Five Facet Mindfulness Questionnaire observe facet. Conclusions. To the best of our knowledge, this is the first quantitative analysis of neurobehavioral effects of MBI in PD. PMID:26101690

  13. Mindfulness Training among Individuals with Parkinson's Disease: Neurobehavioral Effects

    PubMed Central

    Pickut, Barbara; Hirsch, Mark A.; Van Hecke, Wim; Mariën, Peter; Parizel, Paul M.; Crosiers, David; Cras, Patrick

    2015-01-01

    Objective. To investigate possible neurobehavioral changes secondary to a mindfulness based intervention (MBI) training for individuals living with Parkinson's disease (PD). Background. In the context of complementary medicine, MBIs are increasingly being used for stress reduction and in patient populations coping with chronic illness. The use of alternative and complementary medicine may be higher in patients with chronic conditions such as PD. However, behavioral effects of mindfulness training in PD have not yet been reported in the literature and this points to an unmet need and warrants further examination. Methods. A total of 27 out of 30 PD patients completed a randomized controlled longitudinal trial. Questionnaires and the UPDRS I–IV were obtained at baseline and 8-week follow-up. Results. Significant changes after the MBI were found including a 5.5 point decrease on the UPDRS motor score, an increase of 0.79 points on Parkinson's disease questionnaire (PDQ-39) pain item, and a 3.15 point increase in the Five Facet Mindfulness Questionnaire observe facet. Conclusions. To the best of our knowledge, this is the first quantitative analysis of neurobehavioral effects of MBI in PD. PMID:26101690

  14. Mindfulness Training among Individuals with Parkinson's Disease: Neurobehavioral Effects.

    PubMed

    Pickut, Barbara; Vanneste, Sven; Hirsch, Mark A; Van Hecke, Wim; Kerckhofs, Eric; Mariën, Peter; Parizel, Paul M; Crosiers, David; Cras, Patrick

    2015-01-01

    Objective. To investigate possible neurobehavioral changes secondary to a mindfulness based intervention (MBI) training for individuals living with Parkinson's disease (PD). Background. In the context of complementary medicine, MBIs are increasingly being used for stress reduction and in patient populations coping with chronic illness. The use of alternative and complementary medicine may be higher in patients with chronic conditions such as PD. However, behavioral effects of mindfulness training in PD have not yet been reported in the literature and this points to an unmet need and warrants further examination. Methods. A total of 27 out of 30 PD patients completed a randomized controlled longitudinal trial. Questionnaires and the UPDRS I-IV were obtained at baseline and 8-week follow-up. Results. Significant changes after the MBI were found including a 5.5 point decrease on the UPDRS motor score, an increase of 0.79 points on Parkinson's disease questionnaire (PDQ-39) pain item, and a 3.15 point increase in the Five Facet Mindfulness Questionnaire observe facet. Conclusions. To the best of our knowledge, this is the first quantitative analysis of neurobehavioral effects of MBI in PD.

  15. Neurobehavioral and neurochemical effects of prenatal ethanol administration in rats

    SciTech Connect

    Pradhan, S.; Briggs, F. )

    1992-01-01

    Effects of prenatal ethanol exposure in rats on the behavior and on the levels of multiple neurotransmitters in the brain have been investigated. Timed pregnant Sprague-Dawley rats were divided into three groups: ethanol-exposed, pair-fed control and nutritional control. Ethanol was administered through Leiber-DeCarli liquid diet containing 6% ethanol (v/v) throughout the gestation period in ethanol-exposed rats. Male offspring were tested for alternations in neurobehavioral and neurochemical parameters. Animals exposed to ethanol in utero exhibited lower birth weights, delayed motor development, delayed learning and no catch-up growth, as well as significant alterations in levels of dopamine, norepinephrine, serotonin and GABA in discrete brain areas.

  16. Developmental Exposure to a Commercial PBDE mixture, DE·71: Neurobehavioral, Hormonal, and Reproductive Effects

    EPA Science Inventory

    Developmental effects of PBDEs have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial m...

  17. Neurobehavioral, Hormonal, and Reproductive Effects following Developmental Exposure to a Commercial PBDE Mixture, DE-71

    EPA Science Inventory

    Developmental effects caused by PBDEs have been suspected due to their chemically structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabromi...

  18. Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests

    NASA Astrophysics Data System (ADS)

    Hienz, Robert; Davis, Catherine; Weed, Michael; Guida, Peter; Gooden, Virginia; Brady, Joseph; Roma, Peter

    Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests INTRODUCTION Risk assessment of the biological consequences of living in the space radiation environment represents one of the highest priority areas of NASA radiation research. Of critical importance is the need for a risk assessment of damage to the central nervous system (CNS) leading to functional cognitive/behavioral changes during long-term space missions, and the development of effective shielding or biological countermeasures to such risks. The present research focuses on the use of an animal model that employs neurobehavioral tests identical or homologous to those currently in use in human models of risk assessment by U.S. agencies such as the Depart-ment of Defense and Federal Aviation and Federal Railroad Administrations for monitoring performance and estimating accident risks associated with such variables as fatigue and/or alcohol or drug abuse. As a first approximation for establishing human risk assessments due to exposure to space radiation, the present work provides animal performance data obtained with the rPVT (rat Psychomotor Vigilance Test), an animal analog of the human PVT that is currently employed for human risk assessments via quantification of sustained attention (e.g., 'vigilance' or 'readiness to perform' tasks). Ground-based studies indicate that radiation can induce neurobehavioral changes in rodents, including impaired performance on motor tasks and deficits in spatial learning and memory. The present study is testing the hypothesis that radiation exposure impairs motor function, performance accuracy, vigilance, motivation, and memory in adult male rats. METHODS The psychomotor vigilance test (PVT) was originally developed as a human cognitive neurobe-havioral assay for tracking the temporally dynamic changes in sustained attention, and has also been used to track changes in circadian rhythm. In humans the test requires responding to a small, bright

  19. Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests

    NASA Astrophysics Data System (ADS)

    Hienz, Robert; Davis, Catherine; Weed, Michael; Guida, Peter; Gooden, Virginia; Brady, Joseph; Roma, Peter

    Neurobehavioral Effects of Space Radiation on Psychomotor Vigilance Tests INTRODUCTION Risk assessment of the biological consequences of living in the space radiation environment represents one of the highest priority areas of NASA radiation research. Of critical importance is the need for a risk assessment of damage to the central nervous system (CNS) leading to functional cognitive/behavioral changes during long-term space missions, and the development of effective shielding or biological countermeasures to such risks. The present research focuses on the use of an animal model that employs neurobehavioral tests identical or homologous to those currently in use in human models of risk assessment by U.S. agencies such as the Depart-ment of Defense and Federal Aviation and Federal Railroad Administrations for monitoring performance and estimating accident risks associated with such variables as fatigue and/or alcohol or drug abuse. As a first approximation for establishing human risk assessments due to exposure to space radiation, the present work provides animal performance data obtained with the rPVT (rat Psychomotor Vigilance Test), an animal analog of the human PVT that is currently employed for human risk assessments via quantification of sustained attention (e.g., 'vigilance' or 'readiness to perform' tasks). Ground-based studies indicate that radiation can induce neurobehavioral changes in rodents, including impaired performance on motor tasks and deficits in spatial learning and memory. The present study is testing the hypothesis that radiation exposure impairs motor function, performance accuracy, vigilance, motivation, and memory in adult male rats. METHODS The psychomotor vigilance test (PVT) was originally developed as a human cognitive neurobe-havioral assay for tracking the temporally dynamic changes in sustained attention, and has also been used to track changes in circadian rhythm. In humans the test requires responding to a small, bright

  20. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  1. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  2. Neurobehavioral effects among subjects exposed to high static and gradient magnetic fields from a 1.5 Tesla magnetic resonance imaging system--a case-crossover pilot study.

    PubMed

    de Vocht, Frank; van-Wendel-de-Joode, Berna; Engels, Hans; Kromhout, Hans

    2003-10-01

    The interactive use of magnetic resonance imaging (MRI) techniques is increasing in operating theaters. A study was performed on 17 male company volunteers to assess the neurobehavioral effects of exposure to magnetic fields from a 1.5 Tesla MRI system. The subjects' neurobehavioral performances on a neurobehavioral test battery were compared in four 1-hr sessions with and without exposure to magnetic fields, and with and without additional movements. Adverse effects were found for hand coordination (-4%, P < 0.05; Pursuit Aiming II) and near visual contrast sensitivity (-16% and -15%, P < 0.10; Vistech 6000). The results from the remaining tests were inconclusive due to a strong learning effect. No additional effect from gradient fields was detected. The results indicate that working near a 1.5 Tesla MRI system may lead to neurobehavioral effects. Further research is recommended, especially in members of operating teams using interactive MRI systems.

  3. Reproductive and neurobehavioral effects of amaranth administered to mice in drinking water.

    PubMed

    Tanaka, T

    1993-01-01

    The color additive amaranth was given in the drinking water at levels of 0 (control), 0.025, 0.075, and 0.225% from 5 weeks of age in F0 generation until F1 generation mice were weaned, with selected reproductive, developmental and behavioral parameters being measured. Amaranth had little adverse effect upon litter size, litter weight and sex ratio. Average body weight in both sexes of the F1 mice was significantly increased in the 0.025% group in both sexes. Survival index at postnatal day (PND) 21 was reduced in the 0.025% amaranth group. For the neurobehavioral parameters, surface righting at PND 4 in female offspring and olfactory orientation in both sexes were significantly affected by treatment. Several parameters of movement activity of male offspring at 3 weeks of age were affected in amaranth 0.075% group, but those of female offspring were similar in all groups. The dose levels of amaranth in this study produced a little adverse effect on behavioral development in mice.

  4. Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia

    SciTech Connect

    Vibol, Sao; Hashim, Jamal Hisham; Sarmani, Sukiman

    2015-02-15

    contaminated study site, showed clear evidence of neurobehavioral effects. - Highlights: • We measured the level of arsenic concentration in school secondary school children's hair. • As contamination in groundwater is the major source effect on the neurobehavioral performance of school children. • School children in highly and moderately contaminated sites are at risk of As exposure.

  5. Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia.

    PubMed

    Vibol, Sao; Hashim, Jamal Hisham; Sarmani, Sukiman

    2015-02-01

    site, showed clear evidence of neurobehavioral effects.

  6. COMPARISON OF ACUTE NEUROBEHAVIORAL EFFECTS OF N-METHYL CARBAMATE INSECTICIDES.

    EPA Science Inventory

    The acute neurobehavioral and cholinesterase (ChE)-inhibiting effects of N-methyl carbamate insecticides have not been systematically compared. We evaluated five carbamates - carbaryl (CB), propoxur (PP), oxamyl (OM), methomyl (MM), and methiocarb (MC). Adult male Long-Evans ra...

  7. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

    PubMed

    Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2016-10-01

    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m(2)), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. PMID:27448086

  8. Long-term neurobehavioral health effects of methyl parathion exposure in children in Mississippi and Ohio.

    PubMed

    Ruckart, Perri Zeitz; Kakolewski, Kirsten; Bove, Frank J; Kaye, Wendy E

    2004-01-01

    Methyl parathion (MP), an organophosphate pesticide licensed only for agricultural uses, was sprayed illegally for pest control in Mississippi and Ohio residences. To evaluate the association between MP exposure and neurobehavioral development, we assessed children 6 years or younger at the time of the spraying and local comparison groups of unexposed children using the Pediatric Environmental Neurobehavioral Test Battery (PENTB). The PENTB is composed of informant-based procedures (parent interview and questionnaires) and performance-based procedures (neurobehavioral tests for children 4 years or older) that evaluate cognitive, motor, sensory, and affect domains essential to neurobehavioral assessment. Children were classified as exposed or unexposed on the basis of urinary para-nitrophenol levels and environmental wipe samples for MP. Exposed children had more difficulties with tasks involving short-term memory and attention. Additionally, parents of exposed children reported that their children had more behavioral and motor skill problems than did parents of unexposed children. However, these effects were not consistently seen at both sites. There were no differences between exposed and unexposed children in tests for general intelligence, the integration of visual and motor skills, and multistep processing. Our findings suggest that MP might be associated with subtle changes to short-term memory and attention and contribute to problems with motor skills and some behaviors, but the results of the study are not conclusive.

  9. Long-term neurobehavioral health effects of methyl parathion exposure in children in Mississippi and Ohio.

    PubMed Central

    Ruckart, Perri Zeitz; Kakolewski, Kirsten; Bove, Frank J; Kaye, Wendy E

    2004-01-01

    Methyl parathion (MP), an organophosphate pesticide licensed only for agricultural uses, was sprayed illegally for pest control in Mississippi and Ohio residences. To evaluate the association between MP exposure and neurobehavioral development, we assessed children 6 years or younger at the time of the spraying and local comparison groups of unexposed children using the Pediatric Environmental Neurobehavioral Test Battery (PENTB). The PENTB is composed of informant-based procedures (parent interview and questionnaires) and performance-based procedures (neurobehavioral tests for children 4 years or older) that evaluate cognitive, motor, sensory, and affect domains essential to neurobehavioral assessment. Children were classified as exposed or unexposed on the basis of urinary para-nitrophenol levels and environmental wipe samples for MP. Exposed children had more difficulties with tasks involving short-term memory and attention. Additionally, parents of exposed children reported that their children had more behavioral and motor skill problems than did parents of unexposed children. However, these effects were not consistently seen at both sites. There were no differences between exposed and unexposed children in tests for general intelligence, the integration of visual and motor skills, and multistep processing. Our findings suggest that MP might be associated with subtle changes to short-term memory and attention and contribute to problems with motor skills and some behaviors, but the results of the study are not conclusive. PMID:14698930

  10. A new mathematical model for the homeostatic effects of sleep loss on neurobehavioral performance

    PubMed Central

    McCauley, Peter; Kalachev, Leonid V.; Smith, Amber D.; Belenky, Gregory; Dinges, David F.; Van Dongen, Hans P.A.

    2009-01-01

    The two-process model of sleep regulation makes accurate predictions of sleep timing and duration for a variety of experimental sleep deprivation and nap sleep scenarios. Upon extending its application to waking neurobehavioral performance, however, the model fails to predict the effects of chronic sleep restriction. Here we show that the two-process model belongs to a broader class of models formulated in terms of coupled non-homogeneous first-order ordinary differential equations, which have a dynamic repertoire capturing waking neurobehavioral functions across a wide range of wake/sleep schedules. We examine a specific case of this new model class, and demonstrate the existence of a bifurcation: for daily amounts of wakefulness less than a critical threshold, neurobehavioral performance is predicted to converge to an asymptotically stable state of equilibrium; whereas for daily wakefulness extended beyond the critical threshold, neurobehavioral performance is predicted to diverge from an unstable state of equilibrium. Comparison of model simulations to laboratory observations of lapses of attention on a psychomotor vigilance test (PVT), in experiments on the effects of chronic sleep restriction and acute total sleep deprivation, suggests that this bifurcation is an essential feature of performance impairment due to sleep loss. We present three new predictions that may be experimentally verified to validate the model. These predictions, if confirmed, challenge conventional notions about the effects of sleep and sleep loss on neurobehavioral performance. The new model class implicates a biological system analogous to two connected compartments containing interacting compounds with time-varying concentrations as being a key mechanism for the regulation of psychomotor vigilance as a function of sleep loss. We suggest that the adenosinergic neuromodulator/receptor system may provide the underlying neurobiology. PMID:18938181

  11. Adverse effects of anabolic steroids.

    PubMed

    Hickson, R C; Ball, K L; Falduto, M T

    1989-01-01

    Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.

  12. The Effect of One Night's Sleep Deprivation on Adolescent Neurobehavioral Performance

    PubMed Central

    Louca, Mia; Short, Michelle A.

    2014-01-01

    Study Objectives: To investigate the effects of one night's sleep deprivation on neurobehavioral functioning in adolescents. Design: Participants completed a neurobehavioral test battery measuring sustained attention, reaction speed, cognitive processing speed, sleepiness, and fatigue every 2 h during wakefulness. Baseline performance (defined as those test bouts between 09:00 and 19:00 on days 2 and 3, following two 10-h sleep opportunities) were compared to performance at the same clock time the day following total sleep deprivation. Setting: The sleep laboratory at the Centre for Sleep Research. Participants: Twelve healthy adolescents (6 male), aged 14-18 years (mean = 16.17, standard deviation = 0.83). Measurements and Results: Sustained attention, reaction speed, cognitive processing speed, and subjective sleepiness were all significantly worse following one night without sleep than following 10-h sleep opportunities (all main effects of day, P < 0.05). Sleep deprivation led to increased variability on objective performance measures. There were between-subjects differences in response to sleep loss that were task-specific, suggesting that adolescents may not only vary in terms of the degree to which they are affected by sleep loss but also the domains in which they are affected. Conclusions: These findings suggest that one night of total sleep deprivation has significant deleterious effects upon neurobehavioral performance and subjective sleepiness. These factors impair daytime functioning in adolescents, leaving them at greater risk of poor academic and social functioning and accidents and injuries. Citation: Louca M, Short MA. The effect of one night's sleep deprivation on adolescent neurobehavioral performance. SLEEP 2014;37(11):1799-1807. PMID:25364075

  13. Building Zebrafish Neurobehavioral Phenomics: Effects of Common Environmental Factors on Anxiety and Locomotor Activity.

    PubMed

    Stewart, Adam Michael; Kaluyeva, Alexandra A; Poudel, Manoj K; Nguyen, Michael; Song, Cai; Kalueff, Allan V

    2015-10-01

    Zebrafish are emerging as an important model organism for neurobehavioral phenomics research. Given the likely variation of zebrafish behavioral phenotypes between and within laboratories, in this study, we examine the influence and variability of several common environmental modifiers on adult zebrafish anxiety and locomotor activity. Utilizing the novel tank paradigm, this study assessed the role of various laboratory factors, including experimenter/handling, testing time and days, batch, and the order of testing, on the behavior of a large population of experimentally naive control fish. Although time of the day, experimenter identity, and order of testing had little effect on zebrafish anxiety and locomotor activity levels, subtle differences were found for testing days and batches. Our study establishes how zebrafish behaviors are modulated by common environmental/laboratory factors and outlines several implications for zebrafish neurobehavioral phenomics research. PMID:26244595

  14. Building Zebrafish Neurobehavioral Phenomics: Effects of Common Environmental Factors on Anxiety and Locomotor Activity.

    PubMed

    Stewart, Adam Michael; Kaluyeva, Alexandra A; Poudel, Manoj K; Nguyen, Michael; Song, Cai; Kalueff, Allan V

    2015-10-01

    Zebrafish are emerging as an important model organism for neurobehavioral phenomics research. Given the likely variation of zebrafish behavioral phenotypes between and within laboratories, in this study, we examine the influence and variability of several common environmental modifiers on adult zebrafish anxiety and locomotor activity. Utilizing the novel tank paradigm, this study assessed the role of various laboratory factors, including experimenter/handling, testing time and days, batch, and the order of testing, on the behavior of a large population of experimentally naive control fish. Although time of the day, experimenter identity, and order of testing had little effect on zebrafish anxiety and locomotor activity levels, subtle differences were found for testing days and batches. Our study establishes how zebrafish behaviors are modulated by common environmental/laboratory factors and outlines several implications for zebrafish neurobehavioral phenomics research.

  15. Neurobehavioral effects of exposure to propionic acid revisited-Does psychosocial stress interfere with distractive effects in volunteers?

    PubMed

    Pacharra, Marlene; Schäper, Michael; Kleinbeck, Stefan; Blaszkewicz, Meinolf; Golka, Klaus; van Thriel, Christoph

    2016-07-01

    Local irritants stimulate the nervous system via chemosensory pathways that trigger cognitive distraction, subjective complaints about impaired health, and physiological defense reflexes (e.g. eye-blinks). At workplaces and in the environment chemical exposures often co-occur with psychosocial stress. This study investigated if stress modulates adverse effects of exposure to the local irritant and malodorant propionic acid (PA). Forty-eight participants were randomly assigned to an experimental (false negative feedback+salient surveillance) or control group. In a cross-over design, both groups were exposed for 4h to PA in concentrations of 0.3 and 0-20ppm (time-weighted average=10ppm). In the experimental group, the stress protocol induced moderate psychosocial stress as indicated by salivary cortisol and subjective responses. Despite concentration-dependent increases in chemosensory perceptions and symptoms, the level of exposure to PA had no impact upon the results of four out of six neurobehavioral tests. In the sustained attention test, there was a significant increase in error rates that corresponded to the exposure levels. However, a concentration-dependent impairment of spatial working memory and an adverse increase in eye-blink frequency were restricted to the control group. Stressed participants had shorter simple reaction times and high eye-blink frequency irrespective of exposure suggesting enhanced alertness. Psychosocial stress increased complaints, ocular irritation and unspecific symptoms at the end of the 0.3ppm exposure to a level that was comparable with that in the control group during exposure to 0-20ppm. Results indicate that the adverse effects of a local irritant and psychosocial stress are non-additive.

  16. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

  17. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  18. Comparison of neurobehavioral function in workers exposed to a mixture of organic and inorganic lead and in workers exposed to solvents.

    PubMed

    Bolla, K I; Schwartz, B S; Stewart, W; Rignani, J; Agnew, J; Ford, D P

    1995-02-01

    The neurobehavioral effects of lead (organic and inorganic) and organic solvents were compared in 386 U.S. workers (52 reference, 190 lead, and 144 solvent workers). The association between neurobehavioral test performance and duration of exposure to lead or solvents was also examined and compared. The neurobehavioral test battery consisted of examiner and computer-administered neurobehavioral tests, a test of olfactory function, and questionnaires that assessed neuropsychiatric symptoms. Adjusted mean differences on the neurobehavioral test scores were estimated by comparing the exposed group to the referent group using linear regression and adjusting for premorbid intellectual ability, age, and race. Both lead and solvents were associated with diminished neurobehavioral performance in all neurobehavioral areas tested. Specifically, while lead and solvent exposure had the same magnitude of adverse effects on tests of manual dexterity, lead exposure was associated with greater adverse effects on memory and learning tests but with less adverse effects on executive/motor tests and on a test of olfaction than solvent exposure. An elevated number of neuropsychiatric symptoms was reported by 7% of the referent group, 43% of the lead group, and 15% of the solvent group. For exposure duration of < or = 10 years, more neurobehavioral decrements were found in the solvent group relative to the lead group. However, for exposure duration of > or = 18 years, the lead group showed more decrements than the solvent group. Overall, these data suggest differences in neurobehavioral functioning between the lead (organic and inorganic) and solvent exposed workers examined in this study. PMID:7755013

  19. Late Dose-Response Effects of Prenatal Cocaine Exposure on Newborn Neurobehavioral Performance

    PubMed Central

    Tronick, Edward Z.; Frank, Deborah A.; Cabral, Howard; Mirochnick, Mark; Zuckerman, Barry

    2008-01-01

    Objective To determine in a representative sample of full-term urban newborns of English-speaking mothers whether an immediate or late dose-response effect could be demonstrated between prenatal cocaine exposure and newborn neurobehavioral performance, controlling for confounding factors. Methods The Neonatal Behavioral Assessment Scale (NBAS) was administered by masked examiners to a total sample of 251 clinically healthy, full-term infants at 2 days and/or 17 days. Three in utero cocaine exposure groups were defined: heavily exposed (n = 44, >75th percentile self-reported days of use during pregnancy and/or >75th percentile of meconium benzoylecognine concentration); lightly exposed (n = 79, less than both 75th percentiles); and unexposed (n = 101, no positive biological or self-report marker). At the 3-week examination there were 38 heavily exposed, 73 lightly exposed, and 94 unexposed infants. Controlling for infant birth weight, gestational age, infant age at the time of examination, mothers’ age, perinatal risk, obstetric medication, and alcohol, marijuana, and cigarette use, a regression analysis evaluated the effects of levels of cocaine exposure on NBAS performance. Results No neurobehavioral effects of exposure on the newborn NBAS cluster scores or on the qualifier scores were found when confounders were controlled for at 2 to 3 days of age. At 3 weeks, after controlling for covariates, a significant dose effect was observed, with heavily exposed infants showing poorer state regulation and greater excitability. Conclusions These findings demonstrate specific dose-related effects of cocaine on 3-week neurobehavioral performance, particularly for the regulation of arousal, which was not observed in the first few days of life. PMID:8668416

  20. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  1. Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects.

    SciTech Connect

    Kodavanti, Prasada; Coburn, Cary; Moser, Virginia; MacPhail, Robert; Fenton, Suzanne; Stoker, Tammy; Birnbaum, Linda

    2010-06-01

    Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.7, 10.2, or 30.6 mg/kg/day DE-71 in corn oil by oral gavage from gestational day 6 to weaning. DE-71 did not alter maternal or male offspring body weights. However, female offspring were smaller compared with controls from postnatal days (PNDs) 35-60. Although several neurobehavioral endpoints were assessed, the only statistically significant behavioral finding was a dose-by-age interaction in the number of rears in an open-field test. Developmental exposure to DE-71 caused severe hypothyroxinemia in the dams and early postnatal offspring. DE-71 also affected anogenital distance and preputial separation in male pups. Body weight gain over time, reproductive tissue weights, and serum testosterone concentrations at PND 60 were not altered. Mammary gland development of female offspring was significantly affected at PND 21. Congener-specific analysis of PBDEs indicated accumulation in all tissues examined. Highest PBDE concentrations were found in fat including milk, whereas blood had the lowest concentrations on a wet weight basis. PBDE concentrations were comparable among various brain regions. Thus, perinatal exposure to DE-71 leads to accumulation of PBDE congeners in various tissues crossing blood-placenta and blood-brain barriers, causing subtle changes in some parameters of neurobehavior and dramatic changes in circulating thyroid hormone levels, as well as changes in both male and female reproductive endpoints. Some of these effects are similar to those seen with PCBs, and the persistence of these changes requires further investigation.

  2. Early Life Trauma and Attachment: Immediate and Enduring Effects on Neurobehavioral and Stress Axis Development

    PubMed Central

    Rincón-Cortés, Millie; Sullivan, Regina M.

    2014-01-01

    Over half a century of converging clinical and animal research indicates that early life experiences induce enduring neuroplasticity of the HPA-axis and the developing brain. This experience-induced neuroplasticity is due to alterations in the frequency and intensity of stimulation of pups’ sensory systems (i.e., olfactory, somatosensory, gustatory) embedded in mother–infant interactions. This stimulation provides “hidden regulators” of pups’ behavioral, physiological, and neural responses that have both immediate and enduring consequences, including those involving the stress response. While variation in stimulation can produce individual differences and adaptive behaviors, pathological early life experiences can induce maladaptive behaviors, initiate a pathway to pathology, and increase risk for later-life psychopathologies, such as mood and affective disorders, suggesting that infant-attachment relationships program later-life neurobehavioral function. Recent evidence suggests that the effects of maternal presence or absence during this sensory stimulation provide a major modulatory role in neural and endocrine system responses, which have minimal impact on pups’ immediate neurobehavior but a robust impact on neurobehavioral development. This concept is reviewed here using two complementary rodent models of infant trauma within attachment: infant paired-odor-shock conditioning (mimicking maternal odor attachment learning) and rearing with an abusive mother that converge in producing a similar behavioral phenotype in later-life including depressive-like behavior as well as disrupted HPA-axis and amygdala function. The importance of maternal social presence on pups’ immediate and enduring brain and behavior suggests unique processing of sensory stimuli in early life that could provide insight into the development of novel strategies for prevention and therapeutic interventions for trauma experienced with the abusive caregiver. PMID:24711804

  3. Neurobehavioral effects of liraglutide and sitagliptin in experimental models.

    PubMed

    Kamble, Mayur; Gupta, Rachna; Rehan, Harmeet S; Gupta, Lalit K

    2016-03-01

    Glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors are two currently approved therapies for type 2 diabetes mellitus (T2DM). Present study evaluated the effect of liraglutide (a long-acting GLP-1 agonist) and sitagliptin (a DPP-4 inhibitor) on nociception, anxiety, depression-like behavior and cognition in rats or mice. Nociception was assessed using tail-flick test; anxiety-behavior in open-field test and elevated plus maze (EPM) test while depression-like behavior was evaluated in forced swim test (FST) and tail-suspension test (TST). Cognition was assessed in EPM and Morris water maze (MWM) following memory deficit induced by pentylenetetrazole (PTZ) or scopolamine. In tail-flick test sitagliptin (6 mg/kg) produced transient nociceptive effect. Liraglutide (200 µg/kg) reduced peripheral square crossings by rats in open field test as well as reduced closed arm entries in the EPM, indicating a decline in exploratory behavior. In FST and TST models for depression, the duration of immobility with sitagliptin (6 mg/kg) was reduced significantly in comparison to control group suggesting its antidepressant effect. Liraglutide did not show any antidepressant action. In EPM test for cognition, liraglutide and sitagliptin ameliorated the increase in transfer latency caused by PTZ in a dose-dependent manner. In MWM liraglutide and sitagliptin prevented the scopolamine-induced increase of the escape latency. This study shows that sitagliptin has mild antinociceptive effect and anti-depressant effect in the animal models of depression while liraglutide did not have such an effect. Liraglutide showed anxiogenic effects in the animal models. Both liraglutide and sitagliptin produced cognitive improvement in the animal models. PMID:26849938

  4. Effects of long-term etanercept treatment on anxiety- and depression-like neurobehaviors in rats.

    PubMed

    Bayramgürler, Dilek; Karson, Ayşe; Ozer, Cüneyt; Utkan, Tijen

    2013-07-01

    Growing evidence indicates that there is a correlation between depression and inflammation. Administration of anti-tumor necrosis factor (TNF) agents for treatment of chronic inflammatory diseases, such as psoriasis, was associated with decreased depressive symptoms and increased quality of life in some clinical studies. The aim of the present study was to investigate the effects of chronic etanercept, a TNF-α inhibitor, on anxiety- and depression-like neurobehaviors in rats. Male rats were treated for 8 weeks with either saline or etanercept (0.8 mg/kg/week, subcutaneously). The anxiety levels of rats were evaluated using the elevated plus maze, a classical rodent model of anxiety and depression was measured using the force swimming test, a behavioral despair task. The anxiety-like neurobehaviors of the animals were found significantly decreased after the etanercept treatment. Etanercept significantly decreased immobility time in rat model of despair test, seemed to have an antidepressive effect in rats. Compared to saline treatment, long-term etanercept treatment had no effect on the total number and pattern of locomotor activities. Findings of the study supported the hypothesis that TNF-α has a role in the modulation of emotional processes and its inhibition may represent a novel strategy for the treatment of affective disorders.

  5. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  6. Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures.

    PubMed

    Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

    2015-02-01

    The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2 and 15.0% O2), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

  7. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    PubMed

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS).

  8. The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.

    PubMed

    Tsai, Song-Yen; Chou, Hung-Yi; The, Hee-Wen; Chen, Chao-Meei; Chen, Chien-Jen

    2003-08-01

    This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.

  9. A clinical study of the effects of lead poisoning on the intelligence and neurobehavioral abilities of children

    PubMed Central

    2013-01-01

    Background Lead is a heavy metal and important environmental toxicant and nerve poison that can destruction many functions of the nervous system. Lead poisoning is a medical condition caused by increased levels of lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and issues, including the central nervous system. It interferes with the development of the nervous system, and is therefore particularly toxic to children, causing potentially permanent neural and cognitive impairments. In this study, we investigated the relationship between lead poisoning and the intellectual and neurobehavioral capabilities of children. Methods The background characteristics of the research subjects were collected by questionnaire survey. Blood lead levels were detected by differential potentiometric stripping analysis (DPSA). Intelligence was assessed using the Gesell Developmental Scale. The Achenbach Child Behavior Checklist (CBCL) was used to evaluate each child’s behavior. Results Blood lead levels were significantly negatively correlated with the developmental quotients of adaptive behavior, gross motor performance, fine motor performance, language development, and individual social behavior (P < 0.01). Compared with healthy children, more children with lead poisoning had abnormal behaviors, especially social withdrawal, depression, and atypical body movements, aggressions and destruction. Conclusion Lead poisoning has adverse effects on the behavior and mental development of 2–4-year-old children, prescribing positive and effective precautionary measures. PMID:23414525

  10. Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol.

    PubMed

    McKee, R H; Lammers, J H C M; Hoogendijk, E M G; Emmen, H H; Muijser, H; Barsotti, D A; Owen, D E; Kulig, B M

    2006-12-01

    As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans.

  11. Sativex-induced neurobehavioral effects: causal or concausal? A practical advice!

    PubMed

    Russo, Margherita; Rifici, Carmela; Sessa, Edoardo; D'Aleo, Giangaetano; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-01-01

    Nabiximols (Sativex) is an oromucosal spray, containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), used as treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Sativex is thought to not affect cognition or induce any psychiatric problem at the doses generally used. Nonetheless, it is known that the concomitant use of more than one muscle-relaxant drugs can result in additive neuropsychiatric effects. Herein we describe a case of a woman affected by MS and treated with baclofen and methylprednisolone, who developed important behavioral changes, including suicidal ideation, after 4 weeks of Sativex administration. We are not completely able to state if Sativex alone was responsible for our patient's psychiatric symptoms, in reason of the concomitant use of the other drugs.In conclusion, physicians should pay more attention when prescribing drugs to MS patients affected by spasticity, including Sativex, since neurobehavioral side effects may emerge especially in predisposed individuals. PMID:25881038

  12. Adverse effects of general anaesthetics.

    PubMed

    Berthoud, M C; Reilly, C S

    1992-01-01

    This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis. PMID:1418699

  13. Neurobehavioral effects in rat pups whose sires were exposed to alcohol.

    PubMed

    Jamerson, Patricia A; Wulser, Michael J; Kimler, Bruce F

    2004-04-19

    Developmental neurobehavioral effects associated with maternal exposure to alcohol during pregnancy are well described, but little is known about the effects of paternal exposure prior to conception. Using a quasi-experimental, within-subjects design, neurobehavioral outcomes (reflex acquisition, activity, gait) and cerebral cortical layer thickness were assessed in Sprague-Dawley rat pups from breeding pairs where the sires were exposed to alcohol. Comparisons were made on the basis of the timing of conception relative to alcohol exposure: phase 1 (controls), prior to initiation of alcohol exposure; phase 2, during the period of treatment with 20% alcohol; and phase 3, following cessation of alcohol exposure. Phase 2 and 3 pups were noted to attain negative geotaxis and reflex suspension benchmarks earlier than control pups and to have more difficulty with balance. Phase 3 pups were noted to attain righting reflex earlier than controls. In addition, phase 3 pups demonstrated increased levels of reverse maze activity and a shorter and narrower gait. Brain morphometry revealed thickening of cortical sections I-IV and V-VI resulting in overall cortical enlargement in both phase 2 and 3 pups. Further analysis of phase 2 and 3 subphases based on the presumed stages of the spermatogenic cycle during which sires were exposed to alcohol revealed significant differences in maze activity, reflex acquisition, and gait length. These findings suggest pre-conception male exposure to alcohol may have an effect on the offspring and the extent of the effects may vary with the timing of alcohol exposure relative to conception.

  14. Long-term neurobehavioral effects of mild poisonings with organophosphate and n-methyl carbamate pesticides among banana workers.

    PubMed

    Wesseling, Catharina; Keifer, Matthew; Ahlbom, Anders; McConnell, Rob; Moon, Jai-Dong; Rosenstock, Linda; Hogstedt, Christer

    2002-01-01

    Organophosphate poisoning has been associated with chronic neurobehavioral dysfunction, but no epidemiologic data exist with regard to long-term consequences from carbamate poisoning. This cross-sectional study evaluated the neurobehavioral performances of 81 banana workers who, on average 27 months earlier, had received medical attention not requiring hospitalization for mild occupational poisoning by either an organophosphate or a carbamate pesticide. These performances were compared with those of 130 banana workers who had never sought medical attention for pesticide poisoning. Poisoned subjects did less well than controls on tests measuring psychomotor and visuomotor skills, language function, and affect, the differences being significant for coding skills on the Digit-Symbol test and two tests of neuropsychiatric symptoms. These deficits, in particular a marked increase of neuropsychiatric symptoms, occurred among the organophosphate-poisoned subjects, but small deficits in performance were also seen in the carbamate-poisoned subjects. The performances of the previously poisoned subjects who had had contact with cholinesterase inhibitors within three months before testing were particularly poor. These findings in workers with mild poisoning are consistent with previous findings of persistent damage to the central nervous system from organophosphate poisoning. The possibility of persistent neurobehavioral effects associated with poisonings by nmethyl carbamate insecticides cannot be excluded. Workers with histories of poisoning may be more susceptible to neurobehavioral effects with subsequent exposures.

  15. [Cutaneous adverse effects of TNFalpha antagonists].

    PubMed

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  16. Bisphenol A: Human exposure and neurobehavior.

    PubMed

    Mustieles, Vicente; Pérez-Lobato, Rocío; Olea, Nicolás; Fernández, Mariana F

    2015-07-01

    The effect of bisphenol A (BPA) exposure on human brain and behavior is a relatively new issue, and particular concerns have been raised about its potential impact on children. The primary objective of this review was to analyze the current state of knowledge on the association of environmental BPA exposure during pregnancy and/or childhood with child cognitive and/or behavior outcomes. All scientific publications until March 2015 that include examination of this relationship have been reviewed using the MEDLINE/PubMed database. Although research on this issue has not been abundant, an association with altered neurobehavior was reported by eight out of the twelve available articles, including aggressive behavior, attention deficit, hyperactivity disorder, depression and anxiety impairments, mostly in children exposed in utero, indicating disruption of the brain during this critical window of development. Despite the reduced number of studies and their heterogeneity, the results suggest that prenatal BPA exposure may have a negative impact on neurobehavioral functioning in children and that the effects may be sex-dependent. It is therefore necessary to be vigilant towards the potential adverse effects of ubiquitous low-level BPA exposure, although more studies in humans are required to convincingly confirm or rule out the association between BPA exposure and health. Meanwhile, it is desirable to inform women planning or undergoing pregnancy about measures to reduce or avoid exposure to BPA. We discuss some key aspects of the relationship between exposure and neurobehavioral outcomes. PMID:26121921

  17. Neurobehavioral toxicity.

    PubMed Central

    Walker, B.

    2000-01-01

    A growing number of agents are known to perturb one or more of the interconnected processes of the central nervous system. At the same time, there is an increase in the incidence of neurobehavioral disorders that are confronting clinicians with baffling symptoms and presentations that seem uncommon. Fundamental to the assessment of the environmental-relatedness of the syndromes is a work and exposure history, including information different from that routinely obtained in the clinical setting. Exposure examples are described to suggest the scope of inquiry necessary to differentiate neurotoxic syndromes from nonneurotoxic illness. PMID:10745641

  18. Adverse effects of anabolic steroids in athletes.

    PubMed

    Kibble, M W; Ross, M B

    1987-09-01

    The effects of anabolic steroid use on athletic performance and the adverse effects associated with the use of anabolic steroids are reviewed. Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties, some athletes use anabolic steroids in an attempt to improve their athletic performance. However, studies indicate that increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while maintaining high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes also are reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent. However, the reported benefits are tempered by numerous adverse reactions.

  19. Acute Total and Chronic Partial Sleep Deprivation: Effects on Neurobehavioral Functions, Waking EEG and Renin-Angiotensin System

    NASA Technical Reports Server (NTRS)

    Dijk, Derk-Jan

    1999-01-01

    Total sleep deprivation leads to decrements in neurobehavioral performance and changes in electroencephalographic (EEG) oscillations as well as the incidence of slow eye movements ad detected in the electro-oculogram (EOG) during wakefulness. Although total sleep deprivation is a powerful tool to investigate the association of EEG/EOG and neurobehavioral decrements, sleep loss during space flight is usual only partial. Furthermore exposure to the microgravity environment leads to changes in sodium and volume homeostasis and associated renal and cardio-endocrine responses. Some of these changes can be induced in head down tilt bedrest studies. We integrate research tools and research projects to enhance the fidelity of the simulated conditions of space flight which are characterized by complexity and mutual interactions. The effectiveness of countermeasures and physiologic mechanisms underlying neurobehavioral changes and renal-cardio endocrine changes are investigated in Project 3 of the Human Performance Team and Project 3 of the Cardiovascular Alterations Team respectively. Although the. specific aims of these two projects are very different, they employ very similar research protocols. Thus, both projects investigate the effects of posture/bedrest and sleep deprivation (total or partial) on outcome measures relevant to their specific aims. The main aim of this enhancement grant is to exploit the similarities in research protocols by including the assessment of outcome variables relevant to the Renal-Cardio project in the research protocol of Project 3 of the Human Performance Team and by including the assessment of outcome variables relevant to the Quantitative EEG and Sleep Deprivation Project in the research protocols of Project 3 of the Cardiovascular Alterations team. In particular we will assess Neurobehavioral Function and Waking EEG in the research protocols of the renal-cardio endocrine project and renin-angiotensin and cardiac function in the research

  20. Effects of perinatal coexposure to methylmercury and polychlorinated biphenyls on neurobehavioral development in mice.

    PubMed

    Sugawara, Norio; Ohba, Takashi; Nakai, Kunihiko; Kakita, Akiyoshi; Nakamura, Tomoyuki; Suzuki, Keita; Kameo, Satomi; Shimada, Miyuki; Kurokawa, Naoyuki; Satoh, Chieko; Satoh, Hiroshi

    2008-06-01

    Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmental pollutants that cause neurobehavioral deficits in humans. Because exposures to MeHg and PCBs occur through fish consumption, it is necessary to clarify the effects of the interaction of the two pollutants. Therefore, we investigated the effects of perinatal exposure to MeHg and PCBs on the neurobehavioral development in mice. Female mice (C57BL/6Cr) were divided into four groups according to the type of exposure: (1) vehicle control, (2) MeHg alone, (3) PCBs alone, and (4) MeHg + PCBs. The MeHg-exposed groups were fed with a diet containing 5 ppm MeHg (as Hg), from 4 weeks before mating, throughout pregnancy, and lactation. The PCB-exposed groups were given a commercial mixture of PCBs, Aroclor 1,254, at 18 mg/kg body weight in corn oil by gavage every 3 days from day 5 after breeding and continued until postnatal day (PND) 20. Before weaning, an assessment of eye opening showed the interactive effects between MeHg and PCBs on PND 12: The coexposure group showed a similar response to the control group, whereas the MeHg- and PCB-exposed groups showed a high response than the former two groups. We also observed delay in development of grasp reflex by MeHg exposure on PNDs 12 and 14. When the offspring mice were 8 weeks old, the group exposed to PCBs alone showed increases in the frequencies of excrement defecation and urine traces in an open-field test. Analysis of the latency revealed the antagonistic interaction between the MeHg and PCBs: The latency increased by either MeHg or PCB exposure was decreased by coexposure. Treatment with MeHg decreased the distance walked by the mice, and MeHg interacted with PCBs. Moris' water maze test showed that the MeHg-treated mice took a long time to reach the submerged platform; however, this MeHg exposure showed no interaction with PCB exposure. The spontaneous locomotion activity of the mice was not affected by the chemical exposure at 9 weeks of age

  1. Assessment of neurobehavioral and biochemical effects in rats exposed to copper smelter dusts.

    PubMed

    Halatek, Tadeusz; Lutz, Piotr; Krajnow, Aleksander; Stetkiewicz, Jan; Domeradzka, Katarzyna; Swiercz, Radoslaw; Wasowicz, Wojciech

    2011-01-01

    Female Wistar rats were instilled per os by gavage with different copper dust samples: P-25 obtained by passing the test material through a 25 μmsieve, and P-0.1 containing soluble matter and ultra-fine, non-soluble<100 nm particulate matter (PM) fraction. The control group received sterile saline. The effects were studied at day 1, 7, and 30 post-exposure, focusing on bronchoalveolar lavage fluid (BALF) analysis (including biochemistry, cell morphology, cell viability, and Clara cell 16 protein concentration) and pathomorphology of lung. Results of biochemical tests showed a strong pro-inflammatory effect of both particulate fractions. The morphological studies after exposure to P-25 and P-0.1 fractions showed multi-focal infiltrations in the alveoli. Changes in behavioral (radial maze and passive avoidance tests) have shown that memory in groups exposed to dust was impaired. Our findings indicate that both samples of dust from Copper Smelter cause greater and lesser intensity (P-25 > P-0.1) of the symptoms of acute inflammatory reaction immediately 24 h after instillation to rats. Exposure results in dropping CC16 protein level in serum of rats. After one month, previous acute inflammation was resolved and transformed in persistent low-grade inflammation. The low-grade inflammation resulted in induction of neurobehavioral effects probably by changes in "cholinergic anti-inflammatory pathway" in which acetylcholine modulates neurotransmission. PMID:21279893

  2. Effects of Prenatal Cigarette Smoke Exposure on Neurobehavioral Outcomes in Ten-Year-Old Children of Teenage Mothers

    PubMed Central

    Cornelius, Marie D.; De Genna, Natacha M.; Leech, Sharon L.; Willford, Jennifer A.; Goldschmidt, Lidush; Day, Nancy L.

    2010-01-01

    In this prospective study, teenager mothers (mean age = 16; range = 12–18; 70% African American) were interviewed about their tobacco use during pregnancy. When their children were ten, mothers reported on their child’s behavior and the children completed a neuropsychological battery. We examined the association between prenatal cigarette smoke exposure (PCSE) and offspring neurobehavioral outcomes on data from the ten-year phase (n = 336). Multivariate regression analyses were conducted to test if PCSE predicted neurobehavioral outcomes, adjusting for demographic characteristics, maternal psychological characteristics, prenatal exposure to other substances, and exposure to environmental tobacco smoke. Independent effects of PCSE were found. Exposed offspring had more delinquent, aggressive and externalizing behaviors (CBCL). They were more active (Routh, EAS, SNAP) and impulsive (SNAP), and had more problems with peers (SNAP). On the Stroop test, deficits were observed in both baseline response processing measures and on the more complex interference task that requires both selective attention and response inhibition. The significant effects of PCSE on neurobehavioral outcomes were found for exposure to as few as 10 cigarettes per day. These results are consistent with results from an earlier assessment when the children were age 6, demonstrating that the effects of prenatal tobacco exposure can be identified early and are consistent through middle childhood. PMID:21256428

  3. Neurobehavioral effects in offspring of mice given excess aluminum in diet during gestation and lactation.

    PubMed

    Donald, J M; Golub, M S; Gershwin, M E; Keen, C L

    1989-01-01

    Aluminum (Al) as Al lactate in a purified diet (25, 500 or 1000 micrograms Al/g diet) was fed to Swiss-Webster mice from conception through weaning. Weights, food intake and toxic signs were recorded at regular intervals and pregnancy outcome evaluated. Pups were assessed for growth, neurobehavioral development and toxic signs prior to weaning. Offspring were also evaluated with a multi-item neurobehavioral test battery immediately after weaning and again after a 2-week period during which they were all fed control (25 micrograms/g Al) diet. No maternal or reproductive toxicity was detected and there were no group differences in pup mortality, growth, toxic signs, or neurobehavioral development prior to weaning, with the exception of poor performance in a climbing test in the 1000 micrograms Al/g diet group. Parameters significantly affected by Al in the postweaning neurobehavioral testing were foot splay, forelimb and hindlimb grip strengths, and thermal sensitivity. Negative geotaxis was inconsistently affected and startle responses were not affected. These results show that maternal dietary exposure to excess Al during gestation and lactation which do not produce maternal toxicity can result in persistent neurobehavioral deficits in weanling mice.

  4. Dynamic Circadian Modulation in a Biomathematical Model for the Effects of Sleep and Sleep Loss on Waking Neurobehavioral Performance

    PubMed Central

    McCauley, Peter; Kalachev, Leonid V.; Mollicone, Daniel J.; Banks, Siobhan; Dinges, David F.; Van Dongen, Hans P. A.

    2013-01-01

    Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation—and thereby sensitivity to neurobehavioral impairment from sleep loss—is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation—and thus sensitivity to sleep loss—depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work. Citation: McCauley P; Kalachev LV; Mollicone DJ; Banks S; Dinges DF; Van Dongen HPA. Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance. SLEEP 2013;36(12):1987-1997. PMID:24293775

  5. Involvement of the Endocannabinoid System in the Neurobehavioral Effects of Stress and Glucocorticoids

    PubMed Central

    Hill, Matthew N.; McEwen, Bruce S.

    2010-01-01

    The endocannabinoid system is a neuroactive lipid signaling system that functions to gate synaptic transmitter release. Accumulating evidence has demonstrated that this system is responsive to modulation by both stress and glucocorticoids within the hypothalamus and limbic structures; however, the nature of this regulation is more complex than initially assumed. The aim of the current review is to summarize the research to date which examines the effects of acute stress and glucocorticoid administration on endocannabinoid signaling in limbic-hypothalamic-pituitary-adrenal (LHPA), and in turn the role endocannabinoid signaling plays in the neurobehavioral responses to acute stress and glucocorticoid administration. The majority of research suggests that acute stress produces a mobilization of the endocannabinoid 2-arachidonoylglycerol (2-AG) while concurrently reducing the tissue content of the other endocannabinoid ligand anandamide. Genetic and pharmacological studies demonstrate that the reduction in anandamide signaling may be involved in the initiation of HPA axis activation and the generation of changes in emotional behaviour, while the increase in 2-AG signaling may be involved in terminating the stress response, limiting neuronal activation and contributing to changes in motivated behaviours. Collectively, these studies reveal a complex interplay between endocannabinoids and the HPA axis, and further identify endocannabinoid signaling as a critical regulator of the stress response. PMID:19903506

  6. The effects of Cannabis sativa L. seed (hemp seed) on reproductive and neurobehavioral end points in rats.

    PubMed

    Yousofi, Másume; Saberivand, Adel; Becker, Lora A; Karimi, Isaac

    2011-05-01

    This study determined the effects of maternal dietary intake of hemp seed on reproductive and neurobehavioral end points of Wistar rats. Time-mated rats were fed 100% hemp seed (n  =  15), 50% hemp seed (n  =  15) or basal diet (n  =  15) once a day. The amount of food made available was based on control feed consumption records. All dams remained on their respective diets from premating (14 days) throughout gestation and lactation. After weaning, all pups were given their maternal diet until puberty. Mating and delivery weights of dams in all groups did not show significant changes. Number of pregnancies, number and post-natal survival rate of total rat pups, litter size and milk yield were lower in the group that received 100% hemp seed. Offspring that received 50% hemp seed diet expressed reproductive and neurobehavioral end points from a modified Fox battery earlier than rats on 100% hemp seed or basal diet, except acoustic startle results where no differences appeared. In conclusion, this study shows that hemp seed supplementation does not improve the reproductive and neurobehavioral performances of rats. Pregnant women and nursing mothers should be cautious about the using of Cannabis sativa L. byproducts in their diets.

  7. Encouraging spontaneous reporting of adverse effects.

    PubMed

    2015-02-01

    One priority when organising surveillance of health products is to remove barriers to reporting adverse effects. One way to encourage reporting is by providing regular feedback, as practised by the German drug bulletin arznei-telegramm, for example. PMID:25802925

  8. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  9. Comparison of neurobehavioral and biochemical effects in rats exposed to dusts from copper smelter plant at different locations.

    PubMed

    Halatek, Tadeusz; Lutz, Piotr; Stetkiewicz, Jan; Krajnow, Aleksander; Wieczorek, Edyta; Swiercz, Radoslaw; Szymczak, Maria; Wasowicz, Wojciech

    2013-01-01

    Mixed exposure to metals (including arsenic and lead) associated with the neurological and respiratory effects constitute one of the major health problems of copper smelting. Chemical composition of the dust, and the expected health effect of inhalation can be very diverse at different parts of the smelter plant. The aims of this study were to compare lung responses and behavioral effects in female Wistar rats after instillation of dust collected from different production processes at the same smelter department. Dusts collected at two different locations of furnace hall were sifted through 25-μm-mesh sieve. Obtained dust fractions, P-25(I) collected near stove, rich in heavy metals and arsenic, and P-25(II) collected near anode residue storage site, rich in aluminium, were instilled to rats. At 1, 7 and 30 days after dusts instillation, lung injury and inflammation were measured by analyzing sings of lung permeability in the bronchoalveolar lavage fluid (BALF), cell differentiation in BALF sediment and lung morphology. The behavioral studies were done 30 days after exposure. Results of biochemical tests showed a strong pro-inflammatory effect of P-25(I) fractions. Mostly characteristic effects after instillation of P-25(I) samples were 10× increased protein leakages in BALF. Both P-25(I) and P-25(II) fractions caused a reduction of Clara-cell 16 protein concentration (CC16) in BALF and activation of serum butyrylcholinesterase (BChE) at all time points. The morphological studies after exposure to P-25(I) fractions showed multi-focal infiltrations in the alveoli. The behavioral results, especially P-25(II) group rats (in open filed, passive avoidance and hot plate tests), indicated adverse effects in the nervous system, which may be related to changes in the dopaminergic and cholinergic pathway. The symptoms were noted in the form of persistent neurobehavioral changes which might be associated with the content of neurotoxic metals. e.g. Al, Mn and/or As. Decrease

  10. Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. II. Ninety-day study.

    PubMed

    Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

    2015-02-01

    Carbon monoxide (CO), carbon dioxide (CO2) and low-level oxygen (O2) (hypoxia) are submarine atmosphere components of highest concern because of a lack of toxicological data available to address the potential effects from long-duration, combined exposures on female reproductive and developmental health. In this study, subchronic toxicity of mixed atmospheres of these three submarine air components was evaluated in rats. Male and female rats were exposed via inhalation to clean air (0.4 ppm CO; 0.13% CO2; 20.6% O2) (control), a low-dose (5.0 ppm CO; 0.41% CO2; 17.1% O2), a mid-dose (13.9 ppm CO; 1.19 or 1.20% CO2; 16.1% O2) and a high-dose (89.9 ppm CO; 2.5% CO2; 15.0% O2) gas mixture for 23 h per day for 70 d premating and a 14-d mating period. Impregnated dams continued exposure to gestation day 19. Adverse reproductive effects were not identified in exposed parents (P0) or first (F1) and second generation (F2) offspring during mating, gestation or parturition. No adverse changes to the estrous cycle or in reproductive hormone concentrations were identified. The exposure-related effects were reduced weight gains and adaptive up-regulation of erythropoiesis in male rats from the high-dose group. No adverse, dose-related health effects on clinical data or physiological data were observed. Neurobehavioral tests identified no apparent developmental deficits at the tested levels of exposure. In summary, subchronic exposures to the submarine atmosphere gases did not affect the ability of the exposed rats or their offspring to reproduce and did not appear to have any significant adverse health effects.

  11. Obstructive Sleep Apnea and Hypertension in Adolescents: Effect on Neurobehavioral and Cognitive Functioning

    PubMed Central

    Madaeva, Irina; Polyakov, Vladimir; Kolesnikov, Sergey

    2016-01-01

    Background. There are limited published data in regard to the relationship between obstructive sleep apnea (OSA) and hypertension and neurobehavioral and mental status in adolescence. The aim of our study was to evaluate neurobehavioral patterns and cognitive functions in adolescents with hypertension according to absence or presence of OSA. Methods. This was a retrospective cohort study completed at the Scientific Center for Family Health and Human Reproduction Problems. Participants included adolescents aged 14–17 years and referred for 24-hour ambulance blood pressure monitoring (ABPM) and polysomnographic (PSG) studies between 2007 and 2009, inclusive. Results. 18 hypertensive OSA (the 1st group) and 20 hypertensive non-OSA adolescents (the 2nd group) were included in the study. Significant changes of neurobehavioral functioning in OSA patients were shown. Cognitive abilities also were impaired. Verbal and visual memory indexes and attention index were 2.1 and 2.2 times lower, accordingly, in the 1st group than in the 2nd group (P < 0.05). Speech index was significantly 2.8 times lower in OSA patients than in non-OSA patients (P < 0.05). In hypertensive OSA adolescents more significant Spearman correlations between classic sleep parameters and cognitive measures were found compared to patients without OSA. Conclusions. These results suggest that OSA is closely associated with neurobehavioral and cognitive functioning in hypertensive adolescents. PMID:27445534

  12. DIFFERENTIAL PROFILES OF CHOLINESTERASE INHIBITION AND NEUROBEHAVIORAL EFFECTS IN RATS EXPOSED TO FENAMIPHOS AND PROFENOPHOS.

    EPA Science Inventory

    The relationship between cholinesterase (ChE) inhibition and neurobehavioral changes was examined using two ChE-inhibiting organophosphorus pesticides, fenamiphos and profenophos. Both pesticides inhibit blood ChE, yet brain ChE is relatively spared (little to no inhibition up t...

  13. Urinary Metabolites of Organophosphate and Pyrethroid Pesticides and Neurobehavioral Effects in Chinese Children.

    PubMed

    Wang, Na; Huang, Mengying; Guo, Xinyan; Lin, Ping

    2016-09-01

    Organophosphate (OP) and pyrethroid (PYR) pesticides are widely used in China. However, few studies have investigated the neurobehavioral outcomes of Chinese children exposed to low levels of OP and PYR. We investigated urinary metabolite levels and their association with exposure characteristics and the neurobehavior of children. For all children, biomarker measurements were made in the same interval relative to neurobehavioral testing. We analyzed the morning urine samples of 406 children aged 3-6 years from Nanjing, China. The Kruskal-Wallis and Wilcoxon rank sum tests were used to identify the associations between urinary metabolite levels and exposure characteristics. Multiple linear regression models were used to test the associations between urinary metabolite levels and neurobehavioral test scores after adjusting for covariates (e.g., sex, age, and education expense). The detection of 3,5,6-trichloropyridinol (TCP) and 3-phenoxybenzoic acid (3-PBA) in the urine was positively associated with living areas adjacent to agricultural fields and using indoor mosquito repellent incense. These two metabolites were negatively associated with the soaking time of fruits and vegetables. When treated as dichotomous variables, TCP was significantly associated with arithmetic test scores in adjusted models, and 3-PBA was significantly associated with the scores on the Chinese Binet and arithmetic tests. When treated as a continuous variable, higher urinary 3-PBA levels were significantly associated with lower cancellation test scores. Our findings suggest that exposure to organophosphate and pyrethroid pesticides may have a significant impact on children's working memory and verbal comprehension. PMID:27524288

  14. Obstructive Sleep Apnea and Hypertension in Adolescents: Effect on Neurobehavioral and Cognitive Functioning.

    PubMed

    Madaeva, Irina; Berdina, Olga; Polyakov, Vladimir; Kolesnikov, Sergey

    2016-01-01

    Background. There are limited published data in regard to the relationship between obstructive sleep apnea (OSA) and hypertension and neurobehavioral and mental status in adolescence. The aim of our study was to evaluate neurobehavioral patterns and cognitive functions in adolescents with hypertension according to absence or presence of OSA. Methods. This was a retrospective cohort study completed at the Scientific Center for Family Health and Human Reproduction Problems. Participants included adolescents aged 14-17 years and referred for 24-hour ambulance blood pressure monitoring (ABPM) and polysomnographic (PSG) studies between 2007 and 2009, inclusive. Results. 18 hypertensive OSA (the 1st group) and 20 hypertensive non-OSA adolescents (the 2nd group) were included in the study. Significant changes of neurobehavioral functioning in OSA patients were shown. Cognitive abilities also were impaired. Verbal and visual memory indexes and attention index were 2.1 and 2.2 times lower, accordingly, in the 1st group than in the 2nd group (P < 0.05). Speech index was significantly 2.8 times lower in OSA patients than in non-OSA patients (P < 0.05). In hypertensive OSA adolescents more significant Spearman correlations between classic sleep parameters and cognitive measures were found compared to patients without OSA. Conclusions. These results suggest that OSA is closely associated with neurobehavioral and cognitive functioning in hypertensive adolescents. PMID:27445534

  15. Perspective on Lithotripsy Adverse Effects

    NASA Astrophysics Data System (ADS)

    Knoll, Thomas; Wendt-Nordahl, Gunnar

    2008-09-01

    Shock wave lithotripsy (SWL) is an effective and without any doubt the least invasive procedure to treat upper urinary tract calculi. Acute complications are rarely reported and do not require specific treatment in most cases. However, one should be aware that energy levels sufficient for stone breakage are capable of damaging tissue as well, and significant hematoma—not only in the kidney but as well in surrounding organs—has been observed. Furthermore, only little is known about the long-term effects of SWL. Some authors have reported an increased incidence of hypertension and possibly also diabetes mellitus. Such chronic diseases—if indeed related to prior SWL—may be a late result of acute SWL-related trauma but the discussion on the underlying pathogenesis is controversial. Many factors have to be considered, such as the natural history of recurrent stone formers, technical principles of SWL, and differences in treatment protocols. Promising studies are currently underway to optimize stone breakage while limiting potential collateral damage. With this progress, SWL remains a safe treatment option for most urinary calculi.

  16. Neurobehavioral Assessment before Birth

    ERIC Educational Resources Information Center

    DiPietro, Janet A.

    2005-01-01

    The complexities of neurobehavioral assessment of the fetus, which can be neither directly viewed nor manipulated, cannot be understated. Impetus to develop methods for measuring fetal neurobehavioral development has been provided by the recognition that individual differences in neurobehavioral functioning do not originate with birth and…

  17. Pesticide poisoning and neurobehavioral function among farm workers in Jiangsu, People's Republic of China.

    PubMed

    Zhang, Xujun; Wu, Ming; Yao, Hongyan; Yang, Yaming; Cui, Mengjing; Tu, Zhibin; Stallones, Lorann; Xiang, Huiyun

    2016-01-01

    Pesticides remain an integral part of agricultural activities worldwide. Although there have been a number of studies over the last two decades concerning the adverse effects of pesticide poisoning and chronic long term exposures on neurobehavioral function, the impact of recent pesticide poisoning and long term pesticide exposure on neurobehavioral function in Chinese farm workers has not been reported. China is the largest user of pesticides worldwide and figures suggest 53,300-123,000 Chinese people are poisoned every year. A case control study was conducted to examine the impact of recent pesticide poisoning on neurobehavioral function and the relationship between years worked in agriculture and lower performance on neurobehavioral tests. A total of 121 farm workers who self-reported recent pesticide poisonings within the previous 12 months (case group) and 80 farm workers who reported no pesticide poisoning in the previous 12 months (control group) were recruited from three areas of Jiangsu Province, China. The World Health Organization (WHO) recommended neurobehavioral core test battery (NCTB) was used to assess neurobehavioral functioning among cases and controls. Student's t tests and two-way covariance analysis (ANCOVA) were used to test for significant differences in the neurobehavioral test results between the groups. Scores on the Profile of Mood States (POMS) in the recently poisoned group were significantly higher for anger-hostility, depression-dejection, tension-anxiety and lower for vigor-activity compared to controls (p < .05). Digit span, digit symbol, Benton visual retention and pursuit aiming scores were all significantly lower among the recently poisoned group compared to the controls (p < .05). Two-way ANCOVA indicated significantly lower performance in correct pursuit aiming and higher error pursuit aiming amongst the recently poisoned group and those who had worked for more than 30 years in agriculture (p < .05). These findings provide

  18. The multisystem adverse effects of NSAID therapy.

    PubMed

    James, D S

    1999-11-01

    The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) to manage pain and inflammation is limited by adverse side effects. Although effective analgesic and anti-inflammatory agents, NSAIDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The primary adverse events associated with NSAID therapy are upper gastrointestinal (GI) ulceration, perforation, or bleeding, all of which involve mucosal damage of varying severity and can be asymptomatic and occur with little warning. Clinicians who prescribe NSAIDs should be able to identify patients who are at risk of an NSAID-induced GI adverse event and to detect and manage the event should one occur. The use of COX-2-specific inhibitors to manage pain and inflammation may minimize the risks of NSAID-associated toxicities.

  19. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

  20. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

    Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep. PMID:27514301

  1. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options. PMID:25536126

  2. Adverse Effects of Common Drugs: Dietary Supplements.

    PubMed

    Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

    2015-09-01

    Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists.

  3. Psychiatric adverse effects of pediatric corticosteroid use.

    PubMed

    Drozdowicz, Linda B; Bostwick, J Michael

    2014-06-01

    Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions

  4. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  5. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence. PMID:23850228

  6. Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

    PubMed Central

    Bae, Dae-Kwon; Park, Dongsun; Lee, Sun Hee; Yang, Goeun; Kyung, Jangbeen; Kim, Dajeong; Shin, Kyungha; Choi, Ehn-Kyoung; Kim, Gonhyung; Hong, Jin Tae; Kim, Seung U.

    2016-01-01

    Since multiple sclerosis (MS) is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs) with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG-) induced experimental autoimmune encephalomyelitis (EAE) model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse) were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP). The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF). In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS. PMID:27429621

  7. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors.

  8. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  9. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  10. The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

    SciTech Connect

    McInturf, S.M.; Bekkedal, M.Y.V.; Wilfong, E.; Arfsten, D.; Chapman, G.; Gunasekar, P.G.

    2011-07-15

    The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distress vocalizations were elevated in F{sub 1} offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F{sub 1} females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P{sub 0} animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.

  11. Association of Traffic-Related Air Pollution with Children’s Neurobehavioral Functions in Quanzhou, China

    PubMed Central

    Wang, Shunqin; Zhang, Jinliang; Zeng, Xiaodong; Zeng, Yimin; Wang, Shengchun; Chen, Shuyun

    2009-01-01

    Background With the increase of motor vehicles, ambient air pollution related to traffic exhaust has become an important environmental issue in China. Because of their fast growth and development, children are more susceptible to ambient air pollution exposure. Many chemicals from traffic exhaust, such as carbon monoxide, nitrogen dioxide, and lead, have been reported to show adverse effects on neurobehavioral functions. Several studies in China have suggested that traffic exhaust might affect neurobehavioral functions of adults who have occupational traffic exhaust exposure. However, few data have been reported on the effects on neurobehavioral function in children. Objectives The objective of this study was to explore the association between traffic-related air pollution exposure and its effects on neurobehavioral function in children. Methods This field study was conducted in Quanzhou, China, where two primary schools were chosen based on traffic density and monitoring data of ambient air pollutants. School A was located in a clear area and school B in a polluted area. We monitored NO2 and particulate matter with aerodynamic diameter ≤ 10 μm as indicators for traffic-related air pollution on the campuses and in classrooms for 2 consecutive days in May 2005. The children from second grade (8–9 years of age) and third grade (9–10 years of age) of the two schools (n = 928) participated in a questionnaire survey and manual-assisted neurobehavioral testing. We selected 282 third-grade children (school A, 136; school B, 146) to participate in computer-assisted neurobehavioral testing. We conducted the fieldwork between May and June 2005. We used data from 861 participants (school A, 431; school B, 430) with manual neurobehavioral testing and from all participants with computerized testing for data analyses. Results Media concentrations of NO2 in school A and school B campus were 7 μg/m3 and 36 μg/m3, respectively (p < 0.05). The ordinal logistic regression

  12. Agomelatine: a review of adverse effects.

    PubMed

    2013-03-01

    More pharmacovigilance data on agomelatine became available in 2012. The main sources of information were surveillance data from the French national monitoring system, EU periodic safety update reports (PSURs), and the European pharmacovigilance database. The principal adverse effects of agomelatine consist of hepatic, pancreatic, neuropsychiatric, muscular and cutaneous disorders. The harms associated with agomelatine, which has no proven efficacy in depression, clearly outweigh the benefits. Until regulatory agencies decide to withdraw agomelatine from the market, it is up to healthcare professionals to protect patients from this unnecessarily dangerous drug.

  13. Adverse Effects of Psychotropic Medications: A Call to Action.

    PubMed

    Mago, Rajnish

    2016-09-01

    Adverse effects are common, bothersome, and a leading cause of discontinuation of treatment. The methodology for evaluating adverse effects of medications has been greatly neglected, however, especially in comparison to the methodology for assessment of efficacy of medications. Existing methods for assessment and reporting of adverse effects have important limitations leading to lack of much-needed data related to adverse effects. Lastly, there is little systematic research into management of most adverse effects. A series of recommendations are made in this article about how to improve identification, assessment, reporting, and management of adverse effects. PMID:27514294

  14. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386

  15. Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring.

    PubMed

    Singh, K P; Singh, Manoj Kr; Singh, Manish

    2016-08-01

    A tremendous increase has been documented in the recent past in prescribing second generation atypical antipsychotic drugs (AAPDs) to the pregnant women with psychosis, considering their reproductive and teratogenic safety. Among AAPDs, risperidone (RIS) ranked third after olanzapine (OLZ) and quetiapine (QUE) used during pregnancy, as OLZ is associated to substantial weight gain in adults and offspring. Although teratogenic safety of RIS has been established, its potential role in developmental neurotoxicity and related neurobehavioral impairments in adolescents has not been documented so far. Therefore, present study has been undertaken to elucidate the effect of prenatal exposure to risperidone (RIS) on developmental neurotoxicity and apoptotic neurodegeneration in neocortical region of fetal brain; and related functional sequelae in young rat offspring. The pregnant Wistar rats were exposed to RIS at 0.8, 1.0 and 2.0mg/kg, at equivalent therapeutic doses, orally from GD 6 to 21. Half of the pregnant rats were sacrificed and their brains were collected, weighed, and processed for neurohistopathological and apoptotic neurodegenerative evaluation. The remaining dams were allowed to deliver naturally, and their offspring were reared up to 10 weeks for neurobehavioral study. Prenatal exposure to RIS induced significant stunting of fetal body and brain weight, substantial reduction in the thickness of neocortical layers and apoptotic neurodegeneration in fetal brains, and delayed postnatal development and growth of the offspring; as well as long- lasting impact on anxiety like impaired behavioral responses on explorative mazes. Therefore, health care providers should be careful in prescribing atypical antipsychotics in general and RIS in particular, to the pregnant psychotic population. PMID:27184437

  16. The antagonistic effects of L-dopa and eserine on Al-induced neurobehavioral deficits in rats.

    PubMed

    Zheng, Y X; Liang, Y X

    1998-12-01

    The main goals of the study were to elucidate the mechanism of Al-induced behavioral toxicity and to explore the possible link between the changes in the metabolism of monoaminergic or cholinergic transmitters and neurobehavioral effects. Three groups (12 rats in each group) were fed with aluminum chloride in drinking water (1600 mg/l) ad libitum through a 90-day exposure period. The controls were fed with distilled water. From the 60th to 90th day of treatment, two of the three Al-treated groups were administered with L-dopa (220 mg/kg.bw) and eserine (0.4 mg/kg.bw) by gavage, respectively. A two-item neurobehavioral test battery consisting of step down test and Morris water maze task was used for rats after three months treatment. In the step-down test, markedly shortened the step-down latency (SDL) and the number of step-down (NSD) were observed in the Al-treated group (P < 0.05, vs. control). On the contrary, only slight changes were found in the rats treated with aluminum combined with L-dopa or eserine (P > 0.05, vs control). In eserine and L-dopa antagonized groups, the mean escape latencies of Morris water maze approached a level close to that of the controls (P > 0.05). The results showed that the Al-induced memory and learning impairment could be reduced by L-dopa or eserine. It is suggested that the depletion of dopaminergic and cholinergic transmitters in the central nervous system might play an important role in Al-induced neurotoxicity.

  17. Effects of paternal cadmium exposure on the sperm quality of male rats and the neurobehavioral system of their offspring

    PubMed Central

    ZHAO, XIAOGUO; CHENG, ZHENZHEN; ZHU, YI; LI, SHAN; ZHANG, LIANG; LUO, YUNBO

    2015-01-01

    Cadmium (Cd) is a testicular toxicant and an endocrine disruptor in humans and rodents. The aim of the present study was to investigate the effects of paternal Cd exposure on the sperm quality of male rats and the neurobehavioral system of their offspring. A total of 12 male rats were randomized into a control and Cd-treated group (n=6 per group), and 12 female rats were administered distilled water and randomly divided into two groups (n=6 per group). Subsequently, sperm motility, viability, malformation rate of male rats and the neuromotor maturation, antioxidant ability, Cd accumulation in different organs of their offspring were measured. Compared with the control rats, the sperm motility rate and vitality were significantly reduced (P<0.01) and the sperm malformation rate was significantly increased (P<0.01) in the male rats following Cd treatment. Regarding the nervous system development of the offspring, the cliff-avoidance reflex, surface-righting reflex and negative geotaxis results exhibited significant differences between the Cd exposure and control groups (P<0.05). The Cd content in the liver and heart of the offspring of the Cd exposure rats was higher than that in the control rats (P<0.05), and the liver content peaked on postnatal day 21. Furthermore, Cd exposure affected the antioxidant activity of the offspring, which was shown by glutathione, malondialdehyde and superoxide dismutase assays. Collectively, the results indicate that Cd exposure affects the sperm quality of male rats and the neurobehavioral system of their offspring. PMID:26668641

  18. Protective effect of naringin against ischemic reperfusion cerebral injury: possible neurobehavioral, biochemical and cellular alterations in rat brain.

    PubMed

    Gaur, Vaibhav; Aggarwal, Aditi; Kumar, Anil

    2009-08-15

    The present study was conducted with an aim to explore the possible role of naringin against ischemia reperfusion induced-neurobehavioral alterations, oxidative damage, cellular and histopathological alterations in cortex, striatum, hippocampus areas of brain. Male Wistar rats (200-220 g) were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 24 h to induce reperfusion (I/R) cerebral injury. Naringin (50, 100 mg/kg, i.p.) was administered for 7 days continuously before animals were subjected to ischemia reperfusion injury. Various behavioral tests [locomotor activity, neurological score (inclined beam test), transfer latency, resistance to lateral push] and biochemical parameters (lipid peroxidation, nitrite level, reduced glutathione, superoxide dismutase and catalase activity), mitochondrial enzyme dysfunctions (Complex I, II, III and IV) in cortex, striatum, hippocampus of brain and histopathological alterations were assessed subsequently. Seven days naringin (50 and 100 mg/kg) treatment significantly improved neurobehavioral alterations (improved locomotor activity, inclined beam walking and reduced resistance to lateral push, transfer latency) as compared to control ischemia reperfusion. Naringin (50 mg/kg and 100 mg/kg) treatment significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione and catalase activity and mitochondrial enzyme activities in cortex, striatum, cerebellum as compared to control (ischemia reperfusion) animals. In addition, naringin treatment significantly reversed histopathological alterations in cortex, striatum, hippocampus areas as compared to control (ischemia reperfusion). Present study suggests the protective effect of naringin and its therapeutic potential against ischemia reperfusion induced and related behavioral alterations in rats. PMID:19577560

  19. Management of adverse effects of mood stabilizers.

    PubMed

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management.

  20. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  1. Adverse skeletal effects of drugs - beyond Glucocorticoids.

    PubMed

    O'Sullivan, Susannah; Grey, Andrew

    2015-01-01

    Osteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management. PMID:25039381

  2. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  3. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  4. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  5. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  6. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  7. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.5 Assessment of adverse effects. (a)...

  8. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

    Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

  9. Migraine treatment: a chain of adverse effects.

    PubMed

    Veloso, Tiago Sousa; Cambão, Mariana Seixas

    2015-01-01

    This clinical vignette presents a 14 years old female, with a past medical history relevant only for migraine with typical aura of less than monthly frequency, complaining of a severe unilateral headache with rising intensity for the previous 4 h, associated with nausea, vomiting, photophobia and phonophobia. This episode of migraine with aura in a patient with recurrent migraine was complicated by side effects of medical diagnostic and therapeutic procedures (extrapyramidal symptoms, delirium, post-lumbar puncture headache, hospital admission) all of which could have been prevented-quaternary prevention. This case illustrates several important messages in migraine management: (1) use of acetaminophen is not based in high-quality evidence and better options exist; (2) among youngsters, domperidone should be preferred over metoclopramide because it does not cross the blood-brain barrier; (3) moderate to severe migraine crisis can be managed with triptans in teenagers over 12 years old; (4) it is important to recognize adverse drug effects; (5) harmful consequences of medical interventions do occur; (6) the school community must be informed about chronic diseases of the young.

  10. Parent-Directed Intervention for Children With Cancer-Related Neurobehavioral Late Effects: A Randomized Pilot Study

    PubMed Central

    Ross, Paula; Cuevas, Michelle; Turk, Anne; Kim, Heeyoung; Lo, Tracy T. Y.; Wong, Lennie F.; Bhatia, Smita

    2014-01-01

    Objective To evaluate feasibility and preliminary efficacy of an intervention directed at parents of childhood cancer survivors (CCSs) with neurobehavioral late effects to improve targeted parenting skills, and thus to indirectly benefit the child’s educational functioning. Methods 44 CCSs and their parents were randomized. Intervention-arm parents participated in eight individual training sessions augmented by a 3-month telephone support period. Pre- and postparent measures and child performance on Wechsler Individual Achievement Test-II and School Motivation and Learning Strategies Inventory assessed intervention effects. Results 90% of intervention parents completed the program with high adherence/perceived benefit. Between-group effect sizes ranged from d = 0.77 to d = 1.45 for parent knowledge, efficacy, frequency of pro-learning behaviors, and d = 0.21 to d = 0.76 for child academic scores. Parental time spent in intervention activities was associated with academic change. Conclusions A parent-directed intervention to indirectly promote academic functioning in CCSs appears feasible and effective in improving targeted parenting outcomes and for selected child academic outcomes. PMID:24966398

  11. Parent-directed intervention for children with cancer-related neurobehavioral late effects: a randomized pilot study.

    PubMed

    Patel, Sunita K; Ross, Paula; Cuevas, Michelle; Turk, Anne; Kim, Heeyoung; Lo, Tracy T Y; Wong, Lennie F; Bhatia, Smita

    2014-10-01

    OBJECTIVE : To evaluate feasibility and preliminary efficacy of an intervention directed at parents of childhood cancer survivors (CCSs) with neurobehavioral late effects to improve targeted parenting skills, and thus to indirectly benefit the child's educational functioning.  METHODS : 44 CCSs and their parents were randomized. Intervention-arm parents participated in eight individual training sessions augmented by a 3-month telephone support period. Pre- and postparent measures and child performance on Wechsler Individual Achievement Test-II and School Motivation and Learning Strategies Inventory assessed intervention effects.  RESULTS : 90% of intervention parents completed the program with high adherence/perceived benefit. Between-group effect sizes ranged from d = 0.77 to d = 1.45 for parent knowledge, efficacy, frequency of pro-learning behaviors, and d = 0.21 to d = 0.76 for child academic scores. Parental time spent in intervention activities was associated with academic change.  CONCLUSIONS : A parent-directed intervention to indirectly promote academic functioning in CCSs appears feasible and effective in improving targeted parenting outcomes and for selected child academic outcomes. PMID:24966398

  12. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  13. A longitudinal study on the effects of maternal smoking and secondhand smoke exposure during pregnancy on neonatal neurobehavior.

    PubMed

    Hernández-Martínez, Carmen; Arija Val, Victoria; Escribano Subías, Joaquín; Canals Sans, Josefa

    2012-06-01

    Maternal smoking during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant women and their fetuses. The long-term effects of prenatal exposure to smoke on child behavior and development have been the subject of more extensive research than have the short-term effects. Therefore, the aim of this work is to examine the effects of smoke exposure during pregnancy on neonatal behavior, including in our study a group of mothers exposed to secondhand smoke. The behavior of 282 healthy full-term newborns was assessed using the Neonatal Behavior Assessment Scale (NBAS) at 48-72 h of life. Sixty-two mothers smoked during pregnancy (no mother smoked more than 15 cig/day) and 17 were exposed to secondhand smoke. After adjusting for socio-demographic and obstetric factors, both newborns whose mothers smoked and those whose mothers were exposed to secondhand smoke showed significantly lower scores in the habituation cluster than non-smoking mothers. Exposure to secondhand smoke was also related to lower motor system cluster scores as well as some supplementary items and the newborns of smoking mothers showed significantly lower scores in the state regulation cluster and in some items of the state organization cluster than the newborns of non-smoking mothers. We conclude that active and passive smoking during pregnancy affects several aspects of neurobehavioral development, regardless of socio-demographic, obstetric and pediatric factors.

  14. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

    PubMed

    Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

    2015-03-01

    The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development.

  15. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

    PubMed

    Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

    2015-03-01

    The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. PMID:25597916

  16. Neurobehavioral and neurophysiological effects after acute exposure to a single peak of 200 ppm toluene in healthy volunteers.

    PubMed

    Kobald, S Oliver; Wascher, Edmund; Blaszkewicz, Meinolf; Golka, Klaus; van Thriel, Christoph

    2015-05-01

    The solvent toluene has neurotoxic properties that are especially relevant in the working environment. Short-term exposure limits (STELs) vary from 50 ppm up to 300 ppm across countries but their acute effects remain elusive in humans. Several in vitro and in vivo studies elucidated that toluene acutely acts by perturbations of different neurotransmitter systems. More specifically visual evoked potentials (VEPs) of rats are decreased after acute toluene exposure, leading to the assumption that particularly visual attention processes might be a target of toluene in humans. Therefore a visual change detection task was applied to measure both neurobehavioral and neurophysiological effects by using electroencephalography (EEG) after a single peak exposure to 200 ppm toluene. Performance and event-related components of the EEG were examined before and after exposure in a toluene-exposed and a control group. Thirty-three young healthy volunteers participated in this study. The behavioral results of the experiment indicate that toluene impairs the rate of correct responses especially in task conditions in which an irrelevant distractor is given, while the response times did not differ between both groups. The neurophysiological findings hint toward a less efficient visual processing of behaviorally relevant stimuli and an increased distractibility by irrelevant distractors. Thus the present results are a promising starting point for further research specifically targeting visual attention after toluene exposure and the reconsideration of the presently very heterogeneous STELs.

  17. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment.

  18. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... effects. Adverse effects on historic properties include, but are not limited to: (i) Physical destruction... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic...

  19. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution.

    PubMed

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology.

  20. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution

    PubMed Central

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

  1. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution.

    PubMed

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

  2. The neurobehavioral teratology of retinoids: a 50-year history.

    PubMed

    Adams, Jane

    2010-10-01

    This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

  3. Using Literature-Based Discovery to Explain Adverse Drug Effects.

    PubMed

    Hristovski, Dimitar; Kastrin, Andrej; Dinevski, Dejan; Burgun, Anita; Žiberna, Lovro; Rindflesch, Thomas C

    2016-08-01

    We report on our research in using literature-based discovery (LBD) to provide pharmacological and/or pharmacogenomic explanations for reported adverse drug effects. The goal of LBD is to generate novel and potentially useful hypotheses by analyzing the scientific literature and optionally some additional resources. Our assumption is that drugs have effects on some genes or proteins and that these genes or proteins are associated with the observed adverse effects. Therefore, by using LBD we try to find genes or proteins that link the drugs with the reported adverse effects. These genes or proteins can be used to provide insight into the processes causing the adverse effects. Initial results show that our method has the potential to assist in explaining reported adverse drug effects. PMID:27318993

  4. Adverse effects of equine rabies immune gobulin.

    PubMed

    Wilde, H; Chomchey, P; Prakongsri, S; Puyaratabandhu, P; Chutivongse, S

    1989-02-01

    Following a recently published prospective study of 485 recipients of equine rabies immune globulin (ERIG) manufactured by Pasteur Vaccins (Paris), this paper reports a study of 323 postexposure rabies patients receiving ERIG manufactured by the Swiss Vaccine and Serum Institute (Berna). It is concluded that there may be significant differences in adverse reaction rates, reflecting differing manufacturing or purification processes and protein content. Further studies of different ERIG products and of different lots of the same product are needed while ERIG remains an essential component of postexposure rabies treatment in developing countries.

  5. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue...—(1) Resolution without the Council. (i) The agency official shall consult with the SHPO/THPO...

  6. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  7. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  8. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  9. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  10. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify...

  11. THE ADVERSE-EFFECT POLICY FOR AGRICULTURAL LABOR.

    ERIC Educational Resources Information Center

    DELLON, HOWARD N.

    THE BASIC PHILOSOPHY UNDERLYING THE REGULATION OF FOREIGN WORKER IMPORTATIONS INTO THE UNITED STATES FOR AGRICULTURAL EMPLOYMENT IS THAT EMPLOYMENT OF SUCH WORKERS WILL NOT BE PERMITTED IF IT WILL HAVE AN ADVERSE EFFECT ON DOMESTIC WORKERS. THE "ADVERSE-EFFECT" POLICY HAS BEEN FOLLOWED SINCE THE ENACTMENT OF PUBLIC LAW 78 IN 1951 WHICH GOVERNED…

  12. Multiple adverse effects of pyridium: a case report.

    PubMed

    Haigh, Charles; Dewar, James C

    2006-01-01

    Pyridium (phenazopyridine hydrochloride) is often prescribed as an analgesic in patients following trauma, surgery, or infections of the urinary tract. Pyridium toxicity has been previously reported, however, most cases result in a single adverse effect. Herein the authors describe an elderly patient who presented with simultaneous multiple adverse effects, including a previously undocumented myelosuppressive pancytopenia.

  13. Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes.

    PubMed

    Threlkeld, Steven W; Gaudet, Cynthia M; La Rue, Molly E; Dugas, Ethan; Hill, Courtney A; Lim, Yow-Pin; Stonestreet, Barbara S

    2014-11-01

    Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, inter-alpha inhibitor proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72h post-insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72h following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that inter-alpha inhibitor proteins may serve as novel therapeutics for brain injury associated with premature birth and

  14. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic location... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Assessment of adverse...

  15. The CTIS Womb to Classroom Screening Program for the detection of agents with adverse effects on neuropsychological development.

    PubMed

    Adams, Jane; Janulewicz, Patricia A; Kao, Kelly; Jones, Kenneth Lyons; Chambers, Christina

    2012-06-01

    Over the last several decades, federal agencies engaged in the screening of environmental or pharmaceutical agents have recognized the need to conduct research in animal models to identify agents that have classic teratogenic effects as well as effects on neural and behavioral development. Many questions typically addressed in rodent models can be further addressed using real-world, everyday human exposures. Although some postmarketing surveillance programs have been put in place to examine the influences on birth characteristics, it is now urgent that programs be launched to examine the long-term risks associated with exposure to the many medications, drugs, and environmental chemicals for which data are currently unavailable and unexplored. The California Teratogen Information Service (CTIS), established in 1983, and its corresponding Clinical Research Program represent the oldest national program directed at identifying pregnancy risk factors and exposures associated with adverse pregnancy outcome, including behavioral dysfunction. In recognition of the rising rates of developmental disorders involving compromised mental ability, in 2007, CTIS committed to the development of a more comprehensive screening program designed to detect relationships between adverse prenatal exposures and compromised human neurobehavioral development. The "CTIS Womb to Classroom Screening Program for the Detection of Agents with Adverse Effects on Neuropsychological Development" is the first program designed to identify agents not yet known to be of concern.

  16. [Adverse effects of antidepressive agents in hospitalized geriatric patients].

    PubMed

    Korínková, V; Kolibás, E; Králová, M; Novotný, V; Konceoj, V A; Pjatnickij, A N; Andrusenkova, M P

    1992-11-01

    The frequency, intensity and profile of adverse effects of antidepressants was studied in elderly patients. The series consisted of 102 patients with depression admitted to hospitals in Bratislava and Moscow. The adverse effects of amitriptyline (Amitriptylin Spofa) and maprotiline (Ludiomil Ciba-Geigy) were compared. The assessment done on days 0, 7, and 28 of treatment showed that xerostomia had the highest occurrence rate with both preparations studied. In patients treated with amitriptyline adverse effects were more severe and were recorded more frequently, requiring treatment withdrawal in 3 patients. The overall intensity of adverse effects was significantly higher with amitriptyline (p < 0.05). In the group of patients treated with amitriptyline the adverse effects were more marked in those with severe somatic pathology. The risk of amitriptyline treatment in elderly patients is being emphasized along with the need for monitoring and correcting adverse effects of the treatment. Although maprotiline exhibited a lower occurrence rate of adverse effects, cardiac functions should be regularly checked in patients with preexisting cardiac pathology. (Tab. 2, Fig. 3, Ref. 6.).

  17. Neurobehavioral and health-related deficits in solvent-exposed painters.

    PubMed

    Grosch, J W; Neale, A V; Demers, R Y

    1996-11-01

    The health status of 133 solvent-exposed painters was evaluated using the Neurobehavioral Evaluation System (NES) and blood test results from a physical exam. The comparison group consisted of 51 sheetmetal workers, minimally exposed to solvents. Degree of solvent exposure was calculated using three different indices derived from questionnaire responses. Multivariate analyses, adjusted for age, alcohol consumption, and smoking, indicated that painters performed less well on the symbol digit learning and vocabulary tasks. Evidence was also found for a dose-effect relationship, particularly when several features of the work environment were considered in estimating exposure. Degree of solvent exposure predicted levels of serum lead, BUN, and SGOT. These findings indicate that questionnaire-based measures of solvent exposure can be useful predictors of neurobehavioral and health-related deficits. Verbal ability, often used by researchers as a measure of premorbid functioning, may be adversely affected by solvent exposure. PMID:8909612

  18. Effect of the delta-aminolevulinic acid dehydratase gene polymorphism on renal and neurobehavioral function in workers exposed to lead in China.

    PubMed

    Gao, Ai; Lu, Xiao-Ting; Li, Qiu-Ying; Tian, Lin

    2010-09-01

    Effects of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms on the renal and neurobehavioral functions were investigated in Chinese workers from a storage battery plant exposed to inorganic lead. Blood and urine were collected from each worker to determine the ALAD genotypes, blood lead levels (PbB), urinary beta2-MG and urinary NAG activity. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) was used. Of the 135 lead workers tested for ALAD genotype, 126 were ALAD1-1, 9 were ALAD1-2 but none were ALAD2-2. The gene frequencies of ALADl-1 and ALADl-2 were 93.33% and 6.67%, respectively. The workers with ALAD1-2 genotype had significantly higher concentrations of PbB (62.52microg/dl vs. 41.02microg/dl), urinary NAG (22.01U/gCr vs. 13.49U/gCr), urinary beta2-MG (194.98microg/gCr vs. 112.88microg/gCr), and digit span backward (DSB) score (6.67 vs. 5.33) than those of ALAD1-1 genotype. Urinary NAG of ALAD1-2 genotype carriers was significantly higher than that of ALAD1-1 genotype under the same blood lead level (b(i) 0.75 vs. b(i) 0.29). Interaction between PbB and ALAD genotypes has a significant influence on NAG (P=0.02) and beta(2)-MG (P=0.01). It is postulated that the workers with the ALAD2 allele appear to be more susceptible to the effects of lead on renal injury, whereas neurobehavioral functions in ALAD1 homozygote tend to be more vulnerable.

  19. Rare and very rare adverse effects of clozapine

    PubMed Central

    De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

    2015-01-01

    Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

  20. Fewer adverse effects with doxycycline than with minocycline.

    PubMed

    2009-10-01

    (1) In mid-2008 the French National Pharmacovigilance Committee examined spontaneous reports of adverse effects observed during tetracycline therapy; (2) When sales figures are taken into account, reports were more frequent with minocycline than with doxycycline. The proportion of severe adverse effects was also higher with minocycline than with doxycycline; (3) Life-threatening hypersensitivity reactions and autoimmune adverse effects were more frequent with minocycline than with doxycycline; (4) In practice, minocycline has a less favourable risk-benefit balance than doxycycline, particularly in the treatment of acne.

  1. Dynamic circadian modulation in a biomathematical model for the effects of sleep and sleep loss on waking neurobehavioral performance.

    PubMed

    McCauley, Peter; Kalachev, Leonid V; Mollicone, Daniel J; Banks, Siobhan; Dinges, David F; Van Dongen, Hans P A

    2013-12-01

    Recent experimental observations and theoretical advances have indicated that the homeostatic equilibrium for sleep/wake regulation--and thereby sensitivity to neurobehavioral impairment from sleep loss--is modulated by prior sleep/wake history. This phenomenon was predicted by a biomathematical model developed to explain changes in neurobehavioral performance across days in laboratory studies of total sleep deprivation and sustained sleep restriction. The present paper focuses on the dynamics of neurobehavioral performance within days in this biomathematical model of fatigue. Without increasing the number of model parameters, the model was updated by incorporating time-dependence in the amplitude of the circadian modulation of performance. The updated model was calibrated using a large dataset from three laboratory experiments on psychomotor vigilance test (PVT) performance, under conditions of sleep loss and circadian misalignment; and validated using another large dataset from three different laboratory experiments. The time-dependence of circadian amplitude resulted in improved goodness-of-fit in night shift schedules, nap sleep scenarios, and recovery from prior sleep loss. The updated model predicts that the homeostatic equilibrium for sleep/wake regulation--and thus sensitivity to sleep loss--depends not only on the duration but also on the circadian timing of prior sleep. This novel theoretical insight has important implications for predicting operator alertness during work schedules involving circadian misalignment such as night shift work.

  2. Prenatal Methamphetamine Use and Neonatal Neurobehavioral Outcome

    PubMed Central

    Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Grotta, Sheri Della; Fallone, Melissa; LiuPhD, Jing; Lester, Barry M.

    2008-01-01

    Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How prenatal MA exposure affects neonatal neurobehavior is unknown. Objective To examine the neurobehavioral effects of prenatal MA exposure. Design The Infant Development, Environment and Lifestyle (IDEAL) study screened 13,808 subjects and 1632 were eligible and consented. 166 (n=74 exposed) were enrolled in a longitudinal follow up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose-response relationships with amphetamine metabolites. Results After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated physiological stress. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. Conclusions Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose response relationships may represent neurotoxic effects from MA. PMID:18031987

  3. OVERVIEW AND EVALUATION OF NEUROBEHAVIORAL EFFECTS OF FLAME RETARDANTS IN LABORATORY ANIMALS.

    EPA Science Inventory

    Polybrominated diphenyl ether (PBDE) flame retardants are used worldwide and have been detected in numerous environmental, including human, samples. Concern has been raised regarding their potential developmental neurotoxic effects. There is an emerging literature on behavioral...

  4. Selenomethionine protects against adverse biological effects induced by space radiation.

    PubMed

    Kennedy, Ann R; Ware, Jeffrey H; Guan, Jun; Donahue, Jeremiah J; Biaglow, John E; Zhou, Zhaozong; Stewart, Jelena; Vazquez, Marcelo; Wan, X Steven

    2004-01-15

    Ionizing radiation-induced adverse biological effects impose serious challenges to astronauts during extended space travel. Of particular concern is the radiation from highly energetic, heavy, charged particles known as HZE particles. The objective of the present study was to characterize HZE particle radiation-induced adverse biological effects and evaluate the effect of D-selenomethionine (SeM) on the HZE particle radiation-induced adverse biological effects. The results showed that HZE particle radiation can increase oxidative stress, cytotoxicity, and cell transformation in vitro, and decrease the total antioxidant status in irradiated Sprague-Dawley rats. These adverse biological effects were all preventable by treatment with SeM, suggesting that SeM is potentially useful as a countermeasure against space radiation-induced adverse effects. Treatment with SeM was shown to enhance ATR and CHK2 gene expression in cultured human thyroid epithelial cells. As ionizing radiation is known to result in DNA damage and both ATR and CHK2 gene products are involved in DNA damage, it is possible that SeM may prevent HZE particle radiation-induced adverse biological effects by enhancing the DNA repair machinery in irradiated cells.

  5. Selenomethionine protects against adverse biological effects induced by space radiation.

    PubMed

    Kennedy, Ann R; Ware, Jeffrey H; Guan, Jun; Donahue, Jeremiah J; Biaglow, John E; Zhou, Zhaozong; Stewart, Jelena; Vazquez, Marcelo; Wan, X Steven

    2004-01-15

    Ionizing radiation-induced adverse biological effects impose serious challenges to astronauts during extended space travel. Of particular concern is the radiation from highly energetic, heavy, charged particles known as HZE particles. The objective of the present study was to characterize HZE particle radiation-induced adverse biological effects and evaluate the effect of D-selenomethionine (SeM) on the HZE particle radiation-induced adverse biological effects. The results showed that HZE particle radiation can increase oxidative stress, cytotoxicity, and cell transformation in vitro, and decrease the total antioxidant status in irradiated Sprague-Dawley rats. These adverse biological effects were all preventable by treatment with SeM, suggesting that SeM is potentially useful as a countermeasure against space radiation-induced adverse effects. Treatment with SeM was shown to enhance ATR and CHK2 gene expression in cultured human thyroid epithelial cells. As ionizing radiation is known to result in DNA damage and both ATR and CHK2 gene products are involved in DNA damage, it is possible that SeM may prevent HZE particle radiation-induced adverse biological effects by enhancing the DNA repair machinery in irradiated cells. PMID:14744637

  6. Effect of chemically induced propionic acidemia on neurobehavioral development of rats.

    PubMed

    Brusque, A M; Mello, C F; Buchanan, D N; Terracciano, S T; Rocha, M P; Vargas, C R; Wannmacher, C M; Wajner, M

    1999-11-01

    High levels of propionic acid (PPA) comparable to those of human propionic acidemia were achieved in blood (1-5 mmol/l) and brain (1 micromol/g) of rats by administering saline-buffered propionate (pH 7.4) subcutaneously twice a day from the 6th to the 28th day of life. PPA doses ranged from 1.44 to 1.92 micromol/g body weight as a function of animal age. Control rats were treated with saline in the same volumes. Growth and development of physical landmarks were assessed by monitoring the following parameters daily: body weight, upper incisor eruption, eye opening, and hair coat. Development of some reflexes was also monitored, and a specific subset of motor skills was evaluated at days 14 and 21 of life by the free-fall righting test and the spontaneous alternation test. Chronic PPA administration had no effect on body weight, cerebral cortex weight, or cerebellum weight, but caused slight but significant delays in the day of appearance of hair coat and eye opening, indicating an effect of PPA on the development of physical parameters. Free-fall righting was impaired in PPA-treated animals. On the other hand, PPA administration had no effect on the performance of the animals in the spontaneous alternation tests. Long-term effects of early PPA administration were investigated by assessing animal performance in an aversive task (two-way shuttle avoidance task) and in a nonaversive (open-field task) behavioral task at 60 days of age. PPA-treated rats did not habituate to the open field, and presented a lack of retention of the shuttle-avoidance task. Our results suggest that early postnatal PPA administration to rats alters normal development and induces long-term behavioral deficits in aversive and nonaversive tasks. PMID:10548267

  7. Adverse effects of herbal medicines: an overview of systematic reviews.

    PubMed

    Posadzki, Paul; Watson, Leala K; Ernst, Edzard

    2013-02-01

    This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects. PMID:23472485

  8. Adverse effects of herbal medicines: an overview of systematic reviews.

    PubMed

    Posadzki, Paul; Watson, Leala K; Ernst, Edzard

    2013-02-01

    This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects.

  9. Adverse Health Effects of Nighttime Lighting

    NASA Astrophysics Data System (ADS)

    Motta, M.

    2012-06-01

    The effects of poor lighting and glare on public safety are well-known, as are the harmful environmental effects on various species and the environment in general. What is less well-known is the potential harmful medical effects of excessive poor nighttime lighting. A significant body of research has been developed over the last few years regarding this problem. One of the most significant effects is the startling increased risk for breast cancer by excessive exposure to nighttime lighting. The mechanism is felt to be by disruption of the circadian rhythm and suppression of melatonin production from the pineal gland. Melatonin has an anticancer effect that is lost when its production is disrupted. I am in the process of developing a monograph that will summarize this important body of research, to be presented and endorsed by the American Medical Association, and its Council of Science and Public health. This paper is a brief overall summary of this little known potential harmful effect of poor and excessive nighttime lighting.

  10. Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia

    PubMed Central

    Xu, Linlin; Dong, Wenhong; Zhao, Jie; Xu, Yajun

    2015-01-01

    Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs), isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA). PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0) till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE) activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression. PMID:26058015

  11. Neurobehavioral effects of concurrent exposure to cesium-137 and paraquat during neonatal development in mice.

    PubMed

    Heredia, Luis; Bellés, Montserrat; Llovet, Maria Isabel; Domingo, Jose L; Linares, Victoria

    2015-03-01

    As a result of nuclear power plants accidents such as Chernobyl or Fukushima, some people were exposed to external and internal ionizing radiation (IR). Human brain is highly sensitive to IR during fetal and postnatal period when the molecular processes are not completely finished. Various studies have shown that exposure to low doses of IR causes a higher incidence of cognitive impairment. On the other hand, in industrialized countries, people are daily exposed to a number of toxicant pollutants. Exposure to environmental chemicals, such as paraquat (PQ), may potentiate the toxic effects induced by radiation on brain development. In this study, we evaluated the cognitive effects of concomitant exposure to low doses of internal radiation ((137)Cs) and PQ during neonatal brain development. At the postnatal day 10 (PND10), two groups of mice (C57BL/6J) were exposed to (137)Cs (4000 and 8000 Bq/kg) and/or PQ (7 mg/kg). To investigate the spontaneous behavior, learning, memory capacities and anxiety, behavioral tests were conducted in the offspring at two months of age. The results showed that cognitive functions were not significantly affected when (137)Cs or PQ were administered alone. However, alterations in the working memory and anxiety were detected in mice exposed to (137)Cs combined with PQ.

  12. Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia.

    PubMed

    Xu, Linlin; Dong, Wenhong; Zhao, Jie; Xu, Yajun

    2015-06-01

    Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs), isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA). PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0) till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE) activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression. PMID:26058015

  13. Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence.

    PubMed

    Guerri, Consuelo; Pascual, María

    2010-02-01

    Studies over the last decade demonstrate that adolescence is a brain maturation period from childhood to adulthood. Plastic and dynamic processes drive adolescent brain development, creating flexibility that allows the brain to refine itself, specialize, and sharpen its functions for specific demands. Maturing connections enable increased communication among brain regions, allowing greater integration and complexity. Compelling evidence has shown that the developing brain is vulnerable to the damaging effects of ethanol. It is possible to infer, therefore, that alcohol exposure during the critical adolescent developmental stages could disrupt the brain plasticity and maturation processes, resulting in behavioral and cognitive deficits. Recent neuroimaging studies have provided evidence of the impact of human adolescent drinking in brain structure and functions. Findings in experimental animals have also given new insight into the potential mechanisms of the toxic effects of ethanol on both adolescent brain maturation and the short- and long-term cognitive consequences of adolescent drinking. Adolescence is also characterized by the rapid maturation of brain systems mediating reward and by changes in the secretion of stress-related hormones, events that might participate in the increasing in anxiety and the initiation pattern of alcohol and drug consumption. Studies in human adolescents demonstrate that drinking at early ages can enhance the likelihood of developing alcohol-related problems. Experimental evidence suggests that early exposure to alcohol sensitizes the neurocircuitry of addiction and affects chromatin remodeling, events that could induce abnormal plasticity in reward-related learning processes that contribute to adolescents' vulnerability to drug addiction. In this article, we review the potential mechanisms by which ethanol impacts brain development and lead to brain impairments and cognitive and behavioral dysfunctions as well as the neurobiological

  14. Age-Dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical Outcomes Following Traumatic Brain Injury

    PubMed Central

    Glushakov, Alexander V.; Arias, Rodrigo A.; Tolosano, Emanuela; Doré, Sylvain

    2016-01-01

    Cerebral hemorrhages are common features of traumatic brain injury (TBI) and their presence is associated with chronic disabilities. Recent clinical and experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin-binding protein most abundant in blood plasma, is involved in the intrinsic molecular defensive mechanism, though its role in TBI is poorly understood. The aim of this study was to investigate the effects of Hp deletion on the anatomical and behavioral outcomes in the controlled cortical impact model using wildtype (WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp−∕−) in two age cohorts [2–4 mo-old (young adult) and 7–8 mo-old (older adult)]. The data obtained suggest age-dependent significant effects on behavioral and anatomical TBI outcomes and recovery from injury. Moreover, in the adult cohort, neurological deficits in Hp−∕− mice at 24 h were significantly improved compared to WT, whereas there were no significant differences in brain pathology between these genotypes. In contrast, in the older adult cohort, Hp−∕− mice had significantly larger lesion volumes compared to WT, but neurological deficits were not significantly different. Immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) revealed significant differences in microglial and astrocytic reactivity between Hp−∕− and WT in selected brain regions of the adult but not the older adult-aged cohort. In conclusion, the data obtained in the study provide clarification on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp that might be involved in complex pathways differentially affecting acute brain trauma outcomes. PMID:27486583

  15. Adverse health effects of outdoor air pollutants.

    PubMed

    Curtis, Luke; Rea, William; Smith-Willis, Patricia; Fenyves, Ervin; Pan, Yaqin

    2006-08-01

    Much research on the health effects of outdoor air pollution has been published in the last decade. The goal of this review is to concisely summarize a wide range of the recent research on health effects of many types of outdoor air pollution. A review of the health effects of major outdoor air pollutants including particulates, carbon monoxide, sulfur and nitrogen oxides, acid gases, metals, volatile organics, solvents, pesticides, radiation and bioaerosols is presented. Numerous studies have linked atmospheric pollutants to many types of health problems of many body systems including the respiratory, cardiovascular, immunological, hematological, neurological and reproductive/ developmental systems. Some studies have found increases in respiratory and cardiovascular problems at outdoor pollutant levels well below standards set by such agencies as the US EPA and WHO. Air pollution is associated with large increases in medical expenses, morbidity and is estimated to cause about 800,000 annual premature deaths worldwide [Cohen, A.J., Ross Alexander, H., Ostro, B., Pandey, K.D., Kryzanowski, M., Kunzail, N., et al., 2005. The global burden of disease due to outdoor air pollution. J Toxicol Environ Health A. 68: 1-7.]. Further research on the health effects of air pollution and air pollutant abatement methods should be very helpful to physicians, public health officials, industrialists, politicians and the general public. PMID:16730796

  16. Neurobehavioral and cytotoxic effects of vanadium during oligodendrocyte maturation: a protective role for erythropoietin.

    PubMed

    Mustapha, Oluwaseun; Oke, Bankole; Offen, Nils; Sirén, Anna-Leena; Olopade, James

    2014-07-01

    Vanadium exposure has been known to lead to lipid peroxidation, demyelination and oligodendrocytes depletion. We investigated behaviour and glial reactions in juvenile mice after early neonatal exposure to vanadium, and examined the direct effects of vanadium in oligodendrocyte progenitor cultures from embryonic mice. Neonatal pups exposed to vanadium via lactation for 15 and 22 days all had lower body weights. Behavioural tests showed in most instances a reduction in locomotor activity and negative geotaxis. Brain analyses revealed astrocytic activation and demyelination in the vanadium exposed groups compared to the controls. In cell culture, exposure of oligodendrocytes to 300 μM sodium metavanadate significantly increased cell death. Expression of the oligodendrocyte specific proteins, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and oligodendrocyte specific protein (OSP/Claudin) were reduced upon vanadium treatment while simultaneous administration of erythropoietin (EPO; 4-12 U/ml) counteracted vanadium-toxicity. The data suggest that oligodendrocyte damage may explain the increased vulnerability of the juvenile brain to vanadium and support a potential for erythropoietin as a protective agent against vanadium-toxicity during perinatal brain development and maturation. PMID:24927405

  17. Neurobehavioral and cytotoxic effects of vanadium during oligodendrocyte maturation: a protective role for erythropoietin.

    PubMed

    Mustapha, Oluwaseun; Oke, Bankole; Offen, Nils; Sirén, Anna-Leena; Olopade, James

    2014-07-01

    Vanadium exposure has been known to lead to lipid peroxidation, demyelination and oligodendrocytes depletion. We investigated behaviour and glial reactions in juvenile mice after early neonatal exposure to vanadium, and examined the direct effects of vanadium in oligodendrocyte progenitor cultures from embryonic mice. Neonatal pups exposed to vanadium via lactation for 15 and 22 days all had lower body weights. Behavioural tests showed in most instances a reduction in locomotor activity and negative geotaxis. Brain analyses revealed astrocytic activation and demyelination in the vanadium exposed groups compared to the controls. In cell culture, exposure of oligodendrocytes to 300 μM sodium metavanadate significantly increased cell death. Expression of the oligodendrocyte specific proteins, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and oligodendrocyte specific protein (OSP/Claudin) were reduced upon vanadium treatment while simultaneous administration of erythropoietin (EPO; 4-12 U/ml) counteracted vanadium-toxicity. The data suggest that oligodendrocyte damage may explain the increased vulnerability of the juvenile brain to vanadium and support a potential for erythropoietin as a protective agent against vanadium-toxicity during perinatal brain development and maturation.

  18. Environmental enrichment effects on the neurobehavioral profile of selective outbred trait anxiety rats.

    PubMed

    Ravenelle, Rebecca; Byrnes, Elizabeth M; Byrnes, John J; McInnis, Christine; Park, Jin Ho; Donaldson, S Tiffany

    2013-09-01

    Environmental enrichment attenuates the response to psychostimulants and has been shown to reduce both anxiety and stress-related behaviors. Since stress is a major vulnerability factor for addiction, we investigated whether enrichment could reverse stress profiles in high anxious rats as well as reduce their amphetamine sensitivity. Using selectively-bred high and low anxiety males (filial 3) from enriched, social or isolated environments, we tested elevated plus maze exploration, novelty place preference and amphetamine (AMPH; 0.5mg/kg, IP)-induced hyperactivity. We measured plasma corticosterone (CORT) response after forced novel object exposure, phosphorylation of the tropomyosin-related kinase B receptor (pTrkB) in the hippocampus and striatum, and dopamine (D2) receptor mRNA levels in the striatum and nucleus accumbens. Results indicate that high anxiety animals reared in social or enriched environments spent more time on open arms of the EPM while low anxiety animals raised in enriched environments spent more time on open arms when compared to either isolated or social groups. There were no group differences or interactions found for novelty place preference. Enriched environments decreased the response to AMPH and stress-induced CORT regardless of trait but selectively decreased pTrkB and increased D2 mRNA levels in high anxiety animals. The results suggest that selectively-bred trait anxiety rats show state anxiety that is influenced by rearing environments, and D2 protein levels and BDNF/TrkB signaling may differentially contribute to integrating these effects.

  19. Environmental enrichment effects on the neurobehavioral profile of selective outbred trait anxiety rats

    PubMed Central

    Ravenelle, Rebecca; Byrnes, Elizabeth M.; Byrnes, John J.; McInnis, Christine; Park, Jin Ho; Donaldson, S. Tiffany

    2013-01-01

    Environmental enrichment attenuates the response to psychostimulants and has been shown to reduce both anxiety and stress-related behaviors. Since stress is a major vulnerability factor for addiction, we investigated whether enrichment could reverse stress profiles in high anxious rats as well as reduce their amphetamine sensitivity. Using selectively-bred high and low anxiety males (filial 3) from enriched, social or isolated environments, we tested elevated plus maze exploration, novelty place preference and amphetamine (AMPH; 0.5 mg/kg, IP)-induced hyperactivity. We measured plasma corticosterone (CORT) response after forced novel object exposure, phosphorylation of the tropomyosin-related kinase B receptor (pTrkB) in the hippocampus and striatum, and dopamine (D2) receptor mRNA levels in the striatum and nucleus accumbens. Results indicate that high anxiety animals reared in social or enriched environments spent more time on open arms of the EPM while low anxiety animals raised in enriched environments spent more time on open arms when compared to either isolated or social groups. There were no group differences or interactions found for novelty place preference. Enriched environments decreased the response to AMPH and stress-induced CORT regardless of trait but selectively decreased pTrkB and increased D2 mRNA levels in high anxiety animals. The results suggest that selectively-bred trait anxiety rats show state anxiety that is influenced by rearing environments, and D2 protein levels and BDNF/TrkB signaling may differentially contribute to integrating these effects. PMID:23727174

  20. [Endocrinologic adverse effects of psychotropic drugs].

    PubMed

    Elenitza, Irene María

    2005-01-01

    Psychotropic drugs affect the regulatory mechanisms of different neuroendocrine axis. This chapter reviews the interactions between psychotropic drugs and prolactin, the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis. Hyperprolactinemia can cause galactorrhea, amenorrhea, sexual disfunction, impaired spermatogenesis and increased risk for osteoporosis and fractures. Atypical antipsychotics cause less hyperprolactinemia than conventional antipsychotics. Lithium has important effects on thyroid function. During lithium treatment, affectively ill patients show, in varying degrees and combinations, reduced levels of thyroid hormones and clinical evidence of subclinical hypothyroidism, overt hypothyroidism and goiter. Recent literature reports suggest that valproic acid, may be associated with polycistic ovarian syndrome. Until additional data is available, women starting valproate therapy should be warned about the possibility of endocrinology side effects.

  1. Mirtazapine: pharmacology in relation to adverse effects.

    PubMed

    Nutt, D

    1997-01-01

    Mirtazapine is a new antidepressant that falls into the general class of receptor-blocking drugs rather than being an uptake or enzyme inhibitor. It can be described as a noradrenergic and specific serotonergic antidepressant (NaSSA). The unique pharmacology of mirtazapine means that it has a very different side effect profile from the tricyclic antidepressants, producing less alpha 1 adrenergic and muscarinic blockade, and the selective serotonin reuptake inhibitors (SSRIs) and the serotonin-noradrenaline reuptake inhibitors (SNRIs), causing much less nausea and sexual dysfunction by virtue of its blockade of 5-HT2 and 5-HT3 receptors. PMID:9265949

  2. Adverse health effects of indoor moulds.

    PubMed

    Piecková, Elena

    2012-12-01

    Building associated illnesses - sick building syndrome (SBS) as a common example - are associated with staying in buildings with poor indoor air quality. The importance of indoor fungal growth in this phenomenon continues to be evident, even though no causative relation has been established so far. Indoor humidity is strongly associated with the symptoms of SBS. Fungal metabolites that may induce ill health in susceptible occupants comprise beta-D-glucan, mycotoxins, and volatile organic compounds as known irritants and/or immunomodulators. Indoor toxic fungal metabolites might be located in micromycetal propagules (endometabolites), in (bio-)aerosol, detritus, and house dust (exometabolites) as their particular carriers. It is highly probable that hyphal fragments, dust, and particles able to reach the alveoli have the strongest depository and toxic potential. Most fungal spores are entrapped by the upper respiratory tract and do not reach further than the bronchi because of their size, morphology, and the mode of propagation (such as slime heads and aggreggation). This is why studies of the toxic effects of fungal spores prefer directly applying metabolite mixtures over mimicking real exposure. Chronic low-level exposure to a mixture of fungal toxicants and other indoor stressors may have synergistic effects and lead to severe neuroendocrineimmune changes. PMID:23334050

  3. Neurobehavioral and cognitive performances of children exposed to low-dose radiation in the Chernobyl accident: the Israeli Chernobyl Health Effects Study.

    PubMed

    Bar Joseph, N; Reisfeld, D; Tirosh, E; Silman, Z; Rennert, G

    2004-09-01

    Exposure to low levels of ionizing radiation after the Chernobyl accident in the Ukraine could potentially have influenced the neurobehavioral and cognitive performances of exposed children. A cohort study of adolescents who were children at the time of the accident and who subsequently emigrated to Israel was conducted in 1998-2001. A total of 1,629 children (59% of all 2,769 invited) were included in the study (41% from higher contamination areas, 25% from lower contamination areas, 34% from noncontaminated areas). Mean scores of the Raven Standard Progressive Matrices Test were highest in children in all exposure groups whose parents had a high level of education. No overall relation was found between the cognitive function scores of the child and his/her putative radiation exposure level. Conners' test T scores did not differ significantly by level of exposure. Mothers of all exposure groups who were pregnant at the time of the accident gave their children significantly higher Conners' test scores than did those who were not pregnant. Scores for hyperactivity and attention-deficit/hyperactivity disorder were significantly higher among those who were in utero at the time of the accident. These results do not show differences of neurobehavioral or cognitive performance in exposed versus nonexposed children. There is a possible behavioral effect among offspring of pregnant mothers or mothers of very young children in all exposure levels.

  4. Chloroquine cardiomyopathy: beyond ocular adverse effects

    PubMed Central

    Lopez-Ruiz, Nilson; Uribe, Carlos Esteban

    2014-01-01

    A 36-year-old woman who had received long-term treatment with chloroquine for systemic lupus erythematosus developed a third degree atrioventricular block and required a permanent pacemaker. Notably, left ventricular thickening and mild systolic dysfunction were noticed on echocardiography as well as on cardiac MRI. As there was no clear explanation for myocardial findings, the patient underwent an endomyocardial biopsy that demonstrated vacuolar degeneration of myocytes on light microscopy and curvilinear bodies on electron microscopy, both findings consistent with chloroquine toxicity. The drug was withheld and treatment with candesartan and carvedilol was prescribed. At 2-year follow-up, the patient remained asymptomatic and left ventricular systolic function had improved. Physicians who prescribe antimalarial drugs for rheumatic diseases should be aware of the potentially life-threatening effects of chloroquine on the heart. PMID:25225192

  5. Adverse effects of the radioprotector WR2721

    SciTech Connect

    Cairnie, A.B.

    1983-04-01

    S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic - in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy /sup 60/Co ..gamma.. radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approx.200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation.

  6. Neurobehavioral Assessment from Fetus to Infant: The NICU Network Neurobehavioral Scale and the Fetal Neurobehavior Coding Scale

    ERIC Educational Resources Information Center

    Salisbury, Amy L.; Fallone, Melissa Duncan; Lester, Barry

    2005-01-01

    This review provides an overview and definition of the concept of neurobehavior in human development. Two neurobehavioral assessments used by the authors in current fetal and infant research are discussed: the NICU Network Neurobehavioral Assessment Scale and the Fetal Neurobehavior Coding System. This review will present how the two assessments…

  7. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

    PubMed Central

    Ajaltouni, Jean

    2015-01-01

    The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

  8. Adverse effects of anabolic steroids in athletes. A constant threat.

    PubMed

    Maravelias, C; Dona, A; Stefanidou, M; Spiliopoulou, C

    2005-09-15

    Anabolic-androgenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance by augmenting muscular development and strength. AAS administration is often associated with various adverse effects that are generally dose related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organ damage. Among the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and masculinization in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice, hepatic neoplasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviews the reproductive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic and psychologic effects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided, emphasizing that sports goals may be met within the framework of honest competition, free of doping substances.

  9. Apoptosis may involve in prenatally heroin exposed neurobehavioral teratogenicity?

    PubMed

    Ying, Wang; Jang, Farhan Fateh; Teng, Chen; Tai-Zhen, Han

    2009-12-01

    Heroin abuse during pregnancy is a serious problem worldwide. Among all the illicit drugs, heroin is known as the most commonly abused opioid in the United States and China. Most women addicts are of child-bearing age. Heroin abuse during pregnancy, together with related factors like poor nutrition and inadequate maternal care, has been associated with adverse consequences including developmental delay of the offspring and their neurobehavioral teratogenicity. Researchers have done a lot of work to focus mainly on the variation of neurobehavior and its related factors such as the changes of neurotransmitters, receptors and involvement of the limited brain regions, but no one clearly and comprehensively explain the possible mechanism that may participate in the neurobehavioral teratogenicity induced by prenatal heroin exposure. Studies on animals have shown that heroin is a common neuroteratogen which can produce neurobehavioral defects. There must be some underlying mechanisms in the central nervous system which may take part in these defects. We hypothesized that the alterations in developmental apoptosis during embryogenesis could be one of the possible mechanisms which can cause neurobehavioral teratogenicity in prenatally heroin exposed offspring. Heroin is believed to pass through the placenta and blood-brain barrier much more rapidly than morphine due to the presence of acetyl groups and affects the developing brain. So far, it still remains obscure that whether the apoptosis in a particular brain region induced by heroin exposure in uterus is involved in neurobehavioral teratogenicity. Our hypothesis perhaps provides a more logical and possible explanation of the mechanism responsible for neurobehavioral teratogenicity caused by the prenatal heroin exposure during embryonic development. It can help to develop appropriate experimental animal models to understand the detailed mechanisms involved.

  10. Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

    PubMed Central

    Lester, Barry M.; Andreozzi-Fontaine, Lynne; Tronick, Edward; Bigsby, Rosemarie

    2014-01-01

    There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used. PMID:25177897

  11. Neurological adverse effects of methylphenidate may be misdiagnosed as meningoencephalitis.

    PubMed

    Snell, Luke Blagdon; Bakshi, Dinkar

    2015-06-16

    We present a case of adverse neurological effects of methylphenidate therapy for attention deficit and hyperactivity disorder (ADHD). A 7-year-old boy presented to the emergency department (ED) having developed ataxic gait, orofacial dyskinesias and choreoathetosis of the limbs. The results of all blood investigations, EEG and CT scan of the head were unremarkable. Subsequently, a detailed history revealed he was being treated for ADHD, being started on methylphenidate in the past 3 months. Discontinuation of methylphenidate led to significant and rapid amelioration of neurological adverse effects.

  12. Neurobehavioral performance in adolescents is inversely associated with traffic exposure.

    PubMed

    Kicinski, Michal; Vermeir, Griet; Van Larebeke, Nicolas; Den Hond, Elly; Schoeters, Greet; Bruckers, Liesbeth; Sioen, Isabelle; Bijnens, Esmée; Roels, Harry A; Baeyens, Willy; Viaene, Mineke K; Nawrot, Tim S

    2015-02-01

    On the basis of animal research and epidemiological studies in children and elderly there is a growing concern that traffic exposure may affect the brain. The aim of our study was to investigate the association between traffic exposure and neurobehavioral performance in adolescents. We examined 606 adolescents. To model the exposure, we constructed a traffic exposure factor based on a biomarker of benzene (urinary trans,trans-muconic acid) and the amount of contact with traffic preceding the neurobehavioral examination (using distance-weighted traffic density and time spent in traffic). We used a Bayesian structural equation model to investigate the association between traffic exposure and three neurobehavioral domains: sustained attention, short-term memory, and manual motor speed. A one standard deviation increase in traffic exposure was associated with a 0.26 standard deviation decrease in sustained attention (95% credible interval: -0.02 to -0.51), adjusting for gender, age, smoking, passive smoking, level of education of the mother, socioeconomic status, time of the day, and day of the week. The associations between traffic exposure and the other neurobehavioral domains studied had the same direction but did not reach the level of statistical significance. The results remained consistent in the sensitivity analysis excluding smokers and passive smokers. The inverse association between sustained attention and traffic exposure was independent of the blood lead level. Our study in adolescents supports the recent findings in children and elderly suggesting that traffic exposure adversely affects the neurobehavioral function. PMID:25461422

  13. Neurobehavioral, autonomic nervous function and lymphocyte subsets among aluminum electrolytic workers.

    PubMed

    He, S C; Qiao, N; Sheng, W

    2003-01-01

    The purpose of our study is to determine the alteration of neurobehavioral parameters, autonomic nervous function and lymphocyte subsets in aluminum electrolytic workers of long-term aluminum exposure. 33 men who were 35.16 +/- 2.95 (mean +/- S.D) years old occupationally exposed to aluminum for 14.91 +/- 6.31 (mean +/- S.D) years. Air Al level and urinary aluminum concentration was measured by means of graphite furnace atomic absorption spectrophotometer. Normal reference group were selected from a flour plant. Neurobehavioral core test battery (NCTB) recommended by WHO was utilized. Autonomic nervous function test battery recommended by Ewing DJ was conducted on subjects. FAC SCAN was used to measure the lymphocyte subsets of peripheral blood. The mean air aluminum level in the workshop was 6.36 mg/m3, ranged from 2.90 to 11.38 mg/m3. Urinary aluminum of the Al electrolytic workers (40.08 +/- 9.36 microgram/mg.cre) was obviously higher than that of control group (26.84 +/- 8.93 m/mg.cre). Neurobehavioral results showed that the scores of DSY, PAC and PA in Al electrolytic workers were significantly lower than those of control group, The score of POMSC, POMSF and SRT among Al exposed workers were significantly augmented in relation to those of control group. Autonomic nervous function test results showed that R-R interval variability of maximum ratio of immediately standing up in Al electrolytic workers were decreased compare with the control group, while the BP-IS, HR-V, HR-DB, R30:15 had no significant change. Peripheral blood lymphocyte subsets test showed that CD4-CD8+ T lymphocyte in Al electrolytic workers increased. This study suggests that Al exposure exerts adverse effects on neurobehavioral performance, especially movement coordination and negative mood, and parasympathetic nervous function; moreover it increase CD4-CD8+ T lymphocyte subsets.

  14. Amiodarone-induced hypothyroidism and other adverse effects.

    PubMed

    Mosher, Mary C

    2011-01-01

    Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management. PMID:21307683

  15. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  16. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  17. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  18. Skin-lightening cosmetics: frequent, potentially severe adverse effects.

    PubMed

    2011-09-01

    Skin-lightening cosmetics are used by many women and men around the world. The products contain a variety of substances, which are often unknown to the users. Most of these products include topical corticosteroids, hydroquinone and mercury salts. Many other substances may be added. Several surveys and cohort studies, including several thousand individuals, have shown that regular application of skin-lightening cosmetics to large surface areas can have irreversible cutaneous adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch marks and delayed wound healing, and can also mask or, on the contrary, promote or reactivate skin infections. Cases of skin cancer have been attributed to skin-lightening cosmetics. A Senegalese cohort study of 147 women showed a statistically significant increase in the risk of hypertension and diabetes linked to the use of skin-lightening agents. Other systemic adverse effects attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders. Hypersensitivity reactions, including anaphylaxis, have also been attributed to these products. Many skin-lightening cosmetics contain substances that can harm the unborn child. For example, tretinoin is teratogenic while salicylic acid is feto-toxic. In practice, users are often unaware of the risk of severe adverse effects associated with skin-lightening cosmetics. Users should be informed of these adverse effects and encouraged to stop using these products, especially when skin disorders appear.

  19. [Study progress of adverse effects of arsenic on health].

    PubMed

    Kang, Jiaqi; Jin, Yinlong

    2004-05-01

    Adverse effects on health of high arsenic in drinking water and contaminated environment are currently of great concern. This review focuses on metabolism of arsenic and it's impairments to skin, blood circle system, nervous system, reproductive-and-urinary system, digestive system, respiratory system and immune system.

  20. Mixed-effects Poisson regression analysis of adverse event reports

    PubMed Central

    Gibbons, Robert D.; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K.; Bhaumik, Dulal K.; Brown, C. Hendricks; Kapur, Kush; Marcus, Sue M.; Hur, Kwan; Mann, J. John

    2008-01-01

    SUMMARY A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)’s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  1. Indoor air pollution: Acute adverse health effects and host susceptibility

    SciTech Connect

    Zummo, S.M.; Karol, M.H.

    1996-01-01

    Increased awareness of the poor quality of indoor air compared with outdoor air has resulted in a significant amount of research on the adverse health effects and mechanisms of action of indoor air pollutants. Common indoor air agents are identified, along with resultant adverse health effects, mechanisms of action, and likely susceptible populations. Indoor air pollutants range from biological agents (such as dust mites) to chemical irritants (such as nitrogen dioxide, carbon monoxide, sulfur dioxide, formaldehyde, and isocyanates). These agents may exert their effects through allergic as well as nonallergic mechanisms. While the public does not generally perceive poor indoor air quality as a significant health risk, increasing reports of illness related to indoor air and an expanding base of knowledge on the health effects of indoor air pollution are likely to continue pushing the issue to the forefront.

  2. Effect of wettability on adverse mobility immiscible floods

    SciTech Connect

    Vives, M.T.; Chang, Y.C.; Mohanty, K.K.

    1995-12-31

    Many immiscible displacements in reservoirs occur at adverse mobility. Effect of wettability on these displacements is not well understood and often ignored in reservoir simulation. Recent macroscopic theories of viscous fingering treat adverse immiscible flows similar to miscible flows, the mixing in the fingered region being controlled by a Todd-Longstaff-type functional form. The wettability of the medium is taken into account only through the use of appropriate relative permeabilities. The goal of this paper is to understand the macroscopic bypassing in adverse mobility immiscible floods. Immiscible displacements are conducted in a quarter 5-spot model in both drainage and imbibition modes at similar effective mobility ratios and viscous-to-gravity numbers. The level of bypassing and gravity override is visualized and measured. Tertiary water-alternating-gas (WAG) displacements are also conducted at various WAG ratios and viscosity ratios. Fractional flow analysis and numerical simulation are used to understand these displacements. Experiments show that macroscopic viscous fingering is present in adverse viscosity immiscible displacements where no saturation shock is expected from 1-D fractional flow theory. Bypassing due to both fingering and gravity override is higher in the drainage mode than in the imbibition mode, with other key parameters being the same. Optimum WAG ratio in water-wet rock is a function of oil/solvent viscosity ratio. The macroscopic flow theory needs to include capillarity and viscous fingering to match these experimental findings.

  3. Thai traditional massage: Issues causing possible adverse effects.

    PubMed

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed. PMID:26865746

  4. Energy Drink Consumption: Beneficial and Adverse Health Effects

    PubMed Central

    Alsunni, Ahmed Abdulrahman

    2015-01-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents. PMID:26715927

  5. Optimising the retrieval of information on adverse drug effects.

    PubMed

    Golder, Su

    2013-12-01

    Pharmaceutical interventions have brought about many benefits to health, improving the population's well-being and life expectancy. However, these interventions are not without potential harmful side-effects and yet searching for the evidence on adverse effects is challenging. This article summarises a PhD whose main aim was to develop a better understanding of the implications of using different sources and approaches to identifying relevant data on adverse effects. The author is Su Golder, who has recently completed her PhD at the University of York and who has already published several articles on specific aspects of her research, including this journal. This article is the first in the Dissertations into Practice series to report on a PhD study, and it summarises her research in a way which emphasises the implications for practice.

  6. Energy Drink Consumption: Beneficial and Adverse Health Effects.

    PubMed

    Alsunni, Ahmed Abdulrahman

    2015-10-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents. PMID:26715927

  7. Ocular surface adverse effects of ambient levels of air pollution.

    PubMed

    Torricelli, André Augusto Miranda; Novaes, Priscila; Matsuda, Monique; Alves, Milton Ruiz; Monteiro, Mário Luiz Ribeiro

    2011-01-01

    It is widely recognized today that outdoor air pollution can affect human health. Various chemical components that are present in ambient pollution may have an irritant effect on the mucous membranes of the body, particularly those of the respiratory tract. Much less attention has been focused on the adverse effect on the ocular surface, despite the fact that this structure is even more exposed to air pollution than the respiratory mucosa since only a very thin tear film separates the corneal and conjunctival epithelia from the air pollutants. So far, clinical data are the more widespread tools used by ophthalmologists for assessing possible aggression to the ocular surface; however, clinical findings alone appears not to correlate properly with the complaints presented by the patients pointing out the need for further clinical and laboratory studies on the subject. The purpose of this study is to review signs and symptoms associated with chronic long-term exposure to environmental air pollutants on the ocular structures currently defined as the ocular surface and to review clinical and laboratory tests used to investigate the adverse effects of air pollutants on such structures. We also review previous studies that investigated the adverse effects of air pollution on the ocular surface and discuss the need for further investigation on the subject.

  8. Mechanisms and assessment of statin-related muscular adverse effects.

    PubMed

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-09-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers.

  9. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  10. Psychological adverse effects of cannabis smoking: a tentative classification.

    PubMed

    Nigrete, J C

    1973-01-20

    This paper stresses the need for an early definition and description of the "deviant" cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as "problem" users from other smokers.A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions.

  11. Psychological adverse effects of cannabis smoking: a tentative classification.

    PubMed

    Nigrete, J C

    1973-01-20

    This paper stresses the need for an early definition and description of the "deviant" cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as "problem" users from other smokers.A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions. PMID:4569453

  12. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    PubMed Central

    Kitzmiller, Joseph P; Mikulik, Eduard B; Dauki, Anees M; Murkherjee, Chandrama; Luzum, Jasmine A

    2016-01-01

    Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. PMID:27757045

  13. No effects of power line frequency extremely low frequency electromagnetic field exposure on selected neurobehavior tests of workers inspecting transformers and distribution line stations versus controls.

    PubMed

    Li, Li; Xiong, De-fu; Liu, Jia-wen; Li, Zi-xin; Zeng, Guang-cheng; Li, Hua-liang

    2014-03-01

    We aimed to evaluate the interference of 50 Hz extremely low frequency electromagnetic field (ELF-EMF) occupational exposure on the neurobehavior tests of workers performing tour-inspection close to transformers and distribution power lines. Occupational short-term "spot" measurements were carried out. 310 inspection workers and 300 logistics staff were selected as exposure and control. The neurobehavior tests were performed through computer-based neurobehavior evaluation system, including mental arithmetic, curve coincide, simple visual reaction time, visual retention, auditory digit span and pursuit aiming. In 500 kV areas electric field intensity at 71.98% of total measured 590 spots were above 5 kV/m (national occupational standard), while in 220 kV areas electric field intensity at 15.69% of total 701 spots were above 5 kV/m. Magnetic field flux density at all the spots was below 1,000 μT (ICNIRP occupational standard). The neurobehavior score changes showed no statistical significance. Results of neurobehavior tests among different age, seniority groups showed no significant changes. Neurobehavior changes caused by daily repeated ELF-EMF exposure were not observed in the current study. PMID:24379132

  14. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

  15. Adverse effects of creatine supplementation: fact or fiction?

    PubMed

    Poortmans, J R; Francaux, M

    2000-09-01

    The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects

  16. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  17. Genetics of Common Antipsychotic-Induced Adverse Effects.

    PubMed

    MacNeil, Raymond R; Müller, Daniel J

    2016-07-01

    The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria primarily pertain to metabolic dysregulation, extrapyramidal symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation, results have reaffirmed HTR2C as a strong candidate with potential clinical utility, while MC4R and OGFR1 gene loci have emerged as new and promising biomarkers for the prediction of weight gain. As for EPS and TD, additional evidence has accumulated in support of an association with CYP2D6 metabolizer status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with the potential to predict differential susceptibility to TD. Overall, considerable progress has been made within the field of psychiatric PGx, with inroads toward the development of clinical tools that can mitigate AAEs. Going forward, studies placing a greater emphasis on multilocus effects will need to be conducted. PMID:27606321

  18. Psychological adverse effects of cannabis smoking: a tentative classification

    PubMed Central

    Negrete, J. C.

    1973-01-01

    This paper stresses the need for an early definition and description of the “deviant” cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as “problem” users from other smokers. A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions. PMID:4569453

  19. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

    PubMed Central

    Bersani, F. Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M.; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  20. CN-15ADVERSE EFFECTS OF BEVACIZUMAB IN BRAIN TUMOR PATIENTS

    PubMed Central

    Pawar, Tushar; Ladha, Harshad; Mandel, Jacob; Gilbert, Mark; O'Brien, Barbara; Hamza, Mohamed; Armstrong, Terri

    2014-01-01

    BACKGROUND: Bevacizumab is humanized monoclonal antibody inhibiting angiogenesis and the only FDA approved treatment for recurrent glioblastoma. The aim of this study was to look at the occurrence of various adverse effects associated with use of bevacizumab in recurrent glioblastoma. METHODS: In this retrospective chart review, we studied 280 patients with recurrent glioblastoma treated with Bevacizumab between 2005-2011 to characterize the known adverse effects of bevacizumab including hypertension, grade 3-4 myelosuppression, wound healing complications, thrombo-embolic events, stroke, hemorrhage and gastrointestinal complications. RESULTS: The study population included 168 males and 112 females. The median age was 53.5 years(range 8.1-81.3). TREATMENT: Bevacizumab only(58), Bevacizumab + CPT(11), Bevacizumab + TMZ(32) or Bevacizumab + Other(34). Patients were treated at recurrence(1st = 96; 2nd = 126, 3rd = 58). Hypertension was the most common adverse effect occurring in 131(49%). The median duration from treatment start to development was 82 days (Range 7-1143). However, only 33(25%) were started on antihypertensive medication. Grade 3-4 Myelosuppression occurred in 52(19%)causing treatment discontinuation in 8. Thrombo-embolic events were reported in 5%(15) patients including DVT(9), PE(2), Central venous thrombosis(1) and Stroke(3). Thirty-six patients (13%) were on anti-coagulant medication at bevacizumab initiation. Median time to a thromboembolic complication was 113 days (Range 8-1145). Wound healing complications were noted in 7(3%) patients, 3 craniotomy dehiscence and 4 at soft tissue sites. Five patients (2%) developed GI complications, including perforations(3), pancreatitis(1), and diverticulitis(1). Median time to development was 92 days(Range 10-651). There was a high rate 46%(129) of grade 3-4 lymphocytopenia; median time to develop lymphocytopenia was 50 days(Range = 3-564). CONCLUSION: The range of toxicities was similar to other reports

  1. Effects of a rapid-resisted elliptical training program on motor, cognitive and neurobehavioral functioning in adults with chronic traumatic brain injury.

    PubMed

    Damiano, Diane L; Zampieri, Cristiane; Ge, Jie; Acevedo, Ana; Dsurney, John

    2016-08-01

    This small clinical trial utilized a novel rehabilitation strategy, rapid-resisted elliptical training, in an effort to increase motor, and thereby cognitive, processing speed in ambulatory individuals with traumatic brain injury (TBI). As an initial step, multimodal functional abilities were quantified and compared in 12 ambulatory adults with and 12 without TBI. After the baseline assessment, the group with TBI participated in an intensive 8-week daily exercise program using an elliptical trainer and was reassessed after completion and at an 8-week follow-up. The focus of training was on achieving a fast movement speed, and once the target was reached, resistance to motion was increased in small increments to increase intensity of muscle activation. Primary outcomes were: High-Level Mobility Assessment Tool (HiMAT), instrumented balance tests, dual-task (DT) performance and neurobehavioral questionnaires. The group with TBI had poorer movement excursion during balance tests and poorer dual-task (DT) performance. After training, balance reaction times improved and were correlated with gains in the HiMAT and DT. Sleep quality also improved and was correlated with improved depression and learning. This study illustrates how brain injury can affect multiple linked aspects of functioning and provides preliminary evidence that intensive rapid-resisted training has specific positive effects on dynamic balance and more generalized effects on sleep quality in TBI.

  2. Effects of a rapid-resisted elliptical training program on motor, cognitive and neurobehavioral functioning in adults with chronic traumatic brain injury

    PubMed Central

    Zampieri, Cris; Ge, Jie; Acevedo, Ana; Dsurney, John

    2016-01-01

    This small clinical trial utilized a novel rehabilitation strategy, rapid-resisted elliptical training, in an effort to increase motor, and thereby cognitive, processing speed in ambulatory individuals with traumatic brain injury (TBI). As an initial step, multimodal functional abilities were quantified and compared in 12 ambulatory adults with and 12 without TBI. After the baseline assessment, the group with TBI participated in an intensive 8-week daily exercise program using an elliptical trainer and was reassessed after completion and at an 8-week follow-up. The focus of training was on achieving a fast movement speed, and once the target was reached, resistance to motion was increased in small increments to increase intensity of muscle activation. Primary outcomes were: High-Level Mobility Assessment Tool (HiMAT), instrumented balance tests, dual-task (DT) performance and neurobehavioral questionnaires. The group with TBI had poorer movement excursion during balance tests and poorer dual-task (DT) performance. After training, balance reaction times improved and were correlated with gains in the HiMAT and DT. Sleep quality also improved and was correlated with improved depression and learning. This study illustrates how brain injury can affect multiple linked aspects of functioning and provides preliminary evidence that intensive rapid-resisted training has specific positive effects on dynamic balance and more generalized effects on sleep quality in TBI. PMID:27025506

  3. The Cumulative Neurobehavioral and Physiological Effects of Chronic Caffeine Intake: Individual Differences and Implications for the Use of Caffeinated Energy Products

    PubMed Central

    Spaeth, Andrea M; Goel, Namni; Dinges, David F

    2014-01-01

    The use of caffeine-containing energy products (CCEP) has increased worldwide in recent years and research shows that CCEP can improve cognitive and physical performance. All of the top-selling energy drinks contain caffeine, which is likely to be the primary psychoactive ingredient in CCEP. Presumably, individuals consume CCEP to counteract feelings of ‘low-energy’ in situations causing tiredness, fatigue, and/or reduced alertness. This review discusses the scientific evidence for sleep loss, circadian phase, sleep inertia and the time-on-task effect as causes of ‘low energy’ and summarizes research assessing the efficacy of caffeine to counteract decreased alertness and increased fatigue in such situations. The results of a placebo-controlled experiment on healthy adults undergoing three nights of total sleep deprivation (with or without 2 hour naps every 12 hours) are presented to illustrate the physiological and neurobehavioral effects of sustained low-dose caffeine. Individual differences, including genetic factors, in the response to caffeine and to sleep loss are discussed. We conclude with future directions for research on this important and evolving topic. PMID:25293542

  4. Evaluation of reliability of traditional and computerized neurobehavioral tests.

    PubMed

    Sakong, Joon; Kang, Pock-Soo; Kim, Chang-Yoon; Hwang, Tae-Yoon; Jeon, Man-Joong; Park, Si-Young; Lee, Se-Jin; Won, Kyu-Chang; Lee, Sam-Beom; Chung, Jong-Hak

    2007-03-01

    Most Korean blue-collar workers are taking government-mandated medical screening periodically. The periodic neurobehavioral test provides a great chance to evaluate the functional change of the central nervous system. To utilize periodic neurobehavioral tests effectively, the reliability of currently used neurobehavioral tests needs to be evaluated. Test-retest of neurobehavioral tests were conducted to evaluate the reliability of neurobehavioral tests that are commonly used for Korean workers. The test-retest of five computerized tests, simple reaction time, additions, symbol digit, digit span, and finger tapping speed, and five traditional tests, Benton visual retention, digit symbol, digit span, pursuit aiming, and pegboard, were administered to 85 college students and 35 hospital workers over a 1 month interval. Computerized additions was found to have the highest test-retest reliability coefficient (r=0.90), followed by finger tapping speed (nondominant hand, r=0.89; dominant hand, r=0.85), symbol digit (r=0.82), and digit span (r=0.74). However, only two traditional tests, digit symbol (r=0.86) and pursuit aiming (r=0.72), showed a reliability coefficient greater than 0.70. These results suggest that the computerized additions, symbol digit, finger tapping speed, and traditional digit symbol are more satisfactory for periodical evaluation of the central nervous system of workers exposed to neurotoxic substances in Korea.

  5. Adverse health effects of lead exposure on children and exploration to internal lead indicator.

    PubMed

    Wang, Q; Zhao, H H; Chen, J W; Gu, K D; Zhang, Y Z; Zhu, Y X; Zhou, Y K; Ye, L X

    2009-11-15

    Our research on adverse effects of lead exposures on physical and neurobehavioral health of children aged 6-12years in 4 villages, labeled as K, M, L, and X, in rural China, was reported in this article. Lead in blood (PbB), urine (PbU), hairs (PbH), and nails (PbN) were measured by graphite furnace atomic absorption spectrometry. Abbreviated Symptom Questionnaire of Conner's instruments and Revised Raven's Standard Progressive Matrices were applied to evaluate childhood attention deficit/hyperactivity disorders (ADHD) and intelligences. Geometric means (SD) of PbB, PbU, PbH and PbN concentrations were 71.2 microg/L (1.56), 11.7 microg/g (1.75), 12.5 microg/g (2.82), and 25.3 microg/g (2.79), respectively. 54 (17.0%) children had PbB levels of > or =100 microg/L. Boys, 6-10 years old, and living in village K were 2.11, 2.48, and 9.16 times, respectively, more likely to be poisoned by lead than girls, aged 11-12 years, and residing in X. 18 (5.7%) and 37 (11.7%) subjects had ADHD and mental retardations, respectively. Inverse relationships between intelligences and natural log transformed PbU and PbH levels were observed with respective odds ratios (95%CI) of 1.79 (1.00-3.22) and 1.46 (1.06-2.03) or 1.28 (1.04-1.58) and 1.73 (1.18-2.52) by binary or ordinal logistic regression modeling. ADHD prevalence was different by gender and age of subjects. PbU, PbH, and PbN related to PbB positively with respective correlation coefficients of 0.530, 0.477, and 0.181. Receiver operating characteristic (ROC) curves of the three measurements revealed areas under curves (AUCs) being 0.829, 0.758, and 0.687, respectively. In conclusion, children had moderate levels of lead exposures in this rural area. Intelligence declines were associated with internal lead levels among children. ROC analysis suggests PbU an internal lead indicator close to PbB.

  6. Adverse effects of bisphenol A on male reproductive function.

    PubMed

    Manfo, Faustin Pascal Tsagué; Jubendradass, Rajamanickam; Nantia, Edouard Akono; Moundipa, Paul Fewou; Mathur, Premendu Prakash

    2014-01-01

    BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the

  7. Adverse effects of outdoor pollution in the elderly

    PubMed Central

    Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  8. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  9. Adverse effects of outdoor pollution in the elderly.

    PubMed

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  10. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  11. Pharmacovigilance, risks and adverse effects of self-medication.

    PubMed

    Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle; Abadie, Delphine; Lacroix, Isabelle; Berreni, Aurélia; Pugnet, Grégory; Durrieu, Geneviève; Sailler, Laurent; Giroud, Jean-Paul; Damase-Michel, Christine; Montastruc, François

    2016-04-01

    Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

  12. Possible adverse effects of frying with vegetable oils.

    PubMed

    Dobarganes, Carmen; Márquez-Ruiz, Gloria

    2015-04-01

    The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

  13. Symptomatic sinus bradycardia: A rare adverse effect of intravenous ondansetron

    PubMed Central

    Moazzam, Md Shahnawaz; Nasreen, Farah; Bano, Shahjahan; Amir, Syed Hussain

    2011-01-01

    Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind. PMID:21655029

  14. Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

    PubMed Central

    Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

    2012-01-01

    Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

  15. Clinical outcomes and adverse effect monitoring in allergic rhinitis.

    PubMed

    Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

    2005-03-01

    The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably

  16. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. - Highlights: • Botox® injections are the trend nowadays, for both medical and non-medical uses. • They were recently suggested for cryptorchidism and

  17. Aloe vera: A review of toxicity and adverse clinical effects.

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-01

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex.

  18. European guidelines on managing adverse effects of medication for ADHD

    PubMed Central

    Banaschewski, T.; Buitelaar, J.; Coghill, D.; Danckaerts, M.; Dittmann, R. W.; Döpfner, M.; Hamilton, R.; Hollis, C.; Holtmann, M.; Hulpke-Wette, M.; Lecendreux, M.; Rosenthal, E.; Rothenberger, A.; Santosh, P.; Sergeant, J.; Simonoff, E.; Sonuga-Barke, E.; Wong, I. C. K.; Zuddas, A.; Steinhausen, H.-C.; Taylor, E.

    2010-01-01

    The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks. PMID:21042924

  19. Aloe vera: A review of toxicity and adverse clinical effects.

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-01

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex. PMID:26986231

  20. Organophosphate pesticide exposure and neurobehavioral performance in agricultural and non-agricultural Hispanic workers.

    PubMed

    Rothlein, Joan; Rohlman, Diane; Lasarev, Michael; Phillips, Jackie; Muniz, Juan; McCauley, Linda

    2006-05-01

    Our understanding of the health risks of farmworkers exposed to pesticides in their work and home environments is rapidly increasing, although studies designed to examine the possible neurobehavioral effects of low-level chronic pesticide exposure are limited. We measured dialkyl phosphate urinary metabolite levels, collected environmental dust samples from a subset of homes, obtained information on work practices, and conducted neurobehavioral tests on a sample of farmworkers in Oregon. Significant correlations between urinary methyl metabolite levels and total methyl organophosphate (azinphos-methyl, phosmet, malathion) house dust levels were observed. We found the neurobehavioral performance of Hispanic immigrant farmworkers to be lower than that observed in a nonagricultural Hispanic immigrant population, and within the sample of agricultural workers there was a positive correlation between urinary organophosphate metabolite levels and poorer performance on some neurobehavioral tests. These findings add to an increasing body of evidence of the association between low levels of pesticide exposure and deficits in neurobehavioral performance. PMID:16675422

  1. Adverse effects of sucrose-rich diets on uraemic rats.

    PubMed

    Laouari, D; Kleinknecht, C; Burtin, M; Hinglais, N; Lacour, B; Landais, P; Broyer, M

    1990-01-01

    The nature of carbohydrate may affect the tolerance and progression of uraemia. The effects of three diets differing only in their carbohydrate source: namely corn starch (C), glucose (G) or sucrose (S) were examined. Study 1 examined the effects of the three carbohydrate diets on unilaterally nephrectomised control rats and severely uraemic rats. The three carbohydrates produced similar nutritional effects in uninephrectomised rats, whereas sucrose rapidly induced anorexia, stunting and slightly accelerated renal damage in uraemia. Study 2 examined the long-term effects of the three carbohydrates in moderate uraemia under conditions of high and identical carbohydrate intakes. Hyperphagic Zucker uraemic rats (F rats) received a daily allotment of each diet plus pure carbohydrate. Lean uraemic rats (L rats) received the same dietary allotment without the carbohydrate supplement. The F rats fed sucrose showed greater morbidity and mortality but little renal deterioration. Their plasma triglycerides increased dramatically. The L rats fed sucrose had the greatest urinary protein, the least creatinine clearance and the most severe renal damage. Thus, sucrose-rich but not glucose-rich diets have two adverse effects in uraemia: a deterioration in nutritional status, perhaps related to abnormal fructose utilisation, and a long-term effect on the kidney, resulting in accelerated renal deterioration.

  2. Identifying and managing adverse environmental health effects: 3. Lead exposure

    PubMed Central

    Sanborn, Margaret D.; Abelsohn, Alan; Campbell, Monica; Weir, Erica

    2002-01-01

    LEAD LEVELS IN NORTH AMERICAN CHILDREN AND ADULTS have declined in the past 3 decades, but lead persists in the environment in lead paint, old plumbing and contaminated soil. There are also a number of occupations and hobbies that carry a high risk of lead exposure. There is no evidence for a threshold below which lead has no adverse health effects. Blood lead levels previously considered safe are now known to cause subtle, chronic health effects. The health effects of lead exposure include developmental neurotoxicity, reproductive dysfunction and toxicity to the kidneys, blood and endocrine systems. Most lead exposures are preventable, and diagnosing lead poisoning is relatively simple compared with diagnosing health effects of exposures to other environmental toxins. Accurate assessment of lead poisoning requires specific knowledge of the sources, high-risk groups and relevant laboratory tests. In this article we review the multiple, systemic toxic effects of lead and provide current information on groups at risk, prevention, diagnosis and clinical treatment. We illustrate how the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) and specific screening questions are useful tools for physicians to quickly obtain an environmental exposure history and identify patients at high risk of lead exposure. By applying effective primary prevention, case-finding and treatment interventions for lead exposure, both the individual patient and the larger community reap the benefits of better health. PMID:12041847

  3. The dark side of the light: Phototherapy adverse effects.

    PubMed

    Valejo Coelho, Margarida Moura; Apetato, Margarida

    2016-01-01

    Phototherapy is a valuable therapeutic tool in Dermatology, but there may be drawbacks. Acute and long-term adverse effects, of variable severity, include skin erythema, xerosis, pruritus, blistering, altered pigmentation, photoaging, and photocarcinogenesis. Despite concerns over the carcinogenic potential of ultraviolet radiation, most studies have not found an increased risk of non-melanoma or melanoma skin cancer in patients treated with ultraviolet B (broadband and narrowband) and ultraviolet A1 phototherapy. These are therefore considered reasonably safe treatment modalities concerning the development of skin neoplasms, although caution and further investigation are warranted. Photoprotective measures, such as avoidance of concurrent sunlight exposure and covering skin areas not afflicted with disease, or more modern strategies, including phytochemical antioxidants and exogenous DNA repair enzymes, can minimize the hazards of phototherapy. Patients submitted to phototherapeutic regimens should undergo complete, careful dermatologic examination regularly and lifelong. PMID:27638433

  4. Vanadium Exposure-Induced Neurobehavioral Alterations among Chinese Workers

    PubMed Central

    Li, Hong; Zhou, Dinglun; Zhang, Qin; Feng, Chengyong; Zheng, Wei; He, Keping; Lan, Yajia

    2014-01-01

    Vanadium-containing products are manufactured and widely used in the modern industry. Yet the neurobehavioral toxicity due to occupational exposure to vanadium remained elusive. This cross-sectional study was designed to examine the neurotoxic effects of occupational vanadium exposure. A total of 463 vanadium-exposed workers (exposed group) and 251 non-exposed workers (control group) were recruited from a Steel and Iron Group in Sichuan, China. A WHO-recommended neurobehavioral core test battery (NCTB) and event-related auditory evoked potentials test (P300) were used to assess the neurobehavioral functions of all study subjects. A general linear model was used to compare outcome scores between the two groups while controlling for possible confounders. The exposed group showed a statistically significant neurobehavioral alteration more than the control group in the NCTB tests. The exposed workers also exhibited an increased anger-hostility, depression-dejection and fatigue-inertia on the profile of mood states (p<0.05). Performances in the Simple Reaction Time, Digit Span, Benton Visual Retention and Pursuit Aiming were also poorer among exposed workers as compared to unexposed control workers(p<0.05). Some of these poor performances in tests were also significantly related to workers’ exposure duration. P300 latencies were longer in the exposed group than in the control (p<0.05). Longer mean reaction times and more counting errors were also found in the exposed workers (p<0.05). Given the findings of our study and the limitations of neurobehavioral workplace testing, we found evidence of altered neurobehavioral outcomes by occupational exposure to vanadium. PMID:23500660

  5. Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats.

    PubMed

    Das, Saroj Kumar; Patel, Bhupesh; Patri, Manorama

    2016-01-01

    Exposure to persistent genotoxicants like benzo[a]pyrene (B[a]P) during postnatal days causes neurobehavioral changes in animal models. However, neurotoxic potential of B[a]P and its association with 6-hydroxydopamine (6-OHDA) induced neurobehavioral changes are yet to be explored. The growth of rat brain peaks at the first week of birth and continues up to one month with the attainment of adolescence. Hence, the present study was conducted on male Wistar rats at postnatal day 5 (PND 5) following single intracisternal administration of B[a]P to compare with neurobehavioral and neurotransmitter changes induced by 6-OHDA at PND 30. Spontaneous motor activity was significantly increased by 6-OHDA showing similar trend following B[a]P administration. Total distance travelled in novel open field arena and elevated plus maze was significantly increased following B[a]P and 6-OHDA administration. Neurotransmitter estimation showed significant alleviation of dopamine in striatum following B[a]P and 6-OHDA administration. Histopathological studies of striatum by hematoxylin and eosin (H&E) staining revealed the neurodegenerative potential of B[a]P and 6-OHDA. Our results indicate that B[a]P-induced spontaneous motor hyperactivity in rats showed symptomatic similarities with 6-OHDA. In conclusion, early postnatal exposure to B[a]P in rats causing neurobehavioral changes may lead to serious neurodegenerative consequences during adolescence.

  6. Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

    PubMed Central

    Das, Saroj Kumar; Patel, Bhupesh

    2016-01-01

    Exposure to persistent genotoxicants like benzo[a]pyrene (B[a]P) during postnatal days causes neurobehavioral changes in animal models. However, neurotoxic potential of B[a]P and its association with 6-hydroxydopamine (6-OHDA) induced neurobehavioral changes are yet to be explored. The growth of rat brain peaks at the first week of birth and continues up to one month with the attainment of adolescence. Hence, the present study was conducted on male Wistar rats at postnatal day 5 (PND 5) following single intracisternal administration of B[a]P to compare with neurobehavioral and neurotransmitter changes induced by 6-OHDA at PND 30. Spontaneous motor activity was significantly increased by 6-OHDA showing similar trend following B[a]P administration. Total distance travelled in novel open field arena and elevated plus maze was significantly increased following B[a]P and 6-OHDA administration. Neurotransmitter estimation showed significant alleviation of dopamine in striatum following B[a]P and 6-OHDA administration. Histopathological studies of striatum by hematoxylin and eosin (H&E) staining revealed the neurodegenerative potential of B[a]P and 6-OHDA. Our results indicate that B[a]P-induced spontaneous motor hyperactivity in rats showed symptomatic similarities with 6-OHDA. In conclusion, early postnatal exposure to B[a]P in rats causing neurobehavioral changes may lead to serious neurodegenerative consequences during adolescence. PMID:27034665

  7. Neurobehavioral assessment in forensic practice

    PubMed Central

    Woods, George W.; Freedman, David; Greenspan, Stephen

    2013-01-01

    There is a growing awareness among mental health practitioners that many mental disorders previously believed to be primarily behavioral in nature, reflecting character and environment, are actually grounded in brain mal-development or brain disorder. This growing awareness, influenced by the advent of new diagnostic procedures and measures, is also found among forensic practitioners. In this paper, we describe some of the elements involved in conducting a neurobehavioral assessment of cognitive functioning, particularly in capital cases, organizing this material in terms of the professional disciplines – social work, mitigation investigation, psychological, and medical – with which these methods are mainly identified. The paper concludes with a brief discussion of how to integrate the multiple areas of expertise to create an accurate understanding of the neurobehavioral functioning and capacity of the subject. This is the basis from which civil and criminal forensic opinions must emanate. PMID:23059206

  8. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  9. Core Concepts Involving Adverse Psychotropic Drug Effects: Assessment, Implications, and Management.

    PubMed

    Goldberg, Joseph F; Ernst, Carrie L

    2016-09-01

    Adverse effects from psychiatric drugs can profoundly influence treatment adherence and outcomes. Good care involves addressing adverse effects no differently than any other component of treatment. Knowledge about adverse effect assessment and management fosters a proper context that helps clinicians not sacrifice a drug's potential therapeutic benefits because of greater concerns about its tolerability. This article provides an overview of basic concepts related to the assessment and management of suspected adverse effects from psychotropic drugs. Key points are discussed regarding clinical, pharmacogenetic, pharmacokinetic, and pharmacodynamic risk factors for treatment-emergent adverse effects, alongside recommendations for their systematic assessment. PMID:27514295

  10. Identification and Characterization of Adverse Effects in 21st Century Toxicology

    EPA Science Inventory

    The ILSI Health and Environmental Sciences Institute Project Committee on Distinguishing Adverse from Non-Adverse / Adaptive Effects held a workshop in May 2011 to discuss approaches to identifying adverse effects in the context of the 2007 NRC committee report titled “Toxicity T...

  11. Assessment of neurobehavioral response in humans to low-level volatile organic compound (VOC) sources

    SciTech Connect

    Otto, D.A.

    1991-06-01

    Occupants of sick buildings often complain of CNS symptoms including headache and memory loss, but little objective evidence of neurobehavioral effects exists. Available evidence of neurobehavioral effects of low level VOC exposure representative of new buildings is reviewed. Methods suitable for studying the neurobehavioral effects of low-level VOC exposure--including computerized behavioral tests, balance tests and sensory evoked potentials--are reviewed. The use of computerized behavioral tests in conjunction with symptom questionnaires is recommended for low-level VOC studies.

  12. Adverse respiratory effects of outdoor air pollution in the elderly.

    PubMed

    Bentayeb, M; Simoni, M; Baiz, N; Norback, D; Baldacci, S; Maio, S; Viegi, G; Annesi-Maesano, I

    2012-09-01

    Compared to the rest of the population, the elderly are potentially highly susceptible to the effects of outdoor air pollution due to normal and pathological ageing. The purpose of the present review was to gather data on the effects on respiratory health of outdoor air pollution in the elderly, on whom data are scarce. These show statistically significant short-term and chronic adverse effects of various outdoor air pollutants on cardiopulmonary morbidity and mortality in the elderly. When exposed to air pollution, the elderly experience more hospital admissions for asthma and chronic obstructive pulmonary disease (COPD) and higher COPD mortality than others. Previous studies also indicate that research on the health effects of air pollution in the elderly has been affected by methodological problems in terms of exposure and health effect assessments. Few pollutants have been considered, and exposure assessment has been based mostly on background air pollution and more rarely on objective measurements and modelling. Significant progress needs to be made through the development of 'hybrid' models utilising the strengths of information on exposure in various environments to several air pollutants, coupled with daily activity exposure patterns. Investigations of chronic effects of air pollution and of multi-pollutant mixtures are needed to better understand the role of air pollution in the elderly. Lastly, smoking, occupation, comorbidities, treatment and the neighbourhood context should be considered as confounders or modifiers of such a role. In this context, the underlying biological, physiological and toxicological mechanisms need to be explored to better understand the phenomenon through a multidisciplinary approach. PMID:22871325

  13. Transplacental Exposure to AZT Induces Adverse Neurochemical and Behavioral Effects in a Mouse Model: Protection by L-Acetylcarnitine

    PubMed Central

    Venerosi Pesciolini, Aldina; Tramutola, Antonella; Ajmone-Cat, Maria Antonietta; Cinque, Carlo; Alemà, Giovanni Sebastiano; Giovine, Angela; Peluso, Gianfranco; Minghetti, Luisa; Nicolai, Raffaella; Calamandrei, Gemma; Casolini, Paola

    2013-01-01

    Maternal-fetal HIV-1 transmission can be prevented by administration of AZT, alone or in combination with other antiretroviral drugs to pregnant HIV-1-infected women and their newborns. In spite of the benefits deriving from this life-saving prophylactic therapy, there is still considerable uncertainty on the potential long-term adverse effects of antiretroviral drugs on exposed children. Clinical and experimental studies have consistently shown the occurrence of mitochondrial dysfunction and increased oxidative stress following prenatal treatment with antiretroviral drugs, and clinical evidence suggests that the developing brain is one of the targets of the toxic action of these compounds possibly resulting in behavioral problems. We intended to verify the effects on brain and behavior of mice exposed during gestation to AZT, the backbone of antiretroviral therapy during human pregnancy. We hypothesized that glutamate, a neurotransmitter involved in excitotoxicity and behavioral plasticity, could be one of the major actors in AZT-induced neurochemical and behavioral alterations. We also assessed the antioxidant and neuroprotective effect of L-acetylcarnitine, a compound that improves mitochondrial function and is successfully used to treat antiretroviral-induced polyneuropathy in HIV-1 patients. We found that transplacental exposure to AZT given per os to pregnant mice from day 10 of pregnancy to delivery impaired in the adult offspring spatial learning and memory, enhanced corticosterone release in response to acute stress, increased brain oxidative stress also at birth and markedly reduced expression of mGluR1 and mGluR5 subtypes and GluR1 subunit of AMPA receptors in the hippocampus. Notably, administration during the entire pregnancy of L-acetylcarnitine was effective in preventing/ameliorating the neurochemical, neuroendocrine and behavioral adverse effects induced by AZT in the offspring. The present preclinical findings provide a mechanistic hypothesis for

  14. Adverse effects of perinatal nicotine exposure on reproductive outcomes.

    PubMed

    Wong, Michael K; Barra, Nicole G; Alfaidy, Nadia; Hardy, Daniel B; Holloway, Alison C

    2015-12-01

    Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women.

  15. Second-generation antipsychotics and extrapyramidal adverse effects.

    PubMed

    Divac, Nevena; Prostran, Milica; Jakovcevski, Igor; Cerovac, Natasa

    2014-01-01

    Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318

  16. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented. PMID:25648140

  17. Lowest adverse effects concentrations (LOAECs) for formaldehyde exposure.

    PubMed

    Gelbke, Heinz-Peter; Gröters, Sibylle; Morfeld, Peter

    2014-10-01

    In 2012 the Committee for Risk Assessment (RAC) of the European Chemicals Agency concluded that 2ppm formaldehyde represent a Lowest Observed Adverse Effect Concentration (LOAEC) for polypoid adenomas, histopathological lesions and cell proliferation. An analysis of all data shows that a LOAEC of 2ppm it is not justified for cell proliferation and polypoid adenomas. Higher values are also supported by a new statistical analysis. For histopathological lesions a NOAEC of 1ppm may be defined but the lesions at 2ppm cannot be regarded as pre-stages for tumour development. One major uncertainty exists: the description of polypoid adenomas and the lesions at 2ppm often is insufficient and diagnostic uncertainties can only be resolved by a re-evaluation according to modern histomorphological standards. Although the discrepancy between our assessment and that of RAC may seem rather small we feel the LOAECs proposed by RAC must be challenged taking into consideration the broad data base for formaldehyde and the potential impact of any published RAC opinion on the present discussions about appropriate occupational and indoor exposure limits.

  18. Enzymes approved for human therapy: indications, mechanisms and adverse effects.

    PubMed

    Baldo, Brian A

    2015-02-01

    Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

  19. Iron deficiency anemia: adverse effects on infant psychomotor development.

    PubMed

    Walter, T; De Andraca, I; Chadud, P; Perales, C G

    1989-07-01

    In a double-blind, placebo-control prospective cohort study of 196 infants from birth to 15 months of age, assessment was made at 12 months of age of the relationship between iron status and psychomotor development, the effect of a short-term (10-day) trial of oral iron vs placebo, and the effect of long-term (3 months) oral iron therapy. Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic, 30 control, and 127 nonanemic iron-deficient children. Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants (one-way analysis of variance, P less than .0001). Control infants and nonanemic iron-deficient infants performed comparably. No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy. Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores (P less than .05). Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls. These results, in a design in which intervening variables were closely controlled, suggest that when iron deficiency progresses to anemia, but not before, adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy. If these impairments prove to be long standing, prevention of iron deficiency anemia in early infancy becomes the only way to avoid them.

  20. Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects.

    PubMed

    2008-10-01

    (1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type

  1. Use of computerized test batteries for quantifying neurobehavioral outcomes.

    PubMed Central

    Letz, R

    1991-01-01

    Neurobehavioral testing provides for noninvasive assessment of the functional integrity of the nervous system. Neurobehavioral tests have been used as quantitative outcome measures in a number of epidemiologic investigations of the potential effects on the nervous system from exposure to organic solvents, heavy metals, and pesticides. Because of the functional complexity of the nervous system, sets of tests assessing a range of functions have been used, with inconsistency from one study to another. Although there has been recent progress in standardizing a core set of tests for use in occupational epidemiology, major consensus on testing methods has not emerged. Standardization of test methods is essential to provide a consistent database for risk analysis. Automation of data collection provides not only standardization, but also improved time efficiency, of data collection and analysis. The computerized Neurobehavioral Evaluation System (NES) has been developed to address the need for standardized, efficient data acquisition of a range of neurobehavioral variables. Examples of application of NES in epidemiologic studies of workers exposed to solvents are summarized. The need for use of NES as a tool for surveillance and in prospective epidemiologic investigations is emphasized. PMID:2050061

  2. Association between Exposure to Electromagnetic Fields from High Voltage Transmission Lines and Neurobehavioral Function in Children

    PubMed Central

    Huang, Jiongli; Tang, Tiantong; Hu, Guocheng; Zheng, Jing; Wang, Yuyu; Wang, Qiang; Su, Jing; Zou, Yunfeng; Peng, Xiaowu

    2013-01-01

    Background Evidence for a possible causal relationship between exposure to electromagnetic fields (EMF) emitted by high voltage transmission (HVT) lines and neurobehavioral dysfunction in children is insufficient. The present study aims to investigate the association between EMF exposure from HVT lines and neurobehavioral function in children. Methods Two primary schools were chosen based on monitoring data of ambient electromagnetic radiation. A cross-sectional study with 437 children (9 to 13 years old) was conducted. Exposure to EMF from HVT lines was monitored at each school. Information was collected on possible confounders and relevant exposure predictors using standardized questionnaires. Neurobehavioral function in children was evaluated using established computerized neurobehavioral tests. Data was analyzed using multivariable regression models adjusted for relevant confounders. Results After controlling for potential confounding factors, multivariable regression revealed that children attending a school near 500 kV HVT lines had poorer performance on the computerized neurobehavioral tests for Visual Retention and Pursuit Aiming compared to children attending a school that was not in close proximity to HVT lines. Conclusions The results suggest long-term low-level exposure to EMF from HVT lines might have a negative impact on neurobehavioral function in children. However, because of differences in results only for two of four tests achieved statistical significance and potential limitations, more studies are needed to explore the effects of exposure to extremely low frequency EMF on neurobehavioral function and development in children. PMID:23843999

  3. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke

    PubMed Central

    Amos-Kroohs, Robyn M.; Williams, Michael T.; Braun, Amanda A.; Graham, Devon L; Webb, Cynthia L.; Birtles, Todd S.; Greene, Robert M.; Vorhees, Charles V.; Pisano, M. Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of ‘active’ maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6 h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1 h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function. PMID

  4. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

    PubMed

    Amos-Kroohs, Robyn M; Williams, Michael T; Braun, Amanda A; Graham, Devon L; Webb, Cynthia L; Birtles, Todd S; Greene, Robert M; Vorhees, Charles V; Pisano, M Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function. PMID:23314114

  5. Neurobehavioral phenotype of C57BL/6J mice prenatally and neonatally exposed to cigarette smoke.

    PubMed

    Amos-Kroohs, Robyn M; Williams, Michael T; Braun, Amanda A; Graham, Devon L; Webb, Cynthia L; Birtles, Todd S; Greene, Robert M; Vorhees, Charles V; Pisano, M Michele

    2013-01-01

    Although maternal cigarette smoking during pregnancy is a well-documented risk factor for a variety of adverse pregnancy outcomes, how prenatal cigarette smoke exposure affects postnatal neurobehavioral/cognitive development remains poorly defined. In order to investigate the cause of an altered behavioral phenotype, mice developmentally exposed to a paradigm of 'active' maternal cigarette smoke is needed. Accordingly, cigarette smoke exposed (CSE) and air-exposed C57BL/6J mice were treated for 6h per day in paired inhalation chambers throughout gestation and lactation and were tested for neurobehavioral effects while controlling for litter effects. CSE mice exhibited less than normal anxiety in the elevated zero maze, transient hypoactivity during a 1h locomotor activity test, had longer latencies on the last day of cued Morris water maze testing, impaired hidden platform learning in the Morris water maze during acquisition, reversal, and shift trials, and impaired retention for platform location on probe trials after reversal but not after acquisition or shift. CSE mice also showed a sexually dimorphic response in central zone locomotion to a methamphetamine challenge (males under-responded and females over-responded), and showed reduced anxiety in the light-dark test by spending more time on the light side. No differences on tests of marble burying, acoustic startle response with prepulse inhibition, Cincinnati water maze, matching-to-sample Morris water maze, conditioned fear, forced swim, or MK-801-induced locomotor activation were found. Collectively, the data indicate that developmental cigarette smoke exposure induces subnormal anxiety in a novel environment, impairs spatial learning and reference memory while sparing other behaviors (route-based learning, fear conditioning, and forced swim immobility). The findings add support to mounting evidence that developmental cigarette smoke exposure has long-term adverse effects on brain function.

  6. Adverse effects of acupuncture. Which are clinically significant?

    PubMed Central

    Chung, Ainee; Bui, Luke; Mills, Edward

    2003-01-01

    OBJECTIVE: To review potentially serious adverse events associated with acupuncture. QUALITY OF EVIDENCE: Studies in the medical literature primarily provide level II evidence from retrospective reviews, case reports, and prospective surveys of practitioners. MAIN MESSAGE: Both the general public and physicians are becoming more interested in the ancient Chinese medical practice of acupuncture. This paper discusses the basic philosophy of acupuncture and describes adverse events that might be associated with acupuncture treatment. Some events, such as nausea and syncope, can be mild and transient, but rare events, such as septicemia and hepatitis C infection, can be fatal. As the role of acupuncture in today's multidisciplinary clinics increases, the complications of acupuncture, although infrequent, cannot be overlooked. CONCLUSION: Responsible clinicians practising acupuncture and seeing patients who use acupuncture should be aware of the adverse events associated with it. PMID:12943357

  7. Performance on the Defense Automated Neurobehavioral Assessment across controlled environmental conditions.

    PubMed

    Haran, F Jay; Dretsch, Michael N; Bleiberg, Joseph

    2016-01-01

    Neurocognitive assessment tools (NCAT) are commonly used to screen for changes in cognitive functioning following a mild traumatic brain injury and to assist with a return to duty decision. As such, it is critical to determine if performance on the Defense Automated Neurobehavioral Assessment (DANA) is adversely affected by operationally-relevant field environments. Differences in DANA performance between a thermoneutral environment and three simulated operationally-relevant field environments across the thermal stress continuum were calculated for 16 healthy U.S. Navy service members. Practice effects associated with brief test-retest intervals were calculated within each environmental condition. There were no significant differences between the simulated environmental conditions suggesting that performance on the DANA Brief is not impacted by thermal stress. Additionally, there were no significant differences in performance within each simulated environmental condition associated with repeated administrations. PMID:27182844

  8. Fetal Alcohol Spectrum Disorder (FASD): neurobehavioral profile, indications for diagnosis and treatment.

    PubMed

    Coriale, Giovanna; Fiorentino, Daniela; Di Lauro, Francesca; Marchitelli, René; Scalese, Bruna; Fiore, Marco; Maviglia, Marcello; Ceccanti, Mauro

    2013-01-01

    It is now known that exposure to alcohol in utero produces a wide spectrum of morphological and behavioural outcomes in the offspring, commonly referred as fetal alcohol spectrum disorders (FASD). A large body of literature documents cognitive deficits and behavioural-emotional difficulties in children with FASD. Researchers have found that individuals with FASD often experience a range of adverse life outcomes, called secondary disabilities, which include disrupted school experience, troubles with the law, confinement, inappropriate sexual behaviours on repeated occasions, and alcohol/drug related problems. Additionally, despite considerable data published on cognitive and behavioural disabilities in children with FASD, relatively little information is available on behavioural or pharmacological interventions for alcohol affected children. This paper will provide a comprehensive review of the neuropsychological and behavioural effects of prenatal alcohol exposure, including a discussion of the emerging neurobehavioral profile. Finally, we will summarize published intervention studies of FASD focusing on their strengths and weaknesses.

  9. Fetal growth and neurobehavioral outcomes in childhood.

    PubMed

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-12-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  10. Fetal Growth and Neurobehavioral Outcomes in Childhood

    PubMed Central

    Chatterji, Pinka; Lahiri, Kajal; Kim, Dohyung

    2014-01-01

    Using a sample of sibling pairs from a nationally representative U.S. survey, we examine the effects of the fetal growth rate on a set of neurobehavioral outcomes in childhood measured by parent-reported diagnosed developmental disabilities and behavior problems. Based on models that include mother fixed effects, we find that the fetal growth rate, a marker for the fetal environment, is negatively associated with lifetime diagnosis of developmental delay. We also find that the fetal growth rate is negatively associated with disruptive behaviors among male children. These results suggest that developmental disabilities and problem behaviors may play a role in explaining the well-documented association between birth weight and human capital outcomes measured in adulthood. PMID:25464342

  11. A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).

    PubMed

    Sullivan, Alana W; Beach, Elsworth C; Stetzik, Lucas A; Perry, Amy; D'Addezio, Alyssa S; Cushing, Bruce S; Patisaul, Heather B

    2014-10-01

    Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.

  12. Adverse effects of serotonin depletion in developing zebrafish.

    PubMed

    Airhart, Mark J; Lee, Deborah H; Wilson, Tracy D; Miller, Barney E; Miller, Merry N; Skalko, Richard G; Monaco, Paul J

    2012-01-01

    remained unaffected in brain, they were decreased in spinal cord. Five days subsequent to pCPA rescue, 5HT(1A) transcript concentrations remained decreased in brain while SERT transcript levels were elevated in both regions. These findings suggest that reduction of 5HT during early zebrafish development may have an adverse effect on body length, notochordal morphology, locomotor behavior, and serotonin message-related expression.

  13. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP

  14. International monitoring of adverse health effects associated with herbal medicines.

    PubMed

    Farah, M H; Edwards, R; Lindquist, M; Leon, C; Shaw, D

    2000-03-01

    Herbal medicines are used in health care around the world and may increase in importance. There is much uncertainty, however, with regard to their composition, efficacy and safety. There is substantial evidence that herbal medicines can cause serious adverse reactions, but more data are needed as regard their nature, frequency and preventability. In this respect the Uppsala Monitoring Centre of the World Health Organization can play a crucial role. Better reporting of adverse reactions to herbal medicines is needed, in particular with regard to the precise identity and composition of these products. A consistent use by producers, regulators and reporters of the international Latin binomial nomenclature and the use of the new Herbal Anatomical Therapeutic Chemical (ATC) classification are recommended. Copyright (c) 2000 John Wiley & Sons, Ltd. PMID:19025809

  15. Chronic exposure to aluminum and melatonin through the diet: neurobehavioral effects in a transgenic mouse model of Alzheimer disease.

    PubMed

    Di Paolo, Celeste; Reverte, Ingrid; Colomina, Maria Teresa; Domingo, José L; Gómez, Mercedes

    2014-07-01

    Aluminum (Al) is a known neurotoxic element involved in the etiology of some serious neurodegenerative disorders such as Alzheimer disease (AD). Antioxidants like melatonin might protect neurons against the damage produced in AD. The APPSWE (Tg2576) transgenic mouse is one of the most used animal models developed to mimic AD damage. In the present study, wild type and Tg2576 mice were orally exposed during 14 months to Al, melatonin, and citric acid, as well as to all possible combinations between them. At 17 months of age, mice were evaluated for behavior using the open-field test and the Morris water maze. Transgenic animals exposed to melatonin only and to Al plus citric acid plus melatonin showed a good acquisition. No effects on acquisition in the Morris water maze were observed in wild type mice. With respect to the retention of the task, only melatonin wild type animals, and Al plus citric acid plus melatonin transgenic mice showed retention during the acquisition. Control wild type animals and Al plus citric acid plus melatonin transgenic mice showed good long term retention. Melatonin improved learning and spatial memory in Al-exposed transgenic mice.

  16. Effect of alpha-ketoglutarate on neurobehavioral, neurochemical and oxidative changes caused by sub-chronic cyanide poisoning in rats.

    PubMed

    Mathangi, D C; Shyamala, R; Vijayashree, R; Rao, K R; Ruckmani, A; Vijayaraghavan, R; Bhattacharya, R

    2011-03-01

    Recent studies revealed that alpha-ketoglutarate (A-KG) alone or with sodium thiosulfate (STS) provide significant protection against acute and sub-acute cyanide poisoning in rodents. This study addresses the protective effect of A-KG and/or STS in sub-chronic (90 days) cyanide poisoning. Wistar rats were divided into seven groups (n = 10): Control animals, potassium cyanide (KCN) A-KG, STS, KCN + A-KG, KCN + STS and KCN + A-KG + STS. Spontaneous motor activity and motor coordination were recorded every 15th day. Lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in blood, brain, liver and kidney, and glutamate, aspartate and dopamine in discrete regions of brain were measured following 90 days exposure. Cyanide significantly decreased motor coordination, accompanied by increase in LPO (blood, brain and liver) and dopamine (corpus striatum and cerebral cortex) levels, and depletion in GSH (blood, brain and liver), GPx (brain and liver), SOD (brain and liver), and CAT (blood and brain) levels. Although treatment of A-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both afforded the maximum protection. This study shows a promising role of A-KG and STS as treatment regime for long term cyanide exposure.

  17. Neurobehavioral Deficits and Increased Blood Pressure in School-Age Children Prenatally Exposed to Pesticides

    PubMed Central

    Harari, Raul; Julvez, Jordi; Murata, Katsuyuki; Barr, Dana; Bellinger, David C.; Debes, Frodi; Grandjean, Philippe

    2010-01-01

    Background The long-term neurotoxicity risks caused by prenatal exposures to pesticides are unclear, but a previous pilot study of Ecuadorian school children suggested that blood pressure and visuospatial processing may be vulnerable. Objectives In northern Ecuador, where floriculture is intensive and relies on female employment, we carried out an intensive cross-sectional study to assess children’s neurobehavioral functions at 6–8 years of age. Methods We examined all 87 children attending two grades in the local public school with an expanded battery of neurobehavioral tests. Information on pesticide exposure during the index pregnancy was obtained from maternal interview. The children’s current pesticide exposure was assessed from the urinary excretion of organophosphate metabolites and erythrocyte acetylcholine esterase activity. Results Of 84 eligible participants, 35 were exposed to pesticides during pregnancy via maternal occupational exposure, and 23 had indirect exposure from paternal work. Twenty-two children had detectable current exposure irrespective of their prenatal exposure status. Only children with prenatal exposure from maternal greenhouse work showed consistent deficits after covariate adjustment, which included stunting and socioeconomic variables. Exposure-related deficits were the strongest for motor speed (Finger Tapping Task), motor coordination (Santa Ana Form Board), visuospatial performance (Stanford-Binet Copying Test), and visual memory (Stanford-Binet Copying Recall Test). These associations corresponded to a developmental delay of 1.5–2 years. Prenatal pesticide exposure was also significantly associated with an average increase of 3.6 mmHg in systolic blood pressure and a slight decrease in body mass index of 1.1 kg/m2. Inclusion of the pilot data strengthened these results. Conclusions These findings support the notion that prenatal exposure to pesticides—at levels not producing adverse health outcomes in the mother

  18. Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

    ERIC Educational Resources Information Center

    Correll, Christoph U.; Carlson, Harold E.

    2006-01-01

    Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

  19. Prenatal exposure to anti-HIV drugs. long-term neurobehavioral effects of lamivudine (3TC) in CD-1 mice.

    PubMed

    Calamandrei, G; Venerosi, A; Branchi, I; Valanzano, A; Alleva, E

    2000-01-01

    The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3TC at different doses (125, 250, or 500 mg/kg) or vehicle solution (NaCl 0. 9%) from pregnancy day 10 to delivery. Offspring behavior was examined on postnatal day 35 in a 20-min social interaction test. At adulthood different behavioral endpoints were analyzed, including locomotor activity and exploration in an open field following administration of the muscarinic antagonist scopolamine (2 mg/kg), spatial learning in either radial arm or Morris water maze, virgin female behavior in a maternal induction test, and pain sensitivity in a hot-plate test (52 +/- 0.1 degrees C). Our findings confirm the low neurotoxicity of 3TC in comparison to AZT. However some significant behavioral alterations were found, namely (1) a decrease in immobility in the open field test, (2) an increase in the responsiveness to scopolamine shown by the 500-mg/kg 3TC mice (sniffing behavior) in the open field, and (3) a longer escape latency in the first day of the reversal phase in the Morris task (particularly marked in the 250-mg/kg treatment group). No significant changes in either pain sensitivity, social/affiliative, or maternal behavior were found, although a higher occurrence of aggressive behavior toward foster pups was noted in both 125- and 500-mg/kg 3TC females.

  20. [Alteration of neurobehavioral and autonomic nervous function in aluminum electrolytic workers].

    PubMed

    He, Shuchang; Zhang, Aimin; Niu, Qiao; Wang, Sheng; Chen, Yilan

    2003-05-01

    In order to explore the impairment of Aluminum on the neurobehavioral, autonomic nervous function. Neurobehavioral test battery (NCTB) recommended by WHO and autonomic nervous system (ANS) function test recommended by Ewing DJ were conducted in 32 Al electrolytic workers and 34 controls. Results showed that the scores of confusion-bewilderment and tension-anxious in Al exposed workers were higher than that of control group, while the scores of POMSA, POMSD, POMSF and POMSV in Al-exposed group had no obvious change. The scores of DSY, PA and PAC were lower than that of control group. The scores of DSPF, DDSPB, DSP, SANN, SANP and BVR had no significant alteration. R-R interval variability of maximin ratio of immediate standing up, which reflects parasympathetic nervous modification ability in aluminum electrolytic workers, was lower than that of the control group. This implied that Al exposure had adverse impact on workers' mood state, neurobehavioral and parasympathetic nervous function.

  1. Expression of imprinted genes in placenta is associated with infant neurobehavioral development

    PubMed Central

    Green, Benjamin B; Kappil, Maya; Lambertini, Luca; Armstrong, David A; Guerin, Dylan J; Sharp, Andrew J; Lester, Barry M; Chen, Jia; Marsit, Carmen J

    2015-01-01

    Genomic imprinting disorders often exhibit delayed neurobehavioral development, suggesting this unique mechanism of epigenetic regulation plays a role in mental and neurological health. While major errors in imprinting have been linked to adverse health outcomes, there has been little research conducted on how moderate variability in imprinted gene expression within a population contributes to differences in neurobehavioral outcomes, particularly at birth. Here, we profiled the expression of 108 known and putative imprinted genes in human placenta samples from 615 infants assessed by the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scales (NNNS). Data reduction identified 10 genes (DLX5, DHCR24, VTRNA2-1, PHLDA2, NPAP1, FAM50B, GNAS-AS1, PAX8-AS1, SHANK2, and COPG2IT1) whose expression could distinguish between newborn neurobehavioral profiles derived from the NNNS. Clustering infants based on the expression pattern of these genes identified 2 groups of infants characterized by reduced quality of movement, increased signs of asymmetrical and non-optimal reflexes, and increased odds of demonstrating increased signs of physiologic stress and abstinence. Overall, these results suggest that common variation in placental imprinted gene expression is linked to suboptimal performance on scales of neurological functioning as well as with increased signs of physiologic stress, highlighting the central importance of the control of expression of these genes in the placenta for neurobehavioral development. PMID:26198301

  2. [Dealing with adverse effects in phase I trials].

    PubMed

    Heger-Mahn, D; Mahler, M; Hermann, R; Nowak, H; Weber, W; Seibert-Grafe, M

    1995-03-01

    A questionnaire was completed by members of the Association for Applied Human Pharmacology (AGAH) in Germany with the aim of assessing the present situation regarding management of adverse events (AEs). A recommendation for documentation and evaluation of AEs was to be presented after discussion within the AGAH. The questionnaire referred to general questions, documentation of AEs, intensity and causality, coding and serious adverse events (SAE). Percentage return of answered questionnaires was 54.5%. Of the people contacted, 9.1% said they did not carry out phase I trials, and 36.4% did not reply. The survey in the 24 institutes convers an estimated 11200 volunteers who are included in clinical trials each year. The discussion about commencement of AEs documentation and its duration was contentious. Of the respondents, 38.5% AEs only after application of the trial substance, while 61.5% also make a documentation during the pre-trial phase (recruitment, pre-examination, supervision before application). 13.6% document only up to the post-examination and half of those questioned until AE symptoms have disappeared. 22.7% document until disappearance of symptoms only when AEs are definitely associated with the trial substance. A 3-point scale is used by most people questioned for evaluation of the intensity of an AE. Evaluation of causality, mostly undertaken by the examining physician and the director of the clinical trial, is not carried out homogeneously. There are several categories, but four classifications are most commonly used. 62.5% of codings of AEs are carried out according to the WHO Adverse Reaction Terminology.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 40 CFR 174.71 - Submission of information regarding adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... any information regarding adverse effects on human health or the environment alleged to have been... this part. This may include, for example, researchers performing field experiments, breeders making... information. (b) Adverse effects on human health or the environment for purposes of...

  4. FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

    PubMed Central

    Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

    2013-01-01

    SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

  5. Development of Translational Methods in Spectral Analysis of Human Infant Crying and Rat Pup Ultrasonic Vocalizations for Early Neurobehavioral Assessment

    PubMed Central

    Zeskind, Philip Sanford; McMurray, Matthew S.; Garber, Kristin A.; Neuspiel, Juliana M.; Cox, Elizabeth T.; Grewen, Karen M.; Mayes, Linda C.; Johns, Josephine M.

    2011-01-01

    The purpose of this article is to describe the development of translational methods by which spectrum analysis of human infant crying and rat pup ultrasonic vocalizations (USVs) can be used to assess potentially adverse effects of various prenatal conditions on early neurobehavioral development. The study of human infant crying has resulted in a rich set of measures that has long been used to assess early neurobehavioral insult due to non-optimal prenatal environments, even among seemingly healthy newborn and young infants. In another domain of study, the analysis of rat put USVs has been conducted via paradigms that allow for better experimental control over correlated prenatal conditions that may confound findings and conclusions regarding the effects of specific prenatal experiences. The development of translational methods by which cry vocalizations of both species can be analyzed may provide the opportunity for findings from the two approaches of inquiry to inform one another through their respective strengths. To this end, we present an enhanced taxonomy of a novel set of common measures of cry vocalizations of both human infants and rat pups based on a conceptual framework that emphasizes infant crying as a graded and dynamic acoustic signal. This set includes latency to vocalization onset, duration and repetition rate of expiratory components, duration of inter-vocalization-intervals and spectral features of the sound, including the frequency and amplitude of the fundamental and dominant frequencies. We also present a new set of classifications of rat pup USV waveforms that include qualitative shifts in fundamental frequency, similar to the presence of qualitative shifts in fundamental frequency that have previously been related to insults to neurobehavioral integrity in human infants. Challenges to the development of translational analyses, including the use of different terminologies, methods of recording, and spectral analyses are discussed, as well as

  6. Neurobehavioral Impairments Caused by Developmental Imidacloprid Exposure in Zebrafish

    PubMed Central

    Crosby, Emily B.; Bailey, Jordan M.; Oliveri, Anthony N.; Levin, Edward D.

    2015-01-01

    BACKGROUND Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. METHODS Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4 h to 5 d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. RESULTS In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strain of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. DISCUSSION Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. PMID:25944383

  7. Transient Adverse Side Effects During Neurofeedback Training: A Randomized, Sham-Controlled, Double Blind Study.

    PubMed

    Rogel, Ainat; Guez, Jonathan; Getter, Nir; Keha, Eldad; Cohen, Tzlil; Amor, Tali; Todder, Doron

    2015-09-01

    The benefits of clinical neurofeedback training are well known, however, its adverse side-effects are less studied. This research focuses on the transient adverse side effects of neurofeedback training via a double-blind, sham/controlled methodology. Thirty healthy undergraduate students volunteers were randomly divided into three treatment groups: increasing a modified Sensory Motor Rhythm, increasing Upper Alpha, and Sham/control group who receive a random reward. The training sessions were administered for a total of ten sessions. Questionnaires of transient adverse side effects were completed by all volunteers before each session. The results suggest that similar to most medical treatments, neurofeedback can cause transient adverse side effects. Moreover, most participants reported experiencing some side effects. The side effects can be divided into non-specific side effect, associated with the neurofeedback training in general and specific ones associated with the particular protocol. Sensory Motor Rhythm protocol seems to be the most sensitive to side effects.

  8. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    EPA Science Inventory

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe res...

  9. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the criteria of 40 CFR 158.34 for flagging studies for potential adverse effects to the results of the... exceeds criteria. I have applied the criteria of 40 CFR 158.34 for flagging studies for potential adverse... sex. 4 Prenatal developmental toxicityReproduction and fertility Developmental neurotoxicity...

  10. Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

    ERIC Educational Resources Information Center

    Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

    2007-01-01

    Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

  11. Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

    ERIC Educational Resources Information Center

    Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

    2010-01-01

    Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

  12. Neurobehavioral alterations in rats exposed to acrylonitrile in drinking water.

    PubMed

    Rongzhu, L; Suhua, W; Guangwei, X; Fangan, H; Ziqiang, C; Fusheng, J; Kacew, S

    2007-03-01

    This study was carried out on rodents, to explore the neurobehavioral effects of acrylonitrile (AN) administered in drinking water. Thirty, male, Sprague-Dawley rats were randomly divided into three groups: two exposure groups (50 and 200 ppm AN), and one control group (tap water without AN). Three tests, including the open field test, rotarod test and spatial water maze, were applied to evaluate locomotor activities, motor co-ordination and learning and memory, respectively, prior to initiation of the treatment, and at Week 4, 8 and 12 postexposure. There were no consistent changes in the open field test, except for locomotion and grooming episodes. In the rotarod test, AN significantly decreased the latencies to fall in a dose and time-dependent manner. In the spatial water maze test, rats exposed to AN for 12 weeks had significantly more training times and longer escape latencies than control animals. These findings indicate that oral exposure to AN induces neurobehavioral alterations in rats.

  13. The basic science of dermal fillers: past and present Part II: adverse effects.

    PubMed

    Gilbert, Erin; Hui, Andrea; Meehan, Shane; Waldorf, Heidi A

    2012-09-01

    The ideal dermal filler should offer long-lasting aesthetic improvement with a minimal side-effect profile. It should be biocompatible and stable within the injection site, with the risk of only transient undesirable effects from injection alone. However, all dermal fillers can induce serious and potentially long-lasting adverse effects. In Part II of this paper, we review the most common adverse effects related to dermal filler use.

  14. Adverse Effects of Common Drugs: Children and Adolescents.

    PubMed

    Karpa, Kelly Dowhower; Felix, Todd Matthew; Lewis, Peter R

    2015-09-01

    Drug use and harms are increasingly common among newborns, infants, children, and adolescents during ambulatory practice, emergency department, and in-hospital treatment, including treatment in pediatric intensive care units. The pharmacokinetic and pharmacodynamic parameters of drugs often are different for children compared with adults and must be considered before prescribing. Drug exposure and the potential for harms also should be considered for fetuses and breastfeeding infants. As with adult patients, a thorough drug and allergy history (including nonprescription drugs and herbal and dietary supplements) should be obtained and reviewed at each medical visit. Children and adolescents are increasingly at risk of drug harm/overdose through accidental or intentional ingestion of nonprescription and prescription drugs (eg, cough and cold preparations, candy-appearing vitamins, stimulants, narcotics). Parents and caregivers should receive training in the proper use, storage, and administration of all drugs. Prescribing clinicians should be vigilant in withholding unnecessary drugs, such as antibiotics for viral infections. When prescribing, clinicians should be aware of common drugs frequently associated with adverse reactions, including stimulants, antipsychotics, analgesics, asthma therapies, acne therapies, and tumor necrosis factor inhibitors. Scientifically based prescribing practices should be used and consultation with evidence-based resources and pharmacists sought as needed. PMID:26375994

  15. Effectiveness of Micro-Blowing Technique in Adverse Pressure Gradients

    NASA Technical Reports Server (NTRS)

    Welch, Gerard E.; Larosiliere, Louis M.; Hwang, Danny P.; Wood, Jerry R.

    2001-01-01

    The impact of the micro-blowing technique (MBT) on the skin friction and total drag of a strut in a turbulent, strong adverse-pressure-gradient flow is assessed experimentally over a range of subsonic Mach numbers (0.3 less than M less than 0.7) and reduced blowing fractions (0 less than or equal to 2F/C (sub f,o) less than or equal to 1.75). The MBT-treated strut is situated along the centerline of a symmetric 2-D diffuser with a static pressure rise coefficient of 0.6. In agreement with presented theory and earlier experiments in zero-pressure-gradient flows, the effusion of blowing air reduces skin friction significantly (e.g., by 60% at reduced blowing fractions near 1.75). The total drag of the treated strut with blowing is significantly lower than that of the treated strut in the limit of zero-blowing; further, the total drag is reduced below that of the baseline (solid-plate) strut, provided that the reduced blowing fractions are sufficiently high. The micro-blowing air is, however, deficient in streamwise momentum and the blowing leads to increased boundary-layer and wake thicknesses and shape factors. Diffuser performance metrics and wake surveys are used to discuss the impact of various levels of micro-blowing on the aerodynamic blockage and loss.

  16. [Are there cardiovascular adverse effects of inhaled anticholinergics?].

    PubMed

    Nagy, László Béla

    2015-08-01

    The purpose of this review is to discuss the cardiovascular risk associated with inhaled anticholinergics in chronic obstructive pulmonary disease. Several meta-analyses of data for tiotropium raised the possibility of an increased risk for arrhythmia, angina, myocardial infarction, etc. This review includes the data of retrospective studies of databases using databases, randomized controlled trials, and meta-analyses of clinical trials. The conclusions of studies were inconsistent. In most clinical trials the incidence of cardiovascular adverse events was similar in active treatment and placebo groups, especially in patients with previous cardiovascular diseases. Considering meta-analyses, there is little, if any, evidence for the association between anticholinergics and the development of cardiovascular symptoms. The author discusses the presence and function of cholinergic receptor subtypes in human heart, and cardiac functions controlled by the autonomic nervous system via these receptors, their possible role, and pharmacokinetic properties of inhaled anticholinergics. The author concludes that it is not possible to find evidence of increased cardiovascular harm of inhaled anticholinergics.

  17. Use and reported adverse effects of new chemical entities.

    PubMed

    Kennedy, D L; Goetsch, R A; Dreis, M W

    1989-03-01

    Reports submitted to the FDA through 1987 of adverse drug reactions (ADRs) to new chemical entities (NCEs) approved after 1983 are described, and estimates of each NCE's proportionate use in hospitals and within its therapeutic class are reported. This review was limited to those domestic spontaneous ADR reports submitted to the FDA by healthcare professionals. NCEs accounted for approximately 20% of the total number of domestic spontaneous ADR reports received in 1987, 22% of the reports of serious ADRs, and 24% of the reports that listed death as an outcome. Data on the use of these NCEs were obtained through the U.S. Pharmaceutical Market--Drugstores and Hospitals and the National Prescription Audit. Of the 93 drugs designated as NCEs in 1987, 65 had measurable use, with 41% of those used principally in hospitals. Most hospital-use NCEs were injectable antimicrobial agents, surgical drugs, and radioactive diagnostic agents. Because NCEs account for a disproportionate share of the ADRs reported to the FDA, and because of the high use of NCEs in hospitals, hospital pharmacists should be aware of the importance of monitoring and reporting serious ADRs associated with NCEs. PMID:2719041

  18. Adverse effects of extra-articular corticosteroid injections: a systematic review

    PubMed Central

    2010-01-01

    Background To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention). Results The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported. PMID:20836867

  19. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

    PubMed Central

    Trindade, E; Menon, D; Topfer, L A; Coloma, C

    1998-01-01

    BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes

  20. Manual therapy for the cervical spine and reported adverse effects: a survey of Irish manipulative physiotherapists.

    PubMed

    Sweeney, Aoife; Doody, Catherine

    2010-02-01

    The purpose of this study was to determine the use of manipulation and mobilisation by the Chartered Physiotherapists (CMPT) in Manipulative Therapy Ireland and to describe adverse effects associated with the use of these techniques. A 44 item postal survey was sent to all 259 members of the CPMT (response rate 49%, n=127). All 127 respondents used non-High Velocity Thrust Techniques (HVTT) and 27% (n=34) used HVTT. Nine percent (n=12) used HVTT on the upper cervical spine. Twenty six percent (n=33) reported an adverse effect in the previous 2 years. The adverse effects were associated with the use of HVTT (4%, n=5), non-HVTT (20%, n=26) and cervical traction (2%, n=2). The most serious adverse effects were associated with non-HVTT and included 1 drop attack, 1 fainting episode and 1 Transient Ischemic Attack (TIA) 4 days post treatment. Fifty three percent (n=18) of HVTT users and 40% (n=44) of non-HVTT users reported carrying out a vertebrobasilar insufficiency (VBI) assessment. The study shows that VBI assessment may not detect every patient at risk of adverse effects. Large scale studies to investigate the risk of serious adverse reactions are needed. A system of reporting adverse effects on a routine basis could be considered.

  1. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

    NASA Technical Reports Server (NTRS)

    Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

  2. HIV protease inhibitors disrupt astrocytic glutamate transporter function and neurobehavioral performance

    PubMed Central

    Vivithanaporn, Pornpun; Asahchop, Eugene L.; Acharjee, Shaona; Baker, Glen B.; Power, Christopher

    2016-01-01

    Objective: The neurotoxic actions of the HIV protease inhibitors, amprenavir (APV) and lopinavir (LPV) were investigated. Design: With combination antiretroviral therapy (cART), HIV-infected persons exhibit neurocognitive impairments, raising the possibility that cART might exert adverse central nervous system (CNS) effects. We examined the effects of LPV and APV using in-vitro and in-vivo assays of CNS function. Methods: Gene expression, cell viability and amino-acid levels were measured in human astrocytes, following exposure to APV or LPV. Neurobehavioral performance, amino-acid levels and neuropathology were examined in HIV-1 Vpr transgenic mice after treatment with APV or LPV. Results: Excitatory amino-acid transporter-2 (EAAT2) expression was reduced in astrocytes treated with LPV or APV, especially LPV (P < 0.05), which was accompanied by reduced intracellular l-glutamate levels in LPV-treated cells (P < 0.05). Treatment of astrocytes with APV or LPV reduced the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 (P < 0.05) although cell survival was unaffected. Exposure of LPV to astrocytes augmented glutamate-evoked transient rises in [Cai] (P < 0.05). Vpr mice treated with LPV showed lower concentrations of l-glutamate, l-aspartate and l-serine in cortex compared with vehicle-treated mice (P < 0.05). Total errors in T-maze assessment were increased in LPV and APV-treated animals (P < 0.05). EAAT2 expression was reduced in the brains of protease inhibitor-treated animals, which was associated with gliosis (P < 0.05). Conclusion: These results indicated that contemporary protease inhibitors disrupt astrocyte functions at therapeutic concentrations with enhanced sensitivity to glutamate, which can lead to neurobehavioral impairments. ART neurotoxicity should be considered in future therapeutic regimens for HIV/AIDS. PMID:26558720

  3. MicroRNAs control neurobehavioral development and function in zebrafish

    PubMed Central

    Tal, Tamara L.; Franzosa, Jill A.; Tilton, Susan C.; Philbrick, Kenneth A.; Iwaniec, Urszula T.; Turner, Russell T.; Waters, Katrina M.; Tanguay, Robert L.

    2012-01-01

    microRNAs (miRNAs) have emerged as regulators of a broad spectrum of neurodevelopmental processes, including brain morphogenesis, neuronal differentiation, and survival. While the role of miRNAs in establishing and maintaining the developing nervous system is widely appreciated, the developmental neurobehavioral role of miRNAs has yet to be defined. Here we show that transient disruption of brain morphogenesis by ethanol exposure results in behavioral hyperactivity in larval zebrafish challenged with changes in lighting conditions. Aberrations in swimming activity persist in juveniles that were developmentally exposed to ethanol. During early neurogenesis, multiple gene expression profiling studies revealed widespread changes in mRNA and miRNA abundance in ethanol-exposed embryos. Consistent with a role for miRNAs in neurobehavioral development, target prediction analyses identified multiple miRNAs misexpressed in the ethanol-exposed cohorts that were also predicted to target inversely expressed transcripts known to influence brain morphogenesis. In vivo knockdown of miR-9/9* or miR-153c persistently phenocopied the effect of ethanol on larval and juvenile swimming behavior. Structural analyses performed on adults showed that repression of miR-153c during development impacts craniofacial skeletal development. Together, these data support an integral role for miRNAs in the establishment of vertebrate neurobehavioral and skeletal systems.—Tal, T. L., Franzosa, J. A., Tilton, S. C., Philbrick, K. A., Iwaniec, U. T., Turner, R. T., Waters, K. M., Tanguay, R. L. MicroRNAs control neurobehavioral development and function in zebrafish. PMID:22253472

  4. Adverse effects of meditation: a preliminary investigation of long-term meditators.

    PubMed

    Shapiro, D H

    1992-01-01

    Adverse effects of meditation were assessed in twenty-seven long term meditators (average 4.27 years) both retrospectively (time one) and prospectively at one month (time two) and six months (time three) following a meditation retreat. At both time one and time three subjects reported significantly more positive effects than negative from meditation. However, of the twenty-seven subjects, seventeen (62.9%) reported at least one adverse effect, and two (7.4%) suffered profound adverse effects. When subjects at time one were divided into three groups based on length of practice (16.7 months; 47.1 months; 105 months) there were no significant differences in adverse effects. How the data should be interpreted, and their implications both for the clinical and psychotherapeutic use of meditation as a relaxation/self-control strategy, and as a technique for facilitating personal and spiritual growth, are discussed. Limitations of the study and suggestions for future research are also offered.

  5. The Useage of Opioids and their Adverse Effects in Gastrointestinal Practice: A Review

    PubMed Central

    Khansari, MahmoudReza; Sohrabi, MasourReza; Zamani, Farhad

    2013-01-01

    Opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. The effects of opium are principally mediated by the μ-, κ- and δ-opioid receptors. Opioid substances consist of all natural and synthetic alkaloids that are derived from opium. Most of their effects on gastrointestinal motility and secretion result from suppression of neural activity. Inhibition of gastric emptying, increase in sphincter tone, changes in motor patterns, and blockage of peristalsis result from opioid use. Common adverse effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, dependency and tolerance, and respiratory depression. The most common adverse effect of opioid use is constipation. Although stool softeners are frequently used to decrease opioid-induced bowel dysfunction, however they are not efficacious. Possibly, the use of specific opioid receptor antagonists is a more suitable approach. Opioid antagonists, both central and peripheral, could affect gastrointestinal function and visceromotor sensitivity, which suggests an important role for endogenous opioid peptides in the control of gastrointestinal physiology. Underlying diseases or medications known to influence the central nervous system (CNS) often accelerate the opioid’s adverse effects. However, changing the opioid and/or route of administration could also decrease their adverse effects. Appropriate patient selection, patient education and discussion regarding potential adverse effects may assist physicians in maximizing the effectiveness of opioids, while reducing the number and severity of adverse effects. PMID:24829664

  6. Human neurobehavioral toxicology testing: Current perspectives

    SciTech Connect

    Anger, W.K.

    1989-03-01

    Standardized tests or test batteries for neurotoxic effects are needed for premarket testing of chemicals (and related regulatory needs) and for the development of a neurotoxicity data base. Three widely known human test batteries based on past research findings and developed to screen for a broad range of neurotoxic effects are currently in use. One was developed by Finland's Institute of Occupational Health, one was recently recommended by the World Health Organization, and one was recently developed as a computer-implemented battery by US researchers. Each of these batteries assesses many frequently occurring neurotoxic effects, but each is limited by the lack of tests for some motor and sensory functions and affective responses that often occur following chemical exposures. Problems with field or worksite assessments using these test batteries involve age, education, socioeconomic, and job differences between exposed and comparison groups, and the lack of normative data on these batteries. To address some of these problems, the human neurobehavioral test batteries are currently undergoing reliability or validity assessments on a national and international scale. This will provide an assessment of their utility and accelerate development of a data base of neurotoxic effects of chemicals.

  7. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  8. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES... effects of deep seabed mining which cumulatively during commercial recovery have the potential for significant effect. These three effects also occur during mining system tests that may be conducted under...

  9. Prophylactic treatment with melatonin before recurrent neonatal seizures: Effects on long-term neurobehavioral changes and the underlying expression of metabolism-related genes in rat hippocampus and cerebral cortex.

    PubMed

    Ni, Hong; Sun, Qi; Tian, Tian; Feng, Xing; Sun, Bao-liang

    2015-06-01

    Although it has been suggested that the protective effect of melatonin against seizure-induced neurotoxicity involves inhibition of neuronal lipid peroxidation, current data concerning the exact molecular mechanism are still limited. This study was undertaken to investigate the changes in neurobehavioral, cognitive and lipid metabolism-related gene expressions in both hippocampus and cerebral cortex of rats subjected to recurrent neonatal seizures, and the effects of melatonin treatment before seizure (55mg/kg, 1mg/ml). 6-day-old (P6) SD rats were randomly divided into four groups of control (CONT, the same below), melatonin treated control (Mel), recurrent neonatal seizure (RS) and melatonin and RS combination treatment (Mel+RS). Neurological behavioral parameters of brain damage (plane righting reflex, negative geotaxis reaction reflex, Cliff avoidance reflex, forelimb suspension reflex) were observed on P31. Morris water maze test was performed during P29-P35. Then the protein levels of ACAT1, Cathepsin-E and Ca(2+)/calmodulin-dependent protein kinase II (CAMK II) in hippocampus and cerebral cortex were detected by western blot method. As expected, RS group showed a significant delay or reduce of the four reflexes, as well as bad performance in the Morris water maze test. Flurothyl-induced neurobehavioral toxicology was blocked by pre-treatment with melatonin. In parallel with these behavioral changes, gene expression by western blot method demonstrated that rats pretreated with melatonin (Mel+RS) showed a significant down-regulated expression of ACAT-1, Cathepsin-E and up-regulated CAMK II in hippocampus and cerebral cortex when compared with RS group. Our findings provide support for ACAT-1/Cathepsin-E as well as CaMK II being potential targets for the treatment of neonatal seizure-induced brain damage by melatonin.

  10. Preventive Effects of Multi-Lamellar Emulsion on Low Potency Topical Steroid Induced Local Adverse Effect

    PubMed Central

    Sul, Geun Dong; Park, Hyun Jung; Bae, Jong Hwan; Hong, Keum Duck; Park, Byeong Deog; Chun, Jaesun; Jeong, Se Kyoo; Lee, Seung Hun; Ahn, Sung Ku

    2013-01-01

    Background Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. Objective Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. Methods Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. Results Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. Conclusion Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment. PMID:23467730

  11. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  12. [THE ADVERSE EFFECTS OF SMOKING ON THE HANDS].

    PubMed

    Dreyfuss, Daniel; Calif, Edward; Stahl, Shalom

    2015-05-01

    Cigarette smoking is known to cause a multitude of harmful effects throughout the body. There are only a few accounts in the literature of these effects as related to the hands. This is a review of the literature, demonstrating the collected knowledge of decreased hand vascularity due to tobacco use and assessing the evidence connecting smoking and supposed resultant maladies, including Raynaud's phenomenon, hand-arm vibration syndrome, Buerger's disease, Dupuytren's contracture, carpal tunnel syndrome, effects on skin and fingernails, decreased skin and bone healing, complications of digit replantation and complex regional pain syndrome. Also presented is the possible increased risk of congenital hand malformations as related to maternal smoking. PMID:26168646

  13. Possible sertraline-induced extrapyramidal adverse effects in an adolescent.

    PubMed

    Wang, Lian-Fang; Huang, Jin-Wen; Shan, Si-Yang; Ding, Jia-Hong; Lai, Jian-Bo; Xu, Yi; Hu, Shao-Hua

    2016-01-01

    Sertraline has been considered to be a relatively safe selective serotonin reuptake inhibitor for adolescents for a long time. We report herein a case of a 16-year-old Chinese boy with depression who experienced extrapyramidal-like effects, for example, facial spasm, upper limb dystonia, akathisia, and other disturbed behaviors, while being treated with sertraline 200 mg per day. His movement symptoms were significantly alleviated after the discontinuation of sertraline and the administration of scopolamine. This finding indicates that albeit infrequent, sertraline may cause severe extrapyramidal symptoms in adolescent patients, suggesting that clinicians should be alert to the neurological side effects of sertraline in young patients. PMID:27226717

  14. Possible sertraline-induced extrapyramidal adverse effects in an adolescent

    PubMed Central

    Wang, Lian-fang; Huang, Jin-wen; Shan, Si-yang; Ding, Jia-hong; Lai, Jian-bo; Xu, Yi; Hu, Shao-hua

    2016-01-01

    Sertraline has been considered to be a relatively safe selective serotonin reuptake inhibitor for adolescents for a long time. We report herein a case of a 16-year-old Chinese boy with depression who experienced extrapyramidal-like effects, for example, facial spasm, upper limb dystonia, akathisia, and other disturbed behaviors, while being treated with sertraline 200 mg per day. His movement symptoms were significantly alleviated after the discontinuation of sertraline and the administration of scopolamine. This finding indicates that albeit infrequent, sertraline may cause severe extrapyramidal symptoms in adolescent patients, suggesting that clinicians should be alert to the neurological side effects of sertraline in young patients. PMID:27226717

  15. The problems of anticholinergic adverse effects in older patients.

    PubMed

    Feinberg, M

    1993-01-01

    The old saying 'red as a beet, dry as a bone, blind as a bat, hot as a hare, mad as a hatter' is often quoted when describing the autonomic effects of drugs that block the muscarinic cholinergic system. These effects may be subtle or dramatic, yet can be overlooked or discounted as a natural consequence of old age. Elderly patients can be particularly sensitive to the anticholinergic action of drugs because of physiological and pathophysiological changes that often accompany the aging process. The use of multiple drugs, a common finding in older patients, may result in pharmacodynamic and pharmacokinetic drug interactions that heighten anticholinergic effects. While the classic anticholinergic problems of decreased secretions, slowed gastrointestinal motility, blurred vision, increased heart rate, heat intolerance, sedation and possibly mild confusion, may be uncomfortable for a younger patient in relatively good health, these effects can be disastrous for older patients. Even the most common peripheral anticholinergic complaint of dry mouth can reduce the ability to communicate, predispose to malnutrition, promote mucosal damage, denture misfit or dental caries, and increase the risk of serious respiratory infection secondary to loss of antimicrobial activity of saliva. Mydriasis and the inability to accommodate will impair near vision and may precipitate narrow angle glaucoma in predisposed patients, but less obviously could lead to an increased risk of accidents, including falls. Somatic complaints of constipation and urinary hesitancy, could, in the presence of anticholinergic challenge, result in faecal impaction or urinary retention. Cardiac effects may be poorly tolerated. Increases in heart rate may precipitate or worsen angina. Finally, thermoregulatory impairment induced by anticholinergics, which block the ability to sweat, may lead to life threatening hyperthermia. Central anticholinergic effects range from sedation, mild confusion and inability to

  16. Identifying and managing adverse environmental health effects: 4. Pesticides

    PubMed Central

    Sanborn, Margaret D.; Cole, Donald; Abelsohn, Alan; Weir, Erica

    2002-01-01

    PESTICIDE EXPOSURE CAN CAUSE MANY DIFFERENT HEALTH EFFECTS, from acute problems such as dermatitis and asthma exacerbation to chronic problems such as chronic obstructive pulmonary disease and cancer. The resulting clinical presentations are undifferentiated, and specific knowledge of the links to environmental exposures is often required for effective diagnosis. In this article we illustrate the use of the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Drugs and Diet), a history-taking tool that assists physicians in quickly identifying possible environmental exposures. We also provide clinical information on the epidemiology, clinical presentations, treatment and prevention of pesticide exposures. PMID:12054413

  17. Abuse potential and adverse cognitive effects of mitragynine (kratom).

    PubMed

    Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

    2016-01-01

    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug. PMID:25262913

  18. The (Adverse) Effects of Expanding Higher Education: Evidence from Italy

    ERIC Educational Resources Information Center

    Oppedisano, Veruska

    2011-01-01

    Over the period 1995-1998 Italy experienced an expansion of its higher education supply with the aim of reducing regional differences in educational attainment. This paper evaluates the effects of this policy on enrolment, drop out and academic performance. The paper combines differences across provinces in the number of campuses constructed with…

  19. Abuse potential and adverse cognitive effects of mitragynine (kratom).

    PubMed

    Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

    2016-01-01

    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug.

  20. Increasing the Benefits of Chemotherapy by Ameliorating the Adverse Effects

    PubMed Central

    Fernandez, L.A.

    1987-01-01

    When cancer is first diagnosed in most patients, it is usually incurable. Chemotherapy can cause remissions, prolonged disease-free survival, and prolonged survival in general, but it is associated with considerable toxicity to the physical and mental well-being of the patient. The number of side-effects increases when multiple drug combinations are used. In addition, financial and social problems add to the stress of coping with a fatal disease. Therefore both patients and physicians have asked whether survival (sometimes for extra months) with added side-effects of chemotherapy is worthwhile. The “soft” index of quality of life has been measured by many investigators, and a variety of interventions have been found to alleviate some distress. PMID:21263996

  1. Adverse effects of thalidomide administration in patients with neoplastic diseases.

    PubMed

    Dimopoulos, Meletios A; Eleutherakis-Papaiakovou, Vagelis

    2004-10-01

    Thalidomide, a glutamic acid derivative, was withdrawn from clinical use in 1962 due to its severe teratogenic effects. Its recent reinstitution in clinical practice was related to its benefits in leprosy and multiple myeloma. Moreover, the antiangiogenic and immunomodulatory properties of thalidomide have led to its evaluation in several malignant diseases, including myelofibrosis, renal cell cancer, prostate cancer, and Kaposi sarcoma. However, thalidomide use is associated with several side effects: somnolence and constipation are the most common, while deep vein thrombosis and peripheral neuropathy are the most serious. A combination of thalidomide with steroids or chemotherapy is being evaluated in several phase 2 studies. While it is not yet clear whether these combinations will enhance efficacy, they appear to increase the toxicity of thalidomide, and thalidomide analogs are being developed to minimize this toxicity. Ongoing studies will clarify the potential advantages of these agents in the treatment of neoplastic diseases.

  2. In Silico Models for Repeated-Dose Toxicity (RDT): Prediction of the No Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect Level (LOAEL) for Drugs.

    PubMed

    Pizzo, Fabiola; Benfenati, Emilio

    2016-01-01

    The preclinical stage in drug development requires the determination of repeated-dose toxicity (RDT) in animal models. The main outcome of RDT studies is the determination of the no observed adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL). NOAEL is important since it serves to calculate the maximum recommended starting dose (MRSD) which is the safe starting dose for clinical studies in human beings. Since in vivo RDT studies are expensive and time-consuming, in silico approaches could offer a valuable alternative. However, NOAEL and LOAEL modeling suffer some limitations since they do not refer to a single end point but to several different effects and the doses used in experimental studies strongly influence the final results. Few attempts to model NOAEL and LOAEL have been reported. The available database and models for the prediction of NOAEL and LOAEL are reviewed here. PMID:27311467

  3. NEUROBEHAVIORAL TESTING IN HUMAN RISK ASSESSMENT

    PubMed Central

    Rohlman, Diane S.; Lucchini, Roberto; Anger, W. Kent; Bellinger, David C.; van Thriel, Christoph

    2008-01-01

    Neurobehavioral tests are being increasingly used in human risk assessment and there is a strong need for guidance. The field of neurobehavioral toxicology has evolved from research which initially focused on using traditional neuropsychological tests to identify “abnormal cases” to include methods used to detect sub-clinical deficits, to further incorporate the use of neurosensory assessment, and to expand testing from occupational populations to vulnerable populations including older adults and children. Even as exposures in the workplace are reduced, they have been increasing in the environment and research on exposure has now expanded to cross the entire lifetime. These neurobehavioral methods are applied in research and the findings used for regulatory purposes to develop preventative action for exposed populations. This paper reflects a summary of the talks presented at the symposium presented at the 11th meeting of the International Neurotoxicology Association. PMID:18539229

  4. Adverse effects of poor micronutrient status during childhood and adolescence.

    PubMed

    Kapil, Umesh; Bhavna, A

    2002-05-01

    Despite India's substantial progress in human development since its independence in 1947, 5-7% of its children have vitamin A deficiency disorders in selected geographic areas, 53% have iron deficiency anemia, and 9% have goiter. Three micronutrients--vitamin A, iron, and iodine--are among the most important of all the nutrients needed by the body because they are vital for developing normal learning and cognitive functions, immunity, work capacity, and reproductive health. The body cannot synthesize them, so they must be made available through the diet. Deficiencies of these three micronutrients are known to have devastating effects on health. PMID:12035866

  5. Metacognitive Control of Categorial Neurobehavioral Decision Systems.

    PubMed

    Foxall, Gordon R

    2016-01-01

    The competing neuro-behavioral decision systems (CNDS) model proposes that the degree to which an individual discounts the future is a function of the relative hyperactivity of an impulsive system based on the limbic and paralimbic brain regions and the relative hypoactivity of an executive system based in prefrontal cortex (PFC). The model depicts the relationship between these categorial systems in terms of the antipodal neurophysiological, behavioral, and decision (cognitive) functions that engender normal and addictive responding. However, a case may be made for construing several components of the impulsive and executive systems depicted in the model as categories (elements) of additional systems that are concerned with the metacognitive control of behavior. Hence, this paper proposes a category-based structure for understanding the effects on behavior of CNDS, which includes not only the impulsive and executive systems of the basic model but a superordinate level of reflective or rational decision-making. Following recent developments in the modeling of cognitive control which contrasts Type 1 (rapid, autonomous, parallel) processing with Type 2 (slower, computationally demanding, sequential) processing, the proposed model incorporates an arena in which the potentially conflicting imperatives of impulsive and executive systems are examined and from which a more appropriate behavioral response than impulsive choice emerges. This configuration suggests a forum in which the interaction of picoeconomic interests, which provide a cognitive dimension for CNDS, can be conceptualized. This proposition is examined in light of the resolution of conflict by means of bundling. PMID:26925004

  6. Metacognitive Control of Categorial Neurobehavioral Decision Systems.

    PubMed

    Foxall, Gordon R

    2016-01-01

    The competing neuro-behavioral decision systems (CNDS) model proposes that the degree to which an individual discounts the future is a function of the relative hyperactivity of an impulsive system based on the limbic and paralimbic brain regions and the relative hypoactivity of an executive system based in prefrontal cortex (PFC). The model depicts the relationship between these categorial systems in terms of the antipodal neurophysiological, behavioral, and decision (cognitive) functions that engender normal and addictive responding. However, a case may be made for construing several components of the impulsive and executive systems depicted in the model as categories (elements) of additional systems that are concerned with the metacognitive control of behavior. Hence, this paper proposes a category-based structure for understanding the effects on behavior of CNDS, which includes not only the impulsive and executive systems of the basic model but a superordinate level of reflective or rational decision-making. Following recent developments in the modeling of cognitive control which contrasts Type 1 (rapid, autonomous, parallel) processing with Type 2 (slower, computationally demanding, sequential) processing, the proposed model incorporates an arena in which the potentially conflicting imperatives of impulsive and executive systems are examined and from which a more appropriate behavioral response than impulsive choice emerges. This configuration suggests a forum in which the interaction of picoeconomic interests, which provide a cognitive dimension for CNDS, can be conceptualized. This proposition is examined in light of the resolution of conflict by means of bundling.

  7. Metacognitive Control of Categorial Neurobehavioral Decision Systems

    PubMed Central

    Foxall, Gordon R.

    2016-01-01

    The competing neuro-behavioral decision systems (CNDS) model proposes that the degree to which an individual discounts the future is a function of the relative hyperactivity of an impulsive system based on the limbic and paralimbic brain regions and the relative hypoactivity of an executive system based in prefrontal cortex (PFC). The model depicts the relationship between these categorial systems in terms of the antipodal neurophysiological, behavioral, and decision (cognitive) functions that engender normal and addictive responding. However, a case may be made for construing several components of the impulsive and executive systems depicted in the model as categories (elements) of additional systems that are concerned with the metacognitive control of behavior. Hence, this paper proposes a category-based structure for understanding the effects on behavior of CNDS, which includes not only the impulsive and executive systems of the basic model but a superordinate level of reflective or rational decision-making. Following recent developments in the modeling of cognitive control which contrasts Type 1 (rapid, autonomous, parallel) processing with Type 2 (slower, computationally demanding, sequential) processing, the proposed model incorporates an arena in which the potentially conflicting imperatives of impulsive and executive systems are examined and from which a more appropriate behavioral response than impulsive choice emerges. This configuration suggests a forum in which the interaction of picoeconomic interests, which provide a cognitive dimension for CNDS, can be conceptualized. This proposition is examined in light of the resolution of conflict by means of bundling. PMID:26925004

  8. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  9. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  10. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  11. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  12. 18 CFR 292.211 - Petition for initial determination on whether a project has a substantial adverse effect on the...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... determination on whether a project has a substantial adverse effect on the environment (AEE petition). 292.211... for initial determination on whether a project has a substantial adverse effect on the environment... that it has no substantial adverse effect on the environment as specified in § 292.208(b)(1). (b)...

  13. The uses and adverse effects of beryllium on health

    PubMed Central

    Cooper, Ross G.; Harrison, Adrian P.

    2009-01-01

    Context: This review describes the health effects of beryllium exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to beryllium on physiological function and well being. Materials and Methods: The criteria used in the current review for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability, and Health. Articles were classified based on acute and chronic exposure and toxicity of beryllium. Results: The proportions of utilized and nonutilized articles were tabulated. Years 2001–10 gave the greatest match (45.9%) for methodological parameters, followed by 27.71% for 1991–2000. Years 1971–80 and 1981–90 were not significantly different in the information published and available whereas years 1951–1960 showed a lack of suitable articles. Some articles were published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures need to be taken to prevent hazardous exposure to this element, making its biological monitoring in the workplace essential. PMID:20386622

  14. The Adverse Effects of Alcohol on Vitamin A Metabolism

    PubMed Central

    Clugston, Robin D.; Blaner, William S.

    2012-01-01

    The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A), as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered. PMID:22690322

  15. Unexpected adverse effects of Freon 11 and Freon 12 as medication propellants.

    PubMed

    Oenbrink, R J

    1993-06-01

    Metered-dose inhalers are frequently used in treating pulmonary diseases associated with bronchoconstriction, chiefly asthma and chronic bronchitis. These aerosolized medications are not without the potential for adverse effects. The author describes two patients who likely had adverse reactions to the Freon propellants used in the inhalers. These reactions are reported in order to alert physicians to their possible occurrence and to suggest a rational treatment approach. PMID:8349485

  16. Adverse effects of bisphenol A on water louse (Asellus aquaticus).

    PubMed

    Plahuta, Maja; Tišler, Tatjana; Pintar, Albin; Toman, Mihael Jožef

    2015-07-01

    Experiments were performed to study the effects of short and long-term exposure to bisphenol A (BPA) on a freshwater crustacean isopod Asellus aquaticus (L.). Two life stages of isopods were exposed to a range of BPA concentrations, from aqueous and two dietary sources, in the form of with BPA spiked conditioned alder leaf (Alnus glutinosa) discs, or spiked formulated sediment, to determine the relative importance of each source of exposure on the uptake of this contaminant. Several lethal and sublethal endpoints were evaluated in this study to measure the potential effects of BPA on A. aquaticus, including mortality, growth and feeding rate inhibition, mobility inhibition, de-pigmentation and molting disturbances. They signify a correlation to BPA levels and a difference in BPA uptake efficiency from different uptake sources. Results of acute exposure to BPA show a greater sensitivity of test systems using juvenile specimens with a 96 h LC₅₀ of 8.6 mg L(-1) BPA in water medium and a 96 h LC₅₀ of 13.5 mg L(-1) BPA in sediment. In comparison, adult isopods show a 96 h LC₅₀ of 25.1 mg L(-1) BPA in water medium and a 96 h LC₅₀ of 65.1 mg L(-1) BPA in sediment. Observed endpoints of chronic exposures suggest the alder leave discs to be the most efficient uptake source of BPA, in contrast to uptake from water or heterogeneous sediment. Significant (p<0.05) growth inhibition, with a 21d NOEC of 0.5/2.5 mg L(-1) (for juvenile/adult organisms), and feeding rate inhibition, with a 21d NOEC of 0.5/1.0 mg L(-1) (for juvenile/adult organisms), were proven to be the most sensitive toxicity endpoints. An even more sensitive effect turned out to be molting frequency, which was significantly reduced; a 21d NOEC was 1.0 mg L(-1) of BPA for adult organisms and an even lower 21d NOEC of 0.05 mg L(-1) of BPA for juveniles. The observed endpoints are recorded at very low, non-toxic exposure concentrations, indicating that BPA acts as an endocrine disrupting compound, as

  17. Thermal Dose and the Probability of Adverse Effects from HIFU

    NASA Astrophysics Data System (ADS)

    Church, Charles C.

    2007-05-01

    The absorption of high-intensity, focused ultrasound (HIFU) by the body results in brief, intense heating capable of killing cells, tissues or entire organisms, thereby providing the basis for many applications in medical therapy. The object of such therapy is in assuring the destruction of diseased tissue while sparing adjacent, healthy tissue. However, even moderate heating to a few degrees above normal physiological temperatures can perturb biological systems, e.g., by altering normal metabolic processes. In modeling the bioeffects produced by ultrasound-induced heating, the physicist typically relies on bulk tissue properties and ultrasound exposure parameters to calculate the thermal `dose' delivered to the tissue. Although thermal dose is currently given in units of time rather than energy, the concept is quite useful, and its use in quantifying the probability and extent of biological effects expected from therapeutic exposures is demonstrated. The results demonstrate the need for additional experimental data to validate and advance existing theoretical approaches for HIFU exposures.

  18. Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

    2016-01-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  19. Adversity in preschool-aged children: Effects on salivary interleukin-1β.

    PubMed

    Tyrka, Audrey R; Parade, Stephanie H; Valentine, Thomas R; Eslinger, Nicole M; Seifer, Ronald

    2015-05-01

    Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary interleukin (IL)-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records. Contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. The number of past-month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Postchallenge IL-1β displayed positive associations with each adversity variable, but these were not significant. CRP was not significantly associated with any of the adversity variables. Given the evidence suggesting the involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

  20. The adverse effects of obesity on conception and implantation.

    PubMed

    Brewer, Christopher J; Balen, Adam H

    2010-09-01

    Whilst many multiparous women are obese (body mass index >30 kg/m(2)), obesity has been associated with impaired fecundity; however, the mechanism which links obesity to reduced fertility remains to be fully elucidated. Obese women, particularly those with central obesity, are less likely to conceive per cycle. Obese women suffer perturbations to the hypothalamic-pituitary-ovarian axis, menstrual cycle disturbance and are up to three times more likely to suffer oligo-/anovulation. A fine hormonal balance regulates follicular development and oocyte maturation, and it has been observed that obesity can alter the hormonal milieu. Leptin, a hormone produced by adipocytes, is elevated in obese women, and raised leptin has been associated with impaired fecundity. Obesity impairs ovulation but has also been observed to detrimentally affect endometrial development and implantation. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, and so obese women with PCOS often have a more severe phenotype and experience more subfertility. Obesity also impairs the response of women to assisted conception treatments. Weight loss through lifestyle modification or bariatric surgery has been demonstrated to restore menstrual cyclicity and ovulation and improve the likelihood of conception. In this article, we will discuss the effect of obesity upon key reproductive mechanisms and its relation to fertility treatments.

  1. Adverse effects of psychological therapy: An exploratory study of practitioners' experiences from child and adolescent psychiatry.

    PubMed

    Jonsson, Ulf; Johanson, Josefin; Nilsson, Elin; Lindblad, Frank

    2016-07-01

    The scientific knowledge about adverse effects of psychological therapies and how such effects should be detected is limited. It is possible that children and adolescents are particularly vulnerable and need specific support in order to express adverse effects. In this exploratory study, we used a qualitative approach to explore practitioners' experiences of this phenomenon. Fourteen practitioners providing psychological therapy within the Child and Adolescent Psychiatric Service were interviewed. Qualitative content analysis was applied to the data. Four overarching categories brought up by the practitioners were identified: vagueness of the concept (reflecting that the concept was novel and hard to define), psychotherapist-client interaction (encompassing aspects of the interaction possibly related to adverse effects), consequences for the young person (including a range of emotional, behavioural and social consequences) and family effects (e.g. professional complications and decreased autonomy for the parent). Professional discussions on these issues could improve psychological therapy for children and adolescents. Based on our findings and previous research, we propose three basic aspects to consider when adverse effects are detected and managed in this context: typology (form, severity and duration), aetiology (hypothesis about the causes) and perspective (adverse effects seen from the points of view of different interested parties).

  2. Long-term antidepressant use: patient perspectives of benefits and adverse effects

    PubMed Central

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients’ experiences and views of this form of treatment. This study used mixed methods to examine patients’ views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3–15 years), were extracted from an anonymous online survey of patients’ experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

  3. Long-term antidepressant use: patient perspectives of benefits and adverse effects.

    PubMed

    Cartwright, Claire; Gibson, Kerry; Read, John; Cowan, Ondria; Dehar, Tamsin

    2016-01-01

    Long-term antidepressant treatment has increased and there is evidence of adverse effects; however, little is known about patients' experiences and views of this form of treatment. This study used mixed methods to examine patients' views and experiences of long-term antidepressant treatment, including benefits and concerns. Data from 180 patients, who were long-term users of antidepressants (3-15 years), were extracted from an anonymous online survey of patients' experiences of antidepressants in New Zealand. Participants had completed rating scales about the effectiveness of antidepressants, levels of depression before and during antidepressant use, quality of life, and perceived adverse effects. Two open-ended questions allowed participants to comment on personal experiences. The majority (89.4%) reported that antidepressants had improved their depression although 30% reported moderate-to-severe depression on antidepressants. Common adverse effects included withdrawal effects (73.5%), sexual problems (71.8%), and weight gain (65.3%). Adverse emotional effects, such as feeling emotionally numb (64.5%) and addicted (43%), were also common. While the majority of patients were pleased with the benefits of antidepressant treatment, many were concerned about these adverse effects. Some expressed a need for more information about long-term risks and increased information and support to discontinue. PMID:27528803

  4. Road traffic and adverse effects on respiratory health in children.

    PubMed Central

    Wjst, M; Reitmeir, P; Dold, S; Wulff, A; Nicolai, T; von Loeffelholz-Colberg, E F; von Mutius, E

    1993-01-01

    OBJECTIVES--To examine whether road traffic in a big city has a direct effect on pulmonary function and respiratory symptoms in children. DESIGN--Cross sectional study. SETTING--Of all 7445 fourth grade children (aged 9-11 years) in Munich, 6537 were examined. Of the children with German nationality and the same residence during the past five years and known exposure data, 4678 questionnaires and 4320 pulmonary function tests could be analysed. MAIN OUTCOME MEASURES--Variables of pulmonary function by forced expiration and respiratory symptoms reported in a questionnaire; census data on car traffic collected in the school district. RESULTS--Density of car traffic ranged from 7000 to 125,000 cars per 24 hours. Multiple regression analysis of peak expiratory flow showed a significant decrease of 0.71% (95% confidence interval 1.08% to 0.33%) per increase of 25,000 cars daily passing through the school district on the main road. Maximum expiratory flow when 25% vital capacity had been expired was decreased by 0.68% (1.11% to 0.25%). In contrast, response to cold air challenge was not increased. The adjusted odds ratio for the cumulative prevalence of recurrent wheezing with the same exposure was 1.08 (1.01 to 1.16). Cumulative prevalence of recurrent dyspnoea was increased, with an odds ratio of 1.10 (1.00 to 1.20). Lifetime prevalence of asthma (odds ratio 1.04; 0.89 to 1.21) and recurrent bronchitis (1.05; 0.98 to 1.12) were not significantly increased. CONCLUSIONS--High rates of road traffic diminish forced expiratory flow and increase respiratory symptoms in children. Images FIG 1 PMID:7691304

  5. Potential adverse effects of omega-3 Fatty acids in dogs and cats.

    PubMed

    Lenox, C E; Bauer, J E

    2013-01-01

    Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions.

  6. Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van; Cusimano, Michael; Tsao, May; Menard, Cynthia; Kulkarni, Abhaya V.; Schwartz, Michael; Zadeh, Gelareh

    2012-02-01

    Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the

  7. Refining Neurobehavioral Assessment of the High-Risk Infant Using the NICU Network Neurobehavioral Scale.

    PubMed

    Sullivan, Mary C; Miller, Robin J; Fontaine, Lynne Andreozzi; Lester, Barry

    2012-01-01

    Nurses caring for high-risk infants use advanced assessment skills to identify the nature of infant instability and to assure timely intervention. The NICU Network Neurobehavioral Scale (NNNS) is a comprehensive assessment of neurological integrity and behavioral function of infants at risk. Research evidence supports its validity and reliability for clinical and research use. The NNNS offers nurses a neurobehavioral assessment especially suited to high-risk and premature infants.

  8. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

    PubMed Central

    Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles. PMID:24187619

  9. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX.

    PubMed

    Bano, Nusrat; Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m(2)), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m(2)) after few treatment cycles.

  10. The Effect of Lifetime Cumulative Adversity and Depressive Symptoms on Functional Status

    PubMed Central

    Litwin, Howard

    2014-01-01

    Objectives. The study aimed to examine whether lifetime cumulative adversity (LCA) and depressive symptoms moderate time-related trajectories of functional status. Method. A total of 15,073 older adults (mean age = 63.91 at Wave 1) who participated in the first four waves of the Survey of Health, Ageing and Retirement in Europe reported on exposure to negative life events, depressive symptoms and three measures of functional status—difficulty in performing daily and instrumental activities, and functional limitation. Results. Growth–curve models showed that time-related increase in disability and functional limitation was steeper among those exposed to higher levels of lifetime adversity. Moreover, a three-way interaction between time, lifetime adversity, and depressive symptoms emerged across measures of functional status, so that when exposure to lifetime adversity was accompanied by high level of depressive symptoms, the time-related increase in disability and functional limitation was the steepest. Discussion. LCA is associated with a hastening of the disablement process, especially under conditions of high distress. Although the overall modest effects imply that resilience to lifetime adversity is widespread among older adults, prevention and intervention programs should consider that distressed older adults previously exposed to high levels of lifetime adversity are at risk for more rapid impairment in functional status. PMID:24898028

  11. Neurobehavioral and Psychosocial Issues in Klinefelter Syndrome

    ERIC Educational Resources Information Center

    Geschwind, Daniel H.; Dykens, Elisabeth

    2004-01-01

    Klinefelter Syndrome (KS) is a relatively common (1/500 to 1/1,000) genetic syndrome caused by an extra X chromosome in males, leading to an XXY karyotype. In most cases, the physical and neurobehavioral characteristics of KS are relatively mild, and KS is not usually associated with moderate or severe mental retardation. However, KS is often…

  12. Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.

    PubMed

    Yoshitomi, Toru; Ozaki, Yuki; Thangavel, Sindhu; Nagasaki, Yukio

    2013-11-28

    The ultimate goal of cancer chemotherapy is to achieve a cure without causing any adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)), which disintegrates under acidic conditions and exposes nitroxide radicals, leading to strongly scavenging reactive oxygen species (ROS). After intravenous administration of RNP(N) to tumor bearing mice, it effectively accumulated in tumors due to the leaky neovascular and immature lymphatic system and scavenged ROS, resulting in suppression of inflammation and activation of NF-кB, after disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to treatments with anticancer agents, doxorubicin, to tumor-bearing mice significantly suppressed the progression of tumor size, compared to low-molecular weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed adverse effects of doxorubicin to normal organs due to the scavenging ROS and suppression of inflammation, which was confirmed by reduction in lactate dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus anticipated as a novel and ideal adjuvant for cancer chemotherapy.

  13. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

    PubMed Central

    ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

    2013-01-01

    Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

  14. A review of the adverse effects and safety of noradrenergic antidepressants.

    PubMed

    Whiskey, Eromona; Taylor, David

    2013-08-01

    There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose.

  15. Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

    NASA Astrophysics Data System (ADS)

    Herrera, Higmar; Yañez, Elvia; Deras, Diana C.; Reyes, Francianella

    2010-12-01

    This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55±13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

  16. Identifying potential adverse effects using the web: a new approach to medical hypothesis generation

    PubMed Central

    Benton, Adrian; Ungar, Lyle; Hill, Shawndra; Hennessy, Sean; Mao, Jun; Chung, Annie; Leonard, Charles E.; Holmes, John H.

    2011-01-01

    Medical message boards are online resources where users with a particular condition exchange information, some of which they might not otherwise share with medical providers. Many of these boards contain a large number of posts and contain patient opinions and experiences that would be potentially useful to clinicians and researchers. We present an approach that is able to collect a corpus of medical message board posts, de-identify the corpus, and extract information on potential adverse drug effects discussed by users. Using a corpus of posts to breast cancer message boards, we identified drug event pairs using co-occurrence statistics. We then compared the identified drug event pairs with adverse effects listed on the package labels of tamoxifen, anastrozole, exemestane, and letrozole. Of the pairs identified by our system, 75–80% were documented on the drug labels. Some of the undocumented pairs may represent previously unidentified adverse drug effects. PMID:21820083

  17. A review of the adverse effects and safety of noradrenergic antidepressants.

    PubMed

    Whiskey, Eromona; Taylor, David

    2013-08-01

    There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose. PMID:23784737

  18. Antiangiogenic agents and the skin: cutaneous adverse effects of sorafenib, sunitinib, and bevacizumab.

    PubMed

    Ara, M; Pastushenko, E

    2014-12-01

    As new antiangiogenic therapies have been introduced and added to the therapeutic arsenal against various types of cancer, previously unknown adverse effects have been detected. These effects negatively impact patients' quality of life and can even make it necessary to suspend treatment. Adverse skin reactions occur in 90% of patients treated with angiogenesis inhibitors. In some cases, a correlation has been observed between the severity of reactions and treatment efficacy and tumor response. It is therefore extremely important that dermatologists be able to recognize and manage these reactions. Moreover, in order to avoid the unjustified withdrawal of potentially life-extending treatments, dermatologists must be able to differentiate between non-life-threatening reactions and life-threatening reactions that necessitate the suspension of treatment. In this review article, we analyze the main cutaneous adverse effects of the most common antiangiogenic agents. PMID:24766821

  19. Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

    SciTech Connect

    Herrera, Higmar; Yanez, Elvia

    2010-12-07

    This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

  20. The value of glucocorticoid co-therapy in different rheumatic diseases - positive and adverse effects

    PubMed Central

    2014-01-01

    Glucocorticoids play a pivotal role in the management of many inflammatory rheumatic diseases. The therapeutic effects range from pain relief in arthritides, to disease-modifying effects in early rheumatoid arthritis, and to strong immunosuppressive actions in vasculitides and systemic lupus erythematosus. There are multiple indications that adverse effects are more frequent with the longer use of glucocorticoids and use of higher dosages, but high-quality data on the occurrence of adverse effects are scarce especially for dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease activity, risk factors and individual responsiveness of the patient should guide treatment decisions. Monitoring for adverse effects should also be tailored to the patient. Continuously balancing the benefits and risks of glucocorticoid therapy is recommended. There is an ongoing quest for new drugs with glucocorticoid actions without the potential to cause harmful effects, such as selective glucocorticoid receptor agonists, but the application of a new compound in clinical practice will probably not occur within the next few years. In the meantime, basic research on glucocorticoid effects and detailed reports on therapeutic efficacy and occurrence of adverse effects will be valuable in weighing benefits and risks in clinical practice. PMID:25608693

  1. On the Likelihood of Single-Walled Carbon Nanotubes Causing Adverse Marine Ecological Effects

    EPA Science Inventory

    This brief article discusses the ecological effects of single-walled carbon nanotubes (SWNTs)in the marine environment. Based on new research and a review of the scientific literature, the paper concludes that SWNTs are unlikely to cause adverse ecological effects in the marine ...

  2. Topiramate-Induced Somnambulism in a Migraineur: A Probable Idiosyncratic Adverse Effect

    PubMed Central

    Mathew, Thomas; Sarma, G. R. K.; Nadig, Raghunandan; Varghese, Raji

    2012-01-01

    Somnambulism (sleepwalking) is a disorder of arousal that falls under “parasomnia” group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers.1 This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. Citation: Mathew T; Sarma GRK; Nadig R; Varghese R. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect. J Clin Sleep Med 2012;8(2):197-198. PMID:22505867

  3. Neurobehavioral changes in mice exposed to fast neutrons in utero.

    PubMed

    Ishida, Yuka; Ohmachi, Yasushi; Takai, Nobuhiko; Hiraoka, Takeshi; Ogiu, Toshiaki; Nishikawa, Tetsu; Nishimura, Yoshikazu; Shimada, Yoshiya

    2011-01-01

    Epidemiological studies have revealed that radiation causes brain development abnormalities in atomic bomb survivors exposed in utero. Rat and mouse studies have also shown that prenatal exposure to low-linear energy transfer radiation induces developmental brain anomalies. Because the effects of prenatal irradiation on adult behavior patterns remain largely unknown, the present study investigated the effects of neutron exposure in utero on postnatal behavior patterns in mice. [C57BL/6J × C3H/He] hybrid (B6C3F1) mice were exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02-0.2 Gy) or Cs-137 gamma-rays (0.2-1.5 Gy) on embryonic day 13.5. At 5.5-8 months of age, the neurobehavior of male offspring was examined by Rota-rod treadmill and locomotor activity. The accumulation of radio-labeled drug at muscarinic acetylcholine and serotonin receptors in mice from control and neutron-irradiated groups was determined by the tracer method. Locomotor activity during the dark period increased in the 0.02 Gy neutron-irradiated group. Furthermore, at 5.5 months of age, tracer binding in vivo to the muscarinic acetylcholine increased and to the serotonin receptors decreased in the 0.02 Gy neutron-irradiated group. In conclusion, the present study reveals that a certain "low-dose window" may exist for radiation-induced changes in neurobehavior and binding to neurotransmitter receptors, because there was correlation in neurobehavior and binding to neurotransmitter receptors in the 0.02 Gy neutron-irradiated group though there was not correlation in the neutron-irradiated groups more than 0.05 Gy. PMID:21422737

  4. Neurobehavioral changes in mice exposed to fast neutrons in utero.

    PubMed

    Ishida, Yuka; Ohmachi, Yasushi; Takai, Nobuhiko; Hiraoka, Takeshi; Ogiu, Toshiaki; Nishikawa, Tetsu; Nishimura, Yoshikazu; Shimada, Yoshiya

    2011-01-01

    Epidemiological studies have revealed that radiation causes brain development abnormalities in atomic bomb survivors exposed in utero. Rat and mouse studies have also shown that prenatal exposure to low-linear energy transfer radiation induces developmental brain anomalies. Because the effects of prenatal irradiation on adult behavior patterns remain largely unknown, the present study investigated the effects of neutron exposure in utero on postnatal behavior patterns in mice. [C57BL/6J × C3H/He] hybrid (B6C3F1) mice were exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02-0.2 Gy) or Cs-137 gamma-rays (0.2-1.5 Gy) on embryonic day 13.5. At 5.5-8 months of age, the neurobehavior of male offspring was examined by Rota-rod treadmill and locomotor activity. The accumulation of radio-labeled drug at muscarinic acetylcholine and serotonin receptors in mice from control and neutron-irradiated groups was determined by the tracer method. Locomotor activity during the dark period increased in the 0.02 Gy neutron-irradiated group. Furthermore, at 5.5 months of age, tracer binding in vivo to the muscarinic acetylcholine increased and to the serotonin receptors decreased in the 0.02 Gy neutron-irradiated group. In conclusion, the present study reveals that a certain "low-dose window" may exist for radiation-induced changes in neurobehavior and binding to neurotransmitter receptors, because there was correlation in neurobehavior and binding to neurotransmitter receptors in the 0.02 Gy neutron-irradiated group though there was not correlation in the neutron-irradiated groups more than 0.05 Gy.

  5. A replication of the study ‘Adverse effects of spinal manipulation: a systematic review’

    PubMed Central

    2012-01-01

    and related adverse effects. PMID:22998971

  6. Photoreception for circadian, neuroendocrine, and neurobehavioral regulation.

    PubMed

    Hanifin, John P; Brainard, George C

    2007-03-01

    In the art and science of lighting, four traditional objectives have been to provide light that: 1) is optimum for visual performance; 2) is visually comfortable; 3) permits aesthetic appreciation of the space; and 4) conserves energy. Over the past 25 years, it has been demonstrated that there are nonvisual, systemic effects of light in healthy humans. Furthermore, light has been used to successfully treat patients with selected affective and sleep disorders as well as healthy individuals who have circadian disruption due to shift work, transcontinental jet travel, or space flight. Recently, there has been an upheaval in the understanding of photoreceptive input to the circadian system of humans and other mammals. Analytical action spectra in rodents, primates, and humans have identified 446-484 nm (predominantly the blue part of the spectrum) as the most potent wavelength region for neuroendocrine, circadian, and neurobehavioral responses. Those studies suggested that a novel photosensory system, distinct from the visual rods and cones, is primarily responsible for this regulation. Studies have now shown that this new photosensory system is based on a small population of widely dispersed retinal ganglion cells that are intrinsically responsive to light, and project to the suprachiasmatic nuclei and other nonvisual centers in the brain. These light-sensitive retinal ganglion cells contain melanopsin, a vitamin A photopigment that mediates the cellular phototransduction cascade. Although light detection for circadian and neuroendocrine phototransduction seems to be mediated principally by a novel photosensory system in the eye, the classic rod and cone photoreceptors appear to play a role as well. These findings are important in understanding how humans adapt to lighting conditions in modern society and will provide the basis for major changes in future architectural lighting strategies.

  7. Possible involvement of DEC1 on the adverse effects of quinolone antibiotics.

    PubMed

    Shi, Xiaohong; Zheng, Yan; Ma, Wanshan; Wang, Yunshan

    2010-04-30

    Quinolone antibacterial agents are widely used in the clinic because of their high antibacterial activity, broad spectra and favorable pharmacokinetics. However, the adverse effects induced by quinolones, such as tendon/articular toxicity, central nervous system toxicity, phototoxicity and dysglycemia, have greatly restricted their therapeutic use. Differentiated embryo-chondrocyte expressed gene 1 (DEC1), an important transcription factor that has a basic helix-loop-helix domain and is ubiquitously expressed in both human embryonic and adult tissues, has a pivotal function in various biological phenomena, including neurogenesis, neuroregulation, chondrogenesis, cell growth, oncogenesis, immune balance and circandian rhythm. Recently, DEC1 has received increasing attention for its role in maintaining the homeostasis of metabolism and energy. Research has shown that DEC1 may play a vital role in metabolic disease. Although the mechanism of the adverse reactions caused by quinolones has not been clarified, the distribution of these serious adverse effects in tissues and organs is consistent with the expression of DEC1 in corresponding normal tissues. In the present paper, we review evidence showing that DEC1 may take part in the adverse effects induced by quinolone antibiotics. The investigation of the molecular details of the toxicity caused by quinolones may help overcome the shortcomings of the antibiotics and reveal new, useful therapeutic functions besides their antimicrobial effect.

  8. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Flagging of studies for potential adverse effects. 158.34 Section 158.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES General Provisions § 158.34 Flagging...

  9. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Flagging of studies for potential adverse effects. 158.34 Section 158.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES General Provisions § 158.34 Flagging...

  10. 40 CFR 158.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Flagging of studies for potential adverse effects. 158.34 Section 158.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES General Provisions § 158.34 Flagging...

  11. Caregiver Acceptance of Adverse Effects and Use of Cholinesterase Inhibitors in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Oremus, Mark; Wolfson, Christina; Vandal, Alain C.; Bergman, Howard; Xie, Qihao

    2007-01-01

    Caregivers play a determining role in choosing treatments for persons with Alzheimer's disease. The objective of this study was to examine caregivers' willingness to have persons with Alzheimer's disease continue taking cholinesterase inhibitors in the event that any 1 of 11 adverse effects was to occur. Data were gathered via postal questionnaire…

  12. Potassium fertilization mitigates the adverse effects of drought on selected Zea mays cultivars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the present study, the role of potassium (K) in mitigating the adverse effects of drought stress (DS) on 2 maize (Zea mays L.) cultivars, ‘Shaandan 9’ (S9; drought-tolerant) and ‘Shaandan 911’ (S911; drought-sensitive), was assessed. K application increased dry matter (DM) across all growth stage...

  13. ARE ENVIRONMENTAL EXPOSURES TO CHLOROPHENOXY HERBICIDES ASSOCIATED WITH AN INCREASE IN ADVERSE HUMAN HEALTH EFFECTS?

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study because exposures may be widespread, low-dose in nature, and common throughout the study population. Individual risk-factor epidemiology may not be able to initially ident...

  14. ENVIRONMENTAL POLLUTANTS AND ADVERSE HUMAN HEALTH EFFECTS: HAZARD IDENTIFICATION USING INTERREGION COMPARISONS

    EPA Science Inventory

    Background: Associations between adverse health effects and environmental exposures are difficult to study, because exposures may be widespread, low-dose in nature, and common throughout the study population. Therefore, individual risk-factor epidemiology may not be the right to...

  15. Prenatal tobacco exposure is related to neurobehavioral modifications in infants of adolescent mothers

    PubMed Central

    Barros, Marina C. M.; Mitsuhiro, Sandro S.; Chalem, Elisa; Laranjeira, Ronaldo R.; Guinsburg, Ruth

    2011-01-01

    INTRODUCTION: Prenatal tobacco exposure interferes with neonatal outcomes. OBJECTIVE: To determine the neonatal neurobehavioral effects of in utero tobacco exposure. METHODS: This prospective cross-sectional study included healthy, term, with birth weight appropriate for gestacional age neonates without exposure to alcohol, drugs, or infections, born to adolescent mothers without psychiatric disorders or post-traumatic stress. Infants were classified according to in utero tobacco exposure, as identified by the Composite International Diagnostic Interview administered to mothers. Neurobehavior was assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Both tools were administered between 24 and 72 hours after birth. Neurobehavioral outcomes were compared between exposed and non-exposed infants by ANOVA. The associations between neurobehavioral scores and number of cigarettes smoked were studied by linear correlation. RESULTS: During the study, 928 newborns of adolescent mothers were born, and 388 were included in the study. Of these, 23 were exposed to tobacco, and 365 neonates were not exposed. There were no differences between the groups in gestational age, birth weight, post-natal age at the exam, or time between last feeding and exam. Exposed neonates showed higher scores on arousal (p = 0.004), excitability (p = 0.003), and stress/abstinence signals (p = 0.019) and a lower score on regulation (p = 0.025). After adjusting for the type of anesthesia, mode of delivery, gender, age at neurologic exam, exam duration and time between last feeding and exam, differences in arousal and excitability remained significant. The mean number of cigarettes consumed daily was positively correlated with lethargy (p = 0.013) and inversely with attention (p = 0.043). CONCLUSIONS: Neonates exposed in utero to tobacco showed worse neurobehavioral performance between 24 and 48 hours of life. PMID:22179166

  16. Orlistat-associated adverse effects and drug interactions: a critical review.

    PubMed

    Filippatos, Theodosios D; Derdemezis, Christos S; Gazi, Irene F; Nakou, Eleni S; Mikhailidis, Dimitri P; Elisaf, Moses S

    2008-01-01

    Orlistat, an anti-obesity drug, is a potent and specific inhibitor of intestinal lipases. In light of the recent US FDA approval of the over-the-counter sale of orlistat (60 mg three times daily), clinicians need to be aware that its use may be associated with less well known, but sometimes clinically relevant, adverse effects. More specifically, the use of orlistat has been associated with several mild-to-moderate gastrointestinal adverse effects, such as oily stools, diarrhoea, abdominal pain and faecal spotting. A few cases of serious hepatic adverse effects (cholelithiasis, cholostatic hepatitis and subacute liver failure) have been reported. However, the effects of orlistat on non-alcoholic fatty liver disease are beneficial. Orlistat-induced weight loss seems to have beneficial effects on blood pressure. No effect has been observed on calcium, phosphorus, magnesium, iron, copper or zinc balance or on bone biomarkers. Interestingly, the use of orlistat has been associated with rare cases of acute kidney injury, possibly due to the increased fat malabsorption resulting from the inhibition of pancreatic and gastric lipase by orlistat, leading to the formation of soaps with calcium and resulting in increased free oxalate absorption and enteric hyperoxaluria. Orlistat has a beneficial effect on carbohydrate metabolism. No significant effect on cancer risk has been reported with orlistat.Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness. This review considers orlistat-related adverse effects and drug interactions. The clinical relevance and pathogenesis of these effects is also discussed.

  17. [Analysis of the cardiac side effects of antipsychotics: Japanese Adverse Drug Event Report Database (JADER)].

    PubMed

    Ikeno, Takashi; Okumara, Yasuyuki; Kugiyama, Kiyotaka; Ito, Hiroto

    2013-08-01

    We analyzed the cases of side effects due to antipsychotics reported to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) from Jan. 2004 to Dec. 2012. We used the Japanese Adverse Drug Event Report Database (JADER) and analyzed 136 of 216,945 cases using the defined terms. We also checked the cardiac adverse effects listed in the package inserts of the antipsychotics involved. We found cases of Ikr blockade resulting in sudden death (49 cases), electrocardiogram QT prolonged (29 cases), torsade de pointes (TdP, 19 cases), ventricular fibrillation (VF, 10 cases). M2 receptor blockade was observed in tachycardia (8 cases) and sinus tachycardia (3 cases). Calmodulin blockade was involved in reported cardiomyopathy (3 cases) and myocarditis (1 case). Multiple adverse events were reported simultaneously in 14 cases. Our search of package inserts revealed warnings regarding electrocardiogram QT prolongation (24 drugs), tachycardia (23), sudden death (18), TdP (14), VF (3), myocarditis (1) and cardiomyopathy (1). We suggest that when an antipsychotic is prescribed, the patient should be monitored regularly with ECG, blood tests, and/or biochemical tests to avoid adverse cardiac effects. PMID:25069255

  18. Identification and characterization of adverse effects in 21st century toxicology.

    PubMed

    Keller, Douglas A; Juberg, Daland R; Catlin, Natasha; Farland, William H; Hess, Frederick G; Wolf, Douglas C; Doerrer, Nancy G

    2012-04-01

    The practice of toxicology is changing rapidly, as demonstrated by the response to the 2007 NRC report on "Toxicity Testing in the 21(st) Century." New assays are being developed to replace animal testing; yet the use of data from these assays in decision making is not clear. A Health and Environmental Sciences Institute committee held a May 2011 workshop to discuss approaches to identifying adverse effects in the context of the NRC report. Scientists from industry, government, academia, and NGOs discussed two case studies and explored how information from new, high data content assays developed for screening can be used to differentiate adverse effects from adaptive responses. The terms "adverse effect" and "adaptive response" were defined, as well as two new terms, the relevant pathways of toxicological concern (RPTCs) and relevant responses for regulation (RRRs). RPTCs are biochemical pathways associated with adverse events and need to be elucidated before they are used in regulatory decision making. RRRs are endpoints that are the basis for risk assessment and may or may not be at the level of pathways. Workshop participants discussed the criteria for determining whether, at the RPTC level, an effect is potentially adverse or potentially indicative of adaptability, and how the use of prototypical, data-rich compounds could lead to a greater understanding of RPTCs and their use as RRRs. Also discussed was the use of RPTCs in a weight-of-evidence approach to risk assessment. Inclusion of data at this level could decrease uncertainty in risk assessments but will require the use of detailed dosimetry and consideration of exposure context and the time and dose continuum to yield scientifically based decisions. The results of this project point to the need for an extensive effort to characterize RPTCs and their use in risk assessment to make the vision of the 2007 NRC report a reality.

  19. Systematic Review of Adverse Effects from Herbal Drugs Reported in Randomized Controlled Trials.

    PubMed

    Lee, Ji Young; Jun, Seung Ah; Hong, Sung Shin; Ahn, Yo Chan; Lee, Dong Soo; Son, Chang Gue

    2016-09-01

    Herbal drugs have become a popular form of healthcare, raising concerns about their safety. This study aimed to characterize the adverse effects of herbal drugs through a systematic review of results reported in randomized controlled trials (RCTs). Using eight electronic databases including PubMed, the Cochrane library and six Korean medical databases, the frequency of reported toxicity was recorded based on drug composition and indication. Among 4957 potentially relevant articles, 242 papers comprised of 244 studies met our inclusion criteria; these included 111 studies of a single herb and 133 of multiple herbs. These studies accounted for a total 15 441 participants (male = 5590; female = 9851; 7383 for single and 8058 for multiple herb studies). There were 480 cases (3.1%) of adverse events (344 for single, 136 for multiple herb studies; p < 0.01). A total of 259 cases reported blood test abnormalities, including five cases of abnormality in hepatic functional enzymes. The most frequently reported adverse event was digestive symptoms (44.3%), followed by nervous system symptoms (17.3%) and behaviors such as loss of appetite (16.3%). This is the first systematic review of adverse effects of herbal drugs among clinical studies, and the results indicate that herbal drugs are relatively safe. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27196988

  20. Early Malnutrition and Child Neurobehavioral Development: Insights from the Study of Children of Diabetic Mothers.

    ERIC Educational Resources Information Center

    Rizzo, Thomas A.; And Others

    1997-01-01

    Studied whether disturbances in mothers' metabolism (N=139) during pregnancy may exert long-range effects on neurobehavioral development of singleton progeny. Examined detailed pregnancy and perinatal records of mothers who experienced diabetes in pregnancy and intelligence tests of their offspring, administered at ages 7 to 11 years. All…

  1. A Local, Bottom-Up Perspective on Sleep Deprivation and Neurobehavioral Performance

    PubMed Central

    Van Dongen, Hans P.A.; Belenky, Gregory; Krueger, James M.

    2011-01-01

    Waking neurobehavioral performance is temporally regulated by a sleep/wake homeostatic process and a circadian process in interaction with a time-on-task effect. Neurobehavioral impairment resulting from these factors is task-specific, and characterized by performance variability. Several aspects of these phenomena are not well understood, and cannot be explained solely by a top-down (subcortically driven) view of sleep/wake and performance regulation. We present a bottom-up theory, where we postulate that task performance is degraded by local, use-dependent sleep in neuronal groups subserving cognitive processes associated with the task at hand. The theory offers explanations for the temporal dependence of neurobehavioral performance on time awake, time on task, and their interaction; for the effectiveness of task switching and rest breaks to overcome the time-on-task effect (but not the effects of sleep deprivation); for the task-specific nature of neurobehavioral impairment; and for the stochastic property of performance variability. PMID:21906023

  2. Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

    PubMed Central

    Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

    2016-01-01

    Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

  3. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

    PubMed Central

    Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

    2016-01-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

  4. Tissue Expander Placement to Prevent the Adverse Intestinal Effects of Radiotherapy in Malignant Pelvic Tumors.

    PubMed

    Uehara, Shuichiro; Oue, Takaharu; Adachi, Kana; Yoshioka, Yasuo; Nakahata, Kengo; Ueno, Takehisa; Okuyama, Hiroomi

    2016-03-01

    We herein report the findings of 3 patients with primary Ewing sarcoma in a pelvic lesion who underwent the placement of a tissue expander (TE) before radiation therapy to prevent the adverse effects of radiotherapy. The simulation study showed that the TE drastically reduced volume of the intestine that was irradiated at all dose levels. All patients could receive the scheduled dose of radiotherapy without any acute and late complications such as diarrhea, melena, the dislodging of the TE, infection, or the formation of fistulae. In the 4-year (minimum) observation period, we did not observe intestinal complications in any of our patients. TE placement is considered to be a safe and effective method for preventing the adverse effects of radiotherapy in pediatric malignant pelvic tumors.

  5. Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016).

    PubMed

    Mancini, G B John; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic; Pearson, Glen J; Pope, Janet; Tashakkor, A Yashar

    2016-07-01

    The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance. Particularly difficult practice situations are reviewed, including management in young and elderly individuals, and in athletes and labourers. Finally, targeted at specialty practitioners, more detailed analyses of specific but more unusual adverse effects ascribed to statins are updated including evidence regarding new-onset diabetes, cognitive dysfunction, cataracts, and the rare but important immune-mediated necrotizing myopathy. PMID:27342697

  6. Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians.

    PubMed

    Chroni, Elisabeth; Monastirli, Alexandra; Tsambaos, Dionysios

    2010-01-01

    Although neuromuscular adverse effects represent significant clinical manifestations of hypervitaminosis A syndrome, surprisingly little attention has been paid to the potential neuromuscular toxicity of vitamin A derivatives (retinoids). Since isotretinoin and acitretin are currently the two most commonly used oral retinoids in systemic dermatotherapy, this review focuses exclusively on their neuromuscular adverse effects and proposes a neuromuscular algorithm for appropriate monitoring of patients treated with these two compounds. The most frequent CNS adverse effect associated with oral isotretinoin is headache, either as an independent adverse effect or as part of benign intracranial hypertension, which is additionally characterized by nausea and visual changes. Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported. In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis. Creatine phosphokinase, a specific marker of muscle destruction, has been found to be elevated, occasionally by up to 100 times the normal value (with or without muscular symptoms and signs), in a variable percentage of patients receiving isotretinoin treatment and particularly in those undergoing vigorous physical exercise. Oral acitretin has been found to cause peripheral nerve dysfunction, particularly of sensory fibres, which in rare cases leads to clinically evident sensory disturbances. Less clear is the causal relationship between acitretin and benign intracranial hypertension or myopathy, whereas an isolated case of cranial nerve IV (oculomotor) palsy and a further case of thrombotic stroke during treatment with oral acitretin have been reported. Systemic diseases with involvement of nervous and

  7. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume☆

    PubMed Central

    Walsh, Nicholas D.; Dalgleish, Tim; Lombardo, Michael V.; Dunn, Valerie J.; Van Harmelen, Anne-Laura; Ban, Maria; Goodyer, Ian M.

    2014-01-01

    Exposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without (n = 31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life. PMID:25061568

  8. The role of ADHD in academic adversity: disentangling ADHD effects from other personal and contextual factors.

    PubMed

    Martin, Andrew J

    2014-12-01

    Students with attention-deficit/hyperactivity disorder (ADHD) experience significant academic difficulties that can lead to numerous negative academic consequences. With a focus on adverse academic outcomes, this study seeks to disentangle variance attributable to ADHD from variance attributable to salient personal and contextual covariates. Responses from 136 students with ADHD and 3,779 non-ADHD peers from 9 high schools were analyzed using logistic regression. Dependent measures included academic failure, grade repetition, school refusal, changing classes and school, school exclusion, and schoolwork noncompletion. Covariates comprised personal (e.g., sociodemographics, personality, prior achievement, specific learning disabilities, motivation) and contextual (e.g., school size, school socioeconomic status, school average achievement) factors. Findings indicated that, after accounting for personal and contextual covariates, ADHD explained significant variance in numerous adversities (schoolwork noncompletion, school suspension, school expulsion, changing schools, grade repetition). Thus, beyond the effects of numerous personal and contextual covariates, ADHD has a distinct presence in students' academic adversity. Also interesting, after accounting for other personal and contextual factors, was academic adversity with which ADHD was not associated. Findings provide direction for educational intervention targeting ADHD and associated factors found to be significant in the study.

  9. Efficacy and adverse effects of memantine treatment for Alzheimer's disease from randomized controlled trials.

    PubMed

    Jiang, Jue; Jiang, Hong

    2015-09-01

    The role of memantine as a treatment for Alzheimer's disease (AD) has been controversial. In clinical trials, a high dropout rate and numerous adverse events associated with memantine have been observed. However, given the relative scarcity of effective treatments for AD it would seem prudent to re-examine existing evidence to determine whether or not memantine should be used. Eight databases were utilized for randomized controlled trials that were published prior to December 31, 2013 and were according with the inclusion criteria. Trial methods, clinical characteristics, outcomes, and adverse events were extracted and analyzed with Review Manager 5.2. We obtained 2293 studies and determined that 13 of those studies met the inclusion criteria. Memantine therapy showed significant benefits to cognition, mental state, activities of daily life, the clinician's global impression in term with MMSE, SIB, NPI, ADCS-ADL19, CIBIC-Plus, respectively. Memantine therapy did not significantly increase the incidence of total adverse events, serious adverse events, death but it did increase the risk for somnolence.

  10. Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort.

    PubMed

    Paquette, Alison G; Lester, Barry M; Koestler, Devin C; Lesseur, Corina; Armstrong, David A; Marsit, Carmen J

    2014-01-01

    Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scales (NNNS). In 509 infants enrolled in the Rhode Island Child Health Study, placental FKBP5 methylation was measured at intron 7 using quantitative bisulfite pyrosequencing. Placental FKBP5 mRNA was measured in a subset of 61 infants by quantitative PCR, and the SNP rs1360780 was genotyped using a quantitative allelic discrimination assay. Relationships between methylation, expression and NNNS scores were examined using linear models adjusted for confounding variables, then logistic models were created to determine the influence of methylation on membership in high risk groups of infants. FKBP5 methylation was negatively associated with expression (P = 0.08, r = -0.22); infants with the TT genotype had higher expression than individuals with CC and CT genotypes (P = 0.06), and those with CC genotype displayed a negative relationship between methylation and expression (P = 0.06, r = -0.43). Infants in the highest quartile of FKBP5 methylation had increased risk of NNNS high arousal compared to infants in the lowest quartile (OR 2.22, CI 1.07-4.61). TT genotype infants had increased odds of high NNNS stress abstinence (OR 1.98, CI 0.92-4.26). Placental FKBP5 methylation reduces expression in a genotype

  11. Adverse health effects and unhealthy behaviors among medical students using Facebook.

    PubMed

    Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community. PMID:24453859

  12. Adverse health effects and unhealthy behaviors among medical students using Facebook.

    PubMed

    Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community.

  13. Adverse Health Effects and Unhealthy Behaviors among Medical Students Using Facebook

    PubMed Central

    Al-Dubai, Sami Abdo Radman; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T.

    2013-01-01

    Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community. PMID:24453859

  14. Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects

    PubMed Central

    Morgan, Craig; Reininghaus, Ulrich; Reichenberg, Abraham; Frissa, Souci; Hotopf, Matthew; Hatch, Stephani L.

    2014-01-01

    Background There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. Aims To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Method Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. Results There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Conclusions Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors. PMID:24627297

  15. Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

    PubMed

    Vill, K; Müller-Felber, W; Teusch, V; Blaschek, A; Gerstl, L; Huetker, S; Albert, M H

    2016-01-01

    Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug.

  16. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    PubMed Central

    Lund, Ingunn Olea; Bukten, Anne; Storvoll, Elisabet E; Moan, Inger Synnøve; Skurtveit, Svetlana; Handal, Marte; Nordfjærn, Trond; Brunborg, Geir Scott; Rossow, Ingeborg

    2015-01-01

    Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators. PMID:26688663

  17. Technical evaluation report, AGARD Fluid Dynamics Panel Symposium on Effects of Adverse Weather on Aerodynamics

    NASA Technical Reports Server (NTRS)

    Reinmann, J. J.

    1991-01-01

    The purpose of the meeting on Effects of Adverse Weather on Aerodynamics was to provide an update of the stae-of-the-art with respect to the prediction, simulation, and measurement of the effects of icing, anti-icing fluids, and various precipitation on the aerodynamic characteristics of flight vehicles. Sessions were devoted to introductory and survey papers and icing certification issues, to analytical and experimental simulation of ice frost contamination and its effects of aerodynamics, and to the effects of heavy rain and deicing/anti-icing fluids.

  18. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

    PubMed

    Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. PMID:22505867

  19. Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

    PubMed

    Majeed, Abdul; Farooq, Imran; Grobler, Sias R; Rossouw, R J

    2015-12-01

    Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues.

  20. Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

    SciTech Connect

    Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark; Gentili, Fred; Heydarian, Mostafa; Tsao, May; Schwartz, Michael; Prooijen, Monique van; Millar, Barbara-Ann; Menard, Cynthia; Kulkarni, Abhaya V.; Laperriere, Norm; Zadeh, Gelareh

    2012-04-01

    Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

  1. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

    PubMed

    Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

  2. Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.

    PubMed

    Matthews, Edwin J; Kruhlak, Naomi L; Weaver, James L; Benz, R Daniel; Contrera, Joseph F

    2004-12-01

    The FDA's Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (# ADR reports / # shipping units) x 1,000,000. MCASE/MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by > or = 4 ADR reports and > or = 20,000 shipping units during five years of marketing, and an RI > or = 4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects. PMID:16472241

  3. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

    PubMed

    Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

    2014-01-01

    Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects.

  4. Effects of early adversity on young children's diurnal cortisol rhythms and externalizing behavior.

    PubMed

    Bernard, Kristin; Zwerling, Jordana; Dozier, Mary

    2015-12-01

    Early adversity is associated with biological and behavioral dysregulation in early childhood. We examined whether early adversity (i.e., poverty and involvement with child protective services [CPS]) had an indirect effect on externalizing behavior through HPA axis dysregulation, specifically blunted diurnal cortisol patterns. Participants included 94 children between the ages of 3.94 and 6.52 years old, who had a history of CPS involvement (n = 53) or no history of CPS involvement (n = 41). Cortisol samples were collected at wake-up and bedtime across 3 days, and parent-reported externalizing behavior was assessed using the Child Behavior Checklist. Results showed that history of CPS involvement and poverty were associated with blunted cortisol patterns, which in turn led to elevated externalizing behavior. The indirect effect of CPS involvement on externalizing behavior through blunted cortisol was significant, whereas the indirect effect of poverty on externalizing behavior was nonsignificant. Findings add to our understanding of neurobiological mechanisms linking early adversity to psychopathology. PMID:26289841

  5. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    PubMed

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development. PMID:19236116

  6. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    PubMed

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

  7. Possible adverse effect of chromium in occupational exposure of tannery workers.

    PubMed

    Kornhauser, Carlos; Wróbel, Katarzyna; Wróbel, Kazimierz; Malacara, Juan Manuel; Nava, Laura Eugenia; Gómez, Leobardo; González, Rita

    2002-04-01

    Our aim was to investigate the adverse effects of occupational exposure to trivalent chromium. We measured chromium and iron levels in serum and urine and hemoglobin levels in tannery workers and unexposed persons. We studied three groups of subjects. Group 1 included 15 non-smoking male tannery workers highly exposed to chromium from tanning and retanning departments. Group 2 included 14 non-smoking male tannery workers with moderate chromium exposure from dying, drying and finishing departments. Group 3 included 11 healthy, non-smoking male subjects without direct chromium exposure. Higher serum chromium levels were observed in groups 1 and 2 with respect to group 3 (mean values respectively: 0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an inverse association was found between serum chromium and urine iron (-0.524), urine chromium and hemoglobin (-0.594) and between the urine chromium to iron ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse effect on iron metabolism, possibly associated with excessive body chromium accumulation. In conclusion, chromium urine test could be recommended for diagnosis of chromium adverse effect on iron metabolism. Further studies are needed to quantify the relationship between urine chromium and hemoglobin metabolism.

  8. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

    PubMed

    Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

    2014-01-01

    Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. PMID:24176069

  9. Development of glucocorticoid receptor regulation in the rat forebrain: Implications for adverse effects of glucocorticoids in preterm infants

    EPA Science Inventory

    Glucocorticoids are the consensus treatment to avoid respiratory distress in preterm infants but there is accumulating evidence that these agents evoke long-term neurobehavioral deficits. Earlier, we showed that the developing rat forebrain is far more sensitive to glucocorticoi...

  10. The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.

    PubMed

    Siddiqi, Nida; Lamour, Jacqueline M; Hsu, Daphne T

    2015-09-01

    Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA-TL are 1.5-3.0 μg/mL. The objective of this study was to assess the outcomes targeting MPA-TL of 0.8-2.0 μg/mL in pediatric HTR. MPA-TL were retrospectively collected 2-12 months post-transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA-TL. A total of 355 MPA-TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA-TL was 1.7 ± 0.9 μg/mL. African American patients received significantly higher doses (702 ± 235 mg/m(2) ) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One-yr survival was 100%. Targeting a lower range for MPA-TL was not associated with significant rejection or infection. Despite lower MPA-TL, MMF was discontinued in 3/22 patients for adverse effects.

  11. Chemical and microbial exposures in a school building: adverse health effects in children.

    PubMed

    Putus, Tuula; Tuomainen, Anneli; Rautiala, Sirpa

    2004-04-01

    In this cross-sectional study, the authors examined the relationship between an unusual combination of indoor air contaminants in a school and adverse health effects among the attending children. A leaking roof and damp floors, together with gaseous leaks from the sewage system, led to a combined exposure of hydrocarbons, 2-ethylhexanol from plastic floor coverings, and moisture-associated microbes. The health status of 274 children in the school was assessed via repeated symptom questionnaires. Statistical analysis revealed a relationship between the indoor air contaminants and adverse health outcomes such as respiratory irritation, asthmatic symptoms, eye and general symptoms, and increased occurrence of common viral respiratory infections. No association was found between the exposures and doctor-diagnosed asthma, other allergic diseases, or bacterial respiratory infections. Chemical contaminants from the sewer system and damp construction materials were identified as the source of the problem. Remediation of the school building improved the indoor air quality and the health status of the children.

  12. Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

    ERIC Educational Resources Information Center

    Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

    2012-01-01

    Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

  13. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    PubMed Central

    Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

    2014-01-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

  14. Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects.

    PubMed

    Snow, Samantha J; McGee, John; Miller, Desinia B; Bass, Virginia; Schladweiler, Mette C; Thomas, Ronald F; Krantz, Todd; King, Charly; Ledbetter, Allen D; Richards, Judy; Weinstein, Jason P; Conner, Teri; Willis, Robert; Linak, William P; Nash, David; Wood, Charles E; Elmore, Susan A; Morrison, James P; Johnson, Crystal L; Gilmour, Matthew Ian; Kodavanti, Urmila P

    2014-12-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.

  15. Scientific and Regulatory Policy Committee: Recommended ("Best") Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies.

    PubMed

    Kerlin, Roy; Bolon, Brad; Burkhardt, John; Francke, Sabine; Greaves, Peter; Meador, Vince; Popp, James

    2016-02-01

    Recommendations (best practices) are provided by the Society of Toxicologic Pathology's Adversity Working Group for making consistent interpretations of test article-related effects as "adverse" and assigning a "no observed adverse effect level" (NOAEL) in nonclinical toxicity studies. Adverse is a term indicating "harm" to the test animal, while nonadverse indicates lack of harm. Adverse findings in the study reports should be defined in relation to effects on the test species used and within the context of the given study. Test article-related effects should be described on their own merits, and decisions to consider them as adverse or nonadverse should be justified. Related effects may be discussed together; in particular, markers of toxicity that are not in and of themselves adverse ideally should be discussed in conjunction with the causal toxicity to determine adversity. Adverse findings should be identified in subreports (clinical data, pathology data, etc.) if sufficient information is available, and/or in the final study report as individual or grouped findings, but study NOAELs should be established at the level of the overall study report. Interpretations such as "not biologically relevant" or "not toxicologically important" should be avoided unless defined and supported by scientific rationale. Decisions defining adverse findings and the NOAEL in final study reports should combine the expertise of all contributing scientific disciplines. Where possible, use of NOAELs in data tables should be linked to explanatory text that places them in context. Ideally, in nonclinical summary documents, NOAELs from multiple studies are considered together in defining the most important adverse responses in the most sensitive species. These responses are then considered along with an understanding of their likely mechanisms, as well as other information such as variability in species sensitivity, comparative pathology, reversibility and progression, kinetics, and

  16. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole

    PubMed Central

    Hansen, Bent-Are; Bruserud, Øyvind

    2016-01-01

    Hypomagnesemia can be caused by a wide range of diseases (e.g. gastrointestinal disorders, kidney diseases or endocrine disorders), but it can also be a side effect of several drugs. It can be asymptomatic or cause many different clinical symptoms, and the clinical manifestations mainly depend on the rate of development rather than the actual serum magnesium concentration. We here present a 40-year-old female patient with Torsade de pointes ventricular tachycardia and cardiac arrest caused by severe hypomagnesemia as an adverse effect of the proton pump inhibitor omeprazole. PMID:27471598

  17. Reduction in adverse effect on pulmonary function after exposure to filtered diesel exhaust

    SciTech Connect

    Ulfvarson, U.; Alexandersson, R. )

    1990-01-01

    A statistically significant temporary reduction on pulmonary function was measured with spirometry in stevedores on a roll-on-roll-off ro-ro ship who were exposed to diesel exhausts from trucks during a work shift. When all trucks were equipped with specially designed microfilters mounted on the exhaust pipes, this impairment in pulmonary function was reduced. Removal of the particulate fraction of the exhausts by filtering is an important factor in reducing the adverse effect of diesel exhaust on pulmonary function. The particle fraction should be considered when designing an indicator of the biological effects of diesel exhausts.

  18. Adverse effects and tolerability of medications for the treatment of tobacco use and dependence.

    PubMed

    Hays, J Taylor; Ebbert, Jon O

    2010-12-24

    Tobacco use is the leading cause of preventable death and disability in the world. Although gradually declining in most developed countries, the prevalence of tobacco use has increased among developing countries. Treatment for tobacco use and dependence is effective, although long-term abstinence rates remain disappointingly low. In response, new treatments continue to be developed. In addition, many of the pharmacotherapies that have been available for years have found new applications with the use of medication combinations, higher doses and a longer duration of therapy for approved medications. There are now seven medications (nicotine patch, nicotine gum, nicotine lozenge, nicotine inhaler, nicotine nasal spray, bupropion sustained release and varenicline) approved for tobacco dependence treatment in most countries, and many national and professional society practice guidelines recommend their use. Although each of the medications used for tobacco dependence treatment has been rigorously tested for efficacy and safety, broader experience in clinical trials and in observational population-based studies suggests that adverse events associated with these medications are relatively common. Since 2008, two of the medications (varenicline and bupropion) have come under increasing scrutiny because of reports of unexplained serious adverse events (SAEs), including behaviour change, depression, self-injurious thoughts and suicidal behaviour. To date, this association has not been shown to be caused by these medications, but concerns about medication safety continue. Prescribers require a working knowledge of the common adverse effects for all of these medications as well as a more detailed knowledge of the SAE potential. Nicotine replacement therapy (NRT) has been rigorously tested in clinical trials for over 30 years. A number of adverse effects are commonly associated with NRT use, although SAEs are rare. The adverse effects associated with NRT are due to the

  19. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

    PubMed Central

    Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

    2016-01-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

  20. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review

    PubMed Central

    Hirshburg, Jason M.; Kelsey, Petra A.; Therrien, Chelsea A.; Gavino, A. Carlo; Reichenberg, Jason S.

    2016-01-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment.

  1. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review.

    PubMed

    Hirshburg, Jason M; Kelsey, Petra A; Therrien, Chelsea A; Gavino, A Carlo; Reichenberg, Jason S

    2016-07-01

    Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use. Currently, there is no direct link between 5-alpha reductase inhibitor use and depression; however, several small studies have led to depression being listed as a side effect on the medication packaging. Sexual effects including erectile dysfunction and decreased libido and ejaculate were reported in as many as 3.4 to 15.8 percent of men. To date, there are very few studies evaluating 5-alpha reductase inhibitor use in women. Risks include birth defects in male fetuses if used in pregnancy, decreased libido, headache, gastrointestinal discomfort, and isolated reports of changes in menstruation, acne, and dizziness. Overall, 5-alpha reductase inhibitors were well-tolerated in both men and women, but not without risk, highlighting the importance of patient education prior to treatment. PMID:27672412

  2. Monitoring neurotoxins in industry: development of a neurobehavioral test battery.

    PubMed

    Baker, E L; Feldman, R G; White, R F; Harley, J P; Dinse, G E; Berkey, C S

    1983-02-01

    To facilitate the early detection of neurotoxicity in workers exposed to hazardous substances, we assembled a set of noninvasive neurobehavioral tests designed to assess memory, verbal concept formation, visuomotor performance, and mood. The tests were administered to an unexposed reference population and multivariate prediction equations were developed to control for effects of age, gender, and education. To define the briefest test set with appropriate sensitivity and specificity, we applied factor analysis and stepwise logistic regression to data from our referents and a group of lead-exposed workers. As a result, we have identified a comprehensive set of tests that can be administered in less than 40 minutes by trained medical technicians on plant premises and used to detect the early effects of neurotoxic substances on exposed workers. Guidelines for applying this technique to common work-place exposures, including other metals and organic solvents, are discussed.

  3. Polytraumatization and Trauma Symptoms in Adolescent Boys and Girls: Interpersonal and Noninterpersonal Events and Moderating Effects of Adverse Family Circumstances

    ERIC Educational Resources Information Center

    Nilsson, Doris Kristina; Gustafsson, Per E.; Svedin, Carl Goran

    2012-01-01

    The objective of this study was to investigate the cumulative effect of interpersonal and noninterpersonal traumatic life events (IPEs and nIPEs, respectively) on the mental health of adolescents and to determine if the adverse impacts of trauma were moderated by adverse family circumstances (AFC). Adolescents (mean age 16.7 years) from the…

  4. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  5. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  6. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  7. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  8. 42 CFR 493.1808 - Adverse action on any type of CLIA certificate: Effect on Medicare approval.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Adverse action on any type of CLIA certificate... REQUIREMENTS Enforcement Procedures § 493.1808 Adverse action on any type of CLIA certificate: Effect on Medicare approval. (a) Suspension or revocation of any type of CLIA certificate. When CMS suspends...

  9. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update.

    PubMed

    Mancini, G B John; Tashakkor, A Yashar; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic S; Pearson, Glen J; Pope, Janet

    2013-12-01

    The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy. Regarding cognition, the available evidence is not strongly supportive of a major adverse effect of statins. In contrast, the linkage between statin therapy and incident diabetes is more firm. However, this risk is more strongly associated with traditional risk factors for new-onset diabetes than with statin itself and any possible negative effect of new-onset diabetes during statin treatment is far outweighed by the cardiovascular risk reduction benefits. Additional studies are also discussed, which support the principle that systematic statin rechallenge, and lower or intermittent statin dosing strategies are the main methods for dealing with suspected statin intolerance at this time.

  10. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis. PMID:27149222

  11. Determination of an acute no-observed-adverse-effect level (NOAEL) for copper in water.

    PubMed

    Araya, M; McGoldrick, M C; Klevay, L M; Strain, J J; Robson, P; Nielsen, F; Olivares, M; Pizarro, F; Johnson, L A; Poirier, K A

    2001-10-01

    A prospective, double-blind controlled study was designed to determine the acute no-observed-adverse-effect level (NOAEL) of nausea in an apparently healthy population of 179 individuals who drank copper-containing water as the sulfate salt. Subjects were recruited at three different international sites and given a blind, randomly selected dose (0, 2, 4, 6, or 8 mg Cu/L) in a bolus of 200 ml (final total copper dose was equivalent to 0, 0.4, 0.8, 1.2, and 1.6 mg) once weekly over a consecutive 5-week period. Gastrointestinal (GI) symptoms of nausea, abdominal pain, vomiting, or diarrhea were screened for a period of up to 24 h. Nausea was the most frequently reported effect and was reported within the first 15 min of ingestion. For the combined trisite population (n=179), 8, 9, 14, 25, and 44 subjects responded positively to one or more GI symptoms at 0, 2, 4, 6, and 8 mg Cu/L, respectively. Analysis of the data demonstrated a clear dose response to the combined positive GI effects and to nausea alone. Statistically significant greater reporting of effects occurred at 6 and 8 mg Cu/L. Therefore, an acute NOAEL and lowest-observed-adverse-effect level of 4 and 6 mg Cu/L (0.8 and 1.2 mg Cu), respectively, were determined in drinking water for a combined international human population.

  12. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis.

  13. Identifying Adverse Effects of HIV Drug Treatment and Associated Sentiments Using Twitter

    PubMed Central

    Adrover, Cosme; Bodnar, Todd; Huang, Zhuojie

    2015-01-01

    Background Social media platforms are increasingly seen as a source of data on a wide range of health issues. Twitter is of particular interest for public health surveillance because of its public nature. However, the very public nature of social media platforms such as Twitter may act as a barrier to public health surveillance, as people may be reluctant to publicly disclose information about their health. This is of particular concern in the context of diseases that are associated with a certain degree of stigma, such as HIV/AIDS. Objective The objective of the study is to assess whether adverse effects of HIV drug treatment and associated sentiments can be determined using publicly available data from social media. Methods We describe a combined approach of machine learning and crowdsourced human assessment to identify adverse effects of HIV drug treatment solely on individual reports posted publicly on Twitter. Starting from a large dataset of 40 million tweets collected over three years, we identify a very small subset (1642; 0.004%) of individual reports describing personal experiences with HIV drug treatment. Results Despite the small size of the extracted final dataset, the summary representation of adverse effects attributed to specific drugs, or drug combinations, accurately captures well-recognized toxicities. In addition, the data allowed us to discriminate across specific drug compounds, to identify preferred drugs over time, and to capture novel events such as the availability of preexposure prophylaxis. Conclusions The effect of limited data sharing due to the public nature of the data can be partially offset by the large number of people sharing data in the first place, an observation that may play a key role in digital epidemiology in general. PMID:27227141

  14. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

    PubMed

    Sadhasivam, S; Zhang, X; Chidambaran, V; Mavi, J; Pilipenko, V; Mersha, T B; Meller, J; Kaufman, K M; Martin, L J; McAuliffe, J

    2015-10-01

    Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

  15. Mercury exposure from dental amalgam fillings: absorbed dose and the potential for adverse health effects.

    PubMed

    Mackert, J R; Berglund, A

    1997-01-01

    This review examines the question of whether adverse health effects are attributable to amalgam-derived mercury. The issue of absorbed dose of mercury from amalgam is addressed first. The use of intra-oral Hg vapor measurements to estimate daily uptake must take into account the differences between the collection volume and flow rate of the measuring instrument and the inspiratory volume and flow rate of air through the mouth during inhalation of a single breath. Failure to account for these differences will result in substantial overestimation of the absorbed dose. Other factors that must be considered when making estimates of Hg uptake from amalgam include the accurate measurement of baseline (unstimulated) mercury release rates and the greater stimulation of Hg release afforded by chewing gum relative to ordinary food. The measured levels of amalgam-derived mercury in brain, blood, and urine are shown to be consistent with low absorbed doses (1-3 micrograms/day). Published relationships between the number of amalgam surfaces and urine levels are used to estimate the number of amalgam surfaces that would be required to produce the 30 micrograms/g creatinine urine mercury level stated by WHO to be associated with the most subtle, pre-clinical effects in the most sensitive individuals. From 450 to 530 amalgam surfaces would be required to produce the 30 micrograms/g creatinine urine mercury level for people without any excessive gum-chewing habits. The potential for adverse health effects and for improvement in health following amalgam removal is also addressed. Finally, the issue of whether any material can ever be completely exonerated of claims of producing adverse health effects is considered.

  16. Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats.

    PubMed

    Ferreira Seiva, Fábio Rodrigues; Amauchi, Juliana Fujihara; Ribeiro Rocha, Katiucha Karolina; Souza, Gisele Aparecida; Ebaid, Geovana Xavier; Burneiko, Regina Miranda; Novelli, Ethel Lourenzi Barbosa

    2009-03-01

    Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 rats were divided into two groups: (C, N=6) given standard chow and water; (E, N=24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol exposure, (E) group was divided into four subgroups (N=6/group): (E-E) continued drinking 30% ethanol solution; (E-NAC) drinking ethanol solution containing 2 g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacylglycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol

  17. The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).

    PubMed

    Dorato, Michael A; Engelhardt, Jeffery A

    2005-08-01

    The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, "the highest experimental point that is without adverse effect," serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations.

  18. Perspectives on stress resilience and adolescent neurobehavioral function.

    PubMed

    Romeo, Russell D

    2015-01-01

    Interest in adolescence as a crucial stage of neurobehavioral maturation is growing, as is the concern of how stress may perturb this critical period of development. Though it is well recognized that stress-related vulnerabilities increase during adolescence, not all adolescent individuals are uniformly affected by stress nor do stressful experiences inevitability lead to negative outcomes. Indeed, many adolescents show resilience to stress-induced dysfunctions. However, relatively little is known regarding the mechanisms that may mediate resilience to stress in adolescence. The goal of this brief review is to bring together a few separate, yet related lines of research that highlight specific variables that may influence stress resilience during adolescence, including early life programming of the hypothalamic-pituitary-adrenal (HPA) axis, stress inoculation, and genetic predisposition. Though we are far from a clear understanding of the factors that mediate resistance to stress-induced dysfunctions, it is imperative that we identify and delineate these aspects of resilience to help adolescents reach their full potential, even in the face of adversity. PMID:27589663

  19. Study of Adverse Effect Profile of Parenteral Zoledronic Acid in Female Patients with Osteoporosis

    PubMed Central

    Kotian, Prem; Sreenivasan, Sushanth

    2016-01-01

    Introduction Osteoporosis is still a under recognized entity in the population. Osteoporosis-related fractures can be prevented if people at risk can be screened, diagnosed and treated early. Bisphosphonates remain the mainstay of osteoporosis treatment as they have multimodal action. Oral bisphosphonate therapy has, significant gastrointestinal side effects leading to noncompliance. Of late parenteral Zoledronic Acid is being used as once or twice yearly infusion for the treatment of osteoporosis. Aim Our article studies the side effect profile and tolerability of parenteral Zoledronic Acid, one of the most potent bisphosphonate used in clinical practice in patients with osteoporosis. Materials and Methods This study was done in KMC hospitals where 49 patients diagnosed with osteoporosis were included for the study. After obtaining a written informed consent each patient received one infusion of 5 mg Zoledronic Acid as per standard treatment protocol. Patient was monitored for clinical improvement and development of any adverse effects. Conclusion In our study all subjects reported significant pain relief after infusion of Zoledronic Acid. Zoledronic Acid had very few serious adverse effects that can be prevented through pre-infusion screening, maintaining good hydration and careful patient monitoring. In our population the patients only experienced mild symptoms of pyrexia, arthralgia myalgia and influenza like symptoms which resolved with symptomatic treatment. PMID:26894105

  20. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters.

  1. Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects.

    PubMed

    Spinella, Marcello

    2001-12-01

    The widespread availability and use of herbal medicines raise the potential for adverse effects in the epilepsy population. Herbal sedatives (kava, valerian, chamomile, passionflower) may potentiate the effects of antiepileptic medications, increasing their sedative and cognitive effects. Despite some antiseizure effects in animal models, they should not be used in place of standard seizure medications because efficacy has not been established. Anecdotal, uncontrolled observations suggest that herbal stimulants containing ephedrine (ephedra or ma huang) and caffeine (cocoa, coffee, tea, maté, guarana, cola or kola) can exacerbate seizures in people with epilepsy, especially when taken in combination. Ginkgo and ginseng may also exacerbate seizures although the evidence for this is similarly anecdotal and uncertain. St. John's wort has the potential to alter medication pharmacokinetics and the seizure threshold. The essential oils of many plants contain epileptogenic compounds. There is mixed evidence for evening primrose and borage lowering the seizure threshold. Education of both health care providers and patients is the best way to avoid unintentional and unnecessary adverse reactions to herbal medicines. PMID:12609386

  2. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    PubMed

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters. PMID:27165416

  3. Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects

    PubMed Central

    Chen, Qi; Espey, Michael Graham; Drisko, Jeanne; Levine, Mark

    2010-01-01

    Background Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown. Methods and Findings We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study. Conclusions High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit. PMID:20628650

  4. Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial

    PubMed Central

    Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

    2014-01-01

    Objective To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Design Opportunistic addition to an established randomised double blind placebo controlled trial. Setting Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. Participants 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Intervention Participants were randomised to receive an oral dose of either 200 000 IU vitamin D3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. Main outcome measure This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of “psychological” adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. Results 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ2 P=0.03). The number of psychological adverse events—such as fatigue, stress, anxiety, and insomnia

  5. Adverse effects of low level heavy metal exposure on male reproductive function.

    PubMed

    Wirth, Julia J; Mijal, Renée S

    2010-04-01

    Lead, cadmium, mercury, and arsenic, often referred to as "heavy metals", are toxic for wildlife, experimental animals, and humans. While experimental animal and human occupational studies with high exposure levels generally support an adverse role for these metals in human reproductive outcomes, information on the effects of low, environmentally-realistic exposure levels of these metals on male reproductive outcomes is limited. We review the literature on effects of exposure to low levels of these metals on measures of male fertility (semen quality and reproductive hormone levels) and provide supporting evidence from experimental and occupational studies. Potentially modifying effects of genetic polymorphisms on these associations are discussed. A brief review of the literature on the effects of three trace metals, copper, manganese, and molybdenum, that are required for human health, yet may also cause adverse reproductive effects, follows. Overall, there were few studies examining the effects of exposure to low levels of these metals on male reproductive health. For all metals, there were several well-designed studies with sufficient populations appropriately adjusted for potential confounders and many of these reported harmful effects. However, many studies lacked sufficient numbers of participants to be able to detect differences in outcomes between exposed and non-exposed individuals, did not clearly identify the source and characteristics of the participants, and did not control for other exposures that could alter or contribute to the outcomes. The evidence for the effects of low exposure was strongest for cadmium, lead, and mercury and less certain for arsenic. The potential modifying effects of genetic polymorphisms has not been fully explored. Additional studies on the reproductive effects of these toxic ubiquitous metals on male reproduction are required to expand the knowledge base and to resolve inconsistencies.

  6. Adverse Effects in the Pharmacologic Management of Bipolar Disorder During Pregnancy.

    PubMed

    Hogan, Charlotte S; Freeman, Marlene P

    2016-09-01

    Management of bipolar disorder during pregnancy often involves medications with potential adverse effects, including risks to the mother and fetus. Although some specifics are known, many medications continue to have incompletely characterized reproductive safety profiles. Women with bipolar disorder who are planning pregnancy face challenging decisions about their treatment; careful risk-benefit discussions are necessary. With the goal of further informing these discussions, this article reviews the data currently available regarding medication safety in the management of bipolar disorder during pregnancy, with specific attention to lithium, valproic acid, lamotrigine, carbamazepine, and antipsychotic medications. PMID:27514299

  7. [Antivaccine misinformation about rate of adverse effects and toxicity of vaccines].

    PubMed

    Mats, A N; Gol'dshteĭn, A V

    2010-01-01

    Two widely known antivaccine inventions are discussed: "vaccination is accompanied by adverse effects, which exceeded complications of respective infections on frequency and severity" and "vaccines represent appalling conglomerate of toxic substances, which is unnaturally to administer to children". Informational and psychological nature of dissemination of these inventions is analyzed. On the basis of recent literature data conclusion was made about the absence of real toxicity (including neurotoxicity), carcinogenicity, allergenicity and autopathogenicity of phenol, folmaldehyde, aluminium hydroxide, Twin 80, squalen (MF59) and ethylmercury in concentrations found in vaccines of national immunization schedule.

  8. [Herbal medicines and severe adverse effects: uvular angioedema caused by Echballium elaterium].

    PubMed

    Caiozzi, Gianella; Cabrera, Daniel; Mardónez, José Miguel; Saldías, Fernando

    2002-12-01

    Herbal medicine is a growing alternative for established medicine. Many plants and herbs are currently in use for a myriad of diseases and symptoms. However, there are many reports in the literature of life-threatening adverse effects of these drugs. We report a 39 years old male, that consulted for pain in the nostrils and severe nasal obstruction, that appeared two hours after instilling Ecballium elaterirum in the nostrils. On physical examination, uvular edema was observed. The patient was successfully managed with intravenous betametasone and chlorphenamine. PMID:12611242

  9. Tooth-Bleaching: A Review of the Efficacy and Adverse Effects of Various Tooth Whitening Products.

    PubMed

    Majeed, Abdul; Farooq, Imran; Grobler, Sias R; Rossouw, R J

    2015-12-01

    Tooth bleaching (whitening) is one of the most common and inexpensive method for treating discolouration of teeth. Dental aesthetics, especially tooth colour, is of great importance to majority of the people; and discolouration of even a single tooth can negatively influence the quality of life. Therefore, a review of the literature was carried out (limited to aesthetic tooth-bleaching) to provide a broad overview of the efficacy and adverse effects of various tooth whitening products on soft and hard oral tissues. PMID:26691365

  10. Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders.

    PubMed

    Glass, Leila; Ware, Ashley L; Mattson, Sarah N

    2014-01-01

    Alcohol consumption during pregnancy can have deleterious consequences for the fetus, including changes in central nervous system development leading to permanent neurologic alterations and cognitive and behavioral deficits. Individuals affected by prenatal alcohol exposure, including those with and without fetal alcohol syndrome, are identified under the umbrella of fetal alcohol spectrum disorders (FASD). While studies of humans and animal models confirm that even low to moderate levels of exposure can have detrimental effects, critical doses of such exposure have yet to be specified and the most clinically significant and consistent consequences occur following heavy exposure. These consequences are pervasive, devastating, and can result in long-term dysfunction. This chapter summarizes the neurobehavioral, neurologic, and neuroimaging characteristics of FASD, focusing primarily on clinical research of individuals with histories of heavy prenatal alcohol exposure, although studies of lower levels of exposure, particularly prospective, longitudinal studies, will be discussed where relevant.

  11. Predictive Capabilities of Neurobehavioral Diagnostics in Early Childhood.

    PubMed

    Abramova, Oxana

    2016-05-01

    Modern world experiences annual increase in the number of children born with neurological problems, which in the future may stipulate the development of their neurobehavioral and neuropsychological aberrations. Specific functional features of a child's brain development depend on many factors, but there is a strong need for early clinical and psychological identification of a child's development with a view to elaborate preventive measures, which are often more effective than the treatment or correction of dysfunction, already complicated by compensatory bonds. One should note that despite a high interest in the possibility of predicting the future development of the child in the early ontogenesis, few studies have so far been devoted to the search for indicators that could be meaningful for neuropsychology, neurology, and educational, special, and clinical psychology.

  12. Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders.

    PubMed

    Glass, Leila; Ware, Ashley L; Mattson, Sarah N

    2014-01-01

    Alcohol consumption during pregnancy can have deleterious consequences for the fetus, including changes in central nervous system development leading to permanent neurologic alterations and cognitive and behavioral deficits. Individuals affected by prenatal alcohol exposure, including those with and without fetal alcohol syndrome, are identified under the umbrella of fetal alcohol spectrum disorders (FASD). While studies of humans and animal models confirm that even low to moderate levels of exposure can have detrimental effects, critical doses of such exposure have yet to be specified and the most clinically significant and consistent consequences occur following heavy exposure. These consequences are pervasive, devastating, and can result in long-term dysfunction. This chapter summarizes the neurobehavioral, neurologic, and neuroimaging characteristics of FASD, focusing primarily on clinical research of individuals with histories of heavy prenatal alcohol exposure, although studies of lower levels of exposure, particularly prospective, longitudinal studies, will be discussed where relevant. PMID:25307589

  13. Neurobehavioral toxicology of pyrethroid insecticides

    SciTech Connect

    Crofton, K.M.

    1986-01-01

    Pyrethroid insecticides are classified as either Type I or Type II based upon in vivo toxic signs, and neurophysiological and biochemical data. Both axonal sodium channels and the ..gamma..-aminobutyric acid (GABA) receptor complex have been proposed as the major site of action of the Type II pyrethroids. This investigation characterized the behavior and biochemical effects of low dosages of pyrethroids in rats. Type I and II pyrethroids were tested for effects on figure-eight maze activity and the acoustic startle response (ASR). All compounds decreased figure-eight maze activity. Interactions of Type I and II pyrethroids with the three major binding sites on the GABA complex were determined in vivo. Radioligand binding experiments assessed in vitro interactions of pyrethroids with the three major GABA-complex binding sites. None of the pyrethroids competed for (/sup 3/H)-muscimol or (/sup 3/H)-flunitrazepam binding. Only Type II pyrethroids inhibited binding of (/sup 35/S)-t-butylbicyclophosphorothionate (TBPS) in cortical synaptosome preparations with K/sub i/ values of 5 to 10 ..mu..M. The (/sup 35/S)-TBPS data implicate the TBPS/picrotoxinin binding site in the mechanism of Type II pyrethroid toxicity. The results of these experiments support the classification of pyrethroids into two classes, and demonstrate the utility of the figure-eight maze and the ASR in studies to elucidate neurotoxic mechanisms. The interaction of the Type II pyrethroids is probably restricted to the TBPS/picrotoxinin binding domain on the GABA complex as shown by both the in vivo and in vitro studies.

  14. Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial.

    PubMed

    Dabaghzadeh, Fatemeh; Ghaeli, Padideh; Khalili, Hossein; Alimadadi, Abbas; Jafari, Sirous; Akhondzadeh, Shahin; Khazaeipour, Zahra

    2013-03-01

    Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.

  15. Longitudinal in vivo tracking of adverse effects following topical steroid treatment.

    PubMed

    Bower, Andrew J; Arp, Zane; Zhao, Youbo; Li, Joanne; Chaney, Eric J; Marjanovic, Marina; Hughes-Earle, Angela; Boppart, Stephen A

    2016-05-01

    Topical steroids are known for their anti-inflammatory properties and are commonly prescribed to treat many adverse skin conditions such as eczema and psoriasis. While these treatments are known to be effective, adverse effects including skin atrophy are common. In this study, the progression of these effects is investigated in an in vivo mouse model using multimodal optical microscopy. Utilizing a system capable of performing two-photon excitation fluorescence microscopy (TPEF) of reduced nicotinamide adenine dinucleotide (NADH) to visualize the epidermal cell layers and second harmonic generation (SHG) microscopy to identify collagen in the dermis, these processes can be studied at the cellular level. Fluorescence lifetime imaging microscopy (FLIM) is also utilized to image intracellular NADH levels to obtain molecular information regarding metabolic activity following steroid treatment. In this study, fluticasone propionate (FP)-treated, mometasone furoate (MF)-treated and untreated animals were imaged longitudinally using a custom-built multimodal optical microscope. Prolonged steroid treatment over the course of 21 days is shown to result in a significant increase in mean fluorescence lifetime of NADH, suggesting a faster rate of maturation of epidermal keratinocytes. Alterations to collagen organization and the structural microenvironment are also observed. These results give insight into the structural and biochemical processes of skin atrophy associated with prolonged steroid treatment. PMID:26739196

  16. Adverse effects of topical corticosteroids in paediatric eczema: Australasian consensus statement.

    PubMed

    Mooney, Emma; Rademaker, Marius; Dailey, Rebecca; Daniel, Ben S; Drummond, Catherine; Fischer, Gayle; Foster, Rachael; Grills, Claire; Halbert, Anne; Hill, Sarah; King, Emma; Leins, Elizabeth; Morgan, Vanessa; Phillips, Roderic J; Relic, John; Rodrigues, Michelle; Scardamaglia, Laura; Smith, Saxon; Su, John; Wargon, Orli; Orchard, David

    2015-11-01

    Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a child's sleep, education, development and self-esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short-term hypothalamic-pituitary-adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children. PMID:25752907

  17. Adverse effects of topical corticosteroids in paediatric eczema: Australasian consensus statement.

    PubMed

    Mooney, Emma; Rademaker, Marius; Dailey, Rebecca; Daniel, Ben S; Drummond, Catherine; Fischer, Gayle; Foster, Rachael; Grills, Claire; Halbert, Anne; Hill, Sarah; King, Emma; Leins, Elizabeth; Morgan, Vanessa; Phillips, Roderic J; Relic, John; Rodrigues, Michelle; Scardamaglia, Laura; Smith, Saxon; Su, John; Wargon, Orli; Orchard, David

    2015-11-01

    Atopic eczema is a chronic inflammatory disease affecting about 30% of Australian and New Zealand children. Severe eczema costs over AUD 6000/year per child in direct medical, hospital and treatment costs as well as time off work for caregivers and untold distress for the family unit. In addition, it has a negative impact on a child's sleep, education, development and self-esteem. The treatment of atopic eczema is complex and multifaceted but a core component of therapy is to manage the inflammation with topical corticosteroids (TCS). Despite this, TCS are often underutilised by many parents due to corticosteroid phobia and unfounded concerns about their adverse effects. This has led to extended and unnecessary exacerbations of eczema for children. Contrary to popular perceptions, (TCS) use in paediatric eczema does not cause atrophy, hypopigmentation, hypertrichosis, osteoporosis, purpura or telangiectasia when used appropriately as per guidelines. In rare cases, prolonged and excessive use of potent TCS has contributed to striae, short-term hypothalamic-pituitary-adrenal axis alteration and ophthalmological disease. TCS use can also exacerbate periorificial rosacea. TCS are very effective treatments for eczema. When they are used to treat active eczema and stopped once the active inflammation has resolved, adverse effects are minimal. TCS should be the cornerstone treatment of atopic eczema in children.

  18. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  19. Psychiatric symptoms in adolescents: FKBP5 genotype--early life adversity interaction effects.

    PubMed

    Comasco, Erika; Gustafsson, Per A; Sydsjö, Gunilla; Agnafors, Sara; Aho, Nikolas; Svedin, Carl Göran

    2015-12-01

    Psychiatric disorders are multi-factorial and their symptoms overlap. Constitutional and environmental factors influence each other, and this contributes to risk and resilience in mental ill-health. We investigated functional genetic variation of stress responsiveness, assessed as FKBP5 genotype, in relation to early life adversity and mental health in two samples of adolescents. One population-based sample of 909 12-year-old adolescents was assessed using the Life Incidence of Traumatic Events scale and the Strengths and Difficulties Questionnaire. One sample of 398 17-year-old adolescents, enriched for poly-victimized individuals (USSS), was assessed using the Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children (TSCC). The FKBP5 rs1360780 and rs3800373 polymorphisms were genotyped using a fluorescence-based competitive allele-specific PCR. Most prominently among poly-victimized older male adolescents, the least common alleles of the polymorphisms, in interaction with adverse life events, were associated with psychiatric symptoms, after controlling for ethno-socio-economic factors. The interaction effect between rs3800373 and adverse life events on the TSCC sub-scales-anxiety, depression, anger, and dissociation-and with the rs1360780 on dissociation in the USSS cohort remained significant after Bonferroni correction. This pattern of association is in line with the findings of clinical and neuroimaging studies, and implies interactive effects of FKBP5 polymorphisms and early life environment on several psychiatric symptoms. These correlates add up to provide constructs that are relevant to several psychiatric symptoms, and to identify early predictors of mental ill-health.

  20. Adverse Effects of Daylight Saving Time on Adolescents' Sleep and Vigilance

    PubMed Central

    Medina, Diana; Ebben, Matthew; Milrad, Sara; Atkinson, Brianna; Krieger, Ana C.

    2015-01-01

    Study Objectives: Daylight saving time (DST) has been established with the intent to reduce energy expenditure, however unintentional effects on sleep and vigilance have not been consistently measured. The objective of this study was to test the hypothesis that DST adversely affects high school students' sleep and vigilance on the school days following its implementation. Methods: A natural experiment design was used to assess baseline and post-DST differences in objective and subjective measures of sleep and vigilance by actigraphy, sleep diary, sleepiness scale, and psychomotor vigilance testing (PVT). Students were tested during school days immediately preceding and following DST. Results: A total of 40 high school students were enrolled in this study; 35 completed the protocol. Sleep duration declined by an average of 32 minutes on the weeknights post-DST, reflecting a cumulative sleep loss of 2 h 42 min as compared to the baseline week (p = 0.001). This finding was confirmed by sleep diary analyses, reflecting an average sleep loss of 27 min/night (p = 0.004) post-DST. Vigilance significantly deteriorated, with a decline in PVT performance post-DST, resulting in longer reaction times (p < 0.001) and increased lapses (p < 0.001). Increased daytime sleepiness was also demonstrated (p < 0.001). Conclusions: The early March DST onset adversely affected sleep and vigilance in high school students resulting in increased daytime sleepiness. Larger scale evaluations of sleep impairments related to DST are needed to further quantify this problem in the population. If confirmed, measures to attenuate sleep loss post-DST should be implemented. Citation: Medina D, Ebben M, Milrad S, Atkinson B, Krieger AC. Adverse effects of daylight saving time on adolescents' sleep and vigilance. J Clin Sleep Med 2015;11(8):879–884. PMID:25979095

  1. Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

    PubMed Central

    Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

    2015-01-01

    Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global

  2. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

    PubMed Central

    Mills, Nicholas L.; Miller, Mark R.; Lucking, Andrew J.; Beveridge, Jon; Flint, Laura; Boere, A. John F.; Fokkens, Paul H.; Boon, Nicholas A.; Sandstrom, Thomas; Blomberg, Anders; Duffin, Rodger; Donaldson, Ken; Hadoke, Patrick W.F.; Cassee, Flemming R.; Newby, David E.

    2011-01-01

    Aim Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions. PMID:21753226

  3. Efficacy and adverse effects of medical marijuana for chronic noncancer pain

    PubMed Central

    Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

    2015-01-01

    Abstract Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical

  4. Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

    PubMed Central

    Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

    2009-01-01

    Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

  5. Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

    PubMed

    Han, Zhi-Xia; Lei, Zhang-Heng; Zhang, Chun-Lian; Xiong, Wei; Gan, Zhong-Lin; Hu, Ping; Zhang, Qing-Bi

    2015-03-01

    The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P < .001). Sleep quality, prevalence of hypertension, and attention in transportation hub areas were significantly different from those in the other 3 areas (P < .05); only 24.46% of people knew the health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise.

  6. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    PubMed

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  7. [Non-steroid anti-inflammatory drugs and adverse gastrointestinal effects. An unresolved problem].

    PubMed

    López, A

    1999-01-01

    Non-steroid anti-inflammatory drugs are a class of medicine widely used throughout the world. This is a pharmacological group in continuous growth, to which some new molecules have been added in recent years. The great drawback of non-steroid anti-inflammatory drugs are their adverse effects, outstanding of which due to their frequency and importance being those that occur in the gastrointestinal tract. By means of a search in Medline and other databases, this work reviews the latest data published on the incidence of dyspepsia, gastroduodenal lesions, gastrointestinal complications and mortality associated with consumption of non-steroid anti-inflammatory drugs. Similarly, a brief description is made of the mechanism of lesions to the stomach of the non-steroid anti-inflammatory drugs and the different risk factors that condition the appearance of adverse effects at the gastrointestinal level. Finally, an analysis is made of the preventive strategy and the different medicines that can be used to this end and a contrast is made of the evidence extracted from the different published studies and the reality of the use of the different "gastroprotectors". This review concludes with a series of questions that still remain unresolved concerning treatment with non-steroid anti-inflammatory drugs and their lesions to the stomach.

  8. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings.

  9. Physical basis of adverse and therapeutic effects of low intensity microwave radiation.

    PubMed

    Hyland, G J

    2008-05-01

    A physical basis of adverse and therapeutic effects of low intensity microwave radiation is presented based on the concept of oscillatory similitude between the frequency of an external microwave field (together with any lower frequency modulations thereof) and those of certain endogenous dipolar coherent excitations allied to aliveness, which play the role of 'tuned circuits' via which a living organism is electromagnetically sensitised in a non-linear way to external fields too weak to be able to cause heating. From this perspective, an external electromagnetic field affects a living system not as a toxin but rather by perturbing its endogenous electromagnetic activity. The possibility of adverse perturbation is illustrated by reference to the microwave fields used in mobile telecommunications whose signals interfere in a non-thermal way with biofunctionality--in particular, undermining the efficacy of processes that would otherwise afford natural protection against the development of pathology. Therapeutic modalities of microwave exposure, on the other hand, are illustrated using the example of microwave resonance therapy--which can be considered as an electromagnetic version of acupuncture, and as an example of 'quantum medicine'--whose normalising effect on a wide range of pathologies is striking, and which affords a novel alternative to conventional pharmacological interventions.

  10. Adverse environmental health effects of ultra-low relative humidity indoor air.

    PubMed

    Sato, Mikiya; Fukayo, Shingo; Yano, Eiji

    2003-03-01

    In Japan, relative humidity (RH) shows the lowest achievement rate among the various general air quality standards for work environment. It has been mainly contributed by airtight design of modern buildings and occurrence of dry outdoor air in winter. Furthermore, an ultra-dry air environment of nearly 0% RH is often required in sophisticated industries. In order to assess the adverse health effects of the ultra-dry air environment, using a self-reported questionnaire, we have undertaken a study of over 200 employees of a high-tech device developing laboratory having a room at 2.5% RH (ultra-dry room). Those who worked in the ultra-dry room were identified and the prevalence of symptoms was compared with the other workers. Analysis was performed by Wilcoxon's test and Fisher's exact test. In the ultra-dry room, all the twelve workers covered their skin with long-sleeve clothes, paper caps, paper masks and latex gloves. They reported skin symptoms more often (p<0.05) than the other workers (N=143). The prevalence of atopic dermatitis was also higher in the exposed workers (p<0.05). The complaints of workers in the ultra-dry environment were similar to preceding reports concerning moderately dry environmental exposures. The current precautions to protect the workers from the adverse effects of ultra-low RH appear to be insufficient, indicating that additional measures such as selection of appropriate clothing to mere skin coverage should be considered.

  11. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    PubMed

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings. PMID:26321154

  12. Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects

    PubMed Central

    Zhanel, George G; Simor, Andrew E; Vercaigne, Lavern; Mandell, Lionell

    1998-01-01

    OBJECTIVE: To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. DATA SELECTION: MEDLINE search from 1975 to 1997 and follow-up of references. DATA EXTRACTION: Clinical trials comparing imipenem with meropenem, or either imipenem or meropenem with standard therapy in the treatment of serious infections were selected. DATA SYNTHESIS: Imipenem, the first carbapenem, was first marketed in 1987; meropenem was introduced to the market in 1996. In general, imipenem is more active against Gram-positive cocci while meropenem is more active against Gram-negative bacilli. The agents display similar pharmacokinetics. Clinical studies in patients with serious infections (intra-abdominal infection, respiratory infection, septicemia, febrile neutropenia) report similar bacteriological and clinical cure rates with imipenem and meropenem. Meropenem is approved for the treatment of bacterial meningitis, whereas imipenem is not. Adverse effects are similar. CONCLUSIONS: Current literature supports the use of imipenem at a dose of 500 mg every 6 h and meropenem at 1 g every 8 h for the treatment of severe infections. For the treatment of serious infections, imipenem (500 mg every 6 h or 2 g/day [$98/day]) is more economical than meropenem (1 g every 8 h or 3 g/day [$142/day]) based on acquisition cost. PMID:22346545

  13. Low incidence of severe adverse effects after mandibular ridge reconstruction using hydroxylapatite.

    PubMed

    Mercier, P; Bellavance, F

    1999-08-01

    The short and long term adverse effects after ridge reconstruction using hydroxylapatite (HA) are presented in this study. The HA was inserted using a modified tunnelling technique, followed by a lowering of the floor of the mouth and a vestibuloplasty using split thickness skin graft, 4-6 weeks later. The study comprised 637 patients followed for a period of 1 to 10 years (mean 6.0+/-2.6 years). Major loss of HA was seen in 17 patients (2.7%). Donor site visibility (skin graft) appeared to improve greatly over the years from 29.2% to 8.8% at the latest follow-up. Neurosurgery deficits also improved from 11.6% (paraesthesia and dysaesthesia) to 4.6%. Long term follow-up revealed a high percentage of patient satisfaction (97%), indicating that the low incidence of severe adverse effects of the procedure does play a significant role in the appreciation of the procedure and prosthetic care. PMID:10416894

  14. Investigating clandestine drug laboratories: adverse medical effects in law enforcement personnel.

    PubMed

    Burgess, J L; Barnhart, S; Checkoway, H

    1996-10-01

    A retrospective cohort study was conducted among an international group of 46 law enforcement chemists and 13 Washington State clandestine drug laboratory investigation team members with more than 2,800 combined investigations. Each participant completed a questionnaire concerning previous drug laboratory investigations and adverse health effects during response activities. Methamphetamine laboratories accounted for 81-97% of all responses. Total illness incident rates varied between 0.75-3.4% of responses. Most exposures were through inhalation, and many occurred in the years prior to use of personal protective equipment. Symptoms were primarily those of headache and respiratory, mucous membrane, and skin irritation. Most illness episodes occurred during the processing phase of laboratory responses, and none occurred during the entry phase. A majority of illness episodes occurred in laboratories with leak/spills, fire/explosion, or uncontrolled reactions. Responding to an active laboratory was associated with a 7 to 15-fold risk of becoming ill as compared with setup, in-transit, or former (equipment removed) laboratory responses. No other laboratories characteristics were consistently associated with a significantly elevated relative risk of adverse health effects. PMID:8892555

  15. [Antibodies, human leukocyte antigens, and biomodulators in transfusion-related acute adverse effects].

    PubMed

    Martínez Álvarez, Julio César

    2013-01-01

    With the onset of the AIDS epidemic, major changes occurred in blood banking and transfusion medicine. These changes occurred mainly in donor selection and screening tests for infectious diseases, blood centers modified their organizational philosophy regarding quality. Transfusion of blood products are procedures that allow us to correct the haematology deficiencies for which was indicated. But today, despite the strict controls that precede transfusion,recipients may have undesirable effects, which are known as adverse effects or adverse reactions to transfusion. Antibodies and antigens of the HLA system plays a role in a series of events related to transfusion, such as immunological platelet refractoriness, febrile non-haemolytic transfusion reactions, transfusion related acute lung injury (TRALI) and transfusion-associated graft-versus-host disease. The determination of anti-HLA antibodies is evidence that in most developed countries is used on a daily basis in the regular assessment of patients multitransfused or waiting lists for organs from deceased donors. The biomodulators are able to modify biological responses which act in sequence to lead to the differentiation of T lymphocytes. These agents may subcategorizes those which facilitate a normal immune response, those stimulates the immune response, those are capable of inducing immunosuppression not cytotoxic, and those enhancing the ability of the host to tolerate damage by cytotoxic treatment (transfusion or transplant).

  16. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  17. Gratitude buffers the adverse effect of viewing the thin ideal on body dissatisfaction.

    PubMed

    Homan, Kristin J; Sedlak, Brittany L; Boyd, Elizabeth A

    2014-06-01

    Gratitude has robust associations with multiple aspects of well-being. However, little research has explored whether the psychological benefits of gratitude extend to body image. We used a repeated measures experimental design to test whether a brief period of grateful reflection would buffer the adverse effect of exposure to thin-ideal media. Female undergraduates (N=67) completed three sessions one week apart. The conditions were specifically designed to isolate (a) the effects of viewing thin models on body dissatisfaction and (b) the moderating effect of grateful contemplation. Results showed that body dissatisfaction scores were lower for women who engaged in a brief period of grateful contemplation before viewing photographs of thin models than for women who reflected upon life hassles before viewing the same photographs. The magnitude of this decrease depended on BMI. Gratitude offers an innovative direction for future research directed toward helping women to accept their bodies.

  18. Neurobehavioral performance and work experience in Florida farmworkers.

    PubMed

    Kamel, Freya; Rowland, Andrew S; Park, Lawrence P; Anger, W Kent; Baird, Donna D; Gladen, Beth C; Moreno, Tirso; Stallone, Lillian; Sandler, Dale P

    2003-11-01

    Farmworkers experience many work-related hazards, including exposure to neurotoxicants. We compared neurobehavioral performance of 288 farmworkers in central Florida who had done farm work for at least 1 month with 51 controls who had not. Most of the farmworkers had worked in one or more of three types of agriculture: ornamental ferns, nurseries, or citrus fruit. We collected information on farm work history in a structured interview and evaluated neurobehavioral performance using a battery of eight tests. Analyses were adjusted for established confounders including age, sex, education, and acculturation. Ever having done farm work was associated with poor performance on four tests--digit span [odds ratio (OR) = 1.90; 95% confidence interval (CI), 1.02-3.53], tapping (coefficient = 4.13; 95% CI, 0.00-8.27), Santa Ana test (coefficient = 1.34; 95% CI, 0.29-2.39), and postural sway (coefficient = 4.74; 95% CI, -2.20 to 11.7)--but had little effect on four others: symbol digit latency, vibrotactile threshold, visual contrast sensitivity, and grip strength. Associations with farm work were similar in magnitude to associations with personal characteristics such as age and sex. Longer duration of farm work was associated with worse performance. Associations with fern work were more consistent than associations with nursery or citrus work. Deficits related to the duration of work experience were seen in former as well as current farmworkers, and decreased performance was related to chronic exposure even in the absence of a history of pesticide poisoning. We conclude that long-term experience of farm work is associated with measurable deficits in cognitive and psychomotor function. PMID:14594629

  19. Neurobehavioral adaptations to methylphenidate: the issue of early adolescent exposure.

    PubMed

    Marco, Eva M; Adriani, Walter; Ruocco, Lucia A; Canese, Rossella; Sadile, Adolfo G; Laviola, Giovanni

    2011-08-01

    Exposure to psychostimulants, including both abused and therapeutic drugs, can occur first during human adolescence. Animal modeling is useful not only to reproduce adolescent peculiarities but also to study neurobehavioral adaptations to psychostimulant consumption. Human adolescence (generally considered as the period between 9/12 and 18 years old) has been compared with the age window between postnatal days (pnd) 28/35 and 50 in rats and mice. These adolescent rodents display basal hyperlocomotion and higher rates of exploration together with a marked propensity for sensation-seeking and risk-taking behaviors. Moreover, peculiar responses to psychostimulants, including enhanced locomotor sensitization, no drug-induced stereotypy and reduced place conditioning have been described in adolescent rodents. During this age window, forebrain dopamine systems undergo profuse remodeling, thus providing a neuro-biological substrate to explain behavioral peculiarities observed during adolescence, as well as the reported vulnerabilities to several drugs. Further, methylphenidate (MPH, better known as Ritalin®), a psychostimulant extensively prescribed to children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD), raises concerns for its long-term safety. Using magnetic resonance techniques, MPH-induced acute effects appear to be different in adolescent rats compared to adult animals. Moreover, adolescent exposure to MPH seems to provoke persistent neurobehavioral consequences: long-term modulation of self-control abilities, decreased sensitivity to natural and drug reward, enhanced stress-induced emotionality, together with an enhanced cortical control over sub-cortical dopamine systems and an enduring up-regulation of Htr7 gene expression within the nucleus accumbens (NAcc). In summary, additional studies in animal models are necessary to better understand the long-term consequences of adolescent MPH, and to further investigate the safety of

  20. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review.

    PubMed

    Mathiesen, O; Wetterslev, J; Kontinen, V K; Pommergaard, H-C; Nikolajsen, L; Rosenberg, J; Hansen, M S; Hamunen, K; Kjer, J J; Dahl, J B

    2014-11-01

    Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation. PMID:25116762

  1. Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies

    PubMed Central

    Holloway, A. C.; Salomon, A.; Soares, M. J.; Garnier, V.; Raha, S.; Sergent, F.; Nicholson, C. J.; Feige, J. J.; Benharouga, M.

    2013-01-01

    In utero exposure to nicotine is associated with increased risk of numerous adverse fetal and neonatal outcomes, which suggests that it acts directly to affect placental development and the establishment of the fetomaternal circulation (FC). This study used both in vivo [Wistar rats treated with 1 mg/kg nicotine from 2 wk prior to mating until gestational day (GD) 15] and in vitro (RCHO-1 cell line; treated with 10−9 to 10−3M nicotine) models to examine the effects of nicotine on these pathways. At GD 15, control and treated placentas were examined for the impact of nicotine on 1) trophoblast invasion, proliferation, and degree of hypoxia, 2) labyrinth vascularization, 3) expression of key genes of placental development, and 4) expression of placental angiogenic factors. The RCHO-1 cell line was used to determine the direct effects of nicotine on trophoblast differentiation. Our in vivo experiments show that nicotine inhibits trophoblast interstitial invasion, increases placental hypoxia, downregulates labyrinth vascularization as well as key transcription factors Hand1 and GCM1, and decreases local and circulating EG-VEGF, a key placental angiogenic factor. The in vitro experiments confirmed the inhibitory effects of nicotine on the trophoblast migration, invasion, and differentiation processes and demonstrated that those effects are most likely due to a dysregulation in the expression of nicotine receptors and a decrease in MMP9 activity. Taken together, these data suggest that adverse effects of maternal smoking on pregnancy outcome are due in part to direct and endocrine effects of nicotine on the main processes of placental development and establishment of FC. PMID:24368670

  2. Developmental exposure to a mixture of two mechanistically distinct antiandrogens results in cumulative adverse reproductive effects in adult male rats

    EPA Science Inventory

    Typically, toxicological studies have focused on the adverse effects from exposure to single chemicals. However, endocrine disrupting chemicals (EDCs) are detected in the environment as mixtures. Empirical evidence suggests that mixtures of EDCs with the same mechanism of action...

  3. Adapting test timing to the sleep-wake schedule: effects on diurnal neurobehavioral performance changes in young evening and older morning chronotypes.

    PubMed

    Schmidt, Christina; Peigneux, Philippe; Cajochen, Christian; Collette, Fabienne

    2012-05-01

    The synchrony effect refers to the beneficial impact of temporal matching between the timing of cognitive task administration and preferred time-of-day for diurnal activity. Aging is often associated with an advance in sleep-wake timing and concomitant optimal performance levels in the morning. In contrast, young adults often perform better in the evening hours. So far, the synchrony effect has been tested at fixed clock times, neglecting the individual's sleep-wake schedule and thus introducing confounds, such as differences in accumulated sleep pressure or circadian phase, which may exacerbate synchrony effects. To probe this hypothesis, the authors tested older morning and young evening chronotypes with a psychomotor vigilance and a Stroop paradigm once at fixed morning and evening hours and once adapting testing time to their preferred sleep-wake schedule in a within-subject design. The authors observe a persistence of synchrony effects for overall median reaction times during a psychomotor vigilance task, even when testing time is adapted to the specific individual's sleep-wake schedule. However, data analysis also indicates that time-of-day modulations are weakened under those conditions for incongruent trials on Stroop performance and the slowest reaction times on the psychomotor vigilance task. The latter result suggests that the classically observed synchrony effect may be partially mediated by a series of parameters, such as differences in socio-professional timing constraints, the amount of accumulated sleep need, or circadian phase, all leading to differential arousal levels at testing.

  4. Study of the neurological effects of low level methanol in normal subjects and subjects with susceptibility to folate deficiency. Final report

    SciTech Connect

    Osterloh, J.

    1995-04-01

    Very little is known about methanol as an air pollutant and about the effects of low level exposure on neurobehavioral functioning. Folic acid plays an important role in formate metabolism and may influence the concentrations of this toxic metabolite of methanol. The objective of this study is to provide information about whether or not acute exposure to methanol at the current industrial threshold limit value of 200 parts per million (ppm) for four hours would have adverse effects on human neurobehavioral, neurophysiological, and visual performances.

  5. Te Inclusions in CZT Detectors: New Method for Correcting Their Adverse Effects

    SciTech Connect

    Bolotnikov, A.E.; Babalola, S.; Camarda, G.S.; Cui, Y.; Egarievwe, S.U.; Hawrami, R.; Hossain, A.; Yang, G.; James, R.B.

    2009-10-25

    Both Te inclusions and point defects can trap the charge carriers generated by ionizing particles in CdZnTe (CZT) detectors. The amount of charge trapped by point defects is proportional to the carriers’ drift time and can be corrected electronically. In the case of Te inclusions, the charge loss depends upon their random locations with respect to the electron cloud. Consequently, inclusions introduce fluctuations in the charge signals, which cannot be easily corrected. In this paper, we describe direct measurements of the cumulative effect of Te inclusions and its influence on the response of CZT detectors of different thicknesses and different sizes and concentrations of Te inclusions. We also discuss a means of partially correcting their adverse effects.

  6. Exercise in the heat: strategies to minimize the adverse effects on performance.

    PubMed

    Terrados, N; Maughan, R J

    1995-01-01

    Exercise in the heat is usually associated with reduced performance; both dehydration and hyperthermia adversely affect mental and physical performance. For athletes from temperate climates, the negative effects of heat had humidity can be attenuated by a period of acclimatization. This requires up to 10-14 days. Endurance-trained individuals already show some of the adaptations that accompany acclimatization, but further adaptation occurs with training in the heat. Prior dehydration has a negative effect even on exercise of short duration where sweat losses are small. The athlete must begin exercise fully hydrated and regular ingestion of fluids is beneficial where the exercise duration exceeds 40 min. Dilute carbohydrate-electrolyte (sodium) drinks are best for fluid replacement and also supply some substrate for the exercising muscles. Post-exercise rehydration requires electrolyte as well as volume replacement. In extreme conditions, neither acclimatization nor fluid replacement will allow hard exercise to be performed without some risk of heat illness.

  7. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    PubMed Central

    Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form. PMID:27672457

  8. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone.

    PubMed

    Paudel, Robin; Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form. PMID:27672457

  9. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    PubMed Central

    Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

  10. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms.

    PubMed

    Liu, Yonggang; Goodson, Jamie M; Zhang, Bo; Chin, Michael T

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation.

  11. Addressing the potential adverse effects of school-based BMI assessments on children's wellbeing.

    PubMed

    Gibbs, Lisa; O'Connor, Thea; Waters, Elizabeth; Booth, Michael; Walsh, Orla; Green, Julie; Bartlett, Jenny; Swinburn, Boyd

    2008-01-01

    INTRODUCTION. Do child obesity prevention research and intervention measures have the potential to generate adverse concerns about body image by focussing on food, physical activity and body weight? Research findings now demonstrate the emergence of body image concerns in children as young as 5 years. In the context of a large school-community-based child health promotion and obesity prevention study, we aimed to address the potential negative effects of height and weight measures on child wellbeing by developing and implementing an evidence-informed protocol to protect and prevent body image concerns. fun 'n healthy in Moreland! is a cluster randomised controlled trial of a child health promotion and obesity prevention intervention in 23 primary schools in an inner urban area of Melbourne, Australia. Body image considerations were incorporated into the study philosophies, aims, methods, staff training, language, data collection and reporting procedures of this study. This was informed by the published literature, professional body image expertise, pilot testing and implementation in the conduct of baseline data collection and the intervention. This study is the first record of a body image protection protocol being an integral part of the research processes of a child obesity prevention study. Whilst we are yet to measure its impact and outcome, we have developed and tested a protocol based on the evidence and with support from stakeholders in order to minimise the adverse impact of study processes on child body image concerns.

  12. Duration of Internet use and adverse psychosocial effects among European adolescents.

    PubMed

    Secades-Villa, Roberto; Calafat, Amador; Fernández-Hermida, José Ramón; Juan, Montse; Duch, Mariangels; Skärstrand, Eva; Becoña, Elisardo; Talic, Sanela

    2014-01-01

    Despite the significant contributions from previous studies about the prevalence of problematic Internet use (PIU) among adolescents in Europe, important questions remain regarding adverse consequences of PIU. This study aims to assess the relation between duration of Internet use and adverse psychosocial effects among adolescents from six European countries. The final sample included 7,351 adolescents (50.8% male and 49.2% female; mean age: 14.6±1.90) recruited from randomly selected schools within the six study sites. Results showed that 12.9% of adolescents used Internet more than 20 hours per week. There was a significant relationship between duration of Internet use and frequency of alcohol, tobacco, cannabis and other illegal drug use. Duration of Internet use is also significantly associated with school problems, with use of slot machines and with other psychosocial problems. These findings highlight the need to strengthen preventive efforts for reducing PIU and related consequences among adolescents. Key Words: Internet, adolescents, psychosocial problems.

  13. Mediators and Adverse Effects of Child Poverty in the United States.

    PubMed

    Pascoe, John M; Wood, David L; Duffee, James H; Kuo, Alice

    2016-04-01

    The link between poverty and children's health is well recognized. Even temporary poverty may have an adverse effect on children's health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America's children and their families. At this difficult time in the history of our nation's families and immediately after the 50th anniversary year of President Lyndon Johnson's War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is "dedicated to the health of all children," to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty's negative impact on children's health and development. Children inherit not only their parents' genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child's genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation's children and their families.

  14. Mediators and Adverse Effects of Child Poverty in the United States.

    PubMed

    Pascoe, John M; Wood, David L; Duffee, James H; Kuo, Alice

    2016-04-01

    The link between poverty and children's health is well recognized. Even temporary poverty may have an adverse effect on children's health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America's children and their families. At this difficult time in the history of our nation's families and immediately after the 50th anniversary year of President Lyndon Johnson's War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is "dedicated to the health of all children," to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty's negative impact on children's health and development. Children inherit not only their parents' genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child's genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation's children and their families. PMID:26962239

  15. Arrhythmogenic adverse effects of cardiac glycosides are mediated by redox modification of ryanodine receptors

    PubMed Central

    Ho, Hsiang-Ting; Stevens, Sarah C W; Terentyeva, Radmila; Carnes, Cynthia A; Terentyev, Dmitry; Györke, Sandor

    2011-01-01

    Abstract The therapeutic use of cardiac glycosides (CGs), agents commonly used in treating heart failure (HF), is limited by arrhythmic toxicity. The adverse effects of CGs have been attributed to excessive accumulation of intracellular Ca2+ resulting from inhibition of Na+/K+-ATPase ion transport activity. However, CGs are also known to increase intracellular reactive oxygen species (ROS), which could contribute to arrhythmogenesis through redox modification of cardiac ryanodine receptors (RyR2s). Here we sought to determine whether modification of RyR2s by ROS contributes to CG-dependent arrhythmogenesis and examine the relevant sources of ROS. In isolated rat ventricular myocytes, the CG digitoxin (DGT) increased the incidence of arrhythmogenic spontaneous Ca2+ waves, decreased the sarcoplasmic reticulum (SR) Ca2+ load, and increased both ROS and RyR2 thiol oxidation. Additionally, pretreatment with DGT increased spark frequency in permeabilized myocytes. These effects on Ca2+ waves and sparks were prevented by the antioxidant N-(2-mercaptopropionyl) glycine (MPG). The CG-dependent increases in ROS, RyR2 oxidation and arrhythmogenic propensity were reversed by inhibitors of NADPH oxidase, mitochondrial ATP-dependent K+ channels (mito-KATP) or permeability transition pore (PTP), but not by inhibition of xanthine oxidase. These results suggest that the arrhythmogenic adverse effects of CGs involve alterations in RyR2 function caused by oxidative changes in the channel structure by ROS. These CG-dependent effects probably involve release of ROS from mitochondria possibly mediated by NADPH oxidase. PMID:21807619

  16. Ground experiments for finding principles and working out methods for preventing adverse effects of weightlessness on the human organism

    NASA Technical Reports Server (NTRS)

    Kakurin, L. I.; Gregoryev, A. I.; Mikhailov, V. M.; Tishler, V. A.

    1980-01-01

    A comparative assessment of the effectiveness of different prophylactic procedures to prevent the adverse effects of weightlessness is presented. It is concluded that: physical training is most effective but no single method by itself produces the full effect, and an adjustment of regimes to one another enhances the effect. The approved complex of prophylactic procedures affected basic changes occurring in hypokinesia: deficit of muscular activity, no or reduced BP hydrostatic component, reduced volume of blood circulation, reduced hydration level, and the application of various prophylactic complexes during 49 day antiorthostatic hypodynamia eliminated or reduced the adverse effects of weightlessness in simulation.

  17. Do shrubs reduce the adverse effects of grazing on soil properties?

    USGS Publications Warehouse

    Eldridge, David J.; Beecham, Genevieve; Grace, James B.

    2015-01-01

    Increases in the density of woody plants are a global phenomenon in drylands, and large aggregations of shrubs, in particular, are regarded as being indicative of dysfunctional ecosystems. There is increasing evidence that overgrazing by livestock reduces ecosystem functions in shrublands, but that shrubs may buffer the negative effects of increasing grazing. We examined changes in water infiltration and nutrient concentrations in soils under shrubs and in their interspaces in shrublands in eastern Australia that varied in the intensity of livestock grazing. We used structural equation modelling to test whether shrubs might reduce the negative effects of overgrazing on infiltration and soil carbon and nitrogen (henceforth ‘soil nutrients’). Soils under shrubs and subject to low levels of grazing were more stable and had greater levels of soil nutrients. Shrubs had a direct positive effect on soil nutrients; but, grazing negatively affected nutrients by increasing soil bulk density. Structural equation modelling showed that shrubs had a direct positive effect on water flow under ponded conditions but also enhanced water flow, indirectly, through increased litter cover. Any positive effects of shrubs on water flow under low levels of grazing waned at high levels of grazing. Our results indicate that shrubs may reduce the adverse effects of grazing on soil properties. Specifically, shrubs could restrict access to livestock and therefore protect soils and plants beneath their canopies. Low levels of grazing are likely to ensure the retention of soil water and soil carbon and nitrogen in shrubland soils.

  18. Critical Duration of Exposure for Developmental Chlorpyrifos-Induced Neurobehavioral Toxicity

    PubMed Central

    Sledge, Damiyon; Yen, Jerry; Morton, Terrell; Dishaw, Laura; Petro, Ann; Donerly, Susan; Linney, Elwood; Levin, Edward D.

    2011-01-01

    Developmental exposure of rats to the pesticide chlorpyrifos (CPF) causes persistent neurobehavioral impairment. In a parallel series of studies with zebrafish, we have also found persisting behavioral dysfunction after developmental CPF exposure. We have developed a battery of measures of zebrafish behavior, which are reliable and sensitive to toxicant-induced damage. This study determined the critical duration of developmental CPF exposure for causing persisting neurobehavioral effects. Tests of sensorimotor response (tap startle response and habituation), stress response (novel tank diving test) and learning (3-chamber tank spatial discrimination) were conducted with adult zebrafish after early developmental CPF exposure. The CPF exposure level was 100 ng/ml with durations of 0-1, 0-2, 0-3, 0-4 and 0-5 days after fertilization. Developmental CPF exposure had persisting behavioral effects in zebrafish tested as adults. In the tactile startle test, CPF exposed fish showed decreased habituation to startle and a trend toward increased overall startle response. In the novel tank exploration test, exposed fish showed decreased escape diving response and increased swimming activity. In the 3-chamber learning test, the 0-5 day CPF exposure group had a significantly lower learning rate. There was evidence for persisting declines in brain dopamine and norepinepherine levels after developmental CPF exposure. In all of the measures the clearest persistent effects were seen in fish exposed for the full duration of five days after fertilization. In a follow-up experiment there were some indications for persisting behavioral effects after exposure during only the later phase of this developmental window. This study demonstrated the selective long-term neurobehavioral alterations caused by exposure to CPF in zebrafish. The zebrafish model can facilitate the determination of the molecular mechanisms underlying long-term neurobehavioral impairment after developmental toxicant

  19. Evidence for the adverse effect of starvation on bone quality: a review of the literature.

    PubMed

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  20. Mouth breathing: adverse effects on facial growth, health, academics, and behavior.

    PubMed

    Jefferson, Yosh

    2010-01-01

    The vast majority of health care professionals are unaware of the negative impact of upper airway obstruction (mouth breathing) on normal facial growth and physiologic health. Children whose mouth breathing is untreated may develop long, narrow faces, narrow mouths, high palatal vaults, dental malocclusion, gummy smiles, and many other unattractive facial features, such as skeletal Class II or Class III facial profiles. These children do not sleep well at night due to obstructed airways; this lack of sleep can adversely affect their growth and academic performance. Many of these children are misdiagnosed with attention deficit disorder (ADD) and hyperactivity. It is important for the entire health care community (including general and pediatric dentists) to screen and diagnose for mouth breathing in adults and in children as young as 5 years of age. If mouth breathing is treated early, its negative effect on facial and dental development and the medical and social problems associated with it can be reduced or averted.

  1. Diagnostic criteria for adverse health effects in the environs of wind turbines.

    PubMed

    McMurtry, Robert Y; Krogh, Carmen Me

    2014-10-01

    In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed. PMID:25383200

  2. Diagnostic criteria for adverse health effects in the environs of wind turbines.

    PubMed

    McMurtry, Robert Y; Krogh, Carmen Me

    2014-10-01

    In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed.

  3. Diagnostic criteria for adverse health effects in the environs of wind turbines

    PubMed Central

    Krogh, Carmen ME

    2014-01-01

    Summary In an effort to address climate change, governments have pursued policies that seek to reduce greenhouse gases. Alternative energy, including wind power, has been proposed by some as the preferred approach. Few would debate the need to reduce air pollution, but the means of achieving this reduction is important not only for efficiency but also for health protection. The topic of adverse health effects in the environs of industrial wind turbines (AHE/IWT) has proven to be controversial and can present physicians with challenges regarding the management of an exposure to IWT. Rural physicians in particular must be aware of the possibility of people presenting to their practices with a variety of sometimes confusing complaints. An earlier version of the diagnostic criteria for AHE/IWT was published in August 2011. A revised case definition and a model for a study to establish a confirmed diagnosis is proposed. PMID:25383200

  4. The forensic nursing in sexual assaults: the immunochemical diagnosis and prevention of its adverse effects.

    PubMed

    Vitale, Elsa

    2012-04-01

    Sexual assault was a ubiquitous and serious problem in our society. The world's care centers and forensic associations, which were at the forefront of scientific research in sexual assaults, discussed the role of the Forensic Nursing in their early diagnosis and their prevention, but little has been written in literature regarding their appropriate management. This article focuses on the immunochemical laboratory investigation in diagnosis and prevention of its adverse effects in sexual assaults and the role of the Forensic Nursing played in this task. After a careful reading of all the material received from many of the care centers and the associations contacted, a Forensic Nursing Examination Program, with specific immunochemical address, is identified.

  5. Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects.

    PubMed

    de Groot, Anton C

    2013-01-01

    Propolis (bee glue) is the resinous substance that bees collect from living plants for the construction and adaptation of their nests. It has antibacterial, antifungal, and antiviral properties and may have a wide range of other beneficial biological activities. Propolis is available as a dietary supplement, in products for the protection of health and prevention of diseases, in biopharmaceuticals, and as a constituent of (bio)cosmetics. In this article, the following aspects of propolis are reviewed: the nature and chemical composition, its biological properties and applications, contact allergy and allergic contact dermatitis (sensitizing potential, products causing contact allergy, clinical picture, frequency of sensitization, coreactivity and cross-reactivity, the allergens in propolis), and other adverse effects. PMID:24201459

  6. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

    PubMed Central

    Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

    2015-01-01

    Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

  7. Reporter sex and newspaper coverage of the adverse health effects of hormone therapy.

    PubMed

    Nelson, David E; Signorielli, Nancy

    2007-01-01

    Women have used hormone therapy (HT) to relieve menopausal symptoms for decades. Major studies published in JAMA in July 2002 demonstrated adverse health effects from hormone therapy, and the National Institutes of Health halted the Women's Health Initiative clinical trial several years early. We conducted a content analysis of 10 U.S. newspapers in July and August 2002 to examine the role of reporter sex on news coverage on HT. We found substantial sex differences in reporting about HT. Female reporters were much more likely than male reporters to include a self-help frame (66.7% vs. 30.8%, p = 0.002). Female reporters were also much more likely to use women in the public as sources in HT-related articles (33.9% vs. 10.0%, p = 0.039). Reporter sex may play a role in the selection and content of health news articles. PMID:17613459

  8. The multinational drug companies in Zaire: their adverse effect on cost and availability of essential drugs.

    PubMed

    Glucksberg, H; Singer, J

    1982-01-01

    An analysis of the types and costs of drugs imported by seven multinational pharmaceutical companies in Zaire, an underdeveloped country in Africa, reveals that three-fourths of the drugs consisted of expensive and nonessential items. The prices of essential drugs (24 percent of their total imports) were much higher than those of available generic sources (average difference of 300 percent). The importation of nonessential drugs and high prices paid for essential drugs exacerbate the scarcity of needed items because of Zaire's limited supply of hard currency. In addition, two drug firms imported and promoted the sale of aminopyrone-dipyrone analgesic-antipyretics, drugs now rarely used in Western industrialized countries because of potentially fatal complications. Thus, in Zaire, the multinational pharmaceutical industry has an adverse effect on the availability and cost of drugs, as well as on the pattern of drug usage.

  9. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    PubMed

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  10. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal

    PubMed Central

    2016-01-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012–2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  11. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    PubMed

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  12. The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study.

    PubMed

    Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Ko, Chih-Hung

    2008-05-01

    Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome. PMID:17997489

  13. Mitigating Adverse Effects of a Human Mission on Possible Martian Indigenous Ecosystems

    NASA Astrophysics Data System (ADS)

    Lupisella, M. L.

    2000-07-01

    Although human beings are, by most standards, the most capable agents to search for and detect extraterrestrial life, we are also potentially the most harmful. While there has been substantial work regarding forward contamination with respect to robotic missions, the issue of potential adverse effects on possible indigenous Martian ecosystems, such as biological contamination, due to a human mission has remained relatively unexplored and may require our attention now as this presentation will try to demonstrate by exploring some of the relevant scientific questions, mission planning challenges, and policy issues. An informal, high-level mission planning decision tree will be discussed and is included as the next page of this abstract. Some of the questions to be considered are: (1) To what extent could contamination due to a human presence compromise possible indigenous life forms? (2) To what extent can we control contamination? For example, will it be local or global? (3) What are the criteria for assessing the biological status of Mars, both regionally and globally? For example, can we adequately extrapolate from a few strategic missions such as sample return missions? (4) What should our policies be regarding our mission planning and possible interaction with what are likely to be microbial forms of extraterrestrial life? (5) Central to the science and mission planning issues is the role and applicability of terrestrial analogs, such as Lake Vostok for assessing drilling issues, and modeling techniques. Central to many of the policy aspects are scientific value, international law, public concern, and ethics. Exploring this overall issue responsibly requires an examination of all these aspects and how they interrelate. A chart is included, titled 'Mission Planning Decision Tree for Mitigating Adverse Effects to Possible Indigenous Martian Ecosystems due to a Human Mission'. It outlines what questions scientists should ask and answer before sending humans to Mars.

  14. Adverse effects of testosterone replacement therapy: an update on the evidence and controversy

    PubMed Central

    Grech, Anthony; Breck, John

    2014-01-01

    Testosterone replacement therapy (TRT) has been used in millions of men worldwide to treat diminished libido and erectile dysfunction, and to improve strength and physical function. The estimated likelihood of adverse effects of long-term TRT is still essentially unknown, as overall high-quality evidence based upon prospective randomized trials to recommend for or against its use in most men with testosterone deficiency (TD) is lacking. Evidence to suggest that TRT increases cardiovascular morbidity and mortality risks is poor, as results vary across study populations and their baseline comorbidities. While TRT may increase serum prostate-specific antigen levels in some men, it often remains within clinically acceptable ranges, and has not been shown to increase the risk of prostate cancer. Current literature supports that TRT does not substantially worsen lower urinary tract symptoms, and may actually improve symptoms in some men. Limited evidence suggests that TRT may initially worsen obstructive sleep apnea in some men, but that this is not a longstanding effect. TRT may result in erythrocytosis in some men, however long-term studies have not reported significant adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms). Future research will require dedicated focus on evaluation of large, multiethnic cohorts of men through prospective trials to better elucidate both risk and hazard ratios of TRT as it relates to cardiovascular disease, prostate cancer, lower urinary tract symptoms, obstructive sleep apnea, erythrocytosis, and other to-be-determined theoretical risks in men both with and without cardiovascular risk equivalents. PMID:25360240

  15. Adverse effects of testosterone replacement therapy: an update on the evidence and controversy.

    PubMed

    Grech, Anthony; Breck, John; Heidelbaugh, Joel

    2014-10-01

    Testosterone replacement therapy (TRT) has been used in millions of men worldwide to treat diminished libido and erectile dysfunction, and to improve strength and physical function. The estimated likelihood of adverse effects of long-term TRT is still essentially unknown, as overall high-quality evidence based upon prospective randomized trials to recommend for or against its use in most men with testosterone deficiency (TD) is lacking. Evidence to suggest that TRT increases cardiovascular morbidity and mortality risks is poor, as results vary across study populations and their baseline comorbidities. While TRT may increase serum prostate-specific antigen levels in some men, it often remains within clinically acceptable ranges, and has not been shown to increase the risk of prostate cancer. Current literature supports that TRT does not substantially worsen lower urinary tract symptoms, and may actually improve symptoms in some men. Limited evidence suggests that TRT may initially worsen obstructive sleep apnea in some men, but that this is not a longstanding effect. TRT may result in erythrocytosis in some men, however long-term studies have not reported significant adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms). Future research will require dedicated focus on evaluation of large, multiethnic cohorts of men through prospective trials to better elucidate both risk and hazard ratios of TRT as it relates to cardiovascular disease, prostate cancer, lower urinary tract symptoms, obstructive sleep apnea, erythrocytosis, and other to-be-determined theoretical risks in men both with and without cardiovascular risk equivalents. PMID:25360240

  16. Metabolically normal obese people are protected from adverse effects following weight gain

    PubMed Central

    Fabbrini, Elisa; Yoshino, Jun; Yoshino, Mihoko; Magkos, Faidon; Tiemann Luecking, Courtney; Samovski, Dmitri; Fraterrigo, Gemma; Okunade, Adewole L.; Patterson, Bruce W.; Klein, Samuel

    2015-01-01

    BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as “metabolically normal obese” (MNO), but not those defined as “metabolically abnormal obese” (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gai