WorldWideScience

Sample records for development neurotoxicity implications

  1. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  2. Atropa belladonna neurotoxicity: Implications to neurological disorders.

    Science.gov (United States)

    Kwakye, Gunnar F; Jiménez, Jennifer; Jiménez, Jessica A; Aschner, Michael

    2018-06-01

    Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at-risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults, and animal models as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders. Copyright © 2018. Published by Elsevier Ltd.

  3. A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies.

    Science.gov (United States)

    Zanghi, Christine N; Jevtovic-Todorovic, Vesna

    The year 2016 marked the 15th anniversary since anesthesia-induced developmental neurotoxicity and its resulting cognitive dysfunction were first described. Since that time, multiple scientific studies have supported these original findings and investigated possible mechanisms behind anesthesia-induced neurotoxicity. This paper reviews the existing mechanistic literature on anesthesia-induced neurotoxicity in the context of a holistic approach that emphasizes the importance of both neuronal and non-neuronal cells during early postnatal development. Sections are divided into key stages in early neural development; apoptosis, neurogenesis, migration, differentiation, synaptogenesis, gliogenesis, myelination and blood brain barrier/cerebrovasculature. In addition, the authors combine the established literature in the field of anesthesia-induced neurotoxicity with literature from other related scientific fields to speculate on the potential role of non-neuronal cells and to generate new future hypotheses for understanding anesthetic toxicity and its application to the practice of pediatric anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.

    Science.gov (United States)

    Imam, S Z; Islam, F; Itzhak, Y; Slikker, W; Ali, S F

    2000-09-01

    Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

  5. Methylmercury and brain development: imprecision and underestimation of developmental neurotoxicity in humans

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Herz, Katherine T

    2011-01-01

    Methylmercury is now recognized as an important developmental neurotoxicant, though this insight developed slowly over many decades. Developmental neurotoxicity was first reported in a Swedish case report in 1952, and from a serious outbreak in Minamata, Japan, a few years later. Whereas the infant...

  6. Deficient PKR in RAX/PKR Association Ameliorates Ethanol-Induced Neurotoxicity in the Developing Cerebellum.

    Science.gov (United States)

    Li, Hui; Chen, Jian; Qi, Yuanlin; Dai, Lu; Zhang, Mingfang; Frank, Jacqueline A; Handshoe, Jonathan W; Cui, Jiajun; Xu, Wenhua; Chen, Gang

    2015-08-01

    Ethanol-induced neuronal loss is closely related to the pathogenesis of fetal alcohol spectrum disorders. The cerebellum is one of the brain areas that are most sensitive to ethanol. The mechanism underlying ethanol neurotoxicity remains unclear. Our previous in vitro studies have shown that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) regulates neuronal apoptosis upon ethanol exposure and ethanol activates PKR through association with its intracellular activator RAX. However, the role of PKR and its interaction with RAX in vivo have not been investigated. In the current study, by utilizing N-PKR-/- mice, C57BL/6J mice with a deficient RAX-binding domain in PKR, we determined the critical role of RAX/PKR association in PKR-regulated ethanol neurotoxicity in the developing cerebellum. Our data indicate that while N-PKR-/- mice have a similar BAC profile as wild-type mice, ethanol induces less brain/body mass reduction as well as cerebellar neuronal loss. In addition, ethanol promotes interleukin-1β (IL-1β) secretion, and IL-1β is a master cytokine regulating inflammatory response. Importantly, ethanol-promoted IL-1β secretion is inhibited in the developing cerebellum of N-PKR-/- mice. Thus, RAX/PKR interaction and PKR activation regulate ethanol neurotoxicity in the developing cerebellum, which may involve ethanol-induced neuroinflammation. Further, PKR could be a possible target for pharmacological intervention to prevent or treat fetal alcohol spectrum disorder (FASD).

  7. Vulnerability of children and the developing brain to neurotoxic hazards.

    Science.gov (United States)

    Weiss, B

    2000-06-01

    For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.

  8. Comprehensive neurotoxicity assessment

    NARCIS (Netherlands)

    Kulig, B.M.

    1996-01-01

    Significant progress has been made in recent years in terms of both the conceptualization of neurotoxicity assessment strategies as well as in the development of behavioral techniques for evaluating neurotoxic exposures. A tiered approach, for example, has been advocated as an assessment strategy in

  9. [The development of neurotoxic agents as chemical weapons during the National Socialist period in Germany].

    Science.gov (United States)

    López-Muñoz, F; Alamo, C; Guerra, J A; García-García, P

    The discovery and development of the so-called 'nerve agents' (neurotoxic substances to be used as weapons) took place in the Third Reich, largely thanks to the vast amount of progress being made in pharmacology in Germany at that time, both in academic and industrial terms. Furthermore, successive National Socialist governments set up a collaborative network made up of the academia, the chemical industry and military chiefs that also favoured this line of research. The first neurotoxic substance to be incorporated into the category of 'chemical warfare agent' did so almost wholly by chance. As part of the work being carried out on organophosphate-type pesticides and insecticides, Gerald Schrader, a chemist at the I.G. Farben company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an incident involving accidental contamination of laboratory staff with this substance highlighted its potential toxicity. The same group of researchers later synthesised another substance with the same properties, sarin (isopropyl methylphosphonofluoridate). Both agents were studied for use as chemical weapons by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the Nobel Prize in Chemistry in 1938, synthesised pinacolyl methylphosphonofluoridate, otherwise known as soman. Pharmacological studies confirmed that the neurotoxic mechanism of action of these substances was the irreversible inhibition of the enzyme acetylcholinesterase, which is responsible for metabolising acetylcholine. Results also showed that an excess of this neurotransmitter led to a continuous over-stimulation of the cholinergic (nicotinic and muscarinic) receptors, which is what triggers the appearance of the wide range of symptoms of poisoning and their swift fatal effect.

  10. Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

    Science.gov (United States)

    Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.

    2002-09-01

    The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

  11. Interaction of the 106-126 prion peptide with lipid membranes and potential implication for neurotoxicity

    International Nuclear Information System (INIS)

    Dupiereux, Ingrid; Zorzi, Willy; Lins, Laurence; Brasseur, Robert; Colson, Pierre; Heinen, Ernst; Elmoualij, Benaissa

    2005-01-01

    Prion diseases are fatal neurodegenerative disorders characterized by the accumulation in the brain of an abnormally misfolded, protease-resistant, and β-sheet rich pathogenic isoform (PrP sc ) of the cellular prion protein (PrP c ). In the present work, we were interested to study the mode of prion protein interaction with the membrane using the 106-126 peptide and small unilamellar lipid vesicles as model. As previously demonstrated, we showed by MTS assay that PrP 106-126 induces alterations in the human neuroblastoma SH-SY5Y cell line. We demonstrated for the first time by lipid-mixing assay and by the liposome vesicle leakage test that PrP 106-126, a non-tilted peptide, induces liposome fusion thus a potential cell membrane destabilization, as supported by membrane integrity assay (LDH). By circular dichroism (CD) analysis we showed that the fusogenic property of PrP 106-126 in the presence of liposome is associated with a predominantly β-sheet structure. These data suggest that the fusogenic property associated with a predominant β-sheet structure exhibited by the prion peptides contributes to the neurotoxicity of these peptides by destabilizing cellular membranes. The latter might be attached at the membrane surface in a parallel orientation as shown by molecular modeling

  12. Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon: Implications for neurotoxicity

    International Nuclear Information System (INIS)

    Grigoryan, Hasmik; Lockridge, Oksana

    2009-01-01

    Organophosphorus agents cause cognitive deficits and depression in some people. We hypothesize that the mechanism by which organophosphorus agents cause these disorders is by modification of proteins in the brain. One such protein could be tubulin. Tubulin polymerizes to make the microtubules that transport cell components to nerve axons. The goal of the present work was to measure the effect of the organophosphorus agent chlorpyrifos oxon on tubulin polymerization. An additional goal was to identify the amino acids covalently modified by chlorpyrifos oxon in microtubule polymers and to compare them to the amino acids modified in unpolymerized tubulin dimers. Purified bovine tubulin (0.1 mM) was treated with 0.005-0.1 mM chlorpyrifos oxon for 30 min at room temperature and then polymerized by addition of 1 mM GTP to generate microtubules. Microtubules were visualized by atomic force microscopy. Chlorpyrifos oxon-modified residues were identified by tandem ion trap electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry of tryptic peptides. Nanoimaging showed that low concentrations (0.005 and 0.01 mM) of chlorpyrifos oxon yielded short, thin microtubules. A concentration of 0.025 mM stimulated polymerization, while high concentrations (0.05 and 0.1 mM) caused aggregation. Of the 17 tyrosines covalently modified by chlorpyrifos oxon in unpolymerized tubulin dimers, only 2 tyrosines were labeled in polymerized microtubules. The two labeled tyrosines in polymerized tubulin were Tyr 103 in EDAANNY*R of alpha tubulin, and Tyr 281 in GSQQY*R of beta tubulin. In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents.

  13. Age-dependent methamphetamine-induced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity.

    Science.gov (United States)

    Truong, Jannine G; Wilkins, Diana G; Baudys, Jakub; Crouch, Dennis J; Johnson-Davis, Kamisha L; Gibb, James W; Hanson, Glen R; Fleckenstein, Annette E

    2005-09-01

    Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied. In adult rodents, toxic effects of methamphetamine may result partly from aberrant cytosolic dopamine accumulation and subsequent reactive oxygen species formation. The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and perhaps protection against dopamine-associated oxidative consequences. Accordingly, aberrant VMAT-2 function may contribute to the methamphetamine-induced persistent dopaminergic deficits. Hence, this study examined effects of methamphetamine on VMAT-2 in adolescent (postnatal day 40) and young adult (postnatal day 90) rats. Results revealed that high-dose methamphetamine treatment caused greater acute (within 1 h) decreases in vesicular dopamine uptake in postnatal day 90 versus 40 rats, as determined in a nonmembrane-associated subcellular fraction. Greater basal levels of VMAT-2 at postnatal day 90 versus 40 in this purified fraction seemed to contribute to the larger effect. Basal tissue dopamine content was also greater in postnatal day 90 versus 40 rats. In addition, postnatal day 90 rats were more susceptible to methamphetamine-induced persistent dopaminergic deficits as assessed by measuring VMAT-2 activity and dopamine content 7 days after treatment, even if drug doses were adjusted for age-related pharmacokinetic differences. Together, these data demonstrate dynamic changes in VMAT-2 susceptibility to methamphetamine as a function of development. Implications with regard to methamphetamine-induced dopaminergic deficits, as well as dopamine-associated neurodegenerative disorders such as Parkinson's disease, are discussed.

  14. Accelerated oxygen consumption by catecholamines in the presence of aromatic nitro and nitroso compounds. Implications and neurotoxicity of nitro compounds

    International Nuclear Information System (INIS)

    Sridhar, K.

    1981-01-01

    The interactions of catecholamines with nitro and nitroso compounds are studied in view of the possible involvement of catecholamine type neurotransmitters in neurotoxicity caused by hypoxic cell sensitizers. The data reported suggest that neurotoxicity of nitro compounds may be due to depletion of oxygen, catecholamines and ascorbate in nerve tissue with concomitant generation of toxic species such as hydroxyl, hydronitroxyl and superoxide free radicals as well as nitroso and quinonoid derivatives. 5 references, 1 figure

  15. Editor's Highlight: Congener-Specific Disposition of Chiral Polychlorinated Biphenyls in Lactating Mice and Their Offspring: Implications for PCB Developmental Neurotoxicity.

    Science.gov (United States)

    Kania-Korwel, Izabela; Lukasiewicz, Tracy; Barnhart, Christopher D; Stamou, Marianna; Chung, Haeun; Kelly, Kevin M; Bandiera, Stelvio; Lein, Pamela J; Lehmler, Hans-Joachim

    2017-07-01

    Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of 2 environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8-weeks old) were fed daily, beginning 2 weeks prior to conception and continuing throughout gestation and lactation, with 3.1 µmol/kg bw/d of racemic 2,2',3,5',6-pentachlorobiphenyl (PCB 95) or 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in peanut butter; controls received vehicle (peanut oil) in peanut butter. PCB 95 levels were higher than PCB 136 levels in both dams and pups, consistent with the more rapid metabolism of PCB 136 compared with PCB 95. In pups and dams, both congeners were enriched for the enantiomer eluting second on enantioselective gas chromatography columns. OH-PCB profiles in lactating mice and their offspring were complex and varied according to congener, tissue and age. Developmental exposure to PCB 95 versus PCB 136 differentially affected the expression of P450 enzymes as well as neural plasticity (arc and ppp1r9b) and thyroid hormone-responsive genes (nrgn and mbp). The results suggest that the enantioselective metabolism of PCBs to OH-PCBs may influence neurotoxic outcomes following developmental exposures, a hypothesis that warrants further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Cerebellum neurotransmission during postnatal development: [Pt(O,O'-acac)(γ-acac)(DMS)] vs cisplatin and neurotoxicity.

    Science.gov (United States)

    Piccolini, Valeria Maria; Esposito, Alessandra; Dal Bo, Veronica; Insolia, Violetta; Bottone, Maria Grazia; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Bernocchi, Graziella

    2015-02-01

    Several chemotherapeutic drugs are known to cause neurotoxicity. Platinum-based agents in use or in clinical trials display neurotoxic potential accompanied by neurological complications; recent studies have identified a large number of behavioural issues in paediatric oncology patients. To understand the toxicity of platinum drugs at the molecular and cellular levels, this study compares the possible cytotoxic effects of an older platinum compound, cisplatin and a new platinum compound, [Pt(O,O'-acac)(γ-acac)(DMS)], on the CNS of postnatally developing rats, which is much more vulnerable to injury than the CNS of adult rats. Since several drugs interact with neurotransmitters during neuronal maturation, we performed immunostainings with antibodies raised against markers of glutamate and GABA, the major neurotransmitters in the cerebellum. After a single injection of cisplatin at postnatal day 10 (PD10), the labelling of Purkinje cells with the neurotransmitter markers evidenced alterations between PD11 and PD30, i.e. atrophy of the dendrite tree, changes in the distribution of synaptic contacts of parallel and climbing fibres, delay in the elimination of transient synapses on cell soma and severely impaired pinceau formation at the axon hillock. After treatment with [Pt(O,O'-acac)(γ-acac)(DMS)], the sole relevant change concerned the timing of climbing fibres elimination; the transient synapses disappearance on the Purkinje cell soma was delayed in some cells; instead, the growth of Purkinje cell dendrite tree was normal as was the formation of inhibitory synaptic contacts on these neurons. These findings add new evidence not only on the lower neurotoxicity of [Pt(O,O'-acac)(γ-acac)(DMS)] vs cisplatin but also on the involvement of neurotransmitters and relative synaptic connections in the maturation of central nerve tissue. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  17. Reversible Lithium Neurotoxicity: Review of the Literature

    Science.gov (United States)

    Netto, Ivan

    2012-01-01

    Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. Data Sources: A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. Study Selection: A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. Data Extraction: The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Data Synthesis: Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Conclusions: Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate

  18. Reversible lithium neurotoxicity: review of the literatur.

    Science.gov (United States)

    Netto, Ivan; Phutane, Vivek H

    2012-01-01

    Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of

  19. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children

    DEFF Research Database (Denmark)

    Hansen, Tom G

    2015-01-01

    development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide......A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic...... the anesthetics. Currently, there is no need to change current anesthetic clinical practice or to postpone or cancel truly urgent surgeries in young children....

  20. Multiple mechanisms of PCB neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.O.; Stoner, C.T.; Lawrence, D.A. [Univ. of New York, Albany, NY (United States)] [and others

    1996-12-31

    Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.

  1. Biomarkers of adult and developmental neurotoxicity

    International Nuclear Information System (INIS)

    Slikker, William; Bowyer, John F.

    2005-01-01

    Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. A multidisciplinary approach is necessary to assess adult and developmental neurotoxicity due to the complex and diverse functions of the nervous system. The overall strategy for understanding developmental neurotoxicity is based on two assumptions: (1) significant differences in the adult versus the developing nervous system susceptibility to neurotoxicity exist and they are often developmental stage dependent; (2) a multidisciplinary approach using neurobiological, including gene expression assays, neurophysiological, neuropathological, and behavioral function is necessary for a precise assessment of neurotoxicity. Application of genomic approaches to developmental studies must use the same criteria for evaluating microarray studies as those in adults including consideration of reproducibility, statistical analysis, homogenous cell populations, and confirmation with non-array methods. A study using amphetamine to induce neurotoxicity supports the following: (1) gene expression data can help define neurotoxic mechanism(s) (2) gene expression changes can be useful biomarkers of effect, and (3) the site-selective nature of gene expression in the nervous system may mandate assessment of selective cell populations

  2. Health implications of hydropower development

    International Nuclear Information System (INIS)

    Biswas, A.K.

    1982-01-01

    Hydropower development had been neglected in many countries during the past few decades, but the situation dramatically changed during the 1970s owing to the constantly increasing costs of electricity generation by fossil-fuel and nuclear power plants. Currently, hydroelectric generation accounts for approximately 23% of total global electricity supply. Much of the hydropower potential in developing countries of Africa, Asia and Latin America still remains to be exploited. Like any other source of energy, hydropower development has several health impacts. Conceptually, health implications of hydropower development can be divided into two broad categories: short-term and long-term problems. Short-term health impacts occur during the planning, construction and immediate post-construction phases, whereas long-term impacts stem from the presence of large man-made lakes, development of extensive canal systems, alteration of the ecosystem of the area, and changing socio-economic conditions. Longer-term impacts are further classified into two categories: introduction of new diseases and/or intensification of existing ones due to the improvements of the habitats of disease-carrying vectors, and health problems arising from resettlement of the people whose homes and land-holdings are inundated by the reservoirs. All these impacts are discussed in detail. Health impacts of hydropower developments have not yet been studied extensively. It is often implicitly assumed that health impacts of major dams are minor compared with other social and environmental impacts. Future studies could possibly reverse this assumption. (author)

  3. Dopamine transporter down-regulation following repeated cocaine: implications for 3,4-methylenedioxymethamphetamine-induced acute effects and long-term neurotoxicity in mice.

    Science.gov (United States)

    Peraile, I; Torres, E; Mayado, A; Izco, M; Lopez-Jimenez, A; Lopez-Moreno, J A; Colado, M I; O'Shea, E

    2010-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) and cocaine are two widely abused psychostimulant drugs targeting the dopamine transporter (DAT). DAT availability regulates dopamine neurotransmission and uptake of MDMA-derived neurotoxic metabolites. We aimed to determine the effect of cocaine pre-exposure on the acute and long-term effects of MDMA in mice. Mice received a course of cocaine (20 mg*kg(-1), x2 for 3 days) followed by MDMA (20 mg*kg(-1), x2, 3 h apart). Locomotor activity, extracellular dopamine levels and dopaminergic neurotoxicity were determined. Furthermore, following the course of cocaine, DAT density in striatal plasma membrane and endosome fractions was measured. Four days after the course of cocaine, challenge with MDMA attenuated the MDMA-induced striatal dopaminergic neurotoxicity. Co-administration of the protein kinase C (PKC) inhibitor NPC 15437 prevented cocaine protection. At the same time, after the course of cocaine, DAT density was reduced in the plasma membrane and increased in the endosome fraction, and this effect was prevented by NPC 15437. The course of cocaine potentiated the MDMA-induced increase in extracellular dopamine and locomotor activity, following challenge 4 days later, compared with those pretreated with saline. Repeated cocaine treatment followed by withdrawal protected against MDMA-induced dopaminergic neurotoxicity by internalizing DAT via a mechanism which may involve PKC. Furthermore, repeated cocaine followed by withdrawal induced behavioural and neurochemical sensitization to MDMA, measures which could be indicative of increased rewarding effects of MDMA.

  4. Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity.

    Science.gov (United States)

    Manucha, Walter

    Multiple mechanisms underlying glutamate-induced neurotoxicity have recently been discussed. Likewise, a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration, oxidative stress, and inflammation. This article highlights nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, and has many important implications for nerve cell survival and differentiation. Consequently, synaptogenesis, synapse elimination, and neurotransmitter release, are nitric oxide-modulated. Interesting, an emergent role of nitric oxide pathways has been discussed as regards neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevent oxidative damage to neurons through apoptosis inhibition. This review aims to highlight the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity, as well as the development of neurodegenerative diseases development. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Taxane-Induced Peripheral Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Roser Velasco

    2015-04-01

    Full Text Available Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

  6. Occupational Neurotoxic Diseases in Taiwan

    Directory of Open Access Journals (Sweden)

    Chi-Hung Liu

    2012-12-01

    Full Text Available Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

  7. Implication of neuro-genesis during brain development in behavior disorders caused by depleted uranium

    International Nuclear Information System (INIS)

    Legrand, Marie

    2016-01-01

    Humans are continuously exposed to neurotoxic compounds in the environment. The developing brain is more susceptible to neurotoxic compounds and modifications in its growth could lead to disorders in adulthood. Uranium (U) is an environmental heavy metal and induces behavioral disorders as well as affects neurochemistry. The aim of my thesis was to investigate whether depleted uranium (DU) exposure affects neuro-genesis processes, which are implicated in brain development and in synaptic plasticity in adults. While DU increased cell proliferation in the hippocampal neuro-epithelium and decreased cell death at prenatal stages, DU lead to opposite effects in the dentate gyrus at postnatal stages. Moreover, DU had an inhibitory effect on the transition toward neuronal differentiation pathway during development. At adult stage, DU induced a decrease in neuronal differentiation but has no impact in cell proliferation. Finally, DU exposure during brain development caused depressive like behavior at late postnatal and adult stage, and decreased spatial memory at adult stage. Consequently, DU exposure during brain development caused modification in neuro-genesis processes associated to cognitive and emotional disorders at adult age. U could present a threat to human health, especially in pregnant women and children. (author)

  8. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

    Directory of Open Access Journals (Sweden)

    O'Shea Esther

    2011-05-01

    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

  9. Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: Effects of CREB pathway inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Pistollato, Francesca; Louisse, Jochem; Scelfo, Bibiana; Mennecozzi, Milena [Institute for Health and Consumer Protection (IHCP), JRC, Ispra (Italy); Accordi, Benedetta; Basso, Giuseppe [Oncohematology Laboratory, Department of Woman and Child Health, University of Padova, Padova (Italy); Gaspar, John Antonydas [Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Cologne (Germany); Zagoura, Dimitra; Barilari, Manuela; Palosaari, Taina [Institute for Health and Consumer Protection (IHCP), JRC, Ispra (Italy); Sachinidis, Agapios [Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Cologne (Germany); Bremer-Hoffmann, Susanne, E-mail: susanne.bremer@jrc.ec.europa.eu [Institute for Health and Consumer Protection (IHCP), JRC, Ispra (Italy)

    2014-10-15

    According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer a unique opportunity to derive physiologically relevant human cell types to measure molecular and cellular effects of such pathway modulations. Here we compared the neuronal differentiation propensity of hESCs and hiPSCs with the aim to develop novel hiPSC-based tools for measuring pathway perturbation in relation to molecular and cellular effects in vitro. Among other fundamental pathways, also, the cAMP responsive element binding protein (CREB) pathway was activated in our neuronal models and gave us the opportunity to study time-dependent effects elicited by chemical perturbations of the CREB pathway in relation to cellular effects. We show that the inhibition of the CREB pathway, using 2-naphthol-AS-E-phosphate (KG-501), induced an inhibition of neurite outgrowth and synaptogenesis, as well as a decrease of MAP2{sup +} neuronal cells. These data indicate that a CREB pathway inhibition can be related to molecular and cellular effects that may be relevant for neurotoxicity testing, and, thus, qualify the use of our hiPSC-derived neuronal model for studying chemical-induced neurotoxicity resulting from pathway perturbations. - Highlights: • HESCs derived neuronal cells serve as benchmark for iPSC based neuronal toxicity test development. • Comparisons between hESCs and hiPSCs demonstrated variability of the epigenetic state • CREB pathway modulation have been explored in relation to the neurotoxicant exposure KG-501 • hiPSC might be promising tools to translate theoretical AoPs into toxicological in vitro tests.

  10. Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay

    NARCIS (Netherlands)

    Colaianna, M.; Ilmjärv, S.; Peterson, H.; Ilse Kern, I.; Julien, S.; Baquié, M.; allocca, G.; Bosgra, S.; Sachinidis, A.; Hengstler, J.G.; Leist, M.; Krause, K.H.

    2017-01-01

    Identification of neurotoxic drugs and environmental chemicals is an important challenge. However, only few tools to address this topic are available. The aim of this study was to develop a neurotoxicity/developmental neurotoxicity (DNT) test system, using the pluripotent mouse embryonic stem cell

  11. Insecurity and national economic development implications for ...

    African Journals Online (AJOL)

    Insecurity and national economic development implications for Nigeria's vision 20: 2020. ... International Journal of Development and Management Review ... These social menace trigger off a worrisome sense of insecurity that challenge Nigeria's efforts towards national economic development and consequently its vision ...

  12. Developmental neurotoxicity of Propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, P.; Christiansen, S.

    2007-01-01

    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups...... behaviour and hearing function. This supports that exposure to TDC's in general may cause long-lasting developmental neurotoxicity....

  13. The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A: implications for toxicity testing.

    Science.gov (United States)

    Beronius, Anna; Johansson, Niklas; Rudén, Christina; Hanberg, Annika

    2013-09-06

    Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies. However, there are discrepancies in the results reported between the studies. The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies. Forty-four DNT studies of BPA were identified from the open literature. Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database. This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426. Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results. The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring. On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing. However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration. Many studies were also poorly reported, limiting these analyses. No strong conclusions could be drawn from the multivariate analyses. A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results. In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly

  14. Globalisation; Its Implications and Consequences for Developing ...

    African Journals Online (AJOL)

    This paper attempts to look at the concept of globalisations and analyse its implications and consequences for developing nations in Africa. It is premised on the general perception that globalisations is a positive and powerful force for the improved material well-being of humankind, that would aid the developing countries ...

  15. Telomeres: Implications for Cancer Development

    Directory of Open Access Journals (Sweden)

    Aina Bernal

    2018-01-01

    Full Text Available Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR. This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints. Dysfunctional telomeres can suppress cancer development by engaging replicative senescence or apoptotic pathways, but they can also promote tumour initiation. Studies in telomere dynamics and karyotype analysis underpin telomere crisis as a key event driving genomic instability. Significant attainment of telomerase or alternative lengthening of telomeres (ALT-pathway to maintain telomere length may be permissive and required for clonal evolution of genomically-unstable cells during progression to malignancy. We summarise current knowledge of the role of telomeres in the maintenance of chromosomal stability and carcinogenesis.

  16. Cultural Implications of Human Resource Development.

    Science.gov (United States)

    Hiranpruk, Chaiskran

    A discussion of the cultural effects of economic and, by extension, human resource development in Southeast Asia looks at short- and long-term implications. It is suggested that in the short term, increased competition will affect distribution of wealth, which can promote materialism and corruption. The introduction of labor-saving technology may…

  17. Management of paclitaxel-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Manisha Bhutani

    2011-12-01

    Full Text Available Paclitaxel exerts its antitumor activity by promoting microtubule assembly and stabilizing microtubules. Microtubules are important for the development and maintenance of neurons. As a consequence, neurotoxicity is one of the drug’s major side effects. The risk of neurotoxicity depends on dose, duration and schedule of paclitaxel. Risk increases for patients with pre-existing conditions that may cause neuropathy (such as alcohol consumption, diabetes, or renal disease or with simultaneous or prior exposure to other neurotoxic chemotherapy such as platinum-based drugs, vinca alkaloids, immunomodulators, proteasome inhibitors, and epothilones. Patients with paclitaxel-induced neurotoxicity (PINT experience a constellation of symptoms over the course of treatment and beyond, ranging from mild to severe. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. Proprioceptive and motor effects become apparent as neuropathy becomes more advanced. These symptoms may be prolonged, severe, disabling, relatively resistant to intervention and adversely affect activities of daily living and thereby quality of life. Management is mainly symptomatic and supportive. Despite attempts to minimize PINT with changes in dose, vehicle, delivery systems, infusion schedule and premedication or co-treatment with neuroprotective agents, PINT remains dose-limiting in many instances and is a barrier to achieving the desired clinical response.

  18. Exocytosis: using amperometry to study presynaptic mechanisms of neurotoxicity

    NARCIS (Netherlands)

    Westerink, R.H.S.

    2004-01-01

    The development of carbon fiber microelectrode amperometry enabled detailed investigation of the presynaptic response at the single cell level with single vesicle resolution. Consequently, amperometry allowed for detailed studies into the presynaptic mechanisms underlying neurotoxicity. This review

  19. Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

    International Nuclear Information System (INIS)

    Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Soren Peter; Hougaard, Karin Sorig; Hass, Ulla

    2008-01-01

    Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T 4 ) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T 4 during development. This supports the hypothesis that decreased T 4 may be a relevant predictor for long-lasting developmental neurotoxicity

  20. Neurotoxic shellfish poisoning: A review

    NARCIS (Netherlands)

    Apeldoorn ME van; Egmond HP van; Speijers GJA; CSR; ARO

    2001-01-01

    This review contains information on the neurotoxic shellfish poisoning (NSP) syndrome and the provoking toxins called brevetoxins, produced by the dinoflagellate Gymnodinium breve. Data on chemical structures and detection methods for brevetoxins, sources for brevetoxins, marine organisms associated

  1. Neurotoxic shellfish poisoning: A review

    NARCIS (Netherlands)

    Apeldoorn ME van; Egmond HP van; Speijers GJA; CSR; ARO

    2001-01-01

    Dit literatuuroverzicht bevat informatie betreffende het "neurotoxic shellfish poisoning" (NSP) syndroom en de veroorzakende toxines, nl.de brevetoxines, welke geproduceerd worden door de dinoflagellaat Gymnodinium breve. Chemische structuren en detectie-methodes van de brevetoxines,

  2. Effects of glutamate and α2-noradrenergic receptor antagonists on the development of neurotoxicity produced by chronic rotenone in rats

    International Nuclear Information System (INIS)

    Alam, Mesbah; Danysz, Wojciech; Schmidt, Werner Juergen; Dekundy, Andrzej

    2009-01-01

    Systemic inhibition of complex I by rotenone in rats represents a model of Parkinson's disease (PD). The aim of this study was to elucidate whether neramexane (NMDA, nicotinic α9/α10 and 5-HT 3 receptor antagonist), idazoxan (α 2 -adrenoceptor antagonist) or 2-methyl-6-(phenyl-ethyl)-pyrimidine (MPEP, metabotropic glutamate receptor 5 antagonist) prevents rotenone-induced parkinsonian-like behaviours and neurochemical changes in rats. Rotenone (2.5 mg/kg i.p. daily) was administered over 60 days together with saline, neramexane (5 mg/kg i.p., b.i.d.), idazoxan (2.5 mg/kg i.p., b.i.d.) or MPEP (2.5 mg/kg i.p., b.i.d.). The same doses of neramexane, idazoxan and MPEP were administered to rats treated with vehicle instead of rotenone. Treatment-related effects on parkinsonian-like behaviours, such as hypokinesia/rigidity and locomotor activity, were evaluated. Moreover, concentrations of dopamine, serotonin and their metabolites were measured in rats from each experimental group. Over the 60-day treatment period, the rotenone + saline treated animals developed hypokinesia, expressed as an increase in the bar and grid descent latencies in the catalepsy test, and a decrease in locomotor activity. Neramexane and idazoxan partially prevented the development of catalepsy in rotenone-treated rats. Co-administration of MPEP with rotenone resulted only in a decrease in descent latency in the grid test on day 60. Chronic rotenone treatment reduced concentrations of dopamine and serotonin in the anterior striatum, which was blocked by co-treatment with neramexane or idazoxan but not with MPEP. Only neramexane treatment blocked the rotenone-induced decrease in dopamine levels in the substantia nigra pars compacta. In conclusion, neramexane and idazoxan counteracted to some extent the development of parkinsonian symptoms and neurochemical alterations in the rotenone model of Parkinson's disease.

  3. Manganese- and 1-methyl-4-phenylpyridinium-induced neurotoxicity display differences in morphological, electrophysiological and genome-wide alterations: implications for idiopathic Parkinson's disease.

    Science.gov (United States)

    Mythri, Rajeswara Babu; Raghunath, Narayana Reddy; Narwade, Santosh Chandrakant; Pandareesh, Mirazkar Dasharatha Rao; Sabitha, Kollarkandi Rajesh; Aiyaz, Mohamad; Chand, Bipin; Sule, Manas; Ghosh, Krittika; Kumar, Senthil; Shankarappa, Bhagyalakshmi; Soundararajan, Soundarya; Alladi, Phalguni Anand; Purushottam, Meera; Gayathri, Narayanappa; Deobagkar, Deepti Dileep; Laxmi, Thenkanidiyoor Rao; Srinivas Bharath, Muchukunte Mukunda

    2017-11-01

    Idiopathic Parkinson's disease and manganese-induced atypical parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the Parkinson's disease toxin 1-methyl-4-phenylpyridinium ion (MPP + ) and manganese (Mn), followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and Mn mouse models. Morphological analysis highlighted loss of neuronal processes in the MPP + and not the Mn model. Cellular network dynamics of dopaminergic neurons characterized by spike frequency and inter-spike intervals indicated major neuronal population (~ 93%) with slow discharge rates (0-5 Hz). While MPP + exposure suppressed the firing of these neurons, Mn neither suppressed nor elevated the neuronal activity. High-throughput transcriptomic analysis revealed up-regulation of 694 and 603 genes and down-regulation of 428 and 255 genes in the MPP + and Mn models respectively. Many differentially expressed genes were unique to either models and contributed to neuroinflammation, metabolic/mitochondrial function, apoptosis and nuclear function, synaptic plasticity, neurotransmission and cytoskeleton. Analysis of the Janus kinase-signal transducer and activator of transcription pathway with implications for neuritogenesis and neuronal proliferation revealed contrasting profile in both models. Genome-wide DNA methylomics revealed differences between both models and substantiated the epigenetic basis of the difference in the Janus kinase-signal transducer and activator of transcription pathway. We conclude that idiopathic Parkinson's disease and atypical parkinsonism have divergent neurotoxicological manifestation at the dopaminergic neuronal level with implications for pathobiology and evolution

  4. Clinical Neurotoxic Disorders : Past, Present and Future

    Directory of Open Access Journals (Sweden)

    Nag Devika

    2001-01-01

    Full Text Available Neurotoxins have existed on the earth from times immemorial. Old neurotoxic disorders were due to ingestion/ exposure of heavy metals and food like lathyrus sativus over a long period of time. The 20th Century with rapid industrialsation and expanding chemical and drug industry has spawned several new, hitherto unknown disorders. Old disorders continue to exist e.g. fluorosis, arsenicosis, lathyrism, manganism and lead neuropathy, along with new diseases like Minamata disease, subacute myelo optic neuropathy (SMON, MPTP-Parkinsonian syndorme, triorthcresyl phosphate (TOCP neuroparalytic disease, pesticide induced seizures, tremor and neuropathy, solvent encephalopthy, antipileptic drug foetal syndrome and excitotoxin induced behavioural disorders. Studies on pesticides Organochlorine and organophosphates, synthetic pyrethrins, solvents, heavy metals and substances abuse in the Indian context confirm the neurotoxic nature of many synthetic substances. Future problems envisaged are of concern to clinical neurologists as many of these neurotoxic disorders mimic syndromes of well known neurological disease. The new millenium poses a challenge to the clinician as newer compounds in industry, food, drugs and chemical war agents are being developed. Molecular genetics has advanced rapidly with release of the human genome map. Animal cloning and genetically modified plant products have entered the food chain. How safe are these new inventions for the central nervous system is a big question? India cannot afford disasters like Union Carbide′s Bhopal gas leak nor be a silent spectator to manipulative biotechnology. Unless it is proven beyond all doubt to be a safe innovation, Chemicals have to be cautiously introduced in our environment. To Study, ascertain and confirm safety or neurotoxicity is an exciting challenge for the neuroscientists of the 21st century.

  5. Assessing the Developmental Neurotoxicity of 27 ...

    Science.gov (United States)

    Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay, Waalkes, M., Hunter, D.L., Jarema, K., Mundy, W., and S. Padilla. The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for developmental neurotoxicity. As such, we are exploring a behavioral testing paradigm that can assess the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants on zebrafish (Danio rerio). This in vivo assay quantifies the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate using a video tracking system on 6 day post fertilization zebrafish larvae. Each of twenty-seven organophosphorus pesticides was tested for their developmental neurotoxic potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development, followed by 24 hours of depuration and then behavioral testing. Approximately 22% of the chemicals (Acephate, Dichlorvos, Diazoxon, Bensulide,Tribufos, Tebupirimfos) did not produce any behavioral changes after developmental exposure, while many (Malaoxon Fosthiazate, Dimethoate, Dicrotophos, Ethoprop, Malathion, Naled, Diazinon, Methamidophos, Terbufos, Trichlorfon, Phorate, Pirimiphos-methyl, Profenofos, Z-Tetrachlorvinphos, Chlorpyrifos, Coumaphos, Phosmet, Omethoate) produced changes in swi

  6. Promoting biofuels: Implications for developing countries

    International Nuclear Information System (INIS)

    Peters, Joerg; Thielmann, Sascha

    2008-01-01

    Interest in biofuels is growing worldwide as concerns about the security of energy supply and climate change are moving into the focus of policy makers. With the exception of bioethanol from Brazil, however, production costs of biofuels are typically much higher than those of fossil fuels. As a result, promotion measures such as tax exemptions or blending quotas are indispensable for ascertaining substantial biofuel demand. With particular focus on developing countries, this paper discusses the economic justification of biofuel promotion instruments and investigates their implications. Based on data from India and Tanzania, we find that substantial biofuel usage induces significant financial costs. Furthermore, acreage availability is a binding natural limitation that could also lead to conflicts with food production. Yet, if carefully implemented under the appropriate conditions, biofuel programs might present opportunities for certain developing countries

  7. Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

    OpenAIRE

    Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

    2012-01-01

    Topical application of benzalkonium chloride (BAK) to the eye causes dose-related corneal neurotoxicity. Corneal inflammation and reduction in aqueous tear production accompany neurotoxicity. Cessation of BAK treatment leads to recovery of corneal nerve density.

  8. Relative contribution of CTR1 and DMT1 in copper transport by the blood–CSF barrier: Implication in manganese-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Gang [School of Health Sciences, Purdue University, West Lafayette, Indiana 47907 (United States); Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an, Shanxi 710032 (China); Chen, Jingyuan [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an, Shanxi 710032 (China); Zheng, Wei, E-mail: wzheng@purdue.edu [School of Health Sciences, Purdue University, West Lafayette, Indiana 47907 (United States)

    2012-05-01

    The homeostasis of copper (Cu) in the cerebrospinal fluid (CSF) is partially regulated by the Cu transporter-1 (CTR1) and divalent metal transporter-1 (DMT1) at the blood–CSF barrier (BCB) in the choroid plexus. Data from human and animal studies suggest an increased Cu concentration in blood, CSF, and brains following in vivo manganese (Mn) exposure. This study was designed to investigate the relative role of CTR1 and DMT1 in Cu transport under normal or Mn-exposed conditions using an immortalized choroidal Z310 cell line. Mn exposure in vitro resulted in an increased cellular {sup 64}Cu uptake and the up-regulation of both CTR1 and DMT1. Knocking down CTR1 by siRNA counteracted the Mn-induced increase of {sup 64}Cu uptake, while knocking down DMT1 siRNA resulted in an increased cellular {sup 64}Cu uptake in Mn-exposed cells. To distinguish the roles of CTR1 and DMT1 in Cu transport, the Z310 cell-based tetracycline (Tet)-inducible CTR1 and DMT1 expression cell lines were developed, namely iZCTR1 and iZDMT1 cells, respectively. In iZCTR1 cells, Tet induction led to a robust increase (25 fold) of {sup 64}Cu uptake with the time course corresponding to the increased CTR1. Induction of DMT1 by Tet in iZDMT1 cells, however, resulted in only a slight increase of {sup 64}Cu uptake in contrast to a substantial increase in DMT1 mRNA and protein expression. These data indicate that CTR1, but not DMT1, plays an essential role in transporting Cu by the BCB in the choroid plexus. Mn-induced cellular overload of Cu at the BCB is due, primarily, to Mn-induced over-expression of CTR1. -- Highlights: ► This study compares the relative role of CTR1 and DMT1 in Cu transport by the BCB. ► Two novel tetracycline-inducible CTR1 and DMT1 expression cell lines are created. ► CTR1, but not DMT1, plays an essential role in transporting Cu by the BCB. ► Mn-induced cellular Cu overload is due to its induction of CTR1 rather than DMT1. ► Induction of CTR1 by Mn in the BCB

  9. Is Neurotoxicity of Metallic Nanoparticles the Cascades of Oxidative Stress?

    Science.gov (United States)

    Song, Bin; Zhang, YanLi; Liu, Jia; Feng, XiaoLi; Zhou, Ting; Shao, LongQuan

    2016-06-01

    With the rapid development of nanotechnology, metallic (metal or metal oxide) nanoparticles (NPs) are widely used in many fields such as cosmetics, the food and building industries, and bio-medical instruments. Widespread applications of metallic NP-based products increase the health risk associated with human exposures. Studies revealed that the brain, a critical organ that consumes substantial amounts of oxygen, is a primary target of metallic NPs once they are absorbed into the body. Oxidative stress (OS), apoptosis, and the inflammatory response are believed to be the main mechanisms underlying the neurotoxicity of metallic NPs. Other studies have disclosed that antioxidant pretreatment or co-treatment can reverse the neurotoxicity of metallic NPs by decreasing the level of reactive oxygen species, up-regulating the activities of antioxidant enzymes, decreasing the proportion of apoptotic cells, and suppressing the inflammatory response. These findings suggest that the neurotoxicity of metallic NPs might involve a cascade of events following NP-induced OS. However, additional research is needed to determine whether NP-induced OS plays a central role in the neurotoxicity of metallic NPs, to develop a comprehensive understanding of the correlations among neurotoxic mechanisms and to improve the bio-safety of metallic NP-based products.

  10. Local Anesthetic-Induced Neurotoxicity

    NARCIS (Netherlands)

    Verlinde, Mark; Hollmann, Markus W.; Stevens, Markus F.; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

    2016-01-01

    This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk

  11. Neuroprotective effects of statins against amyloid β-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hsin-Hua Li

    2018-01-01

    Full Text Available A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ levels by affecting amyloid precursor protein (APP cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.

  12. Elucidating the neurotoxic effects of MDMA and its analogs.

    Science.gov (United States)

    Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Deruiter, Jack; Clark, Randall; Dhanasekaran, Muralikrishnan

    2014-04-17

    There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world. We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation. MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity. Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Acrylamide neurotoxicity on the cerebrum of weaning rats

    Directory of Open Access Journals (Sweden)

    Su-min Tian

    2015-01-01

    Full Text Available The mechanism underlying acrylamide-induced neurotoxicity remains controversial. Previous studies have focused on acrylamide-induced toxicity in adult rodents, but neurotoxicity in weaning rats has not been investigated. To explore the neurotoxic effect of acrylamide on the developing brain, weaning rats were gavaged with 0, 5, 15, and 30 mg/kg acrylamide for 4 consecutive weeks. No obvious neurotoxicity was observed in weaning rats in the low-dose acrylamide group (5 mg/kg. However, rats from the moderate- and high-dose acrylamide groups (15 and 30 mg/kg had an abnormal gait. Furthermore, biochemical tests in these rats demonstrated that glutamate concentration was significantly reduced, and γ-aminobutyric acid content was significantly increased and was dependent on acrylamide dose. Immunohistochemical staining showed that in the cerebral cortex, γ-aminobutyric acid, glutamic acid decarboxylase and glial fibrillary acidic protein expression increased remarkably in the moderate- and high-dose acrylamide groups. These results indicate that in weaning rats, acrylamide is positively associated with neurotoxicity in a dose-dependent manner, which may correlate with upregulation of γ-aminobutyric acid and subsequent neuronal degeneration after the initial acrylamide exposure.

  14. Investigating the potential neurotoxicity of Ecstasy (MDMA): an imaging approach

    NARCIS (Netherlands)

    Reneman, Liesbeth; Booij, Jan; Majoie, Charles B. L. M.; van den Brink, Wim; den Heeten, Gerard J.

    2001-01-01

    Human users of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') users may be at risk of developing MDMA-induced neuronal injury. Previously, no methods were available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivo neuroimaging

  15. Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

    Directory of Open Access Journals (Sweden)

    Kyoungho Suk

    2011-01-01

    Full Text Available Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.

  16. Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl

    International Nuclear Information System (INIS)

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

    2015-01-01

    In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5 mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0 mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8–12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development. - Highlights: • A single neonatal exposure to chlorpyrifos or carbaryl induced developmental neurotoxic effects. • The neurotoxic effects were not caused by acute AChE inhibition. • The neurotoxic effects manifested as altered levels of neuroproteins in the developing brain. • The neurotoxic effects manifested as adult persistent aberrant behavior and cognitive function.

  17. Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik, E-mail: henrik.viberg@ebc.uu.se

    2015-11-01

    In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5 mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0 mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8–12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development. - Highlights: • A single neonatal exposure to chlorpyrifos or carbaryl induced developmental neurotoxic effects. • The neurotoxic effects were not caused by acute AChE inhibition. • The neurotoxic effects manifested as altered levels of neuroproteins in the developing brain. • The neurotoxic effects manifested as adult persistent aberrant behavior and cognitive function.

  18. Poverty and Brain Development in Children: Implications for Learning

    Science.gov (United States)

    Dike, Victor E.

    2017-01-01

    Debates on the effect of poverty on brain development in children and its implications for learning have been raging for decades. Research suggests that poverty affects brain development in children and that the implications for learning are more compelling today given the attention the issue has attracted. For instance, studies in the fields of…

  19. Development Implications of Liberalization of Trade in Services ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Development Implications of Liberalization of Trade in Services ... disseminated by the United Nations Conference on Trade and Development (UNCTAD). ... The Honourable Chrystia Freeland, Minister of International Trade, announced a ...

  20. A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila

    Science.gov (United States)

    Cassar, Marlène; Issa, Abdul-Raouf; Riemensperger, Thomas; Petitgas, Céline; Rival, Thomas; Coulom, Hélène; Iché-Torres, Magali; Han, Kyung-An; Birman, Serge

    2015-01-01

    Long-term exposure to environmental oxidative stressors, like the herbicide paraquat (PQ), has been linked to the development of Parkinson's disease (PD), the most frequent neurodegenerative movement disorder. Paraquat is thus frequently used in the fruit fly Drosophila melanogaster and other animal models to study PD and the degeneration of dopaminergic neurons (DNs) that characterizes this disease. Here, we show that a D1-like dopamine (DA) receptor, DAMB, actively contributes to the fast central nervous system (CNS) failure induced by PQ in the fly. First, we found that a long-term increase in neuronal DA synthesis reduced DAMB expression and protected against PQ neurotoxicity. Secondly, a striking age-related decrease in PQ resistance in young adult flies correlated with an augmentation of DAMB expression. This aging-associated increase in oxidative stress vulnerability was not observed in a DAMB-deficient mutant. Thirdly, targeted inactivation of this receptor in glutamatergic neurons (GNs) markedly enhanced the survival of Drosophila exposed to either PQ or neurotoxic levels of DA, whereas, conversely, DAMB overexpression in these cells made the flies more vulnerable to both compounds. Fourthly, a mutation in the Drosophila ryanodine receptor (RyR), which inhibits activity-induced increase in cytosolic Ca2+, also strongly enhanced PQ resistance. Finally, we found that DAMB overexpression in specific neuronal populations arrested development of the fly and that in vivo stimulation of either DNs or GNs increased PQ susceptibility. This suggests a model for DA receptor-mediated potentiation of PQ-induced neurotoxicity. Further studies of DAMB signaling in Drosophila could have implications for better understanding DA-related neurodegenerative disorders in humans. PMID:25158689

  1. Transnational Education: Current Developments and Policy Implications

    Science.gov (United States)

    Gu, Jianxin

    2009-01-01

    Ever since the transnational education trend took off since the 1980s, transnational education has come to bearing political, economic and cultural implications. Different approaches have been formulated to achieve specific policy objectives by both importing and exporting countries. Such approaches demonstrate a four dimensional composition,…

  2. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    Jia Luo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  3. A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

    Science.gov (United States)

    Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

    2012-01-01

    The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

  4. A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

    Science.gov (United States)

    Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J

    2012-01-01

    The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

  5. Mechanistic insight into neurotoxicity induced by developmental insults

    International Nuclear Information System (INIS)

    Tamm, Christoffer; Ceccatelli, Sandra

    2017-01-01

    Epidemiological and/or experimental studies have shown that unfavorable prenatal environmental factors, such as stress or exposure to certain neurotoxic environmental contaminants, may have adverse consequences for neurodevelopment. Alterations in neurogenesis can have harmful effects not only for the developing nervous system, but also for the adult brain where neurogenesis is believed to play a role in learning, memory, and even in depression. Many recent advances in the understanding of the complex process of nervous system development can be integrated into the field of neurotoxicology. In the past 15 years we have been using cultured neural stem or progenitor cells to investigate the effects of neurotoxic stimuli on cell survival, proliferation and differentiation, with special focus on heritable effects. This is an overview of the work performed by our group in the attempt to elucidate the mechanisms of developmental neurotoxicity and possibly provide relevant information for the understanding of the etiopathogenesis of complex brain disorders. - Highlights: • The developing nervous system is highly sensitive to toxic insults. • Neural stem cells are relevant models for mechanistic studies as well as for identifying heritable effects due to epigenetic changes. • Depending on the dose, the outcome of exposure to neurotoxicants ranges from altered proliferation and differentiation to cell death. • The elucidation of neurotoxicity mechanisms is relevant for understanding the etiopathogenesis of developmental and adult nervous system disorders.

  6. BMAA neurotoxicity in Drosophila.

    Science.gov (United States)

    Zhou, Xianchong; Escala, Wilfredo; Papapetropoulos, Spyridon; Bradley, Walter G; Zhai, R Grace

    2009-01-01

    We report the establishment of an in vivo model using the fruit fly Drosophila melanogaster to investigate the toxic effects of L-BMAA. We found that dietary intake of BMAA reduced the lifespan as well as the neurological functions of flies. Furthermore, we have developed an HPLC method to reliably detect both free and protein-bound BMAA in fly tissue extracts.

  7. Satirical drama, political corruption and development implications for ...

    African Journals Online (AJOL)

    Satirical drama, political corruption and development implications for Nigeria: a reflection on Ola Rotimi's Our husband has gone mad again. ... The corrupt tendencies of this select few, which come in various forms, have ... from 32 Countries:.

  8. Expertise development in the professions; Implications for teaching and assessment

    NARCIS (Netherlands)

    Boshuizen, Els

    2011-01-01

    Boshuizen, H. P. A. (2011, 30 August - 3 September). Expertise development in the professions; Implications for teaching and assessment. Paper presented at the bi-annual EARLI conferences, Exeter, UK.

  9. What is microglia neurotoxicity (Not)?

    DEFF Research Database (Denmark)

    Biber, Knut; Owens, Trevor; Boddeke, Erik

    2014-01-01

    and vulnerable organ like the brain should host numerous potential killers, we here review the concept of microglia neurotoxicity. On one hand it is discussed that most of our understanding about how microglia kill neurons is based on in vitro experiments or correlative staining studies that suffer from...... the difficulty to discriminate microglia and peripheral myeloid cells in the diseased brain. On the other hand it is described that a more functional approach by mutating, inactivating or deleting microglia is seldom associated with a beneficial outcome in an acute injury situation, suggesting that microglia...

  10. Destination image: Origins, Developments and Implications

    Directory of Open Access Journals (Sweden)

    Sérgio Dominique Ferreira Lopes

    2011-04-01

    Full Text Available Over the last few decades, tourism has become one of the main sectors of the global economy, not only because of its contribution to the Gross Domestic Product (GDP of different countries, but also because of the employment it generates. Since 2009, however, the results of tourism have been severely affected by the economic and financial crisis and it is now essential to analyze the key elements of tourist consumer behavior. In this context, the image that a destination transmits to the market becomes one of the elements which influence tourists the most when choosing a tourist destination. The authors therefore aim to identify the main elements that characterize the image of a tourist destination, as well as their implications for the management of tourist destinations.

  11. Neurotoxic effects of ecstasy on the thalamus

    NARCIS (Netherlands)

    de Win, Maartje M. L.; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D.; Ramsey, Nick F.; den Heeten, Gerard J.; van den Brink, Wim

    2008-01-01

    Background Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. Aims To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine,

  12. Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2007-11-01

    Full Text Available Abstract Background Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132 in neuroblastoma cells and primary cortical neurons. Results Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1 and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2 and cyclo-oxygenase-1 (COX-1, enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. Conclusion As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.

  13. Practical implications of rapid development methodologies

    CSIR Research Space (South Africa)

    Gerber, A

    2007-11-01

    Full Text Available as the acceleration of the system development phases through an iterative construction approach. These methodologies also claim to manage the changing nature of requirements. However, during the development of large and complex systems by a small and technically...

  14. Neurotoxicity

    Science.gov (United States)

    ... may include limb weakness or numbness; loss of memory, vision, and/or intellect; headache; cognitive and behavioral problems; ... may include limb weakness or numbness; loss of memory, vision, and/or intellect; headache; cognitive and behavioral problems; ...

  15. Understanding the Development Implications of Online Outsourcing

    OpenAIRE

    Malik , Fareesa; Nicholson , Brian; Heeks , Richard

    2017-01-01

    Part 10: Global Sourcing and Development; International audience; Online outsourcing (OO) involves global outsourcing of tasks from clients to freelancers via platforms such as Upwork, Guru, Freelancer and Fiverr. Governments and donor agencies in several developing countries are currently starting OO training initiatives to enable access to digital livelihoods for marginalised groups such as youth and women. However, little is known about the impact of these initiatives and in response this ...

  16. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong

    2015-01-01

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd 2+ . Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals

  17. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong, E-mail: dayongw@seu.edu.cn

    2015-02-11

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd{sup 2+}. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals.

  18. MR findings of cyclosporine neurotoxicity

    International Nuclear Information System (INIS)

    Yang, Po Song; Ahn, Kook Jin; Ahn, Bo Young; Jung, Hae An; Kim, Hee Je; Lee, Jae Mun

    1998-01-01

    To analyze the MR findings of cyclosporine-induced neurotoxicity in patients receiving high dose of cyclosporine and to suggest the possible pathogenetic mechanism. The cases of seven patients (2 males, 5 females;18-36 years old) who suffered seizures after receiving high-dose cyclosporine for bone marrow transplantation due to diseases such as aplastic anemia or leukemia were retrospectively reviewed. We evaluated the location and pattern of abnormal signal intensity seen on T2 weighted images, the presence of contrast enhancement, and the changes seen on follow-up MR performed at intervals of 12-30 days after initial MR in five of seven patients. We analyzed levels of blood cyclosporine and magnesium, and investigated the presence of hypertension at the sity of the seizure. Locations of the lesions were bilateral(n=3D5), unilateral(n=3D2), parietal(n=3D6), occipital(n=3D6), temporal(n=3D4), and in the frontal lobe(n=3D3). Frontal lesions showed high signal intensities in the borderline ischemic zone of the frontal lobe between the territory of the anterior and middle cerebral arteries. In six of the seven patients, cortical and subcortical areas including subcortical U-fibers were seen on T2-weighted images to be involved in the parietooccipital lobes. Only one of the seven showed high signal intensity in the left basal ganglia. All lesions showed high signal intensity on T2-weighted images, and iso to low signal intensity on T1-weighted. In five of seven patients there was no definite enhancement, but in the other two, enhancement was slight. In four of seven patients seizures occurred within high therapeutic ranges(250-450ng/ml), while others suffered such attacks at levels below the therapeutic range. After cyclospirine was administered at a reduced dosage or stopped, follow-up MR images showed the complete or near-total disappearance of the abnormal findings previously described. Only two patients had hypertension, and the others normotension. Five of the

  19. MR findings of cyclosporine neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Po Song; Ahn, Kook Jin; Ahn, Bo Young; Jung, Hae An; Kim, Hee Je; Lee, Jae Mun [The Catholic Univ. St Mary' s Hospital, Seoul (Korea, Republic of)

    1998-12-01

    To analyze the MR findings of cyclosporine-induced neurotoxicity in patients receiving high dose of cyclosporine and to suggest the possible pathogenetic mechanism. The cases of seven patients (2 males, 5 females;18-36 years old) who suffered seizures after receiving high-dose cyclosporine for bone marrow transplantation due to diseases such as aplastic anemia or leukemia were retrospectively reviewed. We evaluated the location and pattern of abnormal signal intensity seen on T2 weighted images, the presence of contrast enhancement, and the changes seen on follow-up MR performed at intervals of 12-30 days after initial MR in five of seven patients. We analyzed levels of blood cyclosporine and magnesium, and investigated the presence of hypertension at the sity of the seizure. Locations of the lesions were bilateral(n=3D5), unilateral(n=3D2), parietal(n=3D6), occipital(n=3D6), temporal(n=3D4), and in the frontal lobe(n=3D3). Frontal lesions showed high signal intensities in the borderline ischemic zone of the frontal lobe between the territory of the anterior and middle cerebral arteries. In six of the seven patients, cortical and subcortical areas including subcortical U-fibers were seen on T2-weighted images to be involved in the parietooccipital lobes. Only one of the seven showed high signal intensity in the left basal ganglia. All lesions showed high signal intensity on T2-weighted images, and iso to low signal intensity on T1-weighted. In five of seven patients there was no definite enhancement, but in the other two, enhancement was slight. In four of seven patients seizures occurred within high therapeutic ranges(250-450ng/ml), while others suffered such attacks at levels below the therapeutic range. After cyclospirine was administered at a reduced dosage or stopped, follow-up MR images showed the complete or near-total disappearance of the abnormal findings previously described. Only two patients had hypertension, and the others normotension. Five of the

  20. On the implications of development for moral education | Udokang ...

    African Journals Online (AJOL)

    This paper examines the concept of development and the implication it has for moral education. While using the word “development” in its general understanding as change from one stage to the other, it went beyond this to the psychological. It alludes that in terms of moral education, development is not just any behaviour ...

  1. Culture and Early Language Development: Implications for Assessment and Intervention

    Science.gov (United States)

    Parada, Patricia M.

    2013-01-01

    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  2. Feminist Identity Development: Implications for Feminist Therapy with Women.

    Science.gov (United States)

    McNamara, Kathleen; Rickard, Kathryn M.

    1989-01-01

    Discusses implications of the Downing and Roush (1985) feminist identity development model for feminist therapy with women. Describes potential pitfalls of feminist therapy and emergent issues at subsequent stages of client's identity development. Proposes research agenda for hypothesis testing of model when applied to therapy with women clients.…

  3. Implications for Sustainable Economic Development in Nigeria.

    African Journals Online (AJOL)

    This paper therefore examines the role of psychological empowerment in development of entrepreneurship among women. It is acknowledged that one major problem of underdevelopment in Nigeria is the issue of unemployment, especially among willing and employable Nigerians. Women have also been seen as very ...

  4. Issues in Political Development: Implications for Counsellors ...

    African Journals Online (AJOL)

    Two research questions guided the study. Questionnaire was used for data collection. The data collected were analyzed using mean scores. The findings revealed. that some impediments to political development include; Religious intolerance, poor leadership, structural imbalance, moral decadence, political instability, and ...

  5. Asymmetry of the Brain: Development and Implications.

    Science.gov (United States)

    Duboc, Véronique; Dufourcq, Pascale; Blader, Patrick; Roussigné, Myriam

    2015-01-01

    Although the left and right hemispheres of our brains develop with a high degree of symmetry at both the anatomical and functional levels, it has become clear that subtle structural differences exist between the two sides and that each is dominant in processing specific cognitive tasks. As the result of evolutionary conservation or convergence, lateralization of the brain is found in both vertebrates and invertebrates, suggesting that it provides significant fitness for animal life. This widespread feature of hemispheric specialization has allowed the emergence of model systems to study its development and, in some cases, to link anatomical asymmetries to brain function and behavior. Here, we present some of what is known about brain asymmetry in humans and model organisms as well as what is known about the impact of environmental and genetic factors on brain asymmetry development. We specifically highlight the progress made in understanding the development of epithalamic asymmetries in zebrafish and how this model provides an exciting opportunity to address brain asymmetry at different levels of complexity.

  6. Regional Competitiveness and Its Implications for Development

    OpenAIRE

    Daryono Soebagyo; Triyono Triyono; Yuli Tri Cahyono

    2015-01-01

    This study was conducted to identify regional competitiveness in some areas of Central Java. Regional competitiveness became one of the issues in regional development policy since the enactment of local autonomy.Measurement of regional competitiveness has been mostly done through ranking as a benchmark the competitiveness of the region. Mapping regional competitiveness in Indonesia has been made to all counties and cities, which shows the competitiveness ranking of each region. Competitivenes...

  7. Private health insurance: implications for developing countries.

    Science.gov (United States)

    Sekhri, Neelam; Savedoff, William

    2005-02-01

    Private health insurance is playing an increasing role in both high- and low-income countries, yet is poorly understood by researchers and policy-makers. This paper shows that the distinction between private and public health insurance is often exaggerated since well regulated private insurance markets share many features with public insurance systems. It notes that private health insurance preceded many modern social insurance systems in western Europe, allowing these countries to develop the mechanisms, institutions and capacities that subsequently made it possible to provide universal access to health care. We also review international experiences with private insurance, demonstrating that its role is not restricted to any particular region or level of national income. The seven countries that finance more than 20% of their health care via private health insurance are Brazil, Chile, Namibia, South Africa, the United States, Uruguay and Zimbabwe. In each case, private health insurance provides primary financial protection for workers and their families while public health-care funds are targeted to programmes covering poor and vulnerable populations. We make recommendations for policy in developing countries, arguing that private health insurance cannot be ignored. Instead, it can be harnessed to serve the public interest if governments implement effective regulations and focus public funds on programmes for those who are poor and vulnerable. It can also be used as a transitional form of health insurance to develop experience with insurance institutions while the public sector increases its own capacity to manage and finance health-care coverage.

  8. Neurophysiological evidence of methylmercury neurotoxicity

    DEFF Research Database (Denmark)

    Murata, Katsuyuki; Grandjean, Philippe; Dakeishi, Miwako

    2007-01-01

    neurotoxicity and to examine the usefulness of those measures. METHODS: The reports addressing both neurophysiological measures and methylmercury exposure in humans were identified and evaluated. RESULTS: The neurological signs and symptoms of MD included paresthesias, constriction of visual fields, impairment...... disease (MD; methylmercury poisoning). In recent years, some of these methods have been used for the risk assessment of low-level methylmercury exposure in asymptomatic children. The objectives of this article were to present an overview of neurophysiological findings involved in methylmercury...... of hearing and speech, mental disturbances, excessive sweating, and hypersalivation. Neuropathological lesions involved visual, auditory, and post- and pre-central cortex areas. Neurophysiological changes involved in methylmercury, as assessed by EPs and HRV, were found to be in accordance with both clinical...

  9. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

    Directory of Open Access Journals (Sweden)

    James A. Bourgeois

    2014-01-01

    Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

  10. National environmental plan, development and implications

    International Nuclear Information System (INIS)

    Pinto Martinez, Elias

    1996-01-01

    The causes of the environmental deterioration are analyzed in Colombia, one of them is the based on their economic development related with the inadequate exploitation of the natural resources, since very few they made it in a rational way, what has taken us to a permanent behavior, which it is necessary to modify but to modify it has to arrive to a change of attitude. It also refers to the supposition of a limited existence of the natural resources and the actions that should be carried out

  11. Business development - the function, research propositions, and managerial implications

    DEFF Research Database (Denmark)

    Sørensen, Hans Eibe

    and executives from high-tech firms and venture capitalists in North America, Asia, and Europe to provide a foundation for future research. Business development is an emerging staff function providing an added level of sophistication to the firms' overall strategic management with interesting performance...... implications. The business development function is typically found in progressive firms especially within high-tech industries, but is argued to become critical for all types of firms across industries wishing to grow and accumulate wealth. Research propositions and managerial implications are discussed....

  12. Understanding adolescent development: implications for driving safety.

    Science.gov (United States)

    Keating, Daniel P

    2007-01-01

    The implementation of Graduated Driver Licensing (GDL) programs has significantly improved the crash and fatality rates of novice teen drivers, but these rates remain unacceptably high. A review of adolescent development research was undertaken to identify potential areas of improvement. Research support for GDL was found to be strong, particularly regarding early acquisition of expertise in driving safety (beyond driving skill), and to limitations that reduce opportunities for distraction. GDL regimes are highly variable, and no US jurisdictions have implemented optimal regimes. Expanding and improving GDL to enhance acquisition of expertise and self-regulation are indicated for implementation and for applied research. Driver training that effectively incorporates safety goals along with driving skill is another target. The insurance industry will benefit from further GDL enhancements. Benefits may accrue to improved driver training, improved simulation devices during training, and automated safety feedback instrumentation.

  13. Platform development: implications for portfolio management

    DEFF Research Database (Denmark)

    Hsuan, Juliana; Hansen, Poul H. Kyvsgård

    2007-01-01

    " The challenge of implementing industrial platforms in practice can be described as a configuration problem caused by a considerable number of variables, which often have contradictory influences on the total performance of the firm. Consequently, the specific platform decisions become extremely...... complex, possibly increasing the strategic risks for the firm. This paper reports preliminary findings on platform management process at LEGO, a Danish toy company. Specifically, we report the process of applying games combined with simulations and workshops in the platform development. We also propose...... a framework, based on the portfolio management thinking to evaluate the degree of modularity embedded in a given platform and to which extent it is aligned with other platforms."...

  14. Energy and economic development (environmental implications)

    International Nuclear Information System (INIS)

    Zorzoli, G.B.

    1992-01-01

    An examination, for developed countries, of significant correlations among economic growth, electric energy intensity and elasticity, per capita values of gross national product and greenhouse gas emissions, indicates notable possibilities for a healthier global environment with increased world-wide diffusion of clean and rational energy use technologies coupled with substantial economic growth. This scenario, however, is contrasted by worrisome doubts as to the chances for a successful outcome of recently proposed tenable growth policies when it is pointed out that forecasts, based on current demographic trends, call for a doubling of the world population in the near future. The foreseen unrestrained population explosion, leading to an unprecedented proliferation in the use of fossil fuels, now appears to represent the most serious threat to the global environment

  15. Changes in gene expression linked to methamphetamine-induced dopaminergic neurotoxicity.

    Science.gov (United States)

    Xie, Tao; Tong, Liqiong; Barrett, Tanya; Yuan, Jie; Hatzidimitriou, George; McCann, Una D; Becker, Kevin G; Donovan, David M; Ricaurte, George A

    2002-01-01

    The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity and did so independently of effects on core temperature, DA transporter function, or METH brain levels, suggesting that gene transcription and mRNA translation play a role in METH neurotoxicity. Next, microarray technology, in combination with an experimental approach designed to facilitate recognition of relevant gene expression patterns, was used to identify gene products linked to METH-induced DA neurotoxicity. This led to the identification of several genes in the ventral midbrain associated with the neurotoxic process, including genes for energy metabolism [cytochrome c oxidase subunit 1 (COX1), reduced nicotinamide adenine dinucleotide ubiquinone oxidoreductase chain 2, and phosphoglycerate mutase B], ion regulation (members of sodium/hydrogen exchanger and sodium/bile acid cotransporter family), signal transduction (adenylyl cyclase III), and cell differentiation and degeneration (N-myc downstream-regulated gene 3 and tau protein). Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism. On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury. The precise role of COX1 and other genes in METH neurotoxicity remains to be elucidated.

  16. Manganese: Recent advances in understanding its transport and neurotoxicity

    International Nuclear Information System (INIS)

    Aschner, Michael; Guilarte, Tomas R.; Schneider, Jay S.; Zheng Wei

    2007-01-01

    The present review is based on presentations from the meeting of the Society of Toxicology in San Diego, CA (March 2006). It addresses recent developments in the understanding of the transport of manganese (Mn) into the central nervous system (CNS), as well as brain imaging and neurocognitive studies in non-human primates aimed at improving our understanding of the mechanisms of Mn neurotoxicity. Finally, we discuss potential therapeutic modalities for treating Mn intoxication in humans

  17. Relational Aggression, Victimization, and Language Development: Implications for Practice

    Science.gov (United States)

    Ostrov, Jamie M.; Godleski, Stephanie A.

    2007-01-01

    This review explores the development of relational aggression and relational victimization among peers, with specific emphasis on clinical implications for speech-language pathologists. Developmental manifestations of relational aggression and victimization are reviewed from early childhood through emerging adulthood. The concurrent and…

  18. Some Instructional Implications from a Mathematical Model of Cognitive Development.

    Science.gov (United States)

    Mierkiewicz, Diane B.

    Cognitive development and various educational implications are discussed in terms of Donald Saari's model of the interaction of a learner and the enviroment and the constraints imposed by the inefficiency of the learner's cognitive system. Saari proposed a hierarchical system of cognitive structures such that the relationships between structures…

  19. Diagnosing Organization-Environment "Fit": Implications for Organization Development

    Science.gov (United States)

    Gabarro, John J.

    1974-01-01

    This article has attempted to: (1) describe several dimensions of organization-environment fit; (2) describe some concepts which can be used in diagnosing the degree to which a school system's organization matches the demands and needs of its environment; (3) present some implications of such a diagnosis for OD [organizational development]…

  20. New advances in cystic fibrosis - implications for developing countries

    African Journals Online (AJOL)

    New advances in cystic fibrosis - implications for developing countries. Heather J Zar, Eric Bateman, Michelle Ramsay. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics. Metrics Loading ... Metrics powered by PLOS ALM.

  1. Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo

    International Nuclear Information System (INIS)

    Wu, Qin; Yan, Wei; Liu, Chunsheng; Li, Li; Yu, Liqin; Zhao, Sujuan; Li, Guangyu

    2016-01-01

    Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnα7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. α1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons. - Highlights: • MCLR accumulation induces developmental neurotoxicity in zebrafish embryo. • The decrease of dopamine levels might be associated with the MCLR-induced developmental neurotoxicity in zebrafish larvae. • The alternation of cholinergic system might contribute to the change of neurobehavior in zebrafish larvae exposure with MCLR. - MCLR accumulation induces developmental neurotoxicity by affecting cholinergic system, dopaminergic signaling, and the development of neurons in zebrafish embryo.

  2. General anesthetics in children: neurotoxic or neuroprotective?

    Directory of Open Access Journals (Sweden)

    Jéssica Farias Rebouças

    2017-02-01

    Full Text Available Introduction: general anesthetics are involved in neuroprotection in adults after ischemic events and cognitive impairment, thus, they also may be associated with learning disorders in children exposed to them before three years of age. Objective: Describe about the neurotoxic effects of general anesthetics in experimental animals and children. Method: This is a systematic review, performed from search in databases and on PubMed using the keywords "neurotoxicity" and "general anesthetics," and "general anesthetics," "neurotoxicity", "children", "young child "and" pediatric ". Results: The search resulted in 185 articles. Out of these, 78 met our inclusion criteria. We found that there was a significant evidence of neurotoxicity induced by general anesthetics in experimental animals that were just born, resulting in late and permanent cognitive deficits. This effect was associated with multiple exposures, exposure length of time and combination of drugs. However, some studies found cognitive impairment after a single exposure to anesthetic. Conclusion: There is insufficient evidence to state that general anesthetics are neurotoxic and have the potential to trigger learning and behavior disabilities in children. However, we suggest caution in indicating surgery in children under three years old, analyzing risk-benefit and inserting the family in the decision process.   Keywords: Neurotoxicity; Neuroprotection; Cognitive Impairment; Children; General Anesthesics

  3. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  4. A role for D1 dopamine receptors in striatal methamphetamine-induced neurotoxicity.

    Science.gov (United States)

    Friend, Danielle M; Keefe, Kristen A

    2013-10-25

    Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Importantly, METH-induced hyperthermia is tightly associated with the neurotoxicity, such that simply cooling animals during METH exposure protects against the neurotoxicity. Therefore, it is difficult to determine whether D1 DA receptors per se play an important role in METH-induced neurotoxicity or whether the protection observed simply resulted from a mitigation of METH-induced hyperthermia. To answer this important question, the current study infused a D1 DA receptor antagonist into striatum during METH exposure while controlling for METH-induced hyperthermia. Here we found that even when METH-induced hyperthermia is maintained, the coadministration of a D1 DA receptor antagonist protects against METH-induced neurotoxicity, strongly suggesting that D1 DA receptors play an important role in METH-induced neurotoxicity apart from the mitigation of METH-induced hyperthermia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    International Nuclear Information System (INIS)

    Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Yu, Yingchun; Aschner, Michael

    2009-01-01

    Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F 2 -isoprostanes (F 2 -IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E 2 (PGE 2 ). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F 2 -IsoPs and PGE 2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

  6. Developing Entrepreneurial Resilience: Implications for Human Resource Development

    Science.gov (United States)

    Lee, Jin; Wang, Jia

    2017-01-01

    Purpose: Leadership development has attracted much research attention within the human resource development (HRD) community. However, little scholarly effort has been made to study a special group of leaders--entrepreneurs. This paper aims to fill in this knowledge gap by taking a close look at entrepreneurial resilience, a key ability of…

  7. Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

    Science.gov (United States)

    Johnston, Christopher I.; O'Leary, Margaret A.; Brown, Simon G. A.; Currie, Bart J.; Halkidis, Lambros; Whitaker, Richard; Close, Benjamin; Isbister, Geoffrey K.

    2012-01-01

    Background Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. Methodology/Principal Findings Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5–74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5–15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5–168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4–245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. Conclusions/Significance Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The

  8. Elevated environmental temperature and methamphetamine neurotoxicity

    International Nuclear Information System (INIS)

    Miller, Diane B.; O'Callaghan, James P.

    2003-01-01

    Amphetamines have been of considerable research interest for the last several decades. More recent work has renewed interest in the role of ambient temperature in both the toxicity and neurotoxicity of these drugs. We have determined that the striatal dopaminergic neurotoxicity observed in the mouse is linked in some fashion to both body and environmental temperature. Most studies of d-methamphetamine (d-METH) neurotoxicity are conducted at standard laboratory ambient temperatures (e.g., ∼21-22 deg. C) and utilizing a repeated dosage regimen (e.g., three to four injections spaced 2 h apart). A lowering of the ambient temperature provides neuro protection, while an elevation increases neurotoxicity. d-METH causes long-term depletions of triatal dopamine (DA) that are accompanied by other changes that are indicative of nerve terminal degeneration. These include argyrophilia, as detected by silver degeneration stains, and an elevation in glial fibrillary acidic protein (GFAP), a marker of reactive gliosis in response to injury, as well as a long-term decrease in tyrosine hydroxylase (TH) protein levels. here we show that increasing the ambient temperature during and for some time following dosing increases the neurotoxicity of d-METH. Mice (female 57BL6/J) given a single dosage of d-METH (20 mg/kg s.c.) and maintained at the usual laboratory ambient temperature show minimal striatal damage (an ∼15% depletion of DA and an ∼ 86% increase in GFAP). substantial striatal damage (e.g., an ∼70% depletion of DA and an ∼200% elevation in GFAP) was induced by this regimen if mice were maintained at 27 deg. C for 24 or 72 h following dosing. An increase in neurotoxicity was also apparent in mice kept at an elevated temperature for only 5 or 9 h, but keeping animals at 27 deg. C for 24 or 72 h was the most effective in increasing the neurotoxicity of d-METH. Our data show how a relatively minor change in ambient temperature can have a major impact on the degree of

  9. Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

    Directory of Open Access Journals (Sweden)

    Laxton Kevin

    2010-05-01

    Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

  10. Recovered Alcoholics and Career Development: Implications for Human Resource Development

    Science.gov (United States)

    Gedro, Julie; Mercer, Frances; Iodice, Jody D.

    2012-01-01

    This article presents three issues regarding alcoholism, recovery, and career development. First, alcoholism is a disease that creates health and wellness problems for those it afflicts. It also impacts individual and workplace productivity. Second, alcoholism has a persistent stigmatization. As a result, those alcoholics who are in recovery face…

  11. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  12. Severe neurotoxicity following ingestion of tetraethyl lead.

    Science.gov (United States)

    Wills, Brandon K; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

    2010-03-01

    Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80-90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symptoms including agitation, hallucinations, weakness, and tremor. These symptoms were refractory to escalating doses of benzodiazepines and ultimately required endotracheal intubation and a propofol infusion. Adjunctive therapies included chelation, baclofen, and nutrition provided through a gastrostomy tube. The patient slowly recovered and was discharged in a wheelchair 20 days after ingestion, still requiring tube feeding. Follow-up at 62 days post-ingestion revealed near-resolution of symptoms with residual slurred speech and slight limp. This case highlights the profound neurotoxic manifestations of acute organic lead compounds.

  13. Women Education and Economic Development in Kenya: Implications for Curriculum Development and Implementation Processes

    Science.gov (United States)

    Syomwene, Anne; Kindiki, Jonah Nyaga

    2015-01-01

    This paper is a discussion of the relationship between women education and sustainable economic development in Kenya and its implications for curriculum development and implementation processes. The argument advanced in this paper is that the solution to the development problems in Kenya and other developing nations lies on women education.…

  14. Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, Pernille Reimer; Boberg, Julie

    2008-01-01

    Tac:WH) were dosed with PTU (0, 0.8.1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and Pups in the higher close groups had markedly decreased thyroxine (T-4) levels during the closing period......Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent Studies, indicating that even small changes in the mother's thyroid hormone Status early in pregnancy may Cause adverse effects on her child, have lead to increased...... concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the Study was therefore to provide a detailed knowledge or) the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (Han...

  15. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US....... Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...

  16. Neurotoxicity of fragrance compounds: A review.

    Science.gov (United States)

    Pinkas, Adi; Gonçalves, Cinara Ludvig; Aschner, Michael

    2017-10-01

    Fragrance compounds are chemicals belonging to one of several families, which are used frequently and globally in cosmetics, household products, foods and beverages. A complete list of such compounds is rarely found on the ingredients-list of such products, as "fragrance mixtures" are defined as "trade secrets" and thus protected by law. While some information regarding the general toxicity of some of these compounds is available, their neurotoxicity is known to a lesser extent. Here, we discuss the prevalence and neurotoxicity of fragrance compounds belonging to the three most common groups: phthalates, synthetic musks and chemical sensitizers. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Smartphone Applications - Idea sourcing, and app development: Implications for firms

    Directory of Open Access Journals (Sweden)

    Debbie Vigar-Ellis

    2014-05-01

    Full Text Available With the dramatic increase in smartphone usage and the consequent increase in applications (apps for these smartphones, organisations are constantly looking for new apps to offer customers as well as employees.  Information Systems (IS departments of organisations have traditionally been tasked with the acquisition and/or development of such information technologies within organisations.  This research aimed to determine from IS managers, the smartphone app usage in firms, the sources of app ideas and the locations for app development.  It also investigated various aspects of the success or otherwise of the development process.  Results indicate that while most ideas for apps currently come from IS and marketing departments within the organisation, and development of apps is also done mainly within the organisation , these development strategies are not necessarily the most effective.  Managerial implications are discussed.

  18. Environmental Chemicals and Human Neurotoxicity: Magnitude ...

    African Journals Online (AJOL)

    Olaleye

    altered neurocthemical, electrophysiological or behavioural functions. The adverse effects of neurotoxicity are among the most feared ill health in humans ... chemicals through air, food, or drinking water. The infamous ..... environment can disrupt the neurological control .... that perception and memory gradually fade,.

  19. Pathophysiology of Manganese-Associated Neurotoxicity

    Science.gov (United States)

    Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei

    2012-01-01

    Conference Summary Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms.(Rodier J, 1955) Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures.(Rodier J, 1955; Hobson et al., 2011) The clinical syndrome associated with Mn neurotoxicity has been called manganism. Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers.(Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011) Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers,(Huang et al., 2003) many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system.(Jankovic, 2005) The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from C. elegans

  20. THC Prevents MDMA Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Clara Touriño

    2010-02-01

    Full Text Available The majority of MDMA (ecstasy recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4 were pretreated with THC (3 mg/kg x 4 at room (21 degrees C and at warm (26 degrees C temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1 receptor antagonist AM251 and the CB(2 receptor antagonist AM630, as well as in CB(1, CB(2 and CB(1/CB(2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1 receptor antagonist AM251, neither in CB(1 and CB(1/CB(2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2 cannabinoid antagonist and in CB(2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1 receptor, although CB(2 receptors may also contribute to

  1. Neurotoxicity profile of supermethrin, a new pyrethroid insecticide.

    Science.gov (United States)

    Hornychova, M; Frantik, E; Kubat, J; Formanek, J

    1995-11-01

    The use of a standard two-tier neurotoxicity screening procedure in the context of risk assessment is exemplified. Testing of a new pyrethroid in rats addressed the following sequence of questions: Does the substance evoke neurotoxic symptoms in sublethal doses? Do these symptoms reflect a primary neurotropic action? What are the dynamic characteristics of injury, the clinical profile of effect, and the relative potency of the tested substance compared to similar compounds? - The testing protocol is an animal analogue of a systematic neurological and psychological examination in man. First tier tests (structured observation, motor activity measurement, simple neurological examination) were applied after the first dose, during repeated dosing phase and in the restitution phase. Facultative tests for the second-tier examination (motor activity pattern, learning/retention test, evoked potentials, dynamic motor performance) were selected on the basis of effects revealed by the first-tier testing. Supermethrin evoked acute neurotoxicity in sublethal doses, ranging from 1/30 to 1/15 of LD50. The clinical pattern was similar to other cyano-substituted pyrethroids. Behavioural inhibition was transient and complete tolerance to it developed after 4-week repeated dosing. No indications of long-lasting changes in neuronal excitability or in learning and memory processes were found. Ataxia and excitomotoric phenomena dominated both the acute and the subchronic picture. Marked and persistent motor disturbances, including symptoms of lower motoneuron injury, were limited to individual animals of the highest, near-lethal dose group (27 mg-kg-1). Compared to lambda-cyhalothrin, the effects of supermethrin were 2 to 3 times weaker, disappeared more rapidly, cumulated less, and had higher tendency to tolerance.

  2. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    International Nuclear Information System (INIS)

    Vilela, Luciano R.; Gobira, Pedro H.; Viana, Thercia G.; Medeiros, Daniel C.; Ferreira-Vieira, Talita H.; Doria, Juliana G.; Rodrigues, Flávia; Aguiar, Daniele C.; Pereira, Grace S.; Massessini, André R.; Ribeiro, Fabíola M.; Oliveira, Antonio Carlos P. de; Moraes, Marcio F.D.; Moreira, Fabricio A.

    2015-01-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB 1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB 1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis attenuates

  3. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  4. Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

    Science.gov (United States)

    Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

    2018-03-28

    Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

  5. Innovations in coaching and mentoring: implications for nurse leadership development.

    Science.gov (United States)

    Fielden, Sandra L; Davidson, Marilyn J; Sutherland, Valerie J

    2009-05-01

    This longitudinal study sought to examine ways in which coaching and mentoring relationships impact on the professional development of nurses in terms of career and leadership behaviours, and evaluating the differences and similarities between those coaching and mentoring relationships. According to the UK government, leadership in nursing is essential to the improvement of service delivery, and the development and training of all nurses is vital in achieving effective change. A coaching and mentoring programme was used to explore the comparative advantages of these two approaches for the leadership development of nurses in acute, primary care and mental health settings. A longitudinal in-depth study was conducted to measure differences and similarities between the mentoring and coaching process as a result of a six-month coaching/mentoring programme. Five nurses from six UK Health Care Trusts were allocated to a coaching group (n = 15) or a mentoring group (n = 15), these were coached or mentored by a member of the senior directorate from their own Trust. Qualitative and quantitative data were collected at three time points (T1 = baseline, T2 = 4 months and T3 = 9 months) using semi-structured interviews and questionnaires. While mentoring was perceived to be 'support' and coaching was described as 'action', descriptions of the actual process and content were quite similar. However, while both groups reported significant development in terms of career development, leadership skills and capabilities, mentees reported the highest level of development with significantly higher scores in eight areas of leadership and management and in three areas of career impact. Implications for nurses and health services are discussed.

  6. A logo-leadership intervention: Implications for leadership development

    Directory of Open Access Journals (Sweden)

    Frances Scholtz

    2015-08-01

    Full Text Available Orientation: Logo-leadership development challenges leaders to move beyond financial or individual gain to accepting leadership as a calling. Research purpose: The objective of the study was to ascertain whether an intervention embedded in the life and teachings of logo-therapist Viktor Frankl affects the way aspiring leaders construct leadership in terms of meaning (logo-leadership. Motivation for the study: A consideration of Frankl’s life gives rise to the question of whether aspiring leaders can learn from and use his life teachings as an inspiration in the discovery of meaning for themselves as leaders. Research approach, design and method: Participants comprised 20 students registered for an MCom degree at a South African metropolitan university. The research process involved three phases: (1 a pre-intervention questionnaire, (2 an appreciative inquiry intervention and (3 a post-intervention questionnaire. Framework analysis and a comparative method were used to analyse the data. Main findings: A meaning-centred leadership development intervention may impact the leadership role orientation of aspiring leaders, changing it from a predominantly career orientation to a calling. However, this effect largely occurred on an explicit (extrinsic level. Managerial implications: Organisations that wish to develop logo-leadership may consider using the life teachings and work of Frankl as a development tool. Contribution/value-add: This study contributes theoretically to a relatively new development within the field of Frankl’s logotherapy, leadership with meaning (logo-leadership. On apractical level, this study introduced the concept of logo-leadership for leadership development and suggests that leadership may be influenced by exposure to a leadership intervention.

  7. The development of human visual cortex and clinical implications

    Directory of Open Access Journals (Sweden)

    Siu CR

    2018-04-01

    Full Text Available Caitlin R Siu,1 Kathryn M Murphy1,2 1McMaster Integrative Neuroscience Discovery and Study (MiNDS Program, McMaster University, Hamilton, ON, Canada; 2Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada Abstract: The primary visual cortex (V1 is the first cortical area that processes visual information. Normal development of V1 depends on binocular vision during the critical period, and age-related losses of vision are linked with neurobiological changes in V1. Animal studies have provided important details about the neurobiological mechanisms in V1 that support normal vision or are changed by visual diseases. There is very little information, however, about those neurobiological mechanisms in human V1. That lack of information has hampered the translation of biologically inspired treatments from preclinical models to effective clinical treatments. We have studied human V1 to characterize the expression of neurobiological mechanisms that regulate visual perception and neuroplasticity. We have identified five stages of development for human V1 that start in infancy and continue across the life span. Here, we describe these stages, compare them with visual and anatomical milestones, and discuss implications for translating treatments for visual disorders that depend on neuroplasticity of V1 function. Keywords: development, human visual cortex, amblyopia, synaptic plasticity, glutamatergic, GABAergic, receptors

  8. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

    Science.gov (United States)

    Heisler, Jillian M.; O’Connor, Jason C.

    2015-01-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

  9. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

    Science.gov (United States)

    Heisler, Jillian M; O'Connor, Jason C

    2015-11-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

  10. Neurobehavioural and Neurotoxic Effects of L-ascorbic Acid and L ...

    African Journals Online (AJOL)

    Background: Lead is an environmental toxicant, occupational and environmental exposures remain a serious problem in developing and industrializing countries. Objective: This study is designed to investigate the effects of L-ascorbic acid and L-tryptophan on the neurotoxicity and neurobehavioural alterations in lead ...

  11. A holistic view of anesthesia-related neurotoxicity in children

    Directory of Open Access Journals (Sweden)

    Clausen NG

    2015-11-01

    Full Text Available Nicola G Clausen, Tom G Hansen Department of Anesthesia and Intensive Care, Odense University Hospital, Odense, Denmark Introduction: Animal studies (including in nonhuman primates have shown that most general anesthetics cause enhanced neuroapoptosis in the immature brain with subsequent long-term neurocognitive deficits later in life. Whether human neurons are equally affected is yet unknown, but a final answer to this issue is still pending. To date, most human studies within the field are of observational nature and the results are conflicting. Some studies indicate an association between exposure to anesthesia and surgery while others do not. Objective: This review summarizes results from preclinical and observational studies. Controversies and challenges regarding the interpretation of these results are presented. Crucial aspects of neurocognitive safety during pediatric anesthesia and surgery are highlighted. International initiatives aiming to improve the safe conductance of pediatric anesthesia are introduced. Conclusion: So far, anesthesia-related neurotoxicity in humans remains an area of concern but it cannot be completely excluded. Clinical practice should not be changed until there are definite proofs that anesthetic exposure causes neurocognitive impairment later in life. Withholding necessary and timely surgeries as a consequence of any such concerns could result in worse harm. Focus of current research should also be redirected to include other factors, than merely anesthetics and surgery, that influence the neurocognitive safety of children perioperatively. Keywords: pediatric anesthesia, neurotoxicity, anesthesia safety, neurocognitive development 

  12. Central neurotoxicity of immunomodulatory drugs in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Urmeel H. Patel

    2015-03-01

    Full Text Available Immunomodulatory drugs (IMiDs currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient, lenalidomide (4 patients, and pomalidomide (1 patient was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  13. Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

    Science.gov (United States)

    Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

    2015-02-24

    Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

  14. Bifurcation in epigenetics: Implications in development, proliferation, and diseases

    Science.gov (United States)

    Jost, Daniel

    2014-01-01

    Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of biochemical marks on chromatin. Here, we develop a stochastic model that describes the dynamics of epigenetic marks along a given DNA region. Through mathematical analysis, we show the emergence of bistable and persistent epigenetic states from the cooperative recruitment of modifying enzymes. We also find that the dynamical system exhibits a critical point and displays, in the presence of asymmetries in recruitment, a bifurcation diagram with hysteresis. These results have deep implications for our understanding of epigenetic regulation. In particular, our study allows one to reconcile within the same formalism the robust maintenance of epigenetic identity observed in differentiated cells, the epigenetic plasticity of pluripotent cells during differentiation, and the effects of epigenetic misregulation in diseases. Moreover, it suggests a possible mechanism for developmental transitions where the system is shifted close to the critical point to benefit from high susceptibility to developmental cues.

  15. Implications for Effective Child Development System in Africa

    African Journals Online (AJOL)

    Nneka Umera-Okeke

    Child Rights Campaign and the Nigerian Family: Implications for Effective Child .... of socialization like: day-care centres, schools, peer groups, video bars, recreational parks and new social media have taken over this role. The outcome is that ...

  16. Studies of (±)-3,4-methylenedioxymethamphetamine (MDMA) metabolism and disposition in rats and mice: relationship to neuroprotection and neurotoxicity profile.

    Science.gov (United States)

    Mueller, Melanie; Maldonado-Adrian, Concepcion; Yuan, Jie; McCann, Una D; Ricaurte, George A

    2013-02-01

    The neurotoxicity of (±)-3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to 1) assess the effect of hypothermia on MDMA metabolism, 2) determine whether the neuroprotective effect of hypothermia is related to inhibition of MDMA metabolism, and 3) determine if different neurotoxicity profiles in mice and rats are related to differences in MDMA metabolism and/or disposition in the two species. Rats and mice received single neurotoxic oral doses of MDMA at 25°C and 4°C, and body temperature, pharmacokinetic parameters, and serotonergic and dopaminergic neuronal markers were measured. Hypothermia did not alter MDMA metabolism in rats and only modestly inhibited MDMA metabolism in mice; however, it afforded complete neuroprotection in both species. Rats and mice metabolized MDMA in a similar pattern, with 3,4-methylenedioxyamphetamine being the major metabolite, followed by 4-hydroxy-3-methoxymethamphetamine and 3,4-dihydroxymethamphetamine, respectively. Differences between MDMA pharmacokinetics in rats and mice, including faster elimination in mice, did not account for the different profile of MDMA neurotoxicity in the two species. Taken together, the results of these studies indicate that inhibition of MDMA metabolism is not responsible for the neuroprotective effect of hypothermia in rodents, and that different neurotoxicity profiles in rats and mice are not readily explained by differences in MDMA metabolism or disposition.

  17. Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity.

    Science.gov (United States)

    Ryan, Kristen R; Sirenko, Oksana; Parham, Fred; Hsieh, Jui-Hua; Cromwell, Evan F; Tice, Raymond R; Behl, Mamta

    2016-03-01

    Due to the increasing prevalence of neurological disorders and the large number of untested compounds in the environment, there is a need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect neurological development. Herein, we report on a library of 80 compounds screened for their ability to inhibit neurite outgrowth, a process by which compounds may elicit developmental neurotoxicity, in a high-throughput, high-content assay using human neurons derived from induced pluripotent stem cells (iPSC). The library contains a diverse set of compounds including those that have been known to be associated with developmental neurotoxicity (DNT) and/or neurotoxicity (NT), environmental compounds with unknown neurotoxic potential (e.g., polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs)), as well as compounds with no documented neurotoxic potential. Neurons were treated for 72h across a 6-point concentration range (∼0.3-100μM) in 384-well plates. Effects on neurite outgrowth were assessed by quantifying total outgrowth, branches, and processes. We also assessed the number ofviable cells per well. Concentration-response profiles were evaluated using a Hill model to derive benchmark concentration (BMC) values. Assay performance was evaluated using positive and negative controls and test replicates. Compounds were ranked by activity and selectivity (i.e., specific effects on neurite outgrowth in the absence of concomitant cytotoxicity) and repeat studies were conducted to confirm selectivity. Among the 80 compounds tested, 38 compounds were active, of which 16 selectively inhibited neurite outgrowth. Of these 16 compounds, 12 were known to cause DNT/NT and the remaining 4 compounds included 3 PAHs and 1 FR. In independent repeat studies, 14/16 selective compounds were reproducibly active in the assay, of which only 6 were selective for inhibition of neurite outgrowth. These 6 compounds were

  18. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Science.gov (United States)

    2011-01-01

    Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.). IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v.) prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical) given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA. PMID:22114930

  19. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  20. Involvement of Programmed Cell Death in Neurotoxicity of Metallic Nanoparticles: Recent Advances and Future Perspectives

    Science.gov (United States)

    Song, Bin; Zhou, Ting; Liu, Jia; Shao, LongQuan

    2016-11-01

    The widespread application of metallic nanoparticles (NPs) or NP-based products has increased the risk of exposure to NPs in humans. The brain is an important organ that is more susceptible to exogenous stimuli. Moreover, any impairment to the brain is irreversible. Recently, several in vivo studies have found that metallic NPs can be absorbed into the animal body and then translocated into the brain, mainly through the blood-brain barrier and olfactory pathway after systemic administration. Furthermore, metallic NPs can cross the placental barrier to accumulate in the fetal brain, causing developmental neurotoxicity on exposure during pregnancy. Therefore, metallic NPs become a big threat to the brain. However, the mechanisms underlying the neurotoxicity of metallic NPs remain unclear. Programmed cell death (PCD), which is different from necrosis, is defined as active cell death and is regulated by certain genes. PCD can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. It is involved in brain development, neurodegenerative disorders, psychiatric disorders, and brain injury. Given the pivotal role of PCD in neurological functions, we reviewed relevant articles and tried to summarize the recent advances and future perspectives of PCD involvement in the neurotoxicity of metallic NPs, with the purpose of comprehensively understanding the neurotoxic mechanisms of NPs.

  1. Protective effect of quercetin on bupivacaine-induced neurotoxicity ...

    African Journals Online (AJOL)

    certain side effects, especially neurotoxicity. It has been shown that neurotoxicity caused by local anesthetics such as lidocaine and bupivacaine are related to changes in calcium homeostasis, resulting in intracellular calcium overload [1]. Calcium homeostasis is regulated by many different kinds of calcium channels such.

  2. Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes.

    Science.gov (United States)

    Sriram, Krishnan; Lin, Gary X; Jefferson, Amy M; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J; McKinney, Walter; Jackson, Mark; Chen, Bean T; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L; Roberts, Jenny R; Frazer, David G; Antonini, James M

    2015-02-03

    Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks. Published by Elsevier Ireland Ltd.

  3. Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes

    International Nuclear Information System (INIS)

    Sriram, Krishnan; Lin, Gary X.; Jefferson, Amy M.; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J.; McKinney, Walter; Jackson, Mark; Chen, Bean T.; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L.; Roberts, Jenny R.; Frazer, David G.; Antonini, James M.

    2015-01-01

    Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson’s disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m 3 ; 3 h/day × 5 d/week × 2 weeks) to fumes generated by gas–metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks

  4. Intellectual disability in Africa: implications for research and service development.

    Science.gov (United States)

    McKenzie, Judith Anne; McConkey, Roy; Adnams, Colleen

    2013-09-01

    Although intellectual disability (ID) is probably the largest impairment grouping on the African continent, few indigenous research and evaluation studies have been undertaken. This article is an initial attempt to relate service delivery issues to an African research agenda. We critically analysed the available literature, drawing on academic publications and those of non-governmental agencies. In this process we identified several key issues for further investigation, namely: understanding ID in African contexts, access to education and health care, the provision of appropriate assistance and support, and income generation. We relate our analysis to the recommendations made in the World Report on Disability but with a specific focus on ID in Africa. The need for mainstreaming and prioritising ID in non-disability related and across impairment programmes is highlighted. We note the importance of families and emphasise the need to draw on informal and traditional forms of care and participation. The need for reliable research evidence to support practice is highlighted. We conclude with a call to action by and on behalf of individuals with ID to be included in the development priorities of the continent. Implications for Rehabilitation Service provision for people with intellectual disabilities in Africa is not always well served by insights obtained from western research agendas. Appropriate and effective rehabilitation requires an understanding of the context and the environment in which the disabled person operates. Indigenous research into the provision of support to families and the inclusion of persons with intellectual disability into mainstream programmes as well as disability specific provision is recommended.

  5. Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells

    International Nuclear Information System (INIS)

    Jimenez, Andres; Jorda, Elvira G.; Verdaguer, Ester; Pubill, David; Sureda, Francesc X.; Canudas, Anna M.; Escubedo, Elena; Camarasa, Jordi; Camins, Antoni; Pallas, Merce

    2004-01-01

    The neurotoxic action of the abuse drugs methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on cerebellar granule neurones (CGNs) culture was examined. Treatment for 48 h with METH or MDMA (1-5 mM) induced a higher decrease in viability than 24 h treatment. z.VAD.fmk (100 μM) but not MK-801 nor NBQX recovered control viability values. In both cases, cell death was characterised as apoptotic rather than necrotic by morphology cell observation. Apoptosis measured by flow cytometry indicated an increase in the hypodiploid population after 48 h treatment with METH and MDMA. Apoptosis was reverted by the presence of z.VAD.fmk (100 μM) but not by 10 μM MK-801 or NBQX. Similar results were obtained by analysing nuclear chromatine condensation. These results ruled out excitotoxic participation in amphetamine derivative-induced neurotoxicity in CGNs. Participation of radical oxygen species (ROS) was evaluated using α-tocopherol (1-15 μM) and cytometric studies. The co-treatment with 4 mM METH or MDMA for 48 h partially reverted neurotoxic action and apoptotic features, indicating ROS implication in CGNs death by amphetamine derivatives. Alteration of mitochondrial function induced cytochrome C (Cyt C) release after 48-h treatment with METH and MDMA (4 mM). There was also indication of caspase-3-like activation, measured by immunoanalysis and biochemically. Finally, neurodegenerative action caused by amphetamine derivatives may be prevented by using caspase inhibitors

  6. Involvement of autophagy upregulation in 3,4-methylenedioxymethamphetamine ('ecstasy')-induced serotonergic neurotoxicity.

    Science.gov (United States)

    Li, I-Hsun; Ma, Kuo-Hsing; Kao, Tzu-Jen; Lin, Yang-Yi; Weng, Shao-Ju; Yen, Ting-Yin; Chen, Lih-Chi; Huang, Yuahn-Sieh

    2016-01-01

    It has been suggested that autophagy plays pathogenetic roles in cerebral ischemia, brain trauma, and neurodegenerative disorders. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is an illicit drug that causes long-term serotonergic neurotoxicity in the brain. Apoptosis and necrosis have been implicated in MDMA-induced neurotoxicity, but the role of autophagy in MDMA-elicited serotonergic toxicity has not been investigated. The present study aimed to examine the contribution of autophagy to neurotoxicity in serotonergic neurons in in vitro and in vivo animal models challenged with MDMA. Here, we demonstrated that in cultured rat serotonergic neurons, MDMA exposure induced LC3B-densely stained autophagosome formation, accompanying by a decrease in neurite outgrowth. Autophagy inhibitor 3-methyladenine (3-MA) significantly attenuated MDMA-induced autophagosome accumulation, and ameliorated MDMA-triggered serotonergic neurite damage and neuron death. In contrast, enhanced autophagy flux by rapamycin or impaired autophagosome clearance by bafilomycin A1 led to more autophagosome accumulation in serotonergic neurons and aggravated neurite degeneration. In addition, MDMA-induced autophagy activation in cultured serotonergic neurons might be mediated by serotonin transporter (SERT). In an in vivo animal model administered MDMA, neuroimaging showed that 3-MA protected the serotonin system against MDMA-induced downregulation of SERT evaluated by animal-PET with 4-[(18)F]-ADAM, a SERT radioligand. Taken together, our results demonstrated that MDMA triggers upregulation of autophagy in serotonergic neurons, which appears to be detrimental to neuronal growth. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Systematic review of the neurocognitive outcomes used in studies of paediatric anaesthesia neurotoxicity

    DEFF Research Database (Denmark)

    Clausen, Nicola Groes

    2018-01-01

    Summary Neurotoxicity of anaesthetics in developing brain cells is well documented in preclinical studies, yet results are conflicting in humans. The use of many and different outcome measures in human studies may contribute to this disagreement. We conducted a systematic review to identify all...... for studies investigating neurocognitive outcome after GA in children countries during 1990-2017. Most assessments were performed within cognition, sensory-motor development, academic achievement or neuropsychological diagnosis. Few studies assessed other...... Anaesthesia, General; Child Development; Infant; Review...

  8. Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells.

    Science.gov (United States)

    Gust, Juliane; Hay, Kevin A; Hanafi, Laïla-Aïcha; Li, Daniel; Myerson, David; Gonzalez-Cuyar, Luis F; Yeung, Cecilia; Liles, W Conrad; Wurfel, Mark; Lopez, Jose A; Chen, Junmei; Chung, Dominic; Harju-Baker, Susanna; Özpolat, Tahsin; Fink, Kathleen R; Riddell, Stanley R; Maloney, David G; Turtle, Cameron J

    2017-12-01

    Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19 + cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFNγ, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity. Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404-19. ©2017 AACR. See related commentary by Mackall and Miklos, p. 1371 This article is highlighted in the In This Issue feature, p. 1355 . ©2017 American Association for Cancer Research.

  9. Corneal neurotoxicity due to topical benzalkonium chloride.

    Science.gov (United States)

    Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

    2012-04-06

    The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001). Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production.

  10. Biochemical Factors Modulating Cellular Neurotoxicity of Methylmercury

    Directory of Open Access Journals (Sweden)

    Parvinder Kaur

    2011-01-01

    Full Text Available Methylmercury (MeHg, an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH, fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC; diethyl maleate, (DEM; docosahexaenoic acid, (DHA; selenomethionine, SeM; Trolox and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

  11. Neurotoxic effects of ecstasy on the thalamus.

    Science.gov (United States)

    de Win, Maartje M L; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D; Ramsey, Nick F; Heeten, Gerard J den; van den Brink, Wim

    2008-10-01

    Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study. Effects of ecstasy and other substances were assessed with (1)H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]beta-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses. Ecstasy showed specific effects in the thalamus with decreased [(123)I]beta-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients. Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

  12. Neurotoxicity of general anesthetics: A modern view of the problem

    Directory of Open Access Journals (Sweden)

    A. M. Ovezov

    2015-01-01

    Full Text Available All general anesthetics routinely used in clinical practice are noted to have a neurotoxic effect on the brain in different animal species including primates. The negative effects observed both in young and sexually mature animals include apoptotic neuronal cell death, suppression of neurogenesis and gliogenesis, neuroinflammation, as well as learning and memory impairments. A number of epidemiologic surveys have established an association between anesthesia in patients younger than 3 to 4 years and subsequent learning disabilities and language disorders whereas others have not found this link. In middle-aged and elderly patients, anesthesia is frequently associated with the development of postoperative cognitive dysfunction. The key component of its pathogenesis (general anesthesia itself or other factors, such as operative injury, an inflammatory response, pain syndrome, intraoperative complications, underlying disease in a patient remains unelucidated. It is concluded that there is a need for additional experimental and clinical studies of the pathogenesis of these undesirable phenomena to be prevented and corrected.

  13. L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

    Science.gov (United States)

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Minocycline attenuates colistin-induced neurotoxicity via suppression of apoptosis, mitochondrial dysfunction and oxidative stress.

    Science.gov (United States)

    Dai, Chongshan; Ciccotosto, Giuseppe D; Cappai, Roberto; Wang, Yang; Tang, Shusheng; Xiao, Xilong; Velkov, Tony

    2017-06-01

    Neurotoxicity is an adverse effect patients experience during colistin therapy. The development of effective neuroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. The present study investigates the neuroprotective effect of the synergistic tetracycline antibiotic minocycline against colistin-induced neurotoxicity. The impact of minocycline pretreatment on colistin-induced apoptosis, caspase activation, oxidative stress and mitochondrial dysfunction were investigated using cultured mouse neuroblastoma-2a (N2a) and primary cortical neuronal cells. Colistin-induced neurotoxicity in mouse N2a and primary cortical cells gives rise to the generation of reactive oxygen species (ROS) and subsequent cell death via apoptosis. Pretreatment of the neuronal cells with minocycline at 5, 10 and 20 μM for 2 h prior to colistin (200 μM) exposure (24 h), had an neuroprotective effect by significantly decreasing intracellular ROS production and by upregulating the activities of the anti-ROS enzymes superoxide dismutase and catalase. Minocycline pretreatment also protected the cells from colistin-induced mitochondrial dysfunction, caspase activation and subsequent apoptosis. Immunohistochemical imaging studies revealed colistin accumulates within the dendrite projections and cell body of primary cortical neuronal cells. To our knowledge, this is first study demonstrating the protective effect of minocycline on colistin-induced neurotoxicity by scavenging of ROS and suppression of apoptosis. Our study highlights that co-administration of minocycline kills two birds with one stone: in addition to its synergistic antimicrobial activity, minocycline could potentially ameliorate unwanted neurotoxicity in patients undergoing polymyxin therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions

  15. A review on potential neurotoxicity of titanium dioxide nanoparticles

    Science.gov (United States)

    Song, Bin; Liu, Jia; Feng, Xiaoli; Wei, Limin; Shao, Longquan

    2015-08-01

    As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood-brain barrier (BBB) or through the nose-to-brain pathway, potentially leading to dysfunctions of central nerve system (CNS). Besides, NPs may affect the brain development of embryo by crossing the placental barrier. A few in vivo and in vitro researches have demonstrated that the morphology and function of neuronal or glial cells could be impaired by TiO2 NPs which might induce cell necrosis. Cellular components, such as mitochondrial, lysosome, and cytoskeleton, could also be influenced as well. The recognition ability, spatial memory, and learning ability of TiO2 NPs-treated rodents were significantly impaired, which meant that accumulation of TiO2 NPs in the brain could lead to neurodegeneration. However, conclusions obtained from those studies were not consistent with each other as researchers may choose different experimental parameters, including administration ways, dosage, size, and crystal structure of TiO2 NPs. Therefore, in order to fully understand the potential risks of TiO2 NPs to brain health, figure out research areas where further studies are required, and improve its bio-safety for applications in the near future, how TiO2 NPs interact with the brain is investigated in this review by summarizing the current researches on neurotoxicity induced by TiO2 NPs.

  16. Environment, Biology, and Culture: Implications for Adolescent Development.

    Science.gov (United States)

    Zahn-Waxler, Carolyn

    1996-01-01

    Introduces this special theme issue examining the roles of socialization, biology, and culture as they affect adaptive and maladaptive developmental outcomes. Problems of adolescence addressed include antisocial behavior, depressive symptoms, substance abuse, low achievement, and eating problems. Considers factors implicated in successful…

  17. Local Citation Analysis of Graduate Biology Theses: Collection Development Implications

    Science.gov (United States)

    Miller, Laura Newton

    2011-01-01

    This paper will focus on the citation analysis of graduate masters theses from Carleton University's Biology Department with implications for library collection management decisions. Twenty-five masters theses were studied to determine citation types and percentages, ranking of journals by frequency of citation and by number of authors citing, and…

  18. Implications of population growth for Nigeria's development | Fan ...

    African Journals Online (AJOL)

    Nigeria's population that was 16 million in 1911 is about 140 million today. Attention invariably turns to the implications of this growth to the qualities of life for her inhabitants. The paper notes that high birth rate, low death rate and migration are the sources of the high population growth in Nigeria. The population then ...

  19. Implications of sustainable development considerations for comparability across NDCs

    Science.gov (United States)

    Iyer, G.; Edmonds, J.; Calvin, K. V.; Hartin, C.; McJeon, H. C.; Clarke, L.

    2017-12-01

    The Paris Agreement delegates the establishment of national climate goals to individual governments through the nationally determined contributions (NDCs). Because of the absence of a commonly agreed burden-sharing scheme within the Agreement, assessments of comparability of mitigation efforts were and will continue to be important aspects of international climate change negotiations, as domestic decision-makers are interested in knowing whether other countries undertake comparable levels of effort in reducing emissions. At the same time, there are well-recognized relationships between mitigation and other national priorities, including the Sustainable Development Goals (SDGs). This raises a question about how the linkages of such goals to mitigation might influence comparability assessments. This is an important issue, because countries are expected to include not only perceptions of comparability in the context of climate mitigation, but also relationships of mitigation with the broader SDGs. We use GCAM, a global integrated assessment model that tracks the interactions across economic, energy, agricultural and land-use systems for 32 geopolitical regions under one consistent framework to illustrate the relationships between the NDCs and a subset of the broader SDGs. We study the implications of considering these relationships for comparability assessments. The relationships between mitigation and the broader SDGs are rather complex because of the interconnected nature of human and Earth systems requiring the use of integrated tools such as GCAM that simultaneously track interactions across various human and Earth systems. Our analysis highlights that while some SDG measures are enhanced by the implementation of NDCs, others are degraded. In addition, the NDCs can have effects that extend beyond national boundaries to affect international SDGs and in some instances, also carry global impact. Finally, the distributions of effort across NDCs based on conventional

  20. Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat.

    Science.gov (United States)

    Moallem, Seyed Adel; Mohamadpour, Amir Hooshang; Abnous, Khalil; Sankian, Mojtaba; Sadeghnia, Hamid Reza; Tsatsakis, Aristidis; Shahsavand, Shabnam

    2015-12-01

    Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver-Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity.

    Science.gov (United States)

    Lupien, Sonia J; Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France

    2018-04-01

    For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. North Korea's nuclear weapons development. Implications for future policy

    International Nuclear Information System (INIS)

    Pollack, J.D.

    2010-01-01

    This essay assesses North Korea's long-standing quest for nuclear weapons; alternative strategies for inhibiting Pyongyang's weapons development; and the potential implications for regional security and nonproliferation should the Democratic People's Republic of Korea (DPRK) retain and enhance its weapons programs. North Korea's pursuit of a nuclear weapons capability has long provoked heated debate among policy makers and research analysts about the purposes of engagement with the North, reflecting the repeated frustrations in efforts to negotiate Korean denuclearization. These debates reflect widely divergent views of the North Korean regime; its sustainability as an autonomous political, economic, and military system; and the potential consequences of continued nuclear development in this isolated, highly idiosyncratic state. These questions assume additional salience as North Korea approaches a leadership succession for only the second time in its six-decade history. The effort to inhibit North Korea's pursuit of nuclear weapons is among the longest running and least successful sagas in international security and non-proliferation policy of the past quarter century. In early 2010, Pyongyang claims a rudimentary nuclear capability by possession of weaponized plutonium, the conduct of two nuclear tests, and advances in the production of enriched uranium as an alternative means of fissile material production, though the latter step is nominally justified as a source for reactor fuel. North Korea defends its pursuit of a nuclear deterrent to counter what Pyongyang deems existential threats posed by the United States.Despite the resumption of high-level diplomatic contact between Washington and Pyongyang in late 2009, realization of a non-nuclear Korean Peninsula remains a very remote prospect. The DPRK insists that a peace agreement between the U.S. and North Korea and hence the cessation of 'hostile DPRK-U.S. relations' are necessary before any consideration of

  3. Linear systems solvers - recent developments and implications for lattice computations

    International Nuclear Information System (INIS)

    Frommer, A.

    1996-01-01

    We review the numerical analysis' understanding of Krylov subspace methods for solving (non-hermitian) systems of equations and discuss its implications for lattice gauge theory computations using the example of the Wilson fermion matrix. Our thesis is that mature methods like QMR, BiCGStab or restarted GMRES are close to optimal for the Wilson fermion matrix. Consequently, preconditioning appears to be the crucial issue for further improvements. (orig.)

  4. Neurotoxicity of iodinated radiological contrast media

    International Nuclear Information System (INIS)

    Araujo Pinheiro, R.S. de

    1988-01-01

    We studied during the last ten years the neurotoxicity of artificial iodinated contrast media, with prospective clinical and experimental protocols. The experimental investigation in animals aimed to understand the relationship between the intracarotid injection, the subarachnoid application and the integrity of the blood-brain barrier function. The electro physiologic disturbances and the morphologic observation of pial circulation support the evidence that iodinated artificial contrast media induces significant alterations in brain metabolism and in the autoregulation of the blood flow of the encephalon. Even if many of such phenomena may not be apparent at the clinical level, we supposed that they are always present and that their clinical exteriorization is prevented by the immediate and effective action of homeostatic mechanisms. (author)

  5. The neurotoxicity of pyridinium metabolites of haloperidol

    Directory of Open Access Journals (Sweden)

    Agnieszka Górska

    2015-10-01

    Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

  6. Ecological network analysis for economic systems: growth and development and implications for sustainable development.

    Science.gov (United States)

    Huang, Jiali; Ulanowicz, Robert E

    2014-01-01

    The quantification of growth and development is an important issue in economics, because these phenomena are closely related to sustainability. We address growth and development from a network perspective in which economic systems are represented as flow networks and analyzed using ecological network analysis (ENA). The Beijing economic system is used as a case study and 11 input-output (I-O) tables for 1985-2010 are converted into currency networks. ENA is used to calculate system-level indices to quantify the growth and development of Beijing. The contributions of each direct flow toward growth and development in 2010 are calculated and their implications for sustainable development are discussed. The results show that during 1985-2010, growth was the main attribute of the Beijing economic system. Although the system grew exponentially, its development fluctuated within only a small range. The results suggest that system ascendency should be increased in order to favor more sustainable development. Ascendency can be augmented in two ways: (1) strengthen those pathways with positive contributions to increasing ascendency and (2) weaken those with negative effects.

  7. Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation.

    Science.gov (United States)

    Parrott, J M; Redus, L; Santana-Coelho, D; Morales, J; Gao, X; O'Connor, J C

    2016-10-18

    The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression. Here we utilized two novel transgenic mouse strains to directly test the hypothesis that neurotoxic kynurenine metabolism causes depressive-like behavior following peripheral immune activation. Wild-type (WT) or kynurenine 3-monooxygenase (KMO)-deficient (KMO -/- ) mice were administered either lipopolysaccharide (LPS, 0.5 mg kg -1 ) or saline intraperitoneally. Depressive-like behavior was measured across multiple domains 24 h after immune challenge. LPS precipitated a robust depressive-like phenotype, but KMO -/- mice were specifically protected from LPS-induced immobility in the tail suspension test (TST) and reduced spontaneous alternations in the Y-maze. Direct administration of 3-hydroxykynurenine, the metabolic product of KMO, caused a dose-dependent increase in depressive-like behaviors. Mice with targeted deletion of 3-hydroxyanthranilic acid dioxygenase (HAAO), the enzyme that generates quinolinic acid, were similarly challenged with LPS. Similar to KMO -/- mice, LPS failed to increase immobility during the TST. Whereas kynurenine metabolism was generally increased in behaviorally salient brain regions, a distinct shift toward KMO-dependent kynurenine metabolism occurred in the dorsal hippocampus in response to LPS. Together, these results demonstrate that KMO is a pivotal mediator of hippocampal-dependent depressive-like behaviors induced by peripheral

  8. Perspectives on the Present State and Future of Higher Education Faculty Development in Kazakhstan: Implications for National Human Resource Development

    Science.gov (United States)

    Seitova, Dinara

    2016-01-01

    The article aims at examining the present state of higher education faculty development in Kazakhstan in the context of multidimensional nationwide development reforms and exploring implications for the National Human Resource Development of the country. For the purpose of this research, theoretical human resource development (HRD) and…

  9. Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats

    OpenAIRE

    Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.

    2010-01-01

    This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concent...

  10. Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components.

    Science.gov (United States)

    Li, Shujuan; Chu, Yanjie; Zhang, Ruowen; Sun, Linjia; Chen, Xiaohui

    2018-04-20

    Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

  11. Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components

    Directory of Open Access Journals (Sweden)

    Shujuan Li

    2018-04-01

    Full Text Available Strychnos alkaloids (SAs are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP. An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

  12. Autophagy activation is involved in 3,4-methylenedioxymethamphetamine ('ecstasy'--induced neurotoxicity in cultured cortical neurons.

    Directory of Open Access Journals (Sweden)

    I-Hsun Li

    Full Text Available Autophagic (type II cell death, characterized by the massive accumulation of autophagic vacuoles in the cytoplasm of cells, has been suggested to play pathogenetic roles in cerebral ischemia, brain trauma, and neurodegenerative disorders. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy is an illicit drug causing long-term neurotoxicity in the brain. Apoptotic (type I and necrotic (type III cell death have been implicated in MDMA-induced neurotoxicity, while the role of autophagy in MDMA-elicited neurotoxicity has not been investigated. The present study aimed to evaluate the occurrence and contribution of autophagy to neurotoxicity in cultured rat cortical neurons challenged with MDMA. Autophagy activation was monitored by expression of microtubule-associated protein 1 light chain 3 (LC3; an autophagic marker using immunofluorescence and western blot analysis. Here, we demonstrate that MDMA exposure induced monodansylcadaverine (MDC- and LC3B-densely stained autophagosome formation and increased conversion of LC3B-I to LC3B-II, coinciding with the neurodegenerative phase of MDMA challenge. Autophagy inhibitor 3-methyladenine (3-MA pretreatment significantly attenuated MDMA-induced autophagosome accumulation, LC3B-II expression, and ameliorated MDMA-triggered neurite damage and neuronal death. In contrast, enhanced autophagy flux by rapamycin or impaired autophagosome clearance by bafilomycin A1 led to more autophagosome accumulation in neurons and aggravated neurite degeneration, indicating that excessive autophagosome accumulation contributes to MDMA-induced neurotoxicity. Furthermore, MDMA induced phosphorylation of AMP-activated protein kinase (AMPK and its downstream unc-51-like kinase 1 (ULK1, suggesting the AMPK/ULK1 signaling pathway might be involved in MDMA-induced autophagy activation.

  13. Three Theories of Psychological Development; Implications for Children's Dentistry.

    Science.gov (United States)

    George, James M.; McIver, F. Thomas

    1983-01-01

    A slide-tape series developed for introduction of developmental and learning theories in freshman dental curriculum is described. Theories of social-emotional development, cognitive development, and theories of conditioning and observational learning are included. (MSE)

  14. Comparative developmental neurotoxicity of flame-retardants, polybrominated flame-retardants and organophosphorous compounds, in mice

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, P.; Johansson, N.; Viberg, H.; Fischer, C.; Fredriksson, A. [Dept. of Environmental Toxicology, Uppsala Univ. (Sweden)

    2004-09-15

    Recently we have reported that certain PBDEs, such as 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47), 2,2',4,4',5- pentabromodiphenyl ether (PBDE 99), 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE153) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (PBDE 209) can cause developmental neurotoxic effects when given to neonatal mice. The developmental neurotoxic effects after neonatal exposure to PBDE 209 are suggested to be caused by a metabolite (possible de-brominated one). Neonatal exposure HBCDD has also been shown to cause developmental neurotoxic effects. Neonatal exposure to PBDE 99, PBDE 153 and HBCDD was also found to affect learning and memory in the adult animal. The induction of permanent aberration in spontaneous behaviour was induced during limited period of the neonatal brain development. The altered spontaneous behaviour was also seen to worsen with age. In these studies we have also found that the cholinergic system is one target that is affected, observed as changes in the response of the cholinergic system and a decrease in cholinergic receptors, and is one of the mechanisms underlying the observed behavioural changes. BFRs so far studied TBBPA appears not to cause developmental neurotoxic effects when administered at the same dose levels to neonatal mice. In the present studies we have investigated whether neonatal exposure to three highly brominated dipehenyl ethers, 2,2',3,4,4',5',6'-heptabromodiphenyl ether (PBDE183), 2,2',3'4'4',5,5',6- octabromodiphenyl ether (PBDE 203) and 2,2',3,3',4,4',5',6'-nonabromodiphenyl ether (PBDE 206) can induce developmental neurotoxic effects, such as aberrations in spontaneous behaviour and in learning and memory. Furthermore, neonatal developmental neurotoxicity effects were also studied for two OPs used as FR, triphenyl phosphate and tris(2-chloro-ethyl)phosphate.

  15. L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ya-Ni [Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan, Taiwan (China); Wang, Jiz-Yuh [Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lee, Ching-Tien [Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan, Taiwan (China); Lin, Chih-Hung [Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lai, Chien-Cheng [Far Eastern Memorial Hospital, Department of Surgery, Taipei, Taiwan (China); Wang, Jia-Yi, E-mail: jywang2010@tmu.edu.tw [Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

  16. L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

    International Nuclear Information System (INIS)

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-01-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

  17. Resistance of neuronal nitric oxide synthase-deficient mice to methamphetamine-induced dopaminergic neurotoxicity.

    Science.gov (United States)

    Itzhak, Y; Gandia, C; Huang, P L; Ali, S F

    1998-03-01

    indicate that nNOS(-/-) mice are protected against METH-induced dopaminergic neurotoxicity and locomotor sensitization. It also appears that a partial deficit of dopaminergic transmission in wild-type animals does not prevent the development of sensitization to METH, whereas a deficit in nNOS may attenuate this process.

  18. Serotonergic neurotoxic metabolites of ecstasy identified in rat brain.

    Science.gov (United States)

    Jones, Douglas C; Duvauchelle, Christine; Ikegami, Aiko; Olsen, Christopher M; Lau, Serrine S; de la Torre, Rafael; Monks, Terrence J

    2005-04-01

    The selective serotonergic neurotoxicity of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) depends on their systemic metabolism. We have recently shown that inhibition of brain endothelial cell gamma-glutamyl transpeptidase (gamma-GT) potentiates the neurotoxicity of both MDMA and MDA, indicating that metabolites that are substrates for this enzyme contribute to the neurotoxicity. Consistent with this view, glutathione (GSH) and N-acetylcysteine conjugates of alpha-methyl dopamine (alpha-MeDA) are selective neurotoxicants. However, neurotoxic metabolites of MDMA or MDA have yet to be identified in brain. Using in vivo microdialysis coupled to liquid chromatography-tandem mass spectroscopy and a high-performance liquid chromatography-coulometric electrode array system, we now show that GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA are present in the striatum of rats administered MDMA by subcutaneous injection. Moreover, inhibition of gamma-GT with acivicin increases the concentration of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA in brain dialysate, and there is a direct correlation between the concentrations of metabolites in dialysate and the extent of neurotoxicity, measured by decreases in serotonin (5-HT) and 5-hydroxyindole acetic (5-HIAA) levels. Importantly, the effects of acivicin are independent of MDMA-induced hyperthermia, since acivicin-mediated potentiation of MDMA neurotoxicity occurs in the context of acivicin-mediated decreases in body temperature. Finally, we have synthesized 5-(N-acetylcystein-S-yl)-N-methyl-alpha-MeDA and established that it is a relatively potent serotonergic neurotoxicant. Together, the data support the contention that MDMA-mediated serotonergic neurotoxicity is mediated by the systemic formation of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA (and alpha-MeDA). The mechanisms by which such metabolites access the brain and produce selective

  19. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

    Science.gov (United States)

    Jevtovic-Todorovic, V.; Absalom, A. R.; Blomgren, K.; Brambrink, A.; Crosby, G.; Culley, D. J.; Fiskum, G.; Giffard, R. G.; Herold, K. F.; Loepke, A. W.; Ma, D.; Orser, B. A.; Planel, E.; Slikker, W.; Soriano, S. G.; Stratmann, G.; Vutskits, L.; Xie, Z.; Hemmings, H. C.

    2013-01-01

    Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches. PMID:23722106

  20. Neurotoxicity in long-term survivors of small cell lung cancer

    International Nuclear Information System (INIS)

    Lee, J.S.; Umsawasdi, T.; Lee, Y.Y.; Barkley, H.T. Jr.; Murphy, W.K.; Welch, S.; Valdivieso, M.

    1986-01-01

    Chronic central nervous system neurotoxicity was studied in 38 long-term survivors (greater than or equal to 3 years) of small cell lung cancer who were treated at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1971 and 1980. All but one patient received combination chemotherapy with or without chest irradiation. Twenty-four patients received whole brain irradiation (Group I), 22 for elective and two for therapeutic purposes, while 14 did not (Group II). Abnormalities in computed tomographic (CT) scans of the brain were more frequently observed in Group I than in Group II (70% vs. 0%, p less than 0.01). Clinical central nervous system neurotoxicity developed in three patients in Group I, while none developed in patients in Group II (p less than 0.05). Patients who received methotrexate and procarbazine after whole brain irradiation were at a higher risk for clinical central nervous system neurotoxicity (p less than 0.05), and for development of periventricular white matter changes in CT brain scans (p less than 0.05) than were patients in Group II. Impaired methylation of the myelin sheath is proposed as a possible underlying pathogenic mechanism

  1. The Legal Implications for the Navigation Development of Bystroye Channel

    Directory of Open Access Journals (Sweden)

    Tache Bocaniala

    2009-10-01

    Full Text Available On May 11, 2004, Ukraine began the construction of the Danube - Black Sea Channel (Chilia and Bystroe river branch in the Danube Delta. The project, which had economic, political and even military interests, has been questioned since the formation of national and international environmental organizations (of both countries, which are likely to cause significant negative transboundary impact on the Danube Delta ecosystem. We conclude that, in defiance of the bilateralagreements with the Romanian and the international ones, Ukraine continued its works to complete the project, applying the policy of the complete fact. In this document we intend to highlight anumber of legal implications of the problem and the current international context as well, favorable for directing the demarche to a correct resolution.

  2. The Neurotoxicity of Nitrous Oxide: The Facts and “Putative” Mechanisms

    Science.gov (United States)

    Savage, Sinead; Ma, Daqing

    2014-01-01

    Nitrous oxide is a widely used analgesic agent, used also in combination with anaesthetics during surgery. Recent research has raised concerns about possible neurotoxicity of nitrous oxide, particularly in the developing brain. Nitrous oxide is an N-methyl-d-aspartate (NMDA)-antagonist drug, similar in nature to ketamine, another anaesthetic agent. It has been linked to post-operative cardiovascular problems in clinical studies. It is also widely known that exposure to nitrous oxide during surgery results in elevated homocysteine levels in many patients, but very little work has investigated the long term effect of these increased homocysteine levels. Now research in rodent models has found that homocysteine can be linked to neuronal death and possibly even cognitive deficits. This review aims to examine the current knowledge of mechanisms of action of nitrous oxide, and to describe some pathways by which it may have neurotoxic effects. PMID:24961701

  3. Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

    International Nuclear Information System (INIS)

    Sanchez-Pernaute, Rosario; Brownell, Anna-Liisa; Jenkins, Bruce G.; Isacson, Ole

    2005-01-01

    Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders

  4. The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

    Science.gov (United States)

    Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

    2012-07-01

    Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Stages of Teachers' Careers: Implications for Professional Development.

    Science.gov (United States)

    Christensen, Judith; And Others

    This monograph on the development of teachers' careers synthesizes researchers' prescriptions for early-, mid-, and late-career professional development; and describes successful programs that demonstrate sensitivity to the stages of teachers' growth. The first chapter, "Teachers' Career Development," reviews current adult- and career-stage…

  6. Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

    NARCIS (Netherlands)

    Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

    2018-01-01

    Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of

  7. Current status of RTO development and its implications for Canada

    Energy Technology Data Exchange (ETDEWEB)

    MacDougall, M. [Powerex Corp., Vancouver, BC (Canada)

    2002-07-01

    This presentation includes a corporate review of Powerex, a review of Order 2000, and the current status of the Federal Energy Regulatory Commission's (FERC) efforts regarding Regional Transmission Operators (RTOs). Other topics of discussion include FERC's standard market design, an update of RTO West and implications for Canada. Powerex was incorporated in 1988 as a wholly-owned subsidiary of BC Hydro. British Columbia-based Powerex's heaviest trading is along the western-most states and Alberta, but it is slowly expanding into central and eastern markets. It evolved by selling and buying power at the United States Border. It received US FERC power marketing authorization in 1997 and has since seen sales jump from C$165 million to C$5.4 billion. Currently, the majority of power supply is from utilities other than BC Hydro. The presentation addresses issues such as the Federal Power Act, PUHCA and PURPA, and the 1992 Energy Policy Act which deals with expanded access to the power grid. Power Pool restructuring and FERC orders 888/889 are also discussed. 2 figs.

  8. Current status of RTO development and its implications for Canada

    International Nuclear Information System (INIS)

    MacDougall, M.

    2002-01-01

    This presentation includes a corporate review of Powerex, a review of Order 2000, and the current status of the Federal Energy Regulatory Commission's (FERC) efforts regarding Regional Transmission Operators (RTOs). Other topics of discussion include FERC's standard market design, an update of RTO West and implications for Canada. Powerex was incorporated in 1988 as a wholly-owned subsidiary of BC Hydro. British Columbia-based Powerex's heaviest trading is along the western-most states and Alberta, but it is slowly expanding into central and eastern markets. It evolved by selling and buying power at the United States Border. It received US FERC power marketing authorization in 1997 and has since seen sales jump from C$165 million to C$5.4 billion. Currently, the majority of power supply is from utilities other than BC Hydro. The presentation addresses issues such as the Federal Power Act, PUHCA and PURPA, and the 1992 Energy Policy Act which deals with expanded access to the power grid. Power Pool restructuring and FERC orders 888/889 are also discussed. 2 figs

  9. NEUROTOXIC SNAKEBITE CASES WITH ROLE OF IMAGING

    Directory of Open Access Journals (Sweden)

    Upendranath Upadhyay

    2017-11-01

    Full Text Available BACKGROUND Snakebite cases in India is around 6,00,000 to 16,00,000 with deaths around 11,000 to 25,000 (in Odisha around 1000 snakebite deaths per annum. Highest occurrence is seen in monsoon (June to September probably due to increased exposure to traditional agriculture practice. Imaging plays a limited, but immortal roles in cases with diagnostic dilemma. MATERIALS AND METHODS Total snakebite cases admitted to Hi-Tech Medical College from January 2016 to September 2017, and out of these, the number of cases undergone different imaging studies like x-ray, USG, Doppler, CT scan, CT angiography and MRI studies were included under study. The findings were analysed in background of pathophysiology and toxic action of neurotoxic snake venoms. RESULTS Out of 52 cases admitted in Hi-Tech Medical College, Bhubaneswar, the total 12 cases (23% were undergone imaging study. Out of these, 3 cases sent for MRI study to outside diagnostic center due to non-availability of MRI facilities. Other imaging studies are done in our hospital. CONCLUSION Imaging in few cases plays important and decisive role in situations with diagnostic dilemma in prolonged neurological symptoms, delayed neurological complications in local complications and secondary systemic complications.

  10. Role of Prion Protein Aggregation in Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Tullio Florio

    2012-07-01

    Full Text Available In several neurodegenerative diseases, such as Parkinson, Alzheimer’s, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP, the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126 and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.

  11. Neurotoxicity of subarachnoid hyperbaric bupivacaine in dogs.

    Science.gov (United States)

    Ganem, E M; Vianna, P T; Marques, M; Castiglia, Y M; Vane, L A

    1996-01-01

    The study investigated possible neurotoxic effects of increasing concentrations and doses of bupivacaine administered into the subarachnoid space in dogs. Fifty animals were allocated to five experimental groups: G1, control; G2, 5 mg 0.5 bupivacaine in 10% glucose solution; G3, 10 mg of 1% bupivacaine in 10% glucose solution; G4, 20 mg 2% bupivacaine in 10% glucose solution, and G5, 20 mg 2% bupivacaine in water. After 72 hours of observation, the animals were killed and the spinal cords removed for histologic examination by light microscopy. None of the animals showed any neurologic clinical disturbance following recovery from spinal anesthesia. One case of necrosis of nerve tissue was observed in G3 and four in G4. Increasing concentrations and doses of hyperbaric bupivacaine solutions increased the incidence of nerve tissue damage, which did not occur with hypobaric solutions. These results should contribute to the further understanding of neurologic complications following spinal anesthesia when large doses of local anesthetics in hyperbaric solutions are used.

  12. Accidental hydroxychloroquine overdose resulting in neurotoxic vestibulopathy.

    Science.gov (United States)

    Chansky, Peter B; Werth, Victoria P

    2017-04-12

    Hydroxychloroquine is an oral antimalarial medication commonly used off-label for a variety of rheumatological conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and dermatomyositis. We present a case of a 64-year-old woman who presented with acute onset headache, bilateral tinnitus, and left-sided facial numbness and tingling in the setting of accidentally overdosing on hydroxychloroquine. By the next morning, the patient began to experience worsening in the tingling sensation and it eventually spread to her left arm, thigh and distal extremities. The patient also complained of new onset blurring of her peripheral vision and feeling 'off balance.' Despite a complete neurological and ophthalmological work-up with unremarkable imaging and blood work, the patient has had no improvement in her tinnitus, left-sided paresthesias, visual disturbance or ataxia. This is a unique case of hydroxychloroquine overdose resulting in permanent neurotoxic vestibulopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Neurotoxicity of traffic-related air pollution.

    Science.gov (United States)

    Costa, Lucio G; Cole, Toby B; Coburn, Jacki; Chang, Yu-Chi; Dao, Khoi; Roqué, Pamela J

    2017-03-01

    The central nervous system is emerging as an important target for adverse health effects of air pollution, where it may contribute to neurodevelopmental and neurodegenerative disorders. Air pollution comprises several components, including particulate matter (PM) and ultrafine particulate matter (UFPM), gases, organic compounds, and metals. An important source of ambient PM and UFPM is represented by traffic-related air pollution, primarily diesel exhaust (DE). Human epidemiological studies and controlled animal studies have shown that exposure to air pollution, and to traffic-related air pollution or DE in particular, may lead to neurotoxicity. In particular, air pollution is emerging as a possible etiological factor in neurodevelopmental (e.g. autism spectrum disorders) and neurodegenerative (e.g. Alzheimer's disease) disorders. The most prominent effects caused by air pollution in both humans and animals are oxidative stress and neuro-inflammation. Studies in mice acutely exposed to DE (250-300μg/m 3 for 6h) have shown microglia activation, increased lipid peroxidation, and neuro-inflammation in various brain regions, particularly the hippocampus and the olfactory bulb. An impairment of adult neurogenesis was also found. In most cases, the effects of DE were more pronounced in male mice, possibly because of lower antioxidant abilities due to lower expression of paraoxonase 2. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Selenium protects neonates against neurotoxicity from prenatal exposure to manganese.

    Directory of Open Access Journals (Sweden)

    Xin Yang

    Full Text Available Manganese (Mn exposure can affect brain development. Whether Selenium (Se can protect neonates against neurotoxicity from Mn exposure remains unclear. We investigated this issue in 933 mother-newborn pairs in Shanghai, China, from 2008 through 2009. Umbilical cord serum concentrations of Mn and Se were measured and Neonatal Behavioral Neurological Assessment (NBNA tests were conducted. The scores <37 were defined as the low NBNA. The median concentrations of cord serum Mn and Se were 4.0 µg/L and 63.1 µg/L, respectively. After adjusting for potential confounders, the interaction between Se and Mn was observed. Cord blood Mn levels had different effects on NBNA scores stratified by different cord blood Se levels. With Sedevelopment against neurotoxicity from prenatal exposure to Mn. Se supplementation should be considered during pregnancy, especially in areas with low natural Se.

  15. Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Koon-Ho Chan

    Full Text Available Beta-amyloid (Aβ neurotoxicity is important in Alzheimer's disease (AD pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T(2DM which is characterized by insulin resistance. Interestingly, T(2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance. We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y transfected with the Swedish amyloid precursor protein (Sw-APP mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK activation and enhanced nuclear factor-kappa B (NF-κB activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1 AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif and possibly 2 suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

  16. 17β-estradiol and tamoxifen protect mice from manganese-induced dopaminergic neurotoxicity.

    Science.gov (United States)

    Pajarillo, Edward; Johnson, James; Kim, Judong; Karki, Pratap; Son, Deok-Soo; Aschner, Michael; Lee, Eunsook

    2018-03-01

    Chronic exposure to manganese (Mn) causes neurotoxicity, referred to as manganism, with common clinical features of parkinsonism. 17β-estradiol (E2) and tamoxifen (TX), a selective estrogen receptor modulator (SERM), afford neuroprotection in several neurological disorders, including Parkinson's disease (PD). In the present study, we tested if E2 and TX attenuate Mn-induced neurotoxicity in mice, assessing motor deficit and dopaminergic neurodegeneration. We implanted E2 and TX pellets in the back of the neck of ovariectomized C57BL/6 mice two weeks prior to a single injection of Mn into the striatum. One week later, we assessed locomotor activity and molecular mechanisms by immunohistochemistry, real-time quantitative PCR, western blot and enzymatic biochemical analyses. The results showed that both E2 and TX attenuated Mn-induced motor deficits and reversed the Mn-induced loss of dopaminergic neurons in the substantia nigra. At the molecular level, E2 and TX reversed the Mn-induced decrease of (1) glutamate aspartate transporter (GLAST) and glutamate transporter 1 (GLT-1) mRNA and protein levels; (2) transforming growth factor-α (TGF-α) and estrogen receptor-α (ER-α) protein levels; and (3) catalase (CAT) activity and glutathione (GSH) levels, and Mn-increased (1) malondialdehyde (MDA) levels and (2) the Bax/Bcl-2 ratio. These results indicate that E2 and TX afford protection against Mn-induced neurotoxicity by reversing Mn-reduced GLT1/GLAST as well as Mn-induced oxidative stress. Our findings may offer estrogenic agents as potential candidates for the development of therapeutics to treat Mn-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Nursing and health care reform: implications for curriculum development.

    Science.gov (United States)

    Bowen, M; Lyons, K J; Young, B E

    2000-01-01

    The health care system is undergoing profound changes. Cost containment efforts and restructuring have resulted in cutbacks in registered nurse (RN) positions. These changes are often related to the increased market penetration by managed care companies. To determine how RN graduates perceive these changes and their impact on the delivery of patient care, Healthcare Environment Surveys were mailed to graduates of the classes of 1986 and 1991. Using the Survey's 5-point Likert Scale, we measured the graduates' satisfaction with their salary, quality of supervision they received, opportunities for advancement, recognition for their job, working conditions, the overall job and the changes in their careers over the previous five year period. Our study suggests that the changes in the health care system are having an impact on how health care is being delivered and the way nurses view their jobs. Respondents reported that insurance companies are exerting increased control over patient care and perceive that the quality of patient care is declining. Increased workloads and an increase in the amount of paperwork were reported. Participants perceived that there were fewer jobs available and that job security was decreasing. The percentage of nurses who see job satisfaction as remaining the same or increasing are a majority. However, the relatively high percent of nurses who see job satisfaction as declining should provide a note of warning. The major implications of this study are that the professional nursing curriculum must be modified to include content on communication, organization, legislative/policy skills, and leadership. The nation's health care system is undergoing profound changes. There are numerous forces at work that are effecting the delivery of care and, consequently, the work of health professionals. These forces include significant efforts at cost containment, restructuring and downsizing of hospitals, and the movement of health care delivery out of acute

  18. Teachers as Learners: Implications of Adult Education for Professional Development

    Science.gov (United States)

    Beavers, Amy

    2009-01-01

    Effective communication with teachers is a critical element of any successful professional development. Teachers are the foundational component of any educational system. It is vital that adequate attention is focused on appropriate and effective training of these teachers. Ideally, professional development offers a means of collaborative support…

  19. When Research Meets Development: Antecedents and Implications of Transfer Speed

    NARCIS (Netherlands)

    Du, J.; Leten, B.; Vanhaverbeke, W.; Lopez-Vega, H.

    2014-01-01

    This paper focuses on the organization of new product development in large, R&D-intensive firms. In these firms, research and development activities are often separated. Research is conducted in dedicated research projects at specialized research labs. Once research results are achieved by research

  20. Macroeconomic pressures and their implications for business development in Africa

    DEFF Research Database (Denmark)

    Kuada, John

    2011-01-01

    The paper discusses the complex relationships between macroeconomic pressures, savings, investments and business development in Sub-Sahara African countries......The paper discusses the complex relationships between macroeconomic pressures, savings, investments and business development in Sub-Sahara African countries...

  1. Implications of Bilingual Development for Specific Language Impairments in Turkey

    Science.gov (United States)

    Topbas, Seyhun

    2011-01-01

    The potential impact of bilingualism on children's language development has emerged as a crucial concern for Turkey, but so far it has not been addressed from the point of view of language disorders. This short review examines the potential impact of bilingual language development for language impairments in Turkey, with special emphasis on the…

  2. Implications for a Green Curriculum Application toward Sustainable Development

    Science.gov (United States)

    Sahin, Elvan; Ertepinar, Hamide; Teksoz, Gaye

    2009-01-01

    The aim of present study was two-fold: (1) to determine university students' familiarity and understandings of "sustainable development", (2) to examine their attitudes toward sustainable development, environmental values, and their behaviors toward sustainable life styles. The data collected by on-line administration of a questionnaire…

  3. The Psychological Development of Adults: Implications for Public Administration.

    Science.gov (United States)

    Schott, Richard L.

    1986-01-01

    This article analyzes the major theories of adult lifespan development, reviews some related research into the influence of various stages of development on job and organizational satisfaction, and identifies some important issues that the adult life cycle raises for public administrators and managers. (Author/CT)

  4. Men's Identity Development: Issues and Implications for Residence Life

    Science.gov (United States)

    Scott, David A.; Livingston, Wade G.; Havice, Pamela A.; Cawthon, Tony W.

    2012-01-01

    Young men struggle with privilege and oppression in college and university residence halls just as they do in other educational and social contexts. While discussions and research about adolescent and adult identity development continue, little attention has focused on how a male student's identity development can impact residence life cultures on…

  5. An autophagic mechanism is involved in the 6-hydroxydopamine-induced neurotoxicity in vivo.

    Science.gov (United States)

    He, Xin; Yuan, Wei; Li, Zijian; Feng, Juan

    2017-10-05

    6-hydroxydopamine (6-OHDA) is one of the most common agents for modeling dopaminergic neuron degeneration in Parkinson's disease (PD). So far, the role of autophagy in 6-OHDA-induced neurotoxicity remains controversial and most evidence is collected from in vitro studies. In this study, we determined the role of autophagy activation in 6-OHDA-induced neurotoxicity in a rat model of PD. Following 6-OHDA treatment, we observed a concomitant activation of autophagy and apoptosis. To further explore the interaction between autophagy and apoptosis induced by 6-OHDA, autophagy inhibitor 3-methylademine (3-MA) or cysteine protease inhibitor Z-FA-fmk was applied. We found that both 3-MA and Z-FA-fmk could not only exert immediate protection against 6-OHDA-induced neuronal apoptosis, but also prevent dopaminergic neuron loss in the long-term, which was related to reduced autophagosome formation. Furthermore, by monitoring the sequential changes of mTOR-related signaling pathways, we found that reactive oxygen species (ROS)-mediated AKT/AMPK-mTOR signaling pathway participated in but was not the initial cause of autophagy activation by 6-OHDA. Collectively, our data suggest that 6-OHDA-induced autophagy activation contributes to its neurotoxicity and targeting autophagy activation or cysteine proteases could be promising for developing neuroprotective agents for PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Recombinant AAV8-mediated intrastriatal gene delivery of CDNF protects rats against methamphetamine neurotoxicity

    Science.gov (United States)

    Wang, Lizheng; Wang, Zixuan; Xu, Xiaoyu; Zhu, Rui; Bi, Jinpeng; Liu, Wenmo; Feng, Xinyao; Wu, Hui; Zhang, Haihong; Wu, Jiaxin; Kong, Wei; Yu, Bin; Yu, Xianghui

    2017-01-01

    Methamphetamine (METH) exerts significant neurotoxicity in experimental animals and humans when taken at high doses or abused chronically. Long-term abusers have decreased dopamine levels, and they are more likely to develop Parkinson's disease (PD). To date, few medications are available to treat the METH-induced damage of neurons. Glial cell line-derived neurotrophic factor (GDNF) has been previously shown to reduce the dopamine-depleting effects of neurotoxic doses of METH. However, the effect of cerebral dopamine neurotrophic factor (CDNF), which has been reported to be more specific and efficient than GDNF in protecting dopaminergic neurons against 6-OHDA toxicity, in attenuating METH neurotoxicity has not been determined. Thus, the present study aimed to evaluate the neuroprotective effect of CDNF against METH-induced damage to the dopaminergic system in vitro and in vivo. In vitro, CDNF protein increased the survival rate and reduced the tyrosine hydroxylase (TH) loss of METH-treated PC12 cells. In vivo, METH was administered to rats following human CDNF overexpression mediated by the recombinant adeno-associated virus. Results demonstrated that CDNF overexpression in the brain could attenuate the METH-induced dopamine and TH loss in the striatum but could not lower METH-induced hyperthermia. PMID:28553166

  7. The Role of Astrocytes in Metabolism and Neurotoxicity of the Pyrrolizidine Alkaloid Monocrotaline, the Main Toxin of Crotalaria retusa

    Science.gov (United States)

    Pitanga, Bruno Penas Seara; Nascimento, Ravena P.; Silva, Victor Diógenes A.; Costa, Silvia L.

    2012-01-01

    The metabolic interactions and signaling between neurons and glial cells are necessary for the development and maintenance of brain functions and structures and for neuroprotection, which includes protection from chemical attack. Astrocytes are essential for cerebral detoxification and present an efficient and specific cytochrome P450 enzymatic system. Whilst Crotalaria (Fabaceae, Leguminosae) plants are used in popular medicine, they are considered toxic and can cause damage to livestock and human health problems. Studies in animals have shown cases of poisoning by plants from the genus Crotalaria, which induced damage to the central nervous system. This finding has been attributed to the toxic effects of the pyrrolizidine alkaloid (PA) monocrotaline (MCT). The involvement of P450 enzymatic systems in MCT hepatic and pulmonary metabolism and toxicity has been elucidated, but little is known about the pathways implicated in the bioactivation of these systems and the direct contribution of these systems to brain toxicity. This review will present the main toxicological aspects of the Crotalaria genus that are established in the literature and recent findings describing the mechanisms involved in the neurotoxic effects of MCT, which was extracted from Crotalaria retusa, and its interaction with neurons in isolated astrocytes. PMID:22876233

  8. The role of astrocytes in metabolism and neurotoxicity of the pyrrolizidine alkaloid monocrotaline, the main toxin of Crotalaria retusa.

    Directory of Open Access Journals (Sweden)

    Bruno Penas Seara Pitanga

    2012-08-01

    Full Text Available The metabolic interactions and signalling between neurons and glial cells are necessary for the development and maintenance of brain functions and structures and for neuroprotection, which includes protection from chemical attack. Astrocytes are essential for cerebral detoxification and present an efficient and specific cytochrome P450 enzymatic system. Whilst Crotalaria (Fabaceae, Leguminosae plants are used in popular medicine, they are considered toxic and can cause damage to livestock and human health problems. Studies in animals have shown cases of poisoning by plants from the genus Crotalaria, which induced damage to the central nervous system. This finding has been attributed to the toxic effects of the pyrrolizidine alkaloid (PA monocrotaline (MCT. The involvement of P450 enzymatic systems in MCT hepatic and pulmonary metabolism and toxicity has been elucidated, but little is known about the pathways implicated in the bioactivation of these systems and the direct contribution of these systems to brain toxicity. This review will present the main toxicological aspects of the Crotalaria genus that are established in the literature and recent findings describing the mechanisms involved in the neurotoxic effects of MCT, which was extracted from C. retusa, and its interaction with neurons in isolated astrocytes.

  9. Some technical implications of Klein's concept of 'premature ego development'.

    Science.gov (United States)

    Mitrani, Judith L

    2007-08-01

    In this paper, the author revisits the problem of 'premature ego development' first introduced by Melanie Klein in 1930. She also highlights several developments in post-Kleinian thinking since the publication of that paper, which can be seen as offshoots of or complements to Klein's work. The author proposes a link between this category of precocious development and the absence of the experience of what Bion termed the 'containing object.' She puts forward several technical considerations relevant to analytic work with patients who suffer as a result of early developmental failures and presents various clinical vignettes in order to demonstrate the ways in which these considerations take shape in the analytic setting.

  10. Importance and implications of antibiotic resistance development in ...

    African Journals Online (AJOL)

    The development of ABR in nature is a complex phenomenon with many ... and other farming practices and closer contact with humans and other farm animals. ... Worryingly, there is lack of knowledge of this situation owing to inadequate ...

  11. Importance and implications of antibiotic resistance development in ...

    African Journals Online (AJOL)

    Michaela

    2018-01-24

    Jan 24, 2018 ... would aid in the development of surveillance systems and methods to prevent or .... and alternative production methods to industrialize and optimize food ..... Data on the sales and use of antibiotics in livestock production are ...

  12. The health implications of unconventional natural gas development in Pennsylvania.

    Science.gov (United States)

    Peng, Lizhong; Meyerhoefer, Chad; Chou, Shin-Yi

    2018-06-01

    We investigate the health impacts of unconventional natural gas development of Marcellus shale in Pennsylvania between 2001 and 2013 by merging well permit data from the Pennsylvania Department of Environmental Protection with a database of all inpatient hospital admissions. After comparing changes in hospitalization rates over time for air pollution-sensitive diseases in counties with unconventional gas wells to changes in hospitalization rates in nonwell counties, we find a significant association between shale gas development and hospitalizations for pneumonia among the elderly, which is consistent with higher levels of air pollution resulting from unconventional natural gas development. We note that the lack of any detectable impact of shale gas development on younger populations may be due to unobserved factors contemporaneous with drilling, such as migration. Copyright © 2018 John Wiley & Sons, Ltd.

  13. Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6.

    Science.gov (United States)

    Ladenheim, B; Krasnova, I N; Deng, X; Oyler, J M; Polettini, A; Moran, T H; Huestis, M A; Cadet, J L

    2000-12-01

    Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (METH) neurotoxicity. The involvement of a neuroimmune component in apoptotic cell death after injury or chemical damage suggests that cytokines may play a role in METH effects. In the present study, we examined if the absence of IL-6 in knockout (IL-6-/-) mice could provide protection against METH-induced neurotoxicity. Administration of METH resulted in a significant reduction of [(125)I]RTI-121-labeled dopamine transporters in the caudate-putamen (CPu) and cortex as well as depletion of dopamine in the CPu and frontal cortex of wild-type mice. However, these METH-induced effects were significantly attenuated in IL-6-/- animals. METH also caused a decrease in serotonin levels in the CPu and hippocampus of wild-type mice, but no reduction was observed in IL-6-/- animals. Moreover, METH induced decreases in [(125)I]RTI-55-labeled serotonin transporters in the hippocampal CA3 region and in the substantia nigra-reticulata but increases in serotonin transporters in the CPu and cingulate cortex in wild-type animals, all of which were attenuated in IL-6-/- mice. Additionally, METH caused increased gliosis in the CPu and cortices of wild-type mice as measured by [(3)H]PK-11195 binding; this gliotic response was almost completely inhibited in IL-6-/- animals. There was also significant protection against METH-induced DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled (TUNEL) cells in the cortices. The protective effects against METH toxicity observed in the IL-6-/- mice were not caused by differences in temperature elevation or in METH accumulation in wild-type and mutant animals. Therefore, these observations support the proposition that IL-6 may play an important role in the neurotoxicity of METH.

  14. Development of Europe's gas hubs: Implications for East Asia

    Directory of Open Access Journals (Sweden)

    Xunpeng Shi

    2016-10-01

    Full Text Available Gas trading hubs have been initially developed in the US in 1980s, UK in 1990s, more recently in European in the 2000s and mulled in East Asia now. Due to its freshness and diversification in nationality, governance and culture, the European hub experience can offer valuable lessons for East Asia. This paper seeks to advance understanding of gas hub development in Europe and provide lessons for East Asia. The European experience highlights that market liberalization and transition of gas pricing mechanism are necessary in creating the competitive markets that are needed for functional gas hubs. Political will and regulations further safeguard the competition environment needed for hub development. Natural factors, such as significant domestic production and culture could have a significant impact on the hub development and transition of pricing mechanism. In East Asia, the path to gas trading hubs might be more difficult than in Europe but a growing market creates an opportunity to start new terms with new contracts. Nevertheless, East Asian needs to work hard to development its indigenous gas or LNG trading hubs.

  15. Product Configuration Systems - Implications for Product Innovation and Development

    DEFF Research Database (Denmark)

    Edwards, Kasper; Pedersen, Jørgen Lindgaard

    2004-01-01

    configurations. However, costs are but one parameter on which firms compete and firms must continually innovate new and develop existing products. This paper presents original empirical insights on implementation and use of product configuration systems in a number of Danish industrial firms. The paper discusses...... the organisational changes associated with PCS and how this affects product innovation and development. The paper begins by introducing product configuration systems, which are then placed in context to the firm as a process technology which coordinate different processes: product development, order acquisition......Product Configuration Systems (PCS) is a step in the direction of mass customization in the sense that PCS allows a firm to significantly lower the unit cost of configuration. Thus PCS is a valuable technology for lowering operating costs while retaining a high number of possible product...

  16. Traumatic Brain Injuries during Development: Implications for Alcohol Abuse

    Directory of Open Access Journals (Sweden)

    Zachary M. Weil

    2017-07-01

    Full Text Available Traumatic brain injuries are strongly related to alcohol intoxication as by some estimates half or more of all brain injuries involve at least one intoxicated individual. Additionally, there is mounting evidence that traumatic brain injuries can themselves serve as independent risk factors for the development of alcohol use disorders, particularly when injury occurs during juvenile or adolescent development. Here, we will review the epidemiological and experimental evidence for this phenomenon and discuss potential psychosocial mediators including attenuation of negative affect and impaired decision making as well as neurochemical mediators including disruption in the glutamatergic, GABAergic, and dopaminergic signaling pathways and increases in inflammation.

  17. Multiple neurotoxic effects of haloperidol resulting in neuronal death.

    Science.gov (United States)

    Nasrallah, Henry A; Chen, Alexander T

    2017-08-01

    Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

  18. Development of the Adolescent Brain: Implications for Executive Function and Social Cognition

    Science.gov (United States)

    Blakemore, Sarah-Jayne; Choudhury, Suparna

    2006-01-01

    Adolescence is a time of considerable development at the level of behaviour, cognition and the brain. This article reviews histological and brain imaging studies that have demonstrated specific changes in neural architecture during puberty and adolescence, outlining trajectories of grey and white matter development. The implications of brain…

  19. Inclusive growth versus pro-poor growth: Implications for tourism development

    NARCIS (Netherlands)

    Bakker, Martine; Messerli, H.R.

    2017-01-01

    Inclusive growth and pro-poor growth are terms embraced but not fully understood in the tourism community. This paper discusses the main concepts of inclusive growth and their implication for tourism development across the developing world. Is inclusive growth simply another term for pro-poor in

  20. Observations of a Working Class Family: Implications for Self-Regulated Learning Development

    Science.gov (United States)

    Vassallo, Stephen

    2012-01-01

    Guardians have been implicated in the development of children's academic self-regulation. In this case study, which involved naturalistic observations and interviews, the everyday practices of a working class family were considered in the context of self-regulated learning development. The family's practices, beliefs, dispositions and home…

  1. The Psychology of Writing Development--And Its Implications for Assessment

    Science.gov (United States)

    Camp, Heather

    2012-01-01

    This article reviews key developmental theories that have been adopted by writing development researchers over the last fifty years. It describes how researchers have translated these theories into definitions of writing development capable of influencing curricular design and interpretations of student writing and explores the implications for…

  2. Public Understanding of Sustainable Development: Some Implications for Education

    Science.gov (United States)

    Scott, William

    2015-01-01

    A number of recent surveys of public opinion claim that there is now widespread acceptance of the need for sustainable development, and that the general public, through its social and consumer activity is already successfully engaged. However, in all this, the focus has primarily been on individual and family behaviours such as recycling and…

  3. Indigenous Knowledge and Implications for the Sustainable Development Agenda

    Science.gov (United States)

    Magni, Giorgia

    2017-01-01

    With the adoption of the 2030 Agenda for Sustainable Development, the international community committed to address a great number of challenges. Among those emphasised by the SDGs, some are highly relevant for indigenous groups. Education, poverty, access to justice and climate change are only a few of the issues affecting indigenous people's…

  4. Psychosexual Development in Infants and Young Children: Implications for Caregivers.

    Science.gov (United States)

    Honig, Alice Sterling

    2000-01-01

    Discusses preschoolers' interest in and wonder about sexual anatomical differences, and adults' responses to their questions. Presents Freudian stages of psychosexual development, the relationship between sexual identity and gender role, children's preference for single-sex play groups, sex stereotyped toy preferences, and the role of television…

  5. CD 95 mediated apoptosis in embryogenesis: implication in tooth development.

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Šetková, Jana; Blackburn, J.; Míšek, Ivan; Sharpe, P. T.

    2006-01-01

    Roč. 9, 3 (2006), s. 123-128 ISSN 1397-5927 R&D Projects: GA ČR GA304/04/0101; GA MŠk OC B23.001 Institutional research plan: CEZ:AV0Z50450515 Keywords : fas * embryonic development * odontogenesis Subject RIV: EB - Genetics ; Molecular Biology

  6. Relational Aggression in School Settings: Definition, Development, Strategies, and Implications

    Science.gov (United States)

    Dailey, Alicia L.; Frey, Andy J.; Walker, Hill M.

    2015-01-01

    Relational aggression (RA) is a nonphysical form of aggression whereby the perpetrator's goal is to inflict or threaten damage to relationships, including harm to the target child's social standing or reputation. This form of aggression may result in long-term psychological harm to victims. This article defines RA, summarizes its development, and…

  7. Organisational Learning in International Joint Ventures: Implications for Management Development.

    Science.gov (United States)

    Berrell, Mike; Gloet, Marianne; Wright, Phil

    2002-01-01

    Malaysian and Australian managers enrolled in a training program exhibited differences attributed to national culture in their approaches to learning, influences on management behavior, and ways of knowing. National culture had greater influence on management development and organizational learning than did organizational or systems cultures.…

  8. Implications of Urban Development-Induced Resettlement on Poor ...

    African Journals Online (AJOL)

    They are moved away from their areas of work, their social networks .... for Urban Development and Urban Good Governance (FDRE 2007) discusses the three pillars ... about their experiences of past practices of resettlement. ..... women and single-headed families, empowering such families to enable them to engage in ...

  9. Soil development on stable landforms and implications for landscape studies

    Science.gov (United States)

    Harden, J.W.

    1990-01-01

    Soil development parameters include a wide variety of morphological, chemical, and mineralogical parameters, but some of the best indicators of time and surface stability are derived from field morphology. Over long time-spans, the most common time function for soil development is exponential or logarithmic, in which rates decrease with increasing age. Over shorter time-spans in semi-arid and moister climates, Holocene and Pleistocene soil development functions appear as linear segments, with Holocene rates about 10 to 50 times those of Pleistocene rates. In contrast to significant temporal variation in rates, geographical variation in rates within (a) the southern Great Basin and (b) the east Central Valley of California is on the order of 2 or 3 times. When comparing soil development indices of the semi-arid Great Basin to those of moister central California, Holocene rates are similar, but Pleistocene rates are more than 10 times slower in the Great Basin. In a range of climatic settings, the reasons for declining rates over time are several and are complexly related to erosional history, fluxes in water and dust related to climatic changes, rates of primary mineral dissolution, and intrinsic soil processes. ?? 1990.

  10. Some implications of in situ uranium mining technology development

    International Nuclear Information System (INIS)

    Cowan, C.E.; Parkhurst, M.A.; Cole, R.J.; Keller, D.; Mellinger, P.J.; Wallace, R.W.

    1980-09-01

    A technology assessment was initiated in March 1979 of the in-situ uranium mining technology. This report explores the impediments to development and deployment of this technology and evaluates the environmental impacts of a generic in-situ facility. The report is divided into the following sections: introduction, technology description, physical environment, institutional and socioeconomic environment, impact assessment, impediments, and conclusions

  11. EAL Teacher Agency: Implications for Participation in Professional Development

    Science.gov (United States)

    Gurney, Laura; Liyanage, Indika

    2016-01-01

    Teachers construct their practice, education and professional development within two domains of professionalism: sponsored and independent. The association between these two domains, however, is complex; it is overlapping, inseparable and sometimes uneasy. The complexity is further exacerbated by the codependent nature of association between the…

  12. Fatherhood in Kenyan Ethnic Communities: Implication for Child Development

    Science.gov (United States)

    Lasser, Jon; Fite, Kathleen; Wadende, Akinyi P.

    2011-01-01

    This article reviews the traditional and evolving constructions of fatherhood in Kenyan society, with an emphasis on fatherhood's impact on child development outcomes. Western influence and increased access to technology have changed the role of the Kenyan father, and in turn affected his role in the family. Special attention is given to…

  13. Nanoparticles and potential neurotoxicity: focus on molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Davide Lovisolo

    2018-01-01

    Full Text Available The last decades have seen an explosive increase in the development of nanoparticles and in their use in consumer, industrial and medical applications. Their fast diffusion has also raised widespread concern about the potential toxic effects on living organisms, including humans: at the nanoscale, they can interact with subcellular components such as membranes, proteins, lipids, nucleic acids, thus inducing unpredicted functional perturbations in cells and tissues. The nervous tissue is a particular sensitive target, because its cellular components (mainly neurons and glial cells are tightly regulated and metabolically exigent biological entities. While the literature on the potential toxicity of nanoparticles has grown in parallel with their utilization, the available data on neurotoxicity are less abundant. In particular, information on the neuronal molecular targets of nanoparticles is still largely incomplete. A better understanding of this issue is highly relevant for the rational and controlled design of nanoparticles, both for their general utilization and more specifically for their use in the promising field of nanoneuromedicine. In this review, we will discuss the available information on the mechanisms involved in the interaction between nanoobjects and cells of the nervous system, focusing on the known molecular actors, both at the plasma membrane and in intracellular compartments.

  14. Blood brain barrier permeability and tPA-mediated neurotoxicity

    Science.gov (United States)

    Nassar, Taher; Yarovoi, Sergey; Rayan, Anwar; Lamensdorf, Itschak; Karakoveski, Michael; Vadim, Polianski; Fanne, Rami Abu; Jamal, Mahmud; Cines, Douglas B.; Higazi, Abd Al-Roof

    2015-01-01

    Tissue type plasminogen activator (tPA) induces neuronal apoptosis, disrupt the blood-brain-barrier (BBB), and promotes dilation of the cerebral vasculature. The timing, sequence and contributions of these and other deleterious effects of tPA and their contribution to post-ischemic brain damage after stroke, have not been fully elucidated. To dissociate the effects of tPA on BBB permeability, cerebral vasodilation and protease-dependent pathways, we developed several tPA mutants and PAI-1 derived peptides constructed by computerized homology modeling of tPA. Our data show that intravenous administration of human tPA to rats increases BBB permeability through a non-catalytic process, which is associated with reversible neurotoxicity, brain damage, edema, mortality and contributes significantly to its brief therapeutic window. Furthermore, our data show that inhibiting the effect of tPA on BBB function without affecting its catalytic activity, improves outcome and significantly extends its therapeutic window in mechanical as well as thromboembolic models of stroke. PMID:20060006

  15. Psychosocial implications of disorders of sex development treatment for parents.

    Science.gov (United States)

    Wisniewski, Amy B

    2017-01-01

    Historically, studies of caregivers of children with disorders of sex development (DSD) have been limited. Recent data reveal that parents of young children with DSD report increased stress, anxiety, depression, and decreased quality of life in ways that are similar to parents of children with other types of chronic illnesses. Also similar to other chronic illnesses of childhood, parents of children with DSD exhibit overprotective parenting and perceive their child as being vulnerable. These emotions and behaviors exhibited by parents are concerning as they may limit an affected child's emotional and social development over time. Perhaps, more unique to the situation of DSD is the perceived, or real, child-focused stigma experienced by parents of children with DSD. Interventions to improve parents' psychosocial adaptation to their child's medical condition, including coaching in how to discuss their child's condition in a manner that makes them feel safe and supported, are needed to optimize outcomes for families.

  16. Implications of intelligent, integrated microsystems for product design and development

    International Nuclear Information System (INIS)

    MYERS, DAVID R.; MCWHORTER, PAUL J.

    2000-01-01

    Intelligent, integrated microsystems combine some or all of the functions of sensing, processing information, actuation, and communication within a single integrated package, and preferably upon a single silicon chip. As the elements of these highly integrated solutions interact strongly with each other, the microsystem can be neither designed nor fabricated piecemeal, in contrast to the more familiar assembled products. Driven by technological imperatives, microsystems will best be developed by multi-disciplinary teams, most likely within the flatter, less hierarchical organizations. Standardization of design and process tools around a single, dominant technology will expedite economically viable operation under a common production infrastructure. The production base for intelligent, integrated microsystems has elements in common with the mathematical theory of chaos. Similar to chaos theory, the development of microsystems technology will be strongly dependent on, and optimized to, the initial product requirements that will drive standardization--thereby further rewarding early entrants to integrated microsystem technology

  17. Implications of rural tourism and agritourism in sustainable rural development

    Directory of Open Access Journals (Sweden)

    Flavia-Lorena Cut-Lupulescu

    2014-10-01

    Full Text Available Romania shows: a variety of historical cultural values ​​- folk art, ethnography, folklore, traditions, historical artifacts - a natural harmoniously combined with a varied and picturesque landscape background. All these are facets of Romanian rural tourism in particular. Occurred and developed by the various forms of relief since the time of the Thracian-Dacian, Romanian rural settlements kept and still keeps in good measure ancient customs and traditions, a rich and varied folklore, ethnography and folk original elements that can be travel exploited in a strategy for the organization and development of rural tourism. Rural tourism in our country always practical, but spontaneous, sporadic, random, and mostly unorganized form of manifestation is the beginning of the '20s and '30s, the casual visitor accommodation citizens of rural settlements.

  18. Policy implications in developing a land use management information systems

    Science.gov (United States)

    Landini, A. J.

    1975-01-01

    The current land use map for the city of Los Angeles was developed by the guesstimation process and provides single stage information for each level in the critical geographical hierarchy for land use planning management. Processing and incorporation of LANDSAT data in the land use information system requires special funding; however, computergraphic maps are able to provide a viable information system for city planning and management.

  19. Implications of learning theory for developing programs to decrease overeating.

    Science.gov (United States)

    Boutelle, Kerri N; Bouton, Mark E

    2015-10-01

    Childhood obesity is associated with medical and psychological comorbidities, and interventions targeting overeating could be pragmatic and have a significant impact on weight. Calorically dense foods are easily available, variable, and tasty which allows for effective opportunities to learn to associate behaviors and cues in the environment with food through fundamental conditioning processes, resulting in measurable psychological and physiological food cue reactivity in vulnerable children. Basic research suggests that initial learning is difficult to erase, and that it is vulnerable to a number of phenomena that will allow the original learning to re-emerge after it is suppressed or replaced. These processes may help explain why it may be difficult to change food cue reactivity and overeating over the long term. Extinction theory may be used to develop effective cue-exposure treatments to decrease food cue reactivity through inhibitory learning, although these processes are complex and require an integral understanding of the theory and individual differences. Additionally, learning theory can be used to develop other interventions that may prove to be useful. Through an integration of learning theory, basic and translational research, it may be possible to develop interventions that can decrease the urges to overeat, and improve the weight status of children. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Leadership theory: implications for developing dental surgeons in primary care?

    Science.gov (United States)

    Willcocks, S

    2011-02-12

    The development of leadership in healthcare has been seen as important in recent years, particularly at the clinical level. There have been various specific initiatives focusing on the development of leadership for doctors, nurses and other health care professions: for example, a leadership competency framework for doctors, the LEO programme and the RCN clinical leadership programme for nurses. The NHS has set up a Leadership Council to coordinate further developments. However, there has not been the same focus in dentistry, although the recent review of NHS dental services (Steele review) has proposed a need for leadership initiatives in NHS dentistry as a medium-term action. Central to this will be a need to focus on the leadership role for dental surgeons. Leadership is all the more important in dentistry, given the change of government and the policy of retrenchment, major public sector reform, the emergence of new organisations such as new commissioning consortia, possible changes to the dental contract, new ways of working, and changes to the profession such as the requirements for the revalidation of dental surgeons. The question is: which leadership theory or approach is best for dental surgeons working in primary care? This paper builds on earlier work exploring this question in relation to doctors generally, and GPs, in particular, and planned work on nurses. It will seek to address this question in relation to dental surgeons working in primary care.

  1. Personality traits and chronic disease: implications for adult personality development.

    Science.gov (United States)

    Sutin, Angelina R; Zonderman, Alan B; Ferrucci, Luigi; Terracciano, Antonio

    2013-11-01

    Personality traits have been associated with chronic disease. Less is known about the longitudinal relation between personality and disease and whether chronic disease is associated with changes in personality. Method. Participants from the Baltimore Longitudinal Study of Aging (N = 2,008) completed the Revised NEO Personality Inventory and a standard medical interview at regularly scheduled visits; the Charlson Comorbidity Index, a weighted sum of 19 serious diseases, was derived from this interview. Using data from 6,685 visits, we tested whether personality increased risk of disease and whether disease was associated with personality change. Measured concurrently, neuroticism and conscientiousness were associated with greater disease burden. The impulsiveness facet of neuroticism was the strongest predictor of developing disease across the follow-up period: For every standard deviation increase in impulsiveness, there was a 26% increased risk of developing disease and a 36% increased risk of getting more ill. Personality traits changed only modestly with disease: As participants developed chronic illnesses, they became more conservative (decreased openness). Discussion. This research indicates that personality traits confer risk for disease, in part, through health-risk behaviors. These traits, however, were relatively resistant to the effect of serious disease.

  2. Developments in clinical neuropsychology: implications for school psychological services.

    Science.gov (United States)

    Cleary, Michael J; Scott, Albert J

    2011-01-01

    According to the 2000 Report of the Surgeon General's Conference on Children's Mental Health, a significant percentage of children and adolescents have emotional or behavioral problems serious enough to merit a mental health diagnosis. The No Child Left Behind Act of 2001 and the Individuals With Disabilities Education Improvement Act of 2004 reemphasized the schools' importance in supporting cognitive and behavioral development in students, particularly those identified with learning problems. In this article, we examine the growing specialty of clinical neuropsychology and provide suggestions for integrating this field into school-based psychological services. This article provides a review of the neuropsychological bases for many childhood learning disorders and addresses how school psychologists can work with clinical neuropsychologists to better address the needs of exceptional children through neuropsychological testing. There is substantial neurological evidence for attention-deficit hyperactivity disorder as well as disorders of reading, language, and mathematics. Close collaborative partnerships between clinical neuropsychologists and school psychologists will help develop assessment protocols that are likely to result in more effective intervention services for students with neuropsychological conditions. Schools are being asked to support the physical, cognitive, and emotional development in students, particularly those identified with chronic physical and mental health challenges. Dissatisfaction with minimal screenings, the growing awareness of the neurology of learning disorders, and the passage of the Individuals With Disabilities Education Improvement Act of 2004 obliges all school-based mental health providers to consider how to fully integrate the tools of clinical neuropsychology into school-based psychological services. © 2011, American School Health Association.

  3. Nigerian population growth and its implications for economic development.

    Science.gov (United States)

    Okpala, A O

    1990-12-01

    The population of Nigeria is growing at a rate of 3.75%/year indicating a doubling of the population every 22 years. Demographers estimated the population to be 91,178,000 in 1985. Even though population density is high (288 people/square mile), it is not equally distributed. It is highest in the south and southwest urban areas such as Lagos (1045 people/square mile) and lowest in the northeast (75 people/square mile). Moreover rural-urban migration is growing. A major reason for rural-urban migration is the dual nature of the economy in Nigeria. In urban areas, economic development brings about higher standards of living, but, in rural areas, a subsistence economy predominates. This coupled with rapid population growth results in small or no growth in per capita income. Only if the government were to integrate redistribution policies into complete economic development plans should it consider redistributing the population. It should stress rural development (e.g., incentives for firms to set up in rural areas). Further it should move some government offices to rural areas. The government also needs to adopt population policies encouraging the lowering of fertility levels. If it were to provide education through the secondary and prevocational education level free of charge, educated women will lower their fertility. Sex education should be included in the curriculum. Further the government must play an active role in family planning programs, especially educating rural women about family planning. It should also use the mass media to promote small family size, but it should not dictate family size. It also needs to recognize that population growth puts much pressure on the environment. For example, population growth causes soil erosion, nutrient exhaustion, rapid deforestation, and other problems which render the land unusable for agriculture.

  4. Understanding parenting in Manitoba First nations: implications for program development.

    Science.gov (United States)

    Eni, Rachel; Rowe, Gladys

    2011-01-01

    This qualitative study introduced the "Manitoba First Nation Strengthening Families Maternal Child Health Pilot Project" program and evaluation methodologies. The study provided a knowledge base for programmers, evaluators, and communities to develop relevant health promotion, prevention, and intervention programming to assist in meeting health needs of pregnant women and young families. Sixty-five open-ended, semistructured interviews were completed in 13 communities. Data analysis was through grounded theory. Three major themes emerged from the data: interpersonal support and relationships; socioeconomic factors; and community initiatives. Complex structural, historical events compromise parenting; capacity and resilience are supported through informal and formal health and social supports.

  5. Near field communication recent developments and library implications

    CERN Document Server

    McHugh, Sheli

    2014-01-01

    Near Field Communication is a radio frequency technology that allows objects, such as mobile phones, computers, tags, or posters, to exchange information wirelessly across a small distance. This report on the progress of Near Field Communication reviews the features and functionality of the technology and summarizes the broad spectrum of its current and anticipated applications. We explore the development of NFC technology in recent years, introduce the major stakeholders in the NFC ecosystem, and project its movement toward mainstream adoption. Several examples of early implementation of NFC

  6. Increased Screen Time: Implications for Early Childhood Development and Behavior.

    Science.gov (United States)

    Radesky, Jenny S; Christakis, Dimitri A

    2016-10-01

    The authors review trends in adoption of new digital technologies (eg, mobile and interactive media) by families with young children (ages 0-8 years), continued use of television and video games, and the evidence for learning from digital versus hands-on play. The authors also discuss continued concerns about health and developmental/behavioral risks of excessive media use for child cognitive, language, literacy, and social-emotional development. This evidence is then applied to clinical care in terms of the screening questions providers can use, tools available to providers and parents, and changes in anticipatory guidance. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Reversible metronidazole-induced neurotoxicity after 10 weeks of therapy.

    Science.gov (United States)

    AlDhaleei, Wafa; AlMarzooqi, Ayesha; Gaber, Nouran

    2018-04-20

    Metronidazole is a commonly used antimicrobial worldwide. The most common side effects that have been reported are nausea, vomiting and hypersensitivity reactions. However, neurotoxicity has been reported with the use of metronidazole but rather rare. The most common neurological manifestation is peripheral neuropathy involvement in the form of sensory loss. It is worth mentioning that central neurotoxicity is a rare side effect of metronidazole use but reversible. The manifestations vary from a headache, altered mental status to focal neurological deficits. The diagnosis is mainly by neuroimaging in the setting of acute neurological change in the patient status. Here, we report a case of metronidazole-induced neurotoxicity in a 38-year-old male patient who was admitted with a brain abscess and was started on metronidazole for more than 10 weeks. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

    Science.gov (United States)

    Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

    2016-01-01

    Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

  9. Some implications of in situ uranium mining technology development

    International Nuclear Information System (INIS)

    Cowan, C.E.; Parkhurst, M.A.; Cole, R.J.; Keller, D.; Mellinger, P.J.; Wallace, R.W.

    1980-09-01

    The assessment indicates that there do not appear to be any significant demonstrated negative environmental impacts. Moreover, the impacts of in situ mining compare favorably with those impacts expected from conventional mining techniques. Exposure to radioactive elements is less, atmospheric emissions of radioactive and nonradioactive materials are generally less and socioeconomic impacts are decreased. In fact, because of the generally small and unskilled labor forces associated with in-situ mining, development has provided much needed economic stimulus to economically depressed areas of Texas. There are still, however, several areas of unknowns and several areas of inadequate information that will need to be addressed before a complete quantification evaluation of impacts can be made. These areas include levels of radon emissions and groundwater restoration methods and impacts. Several issues mostly relating to the interaction of industry with state and Federal regulators need to be addressed

  10. The Development of Bimodal Bilingualism: Implications for Linguistic Theory.

    Science.gov (United States)

    Lillo-Martin, Diane; de Quadros, Ronice Müller; Pichler, Deborah Chen

    2016-01-01

    A wide range of linguistic phenomena contribute to our understanding of the architecture of the human linguistic system. In this paper we present a proposal dubbed Language Synthesis to capture bilingual phenomena including code-switching and 'transfer' as automatic consequences of the addition of a second language, using basic concepts of Minimalism and Distributed Morphology. Bimodal bilinguals, who use a sign language and a spoken language, provide a new type of evidence regarding possible bilingual phenomena, namely code-blending, the simultaneous production of (aspects of) a message in both speech and sign. We argue that code-blending also follows naturally once a second articulatory interface is added to the model. Several different types of code-blending are discussed in connection to the predictions of the Synthesis model. Our primary data come from children developing as bimodal bilinguals, but our proposal is intended to capture a wide range of bilingual effects across any language pair.

  11. Public health implications of urban air pollution in developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Schwela, D H [World Health Organisation, Geneva (Switzerland)

    1996-12-31

    Exposure to air pollution is an almost inescapable part of urban life throughout the world. Ambient air pollutant levels in urban areas are generally a reflection of emissions. For sulphur dioxide, total suspended particulate matter and lead, ambient concentrations are declining in the industrialized western countries. For nitrogen dioxide, ambient levels in cities are generally constant, or slightly increasing. For carbon dioxide, they are variable, declining where controls are being applied. In a substantial number of cities, particularly in developing countries, WHO guidelines are being often exceeded for the compounds mentioned. Given the rate at which these cities are growing, the air pollution situation will probably worsen if environmental control measures are not implemented. As a consequence, the health and well-being of urban residents will further deteriorate with high ambient air pollutant concentrations causing increased mortality, morbidity, deficits on pulmonary functions and cardiovascular and neurobehavioural effects. (author)

  12. Public health implications of urban air pollution in developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Schwela, D.H. [World Health Organisation, Geneva (Switzerland)

    1995-12-31

    Exposure to air pollution is an almost inescapable part of urban life throughout the world. Ambient air pollutant levels in urban areas are generally a reflection of emissions. For sulphur dioxide, total suspended particulate matter and lead, ambient concentrations are declining in the industrialized western countries. For nitrogen dioxide, ambient levels in cities are generally constant, or slightly increasing. For carbon dioxide, they are variable, declining where controls are being applied. In a substantial number of cities, particularly in developing countries, WHO guidelines are being often exceeded for the compounds mentioned. Given the rate at which these cities are growing, the air pollution situation will probably worsen if environmental control measures are not implemented. As a consequence, the health and well-being of urban residents will further deteriorate with high ambient air pollutant concentrations causing increased mortality, morbidity, deficits on pulmonary functions and cardiovascular and neurobehavioural effects. (author)

  13. Co-exposure to an ortho-substituted PCB (PCB 153) and methylmercury enhances developmental neurotoxic effects

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, C.; Fredriksson, A.; Eriksson, P. [Dept. Environment. Toxicol., Uppsala Univ. (Sweden)

    2004-09-15

    In our environment there are innumerable hazardous contaminants. Many of these compounds are the well-known persistent organic pollutants (POPs) like PCB and DDT. Another persistent agent in our environment is methylmercury (MeHg). These agents are known to be neurotoxic in laboratory animals and humans. Fetuses and neonates are known to be high-risk groups for exposure to these agents. A naturally occurring circumstance is the exposure to a combination of different persistent compounds. The knowledge of interaction between different toxic agents during development is sparse. In several studies we have shown that low-dose exposure of environmental toxic agents such as PCBs, DDT, BFRs (brominated flame retardants) as well as well-known neurotoxic agents such as nicotine, organophosphorous compounds and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), during the ''BGS'', in neonatal mice can lead to disruption of the adult brain function, and to an increased susceptibility to toxic agents as adults. Our studies concerning developmental neurotoxic effects after neonatal exposure to single PCB congeners have shown that some orthosubstituted PCBs (such as PCB 28, PCB 52, PCB 153) and some co-planar PCBs (such as PCB 77, PCB 126, PCB 169) cause derangement of adult behaviour that can worsen with age. Furthermore, the cholinergic receptors in the brain were also found to be affected8. Just recently we have seen that neonatal co-exposure to an ortho-substituted PCB, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), together with a brominated flame retardant, 2,2',4,4',5-pentabromodiphenylether (PBDE 99), can enhance developmental neurotoxic effects when the exposure occurs during a critical stage of neonatal brain development. The present study was carried out in order to see whether PCB and MeHg could interact to cause enhanced developmental neurotoxic effects on spontaneous behaviour and habituation capability when given to neonatal mice.

  14. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Directory of Open Access Journals (Sweden)

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  15. The Bali Agreement: Implications for Development and the WTO

    Directory of Open Access Journals (Sweden)

    Christophe Bellmann

    2014-05-01

    Full Text Available At the most recent World Trade Organisation (WTO ministerial conference, in December 2013, in Bali, Indonesia, ministers from 160 countries concluded the first multilateral agreement ever negotiated under the auspices of the WTO. After five years of impasse in the moribund Doha Round of trade negotiations, the so-called “Bali package” was enthusiastically welcomed by the world’s governments and international press alike as a critical step towards restoring the credibility of the WTO as a negotiating forum. The centrepiece of the package is without doubt a new agreement on trade facilitation aimed at reducing red tape, and facilitating customs procedures in an effort to cut down the cost of doing business. Other — less far reaching — aspects of the deal focused on food security and a set of issues of particular interest to least developed countries including trade preferences or cotton subsidies. As the dust from the heated Bali negotiations settles, the main challenge for the WTO will now consist in building on this success to re-energise multilateral negotiations and ultimately close the Doha Round. In a world increasingly dominated by regional and bilateral free-trade agreements, members will have to confront the core issues that have divided them for nearly 15 years and find creative solutions to rehabilitate the WTO’s centrality in global trade governance.

  16. Developing Biological ISRU: Implications for Life Support and Space Exploration

    Science.gov (United States)

    Brown, I. I.; Allen, C. C.; Garrison, D. H.; Sarkisova, S. A.; Galindo, C.; Mckay, David S.

    2010-01-01

    Main findings: 1) supplementing very dilute media for cultivation of CB with analogs of lunar or Martian regolith effectively supported the proliferation of CB; 2) O2 evolution by siderophilic cyanobacteria cultivated in diluted media but supplemented with iron-rich rocks was higher than O2 evolution by same strain in undiluted medium; 3) preliminary data suggest that organic acids produced by CB are involved in iron-rich mineral dissolution; 4) the CB studied can accumulate iron on and in their cells; 4) sequencing of the cyanobacterium JSC-1 genome revealed that this strain possesses molecular features which make it applicable for the cultivation in special photoreactors on Moon and Mars. Conclusion: As a result of pilot studies, we propose, to develop a concept for semi-closed integrated system that uses CB to extract useful elements to revitalize air and produce valuable biomolecules. Such a system could be the foundation of a self-sustaining extraterrestrial outpost (Hendrickx, De Wever et al., 2005; Handford, 2006). A potential advantage of a cyanobacterial photoreactor placed between LSS and ISRU loops is the possibility of supplying these systems with extracted elements and compounds from the regolith. In addition, waste regolith may be transformed into additional products such as methane, biomass, and organic and inorganic soil enrichment for the cultivation of higher plants.

  17. Implications of human trafficking in Asia: a scoping review of aftercare initiatives centered on economic development.

    Science.gov (United States)

    Camp, Meghan A; Barner, John R; Okech, David

    2018-01-01

    The trafficking of persons is one of the most egregious violations of human rights in modern society. Given the disproportionate effects across demographic categories of age and gender, as well as concentrated impacts within the developing world, there is a strong need for research and literature on program effectiveness and appropriate aftercare efforts for those persons whose lives and livelihoods have been impacted by trafficking. The purpose of this article is to provide a scoping review of what is known about effectively helping survivors of human trafficking experiencing lack of economic opportunity and the implications for practice and future research regarding the absence of literature. From over 14,000 initial search results, this article focuses on those initiatives (N = 16) that support economic development of the individual or family after being trafficked. Implications arising from the review for trafficking policy, areas for further research, and implications for practitioners are highlighted and discussed.

  18. Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo.

    Science.gov (United States)

    Kaushal, Nidhi; Seminerio, Michael J; Robson, Matthew J; McCurdy, Christopher R; Matsumoto, Rae R

    2013-08-01

    Methamphetamine is a highly addictive psychostimulant drug of abuse, causing hyperthermia and neurotoxicity at high doses. Currently, there is no clinically proven pharmacotherapy to treat these effects of methamphetamine, necessitating identification of potential novel therapeutic targets. Earlier studies showed that methamphetamine binds to sigma (σ) receptors in the brain at physiologically relevant concentrations, where it "acts in part as an agonist." SN79 (6-acetyl-3-(4-(4-(4-florophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one) was synthesized as a putative σ receptor antagonist with nanomolar affinity and selectivity for σ receptors over 57 other binding sites. SN79 pretreatment afforded protection against methamphetamine-induced hyperthermia and striatal dopaminergic and serotonergic neurotoxicity in male, Swiss Webster mice (measured as depletions in striatal dopamine and serotonin levels, and reductions in striatal dopamine and serotonin transporter expression levels). In contrast, di-o-tolylguanidine (DTG), a well established σ receptor agonist, increased the lethal effects of methamphetamine, although it did not further exacerbate methamphetamine-induced hyperthermia. Together, the data implicate σ receptors in the direct modulation of some effects of methamphetamine such as lethality, while having a modulatory role which can mitigate other methamphetamine-induced effects such as hyperthermia and neurotoxicity. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  19. Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes

    Science.gov (United States)

    Gonzalez-Carter, Daniel A.; Leo, Bey Fen; Ruenraroengsak, Pakatip; Chen, Shu; Goode, Angela E.; Theodorou, Ioannis G.; Chung, Kian Fan; Carzaniga, Raffaella; Shaffer, Milo S. P.; Dexter, David T.; Ryan, Mary P.; Porter, Alexandra E.

    2017-03-01

    Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson’s disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag2S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H2S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag2S formation, resulting from CSE-mediated H2S production in microglia, sequesters Ag+ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.

  20. Fertilizer Reduction Policies in Developed Countries: Suitability and Implications

    Directory of Open Access Journals (Sweden)

    LI Fang

    2017-01-01

    Full Text Available This study reviewed and analyzed the specific practices, implementation effects and applicable conditions of fertilizer reduction policies in the EU, US and Japan, explored the common laws and general conditions in the formulation of environmental orientation, and pro vided feasible policy recommendations for the formulation of fertilizer reduction policies in China. This study showed that fertilizer reduction policies in each country had their own advantages and disadvantages, and the applicable conditions were different. The EU's command and control policy was applicable to the situation of less farm households and the same agricultural planting type or farm type. The economic in centive policy in the US was applicable to the situation of more farm households, relatively perfect agricultural market system and sensitive price formation mechanism, while the public participation policy in Japan was applicable to regions with more relevant agricultural groups and strong economy. China should learn from each of these policies and make a comprehensive choice in the formulation of fertilizer reduc tion policies. Therefore, China should proceed from improving the agricultural price mechanism and the pollution-free agricultural products certification system as well as encouraging and supporting the development of large scale production units, and then promote the adoption of environmentally friendly technology through the guidance of market mechanism, ensure the effective implementation of environmental stan dards through farmers' integration and improve farmers' environmental awareness through propaganda guidance, so as to ensure the effective implementation of different types(command and control policy, economic incentive policy and public participation policyof fertilizer reduc tion policies.

  1. AN APROACH OF LOCAL FINANCIAL AUTONOMY AND IMPLICATION OVER SUSTAINABLE DEVELOPMENT IN THE KNOWLEDGE SOCIETY

    Directory of Open Access Journals (Sweden)

    Elena CIGU

    2014-12-01

    Full Text Available Local governments play an important role in sustainable development processes based on their administrative and financial autonomy. Policies and programs undertaken to assure sustainable development by local governments produce benefits for persistence of the knowledge society. This paper will try to highlight the implication of local financial autonomy over sustainable development of local communities in a knowledge society, based especially on local financial autonomy theory approach.

  2. AN APROACH OF LOCAL FINANCIAL AUTONOMY AND IMPLICATION OVER SUSTAINABLE DEVELOPMENT IN THE KNOWLEDGE SOCIETY

    OpenAIRE

    Elena CIGU

    2014-01-01

    Local governments play an important role in sustainable development processes based on their administrative and financial autonomy. Policies and programs undertaken to assure sustainable development by local governments produce benefits for persistence of the knowledge society. This paper will try to highlight the implication of local financial autonomy over sustainable development of local communities in a knowledge society, based especially on local financial autonomy theory approach.

  3. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Naruto, Takuya; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Hiroaki; Yagihashi, Tatsuhiko; Kosaki, Kenjiro; Yokota, Shumpei

    2010-01-01

    One severe side effect of calcineurin inhibitors (CNIs: such as cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp), encoded by ABCB1 gene. In the present study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity. The effects of the polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T, associated with CNI-related neurotoxicity were evaluated in 63 patients with hematopoietic stem cell transplantation.   Of the 63 cases, 15 cases developed CNI-related neurotoxicity. In the CsA patient group (n = 30), age (p = 0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC genotype at ABCB1 C1236T was associated with it, but not significantly so (p = 0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506 patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002) were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G (expressor genotype) was strongly associated with it according to logistic regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4-51.4).   The polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI-related neurotoxicity. This outcome is probably because of CYP3A5 or P-gp functions or metabolites of CNIs. © 2009 John Wiley & Sons A/S.

  4. Non-Serotonergic Neurotoxicity by MDMA (Ecstasy in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Dina Popova

    Full Text Available 3,4-methylenedioxymethamphetamine (MDMA; ecstasy is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT, that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A. The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.

  5. Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells.

    Science.gov (United States)

    Popova, Dina; Forsblad, Andréas; Hashemian, Sanaz; Jacobsson, Stig O P

    2016-01-01

    3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT), that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A). The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm) in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.

  6. Historical Development of Guidance and Counseling and Implications for the Future

    Science.gov (United States)

    Aubrey, Roger F.

    1977-01-01

    The author traces the development of guidance and counseling from the nineteenth century to the present with implications for the future. The impact of the progressive movement, vocational guidance, industrialization, psychometrics, and Carl Rogers are highlighted. The 1950's are singled out as the decade having the greatest effect on counselors.…

  7. Monitoring and Evaluation of an Early Childhood Development Programme: Implications for Leadership and Management

    Science.gov (United States)

    Hodgson, Sarah; Papatheodorou, Theodora; James, Mary

    2014-01-01

    The article aims to discuss preliminary findings from a participatory monitoring and evaluation (M&E) framework, used in a community-based early childhood development (ECD) programme in KwaZulu-Natal South Africa, and their implications for leadership and management. The purposes of the M&E were for LETCEE, the implementing organization,…

  8. Theory Development and Convergence of Human Resource Fields: Implications for Human Performance Technology

    Science.gov (United States)

    Cho, Yonjoo; Yoon, Seung Won

    2010-01-01

    This study examines major theory developments in human resource (HR) fields and discusses implications for human performance technology (HPT). Differentiated HR fields are converging to improve organizational performance through knowledge-based innovations. Ruona and Gibson (2004) made a similar observation and analyzed the historical evolution…

  9. Teacher educators: their identities, sub-identities and implications for professional development

    NARCIS (Netherlands)

    Swennen, J.M.H.; Jones, K.; Volman, M.L.L.

    2010-01-01

    In this article we address the question: 'What sub-identities of teacher educators emerge from the research literature about teacher educators and what are the implications of the sub-identities for the professional development of teacher educators?' Like other professional identities, the identity

  10. Functional groups show distinct differences in nitrogen cycling during early stand development: implications for forest management

    Science.gov (United States)

    Doug P. Aubrey; David R. Coyle; Mark D. Coleman

    2012-01-01

    Background and aims Nutrient acquisition of forest stands is controlled by soil resource availability and belowground production, but tree species are rarely compared in this regard. Here, we examine ecological and management implications of nitrogen (N) dynamics during early forest stand development in productive commercial tree species with narrow (Populus...

  11. Airline network development in Europe and its implications for airport planning

    NARCIS (Netherlands)

    Burghouwt, G.

    2007-01-01

    Order by Fax Printer Friendly PDF Brochure Send to Friend Enquire before Buying Hard Copy Airline Network Development in Europe and its Implications for Airport Planning Ashgate Publishing, March 2007, Pages: 300 Description Table of Contents Enquire before Buying Send to a Friend The ongoing

  12. Socio-Cultural Theories of Cognitive Development: Implications for Teaching Theory in the Visual Arts.

    Science.gov (United States)

    Fielding, Rob

    1989-01-01

    Explicates the socio-cultural developmental theories of Vygotsky and Feuerstein which advocate teacher mediated learning in order to stimulate and accelerate development. Implications for art education include the need for the teacher to become involved in the enculturation of the child into the thinking processes and conceptual organization of…

  13. Water Supply Deficiency and Implications for Rural Development in the Niger-Delta Region of Nigeria

    Science.gov (United States)

    Nkwocha, E. E.

    2009-01-01

    There is a growing concern about the marginalization of the Niger Delta region of Nigeria in terms of infrastructural and social services provision. This study examined the water supply deficiency and its general implications for rural development within the region. Data and other study characteristics were extracted from 501 subjects drawn from…

  14. Specific features of the Galician language and implications for speech technology development

    OpenAIRE

    2008-01-01

    Specific features of the Galician language and implications for speech technology development correspondence: Corresponding author. (Banga, Eduardo Rodriguez) (Banga, Eduardo Rodriguez) Dpto. Filoloxia Galega. Universidade de Santiago. Santiago de Compostela. Spain - (Gonzalez, Manuel Gonzalez) Dpto. Teoria de la Se?al y Comunicaciones. Universidad de Vigo. Vigo. Spain - (Banga, Eduardo Rodriguez) SPAIN (Banga...

  15. The Influnce of Metacognition on Managerial Hiring Decision Making: Implications for Management Development

    OpenAIRE

    Kumar, Angela Ewell

    1998-01-01

    THE INFLUENCE OF METACOGNITION ON MANAGERIAL HIRING DECISION MAKING: IMPLICATIONS FOR MANAGEMENT DEVELOPMENT by Angela Ewell Kumar (ABSTRACT) Cognitive processing has a primary role in decision making. In addition, metacognition, the regulation and knowledge of cognition, affects decision making in a consistent and predictable way. Novices explain situations in a simple way. Novices are more likely to make inappropriate decisions. Research suggests that train...

  16. The Self's Development and Ego Growth: Conceptual Analysis and Implications for Counselors.

    Science.gov (United States)

    Hamachek, Don E.

    1985-01-01

    Self development is conceptualized as surrounded by a series of ego rings that spread out from its center. Erikson's first five psychosocial stages are used as the developmental framework within which self-concept, self-esteem, and ego boundaries are viewed as component parts of the self's growth. Counseling implications are used. (Author/BL)

  17. An Educational Perspective of Autism: Implications for Curriculum Development and Personnel Development.

    Science.gov (United States)

    Donnellan, Anne M.

    The paper addresses the history and current status of educational provisions for autistic students, discusses the requirements for effective education for this population, and analyzes the implications for teacher education practices. A status report cites lack of structure in programs, non-functional and age-inappropriate curricula, largely…

  18. Natural toxins implicated in the development of Parkinson’s disease

    OpenAIRE

    Salama, Mohamed; Arias-Carrión, Oscar

    2011-01-01

    Experimental models of Parkinson’s disease (PD) are of great importance for improving the design of future clinical trials. Various neurotoxic models are available, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat and rotenone. However, no model is considered perfect; each has its own limitations. Based on epidemiological data, a new trend of using environmental toxins in PD modeling seems attractive and has dominated public discussions of th...

  19. Toxicologic evidence of developmental neurotoxicity of environmental chemicals

    DEFF Research Database (Denmark)

    Andersen, H R; Nielsen, J B; Grandjean, P

    2000-01-01

    Developmental neurotoxicity constitutes effects occurring in the offspring primarily as a result of exposure of the mother during pregnancy and lactation. To exert their effect, these chemicals or their metabolites must pass the placenta and/or the blood-brain barrier. In experimental animals, ex...

  20. Protective effect of quercetin on bupivacaine-induced neurotoxicity ...

    African Journals Online (AJOL)

    ... bupivacaine, possibly through inhibition of T-type calcium channel. This finding implies a novel mechanism for neuroprotective effect of quercetin, and its potential for treating toxicity arising from the use of local anesthetic agents. Keywords: Quercetin, Bupivacaine, Local anaesthetic, Neuroprotection, Neurotoxicity, T-type ...

  1. 3-nitropropionic acid neurotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noer, Helle; Kristensen, Bjarne W; Noraberg, Jens

    2002-01-01

    : CA1 > CA3 > fascia dentata. In low glucose much lower concentrations of 3-NP (25 microM) triggered neurotoxicity. One-week-old cultures were less susceptible to 3-NP toxicity than 3-week-old cultures, but the dentate granule cells were relatively more affected in the immature cultures. We found...

  2. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    Directory of Open Access Journals (Sweden)

    Doaa A. Ghareeb

    2015-01-01

    Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

  3. Public Health Perspectives of Preeclampsia in Developing Countries: Implication for Health System Strengthening

    OpenAIRE

    Kayode O. Osungbade; Olusimbo K. Ige

    2011-01-01

    Objectives. Review of public health perspectives of preeclampsia in developing countries and implications for health system strengthening. Methods. Literature from Pubmed (MEDLINE), AJOL, Google Scholar, and Cochrane database were reviewed. Results. The prevalence of preeclampsia in developing countries ranges from 1.8% to 16.7%. Many challenges exist in the prediction, prevention, and management of preeclampsia. Promising prophylactic measures like low-dose aspirin and calcium supplem...

  4. Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies

    DEFF Research Database (Denmark)

    Fox, Donald A; Grandjean, Philippe; de Groot, Didima

    2012-01-01

    and short-term memory in aged Rhesus monkeys following acute 24 h exposure to ketamine during early development. Overall, these presentations addressed fundamental issues in the emerging areas of lifetime neurotoxicity testing, differential vulnerable periods of exposure, nonmonotonic dose-response effects...... with neurodegeneration. Didima de Groot presented results on prenatal exposure of rats to methylazoxymethanol and discussed the results in light of the etiology of western Pacific amyotrophic lateral sclerosis and Parkinson-dementia complex. Merle G. Paule addressed the long-term changes in learning, motivation...

  5. A Retrospective Performance Assessment of the Developmental Neurotoxicity Study in Support of OECD Test Guideline 426

    DEFF Research Database (Denmark)

    Makris, Susan L.; Raffaele, Kathleen; Allen, Sandra

    2009-01-01

    OBJECTIVE: We conducted a review of the history and performance of developmental neurotoxicity mic (DNT) testing in support of the finalization and implementation of Organisation of Economic Co-operation and Development (OECD) DNT test guideline 426 (TG 426). INFORMATION SOURCES AND ANALYSIS......: In this review we summarize extensive scientific efforts that form the foundation for this testing paradigm, including basic neurotoxicology research, interlaboratory collaborative studies, expert workshops, and validation studies, and we address the relevance, applicability, and use of the DNT study in risk...... and international acceptance of new or updated test methods for hazard characterization. Multiple independent, expert scientific peer reviews affirm these conclusions....

  6. Developmental neurotoxicity of pyrethroid insecticides in zebrafish embryos.

    Science.gov (United States)

    DeMicco, Amy; Cooper, Keith R; Richardson, Jason R; White, Lori A

    2010-01-01

    Pyrethroid insecticides are one of the most commonly used residential and agricultural insecticides. Based on the increased use of pyrethroids and recent studies showing that pregnant women and children are exposed to pyrethroids, there are concerns over the potential for developmental neurotoxicity. However, there have been relatively few studies on the developmental neurotoxicity of pyrethroids. In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda-cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC(50), permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spasms were observed, which were reminiscent of the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam ameliorated the spasms, while treatment with the sodium channel antagonist MS-222 ameliorated both spasms and body curvature, suggesting that pyrethroid-induced neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data suggest that zebrafish may be an appropriate alternative model to study the mechanism(s) responsible for the developmental neurotoxicity of pyrethroid insecticides and aid in identification of compounds that should be further tested in mammalian systems.

  7. Diffusion abnormalities of the globi pallidi in manganese neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    McKinney, Alexander M.; Filice, Ross W.; Teksam, Mehmet; Casey, Sean; Truwit, Charles; Clark, H. Brent; Woon, Carolyn; Liu, Hai Ying [Department of Radiology, Medical School, Box 292, 420 Delaware Street S.E., 55455, Minneapolis, MN (United States)

    2004-04-01

    Manganese is an essential trace metal required for normal central nervous system function, which is toxic when in excess amounts in serum. Manganese neurotoxicity has been demonstrated in patients with chronic liver/biliary failure where an inability to excrete manganese via the biliary system causes increased serum levels, and in patients on total parenteral nutrition (TPN), occupational/inhalational exposure, or other source of excess exogenous manganese. Manganese has been well described in the literature to deposit selectively in the globi pallidi and to induce focal neurotoxicity. We present a case of a 53-year-old woman who presented for a brain MR 3 weeks after liver transplant due to progressively decreasing level of consciousness. The patient had severe liver failure by liver function tests and bilirubin levels, and had also been receiving TPN since the transplant. The MR demonstrated symmetric hyperintensity on T1-weighted images in the globi pallidi. Apparent diffusion coefficient (ADC) map indicated restricted diffusion in the globi pallidi bilaterally. The patient eventually succumbed to systemic aspergillosis 3 days after the MR. The serum manganese level was 195 mcg/l (micrograms per liter) on postmortem exam (over 20 times the upper limits of normal). The patient was presumed to have suffered from manganese neurotoxicity since elevated serum manganese levels have been shown in the literature to correlate with hyperintensity on T1-weighted images, neurotoxicity symptoms, and focal concentration of manganese in the globi pallidi. Neuropathologic sectioning of the globi pallidi at autopsy was also consistent with manganese neurotoxicity. (orig.)

  8. A critical review of neonicotinoid insecticides for developmental neurotoxicity

    Science.gov (United States)

    Sheets, Larry P.; Li, Abby A.; Minnema, Daniel J.; Collier, Richard H.; Creek, Moire R.; Peffer, Richard C.

    2016-01-01

    Abstract A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood–brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system. PMID:26513508

  9. A critical review of neonicotinoid insecticides for developmental neurotoxicity.

    Science.gov (United States)

    Sheets, Larry P; Li, Abby A; Minnema, Daniel J; Collier, Richard H; Creek, Moire R; Peffer, Richard C

    2016-02-01

    A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood-brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system.

  10. Dopamine D(1) receptor deletion strongly reduces neurotoxic effects of methamphetamine.

    Science.gov (United States)

    Ares-Santos, S; Granado, N; Oliva, I; O'Shea, E; Martin, E D; Colado, M I; Moratalla, R

    2012-02-01

    Methamphetamine (METH) is a potent, highly addictive psychostimulant consumed worldwide. In humans and experimental animals, repeated exposure to this drug induces persistent neurodegenerative changes. Damage occurs primarily to dopaminergic neurons, accompanied by gliosis. The toxic effects of METH involve excessive dopamine (DA) release, thus DA receptors are highly likely to play a role in this process. To define the role of D(1) receptors in the neurotoxic effects of METH we used D(1) receptor knock-out mice (D(1)R(-/-)) and their WT littermates. Inactivation of D(1)R prevented METH-induced dopamine fibre loss and hyperthermia, and increases in gliosis and pro-inflammatory molecules such as iNOS in the striatum. In addition, D(1)R inactivation prevented METH-induced loss of dopaminergic neurons in the substantia nigra. To explore the relationship between hyperthermia and neurotoxicity, METH was given at high ambient temperature (29 °C). In this condition, D(1)R(-/-) mice developed hyperthermia following drug delivery and the neuroprotection provided by D(1)R inactivation at 23 °C was no longer observed. However, reserpine, which empties vesicular dopamine stores, blocked hyperthermia and strongly potentiated dopamine toxicity in D(1)R(-/-) mice, suggesting that the protection afforded by D(1)R inactivation is due to both hypothermia and higher stored vesicular dopamine. Moreover, electrical stimulation evoked higher DA overflow in D(1)R(-/-) mice as demonstrated by fast scan cyclic voltammetry despite their lower basal DA content, suggesting higher vesicular DA content in D(1)R(-/-) than in WT mice. Altogether, these results indicate that the D(1)R plays a significant role in METH-induced neurotoxicity by mediating drug-induced hyperthermia and increasing the releasable cytosolic DA pool. Copyright © 2011. Published by Elsevier Inc.

  11. Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance.

    Science.gov (United States)

    Mariussen, Espen

    2012-09-01

    Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

  12. Music Preference and the Issues of Social Challenges Among Nigerian Youth: Implications For Moral Development

    Directory of Open Access Journals (Sweden)

    Femi Abiodun

    2017-02-01

    Full Text Available Music is central to youth culture. Central to this study is the question: what type of music do youth listen to and why do they listen to such music? Identifying the music preference of the Nigerian youth is the focus of this paper. The aim is to assess some moral challenges that are inherent in the types of music listened to by students in Nigerian tertiary institutions which by implication represent Nigerian youth. Questionnaire was used to find out the type of music most preferred by the students. Findings reveal that the most preferred music by students especially between ages 18 and 25 is the popular music genre and in particular hip pop and fuji music. Textual analyses of some of the music show that they are agents of socialization and cultural identity but most unsuitable for moral development. Implications of this on moral values include developing wrong emotions which may lead to violent life and wrong associations.

  13. Studies on the assessment of neurotoxicity in children with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Muchi, H.; Satoh, T.; Yamamoto, K.; Karube, T.; Miyao, M.

    1987-01-01

    Central nervous system (CNS) prophylaxis caused a remarkable reduction in the incidence of CNS disease, however there has evolved a growing concern regarding the immediate or late toxicities to the developing CNS. Twenty-eight children with acute lymphoblastic leukemia who survived for more than 2 years were examined for the assessment of neurotoxicity induced by CNS prophylaxis and its treatment. The patients were stratified into three groups: Stratum I, prophylaxis with methotrexate; Stratum II, prophylaxis with cranial irradiation with methotrexate; and Stratum III, with CNS leukemia. Once CNS disease developed the sequelae were frequent and severe, due to the elevated methotrexate levels in the cerebrospinal fluid. CNS prophylaxis with intermediate-dose methotrexate was less toxic to the developing CNS than prophylactic cranial irradiation, especially in children under 5 years of age. Electroencephalograms and evoked potentials are likely to find increasing application in defining the CNS sequelae of acute lymphoblastic leukemia in children and its treatment. Although the sample size was small, the findings delineate specific areas of neurotoxicity

  14. Identifying the sociological implications of the main aspects affecting the optimal sporting career development

    OpenAIRE

    2014-01-01

    M.Phil. (Sport Management) This study is strengthened by several studies that have indicated that the dualist nature of student-athletes is problematic, as well as the management thereof. The study aimed to identify the sociological implications of the main aspects affecting the optimal sporting career development in athletics (throwers) at University of Johannesburg Sport, and offers recommendations for managing student-athletes. The methods utilized for this study included: i) self-desig...

  15. Technological Developments and their Effects on World Trade: Any Implications for Governments?

    OpenAIRE

    Aykut Kibritcioglu

    2001-01-01

    This paper summarizes new developments in world trade, technological changes worldwide and their implications for recent theoretical studies in economics. After defining the economic globalization and schematizing its relations with international trade, economic growth and technological change, dramatic increases in world trade in goods, services and financial assets in last decades are statistically documented in Chapter 2. Theoretical studies of economists on international trade and economi...

  16. Implications of newborn amygdala connectivity for fear and cognitive development at 6-months-of-age

    Science.gov (United States)

    Graham, Alice M.; Buss, Claudia; Rasmussen, Jerod M.; Rudolph, Marc D.; Demeter, Damion V.; Gilmore, John H.; Styner, Martin; Entringer, Sonja; Wadhwa, Pathik D.; Fair, Damien A.

    2015-01-01

    The first year of life is an important period for emergence of fear in humans. While animal models have revealed developmental changes in amygdala circuitry accompanying emerging fear, human neural systems involved in early fear development remain poorly understood. To increase understanding of the neural foundations of human fear, it is important to consider parallel cognitive development, which may modulate associations between typical development of early fear and subsequent risk for fear-related psychopathology. We, therefore, examined amygdala functional connectivity with rs-fcMRI in 48 neonates (M=3.65 weeks, SD=1.72), and measured fear and cognitive development at 6-months-of-age. Stronger, positive neonatal amygdala connectivity to several regions, including bilateral anterior insula and ventral striatum, was prospectively associated with higher fear at 6-months. Stronger amygdala connectivity to ventral anterior cingulate/anterior medial prefrontal cortex predicted a specific phenotype of higher fear combined with more advanced cognitive development. Overall, findings demonstrate unique profiles of neonatal amygdala functional connectivity related to emerging fear and cognitive development, which may have implications for normative and pathological fear in later years. Consideration of infant fear in the context of cognitive development will likely contribute to a more nuanced understanding of fear, its neural bases, and its implications for future mental health. PMID:26499255

  17. Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

    Directory of Open Access Journals (Sweden)

    Svetlana A Dambinova

    2016-10-01

    Full Text Available Concussion is a complex, heterogenous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment.

  18. Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.

    Science.gov (United States)

    Lazcano-Pérez, Fernando; Hernández-Guzmán, Ulises; Sánchez-Rodríguez, Judith; Arreguín-Espinosa, Roberto

    2016-01-01

    Natural products from animal venoms have been used widely in the discovery of novel molecules with particular biological activities that enable their use as potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its venoms are composed of a complex mixture of peptidic compounds with neurotoxic and cytolitic properties that have shown activity on mammalian systems despite the fact that they are naturally targeted against fish and invertebrate preys, mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast source of molecules with a remarkable activity on central nervous system, targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors. In this brief review, we list the amino acid sequences of most cnidarian neurotoxic peptides reported to date. Additionally, we propose the inclusion of a new type of voltage-gated sea anemone sodium channel toxins based on the most recent reports.

  19. Neurotoxicity of dental amalgam is mediated by zinc.

    Science.gov (United States)

    Lobner, D; Asrari, M

    2003-03-01

    The use of dental amalgam is controversial largely because it contains mercury. We tested whether amalgam caused toxicity in neuronal cultures and whether that toxicity was caused by mercury. In this study, we used cortical cell cultures to show for the first time that amalgam causes nerve cell toxicity in culture. However, the toxicity was not blocked by the mercury chelator, 2,3-dimercaptopropane-1-sulphonate (DMPS), but was blocked by the metal chelator, calcium disodium ethylenediaminetetraacetate (CaEDTA). DMPS was an effective mercury chelator in this system, since it blocked mercury toxicity. Of the components that comprise amalgam (mercury, zinc, tin, copper, and silver), only zinc neurotoxicity was blocked by CaEDTA. These results indicate that amalgam is toxic to nerve cells in culture by releasing zinc. While zinc is known to be neurotoxic, ingestion of zinc is not a major concern because zinc levels in the body are tightly regulated.

  20. Commentary on Cross-Cultural Perspectives on Positive Youth Development With Implications for Intervention Research.

    Science.gov (United States)

    Koller, Silvia H; Verma, Suman

    2017-07-01

    There is a growing focus on youth positive development issues among researchers and practitioners around the world. In this special issue of Child Development, each of the international authors provides new perspectives and understanding about youth developmental assets in different cultural settings. The present commentary (a) examines some of the cross-cultural themes that emerge from the four articles by international authors in this issue with implications for positive youth development (PYD) and (b) how intervention science can benefit by incorporating a PYD approach. As evident, youth involved in contexts that provide positive resources from significant others not only were less likely to exhibit negative outcomes, but also were more likely to show evidence of positive development. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  1. The dopamine transporter: role in neurotoxicity and human disease

    International Nuclear Information System (INIS)

    Bannon, Michael J.

    2005-01-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  2. The dopamine transporter: role in neurotoxicity and human disease

    Energy Technology Data Exchange (ETDEWEB)

    Bannon, Michael J [Department of Psychiatry and Behavioral Neuroscience, Pharmacology, and Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2005-05-01

    The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

  3. Oral epithelial stem cells – implications in normal development and cancer metastasis

    Science.gov (United States)

    Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

    2014-01-01

    Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

  4. Spatial Analysis on Future Housing Markets: Economic Development and Housing Implications

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2014-01-01

    Full Text Available A coupled projection method combining formal modelling and other statistical techniques was developed to delineate the relationship between economic and social drivers for net new housing allocations. Using the example of employment growth in Tyne and Wear, UK, until 2016, the empirical analysis yields housing projections at the macro- and microspatial levels (e.g., region to subregion to elected ward levels. The results have important implications for the strategic planning of locations for housing and employment, demonstrating both intuitively and quantitatively how local economic developments affect housing demand.

  5. The role of dopamine receptors in the neurotoxicity of methamphetamine.

    Science.gov (United States)

    Ares-Santos, S; Granado, N; Moratalla, R

    2013-05-01

    Methamphetamine is a synthetic drug consumed by millions of users despite its neurotoxic effects in the brain, leading to loss of dopaminergic fibres and cell bodies. Moreover, clinical reports suggest that methamphetamine abusers are predisposed to Parkinson's disease. Therefore, it is important to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity. Dopamine receptors may be a plausible target to prevent this neurotoxicity. Genetic inactivation of dopamine D1 or D2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D1 receptor inactivation is due to blockade of hypothermia, reduced dopamine content and turnover and increased stored vesicular dopamine in D1R(-/-) mice. However, the neuroprotective impact of D2 receptor inactivation is partially dependent on an effect on body temperature, as well as on the blockade of dopamine reuptake by decreased dopamine transporter activity, which results in reduced intracytosolic dopamine levels in D2R(-/-) mice. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  6. Peripheral Ammonia as a Mediator of Methamphetamine Neurotoxicity

    Science.gov (United States)

    Halpin, Laura E.; Yamamoto, Bryan K.

    2012-01-01

    Ammonia is metabolized by the liver and has established neurological effects. The current study examined the possibility that ammonia contributes to the neurotoxic effects of methamphetamine (METH). The results show that a binge dosing regimen of METH to the rat increased plasma and brain ammonia concentrations that were paralleled by evidence of hepatotoxicity. The role of peripheral ammonia in the neurotoxic effects of METH was further substantiated by the demonstration that the enhancement of peripheral ammonia excretion blocked the increases in brain and plasma ammonia and attenuated the long term depletions of dopamine and serotonin typically produced by METH. Conversely, the localized perfusion of ammonia in combination with METH, but not METH alone or ammonia alone, into the striatum recapitulated the neuronal damage produced by the systemic administration of METH. Furthermore, this damage produced by the local administration of ammonia and METH was blocked by the GYKI 52466, an AMPA receptor antagonist. These findings highlight the importance of ammonia derived from the periphery as a small molecule mediator of METH neurotoxicity and more broadly emphasize the importance of peripheral organ damage as a possible mechanism that mediates the neuropathology produced by drugs of abuse and other neuroactive molecules. PMID:22993432

  7. Thallium Toxicity: General Issues, Neurological Symptoms, and Neurotoxic Mechanisms.

    Science.gov (United States)

    Osorio-Rico, Laura; Santamaria, Abel; Galván-Arzate, Sonia

    2017-01-01

    Thallium (Tl + ) is a ubiquitous natural trace metal considered as the most toxic among heavy metals. The ionic ratio of Tl + is similar to that of potassium (K + ), therefore accounting for the replacement of the latter during enzymatic reactions. The principal organelle damaged after Tl + exposure is mitochondria. Studies on the mechanisms of Tl + include intrinsic pathways altered and changes in antiapoptotic and proapoptotic proteins, cytochrome c, and caspases. Oxidative damage pathways increase after Tl + exposure to produce reactive oxygen species (ROS), changes in physical properties of the cell membrane caused by lipid peroxidation, and concomitant activation of antioxidant mechanisms. These processes are likely to account for the neurotoxic effects of the metal. In humans, Tl + is absorbed through the skin and mucous membranes and then is widely distributed throughout the body to be accumulated in bones, renal medulla, liver, and the Central Nervous System. Given the growing relevance of Tl + intoxication, in recent years there is a notorious increase in the number of reports attending Tl + pollution in different countries. In this sense, the neurological symptoms produced by Tl + and its neurotoxic effects are gaining attention as they represent a serious health problem all over the world. Through this review, we present an update to general information about Tl + toxicity, making emphasis on some recent data about Tl + neurotoxicity, as a field requiring attention at the clinical and preclinical levels.

  8. Protective activities of Vaccinium antioxidants with potential relevance to mitochondrial dysfunction and neurotoxicity.

    Science.gov (United States)

    Yao, Yu; Vieira, Amandio

    2007-01-01

    Both the neurotransmitter dopamine (DA) and a neurotoxic metabolite, 6-hydroxy DA, can be oxidized to generate hydrogen peroxide and other reactive species (ROS). ROS promote oxidative stress and have been implicated in dopaminergic neurodegeneration, e.g., Parkinson's disease (PD). There is also evidence for a relation between catecholamine-mediated oxidative damage in dopaminergic neurons and the effects of these neurotransmitters on the redox state of cytochrome c (Cytc). In neurons and other cells, oxidative stress may be enhanced by abnormal release of Cytc and other mitochondrial proteins into the cytoplasm. Cytc release can result in apoptosis; but sub-apoptogenic-threshold release can also occur, and may be highly damaging in the presence of DA metabolites. Loss of mitochondrial membrane integrity, a pathological situation of relevance to several aging-related neurodegenerative disorders including PD, contributes to release of Cytc; and the level of such release is known to be indicative of the extent of mitochondrial dysfunction. In this context, we have used a Cytc-enhanced 6-hydroxy DA oxidation reaction to gauge dietary antioxidant activities. Anthocyanin-rich preparations of Vaccinium species (Vaccinium myrtillus, Vaccinium corymbosum, and Vaccinium oxycoccus) as well as a purified glycosylated anthocyanidin were compared. The most potent inhibition of oxidation was observed with V. myrtillus preparation: 50% inhibition with 7 microM of total anthocyanins. This activity was 1.5-4 times higher than that for the other preparations or for the purified anthocyanin. Ascorbate (Vitamin C), at up to 4-fold higher concentrations, did not result in significant inhibition in this assay. Antioxidant activity in the assay correlated strongly (r2>0.91, PVaccinium content of anthocyanins and total cyanidins, but not quercetin or myricetin. The results provide evidence for the high potency of anthocyanins towards a potentially neurotoxic reaction, and provide a basis

  9. Dopaminergic Neuron-Specific Deletion of p53 Gene Attenuates Methamphetamine Neurotoxicity.

    Science.gov (United States)

    Lu, Tao; Kim, Paul P; Greig, Nigel H; Luo, Yu

    2017-08-01

    p53 plays an essential role in the regulation of cell death in dopaminergic (DA) neurons and its activation has been implicated in the neurotoxic effects of methamphetamine (MA). However, how p53 mediates MA neurotoxicity remains largely unknown. In this study, we examined the effect of DA-specific p53 gene deletion in DAT-p53KO mice. Whereas in vivo MA binge exposure reduced locomotor activity in wild-type (WT) mice, this was significantly attenuated in DAT-p53KO mice and associated with significant differences in the levels of the p53 target genes BAX and p21 between WT and DAT-p53KO. Notably, DA-specific deletion of p53 provided protection of substantia nigra pars reticulata (SNpr) tyrosine hydroxylase (TH) positive fibers following binge MA, with DAT-p53KO mice having less decline of TH protein levels in striatum versus WT mice. Whereas DAT-p53KO mice demonstrated a consistently higher density of TH fibers in striatum compared to WT mice at 10 days after MA exposure, DA neuron counts within the substantia nigra pars compacta (SNpc) were similar. Finally, supportive of these results, administration of a p53-specific inhibitor (PFT-α) provided a similarly protective effect on MA binge-induced behavioral deficits. Neither DA specific p53 deletion nor p53 pharmacological inhibition affected hyperthermia induced by MA binge. These findings demonstrate a specific contribution of p53 activation in behavioral deficits and DA neuronal terminal loss by MA binge exposure.

  10. The Quality of Relationships in International Development: Institutional and Personal Implications

    Directory of Open Access Journals (Sweden)

    Leslie Groves

    2006-01-01

    Full Text Available In this article, the authors explore some of the personal and organisational implications entailed in satisfying the new demands for greater transparency and accountability in development aid. This calls for changes in the relationships among the different actors inthe international development system. The first part of the article focuses on how the groups of people conceive each other and behave, that is, the “personal” dimension of the construction of the relationship. In this sense, one can observe the role that can be played by the individual development agent to support the change in relationships called for by the new development agenda. In the second part, it examines how the people are connected through their organisations, as well as the institutional mechanisms that can hinder the development of quality relationships, and also how they can be transformed in order to better satisfy the needs of the new poverty reduction agenda.

  11. Advanced Pre-clinical Research Approaches and Models to Studying Pediatric Anesthetic Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Cheng eWang

    2012-10-01

    Full Text Available Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of anesthetic procedures. A great deal of concern has recently arisen regarding the safety of anesthesia in infants and children. Because of obvious limitations, it is not possible to thoroughly explore the effects of anesthetic agents on neurons in vivo in human infants or children. However, the availability of some advanced pre-clinical research approaches and models, such as imaging technology both in vitro and in vivo, stem cell and nonhuman primate experimental models, have provided potentially invaluable tools for examining the developmental effects of anesthetic agents. This review discusses the potential application of some sophisticaled research approaches, e.g., calcium imaging, in stem cell-derived in vitro models, especially human embryonic neural stem cells, along with their capacity for proliferation and their potential for differentiation, to dissect relevant mechanisms underlying the etiology of the neurotoxicity associated with developmental exposures to anesthetic agents. Also, this review attempts to discuss several advantages for using the developing rhesus monkey models (in vivo, when combined with dynamic molecular imaging approaches, in addressing critical issues related to the topic of pediatric sedation/anesthesia. These include the relationships between anesthetic-induced neurotoxicity, dose response, time-course and developmental stage at time of exposure (in vivo studies, serving to provide the most expeditious platform toward decreasing the uncertainty in extrapolating pre-clinical data to the human condition.

  12. Developmental neurotoxicity: methylmercury and prenatal exposure protection in the context of the Minamata Convention

    Directory of Open Access Journals (Sweden)

    Ana Boischio

    2015-09-01

    Full Text Available Mercury is a global pollutant of public environmental health concern due to its long-range atmospheric distribution, environmental distribution, and neurotoxic effects. Following biological methylation, methylmercury (MeHg can be un-evenly bioaccumulated within aquatic food chains. Fish consumption can be a significant route of human exposure to MeHg. MeHg exposure in the prenatal stage, at relatively low levels, has recently been established as harmful during neurological development, potentially leading to intellectual disability. The Minamata Convention on Mercury is a global agreement, currently under ratification, to protect human health and the environment from anthropogenic emissions and releases of mercury and mercury compounds. The resolution regarding the role of the World Health Organization and ministries of health in the implementation of the Convention includes protection of human health from critical exposures to MeHg. Riverside populations living in areas with artisanal small-scale gold mining, and relying heavily on fish consumption, have been identified as the most vulnerable population in terms of MeHg exposure and developmental neurotoxicity. This article focuses on the proper design and dissemination of fish advisories within the context of implementation of the Convention.

  13. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish.

    Science.gov (United States)

    Lisse, Thomas S; Middleton, Leah J; Pellegrini, Adriana D; Martin, Paige B; Spaulding, Emily L; Lopes, Olivia; Brochu, Elizabeth A; Carter, Erin V; Waldron, Ashley; Rieger, Sandra

    2016-04-12

    Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.

  14. Maneb and Paraquat-Mediated Neurotoxicity: Involvement of Peroxiredoxin/Thioredoxin System

    Science.gov (United States)

    Roede, James R.; Hansen, Jason M.; Go, Young-Mi; Jones, Dean P.

    2011-01-01

    Epidemiological and in vivo studies have demonstrated that exposure to the pesticides paraquat (PQ) and maneb (MB) increase the risk of developing Parkinson’s disease (PD) and cause dopaminergic cell loss, respectively. PQ is a well-recognized cause of oxidative toxicity; therefore, the purpose of this study was to determine if MB potentiates oxidative stress caused by PQ, thus providing a mechanism for enhanced neurotoxicity by the combination. The results show that PQ alone at a moderately toxic dose (20–30% cell death in 24 h) caused increased reactive oxygen species (ROS) generation, oxidation of mitochondrial thioredoxin-2 and peroxiredoxin-3, lesser oxidation of cytoplasmic thioredoxin-1 and peroxiredoxin-1, and no oxidation of cellular GSH/GSSG. In contrast, MB alone at a similar toxic dose resulted in no ROS generation, no oxidation of thioredoxin and peroxiredoxin, and an increase in cellular GSH after 24 h. Together, MB increased GSH and inhibited ROS production and thioredoxin/peroxiredoxin oxidation observed with PQ alone, yet resulted in more extensive (> 50%) cell death. MB treatment resulted in increased abundance of nuclear Nrf2 and mRNA for phase II enzymes under the control of Nrf2, indicating activation of cell protective responses. The results show that MB potentiation of PQ neurotoxicity does not occur by enhancing oxidative stress and suggests that increased toxicity occurs by a combination of divergent mechanisms, perhaps involving alkylation by MB and oxidation by PQ. PMID:21402726

  15. Neural differentiation of mouse embryonic stem cells as a tool to assess developmental neurotoxicity in vitro.

    Science.gov (United States)

    Visan, Anke; Hayess, Katrin; Sittner, Dana; Pohl, Elena E; Riebeling, Christian; Slawik, Birgitta; Gulich, Konrad; Oelgeschläger, Michael; Luch, Andreas; Seiler, Andrea E M

    2012-10-01

    Mouse embryonic stem cells (mESCs) represent an attractive cellular system for in vitro studies in developmental biology as well as toxicology because of their potential to differentiate into all fetal cell lineages. The present study aims to establish an in vitro system for developmental neurotoxicity testing employing mESCs. We developed a robust and reproducible protocol for fast and efficient differentiation of the mESC line D3 into neural cells, optimized with regard to chemical testing. Morphological examination and immunocytochemical staining confirmed the presence of different neural cell types, including neural progenitors, neurons, astrocytes, oligodendrocytes, and radial glial cells. Neurons derived from D3 cells expressed the synaptic proteins PSD95 and synaptophysin, and the neurotransmitters serotonin and γ-aminobutyric acid. Calcium ion imaging revealed the presence of functionally active glutamate and dopamine receptors. In addition, flow cytometry analysis of the neuron-specific marker protein MAP2 on day 12 after induction of differentiation demonstrated a concentration dependent effect of the neurodevelopmental toxicants methylmercury chloride, chlorpyrifos, and lead acetate on neuronal differentiation. The current study shows that D3 mESCs differentiate efficiently into neural cells involving a neurosphere-like state and that this system is suitable to detect adverse effects of neurodevelopmental toxicants. Therefore, we propose that the protocol for differentiation of mESCs into neural cells described here could constitute one component of an in vitro testing strategy for developmental neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Neurotoxic Antibodies against the Prion Protein Do Not Trigger Prion Replication.

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    Karl Frontzek

    Full Text Available Prions are the infectious agents causing transmissible spongiform encephalopathies (TSE, progressive, inexorably lethal neurological diseases. Antibodies targeting the globular domain (GD of the cellular prion protein PrPC trigger a neurotoxic syndrome morphologically and molecularly similar to prion disease. This phenomenon raises the question whether such antibodies induce infectious prions de novo. Here we exposed cerebellar organotypic cultured slices (COCS to the neurotoxic antibody, POM1. We then inoculated COCS homogenates into tga20 mice, which overexpress PrPC and are commonly utilized as sensitive indicators of prion infectivity. None of the mice inoculated with COCS-derived lysates developed any signs of disease, and all mice survived for at least 200 days post-inoculation. In contrast, all mice inoculated with bona fide prions succumbed to TSE after 55-95 days. Post-mortem analyses did not reveal any signs of prion pathology in mice inoculated with POM1-COCS lysates. Also, lysates from POM1-exposed COCS were unable to convert PrP by quaking. Hence, anti-GD antibodies do not catalyze the generation of prion infectivity. These data indicate that prion replication can be separated from prion toxicity, and suggest that anti-GD antibodies exert toxicity by acting downstream of prion replication.

  17. Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism.

    Science.gov (United States)

    Costa, Lucio G; Chang, Yu-Chi; Cole, Toby B

    2017-06-01

    Epidemiological and animal studies suggest that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which are characterized by impairment in socialization and in communication and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. Gene-environment interactions may play a relevant role in determining individual susceptibility to air pollution developmental neurotoxicity. Given the worldwide presence of elevated air pollution, studies on its effects and mechanisms on the developing brain, genetic susceptibility, role in neurodevelopmental disorders, and possible therapeutic interventions are certainly warranted.

  18. Investigating Climate Compatible Development Outcomes and their Implications for Distributive Justice: Evidence from Malawi

    Science.gov (United States)

    Wood, Benjamin T.; Quinn, Claire H.; Stringer, Lindsay C.; Dougill, Andrew J.

    2017-09-01

    Governments and donors are investing in climate compatible development in order to reduce climate and development vulnerabilities. However, the rate at which climate compatible development is being operationalised has outpaced academic enquiry into the concept. Interventions aiming to achieve climate compatible development "wins" (for development, mitigation, adaptation) can also create negative side-effects. Moreover, benefits and negative side-effects may differ across time and space and have diverse consequences for individuals and groups. Assessments of the full range of outcomes created by climate compatible development projects and their implications for distributive justice are scarce. This article develops a framework using a systematic literature review that enables holistic climate compatible development outcome evaluation over seven parameters identified. Thereafter, we explore the outcomes of two donor-funded projects that pursue climate compatible development triple-wins in Malawi using this framework. Household surveys, semi-structured interviews and documentary material are analysed. Results reveal that uneven outcomes are experienced between stakeholder groups and change over time. Although climate compatible development triple-wins can be achieved through projects, they do not represent the full range of outcomes. Ecosystem—and community-based activities are becoming popularised as approaches for achieving climate compatible development goals. However, findings suggest that a strengthened evidence base is required to ensure that these approaches are able to meet climate compatible development goals and further distributive justice.

  19. Integrating Youth into Community Development: Implications for Policy Planning and Program Evaluation

    Directory of Open Access Journals (Sweden)

    Rosemary V. Barnett

    2006-09-01

    Full Text Available As non-profits, volunteer groups, and nongovernmental organizations take on increasingly larger roles in contributing to local well-being, the active collaboration between youth and adults is vital to the long-term success of community development efforts. Similarly, as service activities become standardized components of high-school programs, youth are empowered to becoming long-term contributors to local development efforts. Through this process youth engage in shared citizenship, leading to greater investment in their communities. This research was based on the premise that youth, acting as central parts of the community development process, have the capacity to improve local well-being. It reflects input from 12 key informants and 418 youth who participated in a survey conducted on the development issues contributing to their involvement. The findings of this study provide insights into the factors most directly shaping youth attitudes and involvement in their communities, as well as presenting direct implications for applied use.

  20. Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin

    Science.gov (United States)

    Satomi, Machiko; Asama, Toshiyuki; Ebisawa, Yoshiaki; Chisato, Naoyuki; Suno, Manabu; Karasaki, Hidenori; Furukawa, Hiroyuki; Matsubara, Kazuo

    2010-01-01

    Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity. PMID:22811813

  1. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marreilha dos Santos, A.P., E-mail: apsantos@ff.ul.pt [I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal); Lucas, Rui L.; Andrade, Vanda; Mateus, M. Luísa [I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal); Milatovic, Dejan; Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Batoreu, M. Camila [I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon (Portugal)

    2012-02-01

    Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E{sub 2} prostaglandin (PGE{sub 2}) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.

  2. Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity

    International Nuclear Information System (INIS)

    Marreilha dos Santos, A.P.; Lucas, Rui L.; Andrade, Vanda; Mateus, M. Luísa; Milatovic, Dejan; Aschner, Michael; Batoreu, M. Camila

    2012-01-01

    Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model. Exposure biomarkers, inflammatory and oxidative stress biomarkers, as well as behavioral parameters were evaluated. Co-treatment with Mn plus Ebs or Mn plus PAS caused a significant decrease in blood and brain Mn concentrations (compared to rats treated with Mn alone), concomitant with reduced brain E 2 prostaglandin (PGE 2 ) and enhanced brain glutathione (GSH) levels, decreased serum prolactin (PRL) levels, and increased ambulation and rearing activities. Taken together, these results establish that both PAS and Ebs are efficacious in reducing Mn body burden, neuroinflammation, oxidative stress and locomotor activity impairments in a rat model of Mn-induced toxicity. -- Highlights: ► The manuscript is unique in its approach to the neurotoxicity of Mn. ► The manuscript incorporates molecular, cellular and functional (behavioral) analyses. ► Both PAS and Ebs are effective in restoring Mn behavioral function. ► Both PAS and Ebs are effective in reducing Mn-induced oxidative stress. ► Both PAS and Ebs led to a decrease in Mn-induced neuro-inflammation.

  3. Neurotoxicity following the Ingestion of Bilimbi Fruit (Averrhoa bilimbi) in an End-Stage Renal Disease Patient on Hemodialysis.

    Science.gov (United States)

    Caetano, Camille Pereira; de Sá, Cinara Barros; Faleiros, Bruno Antônio Paixão; Gomes, Marcelo Fonseca Coutinho Fernandes; Pereira, Edna Regina Silva

    2017-01-01

    The toxic effects of the ingestion of star fruit (Averrhoa carambola) in chronic kidney disease patients are well described in the literature. Recently, the compound caramboxin has been isolated, explaining the mechanisms of its neurotoxicity. Bilimbi fruit belongs to the family Oxalidaceae, Averrhoa bilimbi species, and exhibits similar biochemical characteristics to star fruit. To report the case of a patient with chronic kidney disease who developed a seizure disorder after the ingestion of bilimbi fruit. A 69-year-old man with chronic kidney disease on hemodialysis therapy had intractable hiccups, myoclonus, and generalized tonic-clonic seizures after the consumption of a moderate amount of bilimbi fruit. The electroencephalogram showed a pattern of seizure disorder despite the use of anticonvulsant drugs. Renal replacement therapy was maintained during the whole period and prescribed according to the patient's hemodynamic status. Despite showing clinical resolution of the seizure disorder, the patient died on the 27th day of hospitalization for infectious complications. The neurologic status without any other known cause and with clear temporal association with the ingestion of the fruit suggests the diagnosis of neurotoxicity. We propose the hypothesis that the bilimbi fruit has neurotoxic effects similar to those exhibited by the star fruit.

  4. Communication for Development: A Personal Experience with Implications for Development Policy

    Science.gov (United States)

    Agunga, Robert

    2012-01-01

    Purpose: Communication for Development (C4D) is a new academic discipline and profession for addressing human dimension concerns in development, such as local participation, integration and capacity building, which are the main issues limiting aid effectiveness. However, my experience in Malawi, one of the poorest countries in Africa and where a…

  5. Science Teachers' Conceptualizations and Implications for the Development of the Professional Development Programs

    Science.gov (United States)

    Kaymakamoglu, Sibel Ersel

    2017-01-01

    This study aimed to investigate the two primary school science teachers' conceptions of professional development, their perceptions of self-improvement and the factors influencing their professional development. In this investigation, a case study approach was adopted. The participant teachers were given a semi-structured interview and the data…

  6. Consumer perception of meat quality and implications for product development in the meat sector

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Bredahl, Lone; Brunsø, Karen

    2004-01-01

    of purchase, based on own experience and informational cues available in the shopping environment, is described, as well as the way in which quality is experienced in the home during and after meal preparation. The relationship between quality expectations and quality experience and its implications...... for consumer satisfaction and repeat purchase intent is addressed. In the second part of the paper, and building on the insights obtained on subjective quality perception, possibilities for consumer-oriented product development in the meat sector are addressed. Issues dealt with here are branding...

  7. Consumer perception of meat quality and implications for product development in the meat sector

    DEFF Research Database (Denmark)

    Grunert, Klaus G.; Bredahl, Lone; Brunsø, Karen

    of purchase, based on own experience and informational cues available in the shopping environment, is described, as well as the way in which quality is experienced in the home during and after meal preparation. The relationship between quality expectations and quality experience and its implications...... for consumer satisfaction and repeat purchase intent is addressed. In the second part of the paper, and building on the insights obtained on subjective quality perception, possibilities for consumer-oriented product development in the meat sector are addressed. Issues dealt with here are branding...

  8. ORGANISATIONAL DETERMINANTS INFLUENCING INFORMATION SYSTEMS REIMPLEMENTATION: SOME IMPLICATIONS TO THE DEVELOPING COUNTRIES

    Directory of Open Access Journals (Sweden)

    Sayyen Teoh

    2010-01-01

    Full Text Available This article presents an in-depth study of global Web-based Marketing Decision Support System reimplementation, in a British-based Fast Moving Consumer Goods (FMCG manufacturer. The paper shows that the success of a system implementation can still be marginal even if the organisation understands the key organisational determinants of success and has influence over them. The paper concludes with a discussion of how implementation planning, user need analysis and communication problems could be overcomed and also some implications to the companies in the developing nations.

  9. Memory profiles of Down, Williams, and fragile X syndromes: implications for reading development.

    Science.gov (United States)

    Conners, Frances A; Moore, Marie S; Loveall, Susan J; Merrill, Edward C

    2011-06-01

    The purpose of this review was to understand the types of memory impairments that are associated with intellectual disability (ID, formerly called mental retardation) and the implications of these impairments for reading development. Specifically, studies on working memory, delayed memory and learning, and semantic/conceptual memory in Down syndrome, Williams syndrome, and fragile X syndrome were examined. A distinct memory profile emerged for each of the 3 etiologies of ID. Memory profiles are discussed in relation to strengths and weaknesses in reading skills in these three etiologies. We suggest that reading instruction be designed to capitalize on relatively stronger memory skills while providing extra support for especially challenging aspects of reading.

  10. Moral competence as a positive youth development construct: conceptual bases and implications for curriculum development.

    Science.gov (United States)

    Ma, Hing Keung

    2006-01-01

    Moral competence refers to the orientation to perform altruistic behavior and the ability to judge moral issues logically, consistently and at an advanced level of development. A brief review of the concepts of altruism and justice is presented. The gender and cultural issues are also discussed. The contents of moral competence program units include four major topics: (1) Fairness, (2) Proper conduct (mainly altruistic and prosocial orientation), (3) Responsibility and altruistic orientation, and (4) Integrity and fairness. The general goal is to help students to develop an altruistic orientation and a judgment structure of a high level of justice. This paper is part of the development of the positive youth development program in Hong Kong.

  11. Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine: testosterone and ICI 182,780 sensitive mechanism

    Directory of Open Access Journals (Sweden)

    Mactutus Charles F

    2005-06-01

    Full Text Available Abstract Background HIV Associated Dementia (HAD is a common complication of human immunodeficiency virus (HIV infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, to produce a significant synergistic neurotoxicity. Using this model system, the neuroprotective potential of gonadal steroids was investigated. Results 17β-Estradiol (17β-E2, but not 17α-estradiol (17α-E2, was protective against this combined neurotoxicity. Progesterone (PROG afforded limited neuroprotection, as did dihydrotestosterone (DHT. The efficacy of 5α-testosterone (T-mediated neuroprotection was robust, similar to that provided by 17β-E2. In the presence of the specific estrogen receptor (ER antagonist, ICI-182,780, T's neuroprotection was completely blocked. Thus, T acts through the ER to provide neuroprotection against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated concentration-dependent neuroprotection, possibly attributable to cholesterol's serving as a steroid hormone precursor in neurons. Conclusion Collectively, the present data indicate that cocaine has a robust interaction with the HIV proteins gp120 and Tat that produces severe neurotoxicity, and this toxicity can be blocked through pretreatment with ER agonists.

  12. Exploring the implications of social change for human development: perspectives, issues and future directions.

    Science.gov (United States)

    Chen, Xinyin

    2015-02-01

    Researchers have investigated the implications of social change for human development from different perspectives. The studies published in this special section were conducted within Greenfield's theoretical framework (2009). The findings concerning links between specific sociodemographic features (e.g., commercial activities, schooling) and individual cognition and social behaviour are particularly interesting because they tap the underlying forces that drive human development. To further understand the issues in these studies and in the field, a pluralist-constructive perspective is discussed, which emphasises the integration of diverse values and practices in both Western and non-Western societies and its effects on the development of sophisticated competencies in individual adaptation to the changing global community. In addition, several issues are highlighted and some suggestions are provided for future explorations in this field. © 2014 International Union of Psychological Science.

  13. Leakage Implications for European Timber Markets from Reducing Deforestation in Developing Countries

    Directory of Open Access Journals (Sweden)

    Mattias Boman

    2012-08-01

    Full Text Available Forest management strategies and policies such as REDD (reduced emissions from deforestation and forest degradation may have unintentional implications for forest sectors in countries not targeted by such policies. The success of a policy effort like REDD would result in a significant reduction in deforestation and forest degradation and an ensuing reduction in the supply of natural forest timber production within participating countries. This could in turn result in price increases, inducing a supply response outside project boundaries with possible implications for forest management as well as global carbon emissions. This paper reviews the literature to discern potential timber market implications for countries sourcing wood products from developing countries affected by REDD related conservation efforts. The literature reviewed shows varying degrees of market effects leakage—policy actions in one place creating incentives for third parties to increase timber harvesting elsewhere through the price mechanism—ranging from negligible to substantial. However, wood products in the studies reviewed are dealt with on quite an aggregated scale and are assumed to be more or less perfect substitutes for wood products outside conservation effort boundaries. The review suggests that a thorough mapping of the end-uses of tropical timber is needed to comprehensively analyze impacts on wood-product markets in regions such as Europe from conservation efforts in tropical developing countries. The types of tropical timber expected to be affected, in which applications they are used, which are the most likely substitutes and where they would be sourced, are issues that, along with empirical analysis of supply and demand price elasticities and degree of substitutability, should be investigated when assessing the overall effectiveness of REDD.

  14. Behavioral competence as a positive youth development construct: conceptual bases and implications for curriculum development.

    Science.gov (United States)

    Ma, Hing Keung

    2006-01-01

    Behavioral competence refers to the ability to use non-verbal and verbal strategies to perform socially acceptable and normative behavior in social interactions. The main objective is to teach our children to be courteous, graceful, and fair so that they behave with respect and responsibility in social interactions with others. The importance of behavioral competence is discussed and it is emphasized that the competence to behave or act effectively must be based on a positive or prosocial motivation or disposition. The behavioral program units cover the following three types of behaviors: applause, criticism, and apology. The general goal is to foster the development of socially acceptable character, manner, and normative behavior. This paper is part of the development of the positive youth development program in Hong Kong.

  15. Recognition for Positive Behavior as a Critical Youth Development Construct: Conceptual Bases and Implications on Youth Service Development

    Directory of Open Access Journals (Sweden)

    Ben M. F. Law

    2012-01-01

    Full Text Available Recognition for positive behavior is an appropriate response of the social environment to elicit desirable external behavior among the youth. Such positive responses, rendered from various social systems, include tangible and intangible reinforcements. The following theories are used to explain the importance of recognizing positive behavior: operational conditioning, observational learning, self-determination, and humanistic perspective. In the current work, culturally and socially desirable behaviors are discussed in detail with reference to Chinese adolescents. Positive behavior recognition is especially important to adolescent development because it promotes identity formation as well as cultivates moral reasoning and social perspective thinking from various social systems. The significance of recognizing positive behavior is illustrated through the support, tutorage, invitation, and subsidy provided by Hong Kong’s social systems in recognition of adolescent volunteerism. The practical implications of positive behavior recognition on youth development programs are also discussed in this work.

  16. Mapping Gray Matter Development: Implications for Typical Development and Vulnerability to Psychopathology

    Science.gov (United States)

    Gogtay, Nitin; Thompson, Paul M.

    2010-01-01

    Recent studies with brain magnetic resonance imaging (MRI) have scanned large numbers of children and adolescents repeatedly over time, as their brains develop, tracking volumetric changes in gray and white matter in remarkable detail. Focusing on gray matter changes specifically, here we explain how earlier studies using lobar volumes of specific…

  17. Prosocial norms as a positive youth development construct: conceptual bases and implications for curriculum development.

    Science.gov (United States)

    Siu, Andrew M H; Cheng, Howard C H; Leung, Mana C M

    2006-01-01

    Prosocial norms are clear, healthy, ethical standards, beliefs, and behavior guidelines that promote prosocial behavior and minimize health risks. The promotion of prosocial norms like altruism, solidarity, and volunteerism is an important aspect of positive youth development programs. From the literature, it is evident that a prosocial orientation is encouraged in traditional Chinese philosophy. Longitudinal studies have shown that prosocial behavior increases gradually over adolescence, and that the development of prosocial behavior is closely linked to the development of moral reasoning, perspective taking, and regulation of personal distress. It is noteworthy that females have a higher prosocial orientation than males, and peer influence could be a major mediating factor of interventions to foster prosocial norms and behavior during adolescence. This review also analyzes the mechanism underlying prosocial behavior using the cost-reward model, social cognitive theory, and stages of moral development. Role modeling, social reinforcements and evaluations, discussion of moral dilemmas, empathy skills training, and foot-in-the-door procedures are identified as useful strategies for fostering prosocial norms and behavior.

  18. Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

    OpenAIRE

    Wills, Brandon K.; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

    2010-01-01

    Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80–90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symp...

  19. The implications of future building scenarios for long-term building energy research and development

    Energy Technology Data Exchange (ETDEWEB)

    Flynn, W.T.

    1986-12-01

    This report presents a discussion of alternative future scenarios of the building environment to the year 2010 and assesses the implications these scenarios present for long-term building energy R and D. The scenarios and energy R and D implications derived from them are intended to serve as the basis from which a strategic plan can be developed for the management of R and D programs conducted by the Office of Buildings and Community Systems, US Department of Energy. The scenarios and analysis presented here have relevance not only for government R and D programs; on the contrary, it is hoped that the results of this effort will be of interest and useful to researchers in both private and public sector organizations that deal with building energy R and D. Making R and D decisions today based on an analysis that attempts to delineate the nexus of events 25 years in the future are clearly decisions made in the face of uncertainty. Yet, the effective management of R and D programs requires a future-directed understanding of markets, technological developments, and environmental factors, as well as their interactions. The analysis presented in this report is designed to serve that need. Although the probability of any particular scenario actually occurring is uncertain, the scenarios to be presented are sufficiently robust to set bounds within which to examine the interaction of forces that will shape the future building environment.

  20. Development of the carapacial ridge: implications for the evolution of genetic networks in turtle shell development.

    Science.gov (United States)

    Moustakas, Jacqueline E

    2008-01-01

    Paleontologists and neontologists have long looked to development to understand the homologies of the dermal bones that form the "armor" of turtles, crocodiles, armadillos, and other vertebrates. This study shows molecular evidence supporting a dermomyotomal identity for the mesenchyme of the turtle carapacial ridge. The mesenchyme of the carapace primordium expresses Pax3, Twist1, Dermo1, En1, Sim1, and Gremlin at early stages and before overt ossification expresses Pax1. A hypothesis is proposed that this mesenchyme forms dermal bone in the turtle carapace. A comparison of regulatory gene expression in the primordia of the turtle carapace, the vertebrate limb, and the vertebral column implies the exaptation of key genetic networks in the development of the turtle shell. This work establishes a new role for this mesodermal compartment and highlights the importance of changes in genetic regulation in the evolution of morphology.

  1. Solvent neurotoxicity in vehicle collision repair workers in New Zealand.

    Science.gov (United States)

    Keer, Samuel; Glass, Bill; Prezant, Bradley; McLean, David; Pearce, Neil; Harding, Elizabeth; Echeverria, Diana; McGlothlin, James; Babbage, Duncan R; Douwes, Jeroen

    2016-12-01

    To assess whether solvent use and workplace practices in the vehicle collision repair industry are associated with symptoms of neurotoxicity in spray painters and panel beaters (auto body repair workers). Neurobehavioural symptoms were assessed using a cross-sectional study design in 370 vehicle collision repair and 211 reference workers using the EUROQUEST questionnaire. Full-shift airborne solvent levels were measured in a subset (n=92) of collision repair workers. Solvent exposures were higher in spray painters than in panel beaters, but levels were below current international exposure standards. Collision repair workers were more likely to report symptoms of neurotoxicity than reference workers with ORs of 2.0, 2.4 and 6.4 (all p<0.05) for reporting ≥5, ≥10 and ≥15 symptoms respectively. This trend was generally strongest for panel beaters (ORs of 2.1, 3.3 and 8.2 for ≥5, ≥10 and ≥15 symptoms respectively). Associations with specific symptom domains showed increased risks for neurological (OR 4.2), psychosomatic (OR 3.2), mood (OR 2.1), memory (OR 2.9) and memory and concentration symptoms combined (OR 2.4; all p<0.05). Workers who had worked for 10-19 years or 20+ years in the collision repair industry reported consistently more symptoms than those who had only worked less than 10 years even after adjusting for age. However, those who worked more than 20 years generally reported fewer symptoms than those who worked 10-19 years, suggesting a possible healthy worker survivor bias. Despite low airborne solvent exposures, vehicle collision repair spray painters and panel beaters continue to be at risk of symptoms of neurotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. INCOME AND ENERGY SOURCES AMONG AGRARIAN HOUSEHOLDS IN NIGERIA: IMPLICATIONS FOR LOW CARBON ENERGY DEVELOPMENT IN LESS DEVELOPED COUNTRIES

    Directory of Open Access Journals (Sweden)

    M. Mkpado

    2012-07-01

    Full Text Available Low-carbon power comes from sources that produce fewer greenhouse gases than do traditional means of power generation. It includes zero carbon power generation sources, such as wind power, solar power, geothermal power and (except for fuel preparation nuclear power, as well as sources with lower-level emissions such as natural and petroleum gas, and also technologies that prevent carbon dioxide from being emitted into the atmosphere, such as carbon capture and storage. This article correlated value of income from different sources to energy sources used by agrarian households in Nigeria and drew implications for low carbon development in Africa. It analysis included use of wind power for irrigation purposes, harnessing solar energy for lightening and possible cost implications. Secondary data were collected from Community Based Monitoring System Nigeria Project. Descriptive statistics, correlation and qualitative analysis were employed. The average annual income of agrarian households from different sources such as crop farming, livestock farming, petty trading, forest exploitation, remittance and labour per day was below the poverty line of $1 per day. The source of energy that had the highest number of significant correlation was electrical energy (low carbon electrical energy. It showed the possibility of pooling resources as farmers group to attract grants or equity financing to build wind mills for irrigation. The study recommended use of energy efficient bulbs to reduce CO2 emissions. This requires creating awareness among rural dwellers of the need to make such change.

  3. Health assessment of gasoline and fuel oxygenate vapors: Neurotoxicity evaluation

    OpenAIRE

    O?Callaghan, James P.; Daughtrey, Wayne C.; Clark, Charles R.; Schreiner, Ceinwen A.; White, Russell

    2014-01-01

    Sprague?Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from ?baseline gasoline? (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrati...

  4. Neurotoxicity from prenatal and postnatal exposure to methylmercury

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Weihe, Pal; Debes, Frodi

    2014-01-01

    exposure appeared to contribute to neurotoxic effects, in particular in regard to visuospatial processing and memory. Thus, addition in the regression analysis of exposure information obtained at a different point in time was not informative and should be avoided. Further studies with better information......, but visuospatial memory revealed a significant negative association. Mutual adjustment caused decreases of the apparent effect of the prenatal exposure. However, such adjustment may lead to underestimations due to the presence of correlated, error-prone exposure variables. In structural equation models, all...

  5. Bilirubin-Induced Neurotoxicity in the Preterm Neonate.

    Science.gov (United States)

    Watchko, Jon F

    2016-06-01

    Bilirubin-induced neurotoxicity in preterm neonates remains a clinical concern. Multiple cellular and molecular cascades likely underlie bilirubin-induced neuronal injury, including plasma membrane perturbations, excitotoxicity, neuroinflammation, oxidative stress, and cell cycle arrest. Preterm newborns are particularly vulnerable secondary to central nervous system immaturity and concurrent adverse clinical conditions that may potentiate bilirubin toxicity. Acute bilirubin encephalopathy in preterm neonates may be subtle and manifest primarily as recurrent symptomatic apneic events. Low-bilirubin kernicterus continues to be reported in preterm neonates, and although multifactorial in nature, is often associated with marked hypoalbuminemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.

    Science.gov (United States)

    Miyanishi, Hiroshi; Okubo, Kataaki; Nobata, Shigenori; Takei, Yoshio

    2013-01-01

    Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.

  7. Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    So Yeon Kim

    2015-11-01

    Full Text Available Hypoxia-inducible factor (HIF prolyl hydroxylases (PHDs are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.

  8. Thyroid hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis.

    Science.gov (United States)

    Sun, Guihong; Roediger, Julia; Shi, Yun-Bo

    2016-12-01

    Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases.

  9. Implications Of Foreign Direct Investment, Financial Development And Real Exchange Rate For Economic Growth In Cameroon

    Directory of Open Access Journals (Sweden)

    Victalice Ngimanang Achamoh

    2016-05-01

    Full Text Available This paper assesses the effects of foreign direct investment (FDI, financial development and real exchange rate (RER on economic growth in Cameroon using Cameroon’s annual time series data spanning the period 1977 - 2010. To address these objectives, residual based Engle-Granger test, the OLS based Autoregressive Distributive Lag (ARDL bound testing and maximum likelihood based Johansen cointegration techniques are employed. Results of Unit roots tests show that all the series possessed unit roots at level or first difference form. The ARDL model and VECM results reveal that the RER has a significant negative effect on economic growth, while FDI and Financial Development relate positively to economic growth. These findings have implications for stimulating economic growth by increasing efficiency of the financial sector in allocating credit to the private sector and preventing real exchange rate appreciation in the shortrun.

  10. Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing

    International Nuclear Information System (INIS)

    Hill, E.J.; Woehrling, E.K.; Prince, M.; Coleman, M.D.

    2008-01-01

    Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro

  11. Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2'-methyl-MPTP.

    Science.gov (United States)

    Sziráki, I; Kardos, V; Patthy, M; Pátfalusi, M; Gaál, J; Solti, M; Kollár, E; Singer, J

    1994-01-01

    The ability of 1-deprenyl to protect against the parkinsonian effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been attributed to the inhibition of conversion of MPTP to MPP+ (1-methyl-4-phenylpyridinium) catalyzed by MAO-B. We report here that deprenyl-treatment in mice has an additional neuroprotective element associated with the rapid metabolization of 1-deprenyl to 1-methamphetamine and 1-amphetamine. 1-Methamphetamine and 1-amphetamine inhibit MPP(+)-uptake into striatal synaptosomes prepared from rats. Post-treatment by 1-deprenyl, 1-methamphetamine, 1-amphetamine (at times when MPTP is no longer present in the striatum of mice) protects against neurotoxicity in C57BL mice by blocking the uptake of MPP+ into dopaminergic neurons, and even against the neurotoxicity induced by 2'CH3-MPTP, which is partly bioactivated by MAO-A. These findings may have clinical implications since deprenyl has recently been found to delay the progression of Parkinson's disease.

  12. [Toxicodynamic properties of liquids used for the cooling of high-power turbines. III. Neurotoxic effects].

    Science.gov (United States)

    Florek, E; Malendowicz, L; Seńczuk, W

    1984-01-01

    Results of neurotoxicity studies indicate that preparations IWiOL -3-n, IWiOL -3-e and OMTI administered intragastrically or intraperitoneally induce neurotoxic effects in hens. Those effects are, however, weaker than those of the standard substance, i.e. triorthocresyl . Yet, they get increased in result of IWiOL -3-e, as compared to IWiOL -3-n administration.

  13. Evaluating the Effects of Chemicals on Nervous System Development

    Science.gov (United States)

    There are thousands of chemicals that lack data on their potential effects on neurodevelopment. EPA is developing New Approach Methods to evaluate these chemicals for developmental neurotoxicity hazard.

  14. Late neurotoxicity after nasopharyngeal carcinoma treatment

    International Nuclear Information System (INIS)

    Siala, W.; Mnejja, W.; Daoud, J.; Khabir, A.; Boudawara, T.; Ben Mahfoudh, K.; Ghorbel, A.; Frikha, M.

    2009-01-01

    Purpose A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy. Patients and methods Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity. Results After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p = 0.02). On multivariate analysis, hyperfractionation and age were insignificant. Conclusion Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study

  15. Neurotoxic response of infant monkeys to methylmercury

    Energy Technology Data Exchange (ETDEWEB)

    Willes, R.F.; Truelove, J.F.; Nera, E.A.

    1978-02-01

    Four infant monkeys were dosed orally with 500 ..mu..g Hg/kg body wt./day (as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28 to 29 days of treatment; the blood Hg levels were 8.0 to 9.4 ..mu..g Hg/g blood. Dosing was terminated at 28 to 29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35 to 43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver followed by occipital cortex and renal cortex. The mean blood/brain ratio was 0.21 +- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

  16. Neurotoxic response of infant monkeys to methylmercury.

    Science.gov (United States)

    Willes, R F; Truelove, J F; Nera, E A

    1978-02-01

    Four infant monkeys were dosed orally with 500 microgram Hg/kg body wt./day /as methylmercury (MeHg) chloride dissolved sodium carbonate) beginning at 1 day of age. Neurological and behavioral signs of MeHg toxicity and blood Hg levels were monitored weekly. At first sign of MeHg intoxication, dosing with MeHg was terminated and the infants were monitored to assess reversal of the signs of MeHg toxicity. The first signs of MeHg toxicity, exhibited as a loss in dexterity and locomotor ability, were observed after 28--29 days of treatment; the blood Hg levels were 8.0--9.4 microgram Hg/g blood. Dosing was terminated at 28--29 days of treatment but the signs of MeHg toxicity continued to develop. The infants became ataxic, blind, comatose and were necropsied at 35--43 days after initiating treatment with MgHg. The mercury concentrations in tissues analyzed after necropsy were highest in liver (55.8 +/- 3.2 microgram Hg/g) followed by occipital cortex (35.6 +/- 4.8 microgram Hg/g) renal cortex (32.8 +/- 1.6 microgram Hg/g). The frontal and temporal cortices had 27.0 +/- 3.4 and 29.6 +/- 4.9 microgram Hg/g respectively while the cerebellar Hg concentration averaged 13.0 +/- 1.5 microgram Hg/g. The mean blood/brain ratio was 0.21 +/- 0.4. Histopathologic lesions were marked in the cerebrum with less severe lesions in the cerebellar nuclei. The Purkinje and granular cells of the cerebellar vermis appeared histologically normal. Lesions were not observed in the peripheral nervous system. The signs of MeHg intoxication, the tissue distribution of MeHg and histopathologic lesions observed in the infant monkeys were similar to those reported for adult monkeys.

  17. Modulation of bilirubin neurotoxicity by the Abcb1 transporter in the Ugt1-/- lethal mouse model of neonatal hyperbilirubinemia.

    Science.gov (United States)

    Bockor, Luka; Bortolussi, Giulia; Vodret, Simone; Iaconcig, Alessandra; Jašprová, Jana; Zelenka, Jaroslav; Vitek, Libor; Tiribelli, Claudio; Muro, Andrés F

    2017-01-01

    Moderate neonatal jaundice is the most common clinical condition during newborn life. However, a combination of factors may result in acute hyperbilirubinemia, placing infants at risk of developing bilirubin encephalopathy and death by kernicterus. While most risk factors are known, the mechanisms acting to reduce susceptibility to bilirubin neurotoxicity remain unclear. The presence of modifier genes modulating the risk of developing bilirubin-induced brain damage is increasingly being recognised. The Abcb1 and Abcc1 members of the ABC family of transporters have been suggested to have an active role in exporting unconjugated bilirubin from the central nervous system into plasma. However, their role in reducing the risk of developing neurological damage and death during neonatal development is still unknown.To this end, we mated Abcb1a/b-/- and Abcc1-/- strains with Ugt1-/- mice, which develop severe neonatal hyperbilirubinemia. While about 60% of Ugt1-/- mice survived after temporary phototherapy, all Abcb1a/b-/-/Ugt1-/- mice died before postnatal day 21, showing higher cerebellar levels of unconjugated bilirubin. Interestingly, Abcc1 role appeared to be less important.In the cerebellum of Ugt1-/- mice, hyperbilirubinemia induced the expression of Car and Pxr nuclear receptors, known regulators of genes involved in the genotoxic response.We demonstrated a critical role of Abcb1 in protecting the cerebellum from bilirubin toxicity during neonatal development, the most clinically relevant phase for human babies, providing further understanding of the mechanisms regulating bilirubin neurotoxicity in vivo. Pharmacological treatments aimed to increase Abcb1 and Abcc1 expression, could represent a therapeutic option to reduce the risk of bilirubin neurotoxicity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Meeting electrification's social objectives in South Africa, and implications for developing countries

    International Nuclear Information System (INIS)

    Gaunt, C.T.

    2005-01-01

    Electrification programmes and projects are usually planned and evaluated on the basis of their economic (financial) and socio-economic performance. It is not usually recognised that electrification is often carried out for social objectives of poverty alleviation and political effect. Examination of electrification in South Africa reveals clearly that initial electrification was to meet economic objectives, later socio-economic objectives were adopted, and recently the objectives were social. Social electrification, particularly rural electrification, is not viable according to usual assessment methods, which are frequently distorted to provide the justification for a project to proceed. The technology of network electrification changed to meet the constraints, challenging usual perceptions about the relative costs of urban and rural electrification and the potential for photovoltaic electrification. Adopting a specification for social electrification allows suitable tariffs for electrification to be identified, indicates how capital investment decisions might be modified for social electrification, and identifies implications for electricity industry restructuring. A better understanding of electrification's social objectives has implications for projects and programmes in other developing countries

  19. Prosocial involvement as a positive youth development construct: conceptual bases and implications for curriculum development.

    Science.gov (United States)

    Cheng, Howard C H; Siu, Andrew M H; Leung, Mana C M

    2006-01-01

    Pro-social involvement programmes are significant and important for the healthy growth of adolescents as well as for the development of society. Pro-social involvement of adolescence refers to paid-job, volunteer works, sport and games. It serves the functions of making adolescents aware of and to accept the social norms and moral standard of the society, which would bring positive changes to the adolescents and consequently benefit the society as a whole. Past studies showed that adolescents who participated in pro-social involvement programmes tended to have positive self-perception, more social skills, and less anti-social behaviors. In Hong Kong, professionals in education and social services have fully recognized the benefits of pro-involvement programmes. They have organized multi-level and diverse pro-social involvement programmes and encouraged adolescents to participate. Through participation, adolescents could be helped to redefine their relationship with the society, and maximize their potentials for growth. The current programme described in this article is designed in the P.A.T.H.S. Project, support by the Hong Kong Jockey Club Charities Trust.

  20. Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms.

    Science.gov (United States)

    Burke, Richard D; Todd, Spencer W; Lumsden, Eric; Mullins, Roger J; Mamczarz, Jacek; Fawcett, William P; Gullapalli, Rao P; Randall, William R; Pereira, Edna F R; Albuquerque, Edson X

    2017-08-01

    Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  1. Implications of sustainability constraints on UK bioenergy development: Assessing optimistic and precautionary approaches with UK MARKAL

    International Nuclear Information System (INIS)

    McDowall, Will; Anandarajah, Gabrial; Dodds, Paul E.; Tomei, Julia

    2012-01-01

    Bioenergy is an important renewable energy resource. However, assessments of the future of bioenergy are beset with uncertainty and contested values, suggesting that a precautionary approach to bioenergy resource development may be warranted. This paper uses UK MARKAL to examine the implications of adopting a precautionary approach to bioenergy development in the UK. The paper reports a detailed review of UK bioenergy resources and sustainability constraints, and develops precautionary and optimistic resource scenarios. The paper then examines the implications of these scenarios using the energy systems model MARKAL, finding that a precautionary approach adds to the cost of decarbonisation, but does not significantly alter the optimal technology mix. In particular, biomass and co-firing CCS emerge as optimal technologies across scenarios. The question of UK land availability for bioenergy production is highlighted within the paper. With less land available for bioenergy production, the costs of decarbonisation will rise; whereas if more land is available for bioenergy, then less land is available for either food production or ecosystem conservation. This paper quantifies one side of this trade-off, by estimating the additional costs incurred when UK land availability for bioenergy production is constrained. - Highlights: ► We assess UK bioenergy resources under optimistic and precautionary approaches. ► Using MARKAL, we find that sustainability constraints add to decarbonisation costs. ► Preferred use of bioenergy is similar in optimistic and precautionary cases. ► Best use of bioenergy is heat and power, not transport, if CCS is available. ► The marginal value of additional land availability to the energy system is high.

  2. CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY: INTERACTION WITH GLUCOCORTICOIDS IN PC12 CELLS

    Science.gov (United States)

    Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

    2012-01-01

    Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on concentrations relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuri to genesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent. PMID:22796634

  3. Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds

    Science.gov (United States)

    Voorhees, Jaymie R.; Rohlman, Diane S.; Lein, Pamela J.; Pieper, Andrew A.

    2017-01-01

    Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally. PMID:28149268

  4. A neurotoxicity assessment of high flash aromatic naphtha.

    Science.gov (United States)

    Douglas, J F; McKee, R H; Cagen, S Z; Schmitt, S L; Beatty, P W; Swanson, M S; Schreiner, C A; Ulrich, C E; Cockrell, B Y

    1993-01-01

    Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide-boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 Aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent also known as High Flash Aromatic Naphtha (HFAN). A program was initiated to assess the toxicological properties of HFAN since there may be human exposure, especially in the workplace. The current study was conducted to assess the potential for neurotoxicity in the rat. Adult male Sprague-Dawley rats of approximately 300 grams body weight, in groups of twenty, were exposed by inhalation to HFAN for 90 days at concentrations of 0, 100, 500, and 1500 ppm. During this period the animals were tested monthly for motor activity and in a functional observation battery. After three months of exposure, for 6 hours/day, 5 days/week, 10 animals/group/sex were sacrificed and selected nervous system tissue was examined histopathologically. No signs of neurotoxicity were seen in any of the evaluated parameters, nor was there evidence of pathologic changes in any of the examined tissues.

  5. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

    Science.gov (United States)

    Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

    2015-01-01

    Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P neuropathy (P peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

  6. Lead neurotoxicity: In vitro and in vivo effects

    International Nuclear Information System (INIS)

    Rowles, T.K.

    1989-01-01

    Neuroglial cells, in particular astroglia, are thought to play a role in the neurotoxicity of lead. Two hypotheses have been proposed as possible cellular mechanism of this neurotoxicity: (1) lead affects intracellular levels of metals which mediate the toxic effects noted, and (2) lead affects intracellular heme biosynthesis which is then toxic to the cells. Zinc was found to have a profound effect on both intracellular lead levels and on cell numbers in lead-treated rat astroglia. A comparison of bovine and rat astroglia in culture indicated that the bovine cell cultures were not more sensitive to lead, even though calves are more sensitive. Lead was also shown to affect intracellular heme biosynthesis by a decrease in 14 C aminolevulinic acid incorporation into extractable heme in lead-treated rat astroglia. Finally, low levels of lead in immature guinea pigs caused changes in tissue levels of lead, iron, copper, and zinc with no change in weight gain or body:brain weight ratios

  7. Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure.

    Science.gov (United States)

    Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

    2016-06-01

    Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131-141, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Rachelle Balez

    2016-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder involving the loss of neurons in the brain which leads to progressive memory loss and behavioral changes. To date, there are only limited medications for AD and no known cure. Nitric oxide (NO has long been considered part of the neurotoxic insult caused by neuroinflammation in the Alzheimer’s brain. However, focusing on early developments, prior to the appearance of cognitive symptoms, is changing that perception. This has highlighted a compensatory, neuroprotective role for NO that protects synapses by increasing neuronal excitability. A potential mechanism for augmentation of excitability by NO is via modulation of voltage-gated potassium channel activity (Kv7 and Kv2. Identification of the ionic mechanisms and signaling pathways that mediate this protection is an important next step for the field. Harnessing the protective role of NO and related signaling pathways could provide a therapeutic avenue that prevents synapse loss early in disease.

  9. Economic benefits of methylmercury exposure control in Europe: Monetary value of neurotoxicity prevention

    Science.gov (United States)

    2013-01-01

    Background Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. Methods Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. Results The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. Conclusions These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial

  10. Evidence for hydroxyl radical scavenging action of nitric oxide donors in the protection against 1-methyl-4-phenylpyridinium-induced neurotoxicity in rats.

    Science.gov (United States)

    Banerjee, Rebecca; Saravanan, Karuppagounder S; Thomas, Bobby; Sindhu, Kizhake M; Mohanakumar, Kochupurackal P

    2008-06-01

    In the present study we provide evidence for hydroxyl radical (*OH) scavenging action of nitric oxide (NO*), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO* donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro *OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced *OH production in the mitochondria. We also tested whether co-administration of NO* donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced *OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in *OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO*, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of *OH in the nigrostriatal degeneration caused by MPP+, indicate the *OH scavenging ability of NO*, and demonstrate protection by NO* donors against MPP+-induced dopaminergic neurotoxicity in rats.

  11. Exploring the notion of a 'capability for uncertainty' and the implications for leader development

    Directory of Open Access Journals (Sweden)

    Kathy Bennett

    2016-10-01

    Full Text Available Orientation: With uncertainty increasingly defining organisational contexts, executive leaders need to develop their ‘capability for uncertainty’ – the ability to engage with uncertainty in their organisational context and to lead others, while simultaneously managing their own experience of uncertainty. However, what constitutes such a holistic ‘capability for uncertainty’ is not clear. Research purpose: The purpose was to gain an understanding of what constitutes a capability for uncertainty. Motivation for the study: Gaining an understanding of what components constitute leaders’ capability for uncertainty would provide a basis for determining what interventions would be relevant for developing leaders towards achieving such a capability. Research approach, design and method: An interpretive qualitative approach was adopted, using interpretative phenomenological analysis to gain an understanding of what capability executive leaders developed through their lived experience of uncertainty. Two purposive samples of six executive leaders from two different South African companies (a private company and a state-owned company, which had both been experiencing long-term organisational uncertainty prior to and up to the time of the study, were used. Data were collected through semi-structured interviews. Main findings: The executives all developed their capability for uncertainty through lived experiences of uncertainty, to a greater or lesser extent. Five components were identified as constituting a holistic capability for uncertainty, as follows: a sense of positive identity, an acceptance of uncertainty, effective sense-making, learning agility and relevant leadership practices during organisational uncertainty. Practical/managerial implications: Organisations need to target and design leader development interventions to specifically develop these components of a holistic capability for uncertainty in executives and leaders, enabling

  12. Weaning stress and gastrointestinal barrier development: Implications for lifelong gut health in pigs

    Directory of Open Access Journals (Sweden)

    Adam J. Moeser

    2017-12-01

    Full Text Available The gastrointestinal (GI barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous systems. Together they act in concert to control normal gut functions (e.g., digestion, absorption, secretion, immunity, etc. whereas at the same time provide a barrier from the hostile conditions in the luminal environment. Breakdown of these critical GI functions is a central pathophysiological mechanism in the most serious GI disorders in pigs. This review will focus on the development and functional properties of the GI barrier in pigs and how common early life production stressors, such as weaning, can alter immediate and long-term barrier function and disease susceptibility. Specific stress-related pathophysiological mechanisms responsible for driving GI barrier dysfunction induced by weaning and the implications to animal health and performance will be discussed.

  13. Developments in National Fuel Alcohol (biofuel) Programs: implications for world sugar trade. Rev. ed.

    International Nuclear Information System (INIS)

    1998-01-01

    This paper focuses on developments in the national fuel alcohol programmes of Brazil, the European Union and USA with the main emphasis on Brazil. A brief history of Brazil's alcohol production is given, and the deregulation of the alcohol sector in Brazil, the impacts of partial liberalisation of Brazil's alcohol sector, government delays in further liberalisation and attempts to manage supply, the PROALCOOL programme, the government's actions to boost ethanol demand, the slump in ethanol output in 1998/1999, and the increase in sugar output are examined. The long term goal of increasing reliance on biofuels in the European Union, the EU's alcohol industry, and ethanol production in France are considered. Market factors affecting ethanol production in the US, the US government's extension of its ethanol tax incentive, the US ethanol sector, and the future demand for ethanol in the US are discussed. The short and medium-term implications for sugar in Brazil, the EU and the US are assessed. (UK)

  14. Experience as Knowledge in a New Product Development Team: Implications for Knowledge Management

    Science.gov (United States)

    Cooper, Lynne P.

    2009-01-01

    This study was conducted to better understand how New Product Development (NPD) team members apply their experiences to meet the task needs of their project. Although "experience" is highly valued in team members, little research has looked specifically at experiences as a type of knowledge, and how this knowledge is used in work settings. This research evaluated nearly 200 instances where team members referenced past experiences during team meetings. During these experience exchanges, team members structured the sharing of their experiences to include three common elements: the source of the experience, the nature of the experience, and the degree of relevance to the current work of the team. The experiences fell into four categories: people (relationships), process, product, and politics. This paper describes how team members structured, applied, and integrated their individual experiences and presents the resulting implications for knowledge management systems that wish to exploit experience knowledge.

  15. Uranium resources and their implications for fission breeder and fusion hybrid development

    International Nuclear Information System (INIS)

    Max, C.E.

    1984-01-01

    Present estimates of uranium resources and reserves in the US and the non-Communist world are reviewed. The resulting implications are considered for two proposed breeder technologies: the liquid metal fast breeder reactor (LMFBR) and the fusion hybrid reactor. Using both simple arguments and detailed scenarios from the published literature, conditions are explored under which the LMFBR and fusion hybrid could respectively have the most impact, considering both fuel-supply and economic factors. The conclusions emphasize strong potential advantages of the fusion hybrid, due to its inherently large breeding rate. A discussion is presented of proposed US development strategies for the fusion hybrid, which at present is far behind the LMFBR in its practical application and maturity

  16. The clean development mechanism (CDM) an international perspective and implications for the LAC region

    International Nuclear Information System (INIS)

    2004-08-01

    This paper addresses activity a) an analysis of international CDM experiences and its potential contribution to the LAC region. The paper begins with a section describing the basic principles of the CDM and retrieves the lessons learned from the first two years of the CDM operation. This is followed by a more detailed review in section 2 of the on-going baseline and monitoring methodology approval process. In section 3, the development value of the CDM is explored. Section 4 describes the current CDM markets, while section 5 reviews the response of host countries to the CDM outside the LAC region. Section 6 describes the various capacity building programs established by Annex 1 countries to support the CDM. In each of the first 6 sections, implications for the LAC region are identified. Section 7 brings these conclusions together into a concise summary. (The author)

  17. The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.

    Science.gov (United States)

    Lu, Lin; Dong, Haixia; Liu, Guixiang; Yuan, Bin; Li, Yizhao; Liu, Huaxiang

    2014-11-01

    Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

  18. The neurotoxic effects of prenatal gabapentin and oxcarbazepine exposure on newborn rats.

    Science.gov (United States)

    Erisgin, Zuleyha; Ayas, Bulent; Nyengaard, Jens R; Ercument Beyhun, N; Terzi, Yuksel

    2017-10-05

    Teratogenicity is a problematic issue for pregnant women because of X-ray radiation, drugs, and genetic and unknown variables. First-generation antiepileptic drugs (AED) like valproic acid are well-known teratogens for developing fetuses. However, their usage is necessary in order to prevent maternal seizures. The underlying mechanism of birth defects associated with AED exposure remains unclear and information about the neurotoxic effects of prenatal exposure to AED is still limited. Oxcarbazepine (OXC) and gabapentin (GBP) are second-generation AED. It still remains unclear how much these drugs are safe during pregnancy. This study aimed to investigate whether any neurotoxic effect of OXC and GBP in utero exposure on the developing brain. Eighteen pregnant Wistar albino rats were divided into six groups. The first group was exposed to OXC at 100 mg/kg/day, the second to GBP at 50 mg/kg/day, and third to saline (0.9% NaCl) at 1.5 ml/day between the first and the fifth days of gestation. The same procedure was applied at the same dosages between the 6th and the 15th days of gestation for the 2nd three groups. Five female offspring (total n = 30, 45 days old) were taken from each group and stereological methods were applied in order to analyze the total and dopaminergic neuron number of the substantia nigra pars compacta (SNc). The result is that the OXC and GBP exposure at different gestational periods may not give rise to congenital malformation and it appears that the GBP exposure during the organogenesis period proliferatively affects the total number of neurons.

  19. Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.

    Science.gov (United States)

    Schiffer, Joshua T; Gottlieb, Sami L

    2017-09-25

    Development of a safe and effective vaccine against herpes simplex virus type 2 (HSV-2) has the potential to limit the global burden of HSV-2 infection and disease, including genital ulcer disease and neonatal herpes, and is a global sexual and reproductive health priority. Another important potential benefit of an HSV-2 vaccine would be to decrease HIV infections, as HSV-2 increases the risk of HIV-1 acquisition several-fold. Acute and chronic HSV-2 infection creates ulcerations and draws dendritic cells and activated CD4+ T cells into genital mucosa. These cells are targets for HIV entry and replication. Prophylactic HSV-2 vaccines (to prevent infection) and therapeutic vaccines (to modify or treat existing infections) are currently under development. By preventing or modifying infection, an effective HSV-2 vaccine could limit HSV-associated genital mucosal inflammation and thus HIV risk. However, a vaccine might have competing effects on HIV risk depending on its mechanism of action and cell populations generated in the genital mucosa. In this article, we review biologic interactions between HSV-2 and HIV-1, consider HSV-2 vaccine development in the context of HIV risk, and discuss implications and research needs for future HSV vaccine development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Sustainable development, demography and sexual and reproductive health: inseparable linkages and their policy implications.

    Science.gov (United States)

    Herrmann, Michael

    2014-05-01

    The greatest challenge today is to meet the needs of current and future generations, of a large and growing world population, without imposing catastrophic pressures on the natural environment. Meeting this challenge depends on decisive policy changes in three areas: more inclusive economic growth, greener economic growth, and population policies. This article focuses on efforts to address and harness demographic changes for sustainable development, which are largely outside the purview of the current debate. Efforts to this end must be based on the recognition that demographic changes are the cumulative result of individual choices and opportunities, and that demographic changes are best addressed through policies that enlarge these choices and opportunities, with a focus on ensuring unrestricted and universal access to sexual and reproductive health information and services, empowering women to fully participate in social, economic and political life, and investing in the education of the younger generation beyond the primary level. The article provides a strong argument for why the Programme of Action that was agreed at the International Conference on Population and Development (ICPD) 20 years ago continues to hold important implications and lessons for the formulation of the post-2015 development agenda, which is expected to supersede the Millennium Development Goals (MDGs). Copyright © 2014 Reproductive Health Matters. Published by Elsevier Ltd. All rights reserved.

  1. The Water Demand of Energy: Implications for Sustainable Energy Policy Development

    Directory of Open Access Journals (Sweden)

    Kaveh Madani

    2013-11-01

    Full Text Available With energy security, climate change mitigation, and sustainable development as three main motives, global energy policies have evolved, now asking for higher shares of renewable energies, shale oil and gas resources in the global energy supply portfolios. Yet, concerns have recently been raised about the environmental impacts of the renewable energy development, supported by many governments around the world. For example, governmental ethanol subsidies and mandates in the U.S. are aimed to increase the biofuel supply while the water footprint of this type of energy might be 70–400 times higher than the water footprint of conventional fossil energy sources. Hydrofracking, as another example, has been recognized as a high water-intensive procedure that impacts the surface and ground water in both quality and quantity. Hence, monitoring the water footprint of the energy mix is significantly important and could have implications for energy policy development. This paper estimates the water footprint of current and projected global energy policies, based on the energy production and consumption scenarios, developed by the International Energy Outlook of the U.S. Energy Information Administration. The outcomes reveal the amount of water required for total energy production in the world will increase by 37%–66% during the next two decades, requiring extensive improvements in water use efficiency of the existing energy production technologies, especially renewables.

  2. Phloem development in nematode-induced feeding sites: The implications of auxin and cytokinin

    Directory of Open Access Journals (Sweden)

    Birgit eAbsmanner

    2013-07-01

    Full Text Available Sedentary plant parasitic nematodes such as root-knot nematodes and cyst nematodes induce giant cells or syncytia, respectively, in their host plant’s roots. These highly specialized structures serve as feeding sites from which exclusively the nematodes withdraw nutrients. While giant cells are symplastically isolated and obtain assimilates by transporter-mediated processes syncytia are massively connected to the phloem by plasmodesmata. To support the feeding sites and the nematode during their development, phloem is induced around syncytia and giant cells. In the case of syncytia the unloading phloem consists of sieve elements and companion cells and in the case of root knots it consists exclusively of sieve elements. We applied immunohistochemistry to identify the cells within the developing phloem that responded to auxin and cytokinin. Both feeding sites themselves did not respond to either hormone. We were able to show that in root knots an auxin response precedes the differentiation of these auxin responsive cells into phloem elements. This process appears to be independent of B-type Arabidopsis response regulators. Using additional markers for tissue identity we provide evidence that around giant cells protophloem is formed and proliferates dramatically. In contrast, the phloem around syncytia responded to both hormones. The presence of companion cells as well as hormone-responsive sieve elements suggests that metaphloem development occurs. The implication of auxin and cytokinin in the further development of the metaphloem is discussed.

  3. Assessment of attention and inhibitory control in rodent developmental neurotoxicity studies.

    Science.gov (United States)

    Driscoll, Lori L; Strupp, Barbara J

    2015-01-01

    In designing screens to assess potential neurotoxicants, the paramount goal is that the selected assessment tools detect dysfunction if it exists. This goal is particularly challenging in the case of cognitive assessments. Cognition is not a unitary phenomenon, and indeed there is growing evidence that different aspects of cognitive functioning are subserved by distinct neural systems. As a result, if a particular neurotoxicant selectively damages certain neural systems but not others, it can impair some cognitive, sensory, or affective functions, but leave many others intact. Accordingly, studies with human subjects use batteries of cognitive tests, cognizant of the fact that no one test is capable of detecting all forms of cognitive dysfunction. In contrast, assessment of cognitive functioning in non-human animal developmental neurotoxicity (DNT) studies typically consists of a single, presumably representative, "learning and memory" task that is expected to detect all potential effects on cognitive functioning. Streamlining the cognitive assessment in these studies saves time and money, but these shortcuts can have serious consequences if the aspect of cognitive functioning that is impaired is not tapped by the single selected task. In particular, executive functioning - a constellation of cognitive functions which enables the organism to focus on multiple streams of information simultaneously, and revise plans as necessary - is poorly assessed in most animal DNT studies. The failure to adequately assess these functions - which include attention, working memory, inhibitory control, and planning - is particularly worrisome in light of evidence that the neural systems that subserve these functions may be uniquely vulnerable to early developmental insults. We illustrate the importance of tapping these areas of functioning in DNT studies by describing the pattern of effects produced by early developmental Pb exposure. Rats exposed to lead (Pb) early in development

  4. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    International Nuclear Information System (INIS)

    Schallreuter, Karin U.; University of Bradford; Elwary, Souna M.; Parkin, Susan M.; Wood, John M.

    2007-01-01

    The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10 -3 M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45 Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H 2 O 2 -mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m 2 surface area with its calcium gradient in the 10 -3 M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue

  5. Astaxanthin attenuates neurotoxicity in a mouse model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    B. Grimmig, L. Daly

    2017-08-01

    Full Text Available Background: Astaxanthin (AXT is a natural carotenoid with diverse biological activities. Although it is best known as a potent antioxidant, recent work suggests additional mechanisms of action that have the potential to oppose the ongoing pathophysiology of Parkinson’s disease (PD. For example, AXT has a putative role in modulating microglial activity and preserving mitochondrial function, thereby implicating this compound as a neuroprotective agent. Both oxidative stress and inflammation are involved in the progression of many neurodegenerative diseases. Therefore, we examined the efficacy for AXT to reduced neurotoxicity in a toxic model of PD in mice. Methods: In this study, we used a 4-week dietary supplementation of algae derived AXT to reduce 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induced dopaminergic cell death. Results: AXT treated mice were protected against the loss of tyrosine hydroxylase (TH staining in the substantia nigra (SN after MPTP exposure compared to the control diet. This effect of preserved TH immunoreactivity was also observed in the striatum. Furthermore, AXT administration was able to interrupt the neuroinflammatory process known to contribute to neurodegeneration in this model. Conclusions: We demonstrate that AXT neuroprotection was associated with attenuated microglial activation as indicated by reduced immunohistochemical detection of IBA-1 in the SN and striatum of AXT treated mice. Altogether, these studies suggest that AXT has neuroprotective property in the central nervous system against MPTP neurodegeneration.

  6. The National Health Service Knowledge and Skills Framework and its implications for continuing professional development in nursing.

    Science.gov (United States)

    Gould, Dinah; Berridge, Emma-Jane; Kelly, Daniel

    2007-01-01

    The National Health Service Knowledge and Skills Framework has been introduced as part of the Agenda for Change Reforms in the United Kingdom to link pay and career progression to competency. The purpose of this paper is to consider the implications for nurses, their managers and the impact on university departments delivering continuing professional development for nurses. The new system has the potential to increase the human resources management aspect of the clinical nurse managers' role and could have legal implications, for example if practitioners perceive that their needs for continuing professional development have been overlooked to the detriment of their pay and career aspirations. The new system also has implications for providers of continuing professional development in the universities and is likely to demand closer liaison between education providers and trust staff who commission education and training. The Knowledge and Skills Framework is of interest to nurses and nurse educators internationally because the system, if effective, could be introduced elsewhere.

  7. Accelerated Urban Expansion in Lhasa City and the Implications for Sustainable Development in a Plateau City

    Directory of Open Access Journals (Sweden)

    Wei Tang

    2017-08-01

    Full Text Available Urbanization challenges regional sustainable development, but a slight expansion mechanism was revealed in a plateau city. We have integrated the urban expansion process and analyzed its determinants in Lhasa (Tibet, and we provide insightful suggestions for urban management and planning for Lhasa. The full continuum of the urban expansion process has been captured using time-series of high-resolution remote sensing data (1990–2015. Four categories of potential determinants involved in economic, demographic, social, and government policy factors were selected, and redundancy analysis was employed to define the contribution rates of these determinants. The results illustrate that considerable urban expansion occurred from 1990 to 2015 in Lhasa, with the area of construction land and transportation land increasing at rates of 117.2% and 564.7%, respectively. The urban expansion in the center of Lhasa can be characterized as temperate sprawl from 1990 through 2008, primarily explained by governmental policies and investment, economic development, tourist growth, and increased governmental investment resulting in faster urban expansion from 2008 to 2015, mainly occurring in the east, south, and west of Lhasa. In contrast with other cities of China, central government investment and “pairing-up support” projects have played an important role in infrastructure construction in Lhasa. The miraculous development of the tourism industry had prominent effects on this economic development and urbanization after 2006, due to the running of the Tibetan Railway. An integrative and proactive policy framework, the “Lhasa development model”, having important theoretical, methodological, and management implications for urban planning and development, has been proposed.

  8. Energy implications of Indian economic development: decade of 1960--70 and after

    Energy Technology Data Exchange (ETDEWEB)

    Diwan, R.

    India is generally known as a poor, overpopulated, and underdeveloped country. Its per capita income, even in 1976-77, is less than 100 U.S. dollars. In the 1971 census India's population was estimated at 550 million, or approximately 15% of the world population. It is projected that the 1976 Indian population is close to 600 million. Its government has been making major efforts attacking the problem of underdevelopment; in these efforts it is assumed that once the country is developed, the twin problems of poverty and overpopulation also will be solved. To remove underdevelopment, India has instituted the mechanism of five-year plans which are an attempt in generating a development process. In this paper the energy implications of this development process are analyzed during the last decade of 1960-1970. Even though changes have taken place in the years 1970-1976, they are not fundamentally or structurally different from the trends established in the ten-year span under study.

  9. Visualizing the future: technology competency development in clinical medicine, and implications for medical education.

    Science.gov (United States)

    Srinivasan, Malathi; Keenan, Craig R; Yager, Joel

    2006-01-01

    In this article, the authors ask three questions. First, what will physicians need to know in order to be effective in the future? Second, what role will technology play in achieving that high level of effectiveness? Third, what specific skill sets will physicians need to master in order to become effective? Through three case vignettes describing past, present, and potential future medical practices, the authors identify trends in major medical, technological and cultural shifts that will shape medical education and practice. From these cases, the authors generate a series of technology-related competencies and skill sets that physicians will need to remain leaders in the delivery of medical care. Physicians will choose how they will be end-users of technology, technology developers, and/or the interface between users and developers. These choices will guide the types of skills each physician will need to acquire. Finally, the authors explore the implications of these trends for medical educators, including the competencies that will be required of educators as they develop the medical curriculum. Examining historical and social trends, including how users adopt current and emerging technologies, allows us to anticipate changes in the practice of medicine. By considering market pressures, global trends and emerging technologies, medical educators and practicing physicians may prepare themselves for the changes likely to occur in the medical curriculum and in the marketplace.

  10. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

    Science.gov (United States)

    Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

    2017-01-01

    The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  11. Immune responses at brain barriers and implications for brain development and neurological function in later life

    Directory of Open Access Journals (Sweden)

    Helen B. Stolp

    2013-08-01

    Full Text Available For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognised that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signalling, or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signalling at the brain barriers that may be an important part of the body’s response to damage or infection. This signalling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation–induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

  12. Estrogen and progesterone signalling in the normal breast and its implications for cancer development.

    Science.gov (United States)

    Hilton, Heidi N; Clarke, Christine L; Graham, J Dinny

    2018-05-05

    The ovarian hormones estrogen and progesterone are master regulators of the development and function of a broad spectrum of human tissues, including the breast, reproductive and cardiovascular systems, brain and bone. Acting through the nuclear estrogen (ER) and progesterone receptors (PR), both play complex and essential coordinated roles in the extensive development of the lobular alveolar epithelial structures of the normal breast during puberty, the normal menstrual cycle and pregnancy. The past decade has seen major advances in understanding the mechanisms of action of estrogen and progesterone in the normal breast and in the delineation of the complex hierarchy of cell types regulated by ovarian hormones in this tissue. There is evidence for a role for both ER and PR in driving breast cancer, and both are favourable prognostic markers with respect to outcome. In this review, we summarize current knowledge of the mechanisms of action of ER and PR in the normal breast, and implications for the development and management of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Neurotoxicity to DRG neurons varies between rodent strains treated with cisplatin and bortezomib.

    Science.gov (United States)

    Podratz, Jewel L; Kulkarni, Amit; Pleticha, Josef; Kanwar, Rahul; Beutler, Andreas S; Staff, Nathan P; Windebank, Anthony J

    2016-03-15

    Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect that can lead to long-term morbidity. Approximately one-third of patients receiving chemotherapy with taxanes, vinca alkaloids, platinum compounds or proteasome inhibitors develop this toxic side effect. It is not possible to predict who will get CIPN, however, genetic susceptibility may play a role. We explored this hypothesis using an established in vitro dorsal root ganglia neurite outgrowth (DRG-NOG) assay to assess possible genetic influences for cisplatin- and bortezomib-induced neurotoxicity. Almost all previous in vitro studies have used rats or mice. We compared DRG-NOG between four genetically defined, inbred mouse strains (C57BL/6J, DBA/2J, BALB/cJ, and C3H/HeJ) and one rat strain (Sprague Dawley). Our studies found differences in cisplatin and bortezomib-induced neurotoxicity between mouse and rat strains and between the different mouse strains. C57BL/6J and Balb/cJ DRG-NOG was more sensitive to cisplatin than DBA/2J and C3H/HeJ DRG-NOG, and all mouse strains were more sensitive to cisplatin than rat. Bortezomib induced a biphasic dose response in DBA/2J and C3H/H3J mice. C57BL/6J DRG-NOG was most sensitive and Balb/cJ DRG-NOG was least sensitive to bortezomib. Our animal data supports the hypothesis that genetic background may play a role in CIPN and care must be taken when rodent models are used to better understand the contribution of genetics in patient susceptibility to CIPN. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity.

    Directory of Open Access Journals (Sweden)

    M Paola Castelli

    Full Text Available Methamphetamine (METH is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS, production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4 × 10 mg/kg, 2 hours apart were pre- or post-treated with Δ9-THC (1 or 3 mg/kg and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP. Results showed that, as compared to corresponding controls (i METH-induced nNOS overexpression in the caudate-putamen (CPu was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (-19% and -28% for 1 mg/kg pre- and post-treated animals; -25% and -21% for 3 mg/kg pre- and post-treated animals; (ii METH-induced GFAP-immunoreactivity (IR was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (-50% and by pre-treatment with 3 mg/kg Δ9-THC (-53%; (iii METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC by pre- and post-treatment with both doses of Δ9-THC (-34% and -47% for 1 mg/kg pre- and post-treated animals; -37% and -29% for 3 mg/kg pre- and post-treated animals. The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the PFC and CPu. Our

  15. A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.

    Science.gov (United States)

    Su, Ping; Liu, Fang

    2017-09-01

    Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. Copyright © 2017. Published by Elsevier Inc.

  16. Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

    Science.gov (United States)

    Ju, Jingjuan; Saul, Nadine; Kochan, Cindy; Putschew, Anke; Pu, Yuepu; Yin, Lihong; Steinberg, Christian E. W.

    2014-01-01

    In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs) and anatoxin-a (ANA). ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have proposed the nematode Caenorhabditis elegans as an appropriate invertebrate model. Therefore, four known neurotoxic compounds (positive compounds: chlorpyrifos, abamectin, atropine, and acrylamide) were chosen to verify the expected impacts on autonomic (locomotion, feeding, defecation) and sensory (thermal, chemical, and mechanical sensory perception) functions in C. elegans. This study is another step towards successfully establishing C. elegans as an alternative neurotoxicity model. By using this protocol, anatoxin-a adversely affected locomotive behavior and pharyngeal pumping frequency and, most strongly, chemotactic and thermotactic behavior, whereas MC-LR impacted locomotion, pumping, and mechanical behavior, but not chemical sensory behavior. Environmental samples can also be screened in this simple and fast way for neurotoxic characteristics. The filtrate of a Microcystis aeruginosa culture, known for its hepatotoxicity, also displayed mild neurotoxicity (modulated short-term thermotaxis). These results show the suitability of this assay for environmental cyanotoxin-containing samples. PMID:24776722

  17. Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes

    DEFF Research Database (Denmark)

    Fritsche, Ellen; Grandjean, Philippe; Crofton, Kevin M

    2018-01-01

    in the environment, with high uncertainty concerning their developmental neurotoxicity (DNT) potential. Closing this data gap with the current test guideline approach is not feasible, because the in vivo bioassays are far too resource-intensive concerning time, money and number of animals. A variety of in vitro...... methods are now available, that have the potential to close this data gap by permitting mode-of-action-based DNT testing employing human stem cells-derived neuronal/glial models. In vitro DNT data together with in silico approaches will in the future allow development of predictive models for DNT effects...

  18. The NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation

    Directory of Open Access Journals (Sweden)

    Shi Fushan

    2012-07-01

    Full Text Available Abstract Background Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal disease-associated prion protein, PrPSc. In prion-infected brains, activated microglia are often present in the vicinity of PrPSc aggregates, and microglial activation is thought to play a key role in the pathogenesis of prion diseases. Although interleukin (IL-1β release by prion-induced microglia has been widely reported, the mechanism by which primed microglia become activated and secrete IL-1β in prion diseases has not yet been elucidated. In this study, we investigated the role of the NACHT, LRR and PYD domains-containing protein (NALP3 inflammasome in IL-1β release from lipopolysaccharide (LPS-primed microglia after exposure to a synthetic neurotoxic prion fragment (PrP106-126. Methods The inflammasome components NALP3 and apoptosis-associated speck-like protein (ASC were knocked down by gene silencing. IL-1β production was assessed using ELISA. The mRNA expression of NALP3, ASC, and pro-inflammatory factors was measured by quantitative PCR. Western blot analysis was used to detect the protein level of NALP3, ASC, caspase-1 and nuclear factor-κB. Results We found that that PrP106-126-induced IL-1β release depends on NALP3 inflammasome activation, that inflammasome activation is required for the synthesis of pro-inflammatory and chemotactic factors by PrP106-126-activated microglia, that inhibition of NF-κB activation abrogated PrP106-126-induced NALP3 upregulation, and that potassium efflux and production of reactive oxygen species were implicated in PrP106-126-induced NALP3 inflammasome activation in microglia. Conclusions We conclude that the NALP3 inflammasome is involved in neurotoxic prion peptide-induced microglial activation. To our knowledge, this is the first time that strong evidence for the involvement of NALP3 inflammasome in prion-associated inflammation has been found.

  19. Developing and Testing a Scale of Moral Thinking and Communication (MTC) Functioning: A Preliminary Study and Its Implications for Moral Development and Education

    Science.gov (United States)

    Lee, Chi-Ming Angela; Thoma, Stephen J.

    2018-01-01

    The purpose of this study was to develop and test a scale assessing students' moral thinking and communication (MTC) functioning as well as to explore the implications for moral development and education. The rationale of MTC functioning, including interaction of four independent competencies: moral awareness, moral judgement, moral discourse, and…

  20. Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Michael K G Stewart

    Full Text Available Pannexin1 (Panx1 subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer.

  1. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats☆

    Science.gov (United States)

    Jin, Minghua; Song, Peilin; Li, Na; Li, Xuejun; Chen, Jiajun

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent. PMID:25538742

  2. Neurobiology of empathy and callousness: implications for the development of antisocial behavior.

    Science.gov (United States)

    Shirtcliff, Elizabeth A; Vitacco, Michael J; Graf, Alexander R; Gostisha, Andrew J; Merz, Jenna L; Zahn-Waxler, Carolyn

    2009-01-01

    Information on the neurobiology of empathy and callousness provides clinicians with an opportunity to develop sophisticated understanding of mechanisms underpinning antisocial behavior and its counterpart, moral decision-making. This article provides an integrated in-depth review of hormones (e.g. peripheral steroid hormones such as cortisol) and brain structures (e.g. insula, anterior cingulate cortex, and amygdala) implicated in empathy, callousness, and psychopathic-like behavior. The overarching goal of this article is to relate these hormones and brain structures to moral decision-making. This review will begin in the brain, but will then integrate information about biological functioning in the body, specifically stress-reactivity. Our aim is to integrate understanding of neural processes with hormones such as cortisol, both of which have demonstrated relationships to empathy, psychopathy, and antisocial behavior. The review proposes that neurobiological impairments in individuals who display little empathy are not necessarily due to a reduced ability to understand the emotions of others. Instead, evidence suggests that individuals who show little arousal to the distress of others likewise show decreased physiological arousal to their own distress; one manifestation of reduced stress reactivity may be a dysfunction in empathy, which supports psychopathic-like constructs (e.g. callousness). This integration will assist in the development of objective methodologies that can inform and monitor treatment interventions focused on decreasing antisocial behavior. Copyright 2009 John Wiley & Sons, Ltd.

  3. Making poverty reduction irreversible: development implications of the Millennium Ecosystem Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bass, Steve

    2006-07-15

    Development is achieved through growing and managing the 'portfolio of assets' available to a household or a nation. Soils, water, plants and animals often make up the biggest chunk of poor people's assets. The Millennium Ecosystem Assessment (MA) has taken stock of these environmental assets worldwide. It reveals that fully sixty percent are being degraded – with poor people disproportionately suffering the consequences such as shortage of clean water, floods and droughts. Yet the MA also identified instances of effective asset management – proven 'Response Options' that deserve scaling up. This briefing note identifies the major developmental implications of the MA, and calls for action in four areas: Information – getting information on environmental assets and hazards to the heart of development planning; Institutional reform – encouraging ecosystem management by poor people and local organisations, and enabling better oversight by national authorities; International cooperation – increasing aid and benchmarking it against just how far off-track we are on MDG7 (the 'environmental sustainability' goal); Investment vehicles and budgets – to support long-term environmental management in key environmentally-sensitive sectors. Action on these is so urgently required that we can no longer avoid asking what it will cost. We propose 'Millennium Ecosystem Budgets', globally and nationally.

  4. Implications of the Recommendations of the Expert Panel on Federal Support to Research and Development

    Directory of Open Access Journals (Sweden)

    Preston Manning

    2012-03-01

    Full Text Available Canada lags behind many of its First World counterparts when it comes to business innovation, and urgently needs to improve its performance if it is to remain competitive and attractive to investment. The Expert Panel Report on Federal Support to Research and Development has recommended several policy initiatives that governments need to enact to close the gap. This paper reviews all six major recommendations made by the Expert Panel and provides thorough assessments of each, with ample consideration given to their implications for the private sector. The two most promising are: (1 the consolidation of research and development spending programs at the federal level and (2 the adoption of smart procurement as a means of spurring innovation in the non-government sector. While some of the other recommendations need refinement and raise concerns about their impact on the economy, the message for government and business is clear: the former can and should facilitate Canadian business innovation by removing tax and regulatory burdens and facilitating better public-private cooperation, while the latter must make innovation a major part of corporate culture. This paper explains the consequences of the Panel’s recommendations for both sectors, identifies the deficiencies, and offers clear-eyed guidance for ameliorating them.

  5. Private sector participation in secondary education in Nigeria: Implications for national development

    Directory of Open Access Journals (Sweden)

    Uyi Kizito Ehigiamusoe

    2012-12-01

    Full Text Available The study examines private sector participation in secondary education in Nigeria and its implications for national development. The population consisted all the providers and recipients of private secondary education in the Federal Capital Territory (FCT. Simple random sampling was used to select 200 providers and recipients of private secondary education across the six Area Councils in the FCT. An instrument designated Private Sector Participation in Secondary Education (PSPSE was used to collect data. The data were analysed using Chi-Square method to test for the acceptance or rejection of the study hypotheses. The findings revealed that the academic performance of students in private secondary schools is better than the academic performance of students in public secondary schools. The study further revealed that private secondary schools have better infrastructure than public secondary schools in Nigeria, but private secondary schools contribute less to the development of human resources than public schools in Nigeria. Recommendations are proffered to make private secondary education more viable and responsive to the needs of the society.

  6. Perspectives on the rhythm–grammar link and its implications for typical and atypical language development

    Science.gov (United States)

    Gordon, Reyna L.; Jacobs, Magdalene S.; Schuele, C. Melanie; McAuley, J. Devin

    2014-01-01

    This paper reviews the mounting evidence for shared cognitive mechanisms and neural resources for rhythm and grammar. Evidence for a role of rhythm skills in language development and language comprehension is reviewed here in three lines of research: (a) behavioral and brain data from adults and children, showing that prosody and other aspects of timing of sentences influence online morpho-syntactic processing; (b) co-morbidity of impaired rhythm with grammatical deficits in children with language impairment; and (c) our recent work showing a strong positive association between rhythm perception skills and expressive grammatical skills in young school-age children with typical development. Our preliminary follow-up study presented here revealed that musical rhythm perception predicted variance in six-year-old children’s production of complex syntax, as well as online reorganization of grammatical information (transformation); these data provide an additional perspective on the hierarchical relations potentially shared by rhythm and grammar. A theoretical framework for shared cognitive resources for the role of rhythm in perceiving and learning grammatical structure is elaborated on in light of potential implications for using rhythm-emphasized musical training to improve language skills in children. PMID:25773612

  7. The effect of residential choice on the travel distance and the implications for sustainable development

    Science.gov (United States)

    Eka Putra, Kaspan

    2018-03-01

    For Medan citizens, the choice of residence location depends on the ability to buy a house. House price is determined by the price of land where the housing is located. The more to the edge of the city the location of a house, then the price will be lower. So that the suburbs of Medan become the residential choice for the citizens of low-income. The residential choice will affect the distance of the journey to the workplace. This study analyzed the effect of residential choice on the travel distance and the implications for the implementation of sustainable development. The data used in this study is the primary data obtained through the survey held in Medan. The research approach is quantitative with the data analysis technique of Structural Equation Model (SEM). The results show that low-income citizens tend to choose the location of suburbs, while they work in the urban area. The location of the residence affects the daily travel distance is very high. The travel distance that is the very high effect the use of private vehicle mode. The use of private vehicles for long travel distance requires a huge energy. The use of very high fuel oils is a waste of energy and can increase air pollution. This is not in accordance with the concept of sustainable development.

  8. Nature of Technology: Implications for design, development, and enactment of technological tools in school science classrooms

    Science.gov (United States)

    Waight, Noemi; Abd-El-Khalick, Fouad

    2012-12-01

    This position paper provides a theory-based explanation informed by philosophy of technology (PoT) of the recurrent documented patterns often associated with attempts to enact technology-supported, inquiry-based approaches in precollege science classrooms. Understandings derived from the history of technological development in other domains (e.g. medicine, transportation, and warfare) reveal numerous parallels that help to explain these recurrent patterns. Historical analyses of major technologies reveal a conglomerate of factors that interact to produce benefits, as well as intended and unintended consequences. On a macro-scale, PoT facilitates understandings of how technologies interact and are impacted by individuals, society, institutions, economy, politics, and culture. At the micro-level, and most relevant to science education, PoT engages the inherent nature of technology along a number of key dimensions: role of culture and values, notions of technological progression, technology as part of systems, technological diffusion, technology as a fix, and the notions of expertise. Overall, the present analysis has implications for the design, development, implementation, and adoption of technological tools for use in precollege science education, and highlights the role of technology as both artifact and process.

  9. Economic and fiscal impacts of large-scale development projects: implications for nuclear waste repositories

    International Nuclear Information System (INIS)

    Leistritz, F.L.; Murdock, S.H.; Texas A and M Univ., College Station)

    1982-01-01

    This paper deals with the local economic and fiscal implications of siting high-level nuclear waste repositories in rural areas. The economic and fiscal effects of repository development fall into two categories: (1) standard impacts similar to those that would be associated with developing any large-scale industrial facility in an isolated area; (2) special impacts that result from the hazardous nature of the nuclear materials stored and from federal ownership of the facility. Standard economic and fiscal impacts include employment effects (direct and secondary), local income changes, alterations in community price structures, effects on community services, and changes in revenues and costs for local jurisdictions. Special impacts include the possibility of diminished activity in other basic economic sectors, negative effects on the area's long-term growth prospects and a consequent dampening of investment in the local trade an service sectors, additional costs for local jurisdictions (e.g., for preparing evacuation plans), and limited local tax revenues resulting from the tax-exempt status of the facility. These special effects are difficult to quantify and require additional analysis. 47 references, 1 figure, 4 tables

  10. Project-Based Market Competition and Policy Implications for Sustainable Developments in Building and Construction Sectors

    Directory of Open Access Journals (Sweden)

    Min-Ren Yan

    2015-11-01

    Full Text Available Building and construction sectors are significant contributors to the global economy, but their energy consumption necessitates greater commitment to sustainable developments. There is therefore a growing demand for green innovation in the form of cleaner production and policies to meet the modern requirements of sustainability. However, the nature in which public work is undertaken is in an environment of project-based market competition, whereby contractors routinely bid for contracts under specific project awarding systems, and variations are accompanied with the unique scope of individual projects before the final goods or services are delivered. A comprehensive understanding of the characteristics and contractors’ behavior in systems could help to identify the leverage points of policies. This paper proposes a system dynamics model, with quantitative analysis and simulations, to demonstrate the problems of a system with different project awarding systems and ineffective market performance. The framework of market efficiency and performance measures has been proposed to evaluate the project-based competition mechanism. Managerial policy implications for market efficiency and sustainable developments can thus be systematically discussed and compared through iterative computer simulations and scenario analysis.

  11. Structuring Ethical Interpretations of the Sustainable Development Goals—Concepts, Implications and Progress

    Directory of Open Access Journals (Sweden)

    Martina Keitsch

    2018-03-01

    Full Text Available The Sustainable Development Goals (SDGs, like the sustainable development (SD concept itself, are open to multifaceted interpretations, and the same is true for their ethical implications. While SDG values are widely accepted as universal, the ethical structure of the SDGs is complex, with differing interpretations and ideas, e.g., on how to regard and value nature. This article is a conceptual attempt to clarify and structure ethical interpretations based on an environmental ethics framework consisting of two branches: anthropocentrism and biocentrism. The aim is to provide an overview of SDG positions and locate them in the wider field of environmental ethics, addressing the human–nature relationship as a recurring topic in the SDGs. Section 1 of this article presents environmental ethics and briefly discusses anthropocentrism and biocentrism. Section 2 outlines ethical similarities of SD and the SDGs and locates representative SDG interpretations within the environmental ethics framework. Section 3 summarizes findings and suggests a possibility of integrating biocentrism and anthropocentrism with regard to the further interpretation and discussion of SDG ethics. Insights from this article will aid researchers in adopting a better overview on ethical positions in the SDG debate.

  12. Making poverty reduction irreversible: development implications of the Millennium Ecosystem Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Bass, Steve

    2006-07-15

    Development is achieved through growing and managing the 'portfolio of assets' available to a household or a nation. Soils, water, plants and animals often make up the biggest chunk of poor people's assets. The Millennium Ecosystem Assessment (MA) has taken stock of these environmental assets worldwide. It reveals that fully sixty percent are being degraded – with poor people disproportionately suffering the consequences such as shortage of clean water, floods and droughts. Yet the MA also identified instances of effective asset management – proven 'Response Options' that deserve scaling up. This briefing note identifies the major developmental implications of the MA, and calls for action in four areas: Information – getting information on environmental assets and hazards to the heart of development planning; Institutional reform – encouraging ecosystem management by poor people and local organisations, and enabling better oversight by national authorities; International cooperation – increasing aid and benchmarking it against just how far off-track we are on MDG7 (the 'environmental sustainability' goal); Investment vehicles and budgets – to support long-term environmental management in key environmentally-sensitive sectors. Action on these is so urgently required that we can no longer avoid asking what it will cost. We propose 'Millennium Ecosystem Budgets', globally and nationally.

  13. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  14. Oxidative stress in MeHg-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2011-11-15

    Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

  15. NPPB and ACAN, two novel SHOX2 transcription targets implicated in skeletal development.

    Directory of Open Access Journals (Sweden)

    Miriam Aza-Carmona

    Full Text Available SHOX and SHOX2 transcription factors are highly homologous, with even identical homeodomains. Genetic alterations in SHOX result in two skeletal dysplasias; Léri-Weill dyschondrosteosis (LWD and Langer mesomelic dysplasia (LMD, while no human genetic disease has been linked to date with SHOX2. SHOX2 is, though, involved in skeletal development, as shown by different knockout mice models. Due to the high homology between SHOX and SHOX2, and their functional redundancy during heart development, we postulated that SHOX2 might have the same transcriptional targets and cofactors as SHOX in limb development. We selected two SHOX transcription targets regulated by different mechanisms: 1 the natriuretic peptide precursor B gene (NPPB involved in the endochondral ossification signalling and directly activated by SHOX; and 2 Aggrecan (ACAN, a major component of cartilage extracellular matrix, regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9 via the protein interaction between SOX5/SOX6 and SHOX. Using the luciferase assay we have demonstrated that SHOX2, like SHOX, regulates NPPB directly whilst activates ACAN via its cooperation with the SOX trio. Subsequently, we have identified and characterized the protein domains implicated in the SHOX2 dimerization and also its protein interaction with SOX5/SOX6 and SHOX using the yeast-two hybrid and co-immunoprecipitation assays. Immunohistochemistry of human fetal growth plates from different time points demonstrated that SHOX2 is coexpressed with SHOX and the members of the SOX trio. Despite these findings, no mutation was identified in SHOX2 in a cohort of 83 LWD patients with no known molecular defect, suggesting that SHOX2 alterations do not cause LWD. In conclusion, our work has identified the first cofactors and two new transcription targets of SHOX2 in limb development, and we hypothesize a time- and tissue-specific functional redundancy between SHOX and SHOX2.

  16. NPPB and ACAN, two novel SHOX2 transcription targets implicated in skeletal development.

    Science.gov (United States)

    Aza-Carmona, Miriam; Barca-Tierno, Veronica; Hisado-Oliva, Alfonso; Belinchón, Alberta; Gorbenko-del Blanco, Darya; Rodriguez, Jose Ignacio; Benito-Sanz, Sara; Campos-Barros, Angel; Heath, Karen E

    2014-01-01

    SHOX and SHOX2 transcription factors are highly homologous, with even identical homeodomains. Genetic alterations in SHOX result in two skeletal dysplasias; Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD), while no human genetic disease has been linked to date with SHOX2. SHOX2 is, though, involved in skeletal development, as shown by different knockout mice models. Due to the high homology between SHOX and SHOX2, and their functional redundancy during heart development, we postulated that SHOX2 might have the same transcriptional targets and cofactors as SHOX in limb development. We selected two SHOX transcription targets regulated by different mechanisms: 1) the natriuretic peptide precursor B gene (NPPB) involved in the endochondral ossification signalling and directly activated by SHOX; and 2) Aggrecan (ACAN), a major component of cartilage extracellular matrix, regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9) via the protein interaction between SOX5/SOX6 and SHOX. Using the luciferase assay we have demonstrated that SHOX2, like SHOX, regulates NPPB directly whilst activates ACAN via its cooperation with the SOX trio. Subsequently, we have identified and characterized the protein domains implicated in the SHOX2 dimerization and also its protein interaction with SOX5/SOX6 and SHOX using the yeast-two hybrid and co-immunoprecipitation assays. Immunohistochemistry of human fetal growth plates from different time points demonstrated that SHOX2 is coexpressed with SHOX and the members of the SOX trio. Despite these findings, no mutation was identified in SHOX2 in a cohort of 83 LWD patients with no known molecular defect, suggesting that SHOX2 alterations do not cause LWD. In conclusion, our work has identified the first cofactors and two new transcription targets of SHOX2 in limb development, and we hypothesize a time- and tissue-specific functional redundancy between SHOX and SHOX2.

  17. Research Review: Social motivation and oxytocin in autism – implications for joint attention development and intervention

    Science.gov (United States)

    Stavropoulos, Katherine K. M.; Carver, Leslie J.

    2013-01-01

    Background and Scope The social motivation hypothesis (SMH) suggests that individuals with autism spectrum disorders (ASD) are less intrinsically rewarded by social stimuli than their neurotypical peers. This difference in social motivation has been posited as a factor contributing to social deficits in ASD. Social motivation is thought to involve the neuropeptide oxytocin. Here, we review the evidence for oxytocin effects in ASD, and discuss its potential role in one important social cognitive behavior. Methods Systematic searches were conducted using the PsychINFO and MEDLINE databases and the search terms “oxytocin”, and “autism”; the same databases were used for separate searches for “joint attention”, “intervention”, and “autism”, using the same inclusion criteria as an earlier 2011 review but updating it for the period 2010 to October 2012. Findings Several studies suggest that giving oxytocin to both individuals with ASD and typically developing individuals can enhance performance on social cognitive tasks. Studies that have attempted to intervene in joint attention in ASD suggest that social motivation may be a particular obstacle to lasting effects. Conclusions The review of the evidence for the SMH suggests a potential role for oxytocin in social motivation deficits in ASD. Because of its importance for later communicative and social development, the focus here is on implications of oxytocin and social motivation in the development of and interventions in joint attention. Joint attention is a central impairment in ASD, and as a result is the focus of several behavioral interventions. In describing this previous research on joint attention interventions in ASD, we pay particular attention to problems encountered in such studies, and propose ways that oxytocin may facilitate behavioral intervention in this area. For future research, integrating behavioral and pharmacological interventions (oxytocin administration) would be a worthwhile

  18. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

    Directory of Open Access Journals (Sweden)

    Wen-Yang Tsai

    2017-07-01

    Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  19. Africa energy future: Alternative scenarios and their implications for sustainable development strategies

    International Nuclear Information System (INIS)

    Ouedraogo, Nadia S.

    2017-01-01

    The long-term forecasting of energy supply and demand is of prime importance in Africa due to the steady increase in energy requirements, the non-availability of sufficient resources, the high dependence on fossil-fuels to meet these requirements, and the global concerns over the energy-induced environmental issues. This paper is concerned with modelling possible future paths for Africa's energy future and the related emissions. Future energy demand is forecasted based on socio-economic variables such as gross domestic product, income per capita, population, and urbanisation. The Long-range Energy Alternative Planning System (LEAP) modelling framework is employed to analyse and project energy demand and the related emissions under alternative strategies for the period of 2010–2040. Results of scenarios including business-as-usual (BAU) policies, moderate energy access and accelerate energy access policies, renewable energies promotion and energy efficiency policies and their environmental implications are provided. The study provides some policy insights and identifies synergies and trade-offs relating to the potential for energy policies to promote universal energy access, enable a transition to renewable energy, and mitigate climate change for a sustainable development. - Highlights: • Possible future paths for Africa's energy future and the related emissions are modelled. • Scenarios using an adaptation of Schwartz's scenario approach, under LEAP are developed. • Under the current energy policies, the universal access to modern energy will not be met by 2030. • Policies to accelerate the changes in energy structure are required for sustainable development. • Investing in Energy efficient strategies has emerged as one of the best solution.

  20. The development of a provincial radiation oncology service: the first year report and its implications for future developments

    International Nuclear Information System (INIS)

    Byram, D.; Joseph, D.; Bulmer, M.

    1996-01-01

    This study compares the actual first year's workload of a new radiation oncology department with that predicted, and assesses the impact of the differences, and their implications for future similar developments. The treatment records and diaries for the Geelong Hospital Radiation Oncology Department were reviewed after the first 12 months of operation. Statistics relating to the number of patients seen, number treated, diagnosis, etc., were evaluated and compared to the original estimates based upon population statistics and likely referral rates. Nine hundred and seven new patients were seen in this period, and from them 718 courses of treatment were initiated. One hundred and eighty-nine cases (20% of referrals) were seen but not treated. A further 102 treatment courses (14% of total) were initiated upon patients who had previously been irradiated. Forty-six per cent of patients were managed by 10 fractions or fewer, and a further 23% by 25 or more fractions. Eighty per cent of patients were managed by one or two fields. Electrons were used in only 14% of cases. Further calculations suggested a further possible 441 cases of referral could be expected, based upon current population statistics. Referral rates for radiation oncology are highly dependent on a number of factors. As a result, estimates of referrals and hence the size of a department required for a given population vary widely. In considering the development of units outside of major cities it is suggested that referrals are likely to be on the high side of estimates and a minimum two-machine unit is essential to cover the given workload. 5 refs., 6 tabs

  1. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients.

    Science.gov (United States)

    Lam, Larry; Chin, Lydia; Halder, Ramesh C; Sagong, Bien; Famenini, Sam; Sayre, James; Montoya, Dennis; Rubbi, Liudmilla; Pellegrini, Matteo; Fiala, Milan

    2016-10-01

    We have investigated transcriptional and epigenetic differences in peripheral blood mononuclear cells (PBMCs) of monozygotic female twins discordant in the diagnosis of amyotrophic lateral sclerosis (ALS). Exploring DNA methylation differences by reduced representation bisulfite sequencing (RRBS), we determined that, over time, the ALS twin developed higher abundances of the CD14 macrophages and lower abundances of T cells compared to the non-ALS twin. Higher macrophage signature in the ALS twin was also shown by RNA sequencing (RNA-seq). Moreover, the twins differed in the methylome at loci near several genes, including EGFR and TNFRSF11A, and in the pathways related to the tretinoin and H3K27me3 markers. We also tested cytokine production by PBMCs. The ALS twin's PBMCs spontaneously produced IL-6 and TNF-α, whereas PBMCs of the healthy twin produced these cytokines only when stimulated by superoxide dismutase (SOD)-1. These results and flow cytometric detection of CD45 and CD127 suggest the presence of memory T cells in both twins, but effector T cells only in the ALS twin. The ALS twin's PBMC supernatants, but not the healthy twin's, were toxic to rat cortical neurons, and this toxicity was strongly inhibited by an IL-6 receptor antibody (tocilizumab) and less well by TNF-α and IL-1β antibodies. The putative neurotoxicity of IL-6 and TNF-α is in agreement with a high expression of these cytokines on infiltrating macrophages in the ALS spinal cord. We hypothesize that higher macrophage abundance and increased neurotoxic cytokines have a fundamental role in the phenotype and treatment of certain individuals with ALS.-Lam, L., Chin, L., Halder, R. C., Sagong, B., Famenini, S., Sayre, J., Montoya, D., Rubbi L., Pellegrini, M., Fiala, M. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients. © FASEB.

  2. The Outcomes of Chinese Visiting Scholars' Experiences at Canadian Universities: Implications for Faculty Development at Chinese Universities

    Science.gov (United States)

    Liu, Qin; Jiang, Yumei

    2015-01-01

    This article examines the outcomes of the overseas experiences of Chinese visiting scholars and the implications of visiting scholar programs for faculty development at Chinese universities. On the basis of semi-structured interviews with 17 returned Chinese visiting scholars who spent six to 12 months in a faculty of education at one of five…

  3. Bionanoscience landscape in South Africa and its implications in the development of a post-graduate curriculum - Presentation

    CSIR Research Space (South Africa)

    Sparrow, R

    2009-11-01

    Full Text Available Africa and its Implications in the Development of a Post-Graduate Curriculum Presented at UWC – Nano-biotechnology Seminar. Dr. Raymond Sparrow Manager of the SynBioTIC Programme. CSIR – Synthetic Biology ERA. 20th November 2009 Nanoscience...

  4. Trends in International Trade in Higher Education: Implications and Options for Developing Countries. Education Working Paper Series, Number 6

    Science.gov (United States)

    Bashir, Sajitha

    2007-01-01

    This paper analyzes the trends, underlying factors and implications of the trade in higher education services. The term "trade in higher education" refers to the purchase of higher education services from a foreign country using domestic resources. The objectives of this paper are to provide policy makers in developing countries, World Bank staff,…

  5. Implications of a neural network model of early sensori-motor development for the field of developmental neurology

    NARCIS (Netherlands)

    van Heijst, JJ; Touwen, BCL; Vos, JE

    This paper reports on a neural network model for early sensori-motor development and on the possible implications of this research for our understanding and, eventually, treatment of motor disorders like cerebral palsy. We recapitulate the results we published in detail in a series of papers [1-4].

  6. Long-Term Implications of Welfare Reform for the Development of Adolescents and Young Adults

    Science.gov (United States)

    Chase-Lansdale, P. Lindsay; Cherlin, Andrew J.; Guttmannova, Katarina; Fomby, Paula; Ribar, David C.; Coley, Rebekah Levine

    2011-01-01

    We draw upon the 3-wave longitudinal dataset called Welfare Children and Families: A Three-City Study to examine the long-term implications for adolescents and young adults (N=783) of mothers’ welfare receipt and labor force participation from 1999 to 2005. In general, changes in mothers’ work and welfare patterns were not associated with deterioration or improvement in youth development (ages 16 to 20 years at wave 3). The few significant associations suggested that youth whose mothers increased employment (net of welfare participation) were more likely to show declines in serious behavior problems and delinquency compared to youth whose mothers were unemployed or employed part-time during the study period. Welfare roll exits (controlling for employment experiences) were unrelated to adolescent and young adult outcomes. Mothers’ employment transitions were linked to improvements in household income and mothers’ self esteem in addition to reductions in financial strain and their own illegal activities. However, these associations did not explain the relation between maternal employment and youths’ improved behavior. These results do not support the predictions of either the supporters or the opponents of welfare reform, an outcome we discuss. PMID:21966077

  7. The psychological development of panic disorder: implications for neurobiology and treatment.

    Science.gov (United States)

    Cosci, Fiammetta

    2012-06-01

    The aim of this study was to survey the available literature on psychological development of panic disorder with or without agoraphobia [PD(A)] and its relationship with the neurobiology and the treatment of panic. Both a computerized (PubMed) and a manual search of the literature were performed. Only English papers published in peer-reviewed journals and referring to PD(A) as defined by the diagnostic classifications of the American Psychiatric Association or of the World Health Organization were included. A staging model of panic exists and is applicable in clinical practice. In a substantial proportion of patients with PD(A), a prodromal phase and, despite successful treatment, residual symptoms can be identified. Both prodromes and residual symptoms allow the monitoring of disorder evolution during recovery via the rollback phenomenon. The different stages of the disorder, as well as the steps of the rollback, have a correspondence in the neurobiology and in the treatment of panic. However, the treatment implications of the longitudinal model of PD(A) are not endorsed, and adequate interventions of enduring effects are missing.

  8. Dynamics of technology shifts in the household sector-implications for clean development mechanism

    International Nuclear Information System (INIS)

    Reddy, B. Sudhakara; Balachandra, P.

    2006-01-01

    The present paper attempts to analyse the dynamics of energy end-use technology shifts in the household sector in India. The technology shifts can be categorized as naturally occurring shifts (with increasing household incomes and availability of energy carriers) and policy-induced shifts (by creating a favourable environment). Initially, the households energy usage patterns, types of energy carriers and the technologies in use are analysed using the data from the National Sample Survey (1999-2000). The energy consumption is disaggregated according to end-use activity and by income groups for rural as well as urban households. It is observed that large variations in energy use exist across different sections of households-urban/rural, low/high-income groups, etc. Further, the paper provides a methodological framework for the diffusion of energy-efficient technologies, and the implications of such diffusions for the Clean Development Mechanism (CDM). It analyses the reasons for the gap between possible and practical implementation of energy-efficient measures, study the reasons for households not using the cost-effective technologies available to them, the benefits of innovation of energy efficiency, and the required policies and specific proposals for government intervention to achieve the potential for the CDM

  9. Thai Learners’ Linguistic Needs and Language Skills: Implications for Curriculum Development

    Directory of Open Access Journals (Sweden)

    Mark B. Ulla

    2017-11-01

    Full Text Available Learners’ success in language learning always has implications for curriculum and instruction. Thus, it is important to take into account the kinds of learning experiences that these learners will find helpful in learning English as a foreign language; and, highlight them when planning a curriculum and adapting classroom activities. This study, with 72 first year engineering students, 3 English for Specific Purposes (ESP teachers of King Mongkut’s University of Technology Thonburi (KMUTT Ratchaburi, and 3 other stakeholders as respondents, aimed to identify the Thai engineering students’ linguistic needs and the language skills needed for them to get a job in the future. It also assessed whether the linguistic needs and the language skills required for the students were addressed in the curriculum. Methods used in this study were modified questionnaire, focus groups and semistructured individual interviews. Findings revealed that students wanted to go abroad and to be successful in their future careers; thus, considered speaking as the most important skill to be developed and should be emphasized in their English classes. Students preferred to learn through engaging classroom activities and strategies, exposure to the language, and use of technology in the classroom. However, the ESP curriculum did not provide these linguistic needs and language skills.

  10. The implication of nutritional psychopedagogy in the matrix of personal development

    Directory of Open Access Journals (Sweden)

    Maria Dorina PASCA

    2010-08-01

    Full Text Available The birth of conceptual nutritional psycho-pedagogy represents the compulsory matrix for the development and maintenance of human and personal value. Thus, it must respond both from the point of view of attitude and behavior through education and from a structural point of view to the social command, enclosing the individual in a quality segment of his existence, starting from the nutritional act. Being a new and interdisciplinary domain, nutritional psycho pedagogy, determines, by the implication in the personalized act of nutrition, the acknowledgment of the fact that “eating is an art” and, at the same time, it makes responsible the ones who sustain that “they live to eat” and/or “they eat to live”. This fact cognitively implies both the acknowledgment and the application of the component elements necessary for the approach of a healthy life style which determines the improvement of the life quality, as a response of personal identity. We wonder: Is the nutritional psycho pedagogy able toanswer the question “Tell me what you eat and I will tell you who you are”.

  11. Agonistic behaviour in juvenile southern rock lobster, Jasus edwardsii (Decapoda, Palinuridae: implications for developing aquaculture

    Directory of Open Access Journals (Sweden)

    Chris Carter

    2014-11-01

    Full Text Available The Southern rock lobster, Jasus edwardsii, is a temperate species of spiny lobster with established well managed fisheries in Australia and New Zealand. It has also been under consideration as a species with aquaculture potential. Agonistic behaviour has important consequences under aquaculture conditions that encompass direct effects, such as damage or death of protagonists, and indirect effects on growth that relate to resource access, principally food and refuge. This study aimed to identify and characterize behaviours and to make a preliminary investigation of their occurrence under tank culture. Juvenile Jasus edwardsii were examined in a flow-through seawater system using a remote video camera system. Twenty-nine behaviours were divided into three sub-groups: aggressive (11, avoidance (6 and others (12. Aggressive behaviours included attacks, pushing, lifting, clasping and carrying an opponent. Avoidance behaviours included moving away in a backwards-, forwards- or side-stepping motion as well as with more vigorous tail flips. These behaviours were components of twelve behavioural groups that described contact, attack and displacement between individuals. Activity was crepuscular with two clear peaks, one in the morning and the other in the evening. The occurrence of behavioural groups was not different between the morning and evening. The frequency of aggressive behaviours was not affected by changes made to stocking density or access to food. The implications of agonistic behaviours are discussed further in relation to developing aquaculture.

  12. Vietnamese Migrant Workers in Thailand - Implications for Leveraging Migration for Development

    Directory of Open Access Journals (Sweden)

    Nancy HUYEN NGUYEN

    2014-05-01

    Full Text Available A greater flow of people to and from each of the Mekong countries is catching the attention of the general public and academic researchers. As one of the fastest growing countries in the GMS, Thailand is attracting the majority of migrant workers from its neighbours. At a smaller scale, when compared with those from Lao PDR, Cambodia and Myanmar, Vietnamese workers are also joining this increasing trend in immigration to Thailand. By analyzing information from secondary data sources, this research paper attempts to provide further insights into the social and economic impacts generated by the Vietnamese migrant workers in Thailand both at home and the host country. The study discovers that moving to Thailand for work has eased the pressures of rural unemployment and underemployment that have plagued Vietnam recently. Meanwhile, Vietnamese workers are helping soothe the stress caused by the increasing demand for unskilled and low skilled labourers in Thailand. The study further learns that the long-established community of Vietnamese migrants in Thailand is encouraging the increasing movement of Vietnamese workers to Thailand. The study findings suggest meaningful implications for future policies in leveraging labour migration for development.

  13. Self-concept of people with intellectual disabilities: Implications for support program development

    Directory of Open Access Journals (Sweden)

    Petrović Boban

    2012-01-01

    Full Text Available Self-concept is defined as a sum of perception, thoughts, feelings, evaluation and prediction about oneself as an experienced object, as a participant in the interaction with physical and social environment. As such, this topic is often encountered in working with children, young people and adults with intellectual disabilities (PWID. However, self-concept of PWID has been investigated mainly through psychometric paradigm, using different types of questionnaires for assessment. This did not provide either enough possibilities for active participation of people with ID in the research process, or the possibilities to reach adequate initial information about self-concept of PWID, which may serve as a baseline for development of support programs for self-determination of PWID. Therefore, this study aimed to examine self-concept of PWID in various domains of interest for PWID: global self-image, personality traits, competencies, difficulties in everyday life, awareness of one's own (intellectual disabilities. The research was conducted through a series of five focus groups, with active participation of PWID, through combined workshop activities and discussions in small groups. Focus groups were conducted once a week and 16 participants were divided into two groups, of different ages (22 to 53 years, sex, type and degree of difficulties. All participants spent most of their lives in institutions. Since 2004, they have been living at supported housing for people with disabilities. Based on the analysis of the participants' testimony, there were three global issues with regard to general self-concept: competences and interests, physical appearance, and social roles. With regard to personality traits, attributes such as 'good', 'obedient', 'valuable' occur most frequently. With regard to their competencies and difficulties, those which are most important for full daily life in supported housing have been cited most often. While they recognize their

  14. A novel antagonistic role of natural compound icariin on neurotoxicity of amyloid β peptide

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    2015-01-01

    Interpretation & conclusions: The results indicated a novel antagonistic role of icariin in the neurotoxicity of Aβ1-42 via inhibiting its aggregation, suggesting that icariin might have potential therapeutic benefits to delay or modify the progression of AD.

  15. Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat

    Science.gov (United States)

    Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household products. Due to the phase-out oforganophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmacokine...

  16. The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

    Science.gov (United States)

    Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

    2016-01-01

    HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

  17. Ethnic Socialization in Neighborhood Contexts: Implications for Ethnic Attitude and Identity Development Among Mexican-Origin Adolescents.

    Science.gov (United States)

    White, Rebecca M B; Knight, George P; Jensen, Michaeline; Gonzales, Nancy A

    2018-05-01

    Neighborhood Latino ethnic concentration, above and beyond or in combination with mothers' and fathers' ethnic socialization, may have beneficial implications for minority adolescents' ethnic attitude and identity development. These hypotheses, along with two competing hypotheses, were tested prospectively (from x¯age = 12.79-15.83 years) in a sample of 733 Mexican-origin adolescents. Neighborhood ethnic concentration had beneficial implications for ethnic identity processes (i.e., ethnic exploration and perceived peer discrimination) but not for ethnic attitudes. For Mexico-born adolescents, high maternal ethnic socialization compensated for living in neighborhoods low on ethnic concentration. Findings are discussed vis-à-vis the ways in which they address major gaps in the neighborhood effects literature and the ethnic and racial identity development literature. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  18. Research review: Social motivation and oxytocin in autism--implications for joint attention development and intervention.

    Science.gov (United States)

    Stavropoulos, Katherine K M; Carver, Leslie J

    2013-06-01

    The social motivation hypothesis (SMH) suggests that individuals with autism spectrum disorders (ASD) are less intrinsically rewarded by social stimuli than their neurotypical peers. This difference in social motivation has been posited as a factor contributing to social deficits in ASD. Social motivation is thought to involve the neuropeptide oxytocin. Here, we review the evidence for oxytocin effects in ASD, and discuss its potential role in one important social cognitive behavior. Systematic searches were conducted using the PsychINFO and MEDLINE databases and the search terms 'oxytocin' and 'autism'; the same databases were used for separate searches for 'joint attention', 'intervention', and 'autism', using the same inclusion criteria as an earlier 2011 review but updating it for the period 2010 to October 2012. Several studies suggest that giving oxytocin to both individuals with ASD and neurotypical individuals can enhance performance on social cognitive tasks. Studies that have attempted to intervene in joint attention in ASD suggest that social motivation may be a particular obstacle to lasting effects. The review of the evidence for the SMH suggests a potential role for oxytocin in social motivation deficits in ASD. Because of its importance for later communicative and social development, the focus here is on implications of oxytocin and social motivation in the development of and interventions in joint attention. Joint attention is a central impairment in ASD, and as a result is the focus of several behavioral interventions. In describing this previous research on joint attention interventions in ASD, we pay particular attention to problems encountered in such studies, and propose ways that oxytocin may facilitate behavioral intervention in this area. For future research, integrating behavioral and pharmacological interventions (oxytocin administration) would be a worthwhile experimental direction to improve understanding of the role of oxytocin in ASD

  19. Let-7a is a direct EWS-FLI-1 target implicated in Ewing's sarcoma development.

    Directory of Open Access Journals (Sweden)

    Claudio De Vito

    Full Text Available Ewing's sarcoma family tumors (ESFT are the second most common bone malignancy in children and young adults, characterized by unique chromosomal translocations that in 85% of cases lead to expression of the EWS-FLI-1 fusion protein. EWS-FLI-1 functions as an aberrant transcription factor that can both induce and suppress members of its target gene repertoire. We have recently demonstrated that EWS-FLI-1 can alter microRNA (miRNA expression and that miRNA145 is a direct EWS-FLI-1 target whose suppression is implicated in ESFT development. Here, we use miRNA arrays to compare the global miRNA expression profile of human mesenchymal stem cells (MSC and ESFT cell lines, and show that ESFT display a distinct miRNA signature that includes induction of the oncogenic miRNA 17-92 cluster and repression of the tumor suppressor let-7 family. We demonstrate that direct repression of let-7a by EWS-FLI-1 participates in the tumorigenic potential of ESFT cells in vivo. The mechanism whereby let-7a expression regulates ESFT growth is shown to be mediated by its target gene HMGA2, as let-7a overexpression and HMGA2 repression both block ESFT cell tumorigenicity. Consistent with these observations, systemic delivery of synthetic let-7a into ESFT-bearing mice restored its expression in tumor cells, decreased HMGA2 expression levels and resulted in ESFT growth inhibition in vivo. Our observations provide evidence that deregulation of let-7a target gene expression participates in ESFT development and identify let-7a as promising new therapeutic target for one of the most aggressive pediatric malignancies.

  20. Effect of melatonin on methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity and methamphetamine-induced behavioral sensitization.

    Science.gov (United States)

    Itzhak, Y; Martin, J L; Black, M D; Ali, S F

    1998-06-01

    Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH

  1. The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

    Science.gov (United States)

    2002-01-01

    1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

  2. Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy.

    Science.gov (United States)

    Wang, Zhenguang; Han, Weidong

    2018-01-01

    Severe cytokine release syndrome (CRS) and neurotoxicity following chimeric antigen receptor T cell (CAR-T) therapy can be life-threatening in some cases, and management of those toxicities is still a great challenge for physicians. Researchers hope to understand the pathophysiology of CRS and neurotoxicity, and identify predictive biomarkers that can forecast those toxicities in advance. Some risk factors for severe CRS and/or neurotoxicity including patient and treatment characteristics have been identified in multiple clinical trials of CAR-T cell therapy. Moreover, several groups have identified some predictive biomarkers that are able to determine beforehand which patients may suffer severe CRS and/or neurotoxicity during CAR-T cell therapy, facilitating testing of early intervention strategies for those toxicities. However, further studies are needed to better understand the biology and related risk factors for CRS and/or neurotoxicity, and determine if those identified predictors can be extrapolated to other series. Herein, we review the pathophysiology of CRS and neurotoxicity, and summarize the progress of predictive biomarkers to improve CAR-T cell therapy in cancer.

  3. Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

    Science.gov (United States)

    Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

    2018-03-13

    Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of fundamental processes in neural tube formation, brain development and neural specification, aiming at illustrating complexity rather than comprehensiveness. We also give a flavor of the wealth of alternative methods in this area. Given the impressive progress in mechanistic knowledge of human biology and toxicology, the time is right for a conceptual approach for designing testing strategies that cover the integral mechanistic landscape of developmental neurotoxicity. The ontology approach provides a framework for defining this landscape, upon which an integral in silico model for predicting toxicity can be built. It subsequently directs the selection of in vitro assays for rate-limiting events in the biological network, to feed parameter tuning in the model, leading to prediction of the toxicological outcome. Validation of such models requires primary attention to coverage of the biological domain, rather than classical predictive value of individual tests. Proofs of concept for such an approach are already available. The challenge is in mining modern biology, toxicology and chemical information to feed intelligent designs, which will define testing strategies for neurodevelopmental toxicity testing. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Neurotoxic effects of carambola in rats: the role of oxalate.

    Science.gov (United States)

    Chen, Chien-Liang; Chou, Kang-Ju; Wang, Jyh-Seng; Yeh, Jeng-Hsien; Fang, Hua-Chang; Chung, Hsiao-Min

    2002-05-01

    Carambola (star fruit) has been reported to contain neurotoxins that cause convulsions, hiccups, or death in uremic patients, and prolong barbiturate-induced sleeping time in rats. The constituent responsible for these effects remains uncertain. Carambola contains a large quantity of oxalate, which can induce depression of cerebral function and seizures. This study was conducted to investigate the role of oxalate in carambola toxicity in rats. The effects on barbiturate-induced sleeping time and death caused by intraperitoneal administration of carambola juice were observed in Sprague-Dawley rats. To obtain a dose-dependent response curve and evaluate the lethal dose, rats were treated with serial amounts of pure carambola juice diluted with normal saline in a volume of 1:1. To test the role of oxalate in the neurotoxic effect of carambola, either 5.33 g/kg carambola after oxalate removal or 5.33 g/kg of pure carambola juice diluted with normal saline were administered intraperitoneally, while the control group was given normal saline before pentobarbital injection. The effects of carambola and oxalate-removed carambola on barbiturate-induced sleeping time were compared with those of saline. To assess the lethal effect of oxalate in carambola, we gave rats chemical oxalate at comparable concentrations to the oxalate content of carambola. Carambola juice administration prolonged barbiturate-induced sleeping time in a dose-dependent manner. The sleeping time of rats that received normal saline and 1.33 g/kg, 2.67 g/kg, 5.33 g/kg, and 10.67 g/kg of carambola juice were 66 +/- 16.6, 93.7 +/- 13.4, 113.3 +/- 11.4, 117.5 +/- 29.0, and 172.5 +/- 38.8 minutes, respectively. The three higher-dose groups had longer sleeping times than controls (p carambola juice. Four of eight rats in the 10.67-g/kg group and all rats in the 21.33 g/kg and chemical oxalate groups died after seizure. Lethal doses of carambola juice were rendered harmless by the oxalate removal procedure

  5. Revisiting the 'paradigm shift' in opioid use: Developments and implications 10 years later.

    Science.gov (United States)

    Fischer, Benedikt; Rehm, Jürgen

    2017-03-23

    A decade ago, we queried the unfolding of a 'paradigm shift' in illicit opioid use in North America, specifically involving a shift away from heroin to prescription opioid (PO) use. Today, this situation is more acute than ever, with prescription opioid misuse, morbidity and mortality amounting to one of the most severe substance use-related public health crises ever, now even impacting life expectancy in key population segments. Despite medical system-based PO dispensing and practices being recognised as core drivers of the PO crisis, effective policy measures have been long absent or limited-including those to reduce medical PO use to levels supported by best evidence for pain care. At the same time, heroin use has been increasing again, now commonly tied into interdependent opioid use trajectories, initiated with POs yet shifting to heroin as influenced by economic or availability factors. For policy, there are now two major and urgent-yet partly conflicting-tasks: one is to reduce the determinants of PO misuse and harms by reducing medical prescribing to levels supported by good evidence, while the other is to effectively protect those many active problematic PO users from acute harms (including overdose mortality) by providing effective treatment and survival aids (e.g. naloxone). Surprisingly, it appears that a major 'homemade' and medical system-induced drug crisis has been at least as challenging for North American policy systems to address as other, more conventional illicit drug problems. Lessons for policy hence need to be urgently identified and applied for the future. [Fischer B, Rehm J. Revisiting the 'paradigm shift' in opioid use: Developments and implications 10 years later. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  6. Consumer perceptions of smart grid development: Results of a Hong Kong survey and policy implications

    International Nuclear Information System (INIS)

    Mah, Daphne Ngar-yin; Vleuten, Johannes Marinus van der; Hills, Peter; Tao, Julia

    2012-01-01

    Consumers have a major role to play in smart grid technologies which can be instrumental in addressing climate change and energy challenges. However, little is known about how consumers perceive, and how they might respond to the opportunities that smart grid technologies offer. This paper reports the results from a Hong Kong survey (n=505). It contributes to the literature by providing a better understanding of the perceptions and behaviour of electricity consumers about the possible deployment of smart grids. Our results indicate that Hong Kong consumers generally welcomed smart grid technologies and had a preference for energy saving, energy efficiency and renewable energy while they showed a high level of opposition to nuclear power. They displayed an interest in playing a much more informed and active role in energy decision-making, but they were sensitive to tariff increases. Motivations and barriers for consumers to support smart grid developments are also discussed. We conclude with a discussion of policy implications for effective consumer engagement. More policy attention is needed on demand-side measures, introducing institutional and regulatory changes, and modifying relationships between consumers, the government and utilities. - Highlights: ► Consumers have a major role in smart grid technologies. ► This paper reports findings of a Hong Kong survey on how consumers perceive and respond. ► Hong Kong consumers are interested in being informed and playing an active role in energy decision-making. ► Motivations and barriers are discussed. ► Policy recommendations for effective consumer engagement are suggested.

  7. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

    2015-02-01

    A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

  8. Acute neurotoxicity after yohimbine ingestion by a body builder.

    Science.gov (United States)

    Giampreti, Andrea; Lonati, Davide; Locatelli, Carlo; Rocchi, Loretta; Campailla, Maria Teresa

    2009-09-01

    Yohimbine is an alkaloid obtained from the Corynanthe yohimbe tree and other biological sources. Yohimbine is currently approved in the United States for erectile dysfunction and has undergone resurgence in street use as an aphrodisiac and mild hallucinogen. In recent years yohimbine use has become common in body-building communities for its presumed lipolytic and sympathomimetic effects. We describe a 37-year-old bodybuilder in which severe acute neurotoxic effects occurred in 2 h after yohimbine ingestion. The patient presented with malaise, vomiting, loss of consciousness, and repeated seizures after ingestion of 5 g of yohimbine during a body-building competition in a gymnasium. His Glasgow Coma Score was 3, requiring orotracheal intubation. Two hours after admission, vital signs were blood pressure 259/107 mmHg and heart rate 140 beats/min. Treatment with furosemide, labetalol, clonidine, and urapidil and gastrointestinal decontamination were performed. Twelve hours later the patient was extubated with normal hemodynamic parameters and neurological examination. The yohimbine blood levels at 3, 6, 14, and 22 h after ingestion were 5,240; 2,250; 1,530; and 865 ng/mL, respectively, with a mean half-life of 2 h. Few data are available about yohimbine toxicity and the related blood levels. This is a case of a large ingestion of yohimbine in which severe hemodynamic and neurological manifestations occurred and elevated blood levels of yohimbine were detected.

  9. Trichloropropane and dichlorohydrin associated with painful peripheral neurotoxicity.

    Science.gov (United States)

    Shi, Xiaobing; Yu, Shengyuan

    2013-10-01

    Trichloropropane (TCP) and dichlorohydrin are widely used in industrial production; however, TCP and dichlorohydrin poisoning are rarely encountered in clinical practice. There have been no cases of peripheral neurotoxicity previously reported. A cluster of 23 patients who had been exposed to high levels of TCP and dichlorohydrin presented with painful peripheral neuropathy, and the pain was assessed using a visual analogue scale (VAS). Nerve conduction studies (NCS) were performed in all patients. All patients demonstrated symmetrical pin-prick pain in a stocking distribution in the lower limbs, with VAS scores between 3 and 10, with an average score of 6.8. NCS showed a mild mixture of axonal and demyelinating sensorimotor polyneuropathy in 14 of the 23 patients. After administration of standard neuropathic pain medication, pain was relieved in most patients. Painful peripheral neuropathy was the primary symptom observed in our patients, which differs from clinical and animal model reports of TCP or dichlorohydrin poisoning. However, the pathogenesis remains unidentified. TCP may be added to the list of industrial products that are toxic to the peripheral sensory nerves. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Diazinon and Cadmium Neurotoxicity in Rats after an Experimental Administration

    Directory of Open Access Journals (Sweden)

    Róbert Toman

    2012-10-01

    Full Text Available The aim of this study was to describe the changes in cholinesterase activity in separate doses and after coadministration of cadmium and diazinon intraperitoneally and to assess toxicity and interactions of diazinon and cadmium on the nervous system in male rats. 40 male rats were randomly divided into three experimental and one control group (10 rats in each group. Blood analyzes were performed 36 hours after an intraperitoneal administration of observed compounds. The statistical evaluation of the results showed significantly (P < 0.01 reduced activity of cholinesterase in all experimental groups. The enzyme activity decreased from the control value 3.69 μkat/L to 1.81 μkat/L (diazinon group, 1.83 μkat/L (cadmium group and 1.35 μkat/L (cadmium+diazinon group. These results indicate that both cadmium and diazinon are potent to manifest the neurotoxic effects. Moreover, a synergistic effect of the co-administered cadmium and diazinon in the nervous system has been observed.

  11. Preconditioning with subneurotoxic allyl nitrile: protection against allyl nitrile neurotoxicity.

    Science.gov (United States)

    Tanii, H; Higashi, T; Saijoh, K

    2010-02-01

    High-dose cruciferous allyl nitrile can induce behavioral abnormalities in rodents, while repeated exposure to allyl nitrile at subneurotoxic levels can increase phase 2 detoxification enzymes in many tissues, although the brain has not been investigated yet. In the present study, we examined the effect of 5 days repeated exposure to subneurotoxic allyl nitrile (0-400 micromol/kg/day) on the brain. Elevated glutathione S-transferase activity was recorded in the striatum, hippocampus, medulla oblongata plus pons, and cortex. Enhancement of quinone reductase activity was observed in the medulla oblongata plus pons, hippocampus, and cortex. In the medulla oblongata plus pons, elevated glutathione levels were recorded. Following repeated subneurotoxic allyl nitrile exposure (0-400 micromol/kg/day), mice were administered a high-dose allyl nitrile (1.2 mmol/kg) which alone led to appearance of behavioral abnormalities. Compared with the 0 micromol/kg/day group, animals in the 200 and 400 micromol/kg/day pre-treatment groups exhibited decreased behavioral abnormalities and elevated GABA-positive cell counts in the substantia nigra pars reticulata and the interpeduncular nucleus. These data suggest that repeated exposure to subneurotoxic levels of allyl nitrile can induce phase 2 enzymes in the brain, which together with induction in other tissues, may contribute to protection against allyl nitrile neurotoxicity. Copyright 2009 Elsevier Ltd. All rights reserved.

  12. Gender differences in the neurotoxicity of metals in children

    International Nuclear Information System (INIS)

    Llop, Sabrina; Lopez-Espinosa, Maria-Jose; Rebagliato, Marisa; Ballester, Ferran

    2013-01-01

    Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on potential neurodevelopment effects in children due to mercury exposure is available, but, a clear pattern regarding gender differences in neurotoxicity is not elucidated. There is also abundant available information on the gender-specific health effects of lead, and exposure to this metal seems to affect boys more than girls. Information regarding gender differences in susceptibility of manganese, cadmium, and arsenic is still too scarce to draw any definite conclusion. More research is highly warranted about this matter. Environmental epidemiological studies should be designed to quantify differential gender-based exposures and outcomes, and this may provide new insights into prevention strategies

  13. Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity evaluation.

    Science.gov (United States)

    O'Callaghan, James P; Daughtrey, Wayne C; Clark, Charles R; Schreiner, Ceinwen A; White, Russell

    2014-11-01

    Sprague-Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) and exposures were for 6h/day, 5days/week for 13weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiplebrain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Pharmacological imaging as a tool to visualise dopaminergic neurotoxicity.

    Science.gov (United States)

    Schrantee, A; Reneman, L

    2014-09-01

    Dopamine abnormalities underlie a wide variety of psychopathologies, including ADHD and schizophrenia. A new imaging technique, pharmacological magnetic resonance imaging (phMRI), is a promising non-invasive technique to visualize the dopaminergic system in the brain. In this review we explore the clinical potential of phMRI in detecting dopamine dysfunction or neurotoxicity, assess its strengths and weaknesses and identify directions for future research. Preclinically, phMRI is able to detect severe dopaminergic abnormalities quite similar to conventional techniques such as PET and SPECT. phMRI benefits from its high spatial resolution and the possibility to visualize both local and downstream effects of dopaminergic neurotransmission. In addition, it allows for repeated measurements and assessments in vulnerable populations. The major challenge is the complex interpretation of phMRI results. Future studies in patients with dopaminergic abnormalities need to confirm the currently reviewed preclinical findings to validate the technique in a clinical setting. Eventually, based on the current review we expect that phMRI can be of use in a clinical setting involving vulnerable populations (such as children and adolescents) for diagnosis and monitoring treatment efficacy. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Documenting PyroCb Development on High-Intensity Boreal Fires: Implications for the Arctic Atmosphere

    Science.gov (United States)

    Stocks, B. J.; Fromm, M. D.; Servranckx, R.; Lindsey, D.

    2007-12-01

    The recent confirmation that smoke from high-intensity boreal forest fires can reach the Upper Troposphere/Lower Stratosphere (UTLS) through pyroconvection and be transported long distances has raised concern over the wider-scale environmental impact of boreal fire smoke. This concern is further elevated as climate change projections indicate a significant increase in the frequency and severity of boreal forest fires over the next century. Smoke in the UTLS is frequently transported to the Arctic and may have important implications for the radiative energy budget in the polar region. Soot deposition from fires may lead to enhanced melting of sea ice and glaciers, and the chemical impact of fire emissions at high altitudes is largely unknown. This knowledge gap will be addressed during the International Polar Year (IPY), as boreal fire emissions will be tracked and documented in detail through aerial, satellite and ground-based measurements, as a key component of the POLARCAT (Polar Study using Aircraft, Remote Sensing, Surface Measurements and Models, of Climate, Chemistry, Aerosols, and Transport) and ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) projects to be conducted in 2008. A large fire in the Canadian Northwest Territories burned throughout the month of June 2007, in a remote region where forest fires are not actively suppressed, eventually reaching 90,000 hectares in size. This fire was monitored for blowup one week in advance; it erupted into pyroconvection on June 25, 2007. We present an analysis of this event combining satellite data with ground-based measurements to document the development and impact of this classic pyroCb event. Under extreme fire danger conditions, the fire burned close to 20,000 hectares on that day. Fire behavior was consistent with predictions using the Canadian Fire Behavior Prediction System, with the fire spreading at 2.7 km/hr, consuming 33,000 kg of fuel hourly, generating an

  16. Mechanistic Bases of Neurotoxicity Provoked by Fatty Acids Accumulating in MCAD and LCHAD Deficiencies

    Directory of Open Access Journals (Sweden)

    Alexandre U. Amaral PhD

    2017-03-01

    Full Text Available Fatty acid oxidation defects (FAODs are inherited metabolic disorders caused by deficiency of specific enzyme activities or transport proteins involved in the mitochondrial catabolism of fatty acids. Medium-chain fatty acyl-CoA dehydrogenase (MCAD and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD deficiencies are relatively common FAOD biochemically characterized by tissue accumulation of medium-chain fatty acids and long-chain 3-hydroxy fatty acids and their carnitine derivatives, respectively. Patients with MCAD deficiency usually have episodic encephalopathic crises and liver biochemical alterations especially during crises of metabolic decompensation, whereas patients with LCHAD deficiency present severe hepatopathy, cardiomyopathy, and acute and/or progressive encephalopathy. Although neurological symptoms are common features, the underlying mechanisms responsible for the brain damage in these disorders are still under debate. In this context, energy deficiency due to defective fatty acid catabolism and hypoglycemia/hypoketonemia has been postulated to contribute to the pathophysiology of MCAD and LCHAD deficiencies. However, since energetic substrate supplementation is not able to reverse or prevent symptomatology in some patients, it is presumed that other pathogenetic mechanisms are implicated. Since worsening of clinical symptoms during crises is accompanied by significant increases in the concentrations of the accumulating fatty acids, it is conceivable that these compounds may be potentially neurotoxic. We will briefly summarize the current knowledge obtained from patients with these disorders, as well as from animal studies demonstrating deleterious effects of the major fatty acids accumulating in MCAD and LCHAD deficiencies, indicating that disruption of mitochondrial energy, redox, and calcium homeostasis is involved in the pathophysiology of the cerebral damage in these diseases. It is presumed that these findings based on the

  17. Leptin-dependent neurotoxicity via induction of apoptosis in adult rat neural stem cells

    Directory of Open Access Journals (Sweden)

    Stéphanie eSEGURA

    2015-09-01

    Full Text Available Adipocyte-derived hormone leptin has been recently implicated in the control of neuronal plasticity. To explore whether modulation of adult neurogenesis may contribute to leptin control of neuronal plasticity, we used the neurosphere assay of neural stem cells derived from the adult rat subventricular zone (SVZ. Endogenous expression of specific leptin receptor (ObRb transcripts, as revealed by RT-PCR, is associated with activation of both ERK and STAT-3 pathways via phosphorylation of the critical ERK/STAT-3 amino acid residues upon addition of leptin to neurospheres. Furthermore, leptin triggered withdrawal of neural stem cells from the cell cycle as monitored by Ki67 labelling. This effect was blocked by pharmacological inhibition of ERK activation thus demonstrating that ERK mediates leptin effects on neural stem cell expansion. Leptin-dependent withdrawal of neural stem cells from the cell cycle was associated with increased apoptosis, as detected by TUNEL, which was preceded by cyclin D1 induction. Cyclin D1 was indeed extensively colocalized with TUNEL-positive apoptotic cells. Cyclin-D1 silencing by specific shRNA prevented leptin-induced decrease of the cell number per neurosphere thus pointing to the causal relationship between leptin actions on apoptosis and cyclin D1 induction. Leptin target cells in SVZ neurospheres were identified by double TUNEL/phenotypic marker immunocytofluorescence as differentiating neurons mostly. The inhibition of neural stem cell expansion via ERK/cyclin D1-triggered apoptosis defines novel biological action of leptin which may be involved in adiposity-dependent neurotoxicity.

  18. Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice

    Science.gov (United States)

    Bortolussi, Giulia; Baj, Gabriele; Vodret, Simone; Viviani, Giulia; Bittolo, Tamara; Muro, Andrés F.

    2014-01-01

    Neonatal jaundice is caused by high levels of unconjugated bilirubin. It is usually a temporary condition caused by delayed induction of UGT1A1, which conjugates bilirubin in the liver. To reduce bilirubin levels, affected babies are exposed to phototherapy (PT), which converts toxic bilirubin into water-soluble photoisomers that are readily excreted out. However, in some cases uncontrolled hyperbilirubinemia leads to neurotoxicity. To study the mechanisms of bilirubin-induced neurological damage (BIND) in vivo, we generated a mouse model lacking the Ugt1a1 protein and, consequently, mutant mice developed jaundice as early as 36 hours after birth. The mutation was transferred into two genetic backgrounds (C57BL/6 and FVB/NJ). We exposed mutant mice to PT for different periods and analyzed the resulting phenotypes from the molecular, histological and behavioral points of view. Severity of BIND was associated with genetic background, with 50% survival of C57BL/6‑Ugt1−/− mutant mice at postnatal day 5 (P5), and of FVB/NJ-Ugt1−/− mice at P11. Life-long exposure to PT prevented cerebellar architecture alterations and rescued neuronal damage in FVB/NJ-Ugt1−/− but not in C57BL/6-Ugt1−/− mice. Survival of FVB/NJ-Ugt1−/− mice was directly related to the extent of PT treatment. PT treatment of FVB/NJ-Ugt1−/− mice from P0 to P8 did not prevent bilirubin-induced reduction in dendritic arborization and spine density of Purkinje cells. Moreover, PT treatment from P8 to P20 did not rescue BIND accumulated up to P8. However, PT treatment administered in the time-window P0–P15 was sufficient to obtain full rescue of cerebellar damage and motor impairment in FVB/NJ-Ugt1−/− mice. The possibility to modulate the severity of the phenotype by PT makes FVB/NJ-Ugt1−/− mice an excellent and versatile model to study bilirubin neurotoxicity, the role of modifier genes, alternative therapies and cerebellar development during high bilirubin conditions. PMID

  19. Zika virus reservoirs: Implications for transmission, future outbreaks, drug and vaccine development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Raj Kalkeri

    2017-10-01

    Full Text Available Zika virus (ZIKV was recently declared as a ‘Global Health Emergency’ by the World Health Organization. Various tissue reservoirs of ZIKV in infected humans and animals models have been observed, the implications of which are not known. Compared to other Flaviviruses, sexual transmission and persistence in the genitourinary tract seem to be unique to ZIKV. ZIKV persistence and shedding in bodily secretions (e.g. saliva, semen is a concern for potential disease spread and could pose challenges in diagnosis, regulatory guidelines and drug/vaccine development. Murine and non-human primate models could be useful to study the role of tissue reservoirs in the development of prophylactic or therapeutic strategies. There is a need for meta-analysis of the ZIKV infection and virus shedding data from infected patients and ZIKV animal models, and additional research is needed to fully comprehend the long term implications of tissue reservoirs on ZIKV disease pathogenesis and biology.

  20. [Neurological syndromes linked with the intake of plants and fungi containing a toxic component (I). Neurotoxic syndromes caused by the ingestion of plants, seeds and fruits].

    Science.gov (United States)

    Carod-Artal, F J

    A wide range of plants, seeds and fruits used for nutritional and medicinal purposes can give rise to neurotoxic symptoms. We review the neurological pathology associated with the acute or chronic consumption of plants, seeds and fruits in human beings and in animals. Of the plants that can trigger acute neurotoxic syndromes in humans, some of the most notable include Mandragora officinalis, Datura stramonium, Conium maculatum (hemlock), Coriaria myrtifolia (redoul), Ricinus communis, Gloriosa superba, Catharanthus roseus, Karwinskia humboldtiana and Podophyllum pelatum. We also survey different neurological syndromes linked with the ingestion of vegetable foodstuffs that are rich in cyanogenic glycosides, Jamaican vomiting sickness caused by Blighia sapida, Parkinson dementia ALS of Guam island and exposition to Cycas circinalis, Guadeloupean parkinsonism and exposition to Annonaceae, konzo caused by ingestion of wild manioc and neurolathyrism from ingestion of Lathyrus sativus, the last two being models of motor neurone disease. Locoism is a chronic disease that develops in livestock feeding on plants belonging to Astragalus and Oxytropis sp., Sida carpinifolia and Ipomea carnea, which are rich in swainsonine, a toxin that inhibits the enzyme alpha mannosidase and induces a cerebellar syndrome. The ingestion of neurotoxic seeds, fruits and plants included in the diet and acute poisoning by certain plants can give rise to different neurological syndromes, some of which are irreversible.

  1. Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity

    International Nuclear Information System (INIS)

    Kalaria, R.N.; Mitchell, M.J.; Harik, S.I.

    1987-01-01

    Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and subhuman primates, but not in rats and many other laboratory animals; mice are intermediate in their susceptibility. Since MPTP causes selective dopaminergic neurotoxicity when infused directly into rat substantia nigra, the authors hypothesized that systemic MPTP may be metabolized by monoamine oxidase and/or other enzymes in rat brain capillaries and possibly other peripheral organs and thus prevented from reaching its neuronal sites of toxicity. They tested this hypothesis by assessing monoamine oxidase in isolated cerebral microvessels of humans, rats, and mice by measuring the specific binding of [ 3 H]pargyline, an irreversible monoamine oxidase inhibitor, and by estimating the rates of MPTP and benzylamine oxidation. [ 3 H]Pargyline binding to rat cerebral microvessels was about 10-fold higher than to human or mouse microvessels. Also, MPTP oxidation by rat brain microvessels was about 30-fold greater than by human microvessels; mouse microvessels yielded intermediate values. These results may explain, at least in part, the marked species differences in susceptibility to systemic MPTP. They also suggest the potential importance of enzyme barriers at the blood-brain interface that can metabolize toxins not excluded by structural barriers, and may provide biological bases for developing therapeutic strategies for the prevention of MPTP-induced neurotoxicity and other neurotoxic conditions including, possibly, Parkinson's disease

  2. A model-based analysis of the implications of shale gas developments for the European gas market

    Energy Technology Data Exchange (ETDEWEB)

    De Joode, J.; Plomp, A.J.; Ozdemir, O. [ECN Policy Studies, Petten (Netherlands)

    2012-04-15

    Shale gas in Europe could potentially be a big thing, especially in particular regions. Whereas test drillings need to confirm the technical recoverability of deposits and further research is needed on the environmental and safety aspects of shale gas production, this paper illustrates that shale gas developments may have substantial implications for regional gas balances, gas flows, and infrastructure requirements throughout Europe in the next decades.

  3. Glutamate in schizophrenia: clinical and research implications.

    Science.gov (United States)

    Goff, D C; Wine, L

    1997-10-30

    The excitatory amino acids, glutamate and aspartate, are of interest to schizophrenia research because of their roles in neurodevelopment, neurotoxicity and neurotransmission. Recent evidence suggests that densities of glutamatergic receptors and the ratios of subunits composing these receptors may be altered in schizophrenia, although it is unclear whether these changes are primary or compensatory. Agents acting at the phencyclidine binding site of the NMDA receptor produce symptoms of schizophrenia in normal subjects, and precipitate relapse in patients with schizophrenia. The improvement of negative symptoms with agents acting at the glycine modulatory site of the NMDA receptor, as well as preliminary evidence that clozapine may differ from conventional neuroleptic agents in its effects on glutamatergic systems, suggest that clinical implications may follow from this model. While geriatric patients may be at increased risk for glutamate-mediated neurotoxicity, very little is known about the specific relevance of this model to geriatric patients with schizophrenia.

  4. C-Reactive Protein Impairs Dendritic Cell Development, Maturation, and Function: Implications for Peripheral Tolerance

    Directory of Open Access Journals (Sweden)

    Rachel V. Jimenez

    2018-03-01

    Full Text Available C-reactive protein (CRP is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE in CRP transgenic mice by shifting CD4+ T cells away from the TH1 and toward the TH2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB, but did not require high levels of human CRP. Herein, we sought to determine if CRP’s influence in EAE might be explained by CRP acting on dendritic cells (DC; antigen presenting cells known to express FcγRIIB. We found that CRP (50 µg/ml reduced the yield of CD11c+ bone marrow-derived DCs (BMDCs and CRP (≥5 μg/ml prevented their full expression of major histocompatibility complex class II and the co-stimulatory molecules CD86 and CD40. CRP also decreased the ability of BMDCs to stimulate antigen-driven proliferation of T cells in vitro. Importantly, if the BMDCs were genetically deficient in mouse FcγRIIB then (i the ability of CRP to alter BMDC surface phenotype and impair T cell proliferation was ablated and (ii CD11c-driven expression of a human FCGR2B transgene rescued the CRP effect. Lastly, the protective influence of CRP in EAE was fully restored in mice with CD11c-driven human FcγRIIB expression. These findings add to the growing evidence that CRP has important biological effects even in the absence of an acute phase response, i.e., CRP acts as a tonic suppressor of the adaptive immune system. The ability of CRP to suppress development, maturation, and function of DCs implicates CRP in the maintenance of peripheral T cell tolerance.

  5. On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

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    El-Gezeery Amina R

    2011-08-01

    Full Text Available Abstract Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA, serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA, serotonin (5HT and dopamine (DA as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6, tumor necrosis factor-α (TNF-α as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE, phosphatidylserine (PS and phosphatidylcholine (PC. Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as

  6. Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao [Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012 (China); Liu, Zengxun [Department of Psychiatry, School of Medicine, Shandong University, Jinan, Shandong, 250012 China (China); Sun, Jinhao, E-mail: sunjinhao@gmail.com [Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012 (China)

    2015-09-25

    Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway.

  7. Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

    International Nuclear Information System (INIS)

    Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao; Liu, Zengxun; Sun, Jinhao

    2015-01-01

    Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway

  8. Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell lines

    International Nuclear Information System (INIS)

    Qian Yongchang; Venkatraj, Jijayanagaram; Barhoumi, Rola; Pal, Ranadip; Datta, Aniruddha; Wild, James R.; Tiffany-Castiglioni, Evelyn

    2007-01-01

    mitochondrial to cytosolic Ca 2+ fluorescence; after 3 days treatment, only 30 μM decreased the ratio. These results are consistent with the finding that paraoxon induced a greater decrease than did DFP of intracellular esterase activity in CCF cells. The changes seen in the ratio of mitochondrial to cytosolic Ca 2+ represent a good indicator of the degree of injury induced by each chemical tested. This work further develops in vitro models that distinguish between compounds that cause OPIDN and those that induce acute neurotoxicity only. The study also exposes additional OP-induced toxicities that may be obscured in vivo

  9. Neurotoxic effects of oxygen in hyperbaric environment: A case report

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    Rabrenović Milorad

    2015-01-01

    neurotoxic effects of oxygen while the patient was in a hyperbaric chamber, not epileptic seizures. Conclusion. This case report suggests that in patients with symptoms of epileptic seizures while undergoing treatment in a hyperbaric chamber, it is always important to think of neurotoxic effects of pure oxygen which occurs at higher pressures and with a longer inhalation of 100% oxygen. In these patients, reexposure to hyperbaric conditions leads to recovery. This effect is important in daily inhalation of 100% oxygen under hyperbaric conditions which is why the use of pure oxygen is controlled and diving is allowed in shallow depths and for a limited time.

  10. Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos

    International Nuclear Information System (INIS)

    Zurich, M.-G.; Honegger, P.; Schilter, B.; Costa, L.G.; Monnet-Tschudi, F.

    2004-01-01

    An in vitro model, the aggregating brain cell culture of fetal rat telencephalon, has been used to investigate the influence of glial cells on the neurotoxicity of two organophosphorus pesticides (OPs), chlorpyrifos and parathion. Mixed-cell aggregate cultures were treated continuously for 10 days between DIV 5 and 15. Parathion induced astrogliosis at concentration at which MAP-2 immunostaining, found here to be more sensitive than neuron-specific enzyme activities, was not affected. In contrast, chlorpyrifos induced a comparatively weak gliotic reaction, and only at concentrations at which neurons were already affected. After similar treatments, increased neurotoxicity of parathion and chlorpyrifos was found in aggregate cultures deprived of glial cells. These results suggest that glial cells provide neuroprotection against OPs toxicity. To address the question of the difference in toxicity between parathion and chlorpyrifos, the toxic effects of their leaving groups, p-nitrophenol and trichloropyridinol, were studied in mixed-cell aggregates. General cytotoxicity was more pronounced for trichloropyridinol and both compounds had similar toxic effects on neuron-specific enzyme activities. In contrast, trichloropyridinol induced a much stronger decrease in glutamine synthetase activity, the enzymatic marker of astrocytes. Trichloropyridinol may exert a toxic effect on astrocytes, compromising their neuroprotective function, thus exacerbating the neurotoxicity of chlorpyrifos. This is in line with the suggestion that glial cells may contribute to OPs neurotoxicity, and with the view that OPs may exert their neurotoxic effects through different mechanisms

  11. Protection against MDMA-induced dopaminergic neurotoxicity in mice by methyllycaconitine: involvement of nicotinic receptors.

    Science.gov (United States)

    Chipana, C; Camarasa, J; Pubill, D; Escubedo, E

    2006-09-01

    Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. Previous studies demonstrated the participation of alpha-7 nicotinic receptors (nAChR) in the neurotoxic effect of methamphetamine. The aim of this paper was to study the role of this receptor type in the acute effects and neurotoxicity of MDMA in mice. In vivo, methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at dopaminergic but not at serotonergic level, without affecting MDMA-induced hyperthermia. Glial activation was also fully prevented by MLA. In vitro, MDMA induced intrasynaptosomal reactive oxygen species (ROS) generation, which was calcium-, nitric-oxide synthase-, and protein kinase C-dependent. Also, the increase in ROS was prevented by MLA and alpha-bungarotoxin. Experiments with reserpine point to endogenous dopamine (DA) as the main source of MDMA-induced ROS. MLA also brought the MDMA-induced inhibition of [3H]DA uptake down, from 73% to 11%. We demonstrate that a coordinated activation of alpha-7 nAChR, blockade of DA transporter function and displacement of DA from intracellular stores induced by MDMA produces a neurotoxic effect that can be prevented by MLA, suggesting that alpha-7 nAChR have a key role in the MDMA neurotoxicity in mice; however, the involvement of nicotinic receptors containing the beta2 subunit cannot be conclusively ruled out.

  12. Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption.

    Science.gov (United States)

    Kita, Taizo; Wagner, George C; Nakashima, Toshikatsu

    2003-07-01

    Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.

  13. The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact

    Directory of Open Access Journals (Sweden)

    Margot Van de Bor

    2013-08-01

    Full Text Available In recent years concern has risen about the increasing prevalence of Autism Spectrum Disorders (ASD. Accumulating evidence shows that exposure to neurotoxic compounds is related to ASD. Neurotransmitters might play a key role, as research has indicated a connection between neurotoxic compounds, neurotransmitters and ASD. In the current review a literature overview with respect to neurotoxic exposure and the effects on neurotransmitter systems is presented. The aim was to identify mechanisms and related factors which together might result in ASD. The literature reported in the current review supports the hypothesis that exposure to neurotoxic compounds can lead to alterations in the GABAergic, glutamatergic, serotonergic and dopaminergic system which have been related to ASD in previous work. However, in several studies findings were reported that are not supportive of this hypothesis. Other factors also might be related, possibly altering the mechanisms at work, such as time and length of exposure as well as dose of the compound. Future research should focus on identifying the pathway through which these factors interact with exposure to neurotoxic compounds making use of human studies.

  14. Attenuation of arsenic neurotoxicity by curcumin in rats

    International Nuclear Information System (INIS)

    Yadav, Rajesh S.; Sankhwar, Madhu Lata; Shukla, Rajendra K.; Chandra, Ramesh; Pant, Aditya B.; Islam, Fakhrul; Khanna, Vinay K.

    2009-01-01

    In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

  15. Tricyclic sesquiterpene copaene prevents H2O2-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hasan Turkez

    2014-02-01

    Full Text Available Aim: Copaene (COP, a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and anticarcinogenic features. But, very little information is known about the effects of COP on oxidative stress induced neurotoxicity. Method: We used hydrogen peroxide (H2O2 exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of COP in H2O2-induced toxicity in rat cerebral cortex cell cultures for the first time. For this purpose, methyl thiazolyl tetrazolium (MTT and lactate dehydrogenase (LDH release assays were carried out to evaluate cytotoxicity. Total antioxidant capacity (TAC and total oxidative stress (TOS parameters were used to evaluate oxidative changes. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG levels, the single cell gel electrophoresis (SCGE or comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Result: The results of this study showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage increased in the H2O2 alone treated cultures. But pre-treatment of COP suppressed the cytotoxicity, genotoxicity and oxidative stress which were increased by H2O2. Conclusion: It is proposed that COP as a natural product with an antioxidant capacity in mitigating oxidative injuries in the field of neurodegenerative diseases. [J Intercult Ethnopharmacol 2014; 3(1.000: 21-28

  16. In vitro comparison of rat and chicken brain neurotoxic esterase

    International Nuclear Information System (INIS)

    Novak, R.; Padilla, S.

    1986-01-01

    A systematic comparison was undertaken to characterize neurotoxic esterase (NTE) from rat and chicken brain in terms of inhibitor sensitivities, pH optima, and molecular weights. Paraoxon titration of phenyl valerate (PV)-hydrolyzing carboxylesterases showed that rat esterases were more sensitive than chicken to paraoxon inhibition at concentrations less than or equal to microM and superimposable with chicken esterases at concentrations of 2.5-1000 microM. Mipafox titration of the paraoxon-resistant esterases at a fixed paraoxon concentration of 100 microM (mipafox concentration: 0-1000 microM) resulted in a mipafox I50 of 7.3 microM for chicken brain NTE and 11.6 microM for rat brain NTE. NTE (i.e., paraoxon-resistant, mipafox-sensitive esterase activity) comprised 80% of chicken and 60% of rat brain paraoxon-resistant activity with the specific activity of chicken brain NTE approximately twice that of rat brain NTE. The pH maxima for NTE from both species was similar showing broad, slightly alkaline optima from pH 7.9 to 8.6. [ 3 H]Diisopropyl phosphorofluoridate (DFP)-labeled NTE from the brains of both species had an apparent mol wt of 160,000 measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In conclusion, NTE from both species was very similar, with the mipafox I50 for rat NTE within the range of reported values for chicken and human NTE, and the inhibitor parameters of the chicken NTE assay were applicable for the rat NTE assay

  17. Gender differences in alcohol-induced neurotoxicity and brain damage.

    Science.gov (United States)

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity.

    Science.gov (United States)

    Virgin, C E; Ha, T P; Packan, D R; Tombaugh, G C; Yang, S H; Horner, H C; Sapolsky, R M

    1991-10-01

    Glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, can damage the hippocampus and impair its capacity to survive coincident neurological insults. This GC endangerment of the hippocampus is energetic in nature, as it can be prevented when neurons are supplemented with additional energy substrates. This energetic endangerment might arise from the ability of GCs to inhibit glucose transport into both hippocampal neurons and astrocytes. The present study explores the GC inhibition in astrocytes. (1) GCs inhibited glucose transport approximately 15-30% in both primary and secondary hippocampal astrocyte cultures. (2) The parameters of inhibition agreed with the mechanisms of GC inhibition of glucose transport in peripheral tissues: A minimum of 4 h of GC exposure were required, and the effect was steroid specific (i.e., it was not triggered by estrogen, progesterone, or testosterone) and tissue specific (i.e., it was not triggered by GCs in cerebellar or cortical cultures). (3) Similar GC treatment caused a decrease in astrocyte survival during hypoglycemia and a decrease in the affinity of glutamate uptake. This latter observation suggests that GCs might impair the ability of astrocytes to aid neurons during times of neurologic crisis (i.e., by impairing their ability to remove damaging glutamate from the synapse).

  19. Contesting 'Environment' Through the Lens of Sustainability: Examining Implications for Environmental Education (EE and Education for Sustainable Development (ESD

    Directory of Open Access Journals (Sweden)

    Helen Kopnina

    2014-10-01

    Full Text Available This article reflects on implications of presenting nature as a social construction, and of commodification of nature. The social construction of nature tends to limit significance of nature to human perception of it. Commodification presents nature in strict instrumental terms as 'natural resources', 'natural capital' or 'ecosystem services'. Both construction and commodification exhibit anthropocentric bias in denying intrinsic value of non-human species. This article will highlight the im-portance of a deep ecology perspective, by elaborating upon the ethical context in which construction and commodification of nature occur. Finally, this article will discuss the implications of this ethical context in relation to environmental education (EE and education for sustainable development (ESD.

  20. An outline of the need for psychology knowledge in health professionals: implications for community development and breast cancer prevention.

    Science.gov (United States)

    Ahmadian, Maryam; Samah, Asnarulkhadi Abu; Saidu, Mohammed Bashir

    2014-01-01

    Knowledge of health and community psychology in health professionals influences psychosocial and community determinants of health and promoting participation in disease prevention at the community level. This paper appraises the potential of knowledge on psychology in health care professionals and its contribution to community empowerment through individual behavior change and health practice. The authors proposed a schematic model for the use of psychological knowledge in health professionals to promote participation in health interventions/disease prevention programs in developing countries. By implication, the paper provides a vision on policies towards supporting breast cancer secondary prevention efforts for community health development in Asian countries.

  1. Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor.

    Science.gov (United States)

    Sagi, Yotam; Weinstock, Marta; Youdim, Moussa B H

    2003-07-01

    (R)-[(N-propargyl-(3R) aminoindan-5-yl) ethyl methyl carbamate] (TV3326) is a novel cholinesterase and brain-selective monoamine oxidase (MAO)-A/-B inhibitor. It was developed for the treatment of dementia co-morbid with extra pyramidal disorders (parkinsonism), and depression. On chronic treatment in mice it attenuated striatal dopamine depletion induced by MPTP and prevented the reduction in striatal tyrosine hydroxylase activity, like selective B and non-selective MAO inhibitors. TV3326 preferentially inhibits MAO-B in the striatum and hippocampus, and the degree of MAO-B inhibition correlates with the prevention of MPTP-induced dopamine depletion. Complete inhibition of MAO-B is not necessary for full protection from MPTP neurotoxicity. Unlike that seen after treatment with other MAO-A and -B inhibitors, recovery of striatal and hippocampal MAO-A and -B activities from inhibition by TV3326 did not show first-order kinetics. This has been attributed to the generation of a number of metabolites by TV3326 that cause differential inhibition of these enzymes. Inhibition of brain MAO-A and -B by TV3326 resulted in significant elevations of dopamine, noradrenaline and serotonin in the striatum and hippocampus. This may explain its antidepressant-like activity, resembling that of moclobemide in the forced-swim test in rats.

  2. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

    Science.gov (United States)

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y; Luo, Guoxiong; Szeto, Hazel H; Beal, M Flint

    2009-09-01

    A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD.

  3. Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice

    Directory of Open Access Journals (Sweden)

    Yue-Qin Zeng

    2018-04-01

    Full Text Available Alzheimer’s disease (AD is pathologically characterized by excessive accumulation of amyloid-beta (Aβ within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology.

  4. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Science.gov (United States)

    Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

  5. UNDERTAKING POSITIVE CONTROL STUDIES AS PART OF DEVELOPMENTAL NEUROTOXICITY TESTING: A REPORT FROM THE ILSI RESEARCH FOUNDATION/RISK SCIENCE INSTITUTE EXPERT WORKING GROUP ON NEURODEVELOPMENTAL ENDPOINTS

    Science.gov (United States)

    Developmental neurotoxicity testing involves functional and neurohistological assessments in offspring during and following maternal and/or neonatal exposure. Data from positive control studies are an integral component in developmental neurotoxicity risk assessments. Positive ...

  6. Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Gaitonde, D.; Sarkar, A.; Kaisary, S.; DeSilva, C.; Dias, C.F.M.; Rao, P.V.S.S.D.P.; Ray; Nagarajan, R.; DeSousa, S.N.; Sarkar, S.; Patill, D.

    can be attributed to neurotoxic substances prevalent in those regions. The high concentration of different neurotoxic metals (lead, cadmium, copper, manganese and iron) and petroleum hydrocarbons in the tissues of the marine snails at Dona Paula, Vasco...

  7. Central Nervous System Infection with Borna Disease Virus Causes Kynurenine Pathway Dysregulation and Neurotoxic Quinolinic Acid Production.

    Science.gov (United States)

    Formisano, Simone; Hornig, Mady; Yaddanapudi, Kavitha; Vasishtha, Mansi; Parsons, Loren H; Briese, Thomas; Lipkin, W Ian; Williams, Brent L

    2017-07-15

    Central nervous system infection of neonatal and adult rats with Borna disease virus (BDV) results in neuronal destruction and behavioral abnormalities with differential immune-mediated involvement. Neuroactive metabolites generated from the kynurenine pathway of tryptophan degradation have been implicated in several human neurodegenerative disorders. Here, we report that brain expression of key enzymes in the kynurenine pathway are significantly, but differentially, altered in neonatal and adult rats with BDV infection. Gene expression analysis of rat brains following neonatal infection showed increased expression of kynurenine amino transferase II (KATII) and kynurenine-3-monooxygenase (KMO) enzymes. Additionally, indoleamine 2,3-dioxygenase (IDO) expression was only modestly increased in a brain region- and time-dependent manner in neonatally infected rats; however, its expression was highly increased in adult infected rats. The most dramatic impact on gene expression was seen for KMO, whose activity promotes the production of neurotoxic quinolinic acid. KMO expression was persistently elevated in brain regions of both newborn and adult BDV-infected rats, with increases reaching up to 86-fold. KMO protein levels were increased in neonatally infected rats and colocalized with neurons, the primary target cells of BDV infection. Furthermore, quinolinic acid was elevated in neonatally infected rat brains. We further demonstrate increased expression of KATII and KMO, but not IDO, in vitro in BDV-infected C6 astroglioma cells. Our results suggest that BDV directly impacts the kynurenine pathway, an effect that may be exacerbated by inflammatory responses in immunocompetent hosts. Thus, experimental models of BDV infection may provide new tools for discriminating virus-mediated from immune-mediated impacts on the kynurenine pathway and their relative contribution to neurodegeneration. IMPORTANCE BDV causes persistent, noncytopathic infection in vitro yet still elicits

  8. In Zucker Diabetic Fatty Rats, Subclinical Diabetic Neuropathy Increases In Vivo Lidocaine Block Duration But Not In Vitro Neurotoxicity

    NARCIS (Netherlands)

    Lirk, Philipp; Flatz, Magdalena; Haller, Ingrid; Hausott, Barbara; Blumenthal, Stephan; Stevens, Markus F.; Suzuki, Suzuko; Klimaschewski, Lars; Gerner, Peter

    2012-01-01

    Background and Objectives: Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. In addition, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity

  9. TRANSFORMATION OF DEVELOPMENTAL NEUROTOXICITY DATA INTO STRUCTURE-SEARCHABLE TOXML DATABASE IN SUPPORT OF STRUCTURE-ACTIVITY RELATIONSHIP (SAR) WORKFLOW.

    Science.gov (United States)

    Early hazard identification of new chemicals is often difficult due to lack of data on the novel material for toxicity endpoints, including neurotoxicity. At present, there are no structure searchable neurotoxicity databases. A working group was formed to construct a database to...

  10. Strategies of Echinococcus species responses to immune attacks: implications for therapeutic tool development.

    Science.gov (United States)

    Zheng, Yadong

    2013-11-01

    Echinococcus species have been studied as a model to investigate parasite-host interactions. Echinococcus spp. can actively communicate dynamically with a host to facilitate infection, growth and proliferation partially via secretion of molecules, especially in terms of harmonization of host immune attacks. This review systematically outlines our current knowledge of how the Echinococcus species have evolved to adapt to their host's microenvironment. This understanding of parasite-host interplay has implications in profound appreciation of parasite plasticity and is informative in designing novel and effective tools including vaccines and drugs for the treatment of echinococcosis and other diseases. © 2013.

  11. The Development of Innovation System Research: Towards meaningful implications for innovation policy?

    DEFF Research Database (Denmark)

    Rakas, Marija; Hain, Daniel

    and private organizations. This proposition has stimulated discussions across academic disciplines and been applied in various fields of study, such as innovation management, economic geography, growth economics, and the study of socio-technological transitions. While the general idea of “system thinking......” nowadays can be considered as pervasive across academic traditions associated with the broader field of innovation studies, we observe significant heterogeneity with respect to the building blocks of the NIS concept emphasized as well as the problems tackled and implications provided. Yet, this diversity...

  12. Music Preference and the Issues of Social Challenges Among Nigerian Youth: Implications For Moral Development

    OpenAIRE

    Femi Abiodun

    2017-01-01

    Music is central to youth culture. Central to this study is the question: what type of music do youth listen to and why do they listen to such music? Identifying the music preference of the Nigerian youth is the focus of this paper. The aim is to assess some moral challenges that are inherent in the types of music listened to by students in Nigerian tertiary institutions which by implication represent Nigerian youth. Questionnaire was used to find out the type of music most preferred by the s...

  13. Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells.

    Science.gov (United States)

    Ferreira, Patrícia Silva; Nogueira, Tiago Bernandes; Costa, Vera Marisa; Branco, Paula Sério; Ferreira, Luísa Maria; Fernandes, Eduarda; Bastos, Maria Lourdes; Meisel, Andreas; Carvalho, Félix; Capela, João Paulo

    2013-02-04

    "Ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) is a widely abused recreational drug, reported to produce neurotoxic effects, both in laboratory animals and in humans. MDMA metabolites can be major contributors for MDMA neurotoxicity. This work studied the neurotoxicity of MDMA and its catechol metabolites, α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA) in human dopaminergic SH-SY5Y cells differentiated with retinoic acid and 12-O-tetradecanoyl-phorbol-13-acetate. Differentiation led to SH-SY5Y neurons with higher ability to accumulate dopamine and higher resistance towards dopamine neurotoxicity. MDMA catechol metabolites were neurotoxic to SH-SY5Y neurons, leading to caspase 3-independent cell death in a concentration- and time-dependent manner. MDMA did not show a concentration- and time-dependent death. Pre-treatment with the antioxidant and glutathione precursor, N-acetylcysteine (NAC), resulted in strong protection against the MDMA metabolites' neurotoxicity. Neither the superoxide radical scavenger, tiron, nor the inhibitor of the dopamine (DA) transporter, GBR 12909, prevented the metabolites' toxicity. Cells exposed to α-MeDA showed an increase in intracellular glutathione (GSH) levels, which, at the 48 h time-point, was not dependent in the activity increase of γ-glutamylcysteine synthetase (γ-GCS), revealing a possible transient effect. Importantly, pre-treatment with buthionine sulfoximine (BSO), an inhibitor of γ-GCS, prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity. Even so, BSO pre-treatment abolished NAC protective effects against α-MeDA neurotoxicity, which were, at least partially, due to GSH de novo synthesis. Inversely, pre-treatment of cells with BSO augmented N-Me-α-MeDA-induced neurotoxicity, but only slightly affected NAC neuroprotection. In conclusion, MDMA catechol metabolites promote differential toxic effects to differentiated dopaminergic human SH

  14. Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

    Directory of Open Access Journals (Sweden)

    Nils Klüver

    Full Text Available Acetylcholinesterase (AChE inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM, in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB and 2,4-dinitrophenol (DNP. A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.

  15. [Martin Klesment. Fertility development in Estonia during the second half of the XX century: the economic context and its implications] / Olaf Mertelsmann

    Index Scriptorium Estoniae

    Mertelsmann, Olaf, 1969-

    2011-01-01

    Arvustus: Martin Klesment. Fertility development in Estonia during the second half of the XX century: the economic context and its implications. Tallinn: Tallinna Ülikool, 2010. (Tallinna Ülikooli sotsiaalteaduste dissertatsioonid, 46)

  16. Ethical Development during the College Years: Theory and Normative Implications for Practice.

    Science.gov (United States)

    Diessner, Rhett

    This paper discusses moral development as an integral part of the educational process and development of college students. The paper's first section places the concept of development within a network of meaning that indicates "ethical development" to be redundant; i.e., if something enhances development, it is ethical, and if it is ethical, it…

  17. Neurotoxic Non-proteinogenic Amino Acid β-N-Methylamino-L-alanine and Its Role in Biological Systems.

    Science.gov (United States)

    Popova, A A; Koksharova, O A

    2016-08-01

    Secondary metabolites of photoautotrophic organisms have attracted considerable interest in recent years. In particular, molecules of non-proteinogenic amino acids participating in various physiological processes and capable of producing adverse ecological effects have been actively investigated. For example, the non-proteinogenic amino acid β-N-methylamino-L-alanine (BMAA) is neurotoxic to animals including humans. It is known that BMAA accumulation via the food chain can lead to development of neurodegenerative diseases in humans such as Alzheimer's and Parkinson's diseases as well as amyotrophic lateral sclerosis. Moreover, BMAA can be mistakenly incorporated into a protein molecule instead of serine. Natural sources of BMAA and methods for its detection are discussed in this review, as well as the role of BMAA in metabolism of its producers and possible mechanisms of toxicity of this amino acid in different living organisms.

  18. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1{alpha}, suppress amyloid {beta}-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Milatovic, Dejan [Department of Pediatrics/Pediatric Toxicology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Splittgerber, Ryan [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Fan, Guo-Huang [Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37221 (United States); Richmond, Ann, E-mail: ann.richmond@vanderbilt.edu [VA Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

    2011-11-15

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-{beta} (A{beta}). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1{alpha} (SDF-1{alpha}), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress A{beta}-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1{alpha} significantly protected neurons from A{beta}-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1{alpha}. Intra-cerebroventricular (ICV) injection of A{beta} led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The A{beta}-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1{alpha}. Additionally, MIP-2 or SDF-1{alpha} was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against A{beta} neurotoxicity in CXCR2-/- mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: Black-Right-Pointing-Pointer Neuroprotective ability of the chemokines MIP2 and CXCL12 against A{beta} toxicity. Black-Right-Pointing-Pointer MIP

  19. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1α, suppress amyloid β-induced neurotoxicity

    International Nuclear Information System (INIS)

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja; Milatovic, Dejan; Splittgerber, Ryan; Fan, Guo-Huang; Richmond, Ann

    2011-01-01

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-β (Aβ). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1α (SDF-1α), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress Aβ-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1α significantly protected neurons from Aβ-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1α. Intra-cerebroventricular (ICV) injection of Aβ led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The Aβ-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F 2 -isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1α. Additionally, MIP-2 or SDF-1α was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against Aβ neurotoxicity in CXCR2−/− mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: ► Neuroprotective ability of the chemokines MIP2 and CXCL12 against Aβ toxicity. ► MIP-2 or CXCL12 prevented dendritic regression and apoptosis in vitro. ► Neuroprotection through activation of Akt, ERK

  20. Greenhouse Gas Implications of Peri-Urban Land Use Change in a Developed City under Four Future Climate Scenarios

    Directory of Open Access Journals (Sweden)

    Alison Rothwell

    2016-12-01

    Full Text Available Present decisions about urbanization of peri-urban (PU areas may contribute to the capacity of cities to mitigate future climate change. Comprehensive mitigative responses to PU development should require integration of urban form and food production to realise potential trade-offs. Despite this, few studies examine greenhouse gas (GHG implications of future urban development combined with impacts on PU food production. In this paper, four future scenarios, at 2050 and 2100 time horizons, were developed to evaluate the potential GHG emissions implications of feeding and housing a growing urban population in Sydney, Australia. The scenarios were thematically downscaled from the four relative concentration pathways. Central to the scenarios were differences in population, technology, energy, housing form, transportation, temperature, food production and land use change (LUC. A life cycle assessment approach was used within the scenarios to evaluate differences in GHG impacts. Differences in GHG emissions between scenarios at the 2100 time horizon, per area of PU land transformed, approximated 0.7 Mt CO2-e per year. Per additional resident this equated to 0.7 to 6.1 t CO2-e per year. Indirect LUC has the potential to be significant. Interventions such as carbon capture and storage technology, renewables and urban form markedly reduced emissions. However, incorporating cross-sectoral energy saving measures within urban planning at the regional scale requires a paradigmatic shift.