Chronic exposure to manganese (Mn) causes the neurodegenerative movement disorder, manganism. A mouse model was developed to elucidate mechanisms involved in the etiology and progression of injury. Twelve-week old female C57Bl/6J mice were exposed to MnCl2 (100 mg/kg/day) by oral gavage daily for 8 weeks. After the experiment striatal dopamine (DA) content was decreased with the manifestation of hypoactivity. A distinct population of neurons was vulnerable to the effects of Mn, including enkephalin (ENK)-positive projection neurons, interneurons expressing neuronal nitric oxide synthetase (nNOS/NOS1), and choline acetyltransferase (ChAT)-expressing interneurons. Activation of surrounding astrocytes occurred with expression of inducible nitric oxide synthase (iNOS/NOS2) and production of nitric oxide (NO)/peroxynitrite (ONOO-). Activated astrocytes were detected primarily near the microvasculature in both the striatum and globus pallidus (GP). It is suggested that Mn exposure may damage the blood-brain barrier (BBB) and induce astrocytosis and NOS2 expression, subsequent NO production may cause the death of adjacent neurons. This hypothesis was also tested in an in vitro co-culture model. Differentiated pheochromocytoma cells (PC12 cells) were co-cultured with primary astrocytes and exposed to Mn and inflammatory cytokines. Mn and cytokines induced NOS2 expression and NO production in astrocytes, which correlated with apoptosis of PC12 cells. Apoptosis of PC12 cells was prevented by overexpression of a phosphorylation-deficient mutant of IκBα that inhibited NOS2 expression in astrocytes. It is concluded that Mn-and cytokine-dependent apoptosis in PC12 cells requires astrocyte-derived NO and nuclear factor κB (NF-κB)-dependent expression of NOS2. To explore possible means of interdicting this inflammatory process in astrocytes, a noval pharmacologic ligands of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, 1,1-Bis(3'-indolyl)-1-(p-trifluoromethylphenyl) methane (DIM-C-pPhCF3) were used in the same co-culture system. DIM-C-pPhCF3 protected PC12 cells from apoptosis through inhibition of NOS2 expression in astrocytes after Mn and cytokines exposure. By contrast, the PPARγ antagonist, 2-chloro-5-nitrobenzanilide (GW9622), had the opposite effect, increasing both NO production in astrocytes and neuronal injury. It is concluded that PPARγ is involved in the regulation of NOS2 expression in astrocytes and that agonists of PPARγ may represent a potential treatment method for Mn neurotoxicity.

Uppsatsen handlar om attityder till naturvetenskap. Syftet med min undersökning är att ta reda på vilken definition pedagogerna hade av NO, vilka attityder som pedagogerna ansåg fanns hos pedagogerna själva, deras kollegor och deras elever i grundskolans tidiga skolår samt vilket förhållningssätt pedagogerna hade till lärande i NO. Jag intervjuade fem pedagoger i skolår F-6 och analyserade deras svar för att få fram likheter och skillnader genom tillämpning av en fenomenografisk analys. Resultatet visade att definitionen av NO var snarlik hos samtliga respondenter samt att de var intresserade av NO och menade att det var viktigt. På grund av att det är ett svårt ämne och eftersom kärnämnena som mäts genom nationella prov ofta går före NO bedrivs inte så mycket naturvetenskaplig undervisning i grundskolans tidiga skolår. Elever lär sig bäst genom en varierad undervisning med mycket praktiskt arbete, men teori är också viktigt för att undervisningen skall passa alla elever.

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OBJECTIUSObjectiu general és la creació d'una escala per la predicció de les conductes de risc que es pugui utilitzar en l'àmbit de la consultaObjectius específics: A) estudiar les associacions entre les conductes de risc (consum de drogues, sexualitat de risc, i seguretat viària); B) identificar factors personals, familiars i escolars que influeixen en la presa de conductes de risc a l'adolescència en una mostra d'adolescents escolaritzats; i C) analitzar la capacitat predictiva de l'escala en les mostres d'adolescents escolaritzats de Barcelona de 1993 i 1999.MATERIAL I MÈTODESS'ha fet servir les dades de l'Enquesta de Salut als Adolescents de la Ciutat de Barcelona 1993. Les variables conductuals són 10 agrupades en tres grans grups: consum de drogues, conducta sexual i seguretat viària. Les variables independents són de tipus personal, familiar i escolar. Per l'anàlisi bivariada, que s'ha fet separadament per gènere, s'ha creuat cadascuna de les 10 variables conductuals entre elles i posteriorment amb cadascuna de les variables independents. S'han calculat els estadístics Xi-quadrat i Odds Ratio (OR) per les variables qualitatives i la t de Student per les variables quantitatives. Totes les variables independents significativament associades amb 5 o més de les variables conductuals en els nois i en les noies han estat introduïdes en una anàlisi multivariada per detectar almenys una conducta de risc. Aquelles variables que es mantenen significatives i compleixen els criteris establerts conformen l'escala. Posteriorment, l'escala s'aplica als resultats de l'Enquesta de Salut als Adolescents Escolaritzats de Barcelona 1999 per confirmar la seva capacitat predictiva. RESULTATSLes deu variables conductuals estan significativament associades entre elles, amb l'excepció del fet de no portar sempre el cinturó de seguretat que no s'associa amb el consum de tabac, alcohol o altres drogues en les noies ni amb els consum de cannabis i altres drogues en els nois. Pel que fa a les variables independents, a més de l'edat i el sexe, hi ha 15 variables que s'associen amb la majoria de les variables conductuals. D'aquestes, només vuit (edat, religiositat, hàbit tabàquic de la mare, consum d'alcohol del pare, relació amb els pares, relació amb l'escola, notes mitjanes, relació amb els mestres) es mantenen significatives en l'anàlisi multivariada. Dues d'aquestes variables (hàbit tabàquic de la mare i consum d'alcohol del pare) han estat finalment excloses perquè depenen de la quantitat consumida. Repetint l'anàlisi multivariada sense elles, no s'observen diferències. Les cinc variables finalment incloses en l'escala reben una puntuació de 0 si son protectores (alt nivell de religiositat, bona relació amb els pares, agrada anar a l'escola, notes mitjanes d'aprovat o més, bona relació amb els mestres) i de 1 en cas contrari, el que dona una puntuació entre 0 i 5. Mitjançant una corba ROC, el millor punt de tall per detectar almenys una conducta de risc és quan la puntuació és >1. Aplicant l'escala als resultats de l'enquesta de 1993, trobem que aquells adolescents que presenten una puntuació >1 tenen significativament més probabilitats de prendre qualsevol de les 10 conductes de risc. Quan ho estratifiquem per edats, totes les variables són significatives pels més joves (14-16 anys), però pels més grans (17-19 anys) no són significatives les dues variables relacionades amb la sexualitat. Quan apliquem l'escala a l'enquesta de 1999, es manté significativa per a totes les variables conductuals menys no portar sempre el cinturó. El mateix succeeix quan ho estratifiquem per edats, però pels més joves tampoc no és significativa per haver conduït intoxicat ni per haver tingut relacions sexuals coitals.CONCLUSIONSLes conductes de risc estan altament relacionades entre elles.Hi ha factors personals, familiars i escolars que estan relacionats amb la presa de conductes de risc.L'escala és senzilla d'aplicar i d'avaluar i permet detectar aquells adolescents que prenen almenys una conducta de risc.L'escala és sobretot un bon predictor del consum de drogues.L'escala permet detectar millor les possibles conductes de risc en els adolescents més joves (14-16 anys).Atès que hi ha una forta associació entre les conductes de risc, encara que l'escala serveixi principalment per la detecció del consum de drogues, també ens està indicant, ni que sigui de manera indirecta, que poden haver-hi altres conductes nocives per a la salut que cal explorar. / PURPOSEThe main purpose is to create a scale to predict risky behaviors that can be used in clinic.Specific objectives are: A) to study the association between risky behaviors (drug use, risk sex and vehicle-related behavior); B) to identify personal, family and school-related factors that influence risk taking among a sample of school-aged adolescents; and C) to analyze the predictive capacity of the scale in the samples of school-aged adolescents of Barcelona of 1993 and 1999.MATERIAL AND METHODSData were drawn from the Barcelona Adolescent Health Survey 1993. There are 10 behavioral variables divided in 3 groups: drug use, sexual risk, and vehicle-related behavior. Independent variables are personal, family and school-related. Bivariate analysis, performed separately by gender, crossed behavioral variables between them and with each independent variable. Chi-square and odds ratio were used to compare qualitative variables and Student's t for quantitative variables. All independent variables statistically significant for 5 or more behavioral variables among boys and among girls were included in a multivariate analysis to detect at least one risky behavior. Statistically significant variables were included in the scale. Afterwards, the scale is applied to the Barcelona Adolescent Health Survey 1999 to confirm its predictive capacity.RESULTSAll the behavioral variables are significantly associated between them, with the exception of not always using the seat-belt that is not significant for tobacco, alcohol or other illegal drugs use among girls nor with cannabis and other illegal drugs use among boys. Fifteen independent variables, plus gender and age are significant for most behavioral variables. Of those, only 8 (age, religiosity, mother' smoking, father's drinking, relationship with parents, relationship with school, grades, relationship with teachers) are significant in the multivariate analysis. Two of these variables (mother' smoking, father's drinking) were not included because they depend on the quantity used. Redoing the multivariate analysis without them no differences were found. The five variables finally included in the scale score 0 if they are protective (high religiosity, good relationship with parents, likes going to school, above mean grade average, good relationship with teachers) and score 1 when risky, giving a final score ranging from 0 to 5. Through ROC curve, the best cut-off point to detect at least one risky behavior is a score over 1. Applying the scale to the 1993 survey, all adolescents with a score >1 are significantly more likely to take any of the 10 risky behaviors. When stratifying by age, all variables are significant for the younger ones (14-16 years), but for the older group (17-19 years) the two risk sex variables are not significant. In applying the scale to the 1999 survey, it is significant for all the variables with the exception of not always using a seat belt. The same is true when we stratify by age, but for the younger group having had sexual intercourse and having driven while intoxicated were not significant.CONCLUSIONSRisky behaviors are significantly linked between them.There are personal, family, and school-related behaviors related to risk taking behaviors.The scale is easy to use and assess and permits to detect those adolescents that take at least one risky behavior.The scale is mainly a good predictor of drug use.The scale works better to detect risk behaviors among younger adolescents (14-16 years).Since there is an association between risk behaviors, even though the scale is more useful to detect drug use, it also indicates, even indirectly, that other risk-taking behaviors that need to be explored may be present.

L'Autoestimulació Elèctrica Intracranial (AEIC) del feix prosencefàlic medial facilita l'adquisició i posterior retenció d'un aprenentatge quan és administrada immediatament després de l'entrenament. Aquest efecte és especialment potent en rates que parteixen de baixos nivells d'aprenentatge, i es creu que és degut a un efecte activador general de l'AEIC sobre diferents estructures encefàliques.Es va decidir estudiar els efectes del tractament d'AEIC post-entrenament sobre l'adquisició i la retenció d'un condicionament d'evitació activa de dos sentits en rates velles (16-17 mesos), i sobre l'adquisició i retenció d'una tasca de memòria declarativa dependent de l'hipocamp (alternança en laberint en T) en rates joves (3 mesos).Per assolir aquests objectius es van realitzar dos experiments amb rates albines de la soca Wistar. En el primer treball vam observar com el tractament d'AEIC post-entrenament va facilitar l'adquisició del condicionament d'evitació activa de dos sentits, sense afectar sobre la retenció a llarg termini. Aquests resultats demostren que els animals vells, que generalment parteixen de baixos nivells d'aprenentatge, mantenen els mecanismes de plasticitat necessaris perquè es faciliti l'adquisició d'aquest condicionament, encara que possiblement de manera menys eficaç que en els animals joves, el que planteja la necessitat de desenvolupar un model de tractament amb AEIC que sigui igual d'efectiu pels diferents grups d'edat.En el segon treball vam constatar un efecte facilitador del tractament d'AEIC post-entrenament sobre l'expressió flexible d'una memòria declarativa, una característica essencial dels aprenentatges que depenen d'aquest sistema de memòria. Aquests efectes no es van observar en la retenció a llarg termini, indicant un efecte específic sobre la fase de consolidació de la informació entre sessions d'aprenentatge.Aquestes dades mostren com els efectes facilitadors del tractament d'AEIC post-entrenament poden ser generalitzar a dues situacions prèviament no estudiades d'alt interès per a l'estudi i desenvolupament de tractaments compensadors dels trastorns de la memòria, com són l'envelliment i les tasques de memòria declarativa. / Intracranial self-stimulation (ICSS) of the medial forebrain bundle improves learning acquisition and subsequent retention when administered immediately after training. This effect is particulary marked in rats with low initial learning levels, and this is thought to be due to a general arousing effect on different structures of the brain.We decided to study post-training ICSS effects on acquisition and retention of a two-way active avoidance conditioning in aged rats (16-17 months), and on acquisition and retention of a hippocampus-dependent declarative memory task (delayed alternation in a T-maze) in young rats (3 months).We conducted two experiments with albino rats of the Wistar strain. In the first, we observed a facilitatory effect of post-training ICSS on the acquisition of the two-way active avoidance conditioning, and no effect on long-term retention. These results show that aged animals, which generally show poor initial learning levels, do maintain the necessary plastic mechanisms for facilitating acquisition of this conditioning, although probably in a less efficient way than young rats, raising the need for developing a model of ICSS equally effective in young and old rats.In the second experiment, we observed a facilitatory effect of post-training ICSS on the flexible expression of declarative memory, which is the hallmark of the learning tasks that depend on this memory system. These effects were not observed in the retention session, suggesting a specific effect on the consolidation phase between learning sessions.This data generalize the facilitatory effects of post-training ICSS to two conditions, never tested before, of high interest for the study and development of compensating treatments for memory disorders, such as aging and declarative memory.

För att öka sin förståelse i ett ämne måste man förstå de väsentliga delarna. När ett nytt ämnesområde ska läras in så är det mycket nya ord och begrepp. Många gånger så behöver vi dessa begrepp för att så småningom kunna förstå helheten. NO-ämnen har en väldigt hög andel sådana begrepp och uttryck. Tyvärr lärs begreppen många gånger in som glosor och då tappas integrationen av orden. Andra studier har visat att elever och studenter använder sig av väldigt lite av typiska ämnesbegrepp när de ska beskriva fenomen. Denna studie belyser elevers attityder till att lära sig begrepp inom NO. Hur de ser på användningen av begrepp och om de anser att de behöver lära sig fler för sin förståelse. Enkäter har lämnats ut till 44 elever i årskurs 8 ut på två olika skolor i sydöstra Sverige. Resultatet visar att elever tycker att det är viktigt att lära sig begrepp och att de har en bra inställning till att lära sig. Slutsatsen är att eleverna anser att det är viktigt med begrepp för sin förståelse för tillfället. Eleverna visar en positiv attityd till att lära sig begrepp men att de inte ser någon användning av begreppen utanför skolan.

Neuropeptide Y (NPY) is a 36-amino-acid polypeptide that exerts its biological action through Gi/Go-protein coupled receptors in the central and peripheral nervous systems. It has been demonstrated to have potent depressor effect in the nucleus tractus solitarii (NTS) of rats, and activation of both NPY Y1 and Y2 receptors would phosphorylate ERK in CHO K1 cell. Brain stem nuclei such as nucleus of tractus solitari (NTS) and rostral ventrolateral medulla (RVLM) are innervated by neurons capable of synthesizing nitric oxide (NO), and inhibition of NO synthesis in these areas cause sustained hypertension and decrease baroreceptor sensitivity. Our previous studies already suggested that NO produced in the braistem nuclei play an important role in cardiovascular regulation. It was shown that NPY induces vasodilation of human subcutaneous arteries by a NO dependent pathway. In the present study, we investigated the molecular signaling mechanisms involved in NPY-induced cardiovascular modulation in NTS. Unilateral microinjection of NPY into the NTS of WKY rats produced prominent depressor and bradycardic effects. Pretreatment with a selective non-peptide neuropeptide Y1 (NPY1) receptor antagonist BIBP3226; Gi/Go-protein inhibitor Pertussis toxin, MEK inhibitor PD98059, significant attenuated the cardiovascular response evoked by NPY. Western blot and immunohistochemistry studies showed NPY and NPY Y1 agonist [Leu31 Pro34] NPY increased ERK1/2 phosphorylation, and PD98059, BIBP3226 attenuated the NPY-induced phosphorylation significantly. Non-selcetive NOS inhibitor L-NAME and eNOS preferential inhibitor L-NIO significantly attenuated the cardiovascular response evoked by NPY, however nNOS preferential inhibitor 7-NI and nNOS specific inhibitor Vinyl-L-NIO did not cause any changes. Western blot and immunohistochemistry studies showed NPY increased eNOS phosphorylation, but not nNOS. Our results showed that NPY induced ERK1/2 phosphorylation through NPY Y1 receptor, and its downstream eNOS-NO pathway involved in NPY mediated cardiovascular effects.

The selective catalytic reduction (SCR) of nitric oxide (NO) with ammonia over vanadia-based (V2O5-WO3/TiO2) and pillared interlayer clay-based (V2O5/Ti-PILC) monolithic honeycomb catalysts using a laboratory laminar-flow reactor was investigated. The experiments used a number of gas compositions to simulate different combustion gases. A Fourier transform infrared (FTIR) spectrometer was used to determine the concentrations of the product species. The major products were nitric oxide (NO), ammonia (NH3), nitrous oxide (N2O), and nitrogen dioxide (NO2). The aim was to delineate the effect of various parameters including reaction temperature, oxygen concentration, NH3-to-NO ratio, space velocity, heating area, catalyst arrangement, and vanadium coating on the removal of nitric oxide. The investigation showed that the change of the parameters significantly affected the removals of NO and NH3 species, the residual NH3 concentration (or NH3 slip), the temperature of the maximum NO reduction, and the temperature of complete NH3 conversion. The reaction temperature was increased from the ambient temperature (25°C) to 450 °C. For both catalysts, high NO and NH3 removals were obtained in the presence of a small amount of oxygen, but no significant influence was observed from 0.1 to 3.0% O2. An increase in NH3-to-NO ratio increased NO reduction but decreased NH3 conversions. For V2O5-WO3/TiO2, the decrease of space velocity increased NO and NH3 removals and broadened the active temperature window (based on NO > 88% and NH3 > 87%) about 50°C. An increase in heating area decreased the reaction temperature of the maximum NO reduction from 350 to 300°C, and caused the active reaction temperature window (between 250 and 400°C) to shift toward 50°C lower reaction temperatures (between 200 and 350°C). The change of catalyst arrangements resulted slight improvement for NO and NH3 removals, therefore, the change might contribute to more gas removals. The catalyst with extra vanadium coating showed higher NO reductions and NH3 conversions than the catalyst without the extra vanadium coating.

Nitric oxide plays an important role in many biological functions. A metallo derivative in biological systems is a protein-bound dinitrosyl iron complex (DNIC), which results from iron-sulfur cluster degradation in the presence of excess NO. Through model complexes I have examined the fundamental properties of a dithiolato-Fe(NO)2 complex, bismercaptoethandiazacyclooctane iron dinitrosyl or (H+bme-daco)Fe(NO)2 as a biomimic of dicysteinate coordination of [Fe(NO)2]. This complex was prepared and fully characterized in my studies. The DNIC moiety is in its oxidized state, {Fe(NO)2}9. Through reaction studies, monitored by IR spectroscopy (H+N2S2)Fe(NO)2 (N2S2 = bme-dach. Bme-pda) has been shown to transfer NO to FeIII in (TPP)FeCl (TPP = meso-tetraphenylporphyrin) as NO-. The remaining mononitrosyl converts into complex (N2S2)Fe(NO). The (N2S2)Fe(NO) complexes (N2S2 = bme-daco, bme*-daco, bme-dach) were prepared by direct reaction of dimeric [(N2S2)Fe]2 and NO gas. The analogous (N2S2)Co(NO) complex (N2S2 = bme-dach) has also been prepared. The series of square pyramidal (N2S2)M(NO) have been studied by cyclic voltammetry and ν(NO) IR spectroscopy.

Chronic exposure to manganese (Mn) causes the neurodegenerative movement disorder, manganism. A mouse model was developed to elucidate mechanisms involved in the etiology and progression of injury. Twelve-week old female C57Bl/6J mice were exposed to MnCl2 (100 mg/kg/day) by oral gavage daily for 8 weeks. After the experiment striatal dopamine (DA) content was decreased with the manifestation of hypoactivity. A distinct population of neurons was vulnerable to the effects of Mn, including enkephalin (ENK)-positive projection neurons, interneurons expressing neuronal nitric oxide synthetase (nNOS/NOS1), and choline acetyltransferase (ChAT)-expressing interneurons. Activation of surrounding astrocytes occurred with expression of inducible nitric oxide synthase (iNOS/NOS2) and production of nitric oxide (NO)/peroxynitrite (ONOO-). Activated astrocytes were detected primarily near the microvasculature in both the striatum and globus pallidus (GP). It is suggested that Mn exposure may damage the blood-brain barrier (BBB) and induce astrocytosis and NOS2 expression, subsequent NO production may cause the death of adjacent neurons. This hypothesis was also tested in an in vitro co-culture model. Differentiated pheochromocytoma cells (PC12 cells) were co-cultured with primary astrocytes and exposed to Mn and inflammatory cytokines. Mn and cytokines induced NOS2 expression and NO production in astrocytes, which correlated with apoptosis of PC12 cells. Apoptosis of PC12 cells was prevented by overexpression of a phosphorylation-deficient mutant of IκBα that inhibited NOS2 expression in astrocytes. It is concluded that Mn-and cytokine-dependent apoptosis in PC12 cells requires astrocyte-derived NO and nuclear factor κB (NF-κB)-dependent expression of NOS2. To explore possible means of interdicting this inflammatory process in astrocytes, a noval pharmacologic ligands of the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, 1,1-Bis(3'-indolyl)-1-(p-trifluoromethylphenyl) methane (DIM-C-pPhCF3) were used in the same co-culture system. DIM-C-pPhCF3 protected PC12 cells from apoptosis through inhibition of NOS2 expression in astrocytes after Mn and cytokines exposure. By contrast, the PPARγ antagonist, 2-chloro-5-nitrobenzanilide (GW9622), had the opposite effect, increasing both NO production in astrocytes and neuronal injury. It is concluded that PPARγ is involved in the regulation of NOS2 expression in astrocytes and that agonists of PPARγ may represent a potential treatment method for Mn neurotoxicity.