Dissertations / Theses on the topic 'COMT'
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Gonçalves, Ana Margarida Ribeiro. "Isoformas da enzima catecol-O-metiltransferase como alvo farmacológico na doença de Parkinson." Master's thesis, Universidade da Beira Interior, 2013. http://hdl.handle.net/10400.6/1636.
Full textThis work is divided in two chapters. Chapter I covers the stage held in Community Pharmacy, on Pharmacy Ferrer - Castelo Branco. Besides describing the facilities and their spatial organization, the technical team and its functions, there is an approach to the informatics system used (Sifarma 2000), and there are also described the various activities carried out during the stage, from the ordering process, reception and storage, providing pharmaceutical care, preparation of compounded medications, dispensing prescribed and non-prescribed medications, billing, among others. Pharmaceutical legislation, involved in pharmaceutical practice is also explored in this chapter. Chapter 2 covers a bibliographic review on the isoforms of catechol-O-metiltransferase enzyme as pharmacological target in Parkinson's disease. Parkinson's disease is a neurodegenerative disease, which is involved in the loss of dopaminergic neurons of the substantia nigra (pars compacta). It affects about 1% of the population over 65 years and it is thought that genetic and environmental factors are at their origin. The catechol-O-methyltransferase (COMT) is present in both eukaryotic and prokaryotic. It is an intracellular protein, and in mammals is distributed uniformly throughout the body, presenting highest activity in the liver, kidney and gastrointestinal tract. Its main function is the metabolism of molecules with catechol structure biologically active, whether endogenous or exogenous. Presents several polymorphisms, where the polymorphism involved in the replacement of Valine by Methionine is the only one in which the function is known. Manifests as two isoforms, the soluble form (S-COMT) and the membrane form (MB-COMT), being the soluble form more prevalent in the body, except the brain. In addition to the distribution in the body, they also differ in subcellular localization, kinetic properties, substrate specificity and molecular weight. Levodopa is considered the most effective therapy in Parkinson's disease, since the 60s. It is administered with decarboxylase inhibitors of aromatic amino acid (DAAA). In patients with motor fluctuations, is co-administered with COMT inhibitors. Currently entacapone is the only available inhibitor, however, opicapone, in the third Phase of clinical trials, presents a greater inhibition, in which a single daily dose is enough, unlike entacapone.
Andersson, Anneli. "Katekol-O-Metyltransferas (COMT), tidigare övergrepp, gen-miljöinteraktion i förutsägelsen för våld." Thesis, Örebro universitet, Institutionen för juridik, psykologi och socialt arbete, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-42712.
Full textSeveral candidate genes have been suggested to play a role in the development of antisocial behavior in association with social and environmental factors. Therefore, the purpose of the present study was to investigate the relationship between the gene Catechol-O-Methyltransferase (COMT) and violence; and to examine whether there were interactions between earlier abuse and COMT in the association of violence. Data were drawn from a Swedish population-based study including 2,500 20-24 year olds. The present study found that depending on which variant of the gene one possess, one will be affected to different degree of adverse environmental factors in association with violence.
CASTELLANO, FILIPPO. "Funzioni Esecutive e Facial Emotion Recognition in Persone Affette da Schizofrenia: ruolo del Polimorfismo del COMT e dell'Abuso di Alcol e Sostanze." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/94538.
Full textBACKGROUND: cognitive and genetic features are increasingly important in the study of schizophrenia. The impairment of executive function (FE) and facial emotion recognition, are central issues in schizophrenic disease. To date, however, the paradigm of the (dis) cognitive functioning in schizophrenia is based on studies that excluded subjects with schizophrenia and a history of substance abuse (SUD)(5), which is actually a phenomenon that showed a derogatory impact on cognition in the population with substance use disorder. The literature has also over the years defined polymorphisms potentially implicated in both schizophrenia and in alcohol and substance use disorders, such as the one (rs4680) related to the gene of catechol-O-methyltransferase (COMT). Given the prevalence of the phenomenon and the association between cognition, functional outcome and genetic polymorphisms, the study of these related in schizophrenic patients with substance abuse is an important issue for a more precise stratification diagnosis, prognosis and treatment. AIM: to evaluate the impact of the COMT polymorphism and alcohol and substance abuse on cognitive performance in a population of subjects with schizophrenia. MATERIALS AND METHODS: this is a observational study. We recruited 62 subjects (M = 50, F = 12) diagnosed with schizophrenia according to DSM-IV (assessed by the Structured Clinical Interview for DSM-IV, SCID I). The sample was subdivided according to the presence or not of alcohol abuse and related substances (evaluated with the Alcohol and Drug Use Scale -Aus and DUS) into two groups (SKZ+SUD and SKZ-SUD), which were then compared with regard to socio-demographic and clinical characteristics (Positive and Negative Syndrome Scale - PANSS). It was then analysed the association between the condition of abuse, COMT polymorphism and score on Intra-Extra Dimensional Shift September (IED), which evaluates the FE and on test Ekman, evaluating the FER, controlling for socio-demographic and clinical variables. RESULTS: the two groups SKZ+SUD (n= 8) and SKZ-SUD (n = 34) show a statistically significant difference by age with mean (SD) of 47.21 (9.41) in abusers and 36.04 (10.09) in non-abusers (p <0.001). Abusers tend to make fewer errors on IED (IED errors adjusted Total 47.32 (47.77) vs 70.59 (70.84); p = 0:26), fewer trials (IED trials Total Adjusted 136.61 (85.65) vs 178.35 (128.02); p = 0:24) to reach the criterion to overcome the stage and a greater number of stages completed (IED stages completed 7.79 (2.11) vs 6.85 (3.12), p = 0:35). Abusers (mean = 41.86 (7:50)) show a score statistically higher (p = 0.02) compared with non-abusers (mean = 35.29 (11.79) on Ekman test. On IED (stage completed), checking for the PANSS, the Met-Met genotype compared with Val-Val genotype was different in the group of abuse compared with the group not abusing (interaction coefficient -4.09 CI [-8.06, -0.13]; p = 0.043): Met-Met show a worse performance than in the group of Val-Val. The same type of interaction is confirmed also with regard to the Ekman , although not reaching statistical significance (interaction with coefficient -6.46 CI [-0.83, 13.76]; p = 0.081). CONCLUSIONS: subjects with schizophrenia and substance abuse seems to be less compromised from a neuropsychological point of view than those without abuse. Furthermore it is shown an interaction between the polymorphism for COMT gene and the condition of alcohol and substance abuse with regard to the FE and FER performance.
da, Silva Costa Isis. "Variations in EEG and motor functions related to COMT gene in patients with fibromyalgia." Doctoral thesis, Universitat de les Illes Balears, 2017. http://hdl.handle.net/10803/399443.
Full textLa fibromialgia (FM) és una síndrome crònica caracteritzada per dolor generalitzat, fatiga, son no reparador, queixes somàtiques i alteracions afectives i cognitives. Encara que existeixen evidències indicant que emocions negatives poden tenir un paper modulador rellevant en el manteniment dels símptomes de la FM, poc es coneix de la influència dels polimorfismes genètics sobre la funció motora, el son i el processament afectiu en la fibromiàlgia. L’objectiu principal d’aquesta tesi doctoral va ser analitzar la influència del polimorfisme val158met del gen de la COMT, que es troba associat a l’activitat enzimàtica de la degradació de les catecolamines, sobre la marxa i l’equilibri, el son i la regulació emocional. Per això, s’ha adoptat un enfocament multidisciplinari en el qual s’han tingut en conte paràmetres biomecànics de la funció motora, l’activitat cerebral durant el son i durant la modulació afectiva del reflex de sobresalt per comparar subjectes que mostren una baixa o alta activitat de COMT (homozigots met i portadors d’al·lel val, respectivament). La funció motora fou avaluada mitjançant l’anàlisi de la marxa i l’equilibri amb gravacions de video en persones sanes i en pacients amb FM (estudi 1). A més, dos grups de pacients amb FM basats en el polimorfisme de la COMT participaren en un registre polisomnogràfic nocturn (estudi 2), i en una tasca experimental ambla presència d’estímuls acústics de sobresalt durant la visualització d’imatges afectives (estudi 3). L’estudi 1 mostrà que les pacients amb FM presenten una disminució significativa en paràmetres de la marxa com són la velocitat, la longitud de cada pas i del pas complet o cadència, així com dèficits en el control postural i de l’equilibri. L’estudi 2 desvetllà que les pacients amb FM amb baixa activitat de l’enzim COMT pareixen estar més impactades físicament, més deprimides i amb pitjor qualitat de son (major nombre de despertars durant la nit, major quantitat de temps en el llit i un son més fragmentat durant la fase REM), que les pacients amb FM amb alta activitat de l’enzim COMT. Per últim, l’estudi 3 mostrà que les pacients con FM amb baixa activitat de l’enzim COMT presenten alteracions significatives en els components primerencs de l’activitat cerebral desencadenada per estímuls agradables o desagradables, comparades amb les pacients con FM amb alta activitat del COMT. Aquests estudis suggereixen: 1) la marxa i l’equilibri es troben alterats en les pacients amb FM comparades amb les persones sense dolor, i 2) que el son i el processament afectiu de les pacients amb FM port estar modulat pel polimorfisme val158met del gen del COMT que regula l’activitat enzimàtica de les catecolamines. En resum, aquests resultats remarquen encara més la idea de que els símptomes de la fibromiàlgia precisen d’una avaluació i d’una intervenció terapèutica de caràcter multidimensional amb l’objectiu de proporcionar les òptimes condicions per la millora de la qualitat de vida d’aquetes pacients. Així mateix, aquestes troballes subratllen la rellevància de considerar els marcadors genètics i neurofuncionales per a una compressió més completa de la síndrome de fibromiàlgia.
Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain, fatigue, unrefreshing sleep, somatic complaints, and affective and cognitive alterations. Although there is recent evidence indicating that negative affect may play a relevant modulatory role for the maintenance of fibromyalgia symptoms, little is known about how genetic polymorphisms may influence motor function, sleep and affective processing in fibromyalgia. The major goal of the present thesis was to analyze the influence of the val158met polymorphism of the COMT gene which is associated with the enzymatic activity level of cathecolamine degradation on gait and balance, sleep and emotional regulation. For this purpose, a multidisciplinary approach taking into account biomechanical parameters of motor function and parameters of the brain activity during sleep and during affective processing was used to compare individuals displaying either low (met homozygotes) or high COMT activity (val carriers). Motor function was assessed by analyzing gait and balance through video recordings in healthy controls and FM patients (study 1). In addition, two subsamples of FM patients based on the val158met polymorphism participated in a night polysomnography recording (study 2) and an experimental task with presentation of startle noise stimuli when viewing affective pictures (study 3). Study 1 showed that FM patients display a significant reduction in gait parameters such as speed, step length and full step, cadence and etc., as well as deficits in postural control and balance. Study 2 revealed that FM patients with low-activity of the COMT enzyme appear to be more physically impacted and depressed, and to have poorer quality of sleep (greater number of awakenings during the night, longer in bed and more fragmented sleep during REM) than FM patients with high-activity of the COMT enzyme. Finally, Study 3 showed that patients with low-activity of the COMT enzyme display significant alterations of the early components of the event-related brain potentials elicited by pleasant and unpleasant stimuli as compared with FM patients displaying high COMT activity. These studies suggest: 1) that gait and balance are altered in patients with FM compared to pain-free controls, and 2) that sleep and affective processing in FM patients may be modulated by the val158met polymorphism of the COMT gene that regulates the enzyme activity of catecholamines. In summary, these findings provide further support for the notion that FM symptoms would require multidimensional assessment and intervention to provide optimal conditions for improving quality of life in these patients. Moreover, our findings underline the relevance of considering genetic and neurofunctional markers for a complete understanding of fibromyalgia.
Barbosa, Marta Cristina Fornelos. "Sistema Nervoso Central: planeamento químico-farmacológico para obtenção de um novo alvo terapêutico para a doença de Parkinson." Master's thesis, [s.n.], 2012. http://hdl.handle.net/10284/3205.
Full textO presente trabalho pretende seguir uma linha de investigação pré-laboral, mas de enorme potencial devido à possibilidade de apresentar uma significativa redução nos custos aquando do lançamento de uma nova solução terapêutica. O trabalho será desenvolvido na área do sistema nervoso central (SNC) e a doença abordada será a doença de Parkinson. No decorrer deste trabalho irá ser feito uma abordagem ao tratamento farmacológico da DP, e realizado um estudo químico-farmacológico de potenciais novos inibidores da COMT. A Doença de Parkinson (DP) é uma patologia cerebral em que ocorre morte dos neurónios numa zona do cérebro designada de substância negra. É a segunda doença neurodegenerativa mais frequente depois da doença de Alzheimer. This work intends to pursue a line of pre-employment investigation, but with great potential due to the possibility of presenting a significant cost reduction at the launch of a new therapeutic solution. The work will be developed in the area of the central nervous system (CNS) and the disease discussed will be Parkinson's disease. We will make an approach to the pharmacological treatment of PD, and we will conduct a chemical and pharmacological study of potential new COMT inhibitors. Parkinson's disease (PD) is a brain pathology in which occurs neuronal death in an area of the brain called substantia nigra. It is the second most common neurodegenerative disorder after Alzheimer's disease.
Ho-Yue-Kuang, Séverine. "Exploration des voies de biosynthèse de l’acide férulique dans les grains et tiges de Brachypodium distachyon." Nantes, 2015. https://archive.bu.univ-nantes.fr/pollux/show/show?id=ed667b2c-bd04-465a-bea7-b1ae49162a58.
Full textFerulic acid plays a key role in grass cell walls, allowing the reticulation between chains of polysaccharides and with lignins. The understanding of its biosynthesis could improve cereals end-uses in allowing the modulation of the cell wall mechanical properties and enzymatical digestibility. The model plant of Poaceae, Brachypodium distachyon, was used to explore the ferulic acid biosynthesis pathways. A reverse genetic strategy has been established to study two candidate enzymes, the COMT and the CCoAOMT selected for their capacity to produce in vitro ferulic acid and feruloylCoA respectively. Since these OMTs are encoded by multigenic families, a selection of candidate genes has been performed based on phylogenetic and transcriptomic analyses. Mutant lines have been obtained through chemical mutagenesis and identified by TILLING for the BdCOMT6 gene. The analysis of these lines showed that BdCOMT6 is a COMT involved in lignin biosynthesis in B. Distachyon stems and grains. However it would not produce the ferulic acid linked to cell walls. RNA interference lines targeting five CCoAOMT genes belonging to a Poaceae specific clade have been generated. Ferulic acid linked to stem cell walls was detected by preliminary analyses of the regenerated plants. Complementary analyses of the next generations are in progress, they will allow to determine if these CCoAOMT genes have a role in the biosynthesis of ferulic acid linked to cell wall. Lignins have been studied in details over the last few years, only stem lignins were characterized in B. Distachyon, this doctoral work allowed to precisely characterize, and for the first time, the structure of the grain lignins
Kawa, Kevin Hideyuki, and Kevin Hideyuki Kawa. "Genetic and Neuroanatomic Factors that Influence Executive Functions in Aging." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/622974.
Full textStitzinger, Johannes. "Der Einfluss genetischer Variationen im COMT Gen auf kognitive Phänotypen." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-59417.
Full textLaatikainen, Linda Maria. "The role of catechol-O-methyltransferase (COMT) in hippocampal function." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:d0c9e1fa-a052-4af7-aaff-00548365e024.
Full textSoares, Rui Filipe Lopes. "Biosynthesis of human membrane-bound Catechol-O-methyltransferase: optimization using Plackett-Burman and Central Composite Design." Master's thesis, Universidade da Beira Interior, 2012. http://hdl.handle.net/10400.6/1120.
Full textCatecol-O-metiltransferase (COMT, CE 2.1.1.6) é uma enzima metiltransferase dependente de S-adenosil-L-metionina (SAM) que catalisa a metilação de substratos catecóis (catecolaminas, catecolestrogénios). Fisiologicamente, é responsável pela eliminação de catecóis biologicamente activos ou tóxicos, tornando-a uma proteína de elevado interesse clínico e utilizada como alvo terapêutico em doenças graves, como a esquizofrenia e a doença de Parkinson. Para suprir as necessidades farmacêuticas, novas estratégias de otimização e produção em larga escala desta enzima são fundamentais. Abordagens de otimização estatística têm demonstrado o seu enorme valor à escala laboratorial e industrial, nomeadamente nos processos de produção biotecnológicos, em que um pequeno detalhe melhorado pode significar um grande passo para o sucesso. Neste trabalho, objetivou-se a otimização do nível de atividade enzimática da proteína recombinante COMT, na sua forma membranar, através do recurso a modelos de otimização estatística como uma abordagem resolutiva. Numa primeira fase de otimização e de seleção dos fatores mais significativos para a atividade enzimática da proteína em estudo foi utilizada a técnica de desenho experimental Plackett-Burman. Após esta seleção foi aplicada a Metodologia de Superfície de Resposta (RSM), através de desenho composto central (DCC), para otimização da concentração dos fatores que revelaram ser mais significativos e, consequentemente, do processo. Foi utilizado o sistema de expressão Brevibacillus choshinensis para a biossíntese da proteína membranar COMT e um meio semi-definido para o seu crescimento. Este meio foi submetido a uma primeira triagem através do desenho experimental Plackett-Burman, avaliando-se desta forma a influência dos parâmetros de cultura (produtos químicos e físicos) nos níveis de actividade enzimática da COMT membranar. Os níveis de actividade enzimática foram medidos num sistema de cromatografia líquida de alta eficiência acoplado a um detector amperométrico. Entre as onze variáveis testadas, a polipeptona, sulfato de amónio, glucose e temperatura foram as variáveis selecionadas dado o seu significativo efeito na actividade enzimática da COMT membranar. Os níveis de atividade enzimática obtidos nesta primeira triagem revelaram-se bastante promissores, sendo mais elevados do que os obtidos com o meio 2SYNm, meio de crescimento mais comum para as células usadas neste trabalho. Foram obtidos valores de 93nmol/h para a actividade enzimática total e cerca 30 nmol/h/mg de actividade enzimática específica com a proteína na sua forma nativa, sem o uso de qualquer tipo de detergentes no processo de solubilização. Com base nos resultados do desenho Plackett Burman foi aplicado o desenho Composto Central para a otimização dos quatro fatores em causa a fim de maximizar a nossa resposta. Este apresentou um valor do coeficiente de correlação múltipla de 0,635 e uma falta de ajuste significativa, demonstrando a falta de adequação do modelo para a otimização do processo.
Sutela, S. (Suvi). "Genetically modified silver birch and hybrid aspen:target and non-target effects of introduced traits." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526206844.
Full textTiivistelmä Puiden ominaisuuksia on mahdollista muuttaa geenitekniikkaa käyttämällä huomattavasti perinteistä jalostusta nopeammin. Geneettisen muuntamisen vaikutuksia puiden ominaisuuksiin ja vuorovaikutussuhteisiin on selvitetty useissa tutkimuksissa geenitekniikkaan liitettyjen riskien arvioimiseksi. Muunnettuja kohdeominaisuuksiaan lukuun ottamatta geneettisesti muunnettujen (GM) puiden ei ole yleisesti ottaen tutkimuksissa havaittu eroavan ympäristövaikutuksiltaan perinteisellä jalostuksella tuotetuista puista. Tässä työssä tutkittiin siirrettyjen geenien vaikutuksia GM-rauduskoivun (Betula pendula Roth) sekä hybridihaavan (Populus tremula L. × tremuloides Michx.) endogeenisten geenituotteiden ja liukoisten fenoliyhdisteiden määriin. Lisäksi työssä tarkasteltiin ligniinirakenteeltaan muunnettujen rauduskoivulinjojen ektomykorritsasymbioosia sekä ligniinimuunnettujen ja Vitreoscilla sp. -bakteerin hemoglobiinia (VHb) tuottavien hybridihaapalinjojen lehtien laatua perhostoukkien ravintona. Biolistisella geeninsiirrolla tuotetuista Amerikan haavan 4-kumaraattikoentsyymi A-ligaasi -geeniä (Pt4CL1) ilmentävistä rauduskoivulinjoista yhdessä havaittiin ligniinin syringyyli- ja guaiasyyliyksikköjen suhteessa muutos. Havaittu muutos aiheutui todennäköisesti koivun Bp4CL1-geenituotteiden määrän vähenemisestä. Myös kaffeaatti/5-hydroksylaatti O-metyylitransferaasi -geeniä (PtCOMT) ilmentävissä, ligniinirakenteeltaan muunnetuissa rauduskoivulinjoissa havaittiin endogeenisen BpCOMT-geenin tuotteiden määrän väheneminen. Tulokset viittaavat siihen, että Bp4CL1- ja BpCOMT-geenien tuottamat entsyymit toimivat rauduskoivun monolignolien biosynteesissä. Ligniiniominaisuuksiltaan muunnettujen rauduskoivujen liukoisista fenoliyhdisteistä todettiin muutoksia ensisijaisesti kanelihappojohdannaisissa, jotka liittyvät läheisesti monolignolien biosynteesireittiin. Ektomykorritsasymbioosissa tai perhostoukkien kasvunopeudessa ei havaittu kasvien geneettisestä muuntamisesta johtuvia eroja. Merkitseviä eroja ei todettu myöskään hybridihaapalinjojen herbivoria-vasteissa. On kuitenkin otettava huomioon, että kaikki tutkimuksen kokeet suoritettiin kasvihuoneissa käyttäen vasta juveniilivaiheessa olevia kasveja. Jotta abioottisten ja bioottisten ympäristötekijöiden sekä GM-puiden vuorovaikutusta olisi mahdollista arvioida kokonaisvaltaisesti, puita pitäisi tutkia pitkäaikaisissa kenttäkokeissa
CRUZ, F. T. "Caracterização Bioquímica e Estrutural da Proteína Catecol O-metiltransferase (COMT) Como Potencial Alvo para Drogas Contra Paracoccidioidomicose." Universidade Federal do Espírito Santo, 2018. http://repositorio.ufes.br/handle/10/7868.
Full textA paracoccidioidomicose (PCM), micose sistêmica causada por fungos do gênero Paracoccidioides, é endêmica na América Latina, sendo o Brasil o país mais afetado. Atualmente, o tratamento com os antifúngicos tradicionais é usualmente longo, de alto custo, restrito a poucas classes de fármacos e com casos de resistência já relatados. A proteína catecol O-metiltransferase (COMT), que não possui estrutura resolvida em Paracoccidioides e nem em outros fungos, catalisa a metilação de um substrato catecol utilizando S-adenosilmetionina e íons Mg2+ como cofatores e parece participar de processos importantes em fungos patogênicos. Assim, sua caracterização bioquímica e estrutural poderia contribuir para o desenvolvimento de novas drogas mais efetivas para o tratamento da PCM. Para estudar a COMT, sua sequência codificadora foi clonada no vetor pET-28aTEV, que adiciona uma cauda de histidinas (His-tag) N-terminal à proteína expressa. O vetor recombinante foi então inserido nas cepas de Escherichia coli BL21, ArcticExpress, Rosetta e Rosetta-gami. A COMT recombinante foi expressa na fração solúvel da ArcticExpress e esta foi submetida à cromatografia de afinidade ao níquel seguida de gel filtração (colunas Ultrahydrogel e Superose 12). O Western blot com anticorpo anti-Histag marcou as duas bandas principais observadas no SDS-PAGE (30 e 60 kDa) da fração obtida após a afinidade. O perfil da gel filtração apresentou três picos principais (frações 1, 2 e 3) que, em SDS-PAGE, mostraram a presença de uma banda proeminente próxima a 60 kDa. As amostras das três frações foram utilizadas em ensaio de atividade para avaliar o consumo de catecol a 35 ºC e pH 7,5 sendo que a fração 2 apresentou maior relação atividade/quantidade de proteína. Cálculos teóricos das massas referentes aos picos da cromatografia de gel filtração indicam que a COMT se comporta como um dímero. A fração 2, apesar de não estar pura, foi submetida a ensaio de desnaturação térmica, onde um processo de agregação ou desnaturação foi detectado em temperaturas acima de 320 K (~47 ºC). O dicroísmo circular da fração 2 indicou um perfil de α-hélice e folhas-β diferente de outras COMT. Um modelo in silico também foi gerado e os dados estruturais obtidos podem contribuir como guia para futuras caracterizações bioquímicas. PALAVRAS-CHAVE: Paracoccidioides, Paracoccidioidomicose, PCM, catecol O-metiltransferase, COMT.
Meloto, Carolina Beraldo 1983. "Caracterização de uma nova isoforma da enzima COMT associada à DTM." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290517.
Full textTese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Catecolamina-O-metiltransferase (COMT) é uma enzima com amplas funções biológicas, inclusive a modulação da dor, exercidas através da metabolização de substratos como a dopamina, adrenalina, e noradrenalina. Já é sabido que a atividade da COMT é geneticamente polimórfica em humanos, e se correlaciona com a percepção individual da dor e eficiência na sua remissão entre pacientes com disfunção temporomandibular (DTM) tratados com propranolol. Por isso, nosso primeiro objetivo foi investigar novos polimorfismos de nucleotídeo único (SNP) que pudessem marcar para este benefício. De fato, encontramos um novo SNP, rs165774 (G>A), que se mostrou associado à DTM ou fenótipos intermediários em duas coortes diferentes. Este polimorfismo, por sua vez, se localiza em proximidade a um segundo SNP, rs165895 (T>C), ambos na região 3' não traduzida (3'UTR) de um mRNA alternativo da COMT ainda não caracterizado. Assim, também foi nossos objetivos (i) verificar a expressão deste transcrito em diferentes tecidos humanos e linhas de células, rastreando-o por RT-PCR (Reverse Transcriptase - Polymerase Chain Reaction); (ii) predizer a estrutura cristalina da enzima codificada por ele, através de modelagem pelo método dinâmico molecular discreto; (iii) expressá-lo em um sistema celular e comparar sua expressão relativa e atividade enzimática às da isoforma convencional, determinando-as por RT-PCR e HPLC (High Performance Liquid Chromatography), respectivamente; e (iv) verificar os efeitos dos SNPs rs165774 e rs165895 sobre este transcrito, criando-se diferentes mutantes por mutação sítio-dirigida e observando seus efeitos sobre a expressão relativa e atividade enzimática. Nossos resultados mostraram que (i) o transcrito alternativo da COMT é expresso em diferentes tecidos humanos e sistemas celulares; (ii) a estrutura cristalina de sua enzima exibe uma região C-terminal único que é distinta da isoforma convencional; e que este transcrito é (iii) menos relativamente expresso e sua enzima menos ativa que o transcrito e a enzima convencionais, respectivamente, e (iv) sofre regulação em nível transcricional pelos SNPs rs165774 e rs165895. Com este estudo, pudemos concluir que o SNP rs165774 é um forte marcador genético para DTM; que juntamente com o SNP rs165895, localizam-se na região 3'UTR de uma forma alternativa de mRNA da COMT que, pela primeira vez, provou ser capaz de codificar para uma isoforma alternativa da enzima que exibe atividade enzimática; e que esta isoforma alternativa de mRNA da COMT sofre efeitos regulatórios, em nível transcricional, causados por ambos os SNPs
Abstract: Catecolamine-O-methyltransferase (COMT) is an enzyme with broad biological functions, including pain modulation, exerted through metabolization of substrates such as dopamine, epinephrine, and norepinephrine. It is well known that COMT activity is genetically polymorphic in humans, and correlates to individual pain perception and efficiency in its remission among temporomandibular disorder (TMD) patients treated with propranolol. Thus, our first aim was to investigate new single nucleotide polymorphism (SNP) that might mark for this benefit. Indeed, we have found a new SNP, rs165774 (G>A), that was associated with TMD or intermediate phenotypes in two different cohorts. This polymorphism, in turn, is in close proximity to a second SNP, rs165895 (T>C), both in the 3' untranslated region (3'UTR) of an alternative COMT mRNA that has not yet been characterized. Therefore, we also aimed to (i) verify the expression of this transcript in different human tissues and cell systems, tracking it through RT-PCR (Reverse Transcriptase - Polymerase Chain Reaction); (ii) predict the crystalline structure of the enzyme encoded by it, modeling it with discrete molecular dynamics; (iii) express it in a cell system and compare its relative expression and enzymatic activity to the conventional isoform, using RT-PCR and HPLC (High Performance Liquid Chromatography), respectively; and (iv) verify the effects of SNPs rs165774 and rs165895 on the transcript, creating different mutants by site-directed mutagenesis and observing their effects on the relative expression and enzymatic activity. Our findings show that (i) the alternative COMT transcript is expressed in different human tissues and cell systems; (ii) the crystalline structure of its enzyme exhibits a unique C-terminus that is distinct from the conventional isoform; and that this transcript is (iii) less relatively expressed and its enzyme is less active than the conventional transcript and enzyme, respectively, and (iv) is regulated, at transcriptional level, by the SNPs rs165774 e rs165895. With this study, we conclude that SNP SNPs rs165774 is a strong genetic marker for TMD; that along with SNPs rs165895, they are located in the 3'UTR of an alternative COMT mRNA which proved, for the first time, to be able of encoding an alternative isoform of the enzyme that exhibits enzymatic activity; and that this alternative COMT mRNA is regulated, at transcriptional level, by both SNPs
Doutorado
Protese Dental
Doutora em Clínica Odontológica
Acosta, Conchucos Oscar. "Polimorfismo en el gen de la catecol o-metil transferasa (comt) y su asociacion con la esquizofrenia en una muestra peruana." Master's thesis, Universidad Nacional Mayor de San Marcos, 2015. https://hdl.handle.net/20.500.12672/4470.
Full textTesis
Herndon, Joseph Menzel. "Methylenedioxymethamphetamine-Induced Neurotoxicity: The Role of Hepatic Enzymes Cytochrome P450 2D6 and Catechol-O-Methyltransferase and Contribution of Microglia." Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/306920.
Full textSantos, Raquel Alves dos. "Polimorfismos nos Genes CYP17, CYP1B1, CYP1A1 e COMT e as Lesões Genômicas Espontâneas em Pacientes com Câncer de Mama." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-11072008-143956/.
Full textBreast cancer (BC) is the second most frequent kind of cancer in worldwide and the most common malignant disease among women. Although cancer is considered a typical aging disease, BC is presenting some distinctive features concerning age-specific incidence rates. Risk factors for breast cancer include early age of menarche and late menopause, hormonal therapies, exposure to environmental pollutants, smoking and alcohol habits, however, increased or prolonged estrogen exposure is the most important risk factor. Estrogen biosynthesis and metabolism requires a great number of enzymatic pathways regulated by different genes with polymorphisms that has been described in association with BC and is well known that estrogens can damage the DNA by increasing the formation of DNA adducts and by inducing 8-hidroxilation of purine bases and breaks in DNA strand. Thus, the aim of the present work was to investigate the levels of DNA damage in BC patients prior chemotherapy or radiotherapy, the possible association of the estrogen metabolizing genes CYP17, CYP1B1, CYP1A1 and COMT polymorphisms on breast cancer risk and also the possible influence of these polymorphisms on the spontaneous levels of DNA damage. Micronucleus test and Comet assay was performed to detect spontaneous DNA damage, using peripheral blood lymphocytes from 45 women diagnosed for Ductal \"in situ\" or invasive breast carcinoma and 85 healthy control women. The results showed that the micronucleus (MNs) frequencies and DNA damage detected by Comet assay were significantly higher in BC group than in controls. The levels of DNA damage were similar in smokers and non-smokers and aging did not influence the frequencies of MNs observed BC patients and in controls. For molecular approach the casuistic comprised of 131 healthy control women and 104 women also diagnosed for Ductal \"in situ\" or invasive breast carcinoma. Comparison of the occurrence of the polymorphisms in CYP17, CYP1A1 and COMT was not statistically different between patients and controls. However, the risk for BC is three-fold increased in non-smokers Leu/Leu group for CYP1B1 (P = 0,04, OR = 3; 95% confidence intervals: 1,1-8,2). The polymorphisms studied in the above mentioned genes did not influence the age of menarche or menopause differently in BC and controls. The influence of CYP17, CYP1B1, CYP1A1 and COMT polymorphisms on the levels of DNA damage was also analyzed and while CYP17 and CYP1A1 did not affect the MNs frequencies or the DNA damage observed by Comet assay in neither in BC nor in control group, the Leu allele of CYP1B1 was significantly associated with the higher levels of DNA damage in control group, but did not interfere on DNA damage detected in BC group. On the other hand in the control group, individuals carrying the Met allele of COMT exhibited lower levels of DNA damage when compared to wild type homozygous, but in BC group the polymorphic homozygous individuals (Met/Met) presented higher levels of DNA than their wild type homozygous or heterozygous counterparts. In conclusion, the present work demonstrated that BC women present an important genomic instability and suggests that estrogens metabolizing polymorphisms may modify the levels of DNA damage in healthy and in BC women.
Leite, Daniela Batista [UNIFESP]. "Análise de polimorfismos nos genes CYP1A1, CYP17, COMT, GSTM1, receptor de estrogênios e progesterona em mulheres com carcinoma de ovário." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/8921.
Full textObjetivos: Avaliar a associação entre os polimorfismos gênicos presentes nos genes do citocromo P450c17 (CYP17), receptor de progesterona (PROGINS) e estrógeno (ER), glutationa S-transferase (GSTM1), catecol-O-metiltransferase (COMT) e polimorfismo do citocromo P450c 1A1 (CYP1A1) em pacientes com e sem carcinoma de ovário e analisar a eventual associação dos referidos polimorfismos com as variáveis clínicas e anatomopatológicas. Métodos: Analisaram-se 103 pacientes com carcinoma de ovário atendidas no Ambulatório de Oncologia Ginecológica do Departamento de Ginecologia da Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM) e no Ambulatório de Oncoginecologia do Serviço de Ginecologia e Obstetrícia do Hospital do Servidor Público Estadual de São Paulo – Francisco Morato Oliveira (HSPE-FMO). O grupo controle I foi constituído por 282 pacientes e o grupo controle II por 141 pacientes atendidas no Setor de Climatério da Disciplina de Endocrinologia Ginecológica do Departamento de Ginecologia da UNIFESP-EPM. O DNA foi extraído a partir de células da mucosa oral e a genotipagem para os polimorfismos foi realizada pela técnica de PCR-RFLP. Resultados: Observamos uma associação significativa entre a frequência do polimorfismo PROGINS e o desenvolvimento do câncer de ovário (p<0,0001). Também foi observada uma associação significativa entre a frequência dos polimorfismos ER-PvuII, ER-XbaI e ER-HaeIII (p=0,03; p<0,00001 e p=0,04, respectivamente) e o desenvolvimento de câncer de ovário e uma tendência de associação entre a presença do polimorfismo ER-MspI (p=0,07) com o carcinoma. Com relação aos polimorfismos presentes nos genes do CYP17, GSTM1, COMT e CYP1A1, não foram observadas diferenças significativas entre o grupo de casos e controles ou entre as outras variáveis de risco analisadas, sugerindo que os mesmos não apresentam uma participação importante no desenvolvimento do carcinoma de ovário em nossa amostra. Não se observou nenhuma relação entre os polimorfismos estudados e TRH, dismenorréia, dispareunia, câncer de mama, hipertensão arterial, diabetes, tipo histológico, estado clínico e grau de diferenciação. Entretanto, foram observadas associações estatisticamente significantes para o polimorfismo PROGINS e antecedentes familiares (p=0,009). Conclusões: Polimorfismos presentes em genes envolvidos na ação dos esteróides sexuais, como PROGINS e ER-α parecem exercer influência no surgimento de condições patológicas como o carcinoma de ovário.
Objectives: To evaluate the association between polymorphisms of cytochrome P450c17 (CYP17), progesterone receptor (PROGINS), gluthatione S-transferase (GSTM1), Catechol-O-methyl transferase (COMT), and cytochrome P450c1A1 CYP1A1) genes in patients with and without ovarian cancer and to analyze the eventual association of these polymorphisms with clinical and pathological variables. Methods: A total of 103 ovarian cancer patients were seen at the Oncological Surgery Outpatients Clinic, Department of Gynecology - Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM) and at the Oncological Gynecology Outpatients Clinic, Division of Gynecology and Obstetrics, Hospital do Servidor Público Estadual de São Paulo – Francisco Morato Oliveira (HSPE-FMO). The control group I comprised 282 patients and control goroup II comprised 141 patients seen at the Climacteric Sector, Division of Gynecological Endocrinology, Department of Gynecology - UNIFESP-EPM. The DNA was extracted from oral mucosa cells and genotyping for PROGINS, GSTM1 and CYP17 polymorphism was carried out by means of PCR-RFLP. Results: A significant association was observed between frequency of PROGINS polymorphism and development of ovarian cancer (p<0.0001). Furthermore, a significant association between the frequency of polymorphisms ER-PvuII, ERXbaI e ER-HaeIII (p = 0.03, p <0.00001 and p = 0.04, respectively) and the development of ovarian cancer and a trend of association between the presence of ER-MspI polymorphism (p=0.07) with the carcinoma. Concerning CYP17, GSTM1, COMT and CYP1A1 polymorphisms, there was no statistically significant difference between the two groups. A significant association between the frequency of PROGINS polymorphism and familial antecedents was observed ((p=0.009). Conclusions: We concluded that differently from CYP17, GSTM1, COMT and CYP1A1 polymorphisms, which had no association between polymorphism and cancer, the PROGINS, ER-PvuII, ER-XbaI and ER-HaeIII polymorphisms were positively associated with ovarian cancer.
TEDE
BV UNIFESP: Teses e dissertações
Duarte, Dante Galileu Guedes. "Estresse precoce e comportamento suicida em pacientes bipolares: estudo de associação com polimorfismos dos genes da COMT e do BDNF." Universidade Federal de Minas Gerais, 2013. http://hdl.handle.net/1843/BUOS-9AXFQE.
Full textO Transtorno Afetivo Bipolar (TAB) é um transtorno psiquiátrico relacionado com altas taxas de tentativas de suicídio. O Estresse precoce é um dos diversos fatores que contribuem para o aparecimento do Comportamento Suicida e influencia negativamente o curso do TAB. Há diversos artigos que corroboram essa associação. Foram selecionados 47 pacientes portadores de TAB tipo 1, que frequentam o Ambulatório de Transtornos Afetivos da Residência de Psiquiatria da Universidade Federal de Minas Gerais (UFMG). Além disso, selecionamos aleatoriamente 48 controles. Foram preenchidas as escalas de depressão de Hamilton, a escala de mania de Young, assim como uma entrevista psiquiátrica estruturada (MINI PLUS 5.0). O Estresse precoce foi avaliado pela Questionário sobre Traumas na Infância (QUESI) e o comportamento suicida pela Escala de Intenção Suicida de Beck (Becks Suicide Scale), Escala de Letalidade de Beck e avaliamos o tipo de tentativa de suicídio, se violenta ou não violentas. Os controles não foram avaliados pelas escalas, apenas pelo MINI PLUS. Polimorfismos dos genes da COMT e BDNF foram avaliados por PCR. As análises estatísticas foram feitas utilizando Kolmogorv-Smirnov, o Teste t de Student ou o teste U de Mann Whitney e o teste do qui-quadrado (X2). As análises estatísticas (genéticas) dos resultados obtidos do material foram realizadas utilizando o programa Unphased 3.0.12. Não foram observadas diferenças significativas entre os pacientes com TAB que foram divididos no grupo com Estresse precoce e sem Estresse precoce, e também quando foram comparados com presença e ausência de comportamento suicida. Não foi encontrada associação alélica ou genotípica entre o SNP estudado para os genes da COMT e BDNF com comportamento suicida e Estresse precoce. Em conclusão, este estudo corroborou com a noção de que o Comportamento Suicida é o resultado de interações complexas entre múltiplas variáveis, incluindo fatores genéticos. Contribuiu, trazendo mais conhecimento sobre o assunto e, com isso, despertando a atenção dos clínicos sobre a importância da prevenção de Comportamento suicida naqueles pacientes que sofreram Estresse precoce. Repetições independentes em amostras maiores e investigações mais aprofundadas sobre o papel do Estresse precoce nessa intrincada rede fazem-se necessárias.
Melton, Amanda M. A. "Influence of COMT gene variant on working memory in survivors of childhood brain tumors /." Full text available from ProQuest UM Digital Dissertations, 2009. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1913291401&SrchMode=1&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1278096109&clientId=22256.
Full textOtt, Cordula. "Assoziation des Single Nucleotid Polymorphismus V108/158M im COMT-Gen mit Suizidalität und Persönlichkeit." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-79505.
Full textStumpenhorst, Katharina. "Separate and interactive effects of catechol-o-methyltransferase and tetrahydrocannabinol on frontostriatal dopamine function." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:e8eb9eba-0e32-4b30-8349-c2678207f547.
Full textJacobs, Sarah. "Development of a COMT PCR multiplex to investigate resilience, anxiety and childhood trauma in a South African population." University of the Western Cape, 2020. http://hdl.handle.net/11394/7923.
Full textAnxiety, resilience and childhood trauma can be categorized as functional behavioural categories, with a wealth of research behind each. The research approach adopted for each, in most cases, is either from a genetic or neuropsychological standpoint, with few studies combining both to better understand all three functional behavioural categories as a multidimensional construct A number of candidate genes have been identified as markers for anxiety, resilience and childhood trauma, of which Catechol-methyl-transferase (COMT) and several respective single nucleotide polymorphisms (SNPs) are included. Although COMT SNPs have been linked to at least one of the functional categories, with a handful of haplotypes identified, to our knowledge no study has investigated the combination of SNPs selected for this study (rs6269, rs4818, rs4680, rs4633, rs737865, rs2075507) as a possible haplotype, specifically in a South African population. The use of SNaPshot for the genotyping of genes is an efficient and reliable means of identifying genotype frequencies and haplotypes in large sample groups, yet when selecting more than two SNPs of interest, the development of a multiplex assay is ideal. The first aim of the study was to design and optimize a multiplex assay to genotype several COMT SNPs. The primer design, multiplex optimization and SNaPshot conditions used showed good working parameters that can be utilized and further improved by optimization. Self-report measures are widely used to measure psychiatric disorders, such as anxiety, and has also been used for the measurement of resilience and childhood trauma. With each functional behavioural category well investigated in its respective domain, there is a need to investigate all three as a collective in a South African population due to the high rate of anxiety and childhood trauma exposure in communities. The second aim of the study was to investigate the prevalence of anxiety, resilience and childhood as functional behavioural categories in the full South African sample group; and the role of sex, through established self-report measures and respective normative data. Additionally, this carried over into investigating the correlation between anxiety, resilience and childhood trauma as a multidimensional construct in both the full South African sample and between sexes. There is a clear relationship which exists between all three functional behavioural categories, as they show a correlation in various dimensions independent of one another. Higher anxiety levels amongst females were reported, with no difference between sexes for resiliency. The empirical data collected from both COMT SNP and self-report measures for male and female where explored and reviewed against current literature for better understanding and insight into the association of COMT SNPs with anxiety, resilience and childhood trauma in a South African population. The results of this study to understand the complexity and association of all three functional behavioural categories as a multidimensional construct will be invaluable and may assist in the identification of possible risk factors which are essential for the promotion of better mental health in society.
Lerner, Christian Daniel. "Strukturbasiertes Design, Synthese und in vitro Bewertung von Bisubstrat-Inhibitoren der Catechol-O-Methyltransferase (COMT) /." [S.l.] : [s.n.], 2003. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=15033.
Full textKorn, Clio. "Contributions of COMT and DAT to regulation of phasic dopamine release and reward-guided behaviour." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:8772a01d-665d-454e-9e3c-bf734331a1c2.
Full textOliveira, Angélica Salatino de. "O polimorfismo Val158Met do gene COMT e TDAH : um estudo de suscetibilidade genética e farcogenética." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/139173.
Full textAttention-Deficit Hyperactivity Disorder (ADHD) is a common psychiatric condition that affects children and adolescents worldwide. This disorder is defined by symptoms of inattention and hyperactivity/impulsivity. Comorbidity with other disorders, such as Disruptive Behaviour Disorders (DBD) is very common. Regarding ADHD‟s neurobiology, there is a hypothesis that children with ADHD have prefrontal cortex (PFC) deficits with inadequate catecholamine transmission. The enzyme catechol-O-methyltransferase (COMT) degrades catecholamines and it has been suggested that it plays a key role in prefrontal cortical functioning. COMT accounts for most of the degradation of dopamine in the PFC. The Val158Met polymorphism is functional. It affects the thermostability of the protein. Several studies suggest that this variation in COMT has a relevant role in ADHD heterogeneity, and it can lead to emergence of DBD. Methylphenidate (MPH) is the most widely used drug to treat ADHD. The effect of MPH on catecholaminergic pathways results in an improvement of the PFC functioning by blockade of dopamine and norepinephrine transporters. Due to action of COMT in catecholaminergic balance, it is necessary to know about the pharmacogenetic effect of COMT in ADHD. A sample of 473 children with ADHD was genotyped for the Val158Met polymorphism. A consensus diagnosis of ADHD with or without comorbidity was achieved through a three-stage process, as previously described in the literature. Around these patients, 251 children with ADHD fulfilled inclusion criteria to participate in the pharmacogenetic study. Potential confounders were evaluated. Dosages of short-acting MPH were augmented until no further clinical improvement was detected or until there were significant adverse events (MPH dose always > 0.3 mg/kg/day). The outcome measure was the parent-rated oppositional subscale of the Swanson, Nolan and Pelham Scale – version IV. The scale was applied by child psychiatrists blinded to genotype at baseline and in the first and third months. Patients homozygous for Val allele showed a higher frequency of DBD (+ 12%) than Met allele carriers (2 = 5.729, p = 0.017, OR = 1.62). We detected 6 significant improvement in SNAP-IV oppositional scores from baseline to the first and three months of treatment (n = 112; F2,231 = 5.35, p = 0.005). A significant effect of the presence of Met allele during three months of treatment (F1,148 = 5.02, p = 0.027), and a significant interaction between the Met allele and treatment over time for the SNAP-IV oppositional scores during this period of treatment (F2,229 = 6.40, p = 0.002) were both observed. Therefore, our results indicate that there is a significant difference in the presence of disruptive behavior disorders in children with ADHD according to Val158Met genotype. This antisocial behavior in children with ADHD seems to be predicted by Val/Val genotype in COMT gene. Moreover, pharmacogenetic results suggest an effect of the COMT genotype on the trajectory of ODD symptoms improvement with MPH treatment in boys with ADHD.
Masjost, Birgit. "Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol o-methyltransferase (COMT) /." [S.l.] : [s.n.], 2000. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=13719.
Full textChoudhry, Zia Ulhaq. "Catechol-O-Methyltransferase (COMT) Val 108158 Met polymorphism and ADHD : pharmaco-behavioural genetic and neurocognitive study." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112389.
Full textGarcía, García Manuel Antonio. "The role of COMT, DAT and DRD2 polymorphisms on brain mechanisms of involuntary attention and cognitive control." Doctoral thesis, Universitat de Barcelona, 2009. http://hdl.handle.net/10803/2722.
Full textThe results of these studies provide evidence for a relevant role of COMT, DAT1 and DRD2 genes in cognitive processes, which helps to understand cognitive disruption associated to dopamine dysregulation in psychiatric disorders.
Els nostres gens juguen un rol important en la manera que enfrontem els canvis de l'ambient i adaptem la nostre conducta adequadament. El present treball de recerca se centra en el paper de tres gens relacionats amb la dopamina (DA) sobre processos cognitius, com el canvi de l'atenció quan és requerit per les demandes ambientals o el processament d'esdeveniments inesperats però potencialment rellevants. L'activitat dopaminèrgica al còrtex prefrontal (PFC) i a l'estriat semblen jugar papers diferents en el processament atencional i interaccionen per a regular l'estabilitat i flexibilitat de l'actualització de la informació contextual. Per això, vam estudiar l'acció de gens que regulaven l'acció de la dopamina del PFC (i.e. Catechol-O-Methyltransferase; COMT), la resposta de dopamina difosa en l'espai extrasinàptic estriatal (i.e. Transportador de Dopamina; DAT) i la concentració de receptors de dopamina de tipus D2 (i.e. receptors D2 de dopamina; DRD2).
Els participants amb diversos al·lels dels gens estudiats van realitzar dues versions diferents d'un paradigma de distracció auditiu visual, en el qual se'ls demanava que ignoressin tons estàndards freqüents i sons ambientals nous rars que precedien els objectius pertinents de la tasca. En dos estudis, vam manipular l'efecte d'un context emocional sobre el processament d'esdeveniments nous inesperats, donada la potencial rellevància d'un esdeveniment nou durant una situació d'amenaça en la qual pot ser nociu. En tres estudis, els participants amb al·lels diferents o combinacions d'al·lels van realitzar un paradigma de commutació de tasca, en el qual l'actualització d'informació sensorial i de tasca es podria dissociar. Al llarg dels sis estudis, se van emprar mesures conductuals i electrofisiològiques enregistrades al cuir cabellut, com els anàlisis de l'electroencefalograma (EEG) al domini del temps promitjant els potencials cerebrals relacionats a esdeveniments (ERP), i l'activitat oscil·latòria cerebral al domini temps- freqüència.
Tres estudis van mostrar el paper del gen del DAT en el control cognitiu de l'atenció, suggerint així la pertinència de la DA estriatal en la flexibilitat cognitiva. Els nostres resultats suggereixen un processament independent del context dels canvis sensorials per la reconfiguració del set de la tasca en individus amb l'al·lel de 9 repeticions de DAT (9R+) relacionats amb una major disponibilitat de dopamina estriatal. Tanmateix, aquests individus van mostrar una detecció primerenca de la rellevància per la tasca dels canvis sensorials. El gen del DAT regulava la modulació del processament de la novetat per un context emocional. Els individus 9R+ van mostrar una resposta cerebral més gran als estimuls novedosos.
Dos estudis van mostrar el paper de la interacció dels gens de la COMT i del DRD2 sobre processos atencionals. S'ha suggerit que els individus amb l'al·lel de COMT Val i l'al·lel de DRD2 A1 (A1+) i COMT Met sense l'al·lel de DRD2 A1 (A1-) mostren una interacció equilibrada de dopamina prefrontal i estriatal. Aquests grups van mostrar distracció conductual, mentre que els individus ValA1- i els individus MetA1+ no van ser distrets per sons nous en un paradigma de distracció visual auditiu. Els grups, tanmateix, no-distrets resultaven processar esdeveniments nous a través de la restauracio d'activitat neuronal a 40 Hz. A més, aquells amb una interacció equilibrada semblaven tornar a configurar la informació de la tasca quan era necessari, mentre que aquells amb dopamina PFC o estriatal extremes tornarien a configurar el set de la tasca després de cada canvi sensorial.
Els resultats dels estudis de la tesi proporcionen una evidència del paper rellevant dels gens de la COMT, el DAT1 i el DRD2 en processos cognitius, i ajuden a entendre els dèficits cognitius associats a la disregulació de la dopamina en trastorns psiquiàtrics.
Wendler, Franziska Verfasser], and Stefan [Akademischer Betreuer] [Pollmann. "Genetic influences on long-term memory control : COMT and retrieval-induced forgetting / Franziska Wendler. Betreuer: Stefan Pollmann." Magdeburg : Universitätsbibliothek, 2014. http://d-nb.info/1054638551/34.
Full textCapitão, Luísa Maria Sousa Ribeiro. "Estudo dos polimorfismos CYP1B1 VAL432 LEU, MTHFR Ala225VAL e COMT VAL158 Met como factores de risco de cancro da mama em mulheres da Beira Interior." Master's thesis, Faculdade de Medicina da Universidade do Porto, 2007. http://hdl.handle.net/10216/22131.
Full textCapitão, Luísa Maria Sousa Ribeiro. "Estudo dos polimorfismos CYP1B1 VAL432 LEU, MTHFR Ala225VAL e COMT VAL158 Met como factores de risco de cancro da mama em mulheres da Beira Interior." Dissertação, Faculdade de Medicina da Universidade do Porto, 2007. http://hdl.handle.net/10216/22131.
Full textCuyàs, Navarro Elisabet. "Pharmacogenetic mechanisms (COMT and hSERT) modulating deleterious effects of MDMA and cannabis on cognitive performance in drug users." Doctoral thesis, Universitat Autònoma de Barcelona, 2011. http://hdl.handle.net/10803/48529.
Full textThe serotonergic and dopaminegic neurotransmission at the prefrontal-cortex and the areas related to the limbic system, are one of the main substrates for the executive functions (involved in different tasks such as organization and control). Some drugs such as MDMA or cannabis are known to alter these neurotransmission systems. Some functional polymorphisms within the catechol-O-methyltransferase (COMT) and the serotonin transporter gene (hSERT) have been associated to interindividual differences in the cognitive performance. The interaction between both genes and ambient factors can explain to some extent, the different susceptibility of drug users to the deleterious effects of these psychoactive substances. The main objective is to study the relationship between several polymorphisms within the serotonergic and dopaminergic neurotransmission systems and the cognitive performance of a sample of MDMA and cannabis users in several neuropsychological tasks (mainly related to memory and executive functions).
Lewandowski, Kathryn Eve. "The role of COMT in schizophrenic-like cognitive impairment and social functioning in children with 22q11 deletion syndrome." Greensboro, N.C. : University of North Carolina at Greensboro, 2007. http://libres.uncg.edu/edocs/etd/1480Lewandowski/umi-uncg-1480.pdf.
Full textTitle from PDF t.p. (viewed Feb. 29, 2008). Directed by Thomas R. Kwapil; submitted to the Dept. of Psychology. Includes bibliographical references (p. 79-111).
Herrmann, Lennard Manes Richard [Verfasser], Siegfried Martin [Gutachter] Muhlack, and Ludgera Martina [Gutachter] Ossege-Pohle. "COMT-Inhibitoren in der Parkinson-Therapie / Lennard Manes Richard Herrmann. Gutachter: Siegfried Martin Muhlack ; Ludgera Martina Ossege-Pohle." Bochum : Ruhr-Universität Bochum, 2016. http://d-nb.info/1102524948/34.
Full textSchuh, Artur Francisco Schumacher. "Farmacogenética da levodopa na doença de Parkinson : estudo de polimorfismos nos genes da COMT, MAO-B e DAT." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/39639.
Full textAlazizi, Adnan. "Molecular Cloning, Expression, purification and Characterization of the Zebrafish Catechol-O-methyltransferases." University of Toledo Health Science Campus / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=mco1303391786.
Full textGiannunzio, Valeria. "Different Types of Decision Making Impairments in Anorexia Nervosa." Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3424927.
Full textLa ricerca sugli aspetti neurocognitivi nell’anoressia nervosa (AN) ha delineato un profilo cognitivo caratterizzato da deficit nell’abilità di set-shifting (flessibilità cognitiva) e da debole coerenza centrale. Un minor accordo emerge in relazione alla compromissione dei profili decisionali frequentemente osservata nelle pazienti con AN dal momento che la complessità della patologia e della funzione esecutiva stessa rendono poco chiara la natura di tali alterazioni e le relazioni con aspetti clinici specifici della malattia o indipendenti da essa. Il nostro studio si propone di valutare la capacità decisionale di un campione di pazienti affette da AN utilizzando l'Iowa Gambling Task, e il Cognitive Bias Task, di analizzare le performance al test utilizzando un modello cognitivo specifico per l’Iowa Gambling Task (Expectancy Valence model), e di studiare le relazioni tra i risultati ottenuti e le caratteristiche cliniche delle pazienti focalizzandoci nella loro relazione con aspetti caratteristici del profilo neuropsicologico e della presentazione della malattia come la precoce età di esordio. Approfondire i correlati anatomici, di connettività strutturale e funzionale delle perfomance ai due task e l’impatto dell’assetto genetico. Il campione, costituito da 310 soggetti di sesso femminile con diagnosi lifetime di AN e 301 soggetti di sesso femminile senza diagnosi di sturbo del comportamento alimentare è stato testato in relazione alle abilità decisionali attraverso l’Iowa Gambling Task. Tutti i soggetti, previo consenso informato, hanno completato una valutazione sia clinica che semistrutturata mediante la somministrazione dell’Intervista Clinica Strutturata (SCID) per il DSM-IV, sezione per i disturbi del comportamento alimentare. E’ stata somministrata una batteria di valutazione neuropsicologica includente: the WCST Wisconsin Card Sorting Test and Trail Making Tet sper la valutazione dell’abilità di astrazione e della flessibilità cognitiva; test di Memoria con interferenza a 10" e 30" per la valutazione della memoria di lavoro; SSRT per la valutazione del controllo inibitorio. E' stato utilizzato inoltre uno specifico modello cognitivo (Expectancy Valence model) al fine di analizzare i risultati ottenuti all'IGT. È stata effettuata una genotipizzazione per valutare l’impatto dei principali polimorfismi ritenuti implicati nelle performance decisionali (158 Val → Met del gene COMT, la variante corta e il polimorfismo a singolo nucleotide A/G (SNP rs25531) del gene del trasportatore della serotonina 5-HTTLPR. Un sottogruppo di 35 soggetti affetti da AN e 34 controlli sani infine si è sottoposto a risonanza magnetica funzionale a riposo. E’ stata condotta un’analisi della connettività funzionale basata su “seed” in specifiche regioni di interesse (network esecutivo, corteccia orbitofrontale, network dell’accumbens ed amigdala). I risultati confermano la presenza di un peggior profilo decisionale all’ IGT nelle pazienti affette da Anoressia nervosa indipendentemente dall’età del soggetto, tuttavia il deficit decisionale sembra essere indipendente dall’IMC nell IGT ma influenzato dal sotto peso nel Cbias. Entrambi i diversi tipi di decision making nelle pazienti non risentono dall’assetto neurocognitivo o dalle variabili cliniche prese in esame. L’assetto genetico sfavorevole nelle pazienti sembrerebbe essere l’omozigosi per l’allele met del gene Comt e per la variante S del trasportatore della serotonina. Rispetto al gruppo di soggetti sani, il profilo decisionale delle pazienti affette da Anoressia Nervosa è risultato peggiore sia allo Iowa Gambling Task (IGT), che valuta le abilità deciosionali di tipo veridico, che al Cognitive Bias Task (Cbias), che valuta le abilità decisionali di tipo adattativo, indipendentemente dal sottotipo diagnostico (restrittivo vs bulumico purgativo), psicopatologia, scolarità o dominanza manuale. La connettività funzionale a riposo esplorata sui seed di interesse (network esecutivo, corteccia orbitofrontale, accumbens e amigdala ) in un sottogruppo di pazienti e controlli ha mostrato nei due gruppi pattern significativamente diversi di correlazione con i punteggi all’IGt e al Cbias. Inoltre pattern neurali differenti a riposo sembrano essere coinvolti nei due diversi task considerati. È stata identificata solo nel gruppo di AN una correlazione positiva tra i punteggi all’IGT e l’attività dell’amigdala. Nelle pazienti una maggior coattivazione all’interno del network esecutivo , orbitofrontale e dell’accumbens è legata a performance decisionali maggiormente indipendenti dal contesto al Cbias, mentre per il network esecutivo accade il contrario nei soggetti sani.
Miguita, Karen. "Estudo de associação de genes candidatos no transtorno obsessivo-compulsivo: investigação dos loci SLC6A4, HTR1B, HTR2A, SLC6A3, COMT e SLC6A2." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5142/tde-23102007-110042/.
Full textObsessive-compulsive disorder (OCD) is a common and heterogeneous psychiatric disorder characterized by obsessions (intrusive and recurrent thoughts, images or impulses) and compulsions (repetitive behaviors or mental acts performed to relive obsessions). OCD prevalence range from 2 to 3% in general population and has approximately equal sex distributions, however men tend to have an earlier age at onset of obsessive-compulsive symptoms comparing to women. Epidemiologic studies have demonstrated that genetic factor is an important component in the etiology of OCD. The aim of this study was to investigate participation of some candidate genes in the susceptibility to OCD and also their effects on clomipramine treatment. We performed a candidate gene study in a total of 215 OCD patients and 865 controls. The loci investigated were: SLC6A4, HTR1B, HTR2A, SLC6A3, COMT and SLC6A2. The same polymorphisms were investigated in a sub-sample of 41 patients treated with clomipramine, and analyzed according to therapeutic response. There were considered good responders to the drug those patients who presented a reduction of 40% or more in Y-BOCS scale. According to this, 27 patients were good responders and 14 poor responders. Genotypic and allelic differences were observed in some results for patients and controls. However, no association was observed in the analyses for clomipramine response. Our results suggest that some polymorphisms investigated may be related to the increase of risk to develop OCD, but they are not associated to therapeutic response to clomipramine.
Wortmann, Viola [Verfasser], and Volker [Akademischer Betreuer] Arolt. "Hippokampale Volumenveränderung und COMT-Val-108/158-Met-Polymorphismus bei Patienten mit akuter unipolarer Depression / Viola Wortmann. Betreuer: Volker Arolt." Münster : Universitäts- und Landesbibliothek der Westfälischen Wilhelms-Universität, 2011. http://d-nb.info/1027017762/34.
Full textNüsser, Corinna. "Neuronale Korrelate von Delay Discounting." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-23427.
Full textFasolo, Juliana Maria de Mello Andrade. "Aplicação de CLAE-DAD-EM e CG-EM na caracterização de Blechnum sp. e abordagens in vitro e in silico para a avaliar o perfil multifuncional do ácido rosmarínico em alvos relacionados à neurodegeneração e toxicidade em células-tronco." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/149457.
Full textMedicinal plants are considered important sources of biologically active compounds. For many chronic diseases, such as neurodegenerations, substances that present simultaneous activities in more than one target related to the etiopathology of these disorders are considered potential therapeutic agents. In this context, the aims of the study were the chemical and biological evaluation of three fern species, occurring in south Brazil: Blechnum binervatum, B. brasiliense and B. occidentale. The bioguided isolation was employed to identify compound(s) with potential activities at in vitro and in silico models associated to neurodegenerative disorders. The biological evaluation of extracts and fractions allowed to highlight the ethyl acetate fraction of B. brasiliense, which was the most active in the stabilization of hydroxyl radicals (IC50: 12.5 μg/mL) and on lipoperoxidation inhibition (IC50: 10.4 μg/mL), being one of the most active sample against nitric oxide (IC50: 55.6 μg/mL). Furthermore, on the inhibition of isoform A from monoamine oxidase (MAO), this fraction showed the lowest IC50 value (28.6 μg/mL). The dichloromethane fractions also presented good results in the MAO-A inhibition, being some of them active as antioxidants, too. Against MAO-B, extracts and fractions of the three species demonstrated reduced effects and all samples were inactive in the acetyl and butyryl cholinesterase inhibition, showing no toxic effects to polymorphonuclear cells (PMN) from Wistar rats, at 1 mg/mL. Using cultured stem cells, the selected extracts and fractions at 100 to 500 μg/mL did not affect cell viability and absence of cytotoxic effects was observed. The chemical analysis by high performance liquid chromatography, coupled to photodiode array detector and mass spectrometry, allowed the identification of caffeoyl quinic acid and caffeoyl shikimic acid isomers in the three studied fern species. B. binervatum presented also glycosilated caffeic acid, isosalvianolic acid A and sulphated rosmarinic acid. Salvianolic acid F was identified in B. binervatum and B. occidentale, as well as, brainic acid isomers. Rosmarinic acid was characterized in B. binervatum and B. brasiliense. Quercetin 3-O-glycoside and vicenin-2 were also found. Analysis by gas chromatography with mass spectrometry showed the diterpene neophytadiene was the major compound in dichloromethane fractions of Blechunm and in hexane fractions of B. occidentale and B. binervatum. For the hexane fraction from B. brasiliense, β-sitosterol was majority. From the ethyl acetate fraction of B. brasiliense was isolated rosmarinic acid, which was shown to be active in antioxidant assays, in the inhibition of catechol-O-methyltransferase (IC50: 26.7 μM) and MAO-A (IC50: 50.1 μM), being suggested a reversible inhibition mechanism against this enzyme. In docking studies were observed molecular interactions between the compound and MAO-A and COMT enzymes, via hydrogen bonds and hydrophobic interactions in enzyme active sites. The compound did not induce toxic effects to rodent PMN cells, at concentrations of 0.5 and 5 mM. The rosmarinic and chlorogenic acids, isolated from B. binervatum extract, did not influence cell viability and did not induce toxicity to stem cells (100 to 500 μM), the rosmarinic acid was also capable to induce cell proliferation. Protective ability against H2O2-induced cell damage (1400 μM) was observed for both substances at concentrations of 10-100 μM, and the results were supported by cellular microscopy images. Rosmarinic acid presented better responses compared with chlorogenic acid, being powerful inhibitor against H2O2-induced damage. The overall results highlights the importance of associated chemical-biological studies of plant species and points at the potential of ferns as sources of bioactive compounds, capable of modulating multiple enzymatic and non-enzymatic targets related to neurodegenerative diseases.
Caldú, i. Ferrús Xavier. "Influència de les variants genètiques de la COMT i el DAT en l'activació cerebral i en el processament cognitiu i emocional." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/2703.
Full textChau, Cecil Ming Yeung. "Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55054.
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Graduate
Godinez, Detre. "The Wisconsin Card Sorting Task: An analysis of the construct validity, heritability, and association with the COMT Val(158)Met polymorphism." Connect to online resource, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3273679.
Full textKube, Johanna [Verfasser]. "Varianten im COMT-Gen und neue Urinmarker zur Risikoabschätzung der Entwicklung einer akuten und chronischen Nierenschädigung nach kardiochirurgischen Eingriffen / Johanna Kube." Magdeburg : Universitätsbibliothek, 2018. http://d-nb.info/1174626607/34.
Full textWright, Galen Egan Buckley. "Molecular genetic analysis of two genes, CYP2D6 and COMT, in the schizophrenia-susceptibility locus on chromosome 22q in the Xhosa population." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20366.
Full textBüttner, Claudia Sophia [Verfasser], and Caroline [Akademischer Betreuer] Jung-Sievers. "Assoziation von Polymorphismen im COMT-Gen mit der Schizophrenie und dem Arbeitsgedächtnis als Endophänotyp / Claudia Sophia Büttner. Betreuer: Caroline Jung-Sievers." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1106854578/34.
Full textDaubitz, Torsten [Verfasser], and Andreas J. [Gutachter] Fallgatter. "Einfluss des COMT-Polymorphismus auf das Sensorische Gating bei erwachsenen ADHS-Patienten und gesunden Kontrollen / Torsten Daubitz. Gutachter: Andreas J. Fallgatter." Würzburg : Universität Würzburg, 2014. http://d-nb.info/1110028075/34.
Full textAkdenizli, Kemal [Verfasser]. "Bedeutung genetischer Polymorphismen in BDNF, Bcl-2 sowie COMT und MAO-A für den Erfolg der Therapie mit Antidepressiva / Kemal Akdenizli." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023783568/34.
Full textArmbruster, Diana. "The impact of serotonergic and dopaminergic genetic variation on endophenotypes of emotional processing." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-63574.
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