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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Molekulargenetische Untersuchung des MAOA-LPR-Polymorphismus an einer Patientengruppe mit Persönlichkeitsstörungen / Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity

Schmidt, Michael Alexander January 2009 (has links) (PDF)
In mehreren klinischen und außerklinischen Populationen werden die allelischen Variationen der Monoaminoxidase-A mit aggressivem, ängstlichem und abhängigem Verhalten in Verbindung gebracht. In unserer Studie haben wir den Einfluss von Allelvariationen der Monoaminoxidase-A auf aggressivitätsassoziierte Persönlichkeitsmerkmale und die Erkrankungswahrscheinlichkeit für Probanden mit Persönlichkeitsstörungen untersucht. Die Hypothese ist, dass ein geschlechtsspezifischer Zusammenhang zwischen der Allelvariation mit konsekutiv geringerer Enzymaktivität und Cluster-B-Persönlichkeitsstörungen nach DSM-VI, antisozialen Persönlichkeitsstörungen, sowie den Persönlichkeitsmerkmalen „Suche nach neuen Erfahrungen“ (TPQ), Neurotizismus, Verträglichkeit und Gewissenhaftigkeit bestehen könnte (NEO-PI-R). Der Genotyp des MAOA-Polymorphismus MAO-LPR wurde an 566 Patienten mit Persönlichkeitsstörungen und an 281 Probanden einer gesunden Kontrollgruppe untersucht. Der MAOA-LPR-Genotyp zeigt eine signifikante Korrelation mit Cluster-B-Persönlichkeitsstörungen nach DSM-IV (chi2=7.77, p=0.005, df=1). Dabei sind 26% der Probanden mit einer Persönlichkeitsstörung aus dem B-Cluster homo- oder hemizygot für den MAOA-Genotyp, der zur Ausprägung einer Variante mit geringer Enzymaktivität führt. Im Vergleich weisen dagegen nur 16.4% der Probanden aus der Kontrollgruppe diesen Genotyp auf. Zusammenhänge zwischen Allelvariationen der MAOA-Aktivität und Persönlichkeitsmerkmalen, die mit impulsivem und aggressivem Verhalten in Verbindung gebracht werden, erweisen sich als unbeständig. Eine Korrelation mit Cluster-C-Persönlichkeitsstörungen kann nicht nachgewiesen werden. Unsere Ergebnisse zeigen einen Zusammenhang zwischen Hemi- und Homzygotität der MAOA-LPR-Variante mit konsekutiv geringer Enzymaktivität und Cluster-B-Persönlichkeitsstörungen. Für den Einfluss der mit geringerer MAOA-Aktivität einhergehenden Variationen des Genotyps auf Aggression, Impulsivität und gewalttätiges Verhalten beim Menschen gibt es Hinweise (Shih et al. 1999). Immer häufiger werden Beweise für ein Zusammenwirken von genetischen Determinanten und Umwelteinflüssen gefunden. Unsere Erkenntnisse unterstützen weiterhin die These, dass die genetische Determination der MAOA-Aktivität auch in bestimmtem Maße zur Ausprägung des Gleichgewichts zwischen hyper- (impulsiv-aggressiv) und hyporeaktivem (ängstlich-depressiv) Verhalten beiträgt. / Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits.
2

Serotonerge Gene und NOS1 als Risikofaktoren für gewalttätiges Verhalten / Serotonergic Genes and NOS1 influence aggressive behaviour

Eujen, Andrea January 2009 (has links) (PDF)
Persönlichkeit im Allgemeinen wird, neben Umwelteinflüssen, durch genetische Komponenten beeinflusst. Bisher konnten jedoch nur wenige funktionelle Genvarianten mit Verhaltenszügen assoziiert werden. Aggressives Verhalten als spezifisches Verhaltensmuster wird durch eine Reihe von Genvariationen beeinflusst, die in serotonerge, dopaminerge und nitrinerge Regelkreise eingreifen. Neben der genetischen Komponente prädisponieren aber hier ganz erheblich auch äußere Faktoren in der Umwelt, wie z.B. das soziale Umfeld, in dem Kinder und Jugendliche aufwachsen, für die Entwicklung von gewalttätigem Verhalten. Ziel der vorliegenden Arbeit war es, einen möglichen Einfluss von vier verschiedenen funktionellen Gen-Polymorphismen (MAOA-uVNTR, DAT-uVNTR, NOS1 Ex1f-uVNTR und NOS1 Ex1c-SNP) auf Gewalttätigkeit bzw. Aggressivität zu untersuchen. Außerdem wurden Gen x Umweltinteraktionen im Bezug auf ungünstige soziale Bedingungen in der Kindheit untersucht. Eine aus 184 Männern bestehende Stichprobe von Straffälligen wurde in eine Gruppe von gewalttätigen und eine Gruppe von nicht-gewalttätigen Straftätern unterteilt. Durch die logistische Regressionsanalyse konnte ermittelt werden, dass der MAO-A Genotyp, wie auch ungünstige soziale Bedingungen in der Kindheit, unabhängig voneinander für gewalttätiges Verhalten prädispositionieren. 45% der Gewalttätigen, aber nur 30% der nicht-gewalttätigen Studienteilnehmer sind Träger des niedrig-aktiven kurzen MAO-A Allels. Die neuronale Isoform der Stickstoffmonoxid-Synthase (NOS-I) wurde, ebenso wie MAO-A, in Tierversuchen mit aggressiven Verhaltensweisen assoziiert. In der vorliegenden Arbeit konnte gezeigt werden, dass es auch einen Zusammenhang zwischen einem funktionellen Promotorpolymorphismus von NOS1 und menschlicher Aggressivität gibt. Im Gegensatz zu MAOA und NOS1 beeinflusst ein funktioneller Polymorphismus im DAT1-Gen Gewalttätigkeit nicht. Diese Ergebnisse legen komplexe Interaktionen zwischen genetischer Variation und Umweltfaktoren nahe und zeigen gleichzeitig, dass aggressives Verhalten nicht durch einfache Vererbungsmodi zu erklären ist. / Almost all domains of human behaviour show significant albeit varying genetic contribution. Molecular personality genetics explore how given candidate genes might influence behavioural traits. Only a few genetic variants have been associated with aggressive behaviour so far. Aggressive behaviour is thought to be critically modulated by serotonergic, nitrinergic and domapinergic function. Besides genetic aspects also early life experience contributes to behavioural traits. The present study aimed to investigate the contribution of four functional polymorphisms involved in serotonergic neurotransmission (MAOA-uVNTR, DAT-uVNTR, NOS1 Ex1f-uVNTR and NOS1 Ex1c-SNP) to the development of violence and to test for gene x environment interactions relating to adverse childhood environment. A cohort of 184 adult male volunteers referred for forensic assessment participated in the study. Each individual was assigned either to a violent or non-violent group. Logistic regression was performed and the best fitting model, with a predictive power of 74%, revealed independent effects of adverse childhood environment and MAOA genotype. High environmental adversity during childhood was significantly associated with violent behavior. 45% of violent, but only 30% of non-violent individuals carried the low-activity, short MAOA allele. Also the functional polymorphism of the neuronal NO Synthase (NOS1 Ex1fc) was significantly associated with the development of aggressive behaviour, whereas the dopamine transporter gene polymorphism (DAT-uVNTR) does not seem to contribute to aggressive behaviour. These findings indicate complex interactions between genetic variation of the serotonergic circuitry and environmental factors arguing against simplistic, mono-causal explanations of violent behavior.
3

L-deprenil previne alterações neuroquímicas e comportamentais induzidas pela isquemia cerebral transitória / L-Deprenyl prevines neurochemicals and comportamentals alterations induced of transiente cerebral ischaemia

Maia, Flávio Damasceno January 2004 (has links)
MAIA, Flávio Damasceno. L-deprenil previne alterações neuroquímicas e comportamentais induzidas pela isquemia cerebral transitória. 2004. 195 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2004. / Submitted by denise santos (denise.santos@ufc.br) on 2012-03-26T16:29:42Z No. of bitstreams: 1 2004_dis_fdmaia.pdf: 1266056 bytes, checksum: 06d1580a329764bceb9fb16945ba714a (MD5) / Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2012-03-27T15:57:47Z (GMT) No. of bitstreams: 1 2004_dis_fdmaia.pdf: 1266056 bytes, checksum: 06d1580a329764bceb9fb16945ba714a (MD5) / Made available in DSpace on 2012-03-27T15:57:47Z (GMT). No. of bitstreams: 1 2004_dis_fdmaia.pdf: 1266056 bytes, checksum: 06d1580a329764bceb9fb16945ba714a (MD5) Previous issue date: 2004 / The present work shows the effects of l-deprenyl (DEP, 5 and 10 mg/kg, po) on memory, as well as on rat brain free radical formation after transient cerebral ischemia (TCI). Wistar rats were anesthetized and submitted to TCI by occlusion of both carotid arteries for 20 minutes. In another experiment, animals were submitted to surgery without ischemia (sham-operated). After surgery, ischaemic rats were treated with DEP (DEP, 5 and 10 mg/kg, po) once and daily for 5 days. One group of animals was left untreated (controls). The parameters studied were, memory acquisition and memory retention, locomotor activity and tiobarbituric acid reactive substances, as an index of lipid peroxidation. After treatment all, animals were submitted to passive avoidance test, water maze test and elevated T maze test, and 24 h later sacrificed and their hippocampi and temporal cortex dissected for evaluation of lipid peroxidation and used for catalase activity determinations. The protein concentration was measured according to the method described by Lowry (1951). In another set of experiments the animals were sacrificied forty eight hours after ischemia for caspase activity evaluation. Results show that DEP significantly reversed ischaemia-induced memory deficits. l-Deprenyl treatment significantly improved memory deficits as compared to ischemic group as measured by The elevated T maze and Water maze tests. A similar result was observed on the passive avoidance test where l-deprenyl improved late but not early memory as compared to the ischemic group. Except for an increased locomotor activity observed in the group treated with 5 mg/kg, no other alteration was detected in this behavioral test. Rats submitted to transient cerebral ischemia (and without l-deprenyl) showed an increase im MDA levels in the hippocampus and the treatment with l-deprenyl (5 and 10 mg/kg) significantly reversed this effect bringing values close to those of the sham-operated controls. A similar profile was observed with nitrite levels. Rats submitted to transient cerebral ischemia show an increase in caspase activity in the hippocampus and the treatment with l-deprenil (10 mg/kg) significantly reversed this effect bringing values close to those of the sham-operated controls. Moreover catalase activity in the hippocampi was not altered by ischemia. In conclusion, the work showed a signifant protective effect of l-deprenyl on memory deficits and lipid hyperperoxidation observed after cerebral ischemia. Possibly, the drug is acting at least in part through its antioxidant and antiapoptotic activities. / O trabalho mostra o tratamento e os efeitos do l-deprenil (DEP), no aprendizado, na memória e na peroxidação lipídica em cérebros de ratos submetidos à isquemia cerebral transitória (ICT). Os animais (ratos Wistar, fêmeas, 200-250g) foram submetidos à isquemia cerebral transitória pela oclusão de ambas as artérias carótidas durante 20 minutos e tratados durante 5 dias com DEP (5 e 10 mg/kg). A temperatura retal foi monitorada e mantida em torno de 37ºC através de uma luz incandescente. O mesmo procedimento foi feito no grupo controle + salina, Falso-operado + salina (FO) com exceção do clampeamento das artérias carótidas. No 6º dia após a indução da isquemia, os animais foram submetidos aos testes de atividade locomotora e memória (esquiva passiva, labirinto em T elevado e labirinto aquático de Morris), a seguir foram sacrificados e os cérebros dissecados sobre gelo (hipocampo e córtex temporal) para as determinações de MDA, nitrito/nitrato e atividade da catalase e atividade da protease caspase-3. No protocolo de avaliação da área total do infarto encontramos após 1 hora de ICT uma área de infarto 38,01 ± 3,44% da área total do cérebro, e após 24 horas de ICT uma área de infarto 22,00 ± 2,90% da área total do cérebro. Os parâmetros fisiológicos estudados não mostraram alterações entre os grupos ICT e FO. Nenhuma alteração na atividade locomotora foi detectada nos grupos FO, ICT, Dep 10 + ICT. Porém, um aumento na atividade locomotora foi observado no grupo Dep 5 + ICT (7,37 ± 1, 77, p< 0,02) quando comparado com o grupo FO, tratado com salina, (4,66 ± 1,54). No teste do Labirinto em T elevado (T Maze) a ICT afetou os processos de aquisição e retenção de memória quando os animais foram testados no mesmo dia (esquiva 1 e 2) quando comparados com o grupo controle (FO). O teste de Kruskall-Wallis mostrou alteração significativa na latência da esquiva inibitória (esquiva 1 e 2 quando comparados com o treino) no falso-operado (FO - treino: 20,34 ± 3,43 s; esquiva 1 - 231,6 ± 34,81 s; esquiva 2 – 247,8 ± 27,25 s; KW = 19,62, p< 0,001), e no grupo l-deprenil (5 e 10 mg/kg) + isquemia (Dep 5 – treino: 110,8 ± 56,16 s; esquiva 1 - 299,8 ± 0,16 s; esquiva 2 – 260 ± 40,00 s; KW = 9,16, p< 0,01. Dep 10 – treino: 29,15 ± 8,64 s; esquiva 1 – 299,80 ± 0,25 s; esquiva 2 299,8 ± 0,25 s; KW = 6,98, p< 0,05). Isto indica uma boa aquisição de memória. Portanto, o resultado do grupo ICT + salina indicou um déficit da memória (ICT – treino: 37,75 ± 11,52 s; esquiva 1 – 116,30 ± 65,46 s; treino 2 – 195,00 ± 64,10 s; KW = 3,90, p< 0,141). Além disso, existiu uma diferença significativa (Teste Mann-Whitney) entre os grupos na esquiva 3 (retenção) quando comparados com o grupo ICT (Dep 5, MW (3) = 18,483, p< 0,0003, Dep 10, MW (3) = 18,483, p< 0,003) significando que a retenção da memória foi aumentada pelo tratamento com a droga. No teste da esquiva passiva os animais do grupo controle (FO + salina) apresentaram uma boa retenção da memória, tanto na fase imediata (memória recente - MR), quanto na fase de consolidação (memória tardia - MT), quando comparadas ao treino (ANOVA) (FO + salina (n-7)- treino - 15,94 ± 4,40 s, MR - 138,84 ± 34,60 s, MT - 196,32 ± 34, 71, p< 0,006). Por outro lado, os animais que sofreram ICT não apresentaram diferença no tempo de latência de entrada no lado escuro quando comparado com o treino, significando um déficit na aprendizagem e memória (ICT (n-7)- treino - 34,37 ± 10,16 s, MR - 105,54 ± 35,21 s, MT - 96,20 ± 33, 44, p< 0,33), e, portanto dano na aquisição e retenção da memória. Comparando os tratamentos observamos um aumento significativo, no tempo de latência de entrada no lado escuro do aparelho, nos ratos tratados com l-deprenil 5 mg/kg quando avaliados na MR (FO + salina- 138,84 ± 34,60s; ICT - 105,54 ± 35,21; ICT + Dep 5- 198,88 ± 38,42s; ICT + Dep 10- 188,06 ± 34,60s; Kruskall-Wallis, KW-9,66, p<0,05, Mann-Whitney, Dep 5 vs ICT, p<0,05), enquanto na MT foi observada uma diminuição significativa, no tempo de latência de entrada no lado escuro do aparelho, nos ratos tratados com l-deprenil (5 e 10 mg/kg) (FO + salina- 196,32 ± 34,71s; ICT - 96,20 ± 33,44s; ICT + Dep 5- 299,83 ± 0,16s; ICT + Dep 10- 264,70 ± 35,28 s; Kruskall-Wallis, KW-14,57, p<0,05, Mann-Whitney, Dep 5 e Dep 10 vs ICT, p<0,05), significando melhora no aprendizado do animal fazendo-o lembrar o choque recebido durante o treino e indicando uma reversão da lesão sofrida com a ICT. No teste do Labirinto Aquático (Water Maze) a ICT promoveu um dano da retenção na memória dos animais em relação ao grupo controle (FO), porém o l-deprenil conseguiu reverter o dano na aquisição da memória induzida pela ICT em ambas as doses (5 e 10 mg/kg), observamos também que o grupo Dep 5 obteve um melhor desempenho na aquisição da memória quando comparado com o grupo Dep 10. (FO (n-10): 5,4 ± 0,84s; FO + DEP 10 (n-10): 9,7 ± 2,28s; ICT (n-9): 32,44 ± 2,95s; ICT + DEP 5 (n-8): 12,88 ± 1,4s; ICT + DEP 10 (n-8): 4,5 ± 0,70s; Kruskall-Wallis, KW-29,07, p<0,05, Mann-Whitney, FO + DEP 10, Dep 5 e Dep 10 vs ICT, p<0,05). Os ratos submetidos a ICT mostraram um aumento de 71% nos níveis de MDA no hipocampo quando comparados com o grupo controle (FO), e o tratamento com l-deprenil reverteu significativamente este efeito (p<0,05). Os valores dos níveis de MDA foram trazidos próximos aqueles valores do grupo controle (FO) em relação aos grupos (ICT + DEP 5 e ICT + DEP 10, 34 e 38%, respectivamente) com ambas as doses de l-deprenil mais ICT (Hipocampo - FO (n-7): 45,4 ± 4,45; ICT (n-7): 77,6 ± 8,97; ICT + DEP 5 (n-7): 51,2 ± 1,68; ICT + DEP 10 (n-7): 48,5 ± 6,70 nmoles/g; p<0,05, ANOVA e Teste de Tukey). No córtex temporal, a ICT não aumentou os níveis de MDA quando comparados com o grupo controle. Portanto, os ratos submetidos a ICT e tratados com altas doses de l-deprenil (10 mg/kg) apresentaram níveis de MDA 30% menor que aqueles mostrados por ambos os grupos FO e ICT (Córtex temporal - FO (n-7): 46,8 ± 4,36; ICT (n-7): 48,7 ± 1,33; ICT + DEP 5 (n-7): 52,5 ± 3,74; ICT + DEP 10 (n-7): 33,4 ± 2,98 nmoles/g; p<0,05, ANOVA e Teste de Tukey). No hipocampo, os níveis de nitrito foram significativamente aumentados após a ICT quando comparados com o grupo controle FO (82% aumento). O DEP 10 reverteu este efeito e os valores foram trazidos para aqueles do controle. Por outro lado, a isquemia não afetou os níveis de nitrito no córtex, entretanto o DEP 5 diminui significativamente os níveis de nitrito quando comparados com os grupos controle e ICT. A ICT mostrou um aumento em 50 % da atividade da protease caspase-3 no hipocampo; e o tratamento com l-deprenil (10 mg/kg) reverteu este efeito trazendo os valores próximos aos do grupo controle (FO), porém o tratamento com DEP 5 não mostrou o mesmo (Valor da Absorbância: FO – 0,083 ± 0,006; ICT - 0,124 ± 0,017; ICT + DEP 10 – 0,080 ± 0,007; ICT + DEP 5 – 0,125 ± 0,007), porém nos animais controle que receberam tratamento com DEP 10 (FO + DEP 10) a atividade da caspase – 3 diminui em 99% em relação ao grupo ICT. Em conclusão mostramos que a administração do l-deprenil diariamente por 5 dias melhorou os danos da memória observados após a isquemia cerebral transitória em ratos. A droga protegeu o cérebro contra a hiperperoxidação e formação de radicais livres observados após o dano isquêmico, como diminui a atividade da caspase – 3. Pelo menos parte desses efeitos é devido ao efeito antioxidante e conseqüentemente inibição da ativação da produção de radicais livres pelo l-deprenil.
4

Synthese und pharmakologisches Screening von Protoberberin-Alkaloiden an Dopamin-Rezeptoren, Monoaminoxidasen und Cytochrom P450 Oxidasen

Meyer, Achim January 2008 (has links)
Zugl.: Halle (Saale), Univ., Diss., 2008
5

Isolierung und Charakterisierung von Inhibitoren der Monoamin-Oxidase aus dem Presssaft schwarzer Johannisbeeren (Ribes nigrum L.) /

Blech, Stefan. January 1994 (has links)
Köln, Universiẗat, Diss. : 1994.
6

Interações agudas do chá de ayahuasca com agentes usados em anestesia (propofol e morfina), observadas em modelos animais / Acute interactions obtained from ayahuasca tea when in association with drugs used in anesthetic procedures (propofol and morphine), observed in animal models

Pires, Júlia Movilla [UNIFESP] 27 May 2009 (has links) (PDF)
Made available in DSpace on 2015-07-22T20:50:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-05-27 / Associação Fundo de Incentivo à Psicofarmacologia (AFIP) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O chá de ayahuasca (AYA) é uma bebida com propriedades psicoativas preparada a partir do cozimento de duas plantas: o cipó Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton (Malpighiaceae) e as folhas de Psychotria viridis (Ruiz & Pav.) (Rubiaceae). A DMT, presente nas folhas da P. viridis, é o principal componente alucinógeno do chá, mas quando ingerida é rapidamente inativada pela MAO-A presente nos intestinos, o que é evitado com a associação das ß-carbolinas inibidoras da MAO que estão presentes na B. caapi. Apesar do aumento do número de usuários deste chá, ainda existem poucos estudos a respeito das possíveis interações de seus princípios ativos com outras drogas, o que torna cada vez mais importante conhecer as possíveis interações entre o chá e fármacos empregados na clínica. No presente trabalho foi avaliada a possível interação do chá de ayahuasca com dois agentes de muita importância em anestesia: propofol e morfina. As doses utilizadas no estudo foram obtidas a partir da dose média consumida pelo ser humano nos rituais (equivalente a 120 mg/kg, encontrada em 70 mL do chá), definidas como 1 vez (1X) até 20 vezes (20X) ou 2400 mg/kg. No teste do “screening” farmacológico (SF) os animais apresentaram alguns sinais de toxicidade, quando administrado por via ip (diminuição da atividade motora, hipersensibilidade a estímulos e tremor intenso). A administração oral do chá (1X e 10X) não provocou alterações no teste do rotarod, mas no teste da atividade motora, os animais que receberam AYA 10X apresentaram efeito bifásico (diminuição inicial da ambulação até 30 min, seguida de aumento entre 2h e 4h). A dose de 10X aumentou o tempo de sono induzido pelo hexabarbital e diminuiu o tempo de “grooming”, em experimento onde este parâmetro foi quantificado. Em relação à associação chá de ayahuasca com morfina, no teste do SF observou-se que os animais apresentaram cauda de “Straub” mais intensa e duradoura quando comparado com o grupo morfina; ataxia e tremores quando comparados com o grupo AYA. No teste da atividade motora, o grupo que recebeu AYA 1X + morfina apresentou menor atividade locomotora do que o grupo que recebeu apenas a morfina, porém após 2h houve aumento da locomoção em relação a todos os outros. Os resultados obtidos no teste da placa quente demonstram uma potencialização dos efeitos da morfina, embora estes resultados não sejam confirmados pelo teste de contorções abdominais (CA) e formalina. Também não foi demonstrada qualquer interação no grupo administrado com a associação de chá e morfina no teste do trânsito intestinal. O chá isoladamente não apresentou efeito antinociceptivo no teste da placa quente, mas apresentou efeito antinociceptivo central e periférico nos testes de CA e formalina. Ao se avaliar qualitativamente o efeito da associação AYA e propofol, no teste do SF observou-se uma potencialização dos tremores induzidos pelo chá, que se manifestaram mais intensos e prolongados. No teste do rota-rod foi observado uma tendência de prejuízo no grupo que recebeu o chá e em seguida o anestésico. Já no teste do tempo de sono, AYA 1X diminuiu este parâmetro, portanto, interferindo com os efeitos do propofol. Em síntese, o conjunto de resultados indica alguma interação no que se refere à associação do chá de ayahuasca com a morfina e o propofol. Essas interações foram discretas e necessitariam de experimentação clínica apropriada para verificar sua ocorrência no ser humano. / Ayahuasca tea (AYA) is a beverage with psychoactive properties, prepared by the cooking of two plants: Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton (Malpighiaceae) (stem bark) and the leaves of Psychotria viridis (Ruiz & Pav.) (Rubiaceae). The major hallucinogenic compound present in P. viridis is DMT, but when it is ingested by oral route it is quickly inactivated by MAO-A present in the bowel, which is avoided by the combination of â- carbolines IMAO, present in B. caapi. Despite the constantly increasing use of AYA, there are few studies about the possible interactions produced by this tea in association with other drugs. The aim of this study was to evaluate the possible interactions between AYA and two other drugs used in anesthesia procedures: morphine and propofol; with doses established from the amount ingested by people in the rituals (equivalent of 120 mg/kg). The doses tested varied from 120 mg/kg (1X or 1 dose), to 2400 mg/kg (20X or 20 doses). Concerning pharmacological screening test (PST), AYA showed some signs of toxicity when administered by ip route (decreased of motor activity, hypersensitivity about stimulus and intense tremor). The oral route was better tolerated than ip. Administration of AYA (1X and 10X) did not interfered with motor coordination in the rota-rod test, but AYA 10X showed a biphasic effect on the motor activity test, because it decreased the initial ambulation (until 30 min), followed by an increase between 2h and 4h. AYA 10X increased the sleeping time induced by hexobarbital, however when AYA was administered 24h before hexobarbital did not occurred any interference in the sleeping time. Concerning grooming, the groups treated with AYA 10X showed a decrease of this signs. Results of association of AYA + morphine on the PST, mice showed Straub tail more intense and durable when compared with morphine group and ataxia and tremor when compared with AYA group. In the test of motor coordination, the group treated with the association of drugs, showed a lower motor activity when compared with the morphine group followed by an increase after 2h when compared to the other groups. The results obtained in hot plate test showed a potencialization of the morphine effects; however these results are not confirmed by abdominal contortions and formalin test. Intestinal transit test did not show any results about interaction. To qualitatively evaluate the effect of the association AYA + propofol in the PST, the data showed a potencialization of tremors induced by AYA more intense and durable. In the rota-rod test was observed a diminishing tendency in the AYA + propofol group. On the sleeping time test, AYA 1X decreased the sleeping time induced by propofol. Therefore, AYA interfered with the propofol effects. In summary, the whole results indicate some association interaction among AYA and morphine and propofol. These interactions were subtle and need proper clinical experimentation to verify its occurrence in humans. / TEDE / BV UNIFESP: Teses e dissertações
7

Estudo computacional das monoaminoxidases A e B com substratos e inibidores

Canto, Vanessa Petry do January 2014 (has links)
A monoaminoxidase (MAO) é uma enzima importante, que pode atuar como alvo terapêutico. Inibidores da MAO-A apresentam atividade no tratamento de distúrbios de humor, enquanto os inibidores seletivos da MAO-B tem uso, especialmente, no tratamento da Doença de Parkinson. O conhecimento das interações ENZIMA-INIBIDOR é importante no planejamento de fármacos. Nesse contexto, foram realizados estudos das enzimas MAO-A e MAO-B com diferentes ligantes, através da combinação das metodologias de docking, Dinâmica Molecular e Ensemble Docking. Foram escolhidos os ligantes derivados da 1,4-naftoquinona (1,4-NQ), lapachol, menadiona, norlapachol, A2, B2 e C2, os inibidores comerciais clorgilina (MAO-A) e selegilina (MAO-B) e os substratos naturais serotonina (MAO-A) e dopamina (MAO-B). Os resultados do docking mostraram interação de todos os ligantes com algum dos resíduos da "gaiola aromática" (FAD, Tyr407/Tyr444 para MAO-A, Tyr398/Tyr435 para MAO-B), uma importante região catalítica da MAO. Além disso, a seletividade observada experimentalmente da menadiona com a MAO-B também foi observada no docking. Através da DM, foi possível observar algumas diferenças conformacionais entre as estruturas da MAO-A e MAO-B, que podem explicar a seletividade entre as duas isoformas, como por exemplo, distâncias entre resíduos do sítio ativo e ligações de hidrogênio. A partir do Ensemble Docking, foi verificado que a conformação do receptor influencia significativamente o escore das interações ENZIMA+LIGANTE para ligantes volumosos. / Monoamine oxidase (MAO) is an important enzyme that acts as therapeutic target. MAO-A inhibitors show pharmacological activity in the treatment of mood disorders, whereas MAO-B inhibitors are used especially in treatment of Parkinson's Disease. Knowledge of enzyme-inhibitor interactions is important in drug design. Therefore, studies of MAO-A and MAO-B enzymes with different ligands were performed by combining docking, Molecular Dynamics and Ensemble Docking methodologies. Ligands derived from 1,4-naphthoquinone, lapachol, menadione, nor-lapachol, A2, B2, C2, commercial inhibitors clorgyline (MAO-A) and selegiline (MAO-B) and the natural substrates serotonin (MAO-A) and dopamine (MAO-B) were chosen. The docking results shows interactions of all ligands with some residue of the "aromatic cage” (FAD cofactor, Tyr407/Tyr444 for MAO-A and Tyr398/Tyr435 for MAO-B), an important catalytic region of MAO. Furthermore, the experimentally observed selectivity of menadione with MAO-B was also observed by Docking. In Molecular Dynamics results, conformational differences were observed between MAO-A and MAO-B structures, which could explain the selectivity observed between isoforms, e.g. distances between residues of the active site and hydrogen bonds. Ensemble Docking results shows that the conformation of the receptor significantly influence the score of ENZYME+LIGAND interactions for bulky ligands.
8

Stress Coping Strategies in Rainbow Trout (<i>Oncorhynchus mykiss</i>)

Schjolden, Joachim January 2005 (has links)
<p>Animals show a great variety in physiological and behavioural responses to stressors. These responses are often bimodally distributed within populations and show consistency on an individual level over time and across situations, which in terrestrial vertebrates have been identified as proactive and reactive stress coping strategies. Proactive animals show lower cortisol responses, higher sympathetic activation and brain serotonergic activity compared to reactive animals. Behaviourally, proactive animals are more aggressive, more active in avoiding stressors, they form routines and show fewer cases of conditioned immobility compared to reactive animals. Our aim has been to reveal if such stress coping strategies exist in fish. Our results show that rainbow trout with high (HR) or low (LR) cortisol responses to stressors differs in sympathetic activation and brain serotonin turnover in the same manner as proactive and reactive mammals. HR fish showed less locomotor activity when reared in large groups (30 individuals) compared to LR fish. When reared in isolation there were no differences between HR and LR fish when exposed to stressors within a familiar environment. The adaption of a proactive coping style among reactive coping individuals when they are challenged within a familiar environment has previously been shown to be distinction between proactive and reactive coping mammals. However, when they were transferred to unfamiliar environments a behavioural difference between the two lines was observed indicating different stress coping strategies akin to those described in mammals. Finally, we observed a consistency over time in the cortisol response of an unselected line of rainbow trout. Fish from this line also demonstrated a correlation between behavioural responses to different stressors. However, there was no apparent connection between these behavioural responses and the cortisol response. Overall, the results of this thesis have strengthened the hypothesis that different stress coping strategies exist in teleost fish.</p>
9

Stress Coping Strategies in Rainbow Trout (Oncorhynchus mykiss)

Schjolden, Joachim January 2005 (has links)
Animals show a great variety in physiological and behavioural responses to stressors. These responses are often bimodally distributed within populations and show consistency on an individual level over time and across situations, which in terrestrial vertebrates have been identified as proactive and reactive stress coping strategies. Proactive animals show lower cortisol responses, higher sympathetic activation and brain serotonergic activity compared to reactive animals. Behaviourally, proactive animals are more aggressive, more active in avoiding stressors, they form routines and show fewer cases of conditioned immobility compared to reactive animals. Our aim has been to reveal if such stress coping strategies exist in fish. Our results show that rainbow trout with high (HR) or low (LR) cortisol responses to stressors differs in sympathetic activation and brain serotonin turnover in the same manner as proactive and reactive mammals. HR fish showed less locomotor activity when reared in large groups (30 individuals) compared to LR fish. When reared in isolation there were no differences between HR and LR fish when exposed to stressors within a familiar environment. The adaption of a proactive coping style among reactive coping individuals when they are challenged within a familiar environment has previously been shown to be distinction between proactive and reactive coping mammals. However, when they were transferred to unfamiliar environments a behavioural difference between the two lines was observed indicating different stress coping strategies akin to those described in mammals. Finally, we observed a consistency over time in the cortisol response of an unselected line of rainbow trout. Fish from this line also demonstrated a correlation between behavioural responses to different stressors. However, there was no apparent connection between these behavioural responses and the cortisol response. Overall, the results of this thesis have strengthened the hypothesis that different stress coping strategies exist in teleost fish.
10

Estudo computacional das monoaminoxidases A e B com substratos e inibidores

Canto, Vanessa Petry do January 2014 (has links)
A monoaminoxidase (MAO) é uma enzima importante, que pode atuar como alvo terapêutico. Inibidores da MAO-A apresentam atividade no tratamento de distúrbios de humor, enquanto os inibidores seletivos da MAO-B tem uso, especialmente, no tratamento da Doença de Parkinson. O conhecimento das interações ENZIMA-INIBIDOR é importante no planejamento de fármacos. Nesse contexto, foram realizados estudos das enzimas MAO-A e MAO-B com diferentes ligantes, através da combinação das metodologias de docking, Dinâmica Molecular e Ensemble Docking. Foram escolhidos os ligantes derivados da 1,4-naftoquinona (1,4-NQ), lapachol, menadiona, norlapachol, A2, B2 e C2, os inibidores comerciais clorgilina (MAO-A) e selegilina (MAO-B) e os substratos naturais serotonina (MAO-A) e dopamina (MAO-B). Os resultados do docking mostraram interação de todos os ligantes com algum dos resíduos da "gaiola aromática" (FAD, Tyr407/Tyr444 para MAO-A, Tyr398/Tyr435 para MAO-B), uma importante região catalítica da MAO. Além disso, a seletividade observada experimentalmente da menadiona com a MAO-B também foi observada no docking. Através da DM, foi possível observar algumas diferenças conformacionais entre as estruturas da MAO-A e MAO-B, que podem explicar a seletividade entre as duas isoformas, como por exemplo, distâncias entre resíduos do sítio ativo e ligações de hidrogênio. A partir do Ensemble Docking, foi verificado que a conformação do receptor influencia significativamente o escore das interações ENZIMA+LIGANTE para ligantes volumosos. / Monoamine oxidase (MAO) is an important enzyme that acts as therapeutic target. MAO-A inhibitors show pharmacological activity in the treatment of mood disorders, whereas MAO-B inhibitors are used especially in treatment of Parkinson's Disease. Knowledge of enzyme-inhibitor interactions is important in drug design. Therefore, studies of MAO-A and MAO-B enzymes with different ligands were performed by combining docking, Molecular Dynamics and Ensemble Docking methodologies. Ligands derived from 1,4-naphthoquinone, lapachol, menadione, nor-lapachol, A2, B2, C2, commercial inhibitors clorgyline (MAO-A) and selegiline (MAO-B) and the natural substrates serotonin (MAO-A) and dopamine (MAO-B) were chosen. The docking results shows interactions of all ligands with some residue of the "aromatic cage” (FAD cofactor, Tyr407/Tyr444 for MAO-A and Tyr398/Tyr435 for MAO-B), an important catalytic region of MAO. Furthermore, the experimentally observed selectivity of menadione with MAO-B was also observed by Docking. In Molecular Dynamics results, conformational differences were observed between MAO-A and MAO-B structures, which could explain the selectivity observed between isoforms, e.g. distances between residues of the active site and hydrogen bonds. Ensemble Docking results shows that the conformation of the receptor significantly influence the score of ENZYME+LIGAND interactions for bulky ligands.

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