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The role of monoamines in post traumatic stress disorder (PTSD) using a time dependent sensitization animal model / Zakkiyya Igbal JeevaJeeva, Zakkiyya Igbal January 2004 (has links)
Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure
to a severely traumatic life-event. It is characterised by a delayed onset of psychological and
physical symptoms including re-experiencing the event, avoidance of reminders associated with
the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also
characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered
monoamine concentrations in the hippocampus and pre-frontal cortex.
The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is
based on the concept of repeated trauma, using three acute stressors (TS) of intense severity
followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The
aims of this study were to determine if the Triple Stressor (TS) induces stress and if the
situational reminder (RS) is necessary for the maintenance of the stress response over time and
whether these two stress responses are qualitatively and quantitively different. This was done to
further validate the TDS model and to characterize the development and progression of the
stress-related pathology of PTSD.
Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical
detection (biochemical correlates) for quantifying the monoamines dopamine (DA),
noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal
cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone
concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to
detect anxiety-like behaviour (behavioural analyses).
The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats
were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2
was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS
and RS were used as stressors. Group 4 was sacrificed immediately after the situational
reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of
unstressed rats were used as Control.
The results of this study found corticosterone concentrations elevated immediately after the TS
(p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results
indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an
enhanced negative feed-back upon re-introduction of the stressful situation.
Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this
study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal
NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day
7 post RS only hippocampal 5HT was decreased significantly (p<0.05).
Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7
days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the
TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is
necessary for the maintenance of the stress response. This model may be useful in the
investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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The role of monoamines in post traumatic stress disorder (PTSD) using a time dependent sensitization animal model / Zakkiyya Igbal JeevaJeeva, Zakkiyya Igbal January 2004 (has links)
Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure
to a severely traumatic life-event. It is characterised by a delayed onset of psychological and
physical symptoms including re-experiencing the event, avoidance of reminders associated with
the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also
characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered
monoamine concentrations in the hippocampus and pre-frontal cortex.
The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is
based on the concept of repeated trauma, using three acute stressors (TS) of intense severity
followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The
aims of this study were to determine if the Triple Stressor (TS) induces stress and if the
situational reminder (RS) is necessary for the maintenance of the stress response over time and
whether these two stress responses are qualitatively and quantitively different. This was done to
further validate the TDS model and to characterize the development and progression of the
stress-related pathology of PTSD.
Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical
detection (biochemical correlates) for quantifying the monoamines dopamine (DA),
noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal
cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone
concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to
detect anxiety-like behaviour (behavioural analyses).
The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats
were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2
was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS
and RS were used as stressors. Group 4 was sacrificed immediately after the situational
reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of
unstressed rats were used as Control.
The results of this study found corticosterone concentrations elevated immediately after the TS
(p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results
indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an
enhanced negative feed-back upon re-introduction of the stressful situation.
Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this
study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal
NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day
7 post RS only hippocampal 5HT was decreased significantly (p<0.05).
Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7
days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the
TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is
necessary for the maintenance of the stress response. This model may be useful in the
investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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A pharmacokinetic-pharmacodynamic relationship study between GABA-ergic drugs and anxiety levels in an animal model of PTSD / Jacolene MyburghMyburgh, Jacolene January 2005 (has links)
Posttraumatic stress disorder (PTSD) is classified as an anxiety disorder and the characteristic symptoms (re-experiencing, avoidance as well as numbing of general responsiveness and hyperarousal) of this disorder develop in response to a traumatic event. The disorder is characterised by hypothalamic-pituitary-adrenal (HPA) axis abnormalities linked with changes in cortisol moreover, the hippocampus and cortex also play a role in the neurobiology. With regard to the neurochemistry of this disorder it is known that gamma amino butyric acid (GABA) is involved however, the precise role of GABA in PTSD and how stress changes GABA concentrations in the brain are still not fully understood. Another aspect regarding PTSD that has not been clearly defined is the treatment of PTSD. Classic anxiolytics such as diazepam is expected to relieve the anxiety linked with PTSD. Studies with this group of drugs have however not produced the concrete evidence needed to establish it as a treatment of choice for PTSD and subsequently other classes of drugs have been investigated as possible treatment options for PTSD. Among these is lamotrigine, which in a clinical study was found to be effective in alleviating symptoms of PTSD. Moreover, a possible pharmacokinetic-pharmacodynamic relationship for each of these drugs has also not been elucidated.
In order to elude on some of these uncertainties, an animal model of PTSD, time dependent sensitisation (TDS), was used. GABA levels in the rat hippocampus and frontal cortex were determined at two different time intervals following the TDS procedure (1 day and 7 days post re-stress). High performance liquid chromatography (HPLC) with electrochemical (EC) detection was used to determine gamma amino butyric acid (GABA) concentrations. To investigate the possible anxiolytic effects of diazepam and lamotrigine in this model, as well as a possible pharmacokinetic-pharmacodynamic relationship for each drug, pharmacokinetic profiles for both drugs were established in order to find the times of peak and trough levels of each drug. Blood samples were collected at different time intervals after drug administration either from the tail vein of rats (lamotrigine) or directly from the heart (diazepam). Subsequently, drug concentrations at each time interval were determined by means of HPLC with ultraviolet (UV) detection. The behaviour of rats was analysed using the elevated plus-maze (EPM) at peak or trough concentrations of the drugs and this was performed after either acute administration of the drug, or after a 14 day chronic treatment regime.
GABA levels in the hippocampus were not found to change statistically significantly in response to stress at either 1 day or 7 days post re-stress. In the frontal cortex, however, GABA levels increased in response to stress at 1 day post re-stress, with a statistically insignificant, but strong trend towards an increase, at 7 days post re-stress. With regard to the pharmacokinetic profiles, the peak concentration of diazepam was found to occur at 60 minutes, with lamotrigine's peak at 120 minutes. The behavioural studies indicated that acute treatment with diazepam 3 mg/kg resulted in a statistically significant increase in both ratio open arm entries and ratio time spent in the open arms at peak level of the drug. After acute treatment with diazepam 3 mg/kg a statistically significant decrease in ratio time spent in open arms was also found when the ratio time spent in open arms at peak level of the drug and the ratio time spent in open arms at trough level of the drug was compared. In response to chronic treatment with diazepam 3 mg/kg for 14 days, test animals exhibited an increase in the ratio open arm entries at trough level of the drug, with a statistically insignificant yet definite trend towards an increase at peak level. Acute treatment with lamotrigine 10 mg/kg resulted in no statistically significant change in EPM parameters. In response to chronic treatment, however, a statistically significant increase was found in ratio time spent in open arms at peak level of the drug, with a statistically insignificant trend towards an increase at trough level.
From the results of this study, we may therefore conclude that GABA-levels in the brain are definitely affected, but in different ways, following TDS-stress. A pharmacokinetic-pharmacodynamic relationship between the drugs' levels and aversive behaviour could also be established. Furthermore it appears that more sustained anxiolytic effects are evident following chronic treatment with both drugs than with acute administration of these drugs. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2006
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Efeito do chá de ayahuasca sobre o comportamento de ratos Wistar no campo aberto e labirinto em cruz elevado e sobre a expressão de EAAC1 no hipocampo e córtex pré-frontal / Effect of ayahuasca beverage on the behavior of Wistar rats in the open field and elevated plus maze and on the expression of EAAC1 in the hippocampus and in the prefrontal cortex.Luana Gonçalves Zamarrenho 19 September 2014 (has links)
O objetivo do presente estudo foi avaliar se ratos tratados com chá de ayahuasca apresentam i) alterações comportamentais no campo aberto e labirinto em cruz elevado (LCE); ii) alterações na expressão do transportador de glutamato (EAAC1) no córtex pré-frontal (CPF) e no hilus do giro denteado do hipocampo (HDG). Doze grupos de ratos Wistar machos (250g, n=10/cada) foram usados. Eles receberam 2 or 4ml/Kg de chá de ayahuasca ou água: dose única (agudo), 3 vezes/dia por 3 dias alternados (subcrônico) e 1 vez/dia por 15 dias (crônico). Trinta minutos após a última ingestão os animais foram submetidos aos testes comportamentais. Vinte e quatro horas após eles foram anestesiados, perfundidos e seus encéfalos seccionados (40-m) no hipocampo e CPF para os experimentos de imunoistoquimica para EAAC1. Comparações estatísticas entre cada grupo tratado com ayahuasca e seu respectivo controle foram feitas utilizando o teste t de Student e consideradas significantes quando p0,05. Apenas a ingestão subcrônica de ayahuasca induziu redução significante na atividade locomotora (27%) no campo aberto. No LCE nenhum dos tratamentos com ayahuasca induziu alterações significantes em ambos numero de entradas e tempo de permanência nos braços abertos. A ingestão subcrônica ou crônica de chá de ayahuasca induziu aumento significante na expressão de EAAC1 no HGD (20-67%). Em contraste, no CPF a expressão de EAAC1 foi significantemente reduzida em ratos tratados com 2 ou 4ml/Kg subcronicamente ou 4ml/Kg cronicamente (17-25%). A ingestão aguda de 2ml/Kg induziu discreto aumento na expressão de EAAC1 (16%). Estes resultados sugerem que i) Ayahuasca induz alterações nas atividades locomotora e exploratória de forma dependente da dose e frequência de ingestão; ii) Ayahuasca não tem efeito no nível de ansiedade; iii) A ingestão aguda, subcrônica e subcrônica de ayahuasca disparam distintos mecanismos no hipocampo e CPF envolvendo a modulação da neurotransmissão glutamatérgica. / This work aimed at investigating whether rats treated with Ayahuasca beverage show i) behavioral alterations in the open field and elevated plus maze (EPM); ii) alterations in the expression of glutamate transporter (EAAC1) in the prefrontal cortex (PFC) and in the hilus of dentate gyrus of the hippocampus (HDG). Twelve groups of male Wistar rats (250g, n=10/each) were used. They received 2ml/Kg or 4ml/Kg of ayauhasca beverage or water: only once (acute), 3 times/day for 3 days (sub-chronic) or once/day for 15 days (chronic). Thirty minutes after the last ingestion the animals were submitted to behavioural tests. After 24 hours they were anaesthetized, perfused and their brains sectioned (40-m) in the hippocampus and PFC for immunohistochemistry (IH) detection of EAAC1. Comparisons between ayahuasca and control groups used Student t test. Significance was set at p0.05. Only sub-chronic ingestion of Ayahuasca induced a decrease in locomotor (27%) activit in the open field. On the EPM all treatments with Ayahuasca induced no significant increase in both number of entries and time spent in the open arms. The sub-chronic and chronic treatments with Ayahuasca induced a significant increase in EAAC1 expression in the HDG (20-67%). In contrast, in the PFC the expression of EAAC1 was significantly decreased in rats treated with 2 or 4ml/Kg sub-chronically or 4ml/Kg chronically (17-25%). Acute ingestion of 2ml/Kg induced a smaller increase in EAAC1-IC (16%). These results suggest that i) Ayahuasca changes the locomotor and exploratory activities in a way depending the dose and frequency of ingestion; ii) Ayahuasca does not have effect on the level of anxiety; iii) Acute, sub-chronic or chronic ingestion of Ayahuasca beverage trigger distinct mechanisms in the PFC and hippocampus involving the modulation of glutamate neurotransmission.
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Efeito ansiolítico do ondansetron, antagonista dos receptores 5-HT3, injetado na amídala de camundongos submetidos à exposição e reexposição no labirinto em cruz elevadoNunciato, Ana Claudia 02 March 2011 (has links)
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Previous issue date: 2011-03-02 / Financiadora de Estudos e Projetos / Against of stimuli that are dangerous, animals manifest defense reactions that cause fear and anxiety. These stimuli activate the serotonergic system, which sends projections to structures involved in defense mechanisms such as the septum, hypothalamus, hippocampus, amygdala and periaqueductal gray modulates the behavioral changes that can be characterized as anxiety. Studies have shown that 5-HT3 receptors are part of this modulation. The elevated plus maze (EPM) is a widely used animal model to evaluate the anxiolytic activity of drugs. Currently, it is known that the retest in rodents (rats and mice) increases the avoidance of it, this phenomenon, which refers to "a display of tolerance" (OTT, One Trial Tolerance). The amygdala is a prosencephalic structures that have significant amount of serotonin (5-HT) in this way, recent results from our laboratory have shown that microinjections of ondansetron antagonist 5-HT3 receptors in the amygdala of mice produced anxiolytic-like effect evaluated in LCE. The aim of this study was to evaluate the involvement of receptors 5-HT3 receptors in the amygdala of mice prior experience the elevated plus-maze (EPM). Conventional measures of anxiety (% of entry and time spent in open arms), locomotor activity (frequency in closed arms) and ethological measures related to risk assessment were recorded. The present study demonstrated that intra-amygdala of ondansetron, antagonist of 5-HT3 receptors, produced anxiolytic-like effects in naive mice and mice prior experience the LCE. The injection of ondansetron in only one of the exhibits produced anxiolytic-like effect, which leads us to conclude that the drug produced no change in memory. Both the Trial 1 and in Trial 2, none treatments affected locomotor activity. So while the amygdala is involved in the neurobiology of the defense reactions such as anxiety response, as it refers to the phenomenon it seems OTT not to participate. / Diante de estímulos que representam perigo os animais manifestam reações de defesa que originam o medo e a ansiedade. Estes estímulos ativam o sistema serotonérgico, o qual emite projeções para estruturas envolvidas nos mecanismos de defesa tais como, septo, hipotálamo, hipocampo, substância cinzenta periaquedutal e amídala, modulando as alterações comportamentais que podem ser caracterizadas como ansiedade. Estudos têm demonstrado que os receptores 5-HT3 fazem parte desta modulação. O labirinto em cruz elevado (LCE) é um modelo animal amplamente utilizado para avaliar a atividade ansiolítica de drogas. Atualmente, sabe-se que o reteste em roedores (ratos e camundongos) aumenta a evitação do mesmo, fenômeno este, que se refere à tolerância de uma exposição (OTT, do inglês One Trial Tolerance). A amídala é uma das estruturas prosencefálicas que apresentam quantidade relevante de serotonina (5-HT), dessa forma, resultados recentes do nosso laboratório demonstram que microinjeções de ondansetron, antagonista dos receptores 5- HT3, na amídala de camundongos, produziu efeito ansiolítico avaliado no LCE. O objetivo deste estudo foi avaliar o envolvimento dos receptores 5-HT3 na amídala de camundongos reexpostos ao labirinto em cruz elevado (LCE). Medidas convencionais de ansiedade (% de entrada e de tempo gasto nos braços abertos), atividade locomotora (freqüência de entrada nos braços fechados) e medidas etológicas relacionadas à avaliação de risco foram registradas. O presente estudo demonstrou que a injeção intra-amídala de ondansetron, antagonista de receptores 5-HT3, produziu efeito ansiolítico tanto em camundongos ingênuos quanto em camundongos reexpostos ao LCE. A injeção de ondansetron em apenas uma das exposições produziu efeito ansiolítico, o que nos leva a concluir que a droga não produziu alteração da memória. Tanto na exposição 1 como na reexposição, nenhum dos tratamentos afetou a atividade locomotora. Portanto, embora a amídala esteja envolvida na neurobiologia das reações de defesa, tais como a resposta de ansiedade, no que se que refere ao fenômeno OTT ela parece não participar.
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Análise da implementação do Enterprise Project Management (EPM) em uma empresa de engenhariaFernandes, Luiz Gustavo da Costa 08 June 2017 (has links)
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Previous issue date: 2017-06-08 / A necessidade de modernização dos processos de trabalho conduziu as empresas na busca por ferramentas que atendessem mais eficientemente aos seus objetivos. Neste contexto, surge o software de gerenciamento de projetos Enterprise Project Management – EPM (versão 2010) da Microsoft, que garante adequados planejamento, organização, monitoramento, controle e avaliação de um projeto, além de facilitar a comunicação entre os stakeholders e antever falhas e problemas de projeto. Deste modo, o presente estudo possui como objetivo analisar os impactos positivos e negativos da implementação do EPM em uma empresa de Engenharia. Esta pesquisa possui abordagem qualitativa, exploratória, utilizando o estudo de caso como método para investigação prática, cujos dados foram coletados por meio de aplicação eletrônica, por e-mail, de questionário on-line específico para os 27 respondentes que integraram o estudo. Quanto ao cenário, trata-se de uma empresa de engenharia responsável por analisar tecnicamente documentos relacionados a plataformas de extração de petróleo. Os dados foram analisados por meio de frequência simples, para as perguntas fechadas, e por meio de análise de conteúdo das perguntas abertas. Os temas foram agrupados e compuseram duas categorias de análises de dados. Assim, foram identificados como aspectos positivos: melhoria no gerenciamento dos recursos; melhoria dos controles dos projetos; centralização de informações, melhoria no planejamento dos projetos e inexistência de malefícios. Os principais aspectos negativos citados foram: Custo de overhead, limitação da ferramenta para projetos grandes e complexos, falta de centralização de algumas funcionalidades e usabilidade do sistema. O estudo concluiu que existem oportunidades de melhorias para a utilização da ferramenta por meio de treinamentos pontuais voltados para todos os integrantes da equipe, de acordo com a especificidade de cada perfil de atuação. Desta forma, será possível usufruir das possibilidades de aplicação da ferramenta por todos os envolvidos, bem como identificar falhas ou práticas inadequadas nos projetos. / The need for modernization of work processes led companies to the search for tools that achieve more effectively their objectives. In this context, the project management software (version 2010) from Microsoft named Enterprise Project Management arises, which ensures proper planning, organization, monitoring, control and evaluation of a project, in addition to facilitating communication among the stakeholders and anticipating project failures and problems. Thus, the present study has as its object the implementation of Enterprise Project Management (EPM) software, version 2010, and as a general objective the evaluation of the positive and negative impacts of the EPM implementation on an Engineering company. This research has a qualitative and exploratory approach such as a case study whose data was collected from a specific online questionnaire sent via e-mail to 27 respondents who participated in the study. Regarding the setting, it is an engineering company responsible for technically analyzing documents related to oil rigs. Data was analyzed through simple frequency for closed questions and through context analysis for open questions. The themes were grouped and composed of two categories of data analysis. So, the positive aspects that have been identified were as follows: resources management improvement; projects controls improvement; centralization of information, projects planning improvement and non-existence of shortcomings. The main negative aspects mentioned were as follows: overhead costs, tool limitation for big and complex projects, lack of centralization of some functionalities and system usability. The study has concluded that there are opportunities of improving the tool usage through providing training to all main stakeholders, according to the specificity of each profile acting in the projects. Thus, it will be possible to take advantage of all possibilities of applying the tool by all the involved parties as well as identifying failures or inappropriate practices in the projects.
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Krystalochemie slíd z Českého středohoří / Crystal chemistry of micas from České středohoříGoll, Jan January 2010 (has links)
Micas from České středohoří mts. have been studied by X-ray difractometry, ICP-MS and electron microprobe. The measurements of trace elements and REEs revealed very low tendency by normalization of chondrite reservoir and primitive mantle. The micas classifications were determined by Tischendorf (2007) and Rieder (1998) as Fe- or Fe-Ti phlogopites. The abundances of Ti are very high up to 0,46 (a.p.f.u.). X-ray powder diffraction revealed double layered polytype 2M1 with space group C/2c.
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Krystalochemie slíd z Českého středohoří / Crystal chemistry of micas from České středohoříGoll, Jan January 2011 (has links)
Six methods have been used to study micas from České středohoří mts.: X-ray difractometry (transmission and reflection), ICP MS, electron microprobe, Mössbauer spectroscopy and termogravimetry. The measurements of trace elements and REE's revealed very low tendency by normalization on chondrite reservoir and primitive mantle. Micas show high contents of TiO2 (9,47 wt.%) and BaO (up to 2,1 wt.%) in separated grains from rock. The micas classifications were determined by Tischendorf (2007) and Rieder (1998) as Fe-phlogopites. X-ray powder diffraction revealed cell dimensions and a common polytype 1M with space group C2/m. By Mössbauer spectroscopy have been studied the rates of Fe2+ /Fe3+ and they were 1,08 - 1,86 (except rock sample, which were 9:1). Termogravimetrical measurement until 1450řC revealed weight jump from 1120řC to 1270řC.
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O ondansetron, antagonista dos receptores 5-HT3, reverte o efeito ansiolítico das injeções de midazolam no hipocampo ventral de camundongos expostos aos modelos labirinto em cruz elevado (LCE) e exposição ao ratoFachini, Gabriel 10 February 2012 (has links)
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Previous issue date: 2012-02-10 / Universidade Federal de Sao Carlos / Animal models have often been used to investigate the neurobiology of emotional states (fear and anxiety). In this sense, the elevated plus maze (EPM) and the rat exposure test are effective to evaluate these states and EPM exposure (aversive stimulus) can result in activation of serotonergic pathways with projections to structures belonging to the defense system, such as , amygdala, septum, hypothalamus, periaqueductal gray (PAG) and hippocampus. The hippocampus has a large amount of serotonin receptors (5- HT) and gamma-aminobutyric acid (GABA). In the present study, we used male mice of Swiss Albino, received surgical implantation of guide cannula and subsequent administration of drugs in the ventral hippocampus. After recovery, the animals were tested in EPM (Experiment 1 and 2) or the test exposure to the rat (Experiment 3 and 4). In Experiment 1, administration of midazolam (3.0 and 30.0 nmol) produced anxiolytic effect characterized by increased percentages of entries and time spent in the open arms of the EPM reduction measures and ethological (risk assessment) as percentages of dives stretched and secured. In Experiment 2, mice received combined injections Saline + Saline, Saline + MDZ, ondansetron (OND) + Saline and MDZ (30.0 nmol) + OND (0.03 nmol, antagonist of 5-HT3). Combined treatment of Sal + MDZ produced anxiolytic effect and this effect was reversed by the combined administration of OND + MDZ. The porcentanges of entries and time spent in open arms were lower (P> 0.05) than those found in group Sal + MDZ. Experiment 3 showed the effects of exposure of mice in the presence of mouse toy (RB = neutral stimulus) or mouse real (VR = aversive stimulus, Long Evans rats), under the administration of midazolam (3.0 14 and 30.0nmol). The animals were exposed to RV shortening the holding box (model effect) compared to animals exposed to RB. Animals treated with MDZ in two doses, there was an increase in transitions between the sides of the apparatus, increased time in the area of operation and increases the latency of escape to the protected area and contact time with the grid. In Experiment 4, we evaluated the effect of combined injection of midazolam and ondansetron protocol (Experiment 2). The MDZ 30.0 nmol produced anxiolytic effects and the blockade of this effect when the mice were combined administration of ondansetron and midazolam in the ventral hippocampus. Data from this study suggest that, first, control over emotional reactions and defense of the ventral hippocampus of mice exposed to EPM test or exposure to the rat are mediated via GABABenzodiazepines. Furthermore, there is a likely cross-modulation between GABAergic interneurons and 5-HT3, for blocking 5-HT3 via ondansetron can decrease the GABA release. / Modelos animais têm sido frequentemente utilizados para a investigação da neurobiologia dos estados emocionais (ansiedade e medo). Neste sentido, o labirinto em cruz elevado (LCE) e teste de exposição ao rato são eficazes para avaliar esses estados e a exposição ao LCE (situação aversiva) pode resultar em ativação das vias serotonérgicas com projeções para estruturas pertencentes ao sistema de defesa, tais como, amídala, septo, hipotálamo, substância cinzenta periaquedutal (SCP) e hipocampo. O hipocampo apresenta grande quantidade de receptores de serotonina (5-HT) e do ácido gama-aminobutírico (GABA). No presente estudo, foram utilizados camundongos machos, da cepa Suíco Albino, que receberam implantação cirúrgica de cânulas guia e posterior administração de drogas no hipocampo ventral. Após recuperação, os animais foram avaliados nos testes LCE (Experimento 1 e 2) ou exposição ao rato (Experimento 3 e 4). No Experimento 1, a administração de midazolam (3,0 e 30 nmol) produziu efeito ansiolítico caracterizado pelo aumento das porcentagens de entradas e tempo gasto nos braços abertos do LCE e redução de medidas etológicas (avaliação de risco) como porcentagens de mergulhos e esticadas protegidas. No Experimento 2, os camundongos receberam injeção combinada de Salina+Salina, Salina+MDZ, ondansetron (OND)+Salina e MDZ (30 nmol) + OND (0,03 nmol, antagonista dos receptores 5-HT3). O tratamento combinado de Sal+MDZ produziu, efeito ansiolítico sendo este revertido pela administração combinada de OND+MDZ. As porcentagens de entradas e tempo gasto nos braços abertos foram menores (P>0,05) do que àqueles encontrados no grupo Sal+MDZ. O Experimento 3 mostrou os efeitos da exposição dos camundongos na presença 12 do rato de brinquedo (RB= estímulo neutro) ou rato de verdade (RV= estímulo aversivo, rato Long Evans), sob a administração de Midazolam (3,0 e 30 nmol). Os animais expostos ao RV apresentaram diminuição do tempo de exploração da caixa (efeito do modelo) quando comparados aos animais expostos ao RB. Para os animais tratados com MDZ nas duas doses, houve aumento nas transições entre os lados do aparato, aumento do tempo na área de exploração e aumentos da latência de fuga para a área protegida e tempo de contato com a grade. No Experimento 4, foi avaliado o efeito da injeção combinada de midazolam e ondansetron (conforme descrito no Experimento 2). O MDZ 30 nmol produziu efeito ansiolítico e a administração combinada de ondansetron e midazolam no hipocampo ventral, reverteu este efeito. Os dados deste trabalho sugerem que, o controle sobre as reações emocionais e de defesa do hipocampo ventral de camundongos expostos ao LCE ou ao teste de exposição ao rato são mediados via receptores GABA-Benzodiazepínicos. Além disso, provavelmente ocorre modulação cruzada entre os interneurônios GABAérgicos e os serotoninérgicos do tipo 5-HT3, pois o bloqueio desses receptores com o ondansetron, pode diminuir a liberação de GABA.
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Implementace systému EPM 2010 pro podporu výuky řízení projektů a portfolia / Implementation of EPM 2010 to support the teaching of project and portfolio managementNedzelský, Roman January 2011 (has links)
This thesis deals with the issue of the project management, project portfolio management and environment settings for the management and portfolio analysis in a fictional organization. In the theoretical introduction there is outlined the situation of the education of the project portfolio management at universities in the Czech Republic, Europe and worldwide, in summary form of founded courses that deal with this issue. Some basic principles of PMI methodology follow to introduce the reader to the project and portfolio management. As a practical part of this thesis there has been project management solution software implemented as a support for the portfolio management education. Microsoft Project 2010 has been selected for this purpose. This part of the thesis guides reader through practical topics like how to set up the whole environment including all utilities and contains a description of services settings. As example there were also sample roles and resources of the company set up, which were subsequently assigned to fictional projects so that the business portfolio analysis based on set of business goals and prioritization of individual projects could have been performed. The contribution of this work can be found mainly in the possibility of portfolio management education and training by using one of the leading software tool that are successfully implemented in a real production environment, and to try out the various acts and practices and also to clarify the various processes in the context of specific projects within the portfolio. Prepared fictional organization and sample data can be especially used as a model for handling various assignments in the upcoming educational courses at VŠE.
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