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The impact of early life seizures on cognitive developmentSheppard, Emilie 01 1900 (has links)
No description available.
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防制重大金融犯罪之研究-以犯罪所得剝奪為中心 / Prevention regulations on major financial fraud-discussing on deprivation proceeds of crime林炤宏, LIN, Chao Hung Unknown Date (has links)
由於政經環境之變遷、公司治理的缺漏和外部監理機制之失調,常導致重大金融犯罪之發生,與其惡害卻由全民負擔之不公現象。於是除嚴刑峻罰外,奠基於任何人均不得從犯罪中獲利之犯罪所得剝奪理念與制度設計,遂於二OO四年金融七法修法時被廣泛納入。惟歷經一段期間之適用後,其法實效性如何?有無源於其他刑事法制無從配合,或囿於司法實務判解之困頓,所導致的扞格?部分國際公約與其他國家之相關法制設計及運作理念,有無值得比較、參研之處,均殊值探研。
本文嘗試先掌握金融犯罪之特性,與近來金融犯罪防制法規之演變。其次,再就我國犯罪所得剝奪法制沿革、犯罪所得之界定、計算為研析,並探索犯罪所得剝奪法制在預防、打擊與抗制金融犯罪等之必要性,以及其應通過之憲法基權保障檢驗。再者,則希能透過偵審案例,探究研現階段我國金融犯罪防制法規,在犯罪所得之暫時保全與終局剝奪上所面臨之實務困境及問題;並瞭解部分重要之國際公約與美、英、日等國家有關法制之設計。最後,則期能歸結相關問題與爭議,並融合法制建構、實務運作、外國法制借鏡等數個層面,提出可能之解決途徑或修法建議。 / Political and economic changes, incomplete of corporate governance, and imbalance of external supervision mechanism are all reasons for occurrence of major financial fraud. The losses and costs of major financial fraud, in general, are always enormous. Unfortunately, most people, instead of offenders, need to bear the huge losses. As a result, except the strategy of severe punishment, the idea and regulations on deprivation proceeds of crime were introduced to combat these problems in 2004. However, after a period of practicing, how about the application and practice of regulations on deprivation proceeds of crime is. Therefore, we are concerned about: are there any problems or difficulties resulting from criminal legal system and the practice of precedent itself? What we can learn from international conventions and other countries’ similar legal system?
The thesis, first of all, attempts to figure out the feature of major financial fraud and the changes of financial regulations. Secondly, we try to explore the history of regulations on deprivation proceeds of crime, the definition and the calculation of proceeds of crime, and whether the regulations on deprivation proceeds of crime are essential for preventing and against major financial fraud or not. Meanwhile, in order to guarantee and protect the fundamental rights of people, we also hope to exam the regulations on deprivation proceeds of crime by the concepts of constitution.
In additions, according to the case study, the thesis also longs for exploring what are the practical problems and dilemmas for current regulations on temporary seizure and final forfeiture procedures. At the same time, comparing with the international conventions and other countries’ similar legal system on laundering, search, freeze, seizure and confiscation of the proceeds from crime is also important and useful for this study. Finally, after concluding the relative problems and debates about this topic, of course, the paper hopes to propose a possible approach or legal amendment by integrating legal system modification, legal practice, and foreign legal system.
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Synaptic Plasticity Induced Through CP-AMPARs is Dependent on the ERK/MAPK Signalling CascadeAsrar, Suhail 15 April 2010 (has links)
Recent literature has shown that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors lacking the GluR2 subunit (thus calcium permeable) are widely expressed in the CNS, especially in interneurons and glia, where they contribute to synaptic transmission and plasticity. Studies have also indicated that calcium permeable AMPARs (CP-AMPARs) are expressed and participate in synaptic regulation in principal neurons, including hippocampal pyramidal neurons. Furthermore, CP-AMPARs and their resultant calcium influx are implicated in various pathophysiological conditions such as ischemia and seizures. However, the synaptic events activated by calcium influx through CP-AMPARs remain unknown. I took advantage of genetically altered mice without (GluR2-/-) or with reduced GluR2 (GluR2+/-), thus allowing the expression and detailed analysis of synaptic CP-AMPARs in hippocampal pyramidal neurons. Utilizing electrophysiological techniques, I demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR-dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor (NMDAR) independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460. Surprisingly, calcium/calmodulin-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDAR-dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR-dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDAR dependent LTP in control studies. In contrast, inhibitors for the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Additional studies with knockout mice revealed that the ERK/MAPK signalling cascade is likely acting through p-21 activated kinase 1 (or PAK1, a Rho-GTPase associated kinase) dependent mechanisms. These results suggest that distinct synaptic signalling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain.
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Synaptic Plasticity Induced Through CP-AMPARs is Dependent on the ERK/MAPK Signalling CascadeAsrar, Suhail 15 April 2010 (has links)
Recent literature has shown that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors lacking the GluR2 subunit (thus calcium permeable) are widely expressed in the CNS, especially in interneurons and glia, where they contribute to synaptic transmission and plasticity. Studies have also indicated that calcium permeable AMPARs (CP-AMPARs) are expressed and participate in synaptic regulation in principal neurons, including hippocampal pyramidal neurons. Furthermore, CP-AMPARs and their resultant calcium influx are implicated in various pathophysiological conditions such as ischemia and seizures. However, the synaptic events activated by calcium influx through CP-AMPARs remain unknown. I took advantage of genetically altered mice without (GluR2-/-) or with reduced GluR2 (GluR2+/-), thus allowing the expression and detailed analysis of synaptic CP-AMPARs in hippocampal pyramidal neurons. Utilizing electrophysiological techniques, I demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR-dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor (NMDAR) independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460. Surprisingly, calcium/calmodulin-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDAR-dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR-dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDAR dependent LTP in control studies. In contrast, inhibitors for the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Additional studies with knockout mice revealed that the ERK/MAPK signalling cascade is likely acting through p-21 activated kinase 1 (or PAK1, a Rho-GTPase associated kinase) dependent mechanisms. These results suggest that distinct synaptic signalling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain.
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Newborn EEG seizure detection using adaptive time-frequency signal processingRankine, Luke January 2006 (has links)
Dysfunction in the central nervous system of the neonate is often first identified through seizures. The diffculty in detecting clinical seizures, which involves the observation of physical manifestations characteristic to newborn seizure, has placed greater emphasis on the detection of newborn electroencephalographic (EEG) seizure. The high incidence of newborn seizure has resulted in considerable mortality and morbidity rates in the neonate. Accurate and rapid diagnosis of neonatal seizure is essential for proper treatment and therapy. This has impelled researchers to investigate possible methods for the automatic detection of newborn EEG seizure. This thesis is focused on the development of algorithms for the automatic detection of newborn EEG seizure using adaptive time-frequency signal processing. The assessment of newborn EEG seizure detection algorithms requires large datasets of nonseizure and seizure EEG which are not always readily available and often hard to acquire. This has led to the proposition of realistic models of newborn EEG which can be used to create large datasets for the evaluation and comparison of newborn EEG seizure detection algorithms. In this thesis, we develop two simulation methods which produce synthetic newborn EEG background and seizure. The simulation methods use nonlinear and time-frequency signal processing techniques to allow for the demonstrated nonlinear and nonstationary characteristics of the newborn EEG. Atomic decomposition techniques incorporating redundant time-frequency dictionaries are exciting new signal processing methods which deliver adaptive signal representations or approximations. In this thesis we have investigated two prominent atomic decomposition techniques, matching pursuit and basis pursuit, for their possible use in an automatic seizure detection algorithm. In our investigation, it was shown that matching pursuit generally provided the sparsest (i.e. most compact) approximation for various real and synthetic signals over a wide range of signal approximation levels. For this reason, we chose MP as our preferred atomic decomposition technique for this thesis. A new measure, referred to as structural complexity, which quantifes the level or degree of correlation between signal structures and the decomposition dictionary was proposed. Using the change in structural complexity, a generic method of detecting changes in signal structure was proposed. This detection methodology was then applied to the newborn EEG for the detection of state transition (i.e. nonseizure to seizure state) in the EEG signal. To optimize the seizure detection process, we developed a time-frequency dictionary that is coherent with the newborn EEG seizure state based on the time-frequency analysis of the newborn EEG seizure. It was shown that using the new coherent time-frequency dictionary and the change in structural complexity, we can detect the transition from nonseizure to seizure states in synthetic and real newborn EEG. Repetitive spiking in the EEG is a classic feature of newborn EEG seizure. Therefore, the automatic detection of spikes can be fundamental in the detection of newborn EEG seizure. The capacity of two adaptive time-frequency signal processing techniques to detect spikes was investigated. It was shown that a relationship between the EEG epoch length and the number of repetitive spikes governs the ability of both matching pursuit and adaptive spectrogram in detecting repetitive spikes. However, it was demonstrated that the law was less restrictive forth eadaptive spectrogram and it was shown to outperform matching pursuit in detecting repetitive spikes. The method of adapting the window length associated with the adaptive spectrogram used in this thesis was the maximum correlation criterion. It was observed that for the time instants where signal spikes occurred, the optimal window lengths selected by the maximum correlation criterion were small. Therefore, spike detection directly from the adaptive window optimization method was demonstrated and also shown to outperform matching pursuit. An automatic newborn EEG seizure detection algorithm was proposed based on the detection of repetitive spikes using the adaptive window optimization method. The algorithm shows excellent performance with real EEG data. A comparison of the proposed algorithm with four well documented newborn EEG seizure detection algorithms is provided. The results of the comparison show that the proposed algorithm has significantly better performance than the existing algorithms (i.e. Our proposed algorithm achieved a good detection rate (GDR) of 94% and false detection rate (FDR) of 2.3% compared with the leading algorithm which only produced a GDR of 62% and FDR of 16%). In summary, the novel contribution of this thesis to the fields of time-frequency signal processing and biomedical engineering is the successful development and application of sophisticated algorithms based on adaptive time-frequency signal processing techniques to the solution of automatic newborn EEG seizure detection.
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Large-scale modeling of epileptic seizures dynamicsProix, Timothée 30 October 2015 (has links)
Les crises épileptiques sont des épisodes paroxysmiques d'activité cérébrale hypersynchrone. Ce travail de thèse s'attache à examiner les mécanismes de propagation des crises d'épilepsie sur une échelle temporelle lente et une grande échelle spatiale dans le cerveau humain et à les appliquer au contexte clinique. Chez les patients souffrant d'épilepsie partielle réfractaire, les crises débutent dans certaines régions localisées du cerveau, dénommées zone épileptogène, avant de recruter des régions distantes. Le succès de l'ablation chirurgicale de la zone epileptogène dépend principalement de sa délimitation adéquate, un problème souvent épineux en pratique clinique. À cela s'ajoute notre compréhension parcellaire des mécanismes à l'origine des crises et de leur propagation. Nous utilisons un modèle mathématique de masse neuronale reproduisant le décours temporel de l'activité moyenne critique et intercritique d'une région cérébrale, guidé de manière autonome par une variable permittive lente. Nous introduisons tout d'abord un couplage permittif lent entre ces masses neuronales, afin de révéler l'importance de la variété lente dans le recrutement des régions cérébrales dans la crise. Nous présentons ensuite un pipeline de traitement des données structurelles et de diffusion IRM pour reconstruire automatiquement le cerveau virtuel d'un patient. Nous utilisons ensuite une analyse de stabilité linéaire et la connectivité large-échelle pour prédire la zone de propagation. Nous appliquons notre méthode à un jeu de données de 15 patients épileptiques et démontrons l'importance du connectome pour prédire la direction de propagation des crises. / Epileptic seizures are paroxysmal hypersynchronizations of brain activity, spanning several temporal and spatial scales. In the present thesis, we investigate the mechanisms of epileptic seizure propagation on a slow temporal and large spatial scale in the human brain and apply them to a clinical context. For patients with partial refractory epilepsy, seizures arise from a localized region of the brain, the so-called epileptogenic zone, before recruiting distant regions. Success of the resective surgery of the epileptogenic zone depends on its correct delineation, which is often difficult in clinical practice. Furthermore, the mechanisms of seizure onset and recruitment are still largely unknown. We use a mathematical neural mass model to reproduce the time course of interictal and ictal mean activity of a brain region, in which the switching between these states is guided by an autonomous slow permittivity variable. We first introduce a slow permittivity coupling function between these neural masses, hypothesizing the importance of the slow manifold in the recruitment of brain regions into the seizure. Before exploring large-scale networks of such coupled systems, we present a processing pipeline for automatic reconstruction of a patient's virtual brain, including surface and connectivity (i.e., connectome), using structural and diffusion MRI, and tractography methods. Using linear stability analysis and large-scale connectivity, we predict the propagation zone. We apply our method to a dataset of 15 epileptic patients and establish the importance of the connectome in determining large-scale propagation of epileptic seizures.
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Computer seizure as technique in forensic investigationNdara, Vuyani 19 March 2014 (has links)
The problem encountered by the researcher was that the South African Police Service Cyber-Crimes Unit is experiencing problems in seizing computer evidence. The following problems were identified by the researcher in practice: evidence is destroyed or lost because of mishandling by investigators; computer evidence is often not obtained or recognised, due to a lack of knowledge and skills on the part of investigators to properly seize computer evidence; difficulties to establish authenticity and initiate a chain of custody for the seized evidence; current training that is offered is unable to cover critical steps in the performance of seizing computer evidence; computer seizure as a technique requires specialised knowledge and continuous training, because the information technology industry is an ever-changing area.
An empirical research design, followed by a qualitative research approach, allowed the researcher to also obtain information from practice. A thorough literature study, complemented by interviews, was done to collect the required data for the research. Members of the South African Police Cyber-crime Unit and prosecutors dealing with cyber-crime cases were interviewed to obtain their input into, and experiences on, the topic.
The aim of the study was to explore the role of computers in the forensic investigation process, and to determine how computers can be seized without compromising evidence. The study therefore also aimed at creating an understanding and awareness about the slippery nature of computer evidence, and how it can find its way to the court of law without being compromised. The research has revealed that computer crime is different from common law or traditional crimes. It is complicated, and therefore only skilled and qualified forensic experts should be used to seize computer evidence, to ensure that the evidence is not compromised. Training of cyber-crime technicians has to be priority, in order to be successful in seizing computers. / Department of Criminology / M.Tech. (Forensic Investigation)
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Herevaluering van polisiebevoegdhede tot visentering en beslaglegging vervat in die Strafproseswet 51 van 1977Meyer, Pieter William 11 1900 (has links)
Text in Afrikaans / "Free people expect much from their police. In such societies
the police stand at the point of balance on the one hand securing
human rights on the other exercising their lawful powers given
to them by Governments in the name of the people, to protect
people and their institutions" (J Alderson Human Rights and
Police Rights. Publication of the Council of Europe.)
This is no small expectation. It means that the police are
expected to maintain and secure the principles of democracy and
human rights, the principles upon which our Constitution is
based. At the same time it is the duty of a police service to
maintain law and order which sometimes require the exercise of
power and the use of force which on the face of it may appear to
violate human dignity and certain rights and freedoms which a
police force is expected to maintain in a democratic society.
The manner of exercising that power has an impact on the
credibility and effectiveness of the police. Human rights law
internationally accepts that a police service needs to be given
the power to, at times restrict certain individual freedoms in
the interests of the security of the community at large. These
restrictions may take place only in a constitutional way. If it
takes place in an unconstitutional way the courts must have the
right to exclude evidence which is unconstitutionally obtained.
At this stage the courts have to formulate such a qualified
exclusionary rule, but the ultimate goal must be to include such
an exclusionary rule in a future Constitution. / Department of Criminal and Procedural Law / LL.M.
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Analysis of thermal effects in circumferential groove journal bearings with reference to the divergent zone / Analyse des effets thermiques dans les paliers hydrodynamiques avec une rainure circonférentielle en tenant compte de la zone divergenteCristea, Alex Florian 12 December 2012 (has links)
Ce travail porte sur l'étude des effets thermiques dans un palier hydrodynamique, alimentée par une rainure circonférentielle (CGJB) sous charge statique, en tenant compte des phénomènes de rupture de film dans la zone divergente. La recherche expérimentale a été réalisée à l'Université de Poitiers ; elle a permis une détermination minutieuse des champs de pression et de température sur la portée située à l’avant d’un CGJB et dans la section médiane de sa rainure. Ces mesures sous un régime stationnaire sont originales par rapport celles existantes, quel que le type de palier, de par le grand nombre de points de mesure, 180 pour la pression et 144 pour la température, l'instrumentation de haute précision, la large plage de conditions d'exploitation (pression spécifique variant de 0,125 à 2 MPa et vitesse linéaire de l’arbre allant de 5,25 à 21 m/s). Des études du régime transitoire de démarrage au régime stationnaire établi ont été effectuées pour de faibles charges. Des expériences effectuées à l'Université "Politehnica" de Bucarest ont montré une bonne corrélation entre la perte de portance, anti-portance et la rupture du film sur un patin Rayleigh (RSP), ce qui est essentiel pour l'évaluation des phénomènes de rupture dans les paliers. Quelques modèles théoriques ont été utilisés pour évaluer les risques de serrage au démarrage qui est une instabilité thermoélastique catastrophique. Les principaux résultats sont l’obtention d’une base fiable de données expérimentales permettant le développement des modèles théoriques avancés et l’infirmation d’une répartition de pression constante dans la zone divergente et de pression et température constantes dans la rainure d'alime / The main objective of the thesis is to study the thermal effects in steadily loaded circumferential groove journal bearings (CGJBs), including cavitation phenomena occurring in the divergent zone of such bearings. Experimental research conducted at University of Poitiers – Institut Pprime – France enabled a thorough determination of film pressure and temperature fields for the front land of a CGJB plus its mid-groove section, and several performance parameters. Measurements of film pressure and temperature fields under steady-state regime surpassed existing works, regardless of journal bearing design, through: sheer number of land measurement locations, 180 for pressure and for 144 temperature; high precision state of art instrumentation; broad range of operating conditions, 0.125 … 2 MPa specific bearing pressure and 5.25 … 21 m/s shaft speeds. Transient start-up to steady-statestabilization regimes have been investigated at low loads. Experiments at University "Politehnica" of Bucharest – Romania showed a correlation between the downforce thrust and film rupture for a Rayleigh step pin (RSP), important in evaluating divergent zone cavitation phenomena. Theoretical research consisted in developing simple models for evaluating CGJBs performance in steady-state and transient start-up regimes. Several theoretical models were employed for assessing start-up seizure, catastrophic transient thermoelastic instability and damage risk. The major result is a reliable experimental data collection that: enables development of advanced theoretical models; disprove flat film pressure distributions in divergent zones, and constant pressure and temperature in the bearing supply groov
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Os Efeitos de Organocalcogêneos e de 2,3-Dimercaptopropanol Sobre Convulsão Química e Letalidade Induzidas por Pentilenotetrazol e 4-Aminopiridina em Camundongos / The Effects of Organochalcogens and 2,3-Dimercaptopropanol on Chemical Seizure and Lethality Induced by Pentylenetetrazol and 4-Aminopyridine in MiceBrito, Verônica Bidinotto 17 August 2007 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Experimental models of seizure in animals have represented an important role for the understanding of the physiological and behavioural alterations associated with the human epilepsy. The induction of partial or generalized seizures is an efficient method for evaluating both the susceptibility to seizures and to investigate new anticonvulsant agents. In this sense, studies showed that the convulsive actions of the diphenyl diselenide (PhSe)2 and 2,3-dimercaptopropanol (BAL) compounds are inhibited by diazepam and phenobarbital, two classic allosteric modulators of the GABAergic system. Therefore, arises the interest of to investigate the interaction of the (PhSe)2 and BAL compounds with convulsive agents that act via blockade and/or modulation of the GABAergic system. This is the case of the pentylenetetrazol (PTZ), which exerts its convulsive action by blocking of Cl- channel of the GABAA receptor complex. Taking into account these facts, the present study had as first objective to investigate the effects of the pre-administration of (PhSe)2 and BAL in the model of chemical seizure PTZ-induced in mice (Article 1). For this purpose, mice were pretreated with (PhSe)2 (150 μmol/kg, i.p.) or BAL (250, 500, or 1000 μmol/kg, i.p.) 10 minutes prior to administration of PTZ. The obtained results showed that the pretreatment with (PhSe)2 reduced the latency for seizure PTZ-induced at doses of 40 and 60 mg/kg, beyond to cause a decrease in the latency for death PTZ-induced at dose of 60 mg/kg. However, the convulsive and lethal action PTZ-induced at dose of 80mg/kg was not affected by the pretreatment with (PhSe)2. Similarly, the pretreatment of the animals with BAL reduced the latency for seizure induced by 40 and 50 mg/kg PTZ. In addition, the latency for death PTZ-induced at dose of 40 mg/kg was significantly decreased by the pretreatment with BAL in all doses tested. Particularly, in the dose of 50 mg/kg of PTZ, a significant decrease in the latency for death occurred only when the mice were pretreated with 500 and 1000 μmol/kg of BAL. These results show that (PhSe)2 and BAL act in synergysm with PTZ potentializing its convulsive action, possibly through a modulation of the GABAergic system. Tacking into account the structural similarities between (PhSe)2 and diphenyl ditelluride (PhTe)2 compounds, our further objective was to investigate the effects of the (PhSe)2 and (PhTe)2 compounds on a model of chemical seizure 4-aminopyridine (4-AP)-induced in mice (Article 2). The convulsive action of this agent occurs through a blockade of K+ channels and activation of Ca2+ channels, with consequent release of neurotransmitters, predominantly the glutamate. Moreover, it was investigated the brain lipid peroxidation level after treatment of the animals with 4-AP, as well the effect of the pretretament with the (PhSe)2 and (PhTe)2 compounds on this level. For this purpose, mice were pretreated with (PhSe)2 and (PhTe)2 (50, 100, or 150 μmol/kg, s.c.) 30 minutes before administration of 4-AP (12 mg/kg, i.p.). The obtained results showed that the pretreatment with (PhSe)2 and (PhTe)2 (50, 100, and 150 μmol/kg) significantly increased the latency for clonic and tonic seizure, as well as inhibited the death 4-AP-induced. In addition, it was observed a significant increase in the brain lipid peroxidation levels after treatment with 4-AP, which was significantly inhibited by pretreatment with the (PhSe)2 and (PhTe)2 compounds. Therefore, these results show that (PhSe)2 and (PhTe)2 increase the latency for seizures, as well as inhibit the death 4-AP-induced. It is possible that this effect result of the modulation of redox sites of NMDA receptors, and/or modulation in the Ca2+ channels activity with consequent alteration in the neurotransmitters release. Moreover, the work provided evidences for the anticonvulsant and antioxidant properties of the (PhSe)2 and (PhTe)2 compounds, which point out for its neuroprotective properties in this model. Of general model, the utilization of the models of chemical seizure PTZ- or 4-AP-induced in mice was a useful method in the investigation of the actions on central nervous system of the (PhSe)2, (PhTe)2, and BAL compounds. The use of these convulsive models provided evidences about the convulsive actions, as well as possible mechanisms of action of the evaluated compounds. / Modelos experimentais de convulsão em animais têm representado um papel importante para a compreensão das alterações fisiológicas e comportamentais associadas com a epilepsia humana. A indução de convulsões parciais ou generalizadas é um método eficiente para avaliar tanto a susceptibilidade às convulsões quanto investigar novos agentes anticonvulsivantes. Neste sentido, estudos demonstraram que as ações convulsivantes dos compostos disseleneto de difenila (PhSe)2 e 2,3-dimercaptopropanol (BAL) são inibidas por diazepam e fenobarbital, dois moduladores alostéricos clássicos do sistema GABAérgico. Logo, surge o interesse de investigar os efeitos da interação dos compostos (PhSe)2 e BAL e agentes convulsivantes que ajam através do bloqueio e/ou modulação do sistema GABAérgico. Este é o caso do agente pentilenotetrazol (PTZ), o qual exerce sua ação convulsiva por meio de um bloqueio do canal de Cl- do complexo do receptor GABAA. Considerando estes fatos, o presente estudo teve como primeiro objetivo investigar os efeitos da pré-administração de (PhSe)2 e BAL no modelo de convulsão química induzida por PTZ em camundongos (Artigo 1). Para este propósito, camundongos foram pré-tratados com (PhSe)2 (150 μmol/kg, i.p.) ou BAL (250, 500 ou 1000 μmol/kg, i.p.) 10 minutos antes da administração de PTZ. Os resultados obtidos demonstraram que o pré-tratamento com (PhSe)2 reduziu a latência para a convulsão induzida por PTZ nas doses de 40 e 60 mg/kg, além de causar um decréscimo na latência para a morte induzida por PTZ na dose de 60 mg/kg. Entretanto, a ação convulsivante e letal induzida por PTZ na dose de 80 mg/kg não foi afetada pelo pré-tratamento com (PhSe)2. Similarmente, o pré-tratamento dos animais com BAL reduziu a latência para a convulsão induzida por 40 e 50 mg/kg de PTZ. Além disso, a latência para a morte induzida por PTZ na dose de 40 mg/kg foi significativamente diminuída pelo pré-tratamento com BAL em todas as doses testadas. Particularmente, na dose de 50 mg/kg de PTZ, decréscimo significativo na latência para a morte ocorreu somente quando os camundongos foram pré-tratados com 500 e 1000 μmol/kg de BAL. Estes resultados demonstram que o (PhSe)2 e BAL agem em sinergismo com o PTZ potencializando sua ação convulsiva, possivelmente através de uma modulação do sistema GABAérgico. Tendo em vista as similaridades estruturais entre os compostos (PhSe)2 e ditelureto de difenila (PhTe)2, nosso próximo objetivo foi investigar o efeito dos compostos (PhSe)2 e (PhTe)2 sobre um modelo de convulsão química induzida por 4-aminopiridina (4-AP) em camundongos (Artigo 2). A ação convulsiva deste agente ocorre através do bloqueio de canais de K+ e ativação de canais de Ca2+, com conseqüente liberação de neurotransmissores, predominantemente o glutamato. Além disso, foram investigados os níveis de peroxidação lipídica cerebral após o tratamento dos animais com 4-AP, bem como o efeito do pré-tratamento com os compostos (PhSe)2 e (PhTe)2 sobre esses níveis. Para este fim, camundongos foram pré-tratados com (PhSe)2 e (PhTe)2 (50, 100 ou 150 μmol/kg, s.c.) 30 minutos antes da administração de 4-AP (12 mg/kg, i.p.). Os resultados obtidos demonstraram que o pré-tratamento com (PhSe)2 e (PhTe)2, nas doses de 50, 100 e 150 μmol/kg, aumentou significativamente a latência para a convulsão clônica e tônica, bem como inibiu a morte induzida por 4-AP. Além disso, observamos um significativo aumento nos níveis de peroxidação lipídica cerebral após o tratamento com 4-AP, o qual foi significativamente inibido pelo pré-tratamento com os compostos (PhSe)2 e (PhTe)2. Portanto, estes resultados demonstram que (PhSe)2 e (PhTe)2 aumentam a latência para as convulsões, bem como inibem a morte induzida por 4-AP. É possível que este efeito resulte da modulação de sítios redox de receptores NMDA, e/ou modulação na atividade de canais de Ca2+ com conseqüente alteração na liberação de neurotransmissores. Além disso, o trabalho forneceu evidências para as propriedades anticonvulsivas e antioxidantes dos compostos (PhSe)2 e (PhTe)2, as quais apontam para suas propriedades neuroprotetoras neste modelo. De forma geral, a utilização dos modelos de convulsão química induzida por PTZ e 4-AP em camundongos foi um método útil na investigação das ações sobre o sistema nervoso central dos compostos (PhSe)2, (PhTe)2 e BAL. O emprego destes modelos convulsivos forneceu evidências acerca das ações convulsivas, bem como possíveis mecanismos de ação dos compostos avaliados.
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