Tecnologias HVDC que utilizam conversores do tipo fonte de tensão, o VSC-HVDC, ainda não são completamente difundidas e aplicadas no Brasil, em contraste com outros países que começaram a estudar e empregar este tipo de transmissão. Comparado com o HVDC tradicional, o VSC-HVDC é uma tecnologia de transmissão mais eficiente e pode superar deficiências encontradas na transmissão em corrente contínua convencional. O VSC-HVDC pode ser utilizado de maneira mais eficiente nas novas redes de energia, para alimentar ilhas, integração de geração eólica, renovação das linhas em centros urbanos, aplicações multiterminais e conexão com sistemas fracos. Por se tratar de uma tecnologia recente, o VSC-HVDC ainda não é amplamente adotado e uma das principais limitações da utilização destes sistemas é a sua fragilidade diante faltas na linha de corrente contínua. Neste contexto, limitadores de corrente de falta (LCF) podem ser utilizados para minimizar o impacto das faltas. A ação dos limitadores é benéfica ao sistema durante condições de falta, contudo, ainda assim é necessária a atuação do sistema de proteção para extinguir a condição faltosa. Portanto, este trabalho visa propor e avaliar um novo esquema de proteção que opere de maneira seletiva e confiável para sistemas VSC-HVDC na presença de LCF baseados em materiais supercondutores ou LCF indutivos. Para tanto, foram implementadas quatro funções de proteção tradicionais das linhas em CC, a saber: direcional de corrente, diferencial, sobrecorrente com restrição de tensão e ondas viajantes, e ainda, foi proposta uma nova função de proteção, a de condutância, a qual apresentou o menor tempo de identificação de falta, considerando as faltas mais severas. Adicionalmente, foi avaliado o comportamento destas funções quando o sistema apresenta os LCF em série com a linha. Foi demonstrado que é possível extrair os benefícios dos LCF sem deteriorar a qualidade dos resultados das funções de proteção, o que aumenta a segurança e confiabilidade dos sistemas VSC-HVDC, uma vez que os impactos das faltas são minimizados e as mesmas são identificadas em um curto intervalo de tempo. / HVDC technology based on voltage source converters, VSC-HVDC, are not yet fully disseminated and applied in Brazil, in contrast to other countries that have begun to study and widely employ this type of transmission technology. When compared with traditional HVDC systems, VSC-HVDC systems are more efficient and can overcome the challenges encountered in the conventional direct current transmission. The VSC-HVDC can be used more efficiently in the new energy networks to feed islands, integration of wind generation, renewal of lines in urban centers, multiterminal applications and connection with weak systems. Because it is a recent technology, VSC-HVDC is not yet widely adopted and a major limitation of using these systems is their weakness against faults in the DC line. In this context, fault current limiters (FCL) can be used to minimize the impact of faults. The action of the limiters is beneficial to the system during fault conditions, however, the use of protection schemes to detect the fault and extinguish the faulty condition is still required. Therefore, this work aims to propose and evaluate a new protection scheme operating in selective and reliable way for VSC-HVDC systems in the presence of FCL based in superconductor materials or inductive FCL. To reach such a goal, in this work it has been implemented four traditional DC lines protection functions, namely: directional current, differential, overcurrent with voltage restraint and traveling waves, and also proposed a new protection function, which is based on the conductance. This last protection function has presented the lowest detection time, when considering the most severe faults. In addition, it was evaluated the behavior of these functions when the system presents the FCL in series with the DC line. It has been shown that it is possible to extract the benefits of FCL without deteriorating the quality of the results of the protection functions, which increases the safety and reliability of the VSC-HVDC systems, since the impact of faults is minimized and they are identified in a short time.

Tecnologias HVDC que utilizam conversores do tipo fonte de tensão, o VSC-HVDC, ainda não são completamente difundidas e aplicadas no Brasil, em contraste com outros países que começaram a estudar e empregar este tipo de transmissão. Comparado com o HVDC tradicional, o VSC-HVDC é uma tecnologia de transmissão mais eficiente e pode superar deficiências encontradas na transmissão em corrente contínua convencional. O VSC-HVDC pode ser utilizado de maneira mais eficiente nas novas redes de energia, para alimentar ilhas, integração de geração eólica, renovação das linhas em centros urbanos, aplicações multiterminais e conexão com sistemas fracos. Por se tratar de uma tecnologia recente, o VSC-HVDC ainda não é amplamente adotado e uma das principais limitações da utilização destes sistemas é a sua fragilidade diante faltas na linha de corrente contínua. Neste contexto, limitadores de corrente de falta (LCF) podem ser utilizados para minimizar o impacto das faltas. A ação dos limitadores é benéfica ao sistema durante condições de falta, contudo, ainda assim é necessária a atuação do sistema de proteção para extinguir a condição faltosa. Portanto, este trabalho visa propor e avaliar um novo esquema de proteção que opere de maneira seletiva e confiável para sistemas VSC-HVDC na presença de LCF baseados em materiais supercondutores ou LCF indutivos. Para tanto, foram implementadas quatro funções de proteção tradicionais das linhas em CC, a saber: direcional de corrente, diferencial, sobrecorrente com restrição de tensão e ondas viajantes, e ainda, foi proposta uma nova função de proteção, a de condutância, a qual apresentou o menor tempo de identificação de falta, considerando as faltas mais severas. Adicionalmente, foi avaliado o comportamento destas funções quando o sistema apresenta os LCF em série com a linha. Foi demonstrado que é possível extrair os benefícios dos LCF sem deteriorar a qualidade dos resultados das funções de proteção, o que aumenta a segurança e confiabilidade dos sistemas VSC-HVDC, uma vez que os impactos das faltas são minimizados e as mesmas são identificadas em um curto intervalo de tempo. / HVDC technology based on voltage source converters, VSC-HVDC, are not yet fully disseminated and applied in Brazil, in contrast to other countries that have begun to study and widely employ this type of transmission technology. When compared with traditional HVDC systems, VSC-HVDC systems are more efficient and can overcome the challenges encountered in the conventional direct current transmission. The VSC-HVDC can be used more efficiently in the new energy networks to feed islands, integration of wind generation, renewal of lines in urban centers, multiterminal applications and connection with weak systems. Because it is a recent technology, VSC-HVDC is not yet widely adopted and a major limitation of using these systems is their weakness against faults in the DC line. In this context, fault current limiters (FCL) can be used to minimize the impact of faults. The action of the limiters is beneficial to the system during fault conditions, however, the use of protection schemes to detect the fault and extinguish the faulty condition is still required. Therefore, this work aims to propose and evaluate a new protection scheme operating in selective and reliable way for VSC-HVDC systems in the presence of FCL based in superconductor materials or inductive FCL. To reach such a goal, in this work it has been implemented four traditional DC lines protection functions, namely: directional current, differential, overcurrent with voltage restraint and traveling waves, and also proposed a new protection function, which is based on the conductance. This last protection function has presented the lowest detection time, when considering the most severe faults. In addition, it was evaluated the behavior of these functions when the system presents the FCL in series with the DC line. It has been shown that it is possible to extract the benefits of FCL without deteriorating the quality of the results of the protection functions, which increases the safety and reliability of the VSC-HVDC systems, since the impact of faults is minimized and they are identified in a short time.

South Africa is a country of great diversity. Different climate zones and a host of different habitats make South Africa the perfect platform for rich floral diversity. This floral diversity lends itself to the study of natural products by discovering new natural drugs that can be used in the treatment of many illnesses. Studies into the antioxidant properties of plants that are used in traditional medicine are an important aspect of research to determine the rationale of the use of plants by traditional healers. Many neurodegenerative diseases, like epilepsy, Parkinson s and Alzheimer s diseases, are linked to oxidative stress. Antioxidants could play a major role as neuroprotective agents and could alter the progression of these diseases. Epilepsy is one of the world s most prevalent central nervous system disorders and affects more than seventy per one thousand children in South Africa. Most of these cases are people in rural areas of South Africa where communities rely on the use of traditional medicine. Cotyledon orbiculata L. var orbiculata (Haw.) DC. is widely used in traditional medicine to treat epilepsy and other central nervous system disorders. The need to screen these plants for activity and toxicity is very important to understand the complex mechanism of action in the treatment of patients. In this study the methanol extract and three different fractions of the methanol extract of Cotyledon orbiculata were used to test for antioxidant activity and toxicity towards neuroblastoma cells. The freeze dried leaves of Cotyledon orbiculata were extracted with methanol using a Soxhlet apparatus. The concentrated extracts were analysed using HPLC (high pressure liquid chromatography) and three major peaks were selected for isolation. Three assays were performed to assess the antioxidant activity and toxicity of the isolated compounds. The thiobarbituric acid assay (TBA) quantifies the extent of the inhibition of lipid peroxidation in rat brain homogenates by the isolated fractions. All of the samples were able to attenuate lipid peroxidation as seen from the results obtained from the TBA assay. The methanol extract showed the best attenuation of lipid peroxidation in the rat brain homogenate with fraction 1 and 2 showing greater attenuation of lipid peroxidation than fraction 3. The nitroblue tetrazolium assay (NBT) quantifies the ability of the fractions to scavenge superoxide radicals in a rat brain homogenate. All samples were able to scavenge superoxide radicals as indicated by the NBT assay. The methanol extract showed the best superoxide scavenging abilities in the assay whereas fraction 1 showed better scavenging abilities than fraction 2 and 3. The 3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide assay (MTT) indicates the toxicity of the fractions towards neuroblastoma cells. The methanol extract and fraction 2 in the highest concentration of 10 mg/ml were the only samples that showed toxicity towards neuroblastoma cells. The molecular structure of a compound from fraction 2 was determined by using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and mass spectroscopy (MS). This compound was identified as diethyl malate. Diethyl malate is an artefact that is generated in HPLC procedures in the presence of malic acid (which naturally occurs in the leaves of Cotyledon orbiculata) and ethanol. The methanol extract of Cotyledon orbiculata has high antioxidant activity and could be due to the presence of malic acid in the leaves of the plant. The rationale in the use of Cotyledon orbiculata in the treatment of epilepsy could not be determined due to the isolation of an artefact, diethyl malate, obtained from the fraction. Further research should include methods to prevent artefact formation and purification of the samples that are obtained. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.

South Africa is a country of great diversity. Different climate zones and a host of different habitats make South Africa the perfect platform for rich floral diversity. This floral diversity lends itself to the study of natural products by discovering new natural drugs that can be used in the treatment of many illnesses. Studies into the antioxidant properties of plants that are used in traditional medicine are an important aspect of research to determine the rationale of the use of plants by traditional healers. Many neurodegenerative diseases, like epilepsy, Parkinson s and Alzheimer s diseases, are linked to oxidative stress. Antioxidants could play a major role as neuroprotective agents and could alter the progression of these diseases. Epilepsy is one of the world s most prevalent central nervous system disorders and affects more than seventy per one thousand children in South Africa. Most of these cases are people in rural areas of South Africa where communities rely on the use of traditional medicine. Cotyledon orbiculata L. var orbiculata (Haw.) DC. is widely used in traditional medicine to treat epilepsy and other central nervous system disorders. The need to screen these plants for activity and toxicity is very important to understand the complex mechanism of action in the treatment of patients. In this study the methanol extract and three different fractions of the methanol extract of Cotyledon orbiculata were used to test for antioxidant activity and toxicity towards neuroblastoma cells. The freeze dried leaves of Cotyledon orbiculata were extracted with methanol using a Soxhlet apparatus. The concentrated extracts were analysed using HPLC (high pressure liquid chromatography) and three major peaks were selected for isolation. Three assays were performed to assess the antioxidant activity and toxicity of the isolated compounds. The thiobarbituric acid assay (TBA) quantifies the extent of the inhibition of lipid peroxidation in rat brain homogenates by the isolated fractions. All of the samples were able to attenuate lipid peroxidation as seen from the results obtained from the TBA assay. The methanol extract showed the best attenuation of lipid peroxidation in the rat brain homogenate with fraction 1 and 2 showing greater attenuation of lipid peroxidation than fraction 3. The nitroblue tetrazolium assay (NBT) quantifies the ability of the fractions to scavenge superoxide radicals in a rat brain homogenate. All samples were able to scavenge superoxide radicals as indicated by the NBT assay. The methanol extract showed the best superoxide scavenging abilities in the assay whereas fraction 1 showed better scavenging abilities than fraction 2 and 3. The 3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide assay (MTT) indicates the toxicity of the fractions towards neuroblastoma cells. The methanol extract and fraction 2 in the highest concentration of 10 mg/ml were the only samples that showed toxicity towards neuroblastoma cells. The molecular structure of a compound from fraction 2 was determined by using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and mass spectroscopy (MS). This compound was identified as diethyl malate. Diethyl malate is an artefact that is generated in HPLC procedures in the presence of malic acid (which naturally occurs in the leaves of Cotyledon orbiculata) and ethanol. The methanol extract of Cotyledon orbiculata has high antioxidant activity and could be due to the presence of malic acid in the leaves of the plant. The rationale in the use of Cotyledon orbiculata in the treatment of epilepsy could not be determined due to the isolation of an artefact, diethyl malate, obtained from the fraction. Further research should include methods to prevent artefact formation and purification of the samples that are obtained. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.

No description available.

In vivo intracranial microdialysis is a valuable technique yielding novel and useful insight into normal or pathological neurochemical processes in the brain by means of sampling of interstitial fluid of cells in a living animal. It's most important advantage is that it can continuously monitor time-related changes in the concentration of neurotransmitters and their metabolites, other neuromodulators, energy substrates, as well as exogenous drugs in the extracellular fluid of specific brain areas of interest. While the development and standardization of the intracranial microdialysis technique in our laboratory was the main aim of the current study, a pilot application study was also performed during which the effect of several locally administered pharmacological agents on brain glutamate levels in a genetic rat model of depression was investigated. Abnormal neuronal glutamate levels have been implicated in various psychiatric conditions including major depressive disorder. The Flinders Sensitive Line (FSL) is a genetic line of Sprague-Dawley rat that displays various behavioral and neurochemical traits akin to that observed in depression. The Flinders Resistant Line (FRL) rat is used as the normal control. The prefrontal cortex is an important brain area involved in the neuropathology of depression. Prefrontal cortical glutamate levels in a small number of FSL and FRL rats were therefore compared at baseline and following local administration of potassium chloride (100 mM), the latter in order to study changes in evoked glutamate release. Ketamine hydrochloride (9 mM) and fluoxetine (30 μM) respectively were also administered via reverse dialysis. Prior to initiating the microdialysis studies, an HPLC-fluorescence method was developed to analyze the levels of glutamate in the microdialysate. As part of the development and standardization of the microdialysis technique, a number of validation studies were performed. This included refining the stereotaxic surgery procedure, determining the most appropriate anesthesia protocol, and standardizing the microdialysis procedure with regard to perfusion fluid, flow rate, sample volume, duration of dialysis, and anatomical verification of probe location. The HPLC-fluorescence method for the analysis of glutamate was also developed and validated. This technique proved to be sensitive and specific for the determination of glutamate with a linearity of 0.991 in the concentration range of standards tested (0.1 – 10 μM) and an intra-assay repeatability (precision value) yielding relative standard deviations of less than 10.5%, Mean elution time was between 24 and 26 minutes for glutamate in the microdialysis sample and the limit of detection and quantification was both 0.1 μM. Results from the application study indicated that baseline values of glutamate in the prefrontal cortex did not differ between FRL and FSL rats during the 1 hour period of dialysis. However, potassium chloride-evoked glutamate release was greater in FSL vs. FRL rats, although this difference was not statistically significant. Local perfusion by reverse dialysis of ketamine hydrochloride produced statistically significant increases in glutamate concentrations at certain time points in FSL rats. Although glutamate levels were also increased in FRL rats in response to ketamine, it was not statistically different compared to baseline levels. Fluoxetine perfusion did not affect glutamate release in either of the two rat groups. In conclusion, we have successfully developed and established an intracranial in vivo microdialysis procedure in our laboratory, as well as standardized and validated a sensitive method to analyze glutamate in microdialysate samples. These techniques were then applied in a small number of FSL vs. FRL rats in order to confirm their application in a typical research scenario. Although the data were too limited to make any valid conclusions about glutamate concentrations in an animal model of depression or the effect of drugs on the release thereof, these novel techniques and analyses will be valuable in future studies. / Thesis (MSc (Pharmacology))--North-West University, Potchefstroom Campus, 2013.

In vivo intracranial microdialysis is a valuable technique yielding novel and useful insight into normal or pathological neurochemical processes in the brain by means of sampling of interstitial fluid of cells in a living animal. It's most important advantage is that it can continuously monitor time-related changes in the concentration of neurotransmitters and their metabolites, other neuromodulators, energy substrates, as well as exogenous drugs in the extracellular fluid of specific brain areas of interest. While the development and standardization of the intracranial microdialysis technique in our laboratory was the main aim of the current study, a pilot application study was also performed during which the effect of several locally administered pharmacological agents on brain glutamate levels in a genetic rat model of depression was investigated. Abnormal neuronal glutamate levels have been implicated in various psychiatric conditions including major depressive disorder. The Flinders Sensitive Line (FSL) is a genetic line of Sprague-Dawley rat that displays various behavioral and neurochemical traits akin to that observed in depression. The Flinders Resistant Line (FRL) rat is used as the normal control. The prefrontal cortex is an important brain area involved in the neuropathology of depression. Prefrontal cortical glutamate levels in a small number of FSL and FRL rats were therefore compared at baseline and following local administration of potassium chloride (100 mM), the latter in order to study changes in evoked glutamate release. Ketamine hydrochloride (9 mM) and fluoxetine (30 μM) respectively were also administered via reverse dialysis. Prior to initiating the microdialysis studies, an HPLC-fluorescence method was developed to analyze the levels of glutamate in the microdialysate. As part of the development and standardization of the microdialysis technique, a number of validation studies were performed. This included refining the stereotaxic surgery procedure, determining the most appropriate anesthesia protocol, and standardizing the microdialysis procedure with regard to perfusion fluid, flow rate, sample volume, duration of dialysis, and anatomical verification of probe location. The HPLC-fluorescence method for the analysis of glutamate was also developed and validated. This technique proved to be sensitive and specific for the determination of glutamate with a linearity of 0.991 in the concentration range of standards tested (0.1 – 10 μM) and an intra-assay repeatability (precision value) yielding relative standard deviations of less than 10.5%, Mean elution time was between 24 and 26 minutes for glutamate in the microdialysis sample and the limit of detection and quantification was both 0.1 μM. Results from the application study indicated that baseline values of glutamate in the prefrontal cortex did not differ between FRL and FSL rats during the 1 hour period of dialysis. However, potassium chloride-evoked glutamate release was greater in FSL vs. FRL rats, although this difference was not statistically significant. Local perfusion by reverse dialysis of ketamine hydrochloride produced statistically significant increases in glutamate concentrations at certain time points in FSL rats. Although glutamate levels were also increased in FRL rats in response to ketamine, it was not statistically different compared to baseline levels. Fluoxetine perfusion did not affect glutamate release in either of the two rat groups. In conclusion, we have successfully developed and established an intracranial in vivo microdialysis procedure in our laboratory, as well as standardized and validated a sensitive method to analyze glutamate in microdialysate samples. These techniques were then applied in a small number of FSL vs. FRL rats in order to confirm their application in a typical research scenario. Although the data were too limited to make any valid conclusions about glutamate concentrations in an animal model of depression or the effect of drugs on the release thereof, these novel techniques and analyses will be valuable in future studies. / Thesis (MSc (Pharmacology))--North-West University, Potchefstroom Campus, 2013.