<p>Den här rapporten beskriver en experimentell studie av Microsoft Network Protection (NAP) och är ämnad för att utvärdera hur mogen tekniken är för att implementeras i en aktiv nätverksmiljö. För att göra studien tog vi hjälp av gymnasieskolan John Bauer i Kalmar. Tester har utförts med DHCP-framtvingning och 802. 1x-framtvingning, dessa är två av NAPs fyra olika framtvingande funktioner. En mindre analys av skolans switchkonfigurationer och interna säkerhet har även gjorts på John Bauers begäran. Testerna har visat att DHCP-framtvingning är en bra och enkel lösning för John Bauers trådade klienter. NAP-funktionen 802. 1x- framtvingning var en större utmaning dock, och blev inte lyckad. Utbudet av information om NAP är än för knapphändig och vi anser därför att inte bara 802.1x framtvingning inte är redo för implementation, utan även framtvingning med DHCP.</p>

A poluição ambiental por metais pesados tem aumentado muito devido às ações antropogênicas tais como as atividades industriais e o uso de fertilizantes fosfatados na agricultura. Entre os metais tóxicos encontrados no meio ambiente, o cádmio (Cd) é um dos que apresenta maior interesse clínico, uma vez que as intoxicações por esse metal são de difícil tratamento. O Cd pode afetar vários órgãos como o fígado, rins, pulmões, ovários, ossos, testículos e cérebro. A toxicologia do Cd é extremamente complexa e tem sido amplamente estudada, mas ainda não está completamente esclarecida. Sendo assim, o objetivo da presente tese foi investigar os efeitos da intoxicação por Cd sobre parâmetros comportamentais e memória, bioquímicos, hematológicos e a bioacumulação desse metal em diferentes tipos celulares de ratos expostos ao cloreto de Cd (CdCl2) ou ao Cd proveniente de batatas contaminadas, e ainda utilizar o antioxidante N-acetilcisteína (NAC) no tratamento deste tipo de intoxicação buscandose avaliar o seu possível efeito protetor. Para tal, foram realizados dois experimentos: a) ratos machos Wistar adultos foram expostos oralmente a 2 mg/kg de Cd e/ou 150 mg/kg de NAC, um dia sim e outro não, durante um período experimental de 30 dias; b) ratos machos Wistar recém desmamados ingeriram, durante 5 meses, dieta a base de bolo contendo 1, 5 ou 25 mg/kg de CdCl2 ou Cd presente em tubérculos de batatas crescidas na presença de 10 μM de CdCl2. A partir desses experimentos pode-se concluir que: a) A intoxicação por CdCl2 causa aumento na concentração de Cd nas estruturas cerebrais (cerebelo, estriado, hipotálamo, hipocampo e córtex cerebral), nos níveis de peroxidação lipídica e na atividade da enzima AChE nas diferentes estruturas cerebrais estudadas ocasionando prejuízos à memória dos ratos. Além disso, a NAC é capaz de diminuir os níveis de peroxidação lipídica e subsequentemente restaurar a atividade da AChE modulando assim, a neurotransmissão colinérgica e melhorando os processos cognitivos. Sendo assim, sugere-se que a NAC possa ser um fármaco promissor em terapias alternativas contra a neurotoxicidade induzida pelo Cd; b) A exposição ao CdCl2 promove um aumento na concentração de Cd no plasma, baço e timo, causa danos hematológicos, não altera a atividade da enzima NTPDase em linfócitos, diminui a atividade da AChE em linfócitos e sangue total bem como da BChE em soro de ratos. Além disso, a NAC foi eficaz em diminuir os efeitos danosos do Cd provavelmente por diminuir os níveis de Cd nos órgãos linfóides, reverter ou amenizar os danos hematológicos e relacionados aos leucócitos mesmo sem alterar a atividade das enzimas colinesterases; c) O CdCl2 aumenta a hidrólise de nucleotídeos de adenina em sinaptossomas de córtex cerebral e diminui em plaquetas de ratos. Provavelmente, o aumento na atividade das enzimas NTPDase e 5’-nucleotidase no SNC causado pelo Cd seja uma resposta compensatória do organismo uma vez que a rápida hidrólise de ATP e ADP favorece a produção de adenosina, uma molécula neuroprotetora. Por outro lado, em plaquetas o Cd causou uma diminuição na atividade da NTPDase e, não alterou a atividade da 5’-nucleotidase sugerindo que a possível elevação no nível de ATP e ADP conduza a um estado hipercoagulável nos ratos intoxicados por esse metal. Além disso, a NAC restaura a atividade dessas enzimas no SNC, mas não apresenta interferência sobre elas em plaquetas; d) A dieta prolongada com CdCl2 ou com Cd proveniente de batatas contaminadas ocasiona aumento no comportamento de ansiedade e prejuízo à memória de ratos o que provavelmente, seja resultado de uma concentração aumentada de Cd e de uma atividade aumentada da AChE e diminuída da Na+,K+-ATPase em diferentes estruturas cerebrais devido a esse metal. Em linhas gerais, os resultados obtidos na presente tese demonstram que apesar de todos os mecanismos propostos pelos quais o Cd poderia afetar o comportamento continuarem a gerar controvérsia, é evidente que a exposição ao CdCl2 tanto a curto quanto a longo prazo, bem como ao Cd proveniente de batatas contaminadas interfere nas funções cerebrais aumentando a concentração de Cd, diminuindo ou aumentando a atividade da AChE, aumentando a lipoperoxidação bem como diminuindo a atividade da Na+,K+-ATPase em diferentes estruturas cerebrais, consequentemente sendo prejudicial ao comportamento animal, como memória e ansiedade. O Cd afeta sistematicamente o organismo dos animais estando presente tanto no plasma, quanto nos órgãos linfóides e no encéfalo alterando, assim, a atividade das enzimas NTPDase, 5’-nucleotidase, AChE e BChE de diferentes tipos celulares. Além disso, a NAC é capaz de reverter ou amenizar vários efeitos danosos causados pelo Cd sugerindo que este fármaco possa ser considerado após estudos adicionais um importante aliado em terapias contra a intoxicação por esse metal. / The environmental pollution by heavy metals has increased greatly due to anthropogenic activities such as industrial activities and the use of phosphate fertilizers in agriculture. Among the toxic metals found in the environment, cadmium (Cd) is a metal that presents the greatest clinical interest, since poisoning by this metal is difficult to treat. Cd may affect various organs such as liver, kidneys, lungs, ovaries, bones, testes and brain. The toxicology of Cd is extremely complex and has been widely studied, but it is not yet fully elucidated. Therefore, the objective of this thesis was to investigate the effects of Cd intoxication on memory as well as behavioral, biochemical, hematological and bioaccumulation parameters of this metal in different cell types of rats exposed to Cd chloride (CdCl2) or Cd from contaminated potatoes. Also, we investigated the antioxidant N-acetylcysteine (NAC) in the treatment of this type of poisoning seeking to evaluate its possible protective effect. Two experiments were performed: i) adult male Wistar rats were exposed orally to 2 mg/kg Cd and/or 150 mg/kg NAC, every other day for 30 days; ii) weaned male Wistar rats fed for 5 months, cake-based diet containing 1, 5 or 25 mg/kg CdCl2 or Cd present in tubers of potatoes grown in the presence of 10 μM of CdCl2. From these experiments we conclude: Firstly, CdCl2 intoxication caused an increase in the Cd concentration in brain structures (cerebellum, striatum, hypothalamus, hippocampus and cerebral cortex), in the levels of lipid peroxidation, and in the AChE activity of different brain structures studied causing damage to memory of rats. NAC was able to reduce the levels of lipid peroxidation and subsequently restore the AChE activity, modulating thereby the cholinergic transmission and improving the cognitive processes. Thus, NAC may be a promising drug for alternative therapies against neurotoxicity induced by Cd. Secondly, the exposure to CdCl2 increased the Cd concentration in plasma, spleen and thymus, caused damages in the hematological parameters, did not alter the NTPDase activity in lymphocytes as well as decreased the AChE activity in lymphocytes and whole blood and the BChE activity in serum of rats. NAC was effective in reducing the harmful effects of Cd probably by decreasing the levels of Cd in the lymphoid organs, reversing or minimizing the hematological damage and related to leukocytes even without changing the activity of cholinesterases. Thirdly, CdCl2 increases the hydrolysis of adenine nucleotides in synaptosomes of cerebral cortex and decreases in platelets of rats. The increase in the NTPDase and 5'-nucleotidase activities in CNS caused by Cd could be a compensatory response of the organism since the rapid hydrolysis of ATP and ADP favors the production of adenosine, a neuroprotective molecule. On the other hand, Cd decreased the NTPDase activity and did not alter 5'-nucleotidase activity in platelets suggesting that the possible increase in the ATP and ADP levels could lead to a hypercoagulable state in rats intoxicated with this metal. NAC restores the activity of these enzymes in the CNS, but had no interference in platelets. Finally, the prolonged diet with CdCl2 or Cd from contaminated potatoes resulted in an increased anxiety-like behavior and damaged memory of rats which was likely to be a result of the increased concentration of Cd, the increased AChE activity and decreased Na+,K+-ATPase activity in the different brain structures studied. In general, the results obtained in this thesis show that despite all the proposed mechanisms by which Cd could affect the behavior still generate controversy, it is clear that the exposure to CdCl2 at both short and long terms as well as to Cd from contaminated potatoes interferes the brain function by increasing Cd concentration, decreasing or increasing the AChE activity, increasing lipid peroxidation and decreasing Na+,K+-ATPase activity in several brain structures, thus being detrimental to the animal behavior influencing memory and anxiety. Cd affected systematically the animal body since it is present in plasma, lymphoid organs and brain, changing the activity of the enzymes NTPDase, 5'-nucleotidase, AChE and BChE of different cell types. In addition, NAC was able to reverse or ameliorate several deleterious effects caused by Cd suggesting that this drug may be, after additional studies, considered an important factor in therapies against intoxication by this metal.

A poluição ambiental por metais pesados tem aumentado muito devido às ações antropogênicas tais como as atividades industriais e o uso de fertilizantes fosfatados na agricultura. Entre os metais tóxicos encontrados no meio ambiente, o cádmio (Cd) é um dos que apresenta maior interesse clínico, uma vez que as intoxicações por esse metal são de difícil tratamento. O Cd pode afetar vários órgãos como o fígado, rins, pulmões, ovários, ossos, testículos e cérebro. A toxicologia do Cd é extremamente complexa e tem sido amplamente estudada, mas ainda não está completamente esclarecida. Sendo assim, o objetivo da presente tese foi investigar os efeitos da intoxicação por Cd sobre parâmetros comportamentais e memória, bioquímicos, hematológicos e a bioacumulação desse metal em diferentes tipos celulares de ratos expostos ao cloreto de Cd (CdCl2) ou ao Cd proveniente de batatas contaminadas, e ainda utilizar o antioxidante N-acetilcisteína (NAC) no tratamento deste tipo de intoxicação buscandose avaliar o seu possível efeito protetor. Para tal, foram realizados dois experimentos: a) ratos machos Wistar adultos foram expostos oralmente a 2 mg/kg de Cd e/ou 150 mg/kg de NAC, um dia sim e outro não, durante um período experimental de 30 dias; b) ratos machos Wistar recém desmamados ingeriram, durante 5 meses, dieta a base de bolo contendo 1, 5 ou 25 mg/kg de CdCl2 ou Cd presente em tubérculos de batatas crescidas na presença de 10 μM de CdCl2. A partir desses experimentos pode-se concluir que: a) A intoxicação por CdCl2 causa aumento na concentração de Cd nas estruturas cerebrais (cerebelo, estriado, hipotálamo, hipocampo e córtex cerebral), nos níveis de peroxidação lipídica e na atividade da enzima AChE nas diferentes estruturas cerebrais estudadas ocasionando prejuízos à memória dos ratos. Além disso, a NAC é capaz de diminuir os níveis de peroxidação lipídica e subsequentemente restaurar a atividade da AChE modulando assim, a neurotransmissão colinérgica e melhorando os processos cognitivos. Sendo assim, sugere-se que a NAC possa ser um fármaco promissor em terapias alternativas contra a neurotoxicidade induzida pelo Cd; b) A exposição ao CdCl2 promove um aumento na concentração de Cd no plasma, baço e timo, causa danos hematológicos, não altera a atividade da enzima NTPDase em linfócitos, diminui a atividade da AChE em linfócitos e sangue total bem como da BChE em soro de ratos. Além disso, a NAC foi eficaz em diminuir os efeitos danosos do Cd provavelmente por diminuir os níveis de Cd nos órgãos linfóides, reverter ou amenizar os danos hematológicos e relacionados aos leucócitos mesmo sem alterar a atividade das enzimas colinesterases; c) O CdCl2 aumenta a hidrólise de nucleotídeos de adenina em sinaptossomas de córtex cerebral e diminui em plaquetas de ratos. Provavelmente, o aumento na atividade das enzimas NTPDase e 5’-nucleotidase no SNC causado pelo Cd seja uma resposta compensatória do organismo uma vez que a rápida hidrólise de ATP e ADP favorece a produção de adenosina, uma molécula neuroprotetora. Por outro lado, em plaquetas o Cd causou uma diminuição na atividade da NTPDase e, não alterou a atividade da 5’-nucleotidase sugerindo que a possível elevação no nível de ATP e ADP conduza a um estado hipercoagulável nos ratos intoxicados por esse metal. Além disso, a NAC restaura a atividade dessas enzimas no SNC, mas não apresenta interferência sobre elas em plaquetas; d) A dieta prolongada com CdCl2 ou com Cd proveniente de batatas contaminadas ocasiona aumento no comportamento de ansiedade e prejuízo à memória de ratos o que provavelmente, seja resultado de uma concentração aumentada de Cd e de uma atividade aumentada da AChE e diminuída da Na+,K+-ATPase em diferentes estruturas cerebrais devido a esse metal. Em linhas gerais, os resultados obtidos na presente tese demonstram que apesar de todos os mecanismos propostos pelos quais o Cd poderia afetar o comportamento continuarem a gerar controvérsia, é evidente que a exposição ao CdCl2 tanto a curto quanto a longo prazo, bem como ao Cd proveniente de batatas contaminadas interfere nas funções cerebrais aumentando a concentração de Cd, diminuindo ou aumentando a atividade da AChE, aumentando a lipoperoxidação bem como diminuindo a atividade da Na+,K+-ATPase em diferentes estruturas cerebrais, consequentemente sendo prejudicial ao comportamento animal, como memória e ansiedade. O Cd afeta sistematicamente o organismo dos animais estando presente tanto no plasma, quanto nos órgãos linfóides e no encéfalo alterando, assim, a atividade das enzimas NTPDase, 5’-nucleotidase, AChE e BChE de diferentes tipos celulares. Além disso, a NAC é capaz de reverter ou amenizar vários efeitos danosos causados pelo Cd sugerindo que este fármaco possa ser considerado após estudos adicionais um importante aliado em terapias contra a intoxicação por esse metal. / The environmental pollution by heavy metals has increased greatly due to anthropogenic activities such as industrial activities and the use of phosphate fertilizers in agriculture. Among the toxic metals found in the environment, cadmium (Cd) is a metal that presents the greatest clinical interest, since poisoning by this metal is difficult to treat. Cd may affect various organs such as liver, kidneys, lungs, ovaries, bones, testes and brain. The toxicology of Cd is extremely complex and has been widely studied, but it is not yet fully elucidated. Therefore, the objective of this thesis was to investigate the effects of Cd intoxication on memory as well as behavioral, biochemical, hematological and bioaccumulation parameters of this metal in different cell types of rats exposed to Cd chloride (CdCl2) or Cd from contaminated potatoes. Also, we investigated the antioxidant N-acetylcysteine (NAC) in the treatment of this type of poisoning seeking to evaluate its possible protective effect. Two experiments were performed: i) adult male Wistar rats were exposed orally to 2 mg/kg Cd and/or 150 mg/kg NAC, every other day for 30 days; ii) weaned male Wistar rats fed for 5 months, cake-based diet containing 1, 5 or 25 mg/kg CdCl2 or Cd present in tubers of potatoes grown in the presence of 10 μM of CdCl2. From these experiments we conclude: Firstly, CdCl2 intoxication caused an increase in the Cd concentration in brain structures (cerebellum, striatum, hypothalamus, hippocampus and cerebral cortex), in the levels of lipid peroxidation, and in the AChE activity of different brain structures studied causing damage to memory of rats. NAC was able to reduce the levels of lipid peroxidation and subsequently restore the AChE activity, modulating thereby the cholinergic transmission and improving the cognitive processes. Thus, NAC may be a promising drug for alternative therapies against neurotoxicity induced by Cd. Secondly, the exposure to CdCl2 increased the Cd concentration in plasma, spleen and thymus, caused damages in the hematological parameters, did not alter the NTPDase activity in lymphocytes as well as decreased the AChE activity in lymphocytes and whole blood and the BChE activity in serum of rats. NAC was effective in reducing the harmful effects of Cd probably by decreasing the levels of Cd in the lymphoid organs, reversing or minimizing the hematological damage and related to leukocytes even without changing the activity of cholinesterases. Thirdly, CdCl2 increases the hydrolysis of adenine nucleotides in synaptosomes of cerebral cortex and decreases in platelets of rats. The increase in the NTPDase and 5'-nucleotidase activities in CNS caused by Cd could be a compensatory response of the organism since the rapid hydrolysis of ATP and ADP favors the production of adenosine, a neuroprotective molecule. On the other hand, Cd decreased the NTPDase activity and did not alter 5'-nucleotidase activity in platelets suggesting that the possible increase in the ATP and ADP levels could lead to a hypercoagulable state in rats intoxicated with this metal. NAC restores the activity of these enzymes in the CNS, but had no interference in platelets. Finally, the prolonged diet with CdCl2 or Cd from contaminated potatoes resulted in an increased anxiety-like behavior and damaged memory of rats which was likely to be a result of the increased concentration of Cd, the increased AChE activity and decreased Na+,K+-ATPase activity in the different brain structures studied. In general, the results obtained in this thesis show that despite all the proposed mechanisms by which Cd could affect the behavior still generate controversy, it is clear that the exposure to CdCl2 at both short and long terms as well as to Cd from contaminated potatoes interferes the brain function by increasing Cd concentration, decreasing or increasing the AChE activity, increasing lipid peroxidation and decreasing Na+,K+-ATPase activity in several brain structures, thus being detrimental to the animal behavior influencing memory and anxiety. Cd affected systematically the animal body since it is present in plasma, lymphoid organs and brain, changing the activity of the enzymes NTPDase, 5'-nucleotidase, AChE and BChE of different cell types. In addition, NAC was able to reverse or ameliorate several deleterious effects caused by Cd suggesting that this drug may be, after additional studies, considered an important factor in therapies against intoxication by this metal.

A poluição ambiental por metais pesados tem aumentado muito devido às ações antropogênicas tais como as atividades industriais e o uso de fertilizantes fosfatados na agricultura. Entre os metais tóxicos encontrados no meio ambiente, o cádmio (Cd) é um dos que apresenta maior interesse clínico, uma vez que as intoxicações por esse metal são de difícil tratamento. O Cd pode afetar vários órgãos como o fígado, rins, pulmões, ovários, ossos, testículos e cérebro. A toxicologia do Cd é extremamente complexa e tem sido amplamente estudada, mas ainda não está completamente esclarecida. Sendo assim, o objetivo da presente tese foi investigar os efeitos da intoxicação por Cd sobre parâmetros comportamentais e memória, bioquímicos, hematológicos e a bioacumulação desse metal em diferentes tipos celulares de ratos expostos ao cloreto de Cd (CdCl2) ou ao Cd proveniente de batatas contaminadas, e ainda utilizar o antioxidante N-acetilcisteína (NAC) no tratamento deste tipo de intoxicação buscandose avaliar o seu possível efeito protetor. Para tal, foram realizados dois experimentos: a) ratos machos Wistar adultos foram expostos oralmente a 2 mg/kg de Cd e/ou 150 mg/kg de NAC, um dia sim e outro não, durante um período experimental de 30 dias; b) ratos machos Wistar recém desmamados ingeriram, durante 5 meses, dieta a base de bolo contendo 1, 5 ou 25 mg/kg de CdCl2 ou Cd presente em tubérculos de batatas crescidas na presença de 10 μM de CdCl2. A partir desses experimentos pode-se concluir que: a) A intoxicação por CdCl2 causa aumento na concentração de Cd nas estruturas cerebrais (cerebelo, estriado, hipotálamo, hipocampo e córtex cerebral), nos níveis de peroxidação lipídica e na atividade da enzima AChE nas diferentes estruturas cerebrais estudadas ocasionando prejuízos à memória dos ratos. Além disso, a NAC é capaz de diminuir os níveis de peroxidação lipídica e subsequentemente restaurar a atividade da AChE modulando assim, a neurotransmissão colinérgica e melhorando os processos cognitivos. Sendo assim, sugere-se que a NAC possa ser um fármaco promissor em terapias alternativas contra a neurotoxicidade induzida pelo Cd; b) A exposição ao CdCl2 promove um aumento na concentração de Cd no plasma, baço e timo, causa danos hematológicos, não altera a atividade da enzima NTPDase em linfócitos, diminui a atividade da AChE em linfócitos e sangue total bem como da BChE em soro de ratos. Além disso, a NAC foi eficaz em diminuir os efeitos danosos do Cd provavelmente por diminuir os níveis de Cd nos órgãos linfóides, reverter ou amenizar os danos hematológicos e relacionados aos leucócitos mesmo sem alterar a atividade das enzimas colinesterases; c) O CdCl2 aumenta a hidrólise de nucleotídeos de adenina em sinaptossomas de córtex cerebral e diminui em plaquetas de ratos. Provavelmente, o aumento na atividade das enzimas NTPDase e 5’-nucleotidase no SNC causado pelo Cd seja uma resposta compensatória do organismo uma vez que a rápida hidrólise de ATP e ADP favorece a produção de adenosina, uma molécula neuroprotetora. Por outro lado, em plaquetas o Cd causou uma diminuição na atividade da NTPDase e, não alterou a atividade da 5’-nucleotidase sugerindo que a possível elevação no nível de ATP e ADP conduza a um estado hipercoagulável nos ratos intoxicados por esse metal. Além disso, a NAC restaura a atividade dessas enzimas no SNC, mas não apresenta interferência sobre elas em plaquetas; d) A dieta prolongada com CdCl2 ou com Cd proveniente de batatas contaminadas ocasiona aumento no comportamento de ansiedade e prejuízo à memória de ratos o que provavelmente, seja resultado de uma concentração aumentada de Cd e de uma atividade aumentada da AChE e diminuída da Na+,K+-ATPase em diferentes estruturas cerebrais devido a esse metal. Em linhas gerais, os resultados obtidos na presente tese demonstram que apesar de todos os mecanismos propostos pelos quais o Cd poderia afetar o comportamento continuarem a gerar controvérsia, é evidente que a exposição ao CdCl2 tanto a curto quanto a longo prazo, bem como ao Cd proveniente de batatas contaminadas interfere nas funções cerebrais aumentando a concentração de Cd, diminuindo ou aumentando a atividade da AChE, aumentando a lipoperoxidação bem como diminuindo a atividade da Na+,K+-ATPase em diferentes estruturas cerebrais, consequentemente sendo prejudicial ao comportamento animal, como memória e ansiedade. O Cd afeta sistematicamente o organismo dos animais estando presente tanto no plasma, quanto nos órgãos linfóides e no encéfalo alterando, assim, a atividade das enzimas NTPDase, 5’-nucleotidase, AChE e BChE de diferentes tipos celulares. Além disso, a NAC é capaz de reverter ou amenizar vários efeitos danosos causados pelo Cd sugerindo que este fármaco possa ser considerado após estudos adicionais um importante aliado em terapias contra a intoxicação por esse metal. / The environmental pollution by heavy metals has increased greatly due to anthropogenic activities such as industrial activities and the use of phosphate fertilizers in agriculture. Among the toxic metals found in the environment, cadmium (Cd) is a metal that presents the greatest clinical interest, since poisoning by this metal is difficult to treat. Cd may affect various organs such as liver, kidneys, lungs, ovaries, bones, testes and brain. The toxicology of Cd is extremely complex and has been widely studied, but it is not yet fully elucidated. Therefore, the objective of this thesis was to investigate the effects of Cd intoxication on memory as well as behavioral, biochemical, hematological and bioaccumulation parameters of this metal in different cell types of rats exposed to Cd chloride (CdCl2) or Cd from contaminated potatoes. Also, we investigated the antioxidant N-acetylcysteine (NAC) in the treatment of this type of poisoning seeking to evaluate its possible protective effect. Two experiments were performed: i) adult male Wistar rats were exposed orally to 2 mg/kg Cd and/or 150 mg/kg NAC, every other day for 30 days; ii) weaned male Wistar rats fed for 5 months, cake-based diet containing 1, 5 or 25 mg/kg CdCl2 or Cd present in tubers of potatoes grown in the presence of 10 μM of CdCl2. From these experiments we conclude: Firstly, CdCl2 intoxication caused an increase in the Cd concentration in brain structures (cerebellum, striatum, hypothalamus, hippocampus and cerebral cortex), in the levels of lipid peroxidation, and in the AChE activity of different brain structures studied causing damage to memory of rats. NAC was able to reduce the levels of lipid peroxidation and subsequently restore the AChE activity, modulating thereby the cholinergic transmission and improving the cognitive processes. Thus, NAC may be a promising drug for alternative therapies against neurotoxicity induced by Cd. Secondly, the exposure to CdCl2 increased the Cd concentration in plasma, spleen and thymus, caused damages in the hematological parameters, did not alter the NTPDase activity in lymphocytes as well as decreased the AChE activity in lymphocytes and whole blood and the BChE activity in serum of rats. NAC was effective in reducing the harmful effects of Cd probably by decreasing the levels of Cd in the lymphoid organs, reversing or minimizing the hematological damage and related to leukocytes even without changing the activity of cholinesterases. Thirdly, CdCl2 increases the hydrolysis of adenine nucleotides in synaptosomes of cerebral cortex and decreases in platelets of rats. The increase in the NTPDase and 5'-nucleotidase activities in CNS caused by Cd could be a compensatory response of the organism since the rapid hydrolysis of ATP and ADP favors the production of adenosine, a neuroprotective molecule. On the other hand, Cd decreased the NTPDase activity and did not alter 5'-nucleotidase activity in platelets suggesting that the possible increase in the ATP and ADP levels could lead to a hypercoagulable state in rats intoxicated with this metal. NAC restores the activity of these enzymes in the CNS, but had no interference in platelets. Finally, the prolonged diet with CdCl2 or Cd from contaminated potatoes resulted in an increased anxiety-like behavior and damaged memory of rats which was likely to be a result of the increased concentration of Cd, the increased AChE activity and decreased Na+,K+-ATPase activity in the different brain structures studied. In general, the results obtained in this thesis show that despite all the proposed mechanisms by which Cd could affect the behavior still generate controversy, it is clear that the exposure to CdCl2 at both short and long terms as well as to Cd from contaminated potatoes interferes the brain function by increasing Cd concentration, decreasing or increasing the AChE activity, increasing lipid peroxidation and decreasing Na+,K+-ATPase activity in several brain structures, thus being detrimental to the animal behavior influencing memory and anxiety. Cd affected systematically the animal body since it is present in plasma, lymphoid organs and brain, changing the activity of the enzymes NTPDase, 5'-nucleotidase, AChE and BChE of different cell types. In addition, NAC was able to reverse or ameliorate several deleterious effects caused by Cd suggesting that this drug may be, after additional studies, considered an important factor in therapies against intoxication by this metal.

Den här rapporten beskriver en experimentell studie av Microsoft Network Protection (NAP) och är ämnad för att utvärdera hur mogen tekniken är för att implementeras i en aktiv nätverksmiljö. För att göra studien tog vi hjälp av gymnasieskolan John Bauer i Kalmar. Tester har utförts med DHCP-framtvingning och 802. 1x-framtvingning, dessa är två av NAPs fyra olika framtvingande funktioner. En mindre analys av skolans switchkonfigurationer och interna säkerhet har även gjorts på John Bauers begäran. Testerna har visat att DHCP-framtvingning är en bra och enkel lösning för John Bauers trådade klienter. NAP-funktionen 802. 1x- framtvingning var en större utmaning dock, och blev inte lyckad. Utbudet av information om NAP är än för knapphändig och vi anser därför att inte bara 802.1x framtvingning inte är redo för implementation, utan även framtvingning med DHCP.

Introduction: Phospholipids amphiphilic structure gives them special properties such as self-aggregation, emulsifying and wetting properties. Among the various structures resulting from the dissolution of phospholipids in water are the liposome, which acts as a drug carrier. They also act as surfactants for wetting by adsorbing on the crystal surface to increase the hydrophilicity of hydrophobic drugs. Surfactants, such as bile salts, have been shown to have a good ability to solubilize and dissolve non-polar lipids. By mixing with bile salts, phospholipids can easily dissolve and form mixed micelles. For the breakdown of fats in the gastrointestinal tract, mixed micelles formed from bile salts and phospholipid play an important role as well as in solubilizing water-insoluble drugs and other drug delivery applications. Aim: Theaim of this project is to study mixtures of the bile salts sodium deoxycholate (NaDC) and sodium cholate (NaC) with the anionic phospholipid DMPG and to determine the mole fraction (composition) in the aggregates at the transition from micelles to bicolts in bile salt / phospholipid mixtures. In addition, we want to determine the average size and structure of the colloidal particles formed in the solutions near the transition. The phospholipid DMPG has a charge and our results will be compared with previous corresponding studies where the zwitterionic phospholipid DMPC was investigated. Methods: The structure and size of micelles and bilayers formed will be determined by Dynamic Light Scattering (DLS) and Static Light Scattering (SLS) and Determination of refractive index increment of NaC and NaDC. Complementary techniques such as surface tension, small angle X-ray scattering (SAXS) and cryo-TEM may be used. Results and Discussion: This study was able to show that aggregates for systems with a molar ratio of 0.05 to 0.20 of both NaC and NaDC at 21 degrees (°C), have an approximate size range between 3 and 10 nm. At 21 ° C the concentration range studied for both NaC and NaDC shows that the particles are larger in size at lower concentrations. Also, increasing the molar ratio of both bile salts, NaC and NaDC in the samples leads to a reduction in the particle size of the system. At 37 °C the system shows a significant increase in the size of the particles for both the bile salts, NaC and NaDC in a size range between 10 and 400 nm. However, at 37 ° C and for both NaC and NaDC in molar ratios of 0.05 and 0.10, the particle size increases with increasing sample concentration but in molar ratios of 0.15 and 0.20, the particle size decreases with increasing sample concentration. At 21 ° C the light scattering experiments for the systems in NaDC and DMPC showed that the size of the micelles decreased with increasing concentrations while the increasing molar ratio led to increased size corresponding to mixed systems of bile salts and DMPG but not at 37 ° C. This difference may be mainly due to the fact that DMPG is an anionic phospholipid that has a charge and the altered conical shape of the bile salts as well as spontaneous curvature at a higher temperature. At 21 ° C the light scattering experiments for the systems in NaDC and DMPC showed that the size of the micelles decreased with increasing concentrations while the increasing molar ratio led to increased size corresponding to mixed systems of bile salts and DMPG but not at 37 ° C. This difference may be mainly due to the fact that DMPG is an anionic phospholipid that has a charge and the altered conical shape of the bile salts as well as spontaneous curvature at a higher temperature. Conclusion: At 37 °C for NaC and NaDC in molar ratios of 0.05 and 0.10 other cmc are obtained, indicating the presence of large structures in the system. Where these large worm-like or rod-like structures are formed by micelles. Accurate prediction of what structures may be present in the system requires more detailed and more appropriate research methods which in turn also need more time to achieve the result. Due to the project's time constraints, it became impossible to use these methods. This difference may be mainly due to the fact that DMPG is an anionic phospholipid that has a charge. The bile salts' end conformation form as well as spontaneous curvature at higher temperatures.

Dopamine (DA) D2 receptor expression parallels DA levels in the brain and these autoreceptors have been shown to be modulated by long-term ethanol exposure. We have previously demonstrated that ventral tegmental area (VTA) GABA neurons also express D2 autoreceptors (D2R), and that DA and D2R agonists markedly enhance the excitability of VTA GABA neurons, opposite to their well-known auto-receptor inhibition of DA neurons. Most importantly, D2R antagonists block ethanol inhibition of VTA GABA neurons and D2R expression in VTA GABA neurons down-regulates with chronic ethanol, as others have shown for whole VTA D2R expression. The aim of this study was to evaluate short-term D2R adaptation in specific brain reward regions i.e., ventral tegmental area (VTA), nucleus accumbens (NAc), temporal lobe cortex, and also in peripheral white blood cells (WBCs) as a potential biomarker for brain DA. To accomplish these studies, we used quantitative RT-PCR to analyze rapid (within 2 hrs) changes in D2R expression from both brain and blood samples of rats from one of four in vivo treatment groups: saline, ethanol (2.5 g/kg, IP), eticlopride (1 mg/kg, IV), or quinpirole (0.1 mg/kg, IV). To verify the qRT-PCR effect we observed from tissue punches of the selected brain regions, we used immunofluorescence to quantify changes in D2R expression between the four treatment groups. To determine whether D2R adaptation in the blood was dependent on communication with the brain, we extracted blood samples and performed the same type of in vivo experiments in vitro. We found that D2R expression was increased in the VTA with ethanol, eticlopride and quinpirole, increased in the NAc with ethanol but decreased with eticlopride and quinpirole, and decreased with ethanol and quinpirole in the temporal lobe cortex. In the in vivo blood experiments, D2R expression decreased in WBCs in all three drug treatment groups. In vitro blood experiments showed increased expression with ethanol treatment and decreased with eticlopride. When compared to saline treated animals, the immunofluorescence in the VTA suggests that D2R expression increased in ethanol and eticlopride, but decreased in quinpirole treated animals. At this point, it is clear that D2R expression shows rapid adaptation when exposed to acute doses of ethanol and D2 targeting drugs in both the brain and blood. More evidence is needed through in vitro studies to determine whether a specific neuro-immune interaction is directing the changes seen in the blood and whether or not chronically exposed animals show significantly decreased D2R expression in the blood.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

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Yes / The ribosome exit site is a focal point for the interaction of protein-biogenesis factors that guide the fate of nascent polypeptides. These factors include chaperones such as NAC, N-terminal-modifying enzymes like Methionine aminopeptidase (MetAP), and the signal recognition particle (SRP), which targets secretory and membrane proteins to the ER. These factors potentially compete with one another in the short time-window when the nascent chain first emerges at the exit site, suggesting a need for regulation. Here, we show that MetAP contacts the ribosome at the universal adaptor site where it is adjacent to the α subunit of NAC. SRP is also known to contact the ribosome at this site. In the absence of NAC, MetAP and SRP antagonize each other, indicating a novel role for NAC in regulating the access of MetAP and SRP to the ribosome. NAC also functions in SRP-dependent targeting and helps to protect substrates from aggregation before translocation. / This work was supported by grants from the BBSRC [H007202/1] and Wellcome Trust [097820/Z/11/A].