Novos agentes terapêuticos que preservem as células <font face=\"Symbol\">&#946 do pâncreas e o controle do peso são importantes para o diabetes melittus tipo 2 (DM-2), constituindo uma importante área de investimento farmacêutico. Com o objetivo de contribuir com a toxinologia comparada de venenos de répteis e com a eventual descoberta de novos agentes insulinotrópicos, o presente estudo realizou a prospecção de compostos hipoglicemiantes análogos à exendina-4 (isolada de lagartos Heloderma) ou inibidores da dipeptidil-peptidase IV (DPP-IV) no veneno da serpente Bothrops jararaca. A espectrometria de massas identificou uma K49 Fosfolipase A2 inédita neste veneno. Inibidores da DPP-IV não foram encontrados. Porém, a existência de frações polipeptídicas deste veneno sem similares estruturais descritos, sem efeito na pressão arterial média, imunologicamente similares à exendina-4 e com efeito hipoglicemiante e provável capacidade de ligação ao receptor do peptídeo glucagon-símile tipo 1, caracterizaram, pela primeira vez, a ação de veneno de serpente sobre o metaboloma. / New therapeutic agents that protect pancreatic <font face=\"Symbol\">&#946 cells and regulate body mass are important to diabetes mellitus type 2 (DM-2). The search for these agents is one of the main objectives of investments made by pharmaceutical industries. To contribute to the comparative toxinology studies of reptile venoms and to reveal new insulinotropic agents, the present investigation searched for hypoglycemiant compounds such as exendin-4 analogues (isolated from Heloderma lizards) or dipeptidyl-peptidase IV (DPP-IV) inhibitors in the venom of the snake Bothrops jararaca. The mass spectrometry analysis identified a novel K-49 Phospholipase A2 in this venom. DPP-IV inhibitors were not found. However, the existence of polypeptide fractions from this venom without structural similarity with reported compounds, without effect on mean arterial blood pressure and with immunological similarity with exendin-4 and probable ability to bind to glucagon-like peptide type 1 receptor, led to the first characterization of snake venom activity on metaboloma.

Neste trabalho visamos otimizar o isolamento da BnP1, uma SVMP presente no veneno de B. neuwiedi, e isolar disintegrinas desse veneno, ambas originadas de precursores tipo P-II, analisando as seqüências de cDNA e a ação sobre plaquetas. A purificação da BnP1 foi por exclusão molecular e troca iônica; duas novas disintegrinas, D2 e D4, foram isoladas por cromatografia em fase reversa; e outra disintegrina, MS, foi caracterizada a partir do SDS-PAGE. As proteínas foram parcialmente seqüenciadas por espectrometria de massas. Diferentes cDNAs foram clonados a partir da glândula de veneno de B. neuwiedi e os precursores da BnP1 e MS se localizaram em um cluster que inclui SVMPs classe P-I e P-II. O precursor de D4 correspondeu a uma SVMP tipicamente P-II. A BnP1, ao contrário das disintegrinas, não inibiu a agregação plaquetária induzida por diferentes agonistas. Este trabalho indica ainda que a biossíntese de SVMPs da classe P-II pode envolver processamento de mRNA, um novo mecanismo de geração de diversidade das SVMPs. / The aim of this study was to optimize the isolation of BnP1, a SVMP from B. neuwiedi venom, and isolate new disintegrins from this venom, both originated from P-II class precursors, and analyze the sequence of their precursors and their action on platelets. BnP1 was isolated by size exclusion and anion-exchange chromatography; the disintegrins D2 and D4 by reverse-phase chromatography and MS was isolated from SDS-PAGE. These proteins were partially sequenced by mass spectrometry. Several SVMPs cDNAs were cloned from B. neuwiedi venom gland, and BnP1 and MS precursors localized in a cluster enclosing P-I and P-II SVMPs. MS cDNA was tipical of P-II class of SVMPs. BnP1, unlike the disintegrins, was not able to inhibit platelet aggregation induced by different agonists. This work suggested that the biosynthesis of class P-II SVMPs include mRNA processing as a further step to generate venom diversity.

Devido à importância da agricultura para a economia do Brasil e para a dieta da população brasileira, um esforço contínuo tem sido feito para preservar a qualidade dos alimentos. Um dos mais importantes critérios de qualidade é a concentração correta dos pesticidas ou a não detecção destes nos alimentos. O objetivo deste trabalho é estudar o efeito matriz na analise de resíduos de pesticidas por cromatografia à gás em manga, a contaminação de mangas compradas na cidade de São Paulo por pesticidas e a otimização de um método multiresíduo neste tipo de matriz. O método empregado foi o utilizado pelo Governo Holandês adaptado de Lucke (1975), e constou da extração com acetona e partição em uma mistura diclorometano:hexano 1:1. O extrato foi concentrado e injetado em cromatógrafo à gás com detector de captura de elétrons e detector fotométrico de chama. Foram analisados 23 princípios ativos diferentes entre herbicidas, inseticidas, fungicidas e acaricidas; a metodologia empregada permitiu um limite de quantificação que variou de 0,01 mg/Kg a 0,30 mg/Kg. A recuperação de amostras fortificadas variou de 70 a 120%. Os resultados mostraram que a matriz apresenta uma grande influência na determinação dos princípios ativos Procloraz, Difenoconazol, Fosmete, Azoxistrobina e sulfato Endosulfam; o único princípio ativo encontrado nas amostras compradas no varejo foi o fungicida Procloraz com valores permitidos pela Legislação Brasileira. / Due to the importance of Agriculture for the economy of Brazil and for the diet of Brazilian population, a continuous effort is being made to preserve its high quality characteristics. One of the most important quality criteria is the right concentration or better not detectable pesticide residues. This work had the objective to study the matrix enhancement effect in gas chromatographic analysis of pesticide residue in mango fruit; the contamination of mango fruit by pesticide bought in Sao Paulo city and the optimization of the multiresidue method in this matrix. The employed method in the analysis was adapted from Lucke (1975), used by Netherlands Government; extraction with acetone and partition in a dichlorometane:hexane (1:1), and Gas Chromatographic determination with ECD and FPD. We studied about 23 active substances among herbicides, fungicides, insecticides and acaricides, the developed method allowed a quantification limit ranging from 0,01 mg/Kg to 0,30 mg/Kg. The recoveries of fortified samples ranged from 70 to 120%. The results showed that the matrix had a effect in the determination of the pesticides: prochoraz,difenoconazol, Fosmete, Azoxistrobina and Endosulfam Sulfate. It was found that the mango fruit were contaminated only by Procloraz; according to the Brazilian legislation, this pesticide can be present in mango.

The build–up of 6Li and 3He, that is, the strong thermal neutron absorbers or the so called "neutron poisons", in the beryllium reflector changes the physical characteristics of the reactor, such as reactivity, neutron spectra, neutron flux level, power distribution, etc.; furthermore,gaseous isotopes such as 3H and 4He induce swelling and embrittlement of the reflector. The SAFARI–1 research reactor, operated by Necsa at Pelindaba in South Africa, uses a beryllium reflector on three sides of the core, consisting of 19 beryllium reflector elements in total. This MTR went critical in 1965, and the original beryllium reflectors are still used. The individual neutron irradiation history of each beryllium reflector element, as well as the impact of beryllium poisoning on reactor parameters, were never well known nor investigated before. Furthermore, in the OSCAR{3 code system used in predictive neutronic calculations for SAFARI–1, beryllium reflector burn–up is not accounted for; OSCAR models the beryllium reflector as a non–burnable, 100% pure material. As a result, the poisoning phenomenon is not accounted for. Furthermore, the criteria and hence the optimum replacement time of the reflector has never been developed. This study presents detailed calculations, using MCNP, FISPACT and the OSCAR{3 code system, to quantify the influence of impurities that were originally present in the fresh beryllium reflector, the beryllium reflector poisoning phenomenon, and further goes on to propose the reflector's replacement criteria based on the calculated fluence and predicted swelling. Comparisons to experimental low power flux measurements and effects of safety parameters are also established. The study concludes that, to improve the accuracy and reliability of the predictive OSCAR code calculations, beryllium re flector burn–up should undoubtedly be incorporated in the next releases of OSCAR. Based on this study, the inclusion of the beryllium reflector burn–up chains is planned for implementation in the currently tested OSCAR–4 code system. In addition to beryllium reflector poisoning, the replacement criteria of the reflector is developed. It is however crucial that experimental measurements on the contents of 3H and 4He be conducted and thus swelling of the reflector be quantifed. In this way the calculated results could be verified and a sound replacement criteria be developed. In the absence of experimental measurements on the beryllium reflector, the analysis and quantifcation of the calculated results is reserved for future studies. / Thesis (M.Sc. Engineering Sciences (Nuclear Engineering))--North-West University, Potchefstroom Campus, 2011.

The build–up of 6Li and 3He, that is, the strong thermal neutron absorbers or the so called "neutron poisons", in the beryllium reflector changes the physical characteristics of the reactor, such as reactivity, neutron spectra, neutron flux level, power distribution, etc.; furthermore,gaseous isotopes such as 3H and 4He induce swelling and embrittlement of the reflector. The SAFARI–1 research reactor, operated by Necsa at Pelindaba in South Africa, uses a beryllium reflector on three sides of the core, consisting of 19 beryllium reflector elements in total. This MTR went critical in 1965, and the original beryllium reflectors are still used. The individual neutron irradiation history of each beryllium reflector element, as well as the impact of beryllium poisoning on reactor parameters, were never well known nor investigated before. Furthermore, in the OSCAR{3 code system used in predictive neutronic calculations for SAFARI–1, beryllium reflector burn–up is not accounted for; OSCAR models the beryllium reflector as a non–burnable, 100% pure material. As a result, the poisoning phenomenon is not accounted for. Furthermore, the criteria and hence the optimum replacement time of the reflector has never been developed. This study presents detailed calculations, using MCNP, FISPACT and the OSCAR{3 code system, to quantify the influence of impurities that were originally present in the fresh beryllium reflector, the beryllium reflector poisoning phenomenon, and further goes on to propose the reflector's replacement criteria based on the calculated fluence and predicted swelling. Comparisons to experimental low power flux measurements and effects of safety parameters are also established. The study concludes that, to improve the accuracy and reliability of the predictive OSCAR code calculations, beryllium re flector burn–up should undoubtedly be incorporated in the next releases of OSCAR. Based on this study, the inclusion of the beryllium reflector burn–up chains is planned for implementation in the currently tested OSCAR–4 code system. In addition to beryllium reflector poisoning, the replacement criteria of the reflector is developed. It is however crucial that experimental measurements on the contents of 3H and 4He be conducted and thus swelling of the reflector be quantifed. In this way the calculated results could be verified and a sound replacement criteria be developed. In the absence of experimental measurements on the beryllium reflector, the analysis and quantifcation of the calculated results is reserved for future studies. / Thesis (M.Sc. Engineering Sciences (Nuclear Engineering))--North-West University, Potchefstroom Campus, 2011.

Abstract The introduction of physiologically and therapeutically effective drugs in anaesthetic treatment has meant a significant change. Their discovery has thus contributed to a minimisation of their negative effects on a living organism. As a result, anaesthesiology has become more controllable and safer. These new drugs translate into more comfort for the patient in the course of anaesthesiology as well as his or her rapid recovery resulting in a shorter period of hospitalisation. The research of new physiologically and therapeutically effective substances is a pre-requisition of a potential higher standard of medical care. Older substances, e.g. Alkuronium and Gallamin, which, due to their undesirable effects, have come out of use, have lost their significance. Nowadays, these substances have been generally replaced by substances with an intermedial effect, e.g. Rokuronium and Cisatrakurium, which, compared with Alkuronium and Gallamin, show a minimum of undesirable effects. One of the foremost objectives of the current pharmaceutical research is to find a replacement of Sukcinylcholin, which, in spite of its known side effects, has had a non-substitutable position in urgent intubation. As a result, its use is limited to out-patient application and a certain selection of patient categories. Let us hope that we shall see a replacement of Sukcinylcholin being introduced in treatment in the near future. This would mean a final solution of problems arising from its side effects limiting its scope of application.

La roue des existences, image célèbre du bouddhisme himalayen, représente les différents mondes de renaissances, les causes et mécanismes de leurs enchaînements, elle illustre enfin la possibilité d’échapper au cycle samsarique. Les dates, la situation géographique, les emplacements des représentations, comme leur complexité et leur variété, suscitent de nombreuses questions qui nous ont conduit à étudier les textes canoniques anciens qui en posent les bases, à analyser les nombreux concepts représentés, mais aussi et surtout à examiner l’iconographie d’un corpus de soixante-dix-neuf roues réparties sur le territoire de quatre pays : l’Inde, le Népal, le Bhoutan et la Chine. Nos observations, résultat d’un long travail sur l’ensemble des informations et des thèmes contenus dans chaque roue, permettent de constater que la roue de la vie était connue dans un vaste territoire qui dépassait largement le monde himalayen, que sa fonction a évolué pendant une période de plus de quinze siècles, qu’il s’agit d’un thème très ancien toujours d’actualité, dont les variations révèlent le degré d’initiative des peintres et témoignent parfois d’ interprétations doctrinales différentes, reflétant des talents divers et le souci systématique de différencier chaque oeuvre des autres peintures. / One of the most famous images of Himalayan Buddhism is the wheel of existence (bhavacakra); it represents the various worlds of rebirths, the causes and mechanisms of their sequences and finally it illustrates the possibility of escaping the samsaric cycle. The age, the geographic situation, the complexity, the location and the variety of the representations raise many questions which lead to study the old canonical texts on which they are based, to analyze the many concepts represented, but also and especially examin the iconography of a corpus of seventy nine wheels to be found over the territory of the four countries which are today, India, Nepal, Bhutan and China. A long and extensive study of the vast amount of information contained in each wheel, makes it possible to say that the wheel of existence was known in a very large territory which greatly exceeded the Himalayan area, that its function evolved over a period of more than fifteen centuries, that it is a very old topic still relevant today and, that the works and the initiatives of the painters reveal variations which show their degrees of initiatives, sometimes different doctrinal interpretations, but also different talents and the systematic concern to be different from each other.

Devido à importância da agricultura para a economia do Brasil e para a dieta da população brasileira, um esforço contínuo tem sido feito para preservar a qualidade dos alimentos. Um dos mais importantes critérios de qualidade é a concentração correta dos pesticidas ou a não detecção destes nos alimentos. O objetivo deste trabalho é estudar o efeito matriz na analise de resíduos de pesticidas por cromatografia à gás em manga, a contaminação de mangas compradas na cidade de São Paulo por pesticidas e a otimização de um método multiresíduo neste tipo de matriz. O método empregado foi o utilizado pelo Governo Holandês adaptado de Lucke (1975), e constou da extração com acetona e partição em uma mistura diclorometano:hexano 1:1. O extrato foi concentrado e injetado em cromatógrafo à gás com detector de captura de elétrons e detector fotométrico de chama. Foram analisados 23 princípios ativos diferentes entre herbicidas, inseticidas, fungicidas e acaricidas; a metodologia empregada permitiu um limite de quantificação que variou de 0,01 mg/Kg a 0,30 mg/Kg. A recuperação de amostras fortificadas variou de 70 a 120%. Os resultados mostraram que a matriz apresenta uma grande influência na determinação dos princípios ativos Procloraz, Difenoconazol, Fosmete, Azoxistrobina e sulfato Endosulfam; o único princípio ativo encontrado nas amostras compradas no varejo foi o fungicida Procloraz com valores permitidos pela Legislação Brasileira. / Due to the importance of Agriculture for the economy of Brazil and for the diet of Brazilian population, a continuous effort is being made to preserve its high quality characteristics. One of the most important quality criteria is the right concentration or better not detectable pesticide residues. This work had the objective to study the matrix enhancement effect in gas chromatographic analysis of pesticide residue in mango fruit; the contamination of mango fruit by pesticide bought in Sao Paulo city and the optimization of the multiresidue method in this matrix. The employed method in the analysis was adapted from Lucke (1975), used by Netherlands Government; extraction with acetone and partition in a dichlorometane:hexane (1:1), and Gas Chromatographic determination with ECD and FPD. We studied about 23 active substances among herbicides, fungicides, insecticides and acaricides, the developed method allowed a quantification limit ranging from 0,01 mg/Kg to 0,30 mg/Kg. The recoveries of fortified samples ranged from 70 to 120%. The results showed that the matrix had a effect in the determination of the pesticides: prochoraz,difenoconazol, Fosmete, Azoxistrobina and Endosulfam Sulfate. It was found that the mango fruit were contaminated only by Procloraz; according to the Brazilian legislation, this pesticide can be present in mango.

Novos agentes terapêuticos que preservem as células <font face=\"Symbol\">&#946 do pâncreas e o controle do peso são importantes para o diabetes melittus tipo 2 (DM-2), constituindo uma importante área de investimento farmacêutico. Com o objetivo de contribuir com a toxinologia comparada de venenos de répteis e com a eventual descoberta de novos agentes insulinotrópicos, o presente estudo realizou a prospecção de compostos hipoglicemiantes análogos à exendina-4 (isolada de lagartos Heloderma) ou inibidores da dipeptidil-peptidase IV (DPP-IV) no veneno da serpente Bothrops jararaca. A espectrometria de massas identificou uma K49 Fosfolipase A2 inédita neste veneno. Inibidores da DPP-IV não foram encontrados. Porém, a existência de frações polipeptídicas deste veneno sem similares estruturais descritos, sem efeito na pressão arterial média, imunologicamente similares à exendina-4 e com efeito hipoglicemiante e provável capacidade de ligação ao receptor do peptídeo glucagon-símile tipo 1, caracterizaram, pela primeira vez, a ação de veneno de serpente sobre o metaboloma. / New therapeutic agents that protect pancreatic <font face=\"Symbol\">&#946 cells and regulate body mass are important to diabetes mellitus type 2 (DM-2). The search for these agents is one of the main objectives of investments made by pharmaceutical industries. To contribute to the comparative toxinology studies of reptile venoms and to reveal new insulinotropic agents, the present investigation searched for hypoglycemiant compounds such as exendin-4 analogues (isolated from Heloderma lizards) or dipeptidyl-peptidase IV (DPP-IV) inhibitors in the venom of the snake Bothrops jararaca. The mass spectrometry analysis identified a novel K-49 Phospholipase A2 in this venom. DPP-IV inhibitors were not found. However, the existence of polypeptide fractions from this venom without structural similarity with reported compounds, without effect on mean arterial blood pressure and with immunological similarity with exendin-4 and probable ability to bind to glucagon-like peptide type 1 receptor, led to the first characterization of snake venom activity on metaboloma.

Neste trabalho visamos otimizar o isolamento da BnP1, uma SVMP presente no veneno de B. neuwiedi, e isolar disintegrinas desse veneno, ambas originadas de precursores tipo P-II, analisando as seqüências de cDNA e a ação sobre plaquetas. A purificação da BnP1 foi por exclusão molecular e troca iônica; duas novas disintegrinas, D2 e D4, foram isoladas por cromatografia em fase reversa; e outra disintegrina, MS, foi caracterizada a partir do SDS-PAGE. As proteínas foram parcialmente seqüenciadas por espectrometria de massas. Diferentes cDNAs foram clonados a partir da glândula de veneno de B. neuwiedi e os precursores da BnP1 e MS se localizaram em um cluster que inclui SVMPs classe P-I e P-II. O precursor de D4 correspondeu a uma SVMP tipicamente P-II. A BnP1, ao contrário das disintegrinas, não inibiu a agregação plaquetária induzida por diferentes agonistas. Este trabalho indica ainda que a biossíntese de SVMPs da classe P-II pode envolver processamento de mRNA, um novo mecanismo de geração de diversidade das SVMPs. / The aim of this study was to optimize the isolation of BnP1, a SVMP from B. neuwiedi venom, and isolate new disintegrins from this venom, both originated from P-II class precursors, and analyze the sequence of their precursors and their action on platelets. BnP1 was isolated by size exclusion and anion-exchange chromatography; the disintegrins D2 and D4 by reverse-phase chromatography and MS was isolated from SDS-PAGE. These proteins were partially sequenced by mass spectrometry. Several SVMPs cDNAs were cloned from B. neuwiedi venom gland, and BnP1 and MS precursors localized in a cluster enclosing P-I and P-II SVMPs. MS cDNA was tipical of P-II class of SVMPs. BnP1, unlike the disintegrins, was not able to inhibit platelet aggregation induced by different agonists. This work suggested that the biosynthesis of class P-II SVMPs include mRNA processing as a further step to generate venom diversity.