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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Atendimentos registrados no Centro de Controle de Intoxicações de Campinas : análise do período de 1998 a 2011 / An analysis of cases registered at the Poison Control Center of Campinas between 1998 and 2011

Costa, Aline de Oliveira, 1987- 02 September 2015 (has links)
Orientador: Herling Gregorio Aguilar Alonzo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T19:40:04Z (GMT). No. of bitstreams: 1 Costa_AlinedeOliveira_M.pdf: 9346622 bytes, checksum: e631fbbeb424ab7ad87d0fa2cdb55851 (MD5) Previous issue date: 2015 / Resumo: A ocorrência de exposições e intoxicações como um problema de saúde pública tem sido amplamente relatada na literatura. Embora o atendimento ao intoxicado possa ser realizado em âmbito hospitalar ou ambulatorial, são os Centros de Informação e Assistência Toxicológica (CIATs) que fornecem as informações especializadas para este atendimento. Na cidade de Campinas, o Centro de Controle de Intoxicações (CCI) é referência nos atendimentos das exposições tóxicas provenientes da região. O presente trabalho teve por objetivo descrever os casos de exposições e intoxicações atendidas pelo CCI de Campinas, no período de janeiro de 1998 a dezembro de 2011. Para tal, foram analisadas variáveis relacionadas ao atendimento, ao paciente, à exposição, ao agente tóxico e à evolução do caso. Os dados utilizados foram obtidos no banco de dados do CCI-Campinas, no qual está contido o registro dos atendimentos realizados no período estudado e analisados através do software Epi InfoTM CDC/WHO versão 7.1.3.10. O trabalho foi aprovado pelo Comitê de Ética em Pesquisa sob parecer nº 515.290/2013. Nos 14 anos estudados foram atendidos 51.665 casos, destes 27,9% foram classificados como exposições e 72,1% como intoxicações. Foi observado que 51,2% dos pacientes eram do sexo masculino e 48,3% do sexo feminino. A faixa etária predominante foi a de 1 a 4 anos com 28,6% dos casos, seguida pela faixa etária de 20 a 24 anos, com 9,4%. A circunstância prevalente foi a acidental, com 60,2% dos registros, seguida pela tentativa de suicídio, com 24,8%. Entre os principais grupos de agentes tóxicos, 32,5% eram medicamentos, 21% animais peçonhentos, 16,5% produtos químicos de uso domiciliar e 9,4% agrotóxicos. Como desfecho, 77,9% dos casos apresentaram a cura como evolução e, 0,6% evoluíram para óbito. A caracterização do perfil dos atendimentos realizados pelo CCI-Campinas, permitiu o conhecimento de suas especificidades e relevância para a saúde pública na região / Abstract: The occurrence of exposures and poisoning as a public health problem has been widely reported in the literature. Although the treatments to poisoned people can be performed in hospitals or outpatient basis, the Poison Control Centers are the service that provides specialized information for treatments. In the city of Campinas, the Poison Control Center is responsible for the treatment for toxic exposure from the region. This present study aims to describe the cases of toxic exposures treated by the Poison Control Centers of Campinas (CCI-Campinas), from january 1998 to december 2011. For this, variables were analyzed regarding treatment, patient, exposure, the toxic agent and evolution of the case. The data used were obtained from the database of the Poison Control Centers of Campinas, which contains the record of treatments made during the study period and analyzed using software Epi InfoTM CDC/WHO version 7.1.3.10. The work was approved by the Research Ethics Committee under report number 515.290/2013. In the 14 years studied 51.665 cases were treated, 27.9% of these were classified as exposures and 72.1% as poisoning. It was observed that 51.2% of patients were male and 48.3% female. The predominant age group was 1-4 years old, with 28.6% of cases, followed by the age group 20-24 years old, 9.4%. The prevalent condition was the accidental one, with 60.2% of the records, followed by attempted suicide, with 24.8%. Among the major groups of toxic agents, 32.5% were medications, 21% were poisonous animals, 16.5% were chemical products for domestic use and 9.4% were pesticides. As an outcome, 77.9% of cases evolved to healing, and 0.6% of cases died. The characterization of the profile of care provided by the CCI-Campinas allowed the knowledge of theis specific features and relevance to public health in the region / Mestrado / Epidemiologia / Mestra em Saúde Coletiva
32

Något främmande i ditt blod : Undersökning av gifter i juridisk medicinska handböcker 1804-1838

Strand, Daniel January 2022 (has links)
Poison has been a problem for doctors for a very long time. During the 19th centuary forensic medicine started to establish themself as their own institution. This essay includes three parts. The first part investigates how poison exist in many different forms, and how doctors during the 19th centuary defined and classified them. Both the definition aswell as the classification of poison varied from doctor to doctor. But with time both the definition and classification started to become standardized, and played a part with the professionalization of poison. The second part investigate the poison in the body, and what kind of methods doctors used in order to prove it was poisoning. Many of the methods used was deemed uncertain, and couldn’t always be used as proof. The methods used towards the begining of the 19th centuary was used a couple decades later, even if the result from them were uncertain. A common problem for the doctors was that the symptoms from the poison shared similarities with different diseases. The third part investigate the doctors role in the forensic medicine field. The doctors towards the begining of the 19th centuary had a problem with their oaths. They were split between two different oaths, that made them sometimes unable to perform their duties a neutral party. Towards the 1830’s there were many reforms that was passed in the medicla field, and with thoes reforms the doctor ended up with only one oath to follow. Which made them able to stay as a neutral party.
33

Étude expérimentale et thermodynamique du système Zr-Er-H / Experimental and thermodynamic study of the system Zr-Er-H

Mascaro, Aurore 12 November 2012 (has links)
Ce travail de thèse s'inscrit dans le cadre du développement d'une solution innovante d'empoisonnement neutronique homogène, par insertion d'erbium, au cœur des gaines de combustible en alliage de zirconium utilisées dans les réacteurs à eau pressurisée. Dans cette étude réalisée par le CEA, la géométrie envisagée est une gaine triplex constituée d'un liner interne faiblement enrichi en erbium, compris entre deux couches d'alliage industriel base zirconium. Dans le cœur du réacteur, l'eau se dissocie à la surface de la gaine. Il est donc intéressant d'évaluer les interactions potentielles entre l'hydrogène et l'alliage Zr-Er du liner. Cela nécessite de connaître le système ternaire Er-H-Zr ainsi que les systèmes binaires associés. Ceci peut être obtenu par détermination expérimentale et grâce à la modélisation thermodynamique. Les deux techniques ont été utilisées au cours de cette thèse. Les systèmes binaires Er-Zr et H-Zr ont été déterminés expérimentalement et modélisés dans la littérature. Le système binaire Er-H en revanche était très mal connu. Nous avons étudié ce système expérimentalement. Il a ensuite été modélisé avec l'approche Calphad. Nous obtenons une nouvelle évaluation du système binaire Er-H, avec des limites de phases différentes de ce qui avait été proposé précédemment. Dans le but de déterminer les limites des domaines de phases et de mettre en évidence l'éventuelle existence d'un composé ternaire dans le système ternaire Er-H-Zr, une étude expérimentale a été menée. Une technique originale a été utilisée : le dosage chimique des éléments d'alliage a été fait par ERDA combinée à la RBS. Cette étude nous a permis de proposer une coupe isotherme expérimentale à 350°C de ce système ternaire. Concernant la modélisation, les trois systèmes binaires ont été rendus compatibles dans le but de calculer le diagramme de phases ternaire par projection des binaires. Le calcul obtenu est en bon accord avec la coupe isotherme expérimentale. Enfin, par le biais de campagnes d'essais de traction, nous avons évalué l'impact de l'ajout d'erbium et/ou d'hydrogène sur le comportement mécanique du zirconium de pureté industrielle. Nous avons ainsi mis en évidence un effet durcissant de l'erbium et de l'hydrogène sans pour autant que ces effets soient corrélés. Aucun de ces résultats n'est rédhibitoire pour l'utilisation de cet alliage Er-Zr en tant que liner dans le concept triplex / This work at CEA is being achieved in the framework of the development of an innovating concept including the neutronic solid burnable poison, such as erbium, inside the cladding of pressurized water reactors. These new claddings are constituted by a liner of a zirconium base alloy slightly enriched in erbium between two liners of industrial zirconium alloys. Into the reactor core, the water dissociates at the surface of the cladding. So it is interesting to evaluate the interactions between the hydrogen released and the Zr-Er alloy. To do so, the Er-H-Zr ternary system has to be determined such similarly to its associated binaries. This can be done by experimental determination and by thermodynamic modelling. Both techniques were used in this work. Er-Zr and H-Zr have already been studied experimentally and modelled, but the Er-H binary system is almost unknown. So, we studied it experimentally. Then, it has been modelled using the Calphad method. We obtain a new evaluation of the Er-H binary system with phases limits rather different than what has been proposed in the literature. In order to determine the phase limits and, the potential existence of a ternary compound in the Er-H-Zr ternary system, an experimental study has been carried out. An original technique has been used to obtain the chemical compositions: ERDA combined with RBS. In this study, we propose a new isothermal section at 350°C of the Er H-Zr ternary system. About the modelling, the compatibility of the three modelled binaries has been checked in order to optimize the ternary system by the projection of the three binaries. The calculation obtained is in good agreement with the experimental isothermal section at 350°C determined in our work. Finally, uniaxial tensile test campaigns have been conducted to evaluate the impact of erbium and/or hydrogen on the mechanical properties of an industrial zirconium pure alloy. We evidenced a hardening effect of erbium and hydrogen but these effects are not correlated. None of these results is prohibitive for the use of this Er Zr alloy as a liner in the triplex concept
34

Crimes de poison dans la Bologne médiévale et moderne (XIVe-XVIIe siècle) / Poison crimes in medieval and modern Bologna (XIV-XVII centuries)

Buyck, Margaux 26 November 2016 (has links)
Longtemps laissé dans l’ombre historiographique, l’empoisonnement fait l’objet cesdernières années d’un intérêt renouvelé de la part des historiens. Dans le sillon de ces ultimes recherches, cette thèse propose une étude sur les crimes de poison à Bologne entre le XIVe et le XVIIe siècle. Si de nombreux chercheurs défendent l’idée que l’empoisonnement est un objet historique « transpériode », aucune étude n’a encore confronté explicitement le Moyen Age à l’époque moderne souvent présentés comme antagonistes. Or, l’analyse du phénomène criminel sur près de quatre siècles permet de mieux appréhender les évolutions et surtout les permanences de l’empoisonnement criminel, de ses modalités et des réactions de la société face à celui-ci. Les archives bolonaises se sont avérées être un terrain de recherches relativement dense, fournissant un corpus de près de 180 affaires dont un nombre important de sources judiciaires inédites. Bologne constitue à ce titre un véritable carrefour pour l’histoire du droit, de la médecine, du fait de son université prestigieuse, mais aussi en ce qui concerne l’étude de la société urbaine. Cette richesse documentaire permet d’envisager une réflexion à l’intersection de l’histoire de la criminalité et de la justice, de l’histoire de la médecine et de l’histoire sociale. Cette approche plurielle de la thématique donne l’opportunité d’élargir l’éventail des témoignages sur l’empoisonnement en confrontant tour à tour doctrines, représentations culturelles et mentales de l’empoisonnement et effectivité du crime et de ses conséquences dans les actes de la pratique. / Long left in the shadow of History, poisoning is subject of a renewed interest byhistorians for the last few years. Following theirs latest researches, this thesis offers a study of poison crimes in Bologna between the XIV and XVII centuries. While many researchers stand for the idea of poison crime as an historical "trans-period" object, no study has yet explicitly faced the middle-age and the modern era often presented as antagonist. But the analysis over nearly four centuries of this criminal phenomenon is insightful on the evolution and especially the persistence of criminal poisoning, its ways and means, and the society reactions to it. The Bolognese archives proved to be a relatively dense research field, providing a corpus of nearly 180 cases, of which a large number of unprecedented/unknown judicial sources. Bologna thus constitutes a true crossroads of legal and medical History, due to its prestigious university, but also on study of urban society. This documentary wealth leads a questioning at the interface of History of crime and justice, History of medicine and social History. This multifaceted approach of the topic is an opportunity to expand the range of testimonies on poisoning and confronts, by turns, doctrine, cultural and mental perception of poisoning and the effectiveness of the crime, and practical consequences.
35

Poison Control Center Foodborne Illness Surveillance

Derby, Mary Patricia January 2008 (has links)
Foodborne illnesses continue to have a negative impact on the nation's health, accounting annually for an estimated 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths in the United States. Syndromic surveillance systems that analyze pre-diagnostic data, such as pharmaceutical sales data are being used to monitor diarrheal disease. The purpose of this study is to evaluate the usefulness of a poison control center (PCC) data collection and triage system for early detection of increases in foodborne illnesses.Data on calls to the Arizona Poison and Drug Information Center (APDIC) reporting suspected foodborne illnesses, and Pima County Health Department (PCHD) enteric illness reports were obtained for July 1, 2002 - June 30, 2007. Prediction algorithms were constructed using the first two and a half years, and validated in the remaining two and a half years. Multiple outcomes were assessed using unadjusted and adjusted raw counts, five and seven day moving averages, and exponentially weighted moving averages. Sensitivity analyses were conducted to evaluate model performance. Increases in PCHD laboratory reports of enteric illnesses were used as a proxy measure for foodborne disease outbreaks.Over the five year study period there were 1,094 APDIC calls reporting suspected foodborne illnesses, and 2,433 PCHD enteric illness cases. Seventy-five percent of cases were reported to PCHD within 23 days of symptom onset. In contrast, 62% of callers contacted APDIC within 24 hours of symptom onset. Forty percent of PCHD cases were missing symptom onset dates, which necessitated constructing and validating predictive algorithms using only those PCHD cases with known symptom onset dates.None of the prediction models performed at sensitivity levels considered acceptable by public health department standards. However, it is possible that a temporal relationship actually exists, but data quality (lack of outbreak dates, and missing symptom onset dates) may have prevented its detection. The study suggests that current surveillance by PCCs is insufficient as a univariate model for syndromic surveillance of diarrheal illness because of low caller volume reporting suspected foodborne illnesses; this can be improved. Methods were discussed to utilize PCCs for active surveillance of foodborne illnesses that are of public health significance.
36

Mutualism Stability and Gall Induction in the Fig and Fig Wasp Interaction

Martinson, Ellen O'Hara January 2012 (has links)
The interaction between figs (Ficus spp.) and their pollinating wasps (fig wasps; Chalcidoidea, Hymenoptera) is a classic example of an ancient and apparently stable mutualism. A striking property of this mutualism is that fig wasps consistently oviposit in the inner flowers of the fig syconium (gall flowers, which develop into galls that house developing larvae), but typically do not use the outer ring of flowers (seed flowers, which are pollinated and develop into seeds). This dissertation explores the potential differences between gall and seed flowers that might influence oviposition choices, and the unknown mechanisms underlying gall formation. To identify the microbial community that could influence oviposition choice, I identified fungi in both flower types across six species of Ficus. I found that whereas fungal communities differed significantly as a function of developmental stages of syconia and lineages of fig trees, communities did not differ significantly between receptive gall and seed flowers. Because secretions from the poison sac that are deposited at oviposition are thought to be important in gall formation by both pollinating fig wasps and non-pollinating, parasitic wasps, I examined poison sac morphology in diverse galling wasps from several species of Ficus in lowland Panama. I found that the size of the poison sac was positively associated with egg number across pollinating and non-pollinating fig wasps. Finally to determine difference in defense and metabolism between gall and seed flowers, and to identify genes involved in galling, I compared gene expression profiles of fig flowers at the time of oviposition choice and early gall development. I found a prominence of flavonoids and defensive genes in both pollinated and receptive gall flowers of Ficus obtusifolia, and revealed detectable differences between gall flowers and seed flowers before oviposition. Several highly expressed genes were also identified that have implications for the mechanism of gall initiation. This dissertation explores previously unstudied aspects of the fig and fig wasp mutualism and provides important molecular tools for future study of this iconic and ecologically important association.
37

Ärztliche Compliance hinsichtlich Empfehlungen des Giftinformationszentrums-Nord / Medical adherence according to recommendations of the GIZ-Nord Poisons Centre

Radamm, Cornelius 17 August 2016 (has links)
Mit Einrichtung der Giftinformationszentren in der zweiten Hälfte des zwanzigsten Jahrhunderts konnten Ärzte erstmalig auf der Basis einer evidenzbasierten klinischen Toxikologie beraten werden. Parallel zu anderen medizinischen Fachgesellschaften wurden von den europäischen und nordamerikanischen Fachgesellschaften Empfehlungen bezüglich verschiedener Therapieformen der klinischen Toxikologie erarbeitet. Als Beispiele sind die Maßnahmen der primären und sekundären Giftentfernung und der Einsatz von Antidota zu nennen. Ob Ärzte den Empfehlungen der Giftinformationszentren folgen, ist bisher wenig untersucht worden. In einer prospektiven Untersuchung anhand von 206 Fällen wurde analysiert, ob und in welchem Ausmaß den Empfehlungen des GIZ-Nord gefolgt wurde. Darüber hinaus wurden Daten zu Alter und Geschlecht der Patienten, zum Vergiftungsmodus und zu den eingenommenen Noxen erhoben. Es wurden folgende Fragestellungen formuliert: 1. In welchem Ausmaß wird den Empfehlungen des GIZ-Nord gefolgt? 2. Gibt es Einflussfaktoren wie Alter und Geschlecht der Patienten, Vergiftungsmodus, die Noxengruppe sowie sprachliche Verständigungsschwierigkeiten der anrufenden Ärzte? 3. Wie hoch ist die Zufriedenheit der Ärzte mit der Beratung des GIZ-Nord? Die Fragen ließen sich folgendermaßen beantworten: 1. Empfehlungen zu diagnostischen Maßnahmen wurden in 89% der Fälle befolgt, therapeutische Maßnahmen zur primären Giftentfernung und den Einsatz eines Antidots betreffend in 74%, Maßnahmen zur sekundären Giftentfernung in 61% und spezifische therapeutische Maßnahmen in 66% der Fälle. Insgesamt wurde den Empfehlungen des GIZ-Nord in 64% der Fälle vollständig gefolgt. 2. Während das Patientengeschlecht und der Vergiftungsmodus “suizidal” keinen Einfluss auf ärztliche Compliance gegenüber den Empfehlungen des GIZ-Nord aufwiesen, waren Compliance-Unterschiede bezüglich des Patientenalters und der eingenommenen Noxen zu erkennen. Im Vergleich zu anderen Altersgruppen wies die Altersgruppe der 15-19-Jährigen eine mit 41% vergleichsweise niedrige Compliance auf. Ebenfalls wiesen sich Antiepileptika wie Carbamazepin und Barbiturate, die bei Vergiftungen einer komplexeren Behandlung bedürfen, als Noxengruppe mit geringerer ärztlicher Compliance aus. Eine auffällige Compliance-Differenz konnte bei sprachlichen Verständigungsschwierigkeiten ärztlicher Anrufer gesehen werden. Eine lückenlose Befolgung konnte in 70% der Fälle bei uneingeschränkter sprachlicher Kommunikation und in 13% bei sprachlichen Verständigungsschwierigkeiten aufgezeigt werden. 3. Eine hohe Zufriedenheit mit der Beratung durch das GIZ-Nord konnte in 97% der Fälle verzeichnet werden.
38

Avaliação da neutralização de importantes atividades tóxicas induzidas pelos principais peixes peçonhentos brasileiros por um soro poliespecífico produzido em murinos. / Evaluation of the neutralization of important toxic activities induced by brazilian fish venoms by murine polyspecific antiserum.

Soliani, Fernanda Miriane Bruni 24 November 2008 (has links)
No Brasil acidentes por peixes peçonhentos como Thalassophryne nattereri, Cathorops spixii, Scorpaena plumieri e Potamotrygon gr orbygnyi vêm sendo relatados. O quadro clínico é caracterizado por efeitos locais e sistêmicos. Para esses acidentes não existe tratamento adequado e eficiente. A soroterapia é um eficiente tratamento para reverter os efeitos causados por venenos. Diante disso nosso objetivo é a obtenção de um soro poliespecifico através da junção de soros monoespecificos produzidos em camundongos e avaliar a sua capacidade de neutralização das atividades tóxicas induzidas pelos principais peixes peçonhentos brasileiros. As alterações induzidas na microcirculação foram abolidas na pré-incubação e no tratamento imediato, somente dano em fibra muscular induzido pelo C. spixii exigiu soro na proporção 1:2. Obtivemos o controle parcial da nocicepção e edema. O efeito sistêmico foi eficientemente neutralizado. Nossos dados nos permitem sugerir o uso de soro poliespecífico nos envenenamentos causados pelos peixes T. nattereri, S. plumieri, C. spixii e P. gr orbygnyi. / Envenoming induced by venomous fish represents a great cost brazilian communities. Victims develop local and systemic symptoms. The most frequent founded are Thalassophryne nattereri, Cathorops spixii, Scorpaena plumieri and Potamotrygon gr orbygnyi. The anti-inflammatory drugs used are not efficient. After the accident, the passive transfer of heterologous specific antibodies allows that immediate toxic effect can be neutralized in the victims. The aim of this work was to produce in mice polyspecific antivenom and evaluation the neutralization of the main toxic effects induced by the brazilian venomous fish. The effects induced in microcirculation were abolished by the polyspecific antiserum, except for the effects caused by C. spixii in muscular fibers where was necessary a proportion of 1:2. The polyspecific antiserum controlled the edematogenic and nociceptive activities and the airway inflammation.These data allow us to suggest the use of polyspecific antiserum in the treatment of the pathological effects provoked by the most frequent brazilian venomous fish.
39

Estudo do processo de densificação de combustíveis urânio-érbio para reatores do tipo água leve / Study of densification the uranium-erbium fuel for light water reactor

Freitas, Artur Cesar de 22 November 2017 (has links)
O processo de sinterização de pastilhas de UO2-Er2O3 tem sido investigado devido à sua importância na indústria nuclear e ao comportamento complexo durante a sinterização. O presente estudo contempla o desenvolvimento de combustíveis nucleares para reatores de potência visando aumentar a sua eficiência no núcleo do reator por meio da elevação da taxa de queima. O érbio é indicado para ciclos mais longos, significando menos paradas para troca de combustível e menos rejeitos. Neste trabalho foi estudado o uso de óxido de érbio variando as concentrações na faixa de 1-9,8%, o qual foi adicionado ao pó de UO2 e ao lubrificante sólido ADS por meio de mistura mecânica, visando verificar a taxa de densificação e um possível bloqueio de sinterização. Os pós foram compactados e as pastilhas foram sinterizadas a 1700°C sob atmosfera de H2. Os resultados demonstram um característico bloqueio da sinterização no sistema UO2-Er2O3, porém de forma mais discreta do que no sistema UO2-Gd2O3, o qual ocorre no intervalo de temperatura de 1500 a 1700°C, retardando a densificação. Os ensaios dilatométricos indicam uma retração de 21,87% quando utilizado o Er2O3 a 1% de concentração em massa. Essa retração é maior do que as encontradas com concentrações superiores ou mesmo sem adição do veneno queimável, nos fornecendo um melhor grau de incorporação do elemento érbio, resultando em pastilhas com densidade adequada para uso como combustível nuclear. / The sintering process of UO2-Er2O3 pellets has been investigated because of its importance in the nuclear industry and the complex behavior during sintering. The present study includes the development of nuclear fuel for power reactor in order to increase the efficiency of the fuel through longer refueling intervals. The erbium is indicated for longer cycles, which means less stops to refueling and less waste. In this work, it was studied the use of erbium oxide by varying the concentrations in the range of 1-9.8%, which was added to UO2 powder through mechanical mixing, aiming to check the rate of densification and a possible sintering blockage. The powders were pressed and sintered at 1700°C under hydrogen atmosphere. The results show a sintering blockade in the UO2-Er2O3 system that occurs in the range of 1500-1700°C temperature. Dilatometric tests indicate a retraction of 21.87% when used Er2O3 at 1% mass concentration. This retraction is greater than is observed with higher concentrations or even without the addition of the burnable poison, providing us with a better degree of incorporation of the element erbium, resulting in pellets with density suitable for use as nuclear fuel.
40

Isolamento, caracterização e atividade anti-leishmania chagasi e anti-trypanosoma cruzi de compostos bioativos de venenos de anfíbios brasileiros / Isolation, characterization, antileishmanial and antitrypanosomal activity of bioactive compounds from brazilian amphibian poisons

Pinto, Erika Gracielle 29 February 2012 (has links)
Dentre as doenças parasitárias tropicais, as causadas por protozoários se apresentam como um grande desafio para a saúde pública, sendo representadas pela leishmaniose e doença de Chagas. Afetam grandes populações marginais ao processo econômico globalizado, e desta forma, não são vistas como mercados potenciais. O presente projeto visou o isolamento de novos compostos naturais de venenos animais com atividade anti-Leishmania e anti-T. cruzi. O presente estudo fracionou por diferentes técnicas cromatográficas, os venenos dos anfíbios Siphonops annulatus, Corythomantis greeningi, Aparasphenodon brunoi e Phyllomedusa hypochondrialis, visando o isolamento de peptídeos e metabólitos secundários através de ensaios biomonitorados. Utilizando-se a espectrometria de massas e seqüenciamento por degradação química de Edman, foi possível a caracterização bioquímica de cinco peptídeos ativos da secreção de Phyllomedusa hypochondrialis, sendo estes a bradicinina, as dermaseptinas 1 e 4 e as filoseptinas 7 e 8. Os peptídeos apresentaram uma Concentração Efetiva 50% (CE50) variando entre 0,7 a 20 ?g/mL em L. (L.) infantum chagasi e T. cruzi, com baixa ou nenhuma citotoxicidade para células de mamíferos nas concentrações testadas. Além disso, a separação química da secreção do anfíbio Siphonops annulatus forneceu uma fração altamente ativa em promastigotas de L. (L.) infantum chagasi, com CE50 0,065 ?g/mL, porém com toxicidade bastante elevada para macrófagos peritoneais e nenhuma seletividade nas formas intracelulares. Estudos ultraestruturais de Leishmania demonstraram severos danos mitocondriais, além da formação de grande vacúolos citoplasmáticos, levando o parasita a morte em poucas horas. O presente estudo demonstrou o potencial de peptídeos e metabólitos secundários de venenos de anfíbios, que se adequadamente estudados, poderão contribuir como novos protótipos de fármacos para a doenças negligenciadas. / Among the tropical parasitic diseases, those caused by protozoa present a major challenge to public health, being represented by leishmaniasis and Chagas disease. Affect large populations marginal to the global economic process, and thus are not seen as potential markets. This project aimed the isolation of new natural compounds in animal venoms with anti-Leishmania activity and anti-T. cruzi. The present study fractionated by different chromatographic techniques, the poisons of the amphibians Siphonops annulatus, Corythomantis greeningi, Aparasphenodon brunoi and Phyllomedusa hypochondrialis, aiming the isolation of peptides and secondary metabolites through bioguided assays. By using mass spectrometry and sequencing by Edman degradation, it was possible to do the biochemical characterization of five active peptides from the poison of Phyllomedusa hypochondrialis, as bradykinin, dermaseptins 1 and 4 and phylloseptins 7 and 8. The peptides showed a 50% Effective Concentration (EC50) ranging from 0.7 to 20 ?g/mL in L. (L.) infantum chagasi and T. cruzi, with little or no cytotoxicity to mammalian cells at the tested concentrations. In addition, the chemical separation of the poison of the amphibian Siphonops annulatus provided a highly active fraction against promastigotes of L. (L.) infantum chagasi, with an EC50 of 0.065 ?g/mL, but highly toxicity to peritoneal macrophages and without selectivity against the intracellular forms of Leishmania. Ultrastructural studies of Leishmania showed severe mitochondrial damages and the formation of large cytoplasmic vacuoles, leading to parasite death within few hours. The present study demonstrated the potential of peptides and secondary metabolites of amphibian poisons, and if adequately studied, may contribute as prototypes of new drugs for neglected diseases.

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