Submitted by Anderson Silva (avargas@icict.fiocruz.br) on 2012-09-13T11:58:10Z No. of bitstreams: 1 Dissertação ClaudioMachado.pdf: 8617223 bytes, checksum: 5938f8ebba53a413c9f171550d4ec9af (MD5) / Made available in DSpace on 2012-09-13T11:58:10Z (GMT). No. of bitstreams: 1 Dissertação ClaudioMachado.pdf: 8617223 bytes, checksum: 5938f8ebba53a413c9f171550d4ec9af (MD5) / Instituto Vital Brazil. Divisão de Herpetologia. Niterói, RJ, Brasil / Nítidas divergências foram verificadas ao comparar os acidentes crotálicos ocorridos no Estado do Rio de Janeiro no período de 2001 a 2010, disponibilizados na Internet pelo Sistema de Informação de Agravos de Notificação (SINAN WEB), com a distribuição geográfica de ocorrência de Crotalus durissus no Estado. Com base nas informações sobre a sintomatologia relatada na literatura especializada, foram verificadas as manifestações clínicas existentes nas fichas de investigação para acidentes com animais peçonhentos e determinados os padrões para reconhecer com segurança os acidentes crotálicos. Dessa forma, com base nos dados de acidentes crotálicos registrados pela Secretaria de Estado de Saúde e Defesa Civil do Rio de Janeiro (SESDEC), foi analisada a coerência na sintomatologia apresentada; a distribuição das freqüências de soro e o número de ampolas aplicadas nos acidentes notificados como crotálicos, nos casos leves, moderados e graves. Concluiu-se que as notificações dos acidentes crotálicos no Estado do Rio de Janeiro neste período não refletem a realidade desse agravo e são feitas sugestões para a melhoria da estrutura da rede de informação para acidentes com animais peçonhentos no Brasil. / Significant differences were observed when comparing crotalic accidents which occurred in the State of Rio de Janeiro for the period 2001-2010, available on the Internet for Information System for Notifiable Diseases (SINAN WEB), with the geographical distribution of Crotalus durissus in the mentioned State. Based on the information of the symptoms reported in the literature, we aimed to assess the existing clinical report forms of accidents with venomous animals and to recognize certain patterns of crotalic accidents. Thus, based on the recorded crotalic accident data registred by State Department of Health and Civil Defense of Rio de Janeiro (SESDEC), we analyzed the consistency of the symptoms presented, the frequency of the distribution of serum and the number of ampoules applied in crotalic accidents reported as in mild, moderate and severe. It was concluded that the reports of crotalic accidents in the State of Rio de Janeiro, for this period, does not reflect the reality of this condition and some suggestions are made for improving the structure of the information network for accidents with venomous animals in Brazil.

Orientador: Leonilda Maria Barbosa dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-07T03:41:32Z (GMT). No. of bitstreams: 1 Castro_FabianoRobertode_M.pdf: 943470 bytes, checksum: 271c21deb3b25015f9737d33adf49814 (MD5) Previous issue date: 2006 / Resumo: A Síndrome de Guillain-Barré (SGB) é uma doença desmielinizante do sistema nervoso periférico (SNP). Baseado principalmente nas similaridades clínicas e histopatológicas a Neurite Experimental Auto-imune (EAN) tem sido extensivamente usada como modelo de estudo da SGB. A EAN é uma doença auto-imune, que pode ser experimentalmente induzida em ratos geneticamente suscetíveis através da imunização com os componentes da mielina de nervos periféricos tais como os peptídeos P0 e P2 , ou ainda por transferência adotiva de lifócitos T CD4+ do tipo Th1. Diferentes tentativas de tratamentos para a SGB têm sido estudadas, dentre elas pode-se citar a plasmaferese, o uso de anticorpos monoclonais, administração de corticóides e a imunossupressão global através da administração de intérferon ß. A utilização de venenos totais de serpentes, ou frações deles, já demonstrou bons resultados na tentativa de tratamento de alguns modelos de doenças auto-imunes como a diabetes auto-imune insulino dependente, lúpus e encefalomielite experimental auto-imune (EAE). No presente trabalho foi estudado o efeito de uma fração do veneno da cascavel sul americana Crotalus durissus terrificus (Cdt), a crotapotina, no modelo de EAN. São apresentadas evidências de que tanto a administração intraperitoneal (IP) como a oral de crotapotina reduz significativamente a gravidade da EAN induzida em ratos Lewis, associada a um significativo declínio na resposta proliferativa das células T neuritogênicas, assim como diminuição de infiltrados de células mononucleares no nervo ciático dos os animais / Abstract: Biomedical research in which venom components are being investigated for their potential as novel therapeutic agents has emerged as an interesting option. Crotapotin which is a fraction of the venom of the rattlesnake Crotalus durissus terrificus, has been described as an antinflammatory that acts on the innate arm of the immune response. Here we have demonstrated that intraperitoneal (IP), as well as oral administration of crotapotin significantly reduces the severity of experimental autoimmune neuritis (EAN), an experimental model for Guillain-Barré Syndrome. The reduction of the severity of the disease is associated with a reduction in the mononuclear cells infiltrating in the sciatic nerve and a significant decrease in the lymphocyte proliferative response to neuritogenic peptide / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Global biodiversity is declining as a direct result of anthropogenic climate change. Ectothermic species have become focal organisms for studying the ecological effects of altered climates due to the clear relationship between environmental temperatures and ectotherms’ basic physiological functions. Historically, examinations of these effects have focused heavily on heliothermic lizards, and most others have tended to focus on single populations or sympatric species within a single community. Addressing the longterm energetic implications of environmental temperature variation will provide valuable insight into the cascading physiological effects that certain populations or species may experience as a result of altered climates. In this study, we used thermal and behavioral data collected between 2010 and 2017 from four distinct populations of Pacific rattlesnakes (Crotalus oreganus) on the Central Coast of California. Two of these populations occupy thermally mild, coastal habitats while the other two occupy more thermally dynamic, inland habitats. Using operative temperature models, surgically implanted temperature loggers, and radiotelemetry, we collected data on the thermal microhabitats available within each of these study sites as well as field active body temperatures for 85 individual snakes. With the addition of a lab-derived preferred body temperature range, we determined the thermal quality of each site and the thermoregulatory accuracy of snakes from each population. Field behavioral observations, gathered from snakes at all four sites simultaneously during the year 2017, revealed how snakes utilize the thermal landscape and adjust thermoregulatory behavior to mitigate the effects of different climates. Although overall thermal quality was best at coastal sites, thermal quality of the microhabitats within each site varied greatly. Consistent with findings in other squamate reptiles, inland snakes thermoregulated more accurately, despite being in more thermally constrained environments. Despite the fact that coastal snakes had lower mean field active body temperatures, the preferred body temperatures of snakes were the same across all four sites. However, field active body temperatures were consistently lower than the preferred range, suggesting there are additional variables that influence thermoregulatory behavior. Using established equations estimating the resting metabolic rates of snakes based on body mass and temperature, we calculated resting metabolic rate and annual baseline maintenance energy expenditure for each population. Coastal snakes, which had lower field active body temperatures, had overall lower metabolic rates than inland snakes, but upon correcting for mass, snakes at neither coastal nor inland sites differed in metabolic rates. Therefore, the majority of the differences observed in metabolic rates are driven by body size and not field-active body temperature. Inland snakes need, on average, approximately 1.6x more food annually than coastal snakes. Due to overall low resting metabolic rates, this translates to snakes at all sites needing less than one ground squirrel (their most common food item on the Central Coast) per year to fuel basic physiological functions. Finally, we used conservative predictive climate change models allowing either 1°C or 2°C increases to predict changes in the thermal quality of each site and ensuing changes in snake metabolic rates and maintenance energy expenditure. Due to the relatively high preferred body temperature of C. oreganus, thermal quality of the environment will actually increase under these climate models; due to an increase in ambient temperature, the proportion of hourly temperatures that fall within the preferred body temperature range will increase. If snake body temperature were to increase as the climate warms, a theoretical increase in body temperature of 1 and 2°C would have a low impact on the overall energetic needs of snakes, still allowing them to meet baseline maintenance energetic needs with only one large meal a year. Furthermore, we expect small increases in ambient temperature to have little impact on rattlesnakes because they are fairly precise thermoregulators, maintaining fairly constant body temperatures regardless of their thermal surroundings. Overall, our results show that studying the thermal ecology of multiple populations of a single species can reveal fine-scale information about the relationship between the thermal landscape and both ectotherm behavior and physiological processes. Additionally, our findings show that some species of large-bodied reptiles may be robust to modest thermal perturbations under conservative climate change predictions.

Orientador: Marcos Hikary Toyama / Resumo: A giroxina é a principal serino protease encontrada no veneno total de Crotalus durissus terrificus. As serino proteases de veneno de serpentes são proteínas que apresentam uma grande similaridade estrutural com a trombina humana incluindo a alta conservação do sitio catalítico. Os resμltados já obtidos pelo nosso grupo revelaram a capacidade dos flavonoides glicosilados de Laguncularia racemosa em reduzir de forma significativa a atividade enzimática das trombinas humanas. A identificação destas molécμlas revelou que dois flavonoides glicosilados (quercetina-3-O-arabinosidio (QAra) e quercetina-3-O-ramnosidio (QRham)) respondem pela inibição da trombina (Rodrigues et al., 2015). Sabe-se que a soroterapia antiveneno não consegue neutralizar de forma eficiente a ação farmacológica das serino proteases e consequentemente não é capaz de neutralizar os danos homeostáticos e teciduais. Neste trabalho, uma nova serino protease foi isolada do veneno total de Crotalus durissus terrificus (cdtsp-2) através de quatro estapas de separação, usando a superdex 75 com uma fase móvel de bicarbonato de amônia pH 8, a cdtsp-2 Estas duas frações foram então fracionadas em coluna de troca iônica em DEAE para separação das principais frações e posteriormente fracionadas em CLAE de fase reversa para confirmar o grau de homologia molecular e em todas as etapas cromatográfica foram acompanhadas pelos ensaios enzimáticos em BApNA. A nova serino protease denominada como Cdtsp-2 (Crotalus durissus terr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Gyroxin is the major serine protease present in Crotalusdurissusterrificus venom. Serine proteases from snake venom are proteins, which exhibit a great structural similarity to hμMan thrombin including the catalytic site conservation. The resμlts already obtained by our group revealed the glycosylated flavonoidsability of Laguncμlariaracemosato significantly reduce the enzymatic activity of hμMan thrombins. The molecμles identification reveals two glycosylated flavonoids (quercetin-3-O-arabinosidiμM (QAra) and quercetin-3-O-rhamnosidiμM(QRham)), which inhibit thrombin (Rodrigues et al., 2015). Antivenomserotherapycan not efficiently neutralize the serine proteases pharmacological action and is not able to neutralize homeostatic and tissue damage. In this work, a new serine protease was isolated from Crotalusdurissusterrificusvenom (cdtsp-2) by throμgh four separation stages , using superdex 75 with a mobile phase of ammoniμM bicarbonate pH 8. These two fractions were fractionated on ion exchange colμMn in DEAE for separation of the major fractions and subsequently fractionated in reverse phase CLAE to confirm the degree of molecμlar homology.All chromatographic steps were monitored by the enzymatic assays in BApNA. The new serine protease called cdtsp-2 (Crotalusdurissusterrificus serine protease 2) is an unpublished protein, with a molecμlar mass of 27 kDa and its N-terminal sequence showed structural differences when compared to the gyroxin of Crotalusdurissusterrificus. Re... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2016-06-02T19:22:12Z (GMT). No. of bitstreams: 1 6572.pdf: 3046018 bytes, checksum: a72ab59cf0526c45a9dee765c02c9f7c (MD5) Previous issue date: 2014-12-18 / Financiadora de Estudos e Projetos / The Sarcoplasmic reticulum calcium ATPase (SERCA), phospholamban (PLB) and the Na+-Ca2+ exchanger (NCX) proteins are essential for the cardiac calcium management and myocardial contractility in vertebrates. The increase in metabolic rate generated from mechanical and physiological process of digestion is known as specific dynamic action (SDA) and represents the energy cost of processing, digestion and absorption of food. In several groups of reptiles, feeding generates a rapid increase in rates of gas exchange, whose peak usually occurs one or two days after feeding, before suffering a slower decline and returning to preprandial values. Ingestion of large quantity of food demands a metabolic elevation and leads to indemnities related in ventricular mass and an increase in myocardial force contraction, avoiding an overload on the cardiovascular system. During the fasting, depletion of body mass occurs and it can also reach the heart muscle. To describe the importance and the changes in SERCA2, PLB and NCX proteins on the effects of feeding/digestion in reptiles broad-snouted caiman (Caiman latirostris), burmese phyton (Python molurus) and also by prolonged fasting in South-American rattlesnake (Crotalus durissus terrificus) Western blotting technique was used. We observed the homology existence between the proteins of reptiles in relation to mammals. The SDA increased expression of SERCA2 protein in three species of reptiles. The SDA can also have unduced the expression of an isoform and/or reduced phosphorylation at some active sites of SERCA2 in ventricular tissue of P. molurus. A direct relationship between the expression of SERCA2 with the PLB expression in C. durissus was observed. However in P. molurus and C. latirostris this relation does not exist. The three reptiles expressed the PLB with molecular mass of 50 kDa, whereas the mouse expressed 25 kDa. The vast evolutionary distance that separates mammals of reptiles may have caused the rise of isoforms between these groups, explaining this difference. The increased expression of NCX along with lower expression of SERCA2 and PLB in C. durissus in food group Fasting compared to the other two groups suggests a higher calcium mobilization in this feeding regime, which would be advantageous from the energy point of view. The expression of NCX with different molecular mass between the three species, a smaller number of consensus regions with the animals phylogenetically more distant and the great plasticity of NCX gene to form distinct proteins, suggest the expression of proteins isoforms with the reptiles studied in this research. / As proteínas Ca2+-ATPase do Retículo Sarcoplasmático (SERCA2), Fosfolambam (PLB) e o Trocador Na+/Ca2+ (NCX) são fundamentais para o manejo do cálcio e a contratilidade miocárdica nos vertebrados. A elevação da taxa metabólica gerada a partir dos processos mecânicos e fisiológicos da digestão é conhecida como "ação dinâmica específica" (SDA) e representa o custo energético do processamento, digestão e absorção dos alimentos. Em vários grupos de répteis, a alimentação gera um rápido aumento nas taxas de troca gasosa, cujo pico ocorre geralmente um dia ou dois após a alimentação, antes de sofrer um declínio mais lento e retornar aos valores pré-prandiais. A ingestão de grandes massas de alimento demanda uma elevação metabólica e leva a uma compensação na massa ventricular e um aumento na força de contração do miocárdio, evitando uma sobrecarga no sistema cardiovascular. Durante o jejum ocorre depleção da estrutura corpórea podendo também atingir o músculo cardíaco. Para descrever a importância e as mudanças nas proteínas SERCA2, PLB e NCX diante os efeitos da alimentação/digestão nos répteis cascavel sul-americana (Crotalus durissus terrificus), na píton (Python molurus) e também do jejum prolongado no jacaré-de-papo-amarelo (Caiman latirostris), utilizada a técnica molecular Western blotting. Observou-se a existência de homologia entre as proteínas dos répteis com relação aos mamíferos. A SDA levou a uma maior expressão da proteína SERCA2 nas três espécies de répteis. A SDA também pode ter induzido a expressão de uma isoforma e/ou uma menor fosforilação em alguns sítios ativos da SERCA2 no tecido ventricular de P. molurus. Uma relação direta entre a expressão da SERCA2 com a expressão do PLB foi verificada somente em C. durissus, não havendo tal relação em P. molurus e C. latirostris. As três espécies de répteis expressaram o PLB com mesma massa molecular, de 50 kDa, e diferente da do rato, que é de 25 kDa. A grande distância evolutiva que separa os répteis dos mamíferos pode ter ocasionado o surgimento de isoformas entre esses grupos, explicando tal diferença. O aumento da expressão do NCX em C. latirostris do grupo alimentar Digestão sugere uma maior mobilização do cálcio e um maior inotropismo de forma frequência-específica através dessa proteína. A maior expressão do NCX juntamente com a menor expressão da SERCA2 e do PLB em C. durissus no grupo alimentar Jejum em relação aos outros dois grupos alimentares sugere uma maior mobilização do cálcio pelo NCX nesse regime de alimentação, o que seria vantajoso do ponto de vista energético. A expressão do NCX com diferentes massas moleculares entre as três espécies estudadas, um menor número de regiões conservadas em animais filogeneticamente mais distantes, e a grande plasticidade do gene da proteína NCX em formar proteínas distintas, sugere a expressão de proteínas isoformas nos répteis estudados.