京都大学 / 新制・課程博士 / 博士(生命科学) / 甲第25512号 / 生博第528号 / 新制||生||70(附属図書館) / 京都大学大学院生命科学研究科高次生命科学専攻 / (主査)教授 松田 道行, 教授 鈴木 淳, 教授 安原 崇哲 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

Submitted by Deyse Queiroz (deysequeirozz@hotmail.com) on 2018-05-29T18:46:19Z No. of bitstreams: 1 JOSÉ ALDENOR DE SOUSA - DISSERTAÇÃO PPGSA PROFISSIONAL 2014..pdf: 1307578 bytes, checksum: c7064a40d0c4cd6a65251e2fac21f6e0 (MD5) / Made available in DSpace on 2018-05-29T18:46:19Z (GMT). No. of bitstreams: 1 JOSÉ ALDENOR DE SOUSA - DISSERTAÇÃO PPGSA PROFISSIONAL 2014..pdf: 1307578 bytes, checksum: c7064a40d0c4cd6a65251e2fac21f6e0 (MD5) Previous issue date: 2014 / Este trabalho teve por objetivo realizar um estudo morfométrico desta espécie de abelha criada em condições artificiais no semiárido brasileiro, com a finalidade de verificar divergência em sua morfologia, de forma a identificar possíveis variações dessa espécie. As abelhas foram coletadas de criadores de abelhas sem ferrão distintos, de duas localidades sendo uma delas o município de São João do Rio do Peixe, Paraíba-PB, sob as coordenadas: lat. 06° 43' 44" S e long. 38° 26' 56" W. E a outra no município de Mossoró sob as coordenadas lati. 5°03'40’’ S, long. 37º23'51’ W. Distantes 262 quilômetros entre si. O período da pesquisa compreendeu os meses de dezembro de 2013 a janeiro do ano de 2014.Foram selecionados aleatoriamente 10 cortiços para nível de coletas dos insetos em cada localidade. Foram coletadas 60 abelhas operárias, sendo 3 abelhas referentes a cada cortiço. Os parâmetros avaliados dentro do estudo morfométrico foram: Comprimento Transversal, Comprimento Longitudinal, Pernas Coletoras Asas Anteriores Asas Posteriores e Peso por Inseto. Em relação a características avaliadas foram constatadas diferenças significativas entre todas quando se trata dos indivíduos das duas localidades. Corroborando a existência de variabilidade morfométricas entre as localidades. Na análise discriminante obtida para classificação de indivíduos entre as localidades, o município de são João do Rio do Peixe obteve uma taxa de classificação Correta de 100,0%, já para Mossoró a taxa foi de 96,67%, sendo que a média geral foi de 98,33%. Pela validação cruzada, estas localidade tiveram, respectivamente, identificação correta de seus indivíduos com taxas de 100% e 93,33%. A média geral da validação cruzada foi de 96,97%. As variações de tamanho encontradas neste trabalho constatadas pela morfometria demonstram que as técnicas são ferramentas importantes na avaliação e no desenvolvimento de estratégias de conservação e de sustentabilidade. / This work was aimed to carry out a morphometric study of this species of bee created in artificial conditions in semi-arid, with the purpose of verifying divergence in its morphology, in order to identify possible variations of this species. Bees were collected from beekeepers without distinct sting of two locations one being the country of São João do Rio do Peixe, Paraíba-PB under the coordinates: lat. 06 ° 43 '44 "S and long. 38 ° 26' 56" W. And the other in the country of Mossoró in the coordinates lati. 5 ° 03'40'' S, long. 37 ° 23'51 "W. 262 km distant from each other. The research was conducted in the period from December 2013 to January of the year 2014. From which 10 artificial nests were randomly selected for level of collections of insects in each location. 60 worker bees were collected, 3 bees for each nest. The morphometric parameters evaluated in the study were: Length Transverse, Longitudinal length, collecting Legs, Wings Earlier, Wings Beyond and Weight by Insect. In relation the characteristics evaluated significant differences among all when it comes to individuals of both locations were found. Confirming the existence of morphometric variability between locations. in discriminant analysis obtained for classification of individuals between locations, the country of São João do Rio do Peixe, obtained a correct classification rate of 100.0%, while for Mossoró rate was 96.67%, while the overall average was 98.33% .By cross-validation, this locality had, respectively, correct identification of individuals with their rates of 100% and 93.33%. The overall average of the cross-validation was 96.97%. Size variations found in this study noted by morphometry demonstrated that these techniques are important tools in the evaluation and development of strategies for the conservation and sustainability.

Submitted by Rosana Amâncio (rosana.amancio@ufcg.edu.br) on 2018-07-24T12:43:26Z No. of bitstreams: 1 MICHAEL RADAN DE VASCONCELOS MARQUES-DISSERTAÇÃO PPGCBio 2017..pdf: 1837127 bytes, checksum: f4dc7603f3a80ef62d6643444175cc48 (MD5) / Made available in DSpace on 2018-07-24T12:43:26Z (GMT). No. of bitstreams: 1 MICHAEL RADAN DE VASCONCELOS MARQUES-DISSERTAÇÃO PPGCBio 2017..pdf: 1837127 bytes, checksum: f4dc7603f3a80ef62d6643444175cc48 (MD5) Previous issue date: 2017-08-10 / CNPq / Em 1956, foram trazidas para o Brasil abelhas africanas numa tentativa de promover um melhoramento genético das espécies existentes no país e aumentar a produção de mel. Um ano depois 26 enxames escaparam e houve cruzamento com abelhas nativas. Dessa forma, surgiu a abelha africanizada. Desde o surgimento das abelhas africanizadas o número de acidentes aumentou significativamente em todo o país. O presente estudo teve por objetivo descrever e analisar as características epidemiológicas dos acidentes por abelhas no Rio Grande do Norte, no período de 2007 a 2014. Os dados foram obtidos da Secretaria Estadual de Saúde do Rio Grande do Norte, através do SINAN (SISTEMA DE INFORMAÇÃO DE AGRAVOS DE NOTIFICAÇÃO) e analisados no SPSS Statistcs versão 22.0 e no Bioestat 5.3. Os acidentes com abelhas no Rio Grande do Norte representaram cerca de 7% do total de agravos com animais peçonhentos. De 2007 a 2014 houve aumento importante do número de casos, entretanto, quando se observou os meses de cada ano não houve variação significativa (p=0,975). Indivíduos do sexo masculino tiveram um predomínio de casos em relação ao sexo feminino, representando 64% das notificações. A Faixa etária mais atingida foi de 20 a 39 anos. Os acidentes relacionados ao trabalho representaram apenas 4% dos casos. O local anatômico mais atingido foi a cabeça, representando 32% dos registros. Cerca dE 47% das vítimas foram atendidas em até 3 horas. Grande parte dos acidentes foi classificada como leve (87%) e 88% evoluíram para cura. A maior parte das manifestações clínicas apresentadas foi local, onde a dor (86,6%) e o edema (82,2%) configuraram as reações locais mais reportadas. As variáveis idade (p=0,173) e tempo de atendimento (p=0,335) não mostraram associação com a presença de manifestações clínicas sistêmicas. Em relação à severidade, as variáveis idade (p=0,000), tempo de atendimento (p=0,004), local anatômico atingido (p=0,026), zona de ocorrência (p=0,000) e sexo (p=0,022), mostraram associação estatisticamente significativa. Esses dados servirão para atualizar as informações epidemiológicas disponíveis. Sendo relevante como forma de propagação de informações relacionadas às abelhas, servindo como levantamento da situação epidemiológica dos casos no Nordeste e principalmente no Rio Grande do Norte. Contribuindo para elaboração de políticas públicas de saúde nessa região, incluindo prevenção dos acidentes e melhoria no atendimento e qualidade do tratamento das vítimas. / In 1956, African bees were brought to Brazil in an attempt to promote a genetic improvement of existing species in the country and increase honey production. A year later 26 swarms escaped and crossing with native bees. In this way, the Africanized bee arised. Since the emergence of the Africanized bees the number of accidents has increased significantly throughout the country. The objective of this study was to describe and analyze the epidemiological characteristics of bees' accidents in Rio Grande do Norte from 2007 to 2014. Data were obtained from the Health Secretariat State of Rio Grande do Norte, through SINAN (NATIONAL SYSTEM FOR NOTIFIABLE DISEASES) and analyzed in SPSS Statistcs version 22.0 and in Bioestat 5.3. Accidents with bees in Rio Grande do Norte accounted for about 7% of the accidents with venomous animals. From 2007 to 2014 there was a significant increase in the number of cases, however, when the months of each year were observed there was no significant variation (p = 0.975). Male subjects hada predominance of cases in relation to the female sex, representing 64% of the notifications. The age group most affected was 20 to 39 years. Work-related accidents accounted for only 4% of cases. The anatomic site most affected was the head, representing 32% of the records. About 47% of the victims were treated within 3 hours. Most of the accidents were classified as mild (87%) and 88% evolved to cure. Most of the clinical manifestations presented were local, where pain (86.6%) and edema (82.2%) were the most reported local reactions. The variables age (p = 0.173) and time of care (p = 0,335) showed no association with the presence of systemic clinical manifestations. Regarding severity, the variables age (p = 0.000), time of care (p = 0.004), anatomical site reached (p = 0.026), zone of occurrence (p = 0.000) and gender (p = 0.022), showed a significant association. This data will serve to update the available epidemiological information.Is relevant as a form as a way of propagating information related to bees, serving as a survey of the epidemiological situation of the cases in the Northeast and especially in Rio Grande do Norte. Contributing to the elaboration of public health policies in this region, including prevention of accidents and improvement in care and quality of treatment of victims.

Fästingburna infektioner är ett ökande problem, och därmed även infektioner orsakade av Rickettsia spp. Syftet med studien var att undersöka risken att drabbas av en infektion efter bett av rickettsiainfekterad fästing. Specificitet och sensitivitet av Fluidigm-PCR jämfördes mot real time polymerase chain reaction (realtids-PCR) vid detektion av Rickettsia spp. i fästingar som bitit människor. Vidare undersöktes om det finns någon korrelation mellan fästingens blodsugningstid och serokonversion mot Rickettsia spp. 753 fästingar lämnades in av 104 deltagare i Sverige och på Åland. Fästingarna analyserades med realtids-PCR för att detektera gltA-genen som är specifik för Rickettsia spp. 3,5 % av fästingarna var positiva för Rickettsia spp. med realtids-PCR. Vid analysering med Fluidigm-PCR av samma material blev 1,3 % av proverna positiva. Beräkningar som gjordes med realtids-PCR som referens visade att Fluidigm-PCR har sämre specificitet och sensitivitet jämfört med realtids-PCR. Deltagare som serokonverterade (n=5) lämnade endast in rickettsianegativa fästingar som därför inte kunde kopplas till infektionen. Därmed kunde inga slutsatser dras om risken att drabbas av en infektion efter bett av rickettsiainfekterad fästing eller om det föreligger någon korrelation mellan fästingens blodsugningstid och serokonversion. / Tick-borne infections are increasing, including infections caused by Rickettsia spp. The aim of this study was to examine the risk of developing an infection after being bitten by a tick infected with Rickettsia spp. Specificity and sensitivity of a Fluidigm-PCR assay were compared to real time polymerase chain reaction (real-time PCR) assay when detecting Rickettsia spp. in ticks that had bitten humans. Possible correlation between the tick's feeding time and seroconversion against Rickettsia spp. was also investigated. A total of 753 ticks from 104 participants in Sweden and the Åland Islands (Finland) were analyzed with real-time PCR to detect the gltA gene specific for Rickettsia spp. 3.5 % of the samples were positive for Rickettsia spp. with real-time PCR, while only 1.3 % of the samples were positive with Fluidigm-PCR. Calculations showed that Fluidigm-PCR assay has lower specificity and sensitivity than the real-time PCR assay. Unfortunately, no conclusions could be drawn considering correlation between the tick's feeding time and seroconversion of the bitten humans since no participants who had seroconverted had also submitted ticks containing Rickettsia spp. Therefore, no conclusions could be drawn considering the risk of developing an infection after being bitten by a tick infected with Rickettsia spp. / STING-studien

Made available in DSpace on 2015-04-11T13:54:58Z (GMT). No. of bitstreams: 1 juliana luiza.pdf: 3875282 bytes, checksum: e88fed331ab492bec9b53ea5c76c15f5 (MD5) Previous issue date: 2013-05-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Accidents caused by freshwater stingrays are characterized by intense pain and pathological changes at the lesion site, which include edema, erythema and, in most cases, necrosis. In this study, mucus and tissue extracts from the dorsal region and sting of freshwater stingrays Potamotrygon motoro and Plesiotrygon iwamae were analyzed by electrophoresis on SDS-PAGE and zymography. The myotoxic activity (local and systemic) induced by extracts in murine model was evaluated by morphometric analysis and enzimatic activity of the phospholipase A2 (indirect hemolysis) in agarose gel. P. motorosting extract showed a diffuse band with 10 kDa, several between 58 and 27 kDa, and proteolytic components above 58 kDa, while the dorsal region extract showed a strong and diffuse band around 41 kDa and a proteolytic component with 6 kDa. P. iwamae showed, in all samples, a diffuse and intense band with 15 kDa and proteolytic components around 6 and 40 kDa. Doses of 140 μg of P. iwamae protein extracts (sting and dorsal region) induced indirect hemolysis after 24 and 48 hours, but the halo diameter was below 10 mm (minimum value set for the technical), showing a weak phospholipase A2activity. Coagulative necrosis of the muscle tissue, muscle fiber regeneration and inflammatory infiltrates, including neutrophils, macrophages and a reduced number of eosinophils and lymphocytes were observed 24 hours after injection of 400 μg of P. motoro and P. iwamae mucus extracts in mice gastrocnemius muscle. These results were also observed, in a lower proportion, in the gastrocnemius muscles of the contralateral legs, showing that extracts of both species were able to induce a systemic rhabdomyolysis when tested in BALB/c mice. / Acidentes por arraias de água doce são caracterizados por dor intensa e alterações patológicas no local da lesão, que incluem edema, eritema e, na maioria dos casos, necrose. Nesta pesquisa, os extratos de muco e tecido do dorso e do ferrão das arraias Plesiotrygon iwamae e Potamotrygon motoro foram analisados por eletroforese em SDS-PAGE e por zimografia. A atividade miotóxica (local e sistêmica) induzida pelos extratos, em modelo murino, foi avaliada por histopatologia e a atividade da enzima fosfolipase A2 (hemólise indireta), em gel de agarose. O extrato do ferrão de P. motoro apresentou uma banda difusa de 10 kDa, várias entre 58 e 27 kDa e componentes proteolíticos acima de 58 kDa, enquanto que o extrato do dorso apresentou uma banda forte difusa com cerca de 41 kDa e um componente proteolítico de 6 kDa. Em P. iwamae, todas as amostras apresentaram uma banda intensa e difusa de 15 kDa e componentes proteolíticos de 6 e 40 kDa. As doses de 140 μg de proteína dos extratos de P. iwamae induziram hemólise indireta nos intervalos de tempo de 24 e 48 horas, porém, não formaram o halo de 10 mm de diâmetro (valor mínimo definido para a técnica), demonstrando uma fraca atividade de fosfolipase A2. Necrose coagulativa do tecido muscular, regeneração das fibras musculares e presença de infiltrados inflamatórios, incluindo neutrófilos, macrófagos, e um número reduzido de eosinófilos e linfócitos foram observados 24 horas após a injeção da dose de 400 μg dos extratos de muco do dorso e do ferrão das arraias P. motoro e P. iwamae no músculo gastrocnêmio dos camundongos. Tais resultados também foram observados, em menor volume, nos músculos gastrocnêmios das patas contralaterais, demonstrando que os extratos das duas espécies foram capazes de induzir a uma rabdomiólise sistêmica quando testados em camundongos BALB/c.

Past research has highlighted various problematic issues related to the use of the RCMP undercover operation entitled the “Mr. Big” sting. In a landmark decision, R v. Hart [2014], the Supreme Court of Canada recognized many problems with it and implemented a new admissibility test that would render confessions obtained by the undercover operation presumptively inadmissible. This research project explores the impact that this new evidentiary rule has had on cases involving “Mr. Big” confession evidence since the Hart decision (2014 to 2016). A content analysis was conducted on 16 cases that applied the new admissibility test. The case analysis revealed several important findings from cases that have applied the new admissibility test following Hart. In order to situate these findings, General Systems Theory was used to illustrate the impact that the court’s interpretation of the new evidentiary rule could have on the different components of the criminal justice system. It will be important for future research to further examine the impact of the new admissibility test in order to enhance our understanding of the influence it has had on cases involving “Mr. Big” sting confession evidence.

<p>  </p> <p>The cGAS-STING axis represents a key pathway towards the activation of innate immunity against pathogens. However, persistent activation can lead to the development of autoimmune diseases, driving the need for the development of antagonists of cGAS-STING pathway. Herein, we describe the discovery of a small molecule STING binder HSD1077 through a STING based fluorescence polarization (FP) displacement assay. Initial SAR studies utilizing the FP displacement assay suggests the presence of pyrazole moieties critical for HSD1077 towards STING Binding. Additionally, we show that HSD1077 serves as an antagonist of the cGAS-STING pathway and effectively suppresses type-1 interferon expression upon 2’-3’cGAMP induction in both murine RAW macrophages and human THP-1 monocytes. HSD1077 in conclusion shows potential as a lead compound towards the further development of anti-inflammatory drugs. </p>

Le développement d'une réponse antivirale contre les virus, incluant le virus de l'immunodéficience humaine (VIH), le virus de la grippe, le virus respiratoire syncytial (VRS) ou le SARS-CoV-2, repose sur l'activation d'adaptateurs intracellulaires qui conduisent à la production d'interférons et de cytokines proinflammatoires. Une activation correctement équilibrée de ces voies permet à la cellule de monter un état antiviral, essentiel pour restreindre la réplication et la propagation du virus. Les acides nucléiques viraux à base d'ADN, présents à l’intérieur de la cellule, peuvent être reconnus par la GMP-AMP Synthase cyclique (cGAS), qui transduit ensuite le signal via l'adaptateur Stimulateur des gènes d'interféron (STING). D'autre part, les acides nucléiques viraux à ARN sont reconnus par les récepteurs de type RIG-I (RLR), qui interagissent ensuite avec l'adaptateur de signalisation antivirale mitochondrial (MAVS). STING et MAVS sont des protéines pivots de signalisation localisées dans des compartiments membranaires, régulées par plusieurs modifications post-traductionnelles (PTM) et, lors de l'activation, elles subissent des événements de polymérisation allant jusqu'à la formation d'agrégats fonctionnels. Des données soutiennent un rôle des espèces réactives de l'oxygène (ROS) dans la régulation des voies dépendantes de STING et MAVS, mais les mécanismes restent mal définis. Les ROS sont connus pour modifier la structure et l'activité des protéines de signalisation via des PTMs oxydatives réversibles sur des cystéines (Cys ox-PTM). Les Cys ox-PTM réversibles consistent en une variété de modifications, les plus étudiées étant la S-sulfénylation (Cys-SOH), la S-glutathionylation (Cys-SSG) et le disulfure (S-S). Afin d’identifier les Cys ox-PTM qui affectent les protéines de signalisation impliquées dans la réponse antivirale, nous avons effectué une identification à l'échelle du protéome des Cys ox-PTM induites par les ROS en utilisant un marquage bioswitch à base de maléimide couplé à la spectrométrie de masse. Nous avons identifié 2720 sites Cys ox-PTM uniques englobant 1473 protéines avec une abondance, localisation et fonctions distinctes. Parmi ceux-ci, nous avons découvert l'oxydation de STING sur la Cys148 et Cys206. Cette dernière étant inductible par le stress oxydatif ou par le ligand naturel 2'3'-cGAMP et joue un rôle inhibiteur pour empêcher l'hyperactivation de STING par la formation de polymères inactifs contenant des liaisons intermoléculaires S-S. En outre, nous avons observé que MAVS était également capable de former des polymères intermoléculaires contenant des S-S en réponse à une infection par des virus à ARN, et que l'ancrage de la protéine à la membrane était essentiel pour la formation de ces polymères. Le couplage du marquage par bioswitch à base de maléimide à l'analyse par immunoblot a confirmé que MAVS était oxydé pendant une infection avec un virus à ARN. Nous avons également constaté que des Cys situées dans des positions clés pour la formation de polymères de MAVS actifs étaient essentielles pour transduire la signalisation en aval et finalement activer le promoteur IFNβ en réponse à l'infection virale. Nos études établissent un mécanisme direct par lequel les ROS contrôlent la réponse immunitaire innée cGAS/STING et RLRs/MAVS-dépendante. Ils offrent un nouveau terrain pour la conception de thérapies ciblant des adaptateurs pertinents pour les infections virales, telles que la vaccination, mais aussi pour les troubles auto-immuns et inflammatoires. / The development of an antiviral response against viruses, including Human Immunodeficiency Virus (HIV), influenza, Respiratory Syncytial Virus (RSV) or SARS-CoV-2, relies on the activation of intracellular adaptors that ultimately lead to the production of interferons and proinflammatory cytokines. Properly balanced activation of these pathways allows the cell to mount an antiviral state, essential to restrict virus replication and spreading. Intracellular DNA viral nucleic acids can be recognized by the cyclic GMP-AMP Synthase (cGAS), which then transduces the signal through the Stimulator of Interferon Genes (STING) adaptor. On the other hand, RNA viral nucleic acids are recognized by the RIG-I-like Receptors (RLRs), which then interact with the Mitochondrial Antiviral Signaling (MAVS) adaptor. STING and MAVS are signaling hub proteins localized in membranous compartments, regulated by several posttranslational modifications (PTMs) and, upon activation, they undergo polymerization events going as far as the formation of functional aggregates. Compelling evidence supports a role of reactive oxygen species (ROS) in the regulation of STING and MAVS-dependent pathways, but the mechanisms remain ill-defined. ROS are known to modify signaling protein structure and activity through reversible oxidative PTM of Cysteines (Cys ox-PTM). Reversible Cys ox-PTMs consist of a variety of modifications, the most widely studied being S-sulfenylation (Cys-SOH), S-glutathionylation (Cys-SSG) and disulfide (S-S). To unveil the Cys ox-PTMs that affect signaling proteins involved in the antiviral response, we performed a proteome wide identification of the Cys ox-PTMs induced by ROS using maleimide-based bioswitch labeling coupled to mass spectrometry. We identified 2720 unique Cys ox-PTM sites encompassing 1473 proteins with distinct abundance, location, and functions. Among these, we uncovered the oxidation of STING at Cys148 and Cys206. The latter was inducible by oxidative stress or by the natural ligand 2’3’-cGAMP and plays an inhibitory role to prevent STING hyperactivation through the formation of inactive polymers containing intermolecular S-S bonds. Further, we observed that MAVS was also able to form intermolecular S-S containing polymers in response to RNA virus infection, and that the anchoring of the protein to the membrane was essential for these polymers to form. Maleimide-based bioswitch labeling couple to immunoblot analysis confirmed that MAVS was oxidized during RNA virus infection. We also found that Cys located in positions key for the formation of active polymers were essential for MAVS to transduce downstream signaling and ultimately activate IFNβ promoter in response to virus infection. Our studies establish a direct mechanism by which ROS control the cGAS/STING and the RLRs/MAVS-dependent innate immune response. They provide new ground for the design of therapies targeting adaptors relevant to viral infections, such as vaccination, but also to autoimmune and inflammatory disorders.

No description available.

Introdução: Escorpionismo é um problema de saúde no Brasil e em outras regiões do mundo. Em 2015, no Brasil, foram relatados 74.598 acidentes e 119 mortes. Neste estudo, foram descritos aspectos clínicos, epidemiológicos, laboratoriais e de vulnerabilidade nestes acidentes. Métodos: Trata-se de estudo clínico prospectivo e observacional conduzido no Hospital Municipal de Santarém (HMS), de Abril de 2008 a Janeiro de 2014. Os pacientes incluídos no estudo foram admitidos pelo autor e não representam o total de pacientes internados no HMS. Além disso, foi realizado estudo qualitativo com base teórica no conceito de vulnerabilidade que inclui as dimensões individual, social e programática. Resultados: Foram descritos 58 acidentes, presumivelmente, causados por T. obscurus na Amazônia Brasileira. A maioria dos acidentes ocorreu durante o trabalho, a maioria dos pacientes incluídos era do sexo masculino 39 (67,2%). Os principais locais de picada foram as extremidades (pés e mãos) com uma frequência de 51 (90%). Os pacientes relataram sensação de \"choques elétricos\" que podem durar horas. A grande maioria dos pacientes apresenta quadro clínico compatível com disfunção cerebelar aguda, que pode ter início minutos e durar até dois dias após a ocorrência do acidente. Apresentaram ataxia cerebelar, disdiadococinesia, dismetria, disartria, dislalia, naúseas e vômitos. Além disso, alguns pacientes, aprentaram mioclonias e fasciculações que também podem ser atribuídas à disfunção cerebelar aguda ou talvez à ação direta sobre o músculo esquelético. Seis pacientes apresentaram rabdomiólise e dois injúria renal aguda. O quadro clínico observado na maioria dos pacientes consiste, principalmente, em disfunção cerebelar aguda e manifestações neuromusculares anormais, que não foram descritos em qualquer outra região do mundo. Também foram realizadas 28 entrevistas quanti-qualitativas com pacientes vítimas de acidente escorpiônico, as quais foram submetidas à técnica de análise de discurso. Pacientes eram, em sua maioria, homens que moravam na área rural e que trabalhavam como agricultores e viviam em condições sócio demográficas desfavoráveis. Discussão: As manifestações apresentadas por esses pacientes são compatíveis com disfunção cerebelar aguda que pode ser explicada, provavelmente, porque algumas toxinas de T. obscurus (da região de Santarém), não só tem a capacidade de atravessar rapidamente, em poucos minutos, a barreira hemato-encefálica, mas também devem apresentar elevada afinidade por canais iônicos presentes nas membranas de células do cerebelo. As mioclonias e fasciculações podem ser atribuídas à disfunção muscular ou cerebelar. A vulnerabilidade individual e social foi evidenciada em vários aspectos: pouco conhecimento em relação ao comportamento de escorpiões e também às medidas preventivas, baixa escolaridade (incluindo analfabetismo), baixa qualificação profissional, trabalho informal, condições precárias de vida (falta de água encanada, energia elétrica, esgoto). Em relação à dimensão programática foi constatada dificuldade de acesso aos serviços de saúde e a falta de antiveneno no centro de referência. Portanto, o estudo destaca as particularidades do escorpionismo em Santarém e os aspectos mais importantes da vulnerabilidade destes pacientes / Introduction: Scorpionism is a health problem in Brazil and in another regions of the world. In 2015, in Brazil 74,598 accidents and 119 deaths were reported. In this study, were described clinical, epidemiologic, laboratory and vulnerability aspects of these unique scorpion accidents. Methods: A prospective and observational study was conducted in the MHS, from April, 2008 to January, 2014. Patients included in the study were admitted by the authors and do not represent the total number of hospitalized patients in the MHS. In addition, a qualitative study was conducted with the theoretical basis of the vulnerability concept, that includes individual, social and programmatic dimension. Results: We described 58 accidents presumably caused by T. obscurus in Brazilian Amazonia. Most patients were stung during work activities and the majority was male 39 (67.2%). The main sites of stung were the extremities (feet and hands), with a frequency of 51 (90%).Patients reported a sensation of \"electric shocks\" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, that started in minutes and could last up to two days after the accident. They presented cerebellar ataxia, dysdiadocokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Also, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or perhaps the result of direct action on skeletal muscle. Six patients had developed rhabdomyolysis and two acute kidney injury. The clinical picture observed in most of our patients consisted mainly from an acute cerebellar dysfunction and abnormal neuromuscular manifestations which is not described in any other region of the world. Twenty-eight quantitative and qualitative interviews with scorpion sting victims. Each patient was submitted to discourse analysis technique. The majority patients were men who live in rural areas, small farmers with unfavorable socio-demographic conditions. Discussion: The manifestations presented by these patients are compatible with acute cerebellar dysfunction which could be explained probably because some toxins from T. obscurus from Santarém region, have not only the capacity to cross quickly, within minutes, the blood-brain and also must have high affinity for ionic channels present in some cerebellar cell membranes. Myoclonus and fasciculation can be attributed to cerebellar or muscle dysfunction. The individual and social vulnerability was demonstrated in several ways: little knowledge about the scorpion behavior and about the preventive measures, low education level (including illiteracy), low-skilled, informal work, precarious living conditions (lack of running water, electricity, basic sanitation). Regarding the programmatic dimension it was found difficult access to health services and lack of antivenom serum in the reference center. Therefore, the study highlights the particularities of scorpionism in Santarem and the most important aspects of vulnerability of these patients