A ordem Characiformes compreende cerca de 1700 espécies formalmente descritas que habitam a região Neotropical e com três famílias exclusivas da região da Etiópica subsaariana. Possui formas herbívoras, carnívoras e detritívoras, sendo uma ordem com hábitos ecológicos diversos. A classificação formal das famílias da ordem é baseada quase que estritamente em caracteres osteológicos e poucos caracteres de outras naturezas são utilizados para estabelecer hipóteses filogenéticas no grupo. Dessa maneira, o estudo do complexo morfológico encefálico preencheu essa lacuna representada pela ausência de novos caracteres de outra natureza morfológica que contribuam para o melhor entendimento das relações de parentesco entre os Characiformes. O presente estudo teve como objetivos principais a descrição e ilustração da macro morfologia encefálica de representantes das famílias de Characiformes e o levantamento de caracteres filogeneticamente informativos relacionados a esse complexo morfológico. Foram examinados 52 táxons terminais e 42 caracteres encefálicos. Adicionalmente a matriz de dados encefálicos, foram incoporados 126 caracteres osteológicos que definem os principais agrupamentos de Characiformes. O comportamento dos caracteres encefálicos foi mapeado através de uma análise de parcimônia, dessa maneira auxiliando a sustentar vários arranjos filogenéticos. Alguns arranjos filogenéticos novos foram obtidos, tais como, a relação de grupo-irmão entre Hemiodontidae + Chalceidae; Cynodontidae + Acestrorhynchidae como clado-irmão de Erythrinoidea; Gasteropelecidae + Triportheidae + Bryconidae sendo mais relacionados entre si; Crenuchidae como grupo-irmão de Characidae. Além dessas relações, corroborramos a elevação de algumas subfamílias de Characidae para o status de família, como Acestrorhynchidae, Bryconidae, Cynodontidae, Iguanodectidae e Triportheidae. A família Characidae tendo Heterocharacinae como ramo basal e sustentada principalmente por caracteres osteológicos tendo adicionalmente, um caráter exclusivo encefálico. Aphyoditeinae + Aphyocharacinae + Cheirodontinae mais relacionados e a subfamília Characinae como um grupo monofilético. / Characiformes comprises about 1.700 formally described species inhabiting the Neotropical region and three exclusives families of sub-Saharan Etiopic. The species of the order have herbivorous, carnivorous and detritivores feeding habits, being an order of several ecological habits. The formal classification of the families of the order is based almost exclusively on osteological characters and very few of characters of other types are used to establish phylogenetic hypotheses in the group. Thus, the present study of brain morphological complex aims to fill this gap represented by the absence of new morphological characters of another nature that might contribute to a better understanding of the relationships among the Characiformes. Thus, the present study had as main objectives the description and illustration of external brain morphology of representatives of all the families of Characiformes and the searching for phylogenetically informative encephalic morphological characters. For this, 52 terminal taxa and 42 brain characters were examined, in addition of brain data set, have been examined 126 osteological characters that define the main groups of Characiformes. The behavior of brain characters was mapped through a parsimony analysis, thus helping to sustain several phylogenetic arrangements of Characiformes. Some new phylogenetic arrangements were obtained, such as: the sister-group relationship between Hemiodontidae + Chalceidae; Cynodontidae + Acestrorhynchidae as clade-sisters of Erythrinoidea; Gasteropelecidae + Triportheidae + Bryconidae forming a monophyletic group; Crenuchidae as sister group of Characidae. In addition to these relationships, we corroboratethe elevation of some subfamilies of Characidae to family status, such as Acestrorhynchidae, Bryconidae, Cynodontidae, Iguanodectidae and Triportheidae. The Characidae family having Heterocharacinae as the most basal clade and sustained mainly by osteological characters, plus an exclusive character of brain nature. Aphyoditeinae + Aphyocharacinae related to Cheirodontinae and, Characinae subfamily as a monophyletic group.

Orientador: Wanda Pereira Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T12:11:11Z (GMT). No. of bitstreams: 1 Teixeira_CibelleAparecidaRossi_M.pdf: 9069606 bytes, checksum: 6f048b79ac0bc6582fd58bc7f6c6a5c2 (MD5) Previous issue date: 2013 / Resumo: O resumo poderá ser visualizado no texto completo da tese digital. / Abstract: The abstract is available with the full electronic document. / Mestrado / Fármacos, Medicamentos e Insumos para Saúde / Mestra em Biociências e Tecnologia de Produtos Bioativos

Orientador: Maria Alice da Cruz Höfling / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T19:45:28Z (GMT). No. of bitstreams: 1 Stavale_LeilaMiguel_M.pdf: 25008584 bytes, checksum: 8754f8fc3865217986eb0137679176e9 (MD5) Previous issue date: 2013 / Resumo: O veneno da aranha Phoneutria nigriventer (PNV), também conhecida como aranha armadeira, é uma mistura complexa de peptídeos com ação neurotóxica em alguns canais iônicos. No sistema nervoso central (SNC) alguns peptídeos do PNV causam permeabilização da barreira hematoencefálica (BHE) e interferem na liberação de neurotransmissores. A BHE, embora essencial para a manutenção da homeostase do SNC, pode representar uma barreira muito restritiva para o acesso de drogas terapêuticas ao microambiente neural. O entendimento dos mecanismos associados à disfunção da BHE é relevante do ponto de vista científico e médico. O objetivo do estudo foi investigar alguns mecanismos envolvidos na neurotoxicidade do veneno da Phoneutria nigriventer em ratos Wistar (Rattus norvegicus). Para esse fim, o efeito vasogênico causado pela neurotoxicidade do veneno no cérebro, foi examinado através da avaliação da expressão de aquaporina 4 (AQP4), uma proteína formadora dos canais de água e abundantemente localizada nos pés astrocitários perivasculares e relacionada com o aparecimento de edema no cérebro. A análise da expressão da proteína foi feita por imunohistoquímica e western blotting e a expressão de RNAm por PCR em tempo real no cerebelo e hipocampo de animais neonatos (14 dias) e adultos (8 semanas). Os resultados obtidos mostraram aumento da expressão de AQP4 e seu RNAm nos animais envenenados, que entretanto foi variável em função do tempo de envenenamento (2, 5 ou 24 h), da região do cerebelo ou hipocampo examinada e da idade dos animais. Os resultados mostraram também intensa marcação anti-AQP4 ao redor de vasos com edema perivascular ou não, como também entre os corpos neuronais e seus prolongamentos. Concluímos que a AQP4 tem papel nas alterações de volume dos astrócitos perivasculares e na formação e resolução do edema ao redor da BHE causado pelo PNV. A dinâmica da expressão da AQP4 no cerebelo e hipocampo em função do tempo, região e idade dos animais sugere a existência de fatores intrínsicos que modulam diferencialmente a funcionalidade da BHE em função do microambiente local. A compreensão dos mecanismos envolvidos no envenenamento por PNV pode contribuir para o desenvolvimento de ferramentas úteis para a intervenção clínica, bem como pode ser relevante para o entendimento dos mecanismos relacionados ao funcionamento da BHE e de proteínas envolvidas na formação de canais de água, como a AQP4 / Abstract: The Phoneutria nigriventer spider venom (PNV), also known as armed-spider, is a complex mixture of ion channels-acting peptides which exhibit neurotoxic action. In the central nervous system (CNS), PNV-containing peptides cause permeabilization of the blood-brain barrier (BBB) and interfere with neurotransmitter release. The BBB, although essential for the maintenance of homeostasis of the CNS, may represent a very restrictive barrier for the access of therapeutic drugs into the neural microenvironment. The understanding of BBB impairment-associated mechanisms are of scientific and medical importance. The aim of this study was to investigate some of the mechanisms involved in the neurotoxicity caused by Phoneutria nigriventer venom in Wistar rats (Rattus norvegicus). To this end, the vasogenic effect caused by the venom neurotoxicity in the brain was examined by evaluating the expression of aquaporin 4 (AQP4), a water channel forming protein abundantly expressed in perivascular astrocytic endfeet processes and associated to the formation and resolution of edema in the brain. The analysis of AQP4 expression was assessed in the cerebellum and hippocampus of neonate (14 day-old) and adult rats (8 week-old) through immunohistochemistry and western blotting, and the expression of mRNA by Real Time-PCR. The results showed increases of AQP4 expression and its mRNA in the envenomed animals, which though showed time- (2, 5 or 24h), regional- (regions of the cerebellum and hippocampus examined) and age-associated differences. Marked anti-AQP4 labeling was found around vessels with or without edema and among the neuron bodies and their processes. We conclude that AQP4 has a role in the volume alterations of the perivascular astrocytes and in the formation and resolution of edema around the BBB induced by PNV. The variability of the dynamics of AQP4 expression in the cerebellum and hippocampus in function of the time, region and animals age suggests the existence of intrinsic factors that modulate the BBB functionality depending on the molecular biology dynamics of the local microenvironment. The understanding of the mechanisms involved in the envenomation by PNV can contribute to the development of useful tools for clinical intervention, and may be relevant for understanding the mechanisms related to the functioning of the BBB and proteins involved in the formation of water channels, such as AQP4 / Mestrado / Histologia / Mestra em Biologia Celular e Estrutural

Orientadores: Simone Appenzeller, Paula Teixeira Fernandes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T07:32:41Z (GMT). No. of bitstreams: 1 Bellini_BrunaSiqueira_M.pdf: 1130318 bytes, checksum: 9b7f75151c4f31744d2033624f479cf0 (MD5) Previous issue date: 2012 / Resumo: O lúpus eritematoso sistêmico (LES) é uma doença autoimune, ainda sem cura, causada por uma disfunção do sistema imunológico. Aproximadamente 15% de todos os casos de LES são diagnosticados na faixa etária pediátrica. Queixas cognitivas não específicas são freqüentes, afetam de 30 a 78% das crianças e adolescentes, e podem ocorrer mesmo na inatividade da doença ou na ausência de outras manifestações neuropsiquiátricas. O objetivo desse estudo foi verificar a frequência de disfunção cognitiva em uma amostra de pacientes com LES juvenil e identificar associações com aspectos clínico-laboratoriais e de tratamento. Pacientes e Métodos: Foi realizado um estudo transversal, incluindo pacientes com idade de inicio da doença ? 16 anos e controles pareados por sexo, idade e escolaridade. Os sujeitos foram divididos em 2 grupos, de acordo com a idade à avaliação: grupo WISC - idade ? 16 anos e 9 meses; grupo WAIS - idade ? 16 anos e 10 meses. Foi aplicada uma bateria de pesquisa constituída por testes adaptados para a população juvenil, selecionados a partir da bateria recomendada pelo Colégio Americano de Reumatologia para avaliação de adultos. Quinze subtestes foram utilizados para avaliar 13 funções cognitivas. Disfunção cognitiva foi identificada através de três diferentes critérios, de acordo com o ponto de corte adotado e o número requerido de funções alteradas. Sintomas de ansiedade e depressão foram avaliados pelas escalas Beck. Atividade da doença foi avaliada pelo SLEDAI e o dano cumulativo pelo SLICC. Presença de anticorpos e uso de medicação também foram avaliados. Análise estatística foi realizada pelo Statistical Package for Social Sciences (SPSS) e foi adotado nível de significância 5% (p<0,05). Resultados: Sessenta e quatro pacientes e 71 controles foram incluidos. A média de idade dos pacientes à avaliação no grupo WISC foi de 13,43±2,10 (média±DP; variação 8-16 anos), com idade média de início da doença de 11,23±3,21 e duração de 2,20±2,63 anos. No grupo WAIS a média de idade à avaliação foi de 20,34±3,42 (variação: 16-29), com idade média de início da doença 13,76±4,08 e duração de 6,59±4,72 anos. Atividade da doença segundo o SLEDAI foi identificada em 40% dos pacientes no grupo WISC e em 48,3% no grupo WAIS. A frequência de disfunção variou de 11,4-60% no grupo WISC e de 10,3-41,4% no grupo WAIS. O critério 1 (disfunção = escore maior que 2DP abaixo da média normativa em 1 função cognitiva ou escores entre 1 e 2 DP abaixo da média em 2 ou mais funções) foi o que contabilizou a maior porcentagem de pacientes com déficit em ambos os grupos. O grupo WAIS apresentou diferença estatisticamente significativa na frequência de disfunção medida pelos critérios 1 e 2. No grupo todo, essa diferença se manteve somente para o critério 2 (disfunção = escore superior a 2 DP abaixo da média normativa em 1 ou mais funções cognitivas e declínio cognitivo = escores entre 1,5 e 1,9 DP abaixoda média em 1 ou mais funções). Velocidade de processamento e flexibilidade mental foram as funções mais afetadas no grupo WISC; no grupo WAIS, velocidade de processamento, destreza motora e memória semântica. Associação com variáveis clínico-laboratoriais e de tratamento diferiram entre os grupos de acordo com o critério de definição adotado. Não houve associação entre disfunção cognitiva e escolaridade, idade de início/duração da doença, dano cumulativo, presença de anticorpos ds-DNA, Ro e Sm, uso de cloroquina e de imunossupressores. Conclusão: Alterações no critério de definição de disfunção cognitiva acarretaram alterações importantes nas taxas de frequência / Abstract: Systemic Lupus Erythematosus (SLE) is an autoimmune disease, caused by an immune system dysfunction. Approximately, 15% of all cases of SLE are diagnosed in childhood. Non-specific cognitive deficits are common, affecting 30-78% of children and adolescents, and occur even in inactivity of disease or other neuropsychiatric manifestations. The aim of this study was to determine the frequency of cognitive impairment in patients with juvenile SLE and to identify the relationship with clinical and treatment aspects. Patients and Methods: We performed a cross-sectional study including patients with age of onset of disease ? 16 years and controls with the same gender, age and education. The subjects were divided in two groups according to the age evaluation: WISC group - age evaluation ? 16 years and 9 months; WAIS group - age evaluation ? 16 years and 10 months. We performed a battery of tests, selected from the American College of Rheumatology battery. Fifteen subtests were used to evaluate 13 cognitive functions. Cognitive dysfunction has been identified using three different criteria, according to the cutoff adopted and the number of abnormal functions required. Symptoms of anxiety and depression were assessed by the Beck scales. Disease activity was assessed by SLEDAI and cumulative damage by SLICC. The presence of antibodies and medication were also evaluated. Statistical analysis was performed using SPSS and significance level was 5% (p<0.05). Results: Sixty-four patients and 71 controls were included. The mean age of patients in the assessment WISC group was 13.43 ± 2.10 (mean ± SD, range 8-16 years) with a mean age of onset of 11.23 ± 3.21 and duration of 2.20 ± 2.63 years. In the WAIS group, the mean age at evaluation was 20.34 ± 3.42 (range: 16-29), with a mean age of onset and duration 13.76 ± 4.08 to 6.59 ± 4.72 years. Disease activity according to SLEDAI was identified in 40% of patients in WISC and 48.3% in WAIS. The frequency of dysfunction ranged from 11.4 to 60% in WISC and from 10.3 to 41.4% in WAIS. The criteria 1 (dysfunction = score of more than 2 SD below the standardized mean in 1 cognitive function, or scores between 1 and 2 SD below the mean in 2 or more functions) had the largest percentage of patients with deficits in both groups. The WAIS group showed a statistically significant difference in the frequency of dysfunction measured by criteria 1 and 2. In the whole group, this difference remained only for the criteria 2 (dysfunction = score more than 2 SD below the normative mean in 1 or more cognitive functions and cognitive decline = scores between 1.5 and 1.9 SD below published norms in 1 or more functions). The most affected cognitive functions in the WISC group were: processing speed and mental flexibility; in the WAIS group were processing speed, motor skills and semantic memory. The relationship with clinical-laboratory variables and treatment differed between the groups, according to the definition criteria adopted. There was no relation between cognitive impairment and education, age of onset / duration of illness, cumulative damage, presence of antibodies ds-DNA, Ro and Sm, chloroquine and use of immunosuppressive therapy. Conclusion: Changes in criteria for defining cognitive dysfunction led to significant changes in frequency rates / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

Abstract The purpose of the present study was to find reliable non-invasive methods for imaging salivary glands and diagnosing primary Sj?gren's syndrome (SS) and to evaluate autonomic function and central nervous system (CNS) disorders in patients with primary SS. The patient population consisted of consecutive patients with primary SS, who fulfilled the International classification criteria for primary SS, from the Division of Rheumatology, Department of Internal Medicine in Oulu University Hospital. Magnetic resonance (MR) imaging and MR sialography of parotid glands were performed on 27 patients and 7 healthy controls and ultrasonography (US) of major salivary glands on 27 patients, 27 healthy controls, and 27 symptomatic controls with sicca symptoms or salivary gland swellings without SS. MR imaging and US showed heterogeneous parenchyma or adipose degeneration of the gland in 81% and 78% of patients, respectively. MR sialography showed ductal system changes, narrowings and dilatations, or cavities in 96% of patients. One healthy control and 2 symptomatic controls had abnormal findings of parotid or submandibular glands on US. Other controls had normal findings. The diagnostic specificity of US was 94%. Parenchymal structural changes on MR imaging and US were associated with anti-Ro/SSA positivity and weakly with the focus score index, but not with salivary or tear secretion, age, disease duration, or features of systemic activity of the disease, such as hypergammaglobulinemia or systemic complications. A comprehensive package of cardiovascular tests, including 24-hour heart rate variability, baroreflex sensitivity test with phenylephrine, Valsalva manoeuvre, deep breathing tests, and active orthostatic test, were conducted on 30 patients and 30 healthy, age and sex-matched, randomly selected population-based controls. No signs of autonomic dysfunction were found in patients compared to controls in any of the tests. The test results were not associated with saliva or tear secretion, age, disease duration, or clinical features of systemic activity of the disease. A case of severe inflammatory CNS disease associated with primary SS was described, and an investigation of the relevant literature was made. Though inflammatory CNS disease is a possible complication of primary SS, there is no consensus regarding its prevalence or significance in the literature. Diagnostics and treatment are empiric. In conclusion, MR imaging, MR sialography, and US yield such a definitive picture of the glandular changes in primary SS that they are promising alternatives for invasive examinations in the diagnostics of primary SS. Comprehensive cardiovascular tests revealed no signs of autonomic dysfunction in patients with primary SS compared to general population.

Abstract During cardiac and aortic surgery, disturbance of the blood supply in the central nervous system occurs when the repair of aortic pathologies is performed or a bloodless operation field is needed in complex cardiac surgery. To enable the suitable operation environment, the technique named hypothermic circulatory arrest (HCA) has been utilized via heart-lung machine. In this method, the core temperature is lowered to the target temperature, after which blood circulation is halted for a certain period of time. A challenge is that the successful usage of HCA, however still involves the risks of postoperative neurological complications and mortality. In cardiac and aortic arch surgery, the brain is at the highest risk for deficits, whereas in the repair of thoracoabdominal aortic aneurysms (TAAAs), spinal cord injury remains the most severe adverse outcome. Adjunctive protective strategies are required to reduce ischemic injury in these settings. In this thesis, Studies I and II focused on the spinal cord and the Study III on the brain. The studies were performed using acute (II, III) or subacute (I) experimental porcine models, primarily aiming to assess the effectiveness of remote ischemic preconditioning (RIPC) in spinal cord protection along with the aim of studying the underlying mechanisms of RIPC in neuroprotection. Studies I and II demonstrated enhanced motor evoked potential (MEP) responses in both hind limbs, indicating spinal cord protection by RIPC. The faster recovery of brain damage marker S100B along with higher cardiac index and lower systemic lactate levels confirmed the cardio- and neuroprotective properties of RIPC in Study III. The protective mechanism of RIPC was associated with increased antioxidant response (II, III). / Tiivistelmä Sydän- ja aorttakirurgiassa, keskushermoston verenkiertoa joudutaan häiritsemään toteutettaessa aortan korjausleikkauksia tai vaikeissa sydänkirurgisissa toimenpiteissä verettömän leikkausalueen saavuttamiseksi. Sydän-keuhkokoneen avulla toteutettava täydellinen verenkierron pysäytys mahdollistaa vaaditut olosuhteet. Tässä menetelmässä ydinlämpötilaa lasketaan ja verenkierron pysäytys toteutaan tavoitellussa kohdelämpötilassa tietyssä aikaikkunassa. Kyseisen menetelmän onnistunut käyttö sisältää kuitenkin riskejä operaatioiden jälkeisiin neurologisiin komplikaatioihin ja kuolleisuuteen. Sydämen ja aortankaaren kirurgiassa aivot ovat suurimmassa vaarassa vaurioille. Rinta- ja vatsa-aortan aneurysmien eli pullistumien korjausleikkauksiin liittyvä selkäydinvaurio on puolestaan yksi vakavimmista ja vaikeimmista seurauksista. Lisäsuojausmenetelmiä tarvitaan vähentämään iskeemistä vauriota näissä asetelmissa. Väitöskirjan osatyöt I ja II keskittyivät selkäytimeen. Osatyö III käsitteli puolestaan aivojen suojausta. Osatyöt toteutettiin akuutteina (II, III) ja subakuutteina (I) kokeellisina porsasmalleina. Tutkimusten tavoitteina oli arvioida esialtistavan perifeerisen raajaiskemian vaikuttavuutta selkäytimen suojauksessa sekä tutkia raajaiskemian taustalla olevia mekanismeja hermokudoksen suojauksessa. Osatöissä I, II havaittiin motoristen herätepotentiaalien parantuneita vasteita molemmissa takajaloissa osoittaen esialtistavan raajaiskemian suojaavan selkäydintä simuloidussa rinta-aortan korjaustoimenpiteessä. Osatyö III keskittyi alhaisessa lämpötilassa toteutettavaan täydelliseen verenkierron pysäytykseen. Tässä tutkimuksessa todetut aivovauriomarkkeri S100B tason nopeampi lasku, korkeampi sydänindeksi ja alhaisemmat laktaattitasot varmistivat raajaiskemian sydän- ja hermokudossuojausvaikutusta. Esialtistavan perifeerisen raajaiskemian suojaava mekanismi voidaan liittää parantuneeseen solujen antioksidanttivasteeseen (II, III).

Le système nerveux est responsable de l’interconnexion interne des animaux multicellulaires. Il leur permet en effet d’intégrer les activités physiologiques de leurs différentes composantes en une seule entité fonctionnelle, capable d’interagir avec son environnement. L’évolution et le développement des systèmes nerveux complexes comptent parmi les questions les plus fascinantes de la recherche en biologie. Afin de mettre en place une diversité de types de cellules neurales et de connexions neurales, les animaux métazoaires ne déploient qu’un nombre étonnamment réduit de signaux développementaux. C’est l’intermodulation dynamique de ces signaux qui va pouvoir induire un patron spatial d’identités et de comportements cellulaires distincts. L’acide rétinoïque (AR) est une petite molécule diffusible dérivée de la vitamine A qui contribue à la mise en place des axes du système nerveux central des vertébrés et est un régulateur crucial de la différentiation neuronale. D’autre part, il a été montré que les signaux à l’AR affectaient le phénotype de neurotransmetteurs exhibé par des sous-populations neuronales et jouent des rôles divers dans la morphogenèse du système nerveux périphérique issu des placodes crâniennes et des cellules des crêtes neurales. Néanmoins, bien que le rôle de l’AR dans la régionalisation du système nerveux central ait été étudié de manière extensive, nous en savons beaucoup moins au sujet de l’action de l’AR sur le développement du système nerveux périphérique, sur l’établissement des différentes identités de neurotransmetteurs, ou quant à comment ces fonctions ont évolué. Bien qu’initialement considéré comme spécifique aux vertébrés, un volume croissant de données indique désormais que l’AR serait impliqué dans le développement du système nerveux de divers taxons, tels que les cnidaires, les mollusques gastropodes ainsi que les cordés invertébrés. En particulier, l’amphioxus, céphalocordé dont l’évolution est lente, est connu pour posséder un système de signalisation à l’AR semblable à celui des vertébrés. Le génome de l’amphioxus présente un haut degré de conservation de sa synténie par rapport à celui des vertébrés et exhibe relativement peu de pertes ou de duplications indépendantes de ses gènes développementaux. Par conséquent, l’embryogenèse ainsi que la morphologie de l’amphioxus ressemble par bien des points à celles des vertébrés, ce qui facilite l’identification des traits ancestraux et dérivés et en fait donc un modèle approprié à la recherche comparative. Cette étude vise à fournir une description détaillée de différentes populations neurales au sein du système nerveux périphérique de l’amphioxus et d’explorer les rôles joués par l’AR dans ce processus. À cette fin, des analyses d’expression de gènes et d’immunohistochimie ont été utilisées, en vue d’identifier les différentes sous-populations de progéniteurs et les différents types de cellules neurales. De plus, les niveaux de signaux à l’AR ont été altérés pharmacologiquement à différents stades de développement de l’amphioxus, pour déterminer leurs effets sur la formation des populations neurales identifiées, ainsi que sur les patrons de prolifération et d’apoptose. Les résultats inclus dans ce travail révèlent la présence de différentes populations de cellules neurales chez l’amphioxus et mettent en lumière leur vraisemblable relation phylogénétique avec les structures leur correspondant chez les vertébrés. Par ailleurs, différents rôles contexte-dépendants de la signalisation à l’AR on été documentés, incluant la mise en place de frontières discrètes dans le système nerveux central et l’ectoderme de l’embryon d’amphioxus, et la régulation du développement des progéniteurs neuraux tardifs dans le système nerveux périphérique de manière spécifique à leur type cellulaire. / The nervous system provides internal interconnection to multi-cellular animals. It enables them to integrate the physiological activities of their different components into one functional entity that can successfully interact with its environment. The evolution and development of complex nervous systems is one of the most fascinating questions of biological research. In order to generate a diversity of neural cell types and neural connections, metazoan animals deploy a surprisingly small number of instructive developmental signals, which crosstalk in a dynamic manner to induce a spatial pattern of cell identities and behaviors.Retinoic acid (RA) is a small diffusible signaling molecule derived from vitamin A that contributes to the axial patterning of the vertebrate central nervous system and functions as a crucial regulator of neuronal differentiation. Moreover, RA signals have been shown to affect the neurotransmitter phenotype of specific neuronal subsets and play distinct roles during the morphogenesis of the peripheral nervous system from cranial placodes and neural crest. However, while the role of RA signaling in the regionalization of the central nervous system has been extensively studied, much less is known about its actions in cranial placodes and neural crest derivatives, in the establishment of different neurotransmitter identities, or how these functions might have evolved.Albeit initially believed to be vertebrate-specific, a growing body of evidence now implicates RA signaling in the nervous system development of various distant taxa, such as cnidarians, gastropod mollusks and invertebrate chordates. In particular, the slow evolving cephalochordates, commonly called amphioxus, are known to possess a vertebrate-like RA signaling system. The amphioxus genome has retained a high degree of synteny with vertebrate genomes and exhibits relatively little losses or independent duplications of developmental genes. Accordingly, amphioxus embryogenesis and morphology also display remarkable similarity with vertebrates, which allows the identification of ancestral as well as newly derived traits and makes these animals attractive models for comparative research.This study aims at providing a detailed description of the development of different neural cell populations in the central and peripheral nervous system of amphioxus and explores the roles played by RA signaling during this process. To this end, gene expression analyses and immunohistochemistry were used, in order to identify distinct subsets of neural progenitors and neural cell types. Furthermore, RA signaling levels were manipulated pharmacologically at different stages of amphioxus development, to assess their effects on the formation of identified neural cell populations as well as on proliferation and apoptosis patterns. The results presented in this work reveal the presence of distinct neural cell populations in amphioxus and highlight their likely phylogenetic relationships with corresponding structures in other chordates. In addition, several context-dependent functions of RA signaling were documented, which include the generation of discrete boundaries in the central nervous system and ectoderm of amphioxus embryos as well as the cell type-specific regulation of late neural progenitor development in the peripheral nervous system. The observed roles of RA signaling in the amphioxus neural tube and peripheral nervous system correspond well to those reported for the vertebrate hindbrain and cranial placodes, supporting the current hypothesis of a close evolutionary relationship between these structures and suggesting that the involvement of RA signals in their development is a conserved feature of chordates.

For decades the opioid receptors have been an attractive therapeutic target for the treatment of pain. Since the first discovery of enkephalin, approximately a dozen endogenous opioid peptides have been known to produce opioid activity and analgesia, but their therapeutics have been limited mainly due to low blood brain barrier penetration and poor resistance to proteolytic degradation. One versatile approach to overcome these drawbacks is the cyclization of linear peptides to cyclic peptides with constrained topographical structure. Compared to their linear parents, cyclic analogs exhibit better metabolic stability, lower offtarget toxicity, and improved bioavailability. Extensive structure-activity relationship studies have uncovered promising compounds for the treatment of pain as well as further elucidate structural elements required for selective opioid receptor activity. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic derivatives. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored. In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches to improve bioavailability are elaborated and concluded with a discourse towards polycyclic peptides.

Orientadores: Sergio Tadeu Matins Marba, Helder José Lessa Zambelli / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T03:05:39Z (GMT). No. of bitstreams: 1 Zomignani_AndreaPeterson_M.pdf: 1128762 bytes, checksum: 59ae9805910c4b220c7bfa8d2e7bcbab (MD5) Previous issue date: 2012 / Resumo: Objetivo: Descrever uma população de recém-nascidos com encefalocele. Método: Estudo restrospectivo, descritivo e analítico por análise dos prontuários de recém-nascidos com diagnóstico de encefalocele, no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Centro de Atenção Integral à Saúde da Mulher (CAISM), da Universidade Estadual de Campinas (UNICAMP). Foram incluídos todos os pacientes nascidos com diagnóstico de encefalocele no período de janeiro/1997 a julho/2008. Foram estudados: idade materna, paridade, pré-natal, apresentação fetal, tipo de parto, sexo, idade gestacional, índice de Apgar, peso, tipo de encefalocele, tratamento cirúrgico, ocorrência de óbitos, período de internação e retardo do desenvolvimento neuropsicomotor (RDNPM). Foram calculadas as frequências para cada variável analisada e a associação entre algumas variáveis foi verificada estatisticamente pelos testes qui-quadrado e exato de Fisher, considerando alfa de 5%. Resultados: Foram analisados 43 casos com prevalência de 1,24/1000 nascimentos. A faixa de idade materna de maior ocorrência foi 18 a 32 anos (83%), em mães não primigestas (65%), que fizeram os exames pré-natais (95%). A apresentação fetal mais recorrente foi cefálica (45%) com parto cesáreo (65%). Foram encontrados mais casos em meninas, com idade gestacional _37 semanas, tendo a maioria das crianças com a malformação nascido a termo (79%). No primeiro minuto houve Apgar menor ou igual a 7 em 58% dos casos. Em 67% dos casos o peso foi adequado, 27% foram baixo peso e 4,6% muito baixo peso. O tipo de encefalocele mais prevalente foi occipital e em 67% dos casos houve cirurgia. O óbito ocorreu em 31% dos recém nascidos e 55% tiveram período de internação de 1 a 15 dias. Em 62% dos casos foi descrito retardo do desenvolvimento neuropsicomotor. Conclusões: A prevalência de encefalocele foi de 1,24/1000 nascimentos e esteve associada às mães jovens e não primigestas. A apresentação cefálica foi à apresentação mais comum e o tipo de parto mais frequente foi parto cesáreo. Foi mais comum a presença de encefalocele em meninas, com idade gestacional _37 semanas, em nascidos a termo, com índice de Apgar baixo e com peso adequado. A maioria teve encefalocele occipital e precisou de cirurgia, sendo a taxa de mortalidade alta. Na maioria dos casos houve RDNPM / Abstract: Objective: To describe a serie of newborns with encephalocele. Method: Retrospective, descriptive and analytical study, with medical records analysis of newborns with encephalocele, born at the Hospital da Mulher Prof. Dr. José Aristodemo Pinotti - Center for Integral Assistance to Women's Health at the University of Campinas (UNICAMP). All the patients born with these conditions were selected from January/1997 until July/2008. It was studied: maternal age, parity, prenatal care, fetal presentation, mode of delivery, gender, gestational age, Apgar score, birth weight, type of encephalocele, surgical treatment, occurrence of death, hospitalization period, delayed neuropsychomotor development. Frequencies were calculated for each variable and the association among then were assessed statistically using the chi-square and Fisher exact test, considering a 5% alpha. Results: There were 43 cases with prevalence of 1,24/100 births. Maternal age range most frequent was 18 to 32 years (83%), in not primigravidae (65%), who made the prenatal care (95%). The most recurrent fetal presentation was cephalic (45%) with cesarean sections (65%). More cases were found in girls, with gestational age _37 weeks, with the majority of infants with malformations born at term (79%). First minute Apgar score was less than or equal to 7 in 58% of the cases. In 67% of the cases the weight was appropriate, 27% were low birth weight, and 4,6% were very low birth weight infants. The most prevalent type of encephalocele was occipital; 67% of the cases were underwent the surgery. Death occurred in 31% of the newborns and hospitalization period, in most cases, was 1 to 15 days. Neuropsychomotor development delay was observed in 62% of the cases. Conclusions: The prevalence of encephalocele was 1,24/1000 births and there was associated with young mothers and not primiparous. The cephalic presentation was common and there were more cesarean sections. It was more common the presence of encephalocele in girls, with gestational age _37 weeks in term newborns with low Apgar score and appropriate weight. Most had occipital encephalocele and needed surgery, and there was a high mortality rate. In most cases there were neurological deficit / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

A crescente importância do ciclo silvestre da raiva envolvendo morcegos e mamíferos terrestres demonstra a importância do estudo da epidemiologia do vírus da raiva nessas espécies. Foram estudadas amostras provenientes de diversas espécies de animais silvestres terrestres procedentes de uma área de Mata Atlântica nativa no litoral Norte do Estado de São Paulo. Este estudo pesquisou a presença de anticorpos contra o vírus da raiva por meio dos Testes de RFFIT, SFIMT e ELISA em amostras de soro de animais capturados em uma área desmatada, transpostos e monitorados em uma área de soltura. E ainda a pesquisa do vírus da raiva por meio das técnicas de IFD, IC e RT-PCR em amostras de sistema nervoso central dos animais encontrados mortos na região. A positividade observada foi de 10,8% na RFFIT, 34,0% no SFIMT e 1,13% no ELISA. Todos as amostras submetidas as técnicas de IFD, IC e RT-PCR apresentaram resultados negativos. Os resultados observados demonstram circulação do vírus entre as espécies silvestres da área. / The emergent importance of rabies in terrestrial wild animals demonstrates the importance of epidemiological studies regarding rabies virus in those animal species. Samples from several wild species from a native Rainforest area in the North coast of São Paulo State Brazil were studied. The aim of the present study was the research of anti-rabies antibodies in those animals using the RFFIT, SFIMT and ELISA techniques in animals captured and monitorated in a release área. And also by rabies virus detection using FAT, MIT and RT-PCR techniques in central nervous system samples from animals found dead in the same area. The observed positivity was 10,8% on RFFIT, 34,0% on SFIMT e 1,13% on ELISA. All samples tested by the FAT, MIT and RT-PCR techniques presented negative results. The observed results are an evidence of rabies virus circulation between wild animal species in the studied area.