Estudamos os efeitos da estimulação elétrica no nucleus basalis magnocelular (Meynert), núcleo colinégico que projeta aferências para o córtex cerebral e tem sido associado a mecanismos de aprendizagem e memória. Verificamos os efeitos eletrofisiológicos induzidos pela estimulação elétrica do núcleo basalis pareado com apresentação de um tom puro. Caracterizamos a dinâmica da atividade elétrica neural do cortex auditivo primário e de núcleos subcorticais relacionados à circuitaria da aprendizagem e memória, durante o condicionamento auditivo nos momentos de aquisição e de revocação além correlacioná-las a dinâmica de freqüência cardiaca, variável que pode exprimir a relevância de um estímulo / Acetilcholine is related to learning and memory and is related to cortical activation. We studied the effects electrically stimulating the basal forebrain - the main cholinergic afferent to the cortex, while presenting paired and unpaired pure tones. Mathematical techniques were used to analyze electrophysiological data. The dynamics from primary auditory cortex and related subcortical nuclei were correlated to the auditory conditioning. We also correlated brain activity to the heart dynamics, considered a reliable measure of learning and conditioning, an interesting approach that uncovers the relevance of stimulus that is not detectable through other behavioral variables

Tensão elevada no osso pode provocar reabsorção óssea. O objetivo deste estudo é avaliar por meio do método dos elementos finitos tridimensionais as áreas de concentração de tensões no osso basal após realização dos orifícios para inserção dos implantes e com implantes osseointegrados, em mandíbulas com três níveis de reabsorção e prótese mucosa-suportada. Foram confeccionados 7 modelos por meio do software de CAD: Rhinoceros 4.0 SR9; 1 (controle)- mandíbula com 15mm de altura e sem orifício; 2- mandíbula com 15mm de altura e 2 orifícios de 3,75mm de diâmetro; 3- mandíbula com 15mm e 2 implantes osseointegrados; 4- mandíbula com 20mm e 2 orifícios; 5- mandíbula com 20mm e 2 implantes osseointegrados 6- mandíbula com 26mm e 2 orifícios e 7- mandíbula com 26mm e 2 implantes osseointegrados. A força aplicada foi de 60N no sentido axial, nos dentes artificiais da prótese removível total reembasada com 2mm de material macio. Após a discretização dos modelos foi realizado o ensaio pelo método dos elementos finitos por meio do Software NEiNastran for Windows Version 10.0.3.997. Os resultados evidenciaram aumento da tensão no osso cortical em relação ao medular. Mandíbulas sem perfuração apresentaram picos de tensão mais elevados que as com implantes osseointegrados. Nas mandíbulas com orifícos os picos de tensão se localizaram no sentido vestíbulo-lingual enquanto nas com implantes esses picos de tensão foram no sentido mésio-distal. Quanto mais reabsorvida a mandíbula maior a tensão transmitida pela base da prótese removível total ao orifício. Conclui-se que as mandíbulas com 15 e 20 mm de altura com orifícios apresentaram maiores picos de tensão que as com implantes osseointegrados, enquanto nas com 26mm de altura não houve diferença entre ambas condições / Increased pressure in the bone can cause resorption. The purpose of this study is to evaluate areas of stress concentration in the basal mandibular bone after perforation for inserting the implants and dental implants in mandibles with three levels of resorption and muco-supported dental prosthesis using the three-dimensional finite element method. 7 models were produced through CAD software: Rhinoceros 4.0 SR9; 1 (control) -15mm jaw height and without perforation; 2- 15mm jaw height and two perforations of 3.75 mm in diameter; 3- 15mm jaw height with 2 osseointegrated dental implants; 4- 20mm jaw height and 2 perforations; 5- 20mm jaw heigth with two osseointegrated dental implants; 6- 26mm jaw height and two perforation; and 7- 26mm jaw height with two osseointegrated dental implants. The force of 60N was applied in the axial direction to the artificial teeth denture provisional recover with 2mm soft material for edentolous tissue conditioner. After discretization of the test models it was performed a trial using the finite element method through NEiNastran Software for Windows Version 10.0.3.997. The results showed increased tension in cortical bone in relation to the medular bone. Mandibles without perforation showed stress peaks higher than those with dental implants. In the jaws with drilling the stress peaks were located in the buccal-lingual direction while in those with implant they were in the mesial-distal direction. The more resorbed jaw greater the tension transmitted by the base of full removable denture to the drilling. The study concluded that the jaws 15 and 20 mm height perforated had higher stress peaks than the ones with dental implants while in the 26mm height perforated no difference between the two conditions was observed

Este trabalho contribui para a evolução dos métodos que lidam com a quantificação de biomassa em plantações florestais em grande escala. Mais especificamente, explora o potencial de novos métodos baseados em sistemas de escaneamento a laser aerotransportado (ALS) que produzem uma representação 3D da estrutura vertical e horizontal acima do solo em plantios de Eucalyptus spp. A abordagem assume que a biomassa acima do solo pode ser estimada de forma precisa quando o perfil vertical da altura do dossel e a área basal são bem conhecidos. Assim, quatro questões foram analisadas: (i) se a função de densidade probabilidade Weibull com dois parâmetros (escala ? e forma ?) consegue descrever com precisão a distribuição vertical de pontos gerada pela tecnologia ALS e gerar um perfil aparente de altura de dossel adequado em plantios de eucalipto; (ii) se quando gerada por tecnologia ALS, a proporção de retornos no subdossel e solo tem relação significativa e positiva com a variável área basal; (iii) qual a qualidade da predição de área basal e de biomassa seca de lenho quando são usadas como variáveis explicativas um percentil baixo de altura da nuvem ALS e o parâmetro de escala da distribuição Weibull ajustada para definir o perfil vertical do dossel; e (iv) qual a qualidade dos mapas de biomassa de lenho de plantios de eucaliptos quando produzidos a partir de dois métodos diferentes, um de interpolação de dados das parcelas de campo (krigagem ordinária) e outro que usa a nuvem de pontos ALS para calibrar as informações das parcelas de campo (regressão linear). Os resultados mostraram que a função Weibull de dois parâmetros ajustou com precisão adequada o perfil das alturas do plantio de eucalipto. Do ponto de vista prático, esse resultado reforça as estratégias de uso dos parâmetros da função Weibull (escala e forma) como métricas que caracterizam adequadamente a estrutura vertical dos povoamentos florestais. A estimativa de área basal em função da proporção de retornos no subdossel e no solo mostrou-se moderada (R² = 0.42 e rRMSE = 7.6%), sendo necessários mais estudos que investiguem essa relação. As predições de área basal e biomassa do lenho foram aprimoradas em função do parâmetro ? da função Weibull, usado como estimador de escala para as alturas do dossel (área basal, R² = 0.77 e rRMSE = 4.8% e biomassa do lenho, R² = 0.89 e rRMSE = 5.1%). As variáveis, percentil 30 e parâmetro de forma (?) da função Weibull, também produziram boas estimativas (R² = 0.82 para área basal e R² = 0.93 para biomassa de lenho). Os mapas de predição de biomassa de lenho mostraram-se mais precisos quando derivados a partir de dados ALS (rRMSE = 5.5% versus 12.7% na interpolação por krigagem ordinária). / This work contributes to the evolution of methods dealing with the quantification of biomass in large-scale forest plantations. More specifically, it explores the potential of new methods based on airborne laser scanning systems to produce a 3D representation of the vertical and horizontal structure of above ground Eucalyptus spp plantations. The approach assumes that above ground biomass can be precisely estimated when the vertical profile of canopy heights and basal area are well known. Thus, four questions are examined: (i) can the Weibull probability density function (pdf) with two parameters (? scale and ? shape) describe accurately the vertical distribution of points generated by the ALS technology and generate an adequate apparent profile of canopy heights for the eucalyptus plantation?; (ii) when generated by the ALS technology, is the proportion of understory returns to ground returns significantly and positively related with basal area?; (iii) how well are basal area and dry stem biomass predicted by models using low height percentile values of the ALS point cloud and the scale parameter of the Weibull distribution describing the vertical canopy profile?; and (iv) how accurate are stem biomass maps of the eucalyptus plantation when two different methods are used, one based on interpolation that uses sample plots information (ordinary kriging) and another that uses the ALS point cloud to calibrate the sample plot information (linear regression)? The results showed that the Weibull pdf with two parameters fitted with adequate accuracy the plantation\'s height profiles. From a practical standpoint, this result reinforces the strategies of using the Weibull parameters (scale and shape) as metrics that adequately characterize the vertical structure of forest stands. Basal area estimates derived from the proportion of understory and ground returns presented only moderated accuracy (R² = 0.42 e rRMSE = 7.6%) and more research is needed to investigate such relationship. Good results were obtained when basal area and stem biomass were fitted as a function of the Weibull ? parameter, as a proxy for the scale of canopy heights (basal area, R² = 0.77 e rRMSE = 4.8%, and stem biomass, R² = 0.89 and rRMSE = 5.1%). The explanatory variables percentile 30 and the Weibull shape parameter (?) also produced good estimates (R² = 0.82 for basal area and R² = 0.93 for stem biomass). Stem biomass prediction maps showed to be more accurate when derived from ALS data (rRMSE = 5.5% against 12.7% derived from ordinary kriging interpolation).

Tensão elevada no osso pode provocar reabsorção óssea. O objetivo deste estudo é avaliar por meio do método dos elementos finitos tridimensionais as áreas de concentração de tensões no osso basal após realização dos orifícios para inserção dos implantes e com implantes osseointegrados, em mandíbulas com três níveis de reabsorção e prótese mucosa-suportada. Foram confeccionados 7 modelos por meio do software de CAD: Rhinoceros 4.0 SR9; 1 (controle)- mandíbula com 15mm de altura e sem orifício; 2- mandíbula com 15mm de altura e 2 orifícios de 3,75mm de diâmetro; 3- mandíbula com 15mm e 2 implantes osseointegrados; 4- mandíbula com 20mm e 2 orifícios; 5- mandíbula com 20mm e 2 implantes osseointegrados 6- mandíbula com 26mm e 2 orifícios e 7- mandíbula com 26mm e 2 implantes osseointegrados. A força aplicada foi de 60N no sentido axial, nos dentes artificiais da prótese removível total reembasada com 2mm de material macio. Após a discretização dos modelos foi realizado o ensaio pelo método dos elementos finitos por meio do Software NEiNastran for Windows Version 10.0.3.997. Os resultados evidenciaram aumento da tensão no osso cortical em relação ao medular. Mandíbulas sem perfuração apresentaram picos de tensão mais elevados que as com implantes osseointegrados. Nas mandíbulas com orifícos os picos de tensão se localizaram no sentido vestíbulo-lingual enquanto nas com implantes esses picos de tensão foram no sentido mésio-distal. Quanto mais reabsorvida a mandíbula maior a tensão transmitida pela base da prótese removível total ao orifício. Conclui-se que as mandíbulas com 15 e 20 mm de altura com orifícios apresentaram maiores picos de tensão que as com implantes osseointegrados, enquanto nas com 26mm de altura não houve diferença entre ambas condições / Increased pressure in the bone can cause resorption. The purpose of this study is to evaluate areas of stress concentration in the basal mandibular bone after perforation for inserting the implants and dental implants in mandibles with three levels of resorption and muco-supported dental prosthesis using the three-dimensional finite element method. 7 models were produced through CAD software: Rhinoceros 4.0 SR9; 1 (control) -15mm jaw height and without perforation; 2- 15mm jaw height and two perforations of 3.75 mm in diameter; 3- 15mm jaw height with 2 osseointegrated dental implants; 4- 20mm jaw height and 2 perforations; 5- 20mm jaw heigth with two osseointegrated dental implants; 6- 26mm jaw height and two perforation; and 7- 26mm jaw height with two osseointegrated dental implants. The force of 60N was applied in the axial direction to the artificial teeth denture provisional recover with 2mm soft material for edentolous tissue conditioner. After discretization of the test models it was performed a trial using the finite element method through NEiNastran Software for Windows Version 10.0.3.997. The results showed increased tension in cortical bone in relation to the medular bone. Mandibles without perforation showed stress peaks higher than those with dental implants. In the jaws with drilling the stress peaks were located in the buccal-lingual direction while in those with implant they were in the mesial-distal direction. The more resorbed jaw greater the tension transmitted by the base of full removable denture to the drilling. The study concluded that the jaws 15 and 20 mm height perforated had higher stress peaks than the ones with dental implants while in the 26mm height perforated no difference between the two conditions was observed

No description available.

Background. Both basal-like subtype and BRCA1-related breast cancers tend to have a poor overall prognosis and lack of effective treatments. Given that the lung cancer drug gefitinib and the leukemia drug dasatinib inhibit proteins also belonging to the molecular signature of this subtype, we and others hypothesized that they might be useful therapies for those two breast cancer subgroups. / Methods. Eight breast cancer cell lines were characterized by immunohistochemistry and western blotting and were treated with both drugs. Response was measured by using the sulphorhodamine B (SRB) assay. / Results. Two out of six basal-like cell lines were sensitive to gefitinib and five of six to dasatinib. BRCA1-related breast cancers were also responsive to dasatinib (three out of four). Moreover, EGFR and caveolin-1 act as markers for dasatinib sensitivity, but do not appear to be the primary targets of this drug. The presence of SRC but not ABL is necessary to achieve a response to dasatinib. / Conclusion. Dasatinib is more effective in the treatment of basal-like breast cancers than gefitinib and acts by inhibiting SRC and other molecules that are yet to be determined.

A fundamental property of living cells is the ability to sense and respond appropriately to changing environmental conditions. In budding yeast (Sacharomyces cerevisiae), changes in extracellular osmotic conditions are sensed by the HOG SAPK pathway, which orchestrates the cell adaptation program required to maximize cell survival upon stress. Although most of the HOG pathway components have been described, little was known about the dynamics of the response. The aim of this thesis was to analyze the dynamic behavior of the HOG pathway. By using a chemical inhibitor and extensive signal quantification we showed that the HOG pathway is controlled by high basal signaling counteracted by a negative feedback regulatory system. This property determines dynamic signaling in terms of faster response times and higher sensitivity to small variations in extracellular stimuli. This thesis also aimed to implement novel strategies for biological computation that allow increasing complexity of circuits. By engineering signaling pathways in yeast, we have shown that distribution of computation tasks among several wired cells reduces wiring constraints and allows scalability of circuit complexity. Moreover, reusability of cells permits implementation of multiple circuits. Overall, our results define novel dynamic properties of the HOG pathway and have been important to achieve a better view of signal transduction process though MAPK pathways. Moreover, we have developed and implemented novel strategies for biological computation that solved fundamental constrains in the field of synthetic biology. / Una propietat cel•lular fonamental és l’habilitat de detectar estímuls i respondre coherentment a un ambient dinàmic. En cèl•lules de llevat (Saccharomyces cerevisiae), els canvis en l’osmolaritat externa són detectats per la via de senyalització de HOG que organitza tot el programa d’adaptació cel•lular, indispensable per assegurar la supervivència cel•lular en estrès osmòtic. Tot i que la gran majoria dels components de la via de HOG han estat identificats, la dinàmica del procés de senyalització és encara força desconeguda. L’objectiu d’aquest projecte de tesis ha estat analitzar el comportament dinàmic de la via de HOG. Gràcies a la utilització d’un al•lel inhibible de la MAPK Hog1 i a la quantificació sistemàtica del procés de senyalització, hem pogut demostrar que en la via de HOG existeix una intensa senyal basal reprimida constantment per un feedback negatiu depenent de la MAPK Hog1. Aquesta tesi també té com a objectiu la implementació de noves estratègies de computació biològica que permetin un increment de la complexitat dels circuits. Gràcies a la bioenginyeria de les vies de senyalització de llevat, hem demostrat que la distribució de la computació en diferents cèl•lules connectades entre elles disminueix les limitacions de connexió i permet incrementar la complexitat dels circuits a un baix cost. En conjunt, els nostres resultats defineixen noves propietats dinàmiques de la via de HOG i han estat importants per tenir una visió global millorada del procés de senyalització per vies de MAPK. A més, hem dissenyat i implementat noves estratègies de computació biològica que han resolt problemes fonamentals del camp de la biologia sintètica.

Les œstrogènes, et en particulier l’œstradiol E2, régulent un nombre considérable de fonctions physiologiques au sein de l’organisme et permettent notamment l’établissement et le maintien des fonctions reproductives chez tous les vertébrés. L’E2 agit localement dans de multiples organes cibles via l’intermédiaire de ses récepteurs : ERα et ERβ. Par son action proliférative contribuant au renouvellement de l’épithélium mammaire, l’E2 ainsi que son récepteur ERα ont été associés au développement pathologique de tumeurs mammaires. Celles-ci sont qualifiées d’hormono-dépendantes car elles répondent pour la majorité d’entre elles à l’utilisation de l’hormonothérapie visant à bloquer leur croissance. Malheureusement, on estime que 30 à 40% des tumeurs mammaires finissent par présenter une résistance aux traitements anti-oestrogéniques, par des mécanismes extrêmement complexes. Les travaux présentés dans ce manuscrit ont pour objectifs de mieux comprendre les mécanismes moléculaires et cellulaires impliqués dans le phénomène d’échappement des cellules tumorales mammaires au contrôle hormonal. Dans le cadre de cette thèse, nous nous sommes intéressés à deux facteurs capables de moduler l’activité d’ERα : l’hypoxie, qui désigne l’appauvrissement en oxygène du microenvironnement cellulaire, et la voie RhoA/MKL1 fréquemment mise en place au cours de la transition épithélio-mésenchymateuse. L’hypoxie est une caractéristique majeure des tumeurs solides, et des études lui suggèrent un rôle dans l’apparition de résistance endocrine. Nous montrons que le stress hypoxique inhibe fortement l’expression d’ERα, principalement au niveau protéique, et qu’il abolit la prolifération et la survie cellulaire induites par l’E2. L’analyse transcriptomique démontre qu’un certain nombre de gènes cibles d’ERα sont également régulés par l’hypoxie, qui peut soit réprimer (CXCL12…) ou bien augmenter leur expression (AREG…). Par ailleurs, l’analyse du cistrome d’ERα démontre une perte massive du nombre d’ERBSs (Estrogen Receptor Binding Site) par l’hypoxie, mais également une apparition d’ERBSs hypoxie-spécifiques. Nos résultats suggèrent que le fort recouvrement de régulation entre ERα et l’hypoxie puisse moduler l’efficacité des thérapies antihormonales. Enfin, l’équipe a démontré que l’activation de la voie RhoA/MKL1 provoque une forte inhibition de la fonction AF1 d’ERα. Afin de mieux appréhender les effets de cette voie de signalisation sur l’activité d’ERα, une lignée cellulaire MCF7 exprimant stablement un mutant constitutivement actif du facteur MKL1 a été générée. Nous montrons que son expression modifie profondément le contexte cellulaire en provoquant le basculement d’un phénotype luminal vers un phénotype basal-like. L’analyse transcriptomique de la réponse à l’E2 montre que le changement d’orientation cellulaire induit par MKL1 abolit toute régulation transcriptionnelle des gènes cibles d’ERα. Ce changement d’orientation cellulaire s’accompagne d’une reprogrammation massive du cistrome d’ERα avec une perte importante de ses sites de fixation à la chromatine, mais également de façon inattendue, un enrichissement en nouveaux ERBSs. Enfin, nous montrons une forte augmentation des interactions « non-génomiques » d’ERα avec des partenaires cytoplasmiques tels que PI3K, MSK1 et Src. Ces données suggèrent que dans des cellules agressives de type mésenchymal exprimant ERα, l’activité du récepteur repose majoritairement sur son action « non-génomique ». De façon intéressante, l’utilisation de l’anti-œstrogène pur ICI 182 780 n’a aucun effet inhibiteur sur ces interactions, pour lesquelles un rôle fonctionnel reste à établir. / Estrogens, and in particular estradiol E2, regulate a considerable number of physiological functions in the body and allow the establishment and maintenance of reproductive functions in all vertebrates. E2 acts locally in multiple target organs via its receptors: ERα and ERβ. By its proliferative action contributing to the renewal of the mammary epithelium, E2 as well as its ERα receptor have been associated with the pathological development of mammary tumors. These are qualified as hormone-dependent because they, for the majority of them, respond to the use of hormone therapy to block their growth. Unfortunately, it is estimated that 30-40% of mammary tumors end up with resistance to anti-estrogen treatments, through extremely complex mechanisms. The work presented in this manuscript aims to better understand the molecular and cellular mechanisms involved in the escape of mammary tumor cells to hormonal control. In this thesis, we looked at two factors that can modulate the ERα activity: hypoxia, which refers to oxygen depletion in the cellular microenvironment, and the RhoA/MKL1 pathway that is frequently activated during the epithelial-mesenchymal transition. Hypoxia is a major feature of solid tumors, and studies suggest a role in the development of endocrine resistance in breast cancer. We show that hypoxic stress strongly inhibits the expression of ERα, mainly at the protein level, and that it abolishes E2-induced cell proliferation and survival. Transcriptomic analysis shows that a certain number of ERα target genes are also regulated by hypoxia, which can either repress (CXCL12) or increase their expression (AREG ...). Moreover, the analysis of the ERα cistrome demonstrates a massive loss of the number of ERBSs (Estrogen Receptor Binding Site) by hypoxia, but also an appearance of hypoxia-specific ERBSs. Our results suggest that the strong regulatory overlap between ERα and hypoxia may modulate the efficacy of anti-hormonal therapies. Finally, the team demonstrated that the activation of the RhoA/MKL1 pathway causes a strong inhibition of the ERα AF1 function. In order to better understand the effects of this signaling pathway on ERα activity, an MCF7 cell line stably expressing a constitutively active mutant of the MKL1 factor was generated. We show that its expression profoundly modifies the cellular context by causing the switch from a luminal phenotype to a basal-like phenotype. The transcriptomic analysis of the E2 response shows that the MKL1 induced change in cell fate abolishes any transcriptional regulation of ERα target genes. This change in cellular orientation is accompanied by massive reprogramming of the ERα cistrome with a significant loss of its chromatin binding sites, but also unexpectedly, an enrichment of new ERBSs. Finally, we show a strong increase of "non-genomic" ERα interactions with cytoplasmic partners such as PI3K, MSK1 and Src. These data suggest that in aggressive mesenchymal cells expressing ERα, the receptor activity is mainly based on its "non-genomic" action. Interestingly, the use of pure anti-estrogen ICI 182 780 has no inhibitory effect on these interactions, for which a functional role remains to be established.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-09-04T23:28:52Z No. of bitstreams: 1 GILDENOR XAVIER MEDEIROS - TESE PPGMV 2012..pdf: 4491976 bytes, checksum: 2cbe5329ba4f65a3e25cfcbe603d09f2 (MD5) / Made available in DSpace on 2018-09-04T23:28:52Z (GMT). No. of bitstreams: 1 GILDENOR XAVIER MEDEIROS - TESE PPGMV 2012..pdf: 4491976 bytes, checksum: 2cbe5329ba4f65a3e25cfcbe603d09f2 (MD5) Previous issue date: 2012-06-29 / Esta tese inclui três artigos sobre epidermólise bolhosa (EB) em animais, uma doença hereditária, cuja principal característica é a formação de bolhas e erosões na pele e mucosas em resposta ao mínimo trauma. O primeiro capítulo é um artigo de revisão que abrange o diagnóstico, a classificação, a epidemiologia, o modo de herança, a clínica, a patologia e as alterações ultraestruturais e moleculares da EB em animais. Baseado no nível ultraestrutural de separação do tecido, a EB é dividida em três tipos: simples, juncional e distrófica. Em humanos estima-se que a EB afeta 1 em 17.000 nascidos vivos, mas em animais a frequência de EB não é estimada. Os achados clínicos e patológicos são semelhantes em todos os tipos de EB, variando apenas na intensidade. A EB é causada por mutações nos genes que expressam as proteínas do citoesqueleto dos queratinócitos ou da zona da membrana basal (ZMB). No segundo capítulo foram descritos em caprinos os achados clínicos, histopatológicos e ultraestruturais da EB distrófica transmitida por um gene autossômico recessivo. Os caprinos apresentaram exungulação, erosões, crostas e cicatrizes na pele e úlceras na cavidade oral. Histologicamente, a pele apresentava uma separação subepidérmica preenchida com fluido eosinofílico claro, restos celulares ou neutrófilos. Ultraestruturalmente, o local de separação foi abaixo da lâmina densa na ZMB. Na pele com formação de bolhas e na pele não envolvida clinicamente, a lâmina basal foi preservada, mas as fibrilas de ancoragem eram escassas e rudimentares. Sugere-se que a doença é similar a EB distrófica recessiva generalizada e severa observada em humanos. No terceiro capítulo é descrito um caso de EB em um bezerro. Ele tinha exungulação de todos os cascos, erosões e crostas generalizadas na pele e úlceras na cavidade oral. Na histologia da pele foi observada separação subepidérmica. No exame ultra-estrutural foi identificado a separação ao nível da lâmina lúcida na ZMB, deixando a lâmina densa unida às papilas dérmicas. Os hemidesmossomos apresentavam-se pequenos, pobremente definidos e sem demarcação clara. Os achados clínicos, histológicos e ultraestruturais encontrados no bezerro são característicos da EB juncional. / This thesis includes three papers on epidermolysis bullosa (EB) in animals, which is an hereditary disease, characterized by the formation of blisters and erosions on the skin and mucous in response to minor mechanical trauma. The first paper reviews the diagnosis, classification, epidemiology, mode of inheritance, clinical, pathology, and ultrastructural and molecular changes of EB reported in animals. Based on the ultrastructural level of tissue separations EB is divided into three types: simplex, junctional, and dystrophic. In humans it is estimated that EB affect 1 in 17000 live births, but in animal the frequency of EB is not estimated. The clinical and pathological findings are similar in all types of EB, varying only in intensity. EB is due to mutations in genes that express the protein constituent the cytoskeleton of the basal keratinocytes or of the basement membrane zone (BMZ). In the second paper, clinical, histopathological, and ultrastructural findings of dystrophic EB in goats transmitted by an autosomal recessive gene are reported. The goats presented with exungulation, erosions, crusts and scars on the skin and ulcers in the oral cavity. Histologically, the skin showed subepidermal separation, with clefts filled with clear eosinophilic fluid, cellular debris or neutrophils. Ultrastructurally, the site of blister formation was the sub-lamina densa in the BMZ. In skin with blister formation and in clinically uninvolved skin, the basal lamina was preserved, but the anchoring fibrils were scarce and rudimentary. It is suggested that the disease is similar to human severe generalized recessive dystrophic EB. In the third paper, a case of EB in a calf is reported. It was presented exungulation of all hooves, widespread erosions and crusts on the skin, and ulcers in the oral cavity. Histologically, the skin showed subepidermal clefts. Ultrastructurally, there was epidermal-dermal separation at the level of the lamina lucida, with the lamina densa attached to the papillary dermis. The hemidesmosomes were poorly defined and small. The clinical, histological and ultrastructural findings are characteristic of junctional EB.

Made available in DSpace on 2015-07-22T20:49:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-24 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Associação Fundo de Incentivo à Psicofarmacologia (AFIP) / Centros de Pesquisa, Inovação e Difusão (CEPID) / Durante o processo de envelhecimento ocorrem alterações neuroquímicas, morfológicas e funcionais, como a redução de algumas das características do sono, da quantidade da massa livre de gordura e da taxa metabólica basal. Estes fatores podem estar relacionados uma vez que a diminuição da taxa metabólica basal ocorre em conseqüência da diminuição da massa livre de gordura. O treinamento físico provavelmente pode minimizar tais efeitos e/ou trazer resultados positivos ao padrão do sono, assim como aos parâmetros da composição corporal e ao metabólico. O objetivo deste estudo foi avaliar os efeitos do treinamento resistido na taxa metabólica basal (TMB), na composição corporal e nos parâmetros do sono, verificando as suas possíveis relações em homens idosos. A amostra foi composta por 37 homens idosos com uma idade entre os 65 e os 75 anos, distribuídos aleatoriamente em dois grupos: o controle (GC) e o resistido (GR). O protocolo incluiu 72 sessões de treinamento resistido progressivo realizado três vezes semanais; e avaliações do metabolismo basal, da composição corporal, do sono (objetiva e subjetiva) e do consumo alimentar. Os resultados demonstraram que a força muscular aumentou em todos os grupos musculares no GR. Nas variáveis morfológicas, somente o GC aumentou a massa gorda e diminuiu a livre de gordura na avaliação final, enquanto que o GR manteve todas as variáveis da composição corporal. A TMB e o consumo energético diário não sofreram alterações em ambos os grupos ao longo das avaliações. Nas variáveis do sono, o GC aumentou o tempo total de sono, os microdespertares e o valor da escala de Pittsburgh, enquanto que o GR reduziu significativamente o percentual do estágio 1 do sono NREM. Houve associação de causa e efeito da massa livre de gordura (kg) e do estágio 1 sobre a TMB com o modelo final de regressão (TMB= 539,81 + 21,99 massa livre de gordura – 26,01 estágio 1), o que explica os 34% da variação da TMB. Em conclusão, os resultados sugeriram que o treinamento resistido, apesar de não alterar as relações entre a TMB, o sono e a composição corporal, foi efetivo para aumentar a força muscular, manter a massa livre de gordura e a TMB, e ainda melhorar a qualidade do sono em idosos saudáveis, refletindo numa qualidade de vida mais ativa para uma longevidade saudável. / During the process of aging, neurochemical, morphological and functional changes occur such as the decline of some characteristics of sleep, the amount of fat free mass and basal metabolic rate. These factors may possibly be related because the decrease in basal metabolic rate is due to the decrease in fat free mass. Physical training can possibly minimize such effects and / or bring positive results to sleep pattern, body composition and metabolism. The objective of this study was to evaluate the effects of resistance training on basal metabolic rate (BMR), body composition and parameters of sleep and to verify their possible relationship in elderly men. The sample consisted of 37 elderly men age 65 to 75 years randomly assigned into two groups: control (CG) and resisted (RG). The protocol included 72 sessions of progressive resistance training performed three times weekly, the evaluation of basal metabolism, body composition, sleep (objective and subjective) and food consumption. The results showed that muscle strength increased in all muscle groups in the RG. In the morphological variables, only the CG had the fat mass increased and decreased fat free mass in the final evaluation, in the other hand the RG remained with the same variables of body composition. The BMR and daily energy consumption remained unchanged in both groups during the evaluations. As far as sleep variables are concerned, the CG increased total sleep time, arousals and score of the scale of Pittsburgh, while the RG significantly reduced the percentage of stage 1 of NREM sleep. There was a chance association of the fat free mass (kg) and stage 1 for the BMR with the final model of regression (BMR = 539.81 + 21.99 mass free of fat - 26.01 stage 1), explaining 34% change in BMR. In conclusion, the results suggest that resistance training, although not altering the relationships between BMR, the sleep and body composition was effective in increasing muscle strength, keep free of fat mass and BMR and to improve the quality of sleep in healthy elderly, reflecting a quality of life more active for a healthy longevity. / FAPESP: 06/05210-0 / CEPID: 98/14303-3 / TEDE / BV UNIFESP: Teses e dissertações