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Orientador: Débora Cristina Damasceno / Coorientador: Yuri Karen Sinzato / Banca: Mara Sandra Hoshida / Banca: Luciane Dias Alargão Dias Melicio / Resumo: Introdução:Muitos estudos mostram a regeneração pancreática em um ambiente diabético e não exploram este processo no organismo saudável. Para compreender melhor os mecanismos envolvidos na regeneração das ilhotas pancreáticas sem o envolvimento do diabete. Objetivo:Avaliar a estrutura morfológicadas ilhotas pancreáticas desde o período neonatal até a idade adulta de ratas. Metodologia:Recém-nascidos do sexo feminino foram distribuídos aleatoriamente em diferentes grupos de estudo para coleta do pâncreas e soro em diferentes períodos de vida (5, 15, 90 dias de vida e no 18,5º dia de prenhez). Para a análise histopatológica, foram considerados os aspectos morfológicos observados na coloração de hematoxilina e eosina (HE). A análise morfométrica foi realizada em sistema computadorizado de imagem (software KS-300, versão 3.0, Zeiss). Para análise imunoistoquímica, foram utilizados os anticorpos anti insulina, anti PDX-1, anti GLP-1, anti Ki-67 e anti caspase-3. A avaliação imunoistoquímica foi realizada por contagem de células positivas através da grade de Weibel modificada. Resultados:Com cinco dias de vida, foi observado menor área comparado a dos outros períodos. Na fase adulta e durante a prenhez, as ratas apresentaram diminuição do número de células positivas para insulina e aumento de células quiescentes comparado às dos dias 5 e 15 de vida pós-natal. Um pico de proliferação celular foi observado no 15°dia de vida e, em todos os momentos estudados, foi observado maior frequência de morte celular das células não-beta (β) das ilhotas pancreáticas (células α, δe PP) em relação às células βpancreáticas. Durante a prenhez, houve diminuição do número de células positivas para GLP-1 em relação aos dias 5 e 15 de vida. Conclusão:As ilhotas pancreáticas apresentaram mudançasem sua morfologia, sobretudo durante os primeiros 15 dias de vida, sendo estas mudanças suficientes para ... / Abstract: Not available / Mestre

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Heart failure, as a result of myocardial infarction, is a major cause of mortality in human. The main cause of heart failure is that when adult cardiomyocytes die in the infarct site they do not regenerate. Instead the infract site is replaced by fibroblasts and collagen scar. It is generally believed that cardiomyocytes have terminally differentiated and can not divide to replace cardiomyocytes that have lost following injury. However, recently published data have provided new evidence that there is a small but continuously turnover of cardiomyocytes in the adult heart. These new findings provide a new theory that the heart does possess a limited ability to regenerate. / I also examined the regenerative ability of cardiomyocyte in adult heart. MRL mice were used because previously it has been reported that the cardiomyocyte could proliferate in response to injury. To understand how the cardiomyocytes in the MRL mouse heart, I used a cryo-injury approach. I discovered that the cardiomyoctyes in MRL mouse hearts were capable of dividing shortly after cryo-injury. These MRL hearts healed without scarring in contrast to C57BL/6 control mice. It was discovered that BMP-2, GATA4 and Nkx2.5 were involved in the healing process. The activation of these genes induced the cardiomyocyte to re-enter the cell cycle so that new cardiomyocytes could replace the cell that have been lost in the infarct site. I also discovered that stem cells may also play a minor role in the healing process. / In summary, my research findings revealed that cardiomyocytes regeneration in the heart is a very complex process that involves the participation of many cells and signalling pathway. There findings raise many intriguing and important questions and are worthy of being addressed in the future. / Stem cell therapy has been proposed as a potential treatment for various myocardial diseases. Chen et al. (2004) found small chemical called reversine that could dedifferentiate C2C12 cells to become stem-like cells. In this study, I demonstrated that reversine could inhibit the growth of C2C12 cell. The presence of reversine in cell culture could significantly inhibit muscle-specific genes MyoD, Myogenin and Myf5 expression. These 3 muscle specific transcriptional genes are essential for maintaining muscle differentiation. The down regulation of these gene showed that reversine could dedifferentiate C2C12 cells. We also discovered that reversine-treated C2C12 cells could differentiate into cardiomyocytes when they were cocultured with cardiomyocytes or when transplanted into the infarct site of a cryo-injured heart. / To investigate the regenerative potential of cardiomyoctyes in adult heart, we tried first to uncover the signals that direct post-natal cardiomyocytes to enter into growth arrest and differentiation. In the first part of my study, I established that the cardiomycytes divided extensively in 2 day-old post-natal hearts and that the majority of these cells entered into growth arrest and terminal differentiation at day 13. Comparative proteomic techniques were used in order to identify proteins that might be associated with cardiomyocytes proliferation during terminal differentiation the mouse heart. Several proteins were found to be differently expressed and amongst them was cyclin I protein. Cyclin I was found strongly expressed in 13 day old hearts. The protein is involved in signaling growth arrested in cells. / Liu, Ye. / "November 2006." / Adviser: Lee Ka Ho. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5658. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 142-172). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Although deafness is a universal problem, effective treatments have remained elusive. In order to develop potential treatments, an overall understanding of the cellular process of auditory hair cell regeneration, which occurs in fish but not mammals, must be established. A previous microarray analysis and qRT-PCR validation of noise-exposed zebrafish showed that growth hormone (GH) was significantly upregulated during the process of auditory hair cell regeneration. Thus, GH may play an important role during hair cell regeneration. However, cellular effects of exogenous GH in the zebrafish auditory hair cell regeneration have not been examined after noise exposure. To understand the effect of GH in hair cell regeneration, adult zebrafish were exposed to a 150 Hz pure tone at a source level of 179 dB re 1 μPa RMS for 36 hours. Afterward the fish were immediately injected intraperitoneally with carp recombinant GH (20 μg/gram of body mass) or buffer (0.1 M, pH 7.4 phosphate buffer) and then placed in a recovery tank. The effect of GH on apoptosis in fish inner ear end organs were examined using TUNEL-labeling. Cell proliferation was measured by BrdU incorporation assay. Hair cell regeneration was determined by phalloidin-labeling to allow visualization of hair cell stereociliary bundles. After GH injection, the numbers of TUNEL-labeled cells showed a significant decrease in all three inner ear end organs (saccule, lagena, utricle), suggesting GH may suppress hair cell death induced by acoustic trauma. Higher levels of cell proliferation were also observed in the ears of GH-injected fish, indicating that GH is capable of activating cell mitosis in the zebrafish auditory system. Following sound exposure, the GH-injected group exhibited greater numbers of saccular hair cell bundles compared to the buffer-injected group. These results indicate that GH promotes hair cell regeneration following acoustic damage. Future studies are needed to examine the potential therapeutic benefits of GH in the mammalian ear.

Objective: Injuries to the marrow cavity result in rapid bone formation followed by regeneration of the marrow. It is not known whether this process is affected by age, although the quality of marrow is markedly different in young and old animals. To test if marrow restoration differs with age, we used the rat tibial bone marrow ablation model, which has been used to examine calcification, osteointegration of metal implants, and remodeling of bone graft substitutes. Methods: Marrow was ablated in the left tibia of seven rats (rNu/rNu) per time point. At 0,7,14,21,28,35 and 42 days post-surgery, treated tibias and contralateral tibias were harvested and fixed in buffered formalin. Both tibias were scanned using microCT and trabecular and cortical BVF/TV calculated. Mid-sagittal sections of decalcified bones were stained with H&E and BVF/TV calculated. Results: MicroCT analysis of 1-month animals showed increased bone formation on day-7 and on day-21 the marrow was restored. Increased bone was seen in 3-month animals on day-7 and day-14, but it was significantly less than in 1-month rats. By day-21, trabecular bone was reduced by 50%. 10-month animals had less trabecular bone at day-7 and 14, but bone remained in the medullary canal through day-1. Histomorphometry indicated that bone formation peaked at day-7 in 1-month rats with remodeling underway by day-14. Bone formation in 3-month rats also peaked at day-7, but restoration occurred by day-21. However, in 10-month rats, peak bone occurred on day-14, with remodeling on day-28. Conclusions: Aged animals produced less primary bone than younger animals and remodeling was initiated later. Differences in micro-CT and histomorphometric analyses may reflect a reduction in calcification of the osteoid in the 10-month old animals. (Supported by Boston Scientific, Inc.)

Thesis (M.S.)--Duquesne University, 2004. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 55-60) and index.

1. A brief historical introduction is given. It deals with the general features of wound healing in which epithelial participation is the dominant feature. 2. In Section A the influence of ascorbic acid on healing of skin wounds in rats is discussed. 3. Second wounds were inflicted at the same site as the initial wounds one month after the latter had healed. 4. In Section B the influence of ascorbic acid on healing of skin wounds in guinea pigs is investigated. 5. In order to discover the action ascorbic acid has on ear wounds, the tips of guinea pigs' ears were cut off. 6. The influence of ascorbic acid on the regeneration of corneal epithelium in guinea pigs is discussed. 7. The effect of ascorbic acid on healing of muco-periosteum was studied. 8. The influence of pantothenic acid on healing of skin wounds in rats was studied. 9. Pantothenic acid (Bepanthen-Salbe) ointment was applied directly to skin wounds.

Made available in DSpace on 2014-08-13T14:51:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-27Bitstream added on 2014-08-13T17:59:32Z : No. of bitstreams: 1 000776793.pdf: 3333104 bytes, checksum: ef4af27a6609c9136872bbf27eeb0084 (MD5) / Introdução:Muitos estudos mostram a regeneração pancreática em um ambiente diabético e não exploram este processo no organismo saudável. Para compreender melhor os mecanismos envolvidos na regeneração das ilhotas pancreáticas sem o envolvimento do diabete. Objetivo:Avaliar a estrutura morfológicadas ilhotas pancreáticas desde o período neonatal até a idade adulta de ratas. Metodologia:Recém-nascidos do sexo feminino foram distribuídos aleatoriamente em diferentes grupos de estudo para coleta do pâncreas e soro em diferentes períodos de vida (5, 15, 90 dias de vida e no 18,5º dia de prenhez). Para a análise histopatológica, foram considerados os aspectos morfológicos observados na coloração de hematoxilina e eosina (HE). A análise morfométrica foi realizada em sistema computadorizado de imagem (software KS-300, versão 3.0, Zeiss). Para análise imunoistoquímica, foram utilizados os anticorpos anti insulina, anti PDX-1, anti GLP-1, anti Ki-67 e anti caspase-3. A avaliação imunoistoquímica foi realizada por contagem de células positivas através da grade de Weibel modificada. Resultados:Com cinco dias de vida, foi observado menor área comparado a dos outros períodos. Na fase adulta e durante a prenhez, as ratas apresentaram diminuição do número de células positivas para insulina e aumento de células quiescentes comparado às dos dias 5 e 15 de vida pós-natal. Um pico de proliferação celular foi observado no 15°dia de vida e, em todos os momentos estudados, foi observado maior frequência de morte celular das células não-beta (β) das ilhotas pancreáticas (células α, δe PP) em relação às células βpancreáticas. Durante a prenhez, houve diminuição do número de células positivas para GLP-1 em relação aos dias 5 e 15 de vida. Conclusão:As ilhotas pancreáticas apresentaram mudançasem sua morfologia, sobretudo durante os primeiros 15 dias de vida, sendo estas mudanças suficientes para ...

CAPES / No Paraná, foram identificados 14 fragmentos florestais de Floresta Ombrófila Mista, onde ocorre a espécie Plinia cauliflora. A maioria dessas populações encontra-se em áreas de reserva legal e sofrem com a colheita extrativista dos frutos (jaboticabas) e outras ações antrópicas. O presente trabalho teve como objetivo determinar classes ontogenéticas, regeneração e distribuição espacial em populações de jaboticabeira (Plinia cauliflora) no Sudoeste do Paraná. Foram determinados os estádios ontogenéticos por meio de amostragem aleatória (n=50). Foram delimitadas unidades amostrais em seis fragmentos localizados em quatro municípios do sudoeste do Paraná. Obteve-se diâmetro, altura e coordenadas cartesianas (x,y). Os dados foram avaliados por meio de estatística descritiva. A distribuição espacial e a dependência espacial foram verificadas através da função O’ring uni e bivariada. Foram encontrados cinco estádios ontogenéticos para jaboticabeira: plântulas (h ≤ 0,10 m); juvenis (h >0,10 m até 1,70 m); imaturo (altura >1,70 m até 5 m); virgem (h > 5 m, sem estruturas reprodutivas); reprodutivos (h > 5 m com estruturas reprodutivas). Os resultados mostram que há diferença estrutural entre os remanescentes, acarretando no potencial de regeneração das populações. As populações de Clevelândia, Pato Branco I e II apresentaram todas as classes ontogenéticas estabelecidas, um maior número de indivíduos nas classes que representam a regeneração (plântulas, juvenis e imaturos) e distribuição de altura e diâmetro do tipo J-invertido. O contrário foi observado nas outras populações. Esses resultados estão atribuídos, principalmente ao histórico de uso das áreas e consequentemente nas maiores chances de existência de possíveis animais dispersores. Esse fato poderá aumentar as chances de germinação e estabelecimento de plântulas de jaboticabeira. A distribuição espacial variou entre populações, apresentando distribuição aleatória na maioria dos estádios ontogenéticos, com exceção das populações de Clevelândia e Chopinzinho II. Não houve dependência espacial entre pares de estádios ontogenéticos em nenhuma das populações. Esses resultados podem estar atribuídos à dispersão ou outros fatores, necessitando de mais estudos. Pode-se concluir que o histórico de manejo das áreas e a contínua ação antrópica em alguns locais parece ser um dos principais empecilhos na regeneração de indivíduos de jaboticabeira e consequente recrutamento em classes de tamanho maiores. / In the Brazilian state of Paraná were identified 14 forest fragments of Mixed Ombrophilous Forest where species Plinia cauliflora occurs. Most of those populations are in a legal reserve area and suffer from extractive harvesting of fruits (jaboticabas) and other anthropogenic actions. Our objective with this work was to determine ontogenetic stages, regeneration and spatial distribution on populations of jaboticabeira (Plinia cauliflora) in the Southwest of Paraná. We determine the ontogenetic stages by random sampling (n=50). We set sample units (70x70m) in six fragments located in four cities in the southwest of Paraná. On those fragments we collected diameter, height and Cartesian coordinates (x, y). Collected data were evaluated through descriptive statistics. Spatial distribution and spatial dependence were verified through the univariate and bivariate O'ring function. We found five ontogenetic stages for jaboticabeira: seedlings (h ≤ 0.10 m); juveniles (h> 0.10 m to 1.70 m); immature (height> 1.70 m to 5 m); virgin (h> 5 m, without reproductive structures); reproductive (h> 5 m with reproductive structures). Results showed that there are structural differences between the remnants which have on effect on potential regeneration of the populations. The populations of Clevelândia, Pato Branco I and II have all ontogenetic classes established. They also, showed a greater individuals numbers of classes which represent regeneration (seedlings, juveniles and immature) as well J-inverted height and diameter distribution. On the other half of populations the opposite situation was noticed. We attributed these results basically by the use of areas historically and consequently greater chances of possible existence dispersing animals which increases chances of germination and establishment of jaboticabeira seedlings. Spatial distribution varied between populations showing a random distribution on most ontogenetic stages exceptionally for Clevelândia and Chopinzinho II populations. There was no spatial dependence between ontogenetic pairs of stages in any population. These results may be attributed to dispersion or other factors which requires further studies. We accomplished that management history of the areas combined with, a continuous anthropic action in some places, seems to be one of the main obstacles in the regeneration of jaboticabeira individuals and consequent recruitment in larger size classes.