As neoplasias mieloproliferativas (NMPs) Filadelfia negativo como a policitemia vera (PV), trombocitemia essencial (TE) e mielofibrose primária (MFP) são desordens clonais da célula tronco hematopoiética caracterizadas pela produção excessiva de células mielóides diferenciadas. Este fenômeno ocorre devido à uma mutação somática (JAK2V617F) que ativa a via JAK-STAT de transdução de forma constitutiva. Esta mutação é mais frequente na PV, ocorrendo em 95% dos casos, e em 50% dos casos de TE e MFP. Outro defeito genético que ocorre é a mutação no receptor de trombopoetina, MPL. As mutações em MPL podem ser germinativas ou somáticas e menos de 10% dos pacientes com TE e MFP apresentam essa alteração genética. Entretanto, grande parte dos pacientes com TE e MFP que não apresentam mutação em JAK2V617F ou MPL podem apresentar mutações somáticas no gene CALR. Em adição às mutações somáticas que causam mieloproliferação, outras alterações genéticas em genes que funcionam como reguladores epigenéticos são encontrados nas NMPs nos genes TET2, IDH1, IDH2 e ASLX1. Objetivo: Estabelecer um perfil genético em pacientes com NMP através da avaliação de mutações nos genes JAK2, CALR, MPL, IDH1, IDH2, TET2 e ASXL1 assim como estabelecer uma correlação laboratorial destas na PV, TE e MFP. Casuística e Métodos: Foram utilizadas amostras de sangue periférico de 104 pacientes que foram enviadas para o Laboratório de Biologia Tumoral do Serviço de Hematologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo para avaliação diagnóstica. Quinze dos 104 pacientes são de pacientes com PV (14,4%), 20/104 (19,2%) com MFP, 20/104 (19,2%) com TE e 49/104 (47,1%) com outras doenças hemtológicas. Foi feita a avaliação da prevalência de mutações somáticas, seja por sequenciamento ou análise de fragmentos, nos genes JAK2 (exon 12 e Y931C), MPL, IDH1, IDH2, CALR, TET2 e ASXL1. PCR-RFLP foi realizada para identificação de mutações em JAK2V617F. Resultados: A mutação JAK2V617F foi observada em 30 (28,8%) pacientes (12 PV, 11 TE e 7 MFP), a mutação JAK2 exon 12 foi observada em apenas um (0,96%) paciente com PV, mutação JAK2Y931C em 4 (3,8%) pacientes (1 PV, 2 TE e 1 MFP) e 8 (7,7%) pacientes apresentaram mutações em CALR (3 TE e 5 MFP). Mutações nos genes epigenéticos como IDH1 foram observadas em 9 (8,7%) pacientes (2 TE, 2 MFP, 1 SMD, e 4 pacientes com suspeita de NMP), mutações em IDH2 estão presentes em 5 (4,8%) pacientes (2 TE, 1 SMD/leucemia e 4 pacientes com suspeita de NMP), mutações em ASXL1 foram identificadas em 13 (12,5%) pacientes (1 PV, 3 TE, 2 MFP, 3 SMD/leucemias e 4 com suspeita de NMP) e finalmente, mutações em TET2 foram encontradas em 33 (31,7%) pacientes (3 PV, 5 TE, 4 MFP, 8 SMD/leucemias e 13 pacientes com suspeita de NMP). Além disso, no caso da PV, os pacientes que apresentam mutações em JAK2V617F apresentam valores aumentados de plaquetas (mediana de 5,41 x 105/mm3 plaquetas) em relação aos pacientes sem a mutação (mediana de 2,06 x 105/mm3 plaquetas), com diferença estatística (p=0,031). Pacientes do mesmo grupo que apresentam mutações em TET2 apresentam, opostamente aos com mutações em JAK2V617F, menores valores de plaquetas (mediana de 1,75 x105/mm3 plaquetas) em relação aos pacientes sem mutações no gene TET2 (mediana de 5,41 x 105/mm3 plaquetas), com diferença estatística (p=0,048). No caso da MFP, os pacientes que apresentam mutações em JAK2V617F apresentam valores maiores de leucócitos (mediana de 1,09 x104/mm3 leucócitos) do que os pacientes que não apresentam a mutação (mediana de 6,99 x103/mm3 leucócitos) com diferença estatística (p=0,046), já os pacientes que apresentam mutações no gene ASXL1 apresentam valores menores de hemácias (mediana de 2,43 x106/mm3 hemácias) em relação aos pacientes que não apresentam mutação (mediana de 3,71 x106/mm3 hemácias) com diferença estatística (p=0,042). Conclusão: O trabalho permitiu fornecer um perfil genético dos pacientes com NMP estudados. Além disso, é possível observar que algumas mutações epigenéticas podem influenciar em diferenças clínicas / Myeloproliferative neoplasms (MPNs) Philadelphia (Ph) chromosome negative, such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are clonal disorders of hematopoietic stem cell characterized by increased proliferation of differentiated myeloid cells. This phenomenon occurs due somatic mutation (JAK2V617F) that constitutively stimulates the JAK-STAT signaling pathway. This mutation is more frequent in PV, around 95%, and between 50% in ET and PMF. Other genetic aberration can be observed in the thrombopoietin (TPO) receptor MPL. Mutations in MPL can be in the germline line or somatic and less than 10% of patients with TE or PMF would harbor this genetic alteration. Otherwise, patients with TE or PMF without JAK2V617F or MPL mutation could present somatic mutations in calreticulin (CALR). In addition to somatic mutations that cause myeloproliferation, other genetic alterations that function as epigenetic regulators were identified in genes as TET2, IDH1, IDH2 e ASLX1 in MPN. Objective: Establish genetic profile in patients with diagnosis of PV, ET, and PMF through genetic alterations in the following genes: JAK2, MPL, CALR, IDH1, IDH2, TET2 e ASXL1, and correlate those alterations with demographic characteristic of the study population. Casuistic and Methods: Peripheral blood samples from 104 patients referred to the Tumor Biology Laboratory of the Department of Hematology of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo for diagnostic investigation were analyzed. Fifteen out 104 samples were from PV patients (14.4%), 20/104 (19.2%) in PMF, 20/104 (19.2%) in ET and 49/104 (47.1%) with other hematologic diseases. Identification of somatic mutations was made, either by direct sequencing or fragment analysis in JAK2 (exon 12 and Y931C), MPL, IDH1, IDH2, CALR, TET2 and ASXL1. PCR-RFLP was performed to identify JAK2V617F mutation. Results: JAK2V617F mutation was observed in 30 (28.8%) patients (12 PV, 11 ET and 7 PMF), JAK2 exon 12 in only one (0.96%) patient with PV, JAK2Y931C in 4 (3.8%) patients (1 PV, 2 ET and 1 PMF), and 8 patients (7.7%) presented CALR mutation (3 ET and 5 PMF). Mutations in the epigenetic genes as IDH1 were observed in 9 (8.7%) patients (2 ET, 2 PMF, 1 MDS and 4 patients with suspected MPN), IDH2 mutations were present in 5 (4.8%) patients (2 ET, 1 MDS/leukemia, and 4 patients with suspected MPN), ASLX1 mutations were identified in 13 (12.5%) patients (1 PV, 3 ET, 2 PMF, 3 MDS/leukemia and 4 with suspected MPN) and finally, TET2 mutations were present in 33 (31.7%) patients (3 PV, 5 ET, 4 PMF, 8 MDS/leukemia, and 13 with suspected MPN). In addition, patients with PV who harbor JAK2V617F have increased platelet counts (median 5.41 x 105/mm3 platelets) compared to those without the mutation (median 2.06 x 105/mm3 platelets, p=0.031). Patients in the same group with TET2 mutation, as opposed to those with JAK2V617F, presented low platelets counts (median of 1.75 x 105/mm3 platelets) compared to those without TET2 mutation (median 5.41 x 105/mm3 platelets, p=0.048). Presence of JAK2V617F in patients diagnosed with PMF have a greater number of leukocytes (median 1.09 x104/mm3 leukocytes) when compared to patients without the mutation (median 6.99 x 103/mm3 leukocytes, p=0.046). Patients with PMF who presented mutations in ASXL1 gene have a lower number of red blood cells (median of 2.43 x 106/mm3) compared to patients without mutations in the same gene (median 3.71 x 106/mm3, p=0.042). Conclusion: The present study allows us to provide a genetic profile of patients with MPN. Furthermore, it is possible to observe that some epigenetic mutations could influence in some clinical differences

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-11-25T10:17:54Z No. of bitstreams: 2 Tese - Omar Zina - 2013.pdf: 1884367 bytes, checksum: ac70615bb4bc9a680a17fead9dac004b (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-11-25T12:28:09Z (GMT) No. of bitstreams: 2 Tese - Omar Zina - 2013.pdf: 1884367 bytes, checksum: ac70615bb4bc9a680a17fead9dac004b (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-11-25T12:28:09Z (GMT). No. of bitstreams: 2 Tese - Omar Zina - 2013.pdf: 1884367 bytes, checksum: ac70615bb4bc9a680a17fead9dac004b (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-09-13 / The aim of this study was to determine the solution-powder ration and to evaluate the setting time, solubility, dimensional change, pH and radiopacity of White structural and non-structural Portland cement, ProRoot MTA® and MTA BIO® associated to 2% glycolic solution of Aloe vera. Five samples of each material were used for each test according to American National Standards Institute/American Dental Association specification 57. Statistical analyses were carried out using ANOVA and Tukey’s test at 5% level of significance. When sample distribution was non-normal, nonparametric analysis of variance were performed with Kruskal-Wallis test (α=0.05). The results revealed no statistical difference in the water-powder ratio among the tested materials. ProRoot MTA® had the longest setting time (116.50 ± 4.08) (P<0.05). White structural and nonstructural Portland cements did not have means values on the radiopacity test (109.76 ± 10.40 and 118.75 ± 15.44, respectively) in accordance with ANSI/ADA, being significantly different from the MTA-based cements (P<0.05), and demonstrated higher mean solubility values (2.30 ± 0.36 and 2.81 ± 0.40, respectively) (P<0.05). The values for dimensional change of all tested materials were considered acceptable by ANSI/ADA. There were no significant differences between the mean pH values recorded for the materials (p>0.05). It was alkaline from the beginning to the end of the tests. MTA BIO presented lower setting time and lower solubility. The cements did not showed a higher solubility than 3%. All the assessed cements showed acceptable values of dimensional variation and high pH during the test time. MTA BIO and ProRoot MTA had adequate radiopacity values. / Esse estudo teve como objetivo determinar propriedades físico-químicas dos cimentos Portland branco estrutural e não estrutural, ProRoot MTA® e MTA BIO® associados à solução glicólica de Aloe vera a 2%. Após o estabelecimento da proporção pó/líquido para cada cimento, foram analisadas as propriedaes físicoquímicas: tempo de endurecimento, alteração dimensional, pH e radiopacidade. Cinco amostras de cada cimento foram usadas para cada teste, seguindo a especificação n. 57 da American National Standards Institute/American Dental Association (ANSI/ADA). A análise estatística foi realizada usando ANOVA e o teste de Tukey em nível de significância de 5%. Quando a distribuição das amostras foi não normal, a análise de variância não paramétrica foi realizada com o teste de Kruskal-Wallis (α=0,05). Os resultados não mostraram diferenças estatisticamente significantes (p>0,05) entre os cimentos em relação à proporção pó/líquido, que variou de 3,14 a 3,52 gramas. O ProRoot MTA® apresentou o tempo de endurecimento mais longo (116,50 min) e o MTA BIO® o menor (66,75 min) (p<0,05). Os cimentos Portland brancos estrutural e não estrutural apresentaram valores médios de solubilidade mais elevados (2,30 e 2,81%, respectivamente) (p<0,05). Todos os cimentos testados apresentaram valores de alteração dimensional semelhantes entre si (1,00%). O pH dos cimentos manteve-se elevado do início ao final do experimento, não havendo diferenças significantes entre os valores médios obtidos (cimento Portland branco estrutural, 11,96; cimento Portland branco não estrutural, 11,80; MTA BIO® 12,07; ProRoot MTA® 11,77) (p>0,05). Os cimentos Portland branco estrutural e não estrutural não apresentaram valores médios em conformidade com ANSI/ADA no teste de radiopacidade (109,76 e 118,75 mmAl, respectivamente), significantemente diferentes dos cimentos MTA BIO® (156,83 mmAl) e ProRoot MTA® (157,95 mmAl) (p<0,05), que apresentaram valores de densidade radiográfica acima do degrau 3 do penetrômetro de alumínio. O MTA BIO® evidenciou menor tempo de endurecimento e menor percentual de solubilidade. Nenhum cimento apresentou solubilidade maior que 3%. Todos os xiv cimentos analisados mostraram valores aceitáveis de alteração dimensional e pH elevado durante todo o período de teste. O MTA BIO® e o ProRoot MTA® apresentaram valores de radiopacidade adequados..

Orientador: Maria Cristina Cintra Gomes Marcondes / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T00:25:10Z (GMT). No. of bitstreams: 1 Tomasin_Rebeka_D.pdf: 4368331 bytes, checksum: 33a1f49902e0d1a423b1a4b7ebe757e9 (MD5) Previous issue date: 2014 / Resumo: Câncer é um nome genérico para um grupo de mais de cem doenças que compartilham algumas características. Talvez a característica mais marcante das neoplasias malignas seja a rápida proliferação de células anormais para além de suas fronteiras usuais, invasão de tecidos adjacentes e finalmente dispersão para órgãos distantes. Anualmente, cerca de oito milhões de pessoas morrem devido ao câncer e outros doze milhões de novos casos são diagnosticados. Dentre os eventos associados à progressão neoplásica, destacam-se as metástases e a caquexia. Metástases são tumores em sítios secundários, sendo responsáveis por cerca de 90% do total de mortes por câncer. Já a caquexia, uma síndrome paraneoplásica, é caracterizada por extensa espoliação de gordura e massa magra, fadiga e alterações metabólicas, prejudicando a qualidade de vida e a sobrevida de cerca de 50-85% dos pacientes, dependendo do tipo de tumor. Com relação às terapias, o grande desafio ainda é combater o tumor sem prejudicar o hospedeiro, o que acredita-se ser possível através de terapias-alvo para genes específicos e/ou tratamentos coadjuvantes, incluindo aqueles que empregam suplementação e/ou drogas derivadas de produtos naturais, que muitas vezes tem menor efeito tóxico ao hospedeiro. Desse modo, este trabalho teve dois objetivos: (1) avaliar a ação da administração oral de Aloe vera e mel sobre o tecido tumoral e o hospedeiro portador de carcinosarcoma de Walker 256; e (2) identificação de genes supressores de metástase através de screen funcional in vivo empregando-se biblioteca de shRNA em modelo de câncer de mama triplo negativo. Em relação ao primeiro objetivo, os resultados sugerem que a associação entre Aloe vera e mel pode modular a proteólise e o estresse oxidativo de maneira diferencial preservando o hospedeiro em detrimento do tecido tumoral. Ainda, o tratamento com Aloe vera e mel parece ser capaz de diminuir a propensão metastática das células tumorais in vivo, através de aumento na expressão de caderina-E e redução na expressão de caderina-N, bem como inibição da angiogênese. Outros experimentos sugerem que os efeitos antitumorais observados in vivo estão, em parte, relacionados à ação imunomodulatória de alguns componentes da Aloe vera. Com relação ao segundo objetivo, foram identificados dezenas de candidatos a genes supressores de metástase. Dentre esses genes, que estão sendo validados, Mnat1, Snd1, Cul5, Gabbr1, Rorb, Adk, Ccnd3, Gdnf, Nr1d1, Ptprs e Ltah4 são os genes-candidatos de maior confiabilidade por cumprirem um ou mais dos seguintes requisitos: (a) diminuição significativa do nível de DNA e RNA em canceres de mama humanos agressivos, sendo assim relacionados à pior prognostico, (b) papel biológico sugestivo, (c) fenótipo marcante durante o screen ou ainda (d) decréscimo significativo na expressão em linhagens de câncer de mama mais agressivas / Abstract: Cancer is a generic name for a group of over a hundred diseases which share some features. The most remarkable feature in cancer disease is the fast proliferation of abnormal cells beyond their usual boundaries, invasion of surrounding tissues and finally spread to distant organs. Every year, cancer is responsible for over eight million deaths and twelve million new cases are diagnosed. Among all the events associated with the neoplastic progression, metastasis and cachexia are major issues. Metastases, which are tumours growing in secondary sites, account for 90% of all cancer deaths. Cachexia, a paraneoplastic syndrome, is characterized by severe fat and lean mass waste, fatigue and metabolic alterations, jeopardizing the quality of life and reducing the survival of about 50-85% of the cancer patients, depending on the tumour type. Regarding to the therapies, the biggest challenge is still fighting the tumour without harming the host, which is believed to be possible by targeted therapies to specific genes and/or adjuvant treatments, including supplementation and drugs derived from natural compounds, which usually have lower side effects in the host. Knowing these points, this work had two aims: (1) evaluate the effects of Aloe vera and honey in both tumour and host tissues in Walker 256-tumour bearing rats; and, (2) identification of metastasis suppressor genes using a functional in vivo shRNA screen in a triple negative breast cancer syngeneic model. Regarding to the first aim, the results suggested that the combination of Aloe vera and honey selectively modulate proteolysis and oxidative stress, damaging the tumour tissue while protected the host. Moreover, the Aloe vera and honey treatment apparently decreases the metastatic potential in vivo, by simultaneous increase in E-cadherin and decrease in N-cadherin expression, while decreased tumour vascularization. Finally, our results suggested the antitumoral effects observed in vivo are, at least partially, related to the immunomodulatory activity of some Aloe vera¿s compounds. Regarding to the second aim, dozens of putative metastasis suppressor genes were identified. High confidence candidates, which would be further analysed are Mnat1, Snd1, Cul5, Gabbr1, Rorb, Adk, Ccnd3, Gdnf, Nr1d1, Ptprs e Ltah4. Their selection was based on meeting the following requirements: (a) significant decrease at DNA or RNA level in highly aggressive human breast cancer carcinomas and thus, worse prognosis, (b) suggestive biological role, (c) occurrence of a remarkable phenotype during the screen, and (d) significant decrease in expression in more aggressive cancer cell lines / Doutorado / Biologia Celular / Doutora em Biologia Celular e Estrutural

The most popular and convenient route of drug administration remains the oral route, however, protein and peptide drugs such as insulin have poor membrane permeability and stability in the gastrointestinal tract. Absorption enhancers can be added to drug delivery systems to overcome the epithelial cell membrane permeability problem. Although previous studies have shown that aloe leaf materials improve the transport of drugs across intestinal epithelia, their performance in solid oral dosage forms has not yet been investigated. Beads containing insulin and each of the selected absorption enhancers (i.e. Aloe ferox, Aloe marlothii and Aloe vera gel materials) were produced by extrusion-spheronisation, using a full factorial design to optimise the formulations based on transepithelial electrical resistance (TEER) reduction of Caco-2 cell monolayers as response. The optimum bead formulations were evaluated in terms of friability, mass variation, particle surface texture, shape, size and dissolution. The transport of insulin across excised pig intestinal tissue from the optimised bead formulations was determined over a 2 h period. The samples obtained from the transport studies were analysed for insulin content by means of high-performance liquid chromatography (HPLC). The results showed that the TEER reduction, as an indication of tight junction modulation, obtained for the bead formulations containing aloe materials was concentration dependent. Furthermore, inclusion of croscarmellose sodium (Ac-di-sol®) as a disintegrant showed an enhanced TEER reduction effect in combination with the aloe gel materials. Dissolution profiles indicated that the beads containing aloe leaf materials in conjunction with insulin, released the insulin within an hour. In accordance with the TEER reduction results, the A. marlothii and A. vera materials containing beads showed similar increased insulin delivery across excised pig intestinal tissue, which was pronouncedly higher than that of the control group (insulin alone). It can be concluded that beads containing aloe leaf materials have high potential as effective delivery systems for protein therapeutics such as insulin via the oral route of administration. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The most popular and convenient route of drug administration remains the oral route, however, protein and peptide drugs such as insulin have poor membrane permeability and stability in the gastrointestinal tract. Absorption enhancers can be added to drug delivery systems to overcome the epithelial cell membrane permeability problem. Although previous studies have shown that aloe leaf materials improve the transport of drugs across intestinal epithelia, their performance in solid oral dosage forms has not yet been investigated. Beads containing insulin and each of the selected absorption enhancers (i.e. Aloe ferox, Aloe marlothii and Aloe vera gel materials) were produced by extrusion-spheronisation, using a full factorial design to optimise the formulations based on transepithelial electrical resistance (TEER) reduction of Caco-2 cell monolayers as response. The optimum bead formulations were evaluated in terms of friability, mass variation, particle surface texture, shape, size and dissolution. The transport of insulin across excised pig intestinal tissue from the optimised bead formulations was determined over a 2 h period. The samples obtained from the transport studies were analysed for insulin content by means of high-performance liquid chromatography (HPLC). The results showed that the TEER reduction, as an indication of tight junction modulation, obtained for the bead formulations containing aloe materials was concentration dependent. Furthermore, inclusion of croscarmellose sodium (Ac-di-sol®) as a disintegrant showed an enhanced TEER reduction effect in combination with the aloe gel materials. Dissolution profiles indicated that the beads containing aloe leaf materials in conjunction with insulin, released the insulin within an hour. In accordance with the TEER reduction results, the A. marlothii and A. vera materials containing beads showed similar increased insulin delivery across excised pig intestinal tissue, which was pronouncedly higher than that of the control group (insulin alone). It can be concluded that beads containing aloe leaf materials have high potential as effective delivery systems for protein therapeutics such as insulin via the oral route of administration. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

The main purpose of this study is to discuss Yvonne Vera‟s representation of various aspects of women‟s identity in a patriarchal and colonial context as they manifest themselves through the women‟s relationships. I explore ways in which the question of self for some of Vera‟s women seems characterised by marginalisation across racial, cultural, ethnic and generational divides. The short stories and novel studied seem to emphasise that for women, under patriarchy and colonialism in Zimbabwe, seeking an independent and fulfilling identity seems to be interpreted as defying society‟s expectations and dictates. However, even as Vera tells of the various women‟s failure to make breakthroughs, she points at a less gender- inflexible future where both men and women will be valued for their true worth, and not their mere biology, through foregrounding the women‟s stories as they challenge and subvert their societies‟ received norms, traditions and values. / English / M.A. (English)

This thesis examines the links between and intersections of violence and subjectivity in a comparative, transatlantic and transnational study of the fiction of four recognized international authors, namely, Toni Morrison, Cormac McCarthy, J. M. Coetzee, and Yvonne Vera. Despite their differing geographical, temporal, cultural and socio-political situations and situatedness, these writers’ common, thematic concerns with taboo topics of violence such as rape, incest, infanticide and necrophilia, situate violence as a constitutive, intimate and intricate part of subjectivity. In providing varied, and not unproblematic, renderings of the mutuality of violence and subjectivity, their novels do not just reveal the ambiguous and ambivalent character and the fragile and tenuous processes of (exercising and asserting) subjectivity; their fiction enacts and engenders its own kind of textual violence that reflects and refracts the (metaphysical and epistemological) violence of the subjective process. Raising crucial questions about the place, role and efficacy of literature in articulating violence and subjectivity, this thesis argues that violence is meaningful to and constitutive of the subjective process in these authors’ works that offer an experiential, lived appreciation of subjectivity. Providing an historical and socio-political contextualization of the novels, the thesis maintains that these authors’ specific interpretations of violence in their fiction necessarily interrogates and reconfigures questions of race and culture, gender and sexuality, as well as morality; that is, it reexamines and repositions conventional interpretations of being and belonging, of subjectivity in general. In this way, their fiction reveals literature’s ability not merely to disprove theory but, through its very textuality, extend and enhance it to reflect the materiality of being.

Tesis para optar al grado de Magíster en Literatura mención Literatura Chilena e Hispanoamericana / Me asiste el convencimiento, otorgado por la experiencia estética, de que la prosa de González Vera representa, en su elegancia, contención y afirmación de la calidad del sujeto, un momento necesario –y diferente– en nuestra literatura, puestos frente a un Chile que persiste en evadir el espejo social, en inventarse mitos de origen que suplen una historia manipulada o traumática, y en confirmar los conceptos de la novela criolla chilena tradicional sobre el sujeto popular, aunque, salvo Martín Rivas, se la haya dejado de leer, y que perduran en la novela moderna, especialmente la de mediados y fines del siglo XX. Por cierto, esto no constituye de ningún modo una crítica al valor literario y estético de la obra de Blest Gana, Donoso y otros, sino que busca destacar la diferencia que propondría González Vera en la evolución de la literatura chilena a hispanoamericana, y en el intento por precisar la relación entre ética anarquista y estética narrativa que podrían subyacer en la prosa del autor. Esta certeza nos lleva a otra, ya mencionada: la prosa gonzalezveriana, en sus opciones éticas y estéticas, constituye uno de los hitos que señalan el paso hacia nuevos referentes de creación en la narrativa chilena moderna.

Made available in DSpace on 2017-07-21T14:35:57Z (GMT). No. of bitstreams: 1 ADRIANA YURIKO KOGA.pdf: 2085290 bytes, checksum: 04ba643fa625913ec2b768408faac0ab (MD5) Previous issue date: 2017-02-23 / Alginate is a polymer extracted from seaweed and traditionally used in various types of wound dressings. It is a polysaccharide which has bioadhesive and swelling characteristics. The ability of alginate to form gel and films provides a favorable environment for healing and re-epithelialization of the injured tissue. Aloe vera (L.) Burm. f., or simply Aloe, is a medicinal plant with analgesic, anti-inflammatory and healing properties. The purpose of this study was to develop an alginate film containing Aloe gel and examine its cutaneous healing effect in vivo. The film was obtained by casting of the aqueous sodium alginate solution containing glycerin and Aloe gel, followed by crosslinking with calcium chloride. The film was characterized by mechanical tensile strength, hydration degree, FTIR spectroscopy, scanning electron microscopy, polysaccharide and calcium release. The wound healing effect was studied by performing surgical wounds in the back of Wistar rats. The animals (n = 60) were divided into three groups: gauze dressings (control), dressing with alginate film and dressing with alginate-aloe film. The retraction of wounds was measured every 3 days. On days 3, 7, 14, 22 five animals from each group were euthanized and samples of skin were removed and fixed in formalin 10%. The samples for histological analysis were stained with hematoxylin-eosin and analyzed for quantification of inflammatory infiltrate, angiogenesis and macrophages. Collagen fibers were evaluated using a picrosirius red staining for differentiation of type I and III fibers. The alginate-aloe film exhibited desirable physical and mechanical characteristics for the wound dressing application. In vivo animal test revealed there was no significant difference among the three groups in wound retraction. The results of histological analysis showed a beneficial effects of alginate-aloe (p=0.04) and alginate films (p=0.05) decreasing the inflammatory infiltrate at 14th days, in relation to the control group. On the 7th day, there was an increased angiogenesis in the control group compared to the group treated with alginate-aloe films (p = 0.04) and alginate (p = 0.024). Treatment with alginate-aloe film increased the number of blood vessels on the 14th day, when compared to the control group (p = 0.004); in addition, it caused decrease of macrophages on day 22, when compared to the other groups (alginate film (p = 0,0) and control (p = 0.007). The evaluation of the collagen fibers showed a significant difference between the alginate-aloe film and control group, with evident decrease of type III fibers (p = 0.05) and increase of type I fibers (p = 0.024) between days 14 and 22, suggesting an improvement in the progression of the healing process. / O alginato é um polímero extraído de algas marinhas e tradicionalmente utilizado na fabricação de curativos. A propriedade de formar géis e filmes faz com que o alginato proporcione um ambiente favorável à cicatrização e a re-epitelização do tecido lesado. Aloe vera (L.) Burm. f., popularmente conhecida como babosa, é uma planta medicinal que apresenta propriedades analgésica, anti-inflamatória e cicatrizante. O objetivo deste trabalho foi desenvolver um filme de alginato contendo gel de babosa e avaliar o seu efeito cicatrizante in vivo. O filme foi obtido por evaporação de uma solução aquosa de alginato de sódio contendo glicerina, gel de babosa e reticulado com cloreto de cálcio. O filme foi caracterizado por ensaios de resistência mecânica a tração, hidratação, espectroscopia no infravermelho (FTIR), microscopia eletrônica de varredura e liberação de polissacarídeos e íons cálcio. Na avaliação do efeito cicatrizante, foi utilizado o modelo de lesão cirúrgica na pele da região cérvico-lombar de ratos Wistar. Os animais (n=60) foram divididos em três grupos: curativos com gaze (controle), curativos com filme de alginato e curativos com filme alginato-babosa. As medidas da retração das feridas foram realizadas a cada 3 dias. Nos dias 3, 7, 14 e 22 cinco animais de cada grupo foram eutanasiados e um fragmento de pele foi retirado e fixado em formol 10%. As análises histológicas dos tecidos foram realizadas utilizando-se coloração hematoxilina eosina para quantificação de infiltrado inflamatório, avaliação da angiogênese e contagem de macrófagos. As fibras colágenas foram avaliadas utilizando a coloração picrosirius red para diferenciação das fibras de tipo I e III. As análises físico-químicas do filme evidenciaram características ideais para a aplicação como curativos. No ensaio do efeito cicatrizante, não houve diferença significativa entre os grupos na avaliação da retração da lesão. Os resultados das análises histológicas mostraram uma diminuição do infiltrado inflamatório com os filmes alginato-babosa (p=0,04) e alginato (p=0,05) no 140 dia, em relação ao grupo controle. No 70 dia, observou-se uma maior angiogênese no grupo controle comparado aos grupos filme alginato-babosa (p=0,04) e alginato (p=0,024). O tratamento com o filme alginato-babosa aumentou o número de vasos sanguíneos no dia 14, quando comparado ao grupo controle (p=0,004); além disso, ocasionou uma diminuição mais expressiva de macrófagos no dia 22, quando comparado aos demais grupos (filme alginato (p=0,0) e controle (p=0,007)). A avaliação das fibras colágenas mostrou uma diferença significativa entre os grupos filme alginato-babosa e controle, com evidente diminuição das fibras tipo III (p=0,05) e aumento das fibras tipo I (p=0,024) entre os dias 14 e 22, sugerindo uma melhora na progressão do processo de cicatrização.

La presente tesis tiene como objetivo evaluar la viabilidad técnica, económica y financiera de un estudio de prefactibilidad para la implementación de una empresa productora y comercializadora de Cerámica de Chulucanas. Los principales estudios realizados en el presente proyecto fueron: Análisis Estratégico, Estudio de Mercado, Estudio Técnico, Estudio de Organización y Legal y Estudio Económico y Financiero. / Tesis