O filo Ctenophora tem sido negligenciado em estudos faunísticos e ecológicos no Brasil. São escassos os registros de espécies e pouco se sabe sobre a distribuição e abundância destes animais em águas brasileiras. Muito dessa falta de informações sobre o grupo se deve às dificuldades em se coletar e preservar espécimes. O presente estudo consistiu em um esforço no sentido de se conhecer um pouco mais sobre os ctenóforos, nos âmbitos faunístico, taxonômico e ecológico. A tese foi dividida em seis capítulos: o primeiro faz uma introdução ao estudo dos Ctenophora; o segundo traz descrições das sete espécies que ocorrem no Canal de São Sebastião; o terceiro traz uma chave de identificação para as treze espécies registradas para a costa brasileira, incluindo um glossário de termos específicos; o quarto aborda o problema taxonômico relativo ao ctenóforo Mnemiopsis leidyi, apresentando uma solução para tal; o quinto contempla a biologia populacional de M. leidyi na costa brasileira, a questão do impacto predatório da espécie em diversas regiões do mundo e sua recente introdução nos mares do Norte e Báltico; o último apresenta considerações gerais sobre os resultados dos capítulos anteriores. Desta forma, procurei abordar diversos aspectos da taxonomia e biologia dos ctenóforos presentes na costa brasileira e espero, assim, ter conseguido efetuar algum avanço no conhecimento deste grupo, ainda muito carente de estudos no Brasil e no mundo. / The phylum Ctenophora is pour studied in Brazil. Species records for the Brazilian coast are scarce in the literature. The distribution patterns and abundance of ctenophores in the region are almost unknown. The scarcity of data aims mostly to the difficulties in collecting and preserving specimens. This study consisted in an effort to increase knowledge on the faunistics, taxonomy and ecology of the ctenophores from Brazilian waters. Dissertation was divided in six chapters. The first on introduces the Ctenophora study. The second presents description of the seven species found in the São Sebastião Channel. The third chapter is an identification key to the species reported for the Brazilian coast, with a glossary on specific terms. The fourth regards the taxonomical problem of Mnemiopsis leidyi and suggests a solution for it. The fifth presents the population biology of M. leidyi from the Brazilian coast, the predatory impact of the species in several areas of the world and its recent introduction in the North and Baltic seas. The last chapter summarizes the final conclusions of the previous chapters. Thus, in hope of fulfilling a gap on these animals knowledge, I tried to contemplate several aspects of taxonomy and biology of the ctenophore species from the Brazilian coast.

A doença de Alzheimer (AD) é uma desordem neurodegenerativa caracterizada pelo declínio progressivo da função cognitiva. Esta é a maior causa de demência, sendo que a grande maioria dos casos da AD é do tipo esporádica (SAD), a qual tem como principal fator de risco o envelhecimento. A injeção intracerebroventricular de estreptozotocina (icv-STZ) tem sido utilizada como modelo experimental da SAD em roedores e representa uma promissora ferramenta para análises etiopatogênicas e avaliação de novas propostas terapêuticas para a AD. O modelo icv-STZ mostra muitos aspectos das anormalidades da SAD, produzindo decréscimo no metabolismo cerebral de glicose e energia, prejuízo cognitivo, estresse oxidativo, astrogliose, perda neuronal e angiopatia amiloide. A geleia real (GR), substância produzida pelas abelhas operárias da espécie Apis mellifera, vem sendo popularmente utilizada há mais de 30 anos em áreas relacionadas à alimentação saudável e medicina natural. Pesquisas apontam que a GR possui uma série de atividades farmacológicas, incluindo ação neuroprotetora, antioxidante, anti-inflamatória e melhora da função cognitiva. O objetivo deste estudo foi investigar os efeitos do tratamento oral prolongado com geleia real em ratos Wistar submetidos ao modelo icv-STZ sobre o aprendizado e memória, e na neuroproteção, esta avaliada pela neurogênese, neurodegeneração e estresse oxidativo. A injeção icv-STZ utilizada neste trabalho induziu efeitos deletérios no hipocampo de ratos, sendo estes representados por déficit cognitivo avaliado no labirinto aquático de Morris, e desenvolveu acentuada neurodegeneração, além da redução da neurogênese e aumento do estresse oxidativo. Por outro lado, a administração oral prolongada da GR foi capaz de induzir efeitos benéficos em animais lesionados pela injeção icv-STZ, ampliando o tempo de retenção da memória espacial operacional dos animais, reduzindo a neurodegeneração, aumentando a proliferação de novos neurônios e reduzindo o nível de estresse oxidativo na região do giro denteado do hipocampo. Assim, a Geleia Real mostrou efeitos benéficos em funções cognitivas e uma ação neuroprotetora no modelo experimental de AD esporádica / Alzheimer\'s disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function. This is the major cause of dementia and the sporadic AD (SAD) represents the majority of cases which aging is the main risk factor. Intracerebroventricular injection of Streptozotocin (icv-STZ) has been used as an experimental model of SAD in rodents and represents a promising tool for etiopathogenic analysis and evaluation of new therapeutic proposals for AD. The icv-STZ model shows many aspects of SAD abnormalities, resulting in decreased brain glucose and energy metabolism, cognitive impairment, oxidative stress, astrogliosis, neuronal loss, and amyloid angiopathy. Royal jelly (RJ), a substance produced by worker honeybees of the Apis mellifera species, has been popularly used for more than 30 years in areas related to healthy eating and natural medicine. Researches indicate that RJ has a series of pharmacological activities, including neuroprotective, antioxidant, anti-inflammatory action and improvement of cognitive function. The objective of this study was to investigate the effects of long-term oral treatment with royal jelly in Wistar rats submitted to the icv-STZ on working memory version of the Morris\' water maze task and neuroprotection, evaluated by neurogenesis, neurodegeneration and oxidative stress. In this work, the icv-STZ injection induced deleterious effects in the hippocampus, which were represented by cognitive impairments, and developed marked neurodegeneration, besides the reduction of neurogenesis and increased oxidative stress. On the other hand, RJ long-term oral administration was able to induce beneficial effects in animals lesioned by icv-STZ injection, increasing the retention time on working spatial memory, reducing neurodegeneration and oxidative stress level and increasing the proliferation of new neurons in the hippocampus. Thus, Royal Jelly showed beneficial effects on cognitive functions and a neuroprotective action in the STZ experimental model of sporadic AD

Orientador: Marcelo Alexandre Prado / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-22T22:06:54Z (GMT). No. of bitstreams: 1 Paludo_MichellyCristiane_M.pdf: 1280298 bytes, checksum: bb9685e07236793df1057ee1e5197779 (MD5) Previous issue date: 2013 / Resumo: A jabuticaba Sabará Myrciaria jabuticaba (Vell.) O. Berg é uma fruta nativa do Brasil e possui grande potencial econômico e comercial. Esta fruta é rica em compostos fenólicos. Entre estes estão as antocianinas, pigmentos vegetais que conferem forte coloração roxa. Estes compostos possuem alta capacidade antioxidante, e estão relacionados a benefícios há saúde e prevenção câncer, doenças cardiovasculares, envelhecimento precoce, entre outros. A geléia de jabuticaba possui uma vida de prateleira longa e como tal fácil de ser comercializada, pois exige menores cuidados no transporte e armazenamento se comparada a fruta in natura, (muito perecível). Assim a geléia pode chegar aos consumidores onde a fruta não é encontrada e ser exportada para países onde não é cultivada, além de ser uma forma de aproveitar as propriedades da fruta durante o decorrer do ano. Neste trabalho foi realizada a extração e quantificação dos compostos fenólicos e das antocianinas totais da jabuticaba, de suas frações (casca, polpa e semente) e de sua geléia, através de métodos rápidos e eficazes, bem como a avaliação de seu potencial antioxidante (in vitro). Como esperado, a casca da jabuticaba concentra o maior teor dos compostos citados acima assim como a maior atividade antioxidante. A geléia consegue manter uma quantidade significativa desses compostos e de sua capacidade antioxidante, provando sua importância como derivado da fruta / Abstract: The jabuticaba Sabara Myrciaria jabuticaba (Vell) O. Berg is a native fruit from Brazil which has a great economic and commercial potential. This fruit contains a significant amount of phenolic compounds, and among those se can find anthocyanins, a plant pigment that provides a dark purple coloration, these compounds brins with them a high antioxidant capacity and are extremely beficial to ones health, preventing cancer, cardiovascular diseases, aging before the time and other benefits. The jabuticaba¿s jam has a long shelf life, which makes it easier to be sold, because less caution with transport and ware houses are required, specially when compared to the fruit `self. With that, the jam can be brought to places where the fruit found be foruns, such as further regions and other countries, and also is a method to have the fruit benefits through the whole year. Therefore, in this research, the extraction of phenolic compounds and total anthocyanins was made, from the Jabuticaba, its parts (peel, pulp and seed) and the its jam as well. This was made through fast and efficient methods, and so was the quantification of these compounds and the evaluation of its antioxidant potential in vitro. As expected the peel contains the higher concentration of the compounds and the biggest antioxidant capacity, the jam may keep a significant part of these compounds and the antioxidant capacity, proving how vital is the fruit and its jam / Mestrado / Ciência de Alimentos / Mestra em Ciência de Alimentos

Orientadores: Alba Regina Monteiro Souza Brito, Anderson Luiz Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T14:15:42Z (GMT). No. of bitstreams: 1 Manzo_LuisPauloBognoni_M.pdf: 4711838 bytes, checksum: 0267d7f30b132c874529cd6a03786252 (MD5) Previous issue date: 2012 / Resumo: A retocolite Ulcerativa Inespecífica e a Doença de Chron são as principais doenças inflamatórias intestinais. Apesar dos crescentes esforços, não se sabe ainda suas causas. Os tratamentos ainda não são eficazes, as drogas atuais são eficazes na indução da remissão mas não determinam sua cura. Os efeitos colaterais são severos, o que acarreta em baixa adesão ao tratamento. Os produtos naturais tem sido fonte de compostos usados por todo o mundo em diferentes áreas da medicina e ciência. O tratamento oral com geléia real na dose de 100 mg/Kg mostrou-se capaz de aumentar os níveis de grupamentos sulfídrica (GSH) e também a atividade da enzima glutationa peroxidase (GSH-Px) em camundongos com colite induzida por TNBS. A expressão de COX-2 e NF-kB também foram diminuídos, tais resultados demonstram efeitos antioxidantes e antiinflamatórios da geléia real nesta dose neste modelo de colite experimental. O Tratamento intrarretal com a proteína MRJP3 (50 ?g/animal) foi capaz de diminuir os níveis de IL-1? no cólon dos camundongos Balb/c submetidos a colite induzida por DSS. Uma vez que os níveis de IL-6 e IL-10 não foram alterados pelo tratamento intrarretal com MRJP3 50 ?g/animal, podemos afirmar que a proteína não atua pela via da IL-10. Estes efeitos antioxidantes e anti-inflamatórios observados durante o desenvolvimento da colite induzida por TNBS e por DSS em camundongos, podem ser de significativa importância pois abrem portas e encorajam novas pesquisas com a geléia real e sua respectiva proteína MRJP3, motivando novos estudos acerca de outos agentes antioxidantes e outros mediadores anti-inflamatórios envolvidos nestes modelos de colite experimental / Abstract: Ulcerative Colitis and Chron's Disease are the two major forms of IBD. Despite all efforts, these complications of the GTI are still lacking an effective therapy for their cure. Side effects, high cost and low adhesion to treatment are among the negative aspects. Natural products have been a source of widely used compounds in distinct areas of medicine and research. Royal Jelly (RJ) 100 mg/Kg was capable of augmenting the levels of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) in mice undergoing TNBS-induced colitis. Furthermore, COX-2 and NF-kB had their expression decreased by the oral administration of RJ 100 mg/Kg. Intra-rectal MRJP3 treatment (50 ?g/animal) was capable of decreasing the levels of IL-1? in mice undergoing DSS-induced colitis, whereas the levels of IL-10 and IL-6 were not altered by MRJP3 50 ?g instillation, what indicates that this decrease is not IL-10-induced. The antioxidant and anti-inflammatory effects observed during the development of DSS and TNBS-induced colitis in mice, may be of crucial importance, since they open and encourage new studies focused on this nourishing substance, especially in experimental models of colitis / Mestrado / Farmacologia / Mestre em Farmacologia

Doctor of Philosophy / Department of Animal Sciences and Industry / Duane L. Davis / Intrauterine growth restriction (IUGR) affects all mammals. In the swine industry IUGR pigs result from intrauterine crowding. Prenatal programming in IUGR pigs has substantial effects on myogenesis and adipogenesis. Prenatal programming due to IUGR is also a problem in humans and long-term effects on adipogenesis are well established for small for gestational age (SGA) babies. Mesenchymal stem cells (MSCs) are the precursors for adipocytes. The umbilical cord contains a population of MSCs in Wharton’s jelly (WJ) and they can be harvested postnatally without ethical issues. Therefore, WJMSCs are proposed as models for studying prenatal programming of adipogenesis. We selected genes from studies of adipogenesis in humans and other species and examined their expression in pig WJ. We assigned pigs within litter as High, Medium, or Low birth weight and evaluated these categories for expression of Cox1, Cox2, EGR1, PPARɣ1, PPARɣ2, and Pref1. Differences due to size classification within litter were limited but there were correlations between weaning weight and delta cycle threshold (ΔCt) for EGR1 (r = 0.28; P < 0.009), PPARɣ1 (r = 0.29; P < 0.007), and PPARɣ2 (r = 0.30; P < 0.005). This may be consistent with the reports for SGA babies where EGR1 is upregulated by prenatal growth restriction. To gain insight into when during pregnancy IUGR affects WJ cells we collected umbilical cords at d 60 and d 95. In d 60 umbilical cords, small fetuses had increased (P = 0.06) Cox1 gene expression. We tested the ability of d 60 WJ cells to undergo adipogenic differentiation using standard protocols and a cycling protocol that exposed the cells to adipogenic differentiation conditions interposed with a rest phase with high insulin. It has been reported that the cycling protocol revealed increased glucose uptake in WJ cells from human SGA babies. We found that d 60 WJ cells did not show adipogenic differentiation in any of the protocols tested however glucose uptake correlated negatively with birth weight at Cycle 0 (P < 0.02; r = 0.61). In summary, pig WJ cells reveal some effects of IUGR but they appear to differ from the relationship demonstrated reported for human SGA babies. A new finding was that at midgestation pig WJ cells do not appear to be competent to complete adipogenesis. We also studied nursing managements to improve outcomes for IUGR pigs. Colostrum intake may be a problem, particularly for light weight pigs and those born later during farrowing. Split suckling is the removal of some pigs to allow others unrestricted nursing access. We temporarily removed the six heaviest pigs and this treatment increased gain and weight by d 7 of age. Colostrum intake was highest for the high birth weight pigs. When we temporarily removed the first half of the litter, colostrum intake was increased for the second half of litter born and the difference in immunocrit was reduced between the two litter halves.

This paper had for aim, making use of the production industry waste of whole orange juice, to draw light orange jam considering alternative and convencional grow and different sucralose concentration, 15%, 20% and 30%. It was considered the physicochemical characteristics and light standards, red and yellow color of the juice, pulp and jelly orange light obtained from alternative and conventional grow. It was done analysis for microbiological and sensory jelly in order to establish the best formulation. The treatments were established: jelly produced with conventional orange juice, jelly pulp obtained from conventional orange, jelly produced with alternative orange juice and jelly made with orange pulp from alternative cultivation. Each one of the treatment had four experiments: a control group produced with sugar and the others varying the concentrations of sucralose, using in this case, 15%, 20% and 30%. For the analysis of soluble solids, as much juice as the orange pulp when considering the different grow, showed no significant difference at 5% level, contrary to findings of acidity, pH and ° Brix / acidity. The juice and pulp either conventional or alternative grow showed a significant difference at 5% level for the parameters of brightness, red (+ a) and yellow (+ b). The sample of alternative orange juice showed higher brightness and yellow, whereas red the highest value was found for the sample of conventional orange pulp. The physicochemical analysis for jelly made with juice as the control group as for those made with sucralose, showed average values for reducing sugar content between 8.133 to 11.03, for the acidity range 0.8 to 1.71, pH soluble solids total the minimum and maximum average were 3.36 to 3.82 and 69.75 to 27.25 respectively. For the jellies made with pulp, alternative grow and sugar showed levels L * and b *, higher compared with other experiments, to values of a * also was the sample in the control group which showed the greatest value, however the raw material was conventional grow. Microbiological analysis to counting of yeasts and molds showed a sample over the limits set down in law and to counting of mesophilic samples showed contamination, all of them made with 30% of sucralose. The formulation determined as favorite was the jelly made with orange pulp from the conventional grow and 15% sweetener, sucralose. The acceptance of products made of sucralose, lets enable the production of light-based industrial waste, adding value and meeting the market demands. It demonstrates that the analysis done showed significant differences as variables of grow as for raw materials and concentrations of sucralose and can not be established correlation between variables. / Este trabalho teve por objetivo, aproveitar o sub produto da indústria de produção de suco de laranja integral, para elaboração de geleia light de laranja considerando cultivo alternativo e convencional e diferentes concentrações de sucralose, 15%, 20% e 30%. Foram avaliadas as características físico químicas, padrões de luminosidade, e tendência de cromaticidade para cor vermelha e cor amarela do suco, polpa e geleia light de laranja obtidas de cultivo alternativo e convencional. Foram realizadas analise microbiológicas e sensoriais nas geleias de forma a se estabelecer a melhor formulação. Os tratamentos estabelecidos foram: geleia produzida com suco de laranja convencional, geleia de polpa obtida de laranja convencional, geleia produzida com suco de laranja alternativo e geleia elaborada com polpa de laranja de cultivo alternativo. Cada um dos tratamentos contou com quatro experimentos: um grupo controle produzido com açúcar e os demais variando as concentrações de sucralose, usando-se no caso, 15%, 20% e 30%. Para as analises de sólidos solúveis totais, tanto o suco quanto a polpa de laranja quando considerado os diferentes cultivos, não apresentaram diferença significativa a nível de 5%, contrario dos dados encontrados para acidez, pH e relação °Brix/Acidez. O suco e a polpa sejam de cultivo convencional ou alternativo apresentaram diferença significativa a um nível de 5% para os parâmetros de luminosidade, e tendência de cromaticidade para cor vermelha (+a) e cor amarela (+b). A amostra de suco de laranja de cultivo alternativo apresentou maiores valores de luminosidade e tendência a cor amarela, considerando que a maior tendência para cor vermelha foi encontrado para a amostra de polpa de laranja convencional. As analises físico químicas para geleia elaboradas com suco, tanto do grupo controle quanto para as elaboradas com sucralose, apresentaram valores médios para açúcares redutores entre 8,133 a 11,03, para acidez a variação foi de 0,8 a 1,71, para pH e sólidos solúveis totais as médias mínimas e máximas foram 3,36 a 3,82 e 69,75 a 27,25 respectivamente. Quando avaliado as geleias elaboradas com polpa, de ambos os cultivos, as médias de açúcares redutores variaram de 8,36 a 11,16, para acidez a variação foi de 0,575 a 1,63, considerando as analises de pH as médias ficaram entre 3,95 a 3,64 e para analise de sólidos solúveis totais a variação foi de 56,5 a 27,25°Brix. Os tratamentos com suco alternativo e 30% de sucralose, suco convencional e 20% de sucralose e geleia elaborada com suco convencional e açúcar apresentaram os maiores índices para L*, a* e b*, respectivamente. Para as geleias produzidas com polpa, as de cultivo alternativo e açúcar apresentaram índices de L* e b*, superiores quando comparados com os demais experimentos, para valores de a* também foi amostra do grupo controle a que apresentou maior valor, contudo a matéria prima era de cultivo convencional. As análises microbiológicas para contagem de bolores e leveduras apresentaram uma amostra acima dos limites estabelecidos na legislação e para contagem de mesófilos duas amostras apresentaram contaminação, todas elas elaboradas com 30% de sucralose. A formulação com maior aceitabilidade foi a geleia elaborada com polpa de laranja de cultivo convencional e 15% de edulcorante, sucralose. A aceitação dos produtos elaborados com sucralose, permite viabilizar a produção de produtos light a base de sub produtos da indústria, agregando valor e atendendo as demandas de mercado. Demonstra-se que as analises realizadas apresentaram diferenças significativas tanto para as variáveis de cultivo, quanto para as matérias primas e concentrações de sucralose, não podendo ser estabelecido correlação entre as variáveis.

Mesenchymal stem cells (MSCs) derived from human adipose tissue and umbilical cord (Wharton’s jelly, UCB) represent a useful source of adult stem cells for cellular therapy and tissue engineering. The biggest concern with the use of MSCs therapeutically relates to their isolation and growth/manipulation ex vivo. This study aimed to establish methods for the routine isolation and characterization of MSCs from human tissues. The objectives were (1) to show that MSCs could be isolated from different human tissues, namely adipose tissue, Wharton’s jelly, and UCB; (2) to confirm the MSC phenotypic profile over at least 10 passages; and (3) to show the multilineage differentiation capacity of the isolated cells. The minimal criteria as defined by the International Society for Cellular Therapy (ISCT) were used to determine whether MSCs were successfully isolated from various human tissues. Two different techniques involving enzymatic digestion or explant cultures were utilized, and compared for isolating MSCs from Wharton’s jelly. Umbilical cord blood has been suggested as another source of MSCs. However, we were unable to grow MSCs from UCB. Proliferation kinetics of isolated MSCs revealed that cords, either from digested cords or cord pieces had a mean PDT from passage 1 to 4 that was approximately 3 fold lower than for the ASCs. Mesenchymal stem cells from adipose tissue and Wharton’s jelly expressed the classical MSC phenotype (CD73+, CD90+, CD105+, CD34-, and CD45-). The cells from Wharton’s jelly showed a more uniform MSC profile over passages, with higher levels of marker expression when compared to ASCs. Variability in phenotype was observed in early ASC passages, whereas WJ-MSCs seemed to attain the MSC phenotype as early as passage 0 for both isolation techniques. Low levels of CD34 positive cells remained in the ASCs. Oil red O staining was used for identifying the lipid droplets in adipogenic differentiation cultures. A colorimetric assay as well as image analysis was used to quantify the differentiation. For the cord samples, both assays produced positive results. Histological examination, however, revealed that the cords did not form lipid droplets. The ASCs showed a statistically significantly greater differentiation capacity into adipocytes compared with the cords (pooled digested and pieces data). Alizarin red S staining was used for identifying calcium deposition during matrix mineralization in osteogenic differentiation cultures. No significant differences in osteogenic differentiation were observed between ASCs and WJ-MSCs. Chondrogenic differentiation was observed for both MSC sources by positive staining of glycosaminoglycans using toluidine blue O. The main findings of the study showed that MSCs, according to the ISCT guidelines, were successfully harvested from adipose tissue. However, due to the lack of adipogenic differentiation of WJ-derived cells, they did not meet the ISCT guidelines to be classified as MSCs, and were referred to as MSC-like cells. Regardless of the isolation technique used, Wharton’s jelly yielded cells with similar proliferation capacity, phenotype, and differentiation capacity. This study did, however, reveal that biological differences do exist between stem cells from different sources. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Immunology / unrestricted

El presente proyecto fue diseñado a partir de la existencia de una saturación del mercado peruano de productos con alto porcentaje en azúcar y bajo aporte nutricional, el cual genera, en niños y adolescentes, desnutrición; y, por ende, la anemia. Una enfermedad frecuente en niños de 2 a 12 años. Al realizar un estudio de mercado en Lima Metropolitana, en la cual se ubicó al mercado meta, se determinó desarrollar la idea de negocio Miski Gelatoz, una gelatina fortificada con hierro henimico y no henimico, permitiendo complementar la alimentación del menor con un postre saludable. Para llevar a cabo el proyecto, se han desarrollado lo siguientes planes: Estratégico, Operativo, Marketing, Recursos Humanos, Responsabilidad Social Empresarial, Financiero y Financiamiento. Respecto a la proyección de ventas y análisis de costos, se han empleado datos reales y actualizados. Asimismo, se implementó el desarrollo del concierge de ventas con el fin de establecer una proyección real en el crecimiento de las ventas en el inicio del negocio. Dicho emprendimiento cuenta con una inversión inicial de S/23,927.78, se obtendrá una pérdida neta de S/ 9,432.84 para el primer año; sin embargo, para finales del segundo año las ganancias se elevan exponencialmente, obteniendo ganancias de S/ 56,186.5 y el tercer año S/ 58,101.51. / This project was designed based on the existence of a saturation in the peruvian market by products with a high percentage of sugar and low nutritional contribution, which generates malnutrition in children and adolescents; and therefore, anemia. A frequent disease in children from 2 to 12 years old. When carrying out a market study in Metropolitan Lima, in which the target market was located, it was determined to develop the business idea Miski Gelatoz, a gelatin fortified with heminic and non-heme iron, allowing the child's diet to be supplemented with a healthy dessert. To carry out the project, the following plans have been developed: Strategic, Operational, Marketing, Human Resources, Corporate Social Responsibility, Financial and Financing. Regarding sales forecasting and cost analysis, actual and updated data have been used. Likewise, the development of activities to measure purchase intention was implemented in order to establish a real projection on sales growth at the start of the business. This undertaking has an initial investment of S / 23,927.78, a net loss of S / 9,432.84 will be obtained for the first year; however, by the end of the second year the earnings rose exponentially, obtaining earnings of S / 56,186.5 and the third year S / 58,101.51. / Trabajo de investigación

Doctor of Philosophy / Department of Anatomy and Physiology / Mark L. Weiss / Graft Versus Host Disease (GVHD) is the major complication following hematopoietic stem cell transplantation. GVHD is activated by immunocompetent T cells presented in the donor grafted tissue. Due to the increased use of bone marrow transplantation to treat diverse malignancies, the incidence of GVHD has shown a notable increase. Depending of the degree of immunological mismatch between donor and host, 50-70% of patients develop GVHD after allogeneic Bone Marrow Transplantation (BMT). Once GVHD develops, mortality reaches up to 50% in humans. Several studies using Mesenchymal Stromal Cells (MSCs) to prevent and treat GVHD have produced controversial results. It is thought that distinct MSCs sources used in those studies might be an important factor that produces different outcomes. For cellular therapy, the most attractive characteristics of MSCs are their reduced immunogenic potential, and their abilities to modulate immune responses. This dissertation addressed the hypothesis that Wharton’s jelly cells (WJCs) would prevent the pathology and death associated with GVHD after BMT. To accomplish this, I created a clinically relevant model of GVHD by transplanting allogeneic bone marrow across minor histocompatibility antigen (HA) barriers in the rat. To enhance alloreactive T-cell stimulation, bone marrow (BM) was co-administered with a fraction of CD8[superscript]+ cells magnetically selected from spleen to induce GVHD. Bone marrow tissue was isolated from a donor rat Fischer 344 (F344, RT1lv) and transplanted into lethally irradiated (10 Gray) Lewis rat (LEW, RT1l). Once GVHD was induced, MSCs derived from umbilical cord WJCs were either co-transplanted at day 0 with bone marrow, or given on day 2 post-BMT intravenously. The prophylactic potential of WJCs in an in vivo GVHD model was assessed as survival time, clinical symptomatology occurrence, and histopathology injuries in target tissues. Results indicate that while co-administration of WJCs with hematopoietic cells on day 0 failed to alleviate GVHD associated symptomatology and mortality. WJCs administered on day 2 post-induction ameliorated GVHD-associated symptomatology, improved engraftment and survival.

Master of Science / Department of Clinical Sciences / Mary Lynn Higginbotham / Objectives – To isolate and maintain canine Wharton’s jelly mesenchymal stromal cells (WJMSCs) in culture, to determine the effects of micellar nanoparticles containing doxorubicin (DOX) on WJMSCs and canine osteosarcoma (OSA) D17 cell viability, and to determine the effects of conditioned media from WJMSCs loaded with micellar nanoparticles containing DOX on OSA D17 cell viability. Sample Population – Canine WJMSCs containing various concentrations of DOX micelles and canine OSA D17 cells. Procedures – WJMSCs were isolated from canine umbilical cords. Micellar nanoparticles containing DOX were prepared and added to culture plates containing canine OSA D17 cells to determine micelle effects on cell growth and viability. Conditioned media from culture plates containing canine WJMSCs incubated with various DOX micelle concentrations was added to OSA D17 cells for conditioned media experiments. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to assess OSA D17 cell viability. A trypan blue stain was also utilized to perform cell counts to determine the effect of the DOX micelles on stromal cell growth. Results – WJMSCs were successfully isolated and maintained in culture. Micellar nanoparticles containing DOX decreased OSA D17 cell viability. OSA D17 cell viability was also decreased following incubation with conditioned media from canine WJMSCs loaded with micellar nanoparticles containing DOX. Significant decreases with the conditioned media of canine WJMSCs loaded with 10μM micelles occurred at 48 hours (p < 0.005) and at 72 and 96 hours (p < 0.0001). Significant decreases were also observed with the 1 μM DOX micelles at 72 hours (p < 0.005) and 96 hours (p < 0.0001). WJMSC numbers decreased in a dose dependent manner following incubation with DOX micelles. Changes in WJMSC number was not caused by increased cell death as all variables produced similar percentages of dead cells. Conclusions – Canine WJMSCs were successfully isolated and maintained in culture. Stromal cells containing DOX micellar nanoparticles induced OSA D17 cell cytotoxicity while inducing an anti-proliferative, rather than cytotoxic effect, on the WJMSC. These data support future in vivo experiments utilizing canine WJMSCs and micellar nanoparticles.