127 research outputs found
Ilustración editorial de 5 historias del libro 100 Cuentos Populares del Ecuador del autor Iván Petroff Rojas
Tesis está enfocada en cambiar el tono editorial
del libro 100 Cuentos Populares del Ecuador del
autor Iván Petroff Rojas, pero manteniendo todo
el texto del libro.
De esta manera mejorar el producto ya existente
para llamar la atención de nuevos lectores y se
interesen en las leyendas ecuatorianas mediante
el uso de ilustraciones análogas que reflejen los
personajes que vivían en la antigüedad en nuestro
país.My thesis is focused on changing completely the
editorial design of the book 100 Cuentos Populares
del Ecuador by the author Iván Petroff Rojas, but
with the text of the book without any change in
that aspect.
In this way the product is already improved to
attract the attention of new readers and they are
interested in Ecuadorian legends through the
use of analogous illustrations that reflect the
characters that lived in antiquity in our country.Licenciado en Diseño GráficoCuenc
Follicle protective action of tamoxifen in dog ovarian explant tissue culture in presence of cyclophosphamide
Women exposed to cytotoxic chemotherapy are at risk of amenorrhea and premature ovarian failure due to the side effects of treatment. Few options are available to women who wish to preserve their germline, including embryo cryopreservation and ovary cryopreservation however these procedures are expensive, invasive, often requires delay of treatment and the presence of a partner. Most importantly all these options fail to protect ovarian function. Thus, there is a clear need to investigate an alternate strategy to protect the ovary from the cytotoxic effects so as to maintain oocyte quality as well as endogenous hormone production to support follicular growth and for maintenance of pregnancy. Recent studies in rodents have demonstrated that tamoxifen treatment prevented follicular loss and apoptosis from chemotherapeutic drugs and radiation-mediated injury. However, rodent models may not predict clinical outcomes. There is a need for a clinical model which would reflect clinical efficacy in humans. We evaluated the ovarian-sparing effect of tamoxifen on ovarian follicle reserve (primordial and primary follicles) of dogs. Ovarian cortical explant tissues from pre-pubertal dogs (N = 10) were collected at elective ovariohysterectomy and randomly assigned and treated for 72 hours with active metabolites of alkylating agent cyclophosphamide (4-hydroxycyclophosphamide; CTX) (0, 1, and 10 mM; C, CTXL, and CTXH) and tamoxifen (4-hydroxytamoxifen; TAM) (0 and 10 mM; C and TAM). Results presented as total normal follicle reserve based on histological morphology. High dose CTXH caused marked follicular loss (P 0.05). This work also developed a dog ovarian cortical explant model to test efficacy and action of drugs in a model that share some genetic, physiological and environmental similarities with humans, have increased life spans and a propensity for tumors. Another goal of this study was to characterize anti-Mullerian hormone (AMH) in dogs with relation to puberty, age, numbers of reserve follicles, stage of estrus cycle and spay status to determine usefulness of AMH as an indicator of ovarian reserves and fertility in dogs. The data presented will show that spayed and intact female dogs can be successfully identified using a readily available human AMH ELISA. The results also demonstrated a significant negative relationship between AMH and advancing age and that there is a significant difference in serum AMH concentrations at anestrus and proestrus. Taken together, the results demonstrate that dog ovarian cortical explant culture system may be an alternative to test effects and actions of chemotherapeutic agents.Thesis (Ph. D.)--Michigan State University. Comparative Medicine and Integrative Biology, 2020Includes bibliographical reference
Abstract 5629: Modeling cyclophosphamide induced ovarian toxicity in a novel translational canine model
Abstract
Reproductive failure following chemotherapy and/or ionizing radiation is a major adverse event, for which there are no established preventive measures. In previous studies, our laboratory has documented that the selective estrogen receptor modulator, tamoxifen (TAM) is effective in both prevention and reversal of ovarian toxicity from cyclophosphamide (CTX) in rodent models. To validate the effectiveness of this approach in a more relevant model system, we have developed a canine ovarian explant tissue model system. Dogs present with many cancers spontaneously and their pathology and treatment approaches mirror those of the human cancers. Thus, canine cancers and their treatments are excellent translational models for human diseases. Furthermore, dogs share the same environment as humans and have longer life spans than rodents. Our laboratory has recently established a dog ovarian explant tissue model system using fresh ovaries collected at the time of ovariohysterectomy. In the current study, we hypothesized that ovarian toxicity induced by CTX will be reduced by co-administration of TAM. Using this system, freshly prepared ovarian cortical tissue sections are cultured in the presence of TAM and CTX. Ovarian tissue viability is assessed by primordial and primary follicle morphometry, where the number of primordial, primary and apoptotic follicles were counted in 9 sections of 1 mm3 of ovarian cortical tissue from each dog, using CTX (at 0, 1 and 10µM) concentrations combined with TAM (0 and10µM). The number and percentage of each follicle was assessed. In addition, granulosa cells proliferation is assessed using bromodeoxyuridine (BrdU) incorporation. Further, we show that, as in women, anti-mullerian hormone (AMH) can be used as an indicator of follicle reserves in the dog, thereby establishing their use as an in-vivo monitoring system to test ovarian viability in future clinical studies. This study is intended to underpin a subsequent canine clinical trial testing TAM as a countermeasure against infertility from cancer treatment in dogs.
Note: This abstract was not presented at the meeting.
Citation Format: Puja Basu, Rebecca Egbert, Evan Pasternak, Brian Petroff, Nucharin Songsasen. Modeling cyclophosphamide induced ovarian toxicity in a novel translational canine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5629. doi:10.1158/1538-7445.AM2017-5629</jats:p
Análisis de los personajes de la obra: "Qué risa, todos lloraban" del autor Huilo Ruales Hualca, desde las dimensiones de la estilística y la semiótica
El siguiente trabajo de investigación Análisis de los personajes de la obra: Qué risa, todos lloraban del autor Huilo Ruales Hualca, desde las dimensiones de la estilística y la semiótica, es un estudio que comprende un análisis en función de los personajes de esta novela, el mismo que se realiza mediante el aporte tanto de la estilística como de la semiótica, dos disciplinas que contribuyen a las posibles significaciones e interpretaciones de estos personajes, a través de sus acciones y sentimientos, de igual manera en cuanto al estilo y algunos recursos que el autor Huilo Ruales refleja en torno a ellos. Estos dos aspectos serán el instrumento clave para cumplir a cabalidad este estudio.The following research investigation Análisis de los personajes de la obra: Quérisa, todosllorabandel autor Huilo Ruales Hualca, desdelasdimensiones de la estilística y la semiótica, author, from the dimensions of stylistic and semiotics", comprises a stylistic study in style and some resources that the author Huilo Ruales reflected in his work, also a semiotic study to contribute to the possible meanings and interpretations of the characters and their actions in the novel. These two aspects will be the instrument key to fully comply with this study.Licenciada en Ciencias de la Educación en la Especialización de Lengua, Literatura y Lenguajes AudiovisualesCuenc
Novel Strategies in Cancer Prevention and Fertility Preservation with Tamoxifen
Women at high risk for breast cancer are often also at high risk for ovarian cancer, reflecting similar risk factors and suggesting intertwined disease pathways and common prevention targets. A novel strategy to overcome obstacles in preventing ovarian neoplasia (low incidence, lack of specific disease markers, and difficulties in tissue sampling), the deadliest gynecologic cancer, may be to develop a prevention strategy that targets breast and ovarian cancer simultaneously. Tamoxifen, a selective estrogen receptor modulator, reduces hormone responsive breast cancer risk by 50% but its effects on risk of ovarian cancer, also hormonal responsive, are unclear. The goals of this work were to 1) develop and characterize a preclinical model of concurrent breast and ovarian cancer and 2) use this dual cancer model to examine the efficacy of tamoxifen to prevent both breast and ovarian cancer. Mammary carcinogens [7,12-dimethylbenz[α]anthracene (DMBA), N-methyl-N-nitrosourea and estradiol (Ey2)] were tested separately in combination with local ovarian DMBA administration to determine the best combined treatment to induce mammary and ovarian cancer concurrently and effectively in the rat. Results showed that systemic Ey2 and ovarian DMBA promoted the highest incidence of dysplasia in the mammary gland and ovary and elevated levels of mammary Ki-67 and cyclooxygenase 2 (COX-2) mimicking the human disease. Next, the ability of tamoxifen to prevent mammary and ovarian cancer simultaneously was evaluated. Tamoxifen which inhibited mammary carcinogenesis and normalized levels of Ki-67 and COX-2, had no effect on (neither accelerated nor inhibited) ovarian cancer progression. In addition, carcinogen treatment increased levels of stem cell markers, Oct-4 and aldehyde dehydrogenase-1, in the mammary gland; interestingly, this expansion was not reversed by tamoxifen. Intriguingly, while examining ovaries from this study, we serendipitously discovered an apparent protective effect of tamoxifen against DMBA-induced follicular destruction and this effect was further investigated. Chemotherapy and environmental toxicants (e.g. DMBA) deplete ovarian follicles and often lead to accelerated ovarian aging and premature ovarian failure; however, there is no established treatment that can protect the ovary from these toxic insults. In vivo, rats were treated with tamoxifen and DMBA or cyclophosphamide (the most ovotoxic chemotherapy) and total numbers of follicles in the ovary were determined. In vitro, ovarian organ culture and oocyte culture were carried out to examine local effects of tamoxifen on DMBA-induced follicle loss and doxorubicin-induced oocyte fragmentation, respectively. We demonstrated for the first time that tamoxifen protects ovarian follicles against not only DMBA- but also chemotherapy (cyclophosphamide and doxorubicin)-induced ovarian damage. Clinically, tamoxifen has already been tested for safe use as an adjuvant therapy for several cancers; therefore, if translated into clinical use, these results may have immediate impact on options for fertility preservation and quality of life in young female cancer patients undergoing chemotherapy. The long term goals of this work are to 1) use the dual cancer model to screen for promising agents that decrease risks for both breast and ovarian cancer and 2) examine the mechanism by which tamoxifen inhibits toxicant-induced ovarian follicle loss
Evaluación de dos métodos para descontaminación de esputo en pacientes con sospecha de tuberculosis pulmonar
El presente estudio tuvo como objetivo comparar dos métodos de descontaminación del esputo
en pacientes con sospecha de tuberculosis, debido a la baja sensibilidad que tiene la
baciloscopia tradicional. Se evaluó la descontaminación de las muestras con hidróxido de sodio
(NaOH) al 4% – N-acetilcisteína (NAC) (método de Petroff modificado) e hipoclorito de sodio
(NaClO) al 5%. Este proyecto de investigación se realizó en el periodo comprendido entre julio
y septiembre de 2019 (3 meses). Los datos fueron recogidos en una guía de observación
previamente diseñada por el autor y validada por tres especialistas en el tema. El autor evaluó
200 muestras de personas con sospecha de tuberculosis pulmonar que acudieron al hospital
durante el periodo de estudio. Los datos se procesaron mediante el paquete de programas IBM
SPSS Statistics Base 22.0 y STAT GRAPHICS Centurion XVI.I. El mejor método se
determinó aplicando un diseño experimental, se utilizó análisis de varianza, anova y Tukey en
las variables: costo, tiempo y eficiencia. El mejor tratamiento de esputo fue la
descontaminación con el método de Petroff modificado (NaOH al 4% – NAC) Este resultado
fue correlacionado y confirmado con el cultivo en medio sólido. Finalmente, se elaboró un
algoritmo de diagnóstico de tuberculosis pulmonar con los resultados obtenidosThe present study aimed to compare two methods of sputum decontamination in patients with
suspected tuberculosis, due to the low sensitivity of traditional smear microscopy.
Decontamination of the samples was evaluated with 4% sodium hydroxide (NaOH) - Nacetylcysteine
(NAC) (modified Petroff method) and 5% sodium hypochlorite (NaClO). This
research project was carried out in the period between July and September 2019 (3 months).
The data were collected in an observation guide previously designed by the author and
validated by three specialists in the field. The author evaluated 200 samples of people with
suspected pulmonary tuberculosis who came to the hospital during the study period. The data
was processed using the IBM SPSS Statistics Base 22.0 and STAT GRAPHICS Centurion
XVI.I. The best method was determined by applying an experimental design, analysis of
variance, anova and Tukey was used in the variables: cost, time and efficiency. The best sputum
treatment was decontamination with the modified Petroff method (4% NaOH - NAC). This
result was correlated and confirmed with the culture in solid medium. Finally, a diagnostic
algorithm for pulmonary tuberculosis was developed with the results obtaine
Computational Molecular Modeling Studies of the Interactions of Estrogens with Their Receptors and Intracellular Estrogen Binding Protein PDIp
The endogenous estrogens are vitally-important female sex hormones with diverse biological functions. Disruption of their actions contributes to the pathogenesis of a number of disease states in humans, such as endocrine disruption, infertility, and development of cancers. My dissertation research sought to explore the potential usefulness of computational molecular modeling tools in studying the interactions of various estrogen derivatives (e.g., endogenous estrogen metabolites, non-aromatic steroids, and synthetic antiestrogens) with human ERs as well as a recently-identified intracellular estrogen-binding protein. The results of my dissertation projects offer important insights into the three-dimensional structural characteristics of the binding interactions of various estrogen analogs with the human ERs and PDIp. These studies provide a platform for the future development of an automated docking-based computational approach that can screen numerous environmental compounds for their potential ability to bind to human ERs as well as other estrogen binding proteins in the body
Análisis socioestilístico de la obra Nuestra piel muerta (2019) de Natalia García Freire
Natalia García Freire es una reconocida periodista y escritora ecuatoriana. En esta
investigación, se realizará un análisis socioestilístico de su primera novela Nuestra piel
muerta, elegida por The New York Times como uno de los mejores libros en español del 2019.
Con el objetivo de determinar los aportes de la autora a la nueva narrativa ecuatoriana
femenina, se llevará a cabo una revisión teórica de los principales aspectos sociales
abordados en la trama y de las figuras narrativas que la componen. Para el desarrollo de esta
investigación se implementará una metodología cualitativa con un enfoque inductivo y
exploratorio. En cuanto al proceso de análisis de la obra en sí misma, el trabajo se organizará
en tres partes: la primera, la contextualización bibliográfica de la obra; la segunda, la definición
de las categorías de carácter social y estilístico empleadas para el estudio de la novela y
finalmente, el análisis de la misma con base en las categorías previamente mencionadas. Se
encontró que la autora aborda desde una perspectiva intimista, temas relacionados con lo
patriarcal, lo familiar y la violencia. En conclusión, la novela cuestiona a partir de la ficción
antiguos paradigmas sociales que continúan vigentes en la actualidad.Natalia García Freire is a renowned ecuadorian journalist and writer. In this research, a socio-
stylistic analysis of her first novel "Nuestra piel muerta" will be conducted, which was chosen
by The New York Times as one of the best books in Spanish in 2019. With the aim of
determining the author's contributions to the new Ecuadorian female narrative, a theoretical
review of the main social aspects addressed in the plot and the narrative figures that compose
it will be carried out. For the development of this research, a qualitative methodology with an
inductive and exploratory approach will be implemented. Regarding the analysis process of
the work itself, the research will be organized into three parts: the first, the bibliographic
contextualization of the work; the second, the definition of the social and stylistic categories
used for the study of the novel, and finally, the analysis of the novel based on the
aforementioned categories. It was found that the author addresses, from an intimate
perspective, themes related to patriarchy, family, and violence. In conclusion, the novel
questions old social paradigms that continue to be relevant in the present through fiction.000-0003-2419-6709Licenciada en Pedagogía de la Lengua y LiteraturaCuenc
THE ROLE OF EPIGENETICS IN TRANSCRIPTIONAL REGULATION OF FXR AND SILENCING FXR EXPRESSION IN HUMAN COLON CANCER
Farnesoid X receptor (FXR) is a ligand activated transcription factor belonging to the nuclear receptor superfamily and bile acids are its endogenous ligands. FXR is a critical regulator of the enterohepatic circulation of bile acids, lipid homeostasis, glucose metabolism, and tumor suppression in liver and intestine. Consequently, FXR has become a very promising therapeutic target for the prevention and/or treatment of cholestasis, hyperlipidemic disorders, metabolic syndrome, and liver and colon cancer. Studies suggest epigenetic mechanisms are critical for proper transcriptional induction of nuclear receptors. Likewise, evidence shows epigenetic mechanisms are responsible for modulating the tissue/cell-specific FXR expression in human colon cancer. However, how epigenetic mechanisms are involved in FXR induced transcription or tissue-specific FXR expression remains elusive. Understanding these mechanisms is crucial for future development of pharmacological modulators of FXR as well as understanding the full physiological roles of FXR. This dissertation was designed to elucidate epigenetic mechanisms involved in tissue-specific FXR induced gene transcription, orphan nuclear receptors critical for regulating FXR function, and epigenetic mechanisms responsible for FXR silencing in colon cancer. In specific aim 1, a genome-wide FXR binding assay was done in mouse liver and intestine. Specific aim 2 focuses on the role of the orphan nuclear receptor hepatocyte nuclear factor 4fnalpha (HNF4&alpha) in regulating liver-specific functions of FXR. And finally, in specific aim 3, DNA methylation of FXR promoter was investigated as the mechanism responsible for FXR silencing in human colon cancer. In conclusion, genome-wide binding of FXR implicates novel epigenetic mechanisms and orphan nuclear receptors in regulating FXR function. Furthermore, this study indicates that HNF4&alpha is at least one orphan nuclear receptor capable of regulating FXR function in the liver. Findings from these first two aims succeeded in progressing drug development fields aimed at finding new FXR modulators for the treatment of multiple metabolic disorders by elucidating novel epigenetic mechanisms that may be investigated as therapeutic targets. Finally, FXR is at least partially down-regulated by DNA methylation in human colon cancer, suggesting a potential mechanism to be targeted for the prevention, treatment, and/or diagnosis of colon cancer
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