Tesis sobre el tema "Apoptosis"
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Heiligtag, Sven. "Induction of apoptosis in neuroblastoma analysis of apoptotic pathways and putative apoptosis-mediating receptors /". [S.l.] : [s.n.], 2001. http://www.sub.uni-hamburg.de/disse/464/Disse.pdf.
Texto completoDevore, Casey Leigh. "DNR1 Regulates apoptosis: new insights into mosquito apoptosis". Thesis, Kansas State University, 2009. http://hdl.handle.net/2097/11972.
Texto completoDepartment of Biology
Rollie Clem
Apoptosis, or programmed cell death, is a crucial conserved process among organisms for deleting damaged unwanted cells, as well as for development and viral defense, and plays an important role in multiple diseases. Too much apoptosis may lead to Alzheimer’s disease, and too little may result in cancer. Therefore, the ability to understand this process is essential for improved medical knowledge today. Apoptosis has been explored in a number of species and pathways seem relatively conserved among most, with unique aspects contained in each, but little is known about apoptosis in mosquitoes. Improved knowledge and growing interest concerning apoptosis in mosquitoes is necessary considering the vast health effects seen across the globe as a result of diseases transferred by the mosquito vector. The Dengue virus mosquito vector Aedes aegypti was the focus here. A new player named defense repressor 1 was discovered in Drosophila melanogaster (DmDnr1), shown to play a role in apoptosis, and the homolog discovered in A. aegypti (AeDnr1). Silencing Dmdnr1 resulted in cells sensitized to apoptosis but was not enough to induce spontaneous apoptosis. In contrast, silencing Aednr1 in the A. aegypti cell line, Aag2, led to spontaneously induced apoptosis. This showed the importance of AeDnr1 as a member of the apoptotic pathway in this species. Epistasis experiments showed that apoptosis induced by silencing Aednr1 requires the initiator caspase Dronc and the effector caspase CASPS8, whereas apoptosis induced by silencing the inhibitor of apoptosis, Aeiap1, also requires Dronc but acts through the effector caspase CASPS7. Further epistasis experiments showed that apoptosis induced by silencing Aednr1 requires the IAP antagonist Mx, but not IMP. This showed for the first time a gene regulating upstream of an IAP antagonist. Biochemical studies showed that AeDnr1 regulates active CASPS8 but not CASPS7, and interacts with Mx and CASPS8 but not AeDronc, CASPS7 nor AeIAP1. Studies also showed Mx competes effectively with CASPS8 but not CASPS7 for AeIAP1 binding, and IMP competes effectively with CASPS7 but not CASPS8 for AeIAP1 binding. An improved apoptosis pathway for the mosquito A. aegypti emerged involving a potential feedback loop with explanations for the upstream IAP antagonist preference as well as the downstream effector caspase preference resulting from apoptosis induced by Aednr1 silencing. Through the discussed research, multiple unique findings resulted. Studying the mosquito model will allow us to find certain gene relations that are more difficult to uncover in the Drosophila model. Because Dnr1 is found in most systems, this improved pathway may shed light not only on a potential role of Dnr1 in apoptosis in insects but higher organisms as well.
Seton, Kristina. "Eosinophil Apoptosis". Doctoral thesis, Uppsala University, Department of Medical Sciences, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3427.
Texto completoApoptosis or programmed cell death is crucial for the resolution of inflammation, and phagocytosis of apoptotic cells initiates the release of actively anti-inflammatory responses from the phagocytes. Eosinophils are one of the most potent inflammatory cells in the body and is involved in a number of diseases, most commonly associated with parasitic infections and allergic diseases. Apoptosis in eosinophils is therefore one of the most important systems to avoid inflammation. This aim of the present investigation was to examine the mechanisms behind, and the consequences of this process in eosinophils. Apoptotic eosinophils have a unique surface receptor expression that indicates abilities to communicate with T-, B- and antigen presenting cells. They have a novel expression of CD49f, indicating an importance for binding to laminin or unknown functions of the VLA-6 receptor, possibly in the concept of phagocytosis of the apoptotic cell.
In apoptotic eosinophils the granules are translocated to the periphery of the cell, probably through a disruption of the cytoskeleton. This translocation makes the granules easily accessible and the apoptotic eosinophil can release considerable amounts of granule proteins in response to specific stimuli. The spontaneous release however, is decreased as compared with living cells.
Furthermore, the survival of eosinophils in response to an allergen challenge is increased in healthy subjects, but not in allergic patients. Mechanistically, this needs further investigation, but one theory is that it is due to the presence of specific IgE in patients in combination with differences in the response from the epithelial cells.
Quarrie, Lynda H. "Mammary apoptosis". Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318886.
Texto completoJoza, Nicholas. "Differential requirement for the mitochondrial apoptosis-inducing factor in apoptotic pathways". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ63071.pdf.
Texto completoSani, Marc-Antoine. "Apoptosis Regulation via the Mitochondrial Pathway : Membrane Response upon Apoptotic Stimuli". Doctoral thesis, Umeå universitet, Kemiska institutionen, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1883.
Texto completoSani, Marc Antoine. "Apoptosis regulation via the mitochondrial pathway : membrane response upon apoptotic stimuli". Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13651/document.
Texto completoThe aim of this thesis was the investigation of the mitochondrial response mechanisms upon apoptotic stimuli. The specific objectives were the biophysical characterization of membrane dynamics and the specific roles of lipids in the context of apoptotic regulation occurring at the mitochondrion and its complex membrane systems. The BH4 domain is an anti-apoptotic specific domain of the Bcl-2 protein. Solid phase peptide synthesis was used to produce large amount of the peptide for biophysical studies. A protocol has been established and optimized, guarantying the required purity for biophysical studies. In detail the purification by high performance liquid chromatography and the characterisation via mass spectroscopy are described. The secondary structure of BH4 changes significantly in the presence of lipid vesicles as observed by infrared spectroscopy and circular dichroism. The BH4 peptide aggregates at the membrane surface and inserts slightly into the hydrophobic part of the membrane. Using nuclear magnetic resonance (NMR) and calorimetry techniques, it could even be shown that the BH4 domain modifies the dynamic and organization of the liposomes which mimic a mitochondrial surface. The second study was on the first helix of the pro-apoptotic protein Bax. This sequence called Bax-a1 has the function to address the cytosolic Bax protein to the mitochondrial membrane upon activation. Once again a protocol has been established for the synthesis and purification of this peptide. The aim was to elucidate the key role of cardiolipin, a mitochondria-specific phospholipid, in the interaction of Bax-a1 with the mitochondrial membrane system. The NMR and circular dichroism studies showed that Bax-a1 interacts with the membrane models only if they contain the cardiolipin, producing a strong electrostatic lock effect which is located at the membrane surface. Finally, a new NMR approach was developed which allows the investigation of the lipid response of isolated active mitochondria upon the presence of apoptotic stimuli. The goal was there to directly monitor lipid specific the occurring changes during these physiological activities
Schmeiser, Katja. "Expression of apoptosis specific proteins (ASPs) during apoptosis and autophagy". Thesis, University of Birmingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394165.
Texto completoCabezas, Somalo Maria. "Polimorfismes genètics i tractament antitumoral: evolució dels pacients amb leucèmia limfoblàstica aguda i inducció de leucèmies secundàries". Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458541.
Texto completoChildren with acute lymphoblastic leukemia (ALL) respond differently to chemotherapy. Genetic polymorphisms together with genetic abnormalities in leukemic cells are probably behind variability in response to chemotherapy in childhood ALL. In the present thesis, we investigated whether copy number variants and/or single nucleotide polymorphism (SNPs) in genes coding for proteins involved in drug metabolism or apoptosis (CYP2D6, GSTT1, GSTM1, SULT1A1, UGT2B17 and TP53) have an impact on the therapeutic outcome of childhood ALL. We observed that patients with GSTM1 non-null genotype showed poor survival and patients carrying at least one allele of the Pro variant of the TP53 Arg72Pro SNP also showed a tendency to poor survival. When combining GSTM1 and TP53 genotypes, our data indicated that they can predict survival with higher significance than GSTM1 alone. To validate these results, an in vitro model was created with leukemic Jurkat cell line by transfection of the two TP53 variants at codon 72, either Pro or Arg and a GSTM1 siRNA into Jurkat cells. Results revealed that Jurkat p53Arg GSTM1 null cells exhibited higher sensitivity to dexamethasone, confirming the results observed in patients. It has been reported that GSTM1 inhibits glucocorticoids-induced cell death and that p53Arg induces apoptosis more efficiently than p53Pro, which is a more efficient activator of cell cycle arrest and DNA damage repair. Therefore, at least one copy of the gene GSTM1 and p53Pro, enough in heterozygosis, would lead to less efficient apoptosis in leukemic cells after the antileukemic treatment and could therefore be related to lower survival. On the other hand, one of the most severe complications after successful cancer therapy is the development of a secondary cancer, mostly a myeloid neoplasm (t-MN). Up to 20% of patients treated for a primary cancer develop t-MN. Constitutional genetic variation is likely to impact on an individual’s risk of developing t-MN. In the present thesis, we analyzed the impact of two polymorphisms in the p53 pathway on the development of t-MN. Results revealed that the TP53 Arg72Pro polymorphism and the MDM2 SNP309 were associated with t-MN risk. The p53Pro and the G allele of MDM2 were overrepresented in t-MN patients. To assess the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro and assessed the number of γ-H2AX foci, chromosome alterations, sister chromatid exchanges, and apoptotic cells, as well as development of chromosomal alterations typical of t-MN, after treatment with an alkylating agent, or a topoisomerase II poison. Jurkat p53Arg cells presented more γ-H2AX foci per cell, higher level of DNA damage and higher apoptotic potential than p53Pro cells. Moreover, Jurkat p53Pro cells presented the t(15;17) translocation and 5q33 deletion whereas Jurkat p53Arg cells did not present the alterations. Therefore, it could be possible that differences in t-MN risk in patients treated with the same doses of chemotherapy and/or radiation are due to the ability of individuals to undergo apoptosis or to repair DNA lesions more or less efficiently related to the TP53 polymorphism.
Deng, Diana Xi. "Metallothionein and apoptosis". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/mq21105.pdf.
Texto completoChurchman, Adrian Thomas. "Endothelial cell apoptosis". Thesis, University of Hertfordshire, 2005. http://hdl.handle.net/2299/14269.
Texto completoNijhuis, Erwin. "Hyperthermia-induced apoptosis". Enschede : University of Twente [Host], 2008. http://doc.utwente.nl/59801.
Texto completoCornélio, Ana Lívia Gomes [UNESP]. "Citotoxicidade e ação antimicrobiana do cimento Portland associado a diferentes agentes radiopacificadores". Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/90397.
Texto completoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A proposta deste estudo foi investigar a citotoxicidade, ação antimicrobiana e pH do cimento Portland puro (CP) e associações com agentes radiopacificadores: óxido de bismuto (CPBi), óxido de zircônio (CPZir), tungstato de cálcio (CPCa). Para avaliar o potencial citotóxico, foram empregadas linhagens celulares de fibroblastos do ligamento periodontal de camundongos (mPDL) e osteosarcoma de ratos (ROS 17/2.8). Ambas foram expostas por 24 horas a diferentes concentrações do CP fresco, CP associado com radiopacificadores e cimento de óxido de zinco eugenol. Peróxido de hidrogênio foi aplicado como controle positivo para apoptose. A viabilidade após incubação com os cimentos foi avaliada pela atividade da enzima desidrogenase mitocondrial. A morfologia celular foi analisada microscopicamente pelo corante violeta de cresilo, e o mecanismo de morte celular foi determinado pela metodologia de laranja de acridina/brometo de etídio. Os dados foram analisados estatisticamente por ANOVA e Tukey post-test (p<0.01). A correlação entre os dois tipos de morte celular e valores de pH foi estabelecido pela correlação linear de Pearson. O ensaio da enzima desidrogenase mitocondrial revelou um padrão significante de morte celular apenas nas altas concentrações dos eluídos de cimento. CP puro não foi citotóxico, mesmo na alta concentração de 100mg/ml. As imagens microscópicas mostraram que nenhuma das formulações de CP causaram danos as linhagens celulares. Análises estatísticas dos dados de apoptose/necrose demonstram que CP e CP mais agentes radiopacificadores promoveram morte por necrose estatisticamente significativa apenas em 100mg/ml. Os resultados mostraram que CP associado com óxido de bismuto, óxido de zircônio ou tungstato de cálcio não foram citotóxicos para mPDL ou ROS 17/2.8, e podem ser boas...
The purpose of this study was to investigate the cytotoxicity, antimicrobial and pH of pure Portland cement (PC), and associations with radiopacifier agents: bismuth oxide (CPBi), zirconium oxide (CPZir), calcium tungstate (CPCA). To assess the potential cytotoxicity, fibroblast cell lines from the periodontal ligament of mice (mPDL) and rat osteosarcoma (ROS 17/2.8) were used. Both were exposed for 24 hours with different concentrations of fresh PC, PC associated with radiopacifiers and eugenol zinc oxide cement. Hydrogen peroxide was used as a positive control for apoptosis. The viability after incubation with the cements was evaluated by mitochondrial dehydrogenase enzyme activity. Cell morphology was examined microscopically by cresyl violet stain, and the mechanism of cell death was determined by the method of acridine orange / ethidium bromide. The data were statistically analyzed by ANOVA and Tukey post-test (p <0.01). The correlation between the two types of cell death and pH values was established by Pearson linear correlation. The mitochondrial dehydrogenase enzyme assay revealed a significant pattern of cell death only at high concentrations of the eluted cement. Pure PC was not cytotoxic, even at high concentration of 100mg/ml. Microscopic images showed that none of the formulations of PC caused damage cell lines. Statistical analysis of apoptosis/necrosis data showed that PC and PC plus radiopacifiers agents promoted death by necrosis statistically significant only at 100mg/ml. The results showed that PC associated with bismuth oxide, zirconium oxide or calcium tungstate were not toxic to ROS 17/2.8 or mPDL, and may be good alternatives as radiopacifier agents. The antimicrobial and pH of Portland cement and radiopacifier agents were evaluated. For antimicrobial activity agar diffusion was... (Complete abstract click electronic access below)
Nieuwenhuijsen, Hendrik. "Untersuchungen zum Einfluss des extrinsischen Apoptoseweges bei dehnungsinduzierter Zellschädigung von alveolären Epithelzellen (Typ II-Zellen) aus der Rattenlunge". Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-146677.
Texto completoLi, MingLi. "Regulation of apoptosis-induced proliferation and non-apoptotic cell death in Drosophila". Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7491/.
Texto completoCossu, F. "STRUCTURAL INSIGHTS INTO INHIBITOR OF APOPTOSIS PROTEINS RECOGNITION BY PRO-APOPTOTIC COMPOUNDS". Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/168360.
Texto completoMansur, Eli. "A participação da leptina no controle da apoptose em timo de ratos wistar". [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310366.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas.
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Resumo: A leptina, hormônio com semelhança funcional e estrutural às citocinas, é conhecida por exercer, além das ações clássicas de controle da ingestão alimentar e termogênese, importantes funções na modulação das respostas do sistema imune. Alguns destes efeitos são dependentes da propriedade da leptina em modular a apoptose das células tímicas. Neste trabalho, utilizamos ratos Wistar para investigar os mecanismos moleculares envolvidos no controle, dependente da leptina, da apoptose no timo. A apoptose foi avaliada por citometria de fluxo e ELISA para determinação de nucleossomos, enquanto que a transdução do sinal foi avaliada por imunoprecipitação, imunoblot e microscopia confocal. O ObR estava expresso na maioria das células tímicas e a sua quantidade relativa reduziu-se progressivamente durante a maturação dos timócitos. A expressão do ObR estava co-localizada com JAK-2 e STAT-3, e a injeção aguda, in vivo , de leptina promoveu a fosforilação em tirosina de JAK-2 e o engajamento de STAT-3. O tratamento com leptina, também, levou à fosforilação em tirosina de IRS1 e fosforilação em serina de Akt. O tratamento crônico com leptina reduziu a apoptose tímica, e este efeito não foi inibido pelo AG490, um inibidor de JAK, mas foi significativamente inibido por LY294002, um inibidor de PI3-Quinase, e por um oligonucleotídeo antisense para IRS1. Portanto, a leptina inibe a apoptose em células tímicas via um mecanismo independente da ativação de JAK-2 mas dependente do engajamento da via IRS1/PI3-Quinase
Abstract: The cytokine-like hormone leptin is known to exert important functions on the modulation of immune responses. Some of these effects are dependent on the property of leptin to modulate the apoptosis of thymic cells. In the present study, we employed Wistar rats to investigate the molecular mechanisms involved in leptin-dependent control of apoptosis in thymus. Apoptosis was evaluated by flow cytometry and ELISA for nucleosome determination, while signal transduction was evaluated by immunoprecipitation, immunoblot and confocal microscopy. The ObR was expressed in most thymic cells and its relative amount reduced progressively during thymocyte maturation. ObR expression was co-localized with JAK-2 and STAT-3, and an acute, in vivo , injection of leptin promoted the tyrosine phosphorylation of JAK-2 and the engagement of STAT-3. The treatment with leptin also led to the tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt. Chronic treatment with leptin reduced thymic apoptosis, an effect that was not inhibited by the JAK inhibitor AG490 but was significantly inhibited by the PI3-kinase inhibitor LY294002 and by an antisense oligonucleotide to IRS1. Thus, leptin inhibits the apoptosis of thymic cells through a mechanism that is independent of the activation of JAK-2 but depends on the engagement of the IRS1/PI3-kinase pathway
Doutorado
Medicina Experimental
Vakkala, née Mustonen M. (Merja). "Apoptosis in breast lesions". Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514256506.
Texto completoSun, Mei Guo. "Mitochondrial structure during apoptosis". Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3273480.
Texto completoTitle from first page of PDF file (viewed August 31, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 129-140).
Barnett, Anna L. "Baculovirus inhibitors of apoptosis". Thesis, Oxford Brookes University, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388865.
Texto completoCook, Stuart Alexander. "Regulation of cardiac apoptosis". Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393164.
Texto completoRossouw, Sophia Catherine. "Apoptosis in Haematopoietic progenitors". Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3179.
Texto completoWard, Carol. "Mechanisms regulating granulocyte apoptosis". Thesis, University of Edinburgh, 1999. http://hdl.handle.net/1842/22722.
Texto completoToft, Neil John. "MSH2, apoptosis, and carcinogenesis". Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/22693.
Texto completoTurunen, née Virkajärvi N. (Nina). "Apoptosis and expression of apoptosis-regulating proteins in hepatocellular, gallbladder and pancreatic carcinomas". Doctoral thesis, Oulun yliopisto, 2000. http://urn.fi/urn:isbn:9514255828.
Texto completoZhuang, Jianguo. "Biochemical mechanisms of apoptosis : ordering of the biochemical events in chemical-induced apoptosis". Thesis, Open University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284375.
Texto completoRuby, Vincent. "Étude des évènements mitochondriaux impliqués dans le contrôle de l'apoptose par rbf1, l'homologue de drosophile du gène suppresseur de tumeur rb". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLV039/document.
Texto completoThe gene rb is the first tumor suppressor discovered in humans. Its prevents the appearance of tumors by regulating negatively the cell cycle. The role of pRb in apoptosis is more complex and the molecular mechanisms triggered by this transcription factor are not completely elucidated. There is a rb homologue in drosophila: rbf1. I participated in the characterization of mitochondrial events induced during activation of apoptosis by Rbf1 in a proliferating tissue of this model organism, the wing disc. In this apoptosis pathway, the Debcl protein, the only drosophila pro-apoptotic member of the Bcl-2 family, is activated and induces recruitment and oligomerization of Drp1, the main effector of mitochondrial fission. This triggers the mitochondrial fragmentation and the accumulation of mitochondrial reactive oxygen species (ROS). Both events participate to the transmission of the apoptotic signal. I have also been able to highlight the implication of factors involved in maintaining mitochondrial quality control which ensures the integrity of the mitochondria and, if necessary, triggers the degradation of damaged elements by mitophagy. Finally, I have contributed to the study of the links between translation and apoptosis induced by Rbf1. In this study, we show that the Poly-A Binding Protein (PABP) can suppress the Rbf1-induced notch phenotype in adults while cell death induced during larval stage was not inhibited but increased. These results prompted us to study the compensation mechanisms induced by the translational apparatus, which allowed us to show that a mRNA translation-related mechanism could counteract the loss of tissue resulting from Rbf1-induced apoptosis independently of apoptosis inhibition
Joselin, Alvin Paul. "The role of the apoptosis and splicing associated protein Acinus during apoptotic nuclear changes". [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=982187599.
Texto completoGama, Vivian. "Regulation of the Anti-apoptotic Protein Ku70 and the Implications for Bax-Mediated Apoptosis". Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1221831227.
Texto completoRovere, Querini Patrizia. "Clearance of dying cells by antigen presenting and scavenger phagocytes : implications for autoimmunity and tolerance". Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323272.
Texto completoEerola, A. K. (Anna-Kaisa). "Apoptosis and apoptosis regulating proteins and factors in small and large cell lung carcinoma". Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514254066.
Texto completoGibson, Hilary D. F. "Proteolytic processing of the X-linked inhibitor of apoptosis protein during Fas-mediated apoptosis". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58456.pdf.
Texto completoGarcia, Andréa Fontes [UNESP]. "Mediadores da via intrínseca da morte celular programada relacionados à infecção in vitro pelo herpesvirus bovino tipo 5". Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/121912.
Texto completoFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O herpesvirus bovino tipo 5 (BoHV-5) é um α-herpesvirus responsável por uma doença neurológica em bovinos jovens e também, ocasionalmente incriminado em alterações reprodutivas. Apesar de vários estudos descreverem as vias do processo de apoptose induzidos por infecções virais, pertencendo à família Herpesviridae, poucas informações estão disponíveis sobre as vias intrínsecas da morte celular programada em interações entre BoHV-5 e seus hospedeiros. O BoHV-5 foi capaz, no presente estudo, de replicar e de produzir efeitos citopátcos, caracterizados por um aumento e fusão celular, tanto em células mesenquimais como nas epiteliais. Os antígenos virais foram detectados em células infectadas pela reação de imunofluorescência nos períodos pós-infecção (p.i) compreendido 48 à 96 h. De acordo com a observação dos períodos p.i., entre 48 e 72 h sinais intensos de fluorescência foram observados para a proteína anti-apoptótica BCL-2 e comparação à proteína apoptótica Bax. As células infectadas revelaram um aumento do fenótipo BCL-2 entre 48 e 96 h p.i por citometria de fluxo. Entre 48 a 96 h p.i a expressão de RNA mensageiro relacionado a proteína Bax não foi verificada em nenhuma célula infectada. Ao contrário, a expressão do RNA mensageiro relacionado a proteína BCL-2 foi quantificada em Log 10 1,6 x 10 2 cópias de fita complementar de DNA (cDNA) em todos os p.i. O BoHV-5 quando está em fase de replicação nas células mesenquimais parece modular a expressão e respectiva transcrição gênica da proteína BCL-2, no sentido de aumentar a produção de partículas virais
Bovine herpesvirus 5 (BoHV-5) is α-herpesvirus responsible for neurological disease in young cattle and also occasionally incriminated in reproductive disorders.In spite of many studies describing the apoptotic pathways induced by viruses belonging to the family Herpesviridae, scare information about intrinsic programmed cell death pathway in host-BoHV-5 interactions is currently available. BoHV-5 was able to replicate and to produce cytopathology characterized by cellular swelling and cell fusion on both mesenchymal and epithelial cell lines. Viral antigens were detected in infected cells by immunofluorescence assay at 48 to 96 h post-infection (p.i.). According to sequential p.i observation, at 48 to 72 h p.i. higher fluorescent signals were visible for anti-apoptotic BCl-2 antigens in comparison to Bax, considered a proapoptotic protein. Infected cells revealed an increase of BCl-2 phenotype population from 48 to 96 h p.i. by flow cytometric analysis. At 48 to 96 h p.i. Bax mRNA was not expressed among of any infected cell monolayers. In contrast, BCl-2 mRNA was quantified Log10 1,6 x 102 cDNA copies at all p.i. for both cells. BoHV-5 replication seems to modulate BCl-2 expression and respective gene transcription in order to enhance production of progeny virus
FAPESP: 22010/52465-9
Smith, Mickaela Cardoso Martinez. "Alterações lisossomais e indução de morte celular programada em celulas leucemicas tratadas com paladaciclo". [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308722.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Estudos experimentais envolvendo a caracterização fármaco-toxicológica de novos fármacos são de grande importância na pesquisa inicial sobre drogas (ERDAL et al., 2005). Sendo assim, neste projeto um dos nossos objetivos iniciais foi avaliar os possíveis efeitos antineoplásicos de uma nova classe de drogas organometálicas contendo paládio como metal de transição, denominada paladaciclo ferroceno 1:2, utilizando para isto, a linhagem de células leucêmica K562 (leucemia mielóide crônica) e Jurkat (leucemia linfóide aguda). Os valores de IC50% obtidos na linhagem K562 após 72 horas de tratamento com o composto paladaciclo foram 4,1 e 2,9 µM, nos testes de redução do MTT e exclusão por azul de trypan, respectivamente. Através da fragmentação de DNA observamos que o composto foi capaz de induzir apoptose nas células K562 e Jurkat. Aspectos morfológicos de apoptose nestas células também foram confirmados através da coloração de acredine orange visualizadas em microscopia de fluorescência nas células K562. Utilizando acredine orange, um corante que tem a característica de se acumular principalmente em lisossomas secundários de células tumorais, nós também analisamos o mecanismo bioquímico envolvido no processo de morte celular das células K562 induzidas pelo composto paladaciclo. Nossos resultados demonstraram que a expressão dos genes envolvidos no controle da apoptose (Bcl-2 e Bax) em ambas as linhagens celulares tratadas com o paladaciclo é similar ao controle sem tratamento. Por outro lado, o composto em estudo (6,0 µM) induziu a permeabilização da membrana lisossomal de células K562 após 5 horas de tratamento com ativação das caspases efetoras da apoptose 3 e 6. Este processo de ativação das caspases também foi observado após 72 horas de incubação com o paladaciclo. Como a catepsina B está abundantemente presente nos lisossomoas e sua liberação para o citosol é esperada após alterações da permeabilidade da membrana lisossomal, investigamos também a ativação de ambas as caspases, descritas acima, após a incubação das células K562 com um inibidor de catepsina B (CA074) por 2 horas antes da exposição ao paladaciclo (6,0 µM). Este estudo forneceu um resultado bastante interessante, pois demonstrou que a ativação das caspases efetoras da morte celular programada foi prevenida, sugerindo assim que a catepsina B está fortemente associada ao processo apoptótico em células K562. Sendo assim, podemos sugerir que o composto paladaciclo apresenta potencial antileucêmico, merecendo estudos adicionais que comprovem sua eficácia terapêutica
Abstract: Experimental studies involving the pharmaco-toxicogical properties of new drugs are of very importance in its initial development (ERDAL et al., 2005). In this study it was evaluated the possible antileukemic effects of a new organometallic class of drugs called palladacycle ferrocene 1:2, using the K562 and Jurkat leukaemia cell lines. The cell death mechanism of cytotoxicity induced by the Biphosphinic Palladacycle Complex (BPC) was studied using a K562 leukaemia cell line. The IC50% values obtained for K562 cells post 72 h of BPC were less than 5.0 µM by using MTT and trypan blue assays. Complex triggers apoptosis in K562 and Jurkat cells, inducing DNA fragmentation, as analysed through electrophoresis. Using the Acridine Orange (AO) vital staining combining fluorescence microscopy it was confirmed the presence these process in K562 cells. Lysosomal membrane permeabilization was also observed in K562 cells post 5 h of BPC, which suggests intralysossomal accumulation by proton-trapping, previous study, revealed that its pKa value ranged from 5.1 to 6.5. Caspase-3, and -6 activity induced by BPC in K562 cells was prevented by the cathepsin B inhibitor (CA-074). These events occurred in the presence of endogenous Bcl-2 and Bax expression. Taken together, these data suggest a novel lysosomal pathway for BPCinduced apoptosis, in which lysosomes are the primary target and cathepsin B acts as death mediator
Mestrado
Farmacologia
Mestre em Farmacologia
Marostica, Marta Contieri. "Efeito do tratamento com inibidores de secreção acida na infecção por Helicobacter Pylori em camundongos". [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311373.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O mecanismo pelo qual o H. pylori provoca a inflamação gástrica inclui a secreção de substâncias pró-inflamatórias pela bactéria e a estimulação da liberação de citocinas induzida pelo contato direto entre a bactéria e as células epiteliais gástricas. A resposta inicial à infecção por H. pylori é predominantemente neutrofílica e estes, liberam mediadores inflamatórios e enzimas proteolíticas que induzem o dano gástrico. Estresse oxidativo ocorre em pacientes infectados com H. pylori onde a expressão de enzimas como a óxido nítrico sintase induzida (iNOS), superóxido dismutase e catalase encontram-se aumentadas. A iNOS participa da resposta inflamatória e promove a apoptose de células na mucosa gástrica. Durante a infecção por H. pylori, observa-se níveis reduzidos da expressão de Bcl-2 e o aumento da expressão de Bax na mucosa gástrica, sugerindo que uma tendência pró-apoptótica na infecção. A erradicação pode ser alcançada pela combinação de antibióticos associada a uma droga anti-ácida. As duas maiores classes de inibidores de secreção ácida são: os inibidores de bomba protônica, como o omeprazol, e os antagonistas de receptor de histamina H2, como a ranitidina. Várias evidências experimentais têm mostrado que o omeprazol apresenta efeitos anti-ulcerogênicos adicionais. Deste modo, o objetivo deste trabalho foi avaliar o efeito do tratamento com omeprazol e ranitidina em um modelo animal de infecção por H. pylori, enfocando possíveis propriedades adicionais destes fármacos Para este estudo foram utilizados camundongos machos C57BL/6 com 4 semanas de idade. Os camundongos receberam por via oro-gástrica suspensão de H. pylori. Na 11ª semana de inóculo, os animais foram tratados (i.p.) com omeprazol (100 mg/kg), ranitidina (100 mg/kg) ou veículo (PBS) durante 7 dias sempre no mesmo horário. As duas drogas inibiram a produção de ácido gástrico no tratamento agudo, porém no tratamento por uma semana, apenas o omeprazol inibiu a secreção ácida. Os animais tratados com omeprazol apresentaram um aumento significativo nos níveis de colonização gástrica e elevado nível de MPO. Ambas as drogas diminuíram as lesões da mucosa provocada pela infecção. O tratamento com omeprazol restaurou a produção de Bcl-2 na mucosa gástrica e não alterou a produção de Bax. O omeprazol não protegeu a mucosa gástrica contra o dano ao DNA gerado pela infecção e o tratamento com ranitidina aumentou os níveis de dano oxidativo ao DNA. Não observamos a presença de propriedades anti-neutrofílicas, atribuídas ao omeprazol, após uma semana de tratamento, sugerindo que essas propriedades são restrita a ensaios in vitro. Entretanto, o omeprazol restaurou a produção de Bcl-2 na mucosa gástrica, sugerindo uma atividade anti-apoptótica dessa droga
Abstract: H. pylori induces gastric inflammation characterized by secretion of pro-inflammatory substances by bacteria and the stimulation of cytokine release by the gastric epithelial cells. The initial response to the H. pylori infection is predominantly by neutrophils and these cells liberate inflammatory mediators and enzymes that induce the gastric damage. Oxidative stress also occurs in infected patients where induced nitric oxide sintase (iNOS), superoxide dismutase and catalase expression were increased. Nitric oxide participates in the inflammatory response and promotes apoptosis of gastric mucosa cells. Eradication therapy can be achieved with antibacterial agents in association with anti-acid drugs. There are two major classes of gastric acid inhibitors: the proton pump inhibitors, such as omeprazole, and the histamine H2 receptor antagonists, such as ranitidine. Some experimental evidence demonstrates that omeprazole has additional pharmacological properties. Thus, the aim of this study was to evaluate the effect of omeprazole and ranitidine treatment on H. pylori-infected mice, focusing on possible additional pharmacological properties. For this study, male C57BL/6 mice that received H. pylori suspension were used. After the 11th week, the mice were treated intraperitoneally (i.p.) with omeprazole (100 mg/kg), ranitidine (100 mg/kg) or vehicle (PBS) for 7 days. Both drugs inhibited the gastric acid production after acute administration; however after one week of treatment just omeprazole inhibited gastric acid secretion. Omeprazole-treated mice presented an increase in H. pylori and MPO levels in gastric mucosa. Both drugs reduced the mucosa damage provoked by H. pylori infection. Omeprazole treatment restored the Bcl-2 production in the gastric mucosa and did not modify Bax production. Omeprazole did not reduce the DNA damage in the gastric mucosa while ranitidine treatment increased it. We conclude that some additional omeprazole-related properties, such as antineutrophil properties, were not observed in H. pylori-infected mice after one week of treatment. However, the antiapoptotic activity of omeprazole could be attributed to an ability to modify the protein expression of Bcl-2, decreased by H. pylori infection
Mestrado
Patologia Clinica
Mestre em Ciências Médicas
Moraes, Juliana Contin. "Apoptose de neuronios hipotalamicos em ratos alimentados com dieta hiperlipidica". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310358.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Durante as últimas décadas tem se observado um aumento surpreendente na prevalência de obesidade e diabetes mellitus em populações de várias regiões do mundo, inclusive no Brasil. Medidas terapêuticas baseadas em mudanças de hábito alimentar e estilo de vida têm se mostrado ineficazes para conter o avanço destas epidemias. Somente a completa caracterização dos mecanismos fisiopatológicos envolvidos no desenvolvimento de ambas as condições deverão apontar potenciais alvos para o desenvolvimento de fármacos mais efetivos e de medidas profiláticas mais eficientes. Diversos estudos epidemiológicos apontam o consumo de dietas ricas em lípides como um dos mais importantes fatores de risco para o desenvolvimento de obesidade e diabetes. Em estudo recente realizado por nosso grupo, verificamos por macroarray de cDNA que em hipotálamo de ratos alimentados com dieta hiperlipídica há um aumento na expressão de genes de codificam proteínas participantes de respostas pró-inflamatórias como TNF-?, IL-2, IL-6 e IL-1?. Além disso, ao realizarmos avaliação histológica da expressão de citocinas como TNF-?, no hipotálamo, observamos que o número de neurônios hipotalâmicos estava aparentemente reduzido nos animais tratados com dieta hiperlípidica. Como muitas destas citocinas pró-inflamatórias podem ativar vias apoptóticas decidimos investigar a ocorrência de apoptose de neurônios em ratos alimentados com dieta hiperlípidica, sendo este o objetivo principal do presente trabalho. Utilizando real-time PCR, TUNEL, imunohistoquímica, imunoblot, e microscopia eletrônica de transmissão, observamos que neurônios do hipotálamo são alvos de apoptose. As sub-populações de neurônios preferencialmente afetadas dependem do background genético do animal, de tal forma que em animais com baixa predisposição para obesidade, tanto neurônios orexigênicos como anorexigênicos são igualmente afetados, enquanto que em cepas com maior predisposição para obesidade, neurônios anorexigênicos são alvos principais da apoptose. Por fim, revelamos que a presença de receptores TLR4 íntegros protegem neurônios da apoptose, sugerindo que essa via de sinalização do sistema imune inato tem papel duplo, participando da indução de inflamação, mas ao mesmo tempo protegendo neurônios de danos irreversíveis. Acreditamos que tais estudos possam contribuir para que se obtenham avanços na caracterização da fisiopatologia da obesidade e da participação de fenômenos nutricionais e inflamatórios na regulação funcional do centro regulador da fome e da termogênese
Abstract: Obesity and diabetes have reached epidemic proportions in several regions of the world. General changes in life-style, including consumption of fat-rich diets, are amongst the most important factors leading to an unprecedented increase in the prevalence of these diseases. The complete characterization of the pathophysiological mechanisms leading to obesity and diabetes may disclose potential targets for the development of specific drugs and development of better prophylactic approaches. Recent work has shown that the consumption of a fat-rich diet for 16 weeks leads to the increased expression of pro-inflammatory cytokines in the hypothalamus, which is accompanied by an apparent reduction in the numbers of neurons in this region. Because many of these cytokines can activate apoptotic pathways we decided to investigate the presence of apoptosis in neurons from rats fed on high-fat diet. Using real-time PCR, TUNEL, immunoblot, immunohistochemistry and transmission electron microscopy we observed increased apoptosis of neurons of the hypothalamus. The subpopulations preferentially affected depend on genetic background. Thus, in a strain genetically protected from obesity, apoptosis affects both, orexigenic and anorexigenic neurons, while in an obesity-prone strain, the anorexigenic neurons are preferentially affected. In addition, we observed that the presence of an intact TLR4 expression protects against apoptosis, suggesting that this receptor of the innate immune system plays a dual role, participating in the activation of an inflammatory response and protecting against further neuronal damage. We believe the present data will contribute to unveil some the pathophysiological mechanisms involved in the development of obesity and the roles played by nutritional and immunological factors in this context
Doutorado
Ciencias Basicas
Doutor em Clínica Médica
Cândido, Larissa Ananias. "Investigação dos mecanismos de resistência ao tratamento com halofuginona em leucemia mieloide aguda". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-06012017-164157/.
Texto completoAcute myeloid leukemia (AML) is a heterogeneous hematological disorder characterized by the clonal expansion of immature myeloid cells exhibiting different types of genetic and epigenetic alterations. A diagnosis is established when a patient presents >= 20% of blast in the bone marrow or in the peripheral blood. The WHO classifies AML in seven subtypes depending on the morphology, immunophenotype, genetics and clinical presentation of the cells. The most common treatment until nowadays is chemotherapy in combination with cytarabine and anthracycline and furthermore also the application of immunotherapeutic agents. Although researchers have attempted to develop new agents targeting directly specific mutations such as FLT3, further studies are necessary to find new therapeutic approaches for other leukemic subtypes aside from acute promyelocytic leukemia (APL). Halofuginone (HF) is a halogenated derivate of Febrifugine, which is a molecule isolated from the plant Dichroa febrifuga. It has been demonstrated that Halofuginone exhibits antifibrotic, anti-cancerogenic, anti-inflammatory and pro-apoptotic properties. We evaluated the induction of apoptosis of HF in the AML cell lines Kasumi-1,THP-1, MV4-11, U937 e OCIAML3, we verified the sensitivity and resistance of these cell lines after treatment, performed a cell cycle analysis, analyzed the activation of proteins associated with apoptosis and the proteins associated with cell proliferation and survival. We established that the Kasumi-1 cell line was sensitive to the treatment of HF displaying a dose IC50 of 125, 58 ng/ml, while the THP-1 cell lines presented resistance displaying a dose IC50 of 786,15 ng/ml . When treated with HF, the Kasumi-1 cell line stopped in the S phase of the cell cycle displaying significant decrease of proliferation, while HF showed no significant on THP-1. Furthermore we performed a western blot and It was demonstrated that the cleavage of caspase 3 appeared after 3 hours of treatment in Kasumi-1 and after 12 hours of treatment in THP-1, while cleavage of caspase 9 appeared after 12 hours in both cell lines. PARP was cleaved in Kasumi-1 after 12 hours of HF treatment, whereas the cleavage of PARP in THP-1 remained the same after 3 hours of treatment. Performing the methodology of Proteome Profiler TM Array - HumanPhospho-Kinase Array we detected 3 proteins modulated in both cell lines, 9 proteins were modulated only in Kasumi-1 cells and 6 in THP-1 cells. Amongst the different tyrosine kinases and signaling pathways that were modulated, we observed that the phosphorylation of Stat3 and Stat5 was diminished in Kasumi-1, while THP-1 presented iii decreased phosphorylation of p53. Our findings confirm that HF exhibits pro-apoptotic effect on Kasumi-1 and is capable of modulating the various proteins important for cell survival.
Massarotto, Giovana. "Mirtilo, gênero Vaccinium, cv. Misty cultivado no Brasil : caracterização química e atividade citotóxica em células de mamíferos". reponame:Repositório Institucional da UCS, 2014. https://repositorio.ucs.br/handle/11338/945.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES.
The blueberry is originally from southern United States which is, characterized by a temperate climate. It was subsequently introduced in Brazil in, 1980. Currently, Vacaria (RS) is the city with the largest fruit production in Brazil, this is mainly because of its geographic region of very cold weather in the mountains, in Campos de Cima da Serra. Blueberries are known to be rich in anthocyanins, a substance found in the skin of the fruit and is associated with significant antioxidant activity with cardiovascular risk reduction, anti-inflammatory activity and antitumor. Hydroalcoholic extracts of whole fruit and skin and pulp fractions of the fruit and the methanol extract of the whole fruit of fruits blueberry of the cultivar Misty were chemically characterized by gas chromatography-mass spectrometry (GC-MS) and high-resolution electrospray ionization mass spectrometry (ESI-HRMS) in negative mode. The chemical identification confirmed the presence of anthocyanins in samples of whole fruit and skin of methanolic and hydroalcoholic extracts, delphinidin, cyanidin, petunidin, malvidin being found, and polyphenolic compounds such as chlorogenic acid, quercetins, proanthocyanidins in the pulp of the hydroalcoholic extract and the whole fruit of the hydroalcoholic and the methanol extract. All the extracts analyzed showed lower cytotoxicity in non-tumor cell line (MRC-5) and selectivity to tumor cell lines (Hep-2, HeLa, HT-29), with less activity in the extract from the pulp in relation to the other samples analyzed. An important decrease in cell viability in tumor cell lines was observed when increasing time of exposure (from 24h to 72h) using methanol extract of the whole fruit. Induction of apoptosis was observed after 24h and 72h exposure to ethanol and methanol extract by ethidium bromide and acridine orange staining, where the majority of tumor lines showed increase in percentage at late apoptosis stages and necrosis. The results here observed suggests that the extract of blueberry, Misty cultivar, presents biological activity in tumor cell lines, but further studies are needed to understand the mechanisms involved in cytotoxicity and evaluate the effectiveness of these species as possible antitumor agent are necessary.
Garcia, Andréa Fontes. "Mediadores da via intrínseca da morte celular programada relacionados à infecção in vitro pelo herpesvirus bovino tipo 5 /". Araçatuba :, 2013. http://hdl.handle.net/11449/121912.
Texto completoCo-orientador: Fábio Erminio Mingatto
Banca: Vera Cláudia Lorenzetti Magalhaes Curci
Banca: Roberto Gameiro de Carvalho
Banca: Mário Jefferson Quirino Louzada
Resumo: O herpesvirus bovino tipo 5 (BoHV-5) é um α-herpesvirus responsável por uma doença neurológica em bovinos jovens e também, ocasionalmente incriminado em alterações reprodutivas. Apesar de vários estudos descreverem as vias do processo de apoptose induzidos por infecções virais, pertencendo à família Herpesviridae, poucas informações estão disponíveis sobre as vias intrínsecas da morte celular programada em interações entre BoHV-5 e seus hospedeiros. O BoHV-5 foi capaz, no presente estudo, de replicar e de produzir efeitos citopátcos, caracterizados por um aumento e fusão celular, tanto em células mesenquimais como nas epiteliais. Os antígenos virais foram detectados em células infectadas pela reação de imunofluorescência nos períodos pós-infecção (p.i) compreendido 48 à 96 h. De acordo com a observação dos períodos p.i., entre 48 e 72 h sinais intensos de fluorescência foram observados para a proteína anti-apoptótica BCL-2 e comparação à proteína apoptótica Bax. As células infectadas revelaram um aumento do fenótipo BCL-2 entre 48 e 96 h p.i por citometria de fluxo. Entre 48 a 96 h p.i a expressão de RNA mensageiro relacionado a proteína Bax não foi verificada em nenhuma célula infectada. Ao contrário, a expressão do RNA mensageiro relacionado a proteína BCL-2 foi quantificada em Log 10 1,6 x 10 2 cópias de fita complementar de DNA (cDNA) em todos os p.i. O BoHV-5 quando está em fase de replicação nas células mesenquimais parece modular a expressão e respectiva transcrição gênica da proteína BCL-2, no sentido de aumentar a produção de partículas virais
Abstract: Bovine herpesvirus 5 (BoHV-5) is α-herpesvirus responsible for neurological disease in young cattle and also occasionally incriminated in reproductive disorders.In spite of many studies describing the apoptotic pathways induced by viruses belonging to the family Herpesviridae, scare information about intrinsic programmed cell death pathway in host-BoHV-5 interactions is currently available. BoHV-5 was able to replicate and to produce cytopathology characterized by cellular swelling and cell fusion on both mesenchymal and epithelial cell lines. Viral antigens were detected in infected cells by immunofluorescence assay at 48 to 96 h post-infection (p.i.). According to sequential p.i observation, at 48 to 72 h p.i. higher fluorescent signals were visible for anti-apoptotic BCl-2 antigens in comparison to Bax, considered a proapoptotic protein. Infected cells revealed an increase of BCl-2 phenotype population from 48 to 96 h p.i. by flow cytometric analysis. At 48 to 96 h p.i. Bax mRNA was not expressed among of any infected cell monolayers. In contrast, BCl-2 mRNA was quantified Log10 1,6 x 102 cDNA copies at all p.i. for both cells. BoHV-5 replication seems to modulate BCl-2 expression and respective gene transcription in order to enhance production of progeny virus
Doutor
Cornélio, Ana Lívia Gomes. "Citotoxicidade e ação antimicrobiana do cimento Portland associado a diferentes agentes radiopacificadores /". Araraquara : [s.n.], 2011. http://hdl.handle.net/11449/90397.
Texto completoBanca: Fernanda de Freitas Anibal
Banca: Joni Augusto Cirelli
Resumo: A proposta deste estudo foi investigar a citotoxicidade, ação antimicrobiana e pH do cimento Portland puro (CP) e associações com agentes radiopacificadores: óxido de bismuto (CPBi), óxido de zircônio (CPZir), tungstato de cálcio (CPCa). Para avaliar o potencial citotóxico, foram empregadas linhagens celulares de fibroblastos do ligamento periodontal de camundongos (mPDL) e osteosarcoma de ratos (ROS 17/2.8). Ambas foram expostas por 24 horas a diferentes concentrações do CP fresco, CP associado com radiopacificadores e cimento de óxido de zinco eugenol. Peróxido de hidrogênio foi aplicado como controle positivo para apoptose. A viabilidade após incubação com os cimentos foi avaliada pela atividade da enzima desidrogenase mitocondrial. A morfologia celular foi analisada microscopicamente pelo corante violeta de cresilo, e o mecanismo de morte celular foi determinado pela metodologia de laranja de acridina/brometo de etídio. Os dados foram analisados estatisticamente por ANOVA e Tukey post-test (p<0.01). A correlação entre os dois tipos de morte celular e valores de pH foi estabelecido pela correlação linear de Pearson. O ensaio da enzima desidrogenase mitocondrial revelou um padrão significante de morte celular apenas nas altas concentrações dos eluídos de cimento. CP puro não foi citotóxico, mesmo na alta concentração de 100mg/ml. As imagens microscópicas mostraram que nenhuma das formulações de CP causaram danos as linhagens celulares. Análises estatísticas dos dados de apoptose/necrose demonstram que CP e CP mais agentes radiopacificadores promoveram morte por necrose estatisticamente significativa apenas em 100mg/ml. Os resultados mostraram que CP associado com óxido de bismuto, óxido de zircônio ou tungstato de cálcio não foram citotóxicos para mPDL ou ROS 17/2.8, e podem ser boas... (Resumo completo, clicar aesso eletrônico abaixo)
Abstract: The purpose of this study was to investigate the cytotoxicity, antimicrobial and pH of pure Portland cement (PC), and associations with radiopacifier agents: bismuth oxide (CPBi), zirconium oxide (CPZir), calcium tungstate (CPCA). To assess the potential cytotoxicity, fibroblast cell lines from the periodontal ligament of mice (mPDL) and rat osteosarcoma (ROS 17/2.8) were used. Both were exposed for 24 hours with different concentrations of fresh PC, PC associated with radiopacifiers and eugenol zinc oxide cement. Hydrogen peroxide was used as a positive control for apoptosis. The viability after incubation with the cements was evaluated by mitochondrial dehydrogenase enzyme activity. Cell morphology was examined microscopically by cresyl violet stain, and the mechanism of cell death was determined by the method of acridine orange / ethidium bromide. The data were statistically analyzed by ANOVA and Tukey post-test (p <0.01). The correlation between the two types of cell death and pH values was established by Pearson linear correlation. The mitochondrial dehydrogenase enzyme assay revealed a significant pattern of cell death only at high concentrations of the eluted cement. Pure PC was not cytotoxic, even at high concentration of 100mg/ml. Microscopic images showed that none of the formulations of PC caused damage cell lines. Statistical analysis of apoptosis/necrosis data showed that PC and PC plus radiopacifiers agents promoted death by necrosis statistically significant only at 100mg/ml. The results showed that PC associated with bismuth oxide, zirconium oxide or calcium tungstate were not toxic to ROS 17/2.8 or mPDL, and may be good alternatives as radiopacifier agents. The antimicrobial and pH of Portland cement and radiopacifier agents were evaluated. For antimicrobial activity agar diffusion was... (Complete abstract click electronic access below)
Mestre
Kogianni, Georgia. "Biological significance of osteocyte apoptosis". Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/24788.
Texto completoDewson, Grant. "Regulation of human eosinophil apoptosis". Thesis, University of Leicester, 2001. http://hdl.handle.net/2381/29380.
Texto completoKing, Diane. "Apoptosis in chronic lymphocytic leukaemia". Thesis, University of Leicester, 2000. http://hdl.handle.net/2381/29360.
Texto completoDimberg, Lina. "Apoptosis Regulation in Multiple Myeloma". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7099.
Texto completoWolbers, Floor. "Apoptosis chip for drug screening". Enschede : University of Twente [Host], 2007. http://doc.utwente.nl/57881.
Texto completoMarani, Michela. "Targeting apoptosis for cancer therapy". Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404985.
Texto completoJohnson, Timothy Scott. "Transglutaminase apoptosis and tumour progression". Thesis, Nottingham Trent University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283035.
Texto completoHegyi, Laszlo. "Macrophage apoptosis and human atherosclerosis". Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627017.
Texto completoChan, Ching Wan. "Apoptosis in breast cancer cells". Thesis, University of Bristol, 2004. http://hdl.handle.net/1983/8971525c-0de9-4e21-9677-ab73d61ae65c.
Texto completoLuccarelli, James. "Small Molecule Modulators of Apoptosis". Thesis, Harvard University, 2017. http://nrs.harvard.edu/urn-3:HUL.InstRepos:32676118.
Texto completo