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Kreps, Amina. "Development of an «In Vivo» eIF4E-RNA immunoprecipitation assay." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123304.
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Although eIF4E plays an important role in the development and progression of cancer, the mechanism through which it acts has not been directly characterised. In order to aid in the progression of this knowledge, an in vivo eIF4E-mRNA immunoprecipitation assay was developed and validated in NIH 3T3 cells. This assay demonstrates its ability to specifically pull down capped mRNAs bound to ectopically expressed 3X-FLAG tagged eIF4E. Mutations in eIF4E that affected cap binding and/or interaction with eIF4G or 4E-BP were also evaluated for their RNA binding potential. Elution of mRNAs from eIF4E with m7GTP competition was not observed following cell lysis, indicating that post-lysis association did not affect the immunoprecipitated mRNA pool. Our assay was able to document small molecule inhibition of eIF4E activity in cells ex vivo. The assay demonstrated a significant, reproducible decrease in mRNA binding following treatment with mTOR kinase inhibitor PP242, and will be useful in the evaluation of the eIF4E-interactome as well as assessing small molecule inhibitors of eIF4E-cap interaction.Bien que le facteur de traduction eIF4E joue un rôle important dans le développement et la progression des cellules cancéreuses, le mécanisme avec lequel il y participe reste encore très méconnu. Afin d'aider à élucider ce rôle, nous avons développé une méthode d'immunoprécipitation vérifiant l'interaction entre eIF4E et les ARNm in vivo à partir de cellules NIH 3T3. Cette méthode permet l'isolement spécifique des ARNm qui sont liés à la protéine eIF4E exprimée de manière ectopique et qui contient une séquence 3X-FLAG. Le mutant eIF4E-W56A, qui empêche la liaison de la protéine au cap, le mutant G139D, qui bloque son interaction à eIF4G ou 4E-BP, ainsi qu'un double mutant ont été utilisés afin de valider la méthode. Notre méthode à permis de démontrer que l'ajout de composés bloquant l'interaction entre eIF4E et les ARNm induit une perte significative d'ARNm recouvré suite à la purification. Par contre, nous n'avons pas observé de pertes d'ARNm lorsque nous avons ajouté le compétiteur de la liaison au cap, le m7GTP, suite à la lyse cellulaire, indiquant que l'interaction potentielle entre eIF4E et les ARNm qui pourrait avoir lieu suite à la lyse est négligeable. De plus, nous avons démontré en utilisant notre méthode qu'une diminution reproductible dans la liaison d'eIF4E aux ARNm est détectée en utilisant l'inhibiteur de la kinase mTOR PP242. Cet inhibiteur, ainsi que les composés qui bloquent l'interaction entre eIF4E et les ARNm seront maintenant utilisés afin d'évaluer la totalité de l'interactome entre eIF4E et les ARNm cellulaires.
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Schmid, Oliver. "Untersuchungen zur Genotoxizität von Formaldehyd in vitro und in vivo." [S.l. : s.n.], 2009. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-66943.
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Herron, R. "The in vivo significance of erythrocyte autoantibodies assessed by in vitro methods." Thesis, University of Portsmouth, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372840.
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Schuster, Sascha. "Ein GFP-basierter in vivo Assay für das Hochdurchsatz-Screening nach Hydrolaseaktivität." [S.l. : s.n.], 2005. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-24718.
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Broström, Oscar. "Development of a single-molecule tracking assay for the lac repressor in Escherichia coli." Thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-388075.
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Gene regulation by transcription factors are one of the key processes that are important to sustain all kinds of life. In the prokaryote Escherichia coli this has shown to especially crucial. The operator sequence to which these transcription factors bind to are very small in comparison to the whole genome of E. coli, thus the question becomes how these proteins can find these sequences quickly. One particularly well-studied transcription factor in this regard is the lac repressor. It has been shown that this transcription factors finds its operators faster than the limit of three dimensional diffusion. The leading model for how the repressor does that is facilitated diffusion and this model has gained more experimental evidence, particularly using single-molecule fluorescence microscopy. This study aimed at measuring the unspecific binding time between the lac repressor and DNA in vivo, but in the end the project evolved to trying to establish a single-molecule tracking assay of the repressor in vivo. In this study a mutant of the repressor was expressed and purified, labelled with a synthetic fluorophore, electroporated into E. coli and tracking was performed under a microscope. One of the three types of experiments were partially analysed with an image analysis software. Unfortunately, analysis was not completed for all experiments which made it difficult to compare the results. In the end the data was compared by eye while also using the results from image analysis. With slight optimism it can be concluded that the assay worked, but it needs more development.
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Tashiro, Takahiro. "In vivo and ex vivo cetuximab sensitivity assay using three-dimensional primary culture system to stratify KRAS mutant colorectal cancer." Kyoto University, 2018. http://hdl.handle.net/2433/232473.
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Bourns, Brenda. "Development and characterization of a new assay to examine telomere-protein interactions in vivo /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/6336.
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Kim, Paula. "A novel TAFIa assay and its use to measure TAFI activation in vivo in primate models and the determination of the kinetics of TAFIa-catalyzed release of bound plasminogen from soluble fibrin degradation products." Thesis, Kingston, Ont. : [s.n.], 2007. http://hdl.handle.net/1974/863.
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Tsuda, Masataka. "In vivo evidence for translesion synthesis by the replicative DNA polymerase δ." Kyoto University, 2017. http://hdl.handle.net/2433/225985.
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Sklenak, Stefanie. "Pathomorphologic analysis and therapeutic in vivo assay on two murine models of uromodulin-associated kidney disease." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-165316.
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Fentiman, Amanda Lorraine. "Development of an ex vivo assay to examine transcription factors required for endothelial to hematopoietic transition." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/48577.
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Hematopoietic stem cells (HSCs) arise from a specialized population of endothelial cells, termed hemogenic endothelium (HE). HE was first identified in the murine dorsal aorta (DA) at embryonic day (E) 10.5. This process is known as endothelial to hematopoietic transition (EHT). Our aim was to identify genes crucial for the development of embryonic HSCs from the endothelium through the process of EHT. We accomplished this through the use of a transgenic mouse model which expresses GFP under the control of an intronic enhancer of the HE gene Runx1. The expression of this enhancer was combined with endothelial and hematopoietic markers to sort specialized endothelial cell populations from the DA of E10.5 embryos. RNA-seq data was generated from these sorted cell populations and 9 possible upstream transcription factors were identified. These candidate transcription factors include both known and novel regulators of EHT, including a novel regulator Meis1.
Additionally, endothelial cell populations isolated from E9.5 embryos were sorted and cultured to develop an ex vivo co-culture assay that supports differentiation of pre-HE cells to HSCs. The effect of oxygen tension on endothelial and hematopoietic cell growth was investigated as a means to better support endothelial and hematopoietic cells. Oxygen transition during culture was found to significantly increase the proportion of wells which produced hematopoietic cells, and may aid in HE cell maintenance in culture. To examine the possibility of using this model to study regulators of EHT, the effect of blocking Notch signalling with a ɣ-secretase inhibitor added to our ex vivo culture was examined. Inhibition of Notch signalling did not significantly affect the generation of hematopoietic cells in our assay. Additionally, we evaluated the hematopoietic activity of tissue isolated from E9.5 Meis1fl/fl VeCre null embryos in this assay. No differences in hematopoietic cell generation were observed between wild-type and Meis1fl/fl VeCre null tissues in culture. Characterization of these embryos at E14.5 suggests that there exists a potential defect in Meis1fl/fl VeCre null embryos in later stages of embryonic hematopoiesis. This project contributes to the further understanding of genes important in EHT, while potentially defining transcriptional networks involved in HSC development.Medicine, Faculty of
Graduate
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Xiao, Zheng [Verfasser]. "Development and application of a novel in vivo EGFP based V(D)J recombination assay / Zheng Xiao." Ulm : Universität Ulm. Medizinische Fakultät, 2002. http://d-nb.info/1015324711/34.
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Meloche, Michèle. "Development and application of a quantitative virulence assay for Haemophilus ducreyi in an in vivo model of infection." Thesis, University of Ottawa (Canada), 1993. http://hdl.handle.net/10393/10955.
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A temperature-dependant rabbit model of Haemophilus ducreyi infection was used as a quantitative virulence assay to evaluate the effect of host factors upon ulcerative cutaneous disease production. New Zealand White rabbits underwent inoculation with H. ducreyi strain #35000 either after iron loading, dexamethasone immunosuppression, prior infection or immunization. Chancroid-like disease was scored for severity, time, culture of lesions, and serologic response. In primary infections, culture-positive ulcerative lesions were consistently produced at and above 105 colony forming units inocula. Iron and dexamethasone treatment increased lesion severity and duration of culture positivity. Infection of previously infected animals produced sterile lesions of greater size and higher cumulative disease score at 105 colony forming units inocula. Infection of immunized animals produced sterile lesions of lesser severity at 105 colony forming units, with protection from ulcer formation. Efficacy of ceftriaxone treatment was tested in naive control and iron loaded rabbits. Antibiotic was injected as a single intramuscular dose of 0.1 mg/Kg and 5 mg/Kg, four days following inoculation with Haemophilus ducreyi #35000. In naive control rabbits, antibiotic treatment at each dose sterilized the lesions within 24 hours with attenuation of disease effect. In naive iron loaded rabbits lesions were sterilized later on day 10 with 0.1 mg/Kg ceftriaxone and on day 5 with 5 mg/Kg ceftriaxone. Virulence scores corroborated the lessened microbiologic efficacy of antibiotic treatment. We conclude that quantitative assay of infection and disease in iron loaded animals, with relative prolongation of disease effect and culture positivity of lesions may be a sensitive model in which to comparatively measure virulence related to bacterial factors. As well, limitations of efficacy or synergy of antibiotic treatments may be evaluated. We conclude that prior antigenic exposure and immune response through infection or immunization attenuates subsequent homologous infection. Disease produced in re-infection is amplified, while disease produced in inoculation after immunization is attenuated at lower inocula. This suggests that while there is inducible immunity to H. ducreyi infection and disease, the disease effect may be in part related to host inflammatory response to bacterial antigen or effect of bacterial toxin. This system of measurement of virulence may be useful towards understanding pathogenesis, and identifying strategy for vaccine development in chancroid.
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Zech, Henrike Barbara Antonia Angelika [Verfasser]. "Vergleich der DNA-Doppelstrangbruch- Reparaturkapazität HPV-positiver und negativer Oropharynxkarzinome im Ex-vivo-Assay / Henrike Barbara Antonia Angelika Zech." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1223620980/34.
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SOUZA, Talita Giselly dos Santos. "Avaliação genotóxica in vivo dos efeitos agudos da mistura dos praguicidas metomil e cipermetrina." Universidade Federal de Pernambuco, 2016. https://repositorio.ufpe.br/handle/123456789/18344.
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CAPES
Os agrotóxicos foram utilizados primeiramente na saúde pública, a fim de combater vetores que causam doenças. Posteriormente seu uso tornou-se intensivo na agricultura, com intenção de melhorar a produção e a aparência dos produtos. Atualmente o Brasil é o maior consumidor de defensivos agrícolas do mundo, e isto é um fato preocupante, visto que a exposição a esses agentes tóxicos pode trazer sérios riscos à saúde humana e meio ambiente. A Cipermetrina (Cp) e Metomil (Mt) são agrotóxicos largamente utilizados na agricultura brasileira. Conquanto a Agência Nacional de Vigilância Sanitária (ANVISA) tenha estabelecido a Ingestão Diária Aceitável (IDA) de ambos isoladamente, é sabido que o consumidor está exposto a misturas de praguicidas por meio de sua dieta. No entanto, a maioria das pesquisas estudam os efeitos dos agrotóxicos isoladamente, sendo limitado o número de trabalhos que analisam as combinações desses compostos. Diante disso, avaliamos o potencial genotóxico, pelo ensaio cometa, e mutagênico, pelo teste do micronúcleo, de misturas de formulações comerciais de Mt e Cp em doses baixas. Setenta camundongos foram distribuídos em sete grupos. O grupo controle negativo (CN) recebeu água destilada (veículo de diluição). O controle positivo (CP) recebeu ciclofosfamida (20 mg/kg). Três grupos receberam misturas: A (0,05mg Mt + 0,0625 mg Cp), B (0,005mg Mt + 0,0125mg Cp) e C (0,0005mg Mt + 0,00125mg Cp). O grupo D recebeu apenas Mt (0,05mg) e o E apenas Cp (0,0625 mg). Os resultados de cada grupo foram comparados entre si pelo teste de Kruskal-Wallis com análise a posteriori, usando a estratégia de testes t par-a-par com correção de Bonferroni (p< 0,05). Todas as misturas apresentaram efeito genotóxico e apenas a mistura na maior concentração (A) foi mutagênica. Quando isolados, apenas a Cp apresentou atividade genotóxica significativa; entretanto, a média do dano de E foi menor que a encontrada nas três misturas estudadas. Desta forma, conclui-se que os efeitos do Mt e Cp são potencializados quando estes estão associados, mesmo em doses baixas, podendo causar danos à saúde.
Pesticides were firstly used in public health in order to tackle disease vectors. Afterwards,in order to improve agricultural production and products good appearance,their use in crops became intensive. Currently, Brazil is the largest consumer of pesticides in the world; the exposure to these toxic agents can pose serious risks to human health and to the environment. Cypermethrin (Cp) and Methomyl (Mt) are pesticides widely used in Brazilian agriculture. While the National Health Surveillance Agency (ANVISA) has established their Acceptable Daily Intake (ADI), consumers are exposed to mixtures of pesticides through food. Nonetheless, most of studies consider the effects of isolated pesticides, when few studies analyze the combinations of compounds. Here, we evaluated the genotoxic and mutagenic effects of low doses of Mt and Cp mixtures obtained from commercial formulations. To do that, seventy mice, divided in seven groups,were used to perform comet assay and micronucleus test. The negative control group received distilled water (dilution vehicle of pesticides),while positive control group received cyclophosphamide (20 mg / kg). Three groups received mixtures of Mt and Cp: A (0.05 mg Mt + 0.0625 mg Cp), B (0.005 mg Mt + 0,0125mg Cp) and C (0,0005mg Mt + 0,00125mg Cp). The D group received only Mt (0.05 mg) and E group received only Cp (0.0625 mg). Kruskal-Wallis test was performed for statistical analysis; subsequently, a multiple comparison was performedusing t tests and Bonferroni correction (α = 0.05). All mixtures presented genotoxic effect and only the mixture at the highest concentration (A) has presented mutagenic effect. The mixtures presented higher genotoxic and mutagenic effects than isolated pesticides at same concentrations (p < 0,05); only Cp showed significant genotoxic activity. Thus, the effects of Mt and Cp are enhanced when they are associated, even at low doses. Results presented here suggest that mixtures of Mt and Cp have different effects in health than that shown by then whenisolated. Therefore, the relationship pesticides-health must be investigated with basis in real exposure patterns.
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Elmore, Calvin Lee. "MODIFICATION OF THE NUCLEOTIDE COFACTOR-BINDING SITE OF CYTOCHROME P450 REDUCTASE TO ENHANCE TURNOVER WITH NADH IN VIVO." UKnowledge, 2003. http://uknowledge.uky.edu/gradschool_diss/467.
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NADPH-cytochrome P450 reductase is the electron transfer partner for the cytochromes P450, heme oxygenase, and squalene monooxygenase, and is a component of the nitric oxide synthases and methionine synthase reductase. P450 reductase shows very high selectivity for NADPH and uses NADH only poorly. Substitution of tryptophan 677 with alanine (W677A) has been shown by others to yield a 3-fold increase in turnover with NADH, but profound inhibition by NADP+ makes the enzyme unsuitable for in vivo applications. In the present study site-directed mutagenesis of amino acids in the 2'-phosphate-binding site of the NADPH domain, coupled with the W677A substitution, was used to generate a reductase that was able to use NADH efficiently in vivo without inhibition by NADP+. Of 11 single, double, and triple mutant proteins, two (R597M/W677A and R597M/K602W/W677A) showed up to a 500-fold increase in catalytic efficiency (kcat/Km) with NADH. Inhibition by NADP+ was reduced by up to four orders of magnitude relative to the W677A protein and was equal to or less than that of the wild-type reductase. Both proteins were 2- to 3-fold more active than wild-type reductase with NADH in reconstitution assays with cytochrome P450 1A2 and with squalene monooxygenase. In a recombinant cytochrome P450 2E1 Ames bacterial mutagenicity assay the R597M/W677A protein increased the sensitivity to dimethylnitrosamine by approximately 2-fold, suggesting that the ability to use NADH afforded a significant advantage in this in vivo assay. In addition to providing a valuable tool for understanding the determinants of nucleotide cofactor specificity in this and related enzymes, these mutants might also lend themselves to creation of bioremediation schemes with increased enzymatic activity and robustness in situ, as well as cost-effective reconstitution of enzyme systems in vitro that do not require the use of expensive reducing equivalents from NADPH.
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Rathore, Dildar S. "Genotoxic effects of oestrogens and nano-NSAIDs: Genotoxic effects of oestrogens in vivo and nano- and bulk forms of NSAIDs on blood samples from prostate cancer patients." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/13822.
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The genotoxicological effects of five intra-peritoneal administered oestrogens (17β- oestradiol, daidzein, diethylstilboestrol, genistein, and equol), were examined. Male hooded- Lister rats were used to examine to what extent DNA damage occurred. The alkaline Comet assay was the chosen method used to assess double-strand DNA breakage by examining the Olive tail moment and %age tail DNA. Tissues from the testis, bone marrow, liver and blood were analysed after an 8-day duration of exposure. Statistically significant increases in DNA damage were observed in the testis with daidzein and in the blood with diethylstilboestrol.
In addition, a further study was carried out to examine the effects of bulk and nanotised forms of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and ibuprofen, in the Comet and micronucleus assays, on whole blood taken from prostate cancer patients or volunteers. These were used because it is known that the sensitivity of DNA to genotoxins can be heightened in patients with cancer. Patients’ and volunteers’ blood was cultured with either the bulk or nano-forms for 44 hours at 37°C, 5% CO2. Data were obtained for the Comet assay as above and the number of binucleated cells scored for the micronucelus assay. The results show the nanotised forms of the NSAIDs decreased the levels of strand breakage and lowered the numbers of micronuclei generated compared with their bulk forms. There was no clear difference between the sensitivity of the healthy controls and the prostate cancer patients, with only one individual showing evidence of heightened sensitivity.
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von, Heideman Anne. "Exploring Cancer Drugs In Vitro and In Vivo : With Special Reference to Chemosensitivity Testing and Early Clinical Development." Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-151826.
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The aims of this thesis were to investigate the utility of in vitro drug sensitivity testing to optimize the use of cancer chemotherapy and to assess the properties of a new cancer drug in a phase I clinical trial. Tumour cells from patients were analysed with the short-term Fluorometric Microculture Cytotoxicity Assay (FMCA). In samples from a wide spectrum of tumour types, the effect of the drug combination FEC (5Fu-epirubicin-cyclophosphamide) was generally appropriately predicted from the effect of the best component drug. However, of samples intermediately sensitive to the best single drug, 45% converted to sensitive when testing the combination. Thus, combination testing may identify advantageous interactions and improve in vitro test performance. In tumour samples from peritoneal carcinomatosis, significant differences in drug sensitivity between diagnoses were observed, cross-resistance between most drugs was modest or absent, and the concentration-effect relationships for two drugs in individual samples varied considerably. Thus, for optimal selection of drugs for intraperitoneal chemotherapy, differences in drug sensitivity at the diagnosis and individual patient level should be considered. In samples from patients with ovarian carcinoma, drug sensitivity was related to tumour grade, histologic subtype and patient treatment status. In a homogeneous subset of patients, the FMCA predicted individual patient tumour response with high sensitivity and specificity. Thus, if carefully interpreted in the context of important clinical variables, in vitro testing could be of value for individualizing chemotherapy in ovarian cancer. Employing a once weekly dosing schedule in a phase I trial, the mechanistically new and preclinically promising NAD depleting drug CHS 828 produced dose limiting thrombocytopenia and gastrointestinal toxicity without clear evidence of anti-tumour efficacy. It is concluded that in vitro drug sensitivity testing could be a way to optimize the use of chemotherapy and that successful development of new cancer drugs needs improved strategies.
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Sklenák, Stefanie [Verfasser], and Rüdiger [Akademischer Betreuer] Wanke. "Pathomorphologic analysis and therapeutic in vivo assay on two murine models of uromodulin-associated kidney disease / Stefanie Sklenak. Betreuer: Rüdiger Wanke." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2013. http://d-nb.info/1046785338/34.
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Zinno, John Peter. "The in vivo Detection of Outer Membrane Lysis during Spore Wall Assembly in Saccharomyces Cerevisiae Using a Novel Split GFP Assay." Thesis, State University of New York at Stony Brook, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10686038.
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The regulation and mechanism of outer membrane (OM) lysis during spore wall assembly is not well understood. Although the timing of OM lysis has been established in previous studies, this event has never been assayed for. To this end, a new method was developed to assay the lysis of the OM during sporulation in Saccharomyces cerevisiae, the split GFP assay. By expressing complementary fragments of GFP in the ascal cytoplasm and the lumen between the OM and the spore plasma membrane (SPM), the lysis of the OM could be detected by the reconstitution of a functional GFP protein in the ascal cytoplasm as a result of these two compartments merging. A screen of several mutant strains with sporulation defects with published TEM images showing whether or not the lyse the OM then verified the split GFP assay for OM lysis as an effective method for detecting this event. This assay was then used to further investigate the sporulation defects associated with mutations in FKS genes, which all have 1,3-β-glucan synthase homology. The results of this assay showed that mutation in FKS2 or FKS3 leads to a reduction on observed OM lysis. This provides further evidence for the current model that proper completion of the β-glucan layer needs to occur before the OM will lyse. In addition, it was shown via dissection that FKS3 is not able to substitute for FKS1, as FKS2 has been shown to do. Although FKS3 is very similar to the other 1,3-β-glucan synthases homologically, the data suggest it has a function distinct from that of FKS1 and FKS2.
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Silva, Cibele da. "Ensaios in vivo e avaliação clínica de bomba de sangue para circulação extracorpórea durante cirurgia cardíaca : spiral pump." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/263520.
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Orientadores: Cecília Amélia de Carvalho Zavaglia, Aron José Pazin de AndradeDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica
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Resumo: Neste trabalho foram elaborados os métodos e realizados estudos In Vivo e Avaliação Clínica de uma Bomba de Sangue para Circulação Extracorpórea (CEC), durante Cirurgia Cardíaca, denominada Spiral Pump® (SP). Esses estudos foram realizados com o objetivo de avaliar o desempenho e segurança da bomba, finalizando assim o projeto e avaliando a SP como um produto em sua aplicação rotineira durante as cirurgias cardíacas. A SP utiliza, simultaneamente, dois princípios de bombeamento, o centrífugo e o axial, proporcionados por sua geometria cônica, visando aumentar a eficiência de bombeamento sem o aumento dos índices de destruição dos elementos figurados do sangue. O primeiro passo para avaliação In Vivo foi à elaboração de um protocolo para avaliação In Vivo animal e sua submissão a Comissão de Ética para Uso de Animais (CEUA) do Instituto Dante Pazzanese de Cardiologia (IDPC). As avaliações In Vivo consistiram em instalação normal da CEC, em animais suínos, utilizando a SP conectada a um módulo de acionamento e, para fins de comparação, foi realizado o mesmo procedimento com a Bio-Pump®. Foram realizados seis experimentos com a SP, sendo o primeiro considerado piloto, e três experimentos com a Bio-Pump®, com duração de seis horas cada. As observações realizadas pela equipe médica e pela perfusionista demonstraram grande semelhança de funcionamento entre as duas bombas, inclusive em relação a vibrações, ruídos e facilidade de utilização. As bombas foram comparadas em relação à medição do trauma, analisado a partir da evolução da hemoglobina livre no plasma (PFH). Analisando os resultados laboratoriais e de hemólise obtidos com a SP e a Bio-Pump®, pode-se verificar que não existem diferenças significativas entre elas. Com resultados satisfatórios nos ensaios In Vivo, a SP foi aprovada para Avaliação Clínica, realizada de acordo com a legislação vigente. Foi elaborado um Protocolo de Pesquisa Clínica que seguiu a Resolução ANVISA número 39 de 05 de junho de 2008, que estabelece requisitos para realização de pesquisa clínica no Brasil. Esse protocolo foi submetido ao Comitê de Ética em Pesquisa (CEP) do IDPC e ao Conselho Nacional de Ética em Pesquisa (CONEP). A pesquisa clínica foi realizada no Centro Cirúrgico do IDPC em um grupo de quarenta pacientes com indicação de cirurgia cardíaca com CEC, com ou sem cardioplegia, ambos os sexos, adultos, peso corporal mínimo de 50 kg. Durante a CEC, a SP substituiu as convencionais bombas de roletes no circuito de CEC. Todos os pacientes foram entrevistados e autorizaram a realização do estudo, assinando do Termo de Consentimento Livre e Esclarecido. Foram coletados dados comumente monitorados durante uma cirurgia cardíaca e foram realizados, nos períodos de pré e pós CEC, exames de Desidrogenase Láctica (U/L), Plaquetas (mil/mm3), Fibrinogênio (mg/dL), além de monitoração da hemólise através de fita de urianálise. Os procedimentos transcorreram de forma habitual, e os parâmetros mantiveram-se dentro do esperado para o estudo, demonstrando a eficiência e segurança da SP como bomba para circulação extracorpórea durante cirurgia cardíaca
Abstract: Were developed methods and studies In Vivo and clinical evaluation were conducted with a blood pump for cardiopulmonary bypass (CPB), during cardiac surgery, the Spiral Pump® (SP). These studies are designed to assess the performance and safety of SP, finalizing the project and evaluating the SP as a product in its routine application during heart surgeries. The SP uses simultaneously, two principles of pumping, axial and centrifugal, provided by its conical geometry, in order to increase pumping efficiency without increased levels of destruction of the figured elements from blood. First step for In Vivo evaluation was the development of a protocol for In Vivo experiments and its submission to the "Ethic Committee for Animal Use" of Institute Dante Pazzanese of Cardiology (IDPC). The In Vivo assessments consisted of normal installation of the CPB in pigs, using the SP connected to a driver console and, for comparison purposes, the same procedure was performed with Bio-Pump®. Six experiments were performed with SP and three experiments with Bio-Pump®, lasting six hours each. Observations made by medical team showed great similarity between two pumps, including characteristics of vibration and noise. Two pumps were compared concerning to measurement of trauma, through the evolution of plasma free hemoglobin (PFH) and the PFH variation (?PFH). Analyzing laboratory results and hemolysis, from In Vivo assays with SP and the Bio-Pump®, we can observe no significant differences between them. With satisfactory results from In Vivo assays, SP was approved for clinical evaluation, carried out in accordance with current legislation. A Clinical Research Protocol was elaborated following ANVISA (National Health Surveillance Agency) resolution number 39 of 2008, which establishes requirements for conducting clinical research in Brazil. This Protocol was submitted to the Ethic Committee Research of IDPC for review and subsequently to National Council of Ethics in Research. Clinical research was conducted at operating room of IDPC in a group of forty patients under cardiac surgery with CPB, both sexes, adults, minimum of 50 kg of body weight. During CPB, SP replaced conventional CPB roller pump. All patients were interviewed and had authorized this study, signing of consent form. Usually monitored data were collected during a heart surgery and additional examinations were carried out at periods of pre and post CEC such as: Lactic dehydrogenase exams (U/L), platelets (1000/mm3), Fibrinogen (mg/dL), as well as monitoring of hemolysis by urianalysis tape. All procedures were as usual way, and all parameters remained as expected for this study, demonstrating the performance and safety of SP as pump for CPB during heart surgery
Mestrado
Materiais e Processos de Fabricação
Mestra em Engenharia Mecânica
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Sansone, Ana Claudia Miranda Brito. "Ocorrência e distribuição de BanLec em cultivares de banana e avaliação da sua atividade imunomoduladora in vivo." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/9/9131/tde-27052015-120249/.
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Lectinas são proteínas cuja principal característica é a de se ligar específica e reversivelmente a carboidratos. BanLec é a lectina presente na polpa de bananas, que se liga especificamente a manose e glicose, e é capaz de induzir a proliferação de células T, podendo estimular a resposta imune. Existem indícios de que o teor de BanLec pode variar dependendo do estádio de amadurecimento e do tipo de cultivar, o que pode afetar a quantidade de BanLec existente na fruta quando consumida in natura e a possível resposta imune frente ao consumo de banana. Por este motivo, um dos objetivos desse trabalho foi determinar os teores e a atividade hemaglutinante de BanLec em extratos de farinha de banana verde, além de bananas das cultivares Pacovan, Figo, Terra, Mysore e Nanicão, nos estádios de maturação verde e maduro, e submetidas a tratamento com 1-MCP e baixa temperatura (para cv. Nanicão). Com vista a atender ao objetivo de avaliar seus efeitos imunomoduladores in vivo, a BanLec foi purificada da cultivar Nanicão e administrada por via oral a camundongos BALB/c. Os ensaios de atividade hemaglutinante dos extratos de banana apontaram para maior quantidade de BanLec no fruto maduro, quando comparado ao verde, e ausência dessa proteína na cultivar Figo. Os parâmetros imunológicos analisados após administração de BanLec aos camundongos demonstram que a resposta imune gerada após ingestão de BanLec é dose dependente, além disso, a administração de 50 µg de BanLec aos animais foi capaz de modular citocinas importantes na resposta imunológica, provavelmente causando um efeito que pode ser interpretado como mais protetor do que patogênico. Com base nos resultados obtidos, podemos concluir que existem diferenças nos teores de BanLec dependendo da cultivar e estádio de maturação analisado, sendo que essa proteína não está presente na polpa de todas as variedades de banana e finalmente, que ela tem grande potencial imunomodulador in vivo, uma vez que ativou citocinas de resposta anti-inflamatória.Lectins are proteins which bind specifically and reversibly to carbohydrates. BanLec is the lectin present in banana pulp, and it binds to mannose and glucose, being capable of inducing T-cell proliferation, and to stimulate the immune response. There are some evidence that the amount of BanLec may vary depending on the maturation stage of the fruit and the cultivar (cv.), which may affect the amount of BanLec and the possible immune response after consumption of banana. Thus, this study aimed to evaluate the amount of BanLec and its hemagglutinating activity in crude extracts of bananas from cultivars Pacovan, Figo, Terra, Mysore and Nanicão, in both unripe and ripe maturation stage, and also fruits which were treated with 1-MCP and low temperature. In addition, in order to access their immunomodulatory effects in vivo, BanLec was purified by affinity chromatography and administered orally to BALB/c mice. The hemagglutinating activity assays indicate higher amount of BanLec in ripe fruit. Moreover, the possible was undetectable in the pulp of banana Figo. The immunological parameters of mice orally fed with BanLec showed that the immunological response is dependent on the amount of protein administrated, in agreement to previous in vitro studies. Besides, 50 µg of BanLec, were able to modulate some cytokines in immune response, causing an effect that seems to be more protective than pathogenic. We conclude that there are important differences in amount of BanLec depending on the cultivar and the maturation stage, and BanLec has a dose-dependent immunomodulatory effect in vivo.
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Ferdusová, Helena. "Syntéza kvantových teček pro in-vivo zobrazování." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2015. http://www.nusl.cz/ntk/nusl-221307.
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The aim of this work was to synthesise water-soluble QDs using different precursors and stabilizers and to determine the toxicity of the synthesized QDs by in vivo imaging. Experiments were performed on water-soluble QDs (MPA-CdTe, MPA-CdTe/ZnS, MSA-CdTe, MSA-CdTe/ZnS, GSH-CdTe, GSH-CdTe/ZnS, TGA-CdTe, TGA-CdTe/ZnS, GSH-ZnSe and GSH-ZnSe/ZnS ) and toxicity was measured. Synthesized QDs were characterized by high intensity (fluorescence spectroscopy), FWHM and zeta potential (ZS Zetasizer) were selected due to their suitability for this task. The toxicity of QDs was determined by the MTT assay on the cell line HEK 293. The experiments show that a core/shell structure is less toxic than a core structure. The results indicate that the toxicity of our synthesized QDs is the lowest for MPA-CdTe (core structure) and MPA-CdTe/ZnS (core/shell structure).
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Jones, C. "The development and application of an in vivo micronucleus assay to monitor chronic exposure of species to genotoxic chemicals in the aquatic environment." Thesis, Swansea University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637456.
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The ability of acute tests to reflect damage induced from continuous exposure to low concentrations of xenobiotics for a prominent part of an animals life span is speculative. The assessment of human risk from exposure to genotoxic chemicals in drinking water, of both agricultural and industrial origin, and from water purification processes, is one such example. An in vivo micronucleus assay has been developed for this purpose. The assay involved the exposure of the amphibian Xenopus laevis from embryo to late tadpole stage. Micronuclei frequencies were estimated from the erythrocyte population and mortality, development, growth and behaviour as well as subtle changes in erythrocyte cell cycle kinetics were additionally assessed. For comparative purposes, an in vitro micronucleus assay for a Xenopus kidney epithelial cell line was developed. Both assays were validated with four CEC suspected aneuploidy inducing compounds, namely hydroquinone, benlate, cadmium, chloride and thimerosal. The results compared well to those observed in mammalian micronucleus assays but some discordance was observed between the in vivo and in vitro results; explanations for the variability are provided. Confirmation of the sensitivity of the Xenopus assays was achieved by the investigation of water sampled from a chlorination and ozone treatment plant, from within the Severn Trent Water Authority catchment area. The results were compared to the established Salmonella Plate Incorporation Mutation assay and were highly comparable. In contrast to most assays, the in vivo assay was sufficiently sensitive that concentration of the water samples was not required. The in vivo assay also proved suitable for the detection of teratogens, the application of which was investigated. The in vivo assay presented in this study, therefore, examines a variety of endpoints and is highly superior to the toxicity assays presently used to monitor water quality.
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Doell, Annika [Verfasser], and Oliver J. [Akademischer Betreuer] Schmitz. "In-vivo characterization of therapeutic antibodies after subcutaneous injection using a LC-MS based immuno-capture assay / Annika Doell ; Betreuer: Oliver J. Schmitz." Duisburg, 2019. http://d-nb.info/1198111380/34.
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Körner, Carolin. "Die Analyse der Inhibition des Monozyten chemotaktischen Proteins-1 (MCP-1) und der Stimulation durch MCP-1 auf die Koloniebildung und die Zytokinexpression von Plattenepithelkarzinomen der Kopf-Hals-Region im FLAVINO-Assay." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-166787.
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Das Monozyten chemotaktische Protein-1 (MCP-1) ist ein CC-Chemokin, das in seiner Rolle als Chemoattraktor auf Monozyten in der Genese von Malignomen eine wesentliche Rolle spielt. Dabei kann es sowohl zur lokalen Tumorabwehr als auch zur Tumorgenese, Tumor-angiogenese und Metastasierung beitragen. Die vorliegende Arbeit untersucht die MCP-1-Inhibition und die Stimulation durch MCP-1 auf die Koloniebildung und die Zytokinexpression von Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC) im FLAVINO-Assay. Dieser ist ein klonogener, qualitätskontrollierter Ex-vivo-Koloniebildungsassay, der an der Klinik für Hals-Nasen-Ohrenheilkunde der Universität Leipzig etabliert und patentiert wurde und unter flavinschützenden Bedingungen durchgeführt wird. Weiterhin wird die Eignung von MCP-1, Interleukin-6 (IL-6), Interleukin-8 (IL-8) und des Vascular endothelial growth factor (VEGF) als Biomarker in HNSCC, die mithilfe von ELISA in Seren und Kulturüberständen quantifiziert wurden, untersucht. Durch die Stimulation durch MCP-1 und dessen Blockade sowie durch in vivo tolerierbare Konzentrationen von Cisplatin, Docetaxel, Cilengitide und Temsirolimus wurde die Expression der untersuchten Zytokine in den Kulturüberständen der HNSCC unterschiedlich moduliert. Cisplatin und MCP-1 supprimierten die Koloniebildung signifikant, während unter Docetaxel und Temsirolimus eine insignifikante Reduktion und durch Cilengitide eine insignifikante Stimulation der Koloniebildung beobachtet wurde. Die MCP-1-Blockade durch einen Anti-MCP-1-Antikörper führte zu keiner signifikanten Modulation der Koloniebildung. MCP-1 und der Anti-MCP-1-Antikörper senkten die Zytokinexpression, während bis auf Cisplatin alle Zytostatika die Zytokinexpressionen steigerten. Bezüglich der kombinierten Testung der Zytostatika und der MCP-1-Blockade bzw. Stimulation unterschieden sich die Proben, sodass additive, synergistische und antagonistische Effekte resultierten. Da durch MCP-1 gesteuerte tumorassoziierte Makrophagen das Mikromilieu eines Tumors wesentlich beeinflussen, gebührt diesen ebenfalls eine besondere Aufmerksamkeit. In dieser Arbeit wurden unter MCP-1 antitumoröse Effekte beobachtet, sodass weitere klinische Testungen der antitumorösen Wirkung des MCP-1 auf HNSCC lohnenswert erscheinen. Die individuelle Chemoresponse-Testung kann dabei helfen, das biologisch heterogene Verhalten der HNSCC besser zu verstehen. In diesem Sinne wäre die klinische Validierung solcher Testsysteme wertvoll.
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Terrazas, Peterson Menezes. "Investigação dos efeitos citotóxico e genotóxico do extrato de salix alba L. análises in vitro, in vivo e histológicas /." Botucatu, 2017. http://hdl.handle.net/11449/152402.
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Orientador: Edson Luis MaistroResumo: A Salix alba L. (SA), popularmente conhecida como Salgueiro Branco, é uma planta utilizada na medicina popular para o tratamento de inflamações crônicas e agudas, infecções, dores, febre, entre outros. A caracterização fitoquímica do extrato da casca desta planta revelou que seu principal componente é a salicina, com uma concentração de 4,94 mg/mL, um precursor do anti-inflamatório ácido acetilsalicílico. Considerando que existem poucos estudos que avaliam a ação tóxica e citotóxica do extrato da SA, o presente estudo foi elaborado visando investigar o potencial citotóxico, genotóxico e mutagênico da SA em células mononucleares do sangue periférico humano e de hepatocarcinoma humano HepG2 in vitro, e em diferentes células de camundongos in vivo, utilizando alguns dos testes tradicionais na área de mutagênese, como o teste do MTT, o Ensaio do Cometa e o Teste do Micronúcleo, bem como a verificação de potencial citotoxicidade por meio de análises histológicas e histoquímicas. Os testes de viabilidade celular e citotoxicidade (azul de tripan e MTT) permitiram a escolha de 3 concentrações do extrato da SA para serem analisadas nos ensaios de genotoxicidade in vitro: 5, 50 e 100 µg/mL. Pelo ensaio cometa com as células mononucleares de sangue periférico, pôde-se observar que as concentrações de 50 e 100 µg/mL acarretaram um aumento estatisticamente significativo de danos no DNA, em comparação ao controle negativo. Já no teste do micronúcleo, as 3 concentrações avaliadas (5, 50 e 1... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Salix alba L. (SA), popularly known as White Willow, is a plant used in folk medicine for the treatment of chronic and acute inflammations, infections, pains, fever, among others. The phytochemical characterization of the bark extract of this plant revealed that its main component is salicin, with a concentration of 4.94 mg/mL, a precursor of the antiinflammatory acetylsalicylic acid. Considering that there are few studies evaluating the toxic and cytotoxic action of SA extract, the present study was designed to investigate the cytotoxic, genotoxic and mutagenic potential of SA bark wood extract in human peripheral blood mononuclear cells and human hepatoma cell line HepG2 in vitro and in different mouse cells in vivo using some of the traditional mutagenesis tests such as the MTT test, the Comet assay and the Micronucleus test, and cytotoxicity in the liver of mice also by histological and histochemical analysis. Cell viability and cytotoxicity tests (trypan blue and MTT) allowed the choice of 3 concentrations of the SA extract to be analyzed in the in vitro genotoxicity assays: 5, 50 and 100 μg/mL. By the comet assay with the peripheral blood mononuclear cells, it was observed that concentrations of 50 and 100 μg/ml resulted in a statistically significant increase in DNA damage, as compared to the negative control. In the micronucleus test, the 3 concentrations evaluated (5, 50 and 100 μg/mL) did not produce significant increases of micronucleated binucleate cells, as well ... (Complete abstract click electronic access below)
Doutor
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Camargo, Camila de Andrade 1980. "Atividade anticâncer de quercetina, narigina, morina e acetoxi DMU no tratamentos terapêutico de ratos inoculados com carcinossarcoma de Walker 256." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314308.
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Orientadores: Hiroshi AoyamaTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Atualmente o câncer é um problema de saúde pública mundial, em virtude do aumento de sua incidência. A anorexia e a perda de peso involuntária são comuns em pacientes oncológicos. Esta condição, também conhecida como caquexia, afeta a capacidade funcional, a resposta ao tratamento, a qualidade de vida e a sobrevida do paciente. Estima-se que aproximadamente dois milhões de pessoas no mundo morrem anualmente devido às conseqüências da via câncer/caquexia. O modelo estudado neste trabalho é o carcinossarcoma de Walker 256 (W256), que tem como característica principal o desenvolvimento da caquexia nos animais portadores, devido ao seu comportamento biológico agressivo, crescimento invasivo e alto potencial de metástase. Os flavonóides, fitocompostos polifenólicos encontrados em plantas, apresentam diversas atividades biológicas, principalmente, devido as suas propriedades antioxidantes e habilidades em modular diversas enzimas ou receptores celulares. Estes compostos possuem efeitos protetores contra doenças relacionadas ao sistema cardiovascular, certas etiologias de câncer, doenças provocadas pela fotossensibilidade e envelhecimento, dentre outras. A proposta do presente estudo foi avaliar os efeitos dos flavonóides quercetina, narigina, morina e do composto acetoxi DMU (um derivado sintético do resveratrol e do DMU-212), na prevenção/atenuação da caquexia e inibição do crescimento do tumor em ratos portadores de W256, num estudo pré-clínico. Ratos machos sadios foram inoculados subcutaneamente, no flanco direito, com as células tumorais e tratados com diferentes doses dos compostos (10, 25 e 35mg/kg), via intraperitoneal, 5 dias consecutivos por semana, durante 50 dias ou até o óbito. A administração de 10mg/kg de quercetina e de 25mg/kg de narigina, morina e do composto acetoxi DMU inibiram cerca de 50% o crescimento do tumor (ED50) quando comparado com os animais controle inoculados com tumor, sem tratamento (grupo Tumor). A ED50 para os tratamentos com quercetina, narigina, morina e acetoxi DMU foi responsável por um aumento de 30, 70, 60 e 70%, respectivamente, na sobrevida dos ratos tratados (p < 0,05) em contraste aos 100% de mortalidade observada no grupo Tumor. Outra conseqüência da administração da ED50 foi a ocorrência de regressão tumoral em 2, 5, 2 e 3 animais, respectivamente, para os tratamentos com quercetina, narigina, morina e acetoxi DMU (n=10). O tratamento com os compostos também foi eficiente em manter os níveis das citocinas TNF-? e IL-6 (no tecido hepático e tumoral do hospedeiro), mediadores do processo caquético, semelhantes aos encontrados nos ratos controle sem tumor (grupo Controle). Já os ratos do grupo Tumor apresentaram altos níveis destas citocinas, tanto nas amostras de fígado como nas de tumor. Os tratamentos promoveram também um alto potencial anti-angiogênico, mostrado através da diminuição na expressão de VEGF e nas atividades das MMP-2 presentes nas amostras de fígado e tumor. Os níveis de VEGF encontrados nos fígados dos ratos do grupo Tumor foram significantemente maiores que os do grupo Controle. Outro efeito do tratamento com os compostos foi uma diminuição significativa na expressão da proteína tirosina fosfatase de baixa massa molecular (nas amostras de fígado e tumor), que havia sido super-expressa em animais do grupo Tumor. As análises dos pesos dos testículos e órgãos reprodutivos acessórios (epidídimo, vesícula seminal, glândula de coagulação e próstata) foram feitas para os animais tratados com narigina e acetoxi DMU. Os resultados indicaram uma redução significativa nos órgãos dos animais do grupo Tumor em comparação com o grupo Controle. Pelo contrário, o tratamento terapêutico de ratos com tumor com a narigina e o acetoxi DMU se mostrou eficaz em proteger a morfologia destes órgãos e inibir esta redução. De acordo com os resultados obtidos, o melhor tratamento foi obtido com o acetoxi DMU. Os resultados obtidos neste trabalho confirmam o efeito dos flavonóides e de acetoxi DMU em diminuir os sintomas da caquexia no modelo tumoral utilizado para experimentação e em inibir o crescimento tumoral, contribuindo, assim, para uma melhor compreensão da ação in vivo destes compostos, tanto no organismo sadio como na presença do tumor
Abstract: Currently, cancer is a public health problem worldwide in virtue of the increase in incidence. Anorexia and involuntary weight loss are common in cancer patients. This condition, also known as cachexia, affects the functional capacity, response to treatment, quality of life and patient survival. It is estimated that approximately two million people worldwide die annually because of cancer cachexia consequences. In this work the Walker 256 carcinosarcoma (W256) is used as an experimental model to establish cancer cachexia in infected animals. Furthermore, it presents an aggressive biological behavior, local invasive growth and high metastasis potential. Flavonoids are polyphenolic compounds with several biological activities mainly due to its antioxidant properties and ability to modulate several enzymes or cellular receptors. These characteristics are associated with the protective effect attributed to these compounds against cardiovascular system diseases, some causes of cancer, diseases caused by photosensitivity and aging, among other. The aim of this study was to evaluate the effects of the flavonoids quercetin, naringin and morin and the compound acetoxy DMU (a synthetic derivative of resveratrol and DMU-212) in the cachexia prevention/attenuation and inhibition of tumor growth in rats bearing W256, in a preclinical study. Healthy male rats were inoculated with tumor cells and treated with different doses of quercetin, naringin, morin and acetoxy DMU (10, 25 and 35mg/kg) intraperitoneally administered, 5 consecutive times a week, during 50 days or until death. The administration of 10 mg/kg quercetin and 25mg/kg naringin, morin and acetoxy DMU inhibited about 50% of tumor growth (ED50) compared with Tumor group (untreated). The ED50 values for the treatment with quercetin, naringin, morin and acetoxy DMU were responsible for a survival increase about 30, 50, 40 and 60%, respectively, in contrast to 100% mortality observed in the tumor group. Another consequence of the ED50 administration was the tumor regression in 2, 5, 2 and 3 animals, respectively, for treatment with quercetin, naringin, morin and acetoxy DMU (n=10). The effect of treatment with these compounds on cytokines mediators of the cachectic process (in liver and tumor tissue) was efficient in maintaining the TNF-? and IL-6 levels similar to those found in control rats (Control group). Tumor group presented high levels of these cytokines in both liver and tumor samples. The treatments also promoted a high potential anti-angiogenic, shown by the decrease in VEGF expression and MMP-2 activity of liver and tumor samples. The VEGF levels found in Tumor group (liver samples) were significantly higher than the Control group. Another effect of treatment with the compounds was a significant decrease in the low molecular weight protein tyrosine phosphatase expression (in liver and tumor tissue), which had been over-expressed in Tumor group. Analyses of testes and accessory reproductive organs weights (epididymis, seminal vesicle, coagulating gland and prostate) were made for animals treated with narigina and acetoxy DMU. The results indicated a significant reduction in Tumor group organs compared with the Control group. On the other hand, the naringin and acetoxi DMU therapeutic treatments of rats with tumor have been proven effective in protecting the morphology of these organs and inhibiting its reduction. According to the results, the best treatment was obtained with the acetoxy DMU. The results of this work confirm the effect of these flavonoids and acetoxi DMU on reducing the cachexia symptoms and tumor growth inhibition, contributing to a better understanding of the action of these compounds in vivo, both in healthy and in tumor organisms
Doutorado
Bioquimica
Doutor em Biologia Funcional e Molecular
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Post, Hannah [Verfasser], and Jennifer E. [Akademischer Betreuer] Hundt. "Development and testing of a novel ex vivo assay for studying “pathological” wound healing in human skin / Hannah Post ; Akademischer Betreuer: Jennifer E. Hundt." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1227903251/34.
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Guilherme, Damasio Viviane Aparecida 1983. "Avaliação da citotoxicidade e das atividades analgésica e anti-inflamatória do ácido p-coumárico intercalado em nanopartículas de hidróxidos duplos lamelares." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314066.
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Orientadoresr: Daniele Ribeiro de Araujo, Eneida de PaulaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Compostos anti-inflamatórios não esteroídais (AINEs) são amplamente utilizados para o combate da inflamação, mas frequentemente acarretam efeitos adversos que impedem a continuação do tratamento. Atualmente, a terapia a base de plantas tem sido bastante empregada a fim de desenvolver novos fármacos que apresentem eficácia analgésica e anti-inflamatória. Nesse contexto, a utilização de sistemas carreadores, como as nanopartículas de hidróxidos duplos lamelares (HDL), visa melhorar propriedades biofarmacêuticas e farmacológicas dos compostos nelas intercalados. Dessa forma, este estudo teve como objetivo caracterizar a interação entre o ácido coumárico (AC), um composto fenólico extraído de plantas, e hidróxido duplo lamelares (HDL), nanopartículas inorgânicas, considerando parâmetros como a cinética de liberação in vitro, a citotoxicidade e as atividades analgésica-antiinflamatória em relação ao fármaco não intercalado. Os ensaios de liberação in vitro foram realizados utilizando uma célula de difusão vertical (com membrana de acetato de celulose, MWCO 1000 Da) e a viabilidade celular avaliada em células 3T3 pelo teste de incorporação do vermelho neutro (VN). Os testes farmacológicos realizados em camundongos swiss foram: a determinação do número de contorções abdominais, teste tail-flick, ensaios de peritonite e teste de formalina para o composto livre e intercalado nas concentrações de 10, 20 ou 30 mg/kg. Os ensaios de liberação in vitro mostraram que a intercalação reduziu significativamente a constante de liberação (Klib) do AC, em relação ao fármaco livre, sendo os valores de Klib de 41,6 ± 1,5 %.h-1 e 32,4 ± 1,5 %.h-1 , para o AC e AC-HDL, respectivamente. A viabilidade celular foi reduzida apenas em concentrações mais elevadas de AC e AC-HDL (10 e 12,5 mM). Porém, mesmo nestas concentrações foi observada porcentagem de viabilidade celular maior que 50%. Por fim, a avaliação farmacológica apontou o AC-HDL como um sistema de liberação com atividades analgésica e anti-inflamatória mais pronunciadas do que as observadas para anti-inflamatórios não esteroidais como a indometacina (p< 0,001). Esses efeitos foram obtidos para teste de tail-flick, quando o AC foi intercalado em HDL aumentou a duração da analgesia (~ 1,7 vezes) quando comparado com o grupo de controle indometacina. Assim, os resultados indicam que o AC intercalado em nanopartículas inorgânicas de HDL apresentou uma taxa de liberação lenta e também induziu uma atividade analgésica - anti-inflamatória, possivelmente, por um mecanismo semelhante ao observado para um anti-inflamatório não esteroidais como a indometacina
Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to avoid inflammation, but these compounds can evoke some side effects, considering these as an important limitation to the treatment. Currently, the plant-based therapy has been widely employed to develop new drugs which have analgesic and anti-inflammatory pharmacological activities. In this context, the use of inorganic nanoparticles is important to improve biopharmaceutical and pharmacological properties of the intercalated molecules. Thus, this study aimed to characterize the interaction between coumaric acid (CA), a phenolic compound extracted from plants, and layered double hydroxide (LDH), inorganic nanoparticles, considering parameters such as the in vitro release kinetics cytotoxicity and analgesic-antiinflammatory activities compared to the non-intercalated-CA. In vitro release tests were performed using a vertical diffusion cell (with cellulose acetate membrane, MWCO 1000 Da) and cell viability assessed in 3T3 cells by the neutral red (NR) uptake test. Pharmacological assays were carried in Swiss mice out in order to determine the number of writhings, tail-flick test, peritonitis test and formalin test for the free compound at three different concentrations (10, 20 or 30 mg/kg). In vitro release tests showed that the release constant (Krel) value was significantly reduced when compared to the non-intercalated CA (Krel values of 41.6 ± 1.5 %.h-1 and 32.4 ± 1.5 %.h-1 for the free CA and CA-HDL, respectively). Cell viability was reduced only at higher concentrations (10 and 12.5 mM) of CA and CA-HDL. However, even at these concentrations the percentage of cell viability was more than 50%. Finally, the pharmacological evaluation reveal the CA-HDL as a drug-release system with more pronounced analgesic-antiinflammatory effects than those observed for classic NSAIDs, such as indomethacin (p <0.001). Those effects were obtained, specially, for tail-flick test, when the treatment with CA-LDH increased the duration of analgesia (~ 1.7 times), when compared with the control group (indomethacin). Thus, the results pointed out that the system CA-LDH showed a slow release rate and also induced in vivo analgesic-anti-inflammatory activities, possibly using similar mechanisms to that observed for classic non-steroidal anti-inflammatory drugs, such as indomethacin
Mestrado
Bioquimica
Mestre em Biologia Funcional e Molecular
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Jonsäll, Linnea. "Mutational analysis of the csgD mRNA leader: search for a mode of regulation." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-208415.
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The CsgD protein is the master regulator of a pathway leading to the formation of curli, in essence regulating the switch between a motile and a sessile lifestyle for bacteria. The 5’-UTR region of the csgD mRNA is a hotspot for multiple regulatory small RNAs (sRNA) involved in a complex regulatory network. Even though it is previously known how the interaction takes place it is unknown how sRNA binding affects the translational activity. In order to suggest a mode of regulation a mutational assay was performed by making changes in the csgD 5’-UTR and investigate what the translational effects were. Mutations in different regions are shown to affect the translation levels in various ways.
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Estruch, Cucarella Guillem. "ASSESSMENT OF THE LONG-TERM IMPACT OF HIGH PLANT PROTEIN DIETS ON THE INTESTINAL STATUS OF THE ON-GROWING GILTHEAD SEA BREAM (Sparus aurata, L.)." Doctoral thesis, Universitat Politècnica de València, 2018. http://hdl.handle.net/10251/113063.
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Aunque el uso de altos niveles de fuentes de proteína vegetal en piensos para doradas de engorde se ha alcanzado con éxito en cuanto al crecimiento, estas dietas todavía están asociadas a efectos negativos en la eficiencia nutricional y en la capacidad inmunitaria. El intestino es el órgano donde se produce la primera interacción entre el pez, los nutrientes y las bacterias del medio, y desarrolla un papel crucial en la digestión de los nutrientes y la respuesta infamatoria e inmune. Esta tesis doctoral se centra en el impacto de distintas dietas con altos niveles de proteína vegetal, y especialmente, en la evaluación del estatus intestinal de las doradas de engorde alimentadas con altos niveles de sustitución de la harina de pescado durante un periodo largo de tiempo.
Los cambios observados en el intestino se caracterizaron mediante el uso de distintas estrategias, como el análisis de la digestibilidad y la retención de amino ácidos, de la excreción de amonio, de la actividad de enzimas digestivos, de los cambios histológico o de la expresión de genes relacionados con la función y el mantenimiento de la arquitectura intestinal, así como técnicas ómicas para el análisis del proteoma y de la microbiota intestinal. Se ensayaron distintos niveles de sustitución de harina de pescado, pero el impacto de las dietas con una sustitución completa, bien complementada con subproductos de origen marino o suplementada con aminoácidos libres sintéticos, recibió mayor atención.
La sustitución completa de la harina de pescado provocó una reducción, aunque ligera, del crecimiento y de la eficiencia digestiva y nutritiva de la dorada de engorde, aunque el impacto sobre el crecimiento era mayor cuando los peces eran alimentados desde la época de juveniles con estas dietas. La digestibilidad y el nivel de síntesis de proteína se vio alterada, aunque no se observaron diferencias significativas en la actividad enzimática digestiva. No obstante, el impacto de las fuentes vegetales cuando no había fuentes de proteína marina en la dieta era especialmente crítico para la supervivencia de los peces. En el intestino de estos peces solo se observaron diferencias menores relacionadas con la inflamación a nivel histológico, pero también se observó una disminución en la expresión génica de genes involucrados en la inflamación y la respuesta inmune. El análisis de la microbiota intestinal reveló cambios significativos en la composición de su composición, especialmente en el intestino posterior, sugiriendo una posible falta de capacidad de regular la respuesta inmune y de modular la colonización de bacterias patógenas tras un largo periodo de alimentación con esta dieta. Por otro lado, el análisis del proteoma de la mucosa intestinal también mostró un claro impacto sobre distintos procesos biológicos relacionados con el mantenimiento del homeostasis intestinal y de la integridad epitelial. Por el contrario, no se observó un impacto de la sustitución de la harina de pescado a nivel de expresión génica o del proteoma cuando se incorporaba a la dieta una fuente de proteína marina complementaria, aunque sí que se observaron algunos signos menores de inflamación.
Por último, se desarrolló un sistema ex vivo para estudiar la respuesta inflamatoria e inmune de la mucosa intestinal a la presencia de distintas bacterias, y se realizó un ensayo preliminar en dorada para evaluar el efecto de la dieta sobre esta respuesta.
En resumen, en este trabajo se ha realizado una evaluación extensa y detallada de los efectos a nivel intestinal de la inclusión de altos niveles de proteína vegetal en la dieta para doradas de engorde. Los resultados indican que las alteraciones en la capacidad inmune, la homeostasis y la microbiota intestinal aparecían solo cuando la proteína procedía exclusivamente de fuentes vegetales, y podrían explicar la mayor mortalidad registrada con esta dieta.Malgrat que la utilització d'alts nivells de proteïna vegetal en pinsos per a dorades en la fase d'engreixament s'ha aconseguit amb èxit en quan al creixement, aquestes dietes encara s'associen amb freqüència amb efectes negatius en l'eficiència nutricional i la capacitat immunitària. L'intestí és l'òrgan on es produeix la primera interacció entre el peix, els nutrients de la dieta i les bactèries de l'ambient, i juga un paper fonamental en la digestió dels nutrients i en la resposta inflamatòria i immune. Aquesta tesi doctoral es centra en l'impacte de diferents dietes experimentals amb un alt nivell de proteïna vegetal, i especialment, en l'avaluació de l'estat de l'intestí de les dorades d'engreixament alimentades durant un llarg període amb alts nivells de substitució de farina de peix. Els distints canvis observats a nivell intestinal es van descriure mitjançant l'ús de distintes estratègies, com l'anàlisi de la digestibilitat i la retenció dels aminoàcids, de l'excreció d'amoni i de l'activitat enzimàtica, dels canvis histològic o de l'expressió de gens relacionats amb la funció i el manteniment de l'estructura intestinal, així com tècniques òmiques per a l'anàlisi del proteoma i de la microbiota intestinal. Es van assatjar diferents nivells de substitució de farina de peix, però l'impacte de les dietes amb substitució completa, bé complementada amb subproductes d'origen marí o suplementada amb aminoàcids lliures sintètics, va rebre major atenció. La substitució completa de la farina de peix va tenir un efecte lleugerament negatiu sobre el creixement i l'eficiència digestiva i nutritiva de la dorada d'engreixament, encara que l'impacte era major quan els peixos eren alimentats des de la fase de juvenils amb aquesta dieta. La digestibilitat i el nivell de síntesis de proteïna es va veure alterada, encara que no s'observaren diferències significatives en l'activitat dels enzims digestius. No obstant, l'impacte de les fonts vegetals quan s'eliminaven per complet les fonts de proteïna marina de la dieta era especialment crític en la supervivència dels peixos. En l'intestí d'aquests peixos sols s'observaren xicotets indicis d'inflamació a nivell histològic, però també es va observar una disminució l'expressió de gens involucrats amb el procés inflamatori i la resposta immune. L'estudi de la microbiota intestinal va revelar canvis significatius en la composició, especialment a l'intestí posterior, suggerint una possible falta de capacitat de regular la resposta immunitària i de modular la colonització per part de patògens després d'un llarg període d'alimentació amb aquesta dieta. D'altra banda, l'anàlisi del proteoma de la mucosa intestinal també va mostrar un impacte clar sobre diferents processos biològics relacionats amb el manteniment de l'homeòstasi intestinal i de la integritat de l'epiteli. Per contra, no es van observar un impacte de la substitució de la farina de peix a nivell d'expressió gènica o proteoma quan s'incloïa a la dieta una font complementària de proteïna d'origen marí, encara que sí que s'observaven alguns signes d'inflamació. Per últim, es va desenvolupar un sistema ex vivo per avaluar la resposta inflamatòria i immune de la mucosa intestinal davant la presència de diferents bactèries, i es va realitzar un assaig preliminar per determinar l'efecte de la dieta sobre aquesta resposta. En resum, en aquest treball s'ha realitzat una avaluació extensa i detallada dels efectes a nivell intestinal de la inclusió d'alts nivells de fonts de proteïna vegetal a les dieta per a les dorades d'engreixament. Els resultats indiquen que les alteracions en la capacitat immunitària, l'homeòstasi i la microbiota intestinal eren observades solament quan la proteïna era exclusivament obtinguda de fonts vegetals, i podrien explicar la major mortalitat observada amb aquesta dieta.
Although the inclusion of plant protein sources at high levels in aquafeeds for on-growing gilthead seabream has been successfully achieved on gilthead seabream in terms of growth, these diets are still associated to detrimental effects in feed efficiency and immune capacity. The intestine is the organ where takes place the first interaction of the host with dietary antigen or environmental bacteria, and plays a major role in the digestion of nutrients and the inflammatory and the immune response. The present PhD thesis focus on the impact of classical formulated high plant protein diets on fish performance, but especially, on evaluation of the intestinal status in on-growing fish long-term fed with high levels of fishmeal replacement. Changes at intestinal level were characterized by using different approaches, including protein and amino acid digestibility and retention and ammonia excretion, digestive enzyme activity, histology, expression of genes related with inflammation, immunity, structure and digestion, but also using whole tissue-level techniques for the analysis of the impact on proteome and gut microbiota. Different levels of fishmeal replacement were assayed, although the impact of diets with total replacement, complemented by inclusion of alternative marine by-products or supplemented by free amino acids, received greater attention. Total fish replacement produced a negative but minor impact on the growth and nutritive and digestive performance of on-growing gilthead seabream. Nevertheless, when fish were fed from juvenile stage with plant protein based diets, a higher negative impact in growth terms was noticed. Digestibility and metabolic use of amino acids was altered, but no differences were observed in the digestive enzyme activities. Nonetheless, feeding fish with total dietary fishmeal replacement by plant protein without any marine protein source was especially critical for survival rate. In these fish, gut histological assessment only revealed minor alterations related with an inflammatory response, but gene expression assay showed a down-regulation of several genes involved in the inflammatory and immune response. Moreover, a drastic change in the microbiota composition was observed, especially at the hindgut, revealing a possible lack of capacity to regulate a defensive response and to face with pathogen colonisation after a long-term coupling with these diet. Likewise, gut mucosa proteome analysis also suggests an impact on biological processes related with the maintenance of gut homeostasis and the epithelial integrity. In contrast, total fishmeal replacement did not induce alterations at transcript or proteomic level when diet was complemented with marine ingredients, although some minor inflammatory signs were reported. On the other hand, an ex vivo system to study the inflammatory and immune response of the gut mucosa to the presence of different bacteria was developed, and a preliminary assay evaluating the impact of the diet on this response was performed. To sum up, present works represents a wide assessment at intestinal level of the effects of including plant protein sources at high levels in aqua feeds for on-growing gilthead seabream. Results indicate that alterations in the immune capacity, the gut homeostasis and the microbiota were observed when protein was exclusively provided by plant sources, and could explain the higher mortality reported with this diet.
Estruch Cucarella, G. (2018). ASSESSMENT OF THE LONG-TERM IMPACT OF HIGH PLANT PROTEIN DIETS ON THE INTESTINAL STATUS OF THE ON-GROWING GILTHEAD SEA BREAM (Sparus aurata, L.) [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/113063
TESIS
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Sarkar, Mohosin M. "Engineering Proteins with GFP: Study of Protein-Protein Interactions In vivo, Protein Expression and Solubility." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261418776.
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Anderson, Patricia Virginia. "Energy determination of corn co-products in finishing pigs and the use of an in vitro organic matter digestibility assay to predict in vivo energy." [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1468060.
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Giora, Cintia Gisela Bezuti. "Avaliação in vivo da qualidade protéica da soja Geneticamente modificada." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/9/9131/tde-13042015-123050/.
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A soja geneticamente modificada tolerante ao herbicida glifosato foi testada em ensaio nutricional. A qualidade protéica da soja foi avaliada durante 14 dias de experimento com ratos machos tipo Wistar recém desmamados. Além de um grupo controle aproteico, quatro dietas testadas continham cerca de 10% de proteínas de diferentes fontes: caseína, soja comercial, soja parental e soja GM. Resultados similares entre os grupos demonstraram o baixo aproveitamento da proteína ingerida, conforme esperado para todas as dietas com soja não suplementadas com metionina e expressos pelos valores de PDCAAS. As análises hematológicas realizadas demonstraram a síntese comprometida de células eritrócitárias e imunológicas nos mesmos grupos experimentais. Este comportamento fisiológico dos animais indica que a ingestão da variedade GM não causou diferença significativa no desenvolvimento dos animais entre as três amostras de soja ensaiadas e tampouco foram observados efeitos adversos em órgãos dos animais e nos parâmetros químicos analisados.A glyphosate tolerant soybean obtained by genetic modification was tested on a nutritional essay. The quality of the soy protein was assessed by a 14-day long experiment with Wistar male rats, three weeks old. Besides the control free protein group, four different diet groups containing about 10 % protein were pooled out: casein, commercial, parental and GM soybeans. Similar results showed the regular low biological value of the consumed soy proteins not supplemented by methionine displayed by PDCAAS values. The hematological analysis pointed to a commitment of the synthesis of erythrocytic and immunologic cells at the experimental soy groups. The overall behavior of the animals indicate the ingestion of the GM variety of soybean did not cause significant differences for the rat development when compared to the other soybean groups, neither side effects on inner organs and chemical analyzed parameters.
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Pereira, Ana Carolina da Silva. "Desenvolvimento de sucos tropicais mistos com elevada capacidade antioxidante e avaliaÃÃo in vivo." Universidade Federal do CearÃ, 2014. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=11607.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorEmpresa Brasileira de Pesquisa AgropecuÃria
O objetivo desta pesquisa foi desenvolver formulaÃÃes de sucos tropicais mistos, baseando-se em dados da Dieta MediterrÃnea (DM), utilizando ferramentas de otimizaÃÃo de processos, para avaliar e quantificar possÃveis efeitos aditivo, sinergÃstico e antagÃnico entre as variÃveis, e avaliar o perfil funcional in vitro e in vivo dos sucos. Foi utilizado um planejamento estatÃstico do tipo fracionado para seleÃÃo das variÃveis (P<0,10), seguido de um delineamento composto central rotacional (DCCR) 25 com P<0,05. As variÃveis independentes foram Ãs concentraÃÃes das polpas de frutas (%) das seis espÃcies de frutas tropicais (camu-camu, acerola, caju, cajÃ, aÃaà e manga) e como variÃveis dependentes a capacidade antioxidante total (TAC) atravÃs do mÃtodo ABTS, polifenÃis totais (TP), Ãcido ascÃrbico e aceitaÃÃo sensorial. Para os ensaios in vivo foram utilizadas duas formulaÃÃes de suco tropical misto: formulaÃÃo A (suco tropical misto de acerola, abacaxi, aÃaÃ, caju, cajà e camu-camu) e formulaÃÃo B (suco tropical misto de acerola, abacaxi, aÃaà e cajÃ), com suas diferentes porcentagens de polpa (%). Ratos machos da linhagem Wistar, recÃm-desmamados foram distribuÃdos em 7 grupos, sendo controle (Ãgua), e seis grupos de animais tratados por gavagem com a reconstituiÃÃo em Ãgua das formulaÃÃes dos sucos liofilizadas nas concentraÃÃes: 100, 200 ou 400mg/kg de peso corpÃreo, durante 30 dias. Foram avaliados os Ãndices nutricionais de consumo de raÃÃo e ganho de peso; anÃlises bioquÃmicas: glicose, triglicerÃdeos, colesterol total, HDL (High Density Lipoprotein), alanina aminotransferase (ALT) e aspartato aminotransferase (AST); peroxidaÃÃo lipÃdica do soro e fÃgado, pelo mÃtodo TBARS (substÃncias reativas ao Ãcido tiobarbitÃrico) e atividade das enzimas antioxidantes, catalase (CAT), superÃxido dismutase (SOD) e glutationa peroxidase (GSH-Px), nos eritrÃcitos, e fÃgado. A partir da anÃlise dos planejamentos estatÃsticos, o camu-camu, a acerola e o aÃaà foram os principais fatores que influenciaram o potencial antioxidante das formulaÃÃes, e o cajà mostrou um efeito positivo sobre a aceitaÃÃo sensorial dos sucos tropicais. Observou-se um efeito antagÃnico entre acerola e camu-camu para a resposta TAC. A formulaÃÃo otimizada foi composta por 20% acerola, 10% de camu-camu, 10% de cajÃ, 10% caju e 10% de aÃaÃ, que correspondeu a um resultado de 155,46 mg.100 g-1 de Ãcido ascÃrbico, 103,01 mg de GAE.100 g-1 para TP, 10,27 ÂM Trolox g-1 para TAC e aproximadamente 6,1 de aceitaÃÃo sensorial. Os grupos tratados com as formulaÃÃes de sucos mistos nÃo apresentaram diferenÃa significativa em relaÃÃo aos Ãndices nutricionais e parÃmetros bioquÃmicos, incluindo a atividade das enzimas ALT e AST, indicando que as formulaÃÃes nÃo ocasionaram danos hepÃticos aos animais. Os resultados demonstraram que a atividade das enzimas SOD e CAT no fÃgado (FA200), e GSH-Px nos eritrÃcitos (FB400), e TBARS no soro e fÃgado (FB100, FA400, FB200, FB400) foi significantemente reduzida nos grupos tratados com os sucos de frutas, quando comparados com o grupo controle, enquanto que o HDL-c aumentou (FB400). Os resultados in vitro e in vivo sugerem que o consumo dos sucos tropicais mistos desenvolvidos neste trabalho foi eficaz na defesa antioxidante endÃgena, sugerindo efetivamente que os sucos de frutas tropicais podem ter significativa relevÃncia para efeitos benÃficos a saÃde.
The aim of this research was to optimize the formulation of mixed tropical juices, based on research into the Mediterranean Dietâ (MD), using a statistical design of fractional type for variable selection (P<0.10), followed by a planning type DCCR (Delineation central composite rotational) 25 with P<0.05, and response surface methodology (RSM), which it was possible to assess. Moreover this investigation proposed to quantify possible additive effects, synergisms and antagonisms between variables, and to evaluate in vitro and in vivo profile of functional the juices. We used six species of tropical fruits (camu-camu, acerola, cashew, yellow mombin, acai and mango). The dependent variables were analyzed: total antioxidant capacity (TAC) using ABTS method, total polyphenols (TP), ascorbic acid and sensory acceptance. The independent variables were the concentrations of fruit pulp (%). For evaluate the in vivo assays were used two formulations of optimized mixed tropical fruit: The formulation (mixed tropical acerola juice, pineapple, acai, cashew, yellow mombin and camu-camu) and formulation B (mixed tropical acerola juice, pineapple, acai and yellow mombin), with different pulp proportions (%) and weaned rats that were divided in 7 groups: control (water), six groups of animals treated by gavage in water to reconstitute lyophilized juice formulations at concentrations of 100, 200 or 400mg/kg for 30 days. The followed analyzes were performed: The nutritional indices of feed intake and weight gain; biochemical analyzes of glucose, triglycerides, total cholesterol, HDL (High Density Lipoprotein), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum lipid peroxidation and liver method TBARS (thiobarbituric acid reactive substances) and activities of antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in erythrocytes and liver. Concerning to the statistical planning and MSR, camu-camu, acerola and acai were the main factors that influenced the antioxidant potential of the juice, and yellow mombin showed a positive effect on sensory acceptability of tropical juice. There was an antagonistic effect between acerola and camu-camu in regarding to TAC. The optimal formulation was composed of 20% acerola, 10% camu-camu, 10% yellow mombin, 10% cashew and 10% acai, which corresponding a result of 155,46 mg.100g-1 ascorbic acid, 103,01 mg GAE. 100 g-1 TP, 10,27 ÂM Trolox g-1 for TAC and sensory acceptance of approximately 6.1. The groups treated with the formulations of mixed juices showed no statistical significant difference in relation to nutritional indices and biochemical parameters, including the activity of the enzymes ALT and AST, indicating that the formulations did not cause liver damage these animals. The results showed that the SOD activity and CAT in the liver (FA200) and GSH-Px in erythrocytes (FB400) and in serum and liver TBARS (FB100, FA400, FB200, FB400) were efficiently reduced in the groups treated with the fruit juices, when compared with the control group, while HDL-c increased (FB400). In conclusion, daily consumption of 200mL of optimized formulation is responsible for approximately 50% of the recommended amount of antioxidants in the Mediterranean diet pattern, therefore, a rich source for these bioactive compounds. The results of in vitro and in vivo studies suggest that consumption of tropical juices mixed evaluated was effective in endogenous antioxidant defense, and effectively suggest that the tropical fruit juices may have significant relevance to the health beneficial effects.
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Freitas, Patrícia Scotini. "Investigação do potencial mutagênico do extrato de frutos de Vaccinium corymbosum (mirtilo) em células do sangue periférico de camundongos Swiss in vivo." Universidade Jose do Rosario Vellano, 2007. http://tede2.unifenas.br:8080/jspui/handle/jspui/70.
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Previous issue date: 2007-04-27Coordenacao de Aperfeicoamento de Pessoal de Nïvel Superior
Blueberry Vaccinium corymbosum is a vegetable very rich in anthocyanins which have strong antioxidant capacity and other potential health benefits and because of that is widely consumed in the world as medicinal plant In this work the mutagenic potential of the crude extract from this plant was studied in mice after acute treatment using the comet and micronucleus assay Animals were treated orally with three different concentrations of the extract (1000 1500 and 2000 mg/kg) Peripheral blood cells of Swiss mice were collected 4 and 24 hours after the treatment for the comet assay and 48 and 72 hours for the micronucleus test The results have shown that the extract of Vaccinium corymbosum did not induce statistically significant increases in the average number of damages to desoxyribonucleic acid in peripheral blood cells However a significant increase in the mean of the micronucleated polychromatic erythrocytes was observed at three tested doses It is suggested that its consumption could be moderate until a definitive risk for humans is established
Vaccinium corymbosum é um vegetal muito rico em antocianinas que tem uma grande capacidade antioxidante e outros potenciais benefícios à saúde e por este motivo é altamente utilizado no mundo inteiro como planta medicinal Neste trabalho foi analisado o potencial mutagênico da administração aguda do extrato bruto de frutos desta planta em células de camundongos utilizando o ensaio cometa e o teste do micronúcleo Os animais foram tratados oralmente com três diferentes concentrações do extrato (1000, 1500 e 2000 mg/kg de peso corporal) Células do sangue periférico de camundongos foram coletados 4 e 24 horas após o tratamento para a realização do ensaio cometa e 48 e 72 horas para o teste do micronúcleo Os resultados mostraram que o extrato de Vaccinium corymbosum não induziu aumentos estatisticamente significativos de danos ao ácido desoxirribonucléico nas células de sangue periférico Entretanto o teste do micronúcleo evidenciou um aumento significativo na média de eritrócitos policromáticos micronucleados nas três concentrações testadas Sugere-se que o consumo deste extrato seja moderado até que seu risco definitivo para os seres humanos seja melhor estabelecido
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Schlegel, Daphne. "Der Einfluss des Integrin-Rezeptor-Inhibitors Cilengitide auf die Ex-vivo-Chemoresponse von Kopf-Hals-Tumoren gegenüber Cisplatin, Docetaxel und Cetuximab im FLAVINO-Assay mit und ohne Bestrahlung." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-150000.
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An 100 Tumorproben mit HNSCC (head and neck squamous cell carcinoma) von 92 Patienten wurde mit Hilfe des FLAVINO-Assays erstmalig das Adhärenzverhalten von Plattenepithelzellen bei unterschiedlichen Beschichtungen untersucht und anschließend eine Ex-vivo-Chemoresponsetestung durchgeführt. Hierbei kamen als Beschichtungsproteine humanes Laminin [L], humanes Fibronektin [hFN], Kollagen I [K] aus Rattenschwänzen und eine vorteilhafte Mischung aus unterschiedlichen extrazellulären Proteinen [ECM] zur Anwendung. Zusätzlich wurde eine ECM-Platte noch mit 2,2 Gy einmalig bestrahlt. Ziel der Chemo-responsetestung war es, den Einfluss des Integrin-Inhibitor Cilengitide [Cil] auf HNSCC gegenüber den Standardtherapeutika Cisplatin [Cis], Docetaxel [DTX] und Cetuximab [Cetux] zu testen und letztendlich eine optimale Kombination zur Verbesserung der Prognose für HNSCC zu gewinnen. 41% der Tumorproben zeigten ein Koloniewachstum, wobei die höchste Koloniebildung auf der bestrahlten ECM-Beschichtung ausgezählt werde konnte, dicht gefolgt von der Kollagenbeschichtung. 10 µM Cil als Monotherapie konnten bei HNSCC eine Koloniereduktion von 23% erzielen, 66,6 µg/ml Cetux von 53% und beide in Kombination 55%. Cis als potente Monosubstanz in Verwendung 6,667 µM erzielten eine fast vollständige Koloniereduktion von 96%, wohingegen 550 nm DTX nur 66% Reduktion erreichten. In binärer, tertiärer und quartärer Kombination aller vier Chemotherapeutika ist nur eine komplette Koloniereduktion zu erreichen, wenn Cis in der Dosierung 6,667 µM verwendet wird. Cil in Kombination mit DTX, Cetux und Cis konnte nach zusätzlicher Bestrahlung eine 100%ige Koloniereduktion erreichen und kann somit als potenter Radiosensitizer angesehen werden.
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Kohl, Tobias [Verfasser]. "Development of a novel protease assay exclusively based on fluorescent proteins and dual-color cross-correlation analysis for both in vitro and in vivo applications = Entwicklung eines FCS- (Fluoreszenz-Korrelationsspektroskopie) basierten Assays für die Detektion intrazellulärer Proteaseaktivität / Tobias Kohl." Ulm : Universität Ulm. Fakultät für Naturwissenschaften, 2004. http://d-nb.info/1015471277/34.
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Staub, Inara. "Avaliação da fotoestabilidade do cetoconazol e determinação da atividade antifúngica e da segurança biológica in vivo e in vitro do xampu de cetoconazol." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2005. http://hdl.handle.net/10183/76832.
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Cetoconazol é um agente antifúngico que possui ação tópica e sistêmica, podendo ser incorporado em diferentes formas farmacêuticas. Como exemplo, pode-se citar o xampu de cetoconazol, que é efetivo no tratamento da dermatite seborréica e pitiríase versicolor. É reconhecido que o cetoconazol, nas formas farmacêuticas xampu e solução, rapidamente altera a coloração se tornando avermelhado. A exposição de fármacos à radiação pode influenciar a estabilidade da formulação, levando a modificações nas propriedades físico-químicas do produto. O objetivo deste trabalho foi avaliar a fotoestabilidade do cetoconazol em xampu e solução. As formulações foram expostas à radiação UV-A (352 nm), UV-C (254 nm) e luz diurna. Métodos foram desenvolvidos e validados para a determinação quantitativa do cetoconazol: cromatografia líquida de alta eficiência e ensaio microbiológico utilizando o método de cilindros em placa. Estudos comparativos entre xampu de cetoconazol e xampu de cetoconazol contendo produtos de degradação foram feitos para avaliar a atividade antifúngica e a segurança biológica in vivo (teste de Draize) e in vitro (teste de citotoxicidade). Os resultados demonstraram diminuição na atividade antifúngica, mas não demonstraram alteração na segurança biológica. Os métodos utilizados para análise do cetoconazol (ensaio microbiológico e CLAE) demonstraram ser lineares, precisos e exatos, sendo úteis no controle de qualidade do fármaco. Os resultados indicam alteração do cetoconazol em presença da luz. Dois produtos de degradação foram isolados e identificados: 1-acetil-4-{4-[2-(2-clorofenil)-2-(1H-imidazolil-1- metil)-1,3-dioxolanil-4-metoxi]fenil}piperazina e 1-acetil-4-{4-[2-(4-clorofenil)-2- (1H-imidazolil-1-metil)-1,3-dioxolanil-4-metoxi]fenil}piperazina. Conseqüentemente, adequada proteção da luz deve ser adotada durante armazenamento das duas formas farmacêuticas contendo o fármaco.Ketoconazole is an antifungal agent with topic and systemic action and can be incorporated into several dosage forms. As an example, it could be mentioned ketoconazole shampoo, which is effective against seborrhoeic dermatitis and pityriasis versicolor. It is remarkable that ketoconazole is rapidly altered in shampoo and solution dosage forms, since its colour turns into red. Exposure of a drug to radiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The aim of this work was to assess the photostability of ketoconazole in shampoo and solution. The formulations were exposed to UV-A (352 nm) and UV-C (254 nm) radiations and daylight. Methods were developed and validated for the quantitative determination of ketoconazole: high performance liquid chromatography and microbiological assay using the cylinder-plate method. Comparative studies between ketoconazole shampoo and ketoconazole shampoo containing degradation products were conducted to evaluated the antifungal activity and biological reactivity in vivo (Draize test) and in vitro (cytotoxity test). The results showed a decrease in antifungal activity but not an alteration on the biological reactivity. The methods used for ketoconazole analysis (microbiological assay and HPLC) were linear, precise and accurate, providing valuable methods for the quality control of this drug. The results indicate alteration in ketoconazole in presence of light. Two photodegradation products were isolated and identified: 1-acetyl-4-{4-[2-(2-chlorophenyl)-2-(1H-imidazol- 1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]phenyl}piperazine and 1-acetyl-4-{4-[2- (4-chlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]phenyl} piperazine. Consequently, adequate light protection should be adopted for storage of these two dosage forms containing the drug.
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Andrade, Cláudia Umbelina Baptista. "MUTAGENICIDADE DO EXTRATO DE CASCA DE Musa paradisiaca (MUSACEAE) EM CÉLULAS DE SANGUE PERIFÉRICO DE CAMUNDONGOS IN VIVO." Universidade Jose do Rosario Vellano, 2007. http://tede2.unifenas.br:8080/jspui/handle/jspui/79.
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Previous issue date: 2007-11-08Plants are a source of many biologically active products and nowadays they are of great interest to the pharmaceutical industry. In the present study, the mutagenic potential of the fruit peels extract from Musa paradisiaca was assessed using the single cell gel electrophoresis (Comet assay) and micronucleus assays. Animals were treated orally with three different concentrations of the extract (1000, 1500 and 2000 mg/kg of body weight). Peripheral blood cells of Swiss mice were collected 24 h after the treatment for the comet assay and 48 and 72 h for the micronucleus test. The results showed that the extract of M. paradisiaca induced statistically significant increases in the average numbers of DNA damage in peripheral blood leukocytes for the two higher doses and a significant increase in the mean of the micronucleated polychromatic erythrocytes at three tested doses. The polychromatic/normochromatic erythrocytes ratio (PCE/NCE) scored in the tested groups was not statistically different from the negative control, showing that the extract presented no cytotoxic effects. The data obtained indicate that fruit peels extract from M. paradisiaca showed mutagenic effect in the peripheral blood cells of Swiss albino mice.
As plantas em geral são fontes de muitos produtos com atividades biológicas, e atualmente são de grande interesse para a indústria farmacêutica. Musa paradisíaca é uma dessas plantas, cuja casca vem sendo utilizada para tratamento de fissuras na pele, devido ao seu poder cicatrizante, e, devido aos seus altos valores energéticos e nutritivos, também tem servido de alimentação alternativa através da farinha. Visto que nunca foi investigado o efeito da casca desta planta sobre o genoma de mamíferos, foi objetivo deste trabalho analisar o potencial mutagênico do extrato de cascas de Musa paradisíaca sobre células sangüíneas de camundongos Swiss in vivo. Para esta avaliação, foram utilizados o ensaio cometa e o teste do micronúcleo. Os animais foram separados em cinco grupos de seis animais cada, onde em três deles foram testadas, por via oral, três diferentes concentrações do extrato (1000, 1500 e 2000 mg/kg de peso corpóreo). As células do sangue periférico foram coletadas 24 horas após o tratamento para a realização do ensaio cometa e 48 e 72h para o teste do micronúcleo. Os resultados obtidos com o ensaio cometa mostraram que o extrato de Musa paradisíaca induziu aumento estatisticamente significativo na quantidade de danos no DNA dos leucócitos de sangue periférico nas duas maiores concentrações do extrato, e, pelo teste do micronúcleo, um aumento também significativo na média de eritrócitos policromáticos micronucleados nas três doses testadas. A relação de eritrócitos policromáticos e normocromáticos (PCE/NCE) em 1000 células por animal não mostrou diferença significativa em relação ao grupo controle negativo, indicando que o extrato não apresenta citotoxicidade. Com base nas condições do ensaio desenvolvido, os dados obtidos revelaram que o extrato de cascas de Musa paradisíaca apresentou efeito mutagênico em células de sangue periférico de camundongos Swiss albinos.
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Pereira, Ana Carolina da Silva. "Desenvolvimento de sucos tropicais mistos com elevada capacidade antioxidante e avaliação in vivo." reponame:Repositório Institucional da UFC, 2014. http://www.repositorio.ufc.br/handle/riufc/14957.
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PEREIRA, A. C. S. Desenvolvimento de sucos tropicais mistos com elevada capacidade antioxidante e avaliação in vivo. 2014. 120 f. Tese (Doutorado em Ciência e Tecnologia de Alimentos) - Centro de Ciências Agrárias, Universidade Federal do Ceará, Fortaleza, 2014.Submitted by Daniel Eduardo Alencar da Silva (dealencar.silva@gmail.com) on 2015-01-26T17:54:51Z No. of bitstreams: 1 2014_tese_acspereira.pdf: 2223617 bytes, checksum: 78f3ce03b26cd1f0155a4bc6fccba9d5 (MD5)
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The aim of this research was to optimize the formulation of mixed tropical juices, based on research into the Mediterranean Diet” (MD), using a statistical design of fractional type for variable selection (P<0.10), followed by a planning type DCCR (Delineation central composite rotational) 25 with P<0.05, and response surface methodology (RSM), which it was possible to assess. Moreover this investigation proposed to quantify possible additive effects, synergisms and antagonisms between variables, and to evaluate in vitro and in vivo profile of functional the juices. We used six species of tropical fruits (camu-camu, acerola, cashew, yellow mombin, acai and mango). The dependent variables were analyzed: total antioxidant capacity (TAC) using ABTS method, total polyphenols (TP), ascorbic acid and sensory acceptance. The independent variables were the concentrations of fruit pulp (%). For evaluate the in vivo assays were used two formulations of optimized mixed tropical fruit: The formulation (mixed tropical acerola juice, pineapple, acai, cashew, yellow mombin and camu-camu) and formulation B (mixed tropical acerola juice, pineapple, acai and yellow mombin), with different pulp proportions (%) and weaned rats that were divided in 7 groups: control (water), six groups of animals treated by gavage in water to reconstitute lyophilized juice formulations at concentrations of 100, 200 or 400mg/kg for 30 days. The followed analyzes were performed: The nutritional indices of feed intake and weight gain; biochemical analyzes of glucose, triglycerides, total cholesterol, HDL (High Density Lipoprotein), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum lipid peroxidation and liver method TBARS (thiobarbituric acid reactive substances) and activities of antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in erythrocytes and liver. Concerning to the statistical planning and MSR, camu-camu, acerola and acai were the main factors that influenced the antioxidant potential of the juice, and yellow mombin showed a positive effect on sensory acceptability of tropical juice. There was an antagonistic effect between acerola and camu-camu in regarding to TAC. The optimal formulation was composed of 20% acerola, 10% camu-camu, 10% yellow mombin, 10% cashew and 10% acai, which corresponding a result of 155,46 mg.100g-1 ascorbic acid, 103,01 mg GAE. 100 g-1 TP, 10,27 µM Trolox g-1 for TAC and sensory acceptance of approximately 6.1. The groups treated with the formulations of mixed juices showed no statistical significant difference in relation to nutritional indices and biochemical parameters, including the activity of the enzymes ALT and AST, indicating that the formulations did not cause liver damage these animals. The results showed that the SOD activity and CAT in the liver (FA200) and GSH-Px in erythrocytes (FB400) and in serum and liver TBARS (FB100, FA400, FB200, FB400) were efficiently reduced in the groups treated with the fruit juices, when compared with the control group, while HDL-c increased (FB400). In conclusion, daily consumption of 200mL of optimized formulation is responsible for approximately 50% of the recommended amount of antioxidants in the Mediterranean diet pattern, therefore, a rich source for these bioactive compounds. The results of in vitro and in vivo studies suggest that consumption of tropical juices mixed evaluated was effective in endogenous antioxidant defense, and effectively suggest that the tropical fruit juices may have significant relevance to the health beneficial effects.
O objetivo desta pesquisa foi desenvolver formulações de sucos tropicais mistos, baseando-se em dados da Dieta Mediterrânea (DM), utilizando ferramentas de otimização de processos, para avaliar e quantificar possíveis efeitos aditivo, sinergístico e antagônico entre as variáveis, e avaliar o perfil funcional in vitro e in vivo dos sucos. Foi utilizado um planejamento estatístico do tipo fracionado para seleção das variáveis (P<0,10), seguido de um delineamento composto central rotacional (DCCR) 25 com P<0,05. As variáveis independentes foram às concentrações das polpas de frutas (%) das seis espécies de frutas tropicais (camu-camu, acerola, caju, cajá, açaí e manga) e como variáveis dependentes a capacidade antioxidante total (TAC) através do método ABTS, polifenóis totais (TP), ácido ascórbico e aceitação sensorial. Para os ensaios in vivo foram utilizadas duas formulações de suco tropical misto: formulação A (suco tropical misto de acerola, abacaxi, açaí, caju, cajá e camu-camu) e formulação B (suco tropical misto de acerola, abacaxi, açaí e cajá), com suas diferentes porcentagens de polpa (%). Ratos machos da linhagem Wistar, recém-desmamados foram distribuídos em 7 grupos, sendo controle (água), e seis grupos de animais tratados por gavagem com a reconstituição em água das formulações dos sucos liofilizadas nas concentrações: 100, 200 ou 400mg/kg de peso corpóreo, durante 30 dias. Foram avaliados os índices nutricionais de consumo de ração e ganho de peso; análises bioquímicas: glicose, triglicerídeos, colesterol total, HDL (High Density Lipoprotein), alanina aminotransferase (ALT) e aspartato aminotransferase (AST); peroxidação lipídica do soro e fígado, pelo método TBARS (substâncias reativas ao ácido tiobarbitúrico) e atividade das enzimas antioxidantes, catalase (CAT), superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px), nos eritrócitos, e fígado. A partir da análise dos planejamentos estatísticos, o camu-camu, a acerola e o açaí foram os principais fatores que influenciaram o potencial antioxidante das formulações, e o cajá mostrou um efeito positivo sobre a aceitação sensorial dos sucos tropicais. Observou-se um efeito antagônico entre acerola e camu-camu para a resposta TAC. A formulação otimizada foi composta por 20% acerola, 10% de camu-camu, 10% de cajá, 10% caju e 10% de açaí, que correspondeu a um resultado de 155,46 mg.100 g-1 de ácido ascórbico, 103,01 mg de GAE.100 g-1 para TP, 10,27 µM Trolox g-1 para TAC e aproximadamente 6,1 de aceitação sensorial. Os grupos tratados com as formulações de sucos mistos não apresentaram diferença significativa em relação aos índices nutricionais e parâmetros bioquímicos, incluindo a atividade das enzimas ALT e AST, indicando que as formulações não ocasionaram danos hepáticos aos animais. Os resultados demonstraram que a atividade das enzimas SOD e CAT no fígado (FA200), e GSH-Px nos eritrócitos (FB400), e TBARS no soro e fígado (FB100, FA400, FB200, FB400) foi significantemente reduzida nos grupos tratados com os sucos de frutas, quando comparados com o grupo controle, enquanto que o HDL-c aumentou (FB400). Os resultados in vitro e in vivo sugerem que o consumo dos sucos tropicais mistos desenvolvidos neste trabalho foi eficaz na defesa antioxidante endógena, sugerindo efetivamente que os sucos de frutas tropicais podem ter significativa relevância para efeitos benéficos a saúde.
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Khalafalla, Reda El-Bastaweisy Ibrahim. "Evaluation of inhibition of Eimeria tenella sporozoites by antibody fragments expressed in pea." Doctoral thesis, Universitätsbibliothek Leipzig, 2009. http://nbn-resolving.de/urn:nbn:de:bsz:15-20091214-113404-9.
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Coccidiosis in chicken causes great economic losses. Increasing resistance of Eimeria species to anticoccidials has forced the search for alternative methods of control. The present study evaluates the anticoccidial activity of some anti-Eimeria tenella antibody fragments expressed in pea plants. Both in vitro and in vivo infection assays including indirect immunofluorescence, in vivo evaluation of antibody neutralization and cell culture invasion-inhibition assays were used to study the inhibitory effect of these antibody fragments on E. tenella sporozoites. Seven of nine antibody fragments (Ab1, Ab4, Ab5, Ab6, Ab7, Ab8 and Ab9) showed binding to sporozoites of E. tenella in an indirect immunofluorescence test. Only two antibodies (Ab4 and Ab5) cross reacted with sporozoites of E. maxima, E. acervulina and E. brunetti. The localization of specific fluorescence differed between species. Ab binding with sporozoites was seen in the area of both anterior and posterior refractile bodies in case of E. tenella, E. brunetti, and E. maxima but was only observed in the posterior refractile body in case of E. acervulina. No antibody binding was observed on merozoites. The suitability of antibody fragments to alter the infectivity of E. tenella sporozoites to Madin Darby Bovine Kidney cells (MDBK) was examined in vitro and the invasion-inhibition rates were quantified by flow cytometry. To assess the inhibitory effect on parasite reproduction, the in vivo antibody neutralization assay was done by retrograde infection of chicken with sporozoites previously incubated with antibody fragments. In vitro invasion rates were reduced by incubation with antibody fragments by approximately 24 to 45 %, with Ab6 and Ab7 showing the most distinct effect. However, proliferation rates (PR) of the respective MDBK cultures were also clearly reduced by 15 to 26 %. PR of MDBK cells treated with 1:1000, 1:100, 1:10 and undiluted mixed antibody fragments were reduced by 1%, 10%, 16%, and 26% with a reduction of invasion rates by 0%, 9%, 15% and 18%, respectively. Immune sera reduced the invasion rates by 16% to 70% and increased PR of the host cells. It appeared that the preparations of the antibody fragments contained compounds cytotoxic to MDBK cells and thus invasion inhibition could not be unequivocally evaluated in vitro. However, after incubation with antibody fragments sporozoites displayed a reduced ability to reproduce after intracloacal application to chicken (especially Ab1, Ab3, Ab5 and Ab9). Other antibody fragments (Ab2, Ab4, Ab6, Ab7 and Ab8) were less capable to reduce sporozoite infectivity and reproduction. More investigations are still required to study the possible use of antibody fragments and their application to infected chicken exposed to coccidiosis.
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Silva, Rangel Moreira. "Avaliação do potencial genotóxico e antigenotóxico da fração aquosa e do isolado pedunculagina da semente de Myrciaria cauliflora (Mart) O. Berg em sistemas in vivo." Universidade Federal de Goiás, 2016. http://repositorio.bc.ufg.br/tede/handle/tede/6817.
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Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG
Myrciaria cauliflora (Mart), commonly known as “Jabuticaba” (Brazilian Grape) occurs in all of South America, especially in Brazil. This species presents medicinal properties and it is popularly used to treat diarrhea and respiratory diseases. It has already been proven several biological activities such as antioxidant, antimutagenic and anti-proliferative. The phytochemical analysis of M. cauliflora detected the presence of several compounds, including the ellagitannin pedunculagin. Due to the widespread use of this species for therapeutic and food purposes, this study aimed to evaluate the genotoxic, antigenotoxic, cytotoxic and anticytotoxic actions of the aqueous fraction (AF) and pedunculagin from M. cauliflora seed, by micronucleus (MN) test and the comet assay in mice bone marrow cells. In order to analyze AF and pedunculagin activities prior to CP’s toxic effects, the animals were co-, pre- and post-treated with these substances. The results showed that AF at 24 h treatment did not show genotoxic or cytotoxic effects in the MN test and comet assay. However, AF showed cytotoxic action, but did not show genotoxic effect at 120 h treatment in the MN test. In the comet assay it was able to significantly reduce the frequency of DNA breaks when compared to the negative control. In the evaluation of the antigenotoxic and anticytotoxic effects, it was observed that in all treatments, in both assays, AF and pedunculagin showed antigenotoxic and anticytotoxic activities, but in the post-treatment pedunculagin increased the cytotoxic effect of CP. In general, our results indicated that AF and pedunculagin were able to protect the mice bone marrow cells against DNA damage induced by CP in the MN test and comet assay. These findings indicated that AF and pedunculagin could be probable candidates for the development of new drugs.
Myrciaria cauliflora (Mart), comumente conhecida como jabuticaba, ocorre em toda América do Sul e especialmente no Brasil. Esta espécie apresenta propriedades medicinais e é popularmente usada para tratar diarreia e doenças respiratórias. A essa espécie já foram atribuídas várias atividades biológicas, tais como: antioxidante, antimutagênica e antiproliferativa. A análise fitoquímica de M. cauliflora detectou a presença de vários compostos, incluindo o elagitanino pedunculagina. Devido ao grande uso desta espécie para fins terapêuticos e alimentícios, este estudo teve como objetivo avaliar as ações genotóxica, antigenotóxica, citotóxica e anticitotóxica da fração aquosa (FA) e do composto pedunculagina da semente de M. cauliflora pelo teste do micronúcleo e ensaio do cometa em células da medula óssea de camundongos. A fim de avaliar a atividade da FA e da pedunculagina frente aos efeitos genotóxicos da CP, os animais foram co, pré e pós-tratados com essas substâncias. Os resultados mostraram que a FA no tempo de 24 horas não apresentou efeitos genotóxico e citotóxico no teste do micronúcleo e no ensaio do cometa. No tempo de 120 horas, pelo teste do micronúcleo, a FA não mostrou ação genotóxica, porém exibiu efeito citotóxico e pelo ensaio do cometa, a frequência de quebras de DNA foi menor, quando comparada ao controle negativo. Na avaliação dos efeitos da antigenotoxicidade e anticitotoxicidade, em ambos os ensaios, a FA e a pedunculagina mostraram atividades antigenotóxica e anticitotóxica, porém, no pós-tratamento, o composto pedunculagina potencializou o efeito citotóxico da CP. De modo geral, nossos resultados indicaram que a FA e a pedunculagina foram capazes de proteger as células da medula óssea de camundongos contra os danos no DNA induzidos pela CP no teste do micronúcleo e no ensaio do cometa. Esses resultados indicaram que a FA e a pedunculagina podem ser prováveis candidatos para o desenvolvimento de novas drogas.
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Gadea, Mateos Joaquín. "Predicción de la fertilidad "in vivo" de los eyaculados de verraco mediante parámetros rutinarios de contrastación seminal, pruebas bioquímicas y el test homólogo de penetración "in vitro"." Doctoral thesis, Universidad de Murcia, 1997. http://hdl.handle.net/10803/10852.
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El objetivo del presente estudio ha sido evaluar la relación entre los parámetros de la calidad seminal y la capacidad de penetración in vitro de ovocitos homólogos (PIVh) con los resultados in vivo de fertilidad y prolificidad.Se han analizado 60 eyaculados realizando sobre cada uno las medicionesclásicas del espermiograma (motilidad, calidad de movimiento, volumen, concentración espermática, estado del acrosoma, morfoanomalías y tinción vital), pruebas bioquímicas (contenido de ATP, calcio, sodio, potasio, magnesio y zinc), ensayos de la funcionalidad del espermatozoide ( test de endósmosis, test del diacetato de carboxifluoresceína, test ORT) y la valoración mediante un test de penetración in vitro homóloga. Los resultados de la valoración in vitro del semen fueron contrastados con los resultados obtenidos en un ensayo in vivo con inseminaciones homospérmicas.En nuestras condiciones experimentales el estudio de los parámetros demotilidad, morfología, acrosomas y de los test de funcionalidad de la membrana puedeser una herramienta útil, en un primer término, para desechar eyaculados de baja calidad, aunque estas técnicas no alcanzan la sensibilidad suficiente para dar un resultado satisfactorio en la predicción de la fertilidad. Sin embargo, los resultados obtenidos muestran que el test de penetración in vitro es la única técnica de las estudiadas capaz de discriminar adecuadamente los eyaculados que darán lugar a los distintos grupos de fertilidad.The purpose of the present study was to evaluate the relationship between theparameters of seminal quality and homologous oocytes in vitro penetration capacityversus the reproductive parameters, fertility and litter size which were bothdetermined in a field trial.Sixty boar ejaculates have been analysed, performing on each of them:conventional semen analysis (motility, volume, sperm concentration, normal acrosome, morphology and structural integrity), biochemical parameters (ATP, calcium, sodium, potassium, magnesium and zinc), functional sperm assays (Hypoosmotic swelling test (HOST), Carboxiflorescin Diacetate Test (DCF), Osmotic Resistance Test (ORT)) and the homologous in vitro penetration test. The results observed upon a in vitro semen valoration were checked with those obtained upon a in vivo trial with homospermic insemination.In our experimental conditions the study of motility, morphology, normalacrosomes and functional test may be a good tool, in a first analysis, to get rid of poor seminal quality ejaculates. Still, this analysis is not accurate enough to bring outsatisfactory results to predict the in vivo fertilization capacity. In the light of theseresults only the homologous in vitro penetration test has been found able todiscriminate the different groups of fertility and litter size. None the less an extensive study is required.
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Kaewthai, Nomchit. "In vitro and in vivo approaches in the characterization of XTH gene products." Doctoral thesis, KTH, Glykovetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-28222.
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ABSTRACT The xyloglucan endo-transglycosylase/hydrolase (XTH) genes are found in all vascular and some nonvascular plants. The XTH genes encode proteins which comprise a subfamily of glycoside hydrolase (GH) family 16 in the Carbohydrate-Active enZYmes (CAZY) classification. The XTH gene products are believed to play intrinsic role in cell wall modification during growth and development throughout the lifetime of the plant. In the present investigation, biochemical and reverse genetic approaches were used to better understand the functions of individual members of the XTH gene family of two important plants: the model organism Arabidopsis thaliana and the grain crop barley (Hordeum vulgare). A phylogenetic tree of the xyloglucan-active enzymes of GH16 has previously been constructed, where enzymes with similar activities have been shown to cluster together. Several members of phylogenetic Group I/II and III-B, predicted to exhibit xyloglucan endo-transglycosylase activity (EC 2.4.1.207) and members of Group III-A, predicted to exhibit xyloglucan endo-hydrolase activity (EC 3.2.1.151), were included to analyze the functional diversity of XTH gene products. A heterologous expression system using the yeast Pichia pastoris was found to be effective for recombinant protein production with a success rate of ca. 50%. XTH gene products were obtained in soluble and active forms for subsequent biochemical characterization. In order to be able to screen larger numbers of protein producing clones, a fast and easy method is required to identify clones expressing active protein in high enough amounts. Thus, a miniaturized XET/XEH assay for high-throughput analysis was developed, which was able to identify activities with good precision and with a reduced time and materials consumption and a reduced work load. Enzyme kinetic analysis indicated that the XET or XEH activity of all XTH gene products characterized in the present study corresponded to predictions based on the previously revised phylogenetic clustering. To gain insight into the biological function of the predominant XEHs AtXTH31 and AtXTH32, which are highly expressed in rapidly developing tissues, a reverse genetic approach was employed using T-DNA insertion lines of the A. thaliana Columbia ecotype. Genotypic and phenotypic characterization, together with in situ assays of XET and XEH activities, in single- and double-knock-out mutants indicated that these Group III-A enzymes are active in expanding tissues of the A. thaliana roots and hypocotyl. Although suppression of in muro XEH activity was clearly observed in the double-knock-out, no significant growth phenotype was observed, with the exception that radicle emergence appeared to be faster than in the wild type plants. Keywords: Arabidopis thaliana, Hordeum vulgare, plant cell wall, xyloglucan, glycoside hydrolase family 16, xyloglucan endo-transglycosylase/hydrolase gene family, xyloglucan endo-transglycosylase, xyloglucan endo-hydrolase, heterologous protein expression, Pichia pastoris, T-DNA insertion, in situ XET/XEH assay, high-throughput screeningQC 20110114
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Silva, Carolina Ribeiro e. "Genética toxicológica da chalcona sulfonamida (CPN): evidências de genoto-xicidade e antimutagenicidade em diferentes sistemas-teste in vivo e in vitro." Universidade Federal de Goiás, 2015. http://repositorio.bc.ufg.br/tede/handle/tede/5596.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In the present study, we investigated the biological effects of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) through bioindicators of genetic damage in bacteria, animal and human. In the Ames Mutagenicity Test, CPN did not significantly increase the number of His+ revertants in Salmonella typhimurium tester strains TA98 and TA100 at all doses tested (p > 0.05). However, CPN presented a moderate mutagenic and toxic profile, due to dose-response relationship observed at all doses tested for TA98 and TA100 strains. In the antimutagenic evaluation of Ames Test, CPN presented antimutagenic activity at all doses tested in TA98 strain (p < 0.05). In the TA100 strain, CPN showed antimutagenic activity in doses over 50 μg/plate. In the Micronucleus Test, the results demonstrated that CPN increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, at all doses tested, demonstrating mutagenic effect of this compound. A decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at 24 h and 48 h, indicating the cytotoxic action of CPN. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at all doses tested in 24 h, demonstrating antimutagenic action (p < 0.05). Also, there was a decrease in the frequency of MNPCE at all tested doses in 48 h, but this decrease was not significant (p > 0.05). Additionally, CPN co-administered with MMC increased PCE/NCE ratio at all doses tested, in both times, demonstrating its anticytotoxic effect. In the Comet Assay, CPN significantly increased the percentage of DNA damages at all doses tested (p < 0.05), demonstrating genotoxic activity. In the analysis of cell cycle kinetics, CPN did not induce significant changes in the cell cycle phases G0/G1, S and G2/M of peripheral blood mononuclear cells (PBMC) (p > 0.05). However, doses of 256 and 512 μmol/L of the CPN presented a significant increase in the percentage of cells in sub-G1 (p < 0.05), which is indicative of apoptosis, indicating cytotoxic action. For apoptosis and necrosis detection using Annexin V/Propidium Iodide stain, CPN showed a cytotoxic effect by inducing late apoptosis and necrosis. Thus, according to tests performed CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities.
Derivados de chalcona sulfonamida tem apresentado importantes atividades biológicas, incluindo atividade antitumoral. No presente estudo, investigou-se os efeitos biológicos da chalcona sulfonamida N-{4-[3-(4-nitrofenil)prop-2-enoil]fenil}-benzenosulfonamida (CPN) mediante a análise de bioindicadores de danos genéticos em sistemas-teste bacteriano, animal e humano. No Teste de Mutagenicidade de Ames, CPN não aumentou significativamente o número de revertentes prototróficas de Salmonella typhimurium, em nenhuma das cepas testadas, TA98 e TA100, em nenhuma das doses (p > 0,05). Entretanto, CPN apresentou um perfil moderado de um composto mutagênico e tóxico, devido à relação dose-resposta observada em todas as doses testadas, para as cepas TA98 e TA100. Na avaliação antimutagênica do Teste de Ames, CPN apresentou atividade antimutagênica para todas as doses testadas na cepa TA98 (p < 0,05). Na cepa TA100, CPN mostrou atividade antimutagênica nas doses acima de 50 μg/placa (p < 0,05). Os resultados do Teste do Micronúcleo demonstraram que CPN aumentou a frequência de eritrócitos policromáticos micronucleados (EPCMN) no tempo de 24 e 48 h, em todas as doses testadas, demonstrando efeito mutagênico deste composto. Uma diminuição na razão de eritrócitos policromáticos/normocromáticos (EPC/ENC) foi observada no tempo de 24 e 48 h, indicando ação citotóxica de CPN. CPN co-administrado com mitomicina C (MMC) diminuiu significativamente a freqüência de EPCMN em todas as doses testadas no tempo de 24 h, demonstrando ação antimutagênica (p < 0,05). Houve também uma diminuição na frequência de EPCMN em todas as doses testadas, no tempo de 48 h, mas a diminuição não foi significativa (p > 0,05). Além disso, CPN co-administrado com MMC aumentou a razão de EPC/ENC em todas as doses testadas, nos tempos de 24 e 48 h, demonstrando efeito anticitotóxico. No Ensaio Cometa, CPN aumentou significativamente a porcentagem de danos no DNA em todas as doses testadas (p < 0,05), demonstrando atividade genotóxica. Na análise da Cinética do Ciclo Celular, CPN não induziu alteração significativa nas fases G0/G1, S e G2/M do ciclo celular de células mononucleares do sangue periférico (PBMC) (p > 0,05). Entretanto, as doses de 256 e 512 μmol/L de CPN apresentaram um aumento significativo na porcentagem de células em sub-G1 (p < 0,05), o qual é um indicativo de apoptose, demonstrando ação citotóxica. Na detecção de apoptose e necrose por coloração com Anexina V/Iodeto de Propídeo, CPN mostrou um efeito citotóxico, pela indução de apoptose tardia e necrose. Assim, de acordo com os ensaios realizados CPN apresentou atividades genotóxica, citotóxica, antigenotóxica e anticitotóxica.
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Berglund, Åke. "Optimisation of Chemotherapy Treatment in Advanced Colorectal Cancer." Doctoral thesis, Uppsala University, Department of Oncology, Radiology and Clinical Immunology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2609.
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Colorectal cancer is one of the most common malignant diseases in Sweden – more than 5000 new cases are diagnosed each year. The overall five-year survival is about 60% and in cases of recurrence the prognosis is poor.
In a phase III study in advanced colorectal cancer the response rate was doubled when 5-FU was given as a bolus injection versus as a short infusion. The toxicity was similar and time to progression was longer in the injection group. However, overall survival was not significantly different. Dose-effect relationships of 5-FU were studied in another phase III study recruiting 312 patients. A decrease from 500 mg/m2 to 400 mg/m2 worsened the treatment results. A low incidence of severe toxicity was seen in both groups. An increase to 600 mg/m2 worsened the toxicity without any improvement of the results.
A cytotoxic drug sensitivity test in different tumour types, mainly gastrointestinal cancer, poorly predicted treatment outcome in a phase II study.
The conventional Nordic Flv regimen was split in a phase I/II trial. An escalation of dose was possible and the response rate was 20%.
Thymidylate synthase (TS) and the gene expression of p53 were investigated by immunohistochemical technique in the primary tumours of 132 patients. None of the markers predicted the later palliative chemotherapy result. However, TS significantly predicted time to recurrence.
Serum markers were analysed before and during FLv treatment to early predict outcomes among 87 patients. TPS is promising, both as a predictive marker before start of treatment and after a short period of treatment. In the same setting, CEA had lower predictive value. S-VEGF and S-bFGF did not yield any prognostic information of later outcome. In all studies B-haemoglobin values, performance status and subjective response were strong markers, both for prediction of objective response and for survival.
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Ribeiro, Juliana Carvalho. "Avaliação do potencial mutagênico e antimutagênico da polpa de açaí (Euterpe olereacea Mart) e do óleo de buriti (Mauritia flexuosa) in vivo." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-29032012-083303/.
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Os corantes são amplamente usados como aditivos na indústria alimentícia. Atualmente, diversas pesquisas têm demonstrado que alguns corantes de origem natural, como por exemplo, polifenóis, antocianinas, carotenóides, dentre outros, são dotados de efeitos benéficos, atuando como promotores da saúde, o que desperta o interesse na produção de alimentos com propriedades funcionais. A polpa de açaí é rica em pigmentos polifenóis e antocianinas, e o óleo de buriti é a maior fonte de - caroteno já identificada em frutos até o momento. No entanto, ainda existem poucos estudos evidenciando os seus efeitos bioativos. O objetivo deste estudo foi avaliar o potencial mutagênico e antimutagênico da polpa de açaí e do óleo de buriti, frente aos danos ao DNA induzidos pelo antitumoral doxorrubicina (DXR), em diferentes tecidos de camundongos Swiss. As metodologias envolvem o teste do micronúcleo em células da medula óssea e em sangue periférico e o ensaio do cometa em células sanguíneas, renais e hepáticas em dois diferentes protocolos de tratamento, sendo um agudo (gavagem e eutanásia após 24 horas) e um sub-agudo (gavagem por 14 dias e eutanásia 24 horas após a última gavagem). Em cada protocolo de tratamento, foram testadas 3 doses diferentes da polpa de açaí (3,33; 10,00 e 16,67g/kg p.c.), usando 8 grupos experimentais (n=6). Seguindo o mesmo delineamento experimental, para cada protocolo de tratamentnoto foram testadas 3 doses do óleo de buriti (100; 200 e 300 mg/Kg p.c.), diluído em óleo de milho, em 10 grupos experimentais (n=6). A DXR (16 mg/kg p.c.; i.p.) foi usada como controle positivo nos testes de antimutagenicidade. Nos ensaios com a polpa de açaí e com o óleo de buriti, em ambos os tratamentos, não houve diferença estatística significativa (p<0,05) entre os grupos tratados apenas com a polpa e o controle negativo, demonstrando ausência de efeitos genotóxicos e mutagênicos. Os tratamentos com as associações de polpa de açaí e DXR mostraram redução significativa (p<0,05) de danos ao DNA induzidos pela DXR em todos os órgão testados, no teste do micronúcleo e no ensaio do cometa, e o tratamento subagudo demonstrou ter sido mais efetivo na inibição da genotoxicidade induzida pela DXR. O óleo de buriti mostrou atividade antimutagênica significativa (p<0,05) em células sanguíneas, no tratamento agudo e no tratamento sub-agudo. No entanto, nota-se que o óleo de milho, usado como solvente nos experimentos com o óleo de buriti interferiu nos resuldados encontrados. A identificação e caracterização de pigmentos naturais polifenóis e antocianinas na polpa de açaí e carotenóides, tocoferóis e compostos fenólicos no óleo de buriti, mencionados na literatura como antimutagênicos e antigenotóxicos, pode justificar os resultados encontrados. Os efeitos antimutagênicos detectados na polpa de açaí e no óleo de buriti encorajam novos estudos, visto que estes podem ter seu uso amplamente explorado na indústria cosmética e farmacêutica, em ações de benefícios à saúde da população e, também na indústria alimentícia, no desenvolvimento de produtos com propriedades funcionais.The dyes are widely used as additives in the food industry. Currently, several studies have shown that some dyes from natural sources, such as polyphenols, anthocyanins, carotenoids, among others, are endowed with beneficial effects, acting as health promoters, which raises the interest in the production of foods with functional properties. The açai is rich in polyphenols and anthocyanins pigments, and the buriti oil is the largest source of -carotene in fruit that has been identified so far. However, there are few studies showing the bioactive effects. The aim of this study was to evaluate the mutagenic and antimutagenic proprieties of the açai pulp and buriti oil, compared to DNA damage induced by the antitumoral doxorubicin (DXR) in different tissues of Swiss mice. The methods involve the micronucleus test in bone marrow and peripheral blood and the comet assay in blood cells, liver and kidney in two different treatment protocols, an acute (gavage and euthanized after 24 hours) and a sub-acute treatment (gavage for 14 days and euthanized 24 hours after the last gavage).In each treatment protocol, we tested three different doses of açai pulp (3.33, 10.00 and 16.67 g/kg b.w.), using eight experimental groups (n=6). Following the same experimental design for each protocol were tested three doses trataments of buriti oil (100, 200 and 300 mg/kg b.w.), diluted in corn oil, in 10 experimental groups (n = 6). The DXR (16 mg/kg b.w., ip) was used as positive control in the antimutagenicity tests. In tests with the pulp and buriti oil in both treatments, there was no statistically significant difference (p<0.05) between groups treated with pulp and negative control, demonstrating a lack of genotoxic and mutagenic . The treatments with associations of açai pulp and DXR showed a significant reduction (p<0.05) in the DNA damages induced by DXR in all organs tested, in the micronucleus test and comet assay, and subacute treatment showed have been more effective in inhibiting the genotoxicity induced by DXR. Buriti oil showed antimutagenic activity (p<0.05) in blood cells, to treat acute and subacute treatment. However, note that the corn oil used as solvent in experiments with buriti oil resuIts interfere in matches. The identification and characterization of natural pigments, polyphenols and anthocyanins in the açai pulp and carotenoids, tocopherols and phenolic compounds in the buriti oil, mentioned in the literature as antimutagenic and antigenotoxicity, can justify the results. The antimutagenic effects found in açai pulp and buriti oil encourage further studies, since they may have fully explored its use in cosmetic and pharmaceutical industry, in shares of health benefits to the population and also in the food industry in developing of products with functional properties.
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Phillips, Roger. "The predictive value of in vitro chemosensitivity tests of anticancer drugs : in vitro chemosensitivity of a panel of murine colon tumours determined by a colony forming assay at drug exposure parameters measured in vivo." Thesis, University of Bradford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329305.
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