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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
151

Inibi??o dos efeitos locais induzidos pelas pe?onhas das serpentes Bothrops erythromelas e Bothrops jararaca pelo extrato aquoso das folhas de Jatropha mollissima (Pohl) Bail

Gomes, Jacyra Antunes dos Santos 27 March 2015 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-25T20:53:39Z No. of bitstreams: 1 JacyraAntunesDosSantosGomes_DISSERT.pdf: 2709008 bytes, checksum: b8536d693075ca072ab23c36cf351557 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-02T20:59:13Z (GMT) No. of bitstreams: 1 JacyraAntunesDosSantosGomes_DISSERT.pdf: 2709008 bytes, checksum: b8536d693075ca072ab23c36cf351557 (MD5) / Made available in DSpace on 2016-08-02T20:59:13Z (GMT). No. of bitstreams: 1 JacyraAntunesDosSantosGomes_DISSERT.pdf: 2709008 bytes, checksum: b8536d693075ca072ab23c36cf351557 (MD5) Previous issue date: 2015-03-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Os acidentes of?dicos representam um s?rio problema em sa?de p?blica nos pa?ses tropicais e subtropicais, sendo o g?nero Bothrops o maior respons?vel pelos acidentes no Brasil e em toda a Am?rica Latina (correspondendo cerca de 90 % dos casos). Os efeitos locais (dor, edema, hemorragia e necrose tecidual) e sist?micos (altera??es cardiovasculares, choque e dist?rbios da coagula??o sangu?nea) causados pela pe?onha das serpentes do g?nero Bothrops s?o devido aos in?meros componentes prot?icos e n?o-prot?icos (carboidratos, lip?dios, nucleot?deos, aminas biog?nicas e v?rios ?ons), que fazem parte da constitui??o da pe?onha. A ?nica forma de terapia cientificamente validada ? a soroterapia antiveneno, que, no entanto, n?o ? eficaz com rela??o aos efeitos locais produzidos e, al?m disso, pode ocasionar s?rias rea??es de hipersensibilidade aos pacientes. Sendo assim, a busca por novas alternativas ? soroterapia se faz importante, e nesse contexto, muitas plantas medicinais v?m se destacando pelo uso popular como antiof?dicas. Dentre essas plantas, pode-se citar a esp?cie Jatropha mollissima (Euphorbiaceae) que apresenta amplo uso popular na medicina tradicional como antiof?dica, anti-inflamat?ria, antimicrobiana e antit?rmica. Portanto, esse trabalho tem como objetivo a avalia??o do potencial neutralizante dos efeitos locais induzidos pelas pe?onhas de Bothrops erythromelas e Bothrops jararaca pelo extrato aquoso das folhas de J. mollissima. O extrato das folhas foi preparado por decoc??o, fracionado (por meio de parti??o l?quido-l?quido) e caracterizado por cromatografia em camada delgada (CCD) e Cromatografia L?quida de Alta Efici?ncia (CLAE). A atividade antiof?dica do extrato foi avaliada nos modelos de edema de pata, peritonite, hemorragia e miotoxicidade induzidos pelas pe?onhas de B. erythromelas e B. jararaca sendo utilizados camundongos Swiss de ambos os sexos. Em todos os modelos o extrato foi avaliado pela via intraperitoneal nas doses de 50, 100 e 200 mg/kg, sendo administrado 30 minutos antes da inje??o da pe?onha (protocolo de pr?-tratamento). Manchas sugestivas da presen?a dos flavon?ides: apigenina, luteolina, orientina, isoorientina, vitexina e vitexina-2-O-ramnos?deo foram detectadas no extrato atrav?s da co-CCD. Por meio de CLAE foram identificados os flavon?ides isoorientina, orientina, vitexina e isovitexina. Todas as doses testadas do extrato de J. mollissima reduziram o edema de pata induzido pelas pe?onhas com intensidade similar ? dexametasona. O extrato aquoso das folhas de J. mollissima, em todas as doses avaliadas, inibiu a migra??o celular induzida por B. erythromelas e B. jararaca promovendo a inibi??o do recrutamento tanto de c?lulas mononucleares quanto das c?lulas polimorfonucleares. A hemorragia local induzida pela pe?onha de B. jararaca foi inibida significativamente pelo extrato. Ambas as pe?onhas foram inibidas pelo extrato na atividade miot?xica. Esses resultados indicam que o extrato aquoso das folhas de J. mollissima apresenta potencial propriedade antiof?dica sobretudo com rela??o ao efeitos locais, o que poderia justificar o uso dessa planta na medicina tradicional e na terapia complementar como antiof?dica. / Snakebites are a serious public health problem in tropical and subtropical countries and Bothrops genus is responsible for the accidents in Brazil and throughout Latin America (90% of cases). The local effects (pain, edema, hemorrhage and myonecrosis) and systemic (cardiovascular alterations, shock and blood clotting disorders) caused by the venom of Bothrops are due to the numerous protein and non-protein components, which are part of the constitution of the poison. The only form of therapy is scientifically validated antivenom serum therapy which, however, is not effective with respect to local effects produced, risk of immunological reactions, high cost and difficult access in some regions. Thus, the search for new alternatives to serum therapy becomes important, and in this context, many medicinal plants have been highlighted by the popular use as antiophidic. Among these plants, we can mention the species Jatropha mollissima (Euphorbiaceae) which has popular use in traditional medicine as antiophidic, anti-inflammatory, antimicrobial and antipyretic. Therefore, this study aims to evaluate the neutralizing potential of local effects induced by the venom of Bothrops erythromelas and Bothrops jararaca with the aqueous extract of the leaves of J. mollissima. The leaf extracts were prepared by decoction, fractionated (by liquid-liquid partition) and characterized by thin layer chromatography (TLC) and High Performance Liquid Chromatography (HPLC). Antiophidic activity of the extract was evaluated in model of paw edema, peritonitis, bleeding and myotoxicity induced by venoms of B. jararaca and B. erythromelas. In all models, the extract was evaluated by intraperitoneal route at the doses of 50, 100 and 200 mg/kg, administered 30 minutes prior to injection of the venom (pretreatment protocol). Stains suggestive of the presence of flavonoids: apigenin, luteolin, orientin, isoorientin, vitexin and vitexin-2-O-rhamnoside were detected in the extract by co-CCD. By means of HPLC were identified isoorientin, orientin, vitexin and isovitexin. All tested doses of J. mollissima extract reduced the paw edema induced by the venom with intensity similar to dexamethasone. The aqueous extract of J. mollissima leaves on all evaluated doses, inhibited cell migration induced by B. jararaca and B. erythromelas promoting inhibition of recruitment of mononuclear cells and the polymorphonuclear cells. Local bleeding induced by B. jararaca venom was significantly inhibited by the extract. Both venoms were inhibited by the extract in myotoxic activity. These results indicate that the aqueous extract of J. mollissima leaves have snakebite potential, particularly with respect to local effects, which may justify the use of this plant in traditional medicine and complementary therapy as anti-venom serum.
152

Caracteriza??o t?rmica e desenvolvimento de m?todo anal?tico para determina??o simult?nea das guanilhidrazonas WE005, WE015 e WE016

Dantas, Monique Gomes 06 February 2015 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-10-26T20:21:40Z No. of bitstreams: 1 MoniqueGomesDantas_DISSERT.pdf: 3471537 bytes, checksum: a73f34ecbaa2b638849e2cfdb0b85408 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-12-20T18:08:05Z (GMT) No. of bitstreams: 1 MoniqueGomesDantas_DISSERT.pdf: 3471537 bytes, checksum: a73f34ecbaa2b638849e2cfdb0b85408 (MD5) / Made available in DSpace on 2016-12-20T18:08:05Z (GMT). No. of bitstreams: 1 MoniqueGomesDantas_DISSERT.pdf: 3471537 bytes, checksum: a73f34ecbaa2b638849e2cfdb0b85408 (MD5) Previous issue date: 2015-02-06 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Guanilhidrazonas s?o uma classe de subst?ncias amplamente estudadas por apresentar grande potencial biol?gico. A an?lise de f?rmacos e medicamentos ? ferramenta importante para garantir qualidade, seguran?a e efic?cia aos novos medicamentos. Nesse estudo foram avaliadas as guanilhidrazonas sint?ticas WE005 (3,4-dimetoxibenzalde?doguanilhidrazona), WE015 (benzalde?doguanilhidrazona) e WE016 (metil-4-formilbenzoatoguanilhidrazona) com o objetivo de caracterizar, desenvolver e validar m?todo anal?tico utilizando t?cnicas t?rmicas (DSC e TG), espectrosc?pica (FTIR), microsc?pica (MEV) e cromatogr?fica (CLUE/DAD). Na caracteriza??o por DSC e TG foram utilizadas as seguintes raz?es de aquecimento: 2,5; 5,0; 10 e 20 ?C/min em atmosfera de nitrog?nio (50 mL/min) at? 500?C (DSC) e 900?C (TG). A an?lise na regi?o do infravermelho m?dio das mol?culas foi realizada a temperatura ambiente e na faixa de fus?o. Os espectros foram comparados atrav?s da correla??o de Pearson utilizando o algoritmo ad hoc. O estudo cin?tico foi feito atrav?s do m?todo de Ozawa. O planejamento fatorial investigou a influ?ncia do comprimento da coluna, fluxo e propor??o de fase m?vel sobre o tempo de reten??o, fator de cauda, resolu??o e n?mero de pratos te?ricos. As t?cnicas t?rmicas foram capazes de caracterizar as mol?culas atrav?s de suas transi??es de fase e etapas na curva termogravim?trica, informando ainda sobre a estabilidade t?rmica, com temperatura inicial de decomposi??o em torno de 240 ?C. O estudo cin?tico mostrou que todas as mol?culas apresentam ordem zero e que a amostra WE016 apresentou maior energia de ativa??o. Os espectros de infravermelho de acordo com a correla??o de Pearson apresentaram mudan?as significativas entre a temperatura ambiente e o espectro da faixa de fus?o. O planejamento fatorial atrav?s dos gr?ficos de superf?cie-resposta e Pareto revelou que a vari?vel de maior influ?ncia sobre todas as vari?veis dependentes foi o comprimento da coluna. O melhor m?todo para a separa??o das guanilhidrazonas deste estudo foi: coluna C18 (50 mm x 2 mm t.p. 2.2 ?m), fase m?vel MeOH:H2O:TEA 40:60:0,1, pH 3,5 ajustado com ?cido ac?tico; fluxo de 0,2 mL/min, temperatura do forno 30 ?C. A concentra??o final das guanilhidrazonas foi de 30 ?g/mL e foram detectadas simultaneamente atrav?s do comprimento de onda de 290 nm. Um m?todo r?pido foi desenvolvido para separar as guanilhidrazonas WE005, WE015 E WE016 por CLUE/DAD. Planejamento fatorial foi uma ferramenta ?til para o desenvolvimento racional do m?todo. / Guanilhidrazonas substances are widely studied for presenting great biological potential, especially antitumor activity, antimicrobial, antimalarial, antifungal and anti-hypertensive. This study assessed the synthetic guanylhydrazones WE005 ((2-[(3,4-dimethoxyphenyl)methylene]-hydrazinecarboximidamide),WE015 (2(phenylmethylene)-hydrazinecarboximidamide) and WE016 (4-[[2-(aminoiminomethyl) hydrazinylidene]methyl]-benzoic acid methyl ester) in order to characterize and develop analytical method using thermal techniques (DSC and TGA), spectroscopic (FTIR ) and microscopic (SEM) and chromatographic (UHPLC / DAD). The characterization by DSC and TG were used the following heating rates: 2.5; 5.0; 10 and 20 ? C / min in a nitrogen atmosphere (50 ml / min) to 500 ? C (DSC) and 900 ? C (TG). The kinetic study was done by Ozawa method. The analysis in the mid-infrared region of molecules was performed at room temperature and the melting temperature. The spectra were compared using Pearson's correlation using ad hoc algorithm. For the development of the analytical method was used factorial design. Thermal techniques have been able to characterize the molecules through their phase transitions and steps in the thermogravimetric curve, and telling about the thermal stability, with an initial decomposition temperature of about 240 ? C. The kinetic study showed that the speed of the thermal decomposition of molecules has zero order and that the WE016 sample showed higher activation energy. Infrared spectra according to the Pearson correlation showed significant changes between the room temperature and the melting range of the spectrum. The factorial design through surface-response graphs and Pareto showed that the most influential variable on all dependent variables was the length of the column. The best method for the separation of guanylhydrazones this study was: C18 column (50 mm x 2 mm tp 2.2 microns), mobile phase MeOH: H2 O: TEA 40: 60: 0.1, pH 3.5 adjusted with acetic acid; flow rate of 0.2 ml / min, oven temperature 30 ? C. The final concentration of guanylhydrazones was 30 mg / mL and were detected simultaneously by a wavelength of 290 nm. A rapid method was developed to separate guanylhydrazones WE005, WE015 and WE016 by CLUE / DAD. Factorial design was a useful tool for the rational development of the method.
153

Associa??o dos polimorfismos do tipo INDEL com o risco de c?ncer colorretal na popula??o do Rio Grande do Norte

Santos, Diego Marques da Costa 30 August 2016 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-20T21:49:24Z No. of bitstreams: 1 DiegoMarquesDaCostaSantos_DISSERT.pdf: 2551094 bytes, checksum: 6ba7eac7b523f238609d30d5347a6556 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-23T18:43:14Z (GMT) No. of bitstreams: 1 DiegoMarquesDaCostaSantos_DISSERT.pdf: 2551094 bytes, checksum: 6ba7eac7b523f238609d30d5347a6556 (MD5) / Made available in DSpace on 2017-03-23T18:43:15Z (GMT). No. of bitstreams: 1 DiegoMarquesDaCostaSantos_DISSERT.pdf: 2551094 bytes, checksum: 6ba7eac7b523f238609d30d5347a6556 (MD5) Previous issue date: 2016-08-30 / O c?ncer colorretal (CCR) ? um tipo de c?ncer que acomete a regi?o do intestino grosso e reto; sendo o terceiro c?ncer mais comum em homens e o segundo em mulheres no mundo. A maior parte da susceptibilidade ao CCR ? proveniente de variantes gen?ticas m?ltiplas, cada uma com um efeito individual que, quando combinada, causa a diversidade de risco para o desenvolvimento desse c?ncer. Dentre os tipos de muta??es encontrados no genoma humano, as inser??es e dele??es (INDEL) s?o a segunda classe mais comum; e o entendimento deste tipo de muta??o possui um potencial de impactar na express?o, na estrutura e at? mesmo fun??o da prote?na. Entretanto, sabe-se relativamente pouco sobre o impacto das INDEL no risco de CCR, especialmente na popula??o miscigenada do Brasil. Dessa forma o objetivo deste trabalho ? realizar um estudo do tipo caso-controle para determinar a associa??o de 16 INDEL com a susceptibilidade ao CCR na popula??o do Rio Grande do Norte. Al?m disso, foi tamb?m avaliado a distribui??o relativa da ancestralidade entre o grupo caso e controle. Os polimorfismos e os marcadores utilizado para a distribui??o da ancestralidade foram genotipados utilizando ABI PRISM 3130 e o GeneMapper ID v3.2. A an?lise estat?stica foi realizada utilizando o R v 3.1. Em rela??o ? ancestralidade gen?mica, foi observada diferen?a significativa na distribui??o da contribui??o Africana entre os grupos. Em rela??o ? an?lise de associa??o entre o polimorfismo e o risco de desenvolver CCR, foi observado que o alelo D do polimorfismo estudado no gene IL4, e o alelo I do polimorfismo do TYMS foram associados com o aumento do risco de desenvolver CCR. No presente trabalho, tamb?m foi avaliado o risco que a combina??o genot?pica do TYMS (rs151264360) e do IL4 (rs79071878) aumenta consideravelmente o risco de ter CCR; e foi observado que se faz necess?rio a presen?a de pelo menos 3 alelos de risco para conferir risco de ter CCR. / Colorectal cancer (CRC) is a type of cancer that affects large intestine and rectum region, and this is the third most common cancer worldwide in men and the second in women. The genetic susceptibility to CRC comes from multiple genetic variants. Individually, these genetic variants have modest effect. However, theses variants, when combined, cause a wide range of risk. Among all mutations types found in the human genome, insertion-deletions (INDEL) are the second most common class, which has a potential impact on the expression, structure and protein function. However, there are a few studies about INDEL impact on CRC risk. Thus the aim of this study is to evaluate the association of 16 INDEL with CRC susceptibility in Rio Grande do Norte population. Furthermore, it was also evaluated the relative ancestry distribution between case and control groups. Polymorphism and marker used for ancestry distribution were genotyped using ABI PRISM 3130 and GeneMapper ID v 3.2. Statistical analysis was performed using the R v 3.1. Regarding the genetic ancestry, there was significant difference in the distribution of the African contribution between groups. Regarding the polymorphism association in CRC risk, it was observed that the D allele of IL4 and I allele of TYMS polymorphisms were associated with increased CRC risk. In this study, it was also evaluated the combined effect of IL4 and TYMS polymorphism in CRC risk, and it was observed that at least 3 allelic risks were necessary to confer CRC risk.
154

Estudo de compatibilidade entre atorvastatina e excipientes por t?cnicas t?rmicas (TG, DSC) e FTIR utilizando correla??o de pearson / Study of compatibility between atorvastatin and excipients by thermal techniques (TG, DSC) and FTIR using pearson correlation

Silva, Edilamar Pereira da 29 July 2016 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-20T21:49:25Z No. of bitstreams: 1 EdilamarPereiraDaSilva_DISSERT.pdf: 3623493 bytes, checksum: a0b5d0f1284a116519496496c1ba17b3 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-23T18:49:31Z (GMT) No. of bitstreams: 1 EdilamarPereiraDaSilva_DISSERT.pdf: 3623493 bytes, checksum: a0b5d0f1284a116519496496c1ba17b3 (MD5) / Made available in DSpace on 2017-03-23T18:49:31Z (GMT). No. of bitstreams: 1 EdilamarPereiraDaSilva_DISSERT.pdf: 3623493 bytes, checksum: a0b5d0f1284a116519496496c1ba17b3 (MD5) Previous issue date: 2016-07-29 / A atorvastatina ? um medicamento antilip?mico do grupo das estatinas, de grande import?ncia para a preven??o de doen?as cardiovasculares e normalmente usada como atorvastatina de c?lcio. O objetivo deste trabalho foi caracterizar a atorvastatina e estudar poss?veis intera??es desta com v?rios excipientes por DSC, TG e FT-IR. As curvas DSC foram obtidas usando o calor?metro SHIMADZU, modelo DSC-60, em cadinho de alum?nio sob raz?o de aquecimento de 20 ?C min-1, em uma temperatura de 25-400 ?C. As curvas foram analisadas usando o software TASYS da SHIMADZU. Os espectros das amostras foram obtidos em um espectrofot?metro ATR-FTIR modelo IRprestige-21 da Shimadzu, no comprimento de onda de 700 a 4000 cm-1 em uma m?dia de 20 varreduras. Avaliou-se a const?ncia espectral da atorvastatina e misturas bin?rias fazendo-se uma correla??o linear entre o espectro te?rico das amostras e o espectro real obtido em temperatura ambiente (25 ?C). O espectro te?rico foi obtido utilizando um algoritmo ad hoc. Por DSC avaliamos intera??es com manitol e laurilsulfato de s?dio, j? que houve desaparecimento do pico do f?rmaco e aparecimento apenas do pico do excipiente, caracterizando intera??o. A partir da avalia??o da correla??o de Pearson, n?o observamos intera??es f?sicas com os excipientes, glicolato de amido, amido pr? gelatinizado, croscarmelose, estearato de magn?sio e lactose, uma vez que o valor do r ficou entre 0,8 e 1,0, portanto boa correla??o. H? intera??es f?sicas com o laurilsulfato de s?dio. Assim, os resultados obtidos por DSC s?o confirmados por FTIR mostrando-se. Essas t?cnicas mostram-se extremamente efetivas no estudo de pr?-formula??o. / Atorvastatin is an antilipemic drug from the statins? group that has a great importance to prevent cardiovascular disease and it is usually used as atorvastatin calcium. The aim of this study was to characterize the atorvastatin and studying possible interactions with different excipients by DSC, TG and FTIR. DSC curves were obtained using a Shimadzu calorimeter, model DSC-60, aluminum pan, under heating rate of 20 ?C min-1 at temperature of 25-400 ?C. Consequently, curves were analyzed using TASYS software from Shimadzu. The spectra of the samples were obtained on a spectrophotometer ATR-FTIR (IRPrestige- 21 Shimadzu), between 700 and 4000 cm-1, on average of 20 scans. We evaluated the atorvastatin and binary mixtures? spectral steadiness by making a linear correlation between the theoretical spectra and the real ones obtained at room temperature (25 ?C). The theoretical spectra were obtained using an ad hoc algorithm. We evaluated by DSC that there are chemical interactions with mannitol and sodium lauryl sulfate because there was disappearance of the drug?s peak and appearance only of the excipients? peaks. With respect to the other excipients, there were only displacements of peaks suggesting physical interactions, it means no incompatibility. From the FTIR evaluation using Person?s correlation, it was not observed any physical interaction between atorvastatin and the following excipients: starch glycolate, pregelatinized starch, croscarmellose, magnesium stearate and lactose, since the value of r was between 0.8 and 1.0; in other words, it means a good correlation. Moreover, it was confirmed a physical interaction with the sodium lauryl sulfate. Finally, the results obtained by DSC were confirmed by FTIR data using the Person?s correlation, so both analytical techniques demonstrated to be extremelly important and effective tools for applying in a preformulation study.
155

Avalia??o da atividade citot?xica e pr?-apopt?tica de Croton blanchetianus baill. em linhagens de c?ncer cervical humano

Carvalho, Kleyton Thiago Costa de 27 July 2016 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-04-03T21:43:19Z No. of bitstreams: 1 KleytonThiagoCostaDeCarvalho_DISSERT.pdf: 2993890 bytes, checksum: 64c5c1e9194dcf2ddec049dc4f793967 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-04-10T19:42:28Z (GMT) No. of bitstreams: 1 KleytonThiagoCostaDeCarvalho_DISSERT.pdf: 2993890 bytes, checksum: 64c5c1e9194dcf2ddec049dc4f793967 (MD5) / Made available in DSpace on 2017-04-10T19:42:28Z (GMT). No. of bitstreams: 1 KleytonThiagoCostaDeCarvalho_DISSERT.pdf: 2993890 bytes, checksum: 64c5c1e9194dcf2ddec049dc4f793967 (MD5) Previous issue date: 2016-07-27 / C?ncer cervical (CC) ? o terceiro tipo de c?ncer mais comum em mulheres no mundo todo e a quarta principal causa de morte em mulheres nos pa?ses em desenvolvimento. Os Papilomav?rus humano (HPV) de alto risco tais como HPV 16, 18, 31 e 33 s?o o principal fator de risco para esse tipo de c?ncer. Entre estes, o HPV-16 e -18 s?o respons?veis por quase 70% dos casos de CC. Quimioterapia com compostos ? base de platina em combina??o com a radioterapia ou a cirurgia ? o tratamento de escolha para CC, mas sua efic?cia ? limitada, especialmente em est?gios avan?ados da doen?a. Al?m disso, estes tratamentos podem facilmente levar a rea??es adversas e resist?ncia ?s drogas. Assim, a busca por novos agentes antitumorais seletivos e de alta efic?cia para o tratamento deste tipo de tumor ? necess?ria. Croton blanchetianus (CB), popularmente conhecida como ?marmeleiro preto?, ? um arbusto pertencente ? fam?lia Euphorbiaceae e amplamente disseminado no nordeste brasileiro. Alguns estudos t?m demonstrado a atividade citot?xica de plantas do g?nero Croton em linhagens tumorais humanas. Contudo, at? o momento, n?o h? nada descrito na literatura quanto ao efeito citot?xico da esp?cie Croton blanchetianus. Assim, o presente trabalho teve como objetivo investigar, in vitro, os efeitos de fra??es obtidas das folhas e raiz de CB nas linhagens de c?ncer cervical humano HeLa e SiHa. As fra??es foram obtidas pelo m?todo de varia??o do pH, a partir do qual foram obtidas duas fra??es ?cidas, uma das folhas (CBaF) e outra da raiz (CBaR), e duas b?sicas, tamb?m das folhas (CBbF) e raiz (CBbR). O perfil fitoqu?mico das fra??es foi avaliado por Cromatografia em camada delgada (CCD). A atividade citot?xica e a avalia??o do tipo de morte celular foram determinados pelos ensaios de MTT e Anexina V/PI, respectivamente, enquanto que para avalia??o de altera??es morfol?gicas nucleares e ensaio do ciclo celular foram utilizados, respectivamente, microscopia de fluoresc?ncia com o corante DAPI e citometria de fluxo. De acordo com os resultados, a maioria das fra??es apresentou terpenos, alcaloides e flavonoides. Al?m disso, todas as fra??es testadas foram capazes de diminuir significativamente a viabilidade celular de HeLa e SiHa de maneira concentra??o e tempo dependentes, promoveram modifica??es morfol?gicas celulares e nucleares, al?m de induzirem apoptose e parada do ciclo celular. Este ? o primeiro estudo que demonstrou os efeitos citot?xicos e pr?-apopt?ticos de CB em linhagens de c?ncer cervical humano. Portanto, CB parece ser uma fonte natural promissora para o desenvolvimento de agentes para o tratamento do CC. No entanto, mais estudos s?o necess?rios para isolar, purificar e elucidar os poss?veis mecanismos de a??o dos compostos ativos. / Cervical cancer (CC) is the third most common cancers in women worldwide and the fourth major cause of cancer death in the woman in developing countries. High-risk human papilloma viruses (HPVs) such as HPV 16, 18, 31 and 33 have been attributed to be the major risk factors for cervical cancer, out of which HPV-16 and -18 account for almost 70% of the cancers. Platinum-based chemotherapy in combination with radiotherapy or surgery is now mainly used to treat CC, but the efficacy is limited especially in advanced-stage disease. Furthermore, these treatments could easily lead to adverse reactions and drug resistance. Thus, it is necessary to seek antitumor drugs of high efficacy for the treatment of this kind of tumor. Croton blanchetianus (CB), known as ?black marmeleiro?, belongs to the family Euphorbiaceae and it is a widely disseminated shrub found in northeast Brazil. Some studies have demonstrated cytotoxic activity of plants of this genus against human tumor cell lines. However, to date, there is nothing described in the literature as to the cytotoxic effect of the Croton blanchetianus. Therefore, the present study aimed to investigate, in vitro, the effects of leaves and root fractions from Croton blanchetianus (CB) against human cervical cancer HeLa and SiHa cells. Fractions were obtained by pH variation method, from which were obtained two acidic fractions, one of the leaves (CBaF) and root (CBaR) and two basic also obtained from leaves (CBbF) and root (CBbR). Phytochemical screening was evaluated by thin layer chromatography. Cytotoxic activity and cell death evaluation were determined with MTT and annexin V/PI assays by flow cytometry, respectively. Nuclear morphological changes were evaluated by fluorescence with DAPI stanning and flow cytometry was used to cycle assay. According to results, most of the fractions exhibited terpenoids, alkaloids and flavonoids. All fractions decreased significantly cell viability of HeLa and SiHa cells in a concentration- and time-dependent manner, promoted cellular and nuclear morphological changes and induced apoptosis and cell cycle arrest. This is the first study that demonstrated cytotoxic and pro apoptotic effects of CB on HeLa and SiHa cells. Therefore, CB appears to be a valuable natural source for the development of agents for the treatment of CC. However, more studies are needed to isolate, purify and elucidate the possible action mechanisms of the active compounds.
156

Desenvolvimento de um m?todo inovador de forma??o de nanoemuls?es para libera??o modificada de praziquantel atrav?s da dilui??o de cristais l?quidos

Souza, Izadora de 31 July 2015 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:21:19Z (GMT) No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) / Made available in DSpace on 2017-06-07T19:21:19Z (GMT). No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) Previous issue date: 2015-07-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Cristais l?quidos (CL) possuem um arranjo molecular bastante estruturado que combina propriedades dos estados l?quido e s?lido, bem como o fluxo dos l?quidos e a ordena??o da estrutura cristalina dos s?lidos. Foram testadas t?cnicas de alta e baixa energia para produzir CL, utilizando oleato de s?dio, fosfatidilcolina de soja, ?leo de soja, N-metilpirrolidona (NMP) e ?gua. As intera??es entre NMP e oleato de s?dio da formula??o foram investigadas. CL obtidos por t?cnica de alta energia foram caracterizados por microscopia de luz polarizada (MLP), reologia e tamanho de part?cula. MLP exibiu estruturas que sugerem presen?a de CL lamelares. Na reologia, as amostras apresentaram viscosidade newtoniana limitante nas curvas de fluxo e uma diminui??o no grau de estrutura??o nos testes oscilat?rios, quando a concentra??o de NMP diminu?a. Uma nova t?cnica para obter sistemas lip?dicos de libera??o de f?rmacos foi desenvolvida a partir da dilui??o de CL produzidos por baixa energia. CL foram produzidos por agita??o magn?tica e, posteriormente, foram dilu?dos com ?gua e solu??o aquosa de NMP 10%, a 25 ? C e 70 ?C, em que foram avaliados tamanho de got?cula e incorpora??o de praziquantel (PRZ). Os sistemas dilu?dos com ?gua apresentaram menor faixa de tamanho (165,22 ? 381,26 nm) e maior faixa de incorpora??o de PRZ (40,96 ? 43,44 mg/mL) quando comparadas com as dilu?das com a solu??o de NMP. N?o houve contribui??o da solu??o de NMP para a forma??o de got?culas menores e para a maior incorpora??o de PRZ. Houve um aumento na solubilidade do PRZ em sistemas dilu?dos com ?gua, aumentando a fra??o sol?vel de f?rmaco em at? 200 vezes quando comparada ? sua solubilidade em ?gua. Testes utilizando Espalhamento de raios-X a baixo ?ngulo e MLP comprovaram a transi??o da mesofase lamelar para sistemas com micelas vermiformes, confirmando o sucesso da nova t?cnica em obter sistemas lip?dicos de libera??o de f?rmacos atrav?s da dilui??o de CL. / Liquid crystalline mesophase (LC) have an organized molecular arrangement and combining properties of liquid and solid state as the flow of liquids and the ordered and crystalline structure of solids. High- and low energy techniques were used to produce LC. N-methylpyrrolidone (NMP) and sodium oleate interactions with the system were investigated. LC fabricated by high-energy method were characterized by polarizing light microscopy (PLM), rheology and droplet size. PLM showed structures that indicated lamellar phases. Surface tension no important difference between the samples was observed. Rheology showed a zero shear viscosity in flow curves with a shear-thinning behavior in oscillatory tests, which with increasing of NMP, there was a decrease in degree of structure. Novel method to obtain lipid based drug delivery system (LBDDS) were developed through LC dilution and drug-loading was tested. LC fabricated with low-energy method was diluted with water and NMP 10% aqueous solution, at 25 ?C and 70 ?C, which droplet size and drug loading were evaluated. The systems diluted with water showed lower range size (165.22 nm- 381.26 nm) and higher drug-loading (40.96 mg/mL - 43.44 mg/mL) when compared with systems diluted by NMP solution. NMP aqueous solution did not contribute to form smaller particle size and higher praziquantel-loading. An increment in the apparent solubility of Praziquantel was achieved from incorporation in dilution of LC with water, increasing the soluble drug fraction approximately 200-fold when compared with water solubility. Small angle X-ray scattering (SAXS) measurements and PLM comproved the transition from lamellar mesophase to worm-like micelle systems confirming the success of new techinique for obtain LBDDS from LC dilution.
157

Estudo das intera??es do praziquantel com ciclodextrinas em sistemas multicomponentes

Souza, Jairo Sotero Nogueira de 28 November 2016 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:30:54Z (GMT) No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) / Made available in DSpace on 2017-06-07T19:30:54Z (GMT). No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) Previous issue date: 2016-11-28 / A utiliza??o de ciclodextrinas para aumentar a solubilidade de f?rmacos em solu??o aquosa tem sido bastante estudada. No presente estudo, o mecanismo de intera??o do praziquantel (PZQ) com a beta-ciclodextrina e com a hidroxipropil-beta-ciclodextrina na presen?a dos co-solventes trietanolamina (TEA) e a N-metilpirrolidona (NMP) foi realizado com o objetivo do aumento da solubilidade do praziquantel. Atrav?s dos diagramas de solubilidade e dos diagramas de Job?s Plot foi poss?vel observar a forma??o de complexos sol?veis com estequiometria 1:1. A presen?a dos co-solventes TEA e NMP diminuiu a estabilidade e solubilidade dos complexos formados, no entanto atrav?s dos estudos de modelagem molecular foi mostrado que este efeito pode facilitar a sa?da do f?rmaco da cavidade e, consequentemente, beneficiar a absor??o do f?rmaco. Os resultados mostraram-se elucidativos e bastantes promissores na obten??o futura de complexos que possam ser utilizados para melhor biodisponibilidade do praziquantel. / The use of cyclodextrin (CD) to enhace the praziquantel (PZQ) water solubility has been widely studied in the literature. In this present paper, the interaction has not yet studied between the PZQ and both the beta-cyclodextrin (?-CD) and hydroxyl-propyl-cyclodextrin (HP-?-CD) or its association with the solvents triethanolamine (TEA) and N-methyl-pyrrolidone (NMP) was carefully conducted with the purpose to enhance the water solubility of the PZQ. The solubility diagrams and job?s plot diagrams showed that water soluble complexes were formed with 1:1 stoichiometry. The association of the complexes with the TEA and NMP diminished considerably the complex stability and its solubility. However, throught the molecular modeling study it was showed that this effect may be beneficial for the output of the drug from the CD cavity, and consequently to benefit the drug absorption. The results showed up adequately enlightening to propose that these systems can be investigated to enhance the PZQ bioavailability.
158

Utiliza??o do subproduto do beneficiamento do sisal (Agave sisalana Perrine): desenvolvimento de nanoemuls?es cosm?ticas e avalia??o da seguran?a e efic?cia

Barreto, Stella Maria Andrade Gomes 31 March 2017 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 StellaMariaAndradeGomesBarreto_DISSERT.pdf: 2589598 bytes, checksum: eb867f2ecba9f71b559518fcc2a0d571 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T20:58:36Z (GMT) No. of bitstreams: 1 StellaMariaAndradeGomesBarreto_DISSERT.pdf: 2589598 bytes, checksum: eb867f2ecba9f71b559518fcc2a0d571 (MD5) / Made available in DSpace on 2017-06-07T20:58:36Z (GMT). No. of bitstreams: 1 StellaMariaAndradeGomesBarreto_DISSERT.pdf: 2589598 bytes, checksum: eb867f2ecba9f71b559518fcc2a0d571 (MD5) Previous issue date: 2017-03-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O beneficiamento das folhas de Agave sisalana fornece a fibra, com valor agregado para a ind?stria de sisal, e o restante do material vegetal, denominado de subproduto, que ? descartado, gera impacto ambiental. Diferentes aplica??es t?m sido atribu?das, no entanto, n?o existem pesquisas cient?ficas que apontem a utiliza??o deste subproduto como mat?ria-prima cosm?tica. O objetivo dessa pesquisa foi obter e caracterizar uma fra??o enriquecida em polissacar?deos (FrE) a partir do subproduto de Agave sisalana, avaliar a seguran?a in vitro e in vivo, bem como a atividade antioxidante in vitro, e, ent?o, desenvolver uma nanoemuls?o hidratante. A partir da por??o l?quida do subproduto foram obtidos o extrato bruto (EB) e duas fra??es. O EB e as fra??es foram avaliados quanto ? presen?a de a??cares, prote?nas e polifenois. A seguran?a foi avaliada por meio dos testes de citotoxicidade e fototoxicidade in vitro utilizando o m?todo colorim?trico do vermelho neutro. A irritabilidade prim?ria foi verificada pelo teste de contato (patch test). A capacidade antioxidante foi avaliada pelos m?todos de sequestro de DPPH e molibd?nio. Diferentes sistemas foram obtidos por meio de pseudodiagrama tern?rio, aditivados ou n?o com 0,5% de FrE. As formula??es selecionadas foram submetidas aos testes de estabilidade preliminar e acelerada por um per?odo de 90 dias. A efic?cia hidratante foi avaliada quanto ao conte?do h?drico do estrato c?rneo e quanto ? perda de ?gua transepidermal por um per?odo de 5 horas. As amostras apresentaram, como constituintes qu?micos, a??cares, polifenois e prote?nas. A FrE n?o apresentou potencial citot?xico ou fotot?xico, n?o foi irritante e pode ser considerada um ativo com propriedade antioxidante. Nanoemuls?es est?veis contendo 40% de fase oleosa, 10% de tensoativos e 50% de fase aquosa foram obtidas. A nanoemuls?o foi capaz de aumentar significativamente o conte?do h?drico e manter a fun??o de barreira da pele ap?s 5h de uma ?nica aplica??o. A fra??o obtida do subproduto industrial de Agave sisalana apresenta um perfil promissor como mat?ria-prima cosm?tica para cuidado da pele com capacidade antioxidante e hidratante, em conjunto com a possibilidade de agregar valor ao res?duo industrial, reduzindo os danos provocados ao meio ambiente pelo descarte desse material. / The processing of the leaves of Agave sisalana provides fiber, with added value for the sisal industry, and the rest of the plant material, known as by-product, is thrown and generates environmental impact. Different applications have been attributed, however, there are no scientific researches that aim to use this product as a cosmetic raw material. The objective of this research was to obtain and characterize polysaccharides-enriched fraction (FrE) from the Agave sisalana by-product of, assess the safety in vitro and in vivo, as well as to evaluate the antioxidant activity in vitro, and then to develop a nanoemulsion with moisturizer effect. From the liquid portion of the by-product obtained the crude extract (EB) and two fractions resulting from extractive process. The EB and the fractions were evaluated for the presence of sugars, proteins and polyphenols. Safety was evaluated by cytotoxicity and phototoxicity in vitro assays using the colorimetric method of Neutral Red. Irritability was evaluated by the primary contact test (patch test). The antioxidant capacity was assessed using the DPPH scavenging tests and molybdenum method. Different systems were obtained by means of pseduodiagrama ternary containing, or not, 0.5% FrE. The selected formulations were submitted to preliminary stability tests and accelerated in different temperatures conditions for a period of 90 days. The moisturizing efficacy was evaluated by water content of the stratum corneum and transepidermal water loss for a period of 5 hours. The samples presented as chemical constituents, sugars, polyphenols and proteins. The FrE showed no phototoxic potential or cytotoxic, and was not irritating to skin of volunteers and can be considered an asset with antioxidant property Nanoemulsion containing 40% oil phase, 50% aqueous phase and 10% surfactants was stable for 90 days.The nanoemulsion was able to significantly increase the water content and maintain skin barrier function after 5 hours from a single application. The fraction obtained from the industrial by-product of Agave sisalana demonstrated a promising profile as raw material for cosmetic skin care with moisturizing and antioxidant capacity, together with the possibility of adding value to industrial waste, reducing the damage caused to the environment by disposing of this material.
159

Estudo da express?o dos genes do metabolismo do ?cido f?lico e associa??o com o desenvolvimento de fendas orais

Soares, Cl?lio Diogo 30 August 2012 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-10-04T21:05:45Z No. of bitstreams: 1 ClelioDiogoSoares_DISSERT.pdf: 3089611 bytes, checksum: d4a3b5a01c7dc8a828197d92e650d07e (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-10-11T22:38:17Z (GMT) No. of bitstreams: 1 ClelioDiogoSoares_DISSERT.pdf: 3089611 bytes, checksum: d4a3b5a01c7dc8a828197d92e650d07e (MD5) / Made available in DSpace on 2017-10-11T22:38:17Z (GMT). No. of bitstreams: 1 ClelioDiogoSoares_DISSERT.pdf: 3089611 bytes, checksum: d4a3b5a01c7dc8a828197d92e650d07e (MD5) Previous issue date: 2012-08-30 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Introdu??o: H? evidencias consider?veis sugerindo que genes relacionados ao metabolismo do folato possuem um papel importante na etiologia das fendas orofaciais. A express?o de genes que possam estar ligados ?s fendas orais requer a presen?a de apropriadas causas ambientais em combina??o com fatores gen?ticos que culminam com a falha na fus?o dos processos faciais. Objetivo: Realizar estudo de associa??o da express?o dos genes da via do metabolismo do acido f?lico - MTHFR, MTR, RFC1, MTRR, com a ocorr?ncia das fendas orais. Metodologia: Foram estudados 50 filhos casos e suas respectivas m?es, e 50 indiv?duos controles e suas respectivas m?es. Inicialmente foram realizadas as an?lises bioqu?micas (Glicose, ALT, AST, Creatinina, Folato, Vitamina B12, Homociste?na), hematol?gicas (hemoglobina, hemat?crito, contagem de hem?cias, os ?ndices hematol?gicos, VCM, HCM e CHCM) e estudo de suas caracter?sticas cl?nicas. Para a realiza??o do estudo de express?o g?nica foi extra?do o RNA total a partir das c?lulas do sangue perif?rico, o qual foi quantificado e analisado quanto a sua pureza e integridade e encaminhado para a obten??o do cDNA a ser utilizado para o estudo de express?o utilizando ensaios pr?-desenhados. Finalmente foi avaliada a influ?ncia de determinados gen?tipos (MTRR A66G; MTHFR C677T; MTHFR A1298C; MTR A2756G; RFC1 A80G) sobre a express?o de RNAm dos respectivos genes estudados. A an?lise estat?stica dos dados foi realizada considerando o n?vel de signific?ncia de 95% (P<0,050) Resultados: Foi evidenciada a presen?a do consumo de ?lcool como fator de risco significativo presente para as m?es caso (P=0,001). Em rela??o as dosagens bioqu?micas n?o foram observadas diferen?as significativas entre os casos e respectivos controles os quais apresentaram valores de AST, ALT e creatinina dentro dos valores de refer?ncia. A dosagem de ?cido f?lico apresentou-se reduzida significativamente para o grupo dos filhos caso (P=0,010) e para suas m?es (P=0,001). Na an?lise hemat?logica n?o foram observadas altera??es em nenhum dos par?metros avaliados como hemoglobina, hemat?crito, contagem de hem?cias, os ?ndices hematol?gicos, VCM, HCM e CHCM dentre os grupos avaliados. A avalia??o da express?o g?nica para o grupo das m?es caso mostrou uma redu??o significativa na express?o do RNAm em todos os genes avaliados: para o gene da metionina sintase (MTR, p=0,008), da metionina sintase redutase (MTRR, p=0,015), do RFC1 (P=0,004) e da MTHFR (P=0,017) comparados com o grupo de m?es controle. No grupo de filhos fissurados, houve uma redu??o significativa na express?o do RNAm para os genes da metionina sintase (MTR, p=0,010) e da metionina sintase redutase (MTRR, p=0,034). Para a an?lise da influencia dos gen?tipos na express?o observou-se que o gen?tipo recessivo (CC) para o polimorfismo A1298C do gene MTHFR poderia estar associada a uma redu??o da express?o de seu RNAm. Conclus?o: Genes do metabolismo de folato relacionados s?o reduzidamente expressos em ambos os grupos caso deste estudo, uma vez que todos os quatro genes (RFC1, MTHFR, MTR, MTR), estavam reduzidos nas m?es e dois genes (MTR, MTRR) em seus filhos. A redu??o da express?o desses genes representa um aumento do risco associado com a presen?a de fendas orais nestes indiv?duos. / Introduction: There is considerable evidence suggesting that folate-related genes play a role in the etiology of oral facial clefts. Clefts are known to have a strong genetic component. The expression profile of genes involved on the pathway and folic acid metabolism which is linked to oral clefts requires appropriate environmental causes in combination with genetic factors that culminate in the failure of fusion of facial processes. Objective: The objective is to perform the association of differential gene expression of folate metabolism genes (MTHFR, MTR, RFC1, MTRR) with the occurrence of oral clefts. Methods: We studied 50 subjects with oral clefts and their mothers, and 50 individuals absent of oral clefts and their mothers, totaling 100 individuals referred cases and 100 controls respectively. For gene expression study, total RNA was extracted from peripheral blood cells, then it was quantified and analyzed for purity by absorbance relation and integrity in MOPS gel. The mRNA samples with good purity and integrity were transcribed to cDNA using reverse transcription kit. The cDNA was used in pre-designed gene expression assays. In a previous study performed by our group were evaluated by PCR-RFLP the MTRR A66G, MTHFR C677T, MTHFR A1298G, MTR A2756G, RFC1 A80G polymorphisms, in this study we evaluated the influence of these polymorphisms on gene expression. It was also performed biochemical, hematological analyzes and a clinical characteristics study of these individuals. We performed statistical analysis considering the significance level of 95% (P <0.050) Results: The consumption of Alcohol was reported as a significant risk factor for the present case mothers (p = 0.001). Regarding the biochemical there were no significant differences between children cases group and their controls which had values of AST, ALT and creatinine within the reference values. The folic acid dosage presented significantly reduced in case mothers group (P = 0.011). In haematological analysis was not observed significant changes in any of the evaluated parameters such as hemoglobin, hematocrit, erythrocyte count, and hematological indices, MCV, MCH and MCHC among the groups. The assessment of gene expression for case mother group showed a significant reduction in mRNA expression in all evaluated genes; for the methionine synthase gene (MTR, p = 0.008), the methionine synthase reductase (MTRR, p = 0.015), the reduced folate carrier 1 (RFC1, P= 0.004) and methylenetetrahydrofolate reductase (MTHFR, P= 0.017) compared with the control group mothers. In the case children group, similar results were obtained, with a significant reduction in mRNA expression of methionine synthase gene (MTR, p = 0.010) and methionine synthase reductase (MTRR, p = 0.034) analysis of genotypes in relation to expression was found that the recessive genotype (CC) for the MTHFR gene A1298C polymorphism is associated with reduced expression of its mRNA. Conclusion: Folate metabolism related genes are low expressed on both case groups of this study, since all four genes (RFC1,MTHFR, MTR, MTR,) were reduced on mothers and two genes (MTR, MTRR) in their children. These down regulated genes represent an increased risk associated with the presence of oral clefts in these individuals.
160

Atividade anti-inflamat?ria e antinociceptiva dos extratos brutos e fra??es de Eugenia uniflora e Libidibia ferrea in vivo

Falc?o, Tamires Rocha 29 June 2017 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-10-04T21:05:46Z No. of bitstreams: 1 TamiresRochaFalcao_DISSERT.pdf: 2502372 bytes, checksum: 96d87924692b74a82d2357b02c75c110 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-10-11T23:24:29Z (GMT) No. of bitstreams: 1 TamiresRochaFalcao_DISSERT.pdf: 2502372 bytes, checksum: 96d87924692b74a82d2357b02c75c110 (MD5) / Made available in DSpace on 2017-10-11T23:24:29Z (GMT). No. of bitstreams: 1 TamiresRochaFalcao_DISSERT.pdf: 2502372 bytes, checksum: 96d87924692b74a82d2357b02c75c110 (MD5) Previous issue date: 2017-06-29 / A esp?cie Libidibia ferrea pertence a fam?lia Fabaceae, popularmente conhecida como pau-ferro ou juc?, sendo utilizada na medicina tradicional como antibacteriana, antiulcerog?nica, anti-inflamat?ria e analg?sica. Eugenia uniflora pertence fam?lia Myrtaceae, sendo conhecida como pitanga, utilizada popularmente no tratamento de diarreia, inflama??o, hiperglicemia e hipertens?o. Considerando a import?ncia das plantas medicinais como fonte de novos medicamentos ?teis para o tratamento de diversas doen?as, e o envolvimento do processo inflamat?rio em in?meras afec??es, e os fortes ind?cios de atividade farmacol?gica associada ? presen?a de subst?ncias bioativas presente nestas esp?cies, delineou-se um estudo pr?-cl?nico com o objetivo de avaliar a atividade anti-inflamat?ria e antinociceptiva dos extratos brutos e fra??es de Libidibia ferrea e Eugenia uniflora, por meio do modelo de peritonite induzido por carragenina, teste de placa quente e contor??es abdominais induzidas por ?cido ac?tico em camundongos Swiss esp?cie Mus musculus. A partir dos materiais vegetais secos e triturados, obteve-se por m?todos gerais de farmacognosia extratos brutos e fra??es de Eugenia uniflora (extrato bruto aquoso, fra??o aquosa, fra??o hex?nica e fra??o acetato de etila) e de Libidibia ferrea (extrato bruto aquoso, extratos brutos extra?dos com etanol 20, 40, 60 e 80%, fra??o acetato de etila e fra??o aquosa). As an?lises cromatogr?ficas dos extratos brutos e fra??es permitiram separar e identificar os taninos hidrolis?veis ?cido g?lico, com tempo de reten??o de aproximadamente 8,7 minutos, e o ?cido el?gico, com tempo de reten??o de 25,1 minutos, foi detectado ainda o flavonoide miricitrina, confirmada com os dados cromatogr?ficos dos padr?es. Na avalia??o da migra??o leucocit?ria, o extrato bruto fra??es de Eugenia uniflora e Libidibia ferrea nas doses de 50 mg/kg, 100 e 200 mg/kg reduziram o n?mero de c?lulas inflamat?rias para o s?tio da inflama??o (p<0,001) comparando os grupos tratados com o grupo controle positivo. A diminui??o do influxo celular foi acompanhada de uma marcante diminui??o da atividade da mieloperoxidase, redu??o de MDA, e mostrou proteger contra a deple??o de glutationa (p<0,001). A administra??o dos extratos brutos e fra??es produziu uma resposta antinociceptiva perif?rica em todas as doses testadas, reduzindo significativamente o n?mero de contor??es abdominais induzidas por ?cido ac?tico em camundongos, por?m demonstrou ter atividade analg?sica central pouco significativa, sendo avaliada pelo teste de placa quente. Os resultados descritos indicam que estas plantas possuem atividades anti-inflamat?rias e antinociceptivas. No entanto, outros estudos s?o necess?rios para elucida??o de suas propriedades farmacol?gicas, estudos de an?lise em n?vel sist?mico e propriedades toxicol?gicas. / The species Libidibia ferrea belongs to the family Fabaceae, popularly known as pau-ferro or juc?, being used in traditional medicine as antibacterial, antiulcerogenic, anti-inflammatory and analgesic. Eugenia uniflora belongs to Myrtaceae family, being known as pitanga, popularly used in the treatment of diarrhea, inflammation, hyperglycemia and hypertension. An analysis of medicinal plants as a source of new drugs for the treatment of several diseases, and involvement of the inflammatory process in numerous diseases, and strong indications of pharmacological activity associated with the presence of bioactive substances present in these species, With the aim of evaluating an anti-inflammatory and antimociceptive activity of the crude extracts and phrases of Libid?bia ferreira and Eugenia uniflora, through the model of carrageenan-induced peritonitis, hot plate test and abdominal contortions induced by acetic acid in Swiss mice Species Mus musculus. From crude and crushed vegetable materials, crude extracts and Eugenia uniflora fractions (crude aqueous extract, aqueous fraction, hexane fraction and ethyl acetate fraction) and Libidibia ferrea (crude aqueous extract, extracts Crude extracted with ethanol 20, 40, 60 and 80%, fraction ethyl acetate and aqueous fraction). The chromatographic analyzes of the extracts and the fractions allowed to separate and identify the gallic acid hydrolysable tannins, with retention time of approximately 8.7 minutes, and ellagic acid, with retention time of 25.1 minutes, also detected the flavonoid myricitrin, Confirmed With the chromatographic data of the standards. In the evaluation of leukocyte migration, the crude extract fractions of Eugenia uniflora and Libidibia ferrea at doses of 50 mg / kg, 100 and 200 mg / kg reduced the number of inflammatory cells to the site of inflammation (p <0.001), comparing the treated groups With the positive control group. The decrease in the cellular influx was accompanied by a decreased marking of myeloperoxidase activity, reduction of MDA, and showed protection against glutathione depletion (p <0.001). The administration of the crude extracts and fractions produced a peripheral antinociceptive response in all the doses tested, reducing the number of product contours by means of an acoustic in mice, but demonstrating little central analgesic activity, being evaluated by the hot plate test. The results indicate that these plants are anti-inflammatory and antinociceptive activities. However, other studies are indispensable for the elucidation of its pharmacological properties, studies of inscription analysis and toxic properties.

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