Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-06-06T18:56:53Z No. of bitstreams: 1 LucasAmaralMachado_DISSERT.pdf: 675823 bytes, checksum: cd1bcc94212045a3a4738ef67078d1cf (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-07T23:51:14Z (GMT) No. of bitstreams: 1 LucasAmaralMachado_DISSERT.pdf: 675823 bytes, checksum: cd1bcc94212045a3a4738ef67078d1cf (MD5) / Made available in DSpace on 2016-06-07T23:51:14Z (GMT). No. of bitstreams: 1 LucasAmaralMachado_DISSERT.pdf: 675823 bytes, checksum: cd1bcc94212045a3a4738ef67078d1cf (MD5) Previous issue date: 2015-03-11 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O objetivo deste estudo foi realizar a extra??o ?leo de r?-touro ?leo de r?-touro e desenvolver uma emuls?o adequada para uso t?pico do mesmo. Duas amostras de ?leo fora obtidas por diferentes m?todos, sendo uma por extra??o a quente e outra utilizando solvente org?nico. As amostras foram fisioquimicamente caracterizadas por t?cnicas de titula??o e seus compostos identificados atrav?s de cromatografia gasosa acoplada a espectrometria de massas (GC/EM). O equil?brio hidrif?lico-lipof?lico requerido (EHLr) do ?leo de r?-touro foi determinado e em seguida um diagrama de fases constru?do. A estabilidade da emuls?o de uso t?pico contendo diferentes adjuvantes farmac?uticos foi determinada. A an?lise de citotoxicidade do ?leo de r?-touro in natura e na emuls?o de uso t?pico foi realizada atrav?s do ensaio de MTT, utilizando linhagem de fibroblastos normais (3T3) e de melanoma (B16F10). O rendimento da extra??o a quente foi de 60,6%. Os principais compostos insaturados encontrados foram o ?cido eicosapentaen?ico (17,6%) e ?cido araquid?nico (8,4%). O estudo de EHLr demonstrou a presen?a de sistemas est?veis com EHL entre 12 e 13,5 e o diagrama de fases revelou a predomin?ncia de sistemas caracterizados como emuls?o (62%). A emuls?o t?pica apresentou tamanho de got?cula igual a 390 nm, polidispers?o de 0,05, potencial zeta -25 mV e manteve-se est?vel durante os 90 dias avaliados. O ?leo de r?-touro e a emuls?o t?pica n?o apresentaram citotoxicidade frente ? linhagem de c?lulas 3T3. No entanto, estes sistemas inviabilizaram significativamente (p > 0,05) o crescimento das c?lulas B16F10. Em conclus?o, o ?leo de r?-touro apresenta caracter?sticas qu?micas desej?veis para o desenvolvimento de sistemas terap?uticos de uso farmac?utico e/ou cosm?tico. / The skin is one of the largest organs of the human body and accounts for about 16% of body weight. The body protection against the external environment microorganisms is one of its most important functions, however is necessary that the skin remain intact for this function be exercised, so that when there is an injury on the skin, the process of restructuring needs to be starts, however this restructuration may also be compromised due to some diseases, justifying even more the need for the development of topical products that promote or accelerate the skin healing. Thus the aim of this study was to extract bullfrog oil and to develop a suitable topical emulsion. Two different oil samples were extracted by hot or organic solvent process. Titration techniques and gas chromatography- mass spectrometry were used to characterize the bullfrog oil. The required hydrophile-lipophile balance (HLBr) of bullfrog oil was determined and a pseudo-ternary phase diagram was constructed. The stability of the topical emulsion was evaluated. Then, cellular viability was determined by MTT assay using normal fibroblasts (3T3) and melanoma (B16F10) cells lines. The hot extraction yield was 60.6%. The major polyunsaturated compounds found were Eicosapentaenoic acid (17.6%) and Arachidonic acid (8.4%). HLBr study demonstrated the presence of stable systems with HLB ranging from 12.1 to 13.5 and the pseudo-ternary phase diagram showed mainly emulsion systems (62%). Topical emulsion showed 390 nm, polydispersity 0.05, zeta potential -25 mV and remained stable for ninety days. The bullfrog oil and topical emulsion did not showed citotoxicity in normal fibroblasts cells. However, these systems showed significantly inhibition of melanoma cells growth. In conclusion, the bullfrog oil presented desirable chemical characteristics required to be used for the development of a pharmaceutical and cosmetic products.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-01-15T22:12:26Z No. of bitstreams: 1 RenataRutckeviskiMoro_DISSERT.pdf: 2237359 bytes, checksum: 38ee9b608bb33566f80348e060646864 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-01-18T14:11:18Z (GMT) No. of bitstreams: 1 RenataRutckeviskiMoro_DISSERT.pdf: 2237359 bytes, checksum: 38ee9b608bb33566f80348e060646864 (MD5) / Made available in DSpace on 2018-01-18T14:11:18Z (GMT). No. of bitstreams: 1 RenataRutckeviskiMoro_DISSERT.pdf: 2237359 bytes, checksum: 38ee9b608bb33566f80348e060646864 (MD5) Previous issue date: 2015-06-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Fontes alternativas de ?leos naturais est?o sendo constantemente avaliadas para atender a demanda por mat?rias-primas naturais para o desenvolvimento de novos produtos. O objetivo deste trabalho foi estudar a estabilidade oxidativa e t?rmica do ?leo de r?-touro (Rana catesbeiana Shaw), assim como desenvolver uma emuls?o baseado em um planejamento experimental com aplica??o para via oral. O tecido adiposo da Rana catesbeiana Shaw foi utilizado como fonte para a produ??o de um ?leo natural a partir do m?todo de extra??o a quente, obtendo rendimento de 60 ? 0,9%. O ?leo de r?-touro foi fisicoquimicamente caracterizado e os ?ndices de per?xido, acidez, iodo e saponifica??o foram respectivamente 1,9 meq O2 / kg; 2,9 KOH / g de ?leo; 104,2 g de I / 100 g de ?leo e 171,2 mg de KOH / g de ?leo. A cromatografia gasosa acoplada a espectrometria de massas foi usada para a determina??o dos compostos presentes no ?leo de r?-touro, apresentando como principais constituintes o ?cido ol?ico (30 %) e o ?cido eicosapentaen?ico (17,6%), que s?o ?cidos graxos insaturados e poliinsaturados, respectivamente. A estabilidade oxidativa foi determinada na presen?a e aus?ncia dos antioxidantes butilhidroxianisol (BHA) e butilhidroxitolueno (BHT), a 60 ? 2 ?C durante 15 dias e a temperatura ambiente durante 120 dias. Foram avaliados os ?ndices de acidez, per?xido, iodo e saponifica??o; dienos e trienos conjugados, tempo de indu??o a oxida??o (Rancimat?) e mudan?as nos espectros de infravermelho. A taxa de oxida??o do ?leo de r?-touro foi dependente da temperatura e o ?leo apresentou-se mais estavel na presen?a de BHT. Durante a oxida??o do ?leo, mudan?as significativas no espectro de absor??o do ultravioleta vis?vel e infravermelho foram observadas. O ?leo apresentou-se est?vel at? 200?C atrav?s da determina??o da estabilidade t?rmica utilizando a calorimetria explorat?ria diferencial e an?lise termogravim?trica. Um produto farmac?utico emulsionado para uso oral a base do ?leo de r?-touro utilizando o planejamento fatorial completo 23 foi desenvolvido, caracterizado e sua estabilidade contendo diferentes adjuvantes farmac?uticos foi avaliada. A emuls?o oral apresentou tamanho de got?cula de 410 ? 8,3 nm, potencial zeta - 38,2 mV, condutividade 1913.8 ?S/cma e pH 6.4. O uso de adjuvantes foi respons?vel por melhorar a estabilidade termooxidativa do ?leo disperso na emuls?o por um per?odo superior a tr?s meses. Portanto, a formula??o desenvolvida exibiu caracter?sticas tecnol?gicas promissoras para estabilidade termooxidativa da emuls?o contendo o ?leo de r?-touro para uso oral. / Alternative sources of natural oils are constantly being investigated to meet the demand for natural raw materials used for the development of new products. The aim of this work was to study the oxidative and thermal stability of the bullfrog oil (Rana catesbeiana Shaw), as well as to develop an emulsion based on an experimental design with application to the oral route. The adipose tissue of Rana catesbeiana Shaw was used as a source for producing natural oil by a hot extraction method, with yield of 60 ? 0.9%. The bullfrog oil was characterized and peroxide, acidity, iodine and saponification values were respectively 1.92 meq O2 / kg; 2.95 KOH / g oil; 104.2 g of I / 100 g oil and 171.2 mg KOH / g of oil. The gas chromatography-mass spectrometry (GC / MS) was used to determine the compounds present in the bullfrog oil. The main constituents are oleic acid (30%) and eicosapentaenoic acid (17.6%), which are monounsaturated and polyunsaturated fatty acids respectively. Oxidative stability was determined in the presence or absence of the antioxidants BHA (butylhydroxyanisole) and BHT (butylhydroxytoluene) at 60 ? 2 ? C for 15 days and at room temperature for 120 days. Values of acidity, peroxide, iodine and saponification; conjugated dienes and trienes, oxidation induction time (Rancimat?) and changes in the infrared spectra were measured. The bullfrog oil oxidation rate was dependent on temperature, and the oil became more stable in the presence of BHT. During the oil oxidation, significant changes in the ultraviolet visible absorption spectrum and infrared were observed. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the oil was stable up to 200 ?C.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-13T20:29:52Z No. of bitstreams: 1 AndreLuizSilvaDavim_TESE.pdf: 2927049 bytes, checksum: c70bf3fe6cd0580d21ea07690845a8e8 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-19T14:43:48Z (GMT) No. of bitstreams: 1 AndreLuizSilvaDavim_TESE.pdf: 2927049 bytes, checksum: c70bf3fe6cd0580d21ea07690845a8e8 (MD5) / Made available in DSpace on 2017-06-19T14:43:48Z (GMT). No. of bitstreams: 1 AndreLuizSilvaDavim_TESE.pdf: 2927049 bytes, checksum: c70bf3fe6cd0580d21ea07690845a8e8 (MD5) Previous issue date: 2017-02-23 / Atualmente os custos no tratamento de pacientes com doen?as inflamat?rias que progridem de forma sist?mica, com destaque para a sepse, s?o muito elevados e representa a maior causa de morte em unidades de terapia intensiva, n?o cardiol?gica, em todo o mundo. No Brasil, a incid?ncia de pacientes com sepse ? cada vez mais frequente. Apesar dos avan?os farmacol?gicos, tecnol?gicos e cir?rgicos, a mortalidade por sepse e/ou doen?as associadas continua alta em todo o mundo, e por isso se busca alternativas terap?uticas de f?cil acesso e baixo custo para conter o avan?o dessa doen?a. Os produtos naturais v?m desempenhando importante papel na ind?stria farmac?utica, pois algumas dessas subst?ncias agem de forma ben?fica sobre o sistema imunol?gico humano. Nos ?ltimos tempos, h? uma crescente investiga??o das poss?veis propriedades biol?gicas e terap?uticas atribu?das ao ?leo de r?-touro, pois esse ?leo vem sendo utilizado de forma indiscriminada pela popula??o no tratamento de diversas doen?as como bronquite, asma, l?quem escleroso, furunculose, cisto seb?ceo e para cicatriza??o de pele e mucosas. Por?m as poss?veis consequ?ncias no consumo excessivo desse ?leo s?o, o aumento da produ??o de eicosanoides derivados do ?cido araquid?nico proinflamat?rio e a defici?ncia na regula??o hep?tica, predispondo ? esteatose podendo progredir para inflama??o hep?tica e fibrose. Muitas hip?teses se baseiam na atua??o dos compostos presentes no ?leo de r?-touro na modula??o da resposta inflamat?ria, impedindo assim a instala??o de inj?rias teciduais. Dessa forma, a microemuls?o apresenta-se como uma poss?vel alternativa para um novo sistema de libera??o de f?rmacos, com o intuito de diminuir a incid?ncia de hepatoxicidade e protegendo o organismo contra instala??o de les?es teciduais em fun??o do quadro s?ptico. Assim, o presente estudo teve como objetivo avaliar o potencial anti-inflamat?rio do ?leo de r?-touro puro e em um sistema microemulsionado em modelo experimental. Neste estudo, foi preparado e caracterizado um sistema microemulsionado (WIV) e, aplicado em ensaios biol?gicos a fim de avaliar o potencial antiinflamat?rio do ?leo puro e em microemuls?o. Foram utilizados o modelo de sepse, induzida pela t?cnica da CLP (cecal ligant puncture), e a les?o muscular induzida pela formalina. Os ensaios foram realizados em modelos murinos, onde os animais foram separados aleatoriamente em grupos e tratados com o ?leo de r?-touro puro e em microemuls?o, atrav?s da t?cnica de gavage para posterior avalia??o do potencial hepatot?xico e anti-inflamat?rio. Para a an?lise do potencial antiinflamat?rio em modelo de sepse, foram realizadas lavagens bronco alveolares com posterior contagem de c?lulas inflamat?rias e an?lises histopatol?gicas do tecido pulmonar. Para a an?lise no modelo de les?o muscular, foi avaliado extens?o horizontal da pata dos animais, bem como feita a an?lise histopatol?gica do tecido muscular. Para a an?lise do potencial hepatot?xico das subst?ncias, foram avaliados a taxa de sobrevida dos animais p?s-sepse e as an?lises histopatol?gicas dos tecidos hep?ticos dos animais. Quando avaliado a toxicidade do ?leo de r?-touro puro e em sistema microemulsionado, foi observado que no grupo em que foi administrado a microemuls?o (ME), o f?gado teve a arquitetura preservada, mas com sinais cl?nicos de esteatose hep?tica, diferentemente do grupo ?leo de r?-touro puro (OR), que apresentou m?ltiplos focos de necrose hepatoc?tica acompanhado de infiltrado de polimorfonucleares. Esses achados evidenciam um quadro de esteatohepatite, ou seja, um est?gio mais avan?ado e um precursor do carcinoma hep?tico. Quando avaliada a sobrevida dos animais, foi observado que no grupo ME a taxa foi significativamente maior quando comparado ao grupo OR. Quando avaliado o potencial antiinflamat?rio da ME e OR em modelo de sepse, foi observado em ambos os grupos potencial de modula??o da resposta inflamat?ria, visto a capacidade de reduzir de forma significativa (P?0.01) a migra??o de leuc?citos para os pulm?es ap?s a indu??o da sepse. Quando analisado a histologia dos tecidos pulmonares dos animais dos dois grupos, foi verificado intenso desgaste nos animais do grupo OR quando comparados com o grupo ME, onde evidenciou-se pouco comprometimento tecidual. No ensaio de les?o muscular, foi observado que o grupo ME e OR apresentaram bom potencial antiedematog?nico at? a segunda hora da indu??o da les?o, quando comparados ao grupo controle (P?0.01), mas n?o sendo observado diferen?as significativas entre os dois grupos at? a vig?sima quarta hora p?s-les?o. Nas an?lises histol?gicas foram observadas maior desgaste no tecido muscular do grupo OR, com intensa presen?a de infiltrado celular (edema) e comprometimento de fibras musculares, n?o sendo observado a mesma intensidade de inj?ria no grupo ME. Assim, conclui-se que o ?leo de r?-touro puro e em sistema microemulsionado apresentam bom potencial anti-inflamat?rio nos modelos avaliados, embora o ?leo puro tenha apresentado alto potencial hepatot?xico, caracterizando que este em um sistema microemulsionado, se mostra com um poss?vel novo sistema de libera??o de f?rmacos (NSLF). / Current costs of treating patients with systemically progressing inflammatory diseases, especially sepsis, are the leading cause of death in non-cardiological intensive care units worldwide. In Brazil, the incidence of sepsis in patients is becoming more frequent. Despite pharmacological, technological and surgical advances, mortality due to sepsis and/or associated diseases remains high worldwide, hence the search for easily accessible and inexpensive therapeutic alternatives to contain the progression of this disease. Natural products have played an important role in the pharmaceutical industry because some of these substances act in a beneficial way on the human immune system. In recent times, there is a growing investigation of the possible biological and therapeutic properties attributed to bullfrog oil, since this oil has been used indiscriminately by the population in the treatment of various diseases, such as bronchitis, asthma, lichen sclerosus, furunculosis, sebaceous cyst, and for healing of skin and mucous membranes. However, the possible consequences of excessive consumption of this oil are increased production of eicosanoids derived from proinflammatory arachidonic acid and deficiency in hepatic regulation, predisposing to steatosis, which may progress to hepatic inflammation and fibrosis. Many hypotheses are based on the performance of the compounds present in bullfrog oil in the modulation of the inflammatory response, thus preventing the onset of tissue injuries. The microemulsion is presented as a possible alternative to a new drug delivery system, in order to reduce the incidence of hepatotoxicity and protect the organism against the installation of tissue lesions as a function of the septic condition. The present study is aimed to evaluate the anti-inflammatory potential of pure bullfrog oil and a microemulsion system in an experimental model. In this study, a microemulsified system (WIV) was determined and characterized, and applied in biological tests to evaluate the anti-inflammatory potential of pure oil and microemulsion. We used the sepsis model, induced by cecal ligant puncture (CLP) technique, and the formalin-induced muscle injury. The tests were performed in murine models, where the animals were randomly separated into groups and treated with pure bullfrog oil and microemulsion, using the gavage technique for further evaluation of the hepatotoxic and anti-inflammatory potential. For the analysis of the anti-inflammatory potential in a sepsis model, bronchoalveolar lavage was performed with subsequent inflammatory cell counts and histopathological analyzes of lung tissue. For the analysis in the muscle injury model, the horizontal extension of the limbs of the animals was evaluated, as well as the histopathological analysis of the muscle tissue. For the analysis of the hepatotoxic potential of the substances, the post-sepsis survival rate and the histopathological analyzes of the hepatic tissues of the animals were evaluated. When evaluating the toxicity of pure bullfrog oil and in a microemulsion system, it was observed that in the group that received the microemulsion (ME), the liver had the architecture preserved, but with clinical signs of hepatic steatosis, unlike the pure bullfrog oil group, which presented multiple outbreaks of hepatocytic necrosis accompanied by polymorphonuclear infiltrates. These findings indicate a picture of steatohepatitis, that is, a more advanced stage and a precursor of hepatic carcinoma. When evaluating the survival of the animals, it was observed that the ME group survival rate was significantly higher when compared to the oil group. When evaluating the anti-inflammatory potential of the ME and the oil group in a sepsis model, the potential for modulation of the inflammatory response was observed in both groups, since the leukocyte migration to the lungs was significantly reduced (P<0.01) after the induction of sepsis. When analyzing the histology of the lung tissues of the animals of both groups, intense wear was observed in the animals of the oil group, when compared with the ME group, where there was little tissue compromise. In the muscle injury test, it was observed that the ME and oil group had good anti-nematode potential until the second hour of injury induction, when compared to the control group (P<0.01), but no significant differences were observed between the two groups until twenty-fourth hour post-injury. In the histological analyzes, greater wear was observed in the oil group muscle tissue, with an intense presence of cellular infiltrate (edema) and muscle fibers involvement, and the same intensity of injury was not observed in the ME group. Thus, it is concluded that pure bullfrog oil and microemulsion system present good anti-inflammatory potential in the evaluated models, although the pure oil showed high hepatotoxic potential, characterizing that in a microemulsified system, it is shown with a possible new drug delivery system (NSLF).

Made available in DSpace on 2014-12-17T14:16:33Z (GMT). No. of bitstreams: 1 EvertonNA_DISSERT.pdf: 1792705 bytes, checksum: 2091882fa52265fca623e2d01c142cfa (MD5) Previous issue date: 2013-06-10 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Natural oils have shown a scientific importance due to its pharmacological activity and renewable character. The copaiba (Copaifera langsdorffii) and Bullfrog (Rana catesbeiana Shaw) oils are used in folk medicine particularly because the anti-inflammatory and antimicrobial activities. Emulsion could be eligible systems to improve the palatability and fragrance, enhance the pharmacological activities and reduce the toxicological effects of these oils. The aim of this work was to investigate the antimicrobial activity of emulsions based on copaiba (resin-oil and essential-oil) and bullfrog oils against fungi and bacteria which cause skin diseases. Firstly, the essential oil was extracted from copaiba oil-resin and the oils were characterized by gas chromatography coupled to a mass spectrometry (GC-MS). Secondly, emulsion systems were produced. A microbiological screening test with all products was performed followed (the minimum inhibitory concentration, the bioautography method and the antibiofilm determination). Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Candida albicans, C. parapsilosis, C. glabrata, C. krusei and C. tropicalis American Type Culture Collection (ATCC) and clinical samples were used. The emulsions based on copaiba oil-resin and essential oil improved the antimicrobial activity of the pure oils, especially against Staphylococcus e Candida resistant to azoles. The bullfrog oil emulsion and the pure bullfrog oil showed a lower effect on the microorganisms when compared to the copaiba samples. All the emulsions showed a significant antibiofilm activity by inhibiting the cell adhesion. Thus, it may be concluded that emulsions based on copaiba and bullfrog oils are promising candidates to treatment of fungal and bacterial skin infections / Os ?leos naturais v?m chamando aten??o da comunidade cient?fica devido a suas atividades farmacol?gicas e seu car?ter renov?vel. Os ?leos de copa?ba (Copaifera langsdorffii) e de r?-touro (Rana catesbeiana Shaw) ganham destaque, especialmente devido a ampla utiliza??o na medicina popular como anti-inflamat?rios e antimicrobianos. Sistemas emulsionados a base destes ?leos podem ser produzidos com a finalidade de melhorar o odor e a palatabilidade dos mesmos, al?m de potencializar a??o e reduzir toxicidade dos seus componentes. O objetivo deste trabalho foi investigar a atividade antimicrobiana de emuls?es contendo ?leos de copa?ba (?leo-resina e ?leo essencial) e ?leo de r?-touro frente a cepas de micro-organismos causadores de infec??es cut?neas. Inicialmente, foi realizada a extra??o de ?leo essencial e sua caracteriza??o qu?mica por cromatografia gasosa acoplada a espectroscopia de massas. Em seguida, foram produzidas emuls?es, ensaios de triagem microbiol?gica, microdilui??o para determina??o de concentra??o inibit?ria m?nima, bioautografia para determina??o dos componentes antimicrobianos e avalia??o da atividade antibiofilme. Foram utilizadas cepas da American Type Culture Collection (ATCC) e cl?nicas de Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Candida albicans, C. parapsilosis, C. glabrata, C. krusei e C. tropicalis. Foi observado que os sistemas emulsionados de ?leo-resina de copa?ba e ?leo essencial de copa?ba contribu?ram na potencializa??o da atividade antimicrobiana, especialmente contra cepas do g?nero Staphylococcus e Candida resistentes aos az?is. A emuls?o de ?leo de r?-touro assim como o ?leo puro, apresentou menor atividade que as amostras de copa?ba, por?m exibiu significativa a??o antibiofilme, demonstrando que este sistema ? um potencial inibidor da ades?o de micro-organismos. Deste modo, pode-se inferir que as emuls?es a base destes ?leos s?o promissores sistemas para o tratamento de infec??es cut?neas f?ngicas e bacterianas