Made available in DSpace on 2016-04-28T20:18:32Z (GMT). No. of bitstreams: 1 2009 - Priscila Andrade Pires.pdf: 1237061 bytes, checksum: 6489ca08dab0e701c25ed611f45a365e (MD5) Previous issue date: 2009-08-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Nonsteroidal anti-inflammatory drugs (NSAID) are widely using in veterinary medicine, having analgesic and anti-inflammatory activity, including reduction of oedema and antipyretic actions. They inhibit the cyclooxygenase enzime (COX). There are two isoforms of COX that are responsible for synthesis of prostaglandins. The COX I is usually a constitutive enzyme expressed in tissues. Prostaglandins, prostacyclin, and thromboxane synthesized by this enzyme are responsible for normal physiologic functions. COX II, on the other hand, is inducible and synthesized by inflammatory cells after stimulation by cytokines and other mediators of inflammation. In some tissues COX II may be constitutive as central nervous system and kidney. All NSAID can cause adverse side effects and their selective degree will be important for the ocurrence of undesirable reaction. The aim of this study was to evaluate the analgesic, antioedematogenic and antipyretic activity of some antiinflammatory used in veterinary clinics, the nonselective drugs, flunixin meglumine (FM) and ketoprofen (CT); the COX II preferential, meloxicam (MX) and carprofen (CP); and COX II selective, firocoxib, after oral administration, as well as their ulcerogenic activity in gastric mucosa, allowing a comparative analyses of their antinociceptive and/or anti-inflammatory actions and their adverse side effects, helping veterinary doctor in the choose of the drug that have better relation cost/risk/benefit of this drugs. To assess the antioedematogenic effect in croton oil-induced mice ear oedema method, the CT (ID50: 3,6 mg/kg) was the most potent drug, followed by CP and FM (ID50: 12,3 and 17,8 mg/kg, respectively). The MX and FC, despite of their effectiveness, showed low activity, didn t producing sufficient effects for determination the ID50 in maximal dose (30 mg/kg). In LPS induced fever in rats, the FC produced antipyretic activity with ID50 2,9 mg/kg, accompanied by CT, CP and FM (ID 50: 3,3; 3,6 and 4 mg/kg, respectively) and with greater dose of meloxicam (ID 50: 30 mg/kg). Evaluating the antinociceptive effect in the acetic acid-induced abdominal writhing model of analgesia in mice, the MX was the most effective drug (ID50: 0,09 mg/kg), followed by FM, FC, CP and CT (ID50: 0,4; 1,9; 2,3; 3,6, respectively), and using this ID50 in the evaluation of ulcerogenic action of this drugs in mice, the FC, FM and MX didn t induce significative gastric injury in 3o and 7o day of treatment. The CT and CP induced ulceration in 3o day, being the CT most intense. However in 7o day, we didn t notice gastric injury, suggesting that adapted gastric mucosa produces increased resistance to subsequent damage by this class of drugs. This results reveal that analgesic activity of almost all of this NSAID is independent of this antiodematogenic and antipyretic actions. The CT has similar ID50 in all pharmacological assays in this study. The gastric ulcerogenic activity has inverse ratio when compared with analgesic effects. / Os anti-inflamat?rios n?o esteroidais (AINES) s?o drogas amplamente usadas na medicina veterin?ria, tendo a??o analg?sica, anti-inflamat?ria, incluindo a redu??o do edema e antipir?tica. Agem inibindo a enzima cicloxigenase (COX), n?o havendo a forma??o de prostan?ides, e os efeitos colaterais promovidos pelos AINES tornam limitante o seu uso. H? duas isoformas de COX: a COX-I, constitutivamente nos tecidos e respons?vel pelas fun??es fisiol?gicas; e a COX-II, induzida ap?s est?mulos inflamat?rios, ?lgicos e t?rmicos. Dessa forma, entendeu-se que o uso de AINES seletivos para a COX-II, diminuiria os efeitos adversos desses f?rmacos, uma vez que garantiria as fun??es homeost?ticas da COX-I. Atualmente, sabe-se que a COX-II tamb?m est? presente constitutivamente em alguns tecidos como o sistema nervoso central e rim. Dessa forma, todos os AINEs podem causar efeitos adversos em maior ou menor intensidade, e o grau de seletividade de cada f?rmaco ser? determinante na ocorr?ncia de rea??es indesej?veis. O objetivo desse trabalho foi avaliar o potencial analg?sico, anti-edematog?nico e antipir?tico dos principais AINES utilizados em medicina veterin?ria, os COX n?o seletivos flunixim meglumine (FM) e cetoprofeno (CT); os COX-II preferenciais meloxicam (MX) e carprofeno (CP) e o COX-II seletivo firocoxibe (FC) ap?s a administra??o oral, bem como a atividade ulcerog?nica sobre a mucosa g?strica, tendo-se assim uma avalia??o comparativa tanto de seu efeito antinociceptivo e/ou antiinflamat?rio, como de rea??es indesej?veis; subsidiando o m?dico veterin?rio cl?nico, no estabelecimento da rela??o custo/benef?cio desses f?rmacos. No teste do edema de orelha induzido pelo ?leo de cr?ton em camundongos, o CT (ID50 = 3,6 mg/kg) foi ? droga mais potente, seguido do CP e FM (ID50 = 12,3 e 17,8 mg/kg, respectivamente). O MX e FC, apesar de efetivos, mostraram baixa atividade n?o produzindo efeito suficiente com a dose m?xima de 30mg/kg, para a determina??o da ID50. Na febre induzida pelo LPS em ratos, o FC produziu atividade antipir?tica com ID50 = 2,9 mg/kg, acompanhado do CT, CP e FM (ID50 = 3,3; 3,6 e 4 mg/kg, respectivamente) e com maiores doses do MX (ID50 = 17,8 mg/kg). Avaliando o potencial analg?sico pelo m?todo das contor??es abdominais com ?cido ac?tico em camundongos, o MX foi o mais potente (ID50 = 0,09 mg/kg), seguido do FM, FC, CP e CT (ID50 = 0,4; 1,9; 2,3 e 3,6 mg/kg, respectivamente) e, utilizando estas ID50 na avalia??o da atividade ulcerog?nica em camundongos, o FC, FM e MX n?o produziram efeitos g?stricos significativos no 3? ou no 7? dia dos tratamentos. O CT e o CP promoveram ulcera??es no 3? dia, sendo o CT de forma mais intensa; n?o se observando altera??es g?stricas no 7? dia, podendo esse efeito estar relacionado ao desenvolvimento de toler?ncia aos danos causados por essa classe de drogas na mucosa. Esses resultados revelam que a atividade analg?sica da quase totalidade desses f?rmacos independe da atividade antiedematog?nica e antipir?tica, tendo o CT revelado ID50 semelhantes em todos os testes farmacol?gicos. A atividade ulcerog?nica g?strica evidenciada, teve rela??o inversa com a atividade analg?sica de todos esses f?rmacos.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-22T19:30:53Z No. of bitstreams: 1 MairaConceicaoJeronimoDeSouzaLima_TESE.pdf: 6599799 bytes, checksum: 12ec2e74167618ab1f1b22a3284a60a5 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-23T23:43:41Z (GMT) No. of bitstreams: 1 MairaConceicaoJeronimoDeSouzaLima_TESE.pdf: 6599799 bytes, checksum: 12ec2e74167618ab1f1b22a3284a60a5 (MD5) / Made available in DSpace on 2016-03-23T23:43:41Z (GMT). No. of bitstreams: 1 MairaConceicaoJeronimoDeSouzaLima_TESE.pdf: 6599799 bytes, checksum: 12ec2e74167618ab1f1b22a3284a60a5 (MD5) Previous issue date: 2015-04-17 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Envenenamentos causados por animais pe?onhentos s?o um grave problema de sa?de p?blica, enquadrando-se nesse cen?rio, principalmente, os escorpi?es e as serpentes. Tityus serrulatus ? considerado o escorpi?o mais venenoso da America do Sul, devido ? alta toxicidade do seu veneno, respons?vel por causar acidentes graves, principalmente em crian?as. A esp?cie Bothrops jararaca ? uma serpente que possui no seu veneno uma mistura complexa de enzimas, pept?deos e outras mol?culas. As toxinas do veneno de B. jararaca induzem respostas inflamat?rias locais e sist?micas. O tratamento de escolha para os casos graves de envenenamento ? a administra??o intravenosa do antiveneno especifico. Por?m, nem sempre esse tratamento est? acess?vel para os moradores de zonas rurais, que fazem uso de extratos de plantas medicinais. Nesse contexto, extratos aquosos, fra??es e compostos isolados de Aspidosperma pyrifolium (pereiro) e Ipomoea asarifolia (salsa), usadas na medicina popular, foram objeto de estudo deste trabalho para avaliar a atividade anti-inflamat?ria nos modelos de peritonite induzida por carragenina e peritonite induzida pelo veneno de T. serrulatus (VTs), e nos no modelo de edema local e infiltrado inflamat?rio induzido pelo veneno de B. jararaca, administrados pela via intravenosa. Os resultados dos ensaios de citotoxidade utilizando o ensaio MTT demonstraram que os extratos aquosos das esp?cies vegetais apresentaram baixa toxicidade para c?lulas provenientes de fibroblasto de embri?o de camundongo (3T3). A an?lise qu?mica dos extratos por Cromatografia L?quida de Alta Efici?ncia revelou a presen?a do flavon?ide rutina, na A. pyrifolium, e rutina, ?cido clorog?nico e ?cido caf?ico, na I. asarifolia. Quanto ? avalia??o farmacol?gica, os resultados demonstraram que o pr?-tratamento com extratos aquosos e fra??es reduziram a migra??o de leuc?citos totais para a cavidade abdominal no modelo de peritonite causada por carragenina e no modelo de peritonite induzida por veneno de T. serrulatus. Ainda, esses grupos apresentaram atividade antiedematog?nica, no modelo de edema local causado pelo veneno de B. jararaca, e reduziram o infiltrado inflamat?rio para o m?sculo. Os soros (antiaracn?dico e anti-botr?pico) espec?ficos para cada veneno atuaram inibindo a a??o inflamat?ria dos venenos e foram utilizados como controles. Os compostos identificados nos extratos, rutina, ?cido clorog?nico e ?cido caf?ico, tamb?m foram testados e, assim como os extratos das plantas, exibiram efeitos anti-inflamat?rios significativos, nas doses testadas. Dessa forma, esses resultados d?o evid?ncias, ?s plantas estudadas, de potencial atividade anti-inflamat?ria. Esse ? o primeiro estudo que avaliou os poss?veis efeitos terap?uticos de A. pyrifolium e I. asarifolia, mostrando o potencial terap?utico que essas esp?cies possuem. / Envenomation caused by venomous animals, mainly scorpions and snakes, are a serious matter of public health. Tityus serrulatus is considered the most venomous scorpion in South America because of the high level of toxicity of its venom. It is responsible for causing serious accidents, mainly with kids. The species Bothrops jararaca is a serpent that has in its venom a complex mixture of enzyme, peptides and other molecules. The toxins of the venom of B. jararaca induce local and systemic inflammatory responses. The treatment chosen to serious cases of envenomation is the intravenous administration of the specific antivenom. However, the treatment is not always accessible to those residents in rural areas, so that they use medicinal plant extracts as the treatment. In this context, aqueous extracts, fractions and isolated compounds of Aspidosperma pyrifolium (pereiro) and Ipomoea asarifolia (salsa, salsa-brava), used in popular medicine, were studied in this research to evaluate the anti-inflammatory activity in the peritonitis models induced by carrageenan and peritonitis induced by the venom of the T. serrulatus (VTs), and in the local oedema model and inflammatory infiltrate induced by the venom of the B. jararaca, administrated intravenously. The results of the assays of cytotoxicity, using the MTT, showed that the aqueous extracts from the plant species presented low toxicity to the cells that came from the fibroblast of the mouse embryo (3T3).The chemical analysis of the extracts by High Performance Liquid Chromatography revealed the presence of the rutin flavonoid, in A. pyrifoliu, and rutin, clorogenic acid and caffeic acid, in I. asarifolia. Concerning the pharmacological evaluation, the results showed that the pre-treatment using aqueous extracts and fractions reduced the total leukocyte migration to the abdominal cavity in the peritonitis model caused by the carrageenan and in the peritonitis model induced by the T. serulatus venom. Yet, these groups presented anti-oedematous activity, in the local oedema model caused by the venom of the B. jararaca, and reduced the inflammatory infiltrate to the muscle. The serum (anti-arachnid and anti-bothropic) specific to each venom acted inhibiting the inflammatory action of the venoms and were used as control. The compounds identified in the extracts were also tested and, similar to the plant extracts, showed meaningful anti-inflammatory effects, in the tested doses. Thus, these results are indicating the potential anti-inflammatory activity of the plants studied. This is the first research that evaluated the possible biological effects of the A. pyrifolium and I. asarifolia, showing the biological potential that these species have.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-08-01T13:42:41Z No. of bitstreams: 1 WalterFerreiraDaSilvaJunior_DISSERT.pdf: 3681902 bytes, checksum: c77d069eecf2bb854fb8c1277fa8cd8c (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-08-07T12:31:10Z (GMT) No. of bitstreams: 1 WalterFerreiraDaSilvaJunior_DISSERT.pdf: 3681902 bytes, checksum: c77d069eecf2bb854fb8c1277fa8cd8c (MD5) / Made available in DSpace on 2017-08-07T12:31:10Z (GMT). No. of bitstreams: 1 WalterFerreiraDaSilvaJunior_DISSERT.pdf: 3681902 bytes, checksum: c77d069eecf2bb854fb8c1277fa8cd8c (MD5) Previous issue date: 2017-05-31 / ?, ? amirina (ABAM) ? uma mistura natural de triterpenos pentac?clicos que possui v?rias atividades biol?gicas, incluindo o efeito anti-inflamat?rio. ? isolada das esp?cies da fam?lia Burseraceae, nas quais a esp?cie Protium heptaphyllum ? a esp?cie mais comumente encontrada na Amaz?nia brasileira. A forma??o de complexo de inclus?o (CI) com a ciclodextrina (CD) e dispers?es s?lidas (DS) com pol?meros hidrof?licos t?m sido aplicadas como alternativas para resolver algumas limita??es que novas entidades qu?micas (NEQ) t?m em comum, principalmente a baixa solubilidade em meios aquosos. Ent?o, o objetivo deste trabalho foi desenvolver CI?s da ABAM (ABAM) com a ?-ciclodextrina (?CD) e com a hidroxipropil-?-ciclodextrina (HP?CD) e DS com a hidroximetilcelulose (HPMC), polietilenoglicol (PEG 6000) e a polivinilpirrolidona (PVP k-30) a fim de melhoras suas propriedades f?sico-qu?mica para torna-la vi?vel numa futura formula??o. Inicialmente, para os CI, foram realizados estudos te?ricos computacionais nos quais foram calculadas as energias de intera??o entre a ?CD e a ABAM e HP?CD e ABAM. Em seguida, foram desenvolvidos os CI?s com ?CD e HP?CD pelos m?todos de mistura f?sica (MF) e malaxagem (MAL). Foi realizada a caracteriza??o f?sico-qu?mica dos CI atrav?s de espectroscopia de infravermelho com transformada Fourier (FTIR), microscopia eletr?nica de varredura (MEV), difra??o de raio-X de p? (DRX), an?lise termogravim?trica (ATG) e calorimetria explorat?ria diferencial (DSC). As DS foram obtidas atrav?s da MF, MAL e RE com o HPMC, PEG e o PVP. Foram utilizadas as mesmas t?cnicas de caracteriza??o que foram realizadas para os CI. Al?m da caracteriza??o para as DS, realizou-se a atividade anti-inflamat?ria in vitro e foram comparadas em rela??o ? suas atividades anti-inflamat?rias com a ABAM. Os estudos de caracteriza??o mostraram a forma??o de CI entre a ABAM e as CD e a forma??o de dispers?es s?lidas entre a ABAM e os pol?meros hidrof?licos. No ensaio de atividade das DS, verificou-se que comparando o efeito, mesma dose da ABAM e mesma dose da DS, tanto as DS quanto a ABAM tiveram atividade anti-inflamat?ria sobre macr?fagos ativados por LPS. Portanto, as DS e CI com ABAM s?o alternativas eficazes para modificar suas caracter?sticas, melhorando propriedades que possam interferir numa futura formula??o terap?utica. / ?, ? amyrin (ABAM) is a natural mixture of triterpenes pentacyclis which has various biological activities, including the anti-inflammatory effect. Are isolated from the species in the family Burseraceae, in which the species Protium heptaphyllum is more commonly found in the brazilian Amazon. The inclusion complexes formation (IC) with the cyclodextrin (CD) and solid dispersions (SD) with hydrophilic polymers have been applied as alternatives to solve some limitations that new chemical entities (NCE) have in common, mainly the low solubility in aqueous environments. So, the objective of this work was to develop IC's the ABAM (ABAM) with ?-cyclodextrin (?CD) and hydroxypropyl-?-cyclodextrin (HP?CD) and SD with the hidroximetilcelulose (HPMC), polyethylene glycol (PEG 6000) and polyvinylpyrrolidone (PVP-30 k). Initially, for the IC, computational theoretical studies were carried out in which interaction energies were calculated between the ?CD and the ABAM and HP?CD and ABAM. Then, the IC's have been developed with ?CD and HP?CD by mixing physical methods (MF) and kneading (KND). The physical and chemical characterization of IC's using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), x-ray diffraction (DRX), thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The DS were obtained through the MF, KND and RE with HPMC, PEG and the PVP. Held the same characterization techniques that were held for the IC. Beyond characterization to the DS, the anti-inflammatory activity in vitro and were compared with respect to their anti-inflammatory activities with the ABAM. The characterization studies showed the formation of CI between the ABAM and the CD and the formation of solid dispersions between the ABAM and hydrophilic polymers. In the activity of DS, it was found that comparing the effect, the same dose of ABAM and same dose of the DS, the DS as the ABAM had anti-inflammatory activity on macrophages activated by LPS. Therefore, the DS and CI with ABAM are effective alternatives to modify their characteristics, improving properties that may interfere in a future therapeutic formulation.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 JonasGabrielDeOliveiraPinheiro_DISSERT.pdf: 2688247 bytes, checksum: d2a64eed33cb23425b53e9d128e55479 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:42:15Z (GMT) No. of bitstreams: 1 JonasGabrielDeOliveiraPinheiro_DISSERT.pdf: 2688247 bytes, checksum: d2a64eed33cb23425b53e9d128e55479 (MD5) / Made available in DSpace on 2017-06-07T19:42:15Z (GMT). No. of bitstreams: 1 JonasGabrielDeOliveiraPinheiro_DISSERT.pdf: 2688247 bytes, checksum: d2a64eed33cb23425b53e9d128e55479 (MD5) Previous issue date: 2017-03-31 / As ?rvores da esp?cie Copaifera multijuga Hayne crescem abundantemente na regi?o da Amaz?nia, apresentando grande visibilidade por seu ?leo-resina, que apresenta atividade anti-inflamat?ria. A forma??o de complexo de inclus?o (CI) com a ciclodextrina (CD) tem sido aplicada como alternativa para resolver algumas limita??es que os ?leos tem em comum, principalmente a baixa solubilidade em ambientes aquosos. Ent?o, o objetivo deste trabalho foi desenvolver CI?s do ?leo-resina de Copaifera multijuga (OCM) com a ?-ciclodextrina (?CD) e com a hidroxipropil-?-ciclodextrina (HP?CD) e avaliar a atividade anti-inflamat?ria deles. Inicialmente, foram realizados estudos te?ricos computacionais nos quais foram calculadas as energias de intera??o entre a ?CD e o ?-cariofileno (?CF), composto mais abundante do OCM. Em seguida, foram preparados os CI?s com ?CD e HP?CD pelos m?todos da mistura f?sica (MF), malaxagem (MAL) e co-precipita??o (CP). Foi realizada a caracteriza??o f?sico-qu?mica dos CI?s por espectroscopia de absor??o na regi?o do infravermelho com transformada Fourier (FTIR), microscopia eletr?nica de varredura (MEV), difra??o de raios X pelo m?todo do p? (DRX), an?lise termogravim?trica (TG) e calorimetria explorat?ria diferencial (DSC). Por fim, os CI?s de ?CD e HP?CD foram comparadas em rela??o ? suas atividades anti-inflamat?rias com o OCM puro. Os estudos te?ricos computacionais mostraram valores energ?ticos de -20,8 kcal?mol-1 e -17,0 kcal?mol-1 da complexa??o com a face menor e com a face maior do ?CF, respectivamente, entrando pela cavidade maior da ?CD. Pelo FTIR, foi poss?vel observar que ocorreu a intera??o entre a ?CD e o OCM por MAL e CP, e entre a HP?CD e o OCM, pelo CP. Na MEV, na DRX e na TG, foi poss?vel concluir que houve intera??o entre a ?CD e o OCM por MAL e CP. No caso da DSC foi observado que ocorreu intera??o entre a ?CD e o OCM e entre a HP?CD e o OCM pelos dois m?todos. O OCM e os CI?s de ?CD e de HP?CD (preparados por CP) mostraram evidente atividades anti-inflamat?rias pela diminui??o do edema de pata, nos n?veis de nitrito e da atividade da enzima mieloperoxidase, evidenciando que os CI?s do OCM com a ?CD e a HP?CD mantiveram a atividade anti-inflamat?ria do OCM. / Copaifera multijuga Hayne trees grows abundantly in Amazon region, presenting wide visibility for its oleoresin, which shows anti-inflammatory activity. The inclusion complex (IC) formation with cyclodextrin (CD) has been applied as alternative to solve some limitations that oils have in common, principally the poor aqueous solubility. Thus, this work aimed the ICs development of Copaifera multijuga oleoresin (CMO) with ?-cyclodextrin (?CD) and with hydroxypropyl-?-cyclodextrin (HP?CD) and evaluating of its anti-inflammatory activities. Initially, it were realized computational theoretical studies, in which were calculated the interaction energies between ?CD e o ?-caryophyllene (?CP), most abundant compound in CMO. Next, it were prepared ?CD and HP?CD IC?s by physical mixture, kneading method (KND) and slurry method (SL). ICs physical-chemical characterization was realized by Fourier transform infrared absorption region spectroscopy (FTIR), scanning electronic microscopy (SEM), powder X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Finally, ?CD and HP?CD IC?s were compared to pure CMO, in relation to its anti-inflammatory activity. Computational theoretical studies showed energetic values of -20.8 kcal?mol-1 and -17.0 kcal?mol-1 of complexation with ?CP minor and lager face, respectively, entering through the ?CD larger cavity side. In FTIR, it was possible observing that occurred interaction between ?CD and CMO by KND and SL, and between HP?CD and CMO by SL. In SEM, in XRD and in TGA, it was possible conclude that there was interaction between ?CD and CMO by KND and SL. In DSC case, it was observed that occurred interaction between ?CD and CMO and between HP?CD and CMO by KND and SL. CMO and ?CD and HP?CD ICs showed evident anti-inflammatory activity by paw edema, nitrite concentration and myeloperoxidase activity decreasing, evidencing that ICs of CMO with ?CD and HP?CD, which keeping the CMO anti-inflammatory activity.