Made available in DSpace on 2014-12-17T14:10:19Z (GMT). No. of bitstreams: 1 MagalyLM.pdf: 1867638 bytes, checksum: 80b497f52832062348a84e06f5fb5e32 (MD5) Previous issue date: 2009-05-14 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Malaria, also popularly known as maleita , intermittent fever, paludism, impaludism, third fever or fourth fever, is an acute infectious febrile disease, which, in human beings, is caused by four species: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Malaria, one of the main infectious diseases in the world, is the most important parasitoses, with 250 million annual cases and more than 1 million deaths per year, mainly in children younger than live years of age. The prophylactic and therapeutic arsenal against malaria is quite restricted, since all the antimalarials currently in use have some limitation. Many plant species belonging to several families have been tested in vivo, using the murine experimental model Plasmodium berghei or in vitro against P. falciparum, and this search has been directed toward plants with antithermal, antimalarial or antiinflammatory properties used in popular Brazilian bolk medicine. Studies assessing the biological activity of medicinal plant essential oils have revealed activities of interest, such as insecticidal, spasmolytic and antiplasmodic action. It has also been scientifically established that around 60% of essential oils have antifungal properties and that 35% exhibit antibacterial properties. In our investigation, essential oils were obtained from the species Vanillosmopsis arborea, Lippia sidoides and Croton zethneri which are found in the bioregion of Araripe-Cear?. The chemical composition of these essential oils was partially characterized and the presence of monoterpenes and sesquiterpenes. The acute toxicity of these oils was assessed in healthy mice at different doses applied on a single day and on four consecutive days, and in vitro cytotoxicity in HeLa and Raw cell lines was determined at different concentrations. The in vivo tests obtained lethal dose values of 7,1 mg/Kg (doses administered on a single day) and 1,8 mg/Kg (doses administered over four days) for 50% of the animals. In the in vitro tests, the inhibitory concentration for 50% of cell growth in Hela cell lines was 588 μg/mL (essential oil from C. zethneri after 48 h), from 340-555 μg/mL (essential oil from L. sidoides, after 24 and 48 h). The essential oil from V. arborea showed no cytotoxicity and none of the essential oils were cytotoxic in Raw cell lines. These data suggest a moderate toxicity in the essential XVIII oils under study, a finding that does not impede their testing in in vivo antimalarial assays. Was shown the antimalarial activity of the essential oils in mice infected with P. berghei was assessed. The three species showed antimalarial activity from 36%-57% for the essential oil from the stem of V. arborea; from 32%-82% for the essential oil from the leaves of L. sidoides and from 40%-70% of reduction for the essential oil from the leaves of C. zethneri. This is the first study showing evidence of antimalarial activity with these species from northeast Brazil. Further studies to isolate the active ingredients of these oils are needed to determine if a single active ingredient accounts for the antimalarial activity or if a complex integration of all the compounds present occurs, a situation reflected in their biological activity / A mal?ria, tamb?m conhecida popularmente como maleita, febre intermitente, paludismo, impaludismo, febre ter?? ou febre quart?, ? uma doen?a infecciosa febril aguda e, em seres humanos, ? causada por quatro esp?cies de plasm?dios: Plasmodium falciparum, P. vivax, P. malariae e P. ovale. A mal?ria permanece como uma das principais doen?as infecciosas no mundo, sendo a mais importante parasitose, com 250 milh?es de casos anuais e mais de 1 milh?o de mortes por ano, principalmente em crian?as menores de cinco anos. O arsenal profil?tico e terap?utico contra a mal?ria est? bastante restrito, pois todos os antimal?ricos em uso atualmente apresentam alguma limita??o. Muitas esp?cies vegetais pertencentes a v?rias fam?lias foram testadas in vivo usando o modelo experimental murino Plasmodium berghei ou in vitro contra o P. falciparum, e essa busca tem sido orientada para plantas usadas no folclore popular brasileiro como antit?rmicas e/ou antimal?ricas ou com atividade antiinflamat?ria. Estudos sobre a avalia??o da atividade biol?gica dos ?leos essenciais de plantas medicinais t?m revelado atividades de interesse, como a??o inseticida, espasmol?tica e antiplasm?dica. Tem sido ainda, estabelecido cientificamente que cerca de 60% dos ?leos essenciais possuem propriedades antif?ngicas e 35% exibem propriedades antibacterianas. Na presente investiga??o, os ?leos essenciais foram obtidos de Vanillosmopsis arborea (Asteraceae), Lippia sidoides (Verbenaceae) e Croton zethneri (Euphorbiaceae), encontradas na biorregi?o do Araripe-Cear?. A composi??o qu?mica dos ?leos essenciais foi parcialmente caracterizada e revelou a presen?a de monoterpenos e sesquiterpenos. Avaliou-se a toxicidade aguda destes ?leos em camundongos sadios, em diferentes doses aplicadas em um ?nico dia e, em quatro dias consecutivos, como tamb?m, verificou-se a citotoxicidade in vitro em duas linhagens de c?lulas: HeLa e Raw, em diferentes concentra??es. Atrav?s dos ensaios in vivo foi poss?vel obter valores de dose letal de 7,1 mg/Kg (doses administradas em ?nico dia) e de 1,8 mg/Kg (doses administradas por quatro dias). Nos ensaios in vitro, a concentra??o inibit?ria para 50% do crescimento celular em linhagens de c?lulas HeLa foi de 588 μg/mL (?leo essencial de C. zethneri ap?s 48 h), de 340 555 μg/mL (?leo essencial de L. sidoides, ap?s 24 e 48 h). O ?leo essencial de V. XVI arborea n?o apresentou citotoxicidade. Todos os ?leos essenciais n?o foram citot?xicos em linhagens de c?lulas Raw. Estes dados obtidos sugerem uma moderada toxicidade dos ?leos essenciais em estudo, que n?o os impossibilitam a test?-los em ensaios antimal?ricos in vivo. Avaliou-se a atividade antimal?rica dos ?leos essenciais em camundongos infectados com P. berghei. Os ensaios foram realizados em diferentes experimentos. As tr?s esp?cies apresentaram atividade antimal?rica de 36 - 57% para o ?leo essencial do caule de V. arborea; de 32 - 82% para o ?leo essencial das folhas de L. sidoides e de 40 - 70% de redu??o para o ?leo essencial das folhas de C. zethneri. Este ? o primeiro estudo de evid?ncia de atividade antimal?rica com essas esp?cies no nordeste brasileiro. Estudos posteriores para isolamento dos princ?pios ativos destes ?leos s?o necess?rios para constatar se um ?nico princ?pio ativo ? o respons?vel pela atividade antimal?rica ou se ocorre intera??o complexa de todos os compostos presentes, refletindo em sua atividade biol?gica

Made available in DSpace on 2014-12-17T14:10:24Z (GMT). No. of bitstreams: 1 AlineMGCO_DISSERT.pdf: 3644884 bytes, checksum: e2e3e578d2fb797531853d76567fdc2b (MD5) Previous issue date: 2011-03-15 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Resistance of Plasmodium falciparum to the usual antimalarials, as well as their adverse effects and high cost, has led to the search of new drugs against malaria. Several of these have been developed from medicinal plants based on ethnopharmacology, including the most widely used antimalarials today: quinine and artemisinin. In the present study schizonticide activity of extracts and fractions of a number of medicinal plants from the Caatinga and Amazon biomes were assessed based on ethnopharmacological and chemosystematic information. These included Ximenia americana, Maytenus rigida, Sideroxylon obtusifolium, Stryphnodendro coriaceum, Bowdichia virgiliodes, Schinopis brasiliensis and Picrolemma sprucei, the last, an Amazon species. Antimalarial tests of blood schizonticides were conducted in Swiss mice infected with P. berghei and in vitro against P. falciparum. In vitro cytotoxicity studies were carried out using HeLa, CHO, 3T3, Raw and HEPG2 cell lines. Except for X. americana, all species exhibited in vivo or in vitro antimalarial activity, inhibiting parasitic growth by up to 79%. Extracts exhibited moderate toxicity with dosedependent kinetics. In this sense, ethnopharmacological and chemosystematic approaches were shown to be useful and promising tools in the search of new drugs. These findings represent a significant contribution to scientific knowledge of the antimalarial potential of Brazilian flora, thereby opening perspectives for the development of new antimalarials / A resist?ncia do Plasmodium falciparum aos antimal?ricos usuais, bem como os seus efeitos adversos e custo elevado, tornam necess?ria a busca de novos medicamentos contra a mal?ria. Diversos f?rmacos foram descobertos a partir de plantas medicinais com base na etnofarmacologia, inclusive os antimal?ricos mais usados atualmente; quinina e artemisinina. Neste trabalho foi avaliada a atividade esquizonticida de extratos e fra??es de algumas plantas medicinais dos Biomas da Caatinga e Amaz?nico a partir de um referencial etnofarmacol?gico e de quimiossistem?tica. S?o elas: Ximenia americana, Maytenus rigida, Sideroxylon obtusifolium, Stryphnodendro coriaceum, Bowdichia virgiliodes, Schinopis brasiliensis e Picrolemma sprucei, sendo esta ?ltima, uma esp?cie amaz?nica. Os testes antimal?ricos de esquizonticidas sangu?neos foram feitos em camundongos Swiss infectados com P. berghei e in vitro contra o P. falciparum. Estudos de citotoxicidade in vitro foram realizados utilizando as linhagens celulares HeLa, CHO, 3T3, Raw e HEPG2. A excess?o da X. americana, todas as esp?cies apresentaram atividade antimal?rica in vivo ou in vitro, inibindo o crescimento do parasito em at? 79%. Os extratos exibiram toxicidade moderada com cin?tica de atividade dose-dependente. Nesse contexto, a abordagem etnofarmacol?gica associada ao perfil quimiossistem?tico, se mostram ferramentas ?teis e promissoras na busca de novos f?rmacos, permitindo contribuir significativamente para o conhecimento cient?fico do potencial antimal?rico da flora brasileira e deste modo, abrir perspectivas para o desenvolvimento de novos antimal?ricos

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-06-26T17:32:22Z No. of bitstreams: 1 2015 - Thamyris Sampaio Vilela.pdf: 3001387 bytes, checksum: d945149445f8ee2765222f5475c7eaa2 (MD5) / Made available in DSpace on 2017-06-26T17:32:22Z (GMT). No. of bitstreams: 1 2015 - Thamyris Sampaio Vilela.pdf: 3001387 bytes, checksum: d945149445f8ee2765222f5475c7eaa2 (MD5) Previous issue date: 2015-02-27 / CAPES / CNPq / FAPERJ / This study aimed to develop a real-time PCR (qPCR) assay for diagnosis of Plasmodium spp. using as target the 18S rDNA and Cyt b genes. A range of 101 blood samples were collected from Gallus gallus in poultry rustic breeds of in Rio de Janeiro, Brazil. The collected bloods were used to prepare blood smears and to extract the deoxyribonucleic acid (DNA) of these samples. There with, molecular protocols were tested, such as the already published conventional PCR (cPCR) and nested PCR (nPCR), designed for Plasmodium spp. In this study two qPCR protocols were developed using primers targeting the Cyt b and 18S rDNA genes. The qPCR detection limit for both genes was 10 copies of the target DNA, which were higher than the detection limit observed in nPCR and cPCR. In qPCR, 69.30% (n = 70/101) samples were positive targeting 18Sr DNA gene and 59.40% (n = 60/101) samples were positive targeting Cyt b gene. In nPCR and cPCR, 54.45% (n = 55/101) and 52.47% (n= 53/101) samples were positive, respectively. In blood smear microscopy, 31 (30.69%) samples were positive. There was no disagreement between the results (p > 0.05) of qPCR for 18Sr DNA and Cyt b genes. Additionally, qPCR was more sensitive than the other techniques discussed, mostly related to blood smear microscopy (p < 0.05). Therefore, the two qPCR developed in the study showed more sensitivity than other techniques and enabled the detection of Plasmodium spp. in poultry even in low parasitemia. / Este estudo teve como objetivo desenvolver um ensaio de PCR em tempo real (qPCR) para o diagn?stico de Plasmodium spp. utilizando os genes 18S rDNA e cyt b. Foram coletadas 101 amostras de sangue de aves da esp?cie Gallus gallus de cria??o r?stica ou org?nica no munic?pio de Serop?dica, Rio de Janeiro. Os sangues coletados foram utilizados na prepara??o de esfrega?os de sangue e para extra??o do ?cido desoxirribonucl?ico (DNA) destas amostras. Protocolos de ensaios moleculares foram testados, tal como o PCR convencional (cPCR), nestedPCR (nPCR) e qPCR para Plasmodium spp. Neste estudo dois protocolos de qPCR foram desenvolvidos utilizando oligoiniciadores desenhados com alvo no citocromo b e 18S rDNA. O limite de detec??o para os dois genes qPCR foi de 10 c?pias do alvo de DNA, que foram maiores do que o limite de detec??o observado em nPCR e cPCR. Em qPCR, 69,30% (n = 70/101) amostras foram positivas com alvo no gene 18SrDNA e 59,40%(n = 60/101) amostras positivas com alvo no gene cyt b. Em nPCR e cPCR, 54,45% (n = 55/101) e 52,47% (n = 53/101) amostras foram positivas, respectivamente. Em microscopia de esfrega?o de sangue, 31 (30,69%) amostras foram positivas. N?o houve discord?ncia entre os resultados (p> 0,05) de qPCR para os genes 18SrDNA e cyt b.. Al?m disso, qPCR foi mais sens?vel do que as outras t?cnicas discutidas, principalmente relacionado com a microscopia ?ptica (p <0,05). Portanto, os dois ensaios de qPCR desenvolvidos neste estudo mostraram mais sensibilidade do que outras t?cnicas e permitiu a detec??o de Plasmodium spp. em aves de cria??o r?stica mesmo com baixa parasitemia.

Made available in DSpace on 2014-12-17T14:10:25Z (GMT). No. of bitstreams: 1 GracielleRD_DISSERT.pdf: 641978 bytes, checksum: 570ea10863ca885dc9cff38e172d53f2 (MD5) Previous issue date: 2012-03-07 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Malaria is a major parasitic disease worldwide, accounting for about 500 million cases and causing 2 million to 3 million deaths annually. Four species are responsible for transmitting this disease to humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale. The parasite resistance to antimalarial drugs and the usual limitations of the vector control implications are contributing to the spread of the disease. The most of significant advances in the search for new antimalarial drugs is based on natural components, the main ones being currently used antimalarial drugs derived from plants. Research on natural products of marine origin (particularly algae) show that some species possess antiplasmodial activity. Knowing that the coast of Rio Grande do Norte is home to several species of algae, the present study was to evaluate, for the first time, the antimalarial activity of ethanolic extracts of seaweed Spatoglossum schroederi, Gracilaria birdiae and Udotea flabellum against Plasmodium falciparum 3D7 strain tests and in vitro using the murine model (Plasmodium berghei) for evaluation in vivo. These species were ground, macerated with ethanol for 24 hours and the extracts concentrated in rotaevaporador (45 ? C ? 5 ? C). For in vitro tests, the extracts were diluted and tested at concentrations between 100 and 1.56 &#956;g/ml (seven concentrations in triplicate), in order to obtain IC50 of each extract. The cytotoxicity tests with macrophages and BGM were performed using the MTT colorimetric assay. BGM macrophages and cells were distributed in 96 wells per plate (1x 105 to macrophages and 1x104 cells per well for BGM) and incubated for 24h at 37 ? C. The ethanol extracts were diluted and tested at concentrations of 100 to 1,56 &#956;g/ml (seven concentrations in triplicate). After periods of 24 hours of incubation with the extracts, 100 &#956;g of MTT was added to each well, and 3 hours elapsed, the supernatant was removed and added 200 &#956;l of DMSO in each well. The absorbance of each well was obtained by reading on a spectrophotometer at 570 nm filter. To evaluate the acute toxicity in vivo, Swiss mice received a single dose (oral) 2000 mg/kg/animal of each extract tested. The parameters of acute toxicity were observed for 8 days. For in vivo tests, Swiss mice were inoculated with 1x105 erythrocytes infected with P. berghei. The treatment was given first to fourth day after infection with 0.2 ml of the extracts in doses of 1000 and 500 mg//g animal. The negative control group received 0.2 ml of 2% Tween-20, whereas the positive control group received sub-dose of chloroquine (5 mg/kg/animal). The assessment of antimalarial activity was done by suppressing suppressing the parasitemia at 5 and 7 days after infection. The growth inhibition of parasites was determined relative to negative control (% inhibition = parasitaemia in control - parasitemia in sample / parasitemia control x 100), the mortality of animals was monitored daily for 30 days The results showed that algae Spatoglossum schroederi and Udotea flabellum showed antimalarial activity in vitro, with reduced parasitemia of 70.54% and 54, respectively. The extracts of the three algae tested showed moderate to high cytotoxicity. Algae S. schroederi and U. flabellum were active against P. berghei only at doses of 500 mg / kg with reduction ranging from 54.58 to 52.65% for the fifth day and from 32.24 to 47.34% for the seventh day, respectively. No toxicity was observed in vivo at the dose tested, over the 8 days of observation. Although preliminary data, the bioactive components in those possible seaweed may be promising for the development of new anti-malarial drugs / A mal?ria ? a maior doen?a paras?tica mundial, respons?vel por cerca de 500 milh?es de casos e causando 2 a 3 milh?es de mortes anualmente. Quatro esp?cies s?o respons?veis pela transmiss?o dessa doen?a ao homem: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae e Plasmodium ovale. A resist?ncia do parasito aos antimal?ricos usuais e as limita??es existentes no combate ao vetor s?o implica??es que contribuem para a expans?o dessa parasitose. Os avan?os mais significativos na busca de novos medicamentos contra a mal?ria baseiam-se em componentes naturais, sendo os principais antimal?ricos atualmente utilizados derivados de plantas. Pesquisas com produtos naturais de origem marinha (particularmente as algas) mostram que algumas esp?cies possuem atividade antiplasm?dica. Sabendo que o litoral do Rio Grande do Norte abriga v?rias esp?cies de algas, o presente estudo consistiu em avaliar, pela primeira vez, a atividade antimal?rica dos extratos etan?licos das algas Spatoglossum schroederi, Gracilaria birdiae e Udotea flabellum contra a cepa 3D7 Plasmodium falciparum em testes in vitro e utilizando o modelo murino (P. berghei) para avalia??o in vivo. As algas foram trituradas, maceradas com etanol por 24 horas e os extratos concentrados em rotaevaporador (45? C ? 5?C). Para os testes in vitro, os extratos foram dilu?dos e testados nas concentra??es entre 100 e 1,56 &#956;g/ml (sete concentra??es em triplicata), com a finalidade de obten??o da CI50 de cada extrato. Os testes de citotoxicidade com macr?fagos e c?lulas BGM foram realizados usando o ensaio colorim?trico MTT. Macr?fagos e c?lulas BGM foram distribu?das em 96 po?os por placa (1x 105 para macr?fagos e 1x104 c?lulas por po?o para BGM), sendo incubadas por 24h a 37?C. Os extratos etan?licos foram dilu?dos e testados nas concentra??es de 100 at? 1,56 &#956;g/ml (sete concentra??es em triplicata). Ap?s per?odos de 24h de incuba??o com os extratos, 100 &#956;l de MTT foi adicionado a cada po?o, e decorridas 3h, o sobrenadante foi removido e adicionou-se 200 &#956;l DMSO em cada po?o. A absorb?ncia de cada po?o foi obtida atrav?s de leitura em espectrofot?metro com filtro de 570 nm. Para avaliar a toxicidade aguda in vivo, camundongos Swiss receberam dose ?nica (oral) de 2000 mg/kg/animal dos extratos testados. Os par?metros de toxicidade aguda foram observados durante 8 dias. Para os testes in vivo, camundongos Swiss foram inoculados com 1x105 hem?cias infectadas com Plasmodium berghei. O tratamento deu-se do primeiro ao quarto dia ap?s a infec??o, com 0,2 ml dos extratos em doses de 1000 e 500 mg/kg/animal. O grupo controle negativo recebeu 0,2 ml de Tween-20 2%, enquanto que o grupo controle positivo recebeu sub-dose de cloroquina (5 mg/kg/animal). A avalia??o da atividade antimal?rica foi feita atrav?s da supress?o da parasitemia no 5? e 7? dias ap?s infec??o. A inibi??o do crescimento dos parasitos foi determinada em rela??o ao grupo controle negativo (% inibi??o = parasitemia do controle parasitemia com amostra/ parasitemia do controle x 100); a mortalidade dos animais foi acompanhada diariamente por 30 dias. Os resultados mostraram que as algas Spatoglossum schroederi e Udotea flabellum apresentaram atividade antimal?rica in vitro, com redu??o da parasitemia de 70,54 e 54%, respectivamente. Os extratos das tr?s algas testadas mostraram citotoxicidade moderada a elevada. As algas S. schroederi e U. flabellum foram ativas contra o P. berghei apenas nas doses de 500 mg/kg com redu??o variando de 54,58 a 52,65% para o quinto dia e 32,24 a 47,34% para o s?timo dia, respectivamente. N?o foi observada toxicidade in vivo para a dose testada, durante os 8 dias de observa??o. Embora sejam dados preliminares, os poss?veis componentes bioativos presentes nessas algas marinhas podem ser promissores para o desenvolvimento de novas drogas antimal?ricas

Made available in DSpace on 2014-12-17T14:10:27Z (GMT). No. of bitstreams: 1 BrunoMSW_DISSERT.pdf: 2493064 bytes, checksum: 67d2a8f0addf9c48ec5976ed766a8e15 (MD5) Previous issue date: 2012-10-15 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Malaria is a disease of global distribution, recognized by governments around the world as a serious public health problem, affecting more than 109 countries and territories and endangering more than 3.3 billion people. The economic costs of this disease are also relevant: the African continent itself has malaria-related costs of about $ 12 billion annually. Nowadays, in addition to chloroquine, Plasmodium falciparum is resistant to many drugs used in the treatment of malaria, such as amodiaquine, mefloquine, quinine and sulfadoxine-pyrimethamine; resistance of Plasmodium vivax to treatments, although less studied, is also reported. Nature, in general, is responsible for the production of most known organic substances, and the plant kingdom is responsible for the most of the chemical diversity known and reported in the literature. Most medicinal plants commercialized in Brazil, however, are of exotic origin, which makes the search for endemic medicinal plants, besides a patent necessity, a fascinating subject of academic research and development. This study aimed to: (i) verify the antimalarial activity of ethanolic and hydroalcoholic extracts of Boerhavia paniculata Rich. And acetonic extract of Clethra scabra Pers. in Swiss albino mice infected by Plasmodium berghei NK65, (ii) observe possible combined effects between the course of infection by P. berghei NK65 and administration of these extracts in Swiss albino mice, and (iii) conduct a preliminary study of the acute toxicity of these extracts in Swiss albino mice. All extracts notable pharmacological activities - with parasite infections inhibitions ranging from 22% to 54%.These characteristics suggest that the activities are relevant, although comparatively lower than the activity displayed by the positive control group (always above 90%). The general framework of survival analysis demonstrates an overall reduction in survival times for all groups. Necroscopy has not pointed no change in color, shape, size and/or consistency in the evaluated organs - the only exception was the livers of rats submitted to treatment to hydroalcoholic extracts: these organs have been presented in a slightly congestive aspect with mass increasing roughly 28% higher than the other two groups and a p-value of 0.0365. The 250 mg/Kg ethanolic group has been pointed out by the Dunn s post test, as the only class with simultaneous inequalities (p<0.05) between positive and negative control groups. The extracts, notably ethanol extract, have, in fact, a vestigial antimalarial activity, although well below from the ones perceived to chloroquine-treated groups; nevertheless, the survival times of the animals fed with the extracts do not rise by presence of such therapy. Both the toxicopharmacological studies of the synergism between the clinical course of malaria and administration of extracts and the isolated evaluation of toxicity allow us to affirm the absence of toxicity of the extracts at the level of CNS and ANS, as well as their non-influence on food and water consumption patterns, until dosages of 500 mg/Kg. Necroscopic analysis leads us to deduct a possible hepatotoxic effect of hydroalcoholic extract at dosages of 500 mg/Kg, and an innocuous tissue activity of the ethanol extract, in the same dosage. We propose a continuation of the studies of these extracts, with protocol modifications capable of addressing more clearly and objectively their pharmacological and toxicological aspects / A mal?ria ? uma doen?a de distribui??o global, reconhecida por governos de todo o mundo como grave problema de sa?de p?blica, ocorrendo em mais de 109 pa?ses e territ?rios e pondo em risco mais de 3,3 bilh?es de pessoas. Os custos econ?micos da doen?a s?o tamb?m relevantes: apenas o continente africano tem um ?nus de cerca de US$12 bilh?es anuais. Hodiernamente, al?m da cloroquina, o Plasmodium falciparum apresenta resist?ncia aos diversos medicamentos usados na rotina, como amodiaquina, mefloquina, quinina e sulfadoxina-pirimetamina; a resist?ncia de Plasmodium vivax, apesar de menos estudada, tamb?m ? relatada. A natureza, de um modo geral, ? a respons?vel pela produ??o da maioria das subst?ncias org?nicas conhecidas, sendo o reino vegetal respons?vel pela maior parcela da diversidade qu?mica conhecida e registrada na literatura. A maioria das plantas medicinais comercializadas no Brasil, contudo, ? de origem ex?tica, o que torna a busca por plantas medicinais end?micas, al?m de uma patente necessidade, um fascinante assunto de pesquisa acad?mica e de desenvolvimento. Este trabalho teve por objetivo: (i) verificar a atividade antimal?rica dos extratos etan?lico e hidroalco?lico de Boerhavia paniculata Rich. e acet?nico de Clethra scabra Pers. em camundongos albinos Swiss infectados por Plasmodium berghei NK65; (ii) observar poss?veis efeitos combinados entre o curso da infec??o por P. berghei NK65 e a administra??o destes extratos em camundongos albinos Swiss; e (iii) realizar um estudo da toxicidade aguda destes extratos em camundongos albinos Swiss. Notam-se, em todos os extratos, atividades farmacol?gicas not?rias com inibi??es da parasitemia variando de 22% a 54% - caracter?sticas estas que sugerem atividades relevantes, apesar de comparativamente inferior ? atividade apresentada pelo grupo controle positivo (sempre superior a 90%). O quadro geral da an?lise de sobreviv?ncia demonstra uma redu??o global dos tempos de sobrevida para todos os grupos testados. A necroscopia n?o apontou, em um quadro geral, qualquer altera??o de cor, forma, tamanho e/ou consist?ncia nos ?rg?os avaliados nos estudos a ?nica exce??o recaiu sobre os f?gados dos animais submetidos ao extrato hidroalco?lico: estes se apresentaram sob um aspecto levemente congestivo, com aumento de massa cerca de 28% superior aos outros dois grupos e um p-valor de 0,0365. O grupo etan?lico 250 mg/Kg foi apontado, pelo p?s-teste de Dunn, como a ?nica classe com desigualdades simult?neas (p< 0,05) entre os grupos controles positivo e negativo. Os extratos analisados, notadamente o extrato etan?lico, apresentam, de fato, uma atividade antiplasm?dica resquicial, embora muito abaixo da percebida para grupos tratados com cloroquina; n?o obstante, os tempos de sobrevida dos animais submetidos aos tratamentos com os extratos n?o se elevam mediante a presen?a de tal terap?utica. Tanto o estudo t?xico-farmacol?gico do sinergismo entre a evolu??o cl?nica da mal?ria e a administra??o dos extratos quanto a avalia??o isolada de toxicidade nos permitem afirmar a aus?ncia de toxicidade dos extratos em n?vel de SNC e SNA, bem como a n?o influ?ncia destes nos padr?es de consumo h?drico e alimentar, at? as doses de 500 mg/Kg. A an?lise necrosc?pica nos leva ? dedu??o de um poss?vel efeito hepatot?xico do extrato hidroalco?lico, em doses de 500 mg/Kg, e uma atividade tecidual in?cua do extrato etan?lico, em mesma dosagem. Propomos uma continua??o dos estudos destes extratos, com modifica??es protocolares capazes de abordar, de forma mais clara e objetiva, seus aspectos farmacol?gicos e toxicol?gicos

Made available in DSpace on 2014-12-17T15:25:14Z (GMT). No. of bitstreams: 1 GABRIEL ANAYA _2011_ MAUS ARES E MALARIA 18.pdf: 5313669 bytes, checksum: 5fc1843255ee310f60cc11e6be2ddbfc (MD5) Previous issue date: 2011-07-27 / The development of epidemiological practices in the last years of the nineteenth and early twentieth century was characterized by both an influence of medical geography and the emergence of microbes and vectors of diseases. Both theories were used to explain outbreaks in Rio Grande do Norte specially in Natal. In this process were organized new institutions linked to public health, unhealthy spaces and prescribed hygiene measures. The redefinitions of the spaces were linked to updated elements of Hippocratic medicine such as aerism and emphasis on medical topography. How the physicians of the town were organized in the face of new meanings and fields of expertise in the demarcation of diseases and regulation of their own practices against the illegal medical practitioners? Likewise, the very occurrence of epidemics mobilized people, urban institutions and apparatuses. But how the Hippocratic legacy that leads to the idea of bad air originated by swamps from the eighteenth and nineteenth century has been linked to new microbial assumptions and disease vectors in the early twentieth century? How an invader from Africa, (the mosquito A. gambiae) mobilized transnational efforts to combat malaria and redefined the epidemiological practices? The aim of this work is to understand how epidemiological practices redefine the way we define spaces, practices and disease from both an approach influenced by a relational history of spaces and a theoretical synergy which includes topics in Science Studies, Post Structuralist Geography and some elements of Feminist Studies. Documentary research were surveyed in the reports of the provincial presidents, government posts to the Provincial Assembly, specialized medical articles and theses, and documents from the Rockefeller Foundation and national and international journals. In this regard shall be given to both material and discursive aspects of space-related practical epidemiological that Natal as much (in general) Rio Grande do Norte between bad air and malaria. / O desenvolvimento de pr?ticas epidemiol?gicas nos ?ltimos anos do s?culo XIX e in?cio do s?culo XX foi caracterizado tanto pela influ?ncia da geografia m?dica quanto pela emerg?ncia dos micr?bios e vetores de doen?as como modelos explicativos. Esses elementos come?aram a se destacar nas quest?es relacionadas ?s epidemias no Rio Grande do Norte com uma maior visibilidade em Natal. Nesse processo foram organizadas novas institui??es ligadas ? sa?de p?blica, houve a demarca??o de espa?os insalubres e foram prescritas medidas de higiene e profilaxia a partir da Inspetoria de Hygiene. A redefini??o dos espa?os devido ? circula??o e prolifera??o de novos pressupostos tamb?m foi articulada a elementos da medicina hipocr?tica atualizados, com ?nfase no aerismo e na topografia m?dica. De que maneira o pr?prio corpo m?dico da cidade se organizou frente aos novos sentidos e especializa??es nas demarca??es das doen?as e na pr?pria regulamenta??o de suas pr?ticas frente aos charlat?es e praticantes de medicina ilegal? Da mesma maneira, a pr?pria ocorr?ncia de epidemias mobilizou pessoas, inaugura??o de institui??es e de aparatos urbanos. Mas de que maneira o legado hipocr?tico que remete ? id?ia de maus ares pantanosos que resultavam das inquieta??es sanitaristas do s?culo XVIII e XIX se articulou aos novos pressupostos microbianos e relativos aos vetores no in?cio do s?culo XX? Como um mosquito invasor , o A. gambiae, vindo da ?frica para Natal, mobilizou esfor?os transnacionais no combate ? mal?ria e com isso ajudou a redefinir as pr?ticas epidemiol?gicas? Pretende-se compreender como as pr?ticas epidemiol?gicas redefinem a maneira de se delimitar espa?os, pr?ticas e doen?as a partir de uma abordagem tanto influenciada por uma perspectiva relacional do espa?o na hist?ria quanto a partir de uma sinergia te?rica que inclui os Estudos da Ci?ncia, Geografia P?s-estruturalista e elementos dos Estudos Feministas. Na pesquisa documental foram pesquisados os Relat?rios dos presidentes de prov?ncia, Mensagens de Governo ? Assembl?ia Provincial, artigos e teses m?dicas especializadas, al?m de documentos da Funda??o Rockefeller e peri?dicos nacionais e internacionais. Nesse sentido ser? privilegiado o aspecto tanto material quanto discursivo dos espa?os ligados ?s pr?ticas epidemiol?gicas que atravessam tanto Natal quanto (de maneira geral) o Rio Grande do Norte entre os maus ares e a mal?ria no per?odo proposto.