Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-05-10T11:50:40Z No. of bitstreams: 1 DIS_FERNANDA_GRENDENE_PACHECO_COMPLETO.pdf: 2728715 bytes, checksum: 93bb3d4fcee10a1e8abba33e2e0e8996 (MD5) / Made available in DSpace on 2016-05-10T11:50:40Z (GMT). No. of bitstreams: 1 DIS_FERNANDA_GRENDENE_PACHECO_COMPLETO.pdf: 2728715 bytes, checksum: 93bb3d4fcee10a1e8abba33e2e0e8996 (MD5) Previous issue date: 2016-03-14 / Introduction: Cutaneous leishmaniasis is caused by Leishmania protozoan and transmitted through the female of Lutzomyia sandflies. The disease can manifest itself in different clinical forms: localized cutaneous leishmaniasis, disseminated cutaneous leishmaniasis, recidivans and diffuse cutaneous leishmaniasis. The North and Northeast (Brazil) are the most affected area by the disease. Pentavalent antimonials and amphotericin B have been the most used drugs for the treatment of this disease but may cause many side effects, which leads the patients to discontinue treatment. Control or progression of the disease has been related to the immune response triggered by the individual. PNP (purine nucleoside phosphorylase) is the key enzyme in the purine salvage route catalyzing the reversible phosphorolysis of purine nucleosides such as deoxyinosine or deoxyguanosine producing their respective bases and deoxyrribose-1-phosphate. The PNP inhibitors can be used for treating diseases caused by disorder mediated by T cells. Immucillin - DI4G (4th generation Immucillin ; 7-((bis(2-hydroxyiethyl)amine)methyl)-1,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one) is considered as a potent inhibitor of PNP. Objective: development of pre-formulation and formulation studies of a pharmaceutical form for topical use containing Immucillin-DI4G as drug candidate for Cutaneous Leishmaniasis treatment. Material and Methods: Characterization of the compound was performed by NMR, FTIR-ATR and HRMS. The stability of the amorphous powder was evaluated over 90 days using a HPLC method for quantification. Formulations have been developed for stability, rheological and spreadability studies over 30 and 90 days. A method for the quantification of Immucillin-DI4G in the formulation was developed and validated using the HPLC. Results and discussion: The Immucillin - DI4G (amorphous powder) was stable up to 30 days when stored at 4 ?C and 25 ?C. Formulation 1 (Immucillin - DI4G 1.1% Carboxyvinylpolymer gel 2%) was stable only when stored at 4 ?C for a period of 60 days. Formulation 1 was considered as a non-Newtonian fluid with pseudoplastic behavior and no alterations in viscosity was observed over 90 days. On the other hand, significant changes in spreadability was observed when topical formulation was stored at 45 ?C. The formulation containing additives (formulation 2) showed an improvement in stability when stored at 45 ?C for a period of 30 days, but there was a significant decrease in drug content when stored at 4 ?C and 25 ?C. Formulations 3 (Immucillin-DI4G a 1,1% Gel-Cream) and 4 (Immucillin-DI4G 1.1% in Hydroxypropylcellulose polymer at 2%) presented significant loss in the drug content in 30 days when stored at 45 ?C. The results shows that further studies should be conducted in order to analyze the possible degradation products looking for design of novel formulations. / Introdu??o: A Leishmaniose Cut?nea ? causada por protozo?rios do g?nero Leishmania e transmitidas atrav?s das f?meas dos mosquitos do g?nero Lutzomyia. A Leishmaniose cut?nea pode se manifestar de diferentes formas cl?nicas: cut?nea localizada, cut?nea disseminada, recidiva c?tis e cut?nea difusa. A regi?o Norte e Nordeste s?o as mais acometidas pela doen?a. Os antimoniais pentavalentes e a anfotericina B s?o os medicamentos mais utilizados para o tratamento desta doen?a, por?m podem causar v?rios efeitos adversos fazendo com que muitos pacientes abandonem o tratamento. O controle ou a progress?o da doen?a est?o diretamente relacionados com a resposta imunol?gica desencadeada pelo indiv?duo. A PNP ? a enzima chave na rota de salvamento de purinas, catalisa a fosfor?lise revers?vel de nucleos?deos pur?nicos como deoxinosina e deoxiguanosina formando suas respectivas bases e deoxirribose-1-fosfato. Os inibidores da PNP podem ser utilizados para tratamento de doen?as causadas por desordem mediada pelas c?lulas T, atrav?s da inibi??o segura e seletiva da prolifera??o da c?lula T. O Immucillin-DI4G (Immucillin de 4? gera??o; 7-((bis(2-hidroxietil)amino)metil)-1,5-diidro-4H-pirrolo[3,2-d]pirimidin-4-ona) ? considerado como um potente inibidor da PNP. Objetivo: desenvolver estudos de pr?-formula??o e formula??o de uma forma farmac?utica de uso t?pico contendo o Immucillin-DI4G como candidato a f?rmaco para tratamento da Leishmaniose Cut?nea. Materiais e M?todos: Foi realizada a caracteriza??o do composto atrav?s do RMN, EMS e FTIR-ATR. A estabilidade do p? amorfo foi avaliada durante 90 dias, o doseamento foi realizado atrav?s do CLAE. Formula??es foram desenvolvidas para o estudo de estabilidade, estudos reol?gicos e espalhabilidade durante 30 e 90 dias. Um m?todo para o doseamento do f?rmaco nas formula??es foi desenvolvido e validado empregando o m?todo de CLAE. Resultados e discuss?o: O Immucillin-DI4G (p? amorfo) mostrou-se est?vel at? 30 dias quando armazenado a 4 ?C e 25 ?C. A formula??o 1(Immucillin-DI4G a 1,1% em Gel pol?mero Carboxivin?lico a 2% ) mostrou-se est?vel apenas quando armazenada a 4 ?C por um per?odo de 60 dias; ? considerada como um Flu?do N?o-Newtoniano de comportamento pseudopl?stico, sem altera??es na viscosidade durante 90 dias, por?m com altera??es significativas na espalhabilidade quando armazenada a 45 ?C. A formula??o que continha aditivos (formula??o 2) apresentou uma melhora na estabilidade quando armazenada a 45 ?C num per?odo de 30 dias, por?m apresentou queda significativa no teor do f?rmaco quando armazenada a 4 ?C e 25 ?C. As formula??es 3 (Immucillin-DI4G a 1,1% em Creme-Gel) e 4 (Immucillin-DI4G a 1,1% em Gel Pol?mero Hidroxipropilcelulose a 2%) apresentaram perdas significativas no teor do f?rmaco em 30 dias quando armazenadas a 45 ?C. Os resultados demonstram que novos estudos devem ser realizados para a an?lise de poss?veis produtos de degrada??o, para poss?veis ajustes nas formula??es.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-05-06T16:55:06Z No. of bitstreams: 1 467931 - Texto Completo.pdf: 1649223 bytes, checksum: 97061538af6c3abdd1bf13692fc0be12 (MD5) / Made available in DSpace on 2015-05-06T16:55:06Z (GMT). No. of bitstreams: 1 467931 - Texto Completo.pdf: 1649223 bytes, checksum: 97061538af6c3abdd1bf13692fc0be12 (MD5) Previous issue date: 2015-02-25 / Depression is a serious and recurrent disease characterized by anhedonia, loss of interest in daily activities, appetite, and sleep disturbances, reduced concentration and psychomotor agitation. Antidepressant drugs currently used have a very slow onset of action, with that comes the need for fast-acting treatments. Therefore, there is a growing interest in NMDA antagonists as a target for the development of new antidepressant drugs. Considering that the purinergic and dopaminergic systems are involved in anxiety, depression, and sleep, we characterize the role of these signaling pathways on antidepressant effects induced by MK-801 in zebrafish. The animals treated with MK-801 at 5, 10, 15, and 20 ?M during 15, 30, and 60 minutes showed higher permanence in the top area of the tank, in comparison with the control group, indicating an antidepressant effect induced by this drug. The animals treated with MK-801 remained within 2 hours in the top of the tank when treated with 5 ?M MK-801 and 4 hours when treated with 20 ?M MK-801, returning to basal levels 24 hours after exposure.The repeated treatment did not induce cumulative effects, since animals treated daily for seven days showed the same pattern of behavioral response observed from the first day until the 7th day. In order to investigate the action of agonists and antagonists of A1 and A2A receptors and the influence of modulation on adenosine levels in antidepressant effects induced by MK-801, animals were pretreated with Caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI before the exposure to MK-801 for 30 minutes. The nonselective adenosine receptor antagonist Caffeine (50 mg/kg) and the selective A1 adenosine receptor antagonist DPCPX (15 mg/kg) blocked the behavioral changes induced by MK-801. Dipyridamole (10 mg/kg), a selective inhibitor of nucleoside transport (NT), exacerbates the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH23390) did not induce changes on the behavioral alterations induced by MK-801. Our results have shown that the antidepressant effects induced by MK-801 in zebrafish are mediated by the activation by A1 adenosine receptor. / A depress?o ? uma doen?a grave, recorrente, caracterizada por anedonia, perda de interesse em atividades di?rias, dist?rbios do apetite e do sono, concentra??o reduzida e agita??o psicomotora. Os f?rmacos antidepressivos utilizados atualmente t?m um in?cio de a??o muito lento, com isso, surge a necessidade de tratamentos de a??o r?pida. Portanto, h? um interesse crescente em antagonistas de receptores NMDA como um alvo para o desenvolvimento de novos f?rmacos antidepressivos. Considerando-se que os sistemas purin?rgicos e dopamin?rgicos est?o envolvidos na ansiedade, sono e depress?o, caracterizamos o papel destas vias de sinaliza??o sobre os efeitos antidepressivos induzidos por MK-801, um antagonista NMDA, em peixe-zebra. Os animais tratados com MK-801 em doses de 5, 10, 15 e 20 ?M durante 15, 30 e 60 minutos apresentaram maior perman?ncia na ?rea superior do aqu?rio, em compara??o com o grupo controle, indicando um efeito antidepressivo induzido por este composto.Os animais tratados com MK-801 permaneceram at? 2 horas na parte superior do aqu?rio quando tratados com 5 ?M de MK-801 e 4 horas quando tratados com 20 ?M MK-801, retornando aos par?metros basais ap?s 24 horas de exposi??o. O tratamento repetido n?o induziu efeitos cumulativos, uma vez que os animais tratados diariamente durante sete dias apresentaram o mesmo padr?o de resposta comportamental observada desde o primeiro at? o dia 7? dia. Com o objetivo de investigar a a??o dos agonistas e antagonistas dos receptores A1 e A2A e a influ?ncia da modula??o dos n?veis de adenosina nos efeitos antidepressivos induzidos por MK-801, os animais foram pr?-tradados com cafe?na, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, Dipiridamol e NBTI por 30 minutos antes da exposi??o ao MK-801. O antagonista n?o seletivo de receptores de adenosina cafe?na (50 mg/kg) e o antagonista seletivo do receptor A1 DPCPX (15 mg/kg) bloquearam as altera??es comportamentais induzido pelo MK-801.O Dipiridamol (10 mg/kg), um inibidor n?o seletivo do transportador de nucleos?deo (NT), exacerbou as altera??es comportamentais induzidos pelo MK-801. Os antagonistas dos receptores de dopamina (sulpirida e SCH23390) n?o apresentaram modifica??es nas altera??es comportamentais induzidas por MK-801. Os nossos resultados sugerem que o efeito antidepressivo induzido por MK-801 em peixe-zebra ? mediado principalmente pela ativa??o do receptor de adenosina A1.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-06-02T14:03:42Z No. of bitstreams: 1 469599 Texto Completo.pdf: 1271665 bytes, checksum: c7c7cda085b0d3d13b2f9dc865eca750 (MD5) / Made available in DSpace on 2015-06-02T14:03:42Z (GMT). No. of bitstreams: 1 469599 Texto Completo.pdf: 1271665 bytes, checksum: c7c7cda085b0d3d13b2f9dc865eca750 (MD5) Previous issue date: 2015-03-18 / Hepatocellular carcinoma is the most prevalent type of tumor among primary tumors affecting the liver. Its development is usually related to a chronic liver disease, which can be caused by a viral infection (hepatitis B and C), alcoholism, cryptogenic cirrhosis, biliary disease and primary hemochromatosis. Rapamycin, an immunosuppressant agent, is currently used as the basis of chemotherapy in the treatment of various cancers, including the liver. By presenting several serious adverse effects in patients undergoing treatment, including nephrotoxicity, it is clear the importance of minimizing these effects without compromising efficacy. In this sense, other drugs may be used concomitantly. One of these drugs is fructose-1,6-bisphosphate (FBP), which has shown therapeutic effect in various pathological situations. Beneficial effects of FBP in organic, liver and kidney deficiencies were also documented. The objective of this study was to evaluate the activity of rapamycin in combination with the FBP in cell proliferation, oxidative stress and inflammation of hepatocellular carcinoma HepG2 cells, analyzing the cytotoxic effects in an attempt to minimize adverse effects and increase the efficacy and safety for patients undergoing treatment.The results demonstrated that the combination of rapamycin and FBP is more efficient than the single use of them, because subtherapeutic doses of rapamycin, when associated to FBP become effective, and this inibition in cell proliferation is not caused by necrosis. In 72 hours of treatment, there was no change in the inflammatory route or in autophagy of cells, but the combination of rapamycin and FBP significantly increased the production of Thiobarbituric acid reactive substances (TBARS) and the cellular apoptosis, a process that can inhibit tumor proliferation. These results demonstrate that this association may be a promising choice for hepatocarcinoma treatment. / O carcinoma hepatocelular ? o tipo de tumor mais prevalente entre os tumores prim?rios que atingem o f?gado. Seu desenvolvimento est? geralmente relacionado a uma doen?a hep?tica cr?nica, a qual pode ser originada por uma infec??o viral (hepatite B e C), alcoolismo, cirrose criptog?nica, doen?as biliares e hemocromatose prim?ria. A rapamicina, um agente imunossupressor, ? atualmente utilizada como base na quimioterapia no tratamento de diversos tipos de c?ncer, inclusive nos hep?ticos. Por apresentar diversos efeitos adversos graves nos pacientes em tratamento, inclusive nefrotoxicidade, ? evidente a import?ncia de minimizar estes efeitos sem comprometimento da efic?cia, neste sentido outras drogas podem ser utilizadas concomitantemente. Uma destas drogas ? a frutose-1,6-bisfosfato (FBP) que tem demonstrado efeito terap?utico em v?rias situa??es patol?gicas. Tamb?m foram documentados efeitos ben?ficos da FBP em defici?ncias org?nicas, renais e hep?ticas. O objetivo deste trabalho foi avaliar a atividade da rapamicina em conjunto com a FBP na prolifera??o celular, estresse oxidativo e processo inflamat?rio de c?lulas HepG2, analisando os efeitos citot?xicos, na tentativa de minimizar os efeitos adversos e aumentar a efic?cia e seguran?a para os pacientes em tratamento.O carcinoma hepatocelular ? o tipo de tumor mais prevalente entre os tumores prim?rios que atingem o f?gado. Seu desenvolvimento est? geralmente relacionado a uma doen?a hep?tica cr?nica, a qual pode ser originada por uma infec??o viral (hepatite B e C), alcoolismo, cirrose criptog?nica, doen?as biliares e hemocromatose prim?ria. A rapamicina, um agente imunossupressor, ? atualmente utilizada como base na quimioterapia no tratamento de diversos tipos de c?ncer, inclusive nos hep?ticos. Por apresentar diversos efeitos adversos graves nos pacientes em tratamento, inclusive nefrotoxicidade, ? evidente a import?ncia de minimizar estes efeitos sem comprometimento da efic?cia, neste sentido outras drogas podem ser utilizadas concomitantemente. Uma destas drogas ? a frutose-1,6-bisfosfato (FBP) que tem demonstrado efeito terap?utico em v?rias situa??es patol?gicas. Tamb?m foram documentados efeitos ben?ficos da FBP em defici?ncias org?nicas, renais e hep?ticas. O objetivo deste trabalho foi avaliar a atividade da rapamicina em conjunto com a FBP na prolifera??o celular, estresse oxidativo e processo inflamat?rio de c?lulas HepG2, analisando os efeitos citot?xicos, na tentativa de minimizar os efeitos adversos e aumentar a efic?cia e seguran?a para os pacientes em tratamento.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-06-09T11:33:18Z No. of bitstreams: 1 470158 - Texto Completo.pdf: 900834 bytes, checksum: c9822e05947627069fb5b4fc9d1f6005 (MD5) / Made available in DSpace on 2015-06-09T11:33:18Z (GMT). No. of bitstreams: 1 470158 - Texto Completo.pdf: 900834 bytes, checksum: c9822e05947627069fb5b4fc9d1f6005 (MD5) Previous issue date: 2015-03-17 / The international market for essential oils has an annual turnover of 1.8 billion dollars, yet the Brazilian participation in this market is only 0.1%. The vast biodiversity found in Brazil, although still little explored in relation to the chemical composition of its flora, places the country in a very promising position in terms of increasing its future participation in the essential oils market. Basil (Ocimum basilicum L.) is a widely cultivated aromatic plant due to its medicinal properties. The importance of this species lies in the plant architecture, coloration and morphology of its leaves and flowers, in addition to the chemical composition of its essentials oils, giving specific aromas and having various uses in the culinary, perfume and pharmaceuticals industries. In this study, two experiments were performed with the aim of studying germination in simulated hypergravity and open-air cultivation, to evaluate the growth of the basil, its yield and essential oil composition. The extraction of the essential oils was carried out by steam distillation in a Clevenger apparatus. Quantitative and qualitative evaluation of the compounds was performed by gas chromatography coupled to a mass spectrometer detector (GC/MS). The mean values for germination under the effect of hypergravity simulation in protocols 1, 2 and 3 ranged from 81% to 87%. After this stage, the seeds exposed to simulated hypergravity were cultivated in the open-air and the fresh basil leaves were collected after 90 days to obtain the essential oils. The overall yield of oil was 0.2mL to 0.3mL and the essential oil was 0.3% to 0.4%. The largest and most predominant compound in this research was eugenol, ranging from 46% to 62%, with the second largest being linalool, which ranged from 22% to 28%. Further research in this area is essential to understand the real impact of simulated hypergravity on basil, and its effect on auxins and gene expression. / O mercado internacional de ?leos essenciais movimenta anualmente 1,8 bilh?es de d?lares e a participa??o brasileira nesse mercado ? de apenas 0,1%. A grande biodiversidade brasileira, ainda pouco explorada em rela??o ? composi??o qu?mica de sua flora, coloca o Brasil numa situa??o muito promissora para aumentar sua participa??o futura no mercado de ?leos essenciais. O manjeric?o (Ocimum basilicum L.) ? uma planta arom?tica largamente cultivada, devido ? suas propriedades medicinais. A import?ncia dessa esp?cie est? na arquitetura da planta, na colora??o e na morfologia das folhas e flores, al?m da composi??o qu?mica de seus ?leos essenciais, originando aromas espec?ficos e tendo utiliza??o variada na gastronomia, perfumaria e ind?stria farmac?utica. Nesse trabalho, foram realizados dois experimentos, com o objetivo de estudar a germina??o por hipergravidade simulada e o cultivo a c?u aberto para avaliar o crescimento do manjeric?o, rendimento e a composi??o do ?leo essencial. A extra??o do ?leo essencial foi feita por arraste a vapor em aparelho Clevenger. A avalia??o quantitativa e qualitativa dos compostos foi realizada por cromatografia gasosa acoplada a um detector de massas (CG/MS). As m?dias de germina??o deste trabalho foram de 81% a 87%. Ap?s essa etapa, as sementes sob efeito de hipergravidade simulada foram cultivadas a c?u aberto e, depois de 90 dias, foram coletadas folhas frescas de manjeric?o para obter ?leos essenciais. O rendimento total de ?leo foi de 0,2 mL a 0,3 mL e de ?leo essencial de 0,3%. a 0,4%. O composto majorit?rio e predominante em nossas pesquisas foi o eugenol, variando entre 46% a 62%, e o segundo maior composto foi o linalol, que ficou entre 22% a 28%. Pesquisas nessa ?rea s?o essenciais para entender o real impacto da hipergravidade simulada no manjeric?o, seu efeito na auxina e sua express?o g?nica.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-06-11T19:45:55Z No. of bitstreams: 1 470271 - Texto Completo.pdf: 601264 bytes, checksum: 631a8bec7a15cd2f97fae4e0bb07768a (MD5) / Made available in DSpace on 2015-06-11T19:45:55Z (GMT). No. of bitstreams: 1 470271 - Texto Completo.pdf: 601264 bytes, checksum: 631a8bec7a15cd2f97fae4e0bb07768a (MD5) Previous issue date: 2015-03-24 / The esophageal and oral tumors are classified as the most frequent malignancies in Brazil. Esophageal cancer is the eighth most common in the world and oral cancer is ranked as the 5th among malignant neoplasms affecting man in Brazil. The lipopolysaccharide (LPS) are characteristic compounds of the cell wall of gram-negative bacteria. They are able to regulate gene expression of pro-inflammatory cytokines by binding to toll-like receptor 4 (TLR4) via NF-kB pathway. Recent studies show that LPS can increase the migration ability of cell lines of human esophageal cancer HKESC-2 by increasing its binding properties. In the meantime, it has not been tested the effect of LPS on esophageal cancer cells OE19 and OE21 and human oral carcinoma HN30. Thus, this study aimed to determine the action of LPS compounds on the proliferation and viability of cell lines of human esophageal cancer and human oral carcinoma HN30. Were used as treatment LPS for OE19 and OE21 cell lines and the PgLPS (lipopolysaccharide of Porphyromonas gingivalis) for HN30 cell line. Cell viability was assessed using the MTT assay and cell counting. The TLR4 expression by real-time PCR was also evaluated. LPS at higher concentrations decreased significantly cell viability in both cell lines, adenocarcinoma (OE19) and squamous esophageal carcinoma (OE21) at different times of treatment. In addition, both cell lines, OE19 and OE21, expressed TLR4 receptor. Taken together, our data demonstrated that LPS at high concentrations might contribute to tumor death, in agreement with previously data. / Os tumores de es?fago e de boca est?o classificados como as neoplasias malignas mais frequentes no Brasil. O c?ncer de es?fago ? o oitavo mais comum no mundo e o c?ncer de boca ? classificado como o 5? dentre as neoplasias malignas que afetam o homem no Brasil. Os lipopolissac?ridos (LPS) s?o compostos caracter?sticos da parede celular de bact?rias gram-negativas. Eles s?o capazes de regular a express?o de genes de citocinas pr?-inflamat?rias, atrav?s da liga??o ao receptor toll-like 4 (TLR4) via NF-kB. Estudos recentes mostram que o LPS pode aumentar a habilidade de migra??o de linhagens c?lulares de c?ncer de es?fago humano HKESC-2 atrav?s do aumento de suas propriedades de ades?o. Entretanto, ainda n?o foi testado o efeito do LPS sobre as c?lulas de c?ncer de es?fago e de carcinoma oral humano HN30. Deste modo, este estudo teve como objetivo determinar a a??o dos compostos de LPS (derivado de bact?rias) sobre a prolifera??o e viabilidade de linhagens celulares de c?ncer de es?fago humano, e de carcinoma oral humano. Foram utilizados como tratamento o LPS para as linhagens OE19 e OE21 e o PgLPS (lipopolissacar?deo da Porphyromonas gingivalis) para a linhagem HN30. A viabiliadade celular foi avaliada utilizando o ensaio MTT e contagem celular. Tamb?m foi avaliada a express?o do receptor TLR4 por PCR em tempo real. LPS em concentra??es mais elevadas reduziu significativamente a viabilidade celular em ambas as linhagens celulares de c?ncer de es?fago, o adenocarcinoma (OE19) e o carcinoma de c?lulas escamosas (OE21) em diferentes tempos de tratamento. Al?m disso, ambas as linhagens celulares, OE19 e OE21, expressaram o receptor TLR4. Avaliados em conjunto, os nossos dados demonstram que o LPS em concentra??es elevadas pode contribuir para a morte tumoral, de acordo com dados pr?vios.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2015-06-25T11:34:05Z No. of bitstreams: 1 471145 - Texto Completo.pdf: 583122 bytes, checksum: b9760b9161356a851110fa2f73635187 (MD5) / Made available in DSpace on 2015-06-25T11:34:05Z (GMT). No. of bitstreams: 1 471145 - Texto Completo.pdf: 583122 bytes, checksum: b9760b9161356a851110fa2f73635187 (MD5) Previous issue date: 2015-03-09 / Glioblastoma multiform (GBM) is a highly aggressive tumor of the central nervous system and has a few available therapies. In GBM, proinflammatory signaling pathways, such as STAT3 and NF- ?B are aberrantly activated and associated with cell proliferation, survival, invasion and resistance to chemotherapy. Therefore, inhibition of these pro-inflammatory pathways has been suggested as a strategy to combat malignant cells. Resolvins of D-series promote resolution of inflammation by decreasing the activation of NF-?B. The Resolvin D2 (RvD2) is derived from a double sequence of docosahexaenoic acid lipoxygenation, which is derived from the essential fatty acid Omega-3. Our hypothesis is that the resolvins, by direct or indirect inhibition of pro-inflammatory pathways, could compromise the survival and growth of glioma. Our goal is to assess the role of RvD2 and its precursor 17 (R) HDHA (HR17) on tumor cell proliferation and survival in murine glioma model. For this, murine glioma cell line (GL261) was treated in vitro with RvD2 and HR17, and cell death and proliferation were evaluated. Furthermore, the effect of RvD2 and HR17 was evaluated in vivo after GL261 brain implantation; histopathological characteristics and immunohistochemistry for activated caspase-3 were evaluated to. It was found that RvD2 GL261 induces apoptosis in vitro. Furthermore, in vivo treatment of RvD2 and HR17 increased the number of tumor cells positive for activated caspase-3, although not alter tumor area. Interestingly, the HR17 treatment reduces tumor mitotic index in vivo. These results suggest that RvD2 and HR17 have a potential role in the induction of apoptosis in murine glioma cells. / Glioblastoma multiforme (GBM) ? um tumor altamente agressivo do Sistema Nervoso Central e possui poucas terapias dispon?veis. Em GBM, vias de sinaliza??o pr?-inflamat?rias, como da STAT3 e NF-?B, s?o aberrantemente ativadas e associadas com a prolifera??o celular, sobreviv?ncia, invas?o e resist?ncia ? quimioterapia. Por conseguinte, a inibi??o dessas vias pr?inflamat?rias tem sido sugerida como uma estrat?gia para combater as c?lulas malignas. As resolvinas da s?rie D promovem resolu??o da inflama??o diminuindo a ativa??o de NF-?B. A Resolvina D2 (RvD2) deriva de uma sequencia de dupla lipoxigena??o do ?cido docosahexaen?ico, o qual ? derivado do ?cido graxo essencial Omega-3. Nossa hip?tese ? que as resolvinas, por inibi??o direta ou indireta de vias pr?-inflamat?rias, poderiam comprometer a sobreviv?ncia e o crescimento do glioma. Nosso objetivo consiste em avaliar o papel da RvD2 e de seu precursor 17(R)HDHA (HR17) sobre a prolifera??o de c?lulas tumorais e sobreviv?ncia em um modelo de glioma murino. Para isso, a linhagem de c?lulas de glioma murino (GL261) foi tratada in vitro com RvD2 e HR17, e amorte celular e prolifera??o foram avaliadas. Al?m disso, o efeito de RvD2 e HR17 foi avaliado in vivo ap?s o implante de GL261 no c?rebro, avaliando-se caracter?sticas histopatol?gicas e a imunohistoqu?mica para caspase-3 ativada. Verificou-se que RvD2 induz apoptose de GL261 in vitro. Al?m disso, o tratamento de RvD2 e HR17 in vivo aumentou o n?mero de c?lulas tumorais positivas para caspase-3 ativada, embora n?o alterassem a ?rea do tumor. Curiosamente, o tratamento HR17 reduz o ?ndice mit?tico tumoral in vivo. Estes resultados sugerem que RvD2 e HR17 t?m um potencial papel na indu??o de apoptose em c?lulas de glioma murino.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-07-26T14:25:23Z No. of bitstreams: 1 DIS_MARCOS_VINICIUS_FORTES_ALBA_COMPLETO.pdf: 1333852 bytes, checksum: c687fbcabc052faa5ed3567c986640e9 (MD5) / Made available in DSpace on 2016-07-26T14:25:23Z (GMT). No. of bitstreams: 1 DIS_MARCOS_VINICIUS_FORTES_ALBA_COMPLETO.pdf: 1333852 bytes, checksum: c687fbcabc052faa5ed3567c986640e9 (MD5) Previous issue date: 2016-02-15 / Nuclear Medicine enables, among other things, the visualization, characterization and quantification of biochemical processes, metabolism, biomarkers and receptors in vivo by molecular imaging. One of the methods of functional imaging available in this area is Positron Emission Tomography (PET), which depends on the administration of a radiopharmaceutical in the studied organism. One disease that can be studied by PET scan is multiple sclerosis (MS) through the access to the TSPO (Translocator protein) receptors density. The radiopharmaceutical [11C]-(R) -PK11195 has high affinity and selectivity for these receptors, which are increased in activated microglia cells in the case of MS. Therefore, the objective of this study was to develop and to validate the production process (synthesis, purification and quality control) of the radiotracer [11C]-(R)-PK11195 in the Radiopharmaceutical Production Center of the Brain Institute of Rio Grande do Sul (BraIns), allowing performing PET scans for the study of MS. The radioisotope was produced in the 16 MeV PETrace cyclotron (GE Healthcare) as [11C]CO2 via the nuclear reaction 14N (p, ?)11C after the bombardment of a gaseous target containing N2 and 0.5% of O2 with protons. The production was performed in the equipment TRACERlab FX-C Pro (GE Healthcare) to meet the requirements of Good Manufacturing Practices (GMP). The radiopharmaceutical quality control was carried out at the BraIns Quality Control Laboratory and the final product was tested for Identity and Radionuclidic Purity, Radiochemical Purity, Specific Activity, Residual Solvents, pH, Sterility, the Filtration Membrane Integrity and Bacterial Endotoxins. The synthesis was performed through the methylation of the precursor (R)-[N-desmethyl]PK11195 using [11C]CH3I (methyl iodide labeled with carbon-11) under the defined optimal conditions: 400 uL of dimethyl sulfoxide (DMSO), approximately 1 mg of precursor, approximately 10 mg of potassium hydroxide (KOH) at 40 ?C for 1 minute. The reaction mixture was then neutralized with 1 mol.L-1 hydrochloric acid and diluted with mobile phase (76% acetonitrile and 24% Milli-Q water). The diluted mixture was injected into a semi-preparative HPLC system for purification. Solid phase extraction (through Sep-Pak C18 cartridges - Waters) was used to remove the solvent. Product elution and formulation was conducted with 0.7 mL of ethanol and 6.3 ml of 0.9% saline (sterile and pyrogen free). Sterilization was performed by filtration on a 0.22 ?m pore membrane and, as well as the filling process, was carried out under laminar flow. The process steps could be optimized and fitted to the equipments and laboratories structure. Radiochemical yield of the process in relation to the [11C ]CH3I start activity was 15.5 ? 2.4 % ( 7471.5 ? 1283.8 MBq ; n = 39 ) . All batches were approved according to the specifications defined and tested in the quality control, reaching Radiochemical Purity levels greater than 99% and a Specific Activity of 39.7 ? 11.1 GBq / micromol , 10 minutes before the injection. All analytical methods were validated and met the requirements established by current regulations. Three consecutive batches were produced and approved by the quality control, so the process could be considered validated. The developed process was suitable for production of adequate doses of the radiopharmaceutical [11C]-(R)-PK11195 for clinical use at BraIns. The production of the radiopharmaceutical labeled with carbon-11 at the institute provides an additional tool for improving health services in the country and to improve the life quality of the patients. / A medicina nuclear possibilita, dentre outras coisas, a visualiza??o, caracteriza??o e quantifica??o de processos bioqu?micos, metab?licos, biomarcadores e receptores, in vivo, atrav?s da imagem molecular. Dentre as modalidades de imagem funcional dispon?veis nesta ?rea est? a Tomografia por Emiss?o de P?sitrons (PET), que depende da administra??o de um radiof?rmaco no organismo estudado. Uma das doen?as pass?veis de estudo atrav?s do exame PET ? a esclerose m?ltipla (EM), atrav?s do acesso ? densidade de receptores TSPO (Prote?na Translocadora). O radiof?rmaco [11C]-(R)-PK11195 possui alta afinidade e seletividade por estes receptores, aumentados nas c?lulas ativadas da micr?glia nos casos de EM. Portanto, o objetivo deste trabalho foi desenvolver e validar o processo produtivo (s?ntese, purifica??o e controle de qualidade) do radiof?rmaco [11C]-(R)-PK11195 no Centro de Produ??o de Radiof?rmacos do Instituto do C?rebro do RS (InsCer), possibilitando a realiza??o de exames PET para o estudo da EM. O radiois?topo foi produzido no C?clotron PETrace 16 MeV (GE Healthcare) na forma de [11C]CO2 atrav?s da rea??o nuclear 14N(p,?)11C, por meio do bombardeamento com pr?tons do alvo gasoso contento N2 e 0,5 % de O2. A produ??o foi realizada no equipamento TRACERlab FX-C pro (GE Healthcare) atendendo ?s exig?ncias de Boas Pr?ticas de Fabrica??o (BPF). O controle de qualidade do radiof?rmaco foi realizado no Laborat?rio de Controle de Qualidade do InsCer e o produto acabado foi submetido ?s an?lises de Identidade e Pureza Radionucl?dica, Pureza Radioqu?mica, Atividade Espec?fica, Solventes Residuais, pH, Esterilidade, Integridade da Membrana Filtrante e Teor de Endotoxinas. A s?ntese foi realizada atrav?s da metila??o do precursor (R)-[N-desmetil]PK11195 utilizando o [11C]CH3I (iodeto de metila marcado com carbono-11) sob as condi??es ?timas definidas: 400 ?L de dimetilsulf?xido (DMSO), aproximadamente 1 mg de precursor, aproximadamente 10 mg de hidr?xido de pot?ssio (KOH), a 40 ?C durante 1 minuto. A mistura de rea??o foi posteriormente neutralizada com ?cido clor?drico 1 mol.L-1 e dilu?da com fase m?vel (acetonitrila 76 % e ?gua Milli-Q 24 %). A mistura dilu?da foi injetada em sistema CLAE semi-preparativo para purifica??o. Extra??o de fase s?lida (atrav?s de cartuchos SepPak C18 ? Waters) foi utilizada para remo??o do solvente. A elui??o e formula??o do produto foi realizada com 0,7 mL de etanol e 6,3 mL de solu??o salina 0,9 % (est?ril e livre de pirog?nios). A esteriliza??o foi realizada atrav?s de filtra??o em membrana de poro de 0,22 ?m e, assim como o envase, ocorreu em fluxo laminar. As etapas do processo foram otimizadas e adequadas aos equipamentos e estrutura dos laborat?rios. O rendimento radioqu?mico do processo em rela??o ? atividade de [11C]CH3I de partida foi de 15,5?2,4 % (7471,5?1283,8 MBq; n=39). Todos os lotes produzidos foram aprovados quanto ?s especifica??es definidas e testadas no controle de qualidade, atingindo Pureza Radioqu?mica maior que 99 % e uma Atividade Espec?fica de 39,7?11,1 GBq/?mol, 10 minutos antes da inje??o. Todas as metodologias anal?ticas foram validadas e atenderam os crit?rios estabelecidos pela norma vigente. Tr?s lotes consecutivos foram produzidos e aprovados no controle de qualidade e o processo p?de ser considerado validado. O processo desenvolvido se mostrou adequado para produ??o do radiof?rmaco [11C]-(R)-PK11195 em doses suficientes para realiza??o de exames em pacientes no InsCer. A produ??o do radiof?rmaco marcado com carbono-11 no instituto disponibiliza mais uma ferramenta para melhoria dos servi?os de sa?de no pa?s e para melhoria da qualidade de vida dos pacientes.

?rea de concentra??o: Planejamento, Gest?o de Integra??o Universidade e Servi?os de Sa?de. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-05-21T18:55:53Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) cynthia_antunes_barbosa.pdf: 1026437 bytes, checksum: 8fad370131a95c857abd1dbdb60bddd8 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-06-05T14:48:08Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) cynthia_antunes_barbosa.pdf: 1026437 bytes, checksum: 8fad370131a95c857abd1dbdb60bddd8 (MD5) / Made available in DSpace on 2018-06-05T14:48:08Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) cynthia_antunes_barbosa.pdf: 1026437 bytes, checksum: 8fad370131a95c857abd1dbdb60bddd8 (MD5) Previous issue date: 2017 / A homologa??o das Diretrizes Curriculares Nacionais do Curso de Gradua??o em Farm?cia por meio dos seus princ?pios, fundamentos, condi??es e procedimentos para a forma??o dos farmac?uticos prop?s mudan?as significativas na concep??o e no modelo de educa??o, com conte?do para a forma??o direcionada para a realidade s?cio econ?mica do pa?s. A concep??o do ensino passou ser pautada para a forma??o de indiv?duos com respostas ?s necessidades concretas da popula??o, direcionada para pesquisa com compet?ncias para a produ??o de novas ideias e conhecimentos, para o fortalecimento do Sistema ?nico de Sa?de, al?m da sua prepara??o voltada para o mercado de trabalho, ficando sob a responsabilidade das institui??es de ensino superior em desenvolver curr?culo e projeto pol?tico pedag?gico para o atendimento desta proposta. Desse modo, considerando a forma??o de recursos humanos farmac?uticos para atua??o no SUS e reflex?es sobre o cen?rio vivenciado, o estudo objetiva identificar o conhecimento de estudantes do curso de gradua??o em farm?cia sobre o SUS e sua rela??o com a matriz curricular da institui??o de ensino. Como objetivos espec?ficos, buscou-se identificar na matriz curricular os conte?dos de forma??o profissional para atua??o no SUS segundo as exig?ncias das Diretrizes Curriculares Nacionais do Curso de Gradua??o em Farm?cia e relacionar o conhecimento dos estudantes com o conte?do de forma??o profissional da matriz curricular de uma institui??o da cidade de Montes Claros-MG. Trata-se de um estudo de caso descritivo, com abordagem qualitativa e quantitativa. Para a coleta de dados foram utilizados como instrumentos um question?rio aplicado aos estudantes do curso de farm?cia e um formul?rio check list com vista a identificar as vari?veis na estrutura curricular do curso de farm?cia e no plano de ensino da disciplina. A an?lise de dados ocorreu em dois momentos, no primeiro foi empregada a an?lise estat?stica descritiva e o Teste Exato de Fisher e o segundo foi marcado pelo emprego da An?lise de Conte?do. Foi poss?vel verificar que a maioria dos estudantes do curso de farm?cia n?o apresenta conhecimento consolidado sobre o SUS. Embora a institui??o de ensino possua uma pol?tica pedag?gica, com inten??o interdisciplinar, em atendimento as diretrizes curriculares, aos princ?pios e diretrizes do SUS, considera-se que exista a necessidade de mudan?as nos processos produtivos, necessariamente relacionados com a mobiliza??o e reorganiza??o interna da institui??o. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ensino em Sa?de, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / The homologation of the National Curricular Guidelines of the Undergraduate Pharmacy Course through its principles, foundations, conditions and procedures for the training of pharmacists proposed significant changes in the conception and the education model, with content for the formation directed to the socioeconomic reality from the country. The conception of education was based on the formation of individuals with answers to the concrete needs of the population, directed to research with competences for the production of new ideas and knowledge, for the strengthening of the Unified Health System, in addition to its preparation for the labor market, and it is the responsibility of higher education institutions to develop a curriculum and pedagogical political project to meet this proposal. Thus, considering the formation of pharmaceutical human resources for action in the SUS and reflections on the scenario experienced, the study aims to identify the knowledge of undergraduate pharmacy students about the SUS and its relationship with the curricular matrix of the educational institution. As specific objectives, it was sought to identify in the curricular matrix the contents of professional training to work in the SUS according to the requirements of the National Curricular Guidelines of the Pharmacy Undergraduate Course and to relate the knowledge of the students with the content of professional formation of the curricular matrix of an institution of the city of Montes Claros-MG. This is a descriptive case study with a qualitative and quantitative approach. For data collection, a questionnaire applied to students of the pharmacy course and a checklist form was used as instruments to identify the variables in the curricular structure of the pharmacy course and in the teaching plan of the discipline. The data analysis took place in two moments, the first one was the descriptive statistical analysis and Fisher's Exact Test and the second was marked by the use of Content Analysis. It was possible to verify that the majority of the students of the course of pharmacy does not present consolidated knowledge about SUS. Although the educational institution has a pedagogical policy, with an interdisciplinary intention, in accordance with the curricular guidelines, SUS principles and guidelines, it is considered that there is a need for changes in the productive processes, necessarily related to the internal mobilization and reorganization of the institution.

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-06-28T19:56:24Z No. of bitstreams: 1 DIS_ANA_HELENA_BRETANHA_LOPES_TORT_COMPLETO.pdf: 1228563 bytes, checksum: 1ae15f2eb2fe5ed55580c78c418cb7be (MD5) / Made available in DSpace on 2016-06-28T19:56:24Z (GMT). No. of bitstreams: 1 DIS_ANA_HELENA_BRETANHA_LOPES_TORT_COMPLETO.pdf: 1228563 bytes, checksum: 1ae15f2eb2fe5ed55580c78c418cb7be (MD5) Previous issue date: 2016-02-15 / Gliomas are primary tumors of the central nervous system that are associated with a high mortality rate; they course with an average survival rate of 2 years after the diagnosis. Less than 5 % of glioma patients survive more than five years after diagnosis, even those treated with state of the art protocols, which include surgery, radiotherapy and chemotherapy. Tumors result from impairments of intracellular signaling pathways, including the p38/MAPK pathway, which, are responsible to control of cell proliferation and tumorigenesis, among other cellular responses. The goal of the present work was to investigate the effects of ML3403, an inhibitor of p38/MAPK, on the viability and proliferation of glioma cells, and to assess its effect when combined with bevacizumab (BVZ). BVZ already used in the clinical setting as anadjuvant for treating gliomas. It is a monoclonal antibody against VEGF-A receptor and thus reduces the signaling involved in tumor angiogenesis. U138 and U251 glioma cells were treated with ML3403 (0.1 to 200 ?M) and BVZ (1 to 200 ?g/mL) and later assessedfor cell viability, by MTT method and proliferation by cell counting. The results demonstrate that treatment with ML3403 reduces glioma cell viability and proliferation. Co-treatment with BVZ does not present any significant effect. The use of p38/MAPK inhibitors may constitute an interesting treatment against glioma progression. / Por serem tumores prim?rios localizados no sistema nervoso central, os gliomas apresentam altas taxas de mortalidade com sobrevida m?dia de dois anos. Menos de 5% dos pacientes com gliomas sobrevivem mais de cinco anos ap?s o diagn?stico, mesmo com os tratamentos mais avan?ados, os quais envolvem cirurgia, radia??o e quimioterapia. Os tumores resultam de diferentes defeitos em vias de sinaliza??o intracelulares, incluindo a via p38/MAPK. Entre as respostas celulares mediadas pela fam?lia de p38/MAPK, destaca-se a regula??o da produ??o do fator de crescimento endotelial vascular (VEGF). O objetivo deste trabalho foi investigar os efeitos de ML3403, um inibidor da p38/MAPK, sobre a viabilidade das c?lulas de glioma, e avaliar o seu efeito combinado com bevacizumab (BVZ). O BVZ, j? utilizado na cl?nica como adjuvante no tratamento de gliomas, ? um anticorpo monoclonal contra o receptor de VEGF-Ae reduz a sinaliza??o envolvida no processo de angiog?nese tumoral. As c?lulas de gliomas U138MG e U251MG foram tratadas com ML3403 (0,1 a 200?M) e BVZ (1 a 200 ?g/mL)e avaliadas para viabilidade celular, atrav?s do m?todo do MTT e prolifera??o celular, atrav?s da contagem do n?mero de c?lulas. Os resultados obtidos demonstraram redu??o da viabilidade e prolifera??o celular ap?s o tratamento com ML3403. O co-tratamento com BVZ n?o apresentou efeito aditivo. A utiliza??o de inibidores da via de sinaliza??o p38/MAPK pode ser considerada como um tratamento promissor na diminui??o do crescimento de gliomas.

Made available in DSpace on 2015-04-14T13:36:00Z (GMT). No. of bitstreams: 1 461830.pdf: 11610575 bytes, checksum: b0aef66ba8914bbe1256a12ea60f4861 (MD5) Previous issue date: 2014-02-24 / The National Examination Performance of Students (ENADE) part of the National System of Higher Education Assessment (SINAES), as a mandatory curriculum component in undergraduate courses (BRAZIL, 2004), in order to monitor the process of academic learning in relation the precepts established by the National Curriculum Guidelines (DCN). In this research there was a critical and reflective analysis of the issues of proof of ENADE held by scholars of Pharmacy in 2010, through the opinion of teachers linked to the School of Pharmacy of institutions, public and private, in the state of Rio Grande do Sul (RS). The main objective was to verify if the character of evidence and evaluation order are consistent with the recommendations by the Pharmacy course (DCNF) for the training and evaluation of general professional National Curriculum Guidelines. Through Qualtrics Survey Software, four separate questionnaires, each containing 10 questions originally transcribed the ENADE and categories of analysis established from the assumptions of DCNF were prepared. The questionnaires were sent by digital means teachers allocated to 18 courses Pharmacy RS of 16 different higher education institutions. From March to September 2013, 131 teachers conducted the analysis of the 40 questions ENADE 2010. Specific issues of component, with a mean score 7.78?2.22 in teacher perception on the appropriateness of the examination, evaluated more exercise capacity in drugs and medicines, critical and reflective skills required of the student and interdisciplinary approach. Questions of General Education, which received an average score 5.16?2.87 in the opinion of the teachers, helped in understanding the social, cultural and economic reality of the environment in which the professional was inserted and lower acuity, assessed the character critical and reflective, humanistic and ethical principles required by DCNF. Thus, the proof of ENADE 2010 held by graduates in Pharmacy presented asymmetric distribution of the aspects of training set. Although it is believed that the current evaluation system of higher education can indeed contribute to improving the quality of vocational training, the proposed test has limitations in the evaluation process with students. These limitations, the present study evidenced through teacher opinion, corroborated findings literary evidenced by Verhine; Dantas (2005); Rothen; Nasciutti (2008); Rodrigues; Peixoto (2009), Dias Sobrinho (2010) and Francisco et al. (2012), who warn about the structuring of the evaluation system and the implementation in the way it currently presents. However, the quest for improvement, it is observed that the national educational policy has focused on constantly improving the quality of education, contextualized by encouraging research like this that drives the construction of an evaluation process that will determine the quality of training for professionals being inserted into society, whether from the general training offered to social needs are being met effectively at all levels of health care. / O Exame Nacional de Desempenho de Estudantes (ENADE) integra o Sistema Nacional de Avalia??o da Educa??o Superior (SINAES), como um componente curricular obrigat?rio nos cursos de gradua??o (BRASIL, 2004), com a finalidade de acompanhar o processo de aprendizagem acad?mica em rela??o aos preceitos estabelecidos pelas Diretrizes Curriculares Nacionais (DCN). Nesta pesquisa realizou-se uma an?lise cr?tico-reflexiva das quest?es da prova do ENADE realizada por acad?micos de Farm?cia em 2010, atrav?s da opini?o de professores vinculados aos cursos de Farm?cia de institui??es, p?blicas e privadas, do estado do Rio Grande do Sul (RS). O objetivo principal foi verificar se o car?ter da prova e o intuito avaliativo s?o condizentes com o preconizado pelas Diretrizes Curriculares Nacionais do curso de Farm?cia (DCNF) para a forma??o e avalia??o do profissional generalista. Por meio do Qualtrics Survey Software, foram elaborados quatro question?rios distintos, cada um contendo 10 quest?es originalmente transcritas do ENADE e as respectivas categorias de an?lise estabelecidas a partir dos pressupostos das DCNF. Os question?rios foram enviados por meio digital a professores alocados a 18 cursos de Farm?cia do RS, de 16 institui??es de ensino superior diferentes. De mar?o a setembro de 2013, 131 professores realizaram a an?lise das 40 quest?es do ENADE 2010. As quest?es do componente Espec?fico, com nota m?dia 7,78?2,22 na percep??o docente quanto ? adequa??o no exame, avaliaram mais a capacidade de exerc?cio em f?rmacos e medicamentos, exigiram habilidade cr?tico-reflexiva do estudante e atua??o interdisciplinar. As quest?es de Forma??o Geral, que receberam em m?dia nota 5,16?2,87 na opini?o dos professores, auxiliaram na compreens?o da realidade social, cultural e econ?mica do meio no qual o profissional estivesse inserido e, em menor acuidade, avaliaram o car?ter cr?tico-reflexivo, humanista e os princ?pios ?ticos exigidos pelas DCNF. Dessa forma, a prova do ENADE 2010 realizada pelos graduandos em Farm?cia apresentou distribui??o assim?trica dos aspectos de forma??o estabelecidos. Muito embora se acredite que o atual sistema de avalia??o do ensino superior possa, de fato, contribuir para a melhoria da qualidade na forma??o profissional, a proposta do exame apresenta limita??es em seu processo de avalia??o junto aos estudantes. Tais limita??es, evidenciadas no presente estudo atrav?s a opini?o dos professores, corroboraram achados liter?rios evidenciados por Verhine; Dantas (2005); Rothen; Nasciutti (2008); Rodrigues; Peixoto (2009); Dias Sobrinho (2010) e Francisco et al. (2012), que advertem quanto a estrutura??o do sistema avaliativo, bem como a execu??o nos moldes em que atualmente se apresenta. Entretanto, na busca pelo aperfei?oamento, observa-se que a pol?tica educacional nacional constantemente tem se voltado para a melhoria na qualidade do ensino, contextualizada pelo incentivo de pesquisas como esta que impulsiona a edifica??o de um processo avaliativo capaz de determinar a qualidade da forma??o dos profissionais que est?o sendo inseridos na sociedade, a saber se, a partir da forma??o generalista oferecida, ?s necessidades sociais est?o sendo supridas de maneira eficaz, em todos os n?veis de aten??o ? sa?de.