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Item Avaliação da atividade tipo ansiolítica do óleo essencial das folhas de Spiranthera odoratissima A. St. Hil. - possível mecanismo envolvido(Universidade Federal de Goiás, 2011-02-28) Galdino, Pablinny Moreira; Costa, Elson Alves; http://lattes.cnpq.br/2607893423583912A ansiedade está entre as patologias crônicas mais comuns em todo o mundo. Em Brasília (capital federal do Brasil) os transtornos de ansiedade afetam 12,1 % da população, sendo o diagnóstico psiquiátrico mais prevalente. Desde a introdução dos benzodiazepínicos na década de 60, eles têm sido os fármacos mais prescritos no tratamento da ansiedade, porém seus efeitos colaterais são proeminentes, tais como sedação, miorelaxamento, ataxia, amnésia e dependência farmacológica. Sendo assim, novas terapias são necessárias no tratamento dos transtornos de ansiedade e o estudo com plantas medicinais pode prover novas opções terapêuticas. A Spiranthera odoratissima A. St. Hillaire (Rutaceae), popularmente conhecida como manacá, é um arbusto encontrado em região de Cerrado utilizado na medicina popular para tratar doenças renais, hepáticas, dores de estômago e cabeça, e reumatismo. O objetivo deste trabalho foi avaliar as atividades farmacológicas do óleo essencial extraído das folhas de S. odoratissima (OEM) no sistema nervoso central, em camundongos, direcionando para o estudo do efeito tipo ansiolítico e possíveis mecanismos envolvidos. O OEM aumentou o número de cruzamentos e o tempo de permanência no centro do campo aberto sem alterar o número total de áreas cruzadas neste teste e o desempenho no teste da barra giratória. No teste do sono induzido por pentobarbital, o OEM reduziu a latência e aumentou o tempo de sono. Nos modelos experimentais de ansiedade, o OEM aumentou o número de comportamentos de mergulhos no teste da placa perfurada, as entradas e o tempo de permanência nos braços abertos no labirinto em cruz elevado (LCE). Além de aumentar também o número de transições e o tempo de permanência no compartimento claro no teste da caixa claro/escuro (CCE). Foi investigado o mecanismo de ação deste efeito tipo ansiolítico através do pré-tratamento com um antagonista benzodiazepínico (flumazenil) ou um antagonista de receptor 5- HT1A (NAN-190) nos testes de LCE e CCE. O efeito tipo ansiolítico do OEM foi antagonizado apenas pelo pré-tratamento com o NAN-190. Em conclusão, estes resultados sugerem que o óleo essencial de S. odoratissima possui efeito tipo ansiolítico sem alterar os parâmetros locomotores, sendo esse efeito mediado via receptor 5HT1A, mas não via sítio benzodiazepínico do receptor GABAA.Item Avaliação dos efeitos cardiovasculares do aceturato de diminazeno (DIZE) em ratos submetidos à sobrecarga pressórica(Universidade Federal de Goiás, 2014-02-12) Macedo, Larissa Matuda; Colugnati, Diego Basile; Castro, Carlos Henrique de; http://lattes.cnpq.br/6354834854727314Activation of the Angiotensin Converting Enzyme 2 (ACE2)-Angiotensin-(1-7) [Ang(1-7)]-Mas Receptor axis results in protective effects in the cardiovascular system. ACE 2 is an important component of Renin-Angiotensin System, because it is able to convert Angiotensin II in Ang-(1-7). Recents studies have shown that diminazene aceturate (DIZE) act as an activator of ACE 2. The objective of this study was to evaluate the cardiovascular effects of chronic treatment with DIZE in pressureoverloaded rats and the possible mechanisms involved in these effects. Male Wistar rats (200-350 g) were divided in four groups: (1) Sham; (2) Coarcted (abdominal aortic banding, CAA); (3) CAA + DIZE (1 mg/kg, gavage); e (4) CAA + DIZE (1 mg/kg, gavage) + A-779 (120 µg/day, osmotic mini-pumps). Twenty one days after surgery procedure, the blood pressure was recorded, the hearts were isolated and perfused according to Langendorff method. Vascular reactivity was measured by isolated aortic ring preparation. In order to evaluate the cardiac hypertrophy, the left ventricular mass index (VMI) was calculated through the ratio of the left ventricular wet weight to tibia length. The cross-sectional area of cardiomyocytes (CSA) was also evaluated. The mRNA levels for ANP, BNP e TGF-β were also evaluated by qRT-PCR. The expression of ACE-2 and ERK1/2, AKT, mTOR, GATA-4, catalase and SOD proteins involved in hypertrophic pathways was analyzed by Western Blot technique. The results are presented as means ± SEM. One-way ANOVA followed by the Newman-Keuls post-test was used to analyze the blood pressure, cardiac morphometric parameters, isolated heart, qRT-PCR and Western Blot experiments. Two-way ANOVA followed by the Bonferroni post-test was used for aortic rings preparation protocols. All statistical analyses were considered significant at P<0.05. Isolated hearts from coarcted rats presented a significant decrease in the left ventricular end systolic pressure (128.1 ± 9.0 vs. 79.1 ± 12.8 mmHg in CAA, P<0.05), left ventricular developed pressure (118.1 ± 8.9 vs. 69.0 ± 12.7 mmHg in CAA, P<0.05), +dP/dt (2295.0 ± 161.8 vs. 1406.0 ± 246.5 mmHg/s in CAA, P<0.05) and dP/dt (1787.0 ± 166.0 vs. 1066.0 ± 181.9 mmHg/s in CAA, P<0.05). The DIZE treatment attenuated all of these effects induced by CAA. Moreover, DIZE treatment increased the coronary flow in hypertrophic hearts (CAA: 11.6 ± 0.8 vs. CAA+DIZE: 15.8 ± 0.6 mL/min, P<0.05). This effect was blocked by A-779. Pressure–overloaded hearts showed a significant increase in VMI (0.17 ± 0.01 vs. 0.21 ± 0.01 g/cm in CAA, P<0.05) and CSA (8.98 ± 0.54 vs. 10.72 ± 0.27 µm in CAA, P<0.05). The chronic treatment with DIZE prevented the heart hypertrophy (10.72 ± 0.27 in CAA vs. 9.25 ± 0.23 µm in CAA+DIZE, P<0.05). Indeed, treatment with A-779 attenuated the antihypertrophic effect induced by DIZE treatment. The coarcted rats presented a increase in mRNA expression of ANP, BNP and TGF-β and the DIZE treatment reverted this effect. The pressure overload decreased the acetylcholine-induced relaxation in aortic rings from coarcted rats and treatment with DIZE was not able to improve this effect. The coarctation decreased the phosphorylation of the AKT, which was not changed by DIZE treatment. The expression of ACE 2, total and phosphorylated ERK1/2, total AKT, mTOR, SOD and catalase was not changed by coarctation or by ACE 2 activation. These results show that the chronic treatment with DIZE was efficient in preventing the left ventricular hypertrophy and cardiac dysfunction induced by pressure overload. These effects were independent of changes in the expression of ACE 2, ERK1/2, AKT, mTOR, SOD and catalase. Thus, DIZE has important therapeutic potential for cardiovascular diseases.Item Produção de filmes poliméricos a base de polissacarídeos de Anacardium occidentale L.(Universidade Federal de Goiás, 2014-03-31) Silva, Fábio Eduardo Fernandes; Fernandes, Kátia Flávia; http://lattes.cnpq.br/9737543228759171; Fernandes, Kátia FláviaIn this study polysaccharides from gummous exudates of Anacardium occidentale (PEJU) were extracted and blended with polyvinyl alcohol (PVA) in order to produce films by casting procedure. The best film formulation was achieved using 6% (w/v) PVA and 6% (w/v) PEJU and 0.5 mL cm-2 ratio of solution to molds area. Under optimized conditions, the films presented 7,58 Kgf cm-2 tensile strength , 186% elongation and 49908,6 in the elastic module. After hydration the films presented good transparency, with values from 50 to 70% of light transmittance at visible spectrum. Maximum hydration occurred after immersion of the films for 20 minutes in different solutions. Hydration resulted in stable structural changes that allow classify these films as Stimule Responsive Materials (SRM). After hydration the films presented 2-fold higher area and swelling index from 1.6 to 2.2 when water and saline solution were respectively used in the process. Absence of cellular toxicity and absence of cell adhesion were observed when human fibroblasts (PDL) were grown in the presence of the PVA/PEJU films. Additionally, tissue response and wound healing were similar both in the presence or absence of the PVA/PEJU films. Immobilization of papain was maximized when reaction occurred at 5 ºC, pH 4.0 and for 60 minutes. After immobilization optimum pH was restricted to pH 8.0, but preserving activity at physiological range (pH 7.0). Immobilized papain showed high stability during storage, including when stored dried. The bioactivity achieved by immobilization of papain on PVA/PEJU films open possibilities of application of this biomaterial in several areas, mainly in the pharmaceutical.Item Desenvolvimento de sistemas lipídicos nanoestruturados contendo paclitaxel: estudos de permeação cutânea(Universidade Federal de Goiás, 2014-01-29) Tosta, Fabiana Vaz; LIma, Eliana Martins; Taveira, Stephânia Fleury; http://lattes.cnpq.br/0382450621383005; Taveira, Stephânia Fleury; Marreto, Ricardo Neves; Lopes, Flávio MarquesPaclitaxel (PTX) is a natural product extracted from the bark of the Pacific Yew and has numerous antitumor actions, including skin cancers. The topical treatment of skin and pre-cancerous lesions cancer is desired, since the systemic treatment has many side effects However, PTX to be incorporated into formulations suitable for it to penetrate the stratum corneum and skin tumors reached. Lipid nanoparticles have potential to increase drug retention in the stratum corneum, thus providing controlled release and great percutaneous absorption. Within this context, the aim of this study was to develop and characterize solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing the antineoplastic PTX and evaluate its permeation into the pig ear skin in vertical diffusion cells type "Franz". Quantification of PTX paclitaxel was performed by high performance liquid chromatography. The NLS and CLNs were obtained by the method of dilution of the microemulsion containingcetylpyridinium chloride, glyceryl behenate, triglycerides of caprylic / capric acid, polysorbate 80 and sorbitan trioleate 85. The particles were characterized by medium size, PdI, zeta potential, encapsulation efficiency, drug loading and recovery. Stability studies were carried out for a period of 30 days with storage at 4 °C (± 2 °C). Theskin permeation studies of the PTX nanoparticles were conducted in “Franz” type diffusion cells in pig ear skin. The NLS obtained showed average size of 314.1 ± 10.9 to 335.9 ± 0.9nm. The CLN obtained with more oil in the lipid matrix (CLN100)showed average size 270.6 ± 13.5 nm. The encapsulation efficiency of the systemsobtained was above 90% when 3.75% was added PTX formulations. The stability studies revealed a trend in increasing the size of the particles PdI along the storage period, but these differences are not statistically significant. The CLN100 increased about 3 times the amount of drug in the stratum corneum (SC) as compared to the administration of unencapsulated drug and also increased by 1.5 times the amount of PTX in the SC in relation to the topical application of other lipid particles. Thus, the lipid particles appear to be promising systems for topical application of PTX.