CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Estudos recentes, realizados no LFE da UFC, mostraram que o extrato aquoso da planta Alpinia zerumbet (Pers.) Burtt. et Smith (EaAz), conhecida popularmente como colÃnia, causa atividade vasodilatadora na aorta torÃcica isolada de rato. Objetivando encontrar o principio ativo desta planta, o EaAz foi fracionado com diferentes solventes e a atividade vasodilatadora das fraÃÃes foi avaliada em anÃis da aorta torÃcica isolada de rato. AlÃm disso, o mecanismo de aÃÃo da fraÃÃo acetato de etila obtida a partir do EaAz foi caracterizado. Ratos machos Wistar (250 a 300 g), oriundos do biotÃrio da UFC, foram sacrificados por deslocamento cervical e a aorta torÃcica removida e dissecada. Montaram-se os anÃis da aorta (4 a 5 mm) em cÃmeras orgÃnicas, contendo soluÃÃo de Krebs, aeradas com carbogÃnio e mantidas a 37ÂC, para a medida de variaÃÃes na tensÃo isomÃtrica. A integridade do endotÃlio foi avaliada utilizando-se a acetilcolina (ACh; 10-5 M) e, posteriormente, o EaAz e as fraÃÃes obtidas do EaAz, hexÃnica (FHxAz), acetato de etila (FAmAz), diclorometano (FDmAz) (0,15; 0,5; 1,5; 5; 15 e 50 g/mL) foram testados em preparaÃÃes contraÃdas com fenilefrina (Phe; 10-8 â 3x10-8 M). A fraÃÃo FAmAz, ACh e nitroprussiato de sÃdio foram testados em preparaÃÃes desprovidas de endotÃlio e tratadas com L-NAME (100 M), caribdotoxina (CTX; 100nM) mais apamina (100 nM), ODQ (30 M), catalase (500 U/mL), superÃxido dismutase (SOD; 500 U/mL) e PEG-catalase (500 U/mL). O EaAz e as fraÃÃes FHxAz e FAmAz foram capazes de relaxar, significativamente, a aorta torÃcica isolada de rato, apresentando os respectivos EC50 19,73, 11,15 e 9,08 (n = 5, 5 e 7, respectivamente, para cada grupo). Contudo, a fraÃÃo FDmAz nÃo apresentou atividade vasodilatadora. Depois, caracterizou-se a resposta vasodilatadora da fraÃÃo FamAz, resposta essa que foi abolida em preparaÃÃes desprovidas de endotÃlio e tratadas com L-NAME (n = 5), ODQ (n = 6) e PEG-Catalase (n = 2). Contudo, o efeito vasodilatador da fraÃÃo FAmAz permaneceu inalterado apÃs tratamento com CTX mais apamina, catalase e SOD na aorta torÃcica de rato (n = 5, 6 e 6, respectivamente, para cada grupo). Segundo nossos resultados, as fraÃÃes FAmAz e FHxAz apresentaram uma maior potÃncia na sua atividade vasodilatadora comparada ao EaAz. Este dado sugere que estas fraÃÃes, possivelmente, contÃm os princÃpios ativos responsÃveis pela atividade vasodilatadora do EaAZ. AlÃm disso, concluiu-se que a atividade vasodilatadora produzida pela FAmAz na aorta torÃcica de rato à dependente do endotÃlio e via NO-GMPc, talvez contando com a participaÃÃo das espÃcies reativas do oxigÃnio ao nÃvel intracelular / Recent studies conducted at the LFE showed that the aqueous extract from Alpinia zerumbet (Pers.) Burtt. et Smith (EaAz), popularly known as ColÃnia, causes vasodilation on isolated rat aortic rings. In order to find the active compound, the EaAz was diluted with different solvents and the vasodilator effect from the different fractions was analyzed on isolated rings of rat aorta. Additionally, the mechanism of action of the ethyl acetate fraction obtained from EaAz was characterized. Male rats Wistar (250 to 300g), provided by the vivarium of UFC, were terminated by cervical dislocation and the thoracic aorta was removed and dissected. The aortic rings (4 to 5 mm) were placed in chambers, which contained Krebs solution and carbogen and were kept at 37o C, in order to measure isometric tension variation. The endothelium integrity was assessed with acetylcholine (ACh; 10-5 M). Afterwards, the EaAz and the other fractions obtained from EaAz, hexane (FHxAz), ethyl acetate (FAmAz), dichloromethane (FDmAz) (0,15; 0,5; 1,5; 5; 15 and 50 g/mL) were tested in preparations that contained phenylephrine (Phe; 10-8 â 3x10-8 M). The FAmAz fraction, ACh and sodium nitroprussiate (SNP; 10-8 M) were tested in preparations without endothelium and treated with L-NAME (100 M), charybdotoxin (CTX; 100nM) plus apamine (100 nM), ODQ (30 M), catalase (500 U/mL), superoxide dismutase (SOD; 500 U/mL) and PEG-catalase (500 U/mL). The EaAz and the FHxAz and FAmAz fractions were able to relax significantly the isolated rat aortic rings, and EC50 was respectively 19,73, 11,15 and 9,08 (n = 5, 5 and 7, respectively, for each group). However, the FDmAz fraction did not present vasodilator activity. The vasodilatory effect of the FAmAz fraction was characterized. The vasodilator activity of the FAmAz fraction was impaired in preparation without endothelium and previously treated with L-NAME (n = 5), ODQ (n = 6) and PEG-Catalase (n = 2). However, the vasodilator activity of the FAmAz fraction remained unchanged after treatment with CTX plus apamin, catalase and SOD on the isolated rat aortic rings (n = 5, 6 and 6, respectively, for each group). The FAmAz and FHxAz fractions presented higher potency in their activity when compared to EaAz. This phenomenon suggests that these fractions possibly contain the active compound responsible for the EaAZ vasodilator effect. In addition, it was concluded that the vasodilator effect caused by the FAmAz fraction on the isolated rat aortic ring is endothelium-dependent and via NO-cGMP. We also believe that the intracellular reactive oxygen species play an important role on the vasodilator mechanism

Orientador: Antonio Condino Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T16:31:53Z (GMT). No. of bitstreams: 1 OliveiraJunior_EdgarBorgesde_M.pdf: 512340 bytes, checksum: d83efc345a2ad7f2aecfc60038e38380 (MD5) Previous issue date: 2006 / Resumo: Investigamos os efeitos do BAY 41-2272 (5-cyclopropyl-2- [1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine) sobre a atividade do sistema NADPH (nicotinamide adenine dinucleotide phosphate) oxidase e expressão do gene CYBB que codifica seu componente principal, a proteína gp91-phox , simultaneamente aos níveis intracelulares de GMPc (cyclic guanosine-3', 5'-monophosphate) e AMPc (cyclic adenosine-3', 5'-monophosphate) em células mielomonocíticas humanas THP-1. ... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da dissertação digital / Abstract: We investigated the effects of the BAY 41-2272 (5-cyclopropyl-2- [1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine) on the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase system, gene expression of gp91-phox, cGMP (cyclic guanosine-3', 5'-monophosphate) levels, and cAMP (cyclic adenosine-3', 5'-monophosphate) levels, in the human myelomonocytic THP-1 cells. ... Note: The complete abstract is available with the full electronic digital dissertation / Mestrado / Mestre em Farmacologia

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The objectives of this study were first, to investigate the effect of stress and ascorbic acid (AA) supplement during stress on intestinal microflora of broilers and layers, and secondly, to determine nitric oxide (NO) production in intestinal tract of broilers during stress, when supplemented with L-arginine, and NO production in cecal bacteria. The intestinal microflora from broilers and layers were analyzed for bacterial populations during stress and when supplemented with ascorbic acid. In both studies, stress response was induced by adrenocorticotropic hormone (ACTH) via a mini osmotic pump for 7 days, and intestinal samples were collected before and after stress response was induced. During stress, there were no significant effects on intestinal bacterial populations, but changes in intestinal microflora were found in stressed layers and broilers. When AA was supplemented during stress, both short-term and long-term, the microbial population was changed. Cecal NO production during stress, cecal bacterial NO production, and large intestinal NO production when L-arginine was supplemented in broilers were determined as nitrite using Griess reagents. The stress response was induced as in the previous studies. The cecal pouches were collected at day 7 after ACTH insertion. Nitric oxide production by the ceca of broilers during stress was decreased. The cecal bacterial NO production was determined in vitro. The cecal bacteria that produced NO were identified as Lactobacillus fermentum, and Clostridium butyricum. Supplementing with L-arginine, Nù -nitro-L- arginine methyl ester (L-NAME), and sodium nitrate did not affect bacterial NO production on MRS agar incubated anaerobically, but sodium nitrate did affect bacterial NO production on tryptic soy and anaerobic agar incubated aerobically and anaerobically, respectively. L-arginine was supplemented in broiler diet to determine the effect on intestinal NO production and microbial populations. Supplemented with L-arginine affected cecal NO production, but did not affect large intestinal NO production or microbial populations. The positive correlation coefficient between NO contents and bacterial populations was only observed in the large intestine when L-arginine was supplemented in the diet.

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