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Item Estudo do efeito relaxante de um novo composto doador de óxido nítrico em preparações de traquéias isoladas de ratos(Universidade Federal de Goiás, 2011-02-22) CASTRO, Patrícia Ferreira da Silva; ROCHA, Matheus Lavorenti; http://lattes.cnpq.br/7459866708740096This study evaluated the mechanisms of relaxation of two nitric oxide (NO) donors, ruthenium complex [Ru(terpy)(bdq)NO+]3+ (Terpy) and sodium nitroprusside (SNP) in isolated trachea of rats. The isolated trachea was sectioned into rings and contracted with carbachol in an organ chamber. The relaxing effect of Terpy and SNP was evaluated at increasing concentrations from 10 nM to 100 μM. Thus, we verified the contribution of the different types of K+ channels, the importance of sGC/cGMP pathway, the inhibition of COX and PDEs, the influence of the extra and intracellular Ca2+ sources and the influence of the epithelium on the relaxing response. The synergism between NO-donor and β-adrenoceptor agonist terbutaline was also verified. Additionally, we have used confocal microscopy in order to analyze the effect of the donors on cytosolic Ca2+ concentration. We have verified that both compounds led to the relaxation of tracheal smooth muscle preparations in a dependent-concentration mode. However, the maximum effect (Emax) induced by Terpy was higher than the effect of SNP. However, the Terpy effects were significantly reduced by pre-contraction with 75 mM KCl. K+ channel blockers like the tetraethylammonium, glybenclamide, BaCl2 and 4-aminopyridine reduced the relaxation to Terpy, while iberiotoxin and apamin did not modify this response. SNP- induced relaxation was significantly reduced by pretreatment with ODQ (sGC inhibitor). On the IBMX (non-selective PDEs inhibitor) increased the relaxation only to SNP. The response to both NO-donors was not altered by indomethacin, thapsigargin (reticular Ca2+-ATPase inhibitor) or ruthenium red (a mitochondrial Ca2+ uniporter inhibitor). The epithelium removal reduced the relaxation only to SNP, and it had no effects on Terpy. In relation to synergic effect of the association of NO-donors and terbutaline, we did not observe any additive effect in the relaxation induced by terbutaline. Terpy was more effective than SNP in reducing the cytosolic Ca2+ concentration measured by confocal microscopy. In conclusion, these results have shown that Terpy induces airway smooth muscle relaxation by cGMP-independent mechanisms. It involves Ca2+ and K+ fluxes (mainly via Kv, Kir and KATP channels) across the membrane, and it is more effective in reducing cytosolic Ca2+ concentration and inducing relaxation in the rat trachea than the SNP. In relation to SNP, the most important relaxation pathway seems to be related to sGC/cGMP pathway and activation of Kir and SKCa channels.Item APLICAÇÃO DO ENSAIO DE DISSOLUÇÃO NA AVALIAÇÃO DA QUALIDADE DE MEDICAMENTOS FITOTERÁPICOS À BASE DE Passiflora sp(Universidade Federal de Goiás, 2008-10-29) COSTA, Ane Rosalina Trento; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267Phytomedicines must to have as active ingredients only products derived from plants. The quality control of these medicines has not yet properly established criteria even with the growing consumption of these drugs worldwide. Among the assays to evaluate the quality there is the test of dissolution, used to examine the release of the active principle from a capsule or tablet in medium that simulates the place of their absorption. Among the nature drugs best known there is Passiflora incarnata L., whose possess sedative action. The C-flavonoid glycosides vitexin and isovitexin are the main components found in aereal parts of Passiflora sp and are used as markers of the genus in the tests of quality control. This study was conducted to apply the test of dissolution to phytotherapy containing passion flower. The method for quantifying of capsules and tablets used was the spectrophotometric assay described in British Pharmacopoeia (2007) to the powder of P. incarnata. The method has been validated for capsules and then used in the tests of dissolution, with apparatus shovel, 37 C ± 0.5 ° C, speed of 50 rpm in 500 mL of the medium of dissolution 0.1 M HCl pH 1.2, collecting 50 ml at the end of 30 minutes. We have investigated an alternative method for quantification of total flavonoids in ultraviolet spectrophotometer , in a wavelength of 269 nm or 350 nm, looking for a more simple and quick method to be used in routine testing, and because be less polluting and unhealthy. In the tests carried out to quantify the levels of total flavonoids found for the manipulated capsules were 2% for powder and 0.975 % for dry extract; for industrialized tablets the levels were 5.5% and 1.52%. The dissolution assay of the pharmaceutical forms at this study showed that the capsules containing dry extract or powder and one of the industrialized tablets showed 87%, 75% e 76%, respectively, of dissolution within 30 minutes of tests. In relation to the proposed alternative method, was selected the wavelength 350 nm for direct quantification of flavonoids presents in the phytomedicines and at the medium of dissolution. It can be noted that the results were consistent and similar to the datas of the validated method: 85% to dry extract, 80% to powder e 75% to one of the industrialized tablets. Whereas the phytomedicines represent a niche market and an opportunity for diversification of the national pharmaceutical industry, it is necessary to defined parameters of quality to ensure its therapeutic action. So, the studies of dissolution are an essential tool which helps to ensuring the quality of these medicines.Item Ensaio de dissolução de fitoterápicos contendo Maytenus ilicifolia Mart ex Reiss (Celastraceae): validação de métodos para quantificação de catequina e epicatequina(Universidade Federal de Goiás, 2010-12-17) LEAL, Ana Flavia Vasconcelos Borges; DINIZ, Danielle Guimarães Almeida; http://lattes.cnpq.br/6801755844853116; BARA, Maria Teresa Freitas; http://lattes.cnpq.br/3914164125498267Maytenus ilicifolia Mart ex Reiss (Celastraceae) popularly known in Brazil as espinheirasanta is used against gastric disorders and ulcers. Quality of herbal medicines is essential to ensure the safety and efficacy of the drug. The dissolution test is an essential tool to assess the quality of herbal medicines in the solid dosage form for oral use. This work aimed to evaluate the dissolution behavior of eleven herbal medicines containing Maytenus ilicifolia, produced with powder or dry extract, purchased in local shops (Goiânia-GO, Brazil). Assay of catechin and epicatechin by high-pressure liquid chromatography (HPLC) and dissolution methods were validated and obtained results allowed the quantification of these markers with precision, accuracy and selectivity. The dissolution profiles have been determined adopting the following conditions: paddle apparatus at 75 rpm and HCl 0.1 M (900 mL at 37°C ± 0.5°C) as dissolution medium. Through the dissolution profiles it has been determined the mathematical model of release (first order), the percentage of catechin and epicatechin dissolved at 45 minutes and the efficiency of dissolution. Capsule containing powder showed rapid release of the markers in the medium (Q>85% in 12 minutes). Tests conducted to verify the quality of herbal medicines were average weight, weight variation, dissolution, chromatographic profile and sensory analysis. It was found that only 45.5% of analyzed herbal medicines products provide satisfactory results. The dissolution test, sensory analysis, average weight, weight variation and chromatographic profile were responsible for noncompliance of, respectively, 18.2%, 18.2%, 18.2%, 9.1% and 36.4% of the samples. Obtained data demonstrated the need to implement these tests in quality control of herbal medicines, so by investigating the release of the active ingredients of these medicines.Item INVESTIGAÇÃO DO POTENCIAL TÓXICO DO EXTRATO BRUTO ETANÓLICO DAS SEMENTES DE ANNONA CORIACEA MART. (ARATICUM) EM CAMUNDONGOS SUBCRONICAMENTE EXPOSTOS(Universidade Federal de Goiás, 2008-09-25) NASCIMENTO, Guilherme Nobre Lima do; FERREIRA, Tales Alexandre Aversi; http://lattes.cnpq.br/1101341437463729; BOZINIS, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018The araticum (Annona coriacea Mart.) is a typical fruit of the brazilian cerrado used popularly to overcome inflammatory processes. The family Annonaceae presents as the main constituents acetogenins, a class of substances with great cytotoxic and genotoxic potential, and cited as responsible for a disease similar to parkinson in a Caribbean population that used the fruit as much as food and for medicinal purposes. The aim of this study was to evaluate the putative activity of crude ethanolic extract of seeds of A. coriacea on the cerebral cortex of mice exposed at doses of 12.5, 25, 50 and 100 mg / kg, and evaluate its activity on different areas of the brain, the liver and kidneys. We used 30 adult male Swiss mice divided into groups control, solvent and treated (12.5, 25, 50 and 100 mg / kg). The extract was administered orally for four days. The target organs were extirpated, fixed in 70% ethanol (v / v) and processed for histological method - hematoxylin and eosin. The analysis of the slides was performed by image processing system for counting cells and other morphometric analysis. The morphological studies showed no significant changes to the brain in different areas, just as no changes were detected in the kidneys. On the other hand, was found a reduction on the frequency of cells per area of the liver, like as an reduction on the consumption of food, water and production of excreta. We conclude with this work a possible hepatotoxic activity induced by exposure to crude ethanol extract of seeds of A. Coriacea Mart., observed by the decrease in frequency of cells per area of the liver, correlated with reductions in consumption of food / water and production of excreta by animals.Item Atividade antitumoral e antiangiogênica de Synadenium umbellatum Pax in vitro e in vivo(Universidade Federal de Goiás, 2008-03-11) NOGUEIRA, Iara Antonia Lustosa; BOZINIS, Marize Campos Valadares; http://lattes.cnpq.br/6157755243167018Synadenium umbellatum Pax is a vegetable belonging to Euphorbiaceae, popularly known as cola-nota , milagrosa , and cancerola , is empirically used as a natural remedy for fighting cancer. In this study we assessed the antitumoral and antiangiogenic activity in vitro and in vivo of ethanolic crude extract and hexanic and chloroformic fractions of S. umbellatum. Citotoxicity assessment tests in vitro were carried out through MTT reduction and Trypan blue exclusion methods, by using Ehrlich ascitic tumor cells and K-562 lineage. Antitumoral and antiangiogenic activity in vivo essays were carried out through Ehrlich ascitic tumor experimental model in Swiss mice. Ethanolic crude extract was tested in 5, 10 and 25 mg/kg/day doses, whereas chloroformic fraction was tested in 1.2; 2.3 and 5.8 mg/kg/day doses, and hexanic fraction in 0.4; 0.8; and 1.9 mg/kg/day doses, for 10 days. The results showed concentration-dependent citotoxic activity, presenting through MTT method the inhibitory concentrations of 50% (Cl 50) 0.4, 0.1, and 0.08 mg/ml for ethanolic crude extract, chloroformic and hexanic fractions, respectively. And in the Trypan blue exclusion test, cell inhibition was 75%, 68%, and 80%, and 95%, 58%, and 64% for Ehrlich ascitic tumor cells and K-562 lineage, respectively. Ethanolic crude extract in the 25mg/kg/day dose increased the animals survival rate, parallely with the reduction of the amount of tumoral cells, beyond present activity on the tumor angiogenesis, and reduce vascular endothelial growth factor levels. Chloroformic and hexanic fractions, in in vivo essays, did not present significant outcomes. Thus, can conclude in the condition this study, that S. umbellatum shows antitumoral and antiangiogenic activity