Navegando por Assunto "Farmacologia"
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Item Acesso aberto (Open Access) Ação da hidroxicloroquina sobre neurônios da retina de embrião de galinha(Universidade Federal do Pará, 2017-03-22) ROSÁRIO, Aldanete Santos; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978Hydroxychloroquine (HCQ) is currently used in the treatment of malaria and autoimmune diseases and others therapeutic purposes. However, this drug is known to cause side effects, including producing visual disturbances, which may be irreversible. The mechanisms that produce these visual disorders are not completely known. HCQ - related retinal toxicity may be due to high metabolic rate, being very susceptible to the action of xenobiotics and oxidative damages. Thus, this work aims to evaluate the effects of the HCQ on retinal cells, as well as their possible mechanisms of cytotoxicity. The model used in this work was of cultures of retina cells from chicken embryo. To evaluate cell viability, mitochondrial activity was measured by MTT. The lysosomal function was evaluated by the incorporation rate of the neutral red dye. The levels of reactive species of general oxygen and superoxide anion were evaluated by the CellROX probe and by Nitro Blue Tetrazolium (NBT) and total glutathione levels were quantified using the Ellman reagent. Viability was tested in mixed cultures (glia and neurons) or enriched cultures of neurons and glia after treatment with HCQ and compared with chloroquine (CQ). Cells were exposed to concentrations of 25μM, 50μM and 75μM for 24 hours. The results show that mixed cultures treated with CQ presented a reduction in viability of 36 and 61% at concentrations of 50μM and 75μM, respectively, whereas HCQ did not alter viability at any of the concentrations tested. However, when cultures enriched with glial cells were exposed to HCQ for 24 hours, the concentration of 75μM had a small reduction in cell viability, while that the reduction in neuronal cells was of 20, 33 and 56% at the concentrations of 25μM, 50μM and 75μM, respectively. Even a shorter treatment time (6 hours) there was loss of viability in retinal neurons. The incorporation of neutral red supravital dye was also altered in neuronal cultures treated with HCQ for 24 hours, with reduction of 19 and 32%, compared to the control for the concentrations of 50μM and 75μM, respectively. HCQ significantly reduced the levels of reactive oxygen species produced by the neuronal cells, mainly superoxide anion, 43, 52 and 61% for the concentrations of 25μM, 50μM and 75μM of HCQ in 24 hours of treatment, respectively. In concentrations of 50μM and 75μM of HCQ for 24 for hours, the levels of total glutathione in neuronal cells presented a reduction of 37 and 53%, respectively. When the glial cell conditioned medium was used in neuronal cells for 6 hours after treatment with HCQ, it completely reversed the drug-induced cytotoxicity. When total glutathione levels were measured in culture of glia treated with HCQ for 24 hours no changes were observed. These results suggest cytotoxic action of CQ in mixed culture of chicken embryo retina cells which is not observed in HCQ treatment. However, HCQ showed cytotoxic action when cells are cultured separately, mainly on neurons, which is reversed by some factor released by glial cells in the extracellular environment, and glutathione is a possible candidate to exert this neuroprotective function.Item Acesso aberto (Open Access) Anti-inflammatory and analgesic activities of Hypericum brasiliense (Willd) standardized extract(2008-09) PERAZZO, Fabio Ferreira; LIMA, Leonardo Mandalho; PADILHA, Marina de Mesquita; ROCHA, Leandro Machado; SOUSA, Pergentino José da Cunha; CARVALHO, José Carlos TavaresThe anti-inflammatory and antinociceptive activities of the standardized leaves extract (HBSE) of Hypericum brasiliense (Guttiferae) were evaluated in animal models. Male Wistar rats were treated with H. brasiliense extract (50, 250 and 500 mg/kg, p.o.) in 3% Tween 80 0.9% saline solution. The treatment of the edema induced by carrageenin with HBSE (500 mg/kg) showed significant inhibition when compared to the control group. At this dose, the edema decreased by 31.25% in the third hour after treatment (edema peak), but the dose of 50 mg/kg has inhibited the edema by 53.13% (p < 0.05). At the dose of 50 mg/kg, the decrease of the edema induced by dextran was similar to that caused by cyproheptadine. The decrease of the formation of granulomatous tissue (6.6%) was comparable to the control group. The HBSE inhibited the abdominal constrictions induced by acetic acid. At a dose of 50 mg/kg, the inhibition of the abdominal constrictions (46.4%) was comparable to that produced by indomethacin (42.9%). A dose of 250 mg/kg inhibited these constrictions by 70.66% when compared to control (p < 0.001). In the hot-plate test, an increase in the latency time was observed at a 50 mg/kg dose. These data suggest that HBSE has anti-inflammatory activity on acute process, developed principally by arachdonic acid derivates and analgesic effect due to its probable involvement in the Central Nervous System.Item Acesso aberto (Open Access) Apoptose de células inflamatórias e evolução clínica do Eritema Nodoso Hansênico: ensaio com Azatioprina(Universidade Federal do Pará, 2008) OLIVEIRA, Miguel Saraty de; XAVIER, Marília Brasil; http://lattes.cnpq.br/0548879430701901Leprosy is a chronic infectious and contagious disease, affecting mainly skin and peripheral nerves, interrupted by outbreaks reaction, classified as Type I or reverse reaction and the reaction type II or erythema nodosum leprosum, usually accompanied by neuritis.Thalidomide and prednisone are widely used in treat ENL, but are not always fully effective, it needs to be investigate other immunosuppressive drugs to control the reaction. The phenomenon of apoptosis of inflammatory cells occurs in leprosy and ENL, but few studies correlating the phenomenon with clinical improvement or worsening of the ENL reaction are available. This report describes the occurrence of apoptosis of inflammatory cells and clinical progression of erythema nodosum leprosum before, during and after the use of azathioprine to treat ENL. The results obtained with 07 patients enrolled in the study indicate that the drug, azathioprine, is effective in treating cases of ENL difficult to treat. This drug may induce remission of ENL, as well as to further decrease the dose of prednisone in use.The phenomenon of apoptosis could be documented using the immunogold with caspase 3 in all cases. There was no significant variation seen between the number of cells highlighted with caspase 3 before and after treatment with azatioprina.No significant correlation between the number of cells highlighted with caspase 3 before and after treatment with azathioprine and clinical improvement shown could be demonstrated.Item Acesso aberto (Open Access) Atividade antimicrobiana, antioxidante e imunomoduladora de Agaricus brasiliensis e Ilex paraguariensis in vitro e em modelo de sepse murino(Universidade Federal do Pará, 2016-09-15) NAVEGANTES, Kely Campos; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Sepsis is an organ dysfunction caused by a dysregulated immune response to an infection, the initial therapeutic approach to sepsis are broad spectrum antimicrobials, which is not sufficient for control of infection, requiring association with other therapies. Thus, Ilex paraguariensis where to be a potent antimicrobial, antioxidant and Agaricus brasiliensis has immunomodulatory properties could be a new source of therapy. Thus, this study aimed to evaluate the antimicrobial effect, antioxidant and immunomodulatory in vitro and in vivo of the extracts. Therefore, in this study, we evaluated the in vitro antimicrobial activity of aqueous extracts from A.brasiliensis and I. paraguariensis against Staphylococcus aureus and Escherichia coli by the method of microdilution and by spectophotometry for determination of minimum inhibitory concentration and cultivation technique on petri dish for minimum bactericidal concentration, cytotoxicity in macrophages was evaluated, nitric oxide (NO) production, proliferation, phagocytosis, equivalent antioxidant capacity to Trolox (TEAC) and determination of the total antioxidant activity by capturing the free radical and reactive species production oxygen (ROS). In the swiss mice with induced sepsis were pretreated with aqueous extracts of A.brasiliensis and I. paraguariensis, after 12 and 24 hours collected their samples and evaluated the survival, leukocyte migration, hemogram, bacterial load, NO production, malondialdehyde (MDA), TEAC and ex vivo we evaluated phagocytic capacity and release of ROS. The A.brasiliensis showed no antimicrobial activity in vitro, remained viable cells reduced the phagocytic capacity, increased NO, but in the presence of LPS reduced, showed proliferative effect, but in the presence of mitogen had antiproliferative effect and has a strong antioxidant activity and capacity to sequester radicals in vitro. I.paraguariensis presented antimicrobial activity as well as cytotoxic effect induced phagocytic capacity increased NO, but in the presence of LPS reduced, had proliferative effect, antioxidant activity and capacity to sequester radicals in vitro. In vivo model of sepsis, both increased the survival of animals, A.brasiliensis reduced leukocyte influx while Ilex increased, only A.brasiliensis had hemogram similar to sham, both extracts reduced bacterial load and levels decreased NO, MDA and increased antioxidant levels in the tissues, in addition, both reduced the production of both extracts present ERO. Although excellent in vitro results, the aqueous extract from A.brasiliensis was found to be most promising as an adjuvant therapy in sepsis that I. paraguariensis due to its high antimicrobial activity, antioxidant and anti-inflammatory in vivo.Item Acesso aberto (Open Access) Avaliação da influência do tratamento com indometacina no aprendizado e na memória espacial em modelo murino de diabetes tipo 1(Universidade Federal do Pará, 2017-05-25) SANTOS, Gabriel Cardoso de Queiroz; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806Diabetes mellitus (DM) is the group of metabolic disorders that has as a common characteristic the disregulation of blood glucose levels, invariably leading to hyperglycemia. This disease has become the most frequent in the adult population, mainly in developing countries, causing several serious consequences such as cardiovascular and renal diseases, factors responsible for a high mortality rate of the individuals affected. In addition that consequences, which are better investigated and described in the literature, other types of complications are observed. Clinical and experimental studies demonstrate that both type 1 and type 2 diabetes mellitus may contribute to the development of cognitive deficits and dementias. However, the mechanisms that lead to such disorders are not yet fully understood. A study using the non-selective non-steroidal anti-inflammatory, indomethacin, has shown that aspects related to impaired neuronal plasticity in diabetes can be reversed, demonstrating that these disorders may be modulated by neuroinflammatory changes. The aim of the present study was to evaluate the influence of chronic treatment with indomethacin on memory and learning in a murine model of type 1 diabetes mellitus (T1DM). Using the open field test, Y-maze test and Morris water maze test we investigated the indomethacin effects on behaviors changes after aloxan inducing T1DM. Indomethacin significantly decrease related behaviors to the anxious state in Open field test. This treatment also reversed space work memory deficits in the Y-maze test, and learning and spatial memory deficits in the Morris Water Maze. Thus, it can be concluded that chronic treatment with indomethacin has beneficial effects on the cognition of mice submitted to type 1 diabetes mellitus.Item Acesso aberto (Open Access) Caracterização físico-química e avaliação toxicológica preliminar do copolímero sulfato de condroitina-co-N-isopropilacrilamida para uso farmacêutico(Universidade Federal do Pará, 2013-07-19) SANCHES, Suellen Christtine da Costa; COSTA, Roseane Maria Ribeiro; http://lattes.cnpq.br/0537372052713559; VASCONCELOS, Flávio de; http://lattes.cnpq.br/3695753129639448The pharmaceutical industry uses polymers as nanoparticles in controlled release formulations and vector for having low cost compared to other methods of preparation of pharmaceutical dosage forms, apparently not being recognized by the body's defense system, provide improved efficacy, reduce toxicity and the dose of administered drug. The sulfate of chondroitin-co-N-isopropylacrylamide (SCM + NIPAAm) is a copolymer proposed for this purpose, from a synthetic polymer reaction, poly Nisopropylacrylamide (PNIPAAm) with thermosensitive characteristics with a natural, Chondroitin sulfate (CS), with bioadhesive characteristics. Thus, the copolymerization may be able to add these properties and to improve its use as a vehicle for controlled-release. This study aimed to characterize physico-chemical of sulfate chondroitin particles and N-isopropylacrylamide and SCM+NIPAAm copolymer (2.5% and 5%) and SCM+PNIPAAm 2.5% and a partial toxicological evaluation of one of these copolymers presenting the best properties of an efficient carrier of drugs, selected from the trials of physic-chemical characterization. To determine the chemical structure of the particulate systems and analyze the chemical components, it was performed Nuclear Magnetic Resonance Spectroscopy (RMN) and Infrared Fourier Transformed Spectroscopy (FTIR), to analyze the morphology of the particles, it was used Electron Microscopy (SEM), The Thermogravimetry and Differential Thermal Analysis (TG/DTA) was used to evaluate the thermal behavior of particulate systems, as well as assist in the analysis of kinetics of degradation (CD, Flynn-Wall-Ozawa method); it was also made in vitro degradation technique and surface charge determining and particles size (Zeta potential analysis, PZ). To evaluate the toxicity, it was performed bioassay in Artemia salina (24 and 48 hours), cell viability (cytotoxicity) on PC-12 cells (MTT method), and also acute oral toxicity in mice. The NMR, FTIR and SEM analysis showed similarity regarding the structural and morphologic aspects between the studied copolymers. TG analyzes showed that SCM+NIPAAm 5% showed higher thermal stability compared to the other copolymers evaluated, since its polymer decomposition occurs at temperatures above around 233 °C. DTA demonstrated temperature values consistent with decomposition thermal events provided by the curves of TG analysis. The stability was confirmed by CD and in vitro degradation study, presenting, respectively, Ea> 100 kJ mol-1 and 48% of its initial weight after three months. Furthermore, SCM+NIPAAm 5% presented particle diameter of less than 200 nm and polydispersity index of 0.35, and the PZ> -30mV, characteristics of a promising candidate as a drug carrier. Regarding toxicological evaluations, SCM+NIPAAm 5% did not show toxicity on bioassay A. saline (LC50> 1000) and in the cellular model evaluated within the concentrations and circumstances of exposure studied. The SCM+NIPAAm 5%, in the oral dose of 2000 mg/kg, did not show any obvious sign of toxicity in mice, which was confirmed by the absence of anatomical and histopathological changes. The copolymerization of chondroitin sulfate and N-isopropylacrylamide in the studied concentration, given its physical-chemical characteristics and toxicological preliminary, presents properties that contribute to propose a system which is a new form of controlled release, especially drugs.Item Acesso aberto (Open Access) Determinação das concentrações plasmáticas e teciduais de itraconazol em pacientes com cromoblastomicose(Universidade Federal do Pará, 2008-09-01) GRISÓLIA, Daniella Paternostro de Araújo; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Chromoblastomycosis is a subcutaneous mycosis caused by deployment transcutaneous of several species of dematiaceous fungi, that is, melanized fungi. Considering the incidence of this disease in the state of Pará and the resulting morbidity of patients affected, with economic and social repercussions, it was made to the optimization of therapeutic schemes adopted, to the best knowledge of the relation dose x response. The itraconazole is one of the few drugs available for treatment, which has marked variability kinetic intra and inter individual, which compromises the establishment of the relation dose and response, as well as tissue and plasma concentrations achieved. In this sense, this work aimed at validation of analytical methodology by High Performance Liquid Chromatography and subsequent determination of itraconazole in samples of plasma and tissue in 20 patients with chromoblastomycosis, assisted in the laboratory of dermatoimmunology Dr. Marcello Candia, Marituba, Pará, who used the drug in doses of 200mg/day and 400mg/day. The technique employed was validated and proved adequate results in accordance with applicable law. Concentrations of plasma and tissue of itraconazole in the dose of 200mg/day were 121.3 87.9 ng/mL and 5.36 5.9 μg/g. The average plasma concentration of itraconazole in patients using 400mg/day was 290 234 ng/mL, and the plasma and tissue mean concentrations of itraconazole in patients who showed no clinical favourable, at doses of 200mg, making it necessary to increase to 400mg were 217 216 and 304 173 ng/mL; 14.87 12.94 e 21.80 6.62 μg/g. The average of relation between tissue and plasma concentrations in patients who had positive developments in clinical in the doses of 200mg/day was 44.29 67.12 and those that did not show positive developments in clinical in the doses of 200mg/day, making necessary to increase to 400mg/day were 68.52 59.90 and 71.71 38.26 respectively.Item Acesso aberto (Open Access) Efeito protetor de antioxidantes na metemoglobina e no dano em dna induzidos pela dapsona-hidroxilamina in vitro(Universidade Federal do Pará, 2016-06-21) GOMES, Antonio Rafael Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Dapsone (DDS) is one of the drugs used in polychemotherapy of leprosy associated with rifampicin and clofazimine. Of these drugs, DDS is primarily responsible for adverse reactions, such as methemoglobinemia and hemolytic anemia. These reactions are related to the DDS metabolite, dapsone hydroxylamine (DDS-NOH). In an attempt to promote the reduction of toxic effects are studied alternative therapies with antioxidants. This work aimed to evaluate the protective effect of N-acetylcysteine (NAC), A. brasiliensis and Glutathione ethyl ester (GSH-EE) in methemoglobin (MetHb) and DNA damage induced by DDS-NOH in vitro , correlating to oxidative stress parameters. For this, suspensions of human erythrocytes to 50% were pre- and post-treated with NAC, A. brasiliensis and GSH-EE in different concentrations, being exposed groups DDS-NOH to induce the formation MetHb. It also assessed whether the activity of enzymes-SOD and CAT and GSH levels, TEAC and MDA. In leukocytes evaluated the induction of ROS intracellularly using DCFH-DA and the damage to DNA by comet assay. The results showed that the DDS-NOH metabolite was capable of inducing MetHb in vitro, this dose-dependent effect. Regarding the pre-treatment, all the antioxidants prevented MetHb formation induced by DDS-NOH, as well as post-treatment. For SOD, only the pre-treatment with NAC and A. brasiliensis reduced SOD activity. In the post-treatment, there was increased when treated with antioxidants. Pre-treatment with NAC and GSH-EE increased CAT activity, moreover A. brasiliensis reduced, as after treatment with antioxidants. As for GSH levels, pre-treatment with NAC and GSH increased A. brasiliensis, on the other hand, did not alter after treatment. Regarding TEAC did not change. With respect to oxidative damage in the pre-treatment A. brasiliensis and GSH-EE reduced MDA. In the post-treatment, there was an increase in group A. brasiliensis and reduced GSH-EE group. Only the NAC was shown to be effective in removing the intracellular ROS induced by DDS-NOH in leukocytes. While in erythrocytes, a NAC and A. brasiliensis were able to reduce this effect. In the study of the comet assay, the DDS-NOH was able to induce DNA damage in peripheral blood leukocytes, however this damage was reduced when treated with NAC and A. brasiliensis. It can be concluded from our data that the evaluated antioxidants have therapeutic potential in the prevention of MetHb and DNA damage induced by DDS-NOH in vitro, more effective NAC against these effects.Item Acesso aberto (Open Access) Estudos farmacognósticos, fitoquímicos e atividade antileishmania de espécies Geissospermum (Apocynaceae)(Universidade Federal do Pará, 2016-11-07) SILVA, João Victor da Silva e; MARINHO, Andrey Moacir do Rosario; http://lattes.cnpq.br/2511998363000599; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649This study aimed to perform pharmacognostic and phytochemical studies, and assess antileishmanial activity and cytotoxicity of Geissospermum vellosii Allemão and Geissospermum sericeum Miers. The pharmacognostic study was carried out as described in the Brazilian Pharmacopoeia, 2010. The ethanol extracts (GVEE and GSEE) were obtained by exhaustive maceration with ethanol (96 ° GL), followed by concentration in rotaevaporator. The ethanol extract was fractionated using two methods: extraction under reflux (fractions of different polarities) and acid-base partition (neutral and alkaloid fractions). The alkaloid fractions (GVAF and GSAF) were fractionated on a chromatographic column with Sephadex LH-20 gel, and the resulting subfractions were analyzed on TLC, and reveled through Dragendorff reagent and ultraviolet (365 nm). The F6GVAF and F6GSAF subfractions, with alkaloids detected and good yield, were subjected to semi-preparative HPLC-DAD, and spectrophotometric methods. For evaluating the antileishmanial activity, promastigote forms of Leishmania amazonensis at a concentration of 5 x 106 parasites/100μL were treated with the samples at different concentrations for 24, 48 and 72h. The analysis was done adding [3- (4,5-dimethylthiazol-2-yl) -2,5- diphenyltetrazolium bromide (MTT) to the samples in an ELISA reader at 490 nm. Cytotoxicity was assessed through cell viability assay with MTT in differentiated THP- 1 cells and HepG2. As a selection criteria, the selectivity index (IS) was calculated as the ratio between the cytotoxic concentration 50% in cell lines, and the inhibitory concentration 50% found for protozoa, considering as promising values ≥ 10. The plant powder was classified as thick (G. vellosii), and very thick (G. sericeum), low density, with pH 4.94 (G. vellosii) and 6.47 (G. sericeum), negative to saponins, with ash and moisture within the parameters established by the Brazilian Pharmacopoeia V. In the phytochemical study, we suggest the isolation of an indole alkaloid (F3F6FAGV) and a β-carbolinic (flavopereirine) from both species. The fractionation of GVEE and GSEE resulted in more cytotoxic subfractions, but the exposure time and refractionation reduced this effect. In the antipromatigota assay, all samples were active, and the fractionation increased the activity. The flavopereirine presented time-dependent activity greater than amphotericin B. However, the flavopereirine in association with indole alkaloid and/or amphotericin B reduced the selectivity of this metabolite. The extracts fractionation increases the selectivity index, and the selectivity of flavopereirin is high (SI = 4893.3). Therefore, the isolation of flavopereirine contributes to reduce cytotoxicity and increase selectivity, showing itself as a promising antileishmanial agent.Item Acesso aberto (Open Access) Estudos farmacognósticos, fitoquímicos e biológicos de Annona glabra L. (Annonaceae)(Universidade Federal do Pará, 2016-05-12) BRÍGIDO, Heliton Patrick Cordovil; MARINHO, Moacir do Rosario Marinho; http://lattes.cnpq.br/2511998363000599; DOLABELA, Maria Fâni; http://lattes.cnpq.br/0458080121943649In this study, the Annona glabra underwent pharmacognostic, phytochemicals and biological studies (leishmanicide and antimicrobial activity). In pharmacognostic studies, we used the methods described in Brazilian Pharmacopoeia V ed. (2010). The ethanolic extract (EE) was obtained by maceration of the powder batch of shells with ethanol. The extract was fractionated by liquid-liquid partition with hexane and 10% aqueous methanol resulting in hexane (HF), and methanol (MF) fractions. The MF was submitted to Sephadex column. This procedure resulted in 46 fractions that were analyzed in thin layer chromatography and revealed with sulfuric acid, Dragendorff, and ultraviolet (360 nm) being assembled into 5 groups according to their chromatographic profiles. Group 3 was purified by column chromatography on a preparative scale yielding the G3-1 sample. EE, MF, HF, Group 2 and G3-1 were analyzed by HPLC-DAD. The G3-1 sample was analysed by mass spectrometry and nuclear magnetic resonance (NMR). To evaluate the antimicrobial activity, methods of agar diffusion (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and microdilution (MIC) were used. The EE and its fractions were subjected to leishmanicide activity test (Leishmania amazonensis). The powder was classified as coarse and low-density, with ash and moisture contents within the parameters established by the Brazilian Pharmacopoeia. In HPLC-DAD, the main peaks of EE and its fractions were presented in UV absorption spectrum of 240 nm to 280 nm, and 300 nm to 400 nm suggestive respectively Band II (Ring A), and band I (ring B ) of flavonoid. The G3-1 chemical structure was identified as flavonoid rutin. In the agar diffusion test, we observed the formation of halos in EE and MF only in Staphylococcus aureus plates. In the microdilution assay, the EE and FM showed MIC> 1000 mg / mL, considered inactive. In antileishman test, the EE showed IC50> 200 / ml. The MF and HF also showed IC50> 200 / ml; however, they inhibited the growth of promastigotes respectively in 20% and 33.7%. The subtractions and G3-1 Group 2 showed IC50> 200 / ml, but the concentration of 200 / ml inhibited the parasite growth by approximately 45%. The EE, fractions, and subfractions were inactive against L. amazonensis amastigotes. However, the HF concentrations of 250 and 125 g / ml inhibited infection in 39.1% and 18.7%. In short, EE and its fractions were shown to be inactive in the antimicrobial and leishmanicide trials, but fractionation contributed to increase activity suggesting that active substances must be at low levels in extract and its fractions.Item Acesso aberto (Open Access) Monitoramento das reações adversas ao novo tratamento da tuberculose(Universidade Federal do Pará, 2016-05-22) RODRIGUES, Miguel Wanzeller; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Tuberculosis is an infectious disease that despite the effective prophylactic and therapeutic resources is one of the most serious problems of global public health. In 2014, there were 67,966 new cases of the disease in Brazil, with the highest incidence rate in the states of Amazonas, Rio de Janeiro, Acre, Pernambuco, Mato Grosso and Pará. Three factors contribute to continuity of tuberculosis in Brazil: the HIV pandemic the development of multiresistant strains and failure of BCG. The lack of adherence to treatment is one of the main reasons the spread of resistance. In order to reduce this problem and minimize adverse reactions, WHO in 2006 recommended a new regimen: 2RHZE (intensive phase) and 4R (maintenance phase), which was adopted by Brazil in 2010. However, adverse reactions requiring discontinuation of treatment has not been estimated with the new regimen, which justifies this study aimed to analyze the occurrence of adverse events in subjects with tuberculosis in the use of new treatment regimen (Isoniazid, Rifampin, Ethambutol, Pyrazinamide). A prospective longitudinal study of 57 subjects with clinical diagnosis, laboratory and radiological tuberculosis. The renal function tests (urea and creatinine) and liver (AST, ALT, alkaline phosphatase, bilirubin and gamma GT) were performed every month of treatment. In the study, Disease affected more males with low education, who used tobacco and alcohol and regardless of age. There were increasing urea values in the last two months of treatment, but creatinine was normal during treatment. Regarding the assessment of liver function, fluctuations were observed in biochemical parameters analyzed, but remained in the normal range. It is noteworthy that a subject has developed framework of cholestatic liver disease, which resolved upon discontinuation of treatment. Early diagnosis, coupled with immediate treatment enables the patient an effective outcome in the fight against tuberculosis, as it keeps the biochemical parameters without major changes, allowing for a better adherence and clinical improvement of the patient.Item Acesso aberto (Open Access) Obtenção e caracterização de carreadores lipídicos nanoestruturados a partir de gordura vegetal de murumuru (Astrocaryum murumuru Mart.)(Universidade Federal do Pará, 2016-05-16) SENA, Luann Wendel Pereira de; SILVA JÚNIOR, José Otávio Carréra; http://lattes.cnpq.br/4437885351749994The nanostructured lipid carrier (NLC) have been proposed as a carrier’s category for pharmaceutical and cosmetic ingredients and an increasing of interest due to a series of advantages when compared to conventional formulations. The Amazonian vegetable fats are considered lipids arrays of great potential for the production of NLC from topical administration, according to the low toxicity and biocompatibility, beyond their emollient properties, protector and moisturizer in the skin. The murumuru (Astrocaryum murumuru Mart.) is an amazon palm and the utility of its fat is promising, because it adds value to the products, favour the growth in the region, in addition to using these resources in a sustainable way. The objective of this research was to obtain and characterize the NLC from the vegetable fat of Murumuru (Astrocaryum murumuru Mart.) by the homogenization technique under high pressure to hot, using ketoconazole as a drug modelling. The gas chromatography showed lauric acid (48,1 %), myristic acid (26,6 %) and oleic acid (8,4 %), as main constituents. The physical-chemical characterization showed acid, iodine, saponification, peroxide, refraction and density values within the limits and standards recommended. The isolated raw materials and the NLC obtained were evaluated using differential scanning calorimetry, where the results about the isolated raw materials used support as was described in Literature and the NLC demonstrated a crystalline structure less ordained. In the tested formulations, the nanoparticles showed average size between 98,60 and 161,56 nm, polydispersibility index between 0,115 and 0,276, zeta potential higher than -30mV and encapsulation efficiency near 100 %. The Transmission Electron Microscopy indicated spherical aspect of the nanoparticles and the! clearance profile showed a zero order kinetic model, with the release of 70,9 % of the encapsulated drug in 8 hours. The nanoparticles remained stable during a period of 60 days. This research showed that the murumuru fat obtained an effective system, with small sizes particles and penetrability in the skin, making possible the formulation propagation in pharmaceutical and cosmetic uses.Item Acesso aberto (Open Access) Obtenção e caracterização de nanoemulsão óleo em água a partir de óleo de açaí (Euterpe oleracea M.)(Universidade Federal do Pará, 2015-05-13) CONTENTE, Denise Maria Loureiro; SILVA JÚNIOR, José Otávio Carréra; http://lattes.cnpq.br/4437885351749994Nanoemulsions have been proposed as an option for drug delivery current systems and increasing interest due to several advantages when compared with traditional formulations. Vegetable oils are considered pharmaceutical ingredients of great value as lipid matrix of these systems, such as oil açaí, of Amazonian origin oil, which has a number of medicinal benefits such as antioxidant and moisturizing activity, and biocompatibility, increases skin elasticity and acts as a physical barrier. The objective of this study was to obtain nanoemulsion O / W, from açaí oil, surfactant and water, through the phase inversion temperature method for topical use. Açaí oil was characterized by physical-chemical tests and on the profile of fatty acids by gas chromatography (GC), spectrometry in the infrared (FT-IR) and thermal analysis by thermogravimetry (TG) and differential scanning calorimetry (DSC). The surfactant, ketoconazole and their binary mixtures with oil açaí were evaluated by DSC. Obtained nanoemulsions making use of açaí oil, BrijTM CS20, water and ketoconazole. The characterization of nanoemulsions was performed on the droplet size, polydispersity index (PI), the zeta potential (PZ), morphology and encapsulation efficiency (EE). The açaí oil showed acid value (3.78 mg KOH / g), iodine value (71 gl2 / 100g), saponification number (199 mg KOH / g), refractive index (1.470) and density (0,950g / ml). In GC analysis showed 68.05% of unsaturated fatty acids, being 47.58% oleic acid. Oxidative stability of açaí oil Rancimat was about 11.79 hours. The FT-IR spectrometric analysis confirmed bands suggestive of unsaturated fatty acids and thermal analysis it was observed that the thermal degradation occurs above 200 ° C. The combinations of raw materials analyzed by DSC was observed that the incorporation of ketoconazole with açaí oil. The nanoemulsion B10 with 0.5% ketoconazole showed 98.31% EE. The transmission electron microscopy showed droplets with spherical shape and after study of PZ (-25.53 ± 10.04 mV), PI (0.37 ± 0.04) and size (128.53 nm ± 10.04) by 30 days, nanoemulsion showed little variation. Thus, it can be said that açaí oil has the potential to be used as a pharmaceutical ingredient can be used as oil phase nanoemulsions loaders of fat-soluble substances.Item Acesso aberto (Open Access) Petiveria alliacea L.: etnobotânica, fitoquímica efeitos neurofarmacológicos e cognitivos(Universidade Federal do Pará, 2016-10-16) LUZ, Diandra Araújo da; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101Petiveria alliacea L. is a shrubby plant, native from tropic regions, used to treat poor memory and improve learning. In the present study, it was evaluated the effects of hydroalcoholic extract of the leaves of P. alliacea (PaLHE, 900 mg/kg) on learning and memory of adult rats, subjected to behavioral tests inhibitory avoidance and Morris Water Maze. In addition, it was performed a thin layer chromatography (TLC) to detect sulphur compound, to correlate them with the investigated responses. Dichloromethane fractions, obtained from aqueous extracts of Alllium sativum and Allium Cepa served as detection patterns. P. alliacea is also present controversial activities on central nervous system (CNS). For this reason, it was realized a bibliographic review of ethnobotanical, phytochemical and neuropharmacological activities of this plant in indexed databases, books, dissertations, thesis and similar scientific sources. According to the results, EHFPa improved short and long term memory, spatial memory and learning. In TLC, the EHFPa produced retention points similar to the standard samples, indicating that there are sulfur compounds in the extract, being possible that they contribute to observed responses. About the review, P. alliacea is popularly used to treat epilepsy, anxiety, poor memory, as a sedative, etc. Such properties have been demonstrated experimentally, varying depending on the dose, preparation, and part of plant used. Phytochemical studies detected several metabolites in P. alliacea, among which sulfur compounds, flavonoids and derivatives classes the most isolated compounds.Item Acesso aberto (Open Access) Potencial cicatrizante do extrato cetônico de Pentaclethra macroloba no processo de reparo de lesões excisionais na pele de camundongos diabéticos(Universidade Federal do Pará, 2017-05-25) GOMES, Mauricio Ferreira; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806Diabetes Mellitus (DM), a disease that attracts the interest of many health professionals, is a chronic pathology that has become a public health concern in recent years. The disease is divided into diabetes type 1 and type 2 , which causes a dysfunction in insulin / glucose physiology. This deregulation causes significant alterations in some biological events, among them, the cicatrization process. The emergence of injury in to a normal person triggers a cascade of cellular and biochemical reactions Aiming to repair the injured tissue. In patients with diabetes, the repair is slower. Several mechanisms are described as important factors in the delay of the healing process in diabetics, among them, excessive production of reactive oxygen species (ROS), reduction of nitric oxide (NO), reduction of the response to growth factors (GFs) And proteins the insulin signaling pathway . The search for therapeutic forms that can help the tissue repair process is in great demand, Because the rate of people with diabetes is increasing over the years. Thus, it is aimed to find pharmacological alternatives for this aspect, in the present study the characterization of the pharmacological effect of the topical application of the ketone extract of the seed Pentaclethra macroloba (Pracaxi) on the tissue regeneration process in diabetic animals was performed. To evaluate the healing effect, an excisional cutaneous wound with biopsy punch was created in diabetic animals and were subsequently treated by topical application of the extract to evaluate the healing potential of the seed. The effect of the treatment was evaluated by some aspects, such as: wound contraction, Reepithelialization, quantity of inflammatory cells, tissue organization and formation of collagen in the extracellular matrix. The results showed that the pracaxi extract presented a healing effect in diabetic mice, stimulating the tissue reconstruction after skin lesions. In this way, the pracaxi becomes a possible alternative for the treatment of tissue lesions in diabetics because it stimulates the healing cascade promoting the best formation of the extracellular matrix.Item Acesso aberto (Open Access) Validação farmacológica da preferência claro-escuro em Danio rerio(Universidade Federal do Pará, 2012-04-23) MAGNO, Lílian Danielle Paiva; GOUVEIA JUNIOR, Amauri; http://lattes.cnpq.br/1417327467050274Anxiety is a complex disorder with large clinical relevance, whose study with animal models is important for research about their mechanisms and drugs for their treatment. The zebrafish appears as a potential animal model for pharmacological research in anxiety. A model of anxiety is the light-dark preference, which has been validated behaviorally in zebrafish, however, requires a pharmacological validation. The objective is to describe the sensitivity of the light-dark preference in zebrafish adults for the most common drugs in clinical anxiety, were administered by immersing the animal in the solution: Benzodiazepines (Clonazepam), 5-HT1A partial agonists (Buspirone), Tricyclic Antidepressant (Imipramine), Antidepressant SSRIs (Fluoxetine and Paroxetine), Antipsychotics (Haloperidol and Risperidone); Psychostimulant (Diethylpropion), Beta blockers (Propranolol) and CNS depressants (Ethanol). The parameters analyzed were the time spent by the animal in a dark environment, the time of the first latency and number of midline crossings. Clonazepam administered 300 s increased the time in the dark at lower concentrations and reduced locomotor activity, administration during 600 s of the intermediate concentration decreased over time in the dark and the first latency, and increased locomotor activity, indicating anxiolytic effect. Buspirone raised the time spent in the dark, probably due to reduction of motor activity. Imipramine and fluoxetine increased time in the dark and the first latency and decreased the number of alternations, indicating anxiogenic action. Paroxetine did not alter the time in the dark, however the first time increased latency and decreased locomotor activity. Haloperidol decreased anxiety in the lowest concentration, curiously raised motor activity at the highest concentration, instead of risperidone, which decreased the activity at the highest concentration. Diethylpropion did not change over time in the dark but increased the time of the first latency and decreased motor activity only at lower concentrations. Propranolol reduced only time in the dark. Ethanol was effective in reducing anxiety with the intermediate concentration and decreased locomotor activity in a lower concentration. Data corroborate with the literature in Danio rerio both intraperitoneal administration in this model as in other models for water delivery and in rodents, when it was possible to compare.