Programa de Pós-Graduação em Ciências Farmacêuticas
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Master Thesis Estudo dos genes do complexo do antígeno leucocitário humano (hla) associados à susceptibilidade ao diabetes mellitus tipo 1(Universidade Federal do Rio Grande do Norte, 2013-03-27) Silva, Heglayne Pereira Vital da; Rezende, Adriana Augusto de; ; http://lattes.cnpq.br/4245215108740331; ; http://lattes.cnpq.br/6778032290382111; Freitas, Janaina Cristiana de Oliveira Crispim; ; http://lattes.cnpq.br/2644540835478572; Cunha, Nathalia de Alencar; ; http://lattes.cnpq.br/5103227378217521Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region, mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1 constituting haplotypes, and further, a combination of more than one haplotype, providing multilocus genotypes are associated with susceptibility, protection and neutrality to DM1. Thus, the aim of present study was to verified the association of polymorphisms of HLA genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied. Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the extraction kit Illustra Triple Prep®, GE Healthcare. For HLA typing was used DNA LABType system by One Lambda kit applying Luminex® technology to the method of PCRSSO typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g, *05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03, *15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8 haplotypes, were significantly associated with T1D protection Despite the major racial Brazilian, even at the regional level, these results are similar to the majority of alleles, genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D, extensively described in the literature for Caucasian population. Children with age at diagnosis less than 5 years of age had significantly higher frequency of the heterozygous genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old. These results also demonstrate strong association of the genetic profile of the class II HLA for this age group, possibly associated with the severity and rapid progression to the onset of T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the prediction of T1DMaster Thesis Preparação e caracterização de sistemas emulsionados contendo benznidazol(Universidade Federal do Rio Grande do Norte, 2013-03-22) Streck, Letícia; ; http://lattes.cnpq.br/2593509584288129; ; http://lattes.cnpq.br/8281814580153631Master Thesis Avaliação da argila atapulgita para potencial uso como excipiente farmacêutico em formas sólidas(Universidade Federal do Rio Grande do Norte, 2013-05-22) Soares, Daiane dos Santos; Moura, Túlio Flávio Accioly Lima e; ; http://lattes.cnpq.br/4452581275123481; ; http://lattes.cnpq.br/4732149898233623; Silva Júnior, Arnóbio Antônio; ; http://lattes.cnpq.br/2593509584288129Clays are natural materials that have great potential for use as excipients for solid dosage forms. Palygorskite is a type of clay that has hydrophilic properties as well as a large surface area, which could contribute to the dissolution of drugs. Thus, the present study aims to evaluate the use of palygorskite clay, from Piaui (Northeast region of Brazil), as a pharmaceutical excipient for solid dosage forms, using rifampicin and isoniazid as the model drugs. The former is a poorly soluble drug often associated with isoniazid for tuberculosis treatment. Palygorskite was characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF), particle size, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and specific surface area (BET). The rheological and technological properties of palygorskite were determined and compared to those of talc, magnesium stearate and Aersosil 200. Mixtures between drugs and palygorskite were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TG) combined with thermal analysis (DTA) and Fourier Transform Infrared Spectroscopy (FT-IR), where the results were compared with those of the individual compounds. In addition, dissolution studies of solid dispersions and capsules containing the drugs, mixed with either palygorskite or a mixture of talc and magnesium stearate, were performed. The results showed that palygorskite has small particles with a high surface area. Its rheological characteristics were better than those of others commonly used glidants and lubricants. There was no interaction between palygorskite and the drugs (rifampicin and isoniazid). Among the dispersions studied, the mixture with palygorskite (5%) showed the highest drug dissolution when compared to other excipients. The dissolution of the rifampicin capsules containing palygosrkite was faster in higher concentrations. However, these differences were statistically different only in the first minutes of the dissolution experiment. The dissolution profile of isoniazid was also statistically different on the initial part of the experiment. The formulations prepared with isoniazid and palygorskite showed higher drug dissolution, but it was in descending order of concentration. According to these results, the palygorskite clay used in this study has great potential for application as an excipient for solid dosage formsMaster Thesis Obtenção e caracterização de complexos de inclusão binários e ternários com praziquantel(Universidade Federal do Rio Grande do Norte, 2012-02-06) Mourão, Layany Carolyny da Silva; Moura, Túlio Flávio Accioly Lima e; ; http://lattes.cnpq.br/4452581275123481; ; http://lattes.cnpq.br/4378347914563891; Fonseca, José Luis Cardozo; ; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788562T6; Chaud, Marco Vinícius; ; http://lattes.cnpq.br/8853705702222360Master Thesis Preparação e caracterização de complexos multicomponentes contendo ciclodextrinas e benznidazol(Universidade Federal do Rio Grande do Norte, 2013-02-28) Melo, Polyanne Nunes de; ; http://lattes.cnpq.br/2593509584288129; ; http://lattes.cnpq.br/6364273379721600; Pereira, Márcia Rodrigues; ; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788568T8The benznidazole (BNZ) is the only alternative for Chagas disease treatment in Brazil. This drug has low solubility, which restricts its dissolution rate. Thus, the present work aimed to study the BNZ interactions in binary systems with beta cyclodextrin (β-CD) and hydroxypropyl-beta cyclodextrin (HP-β-CD), in order to increase the apparent aqueous solubility of drug. The influence of seven hydrophilic polymers, triethanolamine (TEA) and 1-methyl-2- pyrrolidone (NMP) in benznidazole apparent aqueous solubility, as well as the formation of inclusion complexes was also investigated. The interactions in solution were predicted and investigated using phase solubility diagram methodology, nuclear magnetic resonance of protons (RMN) and molecular modeling. Complexes were obtained in solid phase by spray drying and physicochemical characterization included the UV-Vis spectrophotometric spectroscopy in the infrared region, scanning electron microscopy, X-ray diffraction and dissolution drug test from the different systems. The increment on apparent aqueous solubility of drug was achieved with a linear type (AL) in presence of both cyclodextrins at different pH values. The hydrophilic polymers and 1-methyl-2-pyrrolidone contributes to the formation of inclusion complexes, while the triethanolamine decreased the complex stability constant (Kc). The log-linear model applied for solubility diagrams revealed that both triethanolamine and 1-methyl-2-pyrrolidone showed an action cosolvent (both solvents) and complexing (1-methyl-2-pyrrolidone). The best results were obtained with complexes involving 1-methyl-2-pyrrolidone and hydroxypropylbeta- cyclodextrin, with an increased of benznidazole solubility in 27.9 and 9.4 times, respectively. The complexes effectiveness was proven by dissolution tests, in which the ternary complexes and physical mixtures involving 1-methyl- 2-pyrrolidone and both cyclodextrins investigated showed better results, showing the potential use as novel pharmaceutical ingredient, that leads to increased benznidazole bioavailabilityMaster Thesis Avaliação da atividade antimicrobiana de sistemas emulsionados contendo óleos naturais para o tratamento de infecções cutâneas(Universidade Federal do Rio Grande do Norte, 2013-06-10) Alencar, Everton do Nascimento; Egito, Eryvaldo Sócrates Tabosa do; ; http://lattes.cnpq.br/6907806915889763; ; http://lattes.cnpq.br/0168495853673885; Rodriguez, Anselmo Fortunato Ruiz; ; http://lattes.cnpq.br/1747170505344631; Giordani, Raquel Brandt; ; http://lattes.cnpq.br/5032750980466610Natural oils have shown a scientific importance due to its pharmacological activity and renewable character. The copaiba (Copaifera langsdorffii) and Bullfrog (Rana catesbeiana Shaw) oils are used in folk medicine particularly because the anti-inflammatory and antimicrobial activities. Emulsion could be eligible systems to improve the palatability and fragrance, enhance the pharmacological activities and reduce the toxicological effects of these oils. The aim of this work was to investigate the antimicrobial activity of emulsions based on copaiba (resin-oil and essential-oil) and bullfrog oils against fungi and bacteria which cause skin diseases. Firstly, the essential oil was extracted from copaiba oil-resin and the oils were characterized by gas chromatography coupled to a mass spectrometry (GC-MS). Secondly, emulsion systems were produced. A microbiological screening test with all products was performed followed (the minimum inhibitory concentration, the bioautography method and the antibiofilm determination). Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Candida albicans, C. parapsilosis, C. glabrata, C. krusei and C. tropicalis American Type Culture Collection (ATCC) and clinical samples were used. The emulsions based on copaiba oil-resin and essential oil improved the antimicrobial activity of the pure oils, especially against Staphylococcus e Candida resistant to azoles. The bullfrog oil emulsion and the pure bullfrog oil showed a lower effect on the microorganisms when compared to the copaiba samples. All the emulsions showed a significant antibiofilm activity by inhibiting the cell adhesion. Thus, it may be concluded that emulsions based on copaiba and bullfrog oils are promising candidates to treatment of fungal and bacterial skin infectionsMaster Thesis Avaliação do estado nutricional relativo ao selênio e da expressão gênica de selenoproteínas em pacientes com aterosclerose tratados com estatinas(Universidade Federal do Rio Grande do Norte, 2010-05-24) Ferreira, Diana Quitéria Cabral; Schwarzschild, Lúcia de Fátima Campos Pedrosa; ; http://lattes.cnpq.br/1863589790139155; ; http://lattes.cnpq.br/6547360457772911; Rezende, Adriana Augusto de; ; http://lattes.cnpq.br/4245215108740331; Freitas, Janaina Cristiana de Oliveira Crispim; ; http://lattes.cnpq.br/2644540835478572; Cozzolino, Silvia Maria Franciscato; ; http://lattes.cnpq.br/4835658625152534The aim of this study was to determine the effects of the use of rosuvastatin in patients with atherosclerosis, in relation to blood parameters of selenium and selenoproteins, and also observe possible changes in gene expression of selenoproteins in these patients. The sample consisted of 27 adult and elderly patients with a clinical diagnosis of coronary artery disease undergoing angioplasty, treated at Natal Hospital Center hospital, Natal, RN. Patients were treated with rosuvastatin 10 mg/day during four months. Anthropometric variables such as body mass index (BMI) and Waist circumference (WC) were measured before and after treatment, as well as lipid profile, blood glucose and liver enzymes (AST and ALT). The diet of the patients was also analyzed using 24-hour diet recall. We analyzed the concentrations of selenium in plasma and erythrocytes, and also the activity of Glutathione Peroxidase and gene expression by Real Time PCR of selenoproteins GPx1, SelP1 and SelN1. Patients had mean age of 61.0 ± 9.4 years, 59.3% were men and 40.7% were women. After four months of treatment there was significant reduction of CA and, according to BMI, most were overweight. The intake of macronutrients, cholesterol, polyunsaturated fatty acids, monounsaturated and saturated was adequate, but the energy and fiber intake was below the recommendations. Regarding the selenium intake was observed a high prevalence of inadequacy. As expected, after treatment with rosuvastatin, a significant reduction in total cholesterol, LDL and glucose, which was not observed for HDL. Selenium concentrations in plasma and erythrocytes showed no changes, keeping within the established cutoffs. We observed a significant increase in GPx enzyme activity and mRNA expression of GPX1 and SEPN1, but not for gene SEPP1. Thus, it was found that treatment with rosuvastatin did not reduce the expression of selenoproteins. More studies are needed to clarify the effects of rosuvastatin on gene expression of selenoproteins in patients with atherosclerosisMaster Thesis Produção e avaliação de nanoemulsão catiônica como possível vetor não-viral para pIRES2-EGFP(Universidade Federal do Rio Grande do Norte, 2013-03-19) Silva, André Leandro; Egito, Eryvaldo Sócrates Tabosa do; ; http://lattes.cnpq.br/6907806915889763; ; http://lattes.cnpq.br/0712488767870940; Magalhães, Nereide Stella Santos; ; Lajus, Tirzah Braz Petta; ; http://lattes.cnpq.br/9979644969955564Gene therapy is based on the transfer of exogenous genetic material into cells or tissues in order to correct, supplement or silencing a particular gene. To achieve this goal, efficient vehicles, viral or non-viral, should be developed. The aim of this work was to produce and evaluate a nanoemulsion system as a possible carrier for no-viral gene therapy able to load a plasmid model (pIRES2-EGFP). The nanoemulsion was produced by the sonication method, after been choose in a pseudo-ternary phase diagram build with 5 % of Captex 355®, 1.2 % of Tween 80®, 0.8 % of Span 80®, 0.16% of stearylamine and water (to 100 %). Measurements of droplet size, polydispersity index (PI), zeta potential, pH and conductivity, were performed to characterize the system. Results showed droplets smaller than 200 nm (PI < 0.2) and zeta potential > 30 mV. The formulation pH was near to 7.0 and conductivity was that expected to oil in water systems (70 to 90 μS/s) A scale up study, the stability of the system and the best sterilization method were also evaluated. We found that the system may be scaled up considering the time of sonication according to the volume produced, filtration was the best sterilization process and nanoemulsions were stable by 180 days at 4 ºC. Once developed, the complexation efficiency of the plasmid (pDNA) by the system was tested by agarose gel electrophoresis retardation assay.. The complexation efficiency increases when stearylamine was incorporated into aqueous phase (from 46 to 115 ng/μL); regarding a contact period (nanoemulsion / pDNA) of at least 2 hours in an ice bath, for complete lipoplex formation. The nanoemulsion showed low toxicity in MRC-5 cells at the usual transfection concentration, 81.49 % of survival was found. So, it can be concluded that a nanoemulsion in which a plasmid model was loaded was achieved. However, further studies concerning transfectation efficiency should be performed to confirm the system as non-viral gene carrierMaster Thesis Nanopartículas de magnetita com oxacilina obtida por moagem de alta energia para aplicações biomédicas(Universidade Federal do Rio Grande do Norte, 2013-02-26) Carvalho, Juliana Fernandes de; ; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4787041Z8; ; http://lattes.cnpq.br/4339305874295673; Silva Júnior, Arnóbio Antônio; ; http://lattes.cnpq.br/2593509584288129; Rebouças, Gustavo de Oliveira Gurgel; ; http://lattes.cnpq.br/1748071367144485The drug targeting has been the subject of extensive studies in order to develop site-specific treatments that minimize side effects and become more effective anticancer therapy. Despite considerable interest in this class, drugs like antibiotics also have limitations, and have been neglected. Using new pharmaceutical technologies, the use of magnetic vectors appear as promising candidate for drug delivery systems in several studies. Small magnetic particles bound to the drug of interest can be modulated according to the orientation of a magnet outside the body, locating and holding in a specific site. In this work, we propose the use of High Energy Milling (HEM) for synthesis of a magnetic vector with characteristics suitable for biomedical applications by intravenous administration, and for the formation of an oxacillin-carrier complex to obtain a system for treating infections caused by Staphylococcus aureus. The results of the variation of milling time showed that the size and structural properties of the formed material change with increasing milling time, and in 60 hours we found the sample closest to the ideal conditions of the material. The vector-drug system was studied in terms of structural stability and antimicrobial activity after the milling process, which revealed the integrity of the oxacillin molecule and its bactericidal action on cultures of Staphylococcus aureus ATCCMaster Thesis Avaliação dos efeitos de um extrato bruto de cianobactérias contendo microcistinas sobre o desempenho reprodutivo e a embriofetotoxicidade de ratos(Universidade Federal do Rio Grande do Norte, 2013-03-13) Almeida, Cristhiano Sibaldo de; Kujbida, Paula da Silva; ; http://lattes.cnpq.br/2285854300593624; ; ALMEIDA, Cristhiano Sibaldo de.; Almeida, Maria das Graças; ; http://lattes.cnpq.br/0321740024191482; Molica, Renato José Reis; ; http://lattes.cnpq.br/2241687136450672The presence of cyanobacterial blooms in reservoirs intended for supply to the population can create public health problems for many species could produce potentially toxic compounds and these are not eliminated in the conventional procedures used in water treatment plants. So even in amounts less than the maximum allowable limit imposed by MS, cyanotoxins can be present in drinking water distributed to the population, creating a chronic exposure. There is little information about the long-term effects of oral exposure to cyanotoxins. This work aimed to show the exposure orally (v.o) of animals to a crude extract of cyanobacteria containing cyanotoxins to evaluate the reproductive performance of pregnant rats and their offspring and fertility of male rats. The presence of microcystins (MCs) in samples collected during the flowering processes in freshwater reservoirs in the Rio Grande do Norte, was analyzed by enzyme immunoassay and its variants have been identified and quantified by chromatographic methods. It was observed that by administration v.o. cyanobacterial extract containing MCs (40, 100 or 250 ng of MCs / kg / day) did not cause systemic toxicity in adult rats or effect on reproductive performance of male and female rats treated. It was also not observed any changes in skeletal study in the offspring of pregnant rats treated with the extract above. Because the solutions used contained MCs in a concentration equal to or greater than the tolerable daily intake for MCs, the results suggest, therefore, that the development of this work contributed to better assess public health risk as the oral exposure to cyanotoxins, increasing thus the credibility of the maximum allowable limit (LMP) of MCs in drinking water distributed to the population of several countries that use the LMP established by WHO in its legislation