972 resultados para Acesso a medicamentos
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Diabetes Mellitus (DM) and osteoposes are chronic diseases with great socioeconomic consequences, mainly due to the late complications and consequent disabilities. The potential effects of DM on bone metabolism remain a very conroversial issue, and disagreement exists with regard to the clinical implications of diabetic osteopenia and the mechanism of its ocurrence. The issue is further complicated by the contribuicion of the especific factors, such as duration of disease an dthe degree of metabolic control. The objective of this study is to identify the osteopathy in children and adolescents with DM 1 assisted in the hospital of pediatrics, UFRN, through biochemical markers of bone and mineral metabolism and the extent of bone mineral density. The study was composed by 74 diabetics type 1 patients (DM1) of both gender and aged 6 to 20 yars. Normoglicêmic group was composed by 97 healthy subjects of both genders, which showed the same age range of DM1, in addition to same socioeconomic class. These individuals qere students from the networks of public education in the city of Natal-RN, randomly invited to paticipate in our study. Both groups DM1 and NG were divided intofour subgroups, according to the classification of tanner , T1, T2, T3, T4 for achieving a benchmark. Diabetic individuals showed up with a poor glycemic control. the group DN1 T4 showed an incresead value for total protein, albumin, urea and microalbumiuria are predictors of grumelura injury in DM1 patients . The total alkaline phosphatase activitywas kept on high levels for both groups because they are in a stature development age. For osteocalcin there were decreased levels for groups Dm1 T1, T2, and T3 when compared to their NG (s), suggesting that this decrease could be associated with reduction in the number and/or differentiation os osteoblasts thereby contributing to reducing bone formation. There were no changes in the activity of TRAP. The serum concentrations of total and ionized calcium, phosphorus and magnesium were included within the RV. It was observed that the BMD (Z- SCORE ) has always been within the RV for both groups, despite to DM1 T4. Taking all together, our results support the hypothesis that children and adolescents with type 1 DM present the risk in the long run to suffer a reduction in the bone mass, associated to poor glicemic control and disease duration. It could limit the bone growth and increase the probality of development of osteopenia, as well as other complications surch as retinopathy and renal failure
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The 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 bioavailability
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The 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 atherosclerosis
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Natural 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 infections
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
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Clays 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 forms
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
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The study had as objective to evaluate the zinc status by means of dietary intake, zinc in plasma and in erythrocytes and the metallothionein gene expression in patients with atherosclerosis in use of rosuvastatin. The research involved 27 adult and elderly patients of both genders with atherosclerosis that were treated with rosuvastatin (10mg/day) during 4 months. We performed the dosage of lipids, glucose, AST and ALT, ultrasensitive C-reactive protein (hsCRP), plasmatic and erythrocyte zinc and 1 and 2 metallothionein gene expression. The assessment of body mass index (BMI) and abdominal circumference (AC) was performed, besides the analysis of dietary intake of patients. The majority of the evaluated patients presented overweight, before and after the treatment, with no significant difference between the times of the study. It was identified that the AC was significantly reduced in the group (p<0.05) after the intervention. The majority of the patients had intake below the recommendation of calories and fibers and above recommendation of proteins. The mono and polyunsaturated fats were adequate for the majority of the patients, however, the saturated fat and cholesterol were consumed in excess by a great part of the individuals. The intake of zinc was inadequate, being noticed an inadequacy of 100% in the male gender and of 84% in the female. After the treatment with rosuvastatin there was a significant reduction in the total cholesterol (TC) and LDL-c (p<0.01) and no alterations were observed in the HDL-c and triacylglycerols. It was also verified that the reduction of glycemia (p<0.05) and of hsCRP (p<0.01). The analysis did not demonstrate significant differences in the plasmatic and erythrocyte zinc concentration after the treatment. There was, after the treatment, reduction of the MT1F gene (p<0.05) without, however, occurring significant alterations in the MT2A gene. The treatment with rosuvastatin was effective in the reduction of TC and LDL-c, and promoted the reduction of inflammatory marker hsCRP. The zinc in the plasma and erythrocyte was not altered by the use of the medication and there was a reduction in the MT1F gene, possibly due to the reduction of inflammation. The majority of patients presented inadequate intake of zinc and this inadequacy did not have relation with the mineral parameters in plasma and erythrocytes or with the metallothionein gene expression
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Panax ginseng CA Meyer (Araliaceae) is a herbaceous plant widely used in China, South Korea, Japan and other Asian countries for the treatment of various diseases micro circulatory, cerebrovascular, among others, representing one of the drugs used by older man. It has over 30 biologically active ginsenosides with different pharmacological and behavioral effects and inhibitory effect on the NMDA receptor. The amino acid glycine is a co-agonist of the NMDA receptor, activating this receptor. At the cellular level, ketamine is widely known to be NMDA receptor antagonist. The aim of this study was to evaluate the general activity in the open field, and anxiety in elevated plus maze, mice treated with P. ginseng compared with the action of ketamine and glycine, to better understand the action of this herbal medicine at the NMDA receptor. We used 66 adult male rats were divided into six groups: a positive control, treated for 30 days with water by gavage, who received glycine (500mg/kg; po) on days 7, 14, 21 and 28 of treatment, one hour before of behavioral assessment, a negative control was treated for 30 days with water by gavage received ketamine (5mg/kg, ip) on days 7, 14, 21 and 28 of treatment, one hour prior to behavioral evaluation, three experimental groups, receiving 100, 200 or 300 mg / kg P. ginseng by gavage for 30 days and one group treated solely with white water, and is also administered 1 ml of water by gavage one hour prior to behavioral evaluation. Animal behavior in these three groups was also examined on days 7, 14, 21 and 28 of treatment. On day 30 of treatment, the animals were anesthetized with thiopental (70mg/kg) for blood collection and after euthanasia, withdrawal of various organs. There were no changes in weight and body weight gain and weight reasons in organ / body weight. However the consumption of water and food values showed a significant increase. Serum levels of AST was increased in a dose-dependently in the animals treated with doses of P. ginseng, glycine and ketamine as compared to the blank group. Unlike creatinine levels proved to be decreased in all treated groups when compared with white. However, the level of urea in these groups was reduced and no changes were observed in the ALT parameter. Histopathological examination revealed no changes in cell morphology in different tissues. There were no behavioral changes in the elevated plus maze and few changes were observed in the open field, animals treated with P. ginseng, glycine and ketamine when compared to white. These data suggest that the doses of P. ginseng employed were unable to induce general toxicity in rats treated for 30 days and also shows that the general behavior of mice treated with P. ginseng was slightly different from that observed in animals treated with ketamine and glycine. Finally, the study on the elevated plus maze showed that the extract of P. ginseng showed no anxiolytic or anxiogenic action
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Of 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 T1D
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The extraction, chemical and structural characterization of a wide variety of compounds derived from plants has been a major source of bioactive molecules. Several proteases have been isolated in the plant kingdom, with numerous pharmacological and biotechnological applications. Among the proteases isolated from plants, are the fibrinogenolytic, with relevant application in the treatment of disorders in the coagulation cascade, in addition to potential use as a tool in clinical laboratories. In this study, in addition to evaluating the effects of the protein extract of Cnidoscolus urens (L.) Arthur (Euphorbiaceae) in the coagulation cascade also investigates the presence of antimicrobial activity and characterizes the proteolytic activity detected in this extract, aiming to determine their potential pharmacological and biotechnological application. In this way, crude protein extracts obtained from the leaves of C. urens in Tris-HCl 0.05M, NaCl 0.15M, pH 7.5, were precipitated in different concentrations of acetone, and assessed for the presence of proteolytic activity in azocaseína and fibrinogen. The most active fraction (F1.0) in these tests was chosen for assessment of biological activity and biochemical characterization. The Aα chain and Bβ of fibrinogen were completely cleaved at a concentration of 0.18 μg/μL of protein fraction in 4 minutes. Fibrinogenolytic activity presented total inhibition in the presence of E-64 and partial in the presence of EDTA. The fraction demonstrated coagulant activity in plasm and reduced the APTT, demonstrating acting on the factors coagulation of the intrinsic pathway and common, not exerting effects on the PT. Fibrinolytic activity on plasma clot was detected only in SDS-PAGE in high concentrations of fraction, and there were no defibrinating. Although several proteases isolated from plants and venomous animals are classically toxic, the fraction F1.0 of C. urens not expressed hemorrhagic nor hemolytic activities. Fraction F1.0 also showed no antimicrobial activity. In proteolytic activity on the azocasein, the optimal pH was 5.0 and optimum temperature of 60ºC. The enzyme activity has been shown to be sensitive to the presence of salts tested, with inhibition for all compounds. The surfactant triton did not influence the enzyme activity, but the tween-20 and SDS inhibited the activity. In the presence of reducing agents increase in enzyme activity occurred, a typical feature of enzymes belonging to the class of cysteine proteases. Several bands with proteolytic activity were detected in zymogram, in the region of high-molecular-weight, which were inhibited by E-64. In this study, we found that C. urens presents in its constitution cysteine proteases with fibrinogenolytic and procoagulant activity, which may be isolated, with potential application in treatment of bleeding disorders, thrombolytic and clinical laboratory
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Praziquantel (PRZ) is the main drug used for treatment of schistosomiasis in Brazil. It is administered by oral rout as tablets. However, has low aqueous solubility which limits this therapeutic success dosage form and availability of liquid forms. The emulsion systems have great potential and represent an interesting strategy to increase the solubility of drugs. The aim of study was the development and characterization of lipid-emulsified liquid systems of the type oil in water (O / W), the base of soybean oil as the internal phase stabilized by surfactants pair Tween® 80 and Span® 80, for improving the phase biopharmaceutical of PRZ. After selecting the best value of Hydrophilic-Lipophilic Balance (HLB = 11), the parameters of the preparation of the formulations were optimized emulsification technique. The emulsions were successfully obtained; the liquid forms provided exhibited Newtonian behavior and an increase in solubility of PRZ higher than 20 times. The accelerated stability study demonstrated the stability of the emulsions and the effect of cosurfactants investigated. The study of the dynamics of interaction between components in the diagram showed pseudoternary phase regions to obtain O/W emulsions, whereas the study of the interaction of the components and their effect on system structure and the efficiency of incorporation of the drug led to systems with an amount of soluble drug even higher (about 1.5%), which demonstrates the potential of this new input mainly for the treatment of schistosomiasis, which resulted in the filing of patent BR 10 2013 0004 55 3
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Candida albicans is a diploid yeast that in some circumstances may cause oral or oropharyngeal infections. The investigation of natural products is mandatory for the discovery of new targets for antifungal drugs development. This study aimed to determine the genotypes of 48 clinical isolates of C. albicans obtained from the oral cavity of kidney transplant patients from two distinct geographic regions of Brazil. In addition, we investigated three virulence factors in vitro: phospholipase activity, morphogenesis and the ability to evade from polymorphonuclear neutrophils. The expression of these virulence factors in vitro was also investigated in the presence of the crude extract of Eugenia uniflora. The genotype A was the most prevalent (30 isolates; 62.5%), followed by genotype C (15 isolates; 31.5%) and genotype B (3 isolates; 6.25%). When microsatellite technique with primer M13 was applied, 80% of the isolates from the South were placed within the same cluster. All Genotype C strains were grouped together within two different clusters. Genotype C was considered more resistant to PMNs attack than genotypes A and B. Strains isolated from the South of Brazil showed higher ability to combat PMNs phagocytosis. We found a high rate of genotype C strains isolated from the oral cavity of this group of patients. The crude extract of E. uniflora inhibited proper hypha formation and phagocytosis by PMNs, but had no significant effect on phospholipase activity. This study characterized oral C. albicans strains isolated from kidney transplant recipients and will contribute for the better understanding of the pathogenesis and alternative therapeutics for oral candidiasis
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Spondias sp. (Anacardiaceae), popularly known as cajá-umbu, is an endemic plant from Northeastern Brazil, where their leaves are widely used in folk medicine to treat inflammatory processes, while their fruits have a great agro industrial potential. This study was designed to evaluate hepatoprotective, antinociceptive, antioxidant, antimicrobial and anti-inflammatory properties, as well as the acute toxicity and repeated dose 28, using a methanolic extract (MES), a fraction rich in flavonoids (FRF) and a precipitate from Spondias sp.leaves. The antioxidant activity of them was valued to evaluate their free radical scavenger capacity by DPPH test, whereas MES and FRF were used to evaluate while the preventive action on carbon tetrachloride (CCl4)-induced hepatotoxicity. Seven groups (n=5) of female Wistar rats were used as follows: control group, CCl4-intoxicated group treated with EMS (500 mg/kg) for 7 days, three CCl4-intoxicated groups treated with FRF (25, 50 and 75 mg/kg) for 7 days and the CCl4-intoxicated group treated with Legalon ® (silimarina; (phytotherapeutic reference) (50 mg/kg; 7 days). MES and FRF showed a protective action against liver injury induced by CCl4, being observed a significant reduction of serum enzyme activity marker of liver damage (alanine transaminase and aspartate transaminase). On the other hand, the lipid peroxidation (SRAT) decrease, as well as the increase of glutathione content and enzyme activity of antioxidant defense system (SOD, CAT, GPx) toward near normal values indicated the ability of EMS to restore the oxidative imbalance induced by CCl4. The histological analysis confirmed the hepatoprotection, compared to degenerative changes in CCl4-treated group. This hepatoprotetor effect was similar to that shown by Legalon®. The in vitro high antioxidant capacity of extract (93.16 ± 1.00%) showed analogous results to those obtained by Carduus marianus BHT (reference standard). This fact explains the obtained results in vivo. Although no antimicrobial activity was detected, EMS and FRF promoted the antinociceptive effect induced in the second phase by the intraplantar formalin test, evidencing the anti-inflammatory action; confirmed by the carrageenan-induced peritonitis model. The evaluation of the mechanical allodynia (CFA a 80%) demonstrated the involvement of the Spondias sp. chemical composition in the anti-inflammatory activity toward the acute processes. The acute exposure and repeated dose during 28 days did not produce significant changes in the parameters that evaluate toxicity. Together the experimental results reveal, that Spondias sp. leaf extracts have a promising potential in pharmaceutical area, and due to its non-toxic condition present efficiency and security
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Conselho Nacional de Desenvolvimento Científico e Tecnológico