Efeito do estado nutricional bioquímico de retinol e alfatocoferol sobre seus níveis em lactantes

Vitamins A and E are essential nutrients in many biological processes, so that their adequate supply to the neonate is crucial. However, the bioavailability of vitamins may be limited by factors such as maternal nutritional status and the interaction between nutrients. This study aimed to investigate the effect of biochemical nutritional status of retinol and alpha-tocopherol levels in serum and colostrum. The study included 103 healthy puerperal women treated at the reference state maternity hospital (Natal-RN). Colostrum and serum samples were collected fasting in the immediate postpartum period and the analysis of retinol and alpha-tocopherol were determined by high-performance liquid chromatography. Specific cutoff points were adopted to characterize the biochemical status of vitamins A and E. For the total group of lactanting women the average concentration of retinol in serum (1.49 ± 0.4 μmol/L-1) and colostrum (2.18 ± 0.8 μmol/L-1), as well as alpha-tocopherol in serum (26.4 ± 8.0 μmol/L-1) and colostrum (26.1 ± 12.8 μmol/L-1), indicated adequate biochemical state. However, when evaluating the individual, was found a high prevalence of deficient serum (15%) and colostrum retinol (50%), and also alphatocopherol in serum (16%) and colostrum (61%). In women with serum retinol ≥ 1.05 μmol/L-1, found an inverse correlation between serum retinol and alpha-tocopherol in colostrum (p = 0.008, r = -0.28). This association was not observed in women with serum retinol <1.05 μmol/L-1. This situation demonstrates for the first time in humans that high physiological levels of serum retinol, without supplementation, can negatively influence the transfer of alpha-tocopherol in breast milk. Although the diagnosis of satisfactory nutritional status lactanting women showed high risk of subclinical deficiency of vitamins A and E from measurements made in the colostrum

Síntese e caracterização do poli(ácido láctico) para potencial uso em sistemas de liberação controlada de fármacos

With the advances in medicine, life expectancy of the world population has grown considerably in recent decades. Studies have been performed in order to maintain the quality of life through the development of new drugs and new surgical procedures. Biomaterials is an example of the researches to improve quality of life, and its use goes from the reconstruction of tissues and organs affected by diseases or other types of failure, to use in drug delivery system able to prolong the drug in the body and increase its bioavailability. Biopolymers are a class of biomaterials widely targeted by researchers since they have ideal properties for biomedical applications, such as high biocompatibility and biodegradability. Poly (lactic acid) (PLA) is a biopolymer used as a biomaterial and its monomer, lactic acid, is eliminated by the Krebs Cycle (citric acid cycle). It is possible to synthesize PLA through various synthesis routes, however, the direct polycondensation is cheaper due the use of few steps of polymerization. In this work we used experimental design (DOE) to produce PLAs with different molecular weight from the direct polycondensation of lactic acid, with characteristics suitable for use in drug delivery system (DDS). Through the experimental design it was noted that the time of esterification, in the direct polycondensation, is the most important stage to obtain a higher molecular weight. The Fourier Transform Infrared (FTIR) spectrograms obtained were equivalent to the PLAs available in the literature. Results of Differential Scanning Calorimetry (DSC) showed that all PLAs produced are semicrystalline with glass transition temperatures (Tgs) ranging between 36 - 48 °C, and melting temperatures (Tm) ranging from 117 to 130 °C. The PLAs molecular weight characterized from Size Exclusion Chromatography (SEC), varied from 1000 to 11,000 g/mol. PLAs obtained showed a fibrous morphology characterized by Scanning Electron Microscopy (SEM)

Estudo in silico da interação da albumina de soro humano com o ibuprofeno

Currently, computational methods have been increasingly used to aid in the characterization of molecular biological systems, especially when they relevant to human health. Ibuprofen is a nonsteroidal antiinflammatory or broadband use in the clinic. Once in the bloodstream, most of ibuprofen is linked to human serum albumin, the major protein of blood plasma, decreasing its bioavailability and requiring larger doses to produce its antiinflamatory action. This study aimes to characterize, through the interaction energy, how is the binding of ibuprofen to albumin and to establish what are the main amino acids and molecular interactions involved in the process. For this purpouse, it was conducted an in silico study, by using quantum mechanical calculations based on Density Functional Theory (DFT), with Generalized Gradient approximation (GGA) to describe the effects of exchange and correlation. The interaction energy of each amino acid belonging to the binding site to the ligand was calculated the using the method of molecular fragmentation with conjugated caps (MFCC). Besides energy, we calculated the distances, types of molecular interactions and atomic groups involved. The theoretical models used were satisfactory and show a more accurate description when the dielectric constant ε = 40 was used. The findings corroborate the literature in which the Sudlow site I (I-FA3) is the primary binding site and the site I-FA6 as secondary site. However, it differs in identifying the most important amino acids, which by interaction energy, in order of decreasing energy, are: Arg410, Lys414, Ser 489, Leu453 and Tyr411 to the I-Site FA3 and Leu481, Ser480, Lys351, Val482 and Arg209 to the site I-FA6. The quantification of interaction energy and description of the most important amino acids opens new avenues for studies aiming at manipulating the structure of ibuprofen, in order to decrease its interaction with albumin, and consequently increase its distribution

Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Controle de qualidade físico-químico e biodisponibilidade relativa em ratos de suspensões orais de naproxeno sódico obtidas de farmácias de manipulação na cidade do Natal RN

Compounded medicines have been reported by the ANVISA due to decreased of the therapeutic response or toxicity of these formulations. The aim of this work was to investigate the physicochemical quality control among naproxen sodium oral suspensions 25 mg/mL obtained from six compounding pharmacies (A, B, C, D, E and F) and the manufactured suspension (R). In the quality control test, the tests of pH, content, homogeneity, volume and physical and organoleptic characteristics were performed according to the Brazilian Pharmacopoeia. The analytical method for determination of naproxen in suspensions was validate. This method showed excellent precision, accuracy, linearity and specificity. In the content test the suspensions B, C and E showed lower value and the F suspension showed a high value of the content. The products C and E were disapproved in the description of the physical and organoleptic characteristics test. In the pH test, three suspensions were outside specifications (C, E and F). Only the products R, A and D showed satisfactory results in these tests and therefore they were approved for relative bioavailability test. The R, A and D suspensions were orally administered to Wistar rats and the blood samples were taken at time intervals of 10, 20, 40, 60 min, 3, 4, 6, 24 and 48 h. The plasma samples were immediately stored at 80 ºC until analysis of HPLC. The bioanalytical method validation showed specificity, linearity (R2 0.9987), precision, accuracy, good recovery and stability. The chromatographic conditions were: flow rate of 1.2 mL.min-1 with a mobile phase of acetonitrile : sodium phosphate buffer pH 4.0 (50:50, v/v) at 280 nm, using a C18 column. The confidence interval of 90% for the Cmax and AUCt ratio was within the range of 80 - 125% proposed by the FDA. Only one suspension, obtained from the compounding pharmacy D, was considered bioequivalent to the rate of absorption under the conditions proposed by this study. Thus, the results indicate the need for strict supervision from the relevant authorities to ensure the patient safety and the quality of compounded drugs by pharmacies

Estudo de pré-formulação para dose fixa combinada dos tuberculostáticos rifampicina, isoniazida, pirazinamida e etambutol (4 em 1)

According to the global framework regarding new cases of tuberculosis, Brazil appears at the 18th place. Thus, the Ministry of Health has defined this disease as a priority in the governmental policies. As a consequence, studies concerning treatment and prevention have increased. Fixed-dose combination formulations (FDC) are recognized as beneficial and are recommended by WHO, but they present instability and loss on rifampicin bioavailability. The main purpose of this work was to carry out a pre-formulation study with the schedule 1 tuberculosis treatment drugs: rifampicin, isoniazid, pyrazinamide and ethambutol and pharmaceutical excipients (lactose, cellulose, magnesium stearate and talc), in order to develop an FDC product (150 mg of rifampicin + 75 mg of isoniazid + 400 mg of pyrazinamide + 250 mg of ethambutol). The studies consisted of the determination of particle size and distribution (Ferret s diameter) and shape through optical microscopy, as well as rheological and technological properties (bulk and tapped densities, Hausner Factor, Carr s Index, repose angle and flux rate) and interactions among drugs and drug excipient through thermal analysis (DSC, DTA, TG and your derivate). The results showed that, except isoniazid, the other drugs presented poor rheological properties, determined by the physical characteristics of the particles: small size and rod like particles shape for rifampicin; rectangular shape for pyrazinamide and ethambutol, beyond its low density. The 4 drug mixture also not presented flowability, particularly that one containing drug quantity indicated for the formulation of FDC products. In this mixture, isoniazid, that has the best flowability, was added in a lower concentration. The addition of microcrystalline cellulose, magnesium stearate and talc to the drug mixtures improved flowability properties. In DSC analysis probable interactions among drugs were found, supporting the hypothesis of ethambutol and pyrazinamide catalysis of the rifampicin-isoniazid reaction resulting in 3- formylrifamycin isonicotinyl hydrazone (HYD) as a degradation product. In the mixtures containing lactose Supertab® DSC curves evidenced incompatibility among drugs and excipient. In the DSC curves of mixtures containing cellulose MC101®, magnesium stearate and talc, no alterations were observed comparing to the drug profiles. The TG/DTG of the binary and ternary mixtures curves showed different thermogravimetrics profiles relating that observed to the drug isolated, with the thermal decomposition early supporting the evidences of incompatibilities showed in the DSC and DTA curves

Preparação e carcterização de complexos multicomponentes contendo ciclodextrinas e benznidazol

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

Avaliação da suplementação de vitamina E sobre a concentração de alfa-tocoferol no leite materno em mulheres com partos prematuros

The term vitamin E refers to a group of eight molecular compounds which differ in structure and bioavailability, and the RRR-alpha-tocopherol more biologically active form. The composition of vitamin E in breast milk undergoes variations during lactation, colostrum and milk richer in this micronutrient compared to transitional and mature milk. Newborns, especially premature infants are more susceptible to vitamin E deficiency and to prevent the damage caused by this deficiency has been proposed supplementation of neonates with this micronutrient, however, there is no consensus to carry out this intervention. Thus, maternal supplementation with RRRalpha-tocopherol in the postpartum period can be a good alternative to try to raise the alpha-tocopherol levels in breast milk and therefore provide the premature newborn adequate amounts of vitamin E. This study to evaluate the effect of supplementation with 400 UI acetate RRR-alpha-tocopherol in women with premature births, on the concentration of alpha-tocopherol in breast milk colostrum, transitional and mature. The study included 89 healthy adult women were enrolled in the control group (n = 51) and supplemented group (n = 38). Blood samples were collected and milk colostrum soon after birth (0h milk) twenty-four hours, new rate of colostrum milk was collected (24h milk). The transitional and mature milk were collected in seven days (7d milk) and thirty days (30d milk) after delivery, respectively. Supplementation in the supplemented group was held after the collection of blood and 0h milk. The alpha-tocopherol analyzes were performed by high-performance liquid chromatography. Serum levels of alpha-tocopherol less than 516 μg/dL were considered indicative of nutritional deficiency. The average concentration of alphatocopherol in the serum of the control group mothers was 1159.8 ± 292.4 μg/dL and the supplemented group was 1128.3 ± 407.2 μg/dL (p = 0.281). All women had nutritional status in vitamin E suitable. In both groups, it was observed that the concentration of vitamin E in colostrum milk was higher compared to transitional and mature milk. In the supplemented group, the concentration of alpha-tocopherol in the milk increased 60 % after supplementation, from 1339.3 ± 414.2 μg/dL (0h milk) to 2234.7 ± 997.3 μg/dL (24h milk). While the control group values in colostrum 0h and colostrum 24h were similar (p = 0.681). In the control group the follow-on milk alphatocopherol value was 875.3 ± 292.4 μg/dL and in the group supplemented 1352.8 ± 542.3 μg/dL, an increase of 35% in the supplemented group compared to control (p <0.001). In mature milk alpha-tocopherol concentrations between the control group (426.6 ± 187.5 μg/dL) and supplemented (416.4 ± 214.2 μg/dL) were similar (p = 0.853). Only 24h milk supplemented group answered the nutritional requirement of alpha-tocopherol (4 mg/day) of the newborn. These results show that the transport of this micronutrient for milk occurs in a controlled and limited way. Thus, the native vitamin E supplementation increases the concentration of alpha-tocopherol in colostrum and milk and transition does not influence the concentration in mature milk. Only the increase in colostrum milk was sufficient to meet the nutritional requirement of premature newborns.

Efeito do estado nutricional bioquímico de retinol e alfatocoferol sobre seus níveis em lactantes

Vitamins A and E are essential nutrients in many biological processes, so that their adequate supply to the neonate is crucial. However, the bioavailability of vitamins may be limited by factors such as maternal nutritional status and the interaction between nutrients. This study aimed to investigate the effect of biochemical nutritional status of retinol and alpha-tocopherol levels in serum and colostrum. The study included 103 healthy puerperal women treated at the reference state maternity hospital (Natal-RN). Colostrum and serum samples were collected fasting in the immediate postpartum period and the analysis of retinol and alpha-tocopherol were determined by high-performance liquid chromatography. Specific cutoff points were adopted to characterize the biochemical status of vitamins A and E. For the total group of lactanting women the average concentration of retinol in serum (1.49 ± 0.4 μmol/L-1) and colostrum (2.18 ± 0.8 μmol/L-1), as well as alpha-tocopherol in serum (26.4 ± 8.0 μmol/L-1) and colostrum (26.1 ± 12.8 μmol/L-1), indicated adequate biochemical state. However, when evaluating the individual, was found a high prevalence of deficient serum (15%) and colostrum retinol (50%), and also alphatocopherol in serum (16%) and colostrum (61%). In women with serum retinol ≥ 1.05 μmol/L-1, found an inverse correlation between serum retinol and alpha-tocopherol in colostrum (p = 0.008, r = -0.28). This association was not observed in women with serum retinol <1.05 μmol/L-1. This situation demonstrates for the first time in humans that high physiological levels of serum retinol, without supplementation, can negatively influence the transfer of alpha-tocopherol in breast milk. Although the diagnosis of satisfactory nutritional status lactanting women showed high risk of subclinical deficiency of vitamins A and E from measurements made in the colostrum

Síntese e caracterização do poli(ácido láctico) para potencial uso em sistemas de liberação controlada de fármacos

With the advances in medicine, life expectancy of the world population has grown considerably in recent decades. Studies have been performed in order to maintain the quality of life through the development of new drugs and new surgical procedures. Biomaterials is an example of the researches to improve quality of life, and its use goes from the reconstruction of tissues and organs affected by diseases or other types of failure, to use in drug delivery system able to prolong the drug in the body and increase its bioavailability. Biopolymers are a class of biomaterials widely targeted by researchers since they have ideal properties for biomedical applications, such as high biocompatibility and biodegradability. Poly (lactic acid) (PLA) is a biopolymer used as a biomaterial and its monomer, lactic acid, is eliminated by the Krebs Cycle (citric acid cycle). It is possible to synthesize PLA through various synthesis routes, however, the direct polycondensation is cheaper due the use of few steps of polymerization. In this work we used experimental design (DOE) to produce PLAs with different molecular weight from the direct polycondensation of lactic acid, with characteristics suitable for use in drug delivery system (DDS). Through the experimental design it was noted that the time of esterification, in the direct polycondensation, is the most important stage to obtain a higher molecular weight. The Fourier Transform Infrared (FTIR) spectrograms obtained were equivalent to the PLAs available in the literature. Results of Differential Scanning Calorimetry (DSC) showed that all PLAs produced are semicrystalline with glass transition temperatures (Tgs) ranging between 36 - 48 °C, and melting temperatures (Tm) ranging from 117 to 130 °C. The PLAs molecular weight characterized from Size Exclusion Chromatography (SEC), varied from 1000 to 11,000 g/mol. PLAs obtained showed a fibrous morphology characterized by Scanning Electron Microscopy (SEM)