Obtenção de bebidas a base de extrato hidrossolúvel de soja com polpa de frutas

Neste trabalho foram elaboradas bebidas a partir do extrato hidrossolúvel de soja (cultivares CD 206 e BRS 232), com sabor agregado das polpas de maracujá, abacaxi e morango. Também identifi camos qual a melhor forma de cultivar a soja para este fi m. Através de testes de análise sensorial, foi estudada a aceitação do produto pelo consumidor. A preferência do consumidor foi pela bebida obtida a partir do extrato hidrossolúvel de soja da espécie CD 206 com polpa de maracujá

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Production and microestrutural caracterization of solid lipids systems micro and nanoparticulate used for beta-carotene encapsulation

O benefício do consumo de compostos bioativos, como os carotenóides, tem sido amplamente demonstrado pela literatura científica. No entanto, alguns destes bioativos (como os carotenos), devido à sua hidrofobicidade, apresentam dificuldades para serem incorporados em formulações alimentícias aquosas, além de serem, dependendo da matriz alimentícia na qual estão inseridos, dificilmente absorvidos no tratogastrointestinal - ou seja, possuem limitada biodisponibilidade. Tais problemas podem ser contornados através da micro e da nanoencapsulação. O presente trabalho de Mestrado teve como objetivo utilizar a triestearina e o ácido esteárico para a encapsulação do beta-caroteno em micro e nanopartículas lipídicas sólidas, a caracterização físico-química das estruturas formadas e a avaliação da estabilidade química e microestrutural das mesmas. Nos sistemas microparticulados de ácido esteárico (AE) foi utilizado como tensoativo o polisorbato 80 e foram produzidos com 4 e 6% de lipídio, na ausência e na presença de alfa-tocoferol, e todos se mostram extremamente estáveis em relação à distribuição do tamanho médio das partículas, mas somente as partículas que continham alfa-tocoferol conseguiram preservar o beta-caroteno ao longo do período de 7 meses de armazenagem. No caso das micropartículas de triestearina também foram produzidos sistema com 4 e 6% de lipídio total, e a presença do hidrocolóide goma xantana foi essencial para evitar a floculação e permitir a estabilidade do sistema, e foram testadas formulações contendo misturas de tensoativos fosfatidilcolina de soja e polisorbato 60 e fosfatidilcolina de soja e polisorbato 20. Dentre tais sistemas, somente as micropartículas sólidas estabilizadas com polisorbato 60 se mostraram estáveis em relação ao tamanho médio das partículas, e o sistema com menor quantidade de lipídio manteve-se resistente à floculação até o 4º mês de estocagem. Sistemas nanoparticulados foram produzidos com 6% de lipídio total, testando-se uma e duas passagens no homogeneizador à alta pressão. Os dados obtidos indicaram que as nanopartículas lipídicas de AE não diferiram em relação à distribuição de tamanho, mas apresentaram aumento do diâmetro de partícula ao longo do tempo de estocagem. Por sua vez, para as nanopartículas de triestearina os sistemas (tanto com uma quanto com duas passagens no homogeneizador a alta pressão) se mostraram estáveis até cerca de dois meses de armazenagem, em termos de diâmetro médio de partícula, sendo que a distribuição de tamanho se mostrou mais homogênea para o sistema com duas passagens. A microestrutura de todos os sistemas foi avaliada por difratometria de raio-X (DRX) e calorimetria diferencial de varredura (DSC), e a quantidade de beta-caroteno preservada ao longo do tempo foi monitorada espectofometricamente e por colorimetria instrumental. De maneira geral, os sistemas microparticulados se mostraram melhores do que os nanoparticulados, tanto do ponto de vista de estabilidade da estrutura quanto da preservação do beta-caroteno.The benefits from the consumption of bioactive compounds, like carotenoids, have been widely demonstrated for scientific literature. However, some of this compounds (like carotenes), due totheir hydrophobicity, are difficult to be incorporated in aqueous food formulations, and, depending on the food matrices where they are introduced, are hardly absorbed in the gastrointestinal tract - in order words, they present limited bioavailability. These problems can be overcome by micro and nanoencapsulation. In this context, the objective of this study was to investigate the temporal stability of beta-carotene encapsulated in solid lipid micro and nano particles produced with a mixture of stearic acid or tristearin and sunflower oil, monitoring the microstructure of the systems by X-ray diffractometry, differential scanning calorimetry, zeta potential and particle size measurements, and try to link the preservation of beta-carotene with microstructural considerations. The surfactant used for the stearic acid microparticulate systems was polysorbate 80 and formulations with 4 and 6% of total lipid were produced, in the absence and presence of alpha-tocopherol, and all systems showed high stability in terms of average particle diameter and size distribution, but only the particles containing alpha-tocopherol preserved the content of beta-carotene during the storage period of 7 months In the case of the tristearin microparticles the presence of a hydrocolloid (xanthan gum) was essential for avoid flocculation and improves the system stability, and formulations containing mixtures of surfactants (soybean phosphatidylcholine and polysorbate 60 and phosphatidylcholine and polysorbate 20) were tested. Among such systems, only the solidmicroparticles stabilized with phosphatidylcholine and polysorbate 60 showed stability in terms of average particle diameter and size distribution, and the system with less concentration of solid lipid did not show significant destabilization until the 4th month of storage. As for the nanoparticulated systems, formulations with 6% of total lipid were produced, testing one and two passages in high pressure homogenizer. Our results indicated the stearic acid solid nanoparticles did not exhibitalterations of size distribution, but average particle diameter increased along the time. On the other hand, the triestearin nanoparticles (both with one and two passage in high pressure homogeneizer) showed stability until two months of storage, in terms of average particle diameter, and the size distribution demonstrated to be more homogeneous for the systems submitted to two passages. As an overall conclusion, the microparticulated systems seemed to be more stable than the nanoparticulated ones, from the point of view of structure stability as well as in terms of beta-carotene preservation of beta-carotene

Production by phase inversion temperature method, study of physicochemical stability, in vitro digestibility and cytotoxicity of beta-carotene load solid lipid nanoparticle

Nanopartículas lipídicas sólidas (SLN) são sistemas coloidais nanoparticulados muito utilizados para encapsulação de substâncias hidrofóbicas, com o intuito de proteger e aumentar a sua biodisponibilidade. Tais sistemas podem ser produzidos por métodos de baixa energia, como a temperatura de inversão de fase (PIT), a qual é baseada na mudança de solubilidade do tensoativo não iônico polietoxilados com a temperatura. O estudo do comportamento de tais sistemas durante a passagem pelo trato gastrointestinal torna-se interessante, caso deseje-se incorpora-los em matrizes alimentícias. Os modelos in vitro dinâmicos têm sido desenvolvidos para simular mais efetivamente os atributos que ocorrem in vivo, e dentre eles o mais conhecido é o sistema TIM (TNO intestinal model), que simula os principais eventos que ocorrem no lúmen do intestino delgado. Outro parâmetro importante a ser analisado, em nanopartículas passíveis de serem ingeridas, é a citotoxicidade, que pode ser avaliado através do emprego de culturas celulares intestinais e epiteliais. O presente trabalho de doutorado teve como objetivo a utilização de manteiga de cupuaçu e manteiga de murumuru para encapsulação do beta-caroteno em nanopartículas lipídicas sólidas produzidas pelo método PIT, e o estudo de sua citotoxicidade e digestibilidade in vitro dinâmica. Os tensoativos utilizados foram o Cremophor RH 40 e o Span 80, e os sistemas foram produzidos na presença e na ausência de alfa-tocoferol. De maneira geral pode-se dizer que as nanopartículas apresentaram diâmetro médio ao redor de 35 nm com polidispersidade 0,2 e permaneceram estáveis por um período de 4 meses. Os sistemas produzidos com manteiga de murumuru preservaram melhor o beta-caroteno encapsulado e o alfa-tocoferol agiu como um antioxidante na preservação do bioativo. As nanopartículas apresentaram estabilidade física frente às diferentes condições de stress, exceto quando foram expostas em concentrações salinas muito altas e pH básico. No que diz respeito à digestibilidade, as nanopartículas permaneceram estáveis no estômago e começaram a desestabilizar no duodeno; a biodisponibilidade total do beta-caroteno foi de 50 e 49% para respectivamente as partículas de manteiga de murumuru e manteiga de cupuaçu; a lipólise foi de 51% para as nanopartículas de manteiga de cupuaçu e de 49,8% para as nanopartícula de murumuru. Em relação aos estudos em linhagem de células in vitro e a avaliação da toxicidade, pode-se dizer que as linhagens de HEPG-2 apresentaram maior viabilidade celular do que as linhagens de CaCo-2 e a morte celular começou a ser mais pronunciada na diluição de 11,38µg/ml para as células de HEPG-2 e na diluição de 5,69 µg/ml para as células de CaCo-2, portanto, caso se deseje aplicá-las em matrizes alimentícias, é aconselhável respeitar essas concentrações. Além do mais, os resultados mostram que as nanopartículas avaliadas tem um potencial muito bom para encapsular compostos bioativos lipossolúveis e se mostraram um bom veiculo para serem empregadas em alimentos.Solid lipid nanoparticles are colloidal delivery systems used for encapsulation of hydrophobic substances, with the aim to protect and increase bioavailability. Such systems could be produced by low energy methods, like phase inversion temperature (PIT) which is based in the change of solubility nonionic polyethoxylated surfactants with temperature. In order to incorporate these systems in foods, it is important studying their behavior under gastrointestinal tract conditions. The in vitro dynamic models had been developed to simulate more effectively the properties that occur in vivo, between them the TIM system (TNO intestinal model) is one of the most known, which simulates the most important events that occur in the lumen of the small intestine. Other important parameter in nanoparticles that can be ingested is the cytotoxicity that can be evaluated using intestinal and epithelial cell cultures. This doctoral work aimed to use cupuaçu butter and murumuru butter to encapsulate beta-carotene in solid lipid nanoparticles produced by the PIT method, moreover the study of these particles cytotoxicity and digestibility in dynamic in vitro systems. The surfactants used were Chemophor RH 40 and Span 80, and the systems were produced in the presence and absence of alpha-tocopherol. Generally one can say that these nanoparticles present average diameter around 35 nm with polydispersity 0.2 and remain stable during 4 months. The systems based with murumuru butter showed better preservation of the beta-carotene encapsulated and alpha-tocopherol acted like an antioxidant in the bioactive preservation. The nanoparticles presented physical stability faced various stress conditions, with the exception of very high saline concentrations and basic pH. Regarding the digestibility, the nanoparticles remain stable in the stomach and start to destabilize in the duodenum; the total bioavailability of beta-carotene were 50 and 49% to the murumuru butter and cupuaçu butter, respectively; the lipolysis were 51% to the nanoparticles based in cupuaçu butter and 49.8% to the murumuru based nanoparticles. Regarding the studies of in vitro cellular uptake and toxicity one can say that the HEPG-2 present bigger cellular viability than the Caco-2 and the cellular death begin with dilution of 11,38µg/ml for cells of HEPG-2 and with dilution of 5,69 µg/ml for cells of CaCo-2, so if one desire to apply in food matrices it is advisable to respect these concentrations. Furthermore, the results showed that the tested nanoparticles had a very good potential to encapsulate bioactive liposoluble components and are a good way to be applied in food matrices

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Objective: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. Results: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. Interpretation: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

Introduction: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. Methods: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. Results: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). Discussion: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019

Correction to: Eculizumab improves fatigue in refractory generalized myasthenia gravis (Quality of Life Research, (2019), 28, 8, (2247-2254), 10.1007/s11136-019-02148-2)

The article “Eculizumab improves fatigue in refractory generalized myasthenia gravis”, written by “Henning Andersen, Renato Mantegazza, Jing Jing Wang, Fanny O’Brien, Kaushik Patra, James F. Howard Jr. and The REGAIN Study Group” was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 23 March 2019 without open access