Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

Characterization and identification of ascorbyl methylsilanol pectinate for cosmetic formulations application

The ascorbyl methylsilanol pectinate (AMP) presents the same functional properties of ascorbic acid (AA). Besides antioxidant and depigmentant activity, the AMP presents silanol in its chemical structure. The aim of this work was to characterize and indentify the AMP alone and in cosmetic formulations. The following techniques were employed: Fourier Transform Infrared Spectrophotometry, particle size distributions, in vitro antioxidant activity with 2.2-diphenyl-1-picrylhydrazyl (DPPH) and Oxigen Radical Absorbance Capacity Assay and High Performace Liquid Chromatography (HPLC) (developed and validated method) for the active ingredient; Microscopy, HPLC and Normal Stability Assay (NSA) for the emulsions. Particle size distributions results showed that the average size of AMP was 1.0 µm and polydispersity index was 0.1. In DPPH assay AA and AMP were statistically the same. The value of ORAC obtained for AMP was 0.74 and for AA in the literature was 0.95. In the NSA the formulations were stable in conditions of 5.0 and 45.0 ± 2.0 ºC for 90 days. Adequate stability at ambient temperature out of reach of light was also observed. Thus, this works presented an acceptable method for quantification of AMP alone and in cosmetic formulations. AMP was an adequate choice for the incorporation in emulsions with antioxidant efficacy.

Avaliação imunológica promovida pelo consumo de kombucha em camundongos diabéticos / Immunologic evaluation promoted by the consumption of kombucha in diabetic mice

O kombucha é uma bebida fermentada tradicional, originária da China, preparada pela fermentação de chá preto adoçado com cultura mista de bactérias e leveduras chamada Simbiotic Culture of Bacteria and Yeast (SCOBY). Tem sido alegado que o mesmo possui propriedades funcionais, tais como recuperação ou manutenção de peso corporal, atividade antihiperglicêmica, entre outras. Por não existirem estudos suficientes que as comprovem, este trabalho teve por objetivo avaliar a influência do consumo de kombucha como tratamento alternativo para amenizar e/ou retardar sintomas e complicações do Diabetes Mellitus e identificar as possíveis modificações metabólicas, morfológicas e imunológicas ocorridas em camundongos com diabetes tipo 1. De acordo com os resultados obtidos, observou-se que, apesar de ter havido recuperação de massa corpórea próxima daquela que se tinha antes da indução da diabetes, esse efeito não foi exclusivo do kombucha e, embora a influência no controle glicêmico tenha sido maior nos camundongos normoglicêmicos que diabéticos, acredita-se que a administração por um período prolongado pudesse indicar melhores resultados, uma vez que as avaliações histológicas e morfométricas do intestino demonstraram resultados satisfatórios quanto ao aumento da superfície de mucosa e diminuição do infiltrado inflamatório, favorecendo a modulação imunológica. Logo, considera-se necessária a realização de mais trabalhos para comprovação da capacidade funcional do kombucha e elucidação de sua eficácia enquanto tratamento exclusivo e/ou complementar do diabetes

Kombucha is a traditional Chinese fermented beverage prepared by fermenting sweetened black tea with mixed bacterial and yeast culture called Simbiotic Culture of Bacteria and Yeast (SCOBY). It has been claimed that it has functional properties such as body weight recovery or maintenance, antihyperglycemic activity, among others. Because there are not enough studies to prove them, this study aimed to evaluate the influence of kombucha consumption as an alternative treatment to alleviate and/or delay symptoms and complications of Diabetes Mellitus and to identify possible metabolic, morphological and immunological changes in mice with type 1 diabetes. According to the results obtained, it was observed that, although there was a recovery of body mass close to the one obtained before diabetes induction, this effect was not unique to kombucha, and although the influence on glycemic control was greater in normoglycemic rather than diabetic mice, it is believed that administration over a prolonged period could indicate better results, since histological and morphometric evaluations of the intestine showed satisfactory results in terms of mucosal surface enlargement and decreased inflammatory infiltrate, favoring immune modulation. . Therefore, further work is considered necessary to prove the functional capacity of kombucha and to elucidate its effectiveness as an exclusive and / or complementary treatment of diabetes

A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Antitumor efficacy of EDTA co-treatment with cisplatin in tumor-bearing mice

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

Eficacia y optimización de la citometría de flujo en el cribado universal de la infección del tracto urinario / Efficacy and optimisation of flow cytometry in the universal screening of urinary tract infection

Introducción: La citometría de flujo ha mostrado en los últimos años su utilidad en el cribado de infección urinaria y su integración en los Servicios de Microbiología podría evitar la siembra de hasta el 60% de las muestras del área. El propósito de este trabajo es valorar su utilidad en el cribado universal y la rentabilidad diagnóstica en diferentes subpoblaciones. Material y métodos: Se analizaron 1.338 muestras mediante citometría de flujo (Sysmex UF-1000i) y urocultivo en agar CPS. Se informaron como positivos los cultivos con 1 o 2 uropatógenos y recuentos superiores a 105 UFC/ml y en poblaciones especiales, recuentos inferiores con un solo uropatógeno. Resultados: Utilizando un punto de corte de>17,1 bacterias/μl o>29,5 leucocitos/μl se consiguió una sensibilidad del 95,15% y un porcentaje de cribado del 32,14%. De los once falsos negativos, seis presentaban recuentos bajos y en uno se cultivó Candida glabrata. En el estudio por subgrupos se encontraron variaciones estadísticamente significativas respecto al género y la procedencia. El punto de corte en los varones fue inferior con respecto a las mujeres. Sin embargo, se mantuvo estable en las muestras de Atención Primaria, reduciéndose sustancialmente en las hospitalarias. El valor predictivo negativo permaneció siempre por encima del 95%. Conclusión: El sistema de citometría de flujo puede evitar la siembra del 32% de las muestras aplicando criterios estrictos de positividad. En nuestro hospital, habría evitado la siembra de 13.705 orinas en 2016, y podría aumentar combinando los puntos de corte con la procedencia y el género de las muestras

Introduction: Flow cytometry has shown to be useful for ruling out urinary tract infection over the last few years. Its integration into the Microbiology Laboratories could avoid the urine culture of 60% of the samples. The aim of this study is to evaluate the usefulness of flow cytometry in the universal screening, as well as to improve its efficacy by using specific cut-off points in different groups. Material and methods: A total of 1338 urine samples were analysed by flow cytometry (Sysmex UF-1000i), as well as a urine culture in CPS agar. Cultures with one or two pathogens and more than 10,000 CFU/ml, and special cases with less counts but just one pathogen, were considered as positive. Results: A cut-off of >17.1 bacteria/μl or >29.5 leucocytes/μl resulted with a sensitivity of 95.15% and a screening yield of 32.14%. Eleven false negative were obtained, but six of them showed low counts, and another was due to Candida glabrata. On the other hand, statistically significant variations were found as regards gender and origin of the patients. The cut-off of male samples was lower than female ones. However, it remained stable in the samples from Primary Care, and it decreased notably in those from the hospital. The negative predictive value always remained over 95%. Conclusion: Automated flow cytometry can avoid the culture of 32% of samples, even after applying tight positive criteria. In the study hospital, it would have avoided the culture of 13,705 urine samples in the year 2016. These results could improve by combining cut-off points, gender, and origin of patients

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Efficacy and safety of cumaru syrup as complementary therapy in mild persistent asthma: a double-blind, randomized, placebo-controlled study

Amburana cearensis is a medicinal plant known as "cumaru". It is used in Northeast Brazil in the treatment of respiratory diseases. This was a randomized, double-blind, placebo-controlled study, with the aim of evaluating the efficacy and safety of cumaru syrup as complementary therapy in mild persistent asthma. The study consisted of 3 phases, pre-treatment, treatment and post-treatment. The primary efficacy outcome was comparison of the changes reported by patients of the cumaru and placebo groups after treatment, using the "Asthma Quality of Life Questionnaire" (AQLQ). The secondary outcome was the effect of cumaru syrup on lung function based on spirometry. The results showed that in the cumaru group, the proportion of patients who had global improvement in asthma symptoms was significantly greater (61.90%, P=0.0009) than in the placebo group (9.52%). Only the spirometric parameters Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1) showed significant intergroup differences in post-treatment (P<0.05). The hematological and serum chemistry tests performed in the pre-treatment and post-treatment showed no statistically significant differences (P>0.05). Adverse events were reported by 3 patients (14.29%) in the cumaru group and 3 patients (14.29%) in the placebo group. All adverse events were considered non-serious and mild.

Amburana cearensis é uma planta medicinal conhecida como "cumaru". No Nordeste do Brasil é usada no tratamento de doenças respiratórias. Este é um estudo randomizado, duplo-cego e controlado por placebo, com o objetivo de avaliar a eficácia e segurança do xarope de cumaru como terapia complementar da asma persistente leve. O estudo consistiu de três fases, pré-tratamento, tratamento e pós-tratamento. A variável primária para determinação da eficácia foi a comparação das mudanças referidas pelos pacientes dos grupos cumaru e placebo após o tratamento, usando o "Questionário sobre Qualidade de Vida na Asma" (QQVA). A variável secundária foi o efeito do xarope de cumaru na função pulmonar baseado na espirometria. Os resultados mostraram que no grupo cumaru, a proporção de pacientes com melhora global dos sintomas da asma foi significativamente maior (61,90%, P=0.0009) que no grupo placebo (9,52%). Somente os parâmetros espirométricos, capacidade vital forçada (CVF) e volume expiratório forçado no primeiro segundo (VEF1), mostraram diferença intergrupo significtivas no pós-tratamento (P<0.05). Os testes hematológicos e do soro realizados no pré-tratamento e pós-tratamento não mostraram diferenças estatisticamente significativas (P>0.05). Eventos adversos foram reportados por 3 pacientes (14,29%) no grupo cumaru e 3 (14,29%) no grupo placebo. Todos os eventos adversos foram não sérios e leves.

Eficacia de la insulina de administración oral/bucal en el tratamiento de la diabetes mellitus / Efficacy of oral/buccal insulin in the treatment of diabetes mellitus

ObjetivoValorar la eficacia y la seguridad de la insulina de administración oral/bucal.DiseñoRevisión sistemática.Fuentes de datosBases de datos referenciales MEDLINE, EMBASE, Scopus, Current Contents, Web of Science, Cochrane Library, Agencia Europea del Medicamento, Food and Drug Administration, Red Internacional de Agencias de Evaluación de Tecnologías, Red Europea de Detección Precoz de Tecnologías (EuroScan) y varios registros de investigación.Selección de los estudiosSe recuperaron 2 ensayos clínicos. Se excluyeron aquellos estudios que no comparaban la insulina oral/bucal con el tratamiento estándar con insulina inyectada en términos de parámetros clínicos en la población con diabetes.Extracción de datosLectura crítica según la metodología propuesta por el programa CASPe y la escala de Jadad.ResultadosLa insulina bucal produjo una reducción mayor y más temprana en la glucemia posprandial medida a los 30min en el grupo intervención frente al grupo control (reducción de 55mg/dl) y un pico de insulinemia mayor y más rápido (98 frente a 65μU/ml). Respecto a la insulina oral, los niveles de glucemia posprandial fueron equivalentes a los obtenidos con la insulina inyectada, y la concentración máxima de insulina fue superior (110±130 frente a 96,3±69,7μU/ml).ConclusionesLa insulina oral/bucal presentó, al menos, resultados equivalentes al tratamiento estándar. No obstante, los estudios presentaron problemas metodológicos de validez interna y externa.ConclusionesSe precisan estudios de mayor duración para evaluar la eficacia y la seguridad a largo plazo(AU)

ObjectiveTo evaluate the efficacy and safety of administering oral/buccal insulin.DesignSystematic review.Data sourcesReference databases, MEDLINE, EMBASE, Scopus, Current Contents, Web of Science, and Cochrane Library, European Drugs Agency, Food and Drug Administration, International Network of Technological Evaluation Agencies, European Network for New and Emerging Technologies (EuroScan), and gravel research registers.Selection of the studiesTwo clinical trials were found. Those studies that did not compare oral/buccal insulin with the standard treatment with injected insulin in terms of clinical parameters in a population with diabetes were excluded.Extraction of dataCritical reading according to the method proposed by the CASPe program and the Jadad scale.ResultsBuccal insulin produced a greater and earlier reduction in post-prandial blood glucose at 30min in the intervention group compared to the control group (decrease of 55mg/dl) and a higher and more rapid peak blood insulin (98 compared to 65μU/mL). The postprandial levels with oral insulin were similar to those obtained with injected insulin, and had a higher maximum insulin concentration (110±130 vs. 96.3±69.7μU/mL).ConclusionsOral/buccal insulin gives, at least, results similar to the standard treatment. However, the studies had methodological problems of internal and external validity. Studies of longer duration are required to evaluate the long-term efficacy and safety(AU)

Dosis residuales post-aborto con misoprostol. Ensayo clínico aleatorizado / Residual misoprostol dose after pregnancy termination: randomized clinical study

Objetivo: Evaluar la eficacia y seguridad de dos regímenes de dosis residuales después del aborto con 800 miligramos de misoprostol aplicado en la vagina, el primero con 600 miligramos 24 horas después del aborto médico y el segundo con tres dosis de 600 miligramos cada una cada 12 horas después del aborto.Sujetos y métodos: 330 mujeres con gestaciones de hasta 63 días solicitando interrumpir su embarazo, recibieron 800 miligramos misoprostol vaginal cada 24 horas hasta un máximo de tres dosis para abortar. Fueron asignadas aleatoriamente a uno de los dos grupos de dosis residuales. Todas las participantes finalizaron el estudio.Resultados: El aborto completo ocurrió en 304//330 (92,1 por 100, 95 por 100 IC 89,95) sujetos.Conclusiones: La administración de dos dosis extras residuales de 600 miligramos de misoprostol 24 horas post aborto no mejoró dicha tasa (AU)