Gingko biloba extract improves the lipid profile, inflammatory markers, leptin level and the antioxidant status of T2DM patients poorly responding to metformin: A double- blind, randomized, placebo-controlled trial

Abstract The present study aims to evaluate the effects of Ginkgo biloba (GKB) extract as "add- on" therapy with metformin on the lipid profile, inflammatory markers, leptin and the total antioxidant capacity (TAOC) of patients with type 2 diabetes mellitus (T2DM). It is a multi- center, randomized, placebo-controlled double-blinded clinical study. Sixty patients were allocated into two groups: control and treatment groups; they received orally either 120 mg starch/capsule or 120mg GKB/capsule, respectively as an adjuvant with metformin for 90 days. Blood samples were obtained at zero time and after 90 days. The blood was utilized for analysis of the lipid profile, inflammatory markers, leptin, and TAOC. The GKB extract produced a significant decrease in the levels of TG, LDL-c, and CRP, with a significant increase in HDL-c compared to baseline values. There were no significant changes reported in the placebo-treated group. It also produced a significant decrease in the concentrations of IL-6, TNF-α, and leptin compared to baseline values and placebo-treated groups with a significant increase in TAOC compared to baseline values. In conclusion, GKB extract, as an adjuvant with metformin, decreases inflammatory mediators, leptin level and improves the antioxidant status and lipid profile of T2DM patients improperly managed with metformin

Efeitos da suplementacao de Beta-hidroxi-Beta-metilbutirato na eficiencia mecanica em canoístas de elite / Efectos de suplementación de Beta-hidroxi-Beta-methylbutyrate in mechanical efficiency in elite paddlers / Effects of supplementation Beta-hydroxy-Beta-methylbutyrate in mechanical efficiency in elite paddlers

Objetivo. O presente estudo prospectivo, randomizado, duplo‐cego e placebo‐controlado, verificou o efeito da ingestão de 3g/dia‐1 Beta‐hidroxi‐Beta‐metilbutirato sobre os parâmetros da curva força‐tempo em canoístas de elite. Método. Participaram 24 canoístas, homens, de elite, com 21.41±5.35 anos, 173.36±8.27cm e 69.83±10.29kg. Formaram‐se 2 grupos, um suplementado (HMB) e outro placebo (CON), ambos acompanhados por 14 dias e submetidos a teste máximo de 4min (pré e pós) num caiaque ergômetro. Resultados. Apontam melhora na eficiência mecânica em consonância com o aumento significativo do impulso gerado (17.23%, p=0.02), da potência média (26.6%, p=0.01), frequência de remada (13.5%, p=0.04), perante teste máximo de 4min em ergômetro. Conclusão. Houve melhora na capacidade de gerar potência, que pode estar associada com a suplementação de Beta‐hidroxi‐Beta‐metilbutirato, através da diminuição do catabolismo durante o treinamento; contudo, o mecanismo pelo qual isso pode ocorrer ainda é desconhecido (AU)

Objetivo. Este estudio aleatorizado, doble ciego prospectivo, controlado y placebo, tubo como objetivo comprobar el efecto de la ingesta de 3g/día‐1 de Beta‐hidroxi‐Beta‐metilbutirato en los parámetros de la curva fuerza‐tiempo en kayakistas de élite. Método. Veinticuatro kayakistas, hombres, élite con 21.41±5.35 años, 173.36±8.27cm y 69.83±10.29kg. Formado dos grupos, uno suplementado (HMB) y otro placebo (CON), ambos siguieron durante 14 días y sometido a máxima 4min prueba (pre y post) en un ergómetro kayak. Resultados. Se apreció una mejora en la eficiencia mecánica en relación con el aumento significativo del impulso generado (17.23% p=0.02), la potencia media (26.6% p=0.01), frecuencia de carrera (13.5% p=0.04) durante una prueba máxima en ergómetro de 4min. Conclusión. Hubo una mejora en la capacidad para generar energía, que puede estar asociada con la administración de suplementos de Beta‐hidroxi‐Beta‐metilbutirato mediante la reducción de catabolismo durante el entrenamiento, sin embargo, el mecanismo por el que esto puede ocurrir es aún desconocido (AU)

Objective. This prospective, randomized, double‐blind, placebo‐controlled, checked the effect of the intake of 3g/day‐1 of Beta‐Hidroxy‐Beta‐Methylbutyrato on the parameters of the force‐time curve in elite kayakers. Method. 24 paddlers, men, elite with 21.41±5.35 years, 173.36±8.27cm and 69.83±10.29kg. Formed two groups, one supplemented (HMB) and another placebo (CON), both followed for 14 days and subjected to maximum test 4min (pre and post) in a kayak ergometer. Results. Point improvement in mechanical efficiency in line with the significant increase in the generated pulse (17.23% p=0.02), average power (26.6% p=0.01), stroke frequency (13.5% p=0.04) before maximum test 4min ergometer. Conclusion. There was improvement in the ability to generate power, which may be associated with supplementation of Beta‐Hidroxy‐Beta‐Methylbutyrato by reducing catabolism during training, however the mechanism by which this may occur is still unknown (AU)

Fitosomas: un desarrollo tecnológico para mejorar la biodisponibilidad de los extractos vegetales / Phytosomas: um desenvolvimento tecnológico para melhorar a biodisponibilidade de extractos de plantas / Phytosomes: a technological development to improve the bioavailability of herbal extracts

Las plantas son una fuente inestlmable de nutrientes y princpios actívos con propledades muy lnteresantes para la salud. Lamentablemente, el organismo humano tiene dificultad para absorber algunos de ellos. Por ello, aportar y transportar hasta las células del organlsmo estas sustanclas, en cantidad suficiente para que realicen su acción, no siempre es posible, ya que en algunos casos el consumo de cantidades relativamente elevadas de extracto (o lngrediente actlvo) puede tener efectos adversos. Para solventar este problema se han realizado diversas investlgaciones tecnológicas. Entre ellas destaca el desarrollo que ha llevado a la obtencion de "fitosomas", proceso patentado mediante el cual un extracto vegetal estandarizado, una fraccion del mismo, o sus componentes, se unen a fosfolípldos (principalmente fosfatidilcolina) para obtener un complejo molecula-lípido. Este complejo exhibe un mejor perfil farmacocinético y farmacodinámlco y por tanto mejora de forma probada mediante ensayos, su biodisponibilidad. Un ejemplo ampliamente estudiado es el fitosoma de silibina (AU)

Plants are a valuable source of nutrients and active ingredients with interesting health properties. Unfortunately, the human body can have difficulties in absorbing some of them. Therefore, it is not always possible make these substances available to the body cells in sufficient active amount, since in some cases the administration of relatively large amounts of extract (or active ingredient) can cause adverse effects. To solve this problem several technological improvements have been studied. Among them, the development of "phytosomes", which are obtained thanks to a patented process in which a standardized herbal extract, a fraction thereof, or their constituents, are binded to phospholipids (mainly phosphatidylcholine) to obtain a lipid—molecule complex. This complex exhibits better pharmacokinetic and pharmacodynamic profile and it has shown to improve bioavailability. An extensively studied example is the silybin phytosome (AU)

As plantas sao uma valiosa fonte de nutrientes e constituintes activos com propriedades muito interessantes para a saude. Lamentavelmente, o organismo humano tem dificuldade em absorver alguns deles. Por isso, transportar e disponibilizar as celulas do organismo estas substancias em quantidade suficiente para que realizem a sua acgao nem sempre e possivel, uma vez que em alguns casos 0 uso de quantidades relativamente elevadas de extracto (ou da substancia activa) pode ter efeitos adversos. Para resolver este problema realizaram-se varias investigaçoes tecnológicas. Entre elas, destaca-se o desenvolvimento que conduziu a obtengao de "fitossomas", processo patenteado mediante o qual um extracto vegetal padronizado, uma fracçao do mesmo, ou os seus componentes, se unem a fosfolípidos (principalmente fosfatidilcolina) para se obter um complexo molecula-lípido. Este complexo exibe um melhor perfil farmacocinetico e farmacodinamico e, portanto, melhora de forma comprovada mediante ensaios, a sua biodisponibilidade. Um exemplo amplamente estudado e o fitossoma de silibina (AU)

Clinical evaluation of liquid placebos for an herbal supplement, STW5, in healthy volunteers.

BACKGROUND: Although clinical trials are needed to evaluate the efficacy of liquid herbal medicinal products, design of feasible placebos that mimic the appearance, taste, and smell of such products is particularly challenging. OBJECTIVE: The design and feasibility of a liquid placebo for STW5, an herbal medicinal product used for various gastrointestinal problems, was explored in this study. DESIGN: Four sample products-STW5, a fresh and aged version of a placebo made from a seasoning mix (Maggi™), and a placebo with aged artificial flavor and food coloring-were compared in two organoleptic (sensory), single-blind trials with a total of 60 (N=60) healthy volunteers (n(1)=30, n(2)=30). MEASUREMENTS: The appearance, smell, and taste of each solution were evaluated using a Likert scale questionnaire. RESULTS: The liquid placebos evaluated were similar in regard to appearance, smell, and taste. However, participants indicated that for a clinical trial with STW5, the aged Maggi™ placebo would be more viable compared to the fresh Maggi placebo or the aged artificial food coloring placebo with licorice flavor. Participants also noted that the mint flavor and smell of STW5 was distinctly different from the placebo solutions. LIMITATIONS: The trials were conducted in healthy volunteers, not in actual patients. CONCLUSIONS: The aged Maggi™ liquid mix may be more favorable as a placebo than the artificially created one. However, further adjustment will need to be made to the Maggi™ placebo to simulate the complex aromatic composition of STW5 for clinical studies in the future.

Do placebo based validation standards mimic real batch products behaviour? Case studies.

Analytical methods validation is a mandatory step to evaluate the ability of developed methods to provide accurate results for their routine application. Validation usually involves validation standards or quality control samples that are prepared in placebo or reconstituted matrix made of a mixture of all the ingredients composing the drug product except the active substance or the analyte under investigation. However, one of the main concerns that can be made with this approach is that it may lack an important source of variability that come from the manufacturing process. The question that remains at the end of the validation step is about the transferability of the quantitative performance from validation standards to real authentic drug product samples. In this work, this topic is investigated through three case studies. Three analytical methods were validated using the commonly spiked placebo validation standards at several concentration levels as well as using samples coming from authentic batch samples (tablets and syrups). The results showed that, depending on the type of response function used as calibration curve, there were various degrees of differences in the results accuracy obtained with the two types of samples. Nonetheless the use of spiked placebo validation standards was showed to mimic relatively well the quantitative behaviour of the analytical methods with authentic batch samples. Adding these authentic batch samples into the validation design may help the analyst to select and confirm the most fit for purpose calibration curve and thus increase the accuracy and reliability of the results generated by the method in routine application.

Rapid identification and absence of drug tests for AG-013736 in 1mg Axitinib tablets by ion mobility spectrometry and DART™ mass spectrometry.

Axitinib (AG-013736) is a potent investigational drug that has antitumor activity in patients with metastatic renal cell carcinoma and other types of cancers. In this study, ion mobility spectrometry and "direct analysis in real time" (DART™) mass spectrometry were used to rapidly identify AG-013736 in drug substance samples and 1mg Axitinib tablets. The plasmagrams of the sample solutions exhibited a major peak with a reduced ion mobility that was within ±0.0002cm(2)V(-1)s(-1) of that for AG-013736 in an external reference standard solution. The DART ionization source was coupled with both a time-of-flight mass spectrometer and a lower-resolution ion trap mass spectrometer. Samples were analyzed by this technique in as little as 5s with minimal to no sample preparation required. The isotopic masses of the protonated dimer ions of AG-013736 were used to identify AG-013736 in the active tablet. Both techniques were also used to develop low-level limit tests for rapidly verifying the presence or absence of AG-013736 in blinded clinical supplies of active and matching placebo tablets of Axitinib.

Estudio clínico de no-inferioridad y de equivalencia: metodología, análisis e interpretación / Non-inferiority and equivalence clinical trials: methodology, analysis and interpretation of the results

Los estudios controlados con placebo son el método ideal para evaluar la eficacia del tratamiento médico. Debido al gran número de tratamientos de comprobada eficacia en ciertas aplicaciones, los estudios controlados con placebo son a menudo poco éticos. Los estudios de no-inferioridad y de equivalencia son apropiados para evaluar la eficacia de un tratamiento experimental versus un control activo cuando se plantea la hipótesis que el tratamiento experimental puede no ser superior a un tratamiento de comprobada eficacia, pero es clínica y estadísticamente no inferior. El diseño y el reporte de estos estudios deben de seguir las recomendaciones del grupo CONSORT. Para tal fin, es indispensable seleccionar un óptimo control activo. La eficacia del control activo debería ser documentada a través de buenos estudios históricos controlados con placebo; a partir de estos datos es indispensable determinar el margen de no-inferioridad. Los resultados del nuevo tratamiento deben ser comparados con el control activo por análisis múltiples, incluyendo el placebo putativo. El término de no-inferioridad es usado cuando se refiere a un estudio de una sola cola (diferencia en respuesta menor que delta); equivalencia cuando se refiere a estudio de dos colas (diferencia en respuesta entre -Δ y +Δ). Para documentar los planteamientos teóricos se recurre a datos de estudios publicados recientemente, relacionados con moléculas eficaces en el control de la presión arterial y en la reducción de los índices de mortalidad en enfermedades cardiovasculares.

Placebo-controlled trials are the ideal for evaluating medical treatment efficacy. Given the large number of proven effective treatment in several areas, placebo-controlled trials are often unethical. The non-inferiority and equivalence trials are appropriate for evaluation of the efficacy of an experimental treatment versus an active control when it is hypothesized that the experimental treatment may not be superior to a proven effective treatment, but is clinically and statistically not inferior in effectiveness. The design and reporting of these studies must follow the CONSORT statements. An active control must be selected. Good historical placebo-controlled trials documenting the efficacy of the active control must exist. From these historical trials, a margin of non-inferiority must be determined. The results of the new treatment must be compared with active control through multiple analysis, including a putative placebo comparison. The term non-inferority is used when referring to a 1-sided trial (difference in response lower than Δ); equivalence, when referring to 2-sided trials (difference in response between-Δ and +Δ). In order to give practical data, results of published trials related to active molecules effective in the control of blood pressure and in reducing mortality in cardiovascular diseases are used.

Memory impairments in humans after acute tryptophan depletion using a novel gelatin-based protein drink.

Acute tryptophan depletion (ATD) can be used to decrease serotonin levels in the brain. Traditionally, ATD has been established by administering amino acid (AA) mixtures and studies using this method showed that serotonin is involved in learning and memory processes. This study used a recently developed gelatin-based protein drink to examine whether it 1) is superior to the traditional AA method in controlling the tryptophan levels in the placebo condition, 2) impairs long-term memory and 3) differentially affects episodic and spatial memory. Sixteen healthy subjects participated in a double-blind, placebo-controlled study. Memory was assessed using a visual verbal learning test and an object relocation task (spatial memory). Tryptophan ratio significantly decreased after ATD and did not significantly increase in the placebo condition. Delayed recall in the verbal learning test and delayed relocation of objects to positions in the spatial task were impaired after ATD. Spatial short-term memory, however, improved. The current results indicate that the tryptophan levels were essentially neutral in the placebo condition compared with those in the traditional AA mixture. Our study provides further evidence that impairment in long-term episodic and elementary spatial memory after ATD is related to lowered tryptophan levels in plasma.

Determination of rosuvastatin in the presence of its degradation products by a stability-indicating LC method.

A forced degradation study was successfully applied for the development of a stability-indicating assay method for determination of rosuvastatin Ca in the presence of its degradation products. The method was developed and optimized by analyzing the forcefully degraded samples. Degradation of the drug was done at various pH values. Moreover, the drug was degraded under oxidative, photolytic, and thermal stress conditions. Mass balance between assay values of degraded samples and generated impurities was found to be satisfactory. The proposed method was able to resolve all of the possible degradation products formed during the stress study. The developed method was successfully applied for an accelerated stability study of the tablet formulation. The major impurities generated during the accelerated stability study of the tablet formulation were matches with those of the forced degradation study. The developed method was validated for determination of rosuvastatin Ca, and the method was found to be equally applicable to study the impurities formed during routine and forced degradation of rosuvastatin Ca.

Posible efecto beneficioso del chocolate negro en la prevención de enfermedades cardiovasculares / Possible beneficial effect of black chocolate in prevention of cardiovascular disease

No disponible

No disponible

Quetiapina, un nuevo antipsicótico atípico para el tratamiento de la esquizofrenia / Quetiapine, a new atypical antipsychotic drug for the treatment of schizophrenia

No disponible

Analgesia peridural para o trabalho de parto e para o parto: efeitos de adiçäo de um opióide / Effects of the association of an opioid with epidural analgesia for labor and delivery

O objetivo deste estudo foi avaliar a eficácia e segurança da associaçao bupivacaína com sufentanil para a analgesia no trabalho de parto e do parto por meio de um bloqueio peridural contínuo. Realizou-se um ensaio clínico duplo-cego, prospectivo e aleatório, incluindo sessenta mulheres nulíparas da Maternidade do CAISM/UNICAMP. No momento da analgesia, as mulheres foram aleatoriamente alocadas em dois grupos: BS, recebendo 12,5 mg de bupivacaína com adrenalina mais 30 mug de sufentanil e BP, recebendo 12,5 mg de bupivacaína com adrenalina mais placebo. Foram avaliados os parametros relativos à qualidade e duraçao da analgesia, duraçao do trabalho de parto e também possíveis efeitos sobre o recém-nascido. Os resultados mostraram a superioridade da adiçao do sufentanil sobre o grau de analgesia durante o tempo de açao da primeira dose de anestésico local. Nao houve aumento na duraçao do trabalho de parto depois do início da analgesia quando se compararam ambos os grupos, nem qualquer diferença quanto à via de parto. Nao houve também diferenças entre os grupos com relaçao à avaliaçao dos recém-nascidos. Conclui-se que a associaçao de 30 mug de sufentanil à primeira dose de bupivacaína é segura e eficaz, melhorando a qualidade da analgesia, sua duraçao e nao afetando a progressao do trabalho de parto e o resultado neonatal.

Placebo : algunas consideraciones / Placebo, some considerations

El placebo es tan viejo como el hombre mismo. Con el avance de la ciencia ha cobrado una nueva posición y actualmente está presente en muchos de los actos científicos y en la mente de algunos profesionales involucrados en el proceso de la salud. En este trabajo se hace una revisión bibliográfica que no pretende ser exhaustiva y se incluyen algunas consideraciones con la intención única de llamar a reflexión sobre situaciones con las que los profesionales de la salud se encuentran diariamente