Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
J Biotechnol ; 393: 81-90, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39032699

RESUMO

Interleukin-2 (IL-2) has been used in cancer treatment for over 30 years. However, due to its high toxicity, new mutant variants have been developed. These variants retain some of the biological properties of the original molecule but offer other therapeutic advantages. At the Center of Molecular Immunology, the IL-2 no-alpha mutein, an IL-2 agonist with lower toxicity than wtIL-2, has been designed, produced, and is currently being evaluated in a Phase I/II clinical trial. The mutein is produced in E. coli as an insoluble material that must be refolded in vitro to yield a fully active protein. Controlled oxidation steps are essential in the purification process of recombinant proteins produced in E. coli to ensure the proper formation of the disulfide bonds in the molecules. In this case, the new purification process includes a copper-catalyzed air oxidation step to induce disulfide bond establishment. The optimal conditions of pH, copper, protein and detergent concentration for this step were determined through screening. The produced protein demonstrated a conserved 3D structure, higher purity, and greater biological activity than the obtained by established process without the oxidation step. Four batches were produced and evaluated, demonstrating the consistency of the new process.


Assuntos
Cobre , Escherichia coli , Interleucina-2 , Oxirredução , Proteínas Recombinantes , Cobre/química , Interleucina-2/metabolismo , Interleucina-2/genética , Escherichia coli/genética , Humanos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ar , Redobramento de Proteína , Catálise , Concentração de Íons de Hidrogênio
2.
Commun Biol ; 6(1): 828, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558752

RESUMO

Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.


Assuntos
Evolução Molecular Direcionada , Subunidade beta de Receptor de Interleucina-2 , Interleucina-2 , Biblioteca de Peptídeos , Humanos , Subunidade beta de Receptor de Interleucina-2/química , Interleucina-2/química , Interleucina-2/genética , Interleucina-2/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Evolução Molecular Direcionada/métodos , Domínios Proteicos , Animais , Camundongos , Linhagem Celular Tumoral
3.
Front Immunol ; 13: 1021828, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569901

RESUMO

Introduction: The anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs. Methods: To improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice. Results: Both ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice. Discussion: These findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.


Assuntos
Interleucina-2 , Linfoma de Células B , Humanos , Camundongos , Animais , Células Endoteliais/patologia , Recidiva Local de Neoplasia , Rituximab/farmacologia , Rituximab/uso terapêutico , Anticorpos/uso terapêutico
4.
Am J Physiol Cell Physiol ; 320(6): C987-C999, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33881936

RESUMO

Polyamines have been shown to be absolutely required for protein synthesis and cell growth. The serine/threonine kinase, the mechanistic target of rapamycin complex 1 (mTORC1), also plays a fundamental role in the regulation of protein turnover and cell size, including in skeletal muscle, where mTORC1 is sufficient to increase protein synthesis and muscle fiber size, and is necessary for mechanical overload-induced muscle hypertrophy. Recent evidence suggests that mTORC1 may regulate the polyamine metabolic pathway, however, there is currently no evidence in skeletal muscle. This study examined changes in polyamine pathway proteins during muscle hypertrophy induced by mechanical overload (7 days), with and without the mTORC1 inhibitor, rapamycin, and during muscle atrophy induced by food deprivation (48 h) and denervation (7 days) in mice. Mechanical overload induced an increase in mTORC1 signaling, protein synthesis and muscle mass, and these were associated with rapamycin-sensitive increases in adenosylmethione decarboxylase 1 (Amd1), spermidine synthase (SpdSyn), and c-Myc. Food deprivation decreased mTORC1 signaling, protein synthesis, and muscle mass, accompanied by a decrease in spermidine/spermine acetyltransferase 1 (Sat1). Denervation, resulted increased mTORC1 signaling and protein synthesis, and decreased muscle mass, which was associated with an increase in SpdSyn, spermine synthase (SpmSyn), and c-Myc. Combined, these data show that polyamine pathway enzymes are differentially regulated in models of altered mechanical and metabolic stress, and that Amd1 and SpdSyn are, in part, regulated in a mTORC1-dependent manner. Furthermore, these data suggest that polyamines may play a role in the adaptive response to stressors in skeletal muscle.


Assuntos
Hipertrofia/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Poliaminas/metabolismo , Transdução de Sinais/fisiologia , Acetiltransferases/metabolismo , Adenosilmetionina Descarboxilase/metabolismo , Animais , Feminino , Camundongos , Proteínas Musculares/metabolismo , Espermidina Sintase/metabolismo
5.
Poiésis (En línea) ; 38(Ene.-Jun.): 16-30, 2020.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1095663

RESUMO

Se realizó un rastreo bibliográfico sobre la reacomodación de las dinámicas internas en familias que tienen un infante en cuidados paliativos, haciendo hincapié en la importancia de la terapia familiar para entender la enfermedad y resignificarla mediante la técnica narrativa de la metáfora. Teniendo en cuenta lo anterior, cuando llega una crisis significativa al núcleo familiar, como una enfermedad, esta cambia la dinámica familiar, puesto que obliga a movilizarse de manera inesperada para buscar posibles soluciones a la situación que aqueja. En muchos casos, la familia recurre a la terapia familiar como estrategia para fortalecer sus recursos, y la metáfora como herramienta narrativa, es uno de los recursos que se usa para ayudar a resignificar la enfermedad. Ahora bien, en cuanto al rastreo bibliográfico, fue la base del texto reflexivo construido, ya que en el rastreo se evidenció que en la terapia familiar no se encuentra un abordaje específico en los procesos de salud que requieren acompañamiento paliativo, por lo que se hace necesario visibilizar la utilidad de la terapia familiar en estos procesos. Como conclusión, se presenta el uso de la metáfora como posible vía de trabajo con las familias que están pasando por una situación de enfermedad, puesto que facilita la externalización del problema y logran así nuevas narrativas orientadas a la resignificación.


A literature review was carried out on the rearrangement of inner dynamics in families with an infant in palliative care, emphasizing the importance of family therapy to understand the disease and resignify it through the narrative technique of metaphor. Considering the above, when a significant crisis, such as a disease, reaches the family core, family dynamics change since it forces unexpected mobilization to find possible solutions to the situation. In many cases, the family uses family therapy as a strategy to strengthen their resources, and the metaphor, as a narrative tool, is one of the resources used to help resignify the disease. Bibliographic review was the basis of the reflexive text constructed, since the review showed that in family therapy there is no specific approach in health processes that require palliative accompaniment, reason why it is necessary to draw attention to the usefulness of family therapy in this type of processes. In conclusion, the use of metaphor is presented as a possible way of addressing families who are going through a situation of disease, since it facilitates the externalization of the problem and the achievement of new narratives aimed at redefinition of the disease.


Assuntos
Humanos , Terapia Familiar , Cuidados Paliativos , Terapêutica , Metáfora
6.
Arch Med Res ; 50(4): 181-186, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31499478

RESUMO

BACKGROUND: Peripheral neuropathy is one of the most common late complications of diabetes. Vascular endothelial growth factor (VEGF) gene polymorphisms have been associated with the development of peripheral neuropathy in different populations of patients with type 2 diabetes mellitus (DM2). OBJECTIVE: To analyze the prevalence of the +936 C/T VEGF gene polymorphism among patients with DM2 with and without peripheral neuropathy. STUDY DESIGN AND METHODOLOGY: 218 unrelated DM2 patients, 90 with and 128 without peripheral neuropathy were genotyped for the +936 C/T VEGF gene polymorphism using PCR amplification followed by restriction length polymorphism analysis. RESULTS: The CC homozygous VEGF+936 C/T (rs3025039) was the predominant genotype in DM2 patients with peripheral neuropathy, whereas the predominant genotype in patients without neuropathy was the heterozygous C/T. No statistical association was found between genotype distribution and the presence of neuropathy (p = 0.063). The distribution of the genotypes according to the dominant (CC vs. CT + TT) and recessive (TT vs. CT + CC) models showed that the homozygous CC and TT genotypes, respectively, are not risk factors for neuropathy. The CT genotype conferred a protective effect as seen in the over-dominant model (CT vs. CC + TT) (OR = 0.52; 95% CI = 0.300-0.90; p = 0.019). CONCLUSION: We conclude that the VEGF+936 C/T (rs3025039) gene polymorphisms are related to peripheral neuropathy in Mexican DM2 patients, with the heterozygous genotype potentially conferring a protective effect.


Assuntos
Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Rev. luna azul ; 49(0): [109]-[125], 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1121046

RESUMO

Entre los temas más citados que hacen parte de las preocupaciones del mundo actual están la sostenibilidad ambiental y el desarrollo, no solo desde la reflexión de teóricos, humanistas, políticos y otros, sino también desde las agendas y agencias internacionales que los han posicionado como prioridad básica a ser atendida como salvaguarda de la vida en el planeta, en este sentido, la internacionalización de la economía y de los problemas socioculturales como la crisis ambiental y de valores, se tornan en asuntos medulares a considerar en la formación de profesionales. Desde la Educación Superior cubana, el logro de los fines mencionados está estrechamente relacionado con la capacidad de movilización colectiva y de proyección responsable de acciones que ofrece el trabajo en redes, de ahí que el objetivo de la presente disertación sea exponer los principales avances y resultados que ofrece hoy la Red de Medio Ambiente del MES (REDMA), en sus más de 20 años de conformada donde, desde la investigación y el intercambio científico, se integran procesos y políticas en la gestión del conocimiento y la innovación en favor del medioambiente, la prevención de riesgos y peligros, y la adaptación al cambio climático; las vías utilizadas para la compilación y selección de las mejores experiencias fueron el registro de información y la sistematización; los resultados expuestos evidencian sus contribuciones a la formación integral y multifacética de profesionales comprometidos con el desarrollo económico-social y sostenible del país.


Among the most cited issues that are part of the concerns of today's world are environmental sustainability and development, not only from the reflection of theorists, humanists, politicians and others, but also from international agendas and agencies which have positioned them as a basic priority to be addressed as a safeguard of life on the planet. In this sense, the internationalization of the economy and socio-cultural problems, such as the environmental and values crises, become core issues to be considered in the training of professionals. From the Cuban Higher Education, the achievement of the aforementioned purposes is closely related to the capacity of collective mobilization and responsible projection of actions offered by networking. Hence, the objective of this reflection is to present the main advances and results offered today by the Environment Network of the MES (REDMA), in its more than twenty years of formation where, from research and scientific exchange, processes and policies are integrated into knowledge management and innovation in favor of the environment, the prevention of risks and dangers, and the adaptation to climate change. The routes used for the compilation and selection of the best experiences were the registration of information and systematization. The exposed results show their contributions to the comprehensive and multifaceted training of professionals committed to the economic-social sustainable development of the country.


Assuntos
Humanos , Desenvolvimento Sustentável , Educação , Meio Ambiente
8.
Am J Neurodegener Dis ; 5(2): 145-51, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27335704

RESUMO

UNLABELLED: Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central nervous system. Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are implicated in the induction and progression of MS. Evidence suggests that Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory, antioxidant and neuroprotective effects. The aim of the present work was to evaluate the effect of fish oil on the activity of glutathione reductase (GR), content of reduced and oxidized glutathione, and GSH/GSSG ratio in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. Fish oil supplementation resulted in a significant increase in n-3 fatty acids and a decrease n-6 fatty acids. No differences in glutathione reductase activity, content of reduced and oxidized glutathione, and GSH/GSSG ratio were found. CONCLUSION: Glutathione reductase activity was not significantly different between the groups; however, fish oil supplementation resulted in smaller increase in GR compared with control group, suggesting a possible effect on antioxidant defence mechanisms.

9.
Food Chem ; 183: 78-82, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25863613

RESUMO

The antiproliferative effects of a purified white grape pomace extract (PWGPE), as well as of some phenolic standards on colon cancer cells were examined. The phenolic composition of the PWGPE was determined by rapid resolution liquid chromatography/mass spectrometry (RRLC/MS). The PWGPE had 92.6, 43.3 and 6.01mg/g of flavanols, flavonols and phenolic acids, respectively and, along with pure catechin, epicatechin, quercetin and gallic acid, they were all found capable of inhibiting cellular proliferation. PWGPE (100µg/ml) inhibited the proliferation of cells by 52.1% at 48h, whilst catechin, epicatechin, quercetin and gallic acid (60µg/ml) inhibited growth by 65.2%, 62.2%, 81.0% and 71.0%, respectively, at 72h. The PWGPE is an interesting source of phenolic compounds with antiproliferative properties, that could be of interest in the food and pharmaceutical industries.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Neoplasias Colorretais/prevenção & controle , Flavonoides/análise , Hidroxibenzoatos/química , Espectrometria de Massas/métodos , Extratos Vegetais/química , Vitis/química , Catequina/análise , Flavonóis/análise , Humanos , Quercetina/análise
10.
Molecules ; 20(3): 4492-515, 2015 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-25764491

RESUMO

We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer's disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aß42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aß42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aß peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aß lowering effect in vivo might be related to its lower in vitro potency toward Aß aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Aminoquinolinas/administração & dosagem , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Indanos/administração & dosagem , Piperidinas/administração & dosagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Aminoquinolinas/química , Aminoquinolinas/uso terapêutico , Precursor de Proteína beta-Amiloide/genética , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Modelos Animais de Doenças , Donepezila , Células Hep G2 , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Indanos/química , Indanos/uso terapêutico , Camundongos , Estrutura Molecular , Piperidinas/química , Piperidinas/uso terapêutico
11.
Coluna/Columna ; 14(1): 27-32, Jan-Mar/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-741430

RESUMO

OBJECTIVE: To integrate patients with lumbar instability in a multisensor platform in the process of assessment and diagnosis, assigning quantitative parameters for the sagittal balance (SB) and muscle function. METHODS: Experimental study involving adult patients diagnosed with diseases that cause alterations in the SB, that were or were not submitted to surgery with posterior instrumentation and fusion. Each patient underwent anthropometric measurements in body composition scale; a kinesiological analysis using a multisensor platform consisting of depth camera to static/dynamic analysis for the quantitative measurement of SB, and surface electromyography to capture the level of abdominal and lumbar muscles activation and through flexion and extension. RESULTS: Seven adult patients: five females (62.5%)and two men (37.5%) with a mean age 48 years. Images with depth cameras resulted in a SB of from -6.4 to +5.3cm (average -5.7cm). In individuals with positive sagittal balance the percentage of activation (PA) of the abdominal muscles was 58.5% and the lower back lumbar was 75.25%; patients with negative SB integrated the PA of the abdominal muscles of 70.25% and lumbar of 65%; the patient with neutral SB exhibited activation of the abdominal muscles of 87.75% and lumbar muscles of 78.25%. CONCLUSIONS: We observed a trend towards positive SB in patients with overweight and obesity by BMI, as well as increased activation of the abdominal muscles. The multi sensor platform is a useful tool for the diagnosis and prognosis of diseases involving sagittal imbalance. .


OBJETIVO: Integrar os pacientes com instabilidade lombar em uma plataforma multissensor no processo de avaliação e diagnóstico, atribuindo parâmetros quantitativos para o equilíbrio sagital (ES) e função muscular. MÉTODOS: Estudo experimental com pacientes adultos diagnosticados com doenças que causam alterações no ES, submetidos ou não à cirurgia com instrumentação e fusão por via posterior. Em cada paciente realizaram-se medidas antropométricas em balança de composição corporal, análise cinesiológica utilizando uma plataforma multissensor constituída por câmera profundidade para análise estática/dinâmica para medição quantitativa do ES e eletromiografia de superfície para capturar o nível de ativação da musculatura abdominal e lombar por meio de flexão e extensão. RESULTADOS: Sete pacientes adultos: cinco mulheres (62,5%) e dois homens (37,5%) com média de idade de 48 anos. As imagens com câmeras de profundidade resultaram em ES de -6,4+5,3cm (média -5,7cm). Nos indivíduos com equilíbrio sagital positivo, o percentual de ativação (PA) dos músculos abdominais foi 58,5% e dos músculos lombares foi 75,25%; nos pacientes com ES negativo integrado, a PA dos músculos abdominais foi de 70,25% e lombar 65%; o paciente com ES neutro apresentou ativação dos músculos abdominais de 87,75% e dos músculos lombares, de 78,25%. CONCLUSÃO: Observamos uma tendência ao ES positivo em pacientes com sobrepeso e obesidade pelo IMC, bem como ao aumento da ativação dos músculos abdominais. A plataforma multissensor constitui uma ferramenta útil para o diagnóstico e prognóstico de doenças com desequilíbrio sagital. .


OBJETIVO: Integrar a pacientes con inestabilidad lumbar a una plataforma multisensor en su proceso de evaluación y diagnóstico, dando parámetros cuantitativos para el balance sagital (BS) y la función muscular. MÉTODOS: Estudio de tipo experimental con pacientes adultos diagnosticados con patologías que causan alteraciones en el BS, unos no operados, y otros operados con instrumentación y fusión posteriores. Cada paciente fue sometido a mediciones antropométricas en báscula de composición corporal; un análisis kinesiólogo utilizando una plataforma multisensor constituida por cámara de profundidad para el análisis estático/dinámico para la medición cuantitativa del BS, y un electromiógrafo de superficie captó el grado de activación muscular en región abdominal y lumbar, mediante movimientos de flexión y extensión. RESULTADOS: Siete pacientes adultos: cinco mujeres (62.5%), dos hombres (37.5%); media de edad de 48 años. Las imágenes con cámaras de profundidad resultaron en un BS de -6.4 a+5.3cm (promedio-5.7cm). Aquellos con BS positivo el porcentaje de activación (PA) de los músculos abdominales fue de 58.5% y la de los lumbares fue de 75.25%; pacientes con BS negativo integraron un PA de los músculos abdominales de 70.25% y de lumbares de 65%; el paciente con balance sagital neutro tuvo activación de la musculatura abdominal de 87.75% y lumbar de 78.25%. CONCLUSIONES: Observamos tendencia al BS positivo en pacientes con sobrepeso y obesidad por IMC, así como mayor activación de músculos abdominales. La plataforma multisensor constituida es una herramienta útil para el diagnóstico y pronóstico de enfermedades con desbalance sagital. .


Assuntos
Humanos , Instabilidade Articular/diagnóstico , Antropometria , Equilíbrio Postural , Região Lombossacral
12.
Arch Biochem Biophys ; 559: 17-23, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24717599

RESUMO

Accumulating evidence suggest that diets rich in cocoa flavanols may have beneficial effects on cardiovascular health. The major cocoa flavanol monomer, (-)-epicatechin (EC), is readily absorbed and circulates primarily as glucuronidated, sulfated, and O-methylated metabolites in human plasma. However, cellular metabolism, for example in endothelial cells, is less well defined. In the present study we detail the uptake and cellular metabolism of EC and its major in vivo metabolites, (-)-epicatechin-3'-ß-D-glucuronide (E3G), (-)-epicatechin-3'-sulfate (E3S), 3'-O-methyl-(-)-epicatechin-5-sulfate (3ME5S), and 3'-O-methyl-(-)-epicatechin-7-sulfate (3ME7S) in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that EC associates with HUVECs, leading to its intracellular metabolism to 3ME7G and 3ME7S. In contrast, none of the metabolites were taken up by the cells. The metabolic rate and pattern of metabolism in HUVECs was similar to that observed in HepG2 cells, whilst in Caco-2 cells EC was metabolized to E3G, 3ME5G, 3ME7G, 4ME5G, 4ME7G and 3ME7S. Our data support the notion that endothelial cells may contribute significantly to EC metabolism. However, major human circulating metabolites are not accounted for in these model systems underscoring that caution should be taken when drawing conclusions on in vivo flavanol metabolism from in vitro experiments.


Assuntos
Catequina/metabolismo , Células Endoteliais/metabolismo , Absorção , Transporte Biológico , Células CACO-2 , Células Hep G2 , Humanos
13.
J Agric Food Chem ; 62(18): 3979-86, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24083619

RESUMO

Accumulating evidence suggests that diets rich in (poly)phenols may have positive effects on human health. Currently there is limited information regarding the effects of processing on the (poly)phenolic content of berries, in particular in processes related to the baking industry. This study investigated the impact of cooking, proving, and baking on the anthocyanin, procyanidin, flavonol, and phenolic acid contents of wild blueberry using HPLC with UV and fluorescence detection. Anthocyanin levels decreased during cooking, proving, and baking, whereas no significant changes were observed for total procyanidins. However, lower molecular weight procyanidins increased and high molecular weight oligomers decreased during the process. Quercetin and ferulic and caffeic acid levels remained constant, whereas increases were found for chlorogenic acid. Due to their possible health benefits, a better understanding of the impact of processing is important to maximize the retention of these phytochemicals in berry-containing products.


Assuntos
Mirtilos Azuis (Planta)/química , Manipulação de Alimentos/métodos , Frutas/química , Polifenóis/química , Culinária/métodos , Temperatura Alta , Estrutura Molecular
14.
Rev. bras. ciênc. esporte ; 35(4): 847-863, out.-dez. 2013. tab
Artigo em Espanhol | LILACS | ID: lil-705336

RESUMO

El objetivo del estudio fue comparar la presencia curricular de las unidades de aprendizaje de Psicología de la Actividad Física en los planes de estudio de las licenciaturas (pregrado) y posgrado de Educación Física versus Psicología en las universidades que se ofertan en la República Mexicana. Estudio descriptivo y transversal que tuvo de universo 144 programas de estudio de psicología y 68 de educación física; encontrando que en los Posgrados de Psicología el peso porcentual es un poco mayor (16.36) que en los Posgrados de Educación Física (14. 33). Pero al unir pregrado y posgrado se triplica el peso porcentual de las unidades de aprendizaje en las disciplinas de Educación Física (3.13) a diferencia que en psicología (0.93). Estos resultados permiten concluir que, como eje de formación curricular, la psicología de la actividad física y del deporte tiene mayor presencia en Educación Física que en Psicología, lo que significa la necesidad interdisciplinar y transdisicplinar de nuestro objeto de estudio; la unión e interconexión de la psicología y la actividad física y el deporte. Un problema y necesidad enfrentada fue la distinta nomenclatura de los programas de formación curricular tanto de los planes de estudio como de la unidad de aprendizaje, que pueden llevar a la necesidad nacional e internacional de acordar nombres, niveles, carga horaria y competencias (u objetivos) profesionales que pueden facilitar este tipo de análisis, pero sobretodo que faciliten el intercambio académico de estudiantes y profesores.


O presente estudo teve como objetivo comparar o peso percentual das unidades de aprendizagem de psicologia da atividade física na estrutura curricular para a formação profissional inicial e de pós-graduação nos currículos de Educação Física versus Psicologia, em universidades mexicanas. De caráter descritivo e transversal, e tendo como universo 144 currículos de Psicologia e 68 de Educação Física, o estudo mostrou que nos Programas de pós-graduação em Psicologia o peso percentual é um pouco maior (16.36) que nos Programas de Pós-graduação em Educação Física (14.33). Entretanto, ao considerarmos graduação e pós-graduação conjuntamente, o peso percentual das unidades de aprendizagem é três vezes superior nas disicplinas de Educação Física (3.13) em relação às de Psicologia (0.93).


The aim of this study was to compare the percentage of Learning Units in Psychology of Physical Activity in the curriculum structure for the training of the degree (undergraduate) and graduate curricula in Physical Education versus Psychology offered in universities in Mexico. This study was descriptive and cross-sectional, it had an universe of 144 programs of study in Psychology and 68 in Physical Education. We found that percentage in graduate programs of Psychology is slightly higher (16.36) than Graduate programs of Physical Education (14.33). But by combining Undergraduate and Graduate, the percentage of Learning Units in the disciplines of Physical Education (3.13) triples the percentaje weight in Psychology (0.93).These results allow the conclusion that, as the axis of training curriculum, Psychology of Physical Activity and Sport has a greater presence in Physical Education than in Psychology, which means the need interdisciplinary and transdisciplinary of our object of study; the connection and interconnection of the Psychology and the study of Physical Activity and Sport. A problem found during this study which needs to be faced was the nomenclature of the different training programs from both the curriculum plans of study and the learning units, which can lead to national and international agreements on names, levels, load time and professional competences (or targets) to provide this type of analysis, but especially to facilitate academic exchange programs of students and teachers.

15.
Rev. mex. anestesiol ; 8(4): 195-9, oct.-dic. 1985. tab
Artigo em Espanhol | LILACS | ID: lil-33017

RESUMO

Se realizó un análisis del clorhidrato de nalbufina, para control del dolor postoperatorio, en 36 pacientes sometidos a cirugía cardiovascular con circulación extracorpórea, por diversos padecimientos cardiovasculares. El estudio se realizó en el servicio de terapia postquirúrgica del Hospital de Cardiología y Neumología, utilizando nalbufina a razón de 200 microgramos por kilogramo de peso, por vía intravenosa cada 6 horas, aplicando la primera dosis en el momento en que el paciente manifestó dolor. Diez y ocho pacientes estaban intubados y diez y ocho pacientes habían sido extubados. Se observó adecuada analgesia. Hubo sedación sin llegar a depresión respiratoria, no se presentaron cambios hemodinámicos significativos y los gases arteriales mostraron acidosis compensada. No se presentaron alteraciones psicomotoras colaterales


Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Nalbufina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Doenças Cardiovasculares/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA