RESUMO
It was previously reported that crocin, a water-soluble carotenoid isolated from the Crocus sativus L. (saffron), has protective effects on cardiac cells and may neutralize and even prevent the formation of excess number of free radicals; however, functional mechanisms of crocin activity have been poorly understood. In the present research, we aimed to study the functional mechanism of crocin in the heart exposed to oxidative stress. Accordingly, oxidative stress was modeled in vitro on human umbilical vein endothelial cells (HUVECs) and in vivo in mice using cellular stressors. The beneficial effects of crocin were investigated at cellular and molecular levels in HUVECs and mice hearts. Results indicated that oral administration of crocin could have protective effects on HUVECs. In addition, it protects cardiac cells and significantly inhibits inflammation via modulating molecular signaling pathways TLR4/PTEN/AKT/mTOR/NF-κB and microRNA (miR-21). Here we show that crocin not only acts as a direct free radical scavenger but also modifies the gene expression profiles of HUVECs and protects mice hearts with anti-inflammatory action under oxidative stress.
RESUMO
This work focuses on the development and evaluation of a dual nanostructured lipid carrier (NLC)/Carbopol®-based hydrogel system as a potential transporter for the topical delivery of curcumin to the skin. Two populations of different sized negatively charged NLCs (P1, 70-90 nm and P2, 300-350 nm) were prepared and characterized by means of dynamic light scattering. NLCs presented an ovoid platelet shape confirmed by transmission electron microscopy techniques. Curcumin NLC entrapment efficiency and release profiles were assessed by HPLC (high pressure liquid chromatography) and spectrophotometric methods. Preservation and enhancement of curcumin (CUR) antioxidant activity in NLCs (up to 7-fold) was established and cell viability assays on fibroblasts and keratinocytes indicated that CUR-NLCs are non-cytotoxic for concentrations up to 10 µM and exhibited a moderate anti-migration/proliferation effect (20% gap reduction). CUR-NLCs were then embedded in a Carbopol®-based hydrogel without disturbing the mechanical properties of the gel. Penetration studies on Franz diffusion cells over 24 h in CUR-NLCs and CUR-NLCs/gels demonstrated an accumulation of CUR in Strat-M® membranes of 22% and 5%, respectively. All presented data support the use of this new dual CUR-NLC/hydrogel system as a promising candidate for adjuvant treatment in topical dermal applications.
Assuntos
Curcumina , Nanoestruturas , Curcumina/química , Portadores de Fármacos/química , Hidrogéis/metabolismo , Lipídeos/química , Nanoestruturas/química , Pele/metabolismoRESUMO
Desde la creación del cuerpo de médicos-directores de baños a comienzos del siglo XIX, dicho colectivo profesional vivió numerosos conflictos internos y externos en los que se puso en cuestión su autoridad científica y moral como expertos en la gestión de la hidrote-rapia. Aunque los médicos-directores estaban dotados de un papel importante en la gestión de baños y aguas públicas a raíz de las regulaciones existentes, otros actores también pugnaron por ese poder. Este artículo analiza los conflictos que existieron entre médicos-directores de baños y los médicos libres, que defendían tener el mismo acceso al monopolio clínico que los primeros. Tomando como punto de partida un debate que tuvo lugar entre 1866 y 1868, el artículo analiza los diferentes mecanismos legales y discursivos que existían para generar y criticar la autoridad de cada grupo. En una época en la que se estaban determinando los límites de las profesiones científicas y las políticas liberales y de intervención del Estado, el caso de los médicos-directores de baños nos permite analizar los procesos de negociación y legitimación de estatus dentro de una ocupación aún no estabilizada como profesión (AU)
Assuntos
Humanos , História do Século XIX , Diretores Médicos/história , Hidroterapia/história , Balneologia/história , Balneologia/organização & administraçãoRESUMO
The interest of food industry to merchandise natural astaxanthin is growing up. However, it confronts scientific and technological challenges mainly related to its poor water solubility and chemical instability. Here, we present a new quick and efficient green process to simultaneously extract, encapsulate and stabilize astaxanthin from Haematococcus pluvialis. The process is based on the hitherto unexplored combination of supramolecular solvents (SUPRAS), nanostructured liquids generated from amphiphiles through sequential self-assembly and coacervation, and nanostructured lipid carriers (NLCs). These novel nanosystems were characterized by means of dynamic light scattering, AFM and cryoSEM, revealing spherical particles of â¼100â¯nm. Their antioxidant activity was measured by ORAC (20.6⯱â¯3.9⯵M TE) and α-TEAC (2.92⯱â¯0.58⯵M α-TE) assays and their in vitro capacity to inhibit ROS by DHE probe. Results showed that the SUPRAS-NLCs proposed yield high extraction and encapsulation efficiencies (71⯱â¯4%) in combination with a remarkable time stability (180â¯d, 4⯰C).
Assuntos
Antioxidantes/química , Clorofíceas/química , Solventes/química , Antioxidantes/farmacologia , Microscopia Crioeletrônica , Suplementos Nutricionais , Portadores de Fármacos/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipídeos/química , Microscopia de Força Atômica , Nanoestruturas/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/química , Xantofilas/isolamento & purificaçãoRESUMO
Astaxanthin is a xanthophyll carotenoid showing efficient scavenging ability and represents an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies. However, its high lipophilicity and thermolability often limits its antioxidant efficacy in human applications. Here, we developed a formulation of lipid carriers to protect astaxanthin's antioxidant activity. The synthesis of natural astaxanthin-loaded nanostructured lipid carriers using a green process with sunflower oil as liquid lipid is presented. Their antioxidant activity was measured by α-Tocopherol Equivalent Antioxidant Capacity assay and was compared to those of both natural astaxanthin and α-tocopherol. Characterizations by dynamic light scattering, atomic force microscopy, and scattering electron microscopy techniques were carried out and showed spherical and surface negative charged particles with z-average and polydispersity values of ~60 nm and ~0.3, respectively. Astaxanthin loading was also investigated showing an astaxanthin recovery of more than 90% after synthesis of nanostructured lipid carriers. These results demonstrate the capability of the formulation to stabilize astaxanthin molecule and preserve and enhance the antioxidant activity.
Assuntos
Antioxidantes/administração & dosagem , Lipídeos , Nanoestruturas , Antioxidantes/síntese química , Fenômenos Químicos , Portadores de Fármacos , Lipídeos/química , Microscopia de Força Atômica , Estrutura Molecular , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Xantofilas/administração & dosagem , Xantofilas/síntese químicaRESUMO
Positively charged cyclodextrins (PCCDs) are molecular carriers of particular interest for their ability to readily enter into cancer cells. Of main interest, guanidino- and aminoalkyl- PCCDs can be conveniently synthesized and form stable and strong inclusion complexes with various active molecules bearing phosphate groups. We have addressed here the challenge to deliver into cancer cells phosphorylated gemcitabine drugs well known for their instability and inability to permeate cell membranes. NMR data corroborated by semiempirical theoretical calculations have shown that aminoalkyl-CDs form sufficiently stable complexes with both mono- and tri-phosphate forms of gemcitabine by simple mixing of the compounds in aqueous solution at physiological pH. Confocal microscopy and radioactivity counting experiments revealed that the developed systems enabled phosphorylated gemcitabine to penetrate efficiently into aggressive human breast cancer cells (MCF7), eventually leading to a substantial reduction of IC50 values. Moreover, compared to free drugs, phosphorylated metabolites of gemcitabine encapsulated in PCCDs displayed improved in vitro activities also on the aggressive human cancer cells CCRF-CEM Ara-C/8 C, a nucleoside transport-deficient T leukemia cell line. The current study offers the proof-of-principle that phosphorylated nucleoside drugs could be efficiently transported by PCCDs into cancer cells.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Ciclodextrinas/metabolismo , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Linfoma de Células T/metabolismo , Transporte Biológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ciclodextrinas/química , Citarabina/farmacologia , Desoxicitidina/farmacologia , Feminino , Humanos , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Modelos Teóricos , Fosforilação , Células Tumorais Cultivadas , GencitabinaRESUMO
The development of new vascular devices requires to study the effects of materials on blood cells and on coagulation, both in vitro and in vivo. In this study, we have developed a new material by grafting dermatan sulfate (DS) from shark skin onto polyethylene terephthalate (PET). We have evaluated the haemocompatibility of PET-DS material in vitro by measuring thrombin generation, plasma recalcification time, hemolytic activity, and platelet adhesion and in vivo with a model of vascular patch in rat abdominal aorta. In vitro, our results have shown that PET-DS is a nonhemolytic material, able to inhibit thrombin generation and platelet adhesion. In vivo studies by Doppler echographic evaluation 20 days after implantation have shown that the PET-DS patch was integrated in the vessel wall and covered by a layer of cells. In conclusion, PET-DS has good haemocompatibility properties and could be a promising tool for vascular surgery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2001-2009, 2017.
Assuntos
Aorta Abdominal/cirurgia , Plaquetas/metabolismo , Dermatan Sulfato/farmacologia , Teste de Materiais , Adesividade Plaquetária/efeitos dos fármacos , Tubarões , Pele/química , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Dermatan Sulfato/química , Humanos , Masculino , Ratos , Ratos WistarRESUMO
Metal-organic frameworks (MOFs) are coordination polymers of interest for biomedical applications. Of particular importance, nanoparticles made of iron(III) trimesate (MIL-100, MIL standing for Material Institut Lavoisier) (nanoMOFs) can be conveniently synthesised under mild and green conditions. They were shown to be biodegradable, biocompatible and efficient to encapsulate a variety of active molecules. We have addressed here the challenges to encapsulate a highly hydrophilic anticancer prodrug, phosphated gemcitabin (Gem-MP) known for its instability and inability to bypass cell membranes. MIL-100 nanoMOFs acted as efficient "nanosponges", soaking Gem-MP from its aqueous solution with almost perfect efficiency (>98%). Maximal loadings reached â¼30 wt% reflecting the strong interaction between the drug and the iron trimesate matrices. Neither degradation nor loss of crystalline structure was observed after the loading process. Storage of the loaded nanoMOFs in water did not result in drug release over three days. However, Gem-MP was released in media containing phosphates, as a consequence to particle degradation. Drug-loaded nanoMOFs were effective against pancreatic PANC-1 cells, in contrast to free drug and empty nanoMOFs. However, an efflux phenomenon could contribute to reduce the efficacy of the nanocarriers. Size optimization and surface modification of the nanoMOFs are expected to further improve these findings.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Nanopartículas Metálicas , Neoplasias Pancreáticas/tratamento farmacológico , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cristalização , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Desoxicitidina/farmacologia , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Compostos Férricos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Compostos Organometálicos/química , Neoplasias Pancreáticas/patologia , Fosfatos/química , Polímeros/química , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , GencitabinaRESUMO
Astaxanthin, a powerful antioxidant, is a good candidate for the prevention of intracellular oxidative stress. The aim of the study was to compare the antioxidant activity of astaxanthin present in two natural extracts from Haematococcus pluvialis, a microalgae strain, with that of synthetic astaxanthin. Natural extracts were obtained either by solvent or supercritical extraction methods. UV, HPLC-DAD and (HPLC-(atmospheric pressure chemical ionization (APCI)+)/ion trap-MS) characterizations of both natural extracts showed similar compositions of carotenoids, but different percentages in free astaxanthin and its ester derivatives. The Trolox equivalent antioxidant capacity (TEAC) assay showed that natural extracts containing esters displayed stronger antioxidant activities than free astaxanthin. Their antioxidant capacities to inhibit intracellular oxidative stress were then evaluated on HUVEC cells. The intracellular antioxidant activity in natural extracts was approximately 90-times higher than synthetic astaxanthin (5 µM). No modification, neither in the morphology nor in the viability, of vascular human cells was observed by in vitro biocompatibility study up to 10 µM astaxanthin concentrations. Therefore, these results revealed the therapeutic potential of the natural extracts in vascular human cell protection against oxidative stress without toxicity, which could be exploited in prevention and/or treatment of cardiovascular diseases.
Assuntos
Células Endoteliais/efeitos dos fármacos , Microalgas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Carotenoides/metabolismo , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Xantofilas/farmacologiaRESUMO
This Perspective article provides an overview of the recent advancements in the field of intra- and inter-molecular C-N, C-O and C-P bond formation by hydroamination, hydroalkoxylation, hydrophosphination, hydrophosphonylation or hydrophosphinylation of unactivated alkenes, including allenes, 1,3-dienes and strained alkenes, promoted by (chiral) homogeneous catalysts based on earth abundant elements of the s and p blocks, the first row transition metals and the rare-earth metals. The relevant literature from 2009 until late 2014 has been covered.
Assuntos
Alcenos/química , Metais/química , CatáliseRESUMO
Encephalitis lethargica (EL) was an epidemic that spread throughout Europe and North America during the 1920s. Although it could affect both children and adults alike, there were a strange series of chronic symptoms that exclusively affected its younger victims: behavioural disorders which could include criminal propensities. In Britain, which had passed the Mental Deficiency Act in 1913, the concept of mental deficiency was well understood when EL appeared. However, EL defied some of the basic precepts of mental deficiency to such an extent that amendments were made to the Mental Deficiency Act in 1927. I examine how clinicians approached the sequelae of EL in children during the 1920s, and how their work and the social problem that these children posed eventually led to changes in the legal definition of mental deficiency. EL serves as an example of how diseases are not only framed by the society they emerge in, but can also help to frame and change existing concepts within that same society.
Assuntos
Comportamento Criminoso/ética , Comportamento Criminoso/história , Comportamento Criminoso/fisiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/história , Encefalite Viral/complicações , Encefalite Viral/história , Encefalite Viral/psicologia , Política de Saúde/história , Política de Saúde/legislação & jurisprudência , Deficiência Intelectual/etiologia , Deficiência Intelectual/história , Adolescente , Dano Encefálico Crônico/etiologia , Criança , Criminosos/história , Surtos de Doenças/história , Transtornos Disruptivos, de Controle do Impulso e da Conduta/terapia , Educação de Pessoa com Deficiência Intelectual/história , Educação de Pessoa com Deficiência Intelectual/legislação & jurisprudência , Encefalite Viral/reabilitação , Política de Saúde/economia , História do Século XX , Humanos , Institucionalização/economia , Institucionalização/ética , Institucionalização/história , Institucionalização/legislação & jurisprudência , Delinquência Juvenil/ética , Delinquência Juvenil/história , Delinquência Juvenil/legislação & jurisprudência , Assistência de Longa Duração/economia , Assistência de Longa Duração/ética , Assistência de Longa Duração/história , Assistência de Longa Duração/legislação & jurisprudência , Distúrbios do Início e da Manutenção do Sono/etiologia , Reino Unido , Adulto JovemRESUMO
A photoactive, hexagonally structured mesoporous material (Tyl-MCM41) is produced through co-hydrolysis of SiO(2) and a trialkoxysilane-functionalized trityl cation as photoactive species. The formation of the corresponding triphenylmethanol precursor in the material is confirmed by spectroscopic techniques. The hybrid material has an ordered structure with a narrow pore size distribution typical of ordered mesoporous MCM-41-type materials. The triarylcarbinol molecules incorporated into this hybrid structure (Triphol-MCM41) generate trityl cations under acidic conditions, which are photoactive and able to promote the photosensitized dimerization of 1,3-cyclohexadiene in a heterogeneous solid-liquid system. The material is stable and can be recycled without loss of the photochemical activity.
RESUMO
Debido a la situación de crisis que atravesó nuestro país entre 2001 y 2002, la Cruz Roja Alemana y su contra parte de Argentina, con el apoyo de la Oficina Europea de Ayuda Humanitaria (ECHO), plantearon la necesidad de realizar una investigación diagnóstica que permitiera conocer el estado nutricional y las condiciones de vida de la población infantil en situación de pobreza de las provincias del norte argentino.Objetivo. Conocer el estado nutricional de la población de niños y niñas entre 6 meses y 6 años de edad de hogares pobres de nueve provincias del norte argentino.Población, material y métodos. Estudio transversal, en hogares bajo la línea de pobreza, con al menos un hijo entre 6 meses y hasta 6 años de edad. Muestreo probabilístico, estratificado y multietápico (n igual 3.630 encuestas). Se estimaron los indicadores de peso/edad, talla/edad, índices de peso/talla y masa corporal (IMC) según edad y sexo. Se realizaron comparaciones con estándares nacionales e internacionales.Resultados. Tucumán y Santiago del Estero (NOA) y Corrientes y Misiones (NEA) muestran las prevalencias más elevadas de bajo peso así como de baja talla (mas o menos 2 DE). La adecuación peso/talla e IMC mostró sesgos hacia la derecha reflejando, por un lado, la ausencia de emaciación como problema nutricional prevalente y la tendencia de ciertos grupos poblacionales infantiles hacia el riesgo de sobrepeso y obesidad.Conclusiones. El presente componente del proyecto muestra los gradientes de la problemática nutricional en la población estudiada de carácter jurisdiccional.El problema de la desnutrición crónica emerge como prevalente, en tanto el riesgo de obesidad se encuentra presente, hecho que condiciona la necesidad de respuestas diferenciales acordes a la realidad particular de cada provincia.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Antropometria , Estudos Transversais , Estado Nutricional , Áreas de PobrezaRESUMO
Debido a la crisis social que afectó a la Argentina durante los años 2001 y 2002, la Deutsches Rotes Kreuz y su contraparte, la CruzRoja Argentina, con el apoyo de la European Commission of Humanitarian Office (ECHO), propusieron la necesidad de evaluar el estado nutricional y las condiciones de vida de la niñez pobre del norte argentino.Objetivo. Identificar el estado nutricional de los niños entre 6 meses y 6 años pertenecientes a hogares bajo la línea de pobreza de las nueve provincias argentinas del norte, de acuerdo con varias dimensiones socioeconómicas.Población, material y métodos. Estudio transversal y retrospectivo de hogares bajo la línea de pobreza con al menos un niño en edad entre 6 meses y 6años. Se calculó una muestra estratificada, probabilística y multietápica (N igual 3.630). Se estimaron las relaciones de peso/edad, talla/edad y peso/talla según sexo. Las comparaciones se efectuaron según el estándar internacional de la OMS.Resultados. En términos generales, el déficit nutricional se corresponde con los detrimentos de las condiciones socio económicas, con la única excepción del acceso a programas nutricionales y monetarios.El indicador más afectado fue la relación talla/edad, que reflejó un proceso de acortamiento o desnutrición crónica en estos niños. La adecuación peso/talla y el índice de masa corporal mostraron ausencia de emaciación como problema nutricional prevalente y por el contrario, cierta tendencia al sobrepeso en algunos grupos.Conclusiones. El componente presentado aquí demuestra que existen gradientes socio económicos en los problemas nutricionales de la población pobre.Este hecho es de por sí relevante a la hora de considerar las diferentes respuestas y estrategias de programas que deben desarrollarse de acuerdo con la realidad local.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Antropometria , Estudos Transversais , Inquéritos Nutricionais , Pobreza , Áreas de Pobreza , Estudos RetrospectivosRESUMO
Debido a la situación de crisis que atravesó nuestro país entre 2001 y 2002, la Cruz Roja Alemana y su contra parte de Argentina, con el apoyo de la Oficina Europea de Ayuda Humanitaria (ECHO), plantearon la necesidad de realizar una investigación diagnóstica que permitiera conocer el estado nutricional y las condiciones de vida de la población infantil en situación de pobreza de las provincias del norte argentino.Objetivo. Conocer el estado nutricional de la población de niños y niñas entre 6 meses y 6 años de edad de hogares pobres de nueve provincias del norte argentino.Población, material y métodos. Estudio transversal, en hogares bajo la línea de pobreza, con al menos un hijo entre 6 meses y hasta 6 años de edad. Muestreo probabilístico, estratificado y multietápico (n igual 3.630 encuestas). Se estimaron los indicadores de peso/edad, talla/edad, índices de peso/talla y masa corporal (IMC) según edad y sexo. Se realizaron comparaciones con estándares nacionales e internacionales.Resultados. Tucumán y Santiago del Estero (NOA) y Corrientes y Misiones (NEA) muestran las prevalencias más elevadas de bajo peso así como de baja talla (mas o menos 2 DE). La adecuación peso/talla e IMC mostró sesgos hacia la derecha reflejando, por un lado, la ausencia de emaciación como problema nutricional prevalente y la tendencia de ciertos grupos poblacionales infantiles hacia el riesgo de sobrepeso y obesidad.Conclusiones. El presente componente del proyecto muestra los gradientes de la problemática nutricional en la población estudiada de carácter jurisdiccional.El problema de la desnutrición crónica emerge como prevalente, en tanto el riesgo de obesidad se encuentra presente, hecho que condiciona la necesidad de respuestas diferenciales acordes a la realidad particular de cada provincia. (AU)
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Estado Nutricional , Antropometria , Áreas de Pobreza , Demografia , Estudos TransversaisRESUMO
Debido a la crisis social que afectó a la Argentina durante los años 2001 y 2002, la Deutsches Rotes Kreuz y su contraparte, la CruzRoja Argentina, con el apoyo de la European Commission of Humanitarian Office (ECHO), propusieron la necesidad de evaluar el estado nutricional y las condiciones de vida de la niñez pobre del norte argentino.Objetivo. Identificar el estado nutricional de los niños entre 6 meses y 6 años pertenecientes a hogares bajo la línea de pobreza de las nueve provincias argentinas del norte, de acuerdo con varias dimensiones socioeconómicas.Población, material y métodos. Estudio transversal y retrospectivo de hogares bajo la línea de pobreza con al menos un niño en edad entre 6 meses y 6años. Se calculó una muestra estratificada, probabilística y multietápica (N igual 3.630). Se estimaron las relaciones de peso/edad, talla/edad y peso/talla según sexo. Las comparaciones se efectuaron según el estándar internacional de la OMS.Resultados. En términos generales, el déficit nutricional se corresponde con los detrimentos de las condiciones socio económicas, con la única excepción del acceso a programas nutricionales y monetarios.El indicador más afectado fue la relación talla/edad, que reflejó un proceso de acortamiento o desnutrición crónica en estos niños. La adecuación peso/talla y el índice de masa corporal mostraron ausencia de emaciación como problema nutricional prevalente y por el contrario, cierta tendencia al sobrepeso en algunos grupos.Conclusiones. El componente presentado aquí demuestra que existen gradientes socio económicos en los problemas nutricionales de la población pobre.Este hecho es de por sí relevante a la hora de considerar las diferentes respuestas y estrategias de programas que deben desarrollarse de acuerdo con la realidad local. (AU)