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1.
Int J Mol Sci ; 24(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37175934

RESUMO

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1ß, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity.


Assuntos
Disruptores Endócrinos , Humanos , Disruptores Endócrinos/toxicidade , Obesidade , Adipogenia , Adipócitos , Compostos Benzidrílicos/toxicidade , Tecido Adiposo
3.
Pharmaceutics ; 15(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36678861

RESUMO

The biopharmaceutical classification system groups low-solubility drugs into two groups: II and IV, with high and low permeability, respectively. Most of the new drugs developed for common pathologies present solubility issues. This is the case of lurasidone hydrochloride-a drug used for the treatment of schizophrenia and bipolar depression. Likewise, the stability problems of some drugs limit the possibility of preparing them in liquid pharmaceutical forms where hydrolysis and oxidation reactions can be favored. Lurasidone hydrochloride presents the isoindole-1,3-dione ring, which is highly susceptible to alkaline hydrolysis, and the benzisothiazole ring, which is susceptible to a lesser extent to oxidation. Herein, we propose to study the increase in the solubility and stability of lurasidone hydrochloride by the formation of higher-order inclusion complexes with hydroxypropyl-ß-cyclodextrin. Several stoichiometric relationships were studied at between 0.5 and 3 hydroxypropyl-ß-cyclodextrin molecules per drug molecule. The obtained products were characterized, and their solubility and stability were assessed. According to the obtained results, the formation of inclusion complexes dramatically increased the solubility of the drug, and this increased with the increase in the inclusion ratio. This was associated with the loss of crystalline state of the drug, which was in an amorphous state according to infrared spectroscopy, calorimetry, and X-ray analysis. This was also correlated with the stabilization of lurasidone by the cyclodextrin inhibiting its recrystallization. Phase solubility,1H-NMR, and docking computational characterization suggested that the main stoichiometric ratio was 1:1; however, we cannot rule out a 1:2 ratio, where a second cyclodextrin molecule could bind through the isoindole-1,3-dione ring, improving its stability as well. Finally, we can conclude that the formation of higher-order inclusion complexes of lurasidone with hydroxypropyl-ß-cyclodextrin is a successful strategy to increase the solubility and stability of the drug.

4.
Int J Mol Sci ; 22(22)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34830025

RESUMO

Due to the inability to curb the excessive increase in the prevalence of obesity and overweight, it is necessary to comprehend in more detail the factors involved in the pathophysiology and to appreciate more clearly the biochemical and molecular mechanisms of obesity. Thus, understanding the biological regulation of adipose tissue is of fundamental relevance. Connexin, a protein that forms intercellular membrane channels of gap junctions and unopposed hemichannels, plays a key role in adipogenesis and in the maintenance of adipose tissue homeostasis. The expression and function of Connexin 43 (Cx43) during the different stages of the adipogenesis are differentially regulated. Moreover, it has been shown that cell-cell communication decreases dramatically upon differentiation into adipocytes. Furthermore, inhibition of Cx43 degradation or constitutive overexpression of Cx43 blocks adipocyte differentiation. In the first events of adipogenesis, the connexin is highly phosphorylated, which is likely associated with enhanced Gap Junction (GJ) communication. In an intermediate state of adipocyte differentiation, Cx43 phosphorylation decreases, as it is displaced from the membrane and degraded through the proteasome; thus, Cx43 total protein is reduced. Cx is involved in cardiac disease as well as in obesity-related cardiovascular diseases. Different studies suggest that obesity together with a high-fat diet are related to the production of remodeling factors associated with expression and distribution of Cx43 in the atrium.


Assuntos
Adipócitos/metabolismo , Adipogenia , Tecido Adiposo/metabolismo , Comunicação Celular , Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Obesidade/metabolismo , Animais , Humanos
5.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801118

RESUMO

Diabetic retinopathy (DR) is one of the main causes of vision loss in the working age population. It is characterized by a progressive deterioration of the retinal microvasculature, caused by long-term metabolic alterations inherent to diabetes, leading to a progressive loss of retinal integrity and function. The mammalian retina presents an orderly layered structure that executes initial but complex visual processing and analysis. Gap junction channels (GJC) forming electrical synapses are present in each retinal layer and contribute to the communication between different cell types. In addition, connexin hemichannels (HCs) have emerged as relevant players that influence diverse physiological and pathological processes in the retina. This article highlights the impact of diabetic conditions on GJC and HCs physiology and their involvement in DR pathogenesis. Microvascular damage and concomitant loss of endothelial cells and pericytes are related to alterations in gap junction intercellular communication (GJIC) and decreased connexin 43 (Cx43) expression. On the other hand, it has been shown that the expression and activity of HCs are upregulated in DR, becoming a key element in the establishment of proinflammatory conditions that emerge during hyperglycemia. Hence, novel connexin HCs blockers or drugs to enhance GJIC are promising tools for the development of pharmacological interventions for diabetic retinopathy, and initial in vitro and in vivo studies have shown favorable results in this regard.


Assuntos
Conexinas/metabolismo , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Suscetibilidade a Doenças , Junções Comunicantes/metabolismo , Animais , Conexinas/genética , Retinopatia Diabética/patologia , Junções Comunicantes/genética , Expressão Gênica , Humanos , Neuroglia/metabolismo , Retina/metabolismo , Retina/patologia
6.
Antibiotics (Basel) ; 9(9)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872146

RESUMO

Bovine mastitis (BM) is the most prevalent bacterial infection in the livestock sector, affecting the dairy industry greatly. The prevention and treatment of this disease is mainly made via antibiotics, but the increasing antimicrobial resistance of pathogens has affected the efficiency of conventional drugs. Pseudomonas sp. is one of the pathogens involved in this infection. The therapeutic rate of cure for this environmental mastitis-causing pathogen is practically zero, regardless of treatment. Biofilm formation has been one of the main virulence mechanisms of Pseudomonas hence presenting resistance to antibiotic therapy. We have manufactured chitosan nanoparticles (NQo) with tripolyphosphate (TPP) using ionotropic gelation. These NQo were confronted against a Pseudomonas sp. strain isolated from milk samples of cows diagnosed with BM, to evaluate their antimicrobial and antibiofilm capacity. The NQo showed great antibacterial effect in the minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC) and disk diffusion assays. Using sub lethal concentrations, NQo were tested for inhibition of biofilm formation. The results show that the nanoparticles exhibited biofilm inhibition and were capable of eradicate pre-existing mature biofilm. These findings indicate that the NQo could act as a potential alternative to antibiotic treatment of BM.

7.
Biomed Res Int ; 2020: 7453786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149131

RESUMO

Endocrine disruptors (EDs) are defined as environmental pollutants capable of interfering with the functioning of the hormonal system. They are environmentally distributed as synthetic fertilizers, electronic waste, and several food additives that are part of the food chain. They can be considered as obesogenic compounds since they have the capacity to influence cellular events related to adipose tissue, altering lipid metabolism and adipogenesis processes. This review will present the latest scientific evidence of different EDs such as persistent organic pollutants (POPs), heavy metals, "nonpersistent" phenolic compounds, triclosan, polybrominated diphenyl ethers (PBDEs), and smoke-derived compounds (benzo -alpha-pyrene) and their influence on the differentiation processes towards adipocytes in both in vitro and in vivo models.


Assuntos
Adipogenia/fisiologia , Disruptores Endócrinos/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Benzoatos/metabolismo , Poluentes Ambientais/metabolismo , Éteres Difenil Halogenados/metabolismo , Humanos , Metabolismo dos Lipídeos , Fenóis/farmacologia , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pirenos/metabolismo , Fatores de Transcrição , Triclosan/metabolismo
8.
Nanomaterials (Basel) ; 10(2)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32053989

RESUMO

A simple and straightforward technique for coating microplate wells with molecularly imprinted polymer nanoparticles (nanoMIPs) to develop assays similar to the enzyme-linked immunosorbent (ELISA) assay to determine and quantify florfenicol (FF) in real food samples such as liquid milk and salmon muscle is presented here. The nanoMIPs were synthesized by a solid-phase approach with an immobilized FF (template) and characterized using dynamic light scattering, a SPR-2 biosensor system and transmission electron microscopy. Immobilization of nanoMIPs was conducted by preparing a homogenous solution of FF-nanoMIPs in water mixed with polyvinyl alcohol (PVA) 0.2% (w/v) in each well of a microplate. The detection of florfenicol was achieved in competitive binding experiments with a horseradish peroxidase-florfenicol (FF-HRP) conjugate. The assay made it possible to measure FF in buffer and in real samples (liquid milk and salmon muscle) within the range of 60-80 and 90-100 ng/mL, respectively. The immobilized nanoMIPs were stored for six weeks at room temperature and at 5 °C. The results indicate good signal recovery for all FF concentrations in spiked milk samples, without any detrimental effects to their binding properties. The high affinity of nanoMIPs and the lack of a requirement for cold chain logistics make them an attractive alternative to traditional antibodies used in ELISA.

9.
BMC Cell Biol ; 17 Suppl 1: 17, 2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27228968

RESUMO

Mutations in human connexin (Cx) genes have been related to diseases, which we termed connexinopathies. Such hereditary disorders include nonsyndromic or syndromic deafness (Cx26, Cx30), Charcot Marie Tooth disease (Cx32), occulodentodigital dysplasia and cardiopathies (Cx43), and cataracts (Cx46, Cx50). Despite the clinical phenotypes of connexinopathies have been well documented, their pathogenic molecular determinants remain elusive. The purpose of this work is to identify common/uncommon patterns in channels function among Cx mutations linked to human diseases. To this end, we compiled and discussed the effect of mutations associated to Cx26, Cx32, Cx43, and Cx50 over gap junction channels and hemichannels, highlighting the function of the structural channel domains in which mutations are located and their possible role affecting oligomerization, gating and perm/selectivity processes.


Assuntos
Canalopatias/metabolismo , Conexinas/química , Conexinas/metabolismo , Animais , Canalopatias/genética , Conexinas/genética , Junções Comunicantes/metabolismo , Humanos , Ativação do Canal Iônico , Modelos Moleculares , Mutação/genética
10.
Int J Stroke ; 8(7): 591-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24024917

RESUMO

The availability of population-based epidemiological data on the incident risk of stroke is very scarce in Argentina and other Latin American countries. In response to the priorities established by the World Health Organization and the United Nations, PREVISTA was envisaged as a population-based program to determine the risk of first-ever and recurrent stroke and transient ischemic attack incidence and mortality in Tandil, Buenos Aires, Argentina. The study will be conducted according to Standardized Tools for Stroke Surveillance (STEPS Stroke) methodology and will enroll all new (incident) and recurrent consecutive cases of stroke and transient ischemic attack in the City of Tandil between May 1st, 2013 and April 30, 2015. The study will include patients with ischemic stroke, non-traumatic primary intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. To ensure the inclusion of every cerebrovascular event during an observation period of two years, we will instrument an 'intensive screening program', consisting of a comprehensive daily tracking of every potential event of stroke or transient ischemic attack using multiple overlapping sources. Mortality would be determined during follow-up for every enrolled patient. Also, fatal community events would be screened daily through revision of death certificates at funeral homes and local offices of vital statistics. All causes of death will be adjudicated by an ad-hoc committee. The close population of Tandil is representative of a large proportion of Latin-American countries with low- and middle-income economies. The findings and conclusions of PREVISTA may provide data that could support future health policy decision-making in the region.


Assuntos
Acidente Vascular Cerebral/epidemiologia , Argentina/epidemiologia , Humanos , Incidência , Projetos de Pesquisa
11.
Arch. méd. Camaguey ; 16(6): 1731-1743, nov.-dic. 2012.
Artigo em Espanhol | LILACS | ID: lil-665651

RESUMO

El impacto de la ciencia y la innovación tecnológica es considerado como el conjunto de cambios duraderos que se producen en la sociedad. Objetivo: evaluar el impacto en los serviciosde salud de Camagüey de los resultados de proyectos de investigación de los programas científico técnicos territoriales y ramales del MINSAP. Método: se elaboró una propuesta metodológica aplicada sobre el impacto de los resultados de proyectos de investigación, desarrollo e innovación enlos servicios de salud. Para su validación se realizó consulta a especialistas y una prueba con 30 proyectos. Resultados: todos los especialistas valoraron la oportunidad de la propuesta como muy alta o alta, expresaron el reconocimiento de la necesidad de medir con claridad los impactos de las acciones de ciencia e innovación. Los mismos consideraron que el mayor efecto negativo a la implementación de la propuesta debe de esperarse del escepticismo o indiferencia administrativa, opción que alcanzó el mayor número de puntos ponderados y fue considerada en el primer lugar por 10 de las 14 respuestas válidas. Conclusiones: los especialistas consideraron que la metodología es pertinente, de efectividad probable, puede convertirse en una herramienta útil para resolver las limitaciones que se enfrentan en la medición del impacto, es factible de aplicar si se logra erradicarlas debilidades estructurales del sistema de salud. La elaboración de la lista de control constituye el elemento dinámico y fundamental, basada en la definición de proyectos esperados, sus indicadores de resultados y el compromiso de los miembros del equipo de investigación


The impact of scientific and technological innovation is considered as the lasting changes that occur in society. Objective: to assess the impact of research projects results of the territorial and ramal scientific technical programs in health services of Camagüey. Method: a methodological proposal on the impact of the results of technological development and innovation projects in health services was performed. For validation was carried out a specialists’ consultation and a test with 30 projects. Results: all specialists evaluated the opportunity of the proposal as very high or high, who expressed the need to measure clearly the impacts of science and innovationactions. They also considered the greatest negative effect to the proposal implementation should be expected in the skepticism or administrative indifference, option that reached the greatest number of weighted points and it was considered the first place of the 14 valid answers. Conclusions: the methodology was considered relevant by specialists of probable effectiveness; it may become a useful tool to resolve constraints faced in measuring impact, it is feasible to apply if eradicated structural health system weaknesses. The elaboration of the control list constitutes a dynamic and essential element based on the definition of expected projects, its performance indicators and the commitment of the members of the research team


Assuntos
Humanos , Impactos da Poluição na Saúde , Indicadores de Impacto Social , Metodologia como Assunto
12.
Rev. cuba. hig. epidemiol ; 50(3): 300-308, sep.-dic. 2012.
Artigo em Espanhol | LILACS | ID: lil-665662

RESUMO

Introducción: existen problemas en la calidad de las investigaciones de salud sobre la cuales se desea tener una perspectiva desde el punto de vista de algunos profesionales de la atención primaria. Métodos: durante el mes de noviembre de 2011 se realizó una encuesta exploratoria en ocho áreas de salud del municipio de Camagüey . Se procedió a reducir la dimensionalidad de las respuestas mediante la técnica de componentes principales (PCA); se compararon los resultados obtenidos en cada área con la técnica no paramétrica de Kruskal-Wallis. Todos los análisis se realizaron con el programa SPSS 19. Resultados: se caracterizó a los encuestados y sus respuestas. Las respuestas fueron agrupadas en seis constructos con más del 63 porciento de la varianza explicada. Los resultados reflejan que los profesionales de la salud de la atención primaria encuestados en el municipio de Camagüey son conformados por personas con bastante experiencia en la actividad. La técnica PCA permitió reducir la dimensionalidad. Los constructos encontrados en todos los casos demostraron afectaciones potenciales a la calidad de las investigaciones y la producción científica. Conclusiones: las investigaciones necesitan un enfoque transdisciplinar, hay insuficiente conocimiento de estadística e idioma inglés. Se pudo constatar que es insuficiente la divulgación de los esquemas nacionales e internacionales de financiamientos y donaciones para la investigación


Introduction: there are problems in the quality of health research. This work is aimed to get a perspective from some professional point of view from the primary health care. Methods: a survey in eight health areas of Camagüey municipality was carried out in November 2011.The dimension of the answers was reduced by principal component- analysis technique (PCA). The results obtained were compared in each area with Kruskal-Wallis H non-parametric technique. All the analyses were performed using statistical package SPSS 19. Results: people interviewed and their answers were characterized in details. The survey was assessed as reliable as it was possible to group the answers in 6 constructs with more than 63 percent of the explained variation. The results showed that primary health care professionals in Camagüey municipality are experienced enough in this activity. PCA technique allowed reducing the dimension of the answers. The constructs found in all cases showed potential load to the quality of research and scientific production. Conclusions: the investigations need interdisciplinary approach. There is not enough statistic knowledge as well as English language. There is no enough knowledge about the national and international outlines of financings and grants for researching


Assuntos
Avaliação da Pesquisa em Saúde , Atenção Primária à Saúde , Projetos de Pesquisa , Cuba , Coleta de Dados/métodos
13.
Humanidad. med ; 11(1): 99-117, ene.-abr. 2011.
Artigo em Espanhol | LILACS | ID: lil-738720

RESUMO

Este artículo de revisión aborda la temática de la evaluación del impacto de los resultados de la ciencia y la innovación en el desarrollo social, como un elemento indispensable para conocer el cumplimiento de las políticas sociales en ciencia y tecnología. Se abordan las definiciones de impacto, impacto social y evaluación del impacto desde la perspectiva de múltiples autores. Se establece que de las tres dimensiones del impacto, la científica, la económica y la social, es esta última la que presenta mayores dificultades en su medición por las complejas redes de interacciones que se ponen de manifiesto entre la sociedad y los resultados de la ciencia. Se abordan sus diferentes niveles de análisis y se presentan los aspectos generales de dos propuestas metodológicas para su medición.


This review paper focuses on the impact assessment of the results of Science and Innovation over the social development, as an essential element in order to know the achievement of social politics in Science and technology. The definition of impact, social impact and impact assessment, are approached from the perspective of various authors. The main conceptual problems presented by the notion of impact are revised, and three dimension are described, the scientific, the economic and the social, the last one present more difficulty in it measurement because of the complexity of the interaction between society and science result. Two experiences for impact assessment are described, each one with a different methodology and analytical levels.

14.
Arch. méd. Camaguey ; 14(3)mayo-jun. 2010. tab
Artigo em Espanhol | LILACS | ID: lil-577913

RESUMO

Fundamento: la diabetes en el embarazo provoca un estado de resistencia a la insulina y otras alteraciones metabólicas que conducen a un alto riesgo de morbilidad materna y fetal. Objetivo: analizar el comportamiento de la insulinoresistencia y algunos parámetros del metabolismo de glúcidos y lípidos en diabéticas gestacionales y pregestacionales. Método: se realizó un estudio observacional analítico de corte longitudinal en cincuenta y cuatro embarazadas diabéticas pregestacionales y gestacionales. Se le determinaron los valores de las concentraciones séricas de glucosa, insulina, triglicéridos, colesterol y el índice de resistencia a la insulina, según el modelo matemático HOMA-IR (homeostasis model assessment of insulin resistance) entre las semanas diez y catorce del embarazo. A todas las pacientes se les repitieron las determinaciones desde la semana veinte y ocho a la treinta y tres, se compararon los valores obtenidos mediante una prueba de hipótesis de proporciones. Resultados: los valores elevados de triglicéridos y colesterol se presentaron con más frecuencia en el tercer trimestre del embarazo. También en el caso de la insulina los valores elevados predominaron en el tercer trimestre, pero en el caso de la glucosa no hubo diferencia significativa entre ambos momentos. La resistencia a la insulina fue mayor en el tercer trimestre. Conclusiones: a lo largo del embarazo se incrementaron los lípidos séricos, la insulinemia y la resistencia a la insulina en ambos tipos de embarazadas diabéticas. Aunque las diabéticas pregestacionales presentaron valores más elevados de los diferentes parámetros estudiados, el hecho de que estas alteraciones estén presentes en las diabéticas gestacionales condiciona que sean también un grupo de alto riesgo obstétrico.


Background: diabetes in pregnancy causes a resistance state to the insulin and other metabolic alterations that lead to a high risk of maternal and fetal morbidity. Objective: to analyze the insulinoresistence behavior and some parameters of glucide and lipid metabolism in gestation and pregestation diabetic women. Method: an analytic observational study of longitudinal cohort in fifty-four pregestation and gestation diabetic pregnant women was conducted. Values of serumal concentrations of glucose, insulin, triglycerides, cholesterol and resistance index to insulin were determined, according to the mathematical model HOMA-IR (homeostasis model assessment of insulin resistance) among the weeks ten and fourteen of pregnancy. To all patients were repeated the determinations from the week twenty-eight to thirty-three, obtained values were compared by means of a proportion hypothesis test. Results: high values of triglycerides and cholesterol were presented with more frequency in the third trimester of pregnancy. Also in the case of insulin the high values prevailed in the third trimester, but in the case of the glucose there was not significant difference between both moments. The insulin resistance was bigger in the third trimester. Conclusions: along pregnancy serumal lipids, insulinemia and insulin resistance were increased in both types of diabetic pregnant women. Although pregestation diabetic women presented higher values of the different studied parameters, the fact that these alterations are present in gestation diabetic women conditions that also be a group of high obstetric risk.


Assuntos
Humanos , Feminino , Gravidez , Colesterol/sangue , Diabetes Gestacional/metabolismo , Glicemia/análise , Resistência à Insulina , Insulina/sangue , Triglicerídeos/sangue
15.
Arch. méd. Camaguey ; 7(supl.2)nov.-dic. 2003. tab
Artigo em Espanhol | LILACS | ID: lil-462732

RESUMO

La provincia de Camagüey desde 1996 utiliza para la evaluación externa de la calidad de los laboratorios de la atención secundaria desde 1996, además del Programa nacional, el Programa de Evaluación Externa de la Calidad (PEEC), diseñado para la atención primaria (SECAL). Los Promedios de Indices de Varianza (PIV) fueron de 174, 170 y 164 desde esa fecha y hasta 1998. Esta situación nos sugirió la necesidad de detectar aquellos laboratorios que obtienen valores erróneos para corregirlos, por ellos se crearon las condiciones para la evaluación de la veracidad. Mediante la evaluación de los controles por ambos programas se determinaron los evaluados correctamente (que coinciden) y los señalados por uno u otro programa (que no coinciden), durante los años 1999, 2000 y 2001. En nuestro trabajo se calculó la sensibilidad, especificidad, eficiencia e índice de Youden según los resultados de este período, y existió un aumento progresivo en la especificidad, eficiencia e índice de Youden de la mayoría de los componentes evaluados


Assuntos
Humanos , Laboratórios Hospitalares , Garantia da Qualidade dos Cuidados de Saúde
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