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J Am Heart Assoc ; 8(20): e012748, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-31597508


Background Atrial fibrillation often occurs in the setting of hypertension and associated atrial dilation with pathologically increased cardiomyocyte stretch. In the setting of atrial dilation, mechanoelectric feedback has been linked to the development of ectopic beats that trigger paroxysmal atrial fibrillation mainly originating from pulmonary veins (PVs). However, the precise mechanisms remain poorly understood. Methods and Results We identify mechanosensitive, swelling-activated chloride ion channels (ICl,swell) as a crucial component of the caveolar mechanosensitive complex in rat and human cardiomyocytes. In vitro optical mapping of rat PV, single rat PV, and human cardiomyocyte patch clamp studies showed that stretch-induced activation of ICl,swell leads to membrane depolarization and decreased action potential amplitude, which trigger conduction discontinuities and both ectopic and reentrant activities within the PV. Reverse transcription quantitative polymerase chain reaction, immunofluorescence, and coimmunoprecipitation studies showed that ICl,swell likely consists of at least 2 components produced by mechanosensitive ClC-3 (chloride channel-3) and SWELL1 (also known as LRRC8A [leucine rich repeat containing protein 8A]) chloride channels, which form a macromolecular complex with caveolar scaffolding protein Cav3 (caveolin 3). Downregulation of Cav3 protein expression and disruption of caveolae structures during chronic hypertension in spontaneously hypertensive rats facilitates activation of ICl,swell and increases PV sensitivity to stretch 10- to 50-fold, promoting the development of atrial fibrillation. Conclusions Our findings identify caveolae-mediated activation of mechanosensitive ICl,swell as a critical cause of PV ectopic beats that can initiate atrial arrhythmias including atrial fibrillation. This mechanism is exacerbated in the setting of chronically elevated blood pressures.

Hum Vaccin Immunother ; 14(7): 1647-1653, 2018 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-29451833


In an influenza pandemic, two vaccine doses administered 21 days apart may be needed for individuals of all ages to achieve seroprotection. Achieving dose-series completion can be challenging even for routinely recommended vaccines. To prepare for a two-dose influenza pandemic vaccine campaign and promote dose-series completion and correct dosing intervals, CDC and its partners developed a text message-based vaccine reminder system to remind persons who receive a first dose of pandemic influenza vaccine to receive the second dose. Taking advantage of the high prevalence of cell phones in the United States, the system sent second-dose text message reminders and hyperlinks to educational information. The system was pilot tested from November 2015 to April 2016 among graduate public health students enrolled at four United States universities. Universities were selected based on convenience, and each university used a different recruitment method. Among 59 volunteers who pilot tested the system and completed a survey, 57 (92%) felt the system would be helpful during a pandemic. Forty (68%) respondents felt the information included in the messages was informative. Volunteers recommended including actionable ways to stay healthy during a pandemic, though specific suggestions varied. With further development, text reminder systems could be used to promote adherence to a two-dose regimen in a future pandemic, although audience-specific messaging and other complementary systems will likely be needed. Public and private partners can adapt and implement this tool in conjunction with their routine patient information systems to improve dose-series completion and ensure optimal protection during an influenza pandemic.

Gripe Humana/prevención & control , Pandemias/prevención & control , Sistemas Recordatorios/instrumentación , Envío de Mensajes de Texto , Vacunación/estadística & datos numéricos , Teléfono Celular , Humanos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/uso terapéutico , Proyectos Piloto , Salud Pública , Encuestas y Cuestionarios , Estados Unidos
Nutrients ; 7(7): 5646-63, 2015 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-26184298


Fat oxidation has been shown to increase after short term green tea extract (GTE) ingestion and after one bout of intermittent sprinting exercise (ISE). Whether combining the two will result in greater fat oxidation after ISE is undetermined. The aim of the current study was to investigate the combined effect of short term GTE and a single session of ISE upon post-exercise fat oxidation. Fourteen women consumed three GTE or placebo capsules the day before and one capsule 90 min before a 20-min ISE cycling protocol followed by 1 h of resting recovery. Fat oxidation was calculated using indirect calorimetry. There was a significant increase in fat oxidation post-exercise compared to at rest in the placebo condition (p < 0.01). After GTE ingestion, however, at rest and post-exercise, fat oxidation was significantly greater (p < 0.05) than that after placebo. Plasma glycerol levels at rest and 15 min during post-exercise were significantly higher (p < 0.05) after GTE consumption compared to placebo. Compared to placebo, plasma catecholamines increased significantly after GTE consumption and 20 min after ISE (p < 0.05). Acute GTE ingestion significantly increased fat oxidation under resting and post-exercise conditions when compared to placebo.

Tejido Adiposo/metabolismo , Ejercicio Físico/fisiología , Extractos Vegetales/farmacología , Té/química , Catequina/análogos & derivados , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Oxidación-Reducción , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Adulto Joven
J Acquir Immune Defic Syndr ; 43(2): 127-36, 2006 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16951651


The infection of CD4 cells may have significant involvement in the transmission and long-term persistency of HIV. Using HIV clones carrying the enhanced green fluorescent protein (EGFP), we infected epithelial and glioneuronal cell lines derived from the female reproductive tract, brain, colon, and intestine. HIV infection was quantified by counting EGFP-positive cells. Infection was quantified in cell lines from the female reproductive tract, brain tissue, and colon tissue (0.36%-3.15%). Virus replicated in the infected cells and the progeny virus were infectious for CD4 cells, HeLa-CD4, and CEM T lymphocytes. Furthermore, we found that infection of these epithelial and brain cell lines is independent of gp120. The results from the infection of CD4 epithelial cells suggest that HIV can traverse epithelial cell layers by infecting them through a gp120-independent mechanism. Infection of glial and neuronal cell lines suggests that HIV infection of these cells is a probable mechanism for HIV pathogenicity in the brain and a possible cause for persistent infection in patients.

Encéfalo/citología , Colon/citología , Proteína gp120 de Envoltorio del VIH/fisiología , Infecciones por VIH/fisiopatología , VIH-1/fisiología , Antígenos CD4/análisis , Antígenos CD4/genética , Antígenos CD4/metabolismo , Línea Celular , Femenino , Proteínas Fluorescentes Verdes , Humanos
Assay Drug Dev Technol ; 2(1): 63-9, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15090211


The modulation of fatty acid metabolism and especially the stimulation of fatty acid oxidation in liver or skeletal muscle are attractive therapeutic approaches for the treatment of obesity and the associated insulin resistance. However, current beta-oxidation assays are run in very low throughput, which represents an obstacle for drug discovery in this area. Here we describe results for a 48-well beta-oxidation assay using a new instrument design. A connecting chamber links two adjacent wells to form an experimental unit, in which one well contains the beta-oxidation reaction and the other captures CO(2). The experimental units are sealed from each other and from the outside to prevent release of radioactivity from the labeled substrate. CO(2) capture in this instrument is linear with time and over the relevant experimental range of substrate concentration. Cellular viability is maintained in the sealed environment, and cells show the expected responses to modulators of beta-oxidation, such as the AMP kinase activator 5-aminoimidazole carboxamide riboside. Data are presented for different lipid substrates and cell lines. The increased throughput of this procedure compared with previously described methods should facilitate the evaluation of compounds that modulate fatty acid metabolism.

Bioensayo/instrumentación , Ácidos Grasos/metabolismo , Animales , Caprilatos/metabolismo , Dióxido de Carbono/metabolismo , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Separación Celular , Supervivencia Celular/efectos de los fármacos , Glucosa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Técnicas In Vitro , Neoplasias Hepáticas/metabolismo , Oxidación-Reducción , Palmitatos/metabolismo , Ratas , Ratas Sprague-Dawley
Exp Gerontol ; 37(8-9): 1089-95, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12213559


The elderly constitute the most rapidly growing subpopulation in the United States. This age group represents a significant burden on the healthcare system due, in part, to increases in morbidity and mortality associated with an increase in the incidence of intestinal infectious diseases. Our previous studies suggest that impaired homing of IgA immunoblasts from the Peyer's patches to the intestinal lamina propria contributes to the diminished intestinal immune response in the elderly. The present study employs flow cytometry and quantitative immunohistochemistry to assess age-related changes in the numbers of peripheral blood mononuclear cells expressing the homing integrin alpha4beta7 and vascular endothelial cells in the intestine expressing its specific receptor, the address in MAdCAM-1, in inbred Fischer 344 rats. The proportion of alpha4beta7-positive mononuclear cells in young rats is significantly greater than that measured in the blood of senescent animals. Although the density of intestinal lamina propria blood vessels with MAdCAM-1-positive endothelium was greater in young adult rats in comparison to old animals, this difference achieved only borderline statistical significance. This is the first study to examine the expression of these two critical lymphocyte homing molecules as a function of age.

Envejecimiento/inmunología , Inmunoglobulinas/análisis , Integrinas/análisis , Mucoproteínas/análisis , Animales , Movimiento Celular , Citometría de Flujo , Inmunoglobulina A/análisis , Inmunohistoquímica , Leucocitos Mononucleares/química , Leucocitos Mononucleares/fisiología , Masculino , Ratas , Ratas Endogámicas F344