P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients

International Nuclear Information System (INIS)

Tang, Ruoping; Legrand, Ollivier; Marie, Jean-Pierre; Cohen, Simy; Perrot, Jean-Yves; Faussat, Anne-Marie; Zuany-Amorim, Claudia; Marjanovic, Zora; Morjani, Hamid; Fava, Fanny; Corre, Elise

2009-01-01

AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML). This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays. P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC 50 > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells. P-gp activity is not a crucial mechanism of chemoresistance to AVE9633. For patients whose resistance to conventional anthracycline AML regimens is related to ABC protein expression, a combination with AVE9633 could be beneficial. Other mechanisms such as microtubule alteration could play an important role in chemoresistance to AVE9633

Algunas de las aves emblemáticas del Eje Cafetero

Directory of Open Access Journals (Sweden)

Daniel Uribe Restrepo

2016-12-01

La región del Eje Cafetero no es una excepción, por el contrario, su variedad de climas, paisajes y ecosistemas albergan un gran número de especies de aves. Es difícil estimar la cantidad exacta de especies de aves en esta región, pero dicho número con seguridad supera las seiscientas cincuenta especies. Las aves conquistaron con éxito la geografía montañosa de las cordilleras Central y Occidental, y los humedales del valle interandino del río Cauca, irradiando sus múltiples formas, tamaños, colores, cantos y adaptaciones hasta conformar un caleidoscopio de indescriptible belleza.

Trial Watch: Toll-like receptor agonists for cancer therapy.

Science.gov (United States)

Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-08-01

Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.

Plantas usadas por aves en paisajes cafeteros de Nariño, Colombia

OpenAIRE

Yulieth Viviana Castillo R.; Jhon Jairo Calderón L.

2017-01-01

Las plantas son un importante recurso alimenticio para las aves presentes en los paisajes cafeteros, por lo que la heterogeneidad en las diferentes unidades de estos paisajes, garantizan la disponibilidad de alimento. Conocer este tipo de interacciones entre plantas y aves es importante para la conservación de la biodiversidad en paisajes cafeteros. En esta investigación, se presenta la lista inicial de especies de plantas usadas por las aves de paisajes cafeteros en zonas rurales de los muni...

Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

Science.gov (United States)

Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao

2017-09-15

Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC 50 ) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a. Copyright © 2017 Elsevier B.V. All rights reserved.

PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

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Neerupma Silswal

2012-01-01

Full Text Available We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα agonists using isolated mouse aortas and middle cerebral arteries (MCAs. The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC, and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response.

Impactos del AVE en el turismo de Bocairent

OpenAIRE

Francés Gimeno, Andreu

2016-01-01

En el presente trabajo se va a realizar un análisis de los impactos que ha generado la llegada del AVE en la localidad de Bocairent. Población sin estación pero que supuestamente se encuentra dentro del área de influencia y forma parte de una asociación con fines turísticos que se llama AVE Villena y Levante Interior. Para ello se han analizado tanto las condiciones de la localidad, como la de la estación receptiva de turistas, además, de las organizaciones encargadas para atraer a este tipo ...

Piojos (Phthiraptera: Insecta) de aves de la familia Laridae (Aves: Charadriiformes) en Chile

OpenAIRE

GONZÁLEZ-ACUÑA, DANIEL; FISCHER, CHRISTOF; PALMA, RICARDO; MORENO, LUCILA; BARRIENTOS, CARLOS; MUÑOZ, LISANDRO; ARDILES, KAREN; CICCHINO, ARMANDO

2006-01-01

Seis especies de piojos (Phthiraptera: Philopteridae, Menoponidae) fueron colectadas sobre cuatro especies de aves marinas de la familia Laridae en la costa de Chile. Se registran: Saemundssonia sternae (Linnaeus, 1758) y Quadraceps sellatus (Burmeister, 1838) sobre el gaviotín boreal (Sterna hirundo, Linnaeus, 1758); Saemundssonia lari (O. Fabricius, 1780), Quadraceps punctatus (Burmeister, 1838) y Quadraceps ornatus (Grube, 1851) parasitando a la gaviota dominicana (Larus dominicanus Lichte...

ENFERMEDAD DE NEWCASTLE EN AVES DE TRASPATIO DEL EJE CAFETERO COLOMBIANO

Directory of Open Access Journals (Sweden)

Marlyn Romero P

2009-08-01

Full Text Available Objetivo. Evaluar la circulación del virus de la enfermedad de Newcastle (ENC en aves de traspatio de siete municipios del eje cafetero por medio de la técnica ELISA. Materiales y métodos. Fueron encuestados 465 predios para evaluar las normas de bioseguridad de las aves de traspatio de los municipios de Armenia, Circasia, Quimbaya, Montenegro, Filandia, Calarcá y La Tebaida del Departamento del Quindío. Se analizaron 662 muestras de suero para detectar anticuerpos IgG contra el virus de la ENC por ELISA. Resultados. La seroprevalencia de la ENC en la población de aves evaluada fue del 30.7%.(203/662, que corresponde al 38.5% de los predios encuestados. No se encontró asociación entre la especie y la seroreactividad (p=0.21, ni entre la distribución de los anticuerpos por grupos productivos y la edad (p>0.05. Los predios de traspatio son manejados de forma extensiva, albergan en las mismas instalaciones aves de diferentes especies y edades en el 64.3% (299/465, con edades en intervalos entre tres meses y cinco años. Fueron detectadas malas prácticas de manejo de la gallinaza y la mortalidad, sin encontrar asociación estadísticamente significativa entre las variables evaluadas y la presencia de anticuerpos anti-virus de ENC (p>0.05. Conclusiones. Es necesario el establecimiento de planes adecuados de vacunación de las aves de traspatio, la vigilancia epidemiológica activa, la observación de los casos sospechosos, sin dejar de lado la educación y capacitación, sobre el adecuado manejo de los animales, dirigida a los propietarios de las aves como medidas de control de la enfermedad.

ASOCIACIONES ENTRE AVES MARINAS Y SOTALIA GUIANENSIS EN EL SUR DEL GOLFO DE VENEZUELA

Directory of Open Access Journals (Sweden)

NÍNIVE ESPINOZA-RODRÍGUEZ

2015-01-01

Full Text Available Las asociaciones entre aves marinas y mamíferos marinos es un evento común en todos los mares y océanos del mundo. Muchos autores han denominado estas asociaciones como relaciones comensalistas, oportunistas o parasitarias, según el efecto que dicha interacción resulte sobre una o ambas especies relacionadas. Con la finalidad de describir la existencia de agrupaciones entre Sotalia guianensis y aves marinas en la porción sur del Golfo de Venezuela, desde junio 2011 a junio 2012 se realizaron observaciones en plataformas móviles de grupos de este cetáceo y aves marinas, utilizando el protocolo "group-follow" bajo la metodología de "Ad libitum sampling". Todos los avistamientos fueron georreferenciados, realizándose anotaciones de la ocurrencia o no-asociación con aves marinas, de igual forma, se registró la especie y el número de aves presentes al momento de la interacción. Se realizaron 721 avistamientos, de los cuales en 197 eventos se registró asociación entre aves marinas y Sotalia guianensis. Las especies de aves marinas residentes que presentaron mayor frecuencia en eventos de asociación con S. guianensis fueron: Fregata magnificens (49%; n=98, Phalacrocorax brasilianus (29,5%; n=59 y Pelecanus occidentalis (22,5%; n=45; siendo Thalasseus maxima (71%; n=142 la única especie migratoria. Durante las observaciones realizadas en el período de muestreo se notó la presencia de una especie de golondrina (Riparia riparia en un solo evento de agrupación con Sotalia guianensis. Dichas asociaciones aves-delfines, sólo fueron observadas cuando notables congregaciones de peces fueron registrados, donde el o los grupos de delfines realizaban alguna actividad con grandes movimientos de agua, lo que pudiese permitir a las aves realizar un menor gasto energético en la ubicación y la captura de la presa.

Aves acuáticas de la laguna de Acuitlapilco, Tlaxcala, México

Directory of Open Access Journals (Sweden)

Juanita Fonseca

2012-07-01

Full Text Available Estudiamos la abundancia y distribución estacional de las aves acuáticas en la laguna de Acuitlapilco, Tlaxcala, México. De febrero de 2011 a enero de 2012, realizamos censos en puntos de conteo para el registro de las especies. Registramos un total de 36 especies de aves acuáticas con una abundancia total acumulada de 48,794 individuos. Doce de las especies registradas fueron residentes, 10 migratorias y 14 fueron especies transitorias o de registro accidental. Observamos que la mayor riqueza de especies y abundancia de aves fueron en invierno, cuando la mayoría de las especies migratorias llegaron a la laguna. Nuestros resultados muestran que esta área es importante para especies de aves acuáticas tanto residentes como migratorias, y refleja la necesidad de un mayor número de estudios sobre el papel de las lagunas continentales como reservorios de biodiversidad.

The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

DEFF Research Database (Denmark)

Munro, G; Hansen, Rikke Rie; Erichsen, Hk

2012-01-01

BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasin......BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators...

Building a SuAVE browse interface to R2R's Linked Data

Science.gov (United States)

Clark, D.; Stocks, K. I.; Arko, R. A.; Zaslavsky, I.; Whitenack, T.

2017-12-01

The Rolling Deck to Repository program (R2R) is creating and evaluating a new browse portal based on the SuAVE platform and the R2R linked data graph. R2R manages the underway sensor data collected by the fleet of US academic research vessels, and provides a discovery and access point to those data at its website, www.rvdata.us. R2R has a database-driven search interface, but seeks a more capable and extensible browse interface that could be built off of the substantial R2R linked data resources. R2R's Linked Data graph organizes its data holdings around key concepts (e.g. cruise, vessel, device type, operator, award, organization, publication), anchored by persistent identifiers where feasible. The "Survey Analysis via Visual Exploration" or SuAVE platform (suave.sdsc.edu) is a system for online publication, sharing, and analysis of images and metadata. It has been implemented as an interface to diverse data collections, but has not been driven off of linked data in the past. SuAVE supports several features of interest to R2R, including faceted searching, collaborative annotations, efficient subsetting, Google maps-like navigation over an image gallery, and several types of data analysis. Our initial SuAVE-based implementation was through a CSV export from the R2R PostGIS-enabled PostgreSQL database. This served to demonstrate the utility of SuAVE but was static and required reloading as R2R data holdings grew. We are now working to implement a SPARQL-based ("RDF Query Language") service that directly leverages the R2R Linked Data graph and offers the ability to subset and/or customize output.We will show examples of SuAVE faceted searches on R2R linked data concepts, and discuss our experience to date with this work in progress.

Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase

International Nuclear Information System (INIS)

Mattila, Elina; Marttila, Heidi; Sahlberg, Niko; Kohonen, Pekka; Tähtinen, Siri; Halonen, Pasi; Perälä, Merja; Ivaska, Johanna

2010-01-01

T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously expressed intra-cellular non-receptor protein tyrosine phosphatase involved in the negative regulation of several cancer relevant cellular signalling pathways. We have previously shown that interaction between the α-cytoplasmic tail of α1β1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intra-molecular bond in TCPTP. Thus, inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic RTK signalling. However, this is challenging with low molecular weight compounds. We developed a high-throughput compatible assay to analyse activity of recombinant TCPTP in vitro. Using this assay we have screened 64280 small molecules to identify novel agonists for TCPTP. Dose-dependent response to TCPTP agonist was performed using the in vitro assay. Inhibition effects and specificity of TCPTP agonists were evaluated using TCPTP expressing and null mouse embryonic fibroblasts. Western blot analysis was used to evaluate attenuation of PDGFRβ and EGFR phosphorylation. Inhibition of VEGF signalling was analysed with VEGF-induced endothelial cell sprouting assays. From the screen we identified six TCPTP agonists. Two compounds competed with α1-cytoplasmic domain for binding to TCPTP, suggesting that they activate TCPTP similar to α1-cyt by disrupting the intra-molecular bond in TCPTP. Importantly, one of the compounds (spermidine) displayed specificity towards TCPTP in cells, since TCPTP -/- cells were 43-fold more resistant to the compound than TCPTP expressing cells. This compound attenuates PDGFRβ and VEGFR2 signalling in cells in a TCPTP-dependent manner and functions as a negative regulator of EGFR phosphorylation in cancer cells. In this study we showed that small molecules mimicking TCPTP-α1 interaction can be used as TCPTP agonists. These data provide the first proof-of-concept description of the use of high-throughput screening

Presencia y abundancia de aves de la Isla Farallón de San Ignacio, Sinaloa

Directory of Open Access Journals (Sweden)

Miguel Angel Guevara Medina

2015-06-01

Full Text Available Para determinar la presencia y abundancia de aves que utilizan la isla Farallón de San Ignacio, Sinaloa, documentamos las aves observadas durante 46 visitas de cinco días a la isla entre 2003 y 2008. Registramos 57 especies de aves. En la isla anidaron regularmente cinco especies de aves marinas:Sula nebouxii, S. leucogaster, Phaethon aethereus, Phalacrocorax auritus y Larus heermanni. En 2008 anidó una rapaz, Falco peregrinus. Además, observamos 24 especies de aves acuáticas no reproductoras y 27 especies de aves terrestres. La temporada reproductiva de las especies anidantes coincide con la época de alta productividad primaria en el sur del Golfo de California. La isla es importante como sitio de anidación para P. aethereus y es una de las dos colonias más importantes en el Golfo de California. Para el resto de las especies anidantes, la isla tiene una importancia marginal, pues otras islas albergan colonias mayores. Debido a la ausencia de vegetación, las aves terrestres usan la isla sólo de manera ocasional y por breves periodos, especialmente los migrantes neotropicales durante la migración. Al comparar con otras islas de la parte sur del Golfo de California, Farallón de San Ignacio exhibió una riqueza de especies mayor a lo esperado de acuerdo con su tamaño. Esta discordancia se podría explicar por un esfuerzo mayor en el muestreo y posiblemente por la existencia de una mayor cantidad de especies de aves terrestres usando los hábitats costeros de Sinaloa y dispersándose ocasionalmente a islas cercanas.

Sexual dimorphism in Ramphastos toco and Ramphastos dicolorus (Piciformes, Aves

Directory of Open Access Journals (Sweden)

Márcio S. Castro

2003-03-01

Full Text Available Con frecuencia, en la familia Ramphastidae no hay un dimorfismo sexual aparente, excepto en Pteroglossus viridis y en el género Selenidera. Muchos criadores de aves silvestres creen que los especímenes de Ramphastos toco pueden ser sexados usando las caracteríticas del pico. En este estudio, fueron analizadas algunas variables feno-típicas discriminantes en aves cuyo sexo fue previamente determinado con metodos citogenéticos. Un total de 51 especimenes de R. toco y 20 de R. dicolorus fueron estudiados. Los parámetros estadísticos significativos que son útiles para distinguir el sexo en estas especies son la longitud del culmen y del tomium, la longitud del pico corneo inferior y de la cloaca. Usando estos parámetros, los criadores de aves cautivas pueden sexar los especimenes de Ramphastos toco mediante análisis fenotípico y formar parejas reproductoras más rapidamente.

O Comportamento das Aves Poultry Behavior

Directory of Open Access Journals (Sweden)

EJ Campos

2000-08-01

Full Text Available Os estudos sobre o comportamento das aves, principalmente as galinhas, datam de 1912, quando o gênero Gallus passou a ser estudado com mais intensidade na área da Genética. Tais estudos eram simplesmente filosóficos até o início da década de 80, quando uma nova era da produção industrial avícola surgiu, objetivando um maior volume de produção econômica em todas as áreas de exploração. Esse objetivo reativou de maneira científica os estudos de comportamento das aves face à tecnologia de produção empregada nos sistemas de exploração, tornando-os mais acentuados já na década de 90, culminando com um simpósio internacional realizado nos Estados Unidos onde foram traçados os objetivos ou linhas de pesquisas na exploração avícola. O intuito era evitar problemas com os movimentos ambientalistas, traçando novos rumos para uma produção eficiente sem interferir no comportamento das aves já no início do novo milênio. Esta revisão, tem como objetivo principal uma análise científica e filosófica sobre o comportamento das aves em diversos métodos de exploração.Studies on poultry behavior initiated in 1972, at that time, fowls from Gallus domesticus species were the most important animal for the initial studies of Genetic. Since then, just the philosophical concepts where involved in those studies. However, at the beginning of 80 decade, these studies were intensified taking into account technological approaches for an economical industrial poultry production. Meanwhile, the reactions from activists involved in the behavior of the animal subjected to production became more strong at the beginning of 90's as well as those studies on chicken behavior. Finally, in 1998, an international symposium, promoted by chicken behavior scientists were held in the United States, in order to establish new methods of exploitation of poultry without interfering in its normal behavior, at the beginning of new millenium. The main

Atlas de aves: Un metodo para documentar distribucion y seguir poblaciones

Science.gov (United States)

Robbins, C.S.; Dowell, B.A.; Dawson, D.K.; Alvarez-Lopez, Humberto; Kattan, Gustavo; Murcia, Carolina

1988-01-01

Los Atlas de Aves son proyectos nacionales o regionalies para trazar en mapas la distribucion en reproduccion de cada especie de ave. Ese procedimiento se esta usando en Europa, Australia, Nueva Zelanda, Norteamerica, y partes de Africa. El tama?o de los cuadrados varia de medio grado de latitud y Iongitud hasta 5 x 5 km. El trabajo de campo de cada proyecto exige aproxlmadamente cinco a?os, pero los aficionados pueden llevar a cabo la mayor parte del trabajo. Es posible almacenar los resultados en un computador personal. Hay muchos beneficios: (I) se presenta la distribucion corriente de las aves de la nacion, del estado, o de la Iocalidad; (2) se desarrolla nueva informacion especialmente sobre especies raras o en peligro; (3) se descubren areas que tienen una avlfauna sobresaliente o habitats raros y ayuda a su proteccion, (4) se documentan cambios de dlstribucion; (5) se pueden usar para documentar cambios de poblacion, especialmente en los tropicos donde otros metodos son mas dificiles de usar porque hay muchas especies y no hay muchos observadores calificados en la identificacion de sonidos de las aves; (6) son proyectos buenos de investigacion para estudiantes graduados; (7) los turistas y los jefes de excursiones de historia natural pueden contribuir con muchas informaciones

PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

NARCIS (Netherlands)

HOYER, D; BODDEKE, HWGM

The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or

Ritmos circadianos en el metabolismo del calcio en aves de postura.

OpenAIRE

Correa Cardona Héctor Jairo

1999-01-01

Se revisó literatura relacionada con las variaciones circadianas en el metabolismo del calcio en aves de postura y se concluye que la información analizada y discutida suministra evidencia suficiente que demuestra la existencia de ritmos circadianos en diferentes procesos relacionados con el metabolismo y la alimentación del calcio en las aves de postura. Esto demuestra la necesidad de ajustar el momento y la cantidad de calcio a suministrar...

Chronic β2 -adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men.

Science.gov (United States)

Hostrup, Morten; Onslev, Johan; Jacobson, Glenn A; Wilson, Richard; Bangsbo, Jens

2018-01-15

While several studies have investigated the effects of exercise training in human skeletal muscle and the chronic effect of β 2 -agonist treatment in rodent muscle, their effects on muscle proteome signature with related functional measures in humans are still incompletely understood. Herein we show that daily β 2 -agonist treatment attenuates training-induced enhancements in exercise performance and maximal oxygen consumption, and alters muscle proteome signature and phenotype in trained young men. Daily β 2 -agonist treatment abolished several of the training-induced enhancements in muscle oxidative capacity and caused a repression of muscle metabolic pathways; furthermore, β 2 -agonist treatment induced a slow-to-fast twitch muscle phenotype transition. The present study indicates that chronic β 2 -agonist treatment confounds the positive effect of high intensity training on exercise performance and oxidative capacity, which is of interest for the large proportion of persons using inhaled β 2 -agonists on a daily basis, including athletes. Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, β 2 -agonists are frequently used to counteract exercise-induced bronchoconstriction, but the effects β 2 -agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomly assigned 21 trained men to 4 weeks of high intensity training with (HIT+β 2 A) or without (HIT) daily inhalation of β 2 -agonist (terbutaline, 4 mg dose -1 ). Of 486 proteins identified by mass-spectrometry proteomics of muscle biopsies sampled before and after the intervention, 32 and 85 were changing (false discovery rate (FDR) ≤5%) with the intervention in HIT and HIT+β 2 A, respectively. Proteome signature changes were different in HIT and HIT+β 2 A (P�

Differential Kolaviron Attenuated Contractile Responses to Agonists on Isolated Rabbit Aorta in Na+-K+ Pump Blockade.

Science.gov (United States)

Uche, O K; Ofeimun, J O

2017-12-30

The mechanism of kolaviron-induced vascular smooth muscles (VSMs) responses has not been fullycharacterised. The present study investigated the effect and mode of action of kolaviron a biflavanoid-complex and majorcomponent of Garcinia Kola-fraction on differential contractile responses to agonists-[phenylephrine (PHE) and histamine(HIST)] on VSMs of rabbit isolated aortic rings in K+-free physiological salt solution (KFPSS). Cumulative concentrationresponses to PHE and HIST were examined on 2 mm ring segments of the thoracic aortae which were suspended in 20 mlorgan baths containing physiological salt solution (PSS) for measurement of isometric contractions, at 370C and pH 7.4. Themedium was bubbled with 95% O2, 5% CO2, and rings were given an initial load of 1g. Cumulative contractile responses tothe agonists were studied in normal PSS (control) and following 30 minutes exposure to K+-free PSS and/or 800µg/mLkolaviron. Contractile responses were expressed as percentage of 80 mM K+ contractions in normal PSS. Maximalcontractions (Emax) induced by PHE and HIST compared with high K+ contraction in the various preparations weredifferentially altered following exposure to K+-free or 800µg/mL kolaviron in both intact (+E) and endotheliumdenuded (-E) rings. Based on the efficacy (Emax) and potency (EC50) values for the dose-response curves of the agonists, it isconcluded that enhanced differential contractile responses elicited by agonists in K+-free PSS were significantly attenuatedby kolaviron concentration-dependently. This observation probably suggests the existence of another pathway of kolavironmode of action in vascular smooth muscle reactivity.

DETERMINACIÓN DE SEXO EN AVES MEDIANTE HERRAMIENTAS MOLECULARES

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NUBIA E. MATTA CAMACHO

2009-01-01

Full Text Available RESUMEN La ausencia de dimorfismo sexual en los estadios juveniles y durante la edad adulta de gran cantidad de especies de aves, dificulta o imposibilita la determinación del sexo basados en el fenotipo. El empleo de marcadores moleculares para determinar el sexo de las aves es una herramienta útil debido a la exactitud y rapidez de los resultados y a su vez se constituye en un método que minimiza el estrés durante la toma de muestra, comparado con otras técnicas invasivas que pudieran afectar la salud o estabilidad biológica del animal. La determinación temprana del sexo en aves resulta de especial relevancia cuando se consideran programas de conservación ex situ, producción, explotación y estudios de ecología de poblaciones. Esta revisión presenta las metodologías usadas para determinar el sexo, haciendo especial énfasis en herramientas moleculares, presentando sus ventajas y limitaciones. Palabras clave: dimorfismo sexual, aves, CHD, tipificación molecular cromosoma W, cromosoma Z. ABSTRACT The lack of sexual dimorphism in nestling, juvenile or adult birds of large number of avian species, makes it difficult or impossible sex determination based on phenotipic characteristics. To use molecular markers for bird sex determination is a rapid and safe procedure; moreover this methodology minimizes the stress during sampling, compared to other invasive techniques that could affect the health or biological stability of the animal. The early sex determination in birds is of particular importance when considering ex situ conservation programs, production, exploitation or population ecology studies. This review presents the methodologies used to sex determination, making emphasize on molecular tools, showing its advantages and limitations. Keywords: sexual dimorphism, birds, CHD, molecular typing, W chromosome, Z chromosome

Ácaros plumícolas (Acari: Astigmata) em aves do Cerrado do Distrito Federal, Brasil

OpenAIRE

Kanegae,Mieko Ferreira; Valim,Michel; Fonseca,Marcelo Andrade da; Marini,Miguel Ângelo; Freire,Nicolau Maués Serra

2008-01-01

O objetivo do estudo foi identificar os ácaros plumícolas em aves do cerrado. O mesmo foi realizado na Fazenda Água Limpa (FAL), Distrito Federal, Brasil, entre janeiro e agosto de 2002. As aves foram capturadas com rede de neblina e anilhadas. Foram amostradas 696 aves pertencentes a 83 espécies e 25 famílias de Passeriformes e não-Passeriformes. Foram encontrados ácaros plumícolas pertencentes a cinco famílias: Analgidae, Trouessartiidae, Proctophyllodidae, Avenzoariidae e Psoroptoididae. O...

Rahvusvahelise kogemusega personalijuht Ave Kareda: Personalijuhi koostöö juhiga peaks rajanema aususel ja usaldusel / Ave Kareda ; interv. Tiina Saar

Index Scriptorium Estoniae

Kareda, Ave

2009-01-01

Logistikaettevõtte DHL Baltikumi personalijuht Ave Kareda vastab küsimustele, mis puudutavad ettevõtete personalipoliitikat, personalijuhi rolli, personaliosakonna võimalusi juhi ja inimeste vahel, rahvusvahelisuse osatähtsust personalitöös, mentorlust ning juhi ebaeetilisi otsuseid raskes olukorras

PPAR-alpha agonist treatment increases trefoil factor family-3 expression and attenuates apoptosis in the liver tissue of bile duct-ligated rats.

Science.gov (United States)

Karakan, Tarkan; Kerem, Mustafa; Cindoruk, Mehmet; Engin, Doruk; Alper, Murat; Akın, Okan

2013-01-01

Peroxisome proliferators-activated receptor alpha activation modulates cholesterol metabolism and suppresses bile acid synthesis. The trefoil factor family comprises mucin-associated proteins that increase the viscosity of mucins and help protect epithelial linings from insults. We evaluated the effect of short-term administration of fenofibrate, a peroxisome proliferators activated receptor alpha agonist, on trefoil factor family-3 expression, degree of apoptosis, generation of free radicals, and levels of proinflammatory cytokines in the liver tissue of bile duct-ligated rats. Forty male Wistar rats were randomly divided into four groups: 1 = sham operated, 2 = bile duct ligation, 3 = bile duct-ligated + vehicle (gum Arabic), and 4 = bile duct-ligated + fenofibrate (100 mg/kg/day). All rats were sacrificed on the 7 th day after obtaining blood samples and liver tissue. Liver function tests, tumor necrosis factor-alpha and interleukin 1 beta in serum, and trefoil factor family-3 mRNA expression, degree of apoptosis (TUNEL) and tissue malondialdehyde (malondialdehyde, end-product of lipid peroxidation by reactive oxygen species) in liver tissue were evaluated. Fenofibrate administration significantly reduced serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and tumor necrosis factor-alpha and interleukin-1β levels. Apoptosis and malondialdehyde were significantly reduced in the fenofibrate group. Trefoil factor family-3 expression increased with fenofibrate treatment in bile duct-ligated rats. The peroxisome proliferators-activated receptor alpha agonist fenofibrate significantly increased trefoil factor family-3 expression and decreased apoptosis and lipid peroxidation in the liver and attenuated serum levels of proinflammatory cytokines in bile duct-ligated rats. Further studies are needed to determine the protective role of fenofibrate in human cholestatic disorders.

Dopamine D1 receptor agonist treatment attenuates extinction of morphine conditioned place preference while increasing dendritic complexity in the nucleus accumbens core.

Science.gov (United States)

Kobrin, Kendra L; Arena, Danielle T; Heinrichs, Stephen C; Nguyen, Olivia H; Kaplan, Gary B

2017-03-30

The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions. Mice subsequently underwent six days of extinction training designed to diminish the previously learned association. Mice were treated with either 0.5mg/kg SKF81297, 0.8mg/kg SKF81297, or saline immediately after each extinction session. There was a dose-dependent effect, with the highest dose of SKF81297 attenuating extinction, as mice treated with this dose had significantly higher CPP scores than controls. Analysis of medium spiny neuron morphology revealed that in the NAc core, but not in the shell, dendritic arbors were significantly more complex in the morphine conditioned, SKF81297-treated mice compared to controls. In separate experiments using mice conditioned with only saline, SKF81297 administration after extinction sessions had no effect on CPP and produced differing effects on dendritic morphology. At the doses used in our experiments, SKF81297 appears to maintain previously learned opioid conditioned behavior, even in the face of new information. The D1R agonist's differential, rather than unidirectional, effects on dendritic morphology in the NAc core suggests that it may be involved in encoding reward information depending on previously learned behavior. Published by Elsevier B.V.

Identificación de parásitos gastrointestinales en aves silvestres en cautiverio

OpenAIRE

García Corredor, Diego José; Sánchez Parada, Oscar Javier; Pulido Medellín, Martin Orlando; Andrade Becerra, Roy José

2013-01-01

Este trabajo identifica los parásitos gastrointestinales que presentaron las aves silvestres en cautiverio, en el municipio de Tibasosa (Boyacá, Colombia). Se tomaron 100 muestras de materia fecal de aves silvestres correspondientes a 11 familias (Psittacidae, Ramphastidae, Ophistocomidae, Cracidae, Anatidae, Icteridae, Alaudidae, Burhinidae, Phoenicopteridae, Anhimidae y Rallidae) y 16 especies (Ara ararauna, Ara macao, Amazona spp, Amazona ochrocephala, Ramphastos toco,...

Aves ocasionales en la Sabana de Bogotá

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Borrero José Ignacio

1946-08-01

Full Text Available La altiplanicie andina conocida con el nombre de Sabana de Bogotá, situada en la llamada "tierra fría" de los Andes Orientales de Colombia, a 2600 metros sobre el nivel del mar y con temperatura media de 13o C., esta bordeada en todo su derredor por montañas cuya altura en ningún sitio se eleva a menos de 2700 metros y esto solamente en el lado occidental, hacia el valle del Magdalena. Sin embargo, es visitada con alguna frecuencia por aves propias de pisos climáticos más cálidos y aun del llamado "Tropical" o "tierra caliente". Por lo que se ha podido averiguar, las aves visitantes observadas hasta ahora proceden de las vertientes occidentales y del valle del Magdalena; ninguna, con la única posible excepción de Elanoides forticatus yetapa, viene de las faldas orientales que descienden hasta los llanos del Meta pues hacia este lado de la Sabana se hallan las montañas más altas, cuya mayor depresión -la de Chipaque- es de 3150 metros en el sitio por donde pasa la carretera de Bogotá a Villavicencio. Parece por lo tanto que este ramal de la cordillera constituye una barrera infranqueable para las aves que habitan en el oriente de Cundinamarca, mientras que el ramal occidental, de menor altura, no lo es para las que habitan en las vertientes que conducen al Magdalena.

Anticuerpos séricos contra la enfermedad de Newcastle e Influenza Aviar en aves rapaces de Chile.

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Daniel González-Acuña

2012-12-01

Full Text Available Objetivo. Detectar la presencia de anticuerpos séricos sanguíneos contra los virus de la Enfermedad de Newcastle (ENC e Influenza aviar (IA, para comprender la contribución de las aves silvestres en la transmisión de estos virus en Chile. Materiales y métodos. Se analizaron 63 aves pertenecientes a los órdenes Falconiformes y Strigiformes desde centros de rehabilitación de aves de las zonas central y sur de Chile. Se realizaron las pruebas de inhibición de la hemoaglutinación (IHA para detectar anticuerpos contra el virus ENC e inmunodifusión en gel agar (IDGA y ELISA para IA. Resultados. Se detectaron 14 aves positivas (22.2% para anticuerpos séricos contra el virus de la ENC. En cambio, no se registraron anticuerpos séricos sanguíneos para el virus de la IA. Conclusiones. La presencia de aves rapaces positivas en los centros de rescate a los anticuerpos séricos contra el virus de la ENC puede ser explicada por el consumo de carne de pollos que han sido vacunados contra ENC o consumo de aves que han adquirido directamente el virus vacunal a través de los distintos procedimientos de administración (aerosoles, bebederos de la vacuna o por el ingreso a los centros de rescate de aves rapaces migratorias, las que podrían facilitar la diseminación de la infección desde los países de origen, hecho que debe ser investigado.

Interacciones entre el estornino pinto (Sturnus vulgaris) y aves nativas de Argentina por el uso de cavidades

OpenAIRE

Ibañez, Lucía M.; Girini, Juan M.; Palacio, Facundo X.; Fiorini, Vanina D.; Montalti, Diego

2017-01-01

Resumen: El estornino pinto, Sturnus vulgaris, es un ave introducida en Argentina que nidifica en cavidades y puede desplazar a otras aves de sus nidos. Durante las temporadas reproductivas 2010 y 2011 observamos en el parque Pereyra Iraola 3 intentos de usurpación de nidos de aves nativas, hornero (Furnarius rufus), carpintero real (Colaptes melanochloros) y carpintero campestre (C. campestris). Además, en 2 ocasiones se observaron estorninos nidificando en cavidades que estaban construyendo...

Glutamate receptor agonists

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

2011-01-01

The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

Cholesterol regulates contractility and inotropic response to β2-adrenoceptor agonist in the mouse atria: Involvement of Gi-protein-Akt-NO-pathway.

Science.gov (United States)

Odnoshivkina, Yulia G; Sytchev, Vaycheslav I; Petrov, Alexey M

2017-06-01

Majority of cardiac β2-adrenoceptors is located in cholesterol-rich microdomains. Here, we have investigated the underlying mechanisms by which a slight to moderate cholesterol depletion with methyl-β-cyclodextrin (MβCD, 1 and 5mM) interferes with contractility and inotropic effect of β2-adrenergic agonist (fenoterol, 50μM) in the mouse atria. Treatment with MβCD itself increased amplitude of Ca 2+ transient but did not change the contraction amplitude due to a clamping action of elevated NO. Cholesterol depletion significantly attenuated the positive inotropic response to fenoterol which is accompanied by increase in NO generation and decrease in Ca 2+ transient. Influence of 1mM MβCD on the fenoterol-driven changes in both contractility and NO level was strongly attenuated by inhibition of G i -protein (pertussis toxin), Akt (Akt 1/2 kinase inhibitor) or NO-synthase (L-NAME). After exposure to 5mM MβCD, pertussis toxin or Akt inhibitor could recover the β2-agonist effects on contractility, NO production and Ca 2+ transient, while L-NAME only reduced NO level. An adenylyl cyclase activator (forskolin, 50nM) had no influence on the MβCD-induced changes in the β2-agonist effects. Obtained results suggest that slight cholesterol depletion upregulates G i -protein/Akt/NO-synthase signaling that attenuates the positive inotropic response to β2-adrenergic stimulation without altering the Ca 2+ transient. Whilst moderate cholesterol depletion additionally could suppress the enhancement of the Ca 2+ transient amplitude caused by the β2-adrenergic agonist administration in G i -protein/Akt-dependent but NO-independent manner. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arginase attenuates inhibitory nonadrenergic noncholinergic nerve-induced nitric oxide generation and airway smooth muscle relaxation

NARCIS (Netherlands)

Maarsingh, H; Tio, MA; Zaagsma, J; Meurs, H

2005-01-01

Background: Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO) production, presumably by competition with epithelial constitutive NO synthase for the common substrate, L-arginine. Using

La pájara vida: breve historia de la observación de aves en Colombia

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Luis Germán Naranjo

2016-12-01

Colombia tiene una larga tradición ornitológica, pero a pesar de ello la observación de aves como pasatiempo solo en años recientes se hizo popular, lo cual no deja de ser curioso en un país que se enorgullece de tener la máxima riqueza de especies de aves silvestres en su territorio. Si bien la gran mayoría de los estudiosos de las aves son verdaderos apasionados por su oficio, la línea divisoria entre sus afanes y los de quienes se consideran primariamente pajareros apenas se empieza a trazar ya bien entrado el siglo XXI.

Potencial de árvores frutíferas para a atração de aves

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Leonardo Ribeiro Góes-Silva

2012-04-01

Full Text Available O objetivo deste trabalho é avaliar o potencial atrativo de aves presente em oito espécies de árvores frutíferas: Callicarpa reevesii Wall.ex Walp., Ficus microcarpa L.f., Ficus tomentella Miq., Michelia champaca L., Morus nigra L., Nectandra nitidula Nees, Schinus terebinthifolius Raddi e Syagrus romanzoffiana Cham. A interação de aves-plantas foi observada no município de Ouro Fino (MG, nos domínios da Serra da Mantiqueira. As referentes árvores foram observadas durante 24 horas nos períodos em que estavam frutificando, entre julho de 2007 a abril de 2008. Com o uso de ferramentas de análise de diversidade biológica, pode-se constatar que as espécies com maiores potenciais de atração de aves foram Ficus microcarpa, Ficus tomentella, Morus nigra, Nectandra nitidula e Schinus terebinthifolius e as espécies de aves que apresentaram alto índice de interação com as árvores foram Dacnis cayana, Elaenia flavogaster, Tangara cayana, Tersina viridis, Thraupis sayaca, Turdus amaurochalinus e Turdus rufiventris.

Grupos avicaptores del Tardiglaciar : las aves de Berroberria

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C. Diez Fernandez-Lomana

1995-01-01

Full Text Available En este artículo presentamos un estudio sobre marcas de cortes en aves de Berroberria. Los restos proceden de un nivel Magdaleniense superior final datable mediante C14 y con la ayuda de estudios palinológicos y arqueológicos. Los restos avianos pertenecen a la especie Lagopus mutus (perdiz nival y evidencian la caza de esta especie por grupos humanos. El estudio realizado plantea la existencia de poblaciones que recurrían a la caza de aves en épocas del año concretas, las cuales desarrollaron una estrategia de descuartizamiento primario en el lugar de caza y de descarnación en la cavidad. La ausencia de restos avianos quemados, y la minuciosidad en el desmembramiento y deshuesado, implican una búsqueda de carne aviar para un consumo no inmediato. Se postula un acopio de carne, con técnicas de secado y ahumado, para ulteriores necesidades alimenticias, ligadas al encarecimiento de los recursos durante el invierno. Las especies avianas presentes aportan algunas notas sobre las consiciones climáticas que imperaban en la zona.

Chronic β2 -adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men

DEFF Research Database (Denmark)

Hostrup, Morten; Onslev, Johan; Jacobson, Glenn

2018-01-01

Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, β2 -agonists are frequently used to counteract exercise......-induced bronchoconstriction, but the effects β2 -agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomized 21 trained men to four weeks of high intensity training with (HIT + β2 A) or without (HIT) daily inhalation of β2 -agonist (terbutaline, 4 mg...... (P ≤ 0.01) and exercise performance (11.6 vs. 6.1%, P ≤ 0.05) in HIT + β2 A compared to HIT. These findings indicate that daily β2 -agonist treatment attenuates the beneficial effects of high intensity training on exercise performance and oxidative capacity, and causes remodelling of muscle proteome...

Riqueza e densidade de aves que nidificam em cavidades em plantações abandonadas de eucalipto

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Hugo de Siqueira Pereira

2015-05-01

Full Text Available Monoculturas de árvores, como as de espécies de eucalipto, têm substituído florestas naturais, impactando a fauna pela perda de habitat e recursos. Diversas espécies de aves necessitam de ocos em árvores para nidificar. A falta de recursos como cavidades formadas pela degradação da árvore ou locais apropriados para serem criadas cavidades leva a diminuição na abundância das populações destas espécies. Este trabalho tem o objetivo de comparar a riqueza e a densidade de aves que nidificam em ocos em áreas de plantação de eucalipto abandonadas com áreas de vegetação nativa em duas unidades de conservação em Minas Gerais. Em cada tipo de vegetação de cada reserva foram estabelecidos 25 pontos, nas quais foi utilizado o método de contagem por remoção para o levantamento das espécies de aves. A riqueza de espécies de aves de cada área foi estimada por Jackniffe e a densidade foi estimada através do método de máxima verossimilhança; modelos candidatos que poderiam influenciar a abundância das aves foram avaliados utilizando-se o Critério de Informação Akaike (AIC. Os resultados mostraram que a riqueza de espécies foi maior nas áreas de florestas nativas e que a densidade foi significantemente mais alta nas áreas de florestas nativas, e que o tipo de vegetação e a hora do dia influenciam na abundância e detecção das aves. Esses resultados indicam que as plantações de eucaliptos influenciam negativamente a comunidade de aves que nidificam em ocos, provavelmente por causa da falta de cavidades ou de sub-bosque. Plantações de eucaliptos normalmente não substituem as florestas nativas e seu uso deve ser controlado em áreas de conservação.

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

International Nuclear Information System (INIS)

Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

2014-01-01

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

Energy Technology Data Exchange (ETDEWEB)

Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

2014-01-03

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10−/− mice by attenuating the activation of T cells and promoting their apoptosis

International Nuclear Information System (INIS)

Singh, Udai P.; Singh, Narendra P.; Singh, Balwan; Price, Robert L.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

2012-01-01

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10 −/− mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10 −/− mice. After JWH-133 treatment, the percentage of CD4 + T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and toxicity to colon

La ciencia de vida escrita en las aves. Tercera parte: Feekaje “Pava” (Penelope jacquacu

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Aniceto Nejedeka

2014-05-01

Full Text Available Texto bilingüe muinane-español sobre el ave feekaje, “pava” (Penelope jacquacu, elaborado por Aniceto Nejedeka a partir del conocimiento de los mayores de la etnia muinane. Este texto es la tercera parte de un libro que hemos venido publicando por fascículos, titulado La ciencia de vida escrita en las aves. El muinane es una lengua de la familia lingüística bora.

Técnica de Necropsia en Aves

OpenAIRE

L S Martínez-Acevedo

2012-01-01

En aves al igual que en otras especies, la necropsia hace parte integral de la medicina clínica. Esta se realiza con la finalidad de determinar la causa de enfermedad y muerte de un animal, confirmar un diagnóstico clínico o identificar la etiología de una enfermedad por medio de la toma de muestras complementarias. Siempre es indispensable tener en cuenta las diferencias anatómicas y biológicas de cada especie. El examen de necropsia es un procedimiento que debe realizarse de forma sistem...

Relación del Virus del Oeste del Nilo con las Aves Silvestres

OpenAIRE

Diego Soler-Tovar; Victor J Vera

2009-01-01

El Virus del Oeste del Nilo (VON) es un Flavivirus que produce una encefalomielitis y puede afectar aves y mamíferos; los efectos varían desde poco notorios hasta la muerte, y en su difusión es importante la participación de especies animales como las aves donde es transmitido a través de mosquitos vectores. El VON se conoce de Uganda desde 1937 y está ampliamente distribuido en África, el oriente y la región sur y tropical de Eurasia. En el Hemisferio Occidental, el VON fue la primera causa ...

Peroxisome proliferator-activated receptor-gamma agonists suppress tissue factor overexpression in rat balloon injury model with paclitaxel infusion.

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Jun-Bean Park

Full Text Available The role and underlying mechanisms of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ agonist, on myocardial infarction are poorly understood. We investigated the effects of this PPAR-γ agonist on the expression of tissue factor (TF, a primary molecule for thrombosis, and elucidated its underlying mechanisms. The PPAR-γ agonist inhibited TF expression in response to TNF-α in human umbilical vein endothelial cells, human monocytic leukemia cell line, and human umbilical arterial smooth muscle cells. The overexpression of TF was mediated by increased phosphorylation of mitogen-activated protein kinase (MAPK, which was blocked by the PPAR-γ agonist. The effective MAPK differed depending on each cell type. Luciferase and ChIP assays showed that transcription factor, activator protein-1 (AP-1, was a pivotal target of the PPAR-γ agonist to lower TF transcription. Intriguingly, two main drugs for drug-eluting stent, paclitaxel or rapamycin, significantly exaggerated thrombin-induced TF expression, which was also effectively blocked by the PPAR-γ agonist in all cell types. This PPAR-γ agonist did not impair TF pathway inhibitor (TFPI in three cell types. In rat balloon injury model (Sprague-Dawley rats, n = 10/group with continuous paclitaxel infusion, the PPAR-γ agonist attenuated TF expression by 70±5% (n = 4; P<0.0001 in injured vasculature. Taken together, rosiglitazone reduced TF expression in three critical cell types involved in vascular thrombus formation via MAPK and AP-1 inhibitions. Also, this PPAR-γ agonist reversed the paclitaxel-induced aggravation of TF expression, which suggests a possibility that the benefits might outweigh its risks in a group of patients with paclitaxel-eluting stent implanted.

LOS TANINOS EN LA ALIMENTACIÓN DE LAS AVES COMERCIALES

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Carlos López Coello

2006-10-01

Full Text Available Este artículo de revisión aborda la importancia de los ácidos fenólicos, flavonoides, taninos y sus compuestos derivados en la nutrición y alimentación de las aves. Los sorgos café presentan altos tenores de taninos, lo cual les proporciona como ventajas la resistencia a pájaros y a algunas plagas, sin embargo, reducen el valor nutricional del grano para las aves. Las informaciones sobre el contenido de estos compuestos es aún incierta, principalmente en la literatura, donde los sorgos café tienen sólo estimaciones sobre su contenido de taninos. Estos compuestos afectan también la ganancia de peso y la conversión de alimentos. En el aspecto nutricional, los taninos reducen la disponibilidad de metionina, This review article discusses the effects of phenolic acids, flavonoids, tannins and derivatives in poultry feeding and nutrition. The high tannin sorghum is advantageous for grain producers because of its resistance to birds’ attacks and insects, as compared to low tannin cultivar, but the nutritional value is reduced. The information about the amont of these compounds is really uncertain in scientific literature, and the high tannin sorghum has only estimated values for its tannin percentage. It’s clear that tannins affect weight gain and feed efficiency. The tannin can affect necesitando de la suplementación de este aminoácido, mientras para las proteínas los valores de digestibilidad varian de 45.5 a 66.7% en comparación con 89.9% de los sorgos bajos en taninos. Por otro lado, la presencia de taninos combinada con micotoxinas pueden determinar reducciones significativas del comportamiento de las aves. Se sugiere, por tanto, como forma de disminuir los efectos perjudiciales de estos compuestos en raciones formuladas con sorgo café, la suplementación de metionina, no obstante, la utilización de niveles suplementarios de vitaminas y el uso de calentamiento en horno microondas, no mostró resultados positivos

A dopamine receptor d2-type agonist attenuates the ability of stress to alter sleep in mice.

Science.gov (United States)

Jefferson, F; Ehlen, J C; Williams, N S; Montemarano, J J; Paul, K N

2014-11-01

Although sleep disruptions that accompany stress reduce quality of life and deteriorate health, the mechanisms through which stress alters sleep remain obscure. Psychological stress can alter sleep in a variety of ways, but it has been shown to be particularly influential on rapid eye movement (REM) sleep. Prolactin (PRL), a sexually dimorphic, stress-sensitive hormone whose basal levels are higher in females, has somnogenic effects on REM sleep. In the current study, we examined the relationship between PRL secretion and REM sleep after restraint stress to determine whether: 1) the ability of stress to increase REM sleep is PRL-dependent, and 2) fluctuating PRL levels underlie sex differences in sleep responses to stress. Because dopamine D2 receptors in the pituitary gland are the primary regulator of PRL secretion, D2 receptor agonist, 1-[(6-allylergolin-8β-yl)-carbonyl]-1-[3-(dimethylamino) propyl]-3-ethylurea (cabergoline), was used to attenuate PRL levels in mice before 1 hour of restraint stress. Mice were implanted with electroencephalographic/electromyographic recording electrodes and received an ip injection of either 0.3-mg/kg cabergoline or vehicle before a control procedure of 1 hour of sleep deprivation by gentle handling during the light phase. Six days after the control procedure, mice received cabergoline or vehicle 15 minutes before 1 hour of restraint stress. Cabergoline blocked the ability of restraint stress to increase REM sleep amount in males but did not alter REM sleep amount after stress in females even though it reduced basal REM sleep amount in female controls. These data provide evidence that the ability for restraint stress to increase REM sleep is dependent on PRL and that sex differences in REM sleep amount may be driven by PRL.

Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

Energy Technology Data Exchange (ETDEWEB)

Singh, Udai P.; Singh, Narendra P. [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Singh, Balwan [National Primate Research Center, Emory University, Atlanta GA 30329 (United States); Price, Robert L. [Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Mitzi [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States); Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)

2012-01-15

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and

Food partitioning between breeding White-tailed Kites (Elanus leucurus; Aves; Accipitridae and Barn Owls (Tyto alba; Aves; Tytonidae in southern Brazil

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DR. Scheibler

Full Text Available I examined the diet of breeding White-tailed Kites (Elanus leucurus; Aves; Accipitridae and Barn Owls (Tyto alba; Aves; Tytonidae in an agrarian area of southern Brazil by analyzing regurgitated prey remains. The objective was to evaluate how these raptors, which differ markedly in their hunting activity periods (owls are nocturnal and kites diurnal, share their mammalian food component. 2,087 prey consumed by Barn Owls and 1,276 by White-tailed Kites were identified. They presented a high overlap of food-niches (Pianka’s index was 0.98. Based on the daily activity period of their main small mammal prey, a lower overlap would be expected. The crepuscular/nocturnal Mus musculus was the main prey for the diet of breeding Barn Owls (81% and White-tailed Kites (63%. This small exotic rodent provided 63% of the small mammal biomass ingested by owls and 44% by kites. Larger native small mammals were also considered important for the diet of kites, mainly because of their biomass contribution. Although these raptors differ markedly in their hunting activity periods, Barn Owls and White-tailed Kites are very similar predators in southern Brazil, overlapping their diets.

Dos nuevos registros de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae sobre Leptotila megalura (Aves: Columbidae en la Argentina Two new records of chewing lice (Phthiraptera: Ischnocera: Philopteridae on Leptotila megalura (Aves: Columbidae from Argentina

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Leonor Guardia

2008-12-01

Full Text Available Dos especies de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae, Physconelloides ceratoceps Ewing y Columbicola gracilicapitis Carriker, son registradas por primera vez sobre Leptotila megalura Sclater & Salvin ("yerutí yungueña" (Aves: Columbidae. Además, C. gracilicapitis es citada por primera vez para la Argentina.Two species of chewing lice (Phthiraptera: Ischnocera: Philopteridae, Physconelloides ceratoceps Ewing and Columbicola gracilicapitis Carriker are recorded for the first time on Leptotila megalura Sclater & Salvin ("Large-tailed dove" (Aves: Columbidae. In addition, C. gracilicapitis is recorded for the first time in Argentina.

Using the Spanish Online Resource Aula Virtual de Español (AVE to Promote a Blended Teaching Approach in High School Spanish Language Classrooms / Utilisation de la ressource en ligne espagnole AVE pour favoriser l’approche de l’enseignement hybride

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Martine Pellerin

2012-02-01

Full Text Available The study explores the effectiveness of the implementation of blended teaching (BT by combining the Spanish online resource Aula Virtual de Español (AVE with the face-to-face (F2F delivery approach in second language Spanish programs in two high schools in Alberta, Canada. Findings demonstrate the effectiveness of combining the online resource AVE to the F2F teaching approach to promote BT in the Spanish language classroom. The use of BT approach in the language classroom had a positive impact on the students’ attitudes towards the study of the language, the students’ motivation and their participation levels in class, as well as their use of the target language in the classroom. Moreover, the multimodal experiences provided by the use of the online AVE resource combined with the F2F delivery approach responded more to the different learners learning styles and specific needs. Finally, the use of online AVE in conjunction with F2F teaching was also perceived as an effective tool in the preparation for the International Spanish Diplomas (DELE taken by the students in the more advanced Spanish classes. La présente étude explore l’efficacité de l’enseignement hybride combinant l’utilisation de la ressource espagnole en ligne Aula Virtual de Español (AVE et l’interaction face à face dans les programmes d’enseignement de l’espagnol, langue seconde, dans deux écoles secondaires de l’Alberta (Canada. Les résultats démontrent l’efficacité de la combinaison de la ressource en ligne AVE à la prestation face à face pour favoriser l’approche de l’enseignement hybride dans les cours d’espagnol. L’utilisation de l’approche de l’enseignement hybride dans le cours de langue a eu une incidence positive sur l’attitude des élèves relativement à l’apprentissage de la langue, la motivation des élèves et leur taux de participation en classe, ainsi que leur utilisation de la langue d’apprentissage dans la classe

Associations between chewing lice (Insecta, Phthiraptera and albatrosses and petrels (Aves, Procellariiformes collected in Brazil Associações entre malófagos (Insecta, Phthiraptera e albatrozes e petréis (Aves, Procellariiformes capturados no Brasil

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Michel P. Valim

2006-12-01

Full Text Available Chewing lice were searched on 197 skins of 28 species of procellariiform birds collected in Brazil. A total of 38 species of lice were found on 112 skins belonging to 22 bird species. The lice were slide-mounted and identified. A list of lice species found and their host species is given and some host-louse associations are discussed under an evolutionary perspective.Malófagos foram procurados em 197 peles de 28 espécies de aves Procellariiformes capturadas no Brasil. Um total de 38 espécies de piolhos foram encontradas em 112 peles pertencentes a 22 espécies de aves. Os piolhos foram montados em lâminas e identificados. Uma lista com as espécies de piolhos encontradas e seus hospedeiros é dada, além de algumas associações entre os piolhos e as aves serem discutidas sob uma perspectiva evolutiva.

Comunidades de aves y lepidopteros diurnos y las relaciones entre ellas en bosque nuboso y cafetal de Finca Santa Maura, Jinotega

Science.gov (United States)

M. Torrez; W. Arendt; J. M. Maes

2013-01-01

Para evaluar la diversidad de aves y mariposas ninfálidas visitamos la Estación Biológica Juan Roberto Zarruk en Jinotega, donde colectamos datos en todos los hábitats presentes en la finca. Obtuvimos 123 especies de aves y 29 especies de ninfálidos. El hábitat con mayor riqueza para aves fue el cafetal y para ninfálidos el tacotal. Entre las especies más comunes...

Sexual dimorphism in Ramphastos toco and Ramphastos dicolorus (Piciformes, Aves

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Márcio S. Castro

2003-03-01

Full Text Available Con frecuencia, en la familia Ramphastidae no hay un dimorfismo sexual aparente, excepto en Pteroglossus viridis y en el género Selenidera. Muchos criadores de aves silvestres creen que los especímenes de Ramphastos toco pueden ser sexados usando las caracteríticas del pico. En este estudio, fueron analizadas algunas variables feno-típicas discriminantes en aves cuyo sexo fue previamente determinado con metodos citogenéticos. Un total de 51 especimenes de R. toco y 20 de R. dicolorus fueron estudiados. Los parámetros estadísticos significativos que son útiles para distinguir el sexo en estas especies son la longitud del culmen y del tomium, la longitud del pico corneo inferior y de la cloaca. Usando estos parámetros, los criadores de aves cautivas pueden sexar los especimenes de Ramphastos toco mediante análisis fenotípico y formar parejas reproductoras más rapidamente.Phenotypic sexual dimorphism seems to be rare in the Ramphastidae family, except in Pteroglossus viridis and in the genus Selenidera. Many breeders of wild birds believe that specimens of Ramphastos toco can be sexed using bill characteristics. In this study, various discriminant phenotypic variables were analyzed in birds which were sexed cytogenetically. Fifty-one specimens of R. toco and 20 R. dicolorus were studied. The statistically significant parameters which served to distinguish the sex in these species were the length of the culmen and tomium, length of the lower corneous beak and the cloaca. Using these parameters, capitive bird breeders can determine sex of R. toco specimens by phenotypic analysis and form breeding couples more quickly.

Inhibition of oxidative stress-elicited AKT activation facilitates PPARγ agonist-mediated inhibition of stem cell character and tumor growth of liver cancer cells.

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Lanlan Liu

Full Text Available Emerging evidence suggests that tumor-initiating cells (TICs are the most malignant cell subpopulation in tumors because of their resistance to chemotherapy or radiation treatment. Targeting TICs may be a key innovation for cancer treatment. In this study, we found that PPARγ agonists inhibited the cancer stem cell-like phenotype and attenuated tumor growth of human hepatocellular carcinoma (HCC cells. Reactive oxygen species (ROS initiated by NOX2 upregulation were partially responsible for the inhibitory effects mediated by PPARγ agonists. However, PPARγ agonist-mediated ROS production significantly activated AKT, which in turn promoted TIC survival by limiting ROS generation. Inhibition of AKT, by either pharmacological inhibitors or AKT siRNA, significantly enhanced PPARγ agonist-mediated inhibition of cell proliferation and stem cell-like properties in HCC cells. Importantly, in nude mice inoculated with HCC Huh7 cells, we demonstrated a synergistic inhibitory effect of the PPARγ agonist rosiglitazone and the AKT inhibitor triciribine on tumor growth. In conclusion, we observed a negative feedback loop between oxidative stress and AKT hyperactivation in PPARγ agonist-mediated suppressive effects on HCCs. Combinatory application of an AKT inhibitor and a PPARγ agonist may provide a new strategy for inhibition of stem cell-like properties in HCCs and treatment of liver cancer.

Variación temporal y espacial de aves playeras en la laguna Barra de Navidad, Jalisco, en tres temporadas no reproductivas

OpenAIRE

Salvador Hernández; Sergio Serrano; Xóchitl A. Hernández; María Isabel Robles

2012-01-01

Hay un escaso conocimiento de las aves playeras en los humedales costeros de Jalisco, y en particular en la laguna Barra de Navidad. El presente trabajo contribuye al conocimiento de este grupo de aves y describe su distribución temporal y espacial en la laguna Barra de Navidad durante tres temporadas no reproductivas (1999-2000, 2006-2007 y 2008-2009). Se realizaron censos mensuales de noviembre-abril en las tres temporadas con el fin de registrar todas las especies de aves playeras. Se iden...

LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

Energy Technology Data Exchange (ETDEWEB)

Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang, E-mail: fanxiaotang2005@163.com

2016-09-02

Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

International Nuclear Information System (INIS)

Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang

2016-01-01

Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

Variación temporal y espacial de aves playeras en la laguna Barra de Navidad, Jalisco, en tres temporadas no reproductivas

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Salvador Hernández

2012-09-01

Full Text Available Hay un escaso conocimiento de las aves playeras en los humedales costeros de Jalisco, y en particular en la laguna Barra de Navidad. El presente trabajo contribuye al conocimiento de este grupo de aves y describe su distribución temporal y espacial en la laguna Barra de Navidad durante tres temporadas no reproductivas (1999-2000, 2006-2007 y 2008-2009. Se realizaron censos mensuales de noviembre-abril en las tres temporadas con el fin de registrar todas las especies de aves playeras. Se identificaron 19 especies (tres residentes y 16 visitantes de invierno, de las cuales Charadrius wilsonia, Limosa fedoa y Tringa semipalmata presentaron la mayor abundancia. Doce especies son consideradas como prioritarias en la “Estrategia para la Conservación y Manejo de las Aves Playeras y su Hábitat en México”. El mayor número de especies fue registrado en noviembre, diciembre y marzo en la primera y tercera temporada. El mayor número de individuos fue registrado alimentándose en marea baja, principalmente en diciembre, enero y febrero de la primera y tercera temporada. En marea baja hubo un mayor número de especies e individuos alimentándose en la zona C. Esta zona se caracterizó por tener sustratos lodosos expuestos durante marea baja y que fueron aprovechados por las aves para alimentarse. La laguna Barra de Navidad proporcionó hábitats de alimentación y descanso para las aves residentes y migratorias. Sin embargo, estos hábitats se ven amenazados por las actividades humanas realizadas dentro de la laguna, que sin duda tendrán consecuencias negativas para la distribución y abundancia de las aves playeras.

Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy.

Science.gov (United States)

Jakubík, J; Janíčková, H; El-Fakahany, E E; Doležal, V

2011-03-01

Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5'-γ-thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M₂ muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [³⁵S]GTPγS and [³H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M₂ muscarinic acetylcholine receptor. Agonists displayed biphasic competition curves with the antagonist [³H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [³H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from G(i/o) G-proteins but only its dissociation from G(s/olf) G-proteins. These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of G(i/o) versus G(s/olf) G-proteins that are not identified by conventional GTPγS binding. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Blockade of acid sensing ion channels attenuates the augmented exercise pressor reflex in rats with chronic femoral artery occlusion.

Science.gov (United States)

Tsuchimochi, Hirotsugu; Yamauchi, Katsuya; McCord, Jennifer L; Kaufman, Marc P

2011-12-15

We found previously that static contraction of the hindlimb muscles of rats whose femoral artery was ligated evoked a larger reflex pressor response (i.e. exercise pressor reflex) than did static contraction of the contralateral hindlimb muscles which were freely perfused. Ligating a femoral artery in rats results in blood flow patterns to the muscles that are remarkably similar to those displayed by humans with peripheral artery disease. Using decerebrated rats, we tested the hypothesis that the augmented exercise pressor reflex in rats with a ligated femoral artery is attenuated by blockade of the acid sensing ion channel (ASIC) 3. We found that femoral arterial injection of either amiloride (5 and 50 μg kg(-1)) or APETx2 (100 μg kg(-1)) markedly attenuated the reflex in rats with a ligated femoral artery. In contrast, these ASIC antagonists had only modest effects on the reflex in rats with freely perfused hindlimbs. Tests of specificity of the two antagonists revealed that the low dose of amiloride and APETx2 greatly attenuated the pressor response to lactic acid, an ASIC agonist, but did not attenuate the pressor response to capsaicin, a TRPV1 agonist. In contrast, the high dose of amiloride attenuated the pressor responses to lactic acid, but also attenuated the pressor response to capsaicin. We conclude that ASIC3 on thin fibre muscle afferents plays an important role in evoking the exercise pressor reflex in rats with a compromised arterial blood supply to the working muscles.

nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol-Seeking Behavior

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Erin Harshberger

2016-01-01

Full Text Available Recent work suggests that the dynorphin (DYN/kappa opioid receptor (KOR system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0.1–10 mg/kg, i.p. or saline and were tested for the reinstatement of ethanol seeking. Next, the ability of the nonselective opioid receptor antagonist naltrexone (0 or 3.0 mg/kg, s.c. and nor-BNI (0 or 20.0 mg/kg, i.p. to block U50,488-induced reinstatement was examined. Priming injections U50,488 reinstated responding on the previously ethanol-associated lever. Pretreatment with naltrexone reduced the reinstatement of ethanol-seeking behavior. nor-BNI also attenuated KOR agonist-induced reinstatement, but to a lesser extent than naltrexone, when injected 24 hours prior to injections of U50,488, a time point that is consistent with KOR selectivity. While these results suggest that activation of KORs is a key mechanism in the regulation of ethanol-seeking behavior, U50,488-induced reinstatement may not be fully selective for KORs.

SU-C-9A-06: The Impact of CT Image Used for Attenuation Correction in 4D-PET

International Nuclear Information System (INIS)

Cui, Y; Bowsher, J; Yan, S; Cai, J; Das, S; Yin, F

2014-01-01

Purpose: To evaluate the appropriateness of using 3D non-gated CT image for attenuation correction (AC) in a 4D-PET (gated PET) imaging protocol used in radiotherapy treatment planning simulation. Methods: The 4D-PET imaging protocol in a Siemens PET/CT simulator (Biograph mCT, Siemens Medical Solutions, Hoffman Estates, IL) was evaluated. CIRS Dynamic Thorax Phantom (CIRS Inc., Norfolk, VA) with a moving glass sphere (8 mL) in the middle of its thorax portion was used in the experiments. The glass was filled with 18 F-FDG and was in a longitudinal motion derived from a real patient breathing pattern. Varian RPM system (Varian Medical Systems, Palo Alto, CA) was used for respiratory gating. Both phase-gating and amplitude-gating methods were tested. The clinical imaging protocol was modified to use three different CT images for AC in 4D-PET reconstruction: first is to use a single-phase CT image to mimic actual clinical protocol (single-CT-PET); second is to use the average intensity projection CT (AveIP-CT) derived from 4D-CT scanning (AveIP-CT-PET); third is to use 4D-CT image to do the phase-matched AC (phase-matching- PET). Maximum SUV (SUVmax) and volume of the moving target (glass sphere) with threshold of 40% SUVmax were calculated for comparison between 4D-PET images derived with different AC methods. Results: The SUVmax varied 7.3%±6.9% over the breathing cycle in single-CT-PET, compared to 2.5%±2.8% in AveIP-CT-PET and 1.3%±1.2% in phasematching PET. The SUVmax in single-CT-PET differed by up to 15% from those in phase-matching-PET. The target volumes measured from single- CT-PET images also presented variations up to 10% among different phases of 4D PET in both phase-gating and amplitude-gating experiments. Conclusion: Attenuation correction using non-gated CT in 4D-PET imaging is not optimal process for quantitative analysis. Clinical 4D-PET imaging protocols should consider phase-matched 4D-CT image if available to achieve better accuracy

SU-C-9A-06: The Impact of CT Image Used for Attenuation Correction in 4D-PET

Energy Technology Data Exchange (ETDEWEB)

Cui, Y; Bowsher, J; Yan, S; Cai, J; Das, S; Yin, F [Duke University Medical Center, Durham, NC (United States)

2014-06-01

Purpose: To evaluate the appropriateness of using 3D non-gated CT image for attenuation correction (AC) in a 4D-PET (gated PET) imaging protocol used in radiotherapy treatment planning simulation. Methods: The 4D-PET imaging protocol in a Siemens PET/CT simulator (Biograph mCT, Siemens Medical Solutions, Hoffman Estates, IL) was evaluated. CIRS Dynamic Thorax Phantom (CIRS Inc., Norfolk, VA) with a moving glass sphere (8 mL) in the middle of its thorax portion was used in the experiments. The glass was filled with {sup 18}F-FDG and was in a longitudinal motion derived from a real patient breathing pattern. Varian RPM system (Varian Medical Systems, Palo Alto, CA) was used for respiratory gating. Both phase-gating and amplitude-gating methods were tested. The clinical imaging protocol was modified to use three different CT images for AC in 4D-PET reconstruction: first is to use a single-phase CT image to mimic actual clinical protocol (single-CT-PET); second is to use the average intensity projection CT (AveIP-CT) derived from 4D-CT scanning (AveIP-CT-PET); third is to use 4D-CT image to do the phase-matched AC (phase-matching- PET). Maximum SUV (SUVmax) and volume of the moving target (glass sphere) with threshold of 40% SUVmax were calculated for comparison between 4D-PET images derived with different AC methods. Results: The SUVmax varied 7.3%±6.9% over the breathing cycle in single-CT-PET, compared to 2.5%±2.8% in AveIP-CT-PET and 1.3%±1.2% in phasematching PET. The SUVmax in single-CT-PET differed by up to 15% from those in phase-matching-PET. The target volumes measured from single- CT-PET images also presented variations up to 10% among different phases of 4D PET in both phase-gating and amplitude-gating experiments. Conclusion: Attenuation correction using non-gated CT in 4D-PET imaging is not optimal process for quantitative analysis. Clinical 4D-PET imaging protocols should consider phase-matched 4D-CT image if available to achieve better accuracy.

Compost de ave de corral como componente de sustratos

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Lorena Alejandra Barbaro¹

2011-07-01

Full Text Available El sustrato para cultivo es un material que colocado en un contenedor permite el anclaje del sistema radicular, proporcionando agua y nutrientes. Entre los materiales empleados para formular sustratos se encuentran los compost. Entre ellos el compost de cama de ave de corral (CAC, elaborado en base al estiércol de aves mezclado con los materiales que forman su lecho. El objetivo de este trabajo fue evaluar dos compost de CAC como componente de sustrato, mediante el desarrollo de plantas de Coral (Salvia splendens. Uno de los compost contenía cama de stud (CAC+S durante su compostaje. Se formularon sustratos con diferentes proporciones de compost de CAC, compost de corteza de pino y pinocha, luego fueron analizados física y químicamente. A las plantas cultivadas en cada sustrato se midió la longitud y el diámetro del tallo, peso fresco y seco de la parte aérea y radicular. La densidad, porosidad y capacidad de retención de agua de todos los sustratos fueron aceptables. El pH de ambos compost de CAC fue mayor a 6,3, y los valores de las mezclas se encontraron dentro del rango aceptable. Todos los sustratos superaron 1 dS m-1 (1+5 v/v, principalmente los formulados con compost de CAC+S, cuyo material puro contenía altos niveles salinos. Al disminuir el porcentaje de CAC en las mezclas, diminuyó la concentración de cada nutriente. Las plantas cultivadas en el sustrato comercial y en las mezclas con 20% de CAC fueron las que lograron los mayores pesos aéreos y radiculares, diámetro y longitud del tallo. Por lo tanto, el compost de ave de corral podría ser una alternativa viable como componente de sustrato si se lo utiliza hasta un 20%.

PRESENCIA DEL VIRUS DE INFLUENZA AVIAR EN AVES SILVESTRES DE LOS HUMEDALES DE PUERTO VIEJO, LIMA

OpenAIRE

Segovia H., Karen; Icochea D., Eliana; González V., Rosa; Ghersi, Bruno; González Z., Armando

2013-01-01

El objetivo del estudio fue determinar la presencia del virus de influenza aviar (IA) en aves silvestres presentes en los Humedales de Puerto Viejo, en el departamento de Lima. Novecientas muestras de heces frescas de 18 especies de aves silvestres fueron colectadas desde abril de 2008 hasta febrero de 2009. Dichas muestras se analizaron mediante aislamiento viral en huevos embrionados de pollo SPF. Se logró aislar siete cepas de virus de IA de baja patogenicidad del subtipo H12N5 (seis cepas...

Nidificação de aves em duas localidades amazonicas : sucesso e adaptações

OpenAIRE

Yoshika Oniki Willis

1986-01-01

Resumo: As taxas de sucesso em ninhos de aves bera como as características de ninhos e ovos relacionados com o ambiente foram estudadas em duas localidades brasileiras tropicais, Belém e Manaus. As taxas de mortalidade em ninhos de aves, de Belém e Manaus, medidas pela fórmula N/(P + S + N), sugerida por Mayfield (1975) variaram entre 1,5 e 6,8 % por dia para diferentes tipos de ninhos e habitats. Sendo que estas figuras às vezes não são significantemente mais altas que taxas constatadas em z...

Aves de Caldas: la complejidad cotidiana entre la sobrevivencia y la belleza

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Natalia Ruíz Rodgers

2016-12-01

En la región andina central de Colombia, la belleza resulta aún más difícil de analizar debido a que es una región muy heterogénea, con una variación altitudinal amplia, una topografía desigual, condiciones climáticas y edafológicas diversas, diferentes formaciones vegetales (bosque andino, bosque de niebla, páramos, nieves perpetuas y zonas productivas (cafetales, guaduales, ganadería, cultivos de papa, frutales, minería, etc.. Toda esta heterogeneidad produce una gran riqueza de especies, solo Caldas acoge el cuarenta y ocho por ciento de las aves que se encuentran en el país. Esta riqueza se representa además en la importancia que tienen las aves gracias a sus múltiples interacciones, su efecto en el ecosistema y sus diferentes estrategias evolutivas.

Relação entre Triatoma infestans, aves domésticas e o homem num povoado de Santiago del Estero, Argentina

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Gajate Patrícia P.

1994-01-01

Full Text Available Determinou-se a associação entre Triatoma infestans, aves domésticas e o homem no povoado de Trinidad, Santiago del Estero, Argentina. Para coletar triatomíneos foram realizadas quatro amostragens no peridomicílio de seis casas, utilizando-se o método de captura hora/homem (dezembro de 1991 a outubro de 1992. Os anexos foram classificados em antrópicos (onde o homem realiza atividades cotidianas e não-antrópicos. Além disso, determinou-se o perfil alimentar dos barbeiros. De um total de 134 ecótopos investigados, 21% tinham T. infestans; 22% possuíam aves domésticas; e 54% eram antrópicos. Em 25% destes ecótopos foram encontradas aves e T. infestans simultaneamente. As aves foram os únicos animais domésticos associados com o T. infestans, sendo que esta relação só ocorreu nos ecótopos antrópicos. A proporção de ingestas em aves (61/146 foi altamente significativa. Em Trinidad não há galinheiros, utilizando-se, assim, os anexos entrópicos do peridomicílio como local para se construir os ninhos para as aves. tanto pelos elementos usados na preparação dos ninhos como pelo uso posterior dos mesmos, poder-se-ia estabelecer um fluxo periódico de barbeiros do intradomicílio para o peridomicílio, e vice-versa, através do transporte passivo. Esta relação estreita entre Triatoma infestans, aves domésticas e o homem, encontrada nos ecótopos antrópicos, onde também existem outros reservatórios de T. cruzi, como os cães, favorece a manutenção de colônias de barbeiros domiciliares e a transmissão da doença de Chagas ao homem.

Relação entre Triatoma infestans, aves domésticas e o homem num povoado de Santiago del Estero, Argentina

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Patrícia P. Gajate

Full Text Available Determinou-se a associação entre Triatoma infestans, aves domésticas e o homem no povoado de Trinidad, Santiago del Estero, Argentina. Para coletar triatomíneos foram realizadas quatro amostragens no peridomicílio de seis casas, utilizando-se o método de captura hora/homem (dezembro de 1991 a outubro de 1992. Os anexos foram classificados em antrópicos (onde o homem realiza atividades cotidianas e não-antrópicos. Além disso, determinou-se o perfil alimentar dos barbeiros. De um total de 134 ecótopos investigados, 21% tinham T. infestans; 22% possuíam aves domésticas; e 54% eram antrópicos. Em 25% destes ecótopos foram encontradas aves e T. infestans simultaneamente. As aves foram os únicos animais domésticos associados com o T. infestans, sendo que esta relação só ocorreu nos ecótopos antrópicos. A proporção de ingestas em aves (61/146 foi altamente significativa. Em Trinidad não há galinheiros, utilizando-se, assim, os anexos entrópicos do peridomicílio como local para se construir os ninhos para as aves. tanto pelos elementos usados na preparação dos ninhos como pelo uso posterior dos mesmos, poder-se-ia estabelecer um fluxo periódico de barbeiros do intradomicílio para o peridomicílio, e vice-versa, através do transporte passivo. Esta relação estreita entre Triatoma infestans, aves domésticas e o homem, encontrada nos ecótopos antrópicos, onde também existem outros reservatórios de T. cruzi, como os cães, favorece a manutenção de colônias de barbeiros domiciliares e a transmissão da doença de Chagas ao homem.

The construction of women and the situation of exile in Aves exóticas by Reina Roffé

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Nadia Vannesa Mendez

2015-09-01

Full Text Available This article analyze the construction of a different style of woman in the stories compiled in the book´s Reina Roffé Aves Exóticas (2004. The female characters that appear are crossed by different ways of exile, as the political exile caused by military dictatorships. It is also interesting as, in the second edition of Aves, Roffé raises a new reading of the play Frankenstein by Mary Shelley.

Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

Science.gov (United States)

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

Crianza Artificial de Aves Rapaces Nocturnas en Cautiverio

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Carolina Sastre-Corredor

2009-01-01

El objetivo de este trabajo, fue realizar el seguimiento a dos casos de aves rapaces neonatos que ingresaron al Centro de Recepción y Rehabilitación de Fauna Silvestre (CRRFS) de la Secretaria Distrital de Ambiente (SDA), con el fin de registrar, conocer e informar el manejo general de los mismos. Al momento de ingresar el primer grupo de ejemplares al CRRFS, se detectaron varias limitaciones de tipo físico, por ejemplo insumos alimentarios en mal estado o inexistencia de los mismos, y de...

DIAGNÓSTICO DA REALIDADE DOS CRIATÓRIOS DE AVES NA COMUNIDADE BASE FÍSICA – IPANGUAÇU/RN

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José Geraldo Bezerra Galvão Júnior

2010-02-01

Full Text Available Este trabalho objetivou realizar um diagnóstico de caracterização dos sistemas de criação de aves adotados na Comunidade Rural Base Física, município de Ipanguaçu/RN, com o intuito de produzir subsídios para orientação de ações de suporte técnico à comunidade local. Foram elaborados e aplicados 50 questionários, com questões relacionadas ao perfil socioeconômico dos criadores e aos aspectos zootécnicos relativos à criação de aves. Posteriormente, os dados foram agrupados e analisados graficamente, utilizando-se planilha eletrônica. Na análise dos resultados, a maioria dos entrevistados corresponderam ao gênero feminino (70%, faixa etária de 41 a 60 anos (50%, representados em sua maioria por agricultores (52%, apresentando renda familiar de menos de 1 salário mínimo (16%, até 2 salários (20% e acima de 2 salários mínimos (34%. Na análise das respostas referentes aos aspectos zootécnicos da criação de aves, constatou-se um rebanho efetivo de 1046 aves, onde 81% dos entrevistados mantinham a criação para consumo da família. A avicultura representa grande importância na agricultura familiar da região, tanto na questão de segurança alimentar para a família quanto no aspecto econômico. A alimentação foi considerada o principal fator limitante para o desenvolvimento da criação, seguida da área para criação e presença de doenças nas aves. Programas de capacitação e assistência técnica devem ser implantados, para que possa haver um incremento quantitativo e qualitativo da criação de aves, principalmente, ligados aos aspectos de manejo alimentar e sanitário, bem como, no delineamento de modelos produtivos que expressem competitividade no setor. PALAVRAS-CHAVE: avicultura, sistemas de criação, agricultura familiar.

AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery

DEFF Research Database (Denmark)

Lassen, Michael Rud; Dahl, O E; Mismetti, P

2009-01-01

BACKGROUND: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication....... The primary safety outcome was the incidence of major bleeding. RESULTS: The primary efficacy outcome was assessed in 464 patients. There was a significant dose-response across the five AVE5026 groups for VTE prevention (Pincidence of VTE ranging from 5.3% to 44.1% compared with 35...

Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans

DEFF Research Database (Denmark)

Andersen, Hjalte H.; Melholt, Camilla; Hilborg, Sigurd D.

2017-01-01

A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists...... and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value....... (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical “cold-like” counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin...

Nuevos avistamientos de aves para Tamaulipas, México

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Erick Rubén Rodríguez-Ruíz

2012-07-01

Full Text Available Los inventarios y registros avifaunísticos facilitan el conocimiento de la composición de las comunidades de aves y ayudan a la comprensión de las interacciones en los ecosistemas. En este trabajo obtuvimos registros notables de cinco especies de aves de 2005 a 2011 en los municipios de Altamira, El Mante, González, Jaumave, Madero, Matamoros, Miquihuana y Soto La Marina, en el estado de Tamaulipas. Registramos por primera vez la presencia de Aphelocoma californica e Icterus wagleri en el estado, confirmando las predicciones de algunos autores. Con la colecta de un nido, reafirmamos la presencia de Psarocolius montezuma en el sur del estado. Registramos nuevamente la presencia de Falco femoralis en la entidad, especie reportada hace algunos años como extirpada. ParaLepidocolaptes affinis definimos parte de su área de distribución en los límites neotropicales del estado. Las modificaciones antropogénicas en los ecosistemas son algunos de los principales factores que influyen en los movimientos distribucionales de las especies; por esto, es necesario incrementar el esfuerzo de muestreo que permita el registro de un mayor número de especies y así poder tener un mejor conocimiento de su distribución y temporalidad a nivel local y regional para entender su historia natural y ecología a escalas más finas.

The epileptogenic spectrum of opiate agonists.

Science.gov (United States)

Snead, O C; Bearden, L J

1982-11-01

The present authors gave mu, delta, kappa, epsilon and sigma opiate receptor agonists intracerebroventricularly to rats both singly and in combination while monitoring the electroencephalogram from cortical and depth electrodes. Dose-response curves were plotted with naloxone against the changes produced by each agonist, and the effect of a number of anticonvulsant drugs on agonist-induced seizures was ascertained. Each opiate agonist produced a different seizure pattern with a different naloxone dose-response curve and anticonvulsant profile. The order of convulsive potency was epsilon greater than delta greater than mu greater than sigma much greater than kappa. Petit mal-like seizure activity was unique to the delta agonist, leucine-enkephalin, while only the mu agonist, morphine produced generalized convulsive seizures. These experiments raise the possibility that opiate systems in the brain may be involved in the pathogenesis of a wide spectrum of seizure disorders.

Conhecimento de moradores sobre frugivoria por aves em uma região urbanizada e com fragmentos de restinga no sudeste do Brasil

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César Cestari

2009-06-01

Full Text Available http://dx.doi.org/10.5007/2175-7925.2009v22n3p221 O conhecimento ecológico é importante para revelar a consciência ambiental de pessoas, refletindo em ações para conservação no meio ambiente onde vivem. No presente estudo foi avaliado o conhecimento de moradores sobre frugivoria por aves em fragmentos da restinga, um ecossistema ameaçado pela crescente ocupação humana. Entrevistas semi-estruturadas foram aplicadas para 73 moradores em dois bairros da cidade de Itanhaém, litoral sul do estado de São Paulo. A maioria das respostas evidenciou pouca observação de frugivoria por aves em plantas nativas. Os moradores demonstraram dificuldades na identificação de aves frugívoras e na discriminação de plantas nativas da região. No entanto, possuíam conhecimento lógico de processos ecológicos envolvendo as interações entre aves e plantas. A ave popularmente conhecida como tiê-sangue (Ramphocelus bresilius e a palmeira jerivá (Syagrus romanzoffiana foram mais frequentemente citadas. Essas espécies são facilmente encontradas na restinga da região e apresentam características estruturais que atraíram a atenção das pessoas tais como cor vermelho intenso e elevada altura, respectivamente. Dessa forma, as epécies citadas podem ser utilizadas para trabalhos iniciais envolvendo identificação de aves e plantas, e para o aprofundamento da educação ambiental dos moradores locais.

Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.

Science.gov (United States)

Scarlett, Kisha A; White, El-Shaddai Z; Coke, Christopher J; Carter, Jada R; Bryant, Latoya K; Hinton, Cimona V

2018-04-01

G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates Gα13 (GNA13), and subsequently, the small GTPase RhoA, which is required for directional cell migration and the metastatic potential of cancer cells. These studies in prostate cancer cells demonstrate decreased protein expression levels of Gα13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation. Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal rearrangement resulting in the attenuation of cell migration and invasion of an endothelial cell barrier. Finally, a reduction was observed in the expression of integrin α5 (ITGA5) upon heterodimerization, supported by decreased cell adhesion to extracellular matrices in vitro Taken together, the data identify a novel pharmacologic mechanism for the modulation of tumor cell migration and invasion in the context of metastatic disease. Implications: This study investigates a signaling mechanism by which GPCR heterodimerization inhibits cancer cell migration. Mol Cancer Res; 16(4); 728-39. ©2018 AACR . ©2018 American Association for Cancer Research.

MK-801, but not drugs acting at strychnine-insensitive glycine receptors, attenuate methamphetamine nigrostriatal toxicity.

Science.gov (United States)

Layer, R T; Bland, L R; Skolnick, P

1993-10-15

Repeated administration of methamphetamine (METH) results in damage to nigrostriatal dopaminergic neurons. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists and use-dependent cation channel blockers attenuate METH-induced damage. The objectives of the present study were to examine whether comparable reductions in METH-induced damage could be obtained by compounds acting at strychnine-insensitive glycine receptors on the NMDA receptor complex. Four injections of METH (5 mg/kg i.p.) resulted in a approximately 70.9% depletion of striatal dopamine (DA) and approximately 62.7% depletion of dihydroxyphenylacetic acid (DOPAC) content, respectively. A significant protection against METH-induced DA and DOPAC depletion was afforded by the use-dependent channel blocker, MK-801. The competitive glycine antagonist 7-chlorokynurenic acid (7-Cl-KA), the low efficacy glycine partial agonist (+)-3-amino-1-hydroxy-2-pyrrolidone ((+)-HA-966), and the high efficacy partial glycine agonist 1-aminocyclopropane-carboxylic acid (ACPC) were ineffective against METH-induced toxicity despite their abilities to attenuate glutamate-induced neurotoxicity under both in vivo and in vitro conditions. These results indicate that glycinergic ligands do not possess the same broad neuroprotective spectrum as other classes of NMDA antagonists.

A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.

Science.gov (United States)

Ronca, Richard D; Myers, Alyssa M; Ganea, Doina; Tuma, Ronald F; Walker, Ellen A; Ward, Sara Jane

2015-10-01

We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size. Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure. O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice. We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Restos de aves en los yacimientos prehistóricos vascos. Estudios realizados.

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Miguel Elorza

1990-01-01

Full Text Available En el trabajo se indican los estudios realizados, hasta el momento, de arqueozoología de aves en el País Vasco. Se hace especial referencia a los trabajos más antiguos y se presentan varias avifaunas, algunas inéditas, de forma cualitativa.

Effects of agonist efficacy on desensitization of phosphoinositide hydrolysis mediated by m1 and m3 muscarinic receptors expressed in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Hu, J.; Wang, S.Z.; el-Fakahany, E.E.

1991-01-01

Muscarinic receptor agonist-induced desensitization of phosphoinositide (PI) hydrolysis and loss of receptors were studied in Chinese hamster ovary (CHO) cells transfected with the m1 and m3 muscarinic receptor genes. Long-term exposure to the full agonist carbamylcholine (CBC) resulted in a time-dependent attenuation of the maximal PI response and a decrease in agonist potency. This desensitization was accompanied by a parallel loss of maximal ligand binding without an alteration of the binding affinity. The time course of both receptor desensitization and down-regulation was similar in m1 and m3 CHO cells. The PI response to the partial agonist McN-A-343 (McN) in m1 cells was more sensitive to desensitization by CBC than the response to the latter agonist, and this desensitization was faster than receptor down-regulation. Desensitization of the PI response to McN was reflected as a decrease in the maximal response without a marked change in potency. McN induced slow desensitization of the PI response to CBC but a much faster desensitization of its own response. Our data provide evidence that although muscarinic agonist-induced desensitization of PI hydrolysis in CHO cells is due mainly to loss of receptors, there are other important factors which play a role in this process, e.g., receptor-effector uncoupling. The relative contribution of these different mechanisms depends on the efficacy of the agonists used for the receptor desensitization and activation steps

Aves ocasionales en la Sabana de Bogotá y las Lagunas de Fúquene y de Tota

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Borrero José Ignacio

1947-12-01

Full Text Available En números anteriores de esta misma revista publiqué algunas listas preliminares anotando la presencia ocasional de ciertas aves en la Sabana de Bogotá y la Laguna de Fúquene. A continuación hago mención de otras especies que he encontrado en las mismas localidades o también en la Laguna de Tota, Boyacá, a 3015 metros de altitud. Por considerarlo de importancia desde el punto de vista de la distribución geográfica, doy también datos referentes a la presencia de un ave migratoria norteamericana (Colymbus niqricollis californicus en la Laguna de Tota.

Beta 2-adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications.

Science.gov (United States)

Noh, Hyunjin; Yu, Mi Ra; Kim, Hyun Joo; Lee, Ji Hye; Park, Byoung-Won; Wu, I-Hsien; Matsumoto, Motonobu; King, George L

2017-07-01

Macrophage activation is increased in diabetes and correlated with the onset and progression of vascular complications. To identify drugs that could inhibit macrophage activation, we developed a cell-based assay and screened a 1,040 compound library for anti-inflammatory effects. Beta2-adrenergic receptor (β2AR) agonists were identified as the most potent inhibitors of phorbol myristate acetate-induced tumor necrosis factor-α production in rat bone marrow macrophages. In peripheral blood mononuclear cells isolated from streptozotocin-induced diabetic rats, β2AR agonists inhibited diabetes-induced tumor necrosis factor-α production, which was prevented by co-treatment with a selective β2AR blocker. To clarify the underlying mechanisms, THP-1 cells and bone marrow macrophages were exposed to high glucose. High glucose reduced β-arrestin2, a negative regulator of NF-κB activation, and its interaction with IκBα. This subsequently enhanced phosphorylation of IκBα and activation of NF-κB. The β2AR agonists enhanced β-arrestin2 and its interaction with IκBα, leading to downregulation of NF-κB. A siRNA specific for β-arrestin2 reversed β2AR agonist-mediated inhibition of NF-κB activation and inflammatory cytokine production. Treatment of Zucker diabetic fatty rats with a β2AR agonist for 12 weeks attenuated monocyte activation as well as pro-inflammatory and pro-fibrotic responses in the kidneys and heart. Thus, β2AR agonists might have protective effects against diabetic renal and cardiovascular complications. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Mis motiveerib Eesti, Soome ja Tšehhi õpetajaid? / Ave Abroi ; kommenteerinud Kertu Laanesoo

Index Scriptorium Estoniae

Abroi, Ave

2009-01-01

Artikkel on ilmunud Ave Abroi Tartu Ülikooli Euroopa Kolledžis 2008. aastal kaitstud magistritöö "Õpetajate motiveerimise võimalused Euroopa Liidus Eesti, Tšehhi ja Soome näitel" põhjal. Kommenteerib Audentese erakooli inglise keele õpetaja Kertu Laanesoo

Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats.

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Miklós Sárvári

Full Text Available The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands, local estradiol synthesis (P450 aromatase and estrogen reception (ER. Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b and complement (C3, factor B, properdin genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERα gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERα agonist closely resembled those of estradiol, ERβ agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu

The non-biphenyl-tetrazole angiotensin AT1 receptor antagonist eprosartan is a unique and robust inverse agonist of the active state of the AT1 receptor.

Science.gov (United States)

Takezako, Takanobu; Unal, Hamiyet; Karnik, Sadashiva S; Node, Koichi

2018-03-23

Conditions such as hypertension and renal allograft rejection are accompanied by chronic, agonist-independent, signalling by angiotensin II AT 1 receptors. The current treatment paradigm for these diseases entails the preferred use of inverse agonist AT 1 receptor blockers (ARBs). However, variability in the inverse agonist activities of common biphenyl-tetrazole ARBs for the active state of AT 1 receptors often leads to treatment failure. Therefore, characterization of robust inverse agonist ARBs for the active state of AT 1 receptors is necessary. To identify the robust inverse agonist for active state of AT 1 receptors and its molecular mechanism, we performed site-directed mutagenesis, competition binding assay, inositol phosphate production assay and molecular modelling for both ground-state wild-type AT 1 receptors and active-state N111G mutant AT 1 receptors. Although candesartan and telmisartan exhibited weaker inverse agonist activity for N111G- compared with WT-AT 1 receptors, only eprosartan exhibited robust inverse agonist activity for both N111G- and WT- AT 1 receptors. Specific ligand-receptor contacts for candesartan and telmisartan are altered in the active-state N111G- AT 1 receptors compared with the ground-state WT-AT 1 receptors, suggesting an explanation of their attenuated inverse agonist activity for the active state of AT 1 receptors. In contrast, interactions between eprosartan and N111G-AT 1 receptors were not significantly altered, and the inverse agonist activity of eprosartan was robust. Eprosartan may be a better therapeutic option than other ARBs. Comparative studies investigating eprosartan and other ARBs for the treatment of diseases caused by chronic, agonist-independent, AT 1 receptor activation are warranted. © 2018 The British Pharmacological Society.

Analysis of gait in rats with olivocerebellar lesions and ability of the nicotinic acetylcholine receptor agonist varenicline to attenuate impairments.

Science.gov (United States)

Lambert, C S; Philpot, R M; Engberg, M E; Johns, B E; Wecker, L

2015-09-15

Studies have demonstrated that administration of the neuronal nicotinic receptor agonist varenicline to rats with olivocerebellar lesions attenuates balance deficits on a rotorod and balance beam, but the effects of this drug on gait deficits have not been investigated. To accomplish this, male Sprague-Dawley rats were trained to walk on a motorized treadmill at 25 and 35 cm/s and baseline performance determined; both temporal and spatial gait parameters were analyzed. A principal component analysis (PCA) was used to identify the key components of gait, and the cumulative gait index (CGI) was calculated, representing deviations from prototypical gait patterns. Subsequently, animals either remained as non-lesioned controls or received injections of 3-acetylpyridine (3-AP)/nicotinamide to destroy the climbing fibers innervating Purkinje cells. The gait of the non-lesioned group was assessed weekly to monitor changes in the normal population, while the gait of the lesioned group was assessed 1 week following 3-AP administration, and weekly following the daily administration of saline or varenicline (0.3, 1.0, or 3.0mg free base/kg) for 2 weeks. Non-lesioned animals exhibited a 60-70% increased CGI over time due to increases in temporal gait measures, whereas lesioned animals exhibited a nearly 3-fold increased CGI as a consequence of increases in spatial measures. Following 2 weeks of treatment with the highest dose of varenicline (3.0mg free base/kg), the swing duration of lesioned animals normalized, and stride duration, stride length and step angle in this population did not differ from the non-lesioned population. Thus, varenicline enabled animals to compensate for their impairments and rectify the timing of the gait cycle. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

Science.gov (United States)

Banks, Matthew L

2016-08-01

Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

A advertência poética de Hilda Hilst em As aves da noite

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Rubens da Cunha

2017-01-01

Full Text Available Entre 1967 y 1969, Hilda Hilst escribió ocho piezas de teatro, entre ellas, As aves da noite, en la cual relata los últimos momentos de seis prisioneros en la celda del hambre, en un campo de concentración nazi. En este artículo, analizamos As aves da noite como una pieza de advertencia sobre el terror impuesto por cualquier estado totalitario, no solamente el instaurado por el nacionalsocialismo alemán. El análisis fue fundamentado, entre otros pensadores, en Alain Badiou, para quien el siglo XX no ha cumplido la promesa de la modernidad y la vida y por el contrario solamente he cumplido su destino y su designio positivo a través del terror. Nos apoyamos en las ideas de Hannah Arendt para analizar el odio y la violencia de los estados totalitarios.

Alpha-2 agonist attenuates ischemic injury in spinal cord neurons.

Science.gov (United States)

Freeman, Kirsten A; Puskas, Ferenc; Bell, Marshall T; Mares, Joshua M; Foley, Lisa S; Weyant, Michael J; Cleveland, Joseph C; Fullerton, David A; Meng, Xianzhong; Herson, Paco S; Reece, T Brett

2015-05-01

Paraplegia secondary to spinal cord ischemia-reperfusion injury remains a devastating complication of thoracoabdominal aortic intervention. The complex interactions between injured neurons and activated leukocytes have limited the understanding of neuron-specific injury. We hypothesize that spinal cord neuron cell cultures subjected to oxygen-glucose deprivation (OGD) would simulate ischemia-reperfusion injury, which could be attenuated by specific alpha-2a agonism in an Akt-dependent fashion. Spinal cords from perinatal mice were harvested, and neurons cultured in vitro for 7-10 d. Cells were pretreated with 1 μM dexmedetomidine (Dex) and subjected to OGD in an anoxic chamber. Viability was determined by MTT assay. Deoxyuridine-triphosphate nick-end labeling staining and lactate dehydrogenase (LDH) assay were used for apoptosis and necrosis identification, respectively. Western blot was used for protein analysis. Vehicle control cells were only 59% viable after 1 h of OGD. Pretreatment with Dex significantly preserves neuronal viability with 88% viable (P control cells by 50% (P neuron cell culture, OGD mimics neuronal metabolic derangement responsible for paraplegia after aortic surgery. Dex preserves neuronal viability and decreases apoptosis in an Akt-dependent fashion. Dex demonstrates clinical promise for reducing the risk of paraplegia after high-risk aortic surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Nuevos registros de aves en el bosque mesófilo de montaña del noreste de Hidalgo, México

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Miguel Angel Martínez-Morales

2015-06-01

Full Text Available Se reportan nuevos registros y ampliaciones en el área de distribución de Harpagus bidentatus, Glaucidium sanchezi, Attila spadiceus, Cyanolyca nana, Oreoscoptes montanus y Peucedramus taeniatus. Estas seis especies de aves fueron registradas en el bosque mesófilo de montaña del estado de Hidalgo, México. Dos de estas especies (G. sanchezi y C. nana son especies de distribución restringida, lo que eleva a tres el número de especies de distribución restringida en la zona. Esto enfatiza la importancia de esta región en la conservación de la diversidad de aves. Se discuten las implicaciones de estos nuevos registros en la obtención de inventarios completos de la avifauna de la región y en la conservación de su diversidad de aves.

PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies

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Harrihar A. Pershadsingh

2008-01-01

Full Text Available The angiogenic, neovascular proliferative retinopathies, proliferative diabetic retinopathy (PDR, and age-dependent macular degeneration (AMD complicated by choroidal neovascularization (CNV, also termed exudative or “wet” AMD, are common causes of blindness. The antidiabetic thiazolidinediones (TZDs, rosiglitazone, and troglitazone are PPAR agonists with demonstrable antiproliferative, and anti-inflammatory effects, in vivo, were shown to ameliorate PDR and CNV in rodent models, implying the potential efficacy of TZDs for treating proliferative retinopathies in humans. Activation of the angiotensin II type 1 receptor (AT1-R propagates proinflammatory and proliferative pathogenic determinants underlying PDR and CNV. The antihypertensive dual AT1-R blocker (ARB, telmisartan, recently was shown to activate PPAR and improve glucose and lipid metabolism and to clinically improve PDR and CNV in rodent models. Therefore, the TZDs and telmisartan, clinically approved antidiabetic and antihypertensive drugs, respectively, may be efficacious for treating and attenuating PDR and CNV humans. Clinical trials are needed to test these possibilities.

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

Science.gov (United States)

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

Prava trećih država u gospodarskom pojasu obalne države

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Marina Vokić Žužul

2003-12-01

Full Text Available Predmet ovoga rada je analiza prava koja u gospodarskom pojasu obalne države mogu ostvarivati sve obalne i neobalne države. uz detaljan prikaz pravnog uređenja materije u odredbama Konvencije o pravu mora iz 1982., razmatraju se i vladajuća gledišta međunarodnopravne doktrine te rješenja u zakonodavstvima pojedinih zemalja. Posebna pozornost je posvećena ostvarivanju tuh prava u potencijalnom hrvatskom gospodarskom pojasu, prvenstveno mogućim zahtjevima od strane susjednih neobalnih država i država u nepovoljnom geografskom položaju. Sva pitanja razmatrana u ovom radu upućuju na zaključak da ispunjavanje dužnosti prema drugim državama u budućem gospodarskom pojasu RH ne bi trebalo imati utjecaja na donošenje odluke o njegovom proglašenju.

Estudo da eficácia de espuma para a depopulação de aves para situações de emergência sanitária

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Masaio Mizuno Ishizuka

2011-04-01

Full Text Available São inúmeras as dificuldades observadas na depopulação de elevado número de aves e é importante proceder-se à depopulação no interior do próprio aviário por questões de biossegurança do homem em casos de emergência sanitária causada por doenças de aves de elevada transmissibilidade, como a influenza aviária e a doença de Newcastle. Construiu-se o equipamento gerador de espuma para provocar a anóxia física em aves. Verificou-se a eficácia da espuma gerada através do uso de líquido detergente de alta expansão sobre o sacrifício de galinhas, avaliando-se os sinais sensoriais, tempo de morte, letalidade e lesões macro e microscópicas. Duzentas galinhas de postura com 78 semanas de idade foram divididas em dez grupos experimentais e submetidas a diferentes períodos de exposição à espuma, variando de 5min30s minutos a 8min15s minutos. A partir de seis minutos de exposição à espuma 100% das aves foram mortas. A presença de bolhas de espuma na cavidade oral e traqueia foram constatadas em todos os períodos de exposição à espuma, indicando a ocorrência de asfixia física. Congestão nas mucosas da cavidade oral e traqueia foram também observadas em todos os períodos de exposição. No exame histopatológico dos pulmões de todas as aves, observou-se a presença de congestão e hemorragia difusa de moderada intensidade. Nenhuma alteração foi observada na traqueia das aves. A eficácia da espuma como método de depopulação de aves foi constatada neste trabalho, podendo ser recomendada diante da necessidade de atendimento a emergências sanitárias.

Diversidad de aves en el Centro Agropecuario Cotové, Santa Fe de Antioquia, Colombia

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Caty Milena Martínez-Bravo

2013-12-01

Full Text Available En el Centro Agropecuario Cotové, en el municipio de Santa Fe de Antioquia (Colombia, se estudió la diversidad de aves utilizando las metodologías de puntos fijos de conteo y redes de niebla en cinco usos del suelo (Frutales, Sistema silvopastoril, Bosque secundario, Pastoreo con baja densidad de árboles y Pastos de corte, para analizar la influencia sobre la composición, riqueza y abundancia de la avifauna. Se registraron 6 633 individuos de 101 especies, de las cuales 11 especies son migratorias. En términos de abundancia, la mayoría de las especies fueron raras y pocas comunes. Los gremios alimenticios mejor representados fueron insectívoros y frugívoros. El índice de Shannon indica que el Sistema silvopastoril presenta los valores de diversidad alfa más altos y los frutales los más bajos. Los usos del suelo que compartieron más especies fueron sistema Silvopastoril y Pastoreo con baja densidad de árboles. La heterogeneidad ambiental del centro actúa de forma diferente para las especies, beneficia en su mayoría aves de baja y media especificidad de hábitat, y con preferencia de hábitats de borde y áreas abiertas, por lo que se deben implementar acciones de manejo dirigidas a la conservación de áreas de regeneración natural y conectividad entre usos del suelo, para que las poblaciones de especies de aves presentes en la zona puedan ser mantenidas en el tiempo.

Dopaminergic agonists for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Gluud, L L; Gluud, C

2004-01-01

Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

Beta-agonists and animal welfare

Science.gov (United States)

The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

Ecología energética y nutricional en aves herbívoras pequeñas Energetics and nutritional ecology of small herbivorous birds

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M. VICTORIA LOPEZ-CALLEJA

2000-09-01

Full Text Available La herbivoría en aves es una estrategia poco común. Solo el 3% de las aves actuales consumen plantas como fuente de energía. Tanto la composición química de las plantas como las restricciones asociadas al vuelo y digestión en aves pueden explicar el reducido número de pequeños endotermos, como las aves, que son herbívoros. Nuestro objetivo es explicar como las aves herbívoras satisfacen sus requerimientos nutricionales y energéticos cuando consumen dietas extremadamente pobres. Para lo cual nos centramos en Phytotoma rara (Phytotomidae, posiblemente el ave herbívora más pequeña. Phytotoma rara presenta numerosas características, como el rápido tiempo de transito, un efectivo rompimiento de la pared celular, y la alta y constante actividad de las enzimas digestivas, que le permiten disponer de nutrientes y energía celulares, sin los costos energéticos asociados al desarrollo de estructuras anatómicas de fermentación bacteriana o lentos tiempos de transito. Estos son posiblemente adaptaciones cruciales en la evolución de la herbivoría en aves pequeñas.Herbivory is a rare strategy in birds. Only 3% of extant birds exploit plant material as an energy source. Both plant chemical composition and bird constraints associated to flight and digestion may explain why herbivory is so scarce in small endotherms such as birds. Here we tackle the question of how herbivorous birds meet energy/nutrient requirements when feeding on extremely poor diets. We focus on Phytotoma rara (Phytotomidae, possibly the smallest herbivorous bird. From our mini-review we conclude that several features such as the fast passage rates, an effective physical breakdown of cell walls, and constant and high activities of digestive enzymes make available the highly nutritious cell contents to the small herbivore, without the energy costs of anatomical structures for bacterial fermentation or slow passage rates. These are possible crucial adaptations in the

Cativeiro de aves como fonte de Cryptococcus neoformans na cidade de Campo Grande, Mato Grosso do Sul, Brasil

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Filiú Wander Fernando de Oliveira

2002-01-01

Full Text Available Cryptococcus neoformans é a levedura capsulada causadora de criptococose em humanos e animais. A variedade neoformans, encontrada em diversas fontes ambientais, inclusive habitats de aves, é importante causa de mortalidade em indivíduos com AIDS em todo o Mundo. Contudo, ainda não há estudos sobre a sua ecologia na região Centro Oeste brasileira, onde há registro da ocorrência de casos humanos da micose. Para estudar fontes saprofíticas de C. neoformans, na cidade de Campo Grande, foram coletadas 20 amostras de excretas de aves em distintos ambientes. Suspensão das amostras em salina estéril foram semeadas em placas com meio ágar níger. Após 5 dias, colônias mucóides marrom-escuro foram subcultivadas para identificação através de provas morfofisiológicas, determinação da variedade e sorotipagem. C. neoformans var. neoformans sorotipo A foi isolado de 10 (50% das amostras, comprovando a ocorrência saprofítica de C. neoformans na cidade de Campo Grande, relacionada a habitat de aves em cativeiro.

Aves de la confluencia del Caquetá y Orteguaza (Base aérea de Tres Esquinas Colombia

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Dugand Armando

1948-06-01

Full Text Available Los autores enumeran 156 especies y subespecies de aves coleccionadas (410 ejemplares y 24 adicionales observadas entre el 11 de agosto y el 18 de septiembre de 1947 alrededor de la base aérea militar de Tres Esquinas, cerca de la confluencia de los ríos Caquetá y Orteguaza, en la Amazonia colombiana. Entre ellas, 10 se registran por primera vez en la avifauna de Colombia.  La introducción comprende una breve reseña geográfica (un mapa y ecológica (tres fotografías de la región, y algunos datos de interes ornitogeográfico acerca de la presencia allá de tres migratorias (2 del sur y 1 del norte y otras 28 aves que muy raras veces han sido señaladas en Colombia. Además de las diez aves nuevas para este país, se extiende hasta el Alto Caquetá el área de dispersión geográfica de otras 22 (12 colecionadas y 10 observadas que son mas o menos comunes en otras partes del territorio colombiano, pero que hasta ahora no habían sido señaladas en aquella región.

Salmonella Enteritidis em Aves: Retrospectiva no Brasil

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Silva EN

2002-01-01

Full Text Available Salmonella Enteritidis (SE emergiu como um grande problema avícola e de saúde pública no Brasil a partir de 1993. Os estudos epidemiológicos, incluindo a fagotipagem e sonda complementar de rRNA, sugerem a entrada de SE no Brasil via importação de material genético avícola contaminado, provavelmente no final da década de 80. As taxas de crescimento da avicultura brasileira na década de 90 criaram condições favoráveis para a manutenção e proliferação da SE nos plantéis avícolas. Além disso, o uso indiscriminado de antibióticos em aves, particularmente as quinolonas, encorajou a manutenção de lotes positivos para SE. As cepas de SE isoladas de aves têm mostrado alta sensibilidade aos antibióticos de uso comum em avicultura, incluindo as quinolonas. Entretanto, o aumento da resistência antimicrobiana e multirresistência tem sido observado em cepas de origem humana. Os últimos levantamentos realizados no ano de 2001 continuam a mostrar que a SE em materiais avícolas é o principal sorovar responsável pelas infecções humanas. Embora as carcaças de frangos apresentem altas taxas de contaminação por SE, são os ovos e seus derivados - principalmente a maionese caseira - os principais responsáveis pelos surtos humanos. O uso de vacinas específicas em poedeiras e reprodutoras tem se mostrado uma ferramenta auxiliar no controle de SE. O procedimento mais indicado para o controle de SE na avicultura está na aquisição e produção de lotes livres do agente. As rações e matérias primas de origem animal parecem não ser tão importantes na perpetuação do problema de SE, porém, os roedores parecem ser reservatórios ambientais importantes de SE em granjas contaminadas.

Cannabinoid CB1 /CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

Science.gov (United States)

Scherma, Maria; Satta, Valentina; Collu, Roberto; Boi, Maria Francesca; Usai, Paolo; Fratta, Walter; Fadda, Paola

2017-08-01

Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients. The activity-based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic-like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle. Our data show that subchronic treatment with both the natural CB 1 /CB 2 receptor agonist Δ 9 -tetrahydrocannabinol and the synthetic CB 1 /CB 2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone. Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance. © 2017 The British Pharmacological Society.

Peripheral δ-opioid receptors attenuate the exercise pressor reflex.

Science.gov (United States)

Leal, Anna K; Yamauchi, Katsuya; Kim, Joyce; Ruiz-Velasco, Victor; Kaufman, Marc P

2013-10-15

In rats with ligated femoral arteries, the exercise pressor reflex is exaggerated, an effect that is attenuated by stimulation of peripheral μ-opioid receptors on group IV metabosensitive afferents. In contrast, δ-opioid receptors are expressed mostly on group III mechanosensitive afferents, a finding that prompted us to determine whether stimulation of these opioid receptors could also attenuate the exaggerated exercise pressor reflex in "ligated" rats. We found femoral arterial injection of [D-Pen2,D-Pen5]enkephalin (DPDPE; 1.0 μg), a δ-opioid agonist, significantly attenuated the pressor and cardioaccelerator components of the exercise pressor reflex evoked by hindlimb muscle contraction in both rats with ligated and patent femoral arteries. DPDPE significantly decreased the pressor responses to muscle mechanoreflex activation, evoked by tendon stretch, in ligated rats only. DPDPE (1.0 μg) had no effect in either group on the pressor and cardioaccelerator responses to capsaicin (0.2 μg), which primarily stimulates group IV afferents. DPDPE (1.0 μg) had no effect on the pressor and cardioaccelerator responses to lactic acid (24 mM), which stimulates group III and IV afferents, in rats with patent femoral arteries but significantly decreased the pressor response in ligated rats. Western blots revealed the amount of protein comprising the δ-opioid receptor was greater in dorsal root ganglia innervating hindlimbs with ligated femoral arteries than in dorsal root ganglia innervating hindlimbs with patent femoral arteries. Our findings support the hypothesis that stimulation of δ-opioid receptors on group III afferents attenuated the exercise pressor reflex.

The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex

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M. M. Menezes

2013-01-01

Full Text Available Metabotropic glutamate 2/3 (mGlu2/3 receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL and infralimbic (IL cortex. LY354740 (10 and 30 mg/kg, i.p. showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.. Because both compounds inhibit serotonin 2A receptor (5-HT2AR-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

Science.gov (United States)

Albertson, T E; Joy, R M; Stark, L G

1984-03-01

The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Estudo retrospectivo de afecções cirúrgicas em aves

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Patrícia F. Castro

2013-05-01

Full Text Available Avaliaram-se retrospectivamente as cirurgias realizadas em aves no Serviço de Cirurgia de Pequenos Animais do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, durante período de oito anos. De um total de 90 intervenções cirúrgicas para diagnóstico e/ou tratamento de afecções, 27 foram ortopédicas e 63 de tecidos moles. Quanto ao percentual de cirurgias ortopédicas realizadas segundo as diferentes ordens, observou-se: Psittaciformes 85,19%, Piciformes 7,41%, Anseriformes 3,70% e Falconiformes 3,70%. Para as de tecidos moles os Psittaciformes representaram 92,06%, Columbiformes 3,17%, Passeriformes 3,17% e Anseriformes 1,60%. Entre os tipos de afecções ortopédicas encontradas as fraturas apresentaram a maior ocorrência (88,90%, seguidas de luxação (3,70%, avulsão traumática de extremidade (3,70% e artrite/osteomielite (3,70%. Dentre as afecções cirúrgicas de tecidos moles as neoplasias apresentaram a maior ocorrência (30,15%, seguidas das neoformações cutâneas ou de anexos não neoplásicos (17,46%, neoformações cutâneas sem diagnóstico (7,94%, distocia (7,94%, fístula de papo (7,94%, hérnia abdominal (4,76%, sinusite (4,76%, gangrena de extremidade de membros (3,17%, perfuração de esôfago (3,17%, prolapso de cloaca (3,17%, "Necrose avascular de dígito" (1,59%, ferida na região da quilha (1,59%, perfuração de cavidade celomática (1,59%, neoformação em cavidade celomática sem diagnóstico (1,59%, corpo estranho em trato gastrointestinal (1,59% e otite (1,59%. A distribuição das afecções cirúrgicas segundo as espécies acometidas mostrou o "grupo dos papagaios", representado em sua maioria por espécies do gênero Amazona, como prevalente. O conhecimento das afecções cirúrgicas e espécies de aves mais acometidas acrescentam informações para aqueles que já atuam nesta área e servem como indicador de estudo para futuros cirurgiões de aves.

AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study

DEFF Research Database (Denmark)

Lassen, M R; Dahl, O E; Mismetti, P

2009-01-01

BACKGROUND: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication....... The primary safety outcome was the incidence of major bleeding. RESULTS: The primary efficacy outcome was assessed in 464 patients. There was a significant dose-response across the five AVE5026 groups for VTE prevention (Pincidence of VTE ranging from 5.3% to 44.1% compared with 35...

Parasitos de aves e mamíferos silvestres em cativeiro no estado de Pernambuco

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Pauline Marie de Souza Santos

2015-09-01

Full Text Available Resumo: Os animais silvestres são hospedeiros de uma grande variedade de parasitos que podem interferir em sua conservação ex situ. O objetivo deste estudo foi identificar os parasitos gastrointestinais (PGI e ectoparasitos dos animais do Centro de Triagem de Animais Silvestres (CETAS do Instituto Brasileiro de Meio Ambiente e Recursos Naturais Renováveis (IBAMA de Recife, Pernambuco, além de determinar os aspectos do manejo em cativeiro que possam estar relacionados com os parasitos identificados. Foram coletados ectoparasitos e amostras fecais de 223 aves e mamíferos, as quais foram processadas pelos métodos: microscopia direta, flutuação e sedimentação. Helmintos e/ou protozoários foram detectados em 91 (40,8% amostras fecais, sendo 64 (70,3% de aves e 27 (29,7% de mamíferos. Ovos de Capillaria sp., Ascaridida, Spirurida e oocistos de Eimeria sp. foram detectados nas amostras fecais das aves, enquanto ovos de Trichuris trichiura, Strongyloides sp., Toxocara canis, Ancylostoma sp., Strongylida e oocistos de Coccídios foram encontrados nas amostras fecais de mamíferos. Os ectoparasitos identificados em aves foram Colpocephalum turbinatum, Kurodaia (Kurodaia fulvofasciata, Halipeurus sp., Naubates sp., Saemundssonia sp., Austromenopon sp., Paragoniocotes sp., Brueelia sp., Myrsidea sp. and Pseudolynchia sp., enquanto em mamíferos os ectoparasitos identificados foram Rhipicephalus sanguineus, Amblyomma varium, A. calcaratum, A. nodosum, Ornithodoros talaje e Ctenocephalides felis felis. A. calcaratum e O. talaje são registrados pela primeira vez em Pernambuco e T. tetradactyla é apresentado como novo hospedeiro de O. talaje. Nenhum dos animais estudados apresentou sinais clínicos em decorrência da infecção/infestação parasitária. Parasitos com potencial zoonótico como T. trichiura, Strongyloides sp., T. canis e Ancylostoma sp. foram identificados em primatas não humanos e carnívoros. Precárias condições estruturais

Population trends and survival of nesting green sea turtles Chelonia mydas on Aves Island, Venezuela

Science.gov (United States)

Garcia-Cruz, Marco A.; Lampo, Margarita; Peñaloza, Claudia L.; Kendall, William L.; Solé, Genaro; Rodriguez-Clark, Kathryn M.

2015-01-01

Long-term demographic data are valuable for assessing the effect of anthropogenic impacts on endangered species and evaluating recovery programs. Using a 2-state open robust design model, we analyzed mark-recapture data from green turtles Chelonia mydas sighted between 1979 and 2009 on Aves Island, Venezuela, a rookery heavily impacted by human activities before it was declared a wildlife refuge in 1972. Based on the encounter histories of 7689 nesting females, we estimated the abundance, annual survival, and remigration intervals for this population. Female survival varied from 0.14-0.91, with a mean of 0.79, which is low compared to survival of other populations from the Caribbean (mean = 0.84) and Australia (mean = 0.95), even though we partially corrected for tag loss, which is known to negatively bias survival estimates. This supports prior suggestions that Caribbean populations in general, and the Aves Island population in particular, may be more strongly impacted than populations elsewhere. It is likely that nesters from this rookery are extracted while foraging in remote feeding grounds where hunting still occurs. Despite its relatively low survival, the nesting population at Aves Island increased during the past 30 years from approx. 500 to >1000 nesting females in 2009. Thus, this population, like others in the Caribbean and the Atlantic, seems to be slowly recovering following protective management. Although these findings support the importance of long-term conservation programs aimed at protecting nesting grounds, they also highlight the need to extend management actions to foraging grounds where human activities may still impact green turtle populations.

Estudo retrospectivo de afecções cirúrgicas em aves

OpenAIRE

Castro, Patrícia F.; Fantoni, Denise T.; Matera, Julia M.

2013-01-01

Avaliaram-se retrospectivamente as cirurgias realizadas em aves no Serviço de Cirurgia de Pequenos Animais do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, durante período de oito anos. De um total de 90 intervenções cirúrgicas para diagnóstico e/ou tratamento de afecções, 27 foram ortopédicas e 63 de tecidos moles. Quanto ao percentual de cirurgias ortopédicas realizadas segundo as diferentes ordens, observou-se: Psittaciformes 85,19%, Pici...

Saurios como predadores de ectoparásitos de aves guaneras

OpenAIRE

Pérez, José; Jahncke, Jaime

1998-01-01

Las altas densidades de las colonias favorecen el rápido contagio de ectopárasitos en las poblaciones de aves guaneras, destacando la garrapata Ornitodoros amblus, que en algunos casos llega a causar la muerte de los pichones. La lagartija Microlophus peruvianus ha sido introducida en las islas guaneras con la intención de reducir las poblaciones de garrapatas. En el presente estudio se observa que existe una predación sobre ectoparásitos por parte de las poblaciones de saurios en los tres lu...

Aves acuáticas de la Laguna de Agua Dulce y el Estero El Ermitaño, Jalisco, México

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Salvador Hernández Vázquez

2005-06-01

Full Text Available Se analizó la presencia y número de aves acuáticas, así como la distribución estacional y espacial de los diferentes grupos en la laguna de Agua Dulce y el estero El Ermitaño, Jalisco, México, entre diciembre de 1997 a noviembre de 1998. Considerando únicamente el mes de máxima abundancia de cada especie hubo 86 471 aves en ambos humedales (29 686 en Agua Dulce y 56 785 en El ermitaño, y una abundancia acumulada (suma de las abundancias mensuales de 179 808 aves (66 976 en Agua Dulce y 112 832 en Ermitaño. Se identificaron 87 especies de aves, de las cuales 78 especies estuvieron presentes en Agua Dulce y 73 especies en El Ermitaño. La riqueza y abundancia fueron influenciados por la llegada de aves migratorias por lo que el mayor número de especies e individuos se presentó durante el invierno. En general las aves mostraron preferencia por áreas someras, excepto las marinas que prefirieron áreas arenosas y protegidas por dunas como las que se encuentran en Agua Dulce. Los demás grupos como los patos y afines prefirieron las áreas con salinidades bajas, como las que se encuentran al sureste del estero El Ermitaño. La mayor abundancia de aves playeras fue observada en niveles de agua bajos, y al igual que las garzas se les observó con mayor frecuencia en sitios con salinidades altas e influenciados por las variaciones en las mareas, como los que se encuentran cerca de la boca-barra del ErmitañoWater birds from Agua Dulce lake and El Ermitaño estuary, Jalisco, Mexico. Waterbird abundance, and seasonal and spatial distribution, were studied in two natural water pools at Jalisco, México, from December 1997 through November 1998. Maximum monthly abundance in Agua Dulce lake and El Ermitaño estuary was 86 471 birds (29 686 in Agua Dulce and 56 785 in Ermitaño, with a total cummulative abundance of 179 808 individuals (66 976 in Agua Dulce and 112 832 in Ermitaño. A total of 87 waterbirds species were recorded, 78 in Agua Dulce

Radiation Attenuation and Stability of ClearView Radiation Shielding TM-A Transparent Liquid High Radiation Shield.

Science.gov (United States)

Bakshi, Jayeesh

2018-04-01

Radiation exposure is a limiting factor to work in sensitive environments seen in nuclear power and test reactors, medical isotope production facilities, spent fuel handling, etc. The established choice for high radiation shielding is lead (Pb), which is toxic, heavy, and abidance by RoHS. Concrete, leaded (Pb) bricks are used as construction materials in nuclear facilities, vaults, and hot cells for radioisotope production. Existing transparent shielding such as leaded glass provides minimal shielding attenuation in radiotherapy procedures, which in some cases is not sufficient. To make working in radioactive environments more practicable while resolving the lead (Pb) issue, a transparent, lightweight, liquid, and lead-free high radiation shield-ClearView Radiation Shielding-(Radium Incorporated, 463 Dinwiddie Ave, Waynesboro, VA). was developed. This paper presents the motivation for developing ClearView, characterization of certain aspects of its use and performance, and its specific attenuation testing. Gamma attenuation testing was done using a 1.11 × 10 Bq Co source and ANSI/HPS-N 13.11 standard. Transparency with increasing thickness, time stability of liquid state, measurements of physical properties, and performance in freezing temperatures are reported. This paper also presents a comparison of ClearView with existing radiation shields. Excerpts from LaSalle nuclear power plant are included, giving additional validation. Results demonstrated and strengthened the expected performance of ClearView as a radiation shield. Due to the proprietary nature of the work, some information is withheld.

Experimental Salmonella Gallinarum infection in light laying hen lines Infecção experimental por Salmonella Gallinarum de aves leves de postura comercial

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Angelo Berchieri Júnior

2000-03-01

Full Text Available Although the epidemiology of fowl typhoid in chickens supposedly involves a vertical transmission stage, a previous work run by the authors has suggested that this did not happen in a commercial line of laying hens highly susceptible to systemic disease with Salmonella Gallinarum. A new experiment was carried out in two other lines of commercial layers, considerably more resistant than those used in the previous study. Clinical fowl typhoid was not observed, but Salmonella Gallinarum was isolated from the spleen and liver four weeks after infection and, sporadically, from the ovary.Estudo anterior, realizado pelos mesmos autores com aves consideradas susceptíveis ao agente do tifo aviário, sugeriu que a relação entre a bactéria e a aves restringe-se ao período da enfermidade. Neste trabalho avaliou-se a relação hospedeiro-parasita entre Salmonella Gallinarum e aves leves de postura comercial, consideradas mais resistentes ao tifo aviário. As aves não desenvolveram a doença clínica, mas a bactéria foi isolada do baço e do fígado quatro semanas após a infecção e, em algumas ocasiões, também do ovário.

Muuseumihoone autorid : minevikuga tuleb silmitsi seista / Tsuyoshi Tane, Lina Ghotmeh, Dan Dorell ; interv. Ave Randviir

Index Scriptorium Estoniae

Tane, Tsuyoshi

2006-01-01

Eesti Rahva Muuseumi arhitektuurivõistluse võiduprojekti autorid Tsuyoshi Tane, Lina Ghometh ja Dan Dorell omavahelisest koostööst, võistlustööst, vastuseid kriitikale. Teistest premeeritud projektidest. Ave Randviiru kommentaar "Võidutöö teeb ajaloole psühhoanalüüsi"

Dopamine agonist withdrawal syndrome: implications for patient care.

Science.gov (United States)

Nirenberg, Melissa J

2013-08-01

Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

Aves acuáticas del estero El Salado, Puerto Vallarta, Jalisco

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Fabio Germán Cupul Magaña

2015-06-01

Full Text Available El estero El Salado es un cuerpo costero único en la región de Bahía de Banderas, México, que se encuentra sometido a la fuerte presión del crecimiento urbano de la ciudad de Puerto Vallarta, Jalisco. Su evaluación como hábitat para la avifauna acuática puede contribuir al establecimiento de las bases técnicas para la toma de decisiones acertadas en el diseño de estrategias de conservación y explotación de sus hábitats. Con este fin, de junio de 1996 a mayo de 1997, se realizó una visita mensual al estero. En cada visita se realizaron dos transectos de 250 m de largo, de la boca a la cabeza del estero, de acuerdo al método modificado del censo de transecto en banda. Se determinaron 28 especies de aves acuáticas y se contabilizaron 1,304 individuos. De acuerdo con su presencia a lo largo del año, se registraron 16 especies residentes, 11 residentes de invierno y una migratoria. Los resultados ponen de manifiesto la importancia de la zona como espacio de sustentación alimenticia, de descanso y de anidación para aves acuáticas temporales y residentes.

Ruumi kohta arvamuse avaldamiseks ei pea olema arhitekt / Katrin Koov, Ave Kongo ; intervjueerinud Merle Karro-Kalberg

Index Scriptorium Estoniae

Koov, Katrin, 1973-

2016-01-01

Erahuvikoolina tegutseva arhitektuurikooli eestvedamisel töötatakse välja ruumiõppe valikainemoodulit gümnaasiumile. Ruumiõppest räägivad arhitektide liidu president, arhitektuurikooli õpetaja Katrin Koov ja Saue gümnaasiumi kunstiõpetaja Ave Kongo

Echinuria uncinata (Rudolphi (Nematoda, Acuariidae in Netta peposaca (Vieillot (Aves, Anatidae in South America Echinuria uncinata (Rudolphi (Nematoda, Acuariidae em Netta peposaca (Vieillot (Aves, Anatidae na América do Sul

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Eliane F. da Silveira

2006-06-01

Ponta da Antena, Município de Santa Vitória do Palmar, Estado do Rio Grande do Sul, região Sul do Brasil e Alvear, Província de Corrientes, região Norte da Argentina. As amostras foram obtidas no período de 2003 a 2004. Imediatamente após o abate, cada ave foi congelada em gelo seco. As aves foram separadas por sexo, pesadas e medidas. O estado de maturidade de cada ave foi avaliado (juvenil ou adulto com base na presença ou ausência da bolsa de Fabricius. Os granulomas, contendo os nematóides, estavam situados na base do esôfago quase junto à junção com o proventrículo. Duas aves estavam positivas, com um (fistulado e dois granulomas, respectivamente. Uma das aves era proveniente do Brasil (pólo de invernia na planície costeira do Estado do Rio Grande do Sul. A outra da região Norte da Argentina, capturada em um dos pólos de nidificação, antes de empreender sua viagem em direção à costa brasileira ao longo de sua rota de migração. A prevalência da infecção foi de 3,8% e a intensidade média de infecção de 7,2. A morfometria de machos e de fêmeas permitiu a identificação dos espécimes como E. uncinata.

Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

Science.gov (United States)

Newman-Tancredi, A; Rivet, J-M; Cussac, D; Touzard, M; Chaput, C; Marini, L; Millan, M J

2003-09-01

This study employed [(35)S]guanosine 5'- O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT(1A) receptors with those of reference agonists at postsynaptic 5-HT(1A) receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E(max), values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC(50)) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT(1A) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT(1A) receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding, consistent with partial agonist properties. In [(35)S]GTPgammaS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT(1A) receptors, was more potent in the septum (pEC(50) approximately 6.5) than in the dentate gyrus of the hippocampus (pEC(50) approximately 5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 microM) did not enhance [(35)S]GTPgammaS labelling in any structure, S16924 (10 micro M) modestly increased [(35)S]GTPgammaS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 microM)-stimulated [(35)S]GTPgammaS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G

Diversidad de insectos y aves insectivoras de sotobosque en hábitats pertubados de selva lluviosa tropical

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Naranjo Luis Germán

1997-11-01

Full Text Available To examine variation in species composition, stability and diversity of insectivorous birds and their prey in understory habitats of disturbed rainforest, from March 1993 to May 1994 we measured structural variables of the vegetation and quantified bird and insect species richness and diversity at eight plots ranging from 0 to over 10 years of secondary succesion. Of all the vegetation variables, only canopy cover tended. to increase with forest age. Variation of DBH classes and total density of plants among plots explained changes in both insect richness and diversity. While variation in bird species richness and diversity among plots did not show significant trends, the abundance of insectivores was related both to foliage height diversitv and DBH diversity. Insect abundance explained both bird abundance and species richness, and insect richness was an adequate predictor of abundance of insectivorous birds. The polar coordinates of the study plots (Bray-Curtis ordination based on the abundances of insectivorous birds were inversely related to forest age.Para examinar la variación en abundancia y diversidad de aves insectívoras y de sus presas en sotobosque de selva lluviosa tropical perturbada, entre marzo de 1993 y mayo de 1994 medimos variables estructurales de la vegetación y cuantificamos la  abundancia, riqueza y diversidad de insectos y aves en ocho parcelas de 0 a más de 10 años de sucesión secundaria. Exceptuando la cobertura del dosel, que aumentó con la madurez del bosque, la vegetación no presentó tendencias relacionadas con el tiempo de regeneración del bosque. La variación en cuanto a tamaños de tallos (clases de DAP y a la densidad total de plantas entre parcelas estuvo relacionada con las diferencias de riqueza y diversidad de insectos. Aunque la variación en riqueza y diversidad de aves insectívoras no presentó tendencias significativas, su abundancia estuvo relacionada tanto con la diversidad de estratos

Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

Science.gov (United States)

Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

2018-03-06

The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied

Estudio de la fauna de aves de la cueva de Pico Ramos (Muskiz, Bizkaia.

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P. Castaños

1995-01-01

Full Text Available Se estudian los restos de Aves de la cuenca de Pico Ramos. Destaca entre las especies halladas la presencia de Alca Gigante (Pinguinus impennis a cuya extinción y hallazgos holocenos se dedica especial atención. Se ofrecen datos osteométricos y biogeográficos de las restantes especies.

Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors.

Science.gov (United States)

Kotagale, Nandkishor Ramdas; Shirbhate, Saurabh Haridas; Shukla, Pradeep; Ugale, Rajesh Ramesh

2013-08-15

Present study investigated the influence of the sigma (σ₁ and σ₂) receptors within hippocampus on the agmatine induced antinociception in neuropathic rats. Animals were subjected to sciatic nerve ligation for induction of neuropathic pain and observed the paw withdrawal latency in response to thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia. Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of agmatine attenuated neuropathic pain in sciatic nerve ligated rats. Intrahippocampal administration of σ₁ agonist (+)-pentazocine or σ₂ agonist PB28 sensitized whereas, σ₁ antagonist BD1063 or σ₂ antagonist SM21 potentiated antinociceptive effect of agmatine. The behavioral effects correlated with hippocampal tumor necrosis factor-α (TNF-α) levels observed by western blot analysis. These results suggest that both the σ₁ and σ₂ receptor subunits within hippocampus play an important role in antinociceptive action of agmatine against neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

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Menk M

2018-05-01

Full Text Available Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2 receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21 might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9, a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9, and a control group that received mechanical ventilation only (control, n=9. Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6

The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury.

Science.gov (United States)

Rathinasabapathy, Anandharajan; Horowitz, Alana; Horton, Kelsey; Kumar, Ashok; Gladson, Santhi; Unger, Thomas; Martinez, Diana; Bedse, Gaurav; West, James; Raizada, Mohan K; Steckelings, Ulrike M; Sumners, Colin; Katovich, Michael J; Shenoy, Vinayak

2018-01-01

Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT 2 ) receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21), a selective AT 2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg) to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip) either immediately (prevention protocol, BCP) or after 3 days (treatment protocol, BCT) of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition), and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT 2 receptor by C21 attenuates

The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury

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Anandharajan Rathinasabapathy

2018-03-01

Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT2 receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21, a selective AT2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip either immediately (prevention protocol, BCP or after 3 days (treatment protocol, BCT of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition, and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT2 receptor by C21 attenuates

Sports doping: emerging designer and therapeutic β2-agonists.

Science.gov (United States)

Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

2013-10-21

Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future. © 2013.

Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor

DEFF Research Database (Denmark)

Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek

2008-01-01

A library of robust ghrelin receptor mutants with single substitutions at 22 positions in the main ligand-binding pocket was employed to map binding sites for six different agonists: two peptides (the 28-amino-acid octanoylated endogenous ligand ghrelin and the hexapeptide growth hormone......, and PheVI:23 on the opposing face of transmembrane domain (TM) VI. Each of the agonists was also affected selectively by specific mutations. The mutational map of the ability of L-692,429 and GHRP-6 to act as allosteric modulators by increasing ghrelin's maximal efficacy overlapped with the common....... It is concluded that although each of the ligands in addition exploits other parts of the receptor, a large, common binding site for both small-molecule agonists--including ago-allosteric modulators--and the endogenous agonist is found on the opposing faces of TM-III and -VI of the ghrelin receptor....

Exploring the binding energy profiles of full agonists, partial agonists, and antagonists of the α7 nicotinic acetylcholine receptor.

Science.gov (United States)

Tabassum, Nargis; Ma, Qianyun; Wu, Guanzhao; Jiang, Tao; Yu, Rilei

2017-09-01

Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure. This approximate treatment of interactions suggested that full agonists, partial agonists, and antagonists of the α7 nAChR possess distinctive binding energy profiles. Results from docking revealed that ligand binding efficacy may be related to the capacity of the ligand to stabilize conformational states with a closed C loop.

Characterization of a Ca2+ response to both UTP and ATP at human P2Y11 receptors: evidence for agonist-specific signaling.

Science.gov (United States)

White, Pamela J; Webb, Tania E; Boarder, Michael R

2003-06-01

Previous reports on heterologously-expressed human P2Y11 receptors have indicated that ATP, but not UTP, is an agonist stimulating both phosphoinositidase C and adenylyl cyclase. Consistent with these findings, we report that in 1321N1 cells expressing human P2Y11 receptors, UTP stimulation did not lead to accumulation of inositol(poly)phosphates under conditions in which ATP gave a robust, concentration-dependent effect. Unexpectedly, however, both UTP and ATP stimulated increases in cytosolic Ca2+ concentration ([Ca2+]c), with both nucleotides achieving similar EC50 and maximal responses. The responses to maximally effective concentrations of ATP and UTP were not additive. The [Ca2+]c increase in response to UTP was less dependent on extracellular Ca2+ than was the response to ATP. AR-C67085 (2-propylthio-beta,gamma-difluoromethylene-d-ATP, a P2Y11-selective agonist), adenosine 5'-O-(3-thiotriphosphate), and benzoyl ATP were all full agonists with potencies similar to those of ATP and UTP. In desensitization experiments, exposure to ATP resulted in loss of the UTP response; this response was more sensitive to desensitization than that of ATP. Pertussis toxin pretreatment attenuated the response to UTP but left the ATP response unaffected. The presence of 2-aminoethyl diphenylborate differentially affected the responses of ATP and UTP. No mRNA transcripts for P2Y2 or P2Y4 were detectable in the P2Y11-expressing cells. We conclude that UTP is a Ca2+-mobilizing agonist at P2Y11 receptors and that ATP and UTP acting at the same receptor recruit distinct signaling pathways. This example of agonist-specific signaling is discussed in terms of agonist trafficking and differential signal strength.

Gonadotropin releasing hormone agonists: Expanding vistas

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Navneet Magon

2011-01-01

Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy.

Science.gov (United States)

McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Agan, Gozde; Fratantonio, James L; Simpatico, Thomas; Gold, Mark S

2015-06-01

Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid "bad dreams" remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient's regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies.

Sports doping: Emerging designer and therapeutic B2-agonists

NARCIS (Netherlands)

Fragkaki, A.G.; Georgakopoulos, C.; Sterk, S.S.; Nielen, M.W.F.

2013-01-01

Beta2-adrenergic agonists, or ß2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of ß2-agonists is prohibited in sports by the World Anti-Doping

La diversidad en aves como factor determinante de la interacción entre ecosistemas del departamento del Huila

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Alfredo Ramos Moreno

2012-01-01

Full Text Available En este estudio se realizó una descripción y análisis, en primera aproximación, de la oferta en diversidad de aves en el predio La Primavera, vereda Estambul, municipio de Teruel, departamento del Huila. A partir de la información generada, se procedió a comparar los resultados obtenidos con los reportes de aves inventariadas en el estudio GEMA (2006 desarrollado por el Instituto de Investigación de Recursos Biológicos Alexander Von Humboldt, en el Corredor Biológico entre los PNN Puracé y Cueva de Los Guácharos, con el fin de determinar la relación entre estos espacios naturales a partir del concepto de interacción entre ecosistemas, entendido como las relaciones de suministro, flujo e intercambio de materiales, energía o información, que para el casoque compete al estudio se refiere al movimiento de aves de un ecosistema a otro. El predio La Primavera, ubicado en el municipio de Teruel en el occidentedel departamento del Huila, a una altitud promedio de 900 m. s. n. m., perteneciente a la zona de vida de bosque seco tropical, sirvió de sitio de trabajo para la identificación de 32 especies de aves medianteobservación visual directa y captura con redes de niebla, de las cuales hubo dos familias que resultaron comunes a los dos estudios, pertenecientes a laThraupinae (tángaras y Tyrannidae (atrapamoscas, lo cual indica su capacidad de adaptación a pisos altitudinales diferentes. Caso particular merece la especie Tangara vitriolina (tángara rastrojera, la cual está considerada casi endémica, lo que se traduce en una alta vulnerabilidad y de especial cuidado yvigilancia. Se sugiere la realización de otras valoraciones similares en sitios que permitan establecer esta conexión ecosistémica con el fin de identificar aquellas especies que presenten características comunes para ecosistemas diferentes.

EL LABORATORIO CLÍNICO EN HEMATOLOGÍA DE AVES EXÓTICAS

OpenAIRE

Gálvez Martínez, Carlos Fernando; Ramírez Benavides, Ginés Fernando; Osorio, José Henry

2009-01-01

El empleo de las técnicas de laboratorio en la práctica veterinaria, es una herramienta indispensable que aporta información valiosa en el momento de confirmar un diagnóstico. El hemograma es uno de los estudios de rutina con mayor importancia. Los parámetros normales en el hemograma, pueden ser un indicador del buen estado de salud del animal. Sin embargo, un hemograma normal, no excluye la posibilidad de que el ave sea un portador asintomático de entidades como la psitacosis, enfermedades v...

Crescimento e absorção de nutrientes pelo feijoeiro adubado com cama de aves e fertilizantes minerais

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Késia Silva Lourenço

2013-04-01

Full Text Available O feijoeiro é tradicionalmente cultivado em pequenas propriedades, onde é comum o uso de dejetos animais para adubação das culturas. Como é uma cultura de ciclo curto, os nutrientes precisam estar disponíveis logo após a germinação, o que nem sempre acontece quando a fertilização ocorre a partir de fertilizantes orgânicos. Neste trabalho, objetivou-se avaliar a eficiência de diferentes camas de aves em relação aos fertilizantes minerais na produção de matéria seca e na liberação de nutrientes para o feijoeiro, em casa de vegetação. O experimento foi conduzido em 2010, com amostras de um Latossolo Vermelho distroférrico com 16 g kg-1 de matéria orgânica, 1,9 e 84 mg dm-3 de P e K, respectivamente, e pH 6,0. Adotou-se delineamento experimental de blocos casualizados com 10 tratamentos e cinco repetições. As unidades experimentais foram constituídas por vasos com 14 dm³ de solo e cinco plantas de feijão, do cultivar BRS Requinte, durante 60 dias. Os tratamentos consistiram de cinco camas de aves compostas pelos seguintes materiais: palha de milho, bagaço de cana-de-açúcar, palha de pastagem natural, areia ou acícula de Pinus, formulações de nutrientes (NPK, NP, PK e NK e um testemunha, sem nenhum fertilizante. Os fertilizantes minerais com P proporcionaram maior produção de matéria seca da parte aérea (MSPA e de raízes (MSRA do feijoeiro do que as camas de aves, por causa da maior liberação para o solo de N e P disponíveis. Dentre as camas estudadas, aquela constituída por areia foi a que proporcionou os maiores valores de MSPA e de MSRA. As plantas fertilizadas com as camas de aves acumularam, em média, 58,6 % do N e 59,0 % do P, em relação às fertilizadas com os tratamentos que continham N e P minerais. A taxa de recuperação pelas plantas de N e K foi maior para os nutrientes aplicados na forma mineral do que na orgânica. As camas de aves podem ser utilizadas como fertilizantes para a cultura do

Mortandad de aves marinas durante "El Niño 1997-98" en el litoral sur de San Juan de Marcona, Ica -Perú

OpenAIRE

Manuel Apaza; Aída Figari

2014-01-01

Entre agosto de 1997 y abril de 1998, se evaluó, al sur de la punta guanera de San Juan de Marcona, la mortandad de las poblaciones de aves marinas. Especies de alimentación exclusivamente pelágica y de distribución restringida al ámbito de la Corriente Peruana, como las aves guaneras Pelecanus thagus, Sula variegata y Phalacrocorax bougainvillii, el pingüino Spheniscus humboldti y el zarcillo Larosterna inca, mostraron una correlación significativa en el comportamiento mensual, relacionados ...

Registros nuevos y notables de aves acuáticas en Querétaro y estados adyacentes

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Rubén Pineda-López

2013-01-01

Full Text Available Como resultado de muestreos mensuales durante un año en embalses de Querétaro y zonas adyacentes de estados vecinos, así como de visitas a la Sierra de Lobos en Guanajuato, presentamos nuevos registros estatales de aves acuáticas para los estados de Querétaro (Bucephala albeola, Fregata magnificens, Numenius americanus, Hidalgo (Charadrius semipalmatus, Leucophaeus atricilla, Hydroprogne caspia y Guanajuato (Pelecanus occidentalis; además de registros notables de especies poco conocidas en zonas alejadas de las costas mexicanas. Estos registros muestran que los embalses de zonas semiáridas altas de México son más utilizados por especies poco frecuentes que lo que se ha pensado, y elevan a 70 las especies observadas en la zona semiárida de Querétaro, lo que confirma la importancia de los cuerpos de agua artificiales de esta región para la conservación de las aves acuáticas.

Prevention of Salmonella infection by contact using intestinal flora of adult birds and/or a mixture of organic acids Controle da transmissão de Salmonella por contato entre aves de exploração comercial pelo uso de flora intestinal de aves adultas e/ou uma mistura de ácidos orgânicos

Directory of Open Access Journals (Sweden)

Gláucia Helaine de Oliveira

2000-06-01

Full Text Available This study was carried out to assess the ability of competitive exclusion and a mixture of organic acids to prevent Salmonella infection by contact between newly hatched chicks. A bird infected with Salmonella was placed in a box containing non-infected birds, previously treated with a broth culture of faeces of adult birds (CE and/or a mixture of organic acids. The number of Salmonella organisms in the caeca of the contact birds was estimated at 4 and 8 days post-challenge. The birds were infected with Salmonella Typhimurium, Salmonella Enteritidis (both repeated 5 times, Salmonella Agona and Salmonella Infantis (3 repetitions. The same approach was used to test the mixture of organic acids alone. In this case the birds received feed containing 0.8% of a mixture of formic acid (70% and propionic acid (30%. Also, a third trial was carried out with birds inoculated with the broth culture of faeces and fed with feed containing the mixture of organic acids. Appropriate controls were included. Whereas the birds from the control groups and the groups treated with the mixture of organic acids were heavily infected with Salmonella, those pre-treated with CE or CE plus the mixture of organic acids had no viable cells per gram of caecal contents.O presente trabalho avaliou a prevenção da disseminação de quatro sorotipos de Salmonella, de interesse em avicultura e saúde pública (Salmonella Typhimurium, Salmonella Agona, Salmonella Infantis e Salmonella Enteritidis, entre aves recém-nascidas, com o intuito de diminuir a disseminação de salmonelas em rebanhos avícolas por aves que contraíram a infecção pela via vertical. Analisou-se experimentalmente a administração de microbiota intestinal de aves adultas em aves recém-nascidas, a incorporação de uma mistura de ácidos orgânicos na ração e a associação desses dois tratamentos, em grupos onde colocou-se uma ave infectada, para provocar a transmissão por contato. A microbiota

Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats

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Anna Salazar-Degracia

2017-12-01

Full Text Available Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Therapeutic options are still scarce. We hypothesized that cachexia-induced muscle oxidative stress may be attenuated in response to treatment with beta2-adrenoceptor-selective agonist formoterol in rats. In diaphragm and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally with and without treatment with formoterol (0.3 mg/kg body weight/day for seven days, daily subcutaneous injection, redox balance (protein oxidation and nitration and antioxidants and muscle proteins (1-dimensional immunoblots, carbonylated proteins (2-dimensional immunoblots, inflammatory cells (immunohistochemistry, and mitochondrial respiratory chain (MRC complex activities were explored. In the gastrocnemius, but not the diaphragm, of cancer cachectic rats compared to the controls, protein oxidation and nitration levels were increased, several functional and structural proteins were carbonylated, and in both study muscles, myosin content was reduced, inflammatory cell counts were greater, while no significant differences were seen in MRC complex activities (I, II, and IV. Treatment of cachectic rats with formoterol attenuated all the events in both respiratory and limb muscles. In this in vivo model of cancer-cachectic rats, the diaphragm is more resistant to oxidative stress. Formoterol treatment attenuated the rise in oxidative stress in the limb muscles, inflammatory cell infiltration, and the loss of myosin content seen in both study muscles, whereas no effects were observed in the MRC complex activities. These findings have therapeutic implications as they demonstrate beneficial effects of the beta2 agonist through decreased protein oxidation and inflammation in cachectic muscles, especially the gastrocnemius.

Contenido de metales pesados en hígado y plumas de aves marinas afectadas por el accidente del "Prestige" en la costa de Galicia

OpenAIRE

M Pérez López; F Cid Galán; D Hernández Moreno; AL Oropesa Jiménez; AM López Beceiro; LE Fidalgo Álvarez; F Soler Rodríguez

2005-01-01

Las aves marinas son organismos situados en la cumbre de las cadenas alimentarias oceánicas, lo que permite su empleo en programas de biomonitorización para evaluar el efecto de los más diversos contaminantes sobre estos sensibles ecosistemas. En el presente trabajo se han analizado las concentraciones de distintos metales pesados (Pb, Zn, Cd y Cu) en hígado y plumas de tres especies de aves marinas (arao, frailecillo y alca) directamente afectadas por el vertido de crudo...

Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats.

Science.gov (United States)

Kawaura, Kazuaki; Karasawa, Jun-Ichi; Hikichi, Hirohiko

2016-02-01

Negative symptoms of schizophrenia are poorly managed using the currently available antipsychotics. Previous studies indicate that agonists of the metabotropic glutamate (mGlu) 2/3 receptors may provide a novel approach for the treatment of schizophrenia. However, the effects of mGlu2/3 receptor agonists or mGlu2 receptor positive allosteric modulators have not yet been clearly elucidated in animal models of the negative symptoms of schizophrenia. Recently, we reported that the forced swimming test in rats treated with subchronic MK-801, an NMDA receptor antagonist, may be regarded as a useful test to evaluate the activities of drugs against the negative symptoms of schizophrenia. We evaluated the effects of LY379268, an mGlu2/3 receptor agonist, and BINA, an mGlu2 receptor positive allosteric modulator, on the hyperlocomotion induced by acute administration of MK-801 (0.15mg/kg, sc) and on the increase in the immobility time in the forced swimming test induced by subchronic treatment with MK-801 (0.5mg/kg, sc, twice a day for 7 days) in rats. Both LY379268 (3mg/kg, sc) and BINA (100mg/kg, ip) attenuated the increase in the immobility time induced by subchronic treatment with MK-801 at the same doses at which they attenuated the MK-801-induced increase in locomotor activity, but had no effect on the immobility time in saline-treated rats. The present results suggest that stimulation of the mGlu2 receptor attenuates the increase in the immobility time in the forced swimming test elicited by subchronic administration of MK-801, and may be potentially useful for treatment of the negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

Directory of Open Access Journals (Sweden)

Yifei Zhong

Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

Modification of opiate agonist binding by pertussis toxin

Energy Technology Data Exchange (ETDEWEB)

Abood, M.E.; Lee, N.M.; Loh, H.H.

1986-03-05

Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

Modification of opiate agonist binding by pertussis toxin

International Nuclear Information System (INIS)

Abood, M.E.; Lee, N.M.; Loh, H.H.

1986-01-01

Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

Betaine attenuates memory impairment after water-immersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus.

Science.gov (United States)

Kunisawa, Kazuo; Kido, Kiwamu; Nakashima, Natsuki; Matsukura, Takuya; Nabeshima, Toshitaka; Hiramatsu, Masayuki

2017-02-05

GABA mediated neuronal system regulates hippocampus-dependent memory and stress responses by controlling plasticity and neuronal excitability. Here, we demonstrate that betaine ameliorates water-immersion restraint stress (WIRS)-induced memory impairments. This improvement was inhibited by a betaine/GABA transporter-1 (GABA transporter-2: GAT2) inhibitor, NNC 05-2090. In this study, we investigated whether memory amelioration by betaine was mediated by the GABAergic neuronal system. Adult male mice were co-administered betaine and GABA receptor antagonists after WIRS. We also examined whether memory impairment after WIRS was attenuated by GABA receptor agonists. The memory functions were evaluated using a novel object recognition test 3-6 days after WIRS and/or the step-down type passive avoidance test at 7-8 days. The co-administration of the GABA A receptor antagonist bicuculline (1mg/kg) or the GABA B receptor antagonist phaclofen (10mg/kg) 1h after WIRS suppressed the memory-improving effects induced by betaine. Additionally, the administration of the GABA A receptor agonist muscimol (1mg/kg) or the GABA B receptor agonist baclofen (10mg/kg) 1h after WIRS attenuated memory impairments. These results were similar to the data observed with betaine. The treatment with betaine after WIRS significantly decreased the expression of GABA transaminase, and this effect was partially blocked by NNC 05-2090 in the hippocampus. WIRS caused a transient increase in hippocampal GABA levels and the changes after WIRS were not affected by betaine treatment in an in vivo microdialysis study. These results suggest that the beneficial effects of betaine may be mediated in part by changing the GABAergic neuronal system. Copyright © 2016 Elsevier B.V. All rights reserved.

Factores técnicos y ambientales implicados en la electrocución de aves en los tendidos eléctricos

Directory of Open Access Journals (Sweden)

Izquierdo Rosigue, A.

1997-10-01

Full Text Available Technical and environmental factors responsible of bird electrocution have been analyzed in low and medium tension power lines in a bird important area placed in the south of Alicante province (SE Spain. One hundred eighty six dead birds (119 birds of prey have been located in 182 poles inspected. Most species are legally protected and some are in jeopardy. Some pole types with suspended insulators have caused the same number of victims than poles with rigid insulators. Poles with rigid insulators in two levels produce more accidents than poles with one level. A different pole use according to the habitat has been observed. Birds of prey avoid poles in cultures, in the vicinity of roads and in flatlands or in hill tops. Furthermore, more electrocutions occur near bath zones. Poles in high places and located near to human altered habitats, where feeding is easy, are preferred by remainder birds.

Se analizan los factores técnicos y ambientales responsables de la electrocución de aves en tendidos de media y baja intensidad -situados en un área con una valiosa población de aves- en el sur de la provincia de Alicante. Se han localizado 186 aves muertas (119 rapaces en 182 postes visitados. La mayoría han sido especies protegidas, encontrándose, algunas de ellas, especialmente amenazadas. Los resultados muestran que algunos tipos de poste, con aisladores suspendidos, provocan un número de accidentes similar a otros tipos de postes con aisladores rígidos. Los postes con aisladores rígidos en dos planos producen más víctimas que los que presentan un único plano. Se observa que las aves realizan un uso diferente del poste en función del hábitat que lo rodea. Las rapaces evitan los postes situados sobre cultivos, los más próximos a las carreteras y los ubicados en zonas llanas o en las partes más altas de las laderas. Se encuentran más rapaces electrocutadas en aquellos postes próximos a zonas de baño. Para el resto de aves los

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

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Yelena Nersesyan

2017-11-01

Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

Reciprocity of agonistic support in ravens.

Science.gov (United States)

Fraser, Orlaith N; Bugnyar, Thomas

2012-01-01

Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals.

Checklist das aves do Estado do Mato Grosso do Sul, Brasil

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Alessandro Pacheco Nunes

Full Text Available RESUMO Em contraste com vários outros estados brasileiros, apenas recentemente o Mato Grosso do Sul iniciou o inventário organizado de sua avifauna. Relacionamos 630 espécies de aves para o Mato Grosso do Sul, pertencentes a 26 ordens e 74 famílias, que corresponde a 34% da avifauna ocorrente no Brasil. Cerca de 90% dessas espécies apresentam registros comprobatórios de ocorrência no estado conforme as normas propostas pelo CBRO. As demais ainda aguardam documentação comprobatória adequada. Quarenta e cinco espécies foram incluídas na lista terciária por apresentarem problemas de documentação comprobatória devido à ausência de circunstanciação e distribuição incompatível. A grande diversidade de fitofisionomias e paisagens sob influência dos biomas Cerrado, Pantanal, Chaco, Bosques Chiquitanos e Mata Atlântica são responsáveis em parte, pela diversidade de espécies ocorrentes no Mato Grosso do Sul. No entanto, várias dessas fitofisionomias e paisagens já foram suprimidas e/ou alteradas pela pecuária e principalmente monoculturas ( Pinus, Eucalyptus e cana-de-açúcar. Trinta e sete espécies de aves ocorrentes no estado encontram-se presentes em listas de espécies ameaçadas de extinção em âmbito global e/ou nacional. Ainda existem grandes lacunas de conhecimento sobre a avifauna sul-matogrossense, notadamente no Pantanal do Paiaguás e em regiões limítrofes com o estado de Goiás e países como Paraguai (Chaco e a Bolívia (Bosques Chiquitanos. Instituições como Embrapa Pantanal e Universidade Federal de Mato Grosso do Sul, bem como o trabalho de consultores ambientais e observadores de aves foram relevantes no avanço do conhecimento sobre a avifauna no estado. Grande parte dos museus institucionais no exterior abriga exemplares coletados no Mato Grosso do Sul, dentre os quais se destacam o Museum of Comparative Zoology (Cambridge, EUA, o American Museum of Natural History (Nova York, EUA, o The Field

Dos nuevos registros de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae) sobre Leptotila megalura (Aves: Columbidae) en la Argentina

OpenAIRE

Leonor GUARDIA

2008-01-01

Dos especies de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae), Physconelloides ceratoceps Ewing y Columbicola gracilicapitis Carriker, son registradas por primera vez sobre Leptotila megalura Sclater & Salvin (“yerutí yungueña”) (Aves: Columbidae). Además, C. gracilicapitis es citada por primera vez para la Argentina.

Los Anhingidae (Aves: Suliformes) del Neógeno de América del Sur: sistemática, filogenia y paleobiología

OpenAIRE

Diederle, Juan M.

2015-01-01

Los Anhingidae están integrados por aves acuáticas conocidas vulgarmente como anhingas o biguá-víboras (darters o snakebirds en inglés), incluidas en el orden Suliformes. Estas aves llegan a pesar de 1,05-1,81 kg y no tienen dimorfismo sexual en tamaño. Son buenas voladoras y se caracterizan por alternar planeos prolongados y utilizar corrientes termales de aire ascendentes para elevarse. En tierra caminan torpemente, mientras que en el agua pueden nadar y bucear hábilmente propulsadas por su...

Aves marinas de las costas e islas colombianas

Directory of Open Access Journals (Sweden)

Dugand Armando

1947-06-01

Full Text Available La lista de aves marinas que presento en este artículo se refiere en su mayor parte a especies que varios autores (véase Obras citadas han señalado en las costas e islas marítimas de Colombia o en las aguas extraterritoriales del Mar Caribe y del Océano Pacífico inmediatamente próximas a este país. Los ejemplares examinados que menciono fuera de tales referencias pertenecen casi todos a la colección ornitológica del Instituto de Ciencias Naturales y se señalan con las siglas ICN. Unos pocos son del museo de historia natural del Colegio Biffi, en Barranquilla, a cuyo custodio, el Hermano Hildeberto María, doy las gracias por haberme permitido examinarlos. Los que señalo con las palabras Exped. Askoy, seguidas de un numero (de la serie del American Museum of Natural History, forman parte de una interesante colección que nos envió en 1942 el doctor Robert Cushman Murphy, actual Director del Departamento de Aves del American Museum of Natural History, Nueva York. Estos fueron obtenidos por la expedición oceanográfica que, bajo la dirección del doctor Murphy, realizaron en la goleta "Askoy" varios miembros de aquel museo, acompañados por el Comandante Eduardo Fallon, de la Marina Colombiana, en aguas del Pacifico desde Panamá hasta el Ecuador. La Expedición de la "Askoy", que duró de febrero a mayo de 1941, exploró varias bahías y ensenadas en el litoral del Chocó y del Departamento del Valle, así como las islas de Gorgona y Gorgonilla al norte de la costa de Nariño, y el peñón inhabitado de Malpelo, posesión oceánica colombiana situada a unos 500 kilómetros al occidente de Buenaventura, en la latitud de 3° 59' 07" N. y la longitud de 81° 34' 27" W. de Greenwich, según posición determinada por Murphy (1936, I, p. 319, fig. 49 .

Reporte de albinismo en Podiceps major, Pelecanus thagus y Cinclodes fuscus y revisión de aves silvestres albinas del Perú

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Miriam Torres

2013-03-01

Full Text Available Reportamos observaciones de individuos albinos en tres especies de aves peruanas, el Zambullidor Grande (Podiceps major, el Pelícano peruano (Pelecanus thagus y el Churrete cordillerano (Cinclodes fuscus. Los individuos eran albinos parciales casi totalmente blancos, aparentemente adultos, que mostraron un comportamiento normal entre sus conespecíficos. La supervivencia después de varios meses pudo ser comprobada para el Pelícano peruano y el Churrete cordillerano. Debido a que la información publicada sobre albinismo en aves peruanas es muy escasa, se realizó una revisión y se recopilaron registros para otras nueve especies que son también presentados.

Aportación a las patologías de aves en cautividad

OpenAIRE

Melián Melián, Ayose

2015-01-01

Por ello, el objetivo general de la presente tesis doctoral es contribuir a un mayor conocimiento de la Medicina y la Sanidad aviar de las especies en cautividad de una colección zoológica a través de la revisión de los casos clínicos, datos anatomopatológicos y análisis laboratoriales complementarios, Para ello, se emplearon los siguientes objetivos específicos: Objetivos específicos: 1.- Diagnóstico clínico y patológico de enfermedades en aves en cautividad. 2.- Determi...

Naised käsu korras firmade juhatusse! Jah või ei? / Kairi Alt, Aveli Kippari, Karl Koort... [jt.

Index Scriptorium Estoniae

2011-01-01

Küsimusele vastavad Columbus IT Partner Eesti AS personalijuht Kairi Alt, Stele ja Riveli omanik Aveli Kippari, AS Panaviatic'i turundusjuht Karl Koort, OÜ Tarkvara Tehnoloogia Arenduskeskuse tegevjuht Indrek Vainu, AS PricewaterhouseCoopers auditiosakonna direktor Eva Jansen, Kalev Chocolate Factory tootmisjuht Hardo Reinike

Dos nuevos registros de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae sobre Leptotila megalura (Aves: Columbidae en la Argentina

Directory of Open Access Journals (Sweden)

Leonor GUARDIA

2008-01-01

Full Text Available Dos especies de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae, Physconelloides ceratoceps Ewing y Columbicola gracilicapitis Carriker, son registradas por primera vez sobre Leptotila megalura Sclater & Salvin (“yerutí yungueña” (Aves: Columbidae. Además, C. gracilicapitis es citada por primera vez para la Argentina.

Radiological verification survey results at 14 Peck Ave., Pequannock, New Jersey (PJ001V)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Johnson, C.A.

1995-05-01

The U.S. Department of Energy (DOE) conducted remedial action during 1993 at the Pompton Plains Railroad Spur and eight vicinity properties in the Wayne and Pequannock Townships in New Jersey as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). These properties are in the vicinity of the DOE-owned Wayne Interim Storage Site (WISS), formerly the W. R. Grace facility. The property at 14 Peck Ave., Pequannock, New Jersey is one of these vicinity properties. At the request of DOE, a team from Oak Ridge National Laboratory conducted an independent radiological verification survey at this property. The purpose of the survey, conducted between September and December 1993, was to confirm the success of the remedial actions performed to remove any radioactive materials in excess of the identified guidelines. The verification survey included surface gamma scans and gamma readings at 1 meter, beta-gamma scans, and the collection of soil and debris samples for radionuclide analysis. Results of the survey demonstrated that all radiological measurements on the property at 14 Peck Ave. were within applicable DOE guidelines. Based on the results of the remedial action data and confirmed by the verification survey data, the portions of the site that had been remediated during this action successfully meet the DOE remedial action objectives

Radiological verification survey results at 3 Peck Ave., Pequannock, New Jersey (PJ002V)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Johnson, C.A.

1995-05-01

The US Department of Energy (DOE) conducted remedial action during 1993 at the Pompton Plains Railroad Spur and eight vicinity properties in the Wayne and Pequannock Townships in New Jersey as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). These properties are in the vicinity of the DOE-owned Wayne Interim Storage Site (WISS), formerly the W.R. Grace facility. The property at 3 Peck Ave., Pequannock, New Jersey is one of these vicinity properties. At the request of DOE, a team from Oak Ridge National Laboratory conducted an independent radiological verification survey at this property. The purpose of the survey, conducted between September and December 1993, was to confirm the success of the remedial actions performed to remove any radioactive materials in excess of the identified guidelines. The verification survey included surface gamma scans and gamma readings at 1 meter, beta-gamma scans, and the collection of soil and debris samples for radionuclide analysis. Results of the survey demonstrated that all radiological measurements on the property at 3 Peck Ave. were within applicable DOE guidelines. Based on the results of the remedial action data and confirmed by the verification survey data, the portions of the site that had been remediated during this action successfully meet the DOE remedial action objectives

Radiological verification survey results at 15 Peck Ave., Pequannock, New Jersey (PJ005V)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Johnson, C.A.

1995-05-01

The US Department of Energy (DOE) conducted remedial action during 1993 at the Pompton Plains Railroad Spur and eight vicinity properties in the Wayne and Pequannock Townships in New Jersey as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). These properties are in the vicinity of the DOE-owned Wayne Interim Storage Site (WISS), formerly the W.R. Grace facility. The property at 15 Peck Ave., Pequannock, New Jersey is one of these vicinity properties. At the request of DOE, a team from Oak Ridge National Laboratory conducted an independent radiological verification survey at this property. The purpose of the survey, conducted between September and December 1993, was to confirm the success of the remedial actions performed to remove any radioactive materials in excess of the identified guidelines. The verification survey included surface gamma scans and gamma readings at 1 meter, beta-gamma scans, and the collection of soil and debris samples for radionuclide analysis. Results of the survey demonstrated that all radiological measurements on the property at 15 Peck Ave. were within applicable DOE guidelines. Based on the results of the remedial action data and confirmed by the verification survey data, the portions of the site that had been remediated during this action successfully meet the DOE remedial action objectives

Radiological verification survey results at 17 Peck Ave., Pequannock, New Jersey (PJ006V)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Johnson, C.A.

1995-05-01

The US Department of Energy (DOE) conducted remedial action during 1993 at the Pompton Plains Railroad Spur and eight vicinity properties in the Wayne and Pequannock Townships in New Jersey as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). These properties are in the vicinity of the DOE-owned Wayne Interim Storage Site (WISS), formerly the W.R. Grace facility. The property at 17 Peck Ave., Pequannock, New Jersey is one of these vicinity properties. At the request of DOE, a team from Oak Ridge National Laboratory conducted an independent radiological verification survey at this property. The purpose of the survey, conducted between September and December 1993, was to confirm the success of the remedial actions performed to remove any radioactive materials in excess of the identified guidelines. The verification survey included surface gamma scans and gamma readings at 1 meter, beta-gamma scans, and the collection of soil and debris samples for radionuclide analysis. Results of the survey demonstrated that all radiological measurements on the property at 17 Peck Ave. were within applicable DOE guidelines. Based on the results of the remedial action data and confirmed by the verification survey data, the portions of the site that had been remediated during this action successfully meet the DOE remedial action objectives

Radiological verification survey results at 7 Peck Ave., Pequannock, New Jersey (PJ003V)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Johnson, C.A.

1995-05-01

The US Department of Energy (DOE) conducted remedial action during 1993 at the Pompton Plains Railroad Spur and eight vicinity properties in the Wayne and Pequannock Townships in New Jersey as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). These properties are in the vicinity of the DOE-owned Wayne Interim Storage Site (WISS), formerly the W.R. Grace facility. The property at 7 Peck Ave., Pequannock, New Jersey is one of these vicinity properties. At the request of DOE, a team from Oak Ridge National Laboratory conducted an independent radiological verification survey at this property. The purpose of the survey, conducted between September and December 1993, was to confirm the success of the remedial actions performed to remove any radioactive materials in excess of the identified guidelines. The verification survey included surface gamma scans and gamma readings at 1 meter, beta-gamma scans, and the collection of soil samples for radionuclide analysis. Results of the survey demonstrated that all radiological measurements on the property at 7 Peck Ave. were within applicable DOE guidelines. Based on the results of the remedial action data and confirmed by the verification survey data, the portions of the site that had been remediated during this action successfully meet the DOE remedial action objectives

Radiological verification survey results as 13 Peck Ave., Pequannock, New Jersey (PJ004V)

International Nuclear Information System (INIS)

Rodriguez, R.E.; Johnson, C.A.

1995-05-01

The US Department of Energy (DOE) conducted remedial action during 1993 at the Pompton Plains Railroad Spur and eight vicinity properties in the Wayne and Pequannock Townships in New Jersey as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). These properties are in the vicinity of the DOE-owned Wayne Interim Storage Site (WISS), formerly the W.R. Grace facility. The property at 13 Peck Ave., Pequannock, New Jersey is one of these vicinity properties. At the request of DOE, a team from Oak Ridge National Laboratory conducted an independent radiological verification survey at this property. The purpose of the survey, conducted between September and December 1993, was to confirm the success of the remedial actions performed to remove any radioactive materials in excess of the identified guidelines. The verification survey included surface gamma scans and gamma readings at 1 meter, beta-gamma scans, and the collection of soil and debris samples for radionuclide analysis. Results of the survey demonstrated that all radiological measurements on the property at 13 Peck Ave. were within applicable DOE guidelines. Based on the results of the remedial action data and confirmed by the verification survey data, the portions of the site that had been remediated during this action successfully meet the DOE remedial action objectives

Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Directory of Open Access Journals (Sweden)

Jennifer G. Robinson

2008-01-01

Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

Principles of agonist recognition in Cys-loop receptors

DEFF Research Database (Denmark)

Lynagh, Timothy Peter; Pless, Stephan Alexander

2014-01-01

, functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically...

Manual de métodos de campo para el monitoreo de aves terrestres

Science.gov (United States)

C. John Ralph; Geoffrey R. Geupel; Peter Pyle; Thomas E. Martin; David F DeSante; Borja Milá

1996-01-01

El presente manual es una recopilación de métodos de campo para la determinación de índices de abundancia y datos demográficos de poblaciones de aves terrestres en una amplia variedad de hábitats. Está dirigido a biólogos, técnicos de campo, e investigadores de cualquier parte del Continente Americano. Los métodos descritos incluyen cuatro tipos de censos...

Long-acting β2-agonists in asthma

DEFF Research Database (Denmark)

Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten

2018-01-01

Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without...... and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from...... mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue....

Enhanced induction of apoptosis by combined treatment of human carcinoma cells with X rays and death receptor agonists

International Nuclear Information System (INIS)

Hamasu, Taku; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori

2005-01-01

The death receptors Fas and DR5 are known to be expressed not only in immune cells but also in various tumor cells. The aim of the present study was to determine whether X irradiation enhanced induction of apoptosis in Tp53 wild type and Tp53-mutated tumor cell lines treated with agonists against these death receptors. We showed that 5 Gy of X irradiation significantly up-regulated the expression of death receptors Fas and DR5 on the plasma membrane in gastric cancer cell lines MKN45 and MKN28, lung cancer cell line A549, and prostate cancer cell line DU145, and that subsequent treatments with agonistic molecules for these death receptors, Fas antibody CHl1 and TRAIL, increased the formation of active fragment p20 of caspase 3 followed by the induction of apoptosis. This death-receptor-mediated apoptosis was independent of Tp53 status since MKN28 and DU145 were Tp53-mutated. The post-irradiation treatment of the cells with N-acetyl-L-cysteine (NAC) abolished the up-regulation of the expression of Fas and DR5 on the plasma membrane. NAC also attenuated the increase in the formation of p20 and the induction of apoptosis by agonistic molecules. These results suggested that the increase in the induction of apoptosis by combined treatment with X irradiation and CHl1 or TRAIL occurred through a change of the intracellular redox state independent of Tp53 status in human carcinoma cell lines. (author)

Small-molecule AT2 receptor agonists

DEFF Research Database (Denmark)

Hallberg, Mathias; Sumners, Colin; Steckelings, U Muscha

2018-01-01

The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist...... with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8......, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also...

Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.

Science.gov (United States)

Banks, Matthew L; Negus, S Stevens

2017-04-01

Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT 2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT 2A inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT 2C receptor activation nor 5-HT 2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT 2C agonists and 5-HT 2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

Long-acting beta(2)-agonists in management of childhood asthma

DEFF Research Database (Denmark)

Bisgaard, H

2000-01-01

This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

Ascorbic acid enables reversible dopamine receptor 3H-agonist binding

International Nuclear Information System (INIS)

Leff, S.; Sibley, D.R.; Hamblin, M.; Creese, I.

1981-01-01

The effects of ascorbic acid on dopaminergic 3 H-agonist receptor binding were studied in membrane homogenates of bovine anterior pituitary and caudate, and rat striatum. In all tissues virtually no stereospecific binding (defined using 1uM (+)butaclamol) of the 3 H-agonists N-propylnorapomorphine (NPA), apomorphine, or dopamine could be demonstrated in the absence of ascorbic acid. Although levels of total 3 H-agonist binding were three to five times greater in the absence than in the presence of 0.1% ascorbic acid, the increased binding was entirely non-stereospecific. Greater amounts of dopamine-inhibitable 3 H-NPA binding could be demonstrated in the absence of 0.1% ascorbic acid, but this measure of ''specific binding'' was demonstrated not to represent dopamine receptor binding since several other catecholamines and catechol were equipotent with dopamine and more potent than the dopamine agonist (+/-)amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) in inhibiting this binding. High levels of dopamine-displaceable 3 H-agonist binding were detected in fresh and boiled homogenates of cerebellum, an area of brain which receives no dopaminergic innervation, further demonstrating the non-specific nature of 3 H-agonist binding in the absence of ascorbic acid. These studies emphasize that under typical assay conditions ascorbic acid is required in order to demonstrate reversible and specific 3 H-agonist binding to dopamine receptors

Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

Energy Technology Data Exchange (ETDEWEB)

Lukas, R.J.; Bennett, E.L.

1979-01-01

The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

New drive axles for hybrid applications in low-floor city busses. The electric axle AVE 130; Neue Antriebsachse fuer Hybridapplikationen in Niederflur-Stadtbussen. Die Elektroachse AVE 130

Energy Technology Data Exchange (ETDEWEB)

Solka, Ulrich [ZF Passau GmbH (Germany); Mueller, Axel M. [ZF Friedrichshafen AG (Germany)

2009-07-01

The contribution under consideration reports on the mechanically constructional structure of the electrically driven low-floor axle AVE 130 of ZF Friedrichshafen AG (Friedrichshafen, Federal Republic of Germany). The characteristics of the electric drive are presented with the particularities of the implemented asynchronous machine and the road performances which can be developed by a city bus using this axle. Also the system characteristics of a hybrid bus with serial hybrid drive system concerning to aggregate arrangement, mass balances and the interaction of the aggregates in the drive briefly are discussed. The results of numerical simulation regarding fuel saving potential in these systems round the remarks off.

Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

Science.gov (United States)

Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

2014-11-17

Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures

O ambiente virtual como interface na reabilitação pós-AVE: relato de caso

Directory of Open Access Journals (Sweden)

Silvia Leticia Pavão

Full Text Available INTRODUÇÃO: O acidente vascular encefálico (AVE é um quadro neurológico agudo de repercussões amplas, que exige de suas vítimas programas de reabilitação desafiadores na promoção da função. Nesse contexto, a Realidade Virtual (RV é uma ferramenta de interface na reabilitação que pode gerar altos índices de motivação do paciente e permitir adaptação da terapia ao seu nível de função. OBJETIVO: Verificar o efeito da RV por meio de videogame sobre o controle postural de um indivíduo pós-AVE. MATERIAIS E MÉTODOS: Um indivíduo pós-AVE com um ano de lesão foi submetido a um protocolo de reabilitação física com videogame numa frequência de três vezes por semana por um período de 12 semanas. Anteriormente e após o programa foi realizada dinamometria por plataforma de força para análise de variáveis relacionadas ao centro de pressão (COP. RESULTADOS: Na reavaliação, observou-se que a amplitude de deslocamento médio-lateral (x aumentou 67% na condição de olhos abertos (OA e fechados (OF; amplitude anteroposterior (y aumentou 25 e 44% em OA e OF, respectivamente; área aumentou 109 e 141% em OA e OF; velocidade diminuiu 26 e 0,27% em OA e OF. CONCLUSÃO: A RV como interface na reabilitação possivelmente ampliou a exploração da base de suporte para manutenção da estabilidade, constituindo recurso adicional no tratamento desses indivíduos.

Hormones and β-Agonists

NARCIS (Netherlands)

Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

2016-01-01

This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

INTERVENTION PHYSIOTHERAPY IN THE COMMUNITY: REPORT OF CASE OF A PATIENT WITH AVE

Directory of Open Access Journals (Sweden)

Flávia Nogueira e Ferreira

2005-10-01

Full Text Available The objective was verify the benefits of the physical therapist s intervention in the community in attention to AVE patient. This study describes a 74 year-old patient's case, feminine sex, attacked by AVE eight years ago, and possessesed the body s right side committed and was submit to physical therapeutics treatment once a week for four followed following. The patient is accompanied by PSF(Programa de Saúde da Família Inocoop neighborhood in the distrit of Jequié city, in the inclusion s areas of the Unidade de Saúde Padre Hilário Terrosi. She presented sinergismo flexor pattern and disagreements in the deambulação. We emphasized treatment the cinesioterapia with emphasis in PNF s technique, besides measures preventive to decrease complications of the hypertension, diabetes and falls. The movement of abduction foot s fingers was reestablished, as well as extension and deflection of fingers and ankle. In a significant less way, but representing patient's evolution, improvement her posture was gotten and march s aid, obtaining more safety. The patient woke up tocorporal conscience to hemiplégico side. The orientations for improvement of circulatory dynamics, hygiene, posture was valid. Conclusion: The physiotherapist's presence in the community becomes important because contribue for the promotion, prevention, recovery and rehabilitation obeing the beginnings of the current health s model and consequently promoting the improvement the life s quality of the population.

Joomɨ fíivo gaaja kaatɨi aame - La ciencia de vida escrita en las aves. Cuarta parte: Kɨɨñu “Gallineta” (Crypturellus undulatus

Directory of Open Access Journals (Sweden)

Aniceto Nejedeka (Numeyɨ

2014-09-01

Full Text Available Texto bilingüe muinane-español sobre el ave kɨɨñu, “gallineta” (Crypturellus undulatus, elaborado por Aniceto Nejedeka a partir del conocimiento de los mayores de la etnia muinane. Este texto es la cuarta parte de un libro que hemos venido publicando por fascículos, titulado La ciencia de vida escrita en las aves. El muinane es una lengua de la familia lingüística bora.

Hydrogen sulfide inhibits A2A adenosine receptor agonist induced β-amyloid production in SH-SY5Y neuroblastoma cells via a cAMP dependent pathway.

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Bhushan Vijay Nagpure

Full Text Available Alzheimer's disease (AD is the leading cause of senile dementia in today's society. Its debilitating symptoms are manifested by disturbances in many important brain functions, which are influenced by adenosine. Hence, adenosinergic system is considered as a potential therapeutic target in AD treatment. In the present study, we found that sodium hydrosulfide (NaHS, an H2S donor, 100 µM attenuated HENECA (a selective A2A receptor agonist, 10-200 nM induced β-amyloid (1-42 (Aβ42 production in SH-SY5Y cells. NaHS also interfered with HENECA-stimulated production and post-translational modification of amyloid precursor protein (APP by inhibiting its maturation. Measurement of the C-terminal APP fragments generated from its enzymatic cleavage by β-site amyloid precursor protein cleaving enzyme 1 (BACE1 showed that NaHS did not have any significant effect on β-secretase activity. However, the direct measurements of HENECA-elevated γ-secretase activity and mRNA expressions of presenilins suggested that the suppression of Aβ42 production in NaHS pretreated cells was mediated by inhibiting γ-secretase. NaHS induced reductions were accompanied by similar decreases in intracellular cAMP levels and phosphorylation of cAMP responsive element binding protein (CREB. NaHS significantly reduced the elevated cAMP and Aβ42 production caused by forskolin (an adenylyl cyclase, AC agonist alone or forskolin in combination with IBMX (a phosphodiesterase inhibitor, but had no effect on those caused by IBMX alone. Moreover, pretreatment with NaHS significantly attenuated HENECA-elevated AC activity and mRNA expressions of various AC isoforms. These data suggest that NaHS may preferentially suppress AC activity when it was stimulated. In conclusion, H2S attenuated HENECA induced Aβ42 production in SH-SY5Y neuroblastoma cells through inhibiting γ-secretase via a cAMP dependent pathway.

Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis.

Science.gov (United States)

Miranda, Marcos L; Balarini, Michelle M; Bouskela, Eliete

2015-03-01

Dexmedetomidine, an α-2 adrenergic receptor agonist, has already been used in septic patients although few studies have examined its effects on microcirculatory dysfunction, which may play an important role in perpetuating sepsis syndrome. Therefore, the authors have designed a controlled experimental study to characterize the microcirculatory effects of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microcirculation. After skinfold chamber implantation, 49 golden Syrian hamsters were randomly allocated in five groups: (1) control animals; (2) nonendotoxemic animals treated with saline; (3) nonendotoxemic animals treated with dexmedetomidine (5.0 μg kg h); (4) endotoxemic (lipopolysaccharide 1.0 mg/kg) animals treated with saline; and (5) endotoxemic animals treated with dexmedetomidine. Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Mean arterial blood pressure, heart rate, arterial blood gases, and lactate concentrations were also documented. Lipopolysaccharide administration increased leukocyte rolling and adhesion and decreased capillary perfusion. Dexmedetomidine significantly attenuated these responses: compared with endotoxemic animals treated with saline, those treated with dexmedetomidine had less leukocyte rolling (11.8 ± 7.2% vs. 24.3 ± 15.0%; P the end of the experiment. Dexmedetomidine decreased lipopolysaccharide-induced leukocyte-endothelial interactions in the hamster skinfold chamber microcirculation. This was accompanied by a significant attenuation of capillary perfusion deficits, suggesting that dexmedetomidine yields beneficial effects on endotoxemic animals' microcirculation.

Unique interaction pattern for a functionally biased ghrelin receptor agonist

DEFF Research Database (Denmark)

Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.

2011-01-01

Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers...... connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained w......Fw-Isn-NH(2) was found to be a functionally biased agonist. Thus, wFw-Isn-NH(2) mediated potent and efficacious signaling through the Ga(q) and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Ga(12...

Ticks on birds caught on the campus of the Federal Rural University of Rio de Janeiro, Brazil Carrapatos em aves capturadas no campus da Universidade Federal Rural do Rio de Janeiro, Brasil

Directory of Open Access Journals (Sweden)

Ísis Daniele Alves Costa Santolin

2012-09-01

Full Text Available The prevalence of parasitic infections, particularly those caused by ectoparasites, may influence the biology and ecology of wild birds. The aim of this study was to investigate occurrences and identify the species of ticks collected from wild birds caught on the campus of the Federal Rural University of Rio de Janeiro. The birds were caught using mist nets between October 2009 and December 2010. In total, 223 birds were caught, represented by 53 species and 19 families in nine orders. Nineteen birds (n = 7 species were parasitized by immature ticks (prevalence of 8.5%. Forty-four ticks were collected, of which 23 were nymphs and 21 were larvae. There were associations between parasitism by ticks and non-Passeriformes birds, and between parasitism and ground-dwelling birds, which was possibly due to the presence (or inclusion among the captured birds of Vanellus chilensis (Charadriiformes: Charadriidae. All the nymphs collected were identified as Amblyomma cajennense. In general terms, we must emphasize that wild birds in the study area may play the role of dispersers for the immature stages of A. cajennense, albeit non-preferentially.A prevalência das infecções parasitárias e em particular, aquelas causadas por ectoparasitos, pode influenciar na biologia e ecologia das aves silvestres. O objetivo do estudo foi investigar a ocorrência e identificar as espécies de carrapatos coletadas em aves silvestres capturadas no campus da Universidade Federal Rural do Rio de Janeiro. As aves foram coletadas em rede-de-neblina durante o período de outubro de 2009 a dezembro de 2010. No total foram capturadas 223 aves representadas por 53 espécies, 19 famílias em 9 ordens. Parasitismo por formas imaturas de carrapatos, foram encontradas em 19 aves (n = 7 espécies correspondendo a uma prevalência de 8,5%. Foram coletados 44 carrapatos onde 23 estavam em estágio de ninfa e 21 em estágio de larva. Houve associação entre o parasitismo por carrapatos

Two new records of chewing lice (Phthiraptera: Ischnocera: Philopteridae) on Leptotila megalura (Aves: Columbidae) from Argentina

OpenAIRE

Guardia, Leonor

2008-01-01

Dos especies de piojos masticadores (Phthiraptera: Ischnocera: Philopteridae), Physconelloides ceratoceps Ewing y Columbicola gracilicapitis Carriker, son registradas por primera vez sobre Leptotila megalura Sclater & Salvin ("yerutí yungueña") (Aves: Columbidae). Además, C. gracilicapitis es citada por primera vez para la Argentina.Two species of chewing lice (Phthiraptera: Ischnocera: Philopteridae), Physconelloides ceratoceps Ewing and Columbicola gracilicapitis Carriker are recorded for t...

Nota sobre colisiones de aves en las ventanas de edificios universitarios en Puerto Vallarta, México

Directory of Open Access Journals (Sweden)

Fabio Germán Cupul-Magaña

2015-06-01

Full Text Available Esta nota presenta las observaciones de 15 colisiones de aves en ventanas de edificios de la Universidad de Guadalajara en Puerto Vallarta, Jalisco, México, a lo largo de 94 días de estudio (24 de enero al 27 de abril del 2003. Columbina passerina fue la especie que presentó el mayor número de fatalidades: ocho.

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

International Nuclear Information System (INIS)

Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

2011-01-01

Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

Energy Technology Data Exchange (ETDEWEB)

Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

2011-11-18

Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

Record of Spot-winged Pigeon Patagioenas maculosa (Aves: Columbidae in Santa Catarina state, southern Brazil.

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Felipe Lohmann Arend

2009-06-01

Full Text Available We present the first record of the Spot-winged Pigeon Patagioenas maculosa (Aves: Columbidae for Santa Catarina, southern Brazil. One individual was observed on 10 September 2006 in an open area (cattle pasture and shrubby vegetation in the town of Anita Garibaldi (center-south of the state. We suggest that this punctual encounter is a result of the recent expansion of this species’ distribution due to landscape modification in the region.

Nuevos registros de piojos (Insecta: Phthiraptera) en aves domésticas y ornamentales en Chile New records of lice (Insecta: Phthiraptera) from domestic and ornamental birds from Chile

OpenAIRE

D González-Acuña; J Lara; A Cicchino

2009-01-01

Por medio del examen del plumaje de aves domésticas y ornamentales en Chile se reconfirma la presencia de los phthiraptera Menopon gallinae, Goniodes gigas, Goniocotes gallinae y Menacanthus stramineus en la gallina doméstica, Gallus gallus domesticus y se registra además por primera vez en el país la especie Menacanthus pallidulus. En aves ornamentales se registran en pavo, Meleagris gallipavo, la especie M. stramineus, en pavo real, Pavo cristatus las especies Goniodes pavonis y Amrysidea m...

Patrón de actividad y abundancia de aves en un relleno sanitario de Chile central Abundance and activity-pattern of birds at a landfill in central Chile

OpenAIRE

GABRIEL LOBOS; PATRICIO BOBADILLA; ALEJANDRA ALZAMORA; ROBERTO F THOMSON

2011-01-01

Los rellenos sanitarios constituyen un foco de atracción para la avifauna, aunque las implicancias de esta relación no han sido exploradas en el país. Nosotros monitoreamos la actividad de aves en un relleno sanitario ubicado en las proximidades de la ciudad de Santiago, capital administrativa de Chile. Las principales aves en el área fueron la gaviota dominicana (Larus dominicanus Lichtenstein), el tiuque (Milvago chimango Vieillot), la garza boyera {Buculbus ibis Linnaeus) y el águila (Gera...

Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans.

Science.gov (United States)

Andersen, Hjalte H; Melholt, Camilla; Hilborg, Sigurd D; Jerwiarz, Anne; Randers, Amalie; Simoni, Amalie; Elberling, Jesper; Arendt-Nielsen, Lars

2017-01-04

A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcome-parameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensity-dependent manner (p cold-like" counter-irritation with both L-menthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.

Metabolic effects of beta2-agonists in relation to exercise performance

DEFF Research Database (Denmark)

Kalsen, Anders

2015-01-01

athletes. The present PhD thesis is based on four manuscripts in which the acute effects of beta2-agonists on exercise performance were investigated. The aims were 1) to investigate whether supratherapeutic inhalation of beta2-agonists enhances muscle strength, anaerobic performance and aerobic performance......, 2) to uncover the mechanisms behind potential beta2-adrenergic improvements in anaerobic performance, 3) to investigate whether inhalation of beta2-agonists is ergogenic in elite athletes with or without airway hyperresponsiveness (AHR). Results from the studies of the thesis show...... administration of a certain dose, but a further increase in dose does not seem to elicit a greater performance-enhancing effect. Moreover, the effects of beta2-agonists on performance are unaffected by training status and AHR, but athletes with AHR who regularly use beta2-agonists get a reduced ergogenic...

Are camouflaged seeds less attacked by wild birds? Sementes camufladas são menos atacadas por aves silvestres?

Directory of Open Access Journals (Sweden)

Alexandre de Almeida

2010-04-01

Full Text Available Wheat, corn and rice crops in Brazil use seeds treated with systemic insecticide/nematicide carbofuran, mixed to rhodamine B red dye. Carbofuran is toxic and rhodamine B is attractive to wild birds that eat up these seeds, resulting in notable mortality during planting. A field experiment was performed in southeast Brazil to evaluate if camouflaged seeds would be less consumed by wild birds in comparison to commercial seeds with red-colored rhodamine B and aposematic blue seeds. Camouflaged seeds were less removed than seeds with rhodamine B and natural colors. The camouflaging was more effective in the presence of irregularities and litter. There was no removal of blue-colored seeds. As legislation requires treated seeds to receive a different color to avoid accidents with humans, camouflaging may be used as replacement of rhodamine B to reduce mortality rates of wild birds.Plantações de trigo milho e arroz no Brasil utilizam sementes tratadas com o inseticida e nematicida sistêmico carbofuran, associado ao corante vermelho rodamina B. O carbofuran é tóxico e a rodamina B é atrativa às aves silvestres, as quais consomem estas sementes, resultando em notável mortalidade durante o plantio. Um experimento realizado em campo agrícola no sudeste do Brasil mostrou que sementes camufladas foram menos removidas por aves silvestres do que sementes com rodamina B. A camuflagem foi potencializada em presença de irregularidades e serrapilheira no solo. Não houve remoção de sementes de cor azul, mas a formulação granular de cor azul tem causado mortalidade de aves nos USA e Canadá. Como sementes tratadas com agrotóxicos devem, de acordo com a legislação, receber coloração diferenciada para evitar acidentes com humanos, a camuflagem pode ser utilizada, substituindo a rodamina B.

Medidas de vigilancia y contención de la influenza aviar en aves. Implicaciones para la salud pública

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Alejandro Arteaga Rodríguez

2006-01-01

Full Text Available La Influenza Aviar es una enfermedad infecciosa que afecta principalmente a las aves, producida por virus de la gripe A, en la mayoría de los casos de baja patogenicidad. Debido a la rápida mutación de estos virus a formas altamente patógenas, el nivel de riesgo para la sanidad animal y la salud pública puede ser alto. Desde el año 2003, está teniendo lugar un brote de Influenza Aviar en aves producido por el subtipo H5N1 de alta patogenicidad, con transmisión y afectación humana y que presenta un riesgo potencial de producir una nueva pandemia de gripe. Ante estos brotes, es fundamental la colaboración entre los sectores implicados de la Sanidad Animal y Salud Pública que permita localizar con precisión las zonas de actividad de la enfermedad en los animales e intensificar en ellas la vigilancia de los casos en humanos. Las medidas de control de la enfermedad en animales deben ser compatibles con la reducción del riesgo de exposición humana. El objetivo de este artículo es hacer una revisión de las medidas generales desarrolladas contra la Influenza Aviar en aves, destacando los aspectos de coordinación y comunicación entre las autoridades de Sanidad Animal y Salud Pública, teniendo en cuenta que la legislación está sujeta a una renovación rápida y constante en consonancia con la dinámica de esta enfermedad.

Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

International Nuclear Information System (INIS)

Scherer, N.M.; Nathanson, N.M.

1990-01-01

Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA - ). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA + or PKA - cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA - cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA + and PKA - cells was accompanied by desensitization of functional responses. Exposure of PKA + cells to 10 -7 M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 ± 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA + or PKA - cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA - cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA + or PKA - cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%

Subtype selective kainic acid receptor agonists

DEFF Research Database (Denmark)

Bunch, Lennart; Krogsgaard-Larsen, Povl

2009-01-01

(S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands.

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Christopher F Rider

Full Text Available Acting on the glucocorticoid receptor (NR3C1, glucocorticoids are widely used to treat inflammatory diseases. However, glucocorticoid resistance often leads to suboptimal asthma control. Since glucocorticoid-induced gene expression contributes to glucocorticoid activity, the aim of this study was to use a 2 × glucocorticoid response element (GRE reporter and glucocorticoid-induced gene expression to investigate approaches to combat cytokine-induced glucocorticoid resistance. Pre-treatment with tumor necrosis factor-α (TNF or interleukin-1β inhibited dexamethasone-induced mRNA expression of the putative anti-inflammatory genes RGS2 and TSC22D3, or just TSC22D3, in primary human airway epithelial and smooth muscle cells, respectively. Dexamethasone-induced DUSP1 mRNA was unaffected. In human bronchial epithelial BEAS-2B cells, dexamethasone-induced TSC22D3 and CDKN1C expression (at 6 h was reduced by TNF pre-treatment, whereas DUSP1 and RGS2 mRNAs were unaffected. TNF pre-treatment also reduced dexamethasone-dependent 2×GRE reporter activation. This was partially reversed by PS-1145 and c-jun N-terminal kinase (JNK inhibitor VIII, inhibitors of IKK2 and JNK, respectively. However, neither inhibitor affected TNF-dependent loss of dexamethasone-induced CDKN1C or TSC22D3 mRNA. Similarly, inhibitors of the extracellular signal-regulated kinase, p38, phosphoinositide 3-kinase or protein kinase C pathways failed to attenuate TNF-dependent repression of the 2×GRE reporter. Fluticasone furoate, fluticasone propionate and budesonide were full agonists relative to dexamethasone, while GSK9027, RU24858, des-ciclesonide and GW870086X were partial agonists on the 2×GRE reporter. TNF reduced reporter activity in proportion with agonist efficacy. Full and partial agonists showed various degrees of agonism on RGS2 and TSC22D3 expression, but were equally effective at inducing CDKN1C and DUSP1, and did not affect the repression of CDKN1C or TSC22D3

Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits

International Nuclear Information System (INIS)

Ge, Gang-Feng; Shi, Wei-Wen; Yu, Chen-Huan; Jin, Xiao-Yin; Zhang, Huan-Huan; Zhang, Wen-You; Wang, Lu-Chen; Yu, Bing

2017-01-01

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis. - Highlights: • Baicalein attenuated vinorelbine-induced vascular endothelial cell apoptosis. • Baicalein inhibited vinorelbine-induced oxidative stress in HUVECs. • Baicalein inhibited activation of p38/NF-κB signaling. • Baicalein attenuated vinorelbine-induced phlebitis and inflammation in rabbits.

Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits

Energy Technology Data Exchange (ETDEWEB)

Ge, Gang-Feng [Zhejiang Chinese Medical University, Hangzhou 310053 (China); Shi, Wei-Wen [Zhejiang Medical Science and Education Development Center, Hangzhou 310006 (China); Yu, Chen-Huan; Jin, Xiao-Yin; Zhang, Huan-Huan; Zhang, Wen-You [Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013 (China); Wang, Lu-Chen [Zhejiang Chinese Medical University, Hangzhou 310053 (China); Yu, Bing, E-mail: Jellycook2002@163.com [Zhejiang Chinese Medical University, Hangzhou 310053 (China)

2017-03-01

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis. - Highlights: • Baicalein attenuated vinorelbine-induced vascular endothelial cell apoptosis. • Baicalein inhibited vinorelbine-induced oxidative stress in HUVECs. • Baicalein inhibited activation of p38/NF-κB signaling. • Baicalein attenuated vinorelbine-induced phlebitis and inflammation in rabbits.

Effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats.

Science.gov (United States)

Rylkova, Daria; Boissoneault, Jeffrey; Isaac, Shani; Prado, Melissa; Shah, Hina P; Bruijnzeel, Adrie W

2008-06-01

Tobacco addiction is a chronic disorder that is characterized by dysphoria upon smoking cessation and relapse after periods of abstinence. Previous research suggests that Neuropeptide Y (NPY) and Y1 receptor agonists attenuate negative affective states and somatic withdrawal signs. The aim of the present experiments was to investigate the effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. The intracranial self-stimulation procedure was used to assess the effects of nicotine withdrawal on brain reward function as this procedure can provide a quantitative measure of emotional states in rodents. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In the first experiment, NPY did not prevent the elevations in brain reward thresholds associated with precipitated nicotine withdrawal and elevated the brain reward thresholds of the saline-treated control rats. Similar to NPY, [D-His(26)]-NPY did not prevent the elevations in brain reward thresholds associated with precipitated nicotine withdrawal and elevated the brain reward thresholds of the saline-treated control rats. Neither NPY nor [D-His(26)]-NPY affected the response latencies. In a separate experiment, it was demonstrated that the specific Y1 receptor antagonist BIBP-3226 prevented the NPY-induced elevations in brain reward thresholds. NPY attenuated the overall somatic signs associated with precipitated nicotine withdrawal. [D-His(26)]-NPY did not affect the overall somatic signs associated with precipitated nicotine withdrawal, but decreased the number of abdominal constrictions. Both NPY and [D-His(26)]-NPY attenuated the overall somatic signs associated with spontaneous nicotine withdrawal. These findings indicate that NPY and [D-His(26)]-NPY attenuate somatic nicotine withdrawal signs, but do not prevent the deficit in brain reward function associated

Rectification of radiation-induced damage in swiss albino mice by aloe vera leaf extracts (AVE)

International Nuclear Information System (INIS)

Gehlot, P.; Goyal, P. K.

2007-01-01

From the time immemorial man has been exposed to ionizing radiation from the environment in which he lives. Radiation protection concepts and philosophy have been evolving over the past several decades. Materials and Methods: The radioprotective of effect of Aloe vera leaf extract (1000 mg/kg b.wt. orally for 15 consecutive days) has been studied against 6 Gy of gamma radiation in the intestine of Swiss albino mice at various post irradiation intervals viz. 12 hours, 24 hours. and 3, 5, 10, 20 and 30 days. Results: Crypt survival, villus length, apoptic cells, mitotic figures and goblet cells in jejunum were studied after irradiation. Irradiation produced a significant decrease in crypt survival, mitotic figures and villus length; whereas goblet and apoptic cells showed a significant increase from sham irradiated animals. The major changes were observed on day 3 after irradiation. AVE pre-treated irradiated animals resulted in a significant increase in the number of crypt cells, mitotic figures and villus length; whereas the counts of apoptic and goblet cells showed a significant decrease from respective control group at all the autopsy intervals. Irradiated animals resulted in the elevation in lipid peroxidation and a reduction in glutathione activity. On contrary, AVE treatment before irradiation caused a significant depletion in lipid peroxidation and elevation in glutathione activity. Conclusion: The present study suggests the possible radioprotective ability of Aloe vera leaf extract

Ecdysone Agonist: New Insecticides with Novel Mode of Action

Directory of Open Access Journals (Sweden)

Y. Andi Trisyono

2002-12-01

Full Text Available Development of insect resistance to insecticide has been the major driving force for the development of new insecticides. Awareness and demand from public for more environmentally friendly insecticides have contributed in shifting the trend from using broad spectrum to selective insecticides. As a result, scientists have looked for new target sites beyond the nervous system. Insect growth regulators (IGRs are more selective insecticides than conventional insecticides, and ecdysone agonists are the newest IGRs being commercialized, e.g. tebufenozide, methoxyfenozide, and halofenozide. Ecdysone agonists bind to the ecdysteroid receptors, and they act similarly to the molting hormone 20-hydroxyecdysone. The binding provides larvae or nymphs with a signal to enter a premature and lethal molting cycle. In addition, the ecdysone agonists cause a reduction in the number of eggs laid by female insects. The ecdysone agonists are being developed as selective biorational insecticides. Tebufenozide and methoxyfenozide are used to control lepidopteran insect pests, whereas halofenozide is being used to control coleopteran insect pests. Their selectivity is due to differences in the binding affinity between these compounds to the receptors in insects from different orders. The selectivity of these compounds makes them candidates to be used in combinations with other control strategies to develop integrated pest management programs in agricultural ecosystems. Key words: new insecticides, selectivity, ecdysone agonists

Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

Science.gov (United States)

Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

2016-09-08

Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

Reconstitution of high-affinity opioid agonist binding in brain membranes

Energy Technology Data Exchange (ETDEWEB)

Remmers, A.E.; Medzihradsky, F. (Univ. of Michigan Medical School, Ann Arbor (United States))

1991-03-15

In synaptosomal membranes from rat brain cortex, the {mu} selective agonist ({sup 3}H)dihydromorphine in the absence of sodium, and the nonselective antagonist ({sup 3}H)naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with K{sub d} values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 {mu}M guanosine 5{prime}-({gamma}-thio)triphosphate (GTP({gamma}S)) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP({gamma}-{sup 35}S) binding sites by 90% and low K{sub m}, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP({gamma}S) was diminished. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low K{sub m} GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor - guanine nucleotide binding protein complex.

Hypertrophic effect of inhaled beta -agonist with and without concurrent exercise training

DEFF Research Database (Denmark)

Jessen, Søren; Onslev, Johan; Lemminger, Anders

2018-01-01

INTRODUCTION: Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after...... chronic beta2 -agonist inhalation. METHODS: We investigated if inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a four-week intervention of daily terbutaline (8×0.5 mg...

Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists.

Science.gov (United States)

Schaeffer, J I; Haddad, G G

1985-09-01

To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40-60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002-2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5-25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.

FXR agonist activity of conformationally constrained analogs of GW 4064.

Science.gov (United States)

Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

2009-08-15

Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

Aves y endemismo en los bosques relictos de la vertiente occidental andina del norte del Perú y sur del Ecuador

Directory of Open Access Journals (Sweden)

Jeremy N. M. Flanagan

2013-05-01

Full Text Available Los bosques relictos de las vertientes occidentales de los Andes del norte del Perú y el sur del Ecuador forman parte de dos regiones, una la denominada región de endemismo tumbesina (caracterizada principalmente por bosques secos y otra, en altitudes mayores, la región de endemismo del sur de los Andes centrales (caracterizada por bosques nublados y páramo. La región tumbesina es reconocida por albergar gran cantidad de aves endémicas, muchas de las cuales están amenazadas, y también por el alto grado de deforestación y fragmentación de sus hábitats naturales. Este artículo presenta un resumen del estado de conservación de dichas aves y bosques, con recomendaciones para mejorar la conservación de los últimos bosques de la vertiente occidental.

Ensambles de aves en agroecosistemas de la provincia de Buenos Aires: su relación con los patrones de uso de la tierra y las características del paisaje

OpenAIRE

Codesido, Mariano

2010-01-01

Entre enero de 2006 y enero de 2008 se estudió estacionalmente la estructura de los ensambles de aves en los agroecosistemas de las diferentes unidades ecológicas de la Región Pampeana comprendidas dentro de la provincia de Buenos Aires (Pampa Ondulada, Pampa Interior Plana, Pampa Interior Arenosa, Pampa Deprimida y Pampa Austral). Los objetivos generales de la tesis son: a) describir la estructura de los ensambles de aves terrestres de los agroecosistemas de la provincia de Buenos Aires, b) ...

Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

NARCIS (Netherlands)

Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

2013-01-01

Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

DETECCIÓN Y DIFERENCIACIÓN DE Mycoplasma gallisepticum Y Mycoplasma synoviae MEDIANTE LA TÉCNICA DE PCR A PARTIR DE HISOPOS TRAQUEALES DE AVES CON SÍNTOMAS RESPIRATORIOS

Directory of Open Access Journals (Sweden)

CESAR VENTURA

2012-09-01

Full Text Available Los micoplasmas son importantes patógenos en las aves por ser responsables de cuadros respiratorios que ocasionan grandes pérdidas económicas a la industria avícola a nivel mundial. Existen principalmente dos especies de micoplasmas como causantes de enfermedad en aves comerciales, el Mycoplasma gallisepticum (MG y el Mycoplasma synoviae (MS. Teniendo en cuenta su importancia y la necesidad de conocer y diferenciar la presencia de las diferentes especies de micoplasmas presentes en las explotaciones avícolas, se tomaron 91 muestras de hisopos traqueales de aves con síntomas respiratorios, provenientes de igual número de granjas de pollo de engorde, ponedoras comerciales y reproductoras pesadas ubicadas en los departamentos de Cundinamarca y Boyacá y se determinó la presencia de MG y MS por la técnica de PCR. La prevalencia determinada fue de 39,6% para MG y 47,3% para MS, encontrándose diferencias estadísticamente significativas cuando se comparó la positividad a MG y MS y el tipo de explotación (p

MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

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Ni Luh Putu Ayu Maha Iswari

2013-04-01

Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

Effect of GABA receptor agonists or antagonists injected spinally on the blood glucose level in mice.

Science.gov (United States)

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2013-05-01

The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.

Motion Rehab AVE 3D: A VR-based exergame for post-stroke rehabilitation.

Science.gov (United States)

Trombetta, Mateus; Bazzanello Henrique, Patrícia Paula; Brum, Manoela Rogofski; Colussi, Eliane Lucia; De Marchi, Ana Carolina Bertoletti; Rieder, Rafael

2017-11-01

Recent researches about games for post-stroke rehabilitation have been increasing, focusing in upper limb, lower limb and balance situations, and showing good experiences and results. With this in mind, this paper presents Motion Rehab AVE 3D, a serious game for post-stroke rehabilitation of patients with mild stroke. The aim is offer a new technology in order to assist the traditional therapy and motivate the patient to execute his/her rehabilitation program, under health professional supervision. The game was developed with Unity game engine, supporting Kinect motion sensing input device and display devices like Smart TV 3D and Oculus Rift. It contemplates six activities considering exercises in a tridimensional space: flexion, abduction, shoulder adduction, horizontal shoulder adduction and abduction, elbow extension, wrist extension, knee flexion, and hip flexion and abduction. Motion Rehab AVE 3D also report about hits and errors to the physiotherapist evaluate the patient's progress. A pilot study with 10 healthy participants (61-75 years old) tested one of the game levels. They experienced the 3D user interface in third-person. Our initial goal was to map a basic and comfortable setup of equipment in order to adopt later. All the participants (100%) classified the interaction process as interesting and amazing for the age, presenting a good acceptance. Our evaluation showed that the game could be used as a useful tool to motivate the patients during rehabilitation sessions. Next step is to evaluate its effectiveness for stroke patients, in order to verify if the interface and game exercises contribute into the motor rehabilitation treatment progress. Copyright © 2017 Elsevier B.V. All rights reserved.

Efeito de diferentes tratamentos químicos em cama para aves de corte

Directory of Open Access Journals (Sweden)

Walter Lucca

2012-04-01

Full Text Available O objetivo do experimento foi avaliar diferentes tratamentos químicos em cama aviária para frango de corte. Foram 2 utilizadas 500 aves, em delineamento inteiramente casualizado, com cinco tratamentos: Hidróxido de cálcio (500g/m ; Sulfato de Alumínio (500g/m ; Sulfato de cálcio (1000g/m ; Sulfato de cálcio 48% + Filosilicato Expandido 28% (500g/m e testemunha com quatro repetições. As amostras de cama aviária foram coletadas a cada sete dias para determinação do pH, umidade e contagem bacteriana nos meios de cultura Ágar MacConkey, Plate Count Agar (PCA. O peso das aves não se diferenciaram estatisticamente aos 42 dias, porém se observou significância na mortalidade e a conversão alimentar, entretanto em relação ao pH da cama o ideal seria após o término da segunda semana fazer nova aplicação dos produtos químicos. Todos os tratamentos foram eficazes quanto à umidade. Na contagem bacteriana com o meio PCA para mesófilas totais houve redução do desenvolvimento bacteriano, porém com o meio Ágar MacConkey para Enterobactérias totais somente o tratamento a base de Sulfato de cálcio (48% + Filosilicato expandido (28% se mostrou significativo (P < 0,05. Para a análise estatística utilizou-se sistema SISVAR (Sistema de Analise Estatístico e Planejamento de Sistemas, 2006.

Lice (Insecta: Phthiraptera) From species of the families Furnariidae, Tyrannidae, Turdidae and icteridae (Aves: Passeriformes) from Chile

OpenAIRE

González-Acuña, Daniel; Vergara, Francisco; Moreno, Lucila; Barrientos, Carlos; Ardiles, Karen; Cicchino, Armando

2006-01-01

A total of 185 birds (nine captured alive and 176 preserved in a museum), belonging to the families Furnariidae (n=14), Tyrannidae (n=4), Turdidae (n=24) and Icteridae (n=143) (Aves: Passeriformes) were searched for lice (Phthiraptera: Philopteridae, Menoponidae). The species collected and identified were: Furnaricola titicacae Carriker 1949 from Phleocryptes melanops (Vieillot 1817), and Picicola cuniculariae Cicchino 1981 from Geositta rufipennis fasciata (Burmeister 1860) (Furnariidae); Pi...

Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists

DEFF Research Database (Denmark)

Palmer, Daniel; Gonçalves, Juliana P.L.; Hansen, Louise V.

2017-01-01

The melanocortin receptor 4 (MC4R) subtype of the melanocortin receptor family is a target for therapeutics to ameliorate metabolic dysfunction. Endogenous MC4R agonists possess a critical pharmacophore (HFRW), and cyclization of peptide agonists often enhances potency. Thus, 17 cyclized peptides...

Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

Directory of Open Access Journals (Sweden)

Martin B. Oleksiewicz

2008-01-01

Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

Identification of novel selective V2 receptor non-peptide agonists.

Science.gov (United States)

Del Tredici, Andria L; Vanover, Kim E; Knapp, Anne E; Bertozzi, Sine M; Nash, Norman R; Burstein, Ethan S; Lameh, Jelveh; Currier, Erika A; Davis, Robert E; Brann, Mark R; Mohell, Nina; Olsson, Roger; Piu, Fabrice

2008-10-30

Peptides with agonist activity at the vasopressin V(2) receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. Of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V(1b) receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V(2) receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT((R))), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V(2) receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V(2) receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V(2) receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V(2) receptor agonist deficiency.

New feather mites of the subfamily Pterodectinae (Acari: Astigmata: Proctophyllodidae) from passerines (Aves: Passeriformes) in Mato Grosso do Sul, Brazil

Czech Academy of Sciences Publication Activity Database

Mironov, S. V.; Literák, I.; Čapek, Miroslav

2008-01-01

Roč. 1947, - (2008), s. 1-38 ISSN 1175-5326 Institutional research plan: CEZ:AV0Z60930519 Keywords : Acari * Astigmata * feather mites * systematics * Brazil * Proctophyllodidae * Aves * Passeriformes Subject RIV: EG - Zoology Impact factor: 0.740, year: 2008 http://www.mapress.com/zootaxa/2008/f/zt01947p038.pdf

Diversidad de Piojos de Aves Silvestres en Bosque Seco Tropical al Norte del Tolima -resumen-

OpenAIRE

M K Ariza-Lozano; Gloria María Ariza-Lozano; M J Gómez-Martínez

2014-01-01

Los Phthiraptera son insectos ápteros dorsoventralmente aplanados. Se encuentran divididos en cuatro subórdenes de los cuales Amblycera e Ischnocera son los que parasitan aves. En Colombia los estudios de ectoparásitos son escasos en comparación con otros grupos de insectos‚ los existentes poseen un enfoque generalmente taxonómico. Con respecto al departamento del Tolima hasta el momento se ha realizado una única investigación en la que se identificaron los organismos hasta el nivel de famili...

Principles of agonist recognition in Cys-loop receptors

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Timothy eLynagh

2014-04-01

Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

Modelación matemática del consumo de presas y el flujo de energía asociado a la reproducción de Rostrhamus sociabilis (Aves, Falconiformes)

OpenAIRE

Denis, D.; Rodríguez–Ochoa, A.

2017-01-01

El gavilán caracolero (Rostrhamus sociabilis) es un ave rapaz, residente permanente y común en Cuba, clasificada como de alto interés conservacionista en el Plan de Conservación de las Aves Acuáticas de Norteamérica, en parte debido a su dieta altamente especializada en caracoles acuáticos del género Pomacea. En el presente estudio se elabora un modelo matemático en el programa Stella para analizar el consumo y la movilización de energía durante la reproducción del gavilán caracolero, ...

Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

Science.gov (United States)

Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

2010-11-01

Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. © 2010 American Academy of Forensic Sciences.

Small-molecule agonists for the glucagon-like peptide 1 receptor

DEFF Research Database (Denmark)

Knudsen, Lotte Bjerre; Kiel, Dan; Teng, Min

2007-01-01

and independent agonists. Potency of GLP-1 was not changed by the allosteric agonists, but affinity of GLP-1 for the receptor was increased. The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice. Also...

Effect of beta-agonists on LAM progression and treatment.

Science.gov (United States)

Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

2018-01-30

Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

Valor nutricional de Lemna valdiviana Phil (Araceae submetida a diferentes concentrações de fertilização com excremento de aves

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Graça Maria de Oliveira França

2009-06-01

Full Text Available http://dx.doi.org/10.5007/2175-7925.2009v22n3p19 As lemnaceas são plantas aquáticas com grande potencial de uso como matéria prima para ração de peixes devido ao alto valor nutricional. O objetivo deste estudo foi avaliar a composição química e a qualidade nutricional de Lemna valdiviana submetida a diferentes concentrações de adubação com excremento de aves. O experimento foi realizado em delineamento inteiramente casualizado com três repetições. Os tratamentos foram: Controle (sem adubação; T1 – 150g.m-3, T2 – 300g.m-3 e T3 – 450 g.m-3 de excremento de aves fresco, distribuídos em dose única para fertilizar o cultivo de L. valdiviana. A dose que proporcionou a melhor qualidade nutricional de L. valdiviana foi 450g.m-3 de excremento de aves, com teor de proteína bruta de 19,66% na matéria seca, percentual de fibras de 13,06% e teor de 0,26% de P, 1, 63% de N, 0,37% de Na e 1,22% de Ca na massa seca. Os teores alcançados nesse estudo indicam a possibilidade da L. valdiviana ser considerada uma matéria prima de boa qualidade nutricional para ser utilizada em outros experimentos como complemento na ração para peixes.

Generalized concentration addition: a method for examining mixtures containing partial agonists.

Science.gov (United States)

Howard, Gregory J; Webster, Thomas F

2009-08-07

Environmentally relevant toxic exposures often consist of simultaneous exposure to multiple agents. Methods to predict the expected outcome of such combinations are critical both to risk assessment and to an accurate judgment of whether combinations are synergistic or antagonistic. Concentration addition (CA) has commonly been used to assess the presence of synergy or antagonism in combinations of similarly acting chemicals, and to predict effects of combinations of such agents. CA has the advantage of clear graphical interpretation: Curves of constant joint effect (isoboles) must be negatively sloped straight lines if the mixture is concentration additive. However, CA cannot be directly used to assess combinations that include partial agonists, although such agents are of considerable interest. Here, we propose a natural extension of CA to a functional form that may be applied to mixtures including full agonists and partial agonists. This extended definition, for which we suggest the term "generalized concentration addition," encompasses linear isoboles with slopes of any sign. We apply this approach to the simple example of agents with dose-response relationships described by Hill functions with slope parameter n=1. The resulting isoboles are in all cases linear, with negative, zero and positive slopes. Using simple mechanistic models of ligand-receptor systems, we show that the same isobole pattern and joint effects are generated by modeled combinations of full and partial agonists. Special cases include combinations of two full agonists and a full agonist plus a competitive antagonist.

Nitrógeno dietario como un nutriente limitante en aves frugívoras Dietary nitrogen as a limiting nutrient in frugivorous birds

Directory of Open Access Journals (Sweden)

BOSQUE CARLOS

2000-09-01

Full Text Available La pulpa de las frutas es considerada un alimento inadecuado para las aves frugívoras debido a su bajo contenido de proteína. Por lo tanto, se espera que los frugívoros minimicen sus pérdidas de nitrógeno como una adaptación a la frugivoría. En esta revisión examinamos las propiedades de las frutas y los rasgos fisiológicos de los frugívoros que afectan su capacidad para subsistir en base a una dieta de frutas. La mayoría de las frutas tropicales y templadas parecen contener suficiente nitrógeno para satisfacer los requerimientos de los pájaros, si su ingesta de alimento estuviera ajustada para compensar el gasto energético. Los requerimientos, sin embargo, dependen del tamaño corporal. Las aves más grandes deberían requerir alimentos con una relación de nitrógeno a energía más elevada que las aves pequeñas. No obstante, el nitrógeno digerible puede de hecho ser limitante ya que las pulpas de las frutas parecen contener cantidades considerables de nitrógeno no-proteico y una composición de aminoácidos diferente a la requerida por las aves. Ambas características de las frutas conducen a un aumento de las pérdidas de nitrógeno en aves frugívoras al consumir dietas naturales. En términos de sus adaptaciones fisiológicas, esperaríamos que los frugívoros posean una elevada capacidad de extracción de nitrógeno de la dieta y esbozamos la posibilidad de que las bajas pérdidas urinarias de nitrógeno de los frugívoros pudieran estar relacionadas con una baja tasa metabólica. La minimización de las pérdidas endógenas fecales podría ser la adaptación más importante de los frugívoros para subsistir con base en dietas pobres en nitrógeno. No es evidente como los frugívoros especializados pueden tener requerimientos de nitrógeno más bajos que los esperados en comparación a aves de otros grupos dietarios. Finalmente, sugerimos varios tópicos de investigación que conducirían a mejorar nuestra comprensión de

Implementation and Analysis of the Chromakey Augmented Virtual Environment (ChrAVE) Version 3.0 and Virtual Environment Helicopter (VEHELO) Version 2.0 in Simulated Helicopter Training

National Research Council Canada - National Science Library

Hahn, M. E

2005-01-01

The Chromakey Augmented Virtual Environment (ChrAVE) 3.0 System is a training system created to augment initial, refresher, and proficiency training in helicopter aviation using accurate simulation...

Aspectos histomorfométricos y cuantitativos del ovario de Patagioenas maculosa (Aves, Columbidae

Directory of Open Access Journals (Sweden)

Carina Maron

2012-10-01

Full Text Available Se analizaron las variaciones estructurales y cuantitativas del ovario de Patagioenas maculosa (Temminck, 1813 durante el ciclo anual 2005 - 2006. Treinta y cinco hembras adultas se capturaron en el Departamento Río Primero (Córdoba, Argentina. Las gónadas se extrajeron, pesaron y fijaron en formol tamponado a pH 7.0 y procesaron de acuerdo a la técnica de inclusión en parafina. En la mayoría de las aves el análisis morfohistológico del ovario reveló un notorio desarrollo de la gónada desde mayo a febrero, observándose 4 ó 5 folículos vitelogénicos amarillos ≥ de 4 mm y folículos preovulatorios. El incremento del peso gonadal con un valor máximo en setiembre y octubre concordó con las características morfológicas de la fase de recrudescencia gonadal. Luego de la ovipostura, los escasos folículos en desarrollo y abundantes folículos postovulatorios y atrésicos indicaron el comienzo de la regresión ovárica. En los meses de marzo y abril, el ovario exhibió el aspecto del reposo gonadal con abundantes ovocitos primarios, folículos previtelogénicos y vitelogénicos blancos ≤ 2 mm, escasos folículos vitelogénicos amarillos ≥ 2 mm y folículos atrésicos pequeños. El peso mínimo fue registrado en marzo. De los resultados se infiere que P. maculosa ovipone durante la mayor parte del año y que la prolongada actividad gonadal de esta ave estaría relacionada con la gran disponibilidad de alimento en el área de muestreo.

The Good, the Bad, and the Ugly: Agonistic Behaviour in Juvenile Crocodilians

OpenAIRE

Brien, Matthew L.; Lang, Jeffrey W.; Webb, Grahame J.; Stevenson, Colin; Christian, Keith A.

2013-01-01

We examined agonistic behaviour in seven species of hatchling and juvenile crocodilians held in small groups (N = 4) under similar laboratory conditions. Agonistic interactions occurred in all seven species, typically involved two individuals, were short in duration (5-15 seconds), and occurred between 1600-2200 h in open water. The nature and extent of agonistic interactions, the behaviours displayed, and the level of conspecific tolerance varied among species. Discrete postures, non-contact...

Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

Directory of Open Access Journals (Sweden)

Min Gao

Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

Aplicação de pintura cromossômica em espécies da família Accipitridae (Aves, Falconiformes): considerações filogenéticas e evolutivas

OpenAIRE

TAGLIARINI, Marcella Mergulhão

2013-01-01

As análises citogenéticas de diversos Falconiformes mostraram que os acipitrídeos têm uma organização cromossômica atípica na classe Aves, com um número diplóide relativamente baixo (média de 2n= 66) e poucos pares de microcromossomos (4 a 6 pares). Propostas baseadas em citogenética clássica sugeriram que esse fato devia-se à fusão de microcromossomos presentes no cariótipo ancestral das Aves. No intuito de contribuir para o esclarecimento das questões referentes à evolução cromossô...

Valores de energia metabolizável de alguns alimentos obtidos com aves de diferentes idades Metabolizable energy values of feedstuffs obtained from poultry at different ages

Directory of Open Access Journals (Sweden)

Heloisa Helena de Carvalho Mello

2009-05-01

Full Text Available Foram realizados quatro ensaios de metabolismo com a finalidade de determinar a energia metabolizável aparente (EMA e a energia metabolizável aparente corrigida (EMAn de dez alimentos em aves em diversas idades. Os alimentos testados foram: milho, farelo de soja, sorgo, farelo de trigo, farelo de arroz integral, duas farinhas de penas, duas farinhas de vísceras e plasma sangüíneo. Utilizou-se o método de coleta total de excretas, em delineamento experimental inteiramente casualizado, com 11 tratamentos (dez alimentos e uma ração-referência e seis repetições. No primeiro ensaio, foram utilizados 528 pintos de corte machos de 10 a 17 dias de idade, totalizando oito aves por repetição; no segundo ensaio, 396 frangos de corte machos de 26 a 33 dias de idade, com seis aves por repetição; no terceiro ensaio, 264 frangos de corte machos de 40 a 47 dias de idade, com quatro aves por repetição; e, no quarto ensaio, 132 galos, com duas aves por repetição. A idade das aves influenciou os valores de EMA e EMAn do farelo de soja, do sorgo, do farelo de arroz integral, das farinhas de penas e do plasma sangüíneo, enquanto, para o farelo de trigo, teve efeito apenas sobre a EMAn.Four assays were carried out to determine the apparent metabolizable energy (AME and the corrected apparent nitrogen metabolizable energy (AMEn of ten feeds for poultry at different poultry ages. The feeds studied were: corn grain, soybean meal, ground sorghum, wheat bran, integral rice bran, two kinds of feather meal, two kinds of poultry viscera meal and spray-dried plasma. The method of total excreta collection was used to determine the AME and AMEn values. The broiler chicks were distributed on a completely randomized experimental design, with 11 treatments, six replications, with different number of animals by replication according to the assay. In the first assay, 528 male broiler chicks in the period from 10 to 17 days of age were used, with eight animals

Actividad reproductiva de Chelonia mydas (Testudines: Cheloniidae en Isla de Aves, Venezuela (2001-2008 Reproductive activity of Chelonia mydas (Testudines: Cheloniidae in Isla de Aves, Venezuela (2001-2008

Directory of Open Access Journals (Sweden)

Vicente Vera

2012-06-01

Full Text Available Isla de Aves, una isla a 650km de La Guaira, Venezuela, protegida como Refugio de Fauna Silvestre, constituye el segundo sitio de mayor anidación de la tortuga verde (Chelonia mydas (Linnaeus 1758 en el Caribe. El seguimiento de la población comenzó en 1972 y de manera más continua desde 1978. Los datos históricos indican que la captura de hembras en la isla, afectó severamente la población hasta 1978, cuando fue construida una base científico-naval. Durante las temporadas de anidación entre 2001-2008 con excepción de 2003 y 2004, las hembras fueron marcadas con placas metálicas y medidas. Asimismo, se muestreó durante 458 noches, en donde se observaron 5 154 eventos, con un máximo de 53 por noche. Los posibles eventos no observados fueron calculados ajustando la distribución temporal de eventos observados a una curva normal. El total de eventos estimados varió de =637.1±106.6 en 2001 a =2 853±42.5 en 2008 (ANOVA F(6.5gl=60.37, pReproductive activity of Chelonia mydas (Testudines: Cheloniidae in Isla de Aves, Venezuela (2001-2008. The second major nesting-site for green turtles in the Caribbean is Isla de Aves, an island protected as a wildlife refuge since 1972, located at 650km Northeast from La Guaira, Venezuela. In this island, the nesting population monitoring started in 1972 and in a more continuous way after 1978, when a Scientific-Naval Station was established and scientific observations started. Since historical data show that female captures had severely affected population levels in this island before 1978, this study aim to describe recent reproductive activities. For this, during the nesting seasons of 2001-2002 and 2005-2008, nesting females were measured and tagged using metal flipper tags. A total of 458 nights were sampled observing 5 154 female emergences, with a maximum of 53 in a single night. Non-observed emergences were calculated fitting the temporal distribution of observed emergences to a normal curve

Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells

DEFF Research Database (Denmark)

Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla

2009-01-01

: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression...... for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents...... agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates...

Long-acting beta 2-agonists in chronic obstructive pulmonary disease.

Science.gov (United States)

Llewellyn-Jones, Carol

2002-01-01

Until recently, the use of long-acting beta 2-agonists in chronic obstructive pulmonary disease has been understated. There is now evidence that they may offer benefits beyond bronchodilation. This article reviews the management of chronic obstructive pulmonary disease and looks at the place of long-acting beta 2-agonists as a first-line treatment option.

Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

DEFF Research Database (Denmark)

Goncalves de Azavedo, Carlos M. B. P.; Watterson, Kenneth R; Wargent, Ed T

2016-01-01

The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure......-activity relationship studies of a previously disclosed non-acidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although...... a significant fraction of these non-carboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice...

Riqueza y abundancia de aves en bosques ribereños de diferentes anchos en la microcuenca del río Sesesmiles, Copán, Honduras

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Inty T Arcos

2008-03-01

Full Text Available El estudió se realizó en la microcuenca del río Sesesmiles, Departamento de Copán, Honduras. El propósito fue explorar el efecto del ancho de franja de los bosques ribereños sobre la riqueza y abundancia de especies de aves que visitan estos bosques. Se encontraron 1 294 aves pertenecientes a 145 especies en bosques ribereños. La diversidad de aves estuvo ligada al ancho de franja de los bosques ribereños: se encontró mayor número de especies e individuos, en anchos iguales o mayores a 50 m. Las especies pertenecientes al grupo alimenticio de los insectívoros y nectarívoros fueron las más abundantes en las franjas ribereñas. Todas las especies de aves identificadas dependen de los bosques ribereños y responden al ancho del bosque; aún las especies más generalistas tienen algún grado de dependencia a las franjas ribereñas más anchas. Para conservar las poblaciones de aves en los paisajes agrícolas fragmentados es de suma importancia mantener franjas ribereñas que sean mayores a 50 m de ancho y que brinden suficientes habitas y recursos.Richness and abundance of birds in riparian forest belts of varied breadths at the Sesesmiles river microwatershed, Copan, Honduras. Riparian forests protect many species of plants and animals. We studied bird communities in riparian forest belts of the Sesesmiles river microwatershed, Copan, Honduras (140o 43’ 12" - 140o 58’ 35" N, 88o 53’ 23" - 89o 14’ 17" W. The main goal was to explore the effects of belt breadth on the richness and abundance of avian species visiting these forests. We selected 20 belts, and randomly established 30 observation points to monitor bird presence in the dry (March-April 2005 and rainy (June-July 2005 season (N= 60 observations. A total of 1 294 birds belonging to 145 species were recorded. Bird diversity was significantly correlated to the breadth of the riparian belts, with a greater number of species and individuals in belts 50 m wide or wider

Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist.

Science.gov (United States)

Krebs-Kraft, Desiree L; Parent, Marise B

2008-02-01

Although septal infusions of glucose typically have positive effects on memory, we have shown repeatedly that this treatment exacerbates memory deficits produced by co-infusions of gamma-aminobutyric acid (GABA) receptor agonists. The present experiments tested whether this negative interaction between glucose and GABA in the medial septum would be observed in the hippocampus, a brain region where glucose typically has positive effects on memory. Specifically, we determined whether hippocampal infusions of glucose would reverse or exacerbate memory deficits produced by hippocampal co-infusions of the GABA receptor agonist muscimol. Fifteen minutes prior to either assessing spontaneous alternation (SA) or continuous multiple trial inhibitory avoidance (CMIA) training, male Sprague-Dawley-derived rats were given bilateral hippocampal infusions of vehicle (phosphate-buffered saline [PBS], 1 microl/2 min), glucose (33 or 50 nmol), muscimol (0.3 or 0.4 microg, SA or 3 microg, CMIA) or muscimol and glucose combined in one solution. The results indicated that hippocampal infusions of muscimol alone decreased SA scores and CMIA retention latencies. More importantly, hippocampal infusions of glucose, at doses that had no effect when infused alone, attenuated (33 nmol) or reversed (50 nmol) the muscimol-induced memory deficits. Thus, although co-infusions of glucose with muscimol into the medial septum impair memory, the present findings show that an opposite effect is observed in the hippocampus. Collectively, these findings suggest that the memory-impairing interaction between glucose and GABA in the medial septum is not a general property of the brain, but rather is brain region-dependent.

Contamination with retinoic acid receptor agonists in two rivers in the Kinki region of Japan.

Science.gov (United States)

Inoue, Daisuke; Nakama, Koki; Sawada, Kazuko; Watanabe, Taro; Takagi, Mai; Sei, Kazunari; Yang, Min; Hirotsuji, Junji; Hu, Jianying; Nishikawa, Jun-ichi; Nakanishi, Tsuyoshi; Ike, Michihiko

2010-04-01

This study was conducted to investigate the agonistic activity against human retinoic acid receptor (RAR) alpha in the Lake Biwa-Yodo River and the Ina River in the Kinki region of Japan. To accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of RARalpha agonist contamination in the river basins. RARalpha agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with maximum all-trans retinoic acid (atRA) equivalents of 47.6 ng-atRA/L and 23.5 ng-atRA/L being observed in Lake Biwa-Yodo River and Ina River, respectively. The results indicated that RARalpha agonists are always present and widespread in the rivers. Comparative investigation of RARalpha and estrogen receptor alpha agonistic activities at 20 stations along each river revealed that the spatial variation pattern of RARalpha agonist contamination was entirely different from that of the estrogenic compound contamination. This suggests that the effluent from municipal wastewater treatment plants, a primary source of estrogenic compounds, seemed not to be the cause of RARalpha agonist contamination in the rivers. Fractionation using high performance liquid chromatography (HPLC) directed by the bioassay found two bioactive fractions from river water samples, suggesting the presence of at least two RARalpha agonists in the rivers. Although a trial conducted to identify RARalpha agonists in the major bioactive fraction was not completed as part of this study, comparison of retention times in HPLC analysis and quantification with liquid chromatography-mass spectrometry analysis revealed that the major causative contaminants responsible for the RARalpha agonistic activity were not RAs (natural RAR ligands) and 4-oxo-RAs, while 4-oxo-RAs were identified as the major RAR agonists in sewage in Beijing, China. These findings suggest that there are unknown RARalpha agonists with high

Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

Science.gov (United States)

Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

2015-11-18

Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

DEFF Research Database (Denmark)

Schwartz, Thue W; Holst, Birgitte

2007-01-01

Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

Simulaton of the Avedøreværket Unit 1 Cogeneration Plant with DNA

DEFF Research Database (Denmark)

Elmegaard, Brian; Houbak, Niels

2003-01-01

The simulator contest proposed for the ECOS 2003 conference has been solved using the DNA energy system simulator. The contest concerns the steam process of the Avedøreværket Unit 1 (AVV1) power plant. The plant is a 250 MWCHP plant with a maximum district heat production of 330 MJ/s. The plant has...... a net electric efficiency of 42% and a maximum energy utilization of 92%. In this paper it is demonstrated, that the DNA model of AVV1 can calculate the whole flow sheet balance at any load point, i.e., any possible combination of power production and district heat production. The paper also contains...

The treatment of Parkinson's disease with dopamine agonists

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Frank, Wilhelm

2008-06-01

Full Text Available Parkinson’s disease is a chronic degenerative organic disease with unknown causes. A disappearance of cells with melanin in the substantia nigra is considered as biological artefact of the disease, which causes a degenerative loss of neurons in the corpus striatum of mesencephalon. This structure produces also the transmitter substance dopamine. Due to this disappearance of cells dopamine is not produced in a sufficient quantity which is needed for movement of the body. The questions of this report are concerned the efficiency and safety of a treatment with dopamine agonists. Furthermore the cost-effectiveness is investigated as well as ethic questions. The goal is to give recommendation for the use of dopamine agonists to the German health system. A systematic literature search was done. The identified studies have different methodological quality and investigate different hypothesis and different outcome criteria. Therefore a qualitative method of information synthesis was chosen. Since the introduction of L-Dopa in the 1960´s it is considered as the most effective substance to reduce all the cardinal symptoms of Parkinson disease. This substance was improved in the course of time. Firstly some additional substances were given (decarbonxylase inhibitors, catechol-o-transferase inhibitors (COMT-inhibitors, monoaminoxydase-inhibitors (MAO-inhibitors and NMDA-antagonists (N-Methyl-d-aspartat-antagonists. In the practical therapy of Parkinson dopamine agonists play an important role, because they directly use the dopamine receptors. The monotherapy of Parkinson disease is basically possible and is used in early stages of the disease. Clinical practise has shown, that an add on therapy with dopamine agonists can led to a reduction of the dose of L-dopa and a reduction of following dyskinesia. The studies for effectiveness include studies for the initial therapy, monotherapy and add-on-therapy. Basically there is a good effectiveness of dopamine

Dopamine agonist activity of EMD 23,448

International Nuclear Information System (INIS)

Martin, G.E.; Pettibone, D.J.

1985-01-01

EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED 50 greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81μg/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses 3 H]-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED 50 value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the γ-butyrolactone-induced increase in striatal dopa levels (ED 50 = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP. (Author)

Diversidad y distribución de las especies de Mallophaga (Insecta en Aves y Mamíferos de la Comunidad de Madrid

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Martín Mateo, M. P.

2006-05-01

Full Text Available Based on the entomological collection of the Museo Nacional de Ciencias Naturales, MNCN (Madrid, Spain and the literature, a total of 145 species of birds and 12 species of mammals that could be potential hosts of Mallophaga, are cited for Madrid. These species are potential hosts to 306 species of Mallophaga. Only 29 species of birds (20% and 2 species of mammals (14,3% have been searched for the presence of Mallophaga. These species could be potential hosts of 91 different Mallophaga species, but only 40 species (44% are recorded. Each species present in Madrid is indicated with its the host, the material known and respective references.

Se presenta información general sobre la biodiversidad y distribución de los Mallophaga parásitos de aves y mamíferos en la Comunidad de Madrid. Con base en datos obtenidos en colecciones del MNCN (Madrid y revisión de la bibliografía de referencia, se obtienen un total de 145 especies de aves y 12 de mamíferos hospedadores potenciales de 306 especies de malófagos en la Comunidad de Madrid. De ésas, solo 29 especies de aves (20 % y 2 de mamíferos (14,3 % han sido exploradas, las cuales podrían estar parasitadas por, al menos, 91 especies diferentes de malófagos, pero solo se conocen citas de 40 especies (44 %. En cada especie indicada se señalan los hospedadores conocidos, material y referencia correspondiente para cada especie de Mallophaga citada en la Comunidad de Madrid.

Características técnico-sanitarias de expendios de carnes, pescados, aves y huevos de la ciudad de Tunja 2003

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Fred Gustavo Manrique-Abril

2011-02-01

Full Text Available Se presenta una caracterización epidemiológica de los expendios de carnes, pescado y aves de Tunja en el año 2003, resultado del diagnóstico sanitario del municipio y las visitas adelantadas por la unidad de saneamiento. Al partir del compromiso que el sector salud tiene en el componente de ambiente, surge la necesidad de crear un sistema de vigilancia epidemiológica ambiental, cuya metodología y estrategia esté orientada hacia el conocimiento de los factores de riesgo ambientales a que están expuestos los grupos humanos, con el fin de determinar prioridades y orientar los recursos de salud disponibles en el desarrollo de intervenciones; es por eso que se implantó en Tunja la vigilancia de factores de riesgo del consumo en esta estrategia, la cual, incluye la de expendios decarnes y derivados, aves huevos y pescado; entonces, se usaron las actas de inspección sanitaria y se tabuló en EPIINFO 2002 para su análisis con SPSS 11,5. Así se realizó un análisis descriptivo a 173 establecimientos y se encontró que existen condiciones diversas de sanidad respecto de la estructura física, los procesos productivos y el producto para la venta; también hay un incumplimiento de normas técnico-sanitarias, en diferentes sectores de la ciudad, que se priorizan para el control por parte de la autoridad sanitaria. Al 75% de los establecimientos no cumplen con las condiciones higiénico sanitarias en cárnicos; el 66,6% no cuenta con las condiciones en establecimiento de venta de pescados ý el 52,5% delos establecimientos de venta de aves y huevos, no cumplen con las condiciones higiénico sanitarias para tal fin.

Análisis toxicológico y estudio histopatológico de las aves muertas por la catástrofe del petrolero “Prestige”

OpenAIRE

Rodríguez Ledesma, Percy Arturo

2013-01-01

El presente trabajo de investigación es un estudio multidisciplinar que intenta explicar las posibles causas de muerte de las aves marinas afectadas por el derrame del petrolero Prestige en noviembre de 2002, frente a las costas de Galicia.

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

Science.gov (United States)

Madiraju, Padma; Hossain, Ekhtear; Anand-Srivastava, Madhu B

2018-02-07

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP 4-23 , attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP 4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O 2 - ), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP 4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP 4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO - ) in VSMC which were restored to control levels by C-ANP 4-23 treatment. Furthermore, C-ANP 4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP 4-23 , via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP 4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

International Nuclear Information System (INIS)

Molenaar, P.; Malta, E.

1986-01-01

In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-[ 125 I]iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants

Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

Energy Technology Data Exchange (ETDEWEB)

Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

2013-04-26

Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

Low-dose add-back therapy during postoperative GnRH agonist treatment

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Hsiao-Wen Tsai

2016-02-01

Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Scaffold-based pan-agonist design for the PPARα, PPARβ and PPARγ receptors.

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Li-Song Zhang

Full Text Available As important members of nuclear receptor superfamily, Peroxisome proliferator-activated receptors (PPAR play essential roles in regulating cellular differentiation, development, metabolism, and tumorigenesis of higher organisms. The PPAR receptors have 3 identified subtypes: PPARα, PPARβ and PPARγ, all of which have been treated as attractive targets for developing drugs to treat type 2 diabetes. Due to the undesirable side-effects, many PPAR agonists including PPARα/γ and PPARβ/γ dual agonists are stopped by US FDA in the clinical trials. An alternative strategy is to design novel pan-agonist that can simultaneously activate PPARα, PPARβ and PPARγ. Under such an idea, in the current study we adopted the core hopping algorithm and glide docking procedure to generate 7 novel compounds based on a typical PPAR pan-agonist LY465608. It was observed by the docking procedures and molecular dynamics simulations that the compounds generated by the core hopping and glide docking not only possessed the similar functions as the original LY465608 compound to activate PPARα, PPARβ and PPARγ receptors, but also had more favorable conformation for binding to the PPAR receptors. The additional absorption, distribution, metabolism and excretion (ADME predictions showed that the 7 compounds (especially Cpd#1 hold high potential to be novel lead compounds for the PPAR pan-agonist. Our findings can provide a new strategy or useful insights for designing the effective pan-agonists against the type 2 diabetes.

The good, the bad, and the ugly: agonistic behaviour in juvenile crocodilians.

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Matthew L Brien

Full Text Available We examined agonistic behaviour in seven species of hatchling and juvenile crocodilians held in small groups (N = 4 under similar laboratory conditions. Agonistic interactions occurred in all seven species, typically involved two individuals, were short in duration (5-15 seconds, and occurred between 1600-2200 h in open water. The nature and extent of agonistic interactions, the behaviours displayed, and the level of conspecific tolerance varied among species. Discrete postures, non-contact and contact movements are described. Three of these were species-specific: push downs by C. johnstoni; inflated tail sweeping by C. novaeguineae; and, side head striking combined with tail wagging by C. porosus. The two long-snouted species (C. johnstoni and G. gangeticus avoided contact involving the head and often raised the head up out of the way during agonistic interactions. Several behaviours not associated with aggression are also described, including snout rubbing, raising the head up high while at rest, and the use of vocalizations. The two most aggressive species (C. porosus, C. novaeguineae appeared to form dominance hierarchies, whereas the less aggressive species did not. Interspecific differences in agonistic behaviour may reflect evolutionary divergence associated with morphology, ecology, general life history and responses to interspecific conflict in areas where multiple species have co-existed. Understanding species-specific traits in agonistic behaviour and social tolerance has implications for the controlled raising of different species of hatchlings for conservation, management or production purposes.

Structure and biological activity of endogenous and synthetic agonists of GPR119

Science.gov (United States)

Tyurenkov, I. N.; Ozerov, A. A.; Kurkin, D. V.; Logvinova, E. O.; Bakulin, D. A.; Volotova, E. V.; Borodin, D. D.

2018-02-01

A G-protein-coupled receptor, GPR119, is a promising pharmacological target for a new class of hypoglycaemic drugs with an original mechanism of action, namely, increase in the glucose-dependent incretin and insulin secretion. In 2005, the first ligands were found and in the subsequent years, a large number of GPR119 agonists were synthesized in laboratories in various countries; the safest and most promising agonists have entered phase I and II clinical trials as agents for the treatment of type 2 diabetes mellitus and obesity. The review describes the major endogenous GPR119 agonists and the main trends in the design and modification of synthetic structures for increasing the hypoglycaemic activity. The data on synthetic agonists are arranged according to the type of the central core of the molecules. The bibliography includes 104 references.

Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung

Energy Technology Data Exchange (ETDEWEB)

Luo, Yueh-Hsia; Kuo, Yu-Chun; Tsai, Ming-Hsien; Ho, Chia-Chi; Tsai, Hui-Ti; Hsu, Chin-Yu; Chen, Yu-Cheng; Lin, Pinpin, E-mail: pplin@nhri.org.tw

2017-06-01

Exposure to environmental aryl hydrocarbon receptor (AhR) agonists, such as halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs), has great impacts on the development of various lung diseases. As emerging molecular targets for AhR agonists, cytokines may contribute to the inflammatory or immunotoxic effects of environmental AhR agonists. However, general cytokine expression may not specifically indicate environmental AhR agonist exposure. By comparing cytokine and chemokine expression profiles in human lung adenocarcinoma cell line CL5 treated with AhR agonists and the non-AhR agonist polychlorinated biphenyl (PCB) 39, we identified a target cytokine of environmental AhR agonist exposure of in the lungs. Thirteen cytokine and chemokine genes were altered in the AhR agonists-treated cells, but none were altered in the PCB39-treated cells. Interleukin (IL)-24 was the most highly induced gene among AhR-modulated cytokines. Cotreatment with AhR antagonist completely prevented IL-24 induction by AhR agonists in the CL5 cells. Knockdown AhR expression with short-hairpin RNA (shRNA) significantly reduced benzo[a]pyrene (BaP)-induced IL-24 mRNA levels. We further confirmed that gene transcription, but not mRNA stability, was involved in IL-24 upregulation by BaP. Particulate matter (PM) in the ambient air contains some PAHs and is reported to activate AhR. Oropharyngeal aspiration of PM significantly increased IL-24 levels in lung epithelia and in bronchoalveolar lavage fluid of mice 4 weeks after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonists. - Graphical abstract: (A) Cytokine and chemokine gene expressions were examined in CL5 cells treated with AhR and non-AhR agonists. Thirteen cytokines and chemokines genes were altered in the AhR agonist-treated cells, but not in the non-AhR agonist-treated cells. IL-24 was the most highly induced gene among the AhR-modulated cytokines. (B

Mortandad de aves marinas durante "El Niño 1997-98" en el litoral sur de San Juan de Marcona, Ica -Perú

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Manuel Apaza

2014-06-01

Full Text Available Entre agosto de 1997 y abril de 1998, se evaluó, al sur de la punta guanera de San Juan de Marcona, la mortandad de las poblaciones de aves marinas. Especies de alimentación exclusivamente pelágica y de distribución restringida al ámbito de la Corriente Peruana, como las aves guaneras Pelecanus thagus, Sula variegata y Phalacrocorax bougainvillii, el pingüino Spheniscus humboldti y el zarcillo Larosterna inca, mostraron una correlación significativa en el comportamiento mensual, relacionados con la temperatura superficial del mar y con la ausencia del recurso anchoveta Engraulis ringens durante el evento "El Niño". Otras especies consideradas en el análisis presentaron una mortandad diferente, como la gaviota de Franklin Larus pipixcan y la gaviota gris Larus modestus, en ambos casos, las especies se alimentaron de recursos alternativos, como Calosoma sp. y Emeríta analoga, respectivamente.

Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

Science.gov (United States)

Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

2017-11-01

To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The putative imidazoline receptor agonist, harmane, promotes intracellular calcium mobilisation in pancreatic beta-cells.

Science.gov (United States)

Squires, Paul E; Hills, Claire E; Rogers, Gareth J; Garland, Patrick; Farley, Sophia R; Morgan, Noel G

2004-10-06

beta-Carbolines (including harmane and pinoline) stimulate insulin secretion by a mechanism that may involve interaction with imidazoline I(3)-receptors but which also appears to be mediated by actions that are additional to imidazoline receptor agonism. Using the MIN6 beta-cell line, we now show that both the imidazoline I(3)-receptor agonist, efaroxan, and the beta-carboline, harmane, directly elevate cytosolic Ca(2+) and increase insulin secretion but that these responses display different characteristics. In the case of efaroxan, the increase in cytosolic Ca(2+) was readily reversible, whereas, with harmane, the effect persisted beyond removal of the agonist and resulted in the development of a repetitive train of Ca(2+)-oscillations whose frequency, but not amplitude, was concentration-dependent. Initiation of the Ca(2+)-oscillations by harmane was independent of extracellular calcium but was sensitive to both dantrolene and high levels (20 mM) of caffeine, suggesting the involvement of ryanodine receptor-gated Ca(2+)-release. The expression of ryanodine receptor-1 and ryanodine receptor-2 mRNA in MIN6 cells was confirmed using reverse transcription-polymerase chain reaction (RT-PCR) and, since low concentrations of caffeine (1 mM) or thimerosal (10 microM) stimulated increases in [Ca(2+)](i), we conclude that ryanodine receptors are functional in these cells. Furthermore, the increase in insulin secretion induced by harmane was attenuated by dantrolene, consistent with the involvement of ryanodine receptors in mediating this response. By contrast, the smaller insulin secretory response to efaroxan was unaffected by dantrolene. Harmane-evoked changes in cytosolic Ca(2+) were maintained by nifedipine-sensitive Ca(2+)-influx, suggesting the involvement of L-type voltage-gated Ca(2+)-channels. Taken together, these data imply that harmane may interact with ryanodine receptors to generate sustained Ca(2+)-oscillations in pancreatic beta-cells and that this effect

Do Agonistic Motives Matter More Than Anger? Three Studies of Cardiovascular Risk in Adolescents

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Ewart, Craig K.; Elder, Gavin J.; Smyth, Joshua M.; Sliwinski, Martin J.; Jorgensen, Randall S.

2011-01-01

Objective Three motivational profiles have been associated with recurring psychological stress in low-income youth and young adults: Striving to control others (agonistic striving), striving to control the self (transcendence striving), and not asserting control (dissipated striving); Agonistic Striving has been associated with elevated ambulatory blood pressure during daily activities. Three studies tested the hypotheses that: (1) Agonistic Striving is associated with poor anger regulation, and (2) Agonistic Striving and poor anger regulation interactively elevate blood pressure. Design Motivational profiles, anger regulation, and ambulatory blood pressure were assessed in a multiethnic sample of 264 urban youth. Main outcome measures (1) Anger regulation/recovery during laboratory challenge; (2) anger / blood pressure during daily activities (48 hours). Results and conclusion Replication of the profiles in distant cities showed they occur with similar frequency across differences of region, race, and gender. Analyses controlling for body size, race, and gender revealed that individuals with the Agonistic Striving profile had higher ambulatory pressure, especially during social encounters. They became more openly angry and aggressive when challenged, but did not exhibit difficulty regulating anger in the laboratory, nor did they feel more angry during monitoring. However, individuals with the Agonistic Striving profile who did display poor anger regulation in the lab had the highest blood pressure; deficient self-regulatory capability amplified the positive association between Agonistic Striving and cardiovascular risk in both genders and all ethnic groups. Although anger is thought to increase cardiovascular risk, present findings suggest that anger and elevated blood pressure are co-effects of agonistic struggles to control others. PMID:21534673

Avaliação dos comportamentos de aves poedeiras utilizando seqüência de imagens Behavior evaluation of laying hens using image sequences

Directory of Open Access Journals (Sweden)

José A. D. Barbosa Filho

2007-04-01

Full Text Available A grande preocupação com o uso de gaiolas dá-se quanto ao espaço oferecido às aves poedeiras, o qual, certamente, afeta seu bem-estar. Sendo assim, este trabalho teve o objetivo de avaliar aspectos relacionados ao comportamento e bem-estar animal, comparando o sistema de criação alternativo (com cama e ninho com o sistema convencional em gaiolas. Para isso, dois grupos de 20 aves (10 Hy-Line W36 e 10 Hy-Line Brown em início de produção foram divididos em dois sistemas de criação (cama+ninho e gaiolas e colocadas em câmara climática: um grupo a 26 °C e 60% UR (condição de conforto térmico, e outro a 35 °C e 70% UR (condição de estresse térmico, onde eram constantemente monitoradas por câmeras de vídeo. Com base na análise dos comportamentos, verificou-se que o sistema de criação em cama propiciou a expressão de todos os comportamentos naturais relacionados ao conforto das aves, evidenciando o estado de bem-estar das mesmas. Para o sistema em gaiolas, pôde ser constatado que as aves tentavam expressar seus comportamentos naturais, mesmo não tendo condições para isso. Essa impossibilidade de expressão dos comportamentos agravou as condições de estresse provocadas por esse sistema de criação e pela condição ambiental a que as aves foram submetidas.The concern about the use of cages is related to barren environment and the minimal space offered to the laying hens, which negatively affects bird welfare. The present study focused on the aspect evaluation related to the behavior and welfare of birds, making a comparison between the alternative housing system (with litter and nests and the conventional cage system. Two groups of 20 laying hens (10 Hy-Line W36 and 10 Hy-line Brown at the beginning of the production were divided in two breeding systems (litter+nest and cages. Both of them were kept in climatic controlled chambers: one group with an ambient temperature of 26 °C and 60% RH (Thermal Comfort Condition

PDK1/Akt/PDE4D axis identified as a target for asthma remedy synergistic with β2 AR agonists by a natural agent arctigenin.

Science.gov (United States)

Fang, R; Cui, Q; Sun, J; Duan, X; Ma, X; Wang, W; Cheng, B; Liu, Y; Hou, Y; Bai, G

2015-12-01

Asthma is a heterogenetic disorder characterized by chronic inflammation with variable airflow obstruction and airway hyper-responsiveness. As the most potent and popular bronchodilators, β2 adrenergic receptor (β2 AR) agonists bind to the β2 ARs that are coupled via a stimulatory G protein to adenylyl cyclase, thereby improving cAMP accumulation and resulting in airway smooth muscle relaxation. We previously demonstrated arctigenin had a synergistic function with the β2 AR agonist, but the target for this remained elusive. Chemical proteomics capturing was used to enrich and uncover the target of arctigenin in human bronchial smooth muscle cells, and reverse docking and molecular dynamic stimulation were performed to evaluate the binding of arctigenin and its target. In vitro enzyme activities and protein levels were demonstrated with special kits and Western blotting. Finally, guinea pig tracheal muscle segregation and ex vivo function were analysed. Arctigenin bound to PDK1 with an ideal binding free energy -25.45 kcal/mol and inhibited PDK1 kinase activity without changing its protein level. Additionally, arctigenin reduced PKB/Akt-induced phosphorylation of PDE4D, which was first identified in this study. Attenuation of PDE4D resulted in cAMP accumulation in human bronchial smooth muscle. The inhibition of PDK1 showed a synergistic function with β2 AR agonists and relaxed the constriction of segregated guinea pig tracheal muscle. The PDK1/Akt/PDE4D axis serves as a novel asthma target, which may benefit airflow obstruction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dopamine agonist activity of EMD 23,448

Energy Technology Data Exchange (ETDEWEB)

Martin, G E; Pettibone, D J [Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology

1985-01-01

EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.

Ursodeoxycholic acid attenuates colonic epithelial secretory function

Science.gov (United States)

Kelly, Orlaith B; Mroz, Magdalena S; Ward, Joseph B J; Colliva, Carolina; Scharl, Michael; Pellicciari, Roberto; Gilmer, John F; Fallon, Padraic G; Hofmann, Alan F; Roda, Aldo; Murray, Frank E; Keely, Stephen J

2013-01-01

Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl− secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl− secretory responses to the Ca2+ and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n= 18, P acid (LCA). Accordingly, LCA (50–200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea. PMID:23507881

Control algorithms for dynamic attenuators

Energy Technology Data Exchange (ETDEWEB)

Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

2014-06-15

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators

International Nuclear Information System (INIS)

Hsieh, Scott S.; Pelc, Norbert J.

2014-01-01

Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

Control algorithms for dynamic attenuators.

Science.gov (United States)

Hsieh, Scott S; Pelc, Norbert J

2014-06-01

The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.

Science.gov (United States)

Hong, Quan; Zhang, Lu; Das, Bhaskar; Li, Zhengzhe; Liu, Bohan; Cai, Guangyan; Chen, Xiangmei; Chuang, Peter Y; He, John Cijiang; Lee, Kyung

2018-06-01

Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease. Published by Elsevier Inc.

Dopamine agonists and risk: impulse control disorders in Parkinson's disease.

Science.gov (United States)

Voon, Valerie; Gao, Jennifer; Brezing, Christina; Symmonds, Mkael; Ekanayake, Vindhya; Fernandez, Hubert; Dolan, Raymond J; Hallett, Mark

2011-05-01

Impulse control disorders are common in Parkinson's disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a 'Sure' choice and a 'Gamble' choice of moderate risk. To commence each trial, in the 'Gain' condition, individuals started at $0 and in the 'Loss' condition individuals started at -$50 below the 'Sure' amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk ('Gamble Risk'). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the 'Gain' relative to the 'Loss' condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.

Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan.

Science.gov (United States)

Suzuki, Go; Sato, Kentaro; Isobe, Tomohiko; Takigami, Hidetaka; Brouwer, Abraham; Nakayama, Kei

2015-09-15

Glucocorticoids (GCs) are widely used as anti-inflammatory drugs. Our previous study demonstrated that several GCs such as cortisol and dexamethasone (Dex) were frequently detected in effluents collected from Japanese sewage treatment plants (STPs) in 2012. In this study, we used the GC-Responsive Chemical-Activated LUciferase gene eXpression (GR-CALUX) assay to elucidate GC receptor (GR) agonistic activities of ten pure synthetic GCs and selected STP effluents in Japan for assessment of the risks associated with the presence of GR agonists. The tested GCs demonstrated dose-dependent agonistic effects in the GR-CALUX assay and their EC50 values were calculated for estimation of relative potencies (REPs) compared to Dex. The GR agonistic potency was in the rank of: clobetasol propionate > clobetasone butyrate > betamethasone 17-valerate > difluprednate > betamethasone 17,21-dipropionate > Dex > betamethasone > 6α-methylprednisolone > prednisolone > cortisol. The GR agonistic activity in STP effluents as measured in Dex-equivalent (Dex-EQ) activities ranged from effluents in Japan. Copyright © 2015 Elsevier B.V. All rights reserved.

Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity.

Science.gov (United States)

Yao, Yongxue; Harrison, Kathleen A; Al-Hassani, Mohammed; Murphy, Robert C; Rezania, Samin; Konger, Raymond L; Travers, Jeffrey B

2012-03-16

To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity.

Presencia y abundancia de aves que se reproducen en islas de la bahía de Mazatlán, Sinaloa, México

Directory of Open Access Journals (Sweden)

Alberto Piña-Ortiz

2017-04-01

Full Text Available Registramos la presencia y abundancia de aves, así como el hábitat y temporalidad de la reproducción de especies en las islas Pájaros, Venados, Lobos, Hermano Norte y Hermano Sur, ubicadas en la bahía de Mazatlán. Realizamos siete recorridos entre noviembre de 2014 y mayo de 2015; además contábamos con información colectada en mayo de 2004. Observamos un total de 59 especies de aves, de las cuales 15 fueron reproductoras: Dendrocygna autumnalis (pijije ala blanca, Phaethon aethereus (rabijunco pico rojo, Sula leucogaster (bobo café, Pelecanus occidentalis (pelícano café, Ardea herodias (garza morena, Ardea alba (garza blanca, Egretta thula (garza pie dorado, Bubulcus ibis (garza ganadera, Nycticorax nycticorax (pedrete corona negra, Nyctanassa violacea (pedrete corona clara, Eudocimus albus (ibis blanco, Coragyps atratus (zopilote común, Haematopus palliatus (ostrero americano, Larus heermanni (gaviota ploma y Falco peregrinus (halcón peregrino. Para P. aethereus y S. leucogaster no había reportes previos de reproducción en estas islas; además, confirmamos la anidación de L. hermanni. La isla Pájaros fue la que albergó el mayor número de especies reproductoras (10 especies. Pelecanus occidentalis fue la especie más abundante con un total de 1 559 individuos, seguido de Fregata magnificens (fragata magnífica y Sula nebouxii (bobo pata azul con 1 526 y 1 100 individuos, respectivamente; aunque para estas dos últimas especies no hubo registros de reproducción. Las islas se encuentran bajo protección, pero se requiere realizar monitoreos para establecer el estado y tendencias de las poblaciones de aves, así como los efectos de las perturbaciones por actividades humanas y por las especies introducidas.

Long-term outcome of patients with macroprolactinomas initially treated with dopamine agonists

NARCIS (Netherlands)

Kars, Marleen; Pereira, Alberto M.; Smit, Johannes W.; Romijn, Johannes A.

2009-01-01

Dopamine agonists are the first line therapy for the treatment of prolactinomas. The aim of this study was to assess the outcome of macroprolactinomas during long-term follow-up after initial treatment with dopamine agonists. Retrospective follow-up study. We included 72 consecutive patients (age

Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.

Science.gov (United States)

Wang, Yan-Juan; Ren, Qing-Guo; Gong, Wei-Gang; Wu, Di; Tang, Xiang; Li, Xiao-Li; Wu, Fang-Fang; Bai, Feng; Xu, Lin; Zhang, Zhi-Jun

2016-03-22

Tau hyperphosphorylation is an important pathological feature of Alzheimer's disease (AD). To investigate whether escitalopram could inhibit amyloid-β (Aβ)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aβ1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ1-42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3β pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ1-42 induced impairment of neurite outgrowth and spine density, and reversed Aβ1-42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ1-42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.

The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control.

Science.gov (United States)

Decker, M W; Meyer, M D; Sullivan, J P

2001-10-01

Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high-affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain.

Grão de girassol e seus subprodutos: potenciais fontes proteicas para alimentação de aves

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Raimunda Thyciana Vasconcelos Fernandes

2014-05-01

Full Text Available O setor de avicultura pode ser considerado um dos mais desenvolvidos e tecnificados da agropecuária mundial. Os avanços do melhoramento genético aliado ao desenvolvimento da nutrição, sanidade e técnicas de manejo, resultaram na avicultura atual, de alta eficiência e organização com a finalidade de produzir proteína animal de alto valor biológico para o consumo humano a baixo custo. A cadeia produtiva avícola tem íntima relação com a agricultura, principalmente com milho e soja (principais alimentos utilizados na alimentação de aves, no entanto a utilização destes alimentos para nutrição humana e ou refinarias gera uma competição e consequentemente a valorização dos preços destas commodities, o que aumenta o custo de produção e reduz as margens de comercialização. Desta forma, pesquisadores buscam alternativas alimentares economicamente viáveis numa tentativa de minimizar estes custos e manter os índices de desempenho produtivo.  Neste contexto, o grão de girassol e seus subprodutos são caracterizados como uma fonte proteica de boa qualidade capaz de compor dietas para aves.

Mixed bird flocks: patterns of activity and species composition in a region of the Central Andes of Colombia Bandadas mixtas de aves: patrones de actividad y composición de especies en una región de la Cordillera Central de los Andes de Colombia

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Enrique Arbeláez-Cortés

2011-06-01

Full Text Available Mixed bird flocks are groups of individuals from different species that travel and forage together. Such groups are common in several bird communities around the world. We present species composition and activity patterns of mixed bird flocks in a region of the Central Andes of Colombia. We compared the number of species per flock, as well as the number of flocks among 3 different habitats. We tested hypotheses concerning the flocks daily activity and the co-occurrences of species within them. We recorded 75 species, and the species number per flock varied from 4 to 21. Our data suggest that habitat affects the number of flocks but not their species number, and that the activity of flocks is similar throughout the day. In addition, the association of birds in flocks is affected by interspecific facilitation, with some species co-occurrences found more times than expected by chance. We hypothesize that some tanager species could have a role in flock cohesion. We witnessed 2 predator attacks upon flocks, a number of agonistic interactions among flock members, and squirrels following bird flocks. Our results meet some general patterns described for mixed bird flocks.Las bandadas mixtas de aves son grupos de individuos de diferentes especies que viajan y forrajean juntos, y son comunes en varias comunidades de aves alrededor del mundo. Presentamos la composición de especies y los patrones de actividad de las bandadas mixtas de aves en una región de la Cordillera Central de los Andes Colombianos. Comparamos el número de especies por bandada y el número de bandadas en 3 hábitats distintos. Evaluamos hipótesis relacionadas con la actividad de las bandadas durante el día y la presencia simultánea de especies en estos grupos. Observamos 75 especies, y el número de especies por bandada varió entre 4 y 21. Nuestros datos indican que el hábitat parece afectar el número de bandadas pero no su número de especies y que la actividad de las bandadas

Detección de aves exóticas en parques urbanos del centro de México

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Rubén Pineda-López

2013-01-01

Full Text Available Las áreas arboladas urbanas son utilizadas por algunas aves invasoras en su proceso de colonización; la detección temprana de estas especies es una acción necesaria para su vigilancia y control. Utilizamos un muestreo rápido en parques urbanos, que requiere de poco tiempo de planeación y ejecución, como una forma de detección de aves que actualmente aumentan su distribución en México: Streptopelia decaocto (paloma de collar, Myiopsitta monachus (perico monje, Turdus rufopalliatus (mirlo dorso rufo y Sturnus vulgaris (estornino pinto. Realizamos los muestreos en la mayoría de los parques de las ciudades de León de los Aldama, Guanajuato, Aguascalientes y Santiago de Querétaro. Presentamos los primeros registros de M. monachus, T. rufopalliatus y S. vulgaris para la ciudad de León de los Aldama; así como de M. monachus en la de Guanajuato. Además, en Santiago de Querétaro registramos las cuatro especies buscadas; a T. rufopalliatus en Guanajuato, y a S. vulgaris en Aguascalientes. Analizamos las variables asociadas con la presencia de las especies, así como el establecimiento de las especies en cada ciudad en relación con la proporción de parques en que se presentan. Sugerimos que este método es útil para evaluar la distribución actual de estas especies en México y proveer de conocimiento básico para futuros estudios.

Codon usage bias and phylogenetic analysis of mitochondrial ND1 gene in pisces, aves, and mammals.

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Uddin, Arif; Choudhury, Monisha Nath; Chakraborty, Supriyo

2018-01-01

The mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) gene is a subunit of the respiratory chain complex I and involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). To understand the pattern of compositional properties, codon usage and expression level of mitochondrial ND1 genes in pisces, aves, and mammals, we used bioinformatic approaches as no work was reported earlier. In this study, a perl script was used for calculating nucleotide contents and different codon usage bias parameters. The codon usage bias of MT-ND1 was low but the expression level was high as revealed from high ENC and CAI value. Correspondence analysis (COA) suggests that the pattern of codon usage for MT-ND1 gene is not same across species and that compositional constraint played an important role in codon usage pattern of this gene among pisces, aves, and mammals. From the regression equation of GC12 on GC3, it can be inferred that the natural selection might have played a dominant role while mutation pressure played a minor role in influencing the codon usage patterns. Further, ND1 gene has a discrepancy with cytochrome B (CYB) gene in preference of codons as evident from COA. The codon usage bias was low. It is influenced by nucleotide composition, natural selection, mutation pressure, length (number) of amino acids, and relative dinucleotide composition. This study helps in understanding the molecular biology, genetics, evolution of MT-ND1 gene, and also for designing a synthetic gene.

Photon attenuation by intensifying screens

International Nuclear Information System (INIS)

Holje, G.

1983-01-01

The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist.

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Presley, Chaela; Abidi, Ammaar; Suryawanshi, Satyendra; Mustafa, Suni; Meibohm, Bernd; Moore, Bob M

2015-08-01

Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously reported the receptor affinity of 3',5'-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury. Herein, we report the further characterization of SMM-189 as a potent and selective CB2 inverse agonist, which acts as a noncompetitive inhibitor of CP 55,940. The ability of SMM-189 to regulate microglial activation, in terms of chemokine expression and cell morphology, has been determined. Finally, we have determined that SMM-189 possesses acceptable biopharmaceutical properties indicating that the triaryl class of CB2 inverse agonists are viable compounds for continued preclinical development for the treatment of neurodegenerative disorders and traumatic brain injury.

Tracer attenuation in groundwater

Science.gov (United States)

Cvetkovic, Vladimir

2011-12-01

The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination, and reinstatement: relationship to feeding behavior and impulse control.

Science.gov (United States)

Higgins, Guy A; Silenieks, Leo B; Rossmann, Anne; Rizos, Zoe; Noble, Kevin; Soko, Ashlie D; Fletcher, Paul J

2012-04-01

Lorcaserin ((1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl) is a selective 5-HT(2C) receptor agonist with clinical efficacy in phase-III obesity trials. Based on evidence that this drug class also affects behaviors motivated by drug reinforcement, we compared the effect of lorcaserin on behavior maintained by food and nicotine reinforcement, as well as the stimulant and discriminative stimulus properties of nicotine in the rat. Acutely administered lorcaserin (0.3-3 mg/kg, subcutaneous (SC)) dose dependently reduced feeding induced by 22-h food deprivation or palatability. Effects up to 1 mg/kg were consistent with a specific effect on feeding motivation. Lorcaserin (0.6-1 mg/kg, SC) reduced operant responding for food on progressive and fixed ratio schedules of reinforcement. In this dose range lorcaserin also reversed the motor stimulant effect of nicotine, reduced intravenous self-administration of nicotine, and attenuated the nicotine cue in rats trained to discriminate nicotine from saline. Lorcaserin also reduced the reinstatement of nicotine-seeking behavior elicited by a compound cue comprising a nicotine prime and conditioned stimulus previously paired with nicotine reinforcement. Lorcaserin did not reinstate nicotine-seeking behavior or substitute for a nicotine cue. Finally, lorcaserin (0.3-1 mg/kg) reduced nicotine-induced increases in anticipatory responding, a measure of impulsive action, in rats performing the five-choice serial reaction time task. Importantly, these results indicate that lorcaserin, and likely other selective 5-HT(2C) receptor agonists, similarly affect both food- and nicotine-motivated behaviors, and nicotine-induced impulsivity. Collectively, these findings highlight a therapeutic potential for 5-HT(2C) agonists such as lorcaserin beyond obesity into addictive behaviors, such as nicotine dependence.

Interactions of dopaminergic agonists and antagonists with dopaminergic D3 binding sites in rat striatum. Evidence that [3H]dopamine can label a high affinity agonist-binding state of the D1 dopamine receptor

International Nuclear Information System (INIS)

Leff, S.E.; Creese, I.

1985-01-01

The interactions of dopaminergic agonists and antagonists with 3 H-agonist labeled D3 dopaminergic binding sites of rat striatum have been characterized by radioligand-binding techniques. When the binding of [ 3 H]dopamine and [ 3 H]apomorphine to D2 dopamine receptors is blocked by the inclusion of D2 selective concentrations of unlabeled spiroperidol or domperidone, these ligands appear to label selectively the previously termed D3 binding site. Antagonist/[ 3 H]dopamine competition curves are of uniformly steep slope (nH . 1.0), suggesting the presence of a single D3 binding site. The relative potencies of antagonists to inhibit D3 specific [ 3 H]dopamine binding are significantly correlated with their potencies to block D1 dopamine receptors as measured by the inhibition of both dopamine-stimulated adenylate cyclase and [ 3 H]flupentixol-binding activities. The affinities of agonists to inhibit D3 specific [ 3 H]dopamine binding are also correlated with estimates of these agonists affinities for the high affinity binding component of agonist/[ 3 H]flupentixol competition curves. Both D3 specific [ 3 H] dopamine binding and the high affinity agonist-binding component of dopamine/[ 3 H]flupentixol competition curves show a similar sensitivity to guanine nucleotides. Taken together, these data strongly suggest that the D3 binding site is related to a high affinity agonist-binding state of the D1 dopamine receptor

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

In silico discovery of novel Retinoic Acid Receptor agonist structures

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Samuels Herbert H

2001-06-01

Full Text Available Abstract Background Several Retinoic Acid Receptors (RAR agonists have therapeutic activity against a variety of cancer types; however, unacceptable toxicity profiles have hindered the development of drugs. RAR agonists presenting novel structural and chemical features could therefore open new avenues for the discovery of leads against breast, lung and prostate cancer or leukemia. Results We have analysed the induced fit of the active site residues upon binding of a known ligand. The derived binding site models were used to dock over 150,000 molecules in silico (or virtually to the structure of the receptor with the Internal Coordinates Mechanics (ICM program. Thirty ligand candidates were tested in vitro. Conclusions Two novel agonists resulting from the predicted receptor model were active at 50 nM. One of them displays novel structural features which may translate into the development of new ligands for cancer therapy.

A new record of the Restinga Tyrannulet Phylloscartes kronei (Aves, Rynchocyclidae at Ilha do Cardoso State Park, southeastern Brazil (Scientific Note. Novo registro de maria-da-restinga, Phylloscartes kronei (Aves, Rynchocyclidae no Parque Estadual Ilha do Cardoso, Sudeste do Brasil (Nota Científica

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Augusto João PIRATELLI

2014-06-01

Full Text Available During an expedition to Ilha do Cardoso State Park, in Cananéia, São Paulo, Brazil, two individuals of the Restinga Tyrannulet (Phylloscartes kronei, Aves: Rynchocyclidae were captured with a 36 mm mesh mist net in a restinga area (25o 12.243’S and 47o 59.502’W at Núcleo Marujá. This random record highlights the relevance of this protected area for this globally threatened species (vulnerable, where it is apparently abundant, due to the existence of suitable sites for its survival and reproduction. Durante uma expedição ao Parque Estadual Ilha do Cardoso, em Cananéia, SP, dois indivíduos de maria-da-restinga (Phylloscartes kronei, Aves: Rynchocyclidae foram capturados com uma rede de neblina de malha 36 mm em uma área de restinga (25o 12.243’S e 47o 59.502’O, no Núcleo Marujá. Esse registro fortuito ressalta a relevância desta Unidade de Conservação para esta espécie globalmente ameaçada (vulnerável, onde ela aparentemente é abundante, devido à existência de habitats adequados à sua sobrevivência e reprodução.

The convulsive and electroencephalographic changes produced by nonpeptidic delta-opioid agonists in rats: comparison with pentylenetetrazol.

Science.gov (United States)

Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

2006-06-01

delta-Opioid agonists produce convulsions and antidepressant-like effects in rats. It has been suggested that the antidepressant-like effects are produced through a convulsant mechanism of action either through overt convulsions or nonconvulsive seizures. This study evaluated the convulsive and seizurogenic effects of nonpeptidic delta-opioid agonists at doses that previously were reported to produce antidepressant-like effects. In addition, delta-opioid agonist-induced electroencephalographic (EEG) and behavioral changes were compared with those produced by the chemical convulsant pentylenetetrazol (PTZ). For these studies, EEG changes were recorded using a telemetry system before and after injections of the delta-opioid agonists [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenz (SNC80) and [(+)-4-[alpha(R)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide [(+)-BW373U86]. Acute administration of nonpeptidic delta-opioid agonists produced bilateral ictal and paroxysmal spike and/or sharp wave discharges. delta-Opioid agonists produced brief changes in EEG recordings, and tolerance rapidly developed to these effects; however, PTZ produced longer-lasting EEG changes that were exacerbated after repeated administration. Studies with antiepileptic drugs demonstrated that compounds used to treat absence epilepsy blocked the convulsive effects of nonpeptidic delta-opioid agonists. Overall, these data suggest that delta-opioid agonist-induced EEG changes are not required for the antidepressant-like effects of these compounds and that neural circuitry involved in absence epilepsy may be related to delta-opioid agonist-induced convulsions. In terms of therapeutic development, these data suggest that it may be possible to develop delta-opioid agonists devoid of convulsive properties.

PPAR Agonists and Metabolic Syndrome: An Established Role?

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Margherita Botta

2018-04-01

Full Text Available Therapeutic approaches to metabolic syndrome (MetS are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs, blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C. PPAR-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug–drug interactions (i.e., gemfibrozil and myopathy should also be acknowledged.

Suppression of atherosclerosis by synthetic REV-ERB agonist

Energy Technology Data Exchange (ETDEWEB)

Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

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Yiyi Sun

Full Text Available Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (--arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

Nuevos registros de aves con anormalidad pigmentaria en México y propuesta de clave dicotómica para la identificación de casos

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Erick R. Rodríguez-Ruíz

2017-04-01

Full Text Available Las anormalidades pigmentarias en aves han adquirido mayor importancia e interés entre la comunidad ornitológica; sin em- bargo, resulta necesario contar con una herramienta de diagnóstico apropiada que brinde los criterios para lograr un sistema de identificación entre los distintos tipos de anormalidades. Para ello, proponemos una clave dicotómica para su identificación en campo con base en terminología obtenida de literatura especializada y una asociación de caracteres fenotípicos de aves. También, reportamos la presencia de anormalidades pigmentarias en la coloración corporal y de plumaje de cinco especies de aves que han sido observadas de forma ocasional en áreas perturbadas por impacto antropogénico en Tamaulipas, México: melanismo en la tortolita mexicana (Columbina inca, aberración ino en la paloma turca (Streptopelia decaocto, aberración ino en el correcaminos norteño (Geococcyx californianus, leucismo parcial en el pijuy (Crotophaga sulcirostris y leucismo parcial en el tordo de ojo rojo (Molothrus aeneus. Las evidencias de casos actuales sugieren un aparente aumento de especies en vida libre con variación en la pigmentación. Las causas que lo provocan aún son discutibles, por lo cual, relacionar qué factores naturales o artificiales están involucrados en estos padecimientos podrá contribuir a determinar su origen y detectar problemas a nivel de poblaciones. La clave dicotómica propuesta en la identificación de anormalidades pigmentarias puede ser una herramienta continua en contextos modernos, si se unifica la terminología empleada.

Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

International Nuclear Information System (INIS)

Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P.

1991-01-01

Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with [125I]iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells

PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

International Nuclear Information System (INIS)

Rogue, Alexandra; Anthérieu, Sébastien; Vluggens, Aurore; Umbdenstock, Thierry; Claude, Nancy; Moureyre-Spire, Catherine de la; Weaver, Richard J.; Guillouzo, André

2014-01-01

Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

Energy Technology Data Exchange (ETDEWEB)

Rogue, Alexandra [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France); Biologie Servier, Gidy (France); Anthérieu, Sébastien; Vluggens, Aurore [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France); Umbdenstock, Thierry [Technologie Servier, Orléans (France); Claude, Nancy [Institut de Recherches Servier, Courbevoie (France); Moureyre-Spire, Catherine de la; Weaver, Richard J. [Biologie Servier, Gidy (France); Guillouzo, André, E-mail: Andre.Guillouzo@univ-rennes1.fr [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France)

2014-04-01

Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

Effect of β-agonist on the dexamethasone-induced expression of aromatase by the human monocyte cells

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Masatada Watanabe

2017-02-01

Full Text Available Emerging evidence suggests that sex steroids are important for human skin health. In particular, estrogen improves skin thickness, elasticity and moisture of older women. The major source of circulating estrogen is the ovary; however, local estrogen synthesis and secretion have important roles in, for example, bone metabolism and breast cancer development. We hypothesized that infiltrated peripheral monocytes are one of the sources of estrogen in skin tissues. We also hypothesized that, during atopic dermatitis under stress, a decline in the hypothalamus–pituitary–adrenal axis (HPA and facilitation of the (hypothalamus–sympathetic–adrenomedullary system (SAM attenuates estrogen secretion from monocytes. Based on this hypothesis, we tested aromatase expression in the human peripheral monocyte-derived cell line THP-1 in response to the synthetic glucocorticoid dexamethasone (Dex, the synthetic β-agonist isoproterenol (Iso and the β-antagonist propranolol (Pro. Dex mimics glucocorticoid secreted during excitation of the HPA, and Iso mimics catecholamine secreted during excitation of the SAM. We found that aromatase activity and the CYP19A1 gene transcript were both upregulated in THP-1 cells in the presence of Dex. Addition of Iso induced their downregulation and further addition of Pro rescued aromatase expression. These results may suggest that attenuation of estrogen secretion from peripheral monocytes could be a part of the pathology of stress-caused deterioration of atopic dermatitis. Further examination using an in vitro human skin model including THP-1 cells might be a valuable tool for investigating the therapeutic efficacy and mechanism of estrogen treatment for skin health.

Investigation of the mechanism of radioprotective action of adrenoceptor agonists

International Nuclear Information System (INIS)

Kulinskij, V.I.; Klimova, A.D.; Yashunskij, V.G.; Alpatova, T.V.; 4205700SU)

1986-01-01

α-Adrenoceptor agonists of both main groups, i.e. arylalkylamines and imidazolines, have a pronounced radioprotective effect. Their chemical analogs, which fail to stimulate α-adrenoceptors, do not protect mice. The effect of phenylephrine, adrenaline, and noradrenaline comes into play via α 1 -adrenoceptors and that of clonidine, via α 2 -adrenoceptors and also via α 1 -adrenoceptors. Adrenoceptor agonists can probably manifest their radioprotective action via both subtypes of α-adrenoceptors. Possible intracellular mechanisms of the radioprotective action are discussed

Suspension-firing of wood with coal ash addition: Probe measurements of ash deposit build-up at Avedøre Power Plant (AVV2)

DEFF Research Database (Denmark)

Shafique Bashir, Muhammad; Jensen, Peter Arendt; Jappe Frandsen, Flemming

This report is about full-scale probe measurements of deposit build-up and removal conducted at the Avedøreværket Unit 2, a 800 MWth suspension boiler, firing wood and natural gas with the addition of coal ash. Coal ash was used as an additive to capture potassium (K) from wood-firing. Investigat...... to the gas phase as HCl(g). Effect of boiler operational parameters on gas emissions has also been investigated.......This report is about full-scale probe measurements of deposit build-up and removal conducted at the Avedøreværket Unit 2, a 800 MWth suspension boiler, firing wood and natural gas with the addition of coal ash. Coal ash was used as an additive to capture potassium (K) from wood...... and boiler load on ash deposition propensity was investigated. Results of ash deposition propensity showed increasing trend with increasing flue gas temperature. Video monitoring revealed that the deposits formed were not sticky and could be easily removed, and even at very high flue gas temperatures (> 1350...

Contracaecumovale (Nematoda: Anisakidae from Rollandia rolland Quoy & Gaimard 1824 (Aves, Podicipedidae in Argentina Contracaecumovale (Nematoda: Anisakidae de Rollandia rolland Quoy & Gaimard 1824 (Aves, Podicipedidae na Argentina

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Noelia Adelina Galeano

2012-06-01

Full Text Available Necropsy on 15 specimens of white-tufted grebe, Rollandiarolland, caught in the Mar Chiquita and Chascomús lagoons (Buenos Aires province, revealed the presence of Contracaecumovale (Linstow, 1907. This nematode shows a marked specificity for podicipediform birds. The specimens were identified from morphological study on features such as cephalic and esophageal structures and caudal papillae, using both optical and scanning electron microscopy. This is the first record of C. ovale parasitizing R. rolland in Argentina.Necropsia de 15 espécimes de mergulhão-de-orelha-branca, Rollandiarolland, coletados nas lagoas Mar Chiquita e Chascomús (Província de Buenos Aires, revelou a presença de Contracaecumovale (Linstow, 1907. Esse nematóide tem uma marcada especificidade pelas aves podicipediformes. Os espécimes foram identificados a partir de características, tais como estruturas morfológicas cefálicas e esofágicas e papilas caudais, utilizando-se microscopia óptica e microscopia eletrônica de varredura (MEV. Esse é o primeiro registro de C. ovale parasito de R. rolland na Argentina.

Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

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Mohammad Reza Zarrindast

2009-04-01

Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model.

Science.gov (United States)

Kubota, Yasuhiko; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Watabe, Hiroshi; Daimon, Takashi; Sakai, Yoshiki; Akita, Toshiaki; Sawa, Yoshiki

2014-03-01

The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy. Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control. At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05). The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

[Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

Science.gov (United States)

Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

2014-09-01

Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

PPARα agonists up-regulate organic cation transporters in rat liver cells

International Nuclear Information System (INIS)

Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

2006-01-01

It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

Characterization of 12 GnRH peptide agonists - a kinetic perspective.

Science.gov (United States)

Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak-Reppel, Katrin; Fernández-Montalván, Amaury E; IJzerman, Adriaan P; Heitman, Laura H

2016-01-01

Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose. Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. © 2015 The British Pharmacological Society.

USO DA TERAPIA ESPELHO NA AMPLITUDE DE MOVIMENTO E FUNÇÃO DO MEMBRO INFERIOR EM PACIENTES HEMIPARÉTICOS PÓS-AVE

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Livia Danyelle Viana Lima

2017-02-01

Full Text Available Resumo: O exercício associado a terapia espelho potencializa a retenção de habilidades, melhorando o desempenho de atividades motoras de indivíduos hemiparéticos pós-AVE. Este estudo objetivou a análise do efeito da terapia espelho na amplitude de movimento e funcionalidade do membro inferior. Amostra composta de 11 participantes, com hemiparesia em membro inferior, submetidas a fisioterapia convencional. A intervenção constituiu de 10 atendimentos, 30 minutos diários e três vezes por semana. Para avaliação foram usados: Goniometria; Escala Modificada de Ashworth (EMA; Escala de Força de Oxford; Cadência de Subida e Descida de Escada; Time Up And Go Test. Os dados foram coletados antes e após a intervenção da Terapia Espelho e comparados. Segundo resultados do estudo a Terapia Espelho proporcionou ganhos na ADM e função do membro inferior parético pós-AVE, porém não interferiu na espasticidade. Palavras-chave: Acidente Vascular Encefálico, Hemiparesia, Retroalimentação Visual.

Discovery of Azetidinone Acids as Conformationally-Constrained Dual PPARalpha/gamma Agonists

Energy Technology Data Exchange (ETDEWEB)

Wang, W.; Devasthale, P; Farrelly, D; Gu, L; Harrity, T; Cap, M; Chu, C; Kunselman, L; Morgan, N; et. al.

2008-01-01

A novel class of azetidinone acid-derived dual PPAR{alpha}/{gamma} agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARa and PPAR? receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

Contribución al conocimiento de los malófagos (Phthiraptera, Amblycera, Ischnocera de aves peruanas. Parte 1

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Luis A. Gomez-Puerta

2015-12-01

Full Text Available En el presente trabajo se reporta nueve especies de malófagos colectados de aves peruanas. Dos malófagos Amblycera: Heteromenopon laticapitis y Menacanthus pici, así como siete malófagos Ischnocera: Alcedoffula theresae, Brueelia brunneinucha, Chelopistes meleagridis, Columbicola columbae, Paragoniocotes aratingae, Penenirmus jungens y Saemundssonia (Saemundssonia lari, fueron determinados mediante el diagnóstico morfológico. Se realiza una breve descripción de cada malófago, así como la discusión de sus hospederos y distribución.

O potencial do DNA barcode na identificação de espécies de aves neotropicais

OpenAIRE

Priscila Fernanda Mussi Gonçalves

2009-01-01

O presente trabalho foi organizado em cinco capítulos. No primeiro é apresentada uma breve revisão da bibliografia relacionada ao DNA barcode, apontando as aplicações e os limites desse marcador. Os resultados obtidos são apresentados nos três capítulos subsequentes. O segundo capítulo teve como objetivo avaliar o potencial do método de DNA barcoding na distinção de 783 amostras de 228 espécies diferentes de aves neotropicais de 16 ordens baseado na diferença dos valores de divergências intra...

Actividad reproductiva de Chelonia mydas (Testudines: Cheloniidae en Isla de Aves, Venezuela (2001-2008

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Vicente Vera

2012-06-01

Full Text Available Isla de Aves, una isla a 650km de La Guaira, Venezuela, protegida como Refugio de Fauna Silvestre, constituye el segundo sitio de mayor anidación de la tortuga verde (Chelonia mydas (Linnaeus 1758 en el Caribe. El seguimiento de la población comenzó en 1972 y de manera más continua desde 1978. Los datos históricos indican que la captura de hembras en la isla, afectó severamente la población hasta 1978, cuando fue construida una base científico-naval. Durante las temporadas de anidación entre 2001-2008 con excepción de 2003 y 2004, las hembras fueron marcadas con placas metálicas y medidas. Asimismo, se muestreó durante 458 noches, en donde se observaron 5 154 eventos, con un máximo de 53 por noche. Los posibles eventos no observados fueron calculados ajustando la distribución temporal de eventos observados a una curva normal. El total de eventos estimados varió de =637.1±106.6 en 2001 a =2 853±42.5 en 2008 (ANOVA F(6.5gl=60.37, p<0.0001. El intervalo entre reanidaciones fue de =10.7±1.32 días. La frecuencia de anidación se calculó en =1.71±1.6 veces por hembra. El número de hembras estimadas varió entre =373±12.5 para 2001 y =1 669±56.1 para 2008 (ANOVA F(5.6gl=89.42, p<0.0001. La tendencia es significativa (r=0.842, p=0.036. Los resultados indican que el número de hembras que anidan en Isla de Aves ha aumentado, y se sugiere que más de 30 años de protección del área de reproducción está resultando en un creciente número de hembras.

Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats.

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Laurens J Ceulemans

Full Text Available The farnesoid X receptor (FXR is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA could attenuate intestinal ischemia reperfusion injury.In a validated rat model of intestinal IRI (laparotomy + temporary mesenteric artery clamping, 3 conditions were tested (n = 16/group: laparotomy only (sham group; ischemia 60min+ reperfusion 60min + vehicle pretreatment (IR group; ischemia 60min + reperfusion 60min + OCA pretreatment (IR+OCA group. Vehicle or OCA (INT-747, 2*30mg/kg was administered by gavage 24h and 4h prior to IRI. The following end-points were analyzed: 7-day survival; biomarkers of enterocyte viability (L-lactate, I-FABP; histology (morphologic injury to villi/crypts and villus length; intestinal permeability (Ussing chamber; endotoxin translocation (Lipopolysaccharide assay; cytokines (IL-6, IL-1-β, TNFα, IFN-γ IL-10, IL-13; apoptosis (cleaved caspase-3; and autophagy (LC3, p62.It was found that intestinal IRI was associated with high mortality (90%; loss of intestinal integrity (structurally and functionally; increased endotoxin translocation and pro-inflammatory cytokine production; and inhibition of autophagy. Conversely, OCA-pretreatment improved 7-day survival up to 50% which was associated with prevention of epithelial injury, preserved intestinal architecture and permeability. Additionally, FXR-agonism led to decreased pro-inflammatory cytokine release and alleviated autophagy inhibition.Pretreatment with OCA, an FXR-agonist, improves survival in a rodent model of intestinal IRI, preserves the gut barrier function and suppresses inflammation. These results turn

Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

Science.gov (United States)

Chetham, P M; Sefton, W D; Bridges, J P; Stevens, T; McMurtry, I F

1997-04-01

Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53.

Science.gov (United States)

Hsu, Hsi-Hsien; Kuo, Wei-Wen; Ju, Da-Tong; Yeh, Yu-Lan; Tu, Chuan-Chou; Tsai, Ying-Lan; Shen, Chia-Yao; Chang, Sheng-Huang; Chung, Li-Chin; Huang, Chih-Yang

2014-11-28

To investigate the effects of 17β-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test. The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10(-8) mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative

Ibuprofen administration attenuates serum TNF-α levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulation

International Nuclear Information System (INIS)

Cazanave, Sophie; Vadrot, Nathalie; Tinel, Marina; Berson, Alain; Letteron, Philippe; Larosche, Isabelle; Descatoire, Veronique; Feldmann, Gerard; Robin, Marie-Anne; Pessayre, Dominique

2008-01-01

Fas stimulation recruits neutrophils and activates macrophages that secrete tumor necrosis factor-α (TNF-α), which aggravates Fas-mediated liver injury. To determine whether nonsteroidal anti-inflammatory drugs modify these processes, we challenged 24-hour-fasted mice with the agonistic Jo2 anti-Fas antibody (4 μg/mouse), and treated the animals 1 h later with saline or ibuprofen (250 mg/kg), a dual cyclooxygenase (COX)-1 and COX-2 inhibitor. Ibuprofen attenuated the Jo2-mediated recruitment/activation of myeloperoxidase-secreting neutrophils/macrophages in the liver, and attenuated the surge in serum TNF-α. Ibuprofen also minimized hepatic glutathione depletion, Bid truncation, caspase activation, outer mitochondrial membrane rupture, hepatocyte apoptosis and the increase in serum alanine aminotransferase (ALT) activity 5 h after Jo2 administration, to finally decrease mouse mortality at later times. The concomitant administration of pentoxifylline (decreasing TNF-α secretion) and infliximab (trapping TNF-α) likewise attenuated the Jo2-mediated increase in TNF-α, the decrease in hepatic glutathione, and the increase in serum ALT activity 5 h after Jo2 administration. The concomitant administration of the COX-1 inhibitor, SC-560 (10 mg/kg) and the COX-2 inhibitor, celecoxib (40 mg/kg) 1 h after Jo2 administration, also decreased liver injury 5 h after Jo2 administration. In contrast, SC-560 (10 mg/kg) or celecoxib (40 or 160 mg/kg) given alone had no significant protective effects. In conclusion, secondary TNF-α secretion plays an important role in Jo2-mediated glutathione depletion and liver injury. The combined inhibition of COX-1 and COX-2 by ibuprofen attenuates TNF-α secretion, glutathione depletion, mitochondrial alterations, hepatic apoptosis and mortality in Jo2-treated fasted mice

Gain attenuation of gated framing camera

International Nuclear Information System (INIS)

Xiao Shali; Liu Shenye; Cao Zhurong; Li Hang; Zhang Haiying; Yuan Zheng; Wang Liwei

2009-01-01

The theoretic model of framing camera's gain attenuation is analyzed. The exponential attenuation curve of the gain along the pulse propagation time is simulated. An experiment to measure the coefficient of gain attenuation based on the gain attenuation theory is designed. Experiment result shows that the gain follows an exponential attenuation rule with a quotient of 0.0249 nm -1 , the attenuation coefficient of the pulse is 0.00356 mm -1 . The loss of the pulse propagation along the MCP stripline is the leading reason of gain attenuation. But in the figure of a single stripline, the gain dose not follow the rule of exponential attenuation completely, instead, there is a gain increase at the stripline bottom. That is caused by the reflection of the pulse. The reflectance is about 24.2%. Combining the experiment and theory, which design of the stripline MCP can improved the gain attenuation. (authors)

Difracción de luz a través de una pluma de ave

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Hugo Pérez García

2012-01-01

Full Text Available Se ha utilizado una pluma de ave para estudiar la difracción de la luz, tanto de forma cualitativa como cuantitativa. La medida experimental de la separación entre los puntos luminosos del patrón de difracción obtenido con un puntero láser ha permitido determinar el espaciado entre las barbas y entre las bárbulas de la pluma. Los resultados obtenidos muestran un acuerdo satisfactorio con los correspondientes a la estructura típica de una pluma. Los materiales empleados, los conceptos involucrados y los resultados experimentales convierten a esta experiencia en un excelente recurso didáctico para el estudio de la difracción, tanto en los primeros cursos universitarios como en los últimos cursos del Bachillerato.

The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

2003-01-01

The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu......The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic...... interneurons, were examined in hippocampal slice cultures exposed to N-methyl-D-aspartate (NMDA). The NMDA-induced excitotoxicity was quantified by densitometric measurements of propidium iodide (PI) uptake. THIP (100-1000 microM) was neuroprotective in slice cultures co-exposed to NMDA (10 microM) for 48 h......, while muscimol (100-1000 microM) and ATPA (1-3 microM) were without effect. The results demonstrate that direct GABA(A) agonism can mediate neuroprotection in the hippocampus in vitro as previously suggested in vivo....

Nuevo examen de los grabados paleolíticos de El Pendo (Cantabria, España. Consideraciones sobre las aves del arte paleolítico de la Península Ibérica

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García Díez, Marcos

2011-06-01

Full Text Available Birds are very scarce in Palaeolithic rock art. Since 1907 figures of razorbill and raptors (probably vulture have been described at the end of the Pendo cave, both attributed to an Upper Palaeolithic origin (from Aurignacian to Lower Magdalenian, depending on the authors. The new revision of the group of engravings shows the presence of an unambiguous bird, but the morphology of the figure did not permit its precise taxonomic identification. The work also presents a revision of the birds known in Iberian Palaeolithic rock art.

La presencia de aves en el repertorio iconográfico del arte rupestre paleolítico es muy escasa. Desde 1907 se vienen describiendo unas figuras de alca y de rapaz (probablemente buitre en la parte final de la cueva de El Pendo. Los autores las asignan a un momento antiguo, desde el Auriñaciense hasta el Magdaleniense inferior. Una nueva lectura del conjunto de grabados permite apuntar la presencia inequívoca de una imagen de ave, sin características que permitan su identificación taxonómica precisa. El trabajo revisa, además, las imágenes de aves conocidas en el arte rupestre paleolítico de la Península Ibérica.

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

Science.gov (United States)

Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

2016-01-01

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

Attenuation correction for SPECT

International Nuclear Information System (INIS)

Hosoba, Minoru

1986-01-01

Attenuation correction is required for the reconstruction of a quantitative SPECT image. A new method for detecting body contours, which are important for the correction of tissue attenuation, is presented. The effect of body contours, detected by the newly developed method, on the reconstructed images was evaluated using various techniques for attenuation correction. The count rates in the specified region of interest in the phantom image by the Radial Post Correction (RPC) method, the Weighted Back Projection (WBP) method, Chang's method were strongly affected by the accuracy of the contours, as compared to those by Sorenson's method. To evaluate the effect of non-uniform attenuators on the cardiac SPECT, computer simulation experiments were performed using two types of models, the uniform attenuator model (UAM) and the non-uniform attenuator model (NUAM). The RPC method showed the lowest relative percent error (%ERROR) in UAM (11 %). However, 20 to 30 percent increase in %ERROR was observed for NUAM reconstructed with the RPC, WBP, and Chang's methods. Introducing an average attenuation coefficient (0.12/cm for Tc-99m and 0.14/cm for Tl-201) in the RPC method decreased %ERROR to the levels for UAM. Finally, a comparison between images, which were obtained by 180 deg and 360 deg scans and reconstructed from the RPC method, showed that the degree of the distortion of the contour of the simulated ventricles in the 180 deg scan was 15 % higher than that in the 360 deg scan. (Namekawa, K.)

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

Science.gov (United States)

Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

2013-01-01

This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs.

Science.gov (United States)

Moore, Thomas J; Glenmullen, Joseph; Mattison, Donald R

2014-12-01

Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia. To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs. We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System. Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs. We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3 receptor (n = 37; PRR = 8.6, P < .001). Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present

Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist.

Science.gov (United States)

Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L; Litherland, Sally A; Haskell-Luevano, Carrie

2010-06-08

The melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic biomarker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and nonobese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-dPhe-Arg-Trp-NH(2) (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219 V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F, and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface

Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

NARCIS (Netherlands)

Michel-Reher, Martina B.; Michel, Martin C.

2013-01-01

β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

Development of specific dopamine D-1 agonists and antagonists

International Nuclear Information System (INIS)

Sakolchai, S.

1987-01-01

To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo[a,d]cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo[1,2]cyclohepta[3,4,5d,e]isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC 50 of compound 11 for displacement of 3 H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of 3 H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor

Serotonin 2A receptor agonist binding in the human brain with [C]Cimbi-36

DEFF Research Database (Denmark)

Ettrup, A.; da Cunha-Bang, S.; McMahon, Barry P.

2014-01-01

[C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely ....... Thus, we here describe [C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT receptors in the human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 April 2014; doi:10.1038/jcbfm.2014.68....... than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT receptors with [C]Cimbi-36 PET. The two-tissue compartment model using arterial input...

A bumblefoot outbreak and fatal septicemia in captive aquatic birds in Brazil Surto de esparavão e septicemia fatal em aves aquáticas cativas no Brasil

Directory of Open Access Journals (Sweden)

Marcus Vinícius Romero Marques

2009-09-01

Full Text Available A bumblefoot outbreak with different prognosis according to host species was studied in captive aquatic avian species. Six wood ducks (Aix sponsa, three scarlet-ibis (Eudocimus ruber, two black-swans (Cygnus atratus, five white-faced ducks (Dendrocygna viduata and two roseate spoonbills (Platalea ajaja were kept in a common pen with abrasive pavement pond margin, predisposing to podal skin wear. Incoordination and mortality occurred in the two roseate spoonbils and one black swan. Coagulase-positive penicillin-resistant Staphylococcus aureus was isolated from the synovial fluid and from the liver. All birds sharing the pen presented active or cicatricial foot lesions, indicating a possible challenge to the environmental Staphylococci. However, except for the roseate spoonbill and the black swan, which had fatal disease, for all other species the case did not evolve to a clinically debilitating or fatal disease. The different susceptibility to a fatal Staphylococcus aureus coagulase positive infection is discussed.Este trabalho relata um surto de esparavão em aves aquáticas cativas com prognóstico variado conforme a espécie de ave. Foram examinados um marreco carolina (Aix sponsa, três guarás (íbis vermelha (Eudocimus ruber, dois cisnes negros (Cygnus atratus, cinco marrecas piadeiras (Dendrocygna viduata e dois colhereiros (Platalea ajaja mantidos em recinto comunitário, em cativeiro e em criatório. No recinto, a piscina é margeada por borda de cimento abrasivo que possibilita a abrasão da pele podal. Todas as aves apresentaram erosões da pele na face de apoio dos pés, indicando fator predisponente (erosão similar e possível semelhante desafio infeccioso. Entretanto, incoordenação e mortalidade ocorreram em colhereiros e no cisne negro, mas não nas outras espécies. Staphylococcus aureus coagulase positivo e resistente à penicilina foi isolado do líquido sinovial e do fígado das aves recém-mortas e conservadas em geladeira

Seasonal changes in the use of marine food resources by Cinclodes nigrofumosus (furnariidae, aves: carbon isotopes and osmoregulatory physiology Cambios estacionales en el uso de recursos alimenticios marinos en Cinclodes nigrofumosus (furnariidae, aves: isótopos de carbono y fisiología osmoregulatoria

Directory of Open Access Journals (Sweden)

PABLO SABAT

2005-06-01

Full Text Available Passerines lack functional salt glands and to a large extent avoid feeding on marine invertebrates. An exception is Cinclodes nigrofumosus. Previous studies reported that the contents of its gastrointestinal tract had a lower osmolality than seawater suggesting that birds were supplementing their marine invertebrate diet with terrestrial invertebrates and fresh water at certain periods of the year. We report seasonal changes in the diet of C. nigrofumosus at two contrasting coastal localities in Central Chile and document the potential correlation between weather and feeding habits with osmoregulatory features in this species. We expected that C. nigrofumosus would increase its use of osmotically challenging marine dietary sources when fresh water is available. Animals were collected at El Quisco and Los Vilos from central Chile during the mist cool winter and during the hot and dry summer. Immediatly after capture several physiological and morphological variables were determined at the field. We used stable isotope analysis as a proxy variable to measure the relative contribution of marine and terrestrial sources to the diet of Cinclodes nigrofumosus. Our results support the notion that osmoregulatory factors constraint dietary selection: in both localities birds consumed more marine prey when environmental conditions were less stressing, i.e., when lower environment temperatures, higher humidity and more fresh water was available. Our results also indicate that osmoregulatory physiology does not respond in a similar fashion in both seasons and suggest that osmoregulatory physiology of birds is affected by environmental variables in a complex fashionLas aves paseriformes no poseen glándula de la sal funcional y en gran medida evitan el consumo de invertebrados marinos. Una excepción es Cinclodes nigrofumosus. Estudios previos han documentado que el contenido del tracto gastrointestinal posee una osmolalidad menor que el agua de mar, lo que

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke

OpenAIRE

Gorgoraptis, Nikos; Mah, Yee-Haur; Machner, Bjoern; Singh-Curry, Victoria; Malhotra, Paresh; Hadji-Michael, Maria; Cohen, David; Simister, Robert; Nair, Ajoy; Kulinskaya, Elena; Ward, Nick; Greenwood, Richard; Husain, Masud

2012-01-01

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, ...

Potential of beta-adrenergic agonists for increasing protein deposition in ruminants in developing countries

International Nuclear Information System (INIS)

Berschauer, F.

1989-01-01

Various substituted phenylethanolamines, acting on the sympathetic nervous system, have been shown to increase protein retention (via decreased proteolysis) and reduce fat deposition (via increased lipolysis and reduced lipogenesis) in ruminants and monogastrics. Research with finishing lambs in developed countries show various beta-adrenergic agonists to improve growth rate (by 18%), feed conversion (by 12%) and carcass quality (28% increase in area of longissimus dorsi and 33% reduction in subcutaneous fat). Similar effects of beta-agonists on carcass composition of well fed cattle have been reported. The effects of beta-agonists on livestock in developing countries of the tropics have not yet been investigated, but their effects in increasing metabolic rate suggest that treated ruminants would be more vulnerable to hot environments. Beta-agonists appear to improve nitrogen retention to a greater extent in breeds with a lower potential for muscle growth. In view of this, they might be particularly effective in improving nitrogen retention in tropical breeds which have a low growth potential. This aspect, together with the response of undernourished animals in the developing countries, needs investigation. Beta-adrenergic agonists are not yet registered for use in animal production, but product licenses for some of them are expected to be granted soon. (author). 31 refs, 1 fig., 12 tabs

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

Directory of Open Access Journals (Sweden)

Guo S

2017-03-01

Full Text Available Song Guo,1,* Xiaowei Lu,1,* Ruihuan Gu,2 Di Zhang,3 Yijuan Sun,2 Yun Feng1 1Department of Obstetrics and Gynecology, Reproductive Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Gynecology, Shanghai Ji Ai Genetics & In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Jinan Military General Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.Methods: Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each. The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR.Results: The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05. However, the average live litter

Improvement of quantitation in SPECT: Attenuation and scatter correction using non-uniform attenuation data

International Nuclear Information System (INIS)

Mukai, T.; Torizuka, K.; Douglass, K.H.; Wagner, H.N.

1985-01-01

Quantitative assessment of tracer distribution with single photon emission computed tomography (SPECT) is difficult because of attenuation and scattering of gamma rays within the object. A method considering the source geometry was developed, and effects of attenuation and scatter on SPECT quantitation were studied using phantoms with non-uniform attenuation. The distribution of attenuation coefficients (μ) within the source were obtained by transmission CT. The attenuation correction was performed by an iterative reprojection technique. The scatter correction was done by convolution of the attenuation corrected image and an appropriate filter made by line source studies. The filter characteristics depended on μ and SPEC measurement at each pixel. The SPECT obtained by this method showed the most reasonable results than the images reconstructed by other methods. The scatter correction could compensate completely for a 28% scatter components from a long line source, and a 61% component for thick and extended source. Consideration of source geometries was necessary for effective corrections. The present method is expected to be valuable for the quantitative assessment of regional tracer activity

Innate Immune Responses to TLR2 and TLR4 Agonists Differ between Baboons, Chimpanzees and Humans

Science.gov (United States)

Brinkworth, Jessica F.; Pechenkina, Ekaterina A.; Silver, Jack; Goyert, Sanna M.

2012-01-01

Background African catarrhine primates differ in bacterial disease susceptibility. Methods Human, chimpanzee, and baboon blood was stimulated with TLR-detected bacterial agonists and cytokine/chemokine induction assessed by real-time pcr. Results Humans and chimpanzees shared similar cytokine/chemokine responses, while baboon cytokine/chemokine induction differed. Generally, responses were agonist-independent. Conclusions These primates tend to generate species rather than agonist–specific responses to bacterial agonists. PMID:22978822

Registro da pomba-do-orvalho Patagioenas maculosa (Aves: Columbidae no estado de Santa Catarina, sul do Brasil

Directory of Open Access Journals (Sweden)

Ivo Rohling Ghizoni-Jr

2009-08-01

Full Text Available http://dx.doi.org/10.5007/2175-7925.2009v22n2p195 Apresentamos o primeiro registro da pomba-do-orvalho Patagioenas maculosa (Aves: Columbidae para Santa Catarina, região sul do Brasil. Um indivíduo foi observado em 10 de setembro de 2006 em uma área aberta (pastagens para gado e vegetação arbustiva no município de Anita Garibaldi (centro-sul do estado. Sugerimos que este encontro pontual é resultado de uma recente expansão da distribuição desta espécie devido a modificações na paisagem nesta região.

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

Science.gov (United States)

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

Inhibitory GTP binding protein G/sub i/ regulates β-adrenoceptor affinity towards β-agonists

International Nuclear Information System (INIS)

Marbach, I.; Levitzki, A.

1987-01-01

Treatment of S-49 lymphoma cell membranes with pertussis toxin (PT) causes a three-fold reduction of β-adrenoceptor (βAR) affinity towards isoproterenol. A similar treatment with cholera toxin (CT) does not cause such a modulation. The effects were studied by the detailed analysis of 125 I-cyanopindolol (CYP) binding curves in the absence and presence of increasing agonist concentrations. Thus, the authors were able to compare in detail the effects of G/sub s/ and G/sub i/ on the agonist-associated state of the βAR. In contrast to these findings, PT treatment does not have any effect on the displacement of 125 I-CYP by (-)isoproterenol. These results demonstrate that the inhibitory GTP protein G/sub i/ modulates the βAR affinity towards β-agonists. This might be due to the association of G/sub i/ with the agonist-bound βAR x G/sub s/ x C complex within the membrane. This hypothesis, as well as others, is under investigation

Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

Science.gov (United States)

Young, R. B.; Bridge, K. Y.

2003-01-01

Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate CAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of CAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of CAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of CAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of CAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of CAMP by either epinephrine or isoproterenol.

Muscarinic Receptor Agonists and Antagonists

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David R. Kelly

2001-02-01

Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

Effects of cannabinoid and vanilloid receptor agonists and their interaction on learning and memory in rats.

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Shiri, Mariam; Komaki, Alireza; Oryan, Shahrbanoo; Taheri, Masoumeh; Komaki, Hamidreza; Etaee, Farshid

2017-04-01

Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212-2, (3) capsaicin, and (4) WIN55,212-2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212-2, a cannabinoid receptor (CB 1 /CB 2 ) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212-2 (CB 1 /CB 2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212-2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats' cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212-2 on learning and memory.

Aves explorando flores de Erythrina fusca (Leguminosae, Fabaceae durante a estação seca no Pantanal de Mato Grosso Exploitation of Erythrina fusca (Leguminosae, Fabaceae flowers by birds during the dry season in Pantanal of Mato Grosso, Brazil

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Ricardo Parrini

2010-06-01

Full Text Available Estudos recentes têm evidenciado a importância de flores como recurso alimentar de diversas espécies de aves neotropicais. Este estudo teve o objetivo de listar espécies e descrever o comportamento das aves que se alimentaram de recursos florais de Erythrina fusca (Fabaceae no Pantanal Mato-Grossense. Para isso, foram acompanhadas aves que se alimentaram em 14 árvores floridas dessa espécie em um total de cerca de 25 horas de observação. Como resultados, 20 espécies de aves pertencentes a sete famílias taxonômicas foram observadas alimentando-se de recursos florais de E. fusca. Apesar de várias espécies de aves terem apresentado comportamentos destrutivos em maior proporção, algumas espécies, sobretudo das famílias Trochilidae e Icteridae, apresentaram estratégias alimentares compatíveis com o transporte de pólen. O cruzamento dos dados obtidos neste estudo com os da literatura indicam que a família Icteridae pode ter relevante papel na polinização dessa espécie vegetal.Recent studies reported the importance of flowers in the diet of many Neotropical bird species. In this paper we identify and describe the feeding behaviour of bird species that feed on flower resources of Erythrina fusca (Fabaceae in the Pantanal Mato-Grossense, Brazil. We recorded birds foraging in 14 flowered individuals of E. fusca during 25 hours of observation. We recorded 20 bird species belonging to seven families feeding on the flowers. Several of the observed behaviours were destructive, despite some species, especially the Trochilidae and Icteridae, showed feeding strategies that preserve the integrity of the flowers and are compatible with pollen transportation. The comparison of the data gathered in this study with the available literature indicates that the Icteridae may play an important role in pollination of this tree species.

Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

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Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

2015-02-01

To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome.

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Dang, Dien; Cunnington, David; Swieca, John

2011-01-01

The Restless Legs Syndrome is a common sensorimotor disorder, typically amenable to treatment with dopamine agonist therapy. Dopamine agonists have been associated with emergent impulse control disorders (ICDs) when used in patients with Parkinson disease, and ICDs have now been reported in individuals with RLS on dopamine agonist therapy. Our aim was to characterize cases of emergent ICDs in Australian patients with focus on the dopamine agonists implicated and the social significance of ICDs. A series of RLS patients on dopamine agonist therapy were identified with ICDs over a 2-year period. Additional cases of ICDs were found using a mailout questionnaire designed to capture those with high impulsivity. These patients were assessed using the Barratt Impulsiveness Scale, Version 11, and a modified Minnesota Impulse Disorders Interview. Case records and medication schedules were evaluated. Twelve cases of patients with de novo ICDs were found with a range of impulsive behaviors including pathological gambling, kleptomania, compulsive shopping, and hypersexuality. Criminality, suicidality, and marital discord also were featured. These occurred over a wide range of latencies and l-dopa exposures. This group of Australian RLS patients with ICDs display high levels of impulsivity and is the first to use the BIS-11 questionnaire in this setting. Impulse control disorders can occur over a wide range of dopamine agonist therapy types and dose exposures. Impulse control disorder tendencies may persist, despite withdrawal of dopamine agonists. The emergence of ICDs needs careful consideration in light of their potentially devastating financial, social, and marital consequences.

Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks

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Schäffer, Lauge; Brissette, Renee E.; Spetzler, Jane C.; Pillutla, Renuka C.; Østergaard, Søren; Lennick, Michael; Brandt, Jakob; Fletcher, Paul W.; Danielsen, Gillian M.; Hsiao, Ku-Chuan; Andersen, Asser S.; Dedova, Olga; Ribel, Ulla; Hoeg-Jensen, Thomas; Hansen, Per Hertz; Blume, Arthur J.; Markussen, Jan; Goldstein, Neil I.

2003-01-01

Insulin is thought to elicit its effects by crosslinking the two extracellular α-subunits of its receptor, thereby inducing a conformational change in the receptor, which activates the intracellular tyrosine kinase signaling cascade. Previously we identified a series of peptides binding to two discrete hotspots on the insulin receptor. Here we show that covalent linkage of such peptides into homodimers or heterodimers results in insulin agonists or antagonists, depending on how the peptides are linked. An optimized agonist has been shown, both in vitro and in vivo, to have a potency close to that of insulin itself. The ability to construct such peptide derivatives may offer a path for developing agonists or antagonists for treatment of a wide variety of diseases. PMID:12684539

Pharmacological Characterization of 30 Human Melanocortin-4 Receptor Polymorphisms with the Endogenous Proopiomelanocortin Derived Agonists, Synthetic Agonists, and the Endogenous Agouti-Related Protein (AGRP) Antagonist

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Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L.; Litherland, Sally A.; Haskell-Luevano, Carrie

2010-01-01

The melanocortin-4 receptor (MC4R) is a G-protein coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic bio marker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and non-obese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [α-, β, γ2-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface expression by flow

A apropriação e transformação de As Aves, de Aristófanes, por Paul Muldoon

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Munira H Mutran

2003-11-01

Full Text Available Um texto como As Aves, de Aristófanes, produzido em Dionísia em 414 a.C., é passível de diferentes leituras e interpretações. Este artigo examina as relações intertextuais entre o original grego e sua recente tradução pelo poeta irlandês Paul Muldoon; investiga, também, como os motivos predominantes de guerra, política, corrupção e utopia tornaram-se significativos na tradução de 1999.

Estructura de la comunidad y asociación de las aves acuáticas con la heterogeneidad espacial del complejo lagunar Bahía Magdalena-Almejas, Baja California Sur, México

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Bulmara Zárate-Ovando

2008-03-01

Full Text Available Para probar la hipótesis que la heterogeneidad espacial determina la diversidad de aves acuáticas en un humedal costero, comparamos la densidad, diversidad y composición de especies de aves acuáticas entre habitats y otras unidades de paisaje del complejo Bahía Magdalena-Almejas, Baja California Sur, México. Se realizaron censos de aves acuáticas en 329 segmentos de habitat de la línea de costa interna del complejo lagunar, desde febrero 2002 hasta febrero 2003. La densidad de aves fue mayor en invierno y otoño en las tres lagunas del área de estudio; de las zonas, la densidad fue mayor en la costa insular; y de los habitats en playa arenosa y dunas pero en los pocos segmentos de sustrato antrópico la densidad fue alta. La diversidad fue significativamente mayor en otoño; en Canal Santo Domingo; en la costa peninsular; y de los habitats en manglar-dunas y manglar. La modificación del habitat natural costero y el disturbio por tránsito de embarcaciones no tuvieron influencia en la densidad o diversidad de aves acuáticas, pero la riqueza acumulada mayor ocurrió en las costas bien conservadas y sin disturbio. El análisis de la composición de especies mostró diferencias entre las asociaciones de Canal Santo Domingo y Bahía Magdalena. El ambiente pelágico y el manglar tuvieron diferencia mayor en la composición de especies con respecto a las asociaciones de los demás habitats, tales diferencias en elencos de especies por habitat sugieren que la comunidad de aves está estructurada de acuerdo a los recursos naturales disponibles de las lagunas, zonas y habitats, en relación con la complejidad estructural de las unidades de paisaje. Las condiciones ecológicas del complejo lagunar ocasionan que las aves acuáticas piscívoras sean el grupo dominante de esta comunidad.Community structure and association of waterbirds with spatial heterogeneity in the Bahía Magdalena-Almejas wetland complex, Baja California Sur, Mexico. To test

AGONISTIC BEHAVIOR OF LABORATORY MICE

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D. Cinghiţă

2005-01-01

Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

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Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

2016-02-04

Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.

Molecular phylogeny of the spoonbills (Aves: Threskiornithidae) based on mitochondrial DNA

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Chesser, R. Terry; Yeung, Carol K.L.; Yao, Cheng-Te; Tian, Xiu-Hua; Li, Shou-Hsien

2010-01-01

Spoonbills (genus Platalea) are a small group of wading birds, generally considered to constitute the subfamily Plataleinae (Aves: Threskiornithidae). We reconstructed phylogenetic relationships among the six species of spoonbills using variation in sequences of the mitochondrial genes ND2 and cytochrome b (total 1796 bp). Topologies of phylogenetic trees reconstructed using maximum likelihood, maximum parsimony, and Bayesian analyses were virtually identical and supported monophyly of the spoonbills. Most relationships within Platalea received strong support: P. minor and P. regia were closely related sister species, P. leucorodia was sister to the minor-regia clade, and P. alba was sister to the minor-regia-leucorodia clade. Relationships of P. flavipes and P. ajaja were less well resolved: these species either formed a clade that was sister to the four-species clade, or were successive sisters to this clade. This phylogeny is consistent with ideas of relatedness derived from spoonbill morphology. Our limited sampling of the Threskiornithinae (ibises), the putative sister group to the spoonbills, indicated that this group is paraphyletic, in agreement with previous molecular data; this suggests that separation of the Threskiornithidae into subfamilies Plataleinae and Threskiornithinae may not be warranted.

Acute treatment with 17beta-estradiol attenuates astrocyte-astrocyte and astrocyte-neuron communication.

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Rao, Shilpa P; Sikdar, Sujit Kumar

2007-12-01

Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control. (c) 2007 Wiley-Liss, Inc.

Treatment of Obesity-Related Complications with Novel Classes of Naturally Occurring PPAR Agonists.

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Bassaganya-Riera, Josep; Guri, Amir J; Hontecillas, Raquel

2011-01-01

The prevalence of obesity and its associated comorbidities has grown to epidemic proportions in the US and worldwide. Thus, developing safe and effective therapeutic approaches against these widespread and debilitating diseases is important and timely. Activation of peroxisome proliferator-activated receptors (PPARs) α, γ, and δ through several classes of pharmaceuticals can prevent or treat a variety of metabolic and inflammatory diseases, including type II diabetes (T2D). Thus, PPARs represent important molecular targets for developing novel and better treatments for a wide range of debilitating and widespread obesity-related diseases and disorders. However, available PPAR γ agonistic drugs such as Avandia have significant adverse side effects, including weight gain, fluid retention, hepatotoxicity, and congestive heart failure. An alternative to synthetic agonists of PPAR γ is the discovery and development of naturally occurring and safer nutraceuticals that may be dual or pan PPAR agonists. The purpose of this paper is to summarize the health effects of three plant-derived PPAR agonists: abscisic acid (ABA), punicic acid (PUA), and catalpic acid (CAA) in the prevention and treatment of chronic inflammatory and metabolic diseases and disorders.

Emerging GLP-1 receptor agonists

DEFF Research Database (Denmark)

Lund, Asger; Knop, Filip K; Vilsbøll, Tina

2011-01-01

and liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...... development may improve the effects of GLP-1 even further with optimized pharmacokinetic profiles resulting in fewer side effects. Meta-analyses have shown promising effects on cardiovascular disease and data from ongoing multicenter trials with cardiovascular endpoints are expected in 2015....

Niche evolution and diversification in a Neotropical radiation of birds (Aves: Furnariidae).

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Seeholzer, Glenn F; Claramunt, Santiago; Brumfield, Robb T

2017-03-01

Rapid diversification may be caused by ecological adaptive radiation via niche divergence. In this model, speciation is coupled with niche divergence and lineage diversification is predicted to be correlated with rates of niche evolution. Studies of the role of niche evolution in diversification have generally focused on ecomorphological diversification but climatic-niche evolution may also be important. We tested these alternatives using a phylogeny of 298 species of ovenbirds (Aves: Furnariidae). We found that within Furnariidae, variation in species richness and diversification rates of subclades were best predicted by rate of climatic-niche evolution than ecomorphological evolution. Although both are clearly important, univariate regression and multivariate model averaging more consistently supported the climatic-niche as the best predictor of lineage diversification. Our study adds to the growing body of evidence, suggesting that climatic-niche divergence may be an important driver of rapid diversification in addition to ecomorphological evolution. However, this pattern may depend on the phylogenetic scale at which rate heterogeneity is examined. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Local administration of a hedgehog agonist accelerates fracture healing in a mouse model

International Nuclear Information System (INIS)

Kashiwagi, Miki; Hojo, Hironori; Kitaura, Yoshiaki; Maeda, Yujiro; Aini, Hailati; Takato, Tsuyoshi; Chung, Ung-il; Ohba, Shinsuke

2016-01-01

Bone fracture healing is processed through multiple biological stages including the transition from cartilaginous callus to bony callus formation. Because of its specific, temporal and indispensable functions demonstrated by mouse genetic studies, Hedgehog (Hh) signaling is one of the most potent signaling pathways involved in these processes, but the effect of Hh-signaling activation by small compounds on the repair process had not yet been addressed. Here we examined therapeutic effects of local and one shot-administration of the Hh agonist known as smoothened agonist (SAG) on bone fracture healing in a mouse model. A quantitative analysis with three-dimensional micro-computed tomography showed that SAG administration increased the size of both the cartilaginous callus and bony callus at 14 days after the surgery. A histological analysis showed that SAG administration increased the number of cells expressing a proliferation marker and a chondrocyte marker in cartilaginous callus as well as the cells expressing an osteoblast marker in bony callus. These results indicate that the SAG administration resulted in an enhancement of callus formation during bone fracture healing, which is at least in part mediated by an increase in chondrocyte proliferation in cartilaginous callus and the promotion of bone formation in bony callus. Therapeutic strategies with a SAG-mediated protocol may thus be useful for the treatment of bone fractures. - Highlights: • Local administration of a Hh agonist accelerates callus formation. • The Hh agonist administration promotes chondrocyte proliferation in the soft callus. • The Hh agonist administration increases osteoblast formation in the hard callus.

Noteworthy bird records at Lagoa Santa, southeastern Brazil Registros notáveis de aves em Lagoa Santa, sudeste do Brasil

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Marcos Rodrigues

2008-03-01

Full Text Available Lagoa Santa, a small town in southeastern Brazil where naturalist Peter Lund lived, is regarded nowadays as an important historical site for the biological sciences. From 1847 to 1855, J.T. Reinhardt, hosted by Lund, collected 343 bird species. This material is an outstanding reference for many modern ornithological studies. The present paper reports the occurrence of some rare and threatened birds for the region of Lagoa Santa between 1998 and 2005. In this account I list the Rusty-margined Guan Penelope superciliaris Temminck, 1815; the Roseate Spoonbill Platalea ajaja Linnaeus, 1758; the Maguari Stork Ciconia maguari (Gmelin, 1789; the Wood Stork Mycteria americana Linnaeus, 1758; the Black Hawk-eagle Spizaetus tyrannus (Wied, 1820 and the Turquoise-fronted Parrot Amazona aestiva (Linnaeus, 1758. It is also reported the southernmost record for the Blue-and-yellow Macaw Ara ararauna (Linnaeus, 1758 and the range extension of the Crowned Slaty flycatcher Griseotyrannus aurantioatrocristatus (d'Orbigny and Lafresnaye, 1837. These data can be used as a baseline for studies of colonization and extinction.Lagoa Santa, cidade onde viveu Peter Lund é um dos sítios de maior importância histórica para as ciências biológicas. Durante os anos de 1847 e 1855, J.T. Reinhardt, a convite de Lund, coletou 343 espécies de aves que são hoje referência para vários estudos ornitológicos. O presente artigo relata a ocorrência de algumas aves raras e/ou ameaçadas para a região de Lagoa Santa, entre 1998 e 2005. A lista de espécies inclui a jacupemba Penelope superciliaris Temminck, 1815, o colhereiro Platalea ajaja Linnaeus, 1758, a maguari Ciconia maguari (Gmelin, 1789, a cabeça-seca Mycteria americana Linnaeus, 1758, o gavião-pega-macaco Spizaetus tyrannus (Wied, 1820; e o papagaio-verdadeiro Amazona aestiva (Linnaeus, 1758. Relata-se também a ocorrência mais meridional da arara-canindé Ara ararauna (Linnaeus, 1758, e a expansão da distribui

Comparison of the release of microRNAs and extracellular vesicles from platelets in response to different agonists.

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Ambrose, Ashley R; Alsahli, Mohammed A; Kurmani, Sameer A; Goodall, Alison H

2018-07-01

On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP. The released microRNAs were profiled using TaqMan microRNA microarray cards. Platelet-derived EV (pdEV) were characterized by size (Nanoparticle Tracking Analysis, NTA), for procoagulant activity (Annexin-V binding and support of thrombin generation), and for the EV markers CD63 and HSP70. Platelet activation triggered the release of 57-79 different microRNAs, dependent upon agonist, with a core of 46 microRNAs observed with all agonists. There was a high level of correlation between agonists (r 2  > 0.98; p  0.98; p < 0.0001). The 46 microRNAs seen in all samples are predicted to have significant effects on the translation of proteins involved in endocytosis, cell cycle control, and differentiation. MiR-223-3p was the most abundant in all samples and has previously been implicated in myeloid lineage development and demonstrated to have anti-inflammatory effects. Stimulation through GPVI produced a pdEV population with significantly more procoagulant activity than the other agonists. Apyrase significantly reduced microRNA and pdEV release, while aspirin had little effect. These data suggest that all tested agonists trigger the release of a similar microRNA profile while the procoagulant activity of the pdEV was agonist dependent. ADP was shown to play an important role in the release of both microRNAs and pdEV.

Beta agonists in livestock feed: status, health concerns, and international trade.

Science.gov (United States)

Centner, T J; Alvey, J C; Stelzleni, A M

2014-09-01

Since the U.S. Food and Drug Administration approved ractopamine hydrochloride and zilpaterol hydrochloride in animal feeds, usage of those compounds has been a topic of worldwide debate. Ractopamine and zilpaterol are β-adrenergic agonists used as veterinary drugs to increase weight gain in certain animals raised for food. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established maximum residue limits for ractopamine, which were adopted by the Codex Alimentarius Commission (Codex). No maximum residue limits for zilpaterol have been adopted by JECFA, and new reports of animal mobility issues confront the use of this feed additive. However, many countries disagree with the Codex standards and are restricting or banning meat products containing β agonists. The bans by major importers of U.S. meat products have prompted some to advocate that the United States use the World Trade Organization dispute settlement body. This paper looks at the developments to provide a fuller accounting of what the issues may mean to U.S. firms selling meat products containing residues of β agonists.

GnRH antagonist versus long agonist protocols in IVF

DEFF Research Database (Denmark)

Lambalk, C B; Banga, F R; Huirne, J A

2017-01-01

BACKGROUND: Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist...... was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF...

Landing gear noise attenuation

Science.gov (United States)

Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

2011-01-01

A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys

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S. Stevens Negus

2012-01-01

Full Text Available Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+-4-[(αR-α-((2S,5R-4-allyl-2,5-dimethyl-1-piperazinyl-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine. Methadone, morphine, and nalbuphine each produced dose-dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg. SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception.

Overcoming beta-agonist tolerance: high dose salbutamol and ipratropium bromide. Two randomised controlled trials

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Haney Sarah

2007-03-01

Full Text Available Abstract Background Asthmatics treated with long-acting beta-agonists have a reduced bronchodilator response to moderate doses of inhaled short acting beta-agonists during acute bronchoconstriction. It is not known if the response to higher doses of nebulised beta-agonists or other bronchodilators is impaired. We assessed the effect of long-acting beta-agonist treatment on the response to 5 mg nebulised salbutamol and to ipratropium bromide. Methods Two double-blind, placebo-controlled, crossover studies of inhaled formoterol 12 μg twice daily in patients with asthma. High-dose salbutamol: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 5 mg was then administered via nebuliser and the FEV1 was monitored for 20 minutes. Ipratropium: 36 hours after the last dose of 1 week of formoterol or placebo treatment, 11 subjects inhaled 4.5% saline to produce a 20% fall in FEV1. Salbutamol 200 μg or ipratropium bromide 40 μg was then inhaled and the FEV1 was monitored for 30 minutes. Four study arms compared the response to each bronchodilator after formoterol and placebo. Analyses compared the area under the bronchodilator response curves, adjusting for changes in pre-challenge FEV1, dose of provocational agent and FEV1 fall during the challenge procedure. Results The response to nebulised salbutamol was 15% lower after formoterol therapy compared to placebo (95% confidence 5 to 25%, p = 0.008. The response to ipratropium was unchanged. Conclusion Long-acting beta-agonist treatment induces tolerance to the bronchodilator effect of beta-agonists, which is not overcome by higher dose nebulised salbutamol. However, the bronchodilator response to ipratropium bromide is unaffected.

''Spare'' alpha 1-adrenergic receptors and the potency of agonists in rat vas deferens

International Nuclear Information System (INIS)

Minneman, K.P.; Abel, P.W.

1984-01-01

The existence of ''spare'' alpha 1-adrenergic receptors in rat vas deferens was examined directly using radioligand binding assays and contractility measurements. Alpha 1-adrenergic receptors in homogenates of rat vas deferens were labeled with [ 125 I]BE 2254 ( 125 IBE). Norepinephrine and other full alpha 1-adrenergic receptor agonists were much less potent in inhibiting 125 IBE binding than in contracting the vas deferens in vitro. Treatment with 300 nM phenoxybenzamine for 10 min to irreversibly inactivate alpha 1-adrenergic receptors caused a large decrease in the potency of full agonists in causing contraction of this tissue and a 23-48% decrease in the maximal contraction observed. Using those data, equilibrium constants for activation (Kact values) of the receptors by agonists were calculated. These Kact values agreed well with the equilibrium binding constants (KD values) determined from displacement of 125 IBE binding. The reduction in alpha 1-adrenergic receptor density following phenoxybenzamine treatment was determined by Scatchard analysis of specific 125 IBE binding sites and compared with the expected reduction (q values) calculated from the agonist dose-response curves before and after phenoxybenzamine treatment. This suggests that phenoxybenzamine functionally inactivates alpha 1-adrenergic receptors at or near the receptor binding site. These experiments suggest that the potencies of agonists in activating alpha 1-adrenergic receptors in rat vas deferens agree well with their potencies in binding to the receptors. The greater potency of agonists in causing contraction may be due to spare receptors in this tissue. The data also demonstrate that phenoxybenzamine irreversibly inactivates alpha 1-adrenergic receptors in rat vas deferens, but that the decrease in receptor density is much smaller than that predicted from receptor theory

Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.

Science.gov (United States)

Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Jones, Stacey A; Kaldor, Istvan; Liu, Yaping; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Wisely, G Bruce

2008-08-01

Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

Differential activation of G-proteins by μ-opioid receptor agonists

Science.gov (United States)

Saidak, Zuzana; Blake-Palmer, Katherine; Hay, Debbie L; Northup, John K; Glass, Michelle

2006-01-01

We investigated the ability of the activated μ-opioid receptor (MOR) to differentiate between myristoylated Gαi1 and GαoA type Gα proteins, and the maximal activity of a range of synthetic and endogenous agonists to activate each Gα protein. Membranes from HEK293 cells stably expressing transfected MOR were chaotrope extracted to denature endogenous G-proteins and reconstituted with specific purified G-proteins. The Gα subunits were generated in bacteria and were demonstrated to be recognised equivalently to bovine brain purified Gα protein by CB1 cannabinoid receptors. The ability of agonists to catalyse the MOR-dependent GDP/[35S]GTPγS exchange was then compared for Gαi1 and GαoA. Activation of MOR by DAMGO produced a high-affinity saturable interaction for GαoA (Km=20±1 nM) but a low-affinity interaction with Gαi1 (Km=116±12 nM). DAMGO, met-enkephalin and leucine-enkephalin displayed maximal Gα activation among the agonists evaluated. Endomorphins 1 and 2, methadone and β-endorphin activated both Gα to more than 75% of the maximal response, whereas fentanyl partially activated both G-proteins. Buprenorphine and morphine demonstrated a statistically significant difference between the maximal activities between Gαi1 and GαoA. Interestingly, DAMGO, morphine, endomorphins 1 and 2, displayed significant differences in the potencies for the activation of the two Gα. Differences in maximal activity and potency, for Gαi1 versus GαoA, are both indicative of agonist selective activation of G-proteins in response to MOR activation. These findings may provide a starting point for the design of drugs that demonstrate greater selectivity between these two G-proteins and therefore produce a more limited range of effects. PMID:16415903

THE ADVERTISING-VALUE-EQUIVALENT (AVE METHOD IN QUANTIFYING ECONOMIC VALUES OF PUBLIC RELATIONS ACTIVITIES: EXPERIENCE OF A PUBLIC-LISTED COMPANY IN MALAYSIA

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Musa Abu Hassan

2006-01-01

Full Text Available Why should public relations (PR not be evaluated for its economic value? Despite the point of its social or intangible values, the argument goes on and on in most management meetings where PR practitioners always face the challenges of justifying their worth – often in monetary terms. In an open dialogue with Grunig during his visit to Malaysia in 2004, this renowned PR guru also expressed the difficulty of quantifying the actual PR worth. It is best to qualify PR values by assessing its priceless relationships with the company’s stakeholders. However, in our routine business life, especially at the middle management level, the above question seems unavoidable. In enhancing excellence for PR and communication management, Ehling (1992 placed the logic underlying the economic values of PR on the relationship between benefits and costs associated with the implementation of a PR programme. The above question and problem serve as the main objective of this article. In exploring the solutions for the quantification of PR values in Malaysia, economic education is taken as a remedy for the absence of knowledge and skills in making intelligent decisions in the marketplace (Baskin et al., 1997; Lattimor et al., 2004. In this research context, the researchers (a combination of a practitioner and an academician respectively confined the scope to the experience of a selected public-listed company for its PR campaign implemented in 2004. Quantification was attempted by evaluating the assessment in print media exposures. All earned media coverage for that particular PR campaign was measured for the media type, space, position, and the corresponding advertising rate. Monetary value was assigned to every single piece of PR news in the way disbursements are made to paid media for advertising activities. The explication of this advertising-value-equivalent (AVE method in quantifying economic values for PR news with regard to the selected campaign was made

Agonist-induced internalisation of the glucagon-like peptide-1 receptor is mediated by the Gαq pathway.

Science.gov (United States)

Thompson, Aiysha; Kanamarlapudi, Venkateswarlu

2015-01-01

The glucagon-like peptide-1 receptor (GLP-1R) is a G-protein-coupled receptor (GPCR) and an important target in the treatment of type 2 diabetes mellitus (T2DM). Upon stimulation with agonist, the GLP-1R signals through both Gαs and Gαq coupled pathways to stimulate insulin secretion. The agonist-induced GLP-1R internalisation has recently been shown to be important for insulin secretion. However, the molecular mechanisms underlying GLP-1R internalisation remain unknown. The aim of this study was to determine the role of GLP-1R downstream signalling pathways in its internalisation. Agonist-induced human GLP-1R (hGLP-1R) internalisation and activity were examined using a number of techniques including immunoblotting, ELISA, immunofluorescence and luciferase assays to determine cAMP production, intracellular Ca(2+) accumulation and ERK phosphorylation. Agonist-induced hGLP-1R internalisation is dependent on caveolin-1 and dynamin. Inhibition of the Gαq pathway but not the Gαs pathway affected hGLP-1R internalisation. Consistent with this, hGLP-1R mutant T149M and small-molecule agonists (compound 2 and compound B), which activate only the Gαs pathway, failed to induce internalisation of the receptor. Chemical inhibitors of the Gαq pathway, PKC and ERK phosphorylation significantly reduced agonist-induced hGLP-1R internalisation. These inhibitors also suppressed agonist-induced ERK1/2 phosphorylation demonstrating that the phosphorylated ERK acts downstream of the Gαq pathway in the hGLP-1R internalisation. In summary, agonist-induced hGLP-1R internalisation is mediated by the Gαq pathway. The internalised hGLP-1R stimulates insulin secretion from pancreatic β-cells, indicating the importance of GLP-1 internalisation for insulin secretion. Copyright © 2014 Elsevier Inc. All rights reserved.

Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORγt inverse agonists.

Science.gov (United States)

Wang, Yonghui; Yang, Ting; Liu, Qian; Ma, Yingli; Yang, Liuqing; Zhou, Ling; Xiang, Zhijun; Cheng, Ziqiang; Lu, Sijie; Orband-Miller, Lisa A; Zhang, Wei; Wu, Qianqian; Zhang, Kathleen; Li, Yi; Xiang, Jia-Ning; Elliott, John D; Leung, Stewart; Ren, Feng; Lin, Xichen

2015-09-01

A novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORγt inverse agonists was discovered. Binding mode analysis of a RORγt partial agonist (2c) revealed by co-crystal structure in RORγt LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORγt LBD. Detailed SAR exploration led to identification of potent RORγt inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Involvement of the Retinoid X Receptor Ligand in the Anti-Inflammatory Effect Induced by Peroxisome Proliferator-Activated Receptor Agonist In Vivo

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Atsuki Yamamoto

2011-01-01

Full Text Available Peroxisome proliferator-activated receptor γ (PPARγ forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs. It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPARγ agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPARγ-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPARγ agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPAR antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPARγ agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPARγ agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPARγ agonist-induced anti-inflammatory effect.

Dopamine agonist increases risk taking but blunts reward-related brain activity.

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Jordi Riba

Full Text Available The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

Use of ß-adrenergic agonists in hybrid catfish

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Ractopamine hydrochloride (RH) is a potent ß-adrenergic agonist that has been used in some species of fish to improve growth performance and dress out characteristics. While this metabolic modifier has been shown to have positive effects on growth of fish, little research has focused on the mechani...

Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance

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Loosbroock C

2014-12-01

Full Text Available Christopher Loosbroock, Kenneth W Hunter Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, USA Abstract: Tumor necrosis factor-alpha (TNF-α is a central mediator of inflammatory responses elicited by Toll-like receptor agonists, such as the Gram-negative bacterial outer membrane antigen lipopolysaccharide (LPS. TNF-α is responsible for altering vascular permeability and activating infiltrating inflammatory cells, such as monocytes and neutrophils. Interestingly, TNF-α has also demonstrated the ability to induce tolerance to subsequent challenges with TNF-α or LPS in monocyte and macrophage cell populations. Tolerance is characterized by the inability to mount a typical inflammatory response during subsequent challenges following the initial exposure to an inflammatory mediator such as LPS. The ability of TNF-α to induce a tolerant-like state with regard to LPS is most likely a regulatory mechanism to prevent excessive inflammation. We hypothesized that the induction of tolerance or the degree of tolerance is dependent upon the production of TNF-α during the primary response to LPS. To investigate TNF-α-dependent tolerance, human monocytic THP-1 cells were treated with TNF-α-neutralizing antibodies or antagonistic TNF-α receptor antibodies before primary LPS stimulation and then monitored for the production of TNF-α during the primary and challenge stimulation. During the primary stimulation, anti-TNF-α treatment effectively attenuated the production of TNF-α and interleukin-1β; however, this reduced production did not impact the induction of endotoxin tolerance. These results demonstrate that interfering with TNF-α signaling attenuates production of inflammatory cytokines without affecting the induction of tolerance. Keywords: endotoxin tolerance, lipopolysaccharide, tumor necrosis factor-alpha, anti-tumor necrosis factor-alpha, THP-1 cells

Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

Science.gov (United States)

Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

2016-11-10

On the basis of the structural similarity of our previous 5-HT 2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT 2A , 5-HT 2B , and 5-HT 2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT 2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT 2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

Relação entre Triatoma infestans, aves domésticas e o homem num povoado de Santiago del Estero, Argentina The relationship between Triatoma infestans, poultry, and humans in a rural settlement in Santiago del Estero, Argentina

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Patrícia P. Gajate

1994-03-01

Full Text Available Determinou-se a associação entre Triatoma infestans, aves domésticas e o homem no povoado de Trinidad, Santiago del Estero, Argentina. Para coletar triatomíneos foram realizadas quatro amostragens no peridomicílio de seis casas, utilizando-se o método de captura hora/homem (dezembro de 1991 a outubro de 1992. Os anexos foram classificados em antrópicos (onde o homem realiza atividades cotidianas e não-antrópicos. Além disso, determinou-se o perfil alimentar dos barbeiros. De um total de 134 ecótopos investigados, 21% tinham T. infestans; 22% possuíam aves domésticas; e 54% eram antrópicos. Em 25% destes ecótopos foram encontradas aves e T. infestans simultaneamente. As aves foram os únicos animais domésticos associados com o T. infestans, sendo que esta relação só ocorreu nos ecótopos antrópicos. A proporção de ingestas em aves (61/146 foi altamente significativa. Em Trinidad não há galinheiros, utilizando-se, assim, os anexos entrópicos do peridomicílio como local para se construir os ninhos para as aves. tanto pelos elementos usados na preparação dos ninhos como pelo uso posterior dos mesmos, poder-se-ia estabelecer um fluxo periódico de barbeiros do intradomicílio para o peridomicílio, e vice-versa, através do transporte passivo. Esta relação estreita entre Triatoma infestans, aves domésticas e o homem, encontrada nos ecótopos antrópicos, onde também existem outros reservatórios de T. cruzi, como os cães, favorece a manutenção de colônias de barbeiros domiciliares e a transmissão da doença de Chagas ao homem.An association was determined between Triatona infestans, poultry, and humans in Trinidad, in the Province of Santiago del Estero, Argentina. To collect triatomines, four samples were taken at the area immediately surrounding six houses by the one hour/man capture method (December 1991 - October 1992. Peridomiciliary ecotopes were classified as arthropic (where humans carry out daily

Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

Science.gov (United States)

Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

2016-01-01

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists.

Science.gov (United States)

Yanofsky, Stephen D; Shen, Emily S; Holden, Frank; Whitehorn, Erik; Aguilar, Barbara; Tate, Emily; Holmes, Christopher P; Scheuerman, Randall; MacLean, Derek; Wu, May M; Frail, Donald E; López, Francisco J; Winneker, Richard; Arey, Brian J; Barrett, Ronald W

2006-05-12

The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 microm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.

Reconstitution of high affinity α2 adrenergic agonist binding by fusion with a pertussis toxin substrate

International Nuclear Information System (INIS)

Kim, M.H.; Neubig, R.R.

1986-01-01

High affinity α 2 adrenergic agonist binding is thought to occur via a coupling of the α 2 receptor with N/sub i/, the inhibitory guanyl nucleotide binding protein. Human platelet membranes pretreated at pH 11.5 exhibit a selective inactivation of agonist binding and N/sub i/. To further study the mechanism of agonist binding, alkali treated membranes (ATM) were mixed with membranes pretreated with 10 μM phenoxybenzamine to block α 2 receptors (POB-M). The combined membrane pellet was incubated in 50% polyethylene glycol (PEG) to promote membrane-membrane fusion and assayed for binding to the α 2 agonist [ 3 H]UK 14,304 (UK) and the antagonist [ 3 H] yohimbine. PEG treatment resulted in a 2-4 fold enhancement of UK binding whereas yohimbine binding was unchanged. No enhancement of UK binding was observed in the absence of PEG treatment. The reconstitution was dependent on the addition of POB-M. They found that a 1:1 ratio of POB-M:ATM was optimal. Reconstituted binding was inhibited by GppNHp. Fusion of rat C6 glioma cell membranes, which do not contain α 2 receptors, also enhanced agonist binding to ATM. Fusion of C6 membranes from cells treated with pertussis toxin did not enhance [ 3 H] UK binding. These data show that a pertussis toxin sensitive membrane component, possibly N/sub i/, can reconstitute high affinity α 2 agonist binding

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET

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Depalo Raffaella

2012-04-01

Full Text Available Abstract Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Trialkyltin rexinoid-X receptor agonists selectively potentiate thyroid hormone induced programs of xenopus laevis metamorphosis

NARCIS (Netherlands)

Mengeling, Brenda J.; Murk, Albertinka J.; Furlow, J.D.

2016-01-01

The trialkyltins tributyltin (TBT) and triphenyltin (TPT) can function as rexinoid-X receptor (RXR) agonists. We recently showed that RXR agonists can alter thyroid hormone (TH) signaling in a mammalian pituitary TH-responsive reporter cell line, GH3.TRE-Luc. The prevalence of TBT and TPT in the

Protective effects of the angiotensin II ATreceptor agonist compound 21 in ischemic stroke

DEFF Research Database (Denmark)

Bennion, Douglas M; Jones, Chad H; Dang, Alex N

2018-01-01

) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2receptor agonists are blood-brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver...... in certain human central nervous system diseases, the N2B application of AT2receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.......-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective...

Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

International Nuclear Information System (INIS)

Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice; Erchegyi, Judit; Rivier, Jean E.

2010-01-01

Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst 1 -sst 5 ) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst 2 and sst 3 internalization in vitro in HEK293 cells stably expressing the human sst 2 or sst 3 receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst 2 internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst 3 internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst 3 receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor.

Science.gov (United States)

Lin, Wenwei; Yang, Lei; Chai, Sergio C; Lu, Yan; Chen, Taosheng

2016-01-27

Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) are master regulators of endobiotic and xenobiotic metabolism and disposition. Because CAR is constitutively active in certain cellular contexts, inhibiting CAR might reduce drug-induced hepatotoxicity and resensitize drug-resistant cancer cells to chemotherapeutic drugs. We recently reported a novel CAR inhibitor/inverse agonist CINPA1 (11). Here, we have obtained or designed 54 analogs of CINPA1 and used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate their CAR inhibition potency. Many of the 54 analogs showed CAR inverse agonistic activities higher than those of CINPA1, which has an IC50 value of 687 nM. Among them, 72 has an IC50 value of 11.7 nM, which is about 59-fold more potent than CINPA1 and over 10-fold more potent than clotrimazole (an IC50 value of 126.9 nM), the most potent CAR inverse agonist in a biochemical assay previously reported by others. Docking studies provide a molecular explanation of the structure-activity relationship (SAR) observed experimentally. To our knowledge, this effort is the first chemistry endeavor in designing and identifying potent CAR inverse agonists based on a novel chemical scaffold, leading to 72 as the most potent CAR inverse agonist so far. The 54 chemicals presented are novel and unique tools for characterizing CAR's function, and the SAR information gained from these 54 analogs could guide future efforts to develop improved CAR inverse agonists. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

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Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

1994-02-28

Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

The 5-HT(1F) receptor agonist lasmiditan as a potential treatment of migraine attacks

DEFF Research Database (Denmark)

Tfelt-Hansen, Peer C; Olesen, Jes

2012-01-01

Lasmiditan is a novel selective 5-HT(1F) receptor agonist. It is both scientifically and clinically relevant to review whether a 5-HT(1F) receptor agonist is effective in the acute treatment of migraine. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo...

Monitoring of PAEMs and beta-agonists in urine for a small group of experimental subjects and PAEs and beta-agonists in drinking water consumed by the same subjects.

Science.gov (United States)

Liou, Saou-Hsing; Yang, Gordon C C; Wang, Chih-Lung; Chiu, Yu-Han

2014-07-30

This 5-month study contains two parts: (1) to monitor the concentrations of 11 phthalate esters metabolites (PAEMs) and two beta-agonists in human urine samples collected from a small group of consented participants including 16 females and five males; and (2) to analyze the residues of phthalate esters (PAEs) and beta-agonists in various categories of drinking water consumed by the same group of subjects. Each category of human urine and drinking water had 183 samples of its own. The analytical results showed that nine PAEMs were detected in human urine and eight PAEs were detected in drinking water samples. It was found that average concentrations of PAEMs increased as the age increased, but no significant difference between sexes. Further, using the principal component analysis, the loadings of age effect were found to be two times greater than that of gender effect in terms of four DEHP metabolites. Regarding beta-agonists of concern (i.e., ractopamine and salbutamol), they were neither detected in human urine nor drinking water samples in this study. Copyright © 2014 Elsevier B.V. All rights reserved.

Differences in the locomotor-activating effects of indirect serotonin agonists in habituated and non-habituated rats.

Science.gov (United States)

Halberstadt, Adam L; Buell, Mahálah R; Price, Diana L; Geyer, Mark A

2012-07-01

The indirect serotonin (5-HT) agonist 3,4-methylenedioxymethamphetamine (MDMA) produces a distinct behavioral profile in rats consisting of locomotor hyperactivity, thigmotaxis, and decreased exploration. The indirect 5-HT agonist α-ethyltryptamine (AET) produces a similar behavioral profile. Using the Behavioral Pattern Monitor (BPM), the present investigation examined whether the effects of MDMA and AET are dependent on the novelty of the testing environment. These experiments were conducted in Sprague-Dawley rats housed on a reversed light cycle and tested during the dark phase of the light/dark cycle. We found that racemic MDMA (RS-MDMA; 3 mg/kg, SC) increased locomotor activity in rats tested in novel BPM chambers, but had no effect on locomotor activity in rats habituated to the BPM chambers immediately prior to testing. Likewise, AET (5 mg/kg, SC) increased locomotor activity in non-habituated animals but not in animals habituated to the test chambers. These results were unexpected because previous reports indicate that MDMA has robust locomotor-activating effects in habituated animals. To further examine the influence of habituation on MDMA-induced locomotor activity, we conducted parametric studies with S-(+)-MDMA (the more active enantiomer) in habituated and non-habituated rats housed on a standard or reversed light cycle. Light cycle was included as a variable due to reported differences in sensitivity to serotonergic ligands during the dark and light phases. In confirmation of our initial studies, rats tested during the dark phase and habituated to the BPM did not show an S-(+)-MDMA (3 mg/kg, SC)-induced increase in locomotor activity, whereas non-habituated rats did. By contrast, in rats tested during the light phase, S-(+)-MDMA increased locomotor activity in both non-habituated and habituated rats, although the response in habituated animals was attenuated. The finding that habituation and light cycle interact to influence MDMA- and AET

Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists.

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Kawakami, Jun; Morales, Alvaro

2013-01-01

We examined the serum levels of testosterone (T) (total and bioavailable) dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prostate-specific antigen (PSA) in men receiving treatment with luteinizing hormone releasing-hormone (LHRH) agonists for metastatic prostate cancer. In doing this, we want to determine the efficacy of these agents in lowering T levels and whether a possible relationship exists between PSA values, as a surrogate measure of tumour activity, and hormone levels. This was a single centre prospective study of patients on LHRH agonists. Of all the 100 eligible patients, 31 did not qualify (10 were receiving their first injection, 13 were on intermittent hormonal therapy, 7 refused to enter the trial and 1 patient's blood sample was lost). Therefore in total, 69 patients were included in the final analysis. Each patient had their blood sample drawn immediately before the administration of a LHRH agonist. The new proposed criteria of values are more commonly found in patients with suboptimal levels of testosterone receiving LHRH analogs, but the clinical importance of this finding has not been established. There is no significant difference with respect to hormonal levels reached among patients on a variety of LHRH agonists. Total testosterone determinations should be considered in patients on LHRH agonist therapy, particularly when the PSA values begin to rise since it may lead to further beneficial hormonal manipulation.

Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

Science.gov (United States)

Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

2016-05-03

Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

MRI-guided attenuation correction in whole-body PET/MR. Assessment of the effect of bone attenuation

International Nuclear Information System (INIS)

Akbarzadeh, A.; Ay, M.R.; Ahmadian, A.; Riahi Alam, N.; Zaidi, H.

2013-01-01

Hybrid positron emission tomography (PET)/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies. (author)

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists.

Science.gov (United States)

Ortiz, Jose Luis; Ortiz, Amparo; Milara, Javier; Armengot, Miguel; Sanz, Celia; Compañ, Desamparados; Morcillo, Esteban; Cortijo, Julio

2016-01-01

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis.

Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis.

Science.gov (United States)

Zhang, Cheng-Gang; Zhang, Bin; Deng, Wen-Sheng; Duan, Ming; Chen, Wei; Wu, Zhi-Yong

2016-05-14

To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN

Attenuation of Immune-Mediated Renal Injury by Telmisartan, an Angiotensin Receptor Blocker and a Selective PPAR-γ Activator

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Yuki Hamano

2011-09-01

Full Text Available Background/Aims: Anti-glomerular basement membrane (GBM nephritis is characterized by activation of the renin-angiotensin system. This study aimed to determine the question of whether a temporary angiotensin II blockade at the initial stage of anti-GBM nephritis is able to attenuate the disease as well as differences in renoprotection among angiotensin II receptor blockers (ARBs with distinct peroxisome proliferator-activated receptor (PPAR-γ-modulating activities. Methods: C57BL/6J mice were immunized with rabbit IgG, followed by intravenous injection of rabbit anti-mouse antibodies. Mice were then treated with telmisartan, losartan, and telmisartan + GW9662 (a PPAR-γ antagonist for 5 days, or hydralazine for 9 days. On days 8 and 13, mice were sacrificed to obtain tissues for histological analysis. Results: The temporary administration of telmisartan significantly suppressed glomerular damage compared to hydralazine. Losartan showed a similar effect but was less effective. Co-administration of GW9662 attenuated the renoprotective effect of telmisartan, almost to levels observed with losartan. In particular, it limited the decreased infiltration of inflammatory cells and preservation of capillaries in the glomeruli induced by telmisartan. Conclusion: Temporary angiotensin II blockade at the initial stage of anti-GBM disease dramatically inhibited its progression. In addition to a class effect of ARBs, telmisartan modified inflammation and endothelial damage in the kidney through its PPAR-γ-agonistic action.

Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; El-Sayed, Mona; Mikkelsen, Jens D

2011-01-01

of repeated administration of α7 nAChR agonists. We further compare the effect of agonists to that of α7 nAChR positive allosteric modulators (PAMs), which do not induce upregulation of the α7 nAChR. Using the social discrimination test as a measure of short-term memory, we show that the α7 nAChR agonist A......-582941 improves short-term memory immediately after repeated (7× daily), but not a single administration. The α7 nAChR PAMs PNU-120596 and AVL-3288 do not affect short-term memory immediately after a single or repeated administration. This demonstrates a fundamental difference in the behavioral effects...... of agonists and PAMs that may be relevant for clinical development. Importantly, A-582941 and AVL-3288 increase short-term memory 24 hrs after repeated, but not a single, administration, suggesting that repeated administration of both agonists and PAMs may produce sustained effects on cognitive performance...

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

OpenAIRE

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) an...

Presencia de campylobacter jejuni en aves de corral y sus manipuladores

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Fabio Carmona

1985-12-01

Full Text Available En una granja procesadora de aves en la ciudad de Cali, donde se sacrifican 12.000 animales diarios, se escogió para buscar Campylobacter jejuni una muestra de 120 pollos tomando como base una prevalencia del 80% y empleando un muestreo sistemático para dar una mayor cobertura teniendo en cuenta que la procedencia de los animales variaba diariamente. El porcentaje de positividad en materia fecal fue de 98.33% (118/120. Con la finalidad de averiguar el grado de higiene empleado en la manipulación de las canales, se frotó la superficie de ellos antes y después de introducirle las vísceras que es sabido van dentro del pollo al llegar al consumidor; se encontró que las canales con vísceras estaban contaminadas en un 18.33% (11/60 mientras que antes de este procedimiento la contaminación tan solo fue del 8.33% (5/60. También fueron examinadas 62 personas para buscar en ellas el C. jejuni encontrhndose en 5 (8.06% la bacteria. A todas las cepas aisladas se les probó la sensibilidad a la eritromicina usando disco de 15 Ug observándose un 100% de sensibilidad a la droga.

Características técnico-sanitarias de expendios de carnes, pescados, aves y huevos de la ciudad de Tunja 2003

OpenAIRE

Fred Gustavo Manrique-Abril; Diego Alexander Manrique-Abril; Pablo Fernandez; Elena Patricia Castro-Montaña

2011-01-01

Se presenta una caracterización epidemiológica de los expendios de carnes, pescado y aves de Tunja en el año 2003, resultado del diagnóstico sanitario del municipio y las visitas adelantadas por la unidad de saneamiento. Al partir del compromiso que el sector salud tiene en el componente de ambiente, surge la necesidad de crear un sistema de vigilancia epidemiológica ambiental, cuya metodología y estrategia esté orientada hacia el conocimiento de los factores de riesgo ambientales a que están...

Dipeptidyl peptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) agonists

DEFF Research Database (Denmark)

Madsbad, Sten

2012-01-01

Incretin-based therapies, which include the GLP-1 receptor agonists and DPP-4 inhibitors, use the antidiabetic properties of potentiating the GLP-1 receptor signalling via the regulation of insulin and glucagon secretion, inhibition of gastric emptying and suppression of appetite. Most physicians...... will start antidiabetic treatment with metformin, but adding a GLP-1 receptor agonist as the second drug seems to be optimal since more patients will reach an HbA1c below 7% than with a DPP-4 inhibitor or another oral antidiabetic agents and with minimal risk of hypoglycaemia. The GLP-1 receptor agonists...

Attenuation of Morphine Physical Dependence and Blood Levels of Cortisol by Central and Systemic Administration of Ramelteon in Rat

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Majid Motaghinejad

2015-05-01

Full Text Available Background: Chronic administration of morphine cause physical dependence but the exact mechanism of this phenomenon remains unclear. The aim of this study is the assessment of systemic and intracerebroventricular (icv administration of ramelteon (a melatonin receptor agonist on morphine physical dependence. Methods: 88 adult male rats were divided into 2 major groups, namely “systematic” and “central” administration of ramelteon. In the first category, systemic administration of ramelteon at various dosages (10, 20, and 40 mg/kg was assessed on dependent animals and withdrawal signs were compared with positive (received morphine and saline as systemic administration, negative control (saline and group under treatment by ramelteon (40 mg/kg groups. In the second category, central administration of ramelteon at various dosages (25, 50, or 100 μg, was assessed on dependent animals and withdrawal signs were compared with the positive control (received morphine and saline as icv and negative control (saline groups, and the group under treatment by ramelteon (50 μg/5 μl/rat. On the test day, all animals received naloxone (3 mg/kg and were observed for withdrawal signs. Total withdrawal score (TWS was also determined. Finally, to evaluate the stress level of dependent rats, blood cortisols were measured. Results: Central administration of ramelteon in all doses and systemic administration in high doses attenuate withdrawal syndrome in comparison with the dependent positive control group (P<0.05. Both central and systemic administrations of ramelteon can attenuate the blood cortisol level in comparison with the dependent positive control group (P<0.05. Conclusion: In conclusion, we found that central administration of ramelteon attenuated morphine withdrawal symptoms and cortisol level as a stress marker.

Relaxing action of adrenergic β2-agonists on guinea-pig skinned tracheal muscle

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Kayo Nemoto

1999-01-01

Full Text Available Although adrenergic β2-agonist-induced smooth muscle relaxation has been attributed to increased intracellular cyclic AMP (cAMP, a relaxation response has been observed at low β2-agonist concentrations that do not cause increased cAMP To elucidate the mechanism of tracheal muscle relaxation induced by low concentrations of β2-agonists, we used a guinea-pig skinned tracheal smooth muscle preparation to examine the effects on the contractile protein system. The isotonic contraction of β-escin-treated skinned tracheal muscle from guinea-pig was measured. When the intracellular Ca2+ concentration was maintained at 1 μmol/L in the presence of guanosine 5′-triphosphate (GTP; 100 μmol/L, neither isoproterenol (10nmol/L nor salbutamol (60 nmol/L affected Ca2+ sensitivity, but a significant decrease in Ca2+ sensitivity was observed in the presence of okadaic acid (1 μmol/L. The decrease in Ca2+ sensitivity was a slow response and was blocked by pretreatment with propranolol (1 μmol/L. Forskolin (1 μmol/L did not affect Ca2+ sensitivity. These results suggest that adrenergic b 2-agonists may activate protein phosphatase through an unknown pathway involving the β2-receptor, which enhances dephosphorylation of the myosin light chain and/or thin filament proteins, resulting in relaxation of the tracheal smooth muscle.

PET attenuation coefficients from CT images: experimental evaluation of the transformation of CT into PET 511-keV attenuation coefficients.

Science.gov (United States)

Burger, C; Goerres, G; Schoenes, S; Buck, A; Lonn, A H R; Von Schulthess, G K

2002-07-01

The CT data acquired in combined PET/CT studies provide a fast and essentially noiseless source for the correction of photon attenuation in PET emission data. To this end, the CT values relating to attenuation of photons in the range of 40-140 keV must be transformed into linear attenuation coefficients at the PET energy of 511 keV. As attenuation depends on photon energy and the absorbing material, an accurate theoretical relation cannot be devised. The transformation implemented in the Discovery LS PET/CT scanner (GE Medical Systems, Milwaukee, Wis.) uses a bilinear function based on the attenuation of water and cortical bone at the CT and PET energies. The purpose of this study was to compare this transformation with experimental CT values and corresponding PET attenuation coefficients. In 14 patients, quantitative PET attenuation maps were calculated from germanium-68 transmission scans, and resolution-matched CT images were generated. A total of 114 volumes of interest were defined and the average PET attenuation coefficients and CT values measured. From the CT values the predicted PET attenuation coefficients were calculated using the bilinear transformation. When the transformation was based on the narrow-beam attenuation coefficient of water at 511 keV (0.096 cm(-1)), the predicted attenuation coefficients were higher in soft tissue than the measured values. This bias was reduced by replacing 0.096 cm(-1) in the transformation by the linear attenuation coefficient of 0.093 cm(-1) obtained from germanium-68 transmission scans. An analysis of the corrected emission activities shows that the resulting transformation is essentially equivalent to the transmission-based attenuation correction for human tissue. For non-human material, however, it may assign inaccurate attenuation coefficients which will also affect the correction in neighbouring tissue.

Measured attenuation correction methods

International Nuclear Information System (INIS)

Ostertag, H.; Kuebler, W.K.; Doll, J.; Lorenz, W.J.

1989-01-01

Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68 Ge/ 68 Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: Transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. (orig.)

Attenuation coefficients of soils

International Nuclear Information System (INIS)

Martini, E.; Naziry, M.J.

1989-01-01

As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

Variación temporal y espacial de aves playeras en la laguna Barra de Navidad, Jalisco, en tres temporadas no reproductivas Temporal and spatial variation of shorebirds in Barra de Navidad lagoon, Jalisco, during three non-breeding seasons

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Salvador Hernández

2012-09-01

Full Text Available Hay un escaso conocimiento de las aves playeras en los humedales costeros de Jalisco, y en particular en la laguna Barra de Navidad. El presente trabajo contribuye al conocimiento de este grupo de aves y describe su distribución temporal y espacial en la laguna Barra de Navidad durante tres temporadas no reproductivas (1999-2000, 2006-2007 y 2008-2009. Se realizaron censos mensuales de noviembre-abril en las tres temporadas con el fin de registrar todas las especies de aves playeras. Se identificaron 19 especies (tres residentes y 16 visitantes de invierno, de las cuales Charadrius wilsonia, Limosa fedoa y Tringa semipalmata presentaron la mayor abundancia. Doce especies son consideradas como prioritarias en la “Estrategia para la Conservación y Manejo de las Aves Playeras y su Hábitat en México”. El mayor número de especies fue registrado en noviembre, diciembre y marzo en la primera y tercera temporada. El mayor número de individuos fue registrado alimentándose en marea baja, principalmente en diciembre, enero y febrero de la primera y tercera temporada. En marea baja hubo un mayor número de especies e individuos alimentándose en la zona C. Esta zona se caracterizó por tener sustratos lodosos expuestos durante marea baja y que fueron aprovechados por las aves para alimentarse. La laguna Barra de Navidad proporcionó hábitats de alimentación y descanso para las aves residentes y migratorias. Sin embargo, estos hábitats se ven amenazados por las actividades humanas realizadas dentro de la laguna, que sin duda tendrán consecuencias negativas para la distribución y abundancia de las aves playeras.Resident and migratory shorebirds inhabit different kinds of wetlands such as lagoons, rivers and seashores among others. In recent years, these areas have been importantly affected by urban, agriculture and touristic activities, such as the Barra de Navidad lagoon, for which little information is available to support conservation

The relative contribution of fruits and arthropods to the diet of three trogon species (Aves, Trogonidae in the Brazilian Atlantic Forest A contribuição relativa de frutos e artrópodes para a dieta de três espécies de surucuás (Aves, Trogonidae na Mata Atlântica

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Marco Aurélio Pizo

2007-06-01

Full Text Available Trogons are pan-tropical forest birds that eat a mix of fruits and arthropods. With direct observations of wild feeding birds, I assessed the relative contribution of fruits and arthropods to the diet of three trogon species (Trogonviridis, T.surrucura, and T.rufus at Parque Estadual Intervales, southeast Brazil. Fruits and arthropods made the bulk of the food items recorded, with a tendency of frugivory increasing with body mass. The Trogon species differed in the proportion of fruits and arthropods taken, with T.viridis being the most frugivorous species (66% of feeding bouts, n = 47. The relative contribution of fruits and arthropods did not differ between the wet and dry seasons for any species. In the omnivorous gradient, T.viridis is close to the frugivorous extreme, whereas T.surrucura and T.rufus is next to the insectivorous end. Such a distinction may have important consequences for the territoriality and social behavior of these birds.Os surucuás são aves florestais pantropicais que se alimentam de frutos e artrópodes. Com observações diretas de aves forrageando na natureza, estudei a contribuição relativa de frutos e artrópodes para a dieta de três espécies de surucuás (Trogonviridis, T.surrucura, and T.rufus no Parque Estadual Intervales, sudeste do Brasil. Frutos e artrópodes foram os itens mais registrados, com uma tendência do grau de frugivoria aumentar com o aumento da massa corporal da ave. As três espécies diferiram em relação à proporção de frutos e artrópodes de que se alimentam; T.viridisfoi a espécie mais frugívora (66% dos registros, n = 47. As contribuições relativas de frutos e artrópodes para a dieta não diferiram entre as estações seca e úmida para nenhuma das três espécies. A diferença no grau de frugivoria aqui revelada pode ter conseqüências importantes para a territorialidade e organização social dos surucuás.

The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

Science.gov (United States)

Poyurovsky, Michael; Pashinian, Artashes; Levi, Aya; Weizman, Ronit; Weizman, Abraham

2005-03-01

Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

Antagonist-agonist combinations as therapies for heroin addiction: back to the future?

Science.gov (United States)

Nutt, David J

2010-02-01

Psychopharmacology is a powerful approach to the treatment of many psychiatric disorders. In this article I discuss the conceptual and practical issues in relation to the use of mu opioid receptor agonist, antagonist and partial agonist drugs in the treatment of opioid addiction, as this is one therapeutic area where all three types of agents are currently available. The choice of pharmacological agent is largely determined by patient profile, existence of ongoing drug misuse, and the kinetics of the drugs available. These principles, however, can be applied to other disorders as and when other pharmacological approaches become refined in these areas.

Computer-controlled attenuator.

Science.gov (United States)

Mitov, D; Grozev, Z

1991-01-01

Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

Selective Activation of At₂ Receptor Attenuates Progression of Pulmonary Hypertension and Inhibits Cardiopulmonary Fibrosis

DEFF Research Database (Denmark)

Bruce, E; Shenoy, V; Rathinasabapathy, A

2015-01-01

. However, the role of the angiotensin type II receptor (AT2 receptor) in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH....... EXPERIMENTAL APPROACH: A single subcutaneous injection of MCT (50 mg/kg) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2-weeks of MCT administration, a subset of animals began receiving, either 0.03mg/kg C21, 3mg/kg PD-123319, 0.5mg/kg A779 for an additional 2-weeks, after which right......-ventricular hemodynamic parameters were measured and tissues collected for gene expression and histological analyses. KEY RESULTS: Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular...

Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures

International Nuclear Information System (INIS)

Oyama, Takuji; Toyota, Kenji; Waku, Tsuyoshi; Hirakawa, Yuko; Nagasawa, Naoko; Kasuga, Jun-ichi; Hashimoto, Yuichi; Miyachi, Hiroyuki; Morikawa, Kosuke

2009-01-01

The structures of the ligand-binding domains (LBDs) of human peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ) in complexes with a pan agonist, an α/δ dual agonist and a PPARδ-specific agonist were determined. The results explain how each ligand is recognized by the PPAR LBDs at an atomic level. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARα and PPARγ LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD–ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARδ LBD in complex with an α/δ-selective ligand, TIPP-401, and with a related δ-specific ligand, TIPP-204, were also determined. The comparison between the two PPARδ complexes revealed how each ligand exhibits either a ‘dual selective’ or ‘single specific’ binding mode

Imidazopyridine CB2 agonists: optimization of CB2/CB1 selectivity and implications for in vivo analgesic efficacy.

Science.gov (United States)

Trotter, B Wesley; Nanda, Kausik K; Burgey, Christopher S; Potteiger, Craig M; Deng, James Z; Green, Ahren I; Hartnett, John C; Kett, Nathan R; Wu, Zhicai; Henze, Darrell A; Della Penna, Kimberly; Desai, Reshma; Leitl, Michael D; Lemaire, Wei; White, Rebecca B; Yeh, Suzie; Urban, Mark O; Kane, Stefanie A; Hartman, George D; Bilodeau, Mark T

2011-04-15

A new series of imidazopyridine CB2 agonists is described. Structural optimization improved CB2/CB1 selectivity in this series and conferred physical properties that facilitated high in vivo exposure, both centrally and peripherally. Administration of a highly selective CB2 agonist in a rat model of analgesia was ineffective despite substantial CNS exposure, while administration of a moderately selective CB2/CB1 agonist exhibited significant analgesic effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ultrasound fields in an attenuating medium

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.

1993-01-01

of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...... it into a frequency dependent part and frequency independent part. The latter results in an attenuation factor that is multiplied onto the responses from the individual elements, and the frequency dependent part is handled by attenuating the basic one-dimensional pulse. The influence on ultrasound fields from......Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...

NKT-cell glycolipid agonist as adjuvant in synthetic vaccine.

Science.gov (United States)

Liu, Zheng; Guo, Jun

2017-11-27

NKT cells are CD1d-restricted, glycolipid antigen-reactive, immunoregulatory T lymphocytes that can serve as a bridge between the innate and adaptive immunities. NKT cells have a wide range of therapeutic application in autoimmunity, transplant biology, infectious disease, cancer, and vaccinology. Rather than triggering "danger signal" and eliciting an innate immune response, αGalCer-based NKT-cell agonist act via a unique mechanism, recruiting NKT cells which play a T helper-like role even without peptide as Th epitope. Importantly, the non-polymorphism of CD1d render glycolipid a universal helper epitope, offering the potential to simplify the vaccine construct capable of eliciting consistent immune response in different individuals. This review details recent advances in the design of synthetic vaccines using NKT-cell agonist as adjuvant, highlighting the role of organic synthesis and conjugation technique to enhance the immunological actives and to simplify the vaccine constructs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Down-regulation of parathyroid hormone (PTH) receptors in cultured bone cells is associated with agonist-specific intracellular processing of PTH-receptor complexes.

Science.gov (United States)

Teitelbaum, A P; Silve, C M; Nyiredy, K O; Arnaud, C D

1986-02-01

Exposure of cultured embryonic chicken bone cells to the PTH agonists bovine (b) PTH-(1-34) and [8Nle, 18Nle, 34Tyr]bPTH-(1-34)amide [bPTH-(1-34)A] reduces the subsequent cAMP response to the hormone and decreases the specific binding of 125I-labeled PTH to these cultures. To determine whether PTH receptor down-regulation in cultured bone cells is mediated by cellular internalization of PTH-receptor complexes, we measured the uptake of [125I]bPTH-(1-34) into an acid-resistant compartment. Uptake of radioactivity into this compartment was inhibited by incubating cells at 4 C with phenylarsineoxide and unlabeled bPTH-(1-34). Tracer uptake into the acid-resistant compartment at any time was directly proportional to total cell binding at 22 C. Thus, it is likely that PTH-receptor complexes are internalized by bone cells. This mechanism may explain the loss of cell surface receptors after PTH pretreatment. To determine whether internalized PTH-receptor complexes are reinserted into the plasma membrane, we measured PTH binding and PTH stimulation of cAMP production after cells were exposed to monensin, a known inhibitor of receptor recycling. Monensin (25 microM) had no effect on PTH receptor number or affinity and did not alter PTH-stimulated cAMP accumulation. However, monensin (25 microM) incubated with cells pretreated with various concentrations of bPTH-(1-34) for 1 h potentiated the effect of the hormone to reduce subsequent [125I]bPTH-(1-34) binding and PTH-stimulated cAMP accumulation by more than 2 orders of magnitude. Chloroquine also potentiated PTH-induced down-regulation of PTH receptors. By contrast, neither agent influenced PTH binding or PTH-stimulated cAMP production in cells pretreated with the antagonist bPTH-(3-34)A. Thus, monensin potentiated PTH receptor loss only in cells pretreated with PTH agonists, indicating that antagonist-occupied receptors may be processed differently from agonist-occupied receptors in bone cells. The data further suggest

Attenuation in Superconducting Circular Waveguides

Directory of Open Access Journals (Sweden)

K. H. Yeap

2016-09-01

Full Text Available We present an analysis on wave propagation in superconducting circular waveguides. In order to account for the presence of quasiparticles in the intragap states of a superconductor, we employ the characteristic equation derived from the extended Mattis-Bardeen theory to compute the values of the complex conductivity. To calculate the attenuation in a circular waveguide, the tangential fields at the boundary of the wall are first matched with the electrical properties (which includes the complex conductivity of the wall material. The matching of fields with the electrical properties results in a set of transcendental equations which is able to accurately describe the propagation constant of the fields. Our results show that although the attenuation in the superconducting waveguide above cutoff (but below the gap frequency is finite, it is considerably lower than that in a normal waveguide. Above the gap frequency, however, the attenuation in the superconducting waveguide increases sharply. The attenuation eventually surpasses that in a normal waveguide. As frequency increases above the gap frequency, Cooper pairs break into quasiparticles. Hence, we attribute the sharp rise in attenuation to the increase in random collision of the quasiparticles with the lattice structure.

Radiofrequency attenuator and method

Science.gov (United States)

Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

2009-01-20

Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

LENUS (Irish Health Repository)

Ward, Joseph B J

2012-02-01

Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 +\\/- 2.6 and 38.8 +\\/- 6.7% (n=16; P<\\/=0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

LENUS (Irish Health Repository)

Ward, Joseph B J

2011-02-01

Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 ± 2.6 and 38.8 ± 6.7% (n=16; P≤0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

Response of Peripheral Blood Lymphocytes from RAO-affected Horses to b2-Agonist Stimulation

OpenAIRE

Werner Becker, Marianne Patricia

2011-01-01

Recurrent airway obstruction (RAO) affects middle-age horses, inducing bronchoconstriction and airway inflammation. β2-agonists like salbutamol are used as treatment, promoting airway smooth muscle (ASM) relaxation and bronchodilation. In addition to ASM, inflammatory cells express the β2-adrenoreceptors (β2-AR). In other species, β2-agonists promote peripheral blood lymphocyte (PBL) cytokine expression towards a pro-inflammatory phenotype. RAO horses are a good model for evaluating chron...

Resíduos de aves e suínos: Potencialidades

Directory of Open Access Journals (Sweden)

Tiago Luan Hachmann

2014-05-01

Full Text Available O crescimento intenso da população mundial aumenta a demanda por alimentos. As carnes de frango e de suíno são as fontes mais exploradas de proteína na alimentação humana. Porém, com os métodos intensivos de produção, esses sistemas tem gerado insatisfação quanto ao aspecto ambiental e tem sido questionados quanto à sua sustentabilidade. A disposição inadequada dos resíduos gerados nos criatórios de suínos e aves afeta diretamente a qualidade do meio ambiente e a saúde pública. Assim deve-se buscar alternativas para minimizar os impactos causados ao meio, melhorando o aproveitamento e destinação desses resíduos. A aplicação desses resíduos nas áreas de produção agrícola é favorável à, tendo em vista que são uma fonte de nutrientes de grande demanda pelas culturas. Além disso é uma forma sustentável para destinação dos resíduos, já que promove seu reaproveitamento de forma a não poluir o ambiente e com alto retorno econômico. Dessa forma é possível aliar preservação ambiental com progresso econômico, promovendo uma produção sustentável.

PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

Energy Technology Data Exchange (ETDEWEB)

Milton, Flora Aparecida [Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular, Universidade de Brasília (Brazil); Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States); Cvoro, Aleksandra [Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States); Amato, Angelica A. [Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular, Universidade de Brasília (Brazil); Sieglaff, Douglas H.; Filgueira, Carly S.; Arumanayagam, Anithachristy Sigamani [Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States); Caro Alves de Lima, Maria do; Rocha Pitta, Ivan [Laboratório de Planejamento e Síntese de Fármacos – LPSF, Universidade Federal de Pernambuco (Brazil); Assis Rocha Neves, Francisco de [Faculdade de Ciências da Saúde, Laboratório de Farmacologia Molecular, Universidade de Brasília (Brazil); Webb, Paul, E-mail: pwebb@HoustonMethodist.org [Genomic Medicine, Houston Methodist Research Institute, Houston, TX (United States)

2015-08-28

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1 adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation.

PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Milton, Flora Aparecida; Cvoro, Aleksandra; Amato, Angelica A.; Sieglaff, Douglas H.; Filgueira, Carly S.; Arumanayagam, Anithachristy Sigamani; Caro Alves de Lima, Maria do; Rocha Pitta, Ivan; Assis Rocha Neves, Francisco de; Webb, Paul

2015-01-01

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1 adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation

β2 agonists in athletes. An ergogenic aid? = β2 agonistas en deportistas. ¿Una ayuda ergogénica?

Directory of Open Access Journals (Sweden)

Ospina Uribe, Carlos Fernando

2013-01-01

Full Text Available Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB. Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical performance, which can result in a competitive advantage. β2 agonists are prohibited by the WADA (World Anti-Doping Agency, except salbutamol (maximum dose: 1.600 μg over 24 hours and salmeterol. Oral administration of salbutamol can induce ergogenic effects in athletes. It has been documented that when given orally β2 agonists can improve performance in endurance disciplines, increase muscle strength and improve anaerobic power. However, according to scientific evidence, inhaled β2 agonists do not have a relevant performance-enhancing effect in nonasthmatic athletes.

Peroxisome proliferator-activated receptor-γ agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells

International Nuclear Information System (INIS)

Arnold, Ralf; Koenig, Wolfgang

2006-01-01

We have previously shown that peroxisome proliferator-activated receptor-γ (PPARγ) agonists inhibited the inflammatory response of RSV-infected human lung epithelial cells. In this study, we supply evidence that specific PPARγ agonists (15d-PGJ 2 , ciglitazone, troglitazone, Fmoc-Leu) efficiently blocked the RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp-2). All PPARγ agonists under study markedly inhibited the cell surface expression of the viral G and F protein on RSV-infected A549 cells. This was paralleled by a reduced cellular amount of N protein-encoding mRNA determined by real-time RT-PCR. Concomitantly, a reduced release of infectious progeny virus into the cell supernatants of human lung epithelial cells (A549, normal human bronchial epithelial cells (NHBE)) was observed. Similar results were obtained regardless whether PPARγ agonists were added prior to RSV infection or thereafter, suggesting that the agonists inhibited viral gene expression and not the primary adhesion or fusion process

The effect of various opiate receptor agonists on the seizure threshold in the rat. Is dynorphin an endogenous anticonvulsant?

Science.gov (United States)

Przewłocka, B; Stala, L; Lasoń, W; Przewłocki, R

1983-01-01

The effects of various opiate receptor agonists on the seizure threshold after an intravenous infusion of pentylenetetrazol were investigated in rats. The mu- and epsilon-receptor agonists, morphine (20-40 micrograms) and beta-endorphin (5-10 micrograms) show proconvulsant properties towards clonic and tonic seizures. The delta-receptor agonist (D-Ala2,D-Leu5-enkephalin, DADL 5-40 micrograms) and alpha-neoendorphin (20-40 micrograms) show pro- and anticonvulsant properties towards clonic and tonic seizures, respectively. Anticonvulsant properties of DADL are possibly due to its action on the spinal cord, since after the intrathecal injection this effect is still observed. Similarities between DADL and alpha-neoendorphin suggest that they may act through the same receptor. The kappa-receptor agonist dynorphin A (5-20 micrograms) and its degradation-resistant analogue D-Arg-dynorphin1-13 (10 micrograms) show significant anticonvulsant properties. Our present results suggest that the kappa-receptor agonist dynorphin may act physiologically as an endogenous anticonvulsant, in contrast to other opioid peptides.

COEXISTENCIA TRÓFICA DE AVES CARPINTERAS (Picidae EN UN BOSQUE DE Pinus cembroides (Zucc. DEL ÁREA NATURAL PROTEGIDA PEÑA ALTA, SAN DIEGO DE LA UNIÓN, GUANAJUATO

Directory of Open Access Journals (Sweden)

Saúl Ugalde-Lezama

2011-01-01

Full Text Available Estudiar la coexistencia trófica en aves es relevante para su manejo y conservación. Para ello, de enero a octubre de 2008 se identificaron técnicas de cacería y componentes entomológicos de las dietas de aves piciformes. Para la observación de las aves se usó la técnica de búsqueda intensiva en puntos de radio fijo, y para su captura, redes de niebla. Melanerpes formicivorous y Picoides scalaris prefirieron las técnicas de cacería Perforar y Colectar. Dichas técnicas se explicaronpor cinco y cuatro variables (P<0.05, respectivamente. Los estratos más utilizados fueron Pinus cembroides y Quercus spp. Los órdenes de insectos más consumidos fueron Coleóptera y Hemíptera. Las principales familias registradas corresponden a Scolytidae, Curculionidae, Pentatomidae, Cicadellidae, Cleridae y Melyridae. Los insectos más consumidos fueron los tipo Plaga (P, No Plaga (NP y Predadores (PR. Se registró una proporción significativa de individuos (X2=9.19, X2 0.001(5=20.5 de insectos en las dietas. Sin embargo, no fue posible registrar todos los fragmentos (X2=56.33, X2 0.001(5=20.5. El número de individuos (a=0.05, P-value=0.2317 y fragmentos (a=0.05, P-value=0.2606 entre especies fue similar. Siete variables (P<0.05 determinaron la ocurrencia de grasa y el consumo de presas. Los Picidos bajo estudio, a pesar de poseer anatomías, fisiologías y etologías similares, coexistieron tróficamente segregados durante la procuración alimenticia, minimizando de esta manera la competencia interespecífica.

Thrombopoietin-receptor agonists in haematological disorders: The Danish experience

DEFF Research Database (Denmark)

Gudbrandsdottir, Sif; Frederiksen, Henrik; Hasselbalch, Hans

2011-01-01

The objective of this study was to investigate the use of thrombopoietin-receptor agonists (TPO-ra) in patients with refractory primary immune thrombocytopenia (ITP) as well as off-label use of TPO-ra in Danish haematology departments. Hospital medical records from 32 of the 39 patients having re...

GnRH-agonist versus GnRH-antagonist IVF cycles

DEFF Research Database (Denmark)

Papanikolaou, E G; Pados, G; Grimbizis, G

2012-01-01

In view of the current debate concerning possible differences in efficacy between the two GnRH analogues used in IVF stimulated cycles, the current study aimed to explore whether progesterone control in the late follicular phase differs when GnRH antagonist is used as compared with GnRH agonist...

Simultaneous determination of 11 β-agonists in human urine using high-performance liquid chromatography/tandem mass spectrometry with isotope dilution.

Science.gov (United States)

Wang, Xiaoli; Guo, Tao; Wang, Shanshan; Yuan, Jinpeng; Zhao, Rusong

2015-04-01

The misuse of β-agonists constitutes a potential risk to public health and has been forbidden in many countries. In this study, we describe a method for specific, sensitive and rapid detection of β-agonists in human urine. Urine samples were extracted with ethyl acetate, without any additional purification step, and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) with Clenbuterol-D9 and Salbuterol-D3 as internal standards. The intra- and interday precision values of the method were all application of UPLC-MS-MS method in β-agonists detection of human urine will be helpful in veterinary control of β-agonists and for studying the effect of β-agonists on human health. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tachykinin NK₁ receptor antagonist co-administration attenuates opioid withdrawal-mediated spinal microglia and astrocyte activation.

Science.gov (United States)

Tumati, Suneeta; Largent-Milnes, Tally M; Keresztes, Attila I; Yamamoto, Takashi; Vanderah, Todd W; Roeske, William R; Hruby, Victor J; Varga, Eva V

2012-06-05

Prolonged morphine treatment increases pain sensitivity in many patients. Enhanced spinal Substance P release is one of the adaptive changes associated with sustained opioid exposure. In addition to pain transmitting second order neurons, spinal microglia and astrocytes also express functionally active Tachykinin NK₁ (Substance P) receptors. In the present work we investigated the role of glial Tachykinin NK₁ receptors in morphine withdrawal-mediated spinal microglia and astrocyte activation. Our data indicate that intrathecal co-administration (6 days, twice daily) of a selective Tachykinin NK₁ receptor antagonist (N-acetyl-L-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138; 20 μg/injection)) attenuates spinal microglia and astrocyte marker and pro-inflammatory mediator immunoreactivity as well as hyperalgesia in withdrawn rats. Furthermore, covalent linkage of the opioid agonist with a Tachykinin NK₁ antagonist pharmacophore yielded a bivalent compound that did not augment spinal microglia or astrocyte marker or pro-inflammatory mediator immunoreactivity and did not cause paradoxical pain sensitization upon drug withdrawal. Thus, bivalent opioid/Tachykinin NK₁ receptor antagonists may provide a novel paradigm for long-term pain management.

Effects of structural modifications of N-CPM-normorphine derivatives on agonist and antagonist activities in isolated organs.

Science.gov (United States)

Riba, P; Tóth, Z; Hosztafi, S; Friedmann, T; Fürst, S

2003-01-01

The agonistic and antagonistic properties of N-cyclopropylmethyl (N-CPM) morphine derivatives were observed in mouse vas deferens (MVD), longitudinal muscle of guinea pig ileum (GPI) and rabbit vas deferens (LVD). In MVD the K(e) values of the titled compounds (N-CPM-morphine, N-CPM-isomorphine, N-CPM-dihydromorphine, N-CPM-dihydroisomorpPhine, N-CPM-dihydromorphone and naltrexone) were measured for mu-, kappa- and delta-receptors using normorphine, ethylketocyclazocine (EKC) and D-Pen2-D-Pen5-enkephaline (DPDPE) as selective agonists on the receptors, respectively. For mu-receptors of MVD the tested compounds showed similar affinity. For kappa-receptors the non-iso-6-OH derivatives possessed much less affinity than the iso-derivatives. Similar difference could be observed for delta-receptors. The agonistic activities of these compounds in MVD were observed to be between 0-20% of the inhibition of muscle contractions. In GPI the compounds except naltrexone possessed strong agonistic activities effectively antagonized by nor-binaltorphimine (nor-BNI) (K(e) of nor-BNI was 0.23 nM) suggesting that they were strong kappa-receptor agonists. We investigated these agents in LVD too, which contains kappa-receptors, but they did not produce any agonist potencies. It raises the possibility that the kappa-receptor subtypes of LVD and MVD are different from the kappa-receptor subtype of GPI or the vasa deferentia contain much fewer kappa-receptors than GPI and the intrinsic activities of these compounds are too small to reach the 50% inhibition of the contractions.

USO DA TERAPIA ESPELHO NA AMPLITUDE DE MOVIMENTO E FUNÇÃO DO MEMBRO INFERIOR EM PACIENTES HEMIPARÉTICOS PÓS-AVE

OpenAIRE

Livia Danyelle Viana Lima; Bruno Vieira Cortez; Janaína de Moraes Silva

2017-01-01

Resumo: O exercício associado a terapia espelho potencializa a retenção de habilidades, melhorando o desempenho de atividades motoras de indivíduos hemiparéticos pós-AVE. Este estudo objetivou a análise do efeito da terapia espelho na amplitude de movimento e funcionalidade do membro inferior. Amostra composta de 11 participantes, com hemiparesia em membro inferior, submetidas a fisioterapia convencional. A intervenção constituiu de 10 atendimentos, 30 minutos diários e três vezes por semana....

The LCLS Gas Attenuator Revisited

International Nuclear Information System (INIS)

Ryutov, D

2005-01-01

In the report ''X-ray attenuation cell'' [1] a preliminary analysis of the gas attenuator for the Linac Coherent Light Source (LCLS) was presented. This analysis was carried out for extremely stringent set of specifications. In particular, a very large diameter for the unobstructed beam was set (1 cm) to accommodate the spontaneous radiation; the attenuator was supposed to cover the whole range of energies of the coherent radiation, from 800 eV to 8000 eV; the maximum attenuation was set at the level of 10 4 ; the use of solid attenuators was not allowed, as well as the use of rotating shutters. The need to reach a sufficient absorption at the high-energy end of the spectrum predetermined the choice of Xe as the working gas (in order to have a reasonable absorption at a not-too-high pressure). A sophisticated differential pumping system that included a Penning-type ion pump was suggested in order to minimize the gas leak into the undulator/accelerator part of the facility. A high cost of xenon meant also that an efficient (and expensive) gas-recovery system would have to be installed. The main parameter that determined the high cost and the complexity of the system was a large radius of the orifice. The present viewpoint allows for much smaller size of the orifice, r 0 = 1.5 mm. (1) The use of solid attenuators is also allowed (R.M. Bionta, private communication). It is, therefore, worthwhile to reconsider various parameters of the gas attenuator for these much less stringent conditions. This brief study should be considered as a physics input for the engineering design. As a working gas we consider now the argon, which, on the one hand, provides a reasonable absorption lengths and, on the other hand, is inexpensive enough to be exhausted into the atmosphere (no recovery). The absorption properties of argon are illustrated by Fig.1 where the attenuation factor A is shown for various beam energies, based on Ref. [2]. The other relevant parameters for argon are

Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD).

Science.gov (United States)

Ni, Xunjun; Wang, Haiyan

2016-01-01

Silymarin, which derived from the milk thistle plant (silybum marianum), has been used for centuries as a natural remedy for diseases of the liver and biliary tract. Considering the therapeutic potential to liver disease, we tested efficacy of silymarin on hepatic steatosis with a high fat diet (HFD)-induced mouse model of non-alcoholic fatty liver disease (NAFLD), and investigated possible effects on lipid metabolic pathways. In our study, silymarin could attenuate the hepatic steatosis, which was proved by both Oil Red O staining and hepatic triglyceride (TG) level determination. Furthermore, compared with INT-747, a potent and selective FXR agonist, silymarin could preserve plasmatic high-density lipoprotein cholesterol (HDL-C) to a higher level and low-density lipoprotein cholesterol (LDL-C) to a lower level, which benefited more to the circulation system. Through real-time PCR analysis, we clarified a vital protective role of silymarin in mRNA regulation of genes involved in lipid metabolism and oxidative stress. It was also shown that silymarin had no effects on body weight, food intake, and liver transaminase. Taken together, silymarin could attenuate hepatic steatosis in a mouse model of NAFLD through regulation of lipid metabolism and oxidative stress, and benefit to the circulation system. All these findings shed new light on NAFLD treatment.

Quantitative protein and fat metabolism in bull calves treated with beta-adrenergic agonist

DEFF Research Database (Denmark)

Chwalibog, André; Jensen, K; Thorbek, G

1996-01-01

Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with 12 Red Danish bulls during two subsequent 6 weeks trials (Sections A and B) at a mean live weight of 195 and 335 kg respectively. Treatments were control (Group 1) and beta-agonist (L-644...... matter, metabolizable energy and digestible protein was of the same magnitude for all groups. The beta-agonist had no significant effect on protein digestibility and metabolizability of energy, but daily live weight gain was significantly higher in the treated bulls. The utilization of digested protein...

Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist

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Chenxi Zhai

2014-11-01

Full Text Available The transient receptor potential ankyrin 1 (TRPA1 cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.

Novel Zn2+ Modulated GPR39 Receptor Agonists Do Not Drive Acute Insulin Secretion in Rodents.

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Ola Fjellström

Full Text Available Type 2 diabetes (T2D occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion in vivo. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn2+ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO mice and Zucker fatty rats. It is concluded that Zn2+ modulated GPR39 agonists do not acutely stimulate insulin release in rodents.

Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder

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Molly R Belkin

2017-09-01

Full Text Available Clonidine and guanfacine are alpha-2 receptor agonists that decrease sympathetic outflow from the central nervous system. Posttraumatic stress disorder (PTSD is an anxiety disorder that is theorized to be related to a hyperactive sympathetic nervous system. Currently, the only US Food and Drug Administration (FDA-approved medications for PTSD are the selective serotonin reuptake inhibitors (SSRIs sertraline and paroxetine. Sometimes use of the SSRIs may not lead to full remission and symptoms of hyperarousal often persist. This article specifically reviews the literature on alpha-2 receptor agonist use for the treatment of PTSD and concludes that while the evidence base is limited, these agents might be considered useful when SSRIs fail to treat symptoms of agitation and hyperarousal in patients with PTSD.

Maximum likelihood estimation of the attenuated ultrasound pulse

DEFF Research Database (Denmark)

Rasmussen, Klaus Bolding

1994-01-01

The attenuated ultrasound pulse is divided into two parts: a stationary basic pulse and a nonstationary attenuation pulse. A standard ARMA model is used for the basic pulse, and a nonstandard ARMA model is derived for the attenuation pulse. The maximum likelihood estimator of the attenuated...

Adaptaciones musculares relacionadas a áreas corporales que participan activamente en el vuelo de Anhima cornuta (Aves: Anseriformes, Anhimidae

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Marcos Antonio Manzanares

2013-04-01

Full Text Available La forma y correspondencia entre la anatomía muscular y ósea revela en gran medida el hábito locomotor de cualquier ave. Las especies pertenecientes a la Familia Anhimidae son relevantes dentro de las Aves, debido a las adaptaciones óseas (y por lo tanto, musculares que presentan, como la pérdida de procesos uncinados, el desarrollo de espolones metarcapales, la extrema neumatización y el notable desarrollo de forámenes. Se analizaron anatómicamente y numéricamente (superficie de origen e inserción, longitud en reposo y masa los componentes musculares relacionados a las zonas de la columna vertebral, tronco, miembros y cinturas de tres ejemplares de Anhima cornutade distintos sexos y se compararon con lo estudiado en 4 ejemplares de especies relacionadas (Dendrocygna bicolory Dendrocygna viduata, Anatidae. El estudio reveló que en Anhima existe un gran desarrollo de los músculos intercostales e intervertebrales (torácicos y lumbares, evidenciando una adaptación a la ausencia de procesos uncinados. En Anhimaexisten fascículos proporcionalmente menos pesados y de menor tamaño que en Dendrocygna, indicando morfológicamente la ocurrencia de un vuelo menos desarrollado en el primero. Algunos tendones y fibras musculares metacarpales cuya inserción ocurre en el primer dígito en Dendrocygna, en Anhimase insertan en la base de los espolones proximal y distal, demostrando el poco control del vuelo en Anhima. La musculatura de los miembros posteriores en Anhimaes mucho más desarrollada, tanto en tamaño, como en masa proporcional, evidenciando una gran actividad en esta zona en la propulsión del vuelo y en hábitos terrestres

The effects of acute multiple intraperitoneal injections of the GABAB receptor agonist baclofen on food intake in rats.

Science.gov (United States)

Patel, Sunit M; Ebenezer, Ivor S

2008-12-28

This study was undertaken to examine the effects of acute repeated administration of the GABA(B) receptor agonist baclofen on food intake in rats. In Experiment 1, the effects of repeated intraperitoneal (i.p.) injections of the GABA(B) receptor agonist baclofen (1 and 2 mg/kg) at 2 h intervals were investigated on food intake in non-deprived male Wistar rats. Both doses of baclofen significantly increased food intake after the 1st injection (PGABA(B) receptor agonists on food intake and energy homeostasis.

Abundance of two Dendrocincla woodcreepers (aves: Dendrocolaptidae in relation to forest structure in Central Amazonia O uso do habitat por duas espécies de arapaçus Dendrocincla (aves: Dendrocolaptidae em relação a estrutura da floresta na Amazônia Central

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Renato Cintra

2006-01-01

Full Text Available Few studies have been conducted to verify how the structure of the forest affects the occurence and abundance of neotropical birds. Our research was undertaken between January 2002 and July 2004 at the Reserva Ducke, near Manaus (02º55',03º01'S; 59º53',59º59'W in central Amazonia, to verify how the forest structure affects the occurrence and abundance of two bird species: the Plain-brown Woodcreeper Dendrocincla fuliginosa and the White-chinned Woodcreeper Dendrocincla merula. Bird species occurrence was recorded using lines of 20 mist-nets (one sample unit, along 51 1-km transects distributed along 9 pararel 8 km trails covering an area of 6400 ha. Along these transects, we placed 50 x 50m plots where we recorded forest structure components (tree abundance, canopy openness, leaf litter, standing dead trees, logs, proximity to streams, and altitude. We then related these variables to bird occurence and abundance using multiple logistic and multiple linear regression models, respectively. We found that D. fuliginosa frequently used plateau areas; being more abundant in areas with more trees. On the other hand, D. merula occurred more frequently and was more abundant in areas with low tree abundance. Our results suggest that although both species overlap in the reserve (both were recorded in at least 68% of the sampled sites, they differ in the way they use the forest microhabitats. Therefore, local variation in the forest structure may contribute to the coexistence of congeneric species and may help to maintain local alpha diversity.Em florestas neotropicais, poucos estudos tem sido conduzidos para verificar como a estrutura da floresta afeta o uso desse ambiente por aves. Este estudo foi realizado entre Janeiro de 2002 e Julho de 2004 na Reserva Ducke próximo a Manaus (02º55',03º01'S; 59º53',59º59'W, para verificar como a estrutura da floresta afeta a ocorrência e abundância de duas espécies de aves: o Arapaçu-pardo, Dendrocincla

Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

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M.A. Quera Salva

2012-04-01

Full Text Available Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC. Melatonin (N-acetyl-5-hydroxytryptamine is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse.

Xamoterol, a new selective beta-1-adrenoceptor partial agonist, in the treatment of postural hypotension

DEFF Research Database (Denmark)

Mehlsen, J; Trap-Jensen, J

1986-01-01

Three patients severely disabled from postural hypotension were treated with xamoterol, a selective beta-1-adrenoceptor antagonist with a high degree of partial agonist activity. Oral treatment (200 mg b.i.d.) was chosen on the basis of the effects of acute intravenous administration of xamoterol...... and pindolol, a non-selective beta-adrenoceptor antagonist with partial agonist activity. In these patients pindolol had a predominantly antagonist effect, whereas xamoterol had a predominantly agonist effect after intravenous administration. Oral treatment was carried out with placebo control in a single......, supine). During the placebo period (2 weeks) heart rate decreased to pretreatment levels and mean blood pressure was reduced by only 14 mmHg. The patients reported substantial improvement in their condition during active medication. Xamoterol seems to be a useful alternative in the treatment of postural...

Inventario de las aves de un bosque altoandino: comparación de dos métodos

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Stiles Hurd Frank Galfierd

1998-06-01

Full Text Available Capturing birds with mist-nets has been the sole method used or proposed for making species inventories of several Neotropical forests, but this method has rarely been evaluated relative to the use of visual and auditory observations in these forests. This study compares the effectiveness and efficiency of these two methods in the elaboration of the list of bird species on a 15 ha study plot of forest and subparamo vegetation in the Eastern Andes of Colombia. Over ten months we made 11 visits of 4-6 days each, observing and running nets along ca. 3 km of study trails. Of 102 total species recorded, 101 were observed and 50 captured; 52 were observed but not captured vs. only one that was only recorded with the nets. The observations were more efficient in accumulating species, with a mean of 68.4 per visit vs. 17.1 species captured. More than half of the species observed had been recorded after a single visit, and over 90% in six visits; the corresponding figures for mist-net captures were four and nine visits. Compared with the totallist, the mist net sample was biased towards small species « 50 g; some diet groups or foraging guilds were over- or underrepresented in this sample. We conclude that visual and auditory observations are more effective and efficient for making inventories of birds in these forests. Mist nets are a useful supplement to these observations, but not a substitute; their greatest utility lies in obtaining other sorts of data.La captura con redes de niebla ha sido utilizada o propuesta como método único para realizar inventarios de aves en varios bosques neotropicales, pero pocas veces ha sido evaluado en este medio en relación a otros métodos como el de las observaciones visuales y auditivas. Este estudio compara la efectividad y eficiencia de estos dos métodos en la elaboración de la lista de las especies de aves de una parcela de 15 ha de bosque altoandino y subpáramo en la Cordillera Oriental de Colombia

Transire, a Program for Generating Solid-State Interface Structures

Science.gov (United States)

2017-09-14

ARL-TR-8134 ● SEP 2017 US Army Research Laboratory Transire, a Program for Generating Solid-State Interface Structures by...Program for Generating Solid-State Interface Structures by Caleb M Carlin and Berend C Rinderspacher Weapons and Materials Research Directorate, ARL...

Combined inhalation of beta2 -agonists improves swim ergometer sprint performance but not high-intensity swim performance

DEFF Research Database (Denmark)

Kalsen, Anders; Hostrup, Morten; Bangsbo, Jens

2014-01-01

There is a high prevalence of asthma and airway hyperresponsiveness (AHR) in elite athletes, which leads to a major use of beta2 -agonists. In a randomized double-blinded crossover study, we investigated the effects of combined inhalation of beta2 -agonists (salbutamol, formoterol, and salmeterol...

Compensation for nonuniform attenuation in SPECT brain imaging

International Nuclear Information System (INIS)

Glick, S.J.; King, M.A.; Pan, T.S.; Soares, E.J.

1996-01-01

Accurate compensation for photon attenuation is needed to perform quantitative brain single-photon-emission computed tomographic (SPECT) imaging. Bellini's attenuation-compensation method has been used with a nonuniform attenuation map to account for the nonuniform attenuation properties of the head. Simulation studies using a three-dimensional (3-D) digitized anthropomorphic brain phantom were conducted to compare quantitative accuracy of reconstructions obtained with the nonuniform Bellini method to that obtained with the Chang method and to iterative reconstruction using maximum-likelihood expectation maximization (ML-EM). Using the Chang method and assuming the head to be a uniform attenuator gave reconstructions with an average bias of approximately 6-8%, whereas using the Bellini or the iterative ML-EM method with a nonuniform attenuation map gave an average bias of approximately 1%. The computation time required to implement nonuniform attenuation compensation with the Bellini algorithm is approximately equivalent to the time required to perform one iteration of ML-EM. Thus, using the Bellini method with a nonuniform attenuation map provides accurate compensation for photon attenuation within the head, and the method can be implemented in computation times suitable for routine clinical use

(S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors

DEFF Research Database (Denmark)

Ahmadian, H; Nielsen, B; Bräuner-Osborne, Hans

1997-01-01

of the spectroscopic configurational assignments. The activities of 6 and 7 at ionotropic EAA (iGlu) receptors and at mGlu1-7 were studied. (S)-Homo-AMPA (6) was shown to be a specific agonist at mGlu6 (EC50 = 58 +/- 11 microM) comparable in potency with the endogenous mGlu agonist (S)-glutamic acid (EC50 = 20 +/- 3......Our previous publication (J. Med. Chem. 1996, 39, 3188-3194) described (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (Homo-AMPA) as a highly selective agonist at the mGlu6 subtype of metabotropic excitatory amino acid (EAA) receptors. Homo-AMPA has already become a standard agonist...... microM). Although Homo-AMPA did not show significant effects at iGlu receptors, (R)-Homo-AMPA (7), which was inactive at mGlu1-7, turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist (IC50 = 131 +/- 18 microM)....

Diploposthe laevis (Bloch Jacobi (Eucestoda, Hymenolepididae from Netta peposaca (Vieillot (Aves: Anatidae: first record for the Neotropical Region and a new host Diploposthe laevis (Bloch Jacobi (Eucestoda: Hymenolepididae em Netta peposaca (Vieillot (Aves, Anatidae: primeiro registro para Região Neotropical e novo hospedeiro

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Eliane F. da Silveira

2008-03-01

Full Text Available One hundred eight rosy-billed pochards, Netta peposaca (Vieillot, 1816, collected in Brazil and Argentina were examined for endoparasites. Collection sites included the municipalities of Santa Vitória do Palmar and Jaguarão, Rio Grande do Sul State, Brazil (wintering site and Alvear, Corrientes Province, northern Argentina (nesting site. Birds were frozen in dry ice after collection. During necropsy they were categorized according to sex and maturation, either adult or juvenile. The cestode Diploposthe laevis (Bloch Jacobi, 1896 was found (prevalence 68.5%, mean infection was 2. The mean prevalence of D. laevis in Alvear (25.9% was higher than found in Jaguarão and Santa Vitória do Palmar, Rio Grande do Sul (19%, and could be related to the nesting site and to the period when the birds may ingest a higher amount of food. This is the first record of a species of the genus Diploposthe in anatideans from South America, and the first record of the species in N. peposaca. Details of the cirrus pouch and vagina were described based on histological sections.Com o objetivo de conhecer a helmintofauna do marrecão, Netta peposaca (Vieillot, 1816, na América do Sul, 108 aves foram amostradas. Os pontos de captura foram os municípios de Santa Vitória do Palmar e Jaguarão, no Estado do Rio Grande do Sul, sul do Brasil (pólo de invernia, e em Alvear, Província de Corrientes, região norte da Argentina (pólo de nidificação, entre 2002 e 2004. As aves foram congeladas em gelo seco logo após o abate. Durante o procedimento de necropsia tiveram o sexo identificado, e foram classificadas de acordo com estado de maturação sexual, em juvenil e adulto. O cestóide Diploposthe laevis (Bloch Jacobi, 1896 foi encontrado com prevalência média de 68,5% e intensidade média de infecção de dois espécimes por hospedeiro. A prevalência média de D. laevis em Alvear (25,9% foi maior do que a encontrada em Jaguarão e Santa Vitória do Palmar, Rio Grande

α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way

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Andrea Grandi

2017-11-01

Full Text Available The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α7 nAChRs stimulation is still controversial and the potential contribution of α4β2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α7 and α4β2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403 and antagonists (methyllycaconitine and dihydro-β-erythroidine of α7 and α4β2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α4β2 ligands evoked weak and contradictory effects, while α7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune

Attenuation of Vrancea events revisited

International Nuclear Information System (INIS)

Radulian, M.; Popa, M.; Grecu, B.; Panza, G.F.

2003-11-01

New aspects of the frequency-dependent attenuation of the seismic waves traveling from Vrancea subcrustal sources toward NW (Transylvanian Basin) and SE (Romanian Plain) are evidenced by the recent experimental data made available by the CALIXTO'99 tomography experiment. The observations validate the previous theoretical computations performed for the assessment, by means of a deterministic approach, of the seismic hazard in Romania. They reveal an essential aspect of the seismic ground motion attenuation, that has important implications on the probabilistic assessment of seismic hazard from Vrancea intermediate-depth earthquakes. The attenuation toward NW is shown to be a much stronger frequency-dependent effect than the attenuation toward SE and the seismic hazard computed by the deterministic approach fits satisfactorily well the observed ground motion distribution in the low-frequency band (< 1 Hz). The apparent contradiction with the historically-based intensity maps arises mainly from a systematic difference in the vulnerability (buildings eigenperiod) of the buildings in the intra- and extra-Carpathians regions. (author)

Airway Peroxidases Catalyze Nitration of the β2-Agonist Salbutamol and Decrease Its Pharmacological Activity

OpenAIRE

Reszka, Krzysztof J.; Sallans, Larry; Macha, Stephen; Brown, Kari; McGraw, Dennis W.; Kovacic, Melinda Butsch; Britigan, Bradley E.

2011-01-01

β2-Agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β2-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hy...

Improvement of vascular function by acute and chronic treatment with the GPR30 agonist G1 in experimental diabetes mellitus.

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Zi-lin Li

Full Text Available The G-protein coupled estrogen receptor 30 (GPR30 is a seven-transmembrane domain receptor that mediates rapid estrogen responses in a wide variety of cell types. This receptor is highly expressed in the cardiovascular system, and exerts vasodilatory effects. The objective of the present study was to investigate the effects of GPR30 on vascular responsiveness in diabetic ovariectomized (OVX rats and elucidate the possible mechanism involved. The roles of GPR30 were evaluated in the thoracic aorta and cultured endothelial cells. The GPR30 agonist G1 induced a dose-dependent vasodilation in the thoracic aorta of the diabetic OVX rats, which was partially attenuated by the nitric oxide synthase (NOS inhibitor, nitro-L-arginine methylester (L-NAME and the GPR30-selective antagonist G15. Dose-dependent vasoconstrictive responses to phenylephrine were attenuated significantly in the rings of the thoracic aorta following the acute G1 administration in the diabetic OVX rats. This effect of G1 was abolished partially by L-NAME and G15. The acute administration of G1 increased significantly the eNOS activity and the concentration of NO in the endothelial cells exposed to high glucose. G1 treatment induced an enhanced endothelium-dependent relaxation to acetylcholine (Ach in the diabetic OVX rats. Further examination revealed that G1 induced vasodilation in the diabetic OVX rats by increasing the phosphorylation of eNOS. These findings provide preliminary evidence that GPR30 activation leads to eNOS activation, as well as vasodilation, to a certain degree and has beneficial effects on vascular function in diabetic OVX rats.

The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives

DEFF Research Database (Denmark)

Humaidan, Peter; Papanikolaou, E G; Kyrou, D

2012-01-01

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid...... with a GnRH agonist instead of human chorionic gonadotrophin (HCG). The first studies applying this concept, however, showed a very poor pregnancy rate, despite standard luteal-phase support with progesterone. This review discusses the reason for the poor results and the newest studies, using GnRH agonist...

Determination of the attenuation map in emission tomography

CERN Document Server

Zaidi, H

2002-01-01

Reliable attenuation correction methods for quantitative emission computed tomography (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomical structure. Two broad classes of methods have been used to calculate the attenuation map referred to as "transmissionless" and transmission-based attenuation correction techniques. While calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and utilizes different approaches to determine this map including transmission scanning, segmented magnetic resonance images or appropriately scaled X-ray CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acqu...

Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

Science.gov (United States)

Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

2015-01-28

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction

Science.gov (United States)

Xi, Zheng-Xiong; Song, Rui; Li, Xia; Lu, Guan-Yi; Peng, Xiao-Qing; He, Yi; Bi, Guo-Hua; Sheng, Siyuan Peter; Yang, Hong-Ju; Zhang, Haiying; Li, Jin; Froimowitz, Mark; Gardner, Eliot L

2017-01-01

Agonist-replacement therapies have been successfully used for treatment of opiate and nicotine addiction, but not for cocaine addiction. One of the major obstacles is the cocaine-like addictive potential of the agonists themselves. We report here an atypical dopamine (DA) transporter (DAT) inhibitor, CTDP-32476, that may have translational potential for treating cocaine addiction. In vitro ligand-binding assays suggest that CTDP-32476 is a potent and selective DAT inhibitor and a competitive inhibitor of cocaine binding to the DAT. Systemic administration of CTDP-32476 alone produced a slow-onset, long-lasting increase in extracellular nucleus accumbens DA, locomotion, and brain-stimulation reward. Drug-naive rats did not self-administer CTDP-32476. In a substitution test, cocaine self-administration rats displayed a progressive reduction in CTDP-32476 self-administration with an extinction pattern of drug-taking behavior, suggesting significantly lower addictive potential than cocaine. Pretreatment with CTDP-32476 inhibited cocaine self-administration, cocaine-associated cue-induced relapse to drug seeking, and cocaine-enhanced extracellular DA in the nucleus accumbens. These findings suggest that CTDP-32476 is a unique DAT inhibitor that not only could satisfy ‘drug hunger' through its slow-onset long-lasting DAT inhibitor action, but also render subsequent administration of cocaine ineffectual—thus constituting a novel and unique compound with translational potential as an agonist therapy for treatment of cocaine addiction. PMID:27534265

Effects of local anesthetics on cholinergic agonist binding affinity of central nervous system. cap alpha. -bungarotoxin receptors

Energy Technology Data Exchange (ETDEWEB)

Lukas, R.L.; Bennett, E.L.

1979-12-01

In general, pharmacological effects of local anesthetics may be attributed to their ability to reversibly block the propagation of nerve and muscle action potentials. At physiologically potent concentrations, local anesthetics (LA) also act as noncompetitive antagonists of the physiological response of post-synaptic nicotinic acetylcholine receptors (nAChR) to cholinergic agonists, and increase agonist binding affinities of nAChR from electric organ. It is postulated that the primary site of LA action on nAChR function is at the receptor-coupled ionophore. Furthermore, LA-nAChR ionophore interactions are thought to accelerate physiological desensitization of nAChR, manifest biochemically as increased affinity of nAChR for agonist. Specific receptors for ..cap alpha..-bungarotoxin (..cap alpha..-Bgt), a potent competitive antagonist at nAChR sites in the periphery, have been detected in rat central nervous system membrane preparations. The affinity of these central ..cap alpha..-Bgt receptors (..cap alpha..-BgtR) for cholinergic agonists is found to increase on exposure to agonist. Nevertheless, on the basis of inconsistent pharmacological and physiological results, uncertainty remains regarding the relationship between ..cap alpha..-BgtR and authentic nAChR in the CNS, despite a wide body of biochemical and histological evidence consistent with their identity. Reasoning that if CNS ..cap alpha..-BgtR are true in nAChR, coupled to functional ion channels, LA might be expected to cause biochemically measurable increases in ..cap alpha..-BgtR affinity for cholinergic agonists, we have undertaken a study of the effects of LA on the ability of acetylcholine (ACh) to inhibit interaction of ..cap alpha..-BgtR with /sup 3/H-labeled ..cap alpha..-Bgt.

Sulfoximines as potent RORγ inverse agonists.

Science.gov (United States)

Ouvry, Gilles; Bihl, Franck; Bouix-Peter, Claire; Christin, Olivier; Defoin-Platel, Claire; Deret, Sophie; Feret, Christophe; Froude, David; Hacini-Rachinel, Feriel; Harris, Craig S; Hervouet, Catherine; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Parnet, Veronique; Pascau, Coralie; Pascau, Jonathan; Pierre, Romain; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent F

2018-05-01

Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.

Science.gov (United States)

Zhang, Yun-Fang; Zou, Xun-Liang; Wu, Jun; Yu, Xue-Qing; Yang, Xiao

2015-12-01

We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.

In vitro phototoxic potential and photochemical properties of imidazopyridine derivative: a novel 5-HT4 partial agonist.

Science.gov (United States)

Onoue, Satomi; Igarashi, Naoko; Yamauchi, Yukinori; Kojima, Takashi; Murase, Noriaki; Zhou, Yu; Yamada, Shizuo; Tsuda, Yoshiko

2008-10-01

Drug-induced phototoxic skin responses have been recognized as undesirable side effects, and as we previously proposed the determination of reactive oxygen species (ROS) from photo-irradiated compounds can be effective for the prediction of phototoxic potential. In this investigation, we evaluated the photosensitizing properties of imidazopyridine derivative, a novel 5-HT(4) partial agonist, using ROS assay and several analytical/biochemical techniques. Exposure of the compound to simulated sunlight resulted in the significant production of singlet oxygen, which is indicative of its phototoxic potential. In practice, an imidazopyridine derivative under UVA/B light exposure also showed significant photodegradation and even photobiochemical events; peroxidation of fatty acid and genetic damage after DNA-binding, which are considered as causative agents for phototoxic dermatitis. Interestingly, both photodegradation and lipoperoxidation were dramatically attenuated by the addition of radical scavengers, especially singlet oxygen quenchers, suggesting the possible involvement of ROS generation in the phototoxic pathways. In the 3T3 neutral red uptake phototoxicity test, imidazopyridine derivative also showed the phototoxic effect on 3T3 mouse fibroblast cells. These results suggest the phototoxic risk of newly synthesized imidazopyridine derivative and also verify the usefulness of ROS assay for phototoxicity prediction. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

An acoustic eikonal equation for attenuating VTI media

KAUST Repository

Hao, Qi

2016-09-06

We present an acoustic eikonal equation governing the complex-valued travel time of P-waves in attenuating, transversely isotropic media with a vertical symmetry axis (VTI). This equation is based on the assumption that the Pwave complex-valued travel time is independent of the Swave velocity parameter v in Thomsen\\'s notation and the attenuation coefficient A in the Thomsen-type notation for attenuating VTI media. We combine perturbation theory and Shanks transform to develop practical approximations to the attenuating acoustic eikonal equation, capable of admitting analytical description of the attenuation in homogeneous media. For a horizontal, attenuating VTI layer, we also derive non-hyperbolic approximations for the real and imaginary parts of the complex-valued reflection travel time.

Ultrasonic attenuation in superconducting zinc

International Nuclear Information System (INIS)

Auluck, S.

1978-01-01

The differences in the Zn ultrasonic attenuation data of different workers are analyzed. The superconducting energy gaps deduced from our analysis of the ultrasonic-attenuation data of Cleavelin and Marshall are consistent with the gaps deduced from the knowledge of the Fermi surface and the electron-phonon mass enhancement factor

β3-adrenoceptor mediates β3-selective agonist-induced effects on ...

African Journals Online (AJOL)

β3-adrenoceptor mediates β3-selective agonist-induced effects on energy expenditure, insulin secrtion and food ... Journal of the Ghana Science Association ... is usually associated with obesity, also involves defective energy expenditure, ...

Feeding associations between capybaras Hydrochoerus hydrochaeris (Linnaeus (Mammalia, Hydrochaeridae and birds in the Lami Biological Reserve, Porto Alegre, Rio Grande do Sul, Brazil Associações alimentares entre capivaras (Hydrochoerus hydrochaeris (Linnaeus (Mammalia, Hydrochaeridae e aves na Reserva Biológica do Lami, Porto Alegre, Rio Grande do Sul, Brasil

Directory of Open Access Journals (Sweden)

Ana C. Tomazzoni

2005-09-01

Full Text Available Feeding associations between capybaras Hydrochoerus hydrochaeris (Linnaeus, 1766 and some bird species were registered in the Lami Biological Reserve, southern Brazil, through observations in a set of transects established in the five major vegetation types of the study area: shrubby and herbaceous swamps, wet grasslands, sandy grasslands and forests. Data included: date and time, vegetation type, bird species, number of individuals (birds and capybaras, type of prey consumed, foraging strategy of the birds and the behavior of the capybaras in relation to the presence of birds. Five species of birds were registered: Caracara plancus (Miller, 1777, Furnarius rufus (Gmelin, 1788, Machetornis rixosus (Vieillot, 1819, Milvago chimachima (Vieillot, 1816 and Molothrus bonariensis (Gmelin, 1789. The interactions were observed in the shrubby swamp (M. bonariensis, forest (C. plancus and wet grassland (F. rufus, M. rixosus, M. chimachima. The foraging strategies were: (1 use of the capybara as a perch, hunting from its back (M. rixosus, M. bonariensis; (2 use of the capybara as a beater, hunting in the ground (F. rufus, M. rixosus, M. bonariensis; (3 foraging in the skin of the capybara, by picking the ectoparasites (C. plancus, F. rufus, M. chimachima. Strategies (1 and (2 were employed to catch arthropods flushed from the vegetation. Sometimes, capybaras lay down and exposed the abdomen and lateral areas of their bodies to facilitate cleaning by M. chimachima, but the presence of other bird species seemed to be neutral to capybaras.Foram registradas associações alimentares entre capivaras Hydrochoerus hydrochaeris (Linnaeus, 1766 e aves na Reserva Biológica do Lami, sul do Brasil, por meio de observações em um conjunto de transecções estabelecidas nos cinco principais tipos de vegetação existentes na área: banhado arbustivo, banhado herbáceo, campo úmido, campo arenoso e mata. As informações coletadas foram: data, horário, tipo de vegeta

Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1 Signaling Pathway in RAW264.7 and MOVAS Cells

Directory of Open Access Journals (Sweden)

Liping Liu

2017-01-01

Full Text Available Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (α7-nAChR signaling had been demonstrated attenuation of inflammation. This study aimed to determine whether PNU-282987, a selective α7-nAChR agonist, affected activities of matrix metalloproteinase (MMP and inflammatory cytokines in nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at different concentrations (0, 1, 10, and 100 ng/ml for 0–120 min. Nicotine markedly stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2 and c-Jun in RAW264.7 cells. Pretreatment with U0126 significantly suppressed phosphorylation of ERK1/2 and further attenuated nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte chemotactic protein- (MCP- 1, and regulated upon activation normal T cell expressed and secreted (RANTES. Similarly, nicotine treatment also increased phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9, MCP-1, and RANTES were remarkably downregulated. Treatment with α7-nAChR agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS cells, providing a new therapeutic for abdominal aortic aneurysm.

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

Science.gov (United States)

Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

2010-01-01

To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

32 CFR 813.4 - Combat camera operations.

Science.gov (United States)

2010-07-01

... National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE SALES AND SERVICES VISUAL... procedures. (1) When VI support teams are required, the lead wing's VI UTC deploys as primary, whenever possible. If lead wing VI support is not available, the providing command sources the requirement from...

Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists

DEFF Research Database (Denmark)

Sasmal, Pradip K; Krishna, C Vamsee; Sudheerkumar Adabala, S

2015-01-01

Kappa opioid receptor (KOR) is an important mediator of pain signaling and it is targeted for the treatment of various pains. Pharmacophore based mining of databases led to the identification of 2-aminobenzimidazole derivative as KOR agonists with selectivity over the other opioid receptors DOR a...... of novel benzimidazole derivatives as KOR agonists are described. The in vivo proof of principle for anti-nociceptive effect with a lead compound from this series is exemplified....

Estudio de los riesgos ergonómicos presentes durante la construcción de los túneles urbanos de Gerona para el AVE

OpenAIRE

Bermejo Cardona, Anahí

2012-01-01

El objetivo de este estudio es determinar el riesgo ergonómico presente en algunas de las tareas llevadas a cabo durante la construcción de los túneles urbanos de Gerona para el AVE. Primero se realizaron entrevistas con los responsables de seguridad y salud de la obra a los que se les solicitaron los datos de siniestralidad des del inicio de los trabajos. De esta manera se puede conocer el número de bajas médicas por sobreesfuerzos o posturas forzadas. Después se les acompañó durante s...

ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

Energy Technology Data Exchange (ETDEWEB)

Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O

2007-05-15

In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists.

Science.gov (United States)

Liu, Yang; Zhang, Qing; Chen, Lin-Hai; Yang, Hui; Lu, Wei; Xie, Xin; Nan, Fa-Jun

2016-06-09

A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.

Patrón de actividad y abundancia de aves en un relleno sanitario de Chile central Abundance and activity-pattern of birds at a landfill in central Chile

Directory of Open Access Journals (Sweden)

GABRIEL LOBOS

2011-03-01

Full Text Available Los rellenos sanitarios constituyen un foco de atracción para la avifauna, aunque las implicancias de esta relación no han sido exploradas en el país. Nosotros monitoreamos la actividad de aves en un relleno sanitario ubicado en las proximidades de la ciudad de Santiago, capital administrativa de Chile. Las principales aves en el área fueron la gaviota dominicana (Larus dominicanus Lichtenstein, el tiuque (Milvago chimango Vieillot, la garza boyera {Buculbus ibis Linnaeus y el águila (Geranoaetus melanoleucus Swann. La gaviota dominicana alcanzó los valores de abundancia más altos (entre 358 y 1950 individuos por día y destacó por su comportamiento bimodal, directamente relacionado con los niveles de operación en el relleno sanitario. En el caso del águila se registró una conducta carroñera cleptoparásita sobre los tiuques, estos últimos seleccionan desechos orgánicos (pescados, tripas, carne, que les son usurpados por ellas. Finalmente señalamos medidas simples de manejo que deberían disminuir los números de aves en este tipo de actividad industrial.Landfills are considered an attractive habitat for several bird species; however, implications of this condition have not yet been explored in the country. We monitored birds' activity patterns that use a landfill located in the vicinity of Santiago, Chile's capital. Main birds recorded in the area were, Kelp gull (Larus dominicanus Lichtenstein, Chimango caracara (Milvago chimango Vieillot, Cattle egret (Buculbus ibis Linnaeus and Black Chested Eagle (Geranoaetus melanoleucus Swann. Kelp Gull was the most abundant species, (with values between 358 to 1950 individuals per day and that also displayed a bimodal behavior linked directly to the landfill operation levels. In the case of Black Chested Eagle, we observed a kleptoparasitic behavior over Chimango Caracara which selected organic offal (fishes, innards, meat for its feeding and that are stolen by the eagle. Finally we