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1.
PLoS One ; 18(9): e0291270, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37708166

RESUMEN

The dragonfly Trithemis kirbyi Sélys, 1891 recently colonized Western Europe from North Africa. Since its first record in the Iberian Peninsula in 2007, the species has been spreading northward and has become naturally established in the central and eastern Iberian Peninsula, the Balearic Islands and southern France. Despite its worldwide distribution, its rapid colonization of the western Mediterranean area occurred only very recently. The aims of this study were to evaluate (1) whether the species' colonization of the western Mediterranean is related to climate change and rising temperatures, specifically the summer warming peaks that have occurred in the last decade, (2) which climatic variables have most influenced its distribution and dispersal, and (3) its potential future dispersal and colonization capacity towards the eastern Mediterranean. We found that the dispersal and recent establishment of T. kirbyi in southwestern Europe strongly depends on increasing temperatures, particularly summer temperature peaks, which has allowed this species to disperse farther and more effectively than during years with average summer temperatures. The most important variable in the suitability models is the minimum temperature of the coldest month, which, in recent decades, has become less of a limiting factor for ectotherms. According to the models, suitable areas for the species are currently found throughout the eastern Mediterranean parts of Europe, and it is likely that it can naturally colonize these areas as it did in the Iberian Peninsula. Trithemis kirbyi is a model of how climate change and observed rising temperatures have turned previously inhospitable regions into suitable areas for exotic species, which may successfully colonize them naturally if they can reach these promising lands on their own. However, this study serves as a warning that such species can also colonize these new regions with a little help from unsuspecting means, which are often responsible for the increasingly common presence of invasive, noxious taxa in Europe.


Asunto(s)
Odonata , Animales , Cambio Climático , Insectos , Europa (Continente) , España
2.
Molecules ; 27(20)2022 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-36296491

RESUMEN

The use of phytogenic extracts is considered a sustainable strategy for the prevention of fish diseases, including Alliaceae as a potential option due to their variety of bioactive compounds. In this study, we analyzed the antibacterial and antiparasitic potential of propyl-propane-thiosulfinate (PTS) and propyl-propane-thiosulfonate (PTSO) from onions. The in vitro activity against Pseudomonas anguilliseptica, Tenacibaculum maritimum, and Photobacterium damselae of both compounds was tested. In addition, the viability of Sparicotyle chrysophrii larvae was evaluated. Moreover, a diet that consisted of a blend of PTS/PTSO (ALLIUM) was used. A total of 90 gilthead sea bream juveniles were tested against P. damselae subsp. Piscicida after 12 weeks of dietary administration. Furthermore, 150 fish with a rate of 10-15 parasites/fish were fed for 21 days and the number of gill parasites was recorded. All strains were sensitive to both compounds. PTSO showed the highest inhibitory effect against all target strains, while PTS showed higher effectiveness against S. chrysophrii. Fish from ALLIUM group presented the highest probability of survival, increasing up to 91.1%, whereas in the control group, the probability of survival was 66.7%. The number of parasites in the gilthead sea bream decreased in the ALLIUM group over time. These results suggest the inclusion of PTS and PTSO in feed as a natural strategy to prevent antibacterial and antiparasitic fish diseases.


Asunto(s)
Allium , Enfermedades de los Peces , Dorada , Animales , Cebollas , Propano , Antiparasitarios/farmacología , Antibacterianos , Enfermedades de los Peces/tratamiento farmacológico , Extractos Vegetales
3.
Bull Entomol Res ; 111(2): 160-173, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32847632

RESUMEN

The alien cynipid wasp Dryocosmus kuriphilus Yasumatsu, 1951 is a serious pest of chestnuts (Castanea spp.) in Japan, North America and Europe, causing fruit losses while inducing galls in buds. While D. kuriphilus galls have a recognizable and roughly invariable globular shape, their size varies, reaching up to 4 cm in diameter. Among other factors, such variation may depend on different climatic conditions in different attacked areas. Here, we sampled and measured 375 D. kuriphilus galls from 25 localities throughout the Iberian Peninsula, including both cold and rainy northern (Eurosiberian) areas and warm and dry central-southern (Mediterranean) areas, to test the effects of climate and geographical location on gall morphology. The analyses indicate that gall mass and volume follow a pattern that can be associated with a climatic cline. In particular, the Eurosiberian galls were smaller than the Mediterranean galls according to differences in climatic conditions. In the southern areas, the greater insolation regime does not allow the chestnut trees to be distributed at lower altitudes, but the high rainfall and humidity regime of the mountain enclaves allow their presence. These conditions of insolation and precipitation seem to influence the morphological characteristics of the galls of D. kuriphilus.


Asunto(s)
Fagaceae/parasitología , Tumores de Planta/parasitología , Avispas , Animales , Clima , Enfermedades de las Plantas/parasitología , Lluvia , España , Temperatura , Árboles
5.
Gac Med Mex ; 156(5): 446-453, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33372929

RESUMEN

In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.


En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.


Asunto(s)
Factores Biológicos/uso terapéutico , Psoriasis/terapia , Factores de Edad , Femenino , Humanos , Masculino , México , Embarazo , Complicaciones del Embarazo/terapia , Sociedades Médicas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
6.
Gac. méd. Méx ; 156(5): 454-462, sep.-oct. 2020. tab
Artículo en Español | LILACS | ID: biblio-1249945

RESUMEN

Resumen En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.


Abstract In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.


Asunto(s)
Humanos , Masculino , Femenino , Embarazo , Psoriasis/terapia , Factores Biológicos/uso terapéutico , Complicaciones del Embarazo/terapia , Sociedades Médicas , Factores de Edad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , México
8.
Sci Adv ; 6(3): eaax7467, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31998838

RESUMEN

Our nearest neighbor, Proxima Centauri, hosts a temperate terrestrial planet. We detected in radial velocities evidence of a possible second planet with minimum mass m c sin i c = 5.8 ± 1.9M ⊕ and orbital period P c = 5.21 - 0.22 + 0.26 years. The analysis of photometric data and spectro-scopic activity diagnostics does not explain the signal in terms of a stellar activity cycle, but follow-up is required in the coming years for confirming its planetary origin. We show that the existence of the planet can be ascertained, and its true mass can be determined with high accuracy, by combining Gaia astrometry and radial velocities. Proxima c could become a prime target for follow-up and characterization with next-generation direct imaging instrumentation due to the large maximum angular separation of ~1 arc second from the parent star. The candidate planet represents a challenge for the models of super-Earth formation and evolution.

9.
Acta Radiol ; 60(6): 788-797, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30231620

RESUMEN

BACKGROUND: Longitudinal monitoring of potential radiotherapy treatment effects can be determined by dynamic contrast-enhanced ultrasound (DCE-US). PURPOSE: To assess functional parameters by means of DCE-US in a murine subcutaneous model of human prostate cancer, and their relationship to dose deposition and time-frame after treatment. A special focus has been placed to evaluate the vascular heterogeneity of the tumor and on the most suitable data analysis approach that reflects this heterogeneity. MATERIAL AND METHODS: In vivo DCE-US was acquired 24 h and 48 h after radiation treatment with a single dose of 7.5 Gy and 10 Gy, respectively. Tumor vasculature was characterized pixelwise using the Brix pharmacokinetic analysis of the time-intensity curves. RESULTS: Longitudinal changes were detected ( P < 0.001) at 24 h and 48 h after treatment. At 48 h, the eliminating rate constant of the contrast agent from the plasma, kel, was correlated ( P ≤ 0.05) positively with microvessel density (MVD; rτ = 0.7) and negatively with necrosis (rτ = -0.6) for the treated group. Furthermore, Akep, a parameter related to transcapillary transport properties, was also correlated to MVD (rτ = 0.6, P ≤ 0.05). CONCLUSION: DCE-US has been shown to detect vascular changes at a very early stage after radiotherapy, which is a great advantage since DCE-US is non-invasive, available at most hospitals, and is low in cost compared to other techniques used in clinical practice.


Asunto(s)
Medios de Contraste , Aumento de la Imagen/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Ultrasonografía/métodos , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Desnudos , Resultado del Tratamiento
10.
Parasit Vectors ; 11(1): 501, 2018 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-30189883

RESUMEN

BACKGROUND: Biting aquatic insects belonging to the order Hemiptera have been suggested as potential vectors of Mycobacterium ulcerans in endemic areas for Buruli ulcer (BU). If this is the case, these insects would be expected to co-exist with M. ulcerans in the same geographical areas. Here, we studied the geographical distribution of six aquatic Hemiptera families that are thought to be vectors of M. ulcerans and explored their potential geographical overlapping with communities reporting BU cases in endemic countries. METHODS: We have developed ensemble ecological models of predicted distribution for six families of the Hemiptera (Naucoridae, Belostomatidae, Notonectidae, Nepidae, Corixidae and Gerridae) applying a robust modelling framework over a collection of recorded presences and a suite of environmental and topographical factors. Ecological niche factor analysis (ENFA) was first used to identify factors that best described the ecological niches for each hemipteran family. Finally, we explored the potential geographical co-occurrence of these insects and BU in two endemic countries, Cameroon and Ghana. RESULTS: Species of the families Naucoridae and Belostomatidae, according to our models, are widely distributed across Africa, although absent from drier and hotter areas. The other two families of biting Hemiptera, the Notonectidae and Nepidae, would have a more restricted distribution, being more predominant in western and southern Africa. All these four families of biting water bugs are widely distributed across coastal areas of West Africa. They would thrive in areas where annual mean temperature varies between 15-22 °C, with moderate annual precipitation (i.e. 350-1000 mm/annual) and near to water courses. Species of all hemipteran families show preference for human-made environments such as agricultural landscapes and urbanized areas. Finally, our analysis suggests that M. ulcerans and species of these aquatic insects might coexist in the same ecological niches, although there would be variation in species diversity between BU endemic areas. CONCLUSIONS: Our findings predict the geographical co-existence of some species of aquatic hemipteran families and BU. Considering the existing biological evidence that points to some of these aquatic insects as potential phoretic vectors of M. ulcerans, its presence in BU endemic areas should be considered a risk factor. The ecological models here presented may be helpful to inform future environmental based models intended to delineate the potential geographical distribution of BU in the African region.


Asunto(s)
Úlcera de Buruli/transmisión , Ambiente , Hemípteros/microbiología , Insectos Vectores/microbiología , Mycobacterium ulcerans/aislamiento & purificación , Análisis Espacial , Distribución Animal , Animales , Úlcera de Buruli/epidemiología , Úlcera de Buruli/microbiología , Camerún/epidemiología , Vectores de Enfermedades , Geografía , Ghana/epidemiología , Hemípteros/fisiología , Humanos , Mordeduras y Picaduras de Insectos , Agua
11.
Zookeys ; (644): 51-88, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28144185

RESUMEN

A systematic study of the genus Ormyrus (Chalcidoidea, Ormyridae) was conducted based on the morphology and biology of the terminal-instar larvae of ten west European species that are parasitoids of gall wasps and gallflies of the families Cynipidae, Eurytomidae and Tephritidae. The first detailed descriptions are provided of the terminal-instar larvae of these ten species using SEM images to illustrate diagnostic characters with systematic values. A key is provided for the identification of ormyrid larvae associated with galls in Europe, which is based particularly on characters of the head, mouthparts and mandibles. Although only limited informative variation in body shape was found, the setation of the head provided several characters of potential taxonomic value. The larval biology of the ten ormyrid species inhabiting different galls is also summarised. Although Ormyrus larvae are usually solitary idiobiont ectoparasitoids of the host larva of various gall-inhabiting insects, evidence of secondary phytophagy was observed in some species.

12.
N Engl J Med ; 375(11): 1019-32, 2016 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-27626517

RESUMEN

BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).


Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster/prevención & control , Neuralgia Posherpética/prevención & control , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/inmunología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/epidemiología , Riesgo , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunología
14.
J Transl Med ; 13: 383, 2015 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-26682742

RESUMEN

BACKGROUND: This study aims to assess the effect of radiation treatment on the tumour vasculature and its downstream effects on hypoxia and choline metabolism using a multimodal approach in the murine prostate tumour model CWR22. Functional parameters derived from Positron Emission Tomography (PET)/Computer Tomography (CT) with (18)F-Fluoromisonidazole ((18)F-FMISO) and (18)F-Fluorocholine ((18)F-FCH) as well as Dynamic Contrast-Enhanced Ultrasound (DCE-US) were employed to determine the relationship between metabolic parameters and microvascular parameters that reflect the tumour microenvironment. Immunohistochemical analysis was employed for validation. METHODS: PET/CT and DCE-US were acquired pre- and post-treatment, at day 0 and day 3, respectively. At day 1, radiation treatment was delivered as a single fraction of 10 Gy. Two experimental groups were tested for treatment response with (18)F-FMISO and (18)F-FCH. RESULTS: The maximum Standardized Uptake Values (SUVmax) and the mean SUV (SUVmean) for the (18)F-FMISO group were decreased after treatment, and the SUVmean of the tumour-to-muscle ratio was correlated to microvessel density (MVD) at day 3. The kurtosis of the amplitude of the contrast uptake A was significantly decreased for the control tumours in the (18)F-FCH group. Furthermore, the eliminating rate constant of the contrast agent from the plasma k el derived from DCE-US was negatively correlated to the SUVmean of tumour-to-muscle ratio, necrosis and MVD. CONCLUSIONS: The present study suggests that the multimodal approach using (18)F-FMISO PET/CT and DCE-US seems reliable in the assessment of both microvasculature and necrosis as validated by histology. Thus, it has valuable diagnostic and prognostic potential for early non-invasive evaluation of radiotherapy.


Asunto(s)
Colina/análogos & derivados , Misonidazol/análogos & derivados , Monitoreo Fisiológico , Imagen Multimodal , Radioterapia , Animales , Colina/administración & dosificación , Masculino , Ratones , Ratones Desnudos , Misonidazol/administración & dosificación , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X
16.
Onco Targets Ther ; 9: 1305-13, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24092993

RESUMEN

OBJECTIVE: The aim of the study reported here was to assess the disease-free survival and overall survival of patients with endometrial cancer and to determine independent factors affecting the prognosis. MATERIALS AND METHODS: This was a retrospective study of a single-center clinical series of 276 patients (mean age 64 years) with histologically confirmed cancer of the corpus uteri. The standard treatments were extrafascial total hysterectomy and bilateral salpingo-oophorectomy with selective pelvic/para-aortic node dissection, according to risk for recurrence. Actuarial overall survival and disease-free survival were estimated according to the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were used to assess the prognostic significance of the different variables. RESULTS: The estimated median follow-up, determined using the inverse Kaplan-Meier method, was 45 months (95% confidence interval [CI] 41.2-48.8) for disease-free survival and 46 months (95% CI 43.0-49.0) for overall survival. The statistically significant variables affecting disease-free survival and overall survival were age, serous-papillary and clear-cell histological types, outer-half myometrial invasion, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grades G2 and G3, incomplete surgical resection, positive lymph nodes, lymphovascular space invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the multivariate Cox regression model, predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57-9.36, P < 0.001) and tumor grades G2 (HR 4.79, 95% CI 1.73-13.27, P = 0.003) and G3 (HR 7.56, 95% CI 2.75-20.73, P < 0.001). The same variables were also associated with a significantly higher risk of tumor-related mortality. CONCLUSION: FIGO stage and tumor grade were independent prognostic factors of disease-free survival and overall survival in endometrial cancer patients. Outcome was also influenced by histopathologic type, myometrial and lymphovascular space invasion, lymph-node involvement, age, and tumor remnants after surgery, although a larger study sample is probably needed to demonstrate the independent association of these variables with survival.

17.
Ecology ; 88(8): 1877-88, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17824415

RESUMEN

We compiled 46 broadscale data sets of species richness for a wide range of terrestrial plant, invertebrate, and ectothermic vertebrate groups in all parts of the world to test the ability of metabolic theory to account for observed diversity gradients. The theory makes two related predictions: (1) In-transformed richness is linearly associated with a linear, inverse transformation of annual temperature, and (2) the slope of the relationship is near -0.65. Of the 46 data sets, 14 had no significant relationship; of the remaining 32, nine were linear, meeting prediction 1. Model I (ordinary least squares, OLS) and model II (reduced major axis, RMA) regressions then tested the linear slopes against prediction 2. In the 23 data sets having nonlinear relationships between richness and temperature, split-line regression divided the data into linear components, and regressions were done on each component to test prediction 2 for subsets of the data. Of the 46 data sets analyzed in their entirety using OLS regression, one was consistent with metabolic theory (meeting both predictions), and one was possibly consistent. Using RMA regression, no data sets were consistent. Of 67 analyses of prediction 2 using OLS regression on all linear data sets and subsets, two were consistent with the prediction, and four were possibly consistent. Using RMA regression, one was consistent (albeit weakly), and four were possibly consistent. We also found that the relationship between richness and temperature is both taxonomically and geographically conditional, and there is no evidence for a universal response of diversity to temperature. Meta-analyses confirmed significant heterogeneity in slopes among data sets, and the combined slopes across studies were significantly lower than the range of slopes predicted by metabolic theory based on both OLS and RMA regressions. We conclude that metabolic theory, as currently formulated, is a poor predictor of observed diversity gradients in most terrestrial systems.


Asunto(s)
Biodiversidad , Ecosistema , Metabolismo Energético/fisiología , Modelos Biológicos , Temperatura , Animales , Geografía , Invertebrados/crecimiento & desarrollo , Modelos Lineales , Desarrollo de la Planta , Valor Predictivo de las Pruebas , Análisis de Regresión , Especificidad de la Especie
18.
Nature ; 437(7055): 109-11, 2005 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-16136136

RESUMEN

The processes leading to the birth of low-mass stars such as our Sun have been well studied, but the formation of high-mass (over eight times the Sun's mass, M(o)) stars remains poorly understood. Recent studies suggest that high-mass stars may form through accretion of material from a circumstellar disk, in essentially the same way as low-mass stars form, rather than through the merging of several low-mass stars. There is as yet, however, no conclusive evidence. Here we report the presence of a flattened disk-like structure around a massive 15M(o) protostar in the Cepheus A region, based on observations of continuum emission from the dust and line emission from the molecular gas. The disk has a radius of about 330 astronomical units (Au) and a mass of 1 to 8 M(o). It is oriented perpendicular to, and spatially coincident with, the central embedded powerful bipolar radio jet, just as is the case with low-mass stars, from which we conclude that high-mass stars can form through accretion.

19.
Circ Res ; 91(9): 830-6, 2002 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-12411398

RESUMEN

The effects of the antihypertensive agent hydralazine (1 to 100 nmol/L) on the exocytotic process of single adrenal chromaffin cells have been studied using amperometry. Hydralazine does not reduce the frequency of exocytotic spikes but rapidly slows the rate of catecholamine release from individual exocytotic events by reducing the quantal size of catecholamine exocytosis. Confocal and standard epifluorescence microscopy studies show that hydralazine rapidly accumulates within secretory vesicles. The blockade of the vesicular H+ pump with bafilomycin A1 inhibits hydralazine uptake. Experiments with permeabilized cells show that hydralazine displaces catecholamines from secretory vesicles. The drug also displaces vesicular Ca2+, as shown by fura-2 microfluorimetry. These data suggest that hydralazine acts, at least partially, by interfering with the storage of catecholamines. These effects of hydralazine occurred within seconds, and at the tissue concentrations presumably reached in antihypertensive therapy; these concentrations are a thousand times lower than those described for relaxing vascular tissues in vitro. We proposed that these novel effects could explain many of the therapeutic and side effects of this drug that are likely exerted in sympathetic nerve terminals.


Asunto(s)
Médula Suprarrenal/metabolismo , Catecolaminas/metabolismo , Células Cromafines/metabolismo , Exocitosis/efectos de los fármacos , Hidralazina/farmacología , Macrólidos , Vesículas Secretoras/efectos de los fármacos , Médula Suprarrenal/citología , Médula Suprarrenal/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antihipertensivos/farmacocinética , Antihipertensivos/farmacología , Calcio/metabolismo , Bovinos , Células Cultivadas , Células Cromafines/citología , Células Cromafines/efectos de los fármacos , Gránulos Cromafines/efectos de los fármacos , Gránulos Cromafines/metabolismo , Relación Dosis-Respuesta a Droga , Electroquímica , Inhibidores Enzimáticos/farmacología , Exocitosis/fisiología , Colorantes Fluorescentes , Hidralazina/farmacocinética , Concentración de Iones de Hidrógeno/efectos de los fármacos , Líquido Intracelular/metabolismo , Cinética , Nucleótidos/metabolismo , Vesículas Secretoras/metabolismo
20.
J Pharmacol Exp Ther ; 301(2): 631-7, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-11961067

RESUMEN

The role of nongenomic action of estrogens on elicited catecholamine secretion and exocytosis kinetics was studied in perfused rat adrenals and in cultured bovine chromaffin cells. 17beta-Estradiol as well as the estrogen receptor modulators raloxifene and LY117018, but not 17alpha-estradiol, inhibited at the micromolar range the catecholamine output elicited by acetylcholine or high potassium. However, these agents failed to modify the secretion elicited by high Ca(2+) in glands treated with the ionophore A-23187 (calcimycin), suggesting that estrogens did not directly act on the secretory machinery. At the single cell level, estrogens modified the kinetics of exocytosis at nanomolar range. All of the drugs tested except 17alpha-estradiol produced a profound slowing down of the exocytosis as measured by amperometry. LY117018 also reduced the granule content of catecholamines. 17beta-Estradiol reduced the intracellular free Ca(2+) but only at micromolar concentrations, whereas nanomolar concentrations increased the cAMP levels. These effects were reproduced with the nonpermeable drug 17beta-estradiol-horseradish peroxidase and antagonized with nanomolar concentrations of the antiestrogen ICI 182,780 (fulvestrant). Our data suggest the presence of membrane sites that regulate both the exocytotic phenomenon and the total catecholamine release with high and low affinity, respectively.


Asunto(s)
Estradiol/análogos & derivados , Estrógenos/farmacología , Exocitosis/efectos de los fármacos , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Animales , Calcio/metabolismo , Catecolaminas/metabolismo , Bovinos , Células Cromafines/efectos de los fármacos , Células Cromafines/metabolismo , Células Cromafines/fisiología , AMP Cíclico/metabolismo , Estradiol/farmacología , Antagonistas de Estrógenos/farmacología , Exocitosis/fisiología , Fulvestrant , Cinética , Masculino , Ratas , Ratas Sprague-Dawley
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