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1.
J Environ Radioact ; 257: 107068, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36410084

RESUMO

Tritium is released to the environment by nuclear industries in various forms, mainly HTO. In impact studies leading to estimated doses for the population, atmospheric discharges are mainly taken into consideration because they generally lead to values higher than those related to liquid discharges. However, the tritium released in liquid environments can be transferred to the atmosphere by evaporation and then be transported to terrestrial ecosystems by wind. This study was carried out in France near a fuel reprocessing plant (RP) which discharges tritium into the western English Channel. We highlighted the influence of a mass of water enriched with tritium on the HTO levels in atmospheric water vapour downwind through 18 field campaigns. A hydrodynamic model able to simulate tritium activity in the water was coupled with an evaporation an atmospheric transport model. It allows to reconstitute variations in atmospheric tritium on the coast, depending on liquid discharges of tritium from the reprocessing plant. On this basis, when seawater containing 20-100 Bq.L-1 of tritium flows between 0 and 10 km off the coast, variations in atmospheric activity onshore can increase of 2-15 Bq.L-1. Mean tritium quantities released by the sea into the atmosphere in the Western English Channel reached 130 TBq.y-1 over the 2017-2020 period. Emissions were estimated at 0.9-11.3 GBq km-2.y-1 and depends principally on the distance from the liquid discharge point. If we compare the "marine" source term, in HTO form, with the direct source term for gaseous discharges, the marine source term is one order of magnitude greater for the marine region affected by liquid discharges. Finally, we estimate that approximately 1.1% of tritium stock discharged at sea (regulated and controlled) return to the atmosphere each year at the scale of the Western English Channel.


Assuntos
Monitoramento de Radiação , Poluentes Radioativos da Água , Trítio/análise , Ecossistema , Poluentes Radioativos da Água/análise , Atmosfera
2.
Philos Trans A Math Phys Eng Sci ; 378(2178): 20190625, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32713311

RESUMO

The Alderney Race is assumed to have the largest tidal-stream energy potential in the north-western European coastal seas. Interaction of the powerful tidal stream with strong wind, high waves and irregular bathymetry creates hydrodynamic conditions of extreme complexity, with high levels of turbulence. A comprehensive dataset has been created to improve the understanding of physical processes, turbulence, tidal stream and resource variability at the site. The database contains a large amount of oceanographic and meteorological measurements acquired in Alderney Race in 2017-2018. This exceptionally long period of observations (nearly one year) became possible due to modern tools and strategies of data acquisition. The paper presents some significant results from the database analysis. Among many results, we would like to underline the following: (i) a wide range of variability of mean flow and sea state parameters was documented; (ii) exceptionally large values of current velocity (7 m s-1) and significant wave height (8 m) were measured during extreme meteorological conditions; (iii) high-frequency variability of current speed during storm events was also found to be very large, with the standard deviation of velocity reaching 0.3 m s-1 in the bottom boundary layer, and 0.6 m s-1 in the surface layer; and (iv) predominant wind and wave direction relative to the flow impacts the wave height and significantly increases the turbulence kinetic energy of the flow. To our knowledge, this is the largest multi-variable database available on potential tidal energy sites. The results of database analysis can represent a significant advance in environmental conditions and resource characterization and provide advanced information to turbine developers. This article is part of the theme issue 'New insights on tidal dynamics and tidal energy harvesting in the Alderney Race'.

3.
Water Sci Technol ; 78(8): 1782-1791, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30500802

RESUMO

Different combinations of operational parameters including water level, paddle rotational speed and influent flow rate were applied to investigate their impacts on mixing characteristics, residence time distribution and gas transfer rate in a pilot-scale high rate algal pond. In closed condition, the paddle rotational speed had a positive correlation with the Bodenstein number (Bo), water velocity and oxygen volumetric mass transfer coefficient (kLaO2) while increasing water level generated a negative impact on these parameters, although the impact of water level on water linear velocity was small. The amplification effect of water level and paddle rotational speed on the sensitivity of Bo and kLaO2 should be noticed. Moreover, paddle rotational speed had more impact on kLaO2 than on Bo. The study in open condition indicated that effective volume fraction had a positive correlation with inlet flow rate and negative correlation with paddle rotation, while the opposite was observed in the case of Peclet number. The impact of water level variation on these parameters was unclear. Both water level and paddle rotational speed had negative impacts on the short-circuiting index, while no correlation was observed when varying inlet flow rate. In this study, the optimal operational conditions included low water level (0.1 m) and medium paddle rotational speed (11.6 rpm).


Assuntos
Microalgas/fisiologia , Oxigênio/análise , Lagoas , Eliminação de Resíduos Líquidos/métodos
4.
Sci Total Environ ; 645: 854-864, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30032081

RESUMO

Stormwaters is identified as a major source of pollution in waterbodies. Particularly, heavy metals (HMs) and Polycyclic Aromatic Hydrocarbons (PAHs) in stormwater are highly toxic compounds for living organisms. To limit the impact of these micropollutants on hydrosystems quality, stormwater constructed wetlands (SCWs) have been built worldwide. This study aims to i) assess the efficiency of a SCW that combines a sedimentation pond followed by a vertical flow sand filter in urban area (Strasbourg 67, France) and ii) determine micropollutants storage in water and soils during dry periods. Stormwater quality was analysed during 13 sampling sessions and the SCW storage ability during dry period was highlighted. The rainfall events sampled are characterized by very high variability: dry periods lasted from 5 h to 10 d, rain durations varied from 15 min to 22 h and the return periods were between 2 and 4 wk. and 3-6 mo. The inflow stormwater included a high amount of Zn and a variety of PAHs. Cu, Zn and some PAHs concentrations are impacted by hydrological characteristics. During a rain event, the filter catches the majority of both dissolved and particulate micropollutants and the mobilization of particulate micropollution by incoming flow decreases pond removal efficiency. The treatment removal efficiency varied from 50% (naphthalene) to 100% (particulate Zn). Four HMs (Co, Cu, Pb, Zn) were found in the pond and seven (Cd, Cr, Co, Cu, Ni, Pb, Zn) in the filter during a dry period at high concentrations compared to their occurrence in rainfall. A release of HMs from the filter sand to the interstitial water is highlighted. In water and the soil matrix, PAHs occurrence was consistent with their water solubility, logKow and logKoc.

5.
Sci Total Environ ; 637-638: 443-454, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29754079

RESUMO

Urban stormwater affects the general quality of water bodies because of their hydraulic and pollution impacts. Stormwater discharges modify stream water flow and are reported as major source of heavy metals (HMs) in urban streams. Stormwater Constructed Wetlands (SCWs) have been built worldwide to manage stormwater before it is released into hydrosystems. In SCWs, stormwater is stored, evaporated and sometimes infiltrated. Subsequently, the HMs in stormwater can be settled, filtered and bioassimilated by microorganisms. Hence, the efficiency of SCWs in managing stormwater depends on climatic conditions, which change with season. The aim of this study was to investigate the impacts of seasonality on the performance of a 6-year-old constructed wetland made with a pond followed by a vertical flow filter. Hydraulic performance of, physico-chemical behaviour of, and HM mitigation via the SCW were evaluated using over 3 years of monitoring (2015-2017) data. Only 35% of the rain events that occurred in the studied catchment caused a discharge into the pond and 17% into the filter. The SCW was mostly supplied with stormwater in spring and summer and provided peak flow attenuation from 97 to 100% in all seasons. Variations in physico-chemical parameters (temperature, dissolved oxygen, pH, and redox potential) were caused by seasonal and dry/wet weather changes. They were greater in the pond than in the filter, which buffers these variations. The high physico-chemical variations in the pond probably had a deleterious effect on HM storage in the pond sediments. Finally, hydrologic and physico-chemical conditions (antecedent dry period length, pH, redox potential) affected the HM concentrations along the SCW. However, HM removal efficiencies were >97% in all seasons.


Assuntos
Eliminação de Resíduos Líquidos/métodos , Áreas Alagadas , Metais Pesados/análise , Lagoas , Chuva , Rios , Poluentes Químicos da Água/análise
6.
Handb Exp Pharmacol ; 246: 125-145, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28939974

RESUMO

Voltage-gated sodium channels (VGSC) are critical determinants of cellular electrical activity through the control of initiation and propagation of action potential. To ensure this role, these proteins are not consistently delivered to the plasma membrane but undergo drastic quality controls throughout various adaptive processes such as biosynthesis, anterograde and retrograde trafficking, and membrane targeting. In pathological conditions, this quality control could lead to the retention of functional VGSC and is therefore the target of different pharmacological approaches. The present chapter gives an overview of the current understanding of the facets of VGSC life cycle in the context of both cardiac and neuronal cell types.


Assuntos
Canais de Sódio Disparados por Voltagem/metabolismo , Animais , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Humanos , Multimerização Proteica , Transporte Proteico
7.
Physiol Res ; 64(4): 495-503, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25470517

RESUMO

Atrial natriuretic peptide antifibrotic properties are mainly described in cardiac myocytes or in induced cardiac myofibroblasts (Angiotensin II or TGF-beta induced differentiation). In the present work, we investigate the effects of ANP/NPRA/cGMP system in modulating rat cardiac fibroblasts function. Cardiac fibroblasts were isolated from adult Wistar male rats and cultured in the presence of serum in order to induce fibroblasts differentiation. Cultures were then treated with ANP (1 microM), 8-Br-cGMP (100 microM) or IBMX (100 microM), a non-specific phosphodiesterases inhibitor. ANP significantly decreased proliferation rate and collagen secretion. Its effect was mimicked by the cGMP analog, while combining ANP with 8-Br-cGMP did not lead to additional effects. Moreover intracellular cGMP levels were elevated when cells were incubated with ANP confirming that ANP intracellular pathway is mediated by cGMP. Additionally, immunoblotting and immunofluorescence were used to confirm the presence of guanylyl cyclase specific natriuretic peptide receptors A and B. Finally we scanned specific cGMP dependent PDEs via RT-qPCR, and noticed that inhibiting all PDEs led to an important decrease in proliferation rate. Effect of ANP became more prominent after 10 culture days, confirming the importance of ANP in fibroblasts to myofibroblasts differentiation. Uncovering cellular aspects of ANP/NPRA/cGMP signaling system provided more elements to help understand cardiac fibrotic process.


Assuntos
Fator Natriurético Atrial/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Ventrículos do Coração/citologia , Miofibroblastos/citologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Ventrículos do Coração/efeitos dos fármacos , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Ratos , Ratos Wistar
8.
Environ Sci Pollut Res Int ; 22(1): 721-32, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25106519

RESUMO

The use of plants and microorganisms to mitigate sediment contaminated by copper was studied in microcosms that mimic the functioning of a stormwater basin (SWB) connected to vineyard watershed. The impact of phytoremediation and bioaugmentation with siderophore-producing bacteria on the fate of Cu was studied in two contrasted (batch vs. semi-continuous) hydraulic regimes. The fate of copper was characterised following its discharge at the outlet of the microcosms, its pore water concentration in the sediment, the assessment of its bioaccessible fraction in the rhizosphere and the measurement of its content in plant tissues. Physico-chemical (pH, redox potential) and biological parameters (total heterotrophic bacteria) were also monitored. As expected, the results showed a clear impact of the hydraulic regime on the redox potential and thus on the pore water concentration of Cu. Copper in pore water was also dependent on the frequency of Cu-polluted water discharges. Repeated bioaugmentation increased the total heterotrophic microflora as well as the Cu bioaccessibility in the rhizosphere and increased the amount of Cu extracted by Phragmites australis by a factor of ~2. Sugar beet pulp, used as a filter to avoid copper flushing, retained 20% of outcoming Cu and led to an overall retention of Cu higher than 94% when arranged at the outlet of microcosms. Bioaugmentation clearly improved the phytoextraction rate of Cu in a small-scaled SWB designed to mimic the functioning of a full-size SWB connected to vineyard watershed. Highlights: Cu phytoextraction in constructed wetlands much depends on the hydraulic regime and on the frequency of Cu-polluted water discharges. Cu phytoextraction increases with time and plant density. Cu bioaccessibility can be increased by bioaugmentation with siderophore-producing bacteria.


Assuntos
Cobre/isolamento & purificação , Poaceae/metabolismo , Poluentes Químicos da Água/isolamento & purificação , Áreas Alagadas , Bactérias , Biodegradação Ambiental , Cobre/metabolismo , Rizosfera , Sideróforos/metabolismo , Água/análise , Poluentes Químicos da Água/metabolismo
9.
Br J Pharmacol ; 171(21): 4831-49, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25065395

RESUMO

BACKGROUND AND PURPOSE: The most common mutation in cystic fibrosis (CF), F508del, causes defects in trafficking, channel gating and endocytosis of the CF transmembrane conductance regulator (CFTR) protein. Because CF is an orphan disease, therapeutic strategies aimed at improving mutant CFTR functions are needed to target the root cause of CF. EXPERIMENTAL APPROACH: Human CF airway epithelial cells were treated with roscovitine 100 µM for 2 h before CFTR maturation, expression and activity were examined. The mechanism of action of roscovitine was explored by recording the effect of depleting endoplasmic reticulum (ER) Ca(2+) on the F508del-CFTR/calnexin interaction and by measuring proteasome activity. KEY RESULTS: Of the cyclin-dependent kinase (CDK) inhibitors investigated, roscovitine was found to restore the cell surface expression and defective channel function of F508del-CFTR in human CF airway epithelial cells. Neither olomoucine nor (S)-CR8, two very efficient CDK inhibitors, corrected F508del-CFTR trafficking demonstrating that the correcting effect of roscovitine was independent of CDK inhibition. Competition studies with inhibitors of the ER quality control (ERQC) indicated that roscovitine acts on the calnexin pathway and on the degradation machinery. Roscovitine was shown (i) to partially inhibit the interaction between F508del-CFTR and calnexin by depleting ER Ca(2+) and (ii) to directly inhibit the proteasome activity in a Ca(2+) -independent manner. CONCLUSIONS AND IMPLICATIONS: Roscovitine is able to correct the defective function of F508del-CFTR by preventing the ability of the ERQC to interact with and degrade F508del-CFTR via two synergistic but CDK-independent mechanisms. Roscovitine has potential as a pharmacological therapy for CF.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Purinas/farmacologia , Cálcio/metabolismo , Linhagem Celular , Quinases Ciclina-Dependentes/antagonistas & inibidores , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Retículo Endoplasmático/metabolismo , Células Epiteliais , Células HEK293 , Humanos , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transporte Proteico/efeitos dos fármacos , Roscovitina
10.
J Comp Physiol B ; 183(4): 477-89, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23263664

RESUMO

This study investigated the effects of acclimation temperature upon (i) contractility of ventricular strips (ii) calcium movements in ventricular cardiomyocytes during excitation-contraction coupling (ECC), and (iii) the role of the sarcoplasmic reticulum (SR) in myocardial responses, in two marine teleosts, the sea bass (Dicentrarchus labrax) and the common sole (Solea solea). Because of the different sensitivities of their metabolism to temperature variation, both species were exposed to different thermal ranges. Sea bass were acclimated to 10, 15, 20, and 25 °C, and common sole to 6, 12, 18, and 24 °C, for 1 month. Isometric tension developed by ventricular strips was recorded over a range of physiological stimulation frequencies, whereas the depolarization-induced calcium transients were recorded on isolated ventricular cells through hyperpotassic solution application (at 100 mM). The SR contribution was assessed by ryanodine (RYAN) perfusion on ventricular strips and by caffeine application (at 10 mM) on isolated ventricular cells. Rates of contraction and relaxation of ventricular strip, in both species, increased with increasing acclimation temperature. At a low range of stimulation frequency, ventricular strips of common sole developed a positive force-frequency relationship at high acclimation temperature. In both the species, SR Ca(2+)-cycling was dependent on fish species, acclimation temperature and pacing frequency. The SR contribution was more important to force development at low acclimation temperatures in sea bass but at high acclimation temperatures in common sole. The results also revealed that high acclimation temperature causes an increase in the maximum calcium response amplitude on ventricular cells in both the species. Although sea bass and common sole occupy similar environments and tolerate similar environmental temperatures, this study indicated that sea bass and common sole can acclimatize to new thermal conditions, adjusting their cellular process in a different manner.


Assuntos
Aclimatação/fisiologia , Bass/fisiologia , Linguados/fisiologia , Contração Miocárdica/fisiologia , Retículo Sarcoplasmático/fisiologia , Animais , Cafeína/farmacologia , Cálcio/fisiologia , Técnicas In Vitro , Contração Isométrica , Miócitos Cardíacos/fisiologia , Temperatura
11.
Water Res ; 47(3): 1123-35, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23246667

RESUMO

Non-point source pollution as a result of wine-growing activity is of high concern. Stormwater basins (SWB) found downstream of vineyard watersheds could show a potential for the mitigation of runoff water containing herbicides. In this study, mitigation of vinery-used herbicides was studied in microcosms with a very similar functioning to that recorded in SWB. Mitigation efficiency of glyphosate, diuron and 3,4-dichloroaniline (3,4-DCA) was investigated by taking into account hydraulic flow rate, mitigation duration, bioaugmentation and plant addition. Mitigation efficiency measured in water ranged from 63.0% for diuron to 84.2% for 3,4-DCA and to 99.8% for glyphosate. Water-storage duration in the SWB and time between water supplies were shown to be the most influential factors on the mitigation efficiency. Six hours water-storage duration allowed an efficient sorption of herbicides and their degradation by indigenous microorganisms in 5 weeks. Neither bioaugmentation nor plant addition had a significant effect on herbicide mitigation. Our results show that this type of SWB are potentially relevant for the mitigation of these herbicides stemming from wine-growing activity, providing a long enough hydraulic retention time.


Assuntos
Biodegradação Ambiental , Poluentes Químicos da Água , Glicina/análogos & derivados , Glicina/química , Glifosato
12.
J Environ Radioact ; 114: 2-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22172688

RESUMO

Contamination of the marine environment following the accident in the Fukushima Dai-ichi nuclear power plant represented the most important artificial radioactive release flux into the sea ever known. The radioactive marine pollution came from atmospheric fallout onto the ocean, direct release of contaminated water from the plant and transport of radioactive pollution from leaching through contaminated soil. In the immediate vicinity of the plant (less than 500 m), the seawater concentrations reached 68,000 Bq.L(-1) for (134)Cs and (137)Cs, and exceeded 100,000 Bq.L(-1) for (131)I in early April. Due to the accidental context of the releases, it is difficult to estimate the total amount of radionuclides introduced into seawater from data obtained in the plant. An evaluation is proposed here, based on measurements performed in seawater for monitoring purposes. Quantities of (137)Cs in seawater in a 50-km area around the plant were calculated from interpolation of seawater measurements. The environmental halftime of seawater in this area is deduced from the time-evolution of these quantities. This halftime appeared constant at about 7 days for (137)Cs. These data allowed estimation of the amount of principal marine inputs and their evolution in time: a total of 27 PBq (12 PBq-41 PBq) of (137)Cs was estimated up to July 18. Even though this main release may be followed by residual inputs from the plant, river runoff and leakage from deposited sediments, it represents the principal source-term that must be accounted for future studies of the consequences of the accident on marine systems. The (137)Cs from Fukushima will remain detectable for several years throughout the North Pacific, and (137)Cs/(134)Cs ratio will be a tracer for future studies.


Assuntos
Radioisótopos de Césio/análise , Acidente Nuclear de Fukushima , Água do Mar/análise , Poluentes Radioativos da Água/análise , Japão , Centrais Nucleares , Oceano Pacífico , Monitoramento de Radiação
13.
Br J Pharmacol ; 159(1): 93-101, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19703166

RESUMO

INTRODUCTION: Doxorubicin, an anthracycline widely used in the treatment of a broad range of tumours, causes acute QT prolongation. Dexrazoxane has been shown to prevent the QT prolongation induced by another anthracycline, epirubicin, but has not yet been reported to prevent that induced by doxorubicin. Thus, the present study was designed to test whether the acute QT effects induced by doxorubicin could be blocked by dexrazoxane and to explore the mechanism. Results were compared with those obtained with a reference human ether-a-go-go (hERG) channel blocker, moxifloxacin. METHODS: The effects of moxifloxacin (100 microM) and doxorubicin (30 microM), with or without dexrazoxane (from 3 to 30 microM), have been evaluated on the QTc interval in guinea-pig isolated hearts and on I(Kr) (rapid component of the delayed rectifier current) and I(Ks) (slow component of the delayed rectifier current) currents stably expressed in human embryonic kidney 293 cells. RESULTS: Moxifloxacin (100 microM), a potent hERG blocker, prolonged QTc by 22%, and this effect was not prevented by dexrazoxane. Doxorubicin (30 microM) also prolonged QTc by 13%, did not significantly block hERG channels and specifically inhibited I(Ks) (IC(50): 4.78 microM). Dexrazoxane significantly reduced the doxorubicin-induced QTc prolongation and prevented doxorubicin-induced inhibition of I(Ks). CONCLUSION AND IMPLICATIONS: Doxorubicin acutely prolonged the QT interval in guinea-pig heart by selective I(Ks) blockade. This effect was prevented by dexrazoxane. This result is important because it illustrates the danger of neglecting I(Ks) in favour of hERG screening alone, for early preclinical testing for possible induction of torsade de pointes.


Assuntos
Fármacos Cardiovasculares/farmacologia , Doxorrubicina/efeitos adversos , Síndrome do QT Longo/prevenção & controle , Razoxano/farmacologia , Animais , Antibióticos Antineoplásicos/efeitos adversos , Compostos Aza/efeitos adversos , Fármacos Cardiovasculares/administração & dosagem , Linhagem Celular , Canais de Potássio de Retificação Tardia/efeitos dos fármacos , Canais de Potássio de Retificação Tardia/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Fluoroquinolonas , Cobaias , Humanos , Técnicas In Vitro , Concentração Inibidora 50 , Síndrome do QT Longo/induzido quimicamente , Moxifloxacina , Quinolinas/efeitos adversos , Razoxano/administração & dosagem
14.
Ann Cardiol Angeiol (Paris) ; 59(1): 20-4, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19969282

RESUMO

Brain natriuretic peptide (BNP) binds to three types of natriuretic peptide receptors, NPR-A, -B and -C (NPRs). The expression shape of BNP and NPRs seems to be an important modulator factor in the pathogenesis of cardiac hypertrophy. The aim of this study was to evaluate the expression of NPRs in an animal model of pressure overload hypertrophy. Left ventricular hypertrophy was induced by chronic abdominal aortic banding in adult male Wistar rats. After six weeks, NPRs gene expression was evaluated with RT-PCR, BNP plasma concentration and BNP positive myocytes were measured with ELISA and immunohistochemistry techniques respectively. NPR-A and NPR-C mRNA expression was significantly increased in left ventricular hypertrophied cardiomyocytes by 1.6-fold and 2.1-fold respectively (P<0.01). Abdominal aortic banding increased significantly BNP plasma concentration (630+/-8pg/ml vs 106+/-4pg/ml; P<0.01). The percentage of BNP positive cells in normal myocardial tissue were 40% while in the hypertrophied one it raised to 80%. The data suggest that in our left ventricular hypertrophy model, the NPR-A and NPR-C receptors were increased in association to the increased BNP level. This relationship may amplify beneficial paracrine/autocrine effects of BNP on cardiac remodelling in response to hemodynamic overload.


Assuntos
Hipertrofia Ventricular Esquerda/genética , Miócitos Cardíacos/patologia , Receptores do Fator Natriurético Atrial/genética , Animais , Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Expressão Gênica , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/patologia , Masculino , Miocárdio/patologia , Peptídeo Natriurético Encefálico/sangue , Ratos , Ratos Wistar , Receptores do Fator Natriurético Atrial/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Br J Pharmacol ; 153(8): 1697-705, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18297105

RESUMO

BACKGROUND AND PURPOSE: TRPM4 and TRPM5 are calcium-activated non-selective cation channels with almost identical characteristics. TRPM4 is detected in several tissues including heart, kidney, brainstem, cerebral artery and immune system whereas TRPM5 expression is more restricted. Determination of their roles in physiological processes requires specific pharmacological tools. TRPM4 is inhibited by glibenclamide, a modulator of ATP binding cassette proteins (ABC transporters), such as the cystic fibrosis transmembrane conductance regulator (CFTR). We took advantage of this similarity to investigate the effect of hydroxytricyclic compounds shown to modulate ABC transporters, on TRPM4 and TRPM5. EXPERIMENTAL APPROACH: Experiments were conducted using HEK-293 cells permanently transfected to express human TRPM4 or TRPM5. Currents were recorded using the whole-cell and inside-out variants of the patch-clamp technique. KEY RESULTS: The CFTR channel activator benzo[c]quinolizinium MPB-104 inhibited TRPM4 current with an IC(50) in the range of 2 x 10(-5) M, with no effect on single-channel conductance. In addition, 9-phenanthrol, lacking the chemical groups necessary for CFTR activation, also reversibly inhibited TRPM4 with a similar IC(50). Channel inhibition was voltage independent. The IC(50) determined in the whole-cell and inside-out experiments were similar, suggesting a direct effect of the molecule. However, 9-phenanthrol was ineffective on TRPM5, the most closely related channel within the TRP protein family. CONCLUSIONS AND IMPLICATIONS: We identify 9-phenanthrol as a TRPM4 inhibitor, without effects on TRPM5. It could be valuable in investigating the physiological functions of TRPM4, as distinct from those of TRPM5.


Assuntos
Fenantrenos/farmacologia , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/efeitos dos fármacos , Animais , Células CHO , Linhagem Celular , Cricetinae , Cricetulus , Humanos , Concentração Inibidora 50 , Técnicas de Patch-Clamp/métodos , Fenantrenos/administração & dosagem , Quinolizinas/administração & dosagem , Quinolizinas/farmacologia , Transfecção
16.
Biotechnol Lett ; 29(5): 749-54, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17333465

RESUMO

Mineralization of diuron has not been previously demonstrated despite the availability of some bacteria to degrade diuron into 3,4-dichloroaniline (3,4-DCA) and others that can mineralize 3,4-DCA. A bacterial co-culture of Arthrobacter sp. N4 and Delftia acidovorans W34, which respectively degraded diuron (20 mg l(-1)) to 3,4-DCA and mineralized 3,4-DCA, were able to mineralize diuron. Total diuron mineralization (20 mg l(-1)) was achieved with free cells in co-culture. When the bacteria were immobilized (either one bacteria or both), the degradation rate was higher. Best results were obtained with free Arthrobacter sp. N4 cells co-cultivated with immobilized cells of D. acidovorans W34 (mineralization of diuron in 96 h, i.e., 0.21 mg l(-1 )h(-1) vs. 0.06 mg l(-1 )h(-1) with free cells in co-culture).


Assuntos
Arthrobacter/metabolismo , Delftia acidovorans/metabolismo , Diurona/metabolismo , Compostos de Anilina/metabolismo , Arthrobacter/citologia , Biodegradação Ambiental , Proliferação de Células , Células Imobilizadas , Técnicas de Cocultura , Delftia acidovorans/citologia
17.
J Exp Biol ; 209(Pt 20): 4033-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17023597

RESUMO

The present study employed a patch clamp technique in isolated seabass ventricular myocytes to investigate the hypothesis that oleic acid (OA), a mono-unsaturated fatty acid, can exert direct effects upon whole-cell barium currents. Acute application of free OA caused a dose-dependent depression of the whole-cell barium current that was evoked by a voltage step to 0 mV from a holding potential of -80 mV. The derived 50% inhibitory concentration (IC50) was 12.49+/-0.27 micromol l(-1). At a concentration of 30 micromol l(-1), OA significantly reduced the current density to about 45% of control values, but did not modify either the shape of the current-density voltage relationship or the apparent reversal potential. In addition, OA did not modify the voltage dependence of either steady state inactivation or activation curves. Taken together, these results indicate that physiological concentrations of free OA decrease the conductance of the L-type inward current, without altering its properties of selectivity and its voltage dependence. The inhibitory effect of OA upon the L-type calcium channel may translate, in vivo, into a protective effect against arrhythmias induced by Ca2+ overload.


Assuntos
Bário/metabolismo , Bass/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ácido Oleico/farmacologia , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/prevenção & controle , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Técnicas de Patch-Clamp
18.
J Environ Radioact ; 74(1-3): 199-210, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15063548

RESUMO

In this paper we report and compare the concentrations of 234Th and 238U measured in surface and subsurface waters collected in the course of a sampling campaign in the north east Atlantic in June-July 1998. Dissolved 234Th concentrations in surface waters ranged from 5 to 20 Bq m(-3), showing a large deficiency relative to 238U concentrations (typically 42 Bq m-3). This disequilibrium is indicative of active 234Th scavenging from surface waters. Observed 234Th/238U activity ratios, together with corresponding 234Th particulate concentrations, were used to calculate mean residence times for 234Th with respect to scavenging onto particles (tau(diss)) and subsequent removal from surface waters (tau(part)). Residence times in the range 5-30 days were determined for tau(diss) and 4-18 days for tau(part) (n=14). In addition, ultrafiltration experiments at six stations in the course of the same expedition revealed that in north-east Atlantic surface waters a significant fraction (46+/-17%; n=6) of the thorium in the (operationally-defined) dissolved phase (<0.45 microm) is in colloidal form. These observations are consistent with the 'colloidal pumping' model in which it is assumed that 234Th is rapidly absorbed by colloidal particles, which then aggregate, albeit at a slower rate, into larger filterable particles. In essence, colloids act as intermediaries in the transition from the fully dissolved to the filter-retained (>0.45 microm) phase. Thus, the time (tau(c)) for fully dissolved 234Th to appear in the filter-retained fraction is dependent on the rate of colloidal aggregation. Here, we determined tau(c) values in the range 3-17 days.


Assuntos
Modelos Teóricos , Tório/análise , Urânio/análise , Poluentes Radioativos da Água/análise , Oceano Atlântico , Coloides , Monitoramento Ambiental , Filtração , Solubilidade , Tório/química , Urânio/química
19.
EMBO J ; 22(6): 1389-97, 2003 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-12628931

RESUMO

Meiotic crossovers detected by pedigree analysis in the mouse MHC cluster into hotspots. To explore the properties of hotspots, we subjected the class II E(beta) gene to high-resolution sperm crossover analysis. We confirm the presence of a highly localized hotspot 1.0-1.6 kb wide in the second intron of E(beta) and show that it is flanked by DNA which is almost completely recombinationally inert. Mice heterozygous for haplotype s and another MHC haplotype show major haplotype-dependant variation in crossover rate but always the same hotspot, even in crosses including the highly diverged p haplotype. Crossovers in reciprocal orientations occur at similar rates but show different distributions across the hotspot, with the position of centre points in the two orientations shifted on average by 400 bp. This asymmetry results in crossover products showing biased gene conversion in favour of hotspot markers from the non-initiating haplotype, and supports the double-strand break repair model of recombination, with haplotype s as the most efficient crossover initiator. The detailed behaviour of the E(beta) hotspot, including evidence for highly localized recombination initiation, is strikingly similar to human hotspots.


Assuntos
Genes MHC da Classe II , Meiose/genética , Recombinação Genética , Espermatozoides/metabolismo , Alelos , Animais , Sequência de Bases , Troca Genética , Marcadores Genéticos , Variação Genética , Haplótipos , Íntrons , Complexo Principal de Histocompatibilidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Polimorfismo de Nucleotídeo Único
20.
J Membr Biol ; 188(2): 127-35, 2002 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12172638

RESUMO

Cardiac hypertrophy is associated with electrical activity modifications, including sustained depolarization, that lead to a propensity for arrhythmias. The ionic currents underlying the sustained depolarization are not well defined. Similar modifications were reported on adult rat cardiomyocytes in primary culture undergoing dedifferentiation. Using the single-channel measurements on these cells, we identified the appearance of a Ca2+-activated nonselective cation channel (NSCCa) during the dedifferentiation process. In excised inside-out patches the channel presented a linear I/V relationship with a conductance of 26.5 pS. It was equally selective for Na+ and K+ and impermeable to Cl- and Ca2+ ions. The open probability increased with depolarization and with rise in intracellular calcium concentration. The channel activity was reduced by intracellular ATP and suppressed by flufenamic acid. Channel detection increased after incubation with a purinergic receptor agonist (ATPgS) or a PKC activator (PMA). Furthermore, occurrence of the channel developed during the culture. Absent at one day in vitro (d.i.v.), channel activity was present in 5, 46, 27 and 19% of patches after 4, 7, 14 and 21 d.i.v., respectively. We suggest that the channel may be associated with pro-arrhythmic signaling, in particular during the release of transmitters from autonomic nerve endings in the hypertrophied hearts.


Assuntos
Trifosfato de Adenosina/análogos & derivados , Cálcio/metabolismo , Diferenciação Celular/fisiologia , Canais Iônicos/fisiologia , Miócitos Cardíacos/fisiologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Células Cultivadas , Condutividade Elétrica , Ácido Flufenâmico/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Técnicas In Vitro , Ativação do Canal Iônico , Canais Iônicos/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Miócitos Cardíacos/efeitos dos fármacos , Técnicas de Patch-Clamp , Potássio/farmacologia , Proteína Quinase C/farmacologia , Ratos , Ratos Wistar , Sódio/farmacologia , Função Ventricular
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