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1.
ACS Appl Mater Interfaces ; 15(1): 1704-1717, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36541611

RESUMEN

The source-drain electrode with a MoO3 interfacial modification layer (IML) is considered the most promising method to solve electrical contact issues impeding organic thin-film transistors (OTFTs) from commercialization. However, this method raises many concerns because MoO3 might diffuse into organic materials, which causes device instability. In this work, we observed a significant device stability degradation by damaging on/off switching performance caused by MoO3 diffusion. To prevent the MoO3 diffusion, a source-drain electrode with a multilayered interface contact (MIC) consisting of a top-down stack of metal, MoO3 IML, and organic buffer layer (OBL) is proposed. In the MIC device, the MoO3 IML serves well for its intended functions of reducing contact resistance and suppressing minority carrier injection to the OTFT channel. The inclusion of OBL to the MIC helps block MoO3 diffusion and thereby leads to better device stability and an increased on/off ratio. Through combinations with several organic compounds as a buffer layer, the MoO3 diffusion related electrical behaviors of OTFTs are systematically studied. Key parameters related to MoO3 diffusion such as the Fick coefficient and bias-stress stability such as carrier trapping time are extracted from numerical device analysis. Finally, we summarize a general rule of material selection for making robust source-drain contact.

2.
Nat Prod Res ; 37(1): 141-149, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34498966

RESUMEN

A new highly oxygenated cycloheptane derivative crustane (1), along with fourteen known compounds (2-15) were isolated from Penicillium crustosum JT-8. The structure of compound 1 was determined by extensive spectroscopic data, DP4+ probability analyses and dimolybdenum CD method. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with MIC of 4.0 µg/mL.


Asunto(s)
Antibacterianos , Penicillium , Estructura Molecular , Antibacterianos/química , Staphylococcus aureus , Penicillium/química , Pruebas de Sensibilidad Microbiana
3.
Nat Prod Res ; 36(9): 2270-2276, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-33016118

RESUMEN

A new dimeric monoterpene indole alkaloid polonidine A (1), along with five known compounds, cyclopenol (2), verrucosidin (3), fructigenine A (4), 3-O-methylviridicatin (5) and aurantiomides C (6), were isolated from Penicillium polonicum TY12. Their structures were established on the basis of extensive spectroscopic analyses. Compound 1 exhibited moderate cytotoxic activities and moderate antibacterial activity against Bacillus subtilis with MIC of 4.0 µg/mL.


Asunto(s)
Antineoplásicos , Penicillium , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/química , Hongos , Alcaloides Indólicos/farmacología , Estructura Molecular , Penicillium/química
4.
Nat Prod Res ; 36(3): 862-867, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32791858

RESUMEN

A new tremulane sesquiterpene, lactedine (1), along with seven known tremulane sesquiterpenes (2-8) and one known triterpene (9) were isolated from the fungus Irpex lacteus. Their structures were established on the basis of extensive spectroscopic data and DP4+ probability analyses.


Asunto(s)
Polyporales , Sesquiterpenos , Fermentación , Hongos
5.
Phytochemistry ; 187: 112762, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33940379

RESUMEN

Seven previously undescribed sesterterpenes were characterized from Penicillium roqueforti YJ-14 by solid fermentation. Their structures were initially investigated in detail by spectroscopic analyses and HR-ESI-MS and were further confirmed by X-crystallography. In in vitro bioassays, compounds 1, 5 and 7 showed cytotoxic activity against the MCF-7 breast cancer cell line with IC50 values of 7.98 ±â€¯0.93, 6.42 ±â€¯0.41 and 7.32 ±â€¯0.18 µM, respectively. Compounds 5 and 7 displayed significant cytotoxicity against the A549 lung cancer cell line (IC50 values of 4.83 ±â€¯0.22 µM and 4.58 ±â€¯0.85 µM, respectively). In addition, compound 5 showed an obvious inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages with an IC50 value of 9.53 ±â€¯0.16 µM.


Asunto(s)
Penicillium , Hongos , Humanos , Macrófagos , Óxido Nítrico , Sesterterpenos/farmacología
6.
J Aerosol Med Pulm Drug Deliv ; 34(2): 108-114, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33691499

RESUMEN

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.


Asunto(s)
COVID-19/terapia , Tiempo de Internación , Mycobacteriaceae/inmunología , Tomografía Computarizada por Rayos X , Administración por Inhalación , Adolescente , Adulto , Anciano , COVID-19/inmunología , COVID-19/mortalidad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
7.
Ecotoxicol Environ Saf ; 180: 483-490, 2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31121555

RESUMEN

In this study, powdery aerobic activated sludge (PAAS) was first prepared, and the removal rate, sorption capacity and mechanism of sorption uranium on PAAS was investigated. Before and after sorption, the surface morphology and structure of PAAS were characterized systematically using the Fourier transform infrared spectrometer (FTIR), the X-ray photoelectron spectrometer (XPS), and the scanning electron microscope (SEM-EDX). In this work, the sorption mechanism and efficiency of uranium on the PAAS was study with static batch and ion exchange experiments, meanwhile, some influencing factors such as solution pH, contact temperature, adsorbent dose of PAAS and different initial uranium concentrations were studied. The batch sorption experiments illustrated that pH had a little effect in the process of sorption uranium on PAAS and it has a good removal capacity in a wide pH range (pH = 3-8). When the pH of solution was 7, the removal efficiency of about 93% for uranium when the initial concentration of uranium was 10 mg/L and the concentration of PAAS was 1  g/L. The XPS demonstrated that there are some active functional groups for instance carboxyl (-COOH), Hydroxyl (-OH), Amino (-NH2) and so on in the PAAS, and that all can combine with uranium. After sorption, there is an obviously U signal (marked in green) in the PAAS by charactering with the FE-SEM. In addition, kinetic parameters were fitted by the first-order kinetic (R2 = 0.9738) model and the second-order kinetic model (R2 = 0.9998), the pseudo-secondary kinetic model was better to illustrate the sorption process, so the chemical action was dominant, and existed physical sorption. The sorption isotherms date of PAAS was well-fitted to the Langmuir model (R2 = 0.9688). In the experiment of ion exchange, the concentration of Na+ in the solution hardly changed, the release of the other three ions was K+

Asunto(s)
Modelos Teóricos , Aguas del Alcantarillado/química , Uranio/análisis , Aguas Residuales/química , Contaminantes Radiactivos del Agua/análisis , Purificación del Agua/métodos , Adsorción , Aerobiosis , Concentración de Iones de Hidrógeno , Intercambio Iónico , Cinética , Polvos , Temperatura
8.
Exp Lung Res ; 44(8-9): 397-404, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30663438

RESUMEN

Acute lung injury (ALI) is a common clinical syndrome in ICU departments with high mortality. The pathology of ALI is still not clear and there is no specific and efficient treatment against ALI. In this study, we established ALI rat model through lipopolysaccharide administration. We found that hypothermia therapy led to significant improvement in oxygenation index, edema formation and pathological score, demonstrating that hypothermia is beneficial to the recovery of lung function and alleviation of lung injury. Besides, hypothermia resulted in a decrease in plasminogen activator inhibitor-1(PAI-1) concentration, showing the inflammation was partially inhibited. This was also confirmed by a decrease in TNF-α mRNA and protein level in hypothermia group. The effect of hypothermia was mediated by TLR2/MyD88 signaling, which led to the alteration in NF-κB p65 level. Collectively, this study indicated that hypothermia therapy was potentially an efficient therapy against ALI.


Asunto(s)
Lesión Pulmonar Aguda/terapia , Hipotermia Inducida , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 2/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Lipopolisacáridos , Ratas , Transducción de Señal
9.
Heart Lung Circ ; 23(12): 1202-7, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25224460

RESUMEN

OBJECTIVE AND DESIGN: Our study aimed to determine the effect of mild hypothermia (MHT) on the expression of toll-like receptor 2 (TLR2) in lung tissue with acute lung injury. The animals were randomly divided into control, model and mild hypothermia groups. METHODS: A total of 40 rats was used in the study. Acute lung injury was induced by lipopolysaccharide and MHT was maintained at 32.5∼33.0 °C using body surface ice-bag placement combined with animal thermostat system. The ratio of PaO2/FiO2 was recorded. The mRNA and protein expressions of TLR2 were measured by real-time polymerase chain reaction and western blotting respectively. Moreover, enzyme linked immunosorbent assay were used for the quantification of TNF-α. RESULTS: The ratio of PaO2/FiO2 was increased by MHT. TLR2 and TNF-α were increased in the rat lung 1h and 8h in the rats with acute lung injury while they were significantly decreased by MHT. Histological examination revealed that MHT alleviated the degree of inflammation. CONCLUSION: Our study suggested that MHT might improve the lung function by inhibiting the inflammation via down-regulating the expressions of TLR2 in the acute injury lung tissues.


Asunto(s)
Lesión Pulmonar Aguda , Regulación de la Expresión Génica , Hipotermia Inducida , Pulmón/metabolismo , Receptor Toll-Like 2/biosíntesis , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/terapia , Animales , Modelos Animales de Enfermedad , Inflamación/metabolismo , Inflamación/patología , Inflamación/terapia , Pulmón/patología , Masculino , Ratas , Factor de Necrosis Tumoral alfa/biosíntesis
10.
J Insect Physiol ; 67: 105-13, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24992713

RESUMEN

It is generally believed that widely distributed species differ in their thermal plasticity from narrowly distributed species, but how differences in thermal plasticity are regulated at the molecular level remains largely unknown. Here, we conducted a comparative study of two closely related invasive fruit fly species, Bactrocera correcta and Bactroceradorsalis, in China. The two species had overlapping distributions, but B. dorsalis had a much wider range throughout the country and a longer invasive history than B. correcta. We first examined the effects of thermal acclimation on the ability of the two fruit flies to survive heat stress. The heat shock tolerance of B. dorsalis was significantly enhanced by heat hardening at 35, 37, 39 and 41°C, but that of B. correcta was only enhanced by heat hardening at 39°C and 41°C. Thus, the more widespread species has a higher thermal plasticity than the narrowly distributed species. We then determined the expression of Hsp70 and Hsp90 during different developmental stages and their responses to thermal hardening. The expression of both Hsp70 and Hsp90 in larvae was upregulated in response to heat hardening, starting at 35°C for B. dorsalis and at 39°C for B. correcta. The two species exhibited a highly consistent pattern of thermal response in terms of their heat shock survival rates and levels of Hsp gene expression. The results suggest that the difference in thermal plasticity may be responsible for the different distributions of the two species and that Hsp expression may be involved in the regulation of thermal plasticity. Our findings have important implications for the prediction of the thermal limits and ecological responses of related species in nature.


Asunto(s)
Adaptación Fisiológica , Expresión Génica , Proteínas HSP70 de Choque Térmico/fisiología , Proteínas HSP90 de Choque Térmico/fisiología , Respuesta al Choque Térmico/fisiología , Tephritidae/genética , Tephritidae/fisiología , Animales , China , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/genética , Calor , Especies Introducidas , Larva/fisiología , Pupa/fisiología , Especificidad de la Especie
11.
BMJ Open ; 4(6): e004744, 2014 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-24961714

RESUMEN

OBJECTIVE: Daptomycin, a cyclic lipopeptide that exhibits rapid, concentration-dependent bactericidal activity in vitro against a broad spectrum of Gram-positive pathogens, has now, since 2003, been approved in more than 70 countries and regions to treat skin and soft-tissue infections (SSTIs). The purpose of this meta-analysis was to compare the safety and efficacy of daptomycin with other antibiotics, especially with vancomycin which has long been considered the standard therapy for complicated SSTIs. DESIGN: Meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: We thoroughly searched PubMed, EMBASE, Cochrane Central to identify relevant RCTs. Six RCTs with a total of 1710 patients were included in this meta-analysis. RESULTS: The results demonstrated that the efficacy of daptomycin was at par with or maybe better than other first-line antibiotics for treating SSTIs as shown by the OR for clinical success (OR=1.05, 95% CI 0.84 to 1.31, p=0.65, I(2)=0%); daptomycin versus vancomycin subgroup (OR=1.19, 95% CI 0.77 to 1.83, p=0.43, I(2)=0%); overall microbiological success (OR=1.05, 95% CI 0.61 to 1.79, p=0.86, I(2)=42%); microbiological success of daptomycin versus comparators for Staphylococcus aureus (SA, OR=1.05, 95% CI 0.61 to 2.60, p=0.53, I(2)=47%), for methicillin-resistant S. aureus (OR=0.90, 95% CI 0.77 to 1.06, p=0.20, I(2)=56%). However, daptomycin tended to have a similar treatment-related adverse events (AEs) incidence in comparison with other antibiotics (OR=1.06, 95% CI 0.71 to 1.59, p=0.76, I(2)=41%). The trend showed that daptomycin might cause less discontinuation due to AEs and death compared with other first-line antibiotics (OR=0.71, 95% CI 0.46 to 1.10, p=0.12, I(2)=11%). Significantly more patients in the daptomyicn group had creatine phosphokinase elevation than those in the control group; however, it could be reversed when the therapy ended (OR=1.95, 95% CI 1.04 to 3.65, p=0.04, I(2)=0). CONCLUSIONS: This meta-analysis demonstrated that the safety and efficacy of daptomycin was not inferior to that of other first-line drugs, and daptomycin tended to exhibit superior efficacy when compared with vancomycin or with comparators for SA infections; nevertheless, more high-quality RCTs are needed to draw a more credible conclusion.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Daptomicina/uso terapéutico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Antibacterianos/efectos adversos , Daptomicina/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
12.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 24(9): 534-7, 2012 Sep.
Artículo en Chino | MEDLINE | ID: mdl-22938661

RESUMEN

OBJECTIVE: To investigate diagnostic value of creatinine clearance rate (CCr) based on serum cystatin C (SCys C) in acute kidney injury (AKI), and whether it could predict the need for renal replacement therapy (RRT). METHODS: The patients enrolled with the length of intensive care unit (ICU) stay over 3 days were collected from August 2010 to May 2011. According to the diagnosis of AKI during the ICU stay, patients were divided into the AKI group (n=21) and non-AKI group (n=30). After patients were admitted, the level of SCys C and creatinine (SCr) were measured so as to count CCr based on SCys C (SCys C-CCr) or on SCr (SCr-CCr) respectively, meanwhile urine volume and acute physiology and chronic health evaluation II (APACHE II) score were monitored. The value of CCr counted by SCys C and SCr on predict AKI and the correlations between RRT were compared. RESULTS: SCr-CCr and SCys C-CCr in AKI group both were significantly lower than non-AKI group all the way through on admission, and 2 days and 1 day before AKI diagnosed and the day AKI diagnosed. The level of SCys C-CCr on 2 days prior to AKI diagnosed was significantly lower than the day admitted (70.6±8.4 ml×min(-1)×1.73 m(-2) vs. 114.8±15.8 ml×min(-1)×1.73 m(-2), P<0.01), whereas the level of SCr-CCr were not significantly changed (76.4±19.3 ml×min(-1)×1.73 m(-2) vs. 78.7±22.1 ml×min(-1)×1.73 m(-2), P>0.05). Receptor operative curve (ROC) analysis indicated that SCys C-CCr could predict AKI earlier than SCr-CCr, as the area under curve (AUC) of SCys C-CCr and SCr-CCr on 2 days prior to AKI diagnosed were 0.859 and 0.664, respectively, and the sensitivity were 90.5% and 47.6%, the specificity were 76.2% and 81.0%. In AKI group 6 patients were treated with RRT, the AKI patients receiving RRT had significantly higher APACHE II score on admission (29.6±4.5 vs. 17.0±5.6, P<0.05) and less urine volume within 24 hours (740±465 ml vs. 1780±1230 ml, P<0.05) than patients not received RRT, however, SCys C-CCr has no significant difference between the sub-group (50.4±11.2 ml×min(-1)×1.73 m(-2) vs. 53.0±8.4 ml×min(-1)×1.73 m(-2), P>0.05). SCys C-CCr did not predict the need of RRT on the day to diagnose AKI (AUC=0.65). CONCLUSIONS: The sensitivity of SCys C-CCr were high, but its specificity not. The SCys C-CCr may be helpful for excluding diagnose of AKI in high risk patients. However, it could not predict the need for renal replacement therapy on the day AKI diagnosed.


Asunto(s)
Lesión Renal Aguda/metabolismo , Creatinina/metabolismo , Cistatina C/sangre , APACHE , Adulto , Anciano , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Terapia de Reemplazo Renal , Estudios Retrospectivos
13.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 23(4): 236-8, 2011 Apr.
Artículo en Chino | MEDLINE | ID: mdl-21473828

RESUMEN

OBJECTIVE: To investigate the effect of hypothermia (HT) on the concentration of surfactant protein A (SP-A) during lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats. METHODS: Forty male Wistar rats were randomly divided into three groups. The ALI model was reproduced by LPS intratracheal instillation; only saline was instilled intratracheally for control group. Rats in both model group and control group were sacrificed respectively at 1 hour and 8 hours (each n=8). In HT group the body temperature was lowered to 32.5-33.0 centigrade 1 hour after LPS instillation, and 8 rats were sacrificed at 8 hours. The arterial blood gas was determined in all the groups before and 1 hour and 8 hours after instillation of saline or LPS, and the oxygenation index (PaO(2)/FiO(2)) was calculated. The concentration of SP-A in bronchoalveolar lavage fluid (BALF) was determined by enzyme linked immunosorbent assay. The morphological changes in lung tissue of rats were observed under light microscope. RESULTS: At 1 hour after intratracheal instillation of LPS, the PaO(2)/FiO(2) of each group reached the diagnostic criterion of ALI. Compared with control 1 hour group, the SP-A (µg/L) in BALF of model 1 hour group was decreased (53.27±1.95 vs. 74.81±6.55, P<0.01); the SP-A in model 8 hour group and HT 8 hour group (4.35±2.76 and 51.36±2.33) was both obviously decreased compared with control 8 hour group (70.81±5.01, both P<0.01). Compared with model 8 hour group, the SP-A of HT 8 hour group was obviously increased (P<0.01). Results of light microscopic examination, it was revealed that the alveolar structure of control 1 hour group and control 8 hour group was almost normal. Inflammatory response in lung tissues in model 8 hour group was found to be most serious; compared with model 8 hour group, inflammatory response in lung tissues in model 1 hour group and HT 8 hour group was reduced in certain degree. CONCLUSION: A certain extent of HT may reduce lung injury of early endotoxin induced ALI rats by delaying lowering of alveolar SP-A levels.


Asunto(s)
Lesión Pulmonar Aguda/metabolismo , Hipotermia , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Animales , Líquido del Lavado Bronquioalveolar , Lipopolisacáridos , Masculino , Ratas , Ratas Wistar
14.
Eur J Pharmacol ; 640(1-3): 150-6, 2010 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-20483352

RESUMEN

The pharmacological basis of isosorbide mononitrate (ISMN), a widely used drug for cardiovascular diseases, is that it is metabolized to nitric oxide (NO). However, NO is a double-edged sword that results in either beneficial or detrimental effect. Vascular injury is the common consequence of many cardiovascular diseases, but it is not determined whether ISMN influences the restoration of injured artery in vivo. Carotid artery injury was induced by electric stimulation in mice. Vasoconstriction and endothelium-dependent and -independent relaxation were recorded by a multichannel acquisition and analysis system. ISMN (10 mg/kg, p.o.) treatment for 1 week and 1 month had no effect on reendothelialization, histology and function of carotid artery injured by electric stimulation. L-arginine (500 mg/kg, p.o.) and Nomega-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg, p.o.) treatment for 1 week did not affect the reendothelialization process, but L-NAME treatment induced neointimal hyperplasia and inhibited endothelium-dependent relaxation in electrically injured artery. These results suggest that supplement of exogenous or endogenous NO has no effect on the restoration of injured artery, but inhibition of endogenous NO induces neointimal hyperplasia in injured artery. ISMN treatment does not affect the restoration of injured artery.


Asunto(s)
Traumatismos de las Arterias Carótidas/tratamiento farmacológico , Traumatismos de las Arterias Carótidas/fisiopatología , Dinitrato de Isosorbide/análogos & derivados , Animales , Arginina/farmacología , Traumatismos de las Arterias Carótidas/etiología , Traumatismos de las Arterias Carótidas/patología , Estimulación Eléctrica/efectos adversos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Dinitrato de Isosorbide/farmacología , Dinitrato de Isosorbide/uso terapéutico , Ratones
15.
Cell Physiol Biochem ; 25(4-5): 425-32, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20332623

RESUMEN

BACKGROUND/AIMS: 2-aminoethoxydiphenyl borate (2-APB) provokes spontaneous mechanical activity in isolated rat left atria. The present study is to characterize 2-APB-induced ectopic activity in rat atria and to investigate the inhibition of 2-APB-induced ectopic activity by anti-arrhythmic drugs. METHODS: 2-APB-induced ectopic activity was measured through an isometric force transducer connected to a multichannel acquisition and analysis system. Intracellular [Ca2+](i) was measured with fluorescence laser scanning confocal microscopy. Voltage-dependent L- type Ca2+ currents were recorded by using patch-clamp technique. RESULTS: 2-APB dose-dependently increased the ectopic activity of left atria at 1, 5, 10, 20, 50 microM. Anti-arrhythmic drugs, quinidine (10 microM), lidocaine (10 microM), verapamil (5 microM), and amiodarone (50 microM, 100 microuM) inhibited 2-APB-induced ectopic activity. 2-APB-induced ectopic activity was inhibited by Ca2+-free bath, Na+/Ca2+ exchanger blockers, 3',4'-dichlorobenzamil hydrochloride (DHC) and Ni2+, not by non-selective cation channel blocker Gd3+. 2-APB also induced ectopic contractions in ventricular tissue straps and the ectopic contractions were inhibited by quinidine, verapamil and DHC. Lidocaine, verapamil and DHC inhibited 2-APB-induced increase of intracellular Ca2+ concentration in cardiomyocytes. Low molecular weight heparin inhibited phenylephrine (PE)-induced but not 2-APB -induced atria ectopic activity, and the pattern of 2-APB-induced ectopic activity was continuous, distinct from the discontinuous activity induced by PE. CONCLUSION: 2-APB-induced atria ectopic activity was inhibited by classic anti-arrhythmic drugs quinidine, lidocaine, verapamil, amiodarone, and Na+/Ca2+ exchanger blockers. It can be used for testing agents able to affect any of Na+, Ca2+ channel, Na+/Ca2+ exchanger without selectivity.


Asunto(s)
Antiarrítmicos/farmacología , Función del Atrio Izquierdo/efectos de los fármacos , Compuestos de Boro/farmacología , Animales , Compuestos de Boro/antagonistas & inhibidores , Calcio/metabolismo , Canales de Calcio Tipo L/fisiología , Señalización del Calcio , Fenómenos Electrofisiológicos , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Técnicas de Placa-Clamp , Ratas , Ratas Wistar
16.
Hypertension ; 55(4): 946-52, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20177001

RESUMEN

Cardiac hypertrophy involves a remodeling process of the heart in response to diverse pathological stimuli. Both calcineurin/nuclear factor of activated T cells pathway and microRNA-133 (miR-133) have been shown to play a critical role in cardiac hypertrophy. It has been recognized that the expression and activity of calcineurin increases and miR-133 expression decreases in the hypertrophic heart, and inhibition of calcineurin or increase of miR-133 expression protects against cardiac hypertrophy. Here we tested the interaction between miR-133 and calcineurin in cardiac hypertrophy. Cardiac hypertrophy in vivo and in vitro was induced by transverse aortic constriction and phenylephrine treatment. mRNA levels were measured by using real-time PCR methods. Luciferase assays showed that transfection of miR-133 in HEK293 cells downregulated calcineurin expression, which was reversed by cotransfection with the miR-133-specific 2'-O-methyl antisense inhibitory oligoribonucleotides. These results were confirmed in cultured primary cardiomyocytes. miR-133 expression was downregulated, and calcineurin activity was enhanced in both in vivo and in vitro cardiac hypertrophy models. Treatment of cells and animals with cyclosporin A, an inhibitor of calcineurin, prevented miR-133 downregulation. Moreover, the antisense oligodeoxynucleotides against the catalytic subunits of calcineurin Abeta and the decoy oligodeoxynucleotides targeting nuclear factor of activated T cells transcription factor, a calcineurin downstream effector, increased miR-133 expression in cultured primary cardiomyocytes. Our data show that reciprocal repression between miR-133 and calcineurin regulates cardiac hypertrophy.


Asunto(s)
Calcineurina/genética , Cardiomegalia/genética , MicroARNs/genética , Análisis de Varianza , Animales , Western Blotting , Calcineurina/metabolismo , Cardiomegalia/metabolismo , Cardiomegalia/patología , Células Cultivadas , Ciclosporina/farmacología , Inhibidores Enzimáticos/farmacología , Ratones , MicroARNs/metabolismo , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Estadísticas no Paramétricas , Transfección
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