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1.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(7): 2139-43, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30035912

RESUMO

Spectrum denoising is an important part of spectrum detection. As we know, spectral signal is susceptible to thermal noise, mechanical vibration on site and random noise, etc. However, online monitoring systems require to reduce the impact of parameter selection caused by human operation on denoising, so a method based on singular value decomposition is proposed to denoise spectrum signal. An improved effective singular value selection method is also proposed. First, the author specify the maximum peak of the difference spectrum of singular value for the lower bound which named θ1, using the integrated information of singular value and its difference spectrum to select the upper bound, which is called θ2. The interval θ1~θ2 is defined as a fuzzy area. Then, the membership is obtained with Fuzzy C-means clusting and corresponding weight coefficients to the singular values in the fuzzy area are given. Finally, the proposed method is used to denoise UV spectrum signal with different signal to noise ratio. The signal to noise ratio, root mean square error, normalied correlation coefficient and smoothness radio are used to evaluate the result of denoising. The result shows that: based on data-driven, the proposed method has a good denoising effect, which can effectively restore the original signal.

2.
Cell Physiol Biochem ; 36(4): 1305-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26160442

RESUMO

BACKGROUND/AIMS: After myocardial infarction (MI), cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate-conductance calcium-activated potassium Channel (KCa3.1) has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms. METHODS: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs) stimulated by angiotensin II (Ang II) was tested. RESULTS: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways. CONCLUSION: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro-fibrotic effects of CFs.


Assuntos
Ventrículos do Coração/efeitos dos fármacos , Coração/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Pirazóis/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Animais , Células Cultivadas , Colágeno/análise , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibrose , Ventrículos do Coração/patologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Miocárdio/metabolismo
3.
Sheng Li Xue Bao ; 67(5): 505-12, 2015 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-26490068

RESUMO

This study was aimed to investigate the effects of blockade of Ca(2+) activated channel KCa3.1 and voltage-gated potassium channel Kv1.3 of the monocytes/macrophages on inflammatory monocyte chemotaxis. Chemotaxis assay was used to test the inflammatory Ly-6C(hi) monocyte chemotaxis caused by the monocytes/macrophages. The proliferation of monocytes/macrophages was detected by cell counting kit-8 (CCK8). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the C-C motif ligand 7 (CCL7) in cultured media. The results showed that the recruitment of Ly-6C(hi) monocyte induced by monocytes/macrophages was suppressed by the potent Kv1.3 blocker Stichodactyla helianthus neurotoxin (ShK) or the specific KCa3.1 inhibitor TRAM-34. Meanwhile, the proliferation of monocytes/macrophages was significantly inhibited by ShK. The response of Ly-6C(hi) monocyte pretreated with ShK or TRAM-34 to CCL2 was declined. These results suggest that KCa3.1 and Kv1.3 may play an important role in monocytes/macrophages' proliferation and migration.


Assuntos
Canal de Potássio Kv1.3/fisiologia , Macrófagos/citologia , Monócitos/citologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/fisiologia , Movimento Celular , Proliferação de Células , Venenos de Cnidários/farmacologia , Ensaio de Imunoadsorção Enzimática , Humanos , Canal de Potássio Kv1.3/antagonistas & inibidores , Estrutura Terciária de Proteína , Pirazóis/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/antagonistas & inibidores
4.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(2): 438-42, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25970908

RESUMO

As the basis of accurate diagnosis, fault early-warning of gas insulation switchgear (GIS) focuses on the time-effectiveness and the applicability. It would be significant to research the method of unified early-warning for partial discharge (PD) and overheated faults in GIS. In the present paper, SO2 is proposed as the common and typical by-product. The unified monitoring could be achieved through ultraviolet spectroscopy (UV) detection of SO2. The derivative method and Savitzky-Golay filtering are employed for baseline correction and smoothing. The wavelength range of 290-310 nm is selected for quantitative detection of SO2. Through UV method, the spectral interference of SF6 and other complex by-products, e.g., SOF2 and SOF2, can be avoided and the features of trace SO2 in GIS can be extracted. The detection system is featured by compacted structure, low maintenance and satisfactory suitability in filed surveillance. By conducting SF6 decomposition experiments, including two types of PD faults and the overheated faults between 200-400 degrees C, the feasibility of proposed UV method has been verified. Fourier transform infrared spectroscopy and gas chromatography methods can be used for subsequent fault diagnosis. The different decomposition features in two kinds of faults are confirmed and the diagnosis strategy has been briefly analyzed. The main by-products under PD are SOF2 and SO2F2. The generated SO2 is significantly less than SOF2. More carbonous by-products will be generated when PD involves epoxy. By contrast, when the material of heater is stainless steel, SF6 decomposes at about 300 "C and the main by-products in overheated faults are SO2 and SO2F2. When heated over 350 degrees C, SO2 is generated much faster. SOz content stably increases when the GIS fault lasts. The faults types could be preliminarily identified based on the generation features of SO2.

5.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(12): 3312-6, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25881430

RESUMO

By detecting the stable by-products of SF6 through ultraviolet spectroscopy, the present paper achieved the rapid detection of the GIS partial discharge fault. First derivative and the S-G filter were used for the spectral denoising and smoothing. The discharge experiment was used for validating feature selection. Principal component regression was used for the analysis of the concentration of SO2. The concentration of SO2 was used for fuzzy judge. By selecting the appropriate wavelength range (295~305 nm), ultraviolet spectrum can identify SO2 from the complex by-products of SF6. In this paper, firstly, the author reviewed the decomposition mechanism of SF6 under partial discharge, and then verified the rationality of detecting partial discharge by UV, and ultimately achieved the rapid detection of GIS partial discharge and fuzzy judgment of discharge time.

6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(9): 731-5, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24331798

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of tirofiban use immediately after successful percutaneous coronary intervention (PCI) in patients with moderate to high risk non-ST segment elevation acute coronary syndromes (NSTE-ACS). METHODS: NSTE-ACS patients undergoing successful PCI (n = 246) were randomized by the envelope method to tirofiban group (n = 122, 10 µg/kg bolus within 3 min followed by 0.10-0.15 µg×kg(-1)×min(-1) for 36 h i.v.) or control group (n = 124, saline i.v. for 36 h). The primary efficacy composite end point was death, myocardial infarction, target vascular revascularization or ischemic stroke at 30 days. The second end point was the occurrence of composite end point at 7 days or 6 months. Key safety end points were bleeding and thrombocytopenia 3 days after PCI. RESULTS: Baseline characteristics were well-balanced between the two groups (P > 0.05). The primary end point occurred in 0.9% (1/117) patients in the tirofiban group and 3.3% (4/123) patients of those in the control group (P = 0.40). There was no significant difference in the composite end point at 7 days [0.8% (1/122) vs. 3.2% (4/124), P = 0.38] between the groups, however, there was a trend towards lower composite efficacy end points at 6 months in tirofiban group compared to control group [0.9% (1/117) vs. 5.9% (7/118), P = 0.07]. The probability of survival free of composite end point was significantly higher in the tirofiban group than that in the control group (99.2% vs. 94.2%, log-rank test, P = 0.03). There was no GUSTO severe or moderate bleeding or severe thrombocytopenia within 3 days post-PCI. There was no significant difference in mild bleeding [13.1% (16/122) vs. 7.3% (9/124), P = 0.13] or mild thrombocytopenia [0.8% (1/122) vs. 0.8% (1/124), P = 1.00] between the groups. CONCLUSION: Tirofiban use after successful PCI can improve 6-month event-free survival without increasing the risk of bleeding for patients with moderate to high risk NSTE-ACS.


Assuntos
Síndrome Coronariana Aguda/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Tirosina/análogos & derivados , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Prognóstico , Tirofibana , Resultado do Tratamento , Tirosina/administração & dosagem , Tirosina/uso terapêutico
7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(6): 1535-40, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22870634

RESUMO

Infrared spectroscopy analysis of SF6 and its derivative is an important method for operating state assessment and fault diagnosis of the gas insulated switchgear (GIS). Traditional methods are complicated and inefficient, and the results can vary with different subjects. In the present work, the feature extraction methods in machine learning are recommended to solve such diagnosis problem, and a multiscale weighted principal component analysis method is proposed. The proposed method combines the advantage of standard principal component analysis and multiscale decomposition to maximize the feature information in different scales, and modifies the importance of the eigenvectors in classification. The classification performance of the proposed method was demonstrated to be 3 to 4 times better than that of the standard PCA for the infrared spectra of SF6 and its derivative provided by Guangxi Research Institute of Electric Power.

8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(6): 473-6, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22943640

RESUMO

OBJECTIVE: The prognostic value of corrected QT interval (QTc), corrected Tp-e interval (Tp-ec) and Tp-e/QT ratio on occurrence of malignant arrhythmia events (MAE) in acute ST-segment elevation myocardial infarction (STEMI) patients underwent successful thrombolysis was explored and the potential association of these indices with MAE was analyzed. METHODS: Fifty-seven STEMI patients underwent successful thrombolytic therapy within 6 hours after admission and conservative medical treatment were included. QTc, Tp-ec, Tp-e/QT ratio were obtained and calculated in infarct-related electrocardiograph leads and non-infarct-related leads before thrombolysis, (7±1) days and (30±3) days after thrombolysis respectively, and incidence of MAE up to 30 days after thrombolysis was analyzed. Sixty age and gender matched normal subjects served as control group. RESULTS: (1) QTc, Tp-ec, Tp-e/QT in infarct-related and non-infarct-related leads in STEMI group before thrombolysis were significantly higher than those in control group (all P<0.05), and values from the infarct-related leads were significantly higher than those from non-infarct-related leads in STEMI group (all P<0.05). QTc, Tp-ec and Tp-e/QT all significantly and continuously reduced from 7 days and at 30 days post thrombolysis compared the before thrombolysis (P<0.05 vs. before thrombolysis). (2) Tp-ec≥100 ms and Tp-e/QT ratio≥0.25 before thrombolysis in infarct-related leads were linked with higher incidence of MAE within 30 days post thrombolysis in this patient cohort [28.1% (9/32) vs. 40% (1/25), 27.8% (10/36) vs.0, respectively, all P<0.05]. CONCLUSION: QTc, Tp-ec and Tp-e/QT values decreased post successful thrombolysis in STEMI patients and higher Tp-ec and Tp-e/QT values before thrombolysis in STEMI patients were related with higher MAE incidence up to 30 days post successful thrombolysis in this patient cohort.


Assuntos
Eletrocardiografia/métodos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica , Resultado do Tratamento
9.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(7): 575-8, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22943685

RESUMO

OBJECTIVE: To compare the effects of intracoronary infusion of mononuclear stem cells (MNCs) or mesenchymal stem cells (MSCs) in patients with dilated cardiomyopathy (DCM). METHODS: DCM patients with left ventricular ejection fraction(LVEF) < 40% were randomized to intracoronary infusion of MNCs [(5.1 ± 2.0) × 10(8), n = 16] or MSCs [(4.9 ± 1.7) × 10(8), n = 17] or equal volume normal saline (n = 20) through the guiding catheter. Changes of left ventricular end-diastolic diameter (LVEDd), LVEF and myocardium perfusion defects were assessed before and at (30 ± 3) days and (90 ± 7) days after the procedure. Malignant cardiovascular events were also recorded. RESULTS: (1) One month after the procedure, LVEF in transplantation groups significantly increased compared to before procedure (all P < 0.05), and significant increase of LVEF was observed only in MSCs transplantation group compared to control group (P < 0.05). However, absolute changes of LVEDd and perfusion defects of myocardium were similar among and within groups (P > 0.05). (2) Comparing with before procedure and control group, LVEF in transplantation groups increased significantly in three months after the procedure (P < 0.05), but there were no significant differences between transplantation groups (P > 0.05). LVEDd and myocardium perfusion defects in transplantation groups improved significantly compared with that of before procedure (P < 0.05), while significant decrease of myocardium perfusion defects was only observed in patients treated with MSCs compared with control group at three months after procedure (P < 0.05). (3) There were no significant differences in major cardiovascular events between transplantation group and control during follow-up (P > 0.05). CONCLUSIONS: Intracoronary bone marrow stem cells transplantation is safe and effective for DCM patients while the efficacy of MSCs and MNCs transplantation is comparable.


Assuntos
Transplante de Medula Óssea , Cardiomiopatia Dilatada/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(3): 219-24, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22801267

RESUMO

OBJECTIVE: To investigate the effect of Angiotensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy (ADR-DCM). METHODS: Weight-matched adult male Wistar rats were randomly divided into 3 groups: (1) the ADR-DCM group (n = 25), in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks. (2) Ang(1-7) group (n = 25), in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 µg×kg(-1)×h(-1), ip.) for 12 weeks. (3) normal control group (n = 10). Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde (MDA) was measured by TBA methods. The plasma concentration of AngII was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and anti-apoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot. RESULTS: Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16% vs. 40%, P < 0.01). Compared to the control group, left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group (all P < 0.01) while fractional shorting (FS), +dp/dtmax and -dp/dtmax were significantly reduced in ADR-DCM group (all P < 0.01). LVEDD, LVESD and LVEDP were significantly reduced while FS, +dp/dtmax and -dp/dtmax were significantly higher in Ang(1-7) group compared to the ADR-DCM group, but still higher than the control group (all P < 0.01). The concentrations of AngII and MDA were higher in the ADR-DCM group than in the control group (P < 0.01), which were significantly reduced by Ang(1-7) treatment (P < 0.01). The TUNEL-positive cells and apoptosis index, the expression of pro-apoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P < 0.01) which could all be partially reversed by Ang(1-7) treatment (all P < 0.01). CONCLUSION: Ang(1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.


Assuntos
Angiotensina I/farmacologia , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Miócitos Cardíacos/patologia , Fragmentos de Peptídeos/farmacologia , Disfunção Ventricular Esquerda/tratamento farmacológico , Angiotensina I/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Cardiomiopatia Dilatada/induzido quimicamente , Caspase 3/metabolismo , Doxorrubicina/efeitos adversos , Coração/efeitos dos fármacos , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , Ratos , Ratos Wistar , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(5): 1262-5, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21800578

RESUMO

Spectrum intercomparison search means calculating the similarity of question spectrum and standard spectrum in the database to find the same or similar spectrum as the question spectrum. To weaken the impact of irrelevant information on spectrum intercomparison search results and improve the search accuracy, the question spectrum noise is taken for example and the impact of spectrum noise on the calculated similarity results is analyzed; for the characteristics that when infrared spectrum is multi-scale decomposed, the useful information is mainly concentrated in the low-frequency part and the high-frequency part is mainly noise, the infrared spectrum intercomparison search method based on wavelet multi-scale decomposition is proposed; the impact of spectrum decomposition level on the calculated similarity results is analyzed; the entire waveform search method is used as reference method and the search program of both methods is designed with MATLAB 7.0 and the feasibility of infrared spectrum intercomparison search method based on wavelet multi-scale decomposition is confirmed by the experimental results.

12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(6): 1688-91, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-20707177

RESUMO

SF6 gas has been widely used in the power equipments as an excellent electric insulating and arc-quenching medium. In the present paper, a baseline correction method based on the optimum wavelet basis for spectrum detection is proposed to measure the composition content of the SF6 insulating gas to secure the power safety. In this method, the optimum wavelet basis is selected in the wavelet packet according to constructor function on the energy concentration criterion to express the spectrum signal in the time-frequency domain. Then the strong spectrum composition is removed from the spectrum signal with the threshold method to eliminate the interference with the continuous spectrum fitting. Finally we remove the continuous spectrum which is fitting result from the origin spectrum and obtain the useful signal of line spectrum. The intensities of spectral line processed with the proposed algorithm could reflect the concentration of the conponents to be measured in SF6 gas. Experiments to analyze the absorption spectrum of the SF6 insulating gas mixture show that the proposed algorithm can estimate and correct the drifting baseline accurately, and its performance is better than the algorithm based on iterative wavelet.

13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(11): 2967-70, 2010 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-21284164

RESUMO

Pressured SF6 gas is widely used in GIS for electrical insulation as well as for are extinction. And a chemical way for detecting the SF6 and its byproducts is a powerful diagnosis method for GIS. The present paper analyzes the decomposition of insulated gas of GIS (mostly SF6) in three cases with infrared spectrometer. As a result, it was found that the content of S2F10 can be used to decide whether spark or arc discharge leads to the fall down of GIS; CF4 can be used for judging the insulation grade of GIS. Besides, the gas leakage of the GIS should be concerned in the long lifetime of GIS. Finally, it is supposed that a data base containing the history of results from the gas diagnostics for each piece of equipment should be created for future maintenance activities.

14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(5): 1241-5, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-19650462

RESUMO

In the present paper, a wavelet modulus maximum shift-related filter algorithm is proposed for denoising the absorption spectra. Firstly, using the wavelet transform modulus maxima theory, useful signal components and noise components of the binary wavelet coefficients of absorption spectra are identified. Then, the useful signal components are aligned in the wave number domain to correct the "drifting" of modulus maximum across the scales, and the noise components are smoothed. Finally, according to the wavelet interscale dependencies obtained by multiplying the adjacent wavelet subbands preprocessed by the above procedure, important features of signal are enhanced while noises are attenuated further. Compared with the traditional spatially selective noise filtration technique proposed by Xu et al and adaptive multiscale products thresholding technique proposed by Paul Bao et al, the proposed wavelet modulus maximum shift--related filter algorithm has several advantages. First, it does not need estimate of the noise intensity, which could avoid the error introducing and the complex calculation. Meanwhile, there is not iterative calculation in the proposed algorithm, which could eliminate the risk of slow convergence or no convergence of the algorithm. Furthermore, the "drifting" of modulus maximum across the scales could be corrected in the proposed algorithm, which could make up for the loss of the spectrum information caused by the "drifting" phenomenon. Experiments show that the proposed scheme can effectively suppress noise and preserve the useful components in the infrared absorption spectra of SF6 gas.

15.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(2): 165-8, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19719998

RESUMO

OBJECTIVE: To observe the effects of telmisartan on Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes. METHODS: Kv1.3 and Kv1.5 potassium channel currents expressed in Xenopus oocytes were recorded and observed in the absence and presence of telmisartan using standard two-microelectrode voltage clamp techniques. RESULTS: Telmisartan resulted in a concentration- and voltage-dependent inhibition effect on Kv1.3 channel current (IC(50) 2.05 micromol/L)and on Kv1.5 channel current (IC(50) 2.37 micromol/L). CONCLUSIONS: Telmisartan blocks open-state Kv1.3 channel which could be one of the mechanisms related to its immunomodulatory and anti-atherosclerosis effect. Telmisartan also blocks open-state Kv1.5 channel which might partly account for its effect on reducing the incidence of atrial fibrillation.


Assuntos
Benzimidazóis/farmacologia , Benzoatos/farmacologia , Canal de Potássio Kv1.3/efeitos dos fármacos , Canal de Potássio Kv1.5/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Animais , Técnicas In Vitro , Oócitos/metabolismo , Técnicas de Patch-Clamp , Telmisartan , Xenopus
17.
Acta Pharmacol Sin ; 29(8): 913-22, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18664324

RESUMO

AIM: The objectives of this study were to investigate the inhibitory action of telmisartan, a selective angiotensin II type 1 receptor antagonist, on hKv1.5 and human ether-a-go-go-related gene (HERG) channels expressed on Xenopus laevis oocytes. METHODS: hKv1.5 and HERG channels were expressed on Xenopus laevis oocytes and studied using the 2-microelectrode voltage clamp technique. RESULTS: In hKv1.5 channels, telmisartan produced a voltage- and concentration-dependent inhibition; the efficacies of blockade were different at peak and 1.5 s end-pulse currents, which were 7.75%+/-2.39% (half-maximal inhibition concentration [IC50]=2.25+/-0.97 micromol/L) and 52.64%+/-3.77% (IC50=0.82+/-0.39 micromol/L) at 1 micromol/L telmisartan, respectively. Meanwhile, telmisartan accelerated the inactivation of the channels. However, telmisartan exhibited a low affinity for HERG channels (IC50=24.35+/-5.06 micromol/L); the blockade was voltage- and concentration-dependent. Telmisartan preferentially blocked open-state HERG channels. The slow time constants of deactivation were accelerated (n=6, P<0.05), which was inconsistent with the "foot-in-the-door"effect. CONCLUSION: Telmisartan blocks hKv1.5 potassium channels involving open and inactivated states at plasma concentration levels of therapeutic doses; whereas the blockade of HERG channels occurs only at supra plasma concentration levels of therapeutic doses and preferentially in open and closed-state channels.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Canal de Potássio Kv1.5/antagonistas & inibidores , Bloqueadores dos Canais de Potássio , Animais , Relação Dose-Resposta a Droga , Eletrofisiologia , Feminino , Humanos , Oócitos/metabolismo , Técnicas de Patch-Clamp , Telmisartan , Xenopus laevis
18.
Sheng Li Xue Bao ; 60(4): 525-34, 2008 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-18690396

RESUMO

In the present study, we investigated the inhibitory action of ketanserin on wild-type (WT) and Y652 mutant human ether-a-go-go-related gene (HERG) potassium channels expressed in Xenopus oocytes and the effects of changing the channel molecular determinants characteristics on the blockade with and without ketanserin intervention using standard two-microelectrode voltage-clamp techniques. Point mutations were introduced into HERG gene (Y652A and Y652R) and subcloned into the pSP64 plasmid expression vector. Complementary RNAs for injection into oocytes were prepared with SP6 Cap-Scribe after linearization of the expression construct with EcoR I. Clampfit 9.2 software was employed for data collection and analysis. Origin 6.0 software was used to fit the data, calculate time constants and plot histograms. The results showed that ketanserin blocked WT HERG currents in voltage- and concentration-dependent manner and showed minimal tonic blockade of HERG current evaluated by the envelope of tails test. The IC50 value was (0.38+/-0.04) micromol/L for WT HERG potassium channel. The peaks of the I-V relationship for HERG channel suggested a negative shift in the voltage-dependence of activation after using ketanserin, whose midpoint of activation values (V1/2) were (-16.59+/-1.01) mV (control) vs (-20.59+/-0.87) mV (ketanserin) at 0.1 micromol/L, (-22.39+/-0.94) mV at 1 micromol/L, (-23.51+/-0.91) mV at 10 micromol/L, respectively (P<0.05, n=6). Characteristics of blockade were consistent with an open-state channel blockade, because the extent and rate of onset of blockade was voltage-dependent, increasing at more potentials even in the condition of leftward shift of activation curve. Meanwhile, in the different depolarization duration, the fractional blockade of end-pulse step current and peak tail current at 100 ms duration was significantly lower than that at 400 ms and 700 ms, which indicated that following the channel activation fractional blockade was enhanced by the activated channels. Ketanserin could also modulate the inactivation of HERG channel, which shifted the voltage-dependence of WT HERG channel inactivation curve from (-51.71+/-2.15) mV to (-80.76+/-14.98) mV (P<0.05, n=4). The S6 mutation, Y652A and Y652R, significantly attenuated the blockade by ketanserin. The IC50 value were (27.13+/-9.40) micromol/L and (20.20+/-2.80) micromol/L, respectively, increased by approximately 72-fold for Y652A and 53-fold for Y652R compared to that of WT HERG channel blockade [(0.38+/-0.04) micromol/L]. However, between the inhibitory effects of Y652A and Y652R, there was no significant difference. In conclusion, ketanserin blocks WT HERG currents in voltage- and concentration-dependent manner and preferentially blocks open-state HERG channels. Tyr-652 is one of the critical residues in the ketanserin-binding sites.


Assuntos
Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Ketanserina/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Animais , Humanos , Mutação , Oócitos , Técnicas de Patch-Clamp , Xenopus
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 26(10): 1850-3, 2006 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-17205736

RESUMO

Accurate curve fitting of infrared spectrum data is important for building standard spectrum, and is the basic requirement for qualitative and quantitative spectral analysis. In the present paper, B-Spline was used to accurately fit the infrared spectrum data. Based on the max norm distances of B-Spline curve fitting arithmetic, this method not only resolved the curve fitting problem of infrared data, but also provided a convenient way to orient peak values of spectrum. The authors introduced the B-Spline, realized curve fitting of quadratic non-uniform B-Spline curves (for short: NUBSC), and described the precision control of curve fitting of infrared spectrum data.

20.
Sheng Li Xue Bao ; 56(5): 603-8, 2004 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-15497041

RESUMO

Whole cell patch-clamp technique was used to record the changes of persistent sodium current (I(Na.P)) and the effect of administered agents in ventricular myocytes of guinea pig to investigate the essence of I(Na.P) and mechanism of increased I(Na.P) of ventricular myocytes during hypoxia. The results showed: (1) Pro-NO L-arginine(L-Arg) and donor sodium nitroprusside (SNP) increased I(Na.P) in a concentration-dependent manner in normoxia. (2) I(Na.P) increased gradually with the prolongation of hypoxia time. After 15 min of hypoxia, administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, could not significantly recover the increased I(Na.P) [(1.344+/-0.320) vs (1.301+/-0.317) pA/pF, P>0.05, n=5]; (3) During hypoxia the perfusion solution with L-NAME decreased the increased I(Na.P), and the difference was significant compared with pure hypoxia [(0.914+/-0.263), n=5 vs (1.344+/-0.320) pA/pF, P<0.05, n=6], whereas the amplitude of I(Na.P) was still larger than that in normoxia [(0.914+/-0.263) vs (0.497+/-0.149) pA/pF, P<0.05, n=5]; (4) Reducing agent dithiothreitiol (DTT) not only recovered the increased I(Na.P) by L-Arg and administered SNP after hypoxia [(1.449+/-0.522) vs (0.414+/-0.067) pA/pF, P<0.01, n=6, and (1.786+/-0.636) vs (0.436+/-0.141) pA/pF, P<0.01, n=5, respectively], but also decreased the I(Na.P) in normoxia [(0.442+/-0.056) vs (0.396+/-0.057) pA/pF, P<0.01, n=6]. Our results suggest that hypoxia increases I(Na.P) of ventricular myocytes, which is induced by raised NO oxidating sodium channel protein in myocardial membrane during hypoxia. The activity of I(Na.P) in normoxia is related to the oxidation state of the channel protein.


Assuntos
Miócitos Cardíacos/fisiologia , Óxido Nítrico/farmacologia , Canais de Sódio/fisiologia , Animais , Hipóxia Celular/fisiologia , Separação Celular , Feminino , Cobaias , Ventrículos do Coração , Masculino , Miocárdio/citologia , Miócitos Cardíacos/metabolismo , Nitroprussiato/farmacologia , Técnicas de Patch-Clamp
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