Studies on the calcium antagonistic action of tetrandrine: XVI. Hemodynamic effects of tetrandrine on conscious rats

Hu, Guo-Xin; Fang, Da-chao; Jiang, Mingxing

doi:10.1007/bf02933734

Cited by 3 publications

(2 citation statements)

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“…TET is a bis-benzylisoquinoline alkaloid, which is the main active component from the root of S. tetrandra S. Moore (Figure 3 A). It is known that TET acts as a calcium antagonist similar to verapamil, it is yet not clear if TET is also an efflux pump inhibitor as verapamil [ 8 , 22 , 23 ]. We next tested whether TET can reverse drug resistance in 29 IEDR strains identified in Figure 1 B.…”

Section: Resultsmentioning

confidence: 99%

Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates

Zhang

Yan

et al. 2015

BMC Infect Dis

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BackgroundTetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. The aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which Mycobacterium tuberculosis (MTB) has turned resistant via efflux mechanisms.MethodsWe screened 200 MTB clinical isolates using drug sensitivity test to look for those who have turned resistant to the drugs most probably due to efflux mechanisms. We found 29 isoniazid (INH) and ethambutol (EMB) - dual resistant (IEDR) strains. Then we tested if treatment with tetrandrine or verapamil could reverse drug resistance to INH and/or EMB in IEDR isolates.ResultsThere is a parallel resistance among EMB- and INH-resistant strains in the tested clinical isolates. Among INH-resistant strains, 65% was also EMB-resistant. This suggests an involvement of efflux mechanisms which can lead to dual drug resistance in IEDR clinical isolates. Similar to a synthesized efflux pump inhibitor verapamil, tetrandrine treatment together with INH or EMB brought down the MICs from the clinical level of drug resistance to the sensitive range of both drugs. The effective rate reached 82% among IEDR clinical isolates.ConclusionsCombinational application of tetrandrine with INH or EMB increased drug efficacy. Drugs like tetrandrine may help to reduce drug dosage thus alleviate side effects.

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Section: Resultsmentioning

confidence: 99%

Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates

Zhang

Yan

et al. 2015

BMC Infect Dis

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“…Currently, anaerobic organism treatment, especially UASB reactor, has been extensively used in various industrial sewage with high and medium concentration and expanded to urban domestic sewage treatment in recent years [1][2][3]. Anaerobic treatment is principally a pretreatment process and follow-up treatment is needed to reach discharge standard [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Flocculation, Anaerobic and Microaerobic Treatment Process of Normal Temperature Low Concentration Domestic Sewage

Nie

Zhong

Huang

et al. 2012

AMR

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Domestic sewage was treated by adopting flocculation, anaerobic and microaerobic combined process under normal temperature. The result demonstrates: total hydraulic retention time is 5.5h (chemical flocculation 1.0h, UASB reactor 2.0h and MUSB reactor 2.5h). UASB reactor can achieve anaerobic sludge granulation under normal temperature and is fairly feasible for low concentration domestic sewage treatment. Compared with single stage UASB reactor, hydraulic retention time of flocculation-UASB combined technique reduces from 4h to 2h. COD removal rate rises from 45% to 50%-60% and suspended COD is mainly removed. DO of microaerobic MUSB technique after anaerobic treatment is 0.2mg/L-0.5mg/L with air and water ratio of 1:1. Effluent quality is stable, in accordance with first standard of Synthetical Draining Standard of Sewage, GB8978—1996.

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Preclinical Cardiac Safety Assessment??of Drugs

Hanton

2007

Drugs in R & D

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The heart is a frequent site of toxicity of pharmaceutical compounds in humans, and when developing a new drug it is critical to conduct a thorough preclinical evaluation of its possible adverse effects on cardiac structure and function. Changes in cardiac morphology such as myocardial necrosis, hypertrophy or valvulopathy are assessed in regulatory toxicity studies in laboratory animals, although specific models may be needed for a more accurate detection of the risk. The potential proarrhythmic risk of new drugs is a major subject of concern and needs to be fully addressed before treatment of volunteers or patients takes place. In vitro assays are conducted to determine the effects on cardiac ion channels, in particular I(Kr) potassium channel antagonism. Prolongation of the QT interval is assessed in vivo, generally in telemetered dogs. Together, these two tests are considered to detect most arrhythmic drugs. The results of this core battery can be refined by additional studies, in particular assays on isolated cardiac tissues determining changes in cardiac action potential duration, shape and variability over time. Triggering of arrhythmia is assessed in hypokalaemic dogs with artificially created bradycardia, or in vitro in isolated whole hearts. The proarrhythmic risk of the new compound is then evaluated by integrating the results of these different tests. Drug adverse effects on cardiac electrophysiological function, in particular impulse formation and conduction, are evaluated through changes in ECG, generally recorded in dogs, pigs or monkeys. Changes in cardiac contractility occurring either as a primary effect of the drug on cardiac function or as a consequence of cardiac lesions should also be carefully assessed. In telemetered or anaesthetised animals, cardiac contractility is evaluated by measurement of left ventricular pressure and its first derivative over time. Echocardiography allows non-invasive measurement of drug-induced changes in ventricular wall movements and cardiac haemodynamics indicative of effects on contractility. In conclusion, a reliable and accurate evaluation of the cardiac safety of a new pharmaceutical agent is based on the results of in vitro tests, with overall moderate to high throughput, and in vivo experiments assessing the effects of the drug on the heart in its physiological environment. The specific sensitivities of the animals used in these assays to cardiac adverse effects should also be considered. The final evaluation of the cardiac risk is therefore based on an integrated analysis of the results from a battery of tests.

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Studies on the calcium antagonistic action of tetrandrine: XVI. Hemodynamic effects of tetrandrine on conscious rats

Cited by 3 publications

References 1 publication

Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates

Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates

Flocculation, Anaerobic and Microaerobic Treatment Process of Normal Temperature Low Concentration Domestic Sewage

Preclinical Cardiac Safety Assessment??of Drugs

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