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91.
We evaluated the cytotoxic and DNA cross-linking (CL) ability of four second generation platinum coordination complexes (TNO-6, JM-89, JM-8 and JM-9) delivered alone or in combination with 1-beta-D-arabinofuranosyl cytosine (ara-C) to human colon cancer cells (LoVo). Cell survival varied markedly as a function of the particular substitution moiety. JM-8 and JM-9 were virtually ineffective, even at concentrations as high as 50 micrograms/ml. At that concentration cis-diamminedichloroplatinum(II) (cis-DDP) killed greater than 99.99% of the cells. JM-82 was slightly more active while TNO-6 was the only derivative with appreciably higher cytotoxic activity due to an abrogation of the shoulder region of the type C survival curve. The highest CL effect was observed for cis-DDP followed closely by TNO-6. Very little CL effects were demonstrated for the other three analogs JM-82, JM-8 and JM-9 when measured 6 h after treatment. The combination of cis-DDP and ara-C augmented 10-fold the cytotoxic activity of cis-DDP alone, an effect accompanied by an almost 2-fold increase in CL; every other analog failed to interact in a potentiating manner (either cytotoxicity, or CL at 6 h) with the antimetabolite. Thus, it appears clear that the associated moieties of the Pt coordination complex play a fundamental role in reducing the interaction of the analogs with DNA (as reflected by the decreased CL and cytotoxic effects produced by each agent alone) and in totally preventing their interaction with ara-C to yield a potentiating lethal effect. 相似文献
92.
A. V. Nikolayev Yu. V. Kirichek O. I. Ostrovskaya I. I. Maletina K. I. Petko L. M. Yagupol’skii 《Neurophysiology》1999,31(3):191-193
With the use of a patch-clamp technique in the whole-cell configuration, we studied the effects of pinacidil and its fluorine
derivatives on A-type potassium current (I
A) through the membrane of pyramidal neurons of the rat hippocampus. Hydrogen peroxide (10 mM) exerted no influence on the
rate of inactivation ofI
A; therefore, this current is probably mediated by Shal Kv4.2 potassium channels. Pinacidil demonstrated the properties of
a weakI
A blocker: in the 500 μM concentration it blocked about 45% of the current, while 50 μM of pinacidil fluorine derivatives were
capable of blocking up to 30% ofI
A. The effects of pinacidil and its derivatives showed no dependence on the stimulating potential. A similar pattern of the
effects of pinacidil fluorine derivatives, which are an order of magnitude stronger than those of pinacidil itself, allows
us to suppose that the imine nitrogen of the tested compounds is significantly more involved in the molecular interaction
with the site of an A-type potassium channel than the pyridine nitrogen. 相似文献
93.
Mechanisms of changes in human hemodynamics under the conditions of microgravity and prognosis of postflight orthostatic stability 总被引:1,自引:0,他引:1
The mechanisms of hemodynamic responses to orthostatic stresses and orthostatic stability (OS) of cosmonauts were studied before and after short-and long-term spaceflights (SFs) using orthostatic tests, as well as before, during, and after SFs using ultrasonic methods in tests with exposure to lower body negative pressure (LBNP). The capacitance and distensibility of the veins of the lower extremities were studied using occlusive air plethysmography before, during, and after SFs of different durations. A stay in microgravity has been proved to result in detraining of, mainly, the vascular mechanisms of compensating orthostatic perturbations. It has been established that the decrease in OS under the influence of microgravity is determined by a reduction of the vasoconstrictive ability of large blood vessels of the lower extremities; an increase in venous distensibility and capacitance of the legs; and an impairment of blood flow regulation, which leads to a cerebral blood flow deficit in orthostatic stresses, and of the initial individual OS before the flight. The results of preflight studies of hemodynamics by ultrasonic methods at LBNP and the data of orthostatic tests before SFs make it possible to predict the degree of decrease of OS after an SF proceeding in the normal mode. At the same time, the data of ultrasonic blood flow examination provide more a accurate estimation of OS and make it possible to assess the physiological reserves of hemodynamic regulation and to reveal the loss of regulation capacity even in cases where integrated indices (heart rate and blood pressure) are within the normal ranges. 相似文献
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B Daneholt 《Journal of molecular biology》1970,49(2):381-391
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