A comparison of toxicity following two different doses of cyclophosphamide for mobilization of peripheral blood progenitor cells in 116 multiple myeloma patients
Olivier FitoussiVirginie PerreauJM BoironEmmanuelle BouzigonPascale Cony‐MakhoulArnaud PigneuxPhilippe AgapéFrank NicoliniBernard DazeyJosy ReiffersR SalmiGérald Marit
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Nitrogen mustard
Chlormethine (Nitrogen mustard) in small doses proved to have immunopotentiating and anti-inflammatory activities. The influence of two nitrogen mustard derivatives : chlorambucil (1 or 10 micrograms/kg p.o.) and cyclophosphamide (0.03 or 0.3 mg/kg i.v.) as well as busulphan (0.5 or 5 micrograms/kg p.o.)--the agent of ++alkylating cytostatic group were investigated in rabbits. Whole blood count, the number of T and B lymphocytes, serum IgG level, phagocytic and microbicidal activities of neutrophils and the plasma level of free glucocorticoids were estimated. The drugs were used in the doses 10-100 times lower than cytostatic ones. Moreover, the ability of alkylating drugs to enhance or to suppress the changes evoked by lipopolysaccharide of E. coli in examined parameters was assessed. The results were compared with chlormethine data obtained previously. None of two nitrogen mustard derivatives (chlorambucil or cyclophosphamide) in the doses many times lower than cytostatic ones, exhibited an immunostimulating and adjuvant properties characteristic of chlormethine. Such properties did not demonstrate small doses of busulphan, another compound of alkylating drugs.
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This article discusses how to enhance the application of national economy mobilization system in non-military fields from the following aspects: enhancing coordination, establishing complete mobilization organization system, enhancing media mobilization, establishing efficient mobilization information system, improving mobilization mechanism, safeguarding national security, establishing comprehensive legal regulations, assuring the smooth implementation of mobilization.
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Existing work on mobilization can be categorized along two axes: structure vs. culture and bottom-up (individuals) vs. top-down (organizations). Structural top-down mobilization seems now to be complemented with mobilization in which individuals play a larger role and formal organizations are to some extent by-passed.
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5-N,N-Dimethylamiloride protects Ehrlich ascites tumor cells against the antiproliferative effect of nitrogen mustard. The drug reduces the frequency of DNA interstrand cross-links introduced by nitrogen mustard. Cells with a defective choline carrier are not protected against nitrogen mustard by dimethylamiloride. As nitrogen mustard is taken up by the choline carrier, it is concluded that the recently reported inhibition of the choline transport system by amiloride and its dimethyl derivatives (W. Doppler et al., Biochem. Pharmacol., 36: 1645-1649, 1987) is responsible for the protection against the alkylating agent.
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Nitrogen mustard and nor-nitrogen mustard were investigated in Salmonella typhimurium and human lymphocytes for genotoxicity. Point mutations were assessed using the plate test, the conventional spot test and a method in which the substances were not in direct contact with the microorganisms. Both compounds were active, but nornitrogen mustard was far more potent than nitrogen mustard in all bacterial systems. Cytogenetic experiments with human lymphocytes revealed that both compounds induced a dose dependent increase in chromosomal aberrations and sister chromatid exchanges, but that nitrogen mustard was 10 times more potent than nor-nitrogen mustard. Thus, the spectrum of activity for nor-nitrogen mustard and nitrogen mustard differ. Nor-nitrogen mustard was more effective in inducing point mutation damage than nitrogen mustard and a reversal of potency was found for cytogenetic damage. These results indicate that although these two substances induce the same type of DNA lesions the amounts of the different DNA adducts vary.
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The activity of fighting against SARS demonstrates the might of the Mobilization of National Economy. Practice has proven that Mobilization of National Economy is a very important means of national security. This paper analyses the Mobilization in fighting against SARS from 9 aspects, and from the angle of national security, it calls on people to use this opportunity of building up Emergency System to promote all kinds of national security preparation of Mobilization and make it an all-round Mobilization under the name of national security.
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The experiments reported here demonstrate the unexpected finding that, in mice, the pH of nitrogen mustard solution at the time it is injected into the animal appears to determine the toxicity of the material. At certain doses, highly acid solutions of nitrogen mustard show no toxic effects, while alkaline solutions at the same dose are invariably lethal. From further experiments on the antitumor activity of acid solutions of nitrogen mustard, it is cojpcluded that the toxic effect is separable from the antitumor effect.
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