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921.
Orcadian phase dependency in pharmacokinetics and hemodynamic effects on blood pressure and heart rate of different galenic formulations of nifedipine (immediate-release, sustained-release, and i.v. solution) were studied in healthy subjects or in hypertensive patients. Pharmacokinetics of immediate-release but not sustained-release and i.v. nifedipine were dependent on time of day: immediate-release nifedipine had higher Cmax (peak concentration) and shorter tmax (time-to-peak concentration) after morning than evening application, and bioavailibility in the evening was reduced by about 40%. Orcadian rhythm in estimated hepatic blood flow as determined by indocyanine green kinetics may contribute to these chronokinetics. A circadian time dependency was also found in nifedipine-induced effects on blood pressure and heart rate as monitored by 24-h ambulatory blood pressure measurements. In conclusion, the dose response relationship of oral nifedipine is influenced by the circadian organization of the cardiovascular system as well as by the galenic drug formulation. 相似文献
922.
Henrika G. M. Tiedink Laura H. J. De Haan Wim M. F. Jongen Jan H. Koeman 《Cell biology and toxicology》1991,7(4):371-386
4-chloro-methoxyindole is a naturally occurring compound in Vicia faba which can easily react with nitrite to form a N-nitroso compound. In this in vitro study, the potential genotoxic effects of nitrosated 4-chloro-6-methoxyindole and its structural analogue 4-chloroindole were evaluated for the first time by using both Salmonella and Chinese hamster V79 cells. Additionally, the inhibition of gap junctional intercellular communication in V79 cells by these compounds was determined; this is a validated parameter for tumor-promoting activity. Most assays were also performed with nitrosated indole-3-acetonitrile, a naturally occurring compound in brassicas. Both nitrosated chloroindoles were highly mutagenic to Salmonella typhimurium TA100 without the need of exogenous metabolic activation and were potent inducers of Sister Chromatid Exchanges. Nitrosated indole-3-acetonitrile generated the same effects, although at much higher concentrations. Equivocal results were obtained for the nitrosated chloroindoles in a forward mutation assay using the hypoxanthine guaninephosphoribosyltransferase locus. All nitrosated indole compounds significantly inhibited gap junctional intercellular communication. These results indicate that nitrosated chloroindoles and nitrosated indole-3-acetonitrile should be considered as mutagens and agents with potential tumor-promoting capacity.Abbreviations BrdU
5-bromo-2-deoxyuridine
- 4Cl
4-chloroindole
- 4C6MI
4-chloro-6-methoxy-indole
- DMSO
dimethyl sulfoxide
- EBSS
Earle's balanced salt solution
- EMS
ethyl methanesulfonate
- GJIC
gap junctional intercellular communication
- HBSS
Hanks balanced salt solution
- HGPRT
hypoxanthine guaninephosphoribosyl transferase
- I3A
indole-3-acetonitrile
- MNNG
1-methyl-1-nitroso-3-nitroguanidine
- NOC
N-nitroso compounds
- NQO
4-nitroquinolone-N-oxide
- SCE
sister chromatid exchange
- 6TG
6-thioguanine
- TPA
12-O-tetradecanoylphorbol-13-acetate 相似文献
923.
Extension of the range of recognition sequences for triple helix formation by oligonucleotides containing guanines and thymines. 总被引:11,自引:0,他引:11
J S Sun T De Bizemont G Duval-Valentin T Montenay-Garestier C Hélène 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1991,313(13):585-590
Oligodeoxynucleotides containing G and T can bind to homopurine.homopyrimidine sequences on double-stranded DNA by forming C.G x G and T.A x T base triplets. The orientation of the third strand in such triple helices depends on the number of GpT and TpG steps. Therefore a single oligonucleotide can be designed to bind to two consecutive homopurine.homopyrimidine sequences where the two homopurine stretches alternate on the two strands of DNA. The oligonucleotide switches from one homopurine strand to the other at the junction between the two sequences. This result shows that it is possible to extend the range of DNA sequences that can be recognized by a single oligonucleotide. 相似文献
924.
925.
Developmental expression of rat cardiac troponin I mRNA 总被引:4,自引:0,他引:4
S Ausoni C De Nardi P Moretti L Gorza S Schiaffino 《Development (Cambridge, England)》1991,112(4):1041-1051
926.
The North Sea, one of the most productive of the earth's seas and oceans, is also surrounded by some of earth's most densely
populated and heavily industrialized regions. A growing number of signals are being received which indicate that this valuable
ecosystem is increasingly under stress. This has generated a corresponding increase in concern over the steps to be taken
to protect the North Sea. While there are divergent views on what constitutes an ‘ideal’ North Sea, there is a general recognition
that any decisions that are made should be based on a good understanding of this ecosystem. The intention of this paper is
to give an overview of what is presently known, and to identify areas where more studies are needed. A brief summary of the
hydrography and the biota of the North Sea is given. Biotic and abiotic structure justify partitioning the North Sea into
three ecologically different regions: southern, central, and northern. For the most part, neither the top predators,e.g. marine birds and mammals, nor the macroalgae and sea grasses are included in this overview. 相似文献
927.
928.
929.
M Roncel M Hervás J A Navarro M A De la Rosa G Tollin 《European journal of biochemistry》1990,191(3):531-536
In order to compare the oxidation and reduction reactions of c-type cytochromes (cytochrome c552 from the green alga Monoraphidium braunii and horse heart cytochrome c) by different flavins (lumiflavin, riboflavin and FMN), laser flash photolysis studies have been carried out using either reduced or oxidized protein in the presence of triplet or semiquinone flavin, respectively. The reaction kinetics clearly demonstrate that cytochrome oxidation is mediated by the flavin triplet state. The rate constants for reduction are 20-100 times smaller than those for oxidation, indicating that the triplet state is a more effective reactant than is the semiquinone. This is attributed to its excited state nature and correspondingly high free energy content. The rate constants for both the reduction and oxidation of cytochrome c552 by riboflavin are significantly smaller than those obtained with lumiflavin, suggesting a steric interference of the ribityl side chain in the flavin-cytochrome interaction. The comparison between oxidation and reduction indicates that the former process is less affected by steric hindrance than the latter. Both reduction and oxidation of cytochrome c552 by FMN show an ionic strength dependence with the same sign, consistent with a negatively charged reaction site on the cytochrome. The magnitude of the electrostatic effect is slightly smaller for reduction than it is for oxidation. A pattern quite similar to that observed with cytochrome c552 was obtained when parallel experiments were carried out with horse cytochrome c, although differences were observed in the steric and electrostatic properties of the electron transfer site(s) in these two cytochromes. These results suggest that the same or closely adjacent sites on the proteins are involved in the oxidation and reduction reactions. The biochemical implications of this are discussed. 相似文献
930.
The role of positive charges located on the hydrophilic surface of the mitochondrial outer membrane channel was investigated by studying the interaction between LDAO-solubilized porin and a cation-exchanger column. The binding of porin to the column material was inhibited when the elution buffer had a pH of 9 or when 2 mM dextran sulfate was added to the buffer at neutral pH. Interestingly, the addition of a synthetic copolymer of methacrylate, maleate and styrene known as a potent modulator of the voltage-dependence, did not influence the interaction between column material and porin. Incubation of porin with fluorescein isothiocyanate (FITC) resulted in the isolation of a porin fraction in which on average two lysines located on the surface of the pore-forming complex per 35 kDa polypeptide were modified. The voltage-dependence of the fluorescein isothiocyanate modified porin was strongly decreased as compared with the unmodified porin. The experiments presented here give the first biochemical evidence that positively charged lysine residues located on the surface of the channel-forming complex are responsible for the gating of the mitochondrial porin-channel. 相似文献