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991.
M Culea N Palibroda M Chiriac Z Moldovan A D Abraham P T Frangopol 《Biological mass spectrometry》1991,20(11):740-742
A simple, rapid and sensitive method for procaine determination is described. Isotope dilution mass spectrometry with (15N)procaine as internal standard was used. The analysis was performed at 4000 resolution by selected ion monitoring with temperature programming. The sample was measured in underivatized form in the direct inlet system. The method shows good analytical parameters: linearity between 0 and 40 micrograms ml-1, good precision and accuracy. The method was applied to the in vitro pharmacokinetic study of the metabolism of procaine in liver homogenates of Wistar rats. The method is rapid, permitting about six samples to be run per hour. Sensitivity of the method permits analysis at a signal-to-noise ratio of 5:1. 相似文献
992.
Acyclovir triphosphate is a suicide inactivator of the herpes simplex virus DNA polymerase 总被引:27,自引:0,他引:27
The triphosphate form of 9-[(2-hydroxyethoxy)-methyl]guanine (acyclovir), ACVTP, inactivates the herpes simplex virus type 1 DNA polymerase. ACVTP does not innately inactivate resting polymerase, but becomes an inactivator only while being processed as an alternative substrate. Pseudo first-order rates of inactivation were measured at varying concentrations of ACVTP and fixed concentrations of the natural substrate, deoxyguanosine triphosphate. These studies indicated that a reversible enzyme-ACVTP (Michaelis-type) complex is formed at the active site prior to inactivation. The formation of this complex was competitively retarded by deoxyguanosine triphosphate. An apparent dissociation constant (KD) of 3.6 +/- 0.2 (S.D.) nM was determined for ACVTP from this reversible complex. A second method for the estimation of the KD which used the extrapolated initial velocities produced a value of 5.9 +/- 0.4 (S.D.) nM. The rate of conversion of the reversible complex to the inactivated complex, at saturating ACVTP, was calculated to be 0.24 min-1. No reactivation of enzyme activity was detected following isolation of the inactivated complex by rapid desalting on Sephadex G-25. Under these conditions, an overall reactivation rate of 1.5 X 10(-5) min-1 could have been easily detected. Therefore, the overall inhibition constant must have been less than 3 pM. In contrast, when host DNA polymerase alpha was incubated with 14 microM ACVTP, only 60% inhibition of enzyme activity was observed, but inactivation was not detected. These data indicate that ACVTP functions as a suicide inactivator of the herpes simplex virus type 1 DNA polymerase, and is only a weak reversible inhibitor of DNA polymerase alpha. 相似文献
993.
Bacterial pneumonia stimulates macromolecule secretion and ion and water fluxes in sheep trachea 总被引:1,自引:0,他引:1
Phipps R. J.; Torrealba P. J.; Lauredo I. T.; Denas S. M.; Sielczak M. W.; Ahmed A.; Abraham W. M.; Wanner A. 《Journal of applied physiology》1987,62(6):2388-2397
In vivo instillation of Pasteurella haemolytica (greater than or equal to 10(7) colony-forming units/kg) into a lobar bronchus of sheep produced bacterial pneumonia by 7 days postinoculation. Infection was verified bacteriologically and histologically. Macromolecule secretion and ion and water fluxes were subsequently measured in tracheal tissues in vitro and were compared with values from sham-infected sheep. Macromolecules were radiolabeled with 35SO4 and [3H]threonine, and we measured the secretion of macromolecule-bound radiolabel onto the mucosa. Unidirectional fluxes of Cl-, Na+, and water were measured with radioactive tracers under open-circuit and short-circuit conditions. Lung infection increased basal secretion of bound 35SO4 (by 189%) and bound [3H]-threonine (by 110%). It significantly increased net Na+ absorption under open- and short-circuit conditions and induced open-circuit net absorption of Cl- and water (16 +/- 29 microliters X cm-2 X h-1). These changes were associated with specific recruitment of neutrophils and elevated levels of arachidonate metabolites (thromboxane B2 and leukotriene B4) in the airways. Thus the bacterial pneumonia-induced changes in tracheal mucus secretion may be the result of airway inflammation. 相似文献
994.
The transport metabolism of [3H]quinolinic acid in the central nervous system of rabbits and rats were studied. In vitro [3H]quinolinic acid was not readily accumulated by isolated choroid plexus. After the intraventricular injection of tracer quantities of [3H]quinolinic acid, the [3H]quinolinic acid did not enter the brain as readily as concurrently injected [14C]mannitol and was not metabolized, The permeability-surface area constant for [3H]quinolinic acid at the rat blood-brain barrier was 1.5±1.3×10–5 sec–1 compared to 2.8±0.4×10–5 sec–1 for [3H]mannitol. Our results suggest that: 1) [3H]quinolinic acid is transported in the CNS by passive diffusion and 2) is not metabolized. 相似文献
995.
Reynold Spector 《Neurochemical research》1987,12(9):791-796
The unidirectional influx of hypoxanthine across cerebral capillaries, the anatomical locus of the blood=brain barrier, was measured with an in situ rat brain perfusion technique employing [3H]hypoxanthine. Hypoxanthine was transported across the blood-brain barrier by a saturable system with a one-half saturation concentration of approximately 0.4 mM. The permeability-surface area product was 3×10–4 sec–1 with a hypoxanthine concentration of 0.02 M in the perfusate. Adenine (4 mM) and uracil and theophylline (both 10 mM), but not inosine (10 mM) or leucine (1 mM), inhibited hypoxanthine transfer through the blood-brain barrier. Thus, hypoxanthine is transported through the blood-brain barrier by a high-capacity, saturable transport system with a half-saturation concentration about 100 times the plasma hypoxanthine concentration. Although involved in the transport hypoxanthine from blood into brain, this system is not powerful enough to transfer important quantities of hypoxanthine from blood into brain. 相似文献
996.
Extension of the fragment method to calculate amino acid zwitterion and side chain partition coefficients 总被引:6,自引:0,他引:6
The fragment method of calculating partition coefficients (P) has been extended to include the common amino acids (AAs). The results indicate that polar and charged side chains influence the hydrophobicity of atoms in the side chain in a predictable manner. Field effects, as evidenced through polar proximity factors and bond factors, need to be considered for accurate estimation of transfer phenomena. The calculated log P and delta G degree ' values of the 20 AAs agree well with the observed values. Pro calculates to be more hydrophilic than the observed log P. Hydrophobicity scales for peptide side chain residues are compared and evaluated in terms of suitability. Calculated pi values for nonpolar side chain residues agree well with the observed values; calculated values for uncharged polar side chain residues deviate by about 0.6 log units except for Gln and Cys; and polar side chain residues with charged side chains calculate as too hydrophilic. Reasons for the differences are explored. We also suggest that tightly bound water to polar moieties in amino acids and peptides may be transferred into the octanol phase during partitioning experiments. A quantitative methodology is presented which characterizes the thermodynamic partitioning of groups and individual atoms in amino acids and proteins. 相似文献
997.
998.
1. Isopenicillin N synthetase (IPNS) from Cephalosporium acremonium, which requires Fe2+ and O2 for activity, was highly purified for studies of factors affecting its conversion of delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV) into isopenicillin N (IPN). EDTA was used to quench the reaction by removal of Fe2+. 2. IPNS was inactivated during the course of the conversion of LLD-ACV into IPN, although it was relatively stable in the absence of LLD-ACV under otherwise similar conditions. In the presence of GSH and ascorbate each IPNS molecule carried out about 200 catalytic events before inactivation, but the turnover number was decreased 5-fold in the absence of ascorbate. 3. After trace metal ions had been removed from IPNS and other components of the reaction mixture by Chelex-100 resin, only about 10 microM-Fe2+ was required for maximum stimulation. Several other transition-metal ions were inhibitors of the enzyme. 4. Both dithiothreitol (DTT) and GSH stimulated IPNS activity, but GSH, unlike DTT, was not rapidly oxidized in the presence of O2 and Fe2+. 5. IPNS was rapidly inhibited by the thiol-blocking reagents N-ethylmaleimide and 2,2'- and 4,4'-dipyridyl disulphide, but not by 5,5'-dithiobis-(2-nitrobenzoic acid) in the same concentration. Inhibition by 2,2'-dipyridyl disulphide could be reversed by DTT. 相似文献
999.
Differences in the taste quality of maltose and sucrose in rats: issues involving the generalization of conditioned taste aversions 总被引:3,自引:3,他引:0
The present study employed a conditioned taste aversion generalizationparadigm to test the hypothesis that maltose produces tastesensations in the rat which are qualitatively distinguishablefrom sucrose. Since stimulus generalization can occur in boththe quality and intensity domains, an intrachemical (acrossconcentration) generalization gradient was established to aidin the interpretation of the interchemical (across molecules)generalization gradient. Moreover, since the commonly used intaketest is vulnerable to nontaste post-ingestional influences,the present study measured immediate responses to 100 µlstimulus samples, thus increasing our confidence that the behaviorwas under orosensory control. In Experiment 1, naive water deprivedrats were trained in a specially designed gustometer to maintaindrinking-spout contact for intermittent water reinforcement.Following this, rats in the experimental group were given threeexposures to 0.1 M sucrose on separate days, with the firsttwo exposures immediately preceding an injection of LiCl. Acontrol group was treated identically but received distilledwater instead of sucrose. Rats were then tested in the gustometerfor their avoidance of three equimolar concentrations of sucroseand maltose. Rats received ten trials of each stimulus quasi-randomlypresented in two sessions. Results indicated that all sucroseconcentrations were avoided (in experimental group only), butonly the 0.3 M concentration of maltose was avoided. The lowestsucrose concentration was significantly less avoided than thehigher concentrations. Intensity generalization gradients aresuch that intensities weaker than the conditioned stimulus (CS)produce just as much or less of a conditioned response (CR)and intensities stronger than the CS produce just as much ora greater CR than that elicited by the CS itself. Therefore,based on the results of Experimental, it was predicted thatif 0.1 M maltose served as the CS, the order of avoidance shouldbe: 0.3 M sucrose 0.1 M sucrose 0.03 M sucrose 0.3 M maltose 0.1 M maltose 0.03 M maltose, if it were true that maltoseand sucrose produce identical sensations that differ only inintensity. Experiment 2 explicitly tested this prediction usingthe same procedure as Experiment 1 except that 0.1 M maltoseserved as the CS. The observed order of avoidance was 0.3 Mmaltose > 0.1 M maltose > 0.03 M maltose = 0.3 M sucrose= 0.1 M sucrose = 0.03 M sucrose. In both experiments the intrachemicalgeneralization gradient broadened and the interchemical generalizationgradient steepened upon retesting. In conclusion, qualitativedifferences between maltose and sucrose explain the outcomesof these experiments better than differences in the relativeintensity of these sugars at isomolar concentrations. 相似文献
1000.
Hydroxyeicosatetraenoic acids (HETEs) 总被引:14,自引:0,他引:14