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31.
KR Korzekwa N Krishnamachary M Shou A Ogai RA Parise AE Rettie FJ Gonzalez TS Tracy 《Canadian Metallurgical Quarterly》1998,37(12):4137-4147
Some cytochrome P450 catalyzed reactions show atypical kinetics, and these kinetic processes can be grouped into five categories: activation, autoactivation, partial inhibition, substrate inhibition, and biphasic saturation curves. A two-site model in which the enzyme can bind two substrate molecules simultaneously is presented which can be used to describe all of these observed kinetic properties. Sigmoidal kinetic characteristics were observed for carbamazepine metabolism by CYP3A4 and naphthalene metabolism by CYPs 2B6, 2C8, 2C9, and 3A5 as well as dapsone metabolism by CYP2C9. Naphthalene metabolism by CYP3A4 and naproxen metabolism by CYP2C9 demonstrated nonhyperbolic enzyme kinetics suggestive of a low Km, low Vmax component for the first substrate molecule and a high Km, high Vmax component for the second substrate molecule. 7, 8-Benzoflavone activation of phenanthrene metabolism by CYP3A4 and dapsone activation of flurbiprofen and naproxen metabolism by CYP2C9 were also observed. Furthermore, partial inhibition of 7, 8-benzoflavone metabolism by phenanthrene was observed. These results demonstrate that various P450 isoforms may exhibit atypical enzyme kinetics depending on the substrate(s) employed and that these results may be explained by a model which includes simultaneous binding of two substrate molecules in the active site. 相似文献
32.
BR Hoar BB Chomel FJ Argazz Rodriguez PA Colley 《Canadian Metallurgical Quarterly》1998,212(11):1714-1720
PURPOSE: The purpose of this study was to develop an analytical method for the quantitative determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF using Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFT) with Kubelka-Munk function analysis. METHODS: Carbopol 974P NF is a high molecular weight, chemically crosslinked polymer of acrylic acid, that has the C=O stretching band of the unionized carboxylic acid function at 1695 cm(-1). The quantitative determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF is based upon the asymmetrical C=O stretching of the carboxylate anion at 1570 cm(-1) measured by DRIFT spectroscopy. RESULTS: To overcome spectral differences arising from sample preparation (powders, granules and tablets) and in an effort to increase the precision of the analytical method, the following approaches were used: (1) an internal standard, (2) first derivative of the spectrum to eliminate the effect of baseline drift and (3) the ratio of the first derivative of the C=O stretch of the carboxylate anion peak (1570 cm(-1)) in the neutralized Carbopol 974P NF to that of the peak of the internal standard (866 cm(-1)). The above data treatment techniques proved to be superior to the usual methods of peak height or peak area. The calibration curve of the ratio of the first derivative (1570 cm(-1)/866 cm(-1)) was a linear function of the mass of sodium carboxylate over the range from 0.0% to 100.0% neutralization of the carboxylic acid function in Carbopol 974P NF (Fig. 1a). No particle size or sample preparation effects were noted within the experimental error. CONCLUSIONS: DRIFT spectroscopy using the Kubelka-Munk function is a powerful tool for the routine determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF in complex pharmaceutical formulations. 相似文献
33.
MH van Hooff RA Hirasing MB Kaptein C Koppenaal FJ Voorhorst J Schoemaker 《Canadian Metallurgical Quarterly》1998,77(9):898-904
BACKGROUND: Oral contraceptives are prescribed as contraception but also as therapy for menstrual cycle disturbances and acne. We studied the prevalence of oral contraceptive (OC) use and the indications to start OC use among adolescents. METHODS: A cohort consisting of ninth grade secondary school girls (mean age 15.3+/-0.6 (s.d.) years) answered a questionnaire on their menstrual cycle. OC users were asked about duration and reasons for OC-use and the name of the preparation they used. The influence of calendar age, gynecological age and level of education on the prevalence of OC was studied by multiple logistic regression analysis. RESULTS: The response on the questionnaire was 92%. Of 2248 responders 248 (11%) used oral contraceptives: 74% used low dose 'sub 50' preparations, 3% pills with 50 microg estrogen, 3% tri-phase preparations and 17% pills with antiandrogens. Of girls aged 14, 15 and 16 years 4%, 12% and 28% respectively, used OC. Of the 15-year-olds 31% mentioned contraception as most important reason for OC use, 18% menstrual cycle irregularity, 26% dysmenorrhea, 10% acne and 5% other reasons. Calendar age, gynecological age and level of education were independent variables for OC use in general and for OC use for contraception or dysmenorrhea, but less so for OC use for menstrual cycle irregularity or acne. CONCLUSIONS: During adolescence low dose OC's were frequently used. In The Netherlands OC use among girls aged 15 and 16 years doubled in comparison with 1982. One third of the adolescent OC-users mentioned contraception as most important reason to start OC. Gynecological age (a determinant of biological maturation), calendar age (a determinant of biological maturation and lifestyle in peer groups), and level of education (a determinant of lifestyle in peer groups) were associated with OC use. 相似文献
34.
MJ Bruno FJ Hoek B Delzenne DJ van Leeuwen CD Schteingart AF Hofmann GN Tytgat 《Canadian Metallurgical Quarterly》1995,41(4):599-604
Two noninvasive tests for assessing pancreatic exocrine function, the cholesteryl-[14C]octanoate breath test and the HPLCN-benzoyl-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test, were simultaneously performed in nine patients with pancreatic exocrine insufficiency due to chronic pancreatitis and in nine healthy volunteers. 14CO2 output in breath and plasma PABA concentration rose slowly in patients but increased rapidly in healthy subjects. The measurement time giving the best discrimination between both groups was 120 min for the cholesteryl-[14C]octanoate breath test and 90 min for the plasma PABA test. At these points, both single-sample tests had essentially identical diagnostic sensitivity. The diagnostic sensitivities of the two single-sample tests were equal to that of the cumulative 6-h urinary PABA recovery and the cumulative 6-h urinary PABA/PAS ratio. We conclude that, for both the cholesteryl-[14C]octanoate breath test and the plasma PABA test, a single test sample is sufficient for rapid detection of impaired exocrine pancreatic function. 相似文献
35.
JC van der Voet RB Keus AA Hart FJ Hilgers H Bartelink 《Canadian Metallurgical Quarterly》1998,42(2):247-255
Low frequency impedance measurements of pure egg lecithin (phosphatidylcholine) bilayers have revealed the presence of four layers which can be attributed to the acyl chain, carbonyl, glycerol bridge and phosphatidylcholine regions of the lecithin molecule. Measurements on bilayers formed in the presence of unoxidised-cholesterol revealed that cholesterol molecules were located in the hydrocarbon region of the bilayer with its hydroxyl groups aligned with the carbonyl region of the lecithin molecules. Measurements of oxidised-cholesterol lecithin bilayers revealed that these molecules protruded less into the hydrocarbon region and their polar hydroxyl group aligned with the glycerol bridge region of the lecithin molecule. 相似文献
36.
EM Utens HJ Bieman FC Verhulst FJ Meijboom RA Erdman J Hess 《Canadian Metallurgical Quarterly》1998,19(4):647-651
Non-steroidal anti-inflammatory drugs inhibit constitutive (COX-1) and induced cyclooxygenase (COX-2), blocking prostaglandin production. We have compared the effects on nociceptive reflexes of meloxicam, which is COX-2 selective, with indomethacin, which is non-selective, using an in vitro spinal cord preparation. Cords were taken from naive rats, and from rats with carrageenan-induced hyperalgesia of one hindpaw. Reflex thresholds were lower in carrageenan preparations. Superfusion with meloxicam (10-100 microM) dose-dependently inhibited baseline reflexes and wind-up in normal and carrageenan preparations, whereas indomethacin (100-300 microM) had no effect. Thus meloxicam inhibits spinal reflexes, whereas indomethacin does not, despite its high affinity for both COX isoforms. We conclude that meloxicam has spinal antinociceptive actions which cannot be explained by the current concept of COX inhibition. 相似文献
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40.
WC Duckworth CD Saudek A Giobbie-Hurder WG Henderson RR Henry DE Kelley SV Edelman FJ Zieve RA Adler JW Anderson RJ Anderson BP Hamilton TW Donner MS Kirkman NA Morgan 《Canadian Metallurgical Quarterly》1998,21(10):1596-1602
OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels. 相似文献