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41.
The growth-promoting activity of PDGF-BB was studied on the adult osteoclasts in the present study. The PDGF receptor beta was detected on the osteoclast membrane through immunohistochemistry (LSAB method) and immunomicroscopy. The PDGF-BB was exerted on the osteoclasts that adhered to the bone slice at concentrations of 0, 10, 20, 30, and 40 ng/ml. The volume of Howship's lacuna augmented significantly and the number of resorption pits also increased with its dose (p < 0.01). The activity of both total acid phosphatase (ACP) and tartrate-resistant acid phosphatase (TRAP) increased significantly. These results suggest that PDGF-BB promotes adult osteoclastic bone resorption directly through PDGF receptor beta and is believed to play important roles in the bone healing process and reconstruction. 相似文献
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We studied the interaction of azole antimycotics with intravenous (IV) and oral midazolam using a cross-over design in 12 volunteers, who ingested placebo, itraconazole, or fluconazole for 6 days. A 7.5-mg dose of midazolam was ingested on the first day, 0.05 mg/kg was administered IV on the fourth day, and 7.5 mg orally on the sixth day. Itraconazole reduced the clearance of IV midazolam by 69% and fluconazole reduced the clearance of IV midazolam by 51% (P < 0.001). A single dose of itraconazole and fluconazole increased the area under the oral midazolam concentration-time curve [AUC(0-infinity)] 3.5-fold (P < 0.001) and the peak concentration two-fold (P < 0.05) compared to placebo. On the sixth day the AUC(0-infinity) of oral midazolam was almost seven times greater with itraconazole (P < 0.001) and 3.6 times greater with fluconazole (P < 0.001) than without the antimycotics. The psychomotor effects of midazolam were also profoundly increased (P < 0.001). The psychomotor tests demonstrated only a weak interaction between the antimycotics and IV midazolam. When bolus doses of midazolam are given for short- time sedation, the effect of midazolam is not increased to a clinically significant degree by itraconazole and fluconazole, and it can be used in normal doses. However, the use of large doses of IV midazolam increases the risk of clinically significant interactions also after IV midazolam. Use of oral midazolam with itraconazole and fluconazole should be avoided. 相似文献
44.
KT Blackwell 《Canadian Metallurgical Quarterly》1998,38(2):267-280
The influence of high-frequency microstimulation (HFMS) of one of the hemispheres on the parameters of spontaneous gamma-oscillations in the neural network containing callosal cells of the motor cortex of both hemispheres. There were three modes in the background oscillation periods distribution, which corresponded to the frequencies 40-60, 70-100, and 100-200 Hz. These oscillation frequencies were also revealed after the HFMS in neural interactions of the cells, which were active before the HFMS; the frequency 40-60 Hz, which dominated before the HFMS, became even more pronounced. The same three groups of oscillation frequencies were found in the activity of cells which became active after the HFMS. The expression of oscillations, the number of oscillatory interactions, as well as the number of neuronal pairs with additional synchronization decreased after the HFMS, which suggests a decrease in synchronization. Taking into account the results of simulation experiments that the frequency of gamma-oscillations is determined by the strength of inhibitory and excitatory input, we suggest that the long-term posttetanic modifications in the efficacy of synaptic inputs of the neurons of both hemispheres underlie the observed posttetanic changes. 相似文献
45.
KR Romines JK Morris WJ Howe PK Tomich MM Horng KT Chong RR Hinshaw DJ Anderson JW Strohbach SR Turner SA Mizsak 《Canadian Metallurgical Quarterly》1996,39(20):4125-4130
Previously, 3-substituted cycloalkylpyranones, such as 2d, have proven to be effective inhibitors of HIV protease. In an initial series of 3-(1-phenylpropyl) derivatives with various cycloalkyl ring sizes, the cyclooctyl analog was the most potent. We became interested in exploring the influence of other structural changes, such as substitution on the phenyl ring and saturation of the 5,6-double bond, on the cycloalkyl ring size structure-activity relationship (SAR). Saturation of the 5,6-double bond in the pyrone ring significantly impacts the SAR, altering the optimal ring size from eight to six. Substitution of a sulfonamide at the meta position of the phenyl ring dramatically increases the potency of these inhibitors, but it does not change the optimal ring size in either the cycloalkylpyranone or the cycloalkyldihydropyrone series. This work has led to the identification of compounds with superb binding affinity for the HIV protease (Ki values in the 10-50 pM range). In addition, the cycloalkyldihydropyrones showed excellent antiviral activity in cell culture, with ED50 values as low as 1 microM. 相似文献
46.
LA Pagan-Carlo JJ Allan KT Spencer CL Birkett R Myers RE Kerber 《Canadian Metallurgical Quarterly》1998,32(7):2065-2071
OBJECTIVES: This study was performed to determine the efficacy of new encircling overlapping multipulse, multipathway waveforms for transthoracic defibrillation. BACKGROUND: Alternative waveforms for transthoracic defibrillation may improve shock success. METHODS: First, we determined the shock success achieved by three different waveforms at varying energies (18-150 J) in 21 mongrel dogs after short-duration ventricular fibrillation. The waveforms tested included the traditional damped sinusoidal waveform, a single pathway biphasic waveform, and a new encircling overlapping multipulse waveform delivered from six electrode pads oriented circumferentially. Second, in 11 swine we compared the efficacy of encircling overlapping multipulse shocks given from six electrode pads and three capacitors versus encircling overlapping shocks given from a device utilizing three electrodes and one capacitor. RESULTS: In the first experiment, the encircling overlapping waveform performed significantly better than biphasic and damped sinusoidal waveforms at lower energies. The shock success rate of the overlapping waveform (six pads) ranged from 67+/-4% (at 18-49 J energy) to 99+/-3% at > or = 150 J; at comparable energies biphasic waveform shock success ranged from 26+/-5% (p < 0.01 vs. encircling overlapping waveforms) to 99+/-5% (p = NS). Damped sinusoidal waveform shock success ranged from 4+/-1% (p < 0.01 vs. encircling overlapping waveform) to 73+/-9% (p = NS). In the second experiment the three electrode pads, one capacitor encircling waveform achieved shock success rates comparable with the six-pad, three-capacitor waveform; at 18-49 J, success rates were 45+/-15% versus 57+/-12%, respectively (p = NS). At 100 J, success rates for both were 100%. CONCLUSIONS: We conclude that encircling overlapping multipulse multipathway waveforms facilitate transthoracic defibrillation at low energies. These waveforms can be generated from a device that requires only three electrodes and one capacitor. 相似文献
47.
W Chen Y Zhou J Nichols KT Chung RW Hart MW Chou 《Canadian Metallurgical Quarterly》1996,19(1-2):21-39
Hepatic microsomal xenobiotic metabolizing enzyme activities of laboratory animals can be modulated by Dietary restriction (DR). The modulation of xenobiotic metabolizing enzyme activities can affect the metabolic activation of chemical carcinogens. Acute DR (60% of the food consumption of ad libitum (AL)-fed mice for 7 weeks) reduced the body weights of the male B6C3F1 mice, and increased mouse pulmonary cytochrome P4501A1-dependent BaP metabolizing enzyme activity. The effects of DR on the formation of the specific BaP-DNA adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (BaP-N2-dG) in mouse lung can be detected by using 32P-postlabeling technique. In both AL- and DR-mice total BaP-DNA adduct formation in lung reached a peak at 48 hours after treatment with [3H]BaP and the in vivo formation of BaP-N2-dG was greater in DR mouse lung than in that of AL-animals by 22%. DR increased in vitro BaP-N2-dG formation by 39% when calf-thymus DNA was incubated with BaP using liver microsomes obtained from DR- or AL-mice as the enzyme source. The formation of the specific BaP-N2-dG adducts, measured by 32P-postlabeling, was only 20% of the total [3H]BaP-DNA adducts as determined by liquid scintillation counting. The increase of BaP-DNA adduct formation in mouse lung was correlated to the enhancement of the mouse pulmonary BaP metabolizing enzyme activity. Our results indicated that the effect of DR on the metabolic activation of BaP in mouse lung was dependent upon the mouse lung cytochrome P4501A1-dependent BaP metabolizing enzymes activities which was significantly increased by DR. 相似文献
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