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1.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
2.
Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of nteeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth nteeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔEWSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔEWSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL. 相似文献
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Rodolphe Korichi Sophie Mac-Mary Ahmed Elkhyat Jean-Marie Sainthillier Pascal Ränsch Philippe Humbert Eric Viviant Germaine Gazano Christian Mahé 《Skin research and technology》2006,12(3):206-210
BACKGROUND/AIMS: The purpose of this work was to develop a new sensor for objective in vivo measurement of the cutaneous temperature based on micro-electro-mechanical systems (MEMS), and to compare these performances with those of a classical thermocouple. Research on this new sensor was carried out to allow the quantification of the thermal properties of the made-up skin. METHODS: Sixteen female subjects divided into two different age groups (18-35 and >50 years old) were recruited for this study. Several zones of the face and forearms were made up at random with foundations containing or not a thermoregulator raw material. The quantity of foundation applied on the skin was standardized and measurements were carried out first before make-up, and then 10 s and 5 min after make-up. The new sensor and the thermocouple were used successively on each zone. The cutaneous temperature was expressed in degrees celsius. RESULTS/CONCLUSION: The two systems are similar in terms of repeatability and reproducibility, with some differences in sensibility. The data measured by the MEMS sensor appear lower than those measured by the thermocouple. After make-up, the MEMS sensor detects a progressive increase of the temperature in time whereas the thermocouple detects a decrease. We found the same evolution on the face but in a more attenuated way. These results tend to show that the devices do not measure the same phenomenon. The thermocouple appears more sensitive to the thermal response of the made-up surface whereas the MEMS sensor appears more sensitive to the heat transfers in the interface between the skin and make-up. 相似文献
6.
As a consequence of the time-varying magnetic field induced by eddy currents, frequency drifting occurs when the sampling window of localized spectroscopy continuously shifts. The frequency drifting and the concomitant phase variations can severely affect spectroscopy results when data are acquired with multiple echo times (TEs), such as in the measurement of glutamate (Glu) concentration using the TE-averaged method. Specifically, the averaged spectra are further broadened and distorted in the presence of residual eddy currents, and editing of the coupled spins of Glu C4 protons is affected, resulting in errors in the measured relative intensity ratio. Postacquisition correction using unsuppressed water as reference can effectively minimize this detrimental effect, as manifested by the significantly enhanced signal intensity. Also, it is demonstrated that the methyl signals of creatine (Cr) at 3.0 ppm and choline (Cho) at 3.2 ppm can be used as internal references in finding frequency and phase disparities between different TEs. 相似文献
7.
Sachiko Goto Akiyoshi Tsuji Teiko Murai Minoru Nishida Hiroko Tsukano Haruo Watanabe 《Journal of infection and chemotherapy》1998,4(1):16-19
Although there are effective antibacterial agents against plague, newer antibacterial agents have been developed which show
more potent activity against other bacterial organisms, but have not been tested againstYersinia pestis. A strain ofYersinia pestis was selected (no. 22; National Institute of Infectious Diseases, Tokyo, Japan) that caused a systemic infection in mice.Y. pestis no. 22 was intraperitoneally inoculated into DDY-strain mice, and 13 oral or 6 injectable antibacterial drugs given to the
infected mice at varying doses 1 and 24 hours after infection. Levofloxacin, sparfloxacin and ofloxacin were the most effective
oral agents against the infection, and prulifloxacin and pazufloxacin were also effective but to a lesser extent. Also, gentamicin
and arbekacin were the most potent injectable antibacterial agents againstY. pestis. These results suggest that there are several new drugs, both oral and injectable, which exert excellent in vivo antibacterial
activity against a mouse infection model and may be useful for the clinical treatment of plague. 相似文献
8.
Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of
galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated
insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect
of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin
lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80
pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas
arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets
was dose-dependently suppressed by galanin (10-6-10-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower
dose levels, the peptide also inhibits basal glucagon release. 相似文献
9.
目的建立人离体骨肉瘤血管亲和筛选模型。方法(1)建立模型。术前对患肢局部行数字减影造影检查,标记肿瘤固有动脉大致走行,术后小心修剪,并连接类似于Langendorff的灌流装置,监控模型血管内的pH值、温度、氧分压等;(2)对噬菌体十二肽库进行筛选。结果28例骨肉瘤离体标本均建模成功,可直接用于灌流实验,并筛选出具有较高特异性的亲和短肽(基序为RLTR),各项指标显示离体骨肉瘤较好模拟了人体内的环境。结论建立人离体骨肉瘤血管亲和筛选模型是可行的,可直接用于对噬菌体随机肽库的亲和筛选,为骨肉瘤的靶向化疗提供参考。 相似文献
10.
Skoug John W. Borin Marie T. Fleishaker Joseph C. Cooper Anne M. 《Pharmaceutical research》1991,8(12):1482-1488
The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets. 相似文献