Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics

Concomitant administration of botanical supplements with drugs that are P-glycoprotein (P-gp) substrates may produce clinically significant herb-drug interactions. This study evaluated the effects of St. John's wort and Echinacea on the pharmacokinetics of digoxin, a recognized P-gp substrate. Eighteen healthy volunteers were randomly assigned to receive a standardized St. John's wort (300 mg three times daily) or Echinacea (267 mg three times daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (300 mg twice daily, 7 days) and clarithromycin (500 mg twice daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin 0.25 mg) was administered orally before and after each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), elimination half-life, and maximum serum concentration were used to assess the effects of St. John's wort, Echinacea, rifampin, and clarithromycin on digoxin disposition. St. John's wort and rifampin both produced significant reductions (p < 0.05) in AUC((0-3)), AUC((0-24)), and C(max), while clarithromycin increased these parameters significantly (p < 0.05). Echinacea supplementation did not affect digoxin pharmacokinetics. Clinically significant P-gp-mediated herb-drug interactions are more likely to occur with St. John's wort than with Echinacea.     

Pretraining enhances recovery from visuospatial deficit following cerebellar dentate nucleus lesion.

Following bilateral lesions targeting lateral deep cerebellar nuclei, rats were subjected to a bridge test as a measure of visuomotor coordination and were trained on the Morris water maze (MWM) as a measure of visuospatial processing. Lesioned rats were significantly impaired in visuospatial processing, but not visuomotor coordination, relative to sham rats. In a 2nd experiment, rats were pretrained on a delayed spatial alternation task (T maze) before MWM training. Pretraining reversed the visuospatial deficit caused by the lesions as compared with nonpretrained rats. Results suggest that lateral deep cerebellar nuclei contribute to visuospatial processing with a negligible contribution to visuomotor skills and that visuospatial deficits resulting from lateral nuclei damage can be reversed with pretraining on a spatial working memory task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Investigation on nanocrystalline copper-doped zirconia thin films for optical sensing of carbon monoxide at high temperature

Nanocrystalline copper-doped zirconia (CDZ; Cu:Zr = 16:84) thin films have been synthesized on long-period fiber gratings (CDZ-LPFG) by a polymeric precursor method. The CDZ-LPFG device was demonstrated to have high sensitivity and good reversibility for low-concentration CO sensing at high temperatures. The CDZ-LPFG responds with red shifts of its resonant wavelength (λ_R) to CO-containing gases and the λ_R shift reverses when it is exposed to air. The optical response of the CDZ-LPFG to CO is due primarily to the CDZ refractive index variations resulted from the reversible redox reactions (i.e. Cu²⁺ ⇔ Cu⁺) in reducing and oxidizing atmospheres. The magnitude of the λ_R shift exhibited a strong dependence on CO concentration in a range from 0 to 1000 ppm that is potentially useful for quantitative measurement.     

Automated statistical approach to Langley evaluation for a solar radiometer

We present a statistical approach to Langley evaluation (SALE) leading to an improved method of calibration of an automated solar radiometer. Software was developed with the SALE method to first determine whether a day is a good calibration day and then to automatically calculate an intercept value for the solar radiometer. Results from manual processing of calibration data sets agree with those of the automated method to within the errors of each approach.     

1536孔板的洗涤：评价一种新型的双列吸液系统

基面效价测定（如酶联免疫及基于细胞的实验）通常需要程序洗板（1536孔）,这就使得一些高通量筛选实验室由于缺乏可靠的设备而无法常规进行这种实验。目前的1536孔板洗板机是采用8支针同时孔内加液,单列32支吸头从孔内一次性吸取液体,每次一列。事实上,这种多步操作严重地影响了实验效率。经统计,如果测定中包含洗板步骤,每24h的测试量为100板,而除去此限速步骤,相同时间内的测定量可增至500。因此,我们发明了一种64支吸头双列吸液装置用以弥补这种差距。结果表明此方法有效地提高了工作效率,并同样获得了较好的实验数据。     

Assessment of alkali–silica reaction damage through quantification of concrete nonlinearity

A newly developed nondestructive evaluation technique, Nonlinear Impact Resonance Acoustic Spectroscopy (NIRAS), is applied to concrete specimens in an ongoing assessment of aggregate alkali reactivity during standard concrete prism testing. NIRAS measures the nonlinearity in a specimen caused by the inception and growth of microcracks throughout the sample and debonding at the aggregate/cement interface. NIRAS is used to exploit the nonlinear effect of excitation amplitude dependent resonance frequency changes, which are related to nonlinearity measurements of concrete samples cast with aggregates of varying reactivity. To relate microstructural changes to changes in nonlinearity and expansion, sample characterization is performed with uranyl-acetate staining. The results demonstrate the utility of NIRAS for not only assessing the potential for ASR under standardized test conditions, but for more general damage characterization in concrete and assessment of “job mixtures.” NIRAS can distinguish reactive from nonreactive aggregates without ambiguity, as supported by sample characterization results.     

Probabilistic evaluation of concrete freeze-thaw design guidance

A novel limit-state function using Powers’ models is developed to assess current freeze-thaw exposure categories and design criteria for concrete placements established by American, Canadian, and European standards organizations. Based upon performance assessments by standardized accelerated testing, the current specifications are shown to provide sufficient levels of reliability pending an appropriate mean air-void spacing factor. Sensitivity assessments of the model demonstrate that the spacing factor, saturation state, permeability, and freezing rate significantly influence the response of the air-entrained concrete. The model is validated with a large dataset derived from standard freeze-thaw tests, and an equation is developed to probabilistically design concrete for freeze-thaw resistance.     

Analytical solution for integrating sphere spectral efficiency inclusive of atmospheric attenuation

An analytical solution to the attenuation of flux within an integrating sphere due to spherical integrating source coating, exit port escape, and atmospheric absorption is derived employing a geometric probability distribution of completed sphere transits. This is used to determine the mean number of completed sphere transits and its variance. Equations that provide the attenuation ratios for the three extinction mechanisms are derived using the energy balance and summation of reflection methods. The mean length of a transit of the sphere and its variance are presented and used to derive expressions for the mean and variance of photon path lengths in the sphere.     

Time to failure for concrete exposed to severe sulfate attack

In the 1940s, the U.S. Bureau of Reclamation (USBR) began a long-term, nonaccelerated laboratory test program to determine the influence of a variety of concrete-mix parameters on resistance to severe sulfate exposure conditions. This paper reports the time of failure of these samples as influenced by their water-to-cement (w/c) ratio, cement composition, and percent replacement of cement with fly ash. The analysis indicates that there is a “safe zone” for concrete made with w/c ratio lower than 0.45 and cement with unhydrated tricalcium aluminate (C₃A) content lower than 8% where failure did not occur within the 40-year exposure period. As expected, concrete samples cast with high amount of C₃A failed after a relatively short time of sulfate exposure. Expansion tests indicated that cements containing high amounts of C₃S may lead to premature failure of concrete, even when moderate w/c ratios are used. Samples prepared with 25% and 45% replacement of cement with fly ash showed significantly less expansion than comparable mixtures containing no pozzolans.