Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection

Since diabetes mellitus and osteoarthritis are highly prevalent diseases, combinations of antidiabetic agents like repaglinide (REP) and non-steroidal anti-inflammatory drugs (NSAID) like celecoxib (CEL) could be commonly used in clinical practice. In this study, a simple and sensitive bioanalytical HPLC method combined with fluorescence detector (HPLC-FL) was developed and fully validated for simultaneous quantification of REP and CEL. A simple protein precipitation procedure and reversed C18 column with an isocratic mobile phase (mixture of ACN and pH 6.0 phosphate buffer) were employed for sample preparation and chromatographic separation. The fluorescence detector was set at a single excitation/emission wavelength pair of 240 nm/380 nm. The linearity (10–2000 ng/mL), accuracy, precision, extraction recovery, matrix effect, and stability for this method were validated as per the current FDA guidance. The bioanalytical method was applied to study pharmacokinetic interactions between REP and CEL in vivo, successfully showing that concurrent administration with oral REP significantly altered the pharmacokinetics of oral CEL. Furthermore, an in vitro metabolism and protein binding study using human materials highlighted the possibility of metabolism-based interactions between CEL and REP in clinical settings.

Profiling of fine- and coarse-mode particles with LIRIC (LIdar/Radiometer Inversion Code)

The paper investigates numerical procedures that allow determining the dependence on altitude of aerosol properties from multi wavelength elastic lidar signals. In particular, the potential of the LIdar/Radiometer Inversion Code (LIRIC) to retrieve the vertical profiles of fine and coarse-mode particles by combining 3-wavelength lidar measurements and collocated AERONET (AErosol RObotic NETwork) sun/sky photometer measurements is investigated. The used lidar signals are at 355, 532 and 1064 nm. Aerosol extinction coefficient (αL), lidar ratio (LRL), and Ångstrom exponent (ÅL) profiles from LIRIC are compared with the corresponding profiles (α, LR, and Å) retrieved from a Constrained Iterative Inversion (CII) procedure to investigate the LIRIC retrieval ability. Then, an aerosol classification framework which relies on the use of a graphical framework and on the combined analysis of the Ångstrom exponent (at the 355 and 1064 nm wavelength pair, Å(355, 1064)) and its spectral curvature (ΔÅ = Å(355, 532)–Å(532, 1064)) is used to investigate the ability of LIRIC to retrieve vertical profiles of fine and coarse-mode particles. The Å-ΔÅ aerosol classification framework allows estimating the dependence on altitude of the aerosol fine modal radius and of the fine mode contribution to the whole aerosol optical thickness, as discussed in Perrone et al. (2014). The application of LIRIC to three different aerosol scenarios dealing with aerosol properties dependent on altitude has revealed that the differences between αL and α vary with the altitude and on average increase with the decrease of the lidar signal wavelength. It has also been found that the differences between ÅL and corresponding Å values vary with the altitude and the wavelength pair. The sensitivity of Ångstrom exponents to the aerosol size distribution which vary with the wavelength pair was responsible for these last results. The aerosol classification framework has revealed that the deviations between LIRIC and the corresponding CII-procedure retrieval products are due to the fact that LIRIC does not allow to the modal radius of fine mode particles to vary with the altitude. It is shown that this represents the main source of uncertainties in LIRIC results. The plot on the graphical framework of the Å-ΔÅ data points retrieved from the CII-procedure has indicated that the fine-mode-particle modal radius can vary with altitude when particles from different sources and/or from different advection routes contribute to the aerosol load. Analytical back trajectories combined with linear particle depolarization ratio profiles from lidar measurements at 355 nm and dust concentrations from the Barcelona Supercomputing Center-Dust REgional Atmospheric Model (BSC-DREAM) have been used to demonstrate the dependence on altitude of the aerosol properties.

Evolution of multispectral aerosol optical properties in a biogenically-influenced urban environment during the CARES campaign

Ground-based aerosol measurements made in June 2010 within Sacramento urban area (site T0) and at a 40-km downwind location (site T1) in the forested Sierra Nevada foothills area are used to investigate the evolution of multispectral optical properties as the urban aerosols aged and interacted with biogenic emissions. Along with black carbon and non-refractory aerosol mass and composition observations, spectral absorptio (βabs), scattering (βsca), and extinction (βext) coefficients for wavelengths ranging from 355 to 1064 nm were measured at both sites using photoacoustic (PA) instruments with integrating nephelometers and using cavity ring-down (CRD) instruments. The daytime average Ångström exponent of absorption (AEA) was ~1.6 for the wavelength pair 405 and 870 nm at T0, while it was ~1.8 for the wavelength pair 355 and 870 nm at T1, indicating a modest wavelength-dependent enhancement of absorption at both sites throughout the study. The measured and Mie theory calculations of multispectral βsca showed good correlation (R2=0.85–0.94). The average contribution of supermicron aerosol (mainly composed of sea salt particles advected in from the Pacific Ocean) to the total scattering coefficient ranged from less than 20% at 405 nm to greater than 80% at 1064 nm. From 22 to 28 June, secondary organic aerosol mass increased significantly at both sites due to increased biogenic emissions coupled with intense photochemical activity and air mass recirculation in the area. During this period, the short wavelength scattering coefficients at both sites gradually increased due to increase in the size of submicron aerosols. At the same time, BC mass-normalized absorption cross-section (MAC) values for ultraviolet wavelengths at T1 increased by ~60% compared to the relatively less aged urban emissions at the T0 site. In contrast, the average MAC values for 870 nm wavelength were identical at both sites. These results suggest formation of moderately brown secondary organic aerosols formed in biogenically-influenced urban air.

Probabilistic analysis of fluorescence signals for monitoring dual reticulation water recycling schemes

Improved techniques are required for the detection of inadvertent cross-connections between recycled water and potable water systems in dual reticulation schemes. The aim of this research was to assess the potential for fluorescence spectroscopy to be developed as a tool to distinguish recycled water from potable water. Weekly grab samples of recycled and potable water were obtained over 12 weeks from within an Australian dual reticulation site and analysed for fluorescence excitation-emission matrix (EEM), dissolved organic carbon (DOC), electrical conductivity (EC), and pH. Probabilistic techniques including distribution function fitting and Monte Carlo simulation were used to assess the ability to distinguish between recycled water and potable water sample pairs and the reliability of doing so. Fluorescence EEM spectroscopy was determined to be the most effective for the reliable differentiation by monitoring the protein-like fluorescence at peak T1—an excitation-emission wavelength pair of λex/em=300/350 nm. While EC could distinguish between recycled and potable water, it was shown to be less sensitive and less reliable than peak T1 fluorescence.

Theoretical analysis of crosstalk between oxygenated and deoxygenated haemoglobin in focal brain-activation measurements by near-infrared topography

The crosstalk between concentration changes in oxygenated haemoglobin and deoxygenated haemoglobin calculated by the modified Lambert-Beer law in near-infrared topography is theoretically investigated. The changes in intensity detected with probe pairs on the scalp caused by the concentration change in either oxygenated or deoxygenated haemoglobin induced by the focal brain activation is predicted by Monte Carlo simulation. The topographic images of the changes in oxygenated and deoxygenated haemoglobin are obtained from the changes in the intensity of light at two wavelengths detected by probe pairs to evaluate the crosstalk. The crosstalk slightly depends on the positional relationship between the probe arrangement and the focal brain activation and is minimised when the focal brain activation is located below a measurement point that is the midpoint between a probe pair. The 690-/830-nm wavelength pair is practically effective for reducing the crosstalk, especially the crosstalk from oxygenated haemoglobin to deoxygenated haemoglobin, in the NIR topography.

Re-evaluation of the 1950–1962 total ozone record from Longyearbyen, Svalbard

The historical total ozone measurements taken with Dobson Spectrophotometer #8 at Longyearbyen (78.2° N, 15.6° E), Svalbard, Norway, in the period 1950–1962 have been re-analyzed and homogenized based on the original measurement logs, using present-day procedures. In lack of sufficient calibration information, an empirical quality assessment was performed, based on a climatological comparison with ozone measurements in Tromsø, using TOMS data at both sites in the period 1979–2001, and ground-based Dobson data in the period 1950–1962. The assessment revealed that the C wavelength pair direct-sun (DS) measurements are most trustworthy (and most frequent), while the WMO standard reference mode AD direct-sun has a systematic bias. Zenith-blue (ZB) measurements at solar zenith angles (SZA) <78° were adjusted to DS data using different empirical functions before and after 1957 (the start of the International Geophysical Year). ZB measurements at larger SZAs were homogenized by means of a normalization function derived from days with measurements over a wide range of SZAs. Zenith-cloudy measurements, which are particularly frequent during the summer months, were homogenized by applying correction factors depending on the cloud type (high thin clouds and medium to low thick clouds). The combination of all measurements yields a total of 4685 single values, covering 1637 days from September 1950 to September 1962; moon measurements during the polar night add another 137 daily means. The re-evaluated data show a convincing consistence with measurements since 1979 (TOMS, SAOZ, Dobson) as well as with the 1957–1962 data stored at the World Ozone and UV Data Centre (WOUDC).

Re-evaluation of the 1950–1962 total ozone record from Longyearbyen, Svalbard

The historical total ozone measurements taken with Dobson Spectrophotometer #8 at Longyearbyen, Svalbard, Norway, in the period 1950–1962 have been re-analyzed and homogenized based on the original measurement logs, using updated relevant parameters. In lack of sufficient calibration information, an empirical quality assessment was performed, based on a climatological comparison with ozone measurements in Tromsø, using TOMS data at both sites in the period 1979–2001, and Dobson data in the period 1950–1962. The assessment revealed that, as in the case of the Tromsø measurements, the C wavelength pair direct-sun measurements are most trustworthy (and most frequent), while the WMO standard reference mode AD direct-sun has a systematic bias relative to this data set. Zenith-blue (ZB) measurements at solar zenith angles (SZA) <80° were homogenized using two different polynomials before and from 1957; also ZB measurements at larger SZAs were homogenized by means of a normalization function derived from days with measurements over a wide range of SZAs. CC' zenith-cloudy measurements, which are particularly frequent during the summer months, were homogenized by applying correction factors for only two different cloud types: high thin clouds and medium/low/thick clouds; a further diversification of corrections reflecting cloud conditions did not prove significant. The combination of all measurements yields a total of 4837 single values, covering 1676 days from September 1950 to September 1962; moon measurements during the polar night add another 137 daily means. The re-evaluated data show a convincing agreement with measurements since 1979 (TOMS, SAOZ, Dobson) as well as with the 1957–1962 data stored at the World Ozone and UV Data Centre (WOUDC).