Genotyping cytochrome P450 3A5 using the Light Cycler.

Cytochrome P450 3A5 (CYP3A5) is involved in the biotransformation of many orally administered drugs, some of which are dose optimized using therapeutic drug monitoring. The CYP3A5 gene exhibits variable inter-individual expression, which is related to a single-nucleotide polymorphism. Producers of the enzyme possess at least one CYP3A5*1 allele. Knowledge of patients' CYP3A5 genotype, in conjunction with therapeutic drug monitoring (TDM), may aid patient management. Real-time polymerase chain reaction (PCR) was used to genotype the A6986G mutation of the CYP3A5 gene. Specific primers were employed to generate a DNA product, co-amplified with two internal hybridization probes, using a LightCycler. DNA melt curve analysis readily identified the genotypes CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3. Results were confirmed using DNA sequencing with 100% correlation. Genotypes were determined from 263 individuals and compared with the genotypes of a pseudogene CYP3AP1, which is in disequilibrium with CYP3A5. This is a rapid and reliable method for genotyping the CYP3A5 polymorphism which may be used as an important adjunct to the TDM service offered by laboratories to optimize drug prescription

Sources of Wintertime Atmospheric Organic Pollutants in a Large Canadian City: Insights from Particle and Gas Phase Measurements

Although atmospheric organic pollutants have been extensively studied to elucidate summertime urban photochemical air pollution, uncertainties remain concerning the quality of wintertime air in large northern North American cities. Here, we used online mass spectrometric measurements of volatile organic compounds (VOCs) and organic aerosol (OA), combined with positive matrix factorization (PMF), to identify sources of organic pollutants in downtown Toronto, Canada during February–March 2023. In some cases, comparable PMF factors were identified for both VOCs and OA, such as from traffic, cooking, and background oxygenated sources. However, VOC PMF yielded additional information, such as a factor associated with human-related emissions of VOCs. Additionally, VOC PMF yields two traffic factors: one likely related to gasoline and one to diesel use. Despite cold and relatively dark conditions, the OA and VOC oxygenated factors both grow in intensity during the daytime, indicative of photochemical activity, whereas the traffic and cooking factors were enhanced in the morning and late evening due to the timing of vehicle use, cooking, and boundary layer effects. This study illustrates the benefits that arise from the parallel source–receptor analyses of organic gases and aerosol particles

Analysis of Chamber Data

In this chapter, we focus on aspects of analysis of typical simulation chamber experiments and recommend best practices in term of data analysis of simulation chamber results relevant for both gas phase and particulate phase atmospheric chemistry. The first two sections look at common gas-phase measurements of relative rates and product yields. The simple yield expressions are extended to account for product removal. In the next two sections, we examine aspects of particulate phase chemistry looking firstly at secondary organic aerosol (SOA) yields including correction for wall losses, and secondly at new particle formation using a variety of methods. Simulations of VOC oxidation processes are important components of chamber work and one wants to present methods that lead to fundamental chemistry and not to specific aspects of the chamber that the experiment was carried out in. We investigate how one can analyse the results of a simulation experiment on a well-characterized chemical system (ethene oxidation) to determine the chamber-specific corrections. Finally, we look at methods of analysing photocatalysis experiments, some with a particular focus on NOx reduction by TiO2-doped surfaces. In such systems, overall reactivity is controlled by both chemical processes and transport. Chambers can provide useful practical information, but care needs to be taken in extrapolating results to other conditions. The wider impact of surfaces on photosmog formation is also considered.Peer reviewe

Combined effects of water column nitrate enrichment, sediment type and irradiance on growth and foliar nutrient concentrations of Potamogeton alpinus

Contains fulltext : 32334.pdf (publisher's version ) (Closed access