Characterization of PM10-bound polycyclic aromatic hydrocarbons and associated carcinogenic risk in Bangkok, Thailand

Concentrations of ambient particulate-bound polycyclic aromatic hydrocarbons (pPAHs) were measured in PM10 samples collected at roadside, industrial and urban background sites in Bangkok between May 2013 and May 2014. The annual average PM10 concentrations were not significantly different between the roadside (56.4 ± 27.3 µg m−3) and industrial (51.0 ± 31.1 µg m−3) sites. The lowest annual mean PM10 was observed at the urban background site (39.8 ± 22.2 µg m−3). Seasonal variations of pPAHs were observed at the three sampling sites. The total pPAHs ranged between 1.09 and 13.10 ng m−3 (mean 4.85 ± 2.51 ng m−3), 1.49 and 9.39 ng m−3 (mean 3.84 ± 2.01 ng m−3) and 0.77 and 5.20 ng m−3 (mean 2.28 ± 1.16 ng m−3) at the roadside, industrial and urban background sites, respectively. The observed annual average benzo[a]pyrene concentrations were 0.47 ± 0.39 ng m−3, 0.35 ± 0.27 ng m−3 and 0.24 ± 0.19 ng m−3 at the roadside, industrial and urban background sites. Long-term carcinogenic health risk of inhalation exposure expressed as the toxicity equivalent to benzo[a]pyrene concentrations were calculated as 0.83, 0.72 and 0.39 ng m−3 at the industrial, roadside and urban background sites, respectively. The composition of pPAHs plays an important role in the carcinogenicity of a PAHs mixture

In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans

Practical internal and external cooling methods do not influence rapid recovery from simulated taekwondo performance

10.1016/j.jesf.2023.05.003Journal of Exercise Science and Fitness213286-29

Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen

Insee Sensorn,1 Ekaphop Sirachainan,2 Montri Chamnanphon,3 Ekawat Pasomsub,4 Narumol Trachu,5 Porntip Supavilai,1 Chonlaphat Sukasem,3 Darawan Pinthong11Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand; 2Division of Medical Oncology, Department of Medicine, 3Division for Pharmacogenomics and Personalized Medicine, 4Division for Virology, Department of Pathology, 5Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandBackground: Pharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug-metabolizing enzymes and transporters also play a role in tamoxifen metabolic pathways. The aim of this study is to investigate the impact of CYP3A4/5, ABCB1, and ABCC2 polymorphisms on the risk of recurrence in Thai patients who received tamoxifen adjuvant therapy.Methods: Patients with early-stage breast cancer who received tamoxifen adjuvant therapy were recruited in this study. All six single-nucleotide polymorphisms (SNPs), including CYP3A4*1B (-392 A>G)/*18(878 T>C), CYP3A5*3(6986 G>A), ABCB1 3435 C>T, ABCC2*1C (-24 C>T), and ABCC2 68231 A>G, were genotyped using real-time polymerase chain reaction assays. The impacts of genetic variants on disease-free survival (DFS) were analyzed using the Kaplan–Meier method and Cox regression analysis.Results: The ABCB1 3435 C>T was found to have the highest allele frequency among other variants; however, CYP3A4*1B/*18 could not be found in this study. Patients with heterozygous ABCB1 3435 CT genotype showed significantly shorter DFS than those with homozygous 3435 CC genotype (P = 0.041). In contrast, patients who carried homozygous 3435 TT genotype showed no difference in DFS from wild-type 3435 CC patients. Cox regression analysis showed that the relative risk of recurrence was increased by five times (P = 0.043; hazard ratio = 5.11; 95% confidence interval: 1.05–24.74) in those patients carrying ABCB1 3435 CT genotype compared to those with ABCB1 3435 CC.Conclusion: ABCB1 3435 C>T is likely to have a clinically significant impact on recurrence risk in Thai patients with breast cancer who receive tamoxifen adjuvant therapy.Keywords: breast cancer, CYP3A4/5, drug transporters, pharmacogenetics, disease-free survival, tamoxife

ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen

Insee Sensorn,1,* Chonlaphat Sukasem,2,* Ekaphop Sirachainan,3 Montri Chamnanphon,2 Ekawat Pasomsub,4 Narumol Trachu,5 Porntip Supavilai,1 Darawan Pinthong,1 Sansanee Wongwaisayawan6 1Department of Pharmacology, Faculty of Science, Mahidol University, 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 4Division of Virology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 5Research Center, Faculty of Medicine, Ramathibodi Hospital, 6Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand *These authors contributed equally to this work Background: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim of this study is to investigate the impact of CYP3A5, CYP2D6, ABCB1, and ABCC2 polymorphisms on the risk of all distant and organ-specific metastases in Thai patients who received tamoxifen adjuvant therapy. Methods: Genomic DNA was extracted from blood samples of 73 patients with breast cancer who received tamoxifen adjuvant therapy. CYP3A5 (6986A>G), CYP2D6 (100C>T), ABCB1 (3435C>T), and ABCC2 (-24C>T) were genotyped using allelic discrimination real-time polymerase chain reaction assays. The impacts of prognostic clinical factors and genetic variants on disease-free survival were analyzed using the Kaplan–Meier method and Cox regression analysis. Results: In the univariate analysis, primary tumor size >5 cm was significantly associated with increased risk of distant metastasis (P=0.004; hazard ratio [HR] =3.05; 95% confidence interval [CI], 1.44–6.47). In the multivariate analysis, tumor size >5 cm remained predictive of distant metastasis (P<0.001; HR=5.49; 95% CI, 2.30–13.10). ABCC2 -24CC were shown to be associated with increased risk of distant metastasis (P=0.040; adjusted HR=2.34; 95% CI, 1.04–5.27). The combined genotype of ABCC2 -24CC – ABCB1 3435 CT+TT was associated with increased risk of distant and bone metastasis (P=0.020; adjusted HR=2.46; 95% CI, 1.15–5.26 and P=0.040; adjusted HR=3.70; 95% CI, 1.06–12.89, respectively). Conclusion: This study indicates that polymorphisms of ABCC2 and ABCB1 are independently associated with bone metastasis. Further prospective studies with larger sample sizes are needed to verify this finding. Keywords: breast cancer, tamoxifen, ABCB1, ABCC2, pharmacogenetics, distant metastasi