Background L-Citrulline is a neutral amino acid and a major precursor of L-arginine in the nitric oxide (NO) cycle. Recently it has been reported that L-citrulline prevents neuronal cell death and protects cerebrovascular injury, therefore, L-citrulline may have a neuroprotective effect to improve cerebrovascular dysfunction. Therefore, we aimed to clarify the brain transport mechanism of L-citrulline through blood-brain barrier (BBB) using the conditionally immortalized rat brain capillary endothelial cell line (TR-BBB cells), as an in vitro model of the BBB.MethodsThe uptake study of [14C] L-citrulline, quantitative real-time polymerase chain reaction (PCR) analysis, and rLAT1, system b0,+, and CAT1 small interfering RNA study were performed in TR-BBB cells.ResultsThe uptake of [14C] L-citrulline was a time-dependent, but ion-independent manner in TR-BBB cells. The transport process involved two saturable components with a Michaelis–Menten constant of 30.9 ± 1.0 μM (Km1) and 1.69 ± 0.43 mM (Km2). The uptake of [14C] L-citrulline in TR-BBB cells was significantly inhibited by neutral and cationic amino acids, but not by anionic amino acids. In addition, [14C]L-citrulline uptake in the cells was markedly inhibited by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), which is the inhibitor of the large neutral amino acid transporter 1 (LAT1), B0, B0,+ and harmaline, the inhibitor of system b0,+. Gabapentin and L-dopa as the substrates of LAT1 competitively inhibited the uptake of [14C] L-citrulline. IC50 values for L-dopa, gabapentin, L-phenylalanine and L-arginine were 501 μM, 223 μM, 68.9 μM and 33.4 mM, respectively. The expression of mRNA for LAT1 was predominantly increased 187-fold in comparison with that of system b0,+ in TR-BBB cells. In the studies of LAT1, system b0,+ and CAT1 knockdown via siRNA transfection into TR-BBB cells, the transcript level of LAT1 and [14C] L-citrulline uptake by LAT1 siRNA were significantly reduced compared with those by control siRNA in TR-BBB cells.ConclusionsOur results suggest that transport of L-citrulline is mainly mediated by LAT1 in TR-BBB cells. Delivery strategy for LAT1-mediated transport and supply of L-citrulline to the brain may serve as therapeutic approaches to improve its neuroprotective effect in patients with cerebrovascular disease.

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BackgroundThe effects on particulate matter (PM) and ozone on health are being reported by a number of studies. The effects of these air pollutants are likely to be stronger in the elderly population, but studies in this regard are scarce. The purpose of this study was to study the effects of PM ≤ 2.5 μm and ozone on chronic health effects of the elderly population.MethodsIn order to analyze the health status of the elderly population, National Statistical Office Mortality records were used. In this study, we calculated the number of deaths in Seoul of people who were 60 years or older between 2002 and 2012. The current study analyzed each disorder separately and the lag effect. PM and ozone were analyzed using the single exposure model, as well as the adjusted multi exposure model.ResultsIn the single exposure analysis with PM2.5 as the exposure variable, with the increase of 10 μg/m3, the number of deaths increased by 1.0039 fold, and vascular disease 1.0053 fold. In the multi exposure model adjusting for ozone, the number of deaths increased by 1.0037 fold, and vascular disease 1.0049 fold. In the single exposure analysis with ozone as the exposure variable, with the increase of 10 ppb, the number of deaths increased by 1.0038 fold, and in the multi exposure model adjusting for PM2.5, the number of deaths increased by 1.0027 fold. These results differed depending on the period or season. There was a 5-day lag effect between PM2.5 and deaths in the multi exposure model, and 1.0028 fold when adjusted for ozone. There was a 1-day lag effect in single exposure models with ozone as the main variable, and 1.0027 fold increase in deaths.ConclusionIn our study, an increase in the number of deaths in the elderly population in accordance with the increase in the PM2.5 and ozone was found. The association found in our study could also influence socioeconomic burden. Future studies need to be performed in regards to younger population, as well as other air pollutants.

Objectives: Healthcare workers in hospitals (HHCWs), a notably increasing workforce, face various occupational hazards. A high incidence of cancer among HHCWs has been observed; however, the cancer incidence status among HHCWs in South Korea is yet to be studied. This study aimed to assess cancer incidence among HHCWs in South Korea. Methods: We constructed a retrospective cohort of HHCWs using National Health Insurance claims data, including cancer incidence status and vital status, from 2007 to 2015. Those who had worked in hospitals for at least three years were defined as HHCWs. Standardized incidence ratios (SIRs) for all cancer types and standardized mortality ratios were calculated. Results: A total of 107,646 HHCWs were followed up, and the total follow-up duration was 905,503 person-years. Compared to the total workers, female HHCWs showed significantly higher SIR for all cancers (observed cases = 1480; SIR = 1.25; 95% confidence interval [CI] = 1.06–1.47). The incidence of breast cancer among female HHCWs was significantly higher compared to that among total workers (observed cases = 376; SIR = 1.21; 95% CI = 1.09–1.36). Conclusions: Our findings indicate that female HHCWs have an elevated probability of developing cancer, which suggests that occupational risk factors such as night-shift work, anti-neoplastic medications, stressful jobs, and ionizing radiation should be assessed. Further investigation and occupational environment improvement activities are required.

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