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AIM To evaluate whether the use of non-thermal plasma (NTP) could reduce triethylene glycol dimethacrylate (TEGDMA)-mediated damage in MDPC-23 cells. METHODOLOGY The effects of NTP and TEGDMA on MDPC-23 cell proliferation were tested using WST-1 assays after pretreatment with NTP for 1 min and exposure to TEGDMA. Live/Dead assays were used to visualize cell death. To monitor the effects of NTP and TEGDMA on the cell cycle and apoptotic cell death, flow cytometry was performed. Western blotting was used to assess changes in protein levels mediated by NTP and TEGDMA treatment, and enzyme-linked immunosorbent assays were performed to evaluate the effects of NTP and TEGDMA on prostaglandin E2 (PGE2 ) expression. One-way analysis of variance and Duncan's post hoc tests were used for statistical analysis. RESULTS NTP treatment effectively protected cells from TEGDMA-mediated cell damage and blocked TEGDMA-mediated cell growth inhibition (p

BACKGROUND AND OBJECTIVE: Mixed inhaler device use for asthma is associated with worse inhaler technique and outcomes. Given that relievers are commonly prescribed as pressurized metred-dose inhalers (pMDI), changing preventers from dry powder inhalers (DPI) to pMDI may improve asthma outcomes. This study aimed to assess the persistence and effectiveness of switching from DPI to pMDI for inhaled corticosteroid and long-acting β2 -agonist combination therapy (ICS/LABA).METHODS: This was a historical cohort study using Ajou University Hospital (Korea) patient records. Persistence of switch was defined as receiving ≥1 pMDI and no DPI after the switch. Effectiveness of switch was assessed as the proportion without severe asthma exacerbation and the proportion achieving risk domain asthma control (RDAC; no asthma-related hospitalization, antibiotics without upper respiratory diagnosis or acute course of oral corticosteroids) and overall asthma control (OAC; RDAC and ≤ 200 μg salbutamol/≤500 μg terbutaline average daily dose) comparing 1 year after and before the switch.RESULTS: Within 85 patients who switched from DPI to pMDI and persisted for a year, higher proportion were free from asthma exacerbation after the switch (mean difference in proportion = 0.129, 95% CI: 0.038-0.220). Switching to pMDI was also associated with better RDAC (75.3% vs 57.7%, P = 0.001) and OAC (57.7% vs 45.9%, P = 0.021). From the entire 117 patients who switched to fixed-dose combination (FDC)/ICS LABA pMDI, 76.1% (95% CI: 69.0-100.0%) patients persisted in the following 6 months.CONCLUSION: Switching to and persisting with pMDI was associated with decreased asthma exacerbations and improved asthma control. The majority of patients persisted with the switch to pMDI for ICS/LABA treatment.

OBJECTIVES To investigate the association between lower urinary tract symptoms (LUTS) and cardiovascular disease (CVD) risk in women, as severe LUTS are known to be associated with CVD risk in men but few studies have focused on this issue in women. SUBJECTS AND METHODS A total of 1014 ostensibly healthy women, who participated in a voluntary health check in a health promotion centre from November 2013 to October 2015, were enrolled. LUTS were assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). CVD risk scores were calculated using the Framingham risk score and the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) score. Correlation, partial correlation, and multiple logistic regression analyses were conducted. RESULTS The mean age and body mass index (BMI) of the women were 51 years and 22.6 kg/m2 , respectively. The ASCVD score showed significant positive correlations with IPSS items Question 2 (Q2), Q3, Q5, and Q7 (all P < 0.05), total IPSS (P = 0.001), IPSS storage (P = 0.006) and IPSS voiding symptoms scores (P = 0.001) based on partial correlation analysis after adjustment for BMI. For the OABSS, the ASCVD score showed significant positive correlations with OABSS items Q2, Q3, and Q4 (P < 0.001, P = 0.017, and P < 0.001, respectively) and total OABSS (P < 0.001). Multiple logistic regression analysis showed that the moderate-severe risk groups of the OABSS and IPSS were associated with the ASCVD risk score in adjusted models (P < 0.001) compared to the none-mild OABSS and mild IPSS groups. After adjustment for age and BMI, IPSS storage score was significantly related with the ASCVD risk score (B = 0.855, P = 0.016) CONCLUSIONS: LUTS, especially storage symptoms, might be risk factors for predicting future CVD risk in women. Further prospective or cohort studies are needed to validate this possibility.

Aim Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease owing to an immunological abnormality, along with traditional risk factors. We found that carotid artery intima-media thickness (cIMT) and plaque were associated with age, body mass index (BMI) and disease activity in a previous study 4 years ago. Our aim was to identify risk factors associated with progression of subclinical atherosclerosis in SLE. Methods We assessed cIMT and plaque using Doppler ultrasonography in 61 Korean women with SLE who were enrolled in the previous study 4 years ago. Results The mean cIMT of the patients was 0.39 ± 0.09 mm; 11 patients had carotid plaques, which was similar to the results of the previous study. Twenty-one patients had increased cIMT, and new carotid plaque had developed in seven patients. Patients with increased cIMT had a lower BMI and took fewer non-steroidal anti-inflammatory drugs and higher 4 year cumulative glucocorticoid dose than patients without increased cIMT. The 4 year cumulative glucocorticoid dose was higher in patients with carotid plaque than in those without. On multivariate regression analysis, BMI (odds ratio [OR] = 0.67, P = 0.034) was associated with increased cIMT, and the 4 year cumulative glucocorticoid dose was associated with increased cIMT (OR = 6.994, P = 0.025) and carotid plaque (OR = 5.651, P = 0.031). Conclusion This prospective follow-up study on cIMT and plaque in patients with SLE showed that low BMI and 4 year cumulative glucocorticoid dose were associated with the progression of subclinical atherosclerosis.

PURPOSE Researchers recently suggested intravenous paracetamol as a potential cause of hypotension. We aimed to investigate risk factors of paracetamol- and propacetamol-associated adverse drug reactions (ADRs) in Korean individuals. METHODS All adverse hypotension cases, regardless of suspected drug, and all ADRs associated with paracetamol and propacetamol use were collected from the Korea Adverse Event Reporting System database between 2011 and 2014. The seriousness, causality, and type of ADR were classified. RESULTS Of 4,771 cases of adverse hypotension, 403 (8.4%) were reported to be related to propacetamol. This was comparable to the rate of hypotension associated with fentanyl (454, 9.5%), the major suspected drug of hypotension. Paracetamol-associated hypotension accounted for merely 1.2% (55 cases) of all hypotension cases. Among ADRs associated with propacetamol use, hypotension was the most common (37.1%), whereas cutaneous reactions were the primary paracetamol-associated ADR. Propacetamol/paracetamol-associated hypotension was frequently recorded in older patients (≥54 years) (53.9 ± 25.8 vs. 42.8 ± 21.7, P

Objective The aim of this study is to evaluate the risk for hip fracture associated with adverse drug reactions caused by α1-adrenergic (alpha) blockers to treat female voiding dysfunction. Methods Information from the Health Insurance Review and Assessment Service database from January 1, 2008 to December 31, 2012 was used. Hip fracture women patients who received a prescription for an alpha blocker due to voiding dysfunction were the cases. A 30-day hazard period after administration of an alpha blocker was set. The 30-day control period was defined as 360 days before administration. The standardized incidence ratio and hazard ratio for the risk of hip bone fracture as related to alpha blocker use were analyzed. Results The study cohort included 287 383 subjects having a mean age of 65.1 ± 9.7 years in the study cohort. A total of 170 and 79 hip fracture cases were diagnosed in the hazard period and control period, respectively. The incidence of newly diagnosed hip fractures per 100 000 person-years was 763.4 in the hazard period and 348.5 in the control period. The hazard ratio for hip fracture after use of an alpha blocker was 2.19 (95% confidence interval, 1.74–2.77). Conclusions Alpha blockers to treat voiding dysfunction may have association with the risk for hip fracture in elderly women.

SummaryBackground To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). Objective To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. Methods An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. Results A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4 and LTE4/PGF2α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4 and LTE4/PGF2α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4 levels were significantly correlated with the fall in FEV1% after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). Conclusions and Clinical Relevance Serum metabolite level of LTE4 and LTE4/PGF2α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

In this study, seven quenchers (derived from either anthraquinone, phthalimidylazo, or dipyrromethene chromophores) were prepared as candidates for additives to suppress fluorescence in blue colour filters and thus improve their contrast ratio. To reduce fluorescence effectively, quenchers must have typical properties such as spectral compatibility by which the absorbance spectrum of the quencher overlaps the fluorescence emission spectrum, exhibit high molar extinction coefficients, and exert little influence on the colour of the blue filter. The seven quenchers possessed absorption maxima of approximately 570–620 nm and reduced fluorescence (by more than 24%). Those quenchers tested in filter coatings increased their contrast ratios by about 50%. They thus effectively quenched fluorescence of the blue filter but without greatly affecting the chromaticity coordinates of the filters.

Four thermally stable and solvent soluble dyes were prepared from diketopyrrolopyrrole pigment via an N-alkylation reaction. To improve the thermal stability of the dyes, a hydroxyl functional group that could react with blocked polyisocyanates was introduced into the dyes. The prepared dyes had absorption maxima near 500 nm, and the chromaticity diagrams of all synthesised dyes exhibited smaller x and y values than those of CI Pigment Red 254, indicating that the colour of the synthesised dyes was close to an orange shade. The dyes reacting with blocked polyisocyanates showed extremely high thermal stability compared with analogous dyes not reacting with polyisocyanates.

Cite this as: N. S. Palikhe, S.-H. Kim,H.-Y. Lee, J.-H. Kim, Y.-M. Ye and H.-S. Park, Clinical & Experimental Allergy, 2011 (41) 179–185. Summary Background The thromboxane A2 receptor (TBXA2R) is a potent broncho- and vaso-constrictor and is associated with leukotriene synthesis. Polymorphisms in the TBXA2R gene have been linked to atopy, asthma, and atopic dermatitis. This study evaluated the association between genetic TBXA2R variants and the development of acetyl salicylic acid (ASA)-intolerant acute urticaria (AIAU). Methods AIAU patients (n=167), ASA-intolerant chronic urticaria (AICU) patients (n=149), and healthy controls (NC) (n=265) were included. All patients were enrolled at Ajou University Hospital in Suwon, Korea. Two TBXA2R polymorphisms (−4684T>C and 795T>C) were genotyped by primer extension using a SNAPshot ddNTP primer extension kit. Luciferase activity was measured using a dual-luciferase reporter assay kit. An electrophoretic mobility shift assay (EMSA) was performed using a nuclear extract from a human mast cell line (HMC-1). Results Genetic association data demonstrated that compared with NC subjects, AIAU patients had a significantly higher frequency of the homozygous TT genotype of TBXA2R−4684T>C (P=0.005, Pcorr=0.03). No differences were identified between the AICU and the NC groups. Luciferase activity, reflecting promoter activity, was significantly lower with the TBXA2R−4684T-containing construct than with the −4684C-containing construct (P

The synthesis and spectroscopic properties of monoazo dye series, whose members consist of N-alkylphthalimide diazo components combined with a coupling component containing two ester groups, are reported. Such colourants are potentially alkali-clearable as a consequence not only of the presence of diester functionality on the coupler, but also through use of the base-sensitive phthalimide system. Shortening the N-alkyl group by removing one or two methylene units from a butyl chain made little difference to absorption properties, as would be expected given the relatively minor differences in inductive character produced. Shifts in the absorption maximum of the dyes associated with dibromination of the phthalimidylazo motif and its subsequent cyanodehalogenation were in agreement with theory and literature data for related series. Diester substitution on the coupling component brought about hypsochromism and hypochromism.

The coloration and fastness properties of 18 carbocyclic monoazo disperse dyes bearing a phthalimide ring fused to the aromatic ring of their diazo components have been investigated. In each case, the phthalimidyl nitrogen atom was substituted with either a butyl, sec-butyl or isopropyl group, while the adjoined phenyl ring bore a substitution pattern typical of commercial colorants. Dye uptake and build-up onto both conventional and microfibre polyester through exhaustion dyeing were examined: while the expected tendency of greater exhaustion on microfibre was noted, there were few clear trends with respect to dye structure. The nature of the N-alkyl group made no consistent difference to dye uptake. Attempts to explain the observed percentage exhaustion values by mapping them to calculated partition coefficient or solubility parameter values were unsuccessful. Wash fastness tended to be best for blue dicyano-substituted derivatives, which may be as a result in part of these substituents promoting hydrolysis of the adjacent phthalimide ring to give more soluble phthalate species. In contrast, the dicyano dyes had relatively poor photostability compared with their unsubstituted analogues.

A set of azo dyes has been synthesised using N-substituted phthalimides as diazo components. 3,5-Dibromo-N-substituted-phthalimidylazo derivatives were cyanated by cyanodehalogenation to give dicyano analogues. All of the synthesised intermediates and dyes have been characterised by mass spectrometry, 1H-NMR or elemental analyses. The gamut of colour of the prepared dyes spanned much of the visible spectrum: absorption maxima of the dyes in formamide were observed in the range 436 to 609 nm. Consistent with results seen in previous studies of non-phthalimido monoazo disperse dyes, replacement of dibromo groups with dicyano functions in the phthalimide-based set led to large bathochromic shifts in absorption maxima, as did the introduction of acetylamino groups onto the coupler ring ortho to the azo link. However, switching an N-propyl function on the imido ring for a benzyl or 3-cyanopropyl substituent had little effect on absorption maxima. Good correlations between the observed absorption maxima of certain dyes and those of model analogues predicted by Pariser–Parr–Pople molecular orbital calculations were observed when steric effects were absent.

Monoclinic phases, as intermediate phases at the morphotropic phase boundary, have been considered as the origin of high piezoelectricity in various piezoelectric systems. However, those monoclinic phases have seldom been experimentally observed at the phase boundary in lead-free (K,Na)NbO3 (KNN)-based materials. This work shows that KNN epitaxial thin films demonstrate a monoclinic M-C phase stabilized by elastic strain at room temperature, which is identified by both synchrotron X-ray reciprocal space mapping and piezoresponse force microscopy. It is revealed that the piezoelectricity is greatly enhanced at 170 degrees C due to the monoclinic M-C-M-A phase boundary. The discovery of monoclinic phases in this work may open an avenue for developing a new thermotropic phase boundary in KNN-based materials. The results also provide a guide for the exploration of high piezoelectricity driven by monoclinic phases in lead-free piezoelectric materials.

Biotransformation is the major clearance mechanism of therapeutic agents from the body. Biotransformation is known not only to facilitate the elimination of drugs by changing the molecular structure to more hydrophilic, but also lead to pharmacological inactivation of therapeutic compounds. However, in some cases, the biotransformation of drugs can lead to the generation of pharmacologically active metabolites, responsible for the pharmacological actions. This review provides an update of the kinds of pharmacologically active metabolites and some of their individual pharmacological and pharmacokinetic aspects, and describes their importance as resources for drug discovery and development.