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Eunhye Seo,Yesung Lee,Eunchan Mun,Dae Hoon Kim,Youshik Jeong,Jaehong Lee,Jinsook Jeong,Woncheol Lee 대한직업환경의학회 2022 대한직업환경의학회지 Vol.34 No.-
Background: Long working hours are known to account for approximately one-third of the total expected work-related diseases, and much interest and research on long working hours have recently been conducted. Additionally, as the prevalence of prediabetes and the high-risk group for diabetes are increasing worldwide, interest in prediabetes is also rising. However, few studies have addressed the development of type 2 diabetes and long working hours in prediabetes. Therefore, the aim of this longitudinal study was to evaluate the relationship between long working hours and the development of diabetes in prediabetes. Methods: We included 14,258 prediabetes participants with hemoglobinA1c (HbA1c) level of 5.7 to 6.4 in the Kangbuk Samsung Cohort Study. According to a self-reported questionnaire, we evaluated weekly working hours, which were categorized into 35–40, 41–52, and > 52 hours. Development of diabetes was defined as an HbA1c level ≥ 6.5%. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of diabetes were estimated using Cox proportional hazards analyses with weekly working 35–40 hours as the reference. Results: During a median follow-up of 3.0 years, 776 participants developed diabetes (incidence density, 1.66 per 100 person-years). Multivariable-adjusted HRs of development of diabetes for weekly working > 52 hours compared with working 35–40 hours were 2.00 (95% CI: 1.50–2.67). In subgroup analyses by age (< 40 years old, ≥ 40 years old), sex (men, women), and household income (< 6 million KRW, ≥ 6 million KRW), consistent and significant positive associations were observed in all groups. Conclusions: In our large-scale longitudinal study, long working hours increases the risk of developing diabetes in prediabetes patients.
Validation protocol for whole-body dosimetry in an agricultural exposure study
Lee, Jiho,Kim, Eunhye,Shin, Yongho,Lee, Jonghwa,Lee, Junghak,Maasfeld, Wolfgang,Kim, Jeong-Han The Korean Society for Applied Biological Chemistr 2018 Applied Biological Chemistry (Appl Biol Chem) Vol.61 No.1
Agricultural workers exposed to pesticides can experience adverse health impacts depending on toxicity and exposure amount. Whole-body dosimetry (WBD) is the most reliable, practical, and realistic method for measuring exposure. Since validation of analytical and experimental methodologies is critical for quantitative determination of exposure, we conducted a validation procedure to design an essential protocol for WBD exposure studies. Using the fungicide kresoxim-methyl, matrixmatched standards were prepared with various matrices including outer cloth, inner cloth, washing solution for gloves and hands, gauze, and glass fiber filter (IOM sampler) to determine the instrumental limit of quantitation for high-performance liquid chromatography (HPLC) (2 ng) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) (10 pg). Method limits of quantitation (MLOQ) were also set for HPLC (0.1 mg/L) and LC-MS/MS (0.005 mg/L). We observed good analysis repeatability (coefficient of variation < 6%), and the linearity of the calibration curves was reasonable ($r^2$ > 0.998) in the range of 0.001-10 mg/L in various matrices. Recovery tests were carried out at three levels of concentration (MLOQ, 10 MLOQ, and 100 MLOQ) and resulted in good recoveries (72.7-105.6%). We did not observe breakthrough of the compound in tests of holding capacity for glass fiber pesticide filters. The procedures established in the present study are applicable as an essential, comprehensive protocol for exposure assessment studies using WBD.
Lee, Seongjin,Cha, Eunhye,Lee, Jongcheol,Lee, Jongdeok,Song, Inja,Kim, Sungchul KOREAN PHARMACOPUNCTURE INSTITUTE 2017 Journal of pharmacopuncture Vol.20 No.1
Objectives: Studies involving patients with spinobulbar muscular atrophy (SBMA), which is often referred to as Kennedy's disease, similar to those involving patients with progressive muscular disease (PMD), are rare. This paper reports a case study involving the use of Korean medicine to treat a patient with SBMA. Methods: We treated a patient with SBMA with unique symptoms by using various kinds of pharmacopuncture and herbal medicines for about two and a half years. After the treatment had ended, we evaluated the patient's conditions and the side effects of the treatment. Results: After treatment, the patient's symptoms were stabilized, and the patient suffered no abnormalities or side effects. No special changes in condition were noted during treatment period, and the patient was very satisfied with his response to treatment. Conclusion: Existing treatments have some considerable after effects and are difficult to apply in domestic clinics. In this regard, our findings should open possibilities for new clinical guidelines. Nevertheless, the limitations associated with this case study should be resolved, and more studies need to be conducted.
Lee, Boah,Park, Seung Ju,Lee, Seulgi,Park, Seung Eun,Lee, Eunhye,Song, Ji-Joon,Byun, Youngjoo,Kim, Seyun Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.3
Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.
Eunhye Kim,문준관,Hoon Choi,Su-Myoung Hong,Dong-Hyuk Lee,Hyomin Lee,김정한 한국응용생명화학회 2012 Applied Biological Chemistry (Appl Biol Chem) Vol.55 No.1
Exposure and risk assessments were conducted to evaluate safety of speed spayer (SS) and power sprayer (PS) used for treatment of insecticide methomyl in apple orchard on the operator. Dermal patches, gloves, socks, and masks were used to monitor the potential dermal exposure, and personal air monitor with XAD-2 resins was used to evaluate the potential inhalation exposure. Validation of methods for limit of detection, limit of quantitation, recovery, reproducibility, linearity of calibration, trapping efficiency, and breakthrough tests were performed to obtain reasonable results for quantitative exposure study of methomyl. During application of methomyl, PS resulted in more dermal exposure than SS. Important contaminated parts of body were upper arms, thigh, chest, shin, hand, forearm, and head for both SS and PS. Exposure rate was 44–176 mL/h. Although the level of inhalation exposure was very low during application, relatively higher level was observed for PS than for SS. During mixing/loading, more dermal exposure occurred by SS than that of PS probably due to drift of wettable powder (WP) formulation. Exposure was mostly observed on hand, and 99.9% of hand exposure to soluble liquid formulation (215 mg) in PS was from spill of liquid formulation on gloves. However, the body exposure ratio to total mixing/loading amount and inhalation exposure during mixing/loading was very low. Margin of safety in risk assessment was much larger than 1 in all cases, indicating low risk.
Lee, Jonghwa,Kim, Leesun,Shin, Yongho,Lee, Junghak,Lee, Jiho,Kim, Eunhye,Moon, Joon-Kwan,Kim, Jeong-Han American Chemical Society 2017 Journal of agricultural and food chemistry Vol.65 No.16
<P>A multiresidue method for the simultaneous and rapid analysis of 360 pesticides in representative agricultural produce (brown rice, orange, spinach, and potato) was developed using a modified QuEChERS procedure combined with gas chromatography tandem mass spectrometry (GC-MS/MS). Selected reaction monitoring transition parameters (e.g., collision energy, precursor and product ions) in MS/MS were optimized to achieve the best selectivity and sensitivity for a wide range of GC-amenable pesticides. A short (20 m) microbore (0.18 mm i.d.) column resulted in better signal-to-noise ratio with reduced analysis time than a conventional narrowbore column (30 m X 0.25 mm i.d.). The priming injection dramatically increased peak areas by masking effect on a new GC liner. The limit of quantitation was <0.01 mg/kg, and the correlation coefficients (r(2)) of matrix-matched standards were >0.99 within the range of 0.0025-0.1 mg/kg. Acetonitrile with 0.1% formic acid without additional buffer salts was used for pesticide extraction, whereas only primary secondary amine (PSA) was used for dispersive solid phase extraction (dSPE) cleanup, to achieve good recoveries for most of the target analytes. The recoveries ranged from 70 to 120% with relative standard deviations of <= 20% at 0.01 and 0.05 mg/kg spiking levels (n = 6) in all samples, indicating acceptable accuracy and precision of the method. Seventeen real samples from local markets were analyzed by using the optimized method, and 14 pesticides in 11 incurred samples were found at below the maximum residue limits.</P>
Lee, Hyeri,Riu, Myoungjoo,Kim, Eunhye,Moon, Joon-Kwan,Choi, Hoon,Do, Jung-A,Oh, Jae-Ho,Kwon, Ki-Sung,Lee, Young Deuk,Kim, Jeong-Han 한국응용생명화학회 2013 Applied Biological Chemistry (Appl Biol Chem) Vol.56 No.2
A single residue analytical method was developed for herbicide chlorpropham in various crops. Brown rice, apple, mandarin, Kimchi cabbage, green pepper, potato, and soybean were selected as representative crops, and clean-up system, partition solvent, and extraction solvent were optimized. For high performance liquid chromatography (HPLC), $C_{18}$ column was used with elution solvents of water and acetonitrile. Limit of quantitation (LOQ) of chlorpropham was 2 ng (S/N >20), and excellent linearity ($R^2$=1.000) was achieved. Method limit of quantitation (MLOQ) was 0.02 mg/kg. For recovery tests, crop samples were macerated and fortified with chlorpropham standard solution at three fortification levels (MLOQ, 10 MLOQ, and 100 MLOQ). And then those were extracted with acetonitrile, concentrated and partitioned with n-hexane. The n-hexane layer was then concentrated, cleaned-up through Florisil$^{(R)}$ column with ethyl acetate:n-hexane (5:95, v/v) prior to concentration and analysis with HPLC. Good recoveries from 76.8 to 107.9% with coefficients of variation of less than 10% were obtained, regardless of sample type, which satisfies the criteria of Korea Food and Drug Administration. Those results were confirmed with liquid chromatography-mass spectrometry (LC-MS). The method established in this study could be applied to most of crops as an official and general method for the analysis of chlorpropham residue.