PURPOSE: Caffeine shows wide interindividual pharmacokinetic (PK) variation, and therapeutic drug monitoring (TDM) may be needed. The PK profile of caffeine in Korean preterm neonates was investigated, and factors influencing the clearance of caffeine were analyzed. METHODS: Fifty-nine preterm neonates receiving caffeine for apnea of prematurity were enrolled in the study (gestational age, 29.5±2.2 weeks and birth weight [BW], 1,318±358 g). Caffeine (20 mg/kg) was intravenously administered to each neonate as a loading dose, followed by a maintenance dose of 5-10 mg/kg/d. A total of 190 serum concentrations were measured for population PK analysis and modeling using nonlinear mixed-effects model (NONMEM®) software. RESULTS: The mean serum concentration of caffeine was 15.4±4.5 mg/L (range 7.8-33.0 mg/L). High serum concentrations (>20 mg/L) were noted in 36 samples (29%). At the first measurement of serum caffeine, the mean postmenstrual age was 33.9±2.3 weeks, mean BW was 1,802±471 g, mean duration of treatment was 7.4±9.4 days, and mean sampling time after the last dose was 21.8±2.1 hours. In the population PK analysis, the clearance was 0.033 L/h and volume of distribution was 0.371 L. Typical clearance was calculated as 0.0293×(BW/70)1.33. Among the subjects receiving 5 mg/kg/d caffeine, the most significant risk factor associated with high serum concentrations (>20 mg/L) was low BW (P=0.024). CONCLUSION: BW was the only covariate that influenced caffeine clearance in preterm neonates. Preterm neonates with low BW should be carefully monitored for apnea and adverse reactions in addition to undergoing TDM.
Apnea* ; Birth Weight ; Caffeine* ; Drug Monitoring ; Humans ; Infant, Newborn ; Infant, Premature* ; Pharmacokinetics* ; Risk Factors

PURPOSE: This study aimed to evaluate the effects of postnatal acidosis on the short-term clinical outcomes or neonatal mortality in very low birth weight (VLBW) infants. METHODS: We retrospectively reviewed the data of 157 VLBW infants. The study population was divided into three categories: two acidosis groups and one control group, based on blood pH, base excess, and partial pressure of carbon dioxide. The primary outcome variables were massive pulmonary hemorrhage (MPH), apnea, and early death. The secondary outcomes were intraventricular hemorrhage (grade III-IV), necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, and death before 36 weeks' postmenstrual age. RESULTS: After adjustment for birth weight, gestational age and Apgar score, compared to the control group (n=97), MPH and early death were more common in acidosis 1 (n=21) and acidosis 2 (n=39) groups, respectively. There were no differences between the acidosis groups and the control group with respect to other important neonatal outcomes. CONCLUSION: Postnatal acidosis was related to an increased risk of MPH and early neonatal mortality in VLBW infants.
Acidosis* ; Apgar Score ; Apnea ; Birth Weight ; Bronchopulmonary Dysplasia ; Carbon Dioxide ; Enterocolitis, Necrotizing ; Gestational Age ; Hemorrhage ; Humans ; Hydrogen-Ion Concentration ; Infant Mortality ; Infant* ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Very Low Birth Weight* ; Partial Pressure ; Prognosis ; Retinopathy of Prematurity ; Retrospective Studies

BACKGROUND: Immigration to South Korea from neighboring Asian countries has risen dramatically, primarily due to marriage between Korean men and foreign women. Although Filipino women rank fourth among married immigrant women, little is known about the health condition of this population. This manuscript focuses on the design and methods of Filipino women's diet and health study (FiLWHEL). SUBJECTS/METHODS: FiLWHEL is a cohort of Filipino women married to Korean men, aged 19 years old or over. The data collection comprised three parts: questionnaire, physical examination, and biospecimen collection. Questionnaires focused on demographic factors, diet, other health-related behaviors, acculturation and immigration-related factors, medical history, quality of life, and children's health information. Participants visited the recruitment site and answered the structured questionnaires through a face-to-face interview. We also measured their anthropometric features and collected fasting blood samples, toenails, and DNA samples. Recruitment started in 2014. RESULTS/CONCLUSIONS: Collection of data is ongoing, and we plan to prospectively follow our cohort participants. We expect that our study, which is focused on married Filipino women immigrants, can elucidate nutritional/health status and the effects of transitional experiences from several lifestyle factors.
Acculturation ; Asian Continental Ancestry Group ; Child Health ; Cohort Studies ; Data Collection ; Demography ; Diet* ; DNA ; Emigrants and Immigrants ; Emigration and Immigration ; Fasting ; Female ; Humans ; Korea ; Life Style ; Male ; Marriage ; Methods* ; Nails ; Physical Examination ; Prospective Studies ; Quality of Life

BACKGROUND/OBJECTIVES: This study was performed to measure fat-soluble vitamins and minerals in breast milk of Korean lactating mothers who exclusively breastfed their babies. SUBJECTS/METHODS: Breast milk samples were collected from 334 mothers. Concentrations of retinol and α-tocopherol were analyzed by high performance liquid chromatography ultraviolet spectrometry while concentrations of minerals were measured by inductively coupled plasma optical emission spectrometry. RESULTS: Retinol and α-tocopherol contents of breast milk were 39.58 ± 19.64 µg/dL and 0.23 ± 0.13 mg/dL, respectively. Average sodium, potassium, calcium, phosphorus, and magnesium levels in breast milk were 11.11 ± 5.16, 38.56 ± 9.01, 27.87 ± 6.10, 13.56 ± 3.30, and 3.05 ± 0.65 mg/dL, respectively. Contents of trace elements such as iron, zinc, copper, and manganese were 40.26 ± 46.21, 98.40 ± 62.47, 24.09 ± 9.03, and 0.90 ± 1.63 µg/dL, respectively. Fat-soluble vitamin concentration was positively correlated with total fat in milk samples, but no significant differences were observed in levels of retinol, α-tocopherol, or minerals based on whether or not lactating women were taking dietary supplements. CONCLUSIONS: Micronutrient contents of breast milk samples from Korean lactating women were comparable to those of other nations. Retinol and α-tocopherol levels were correlated and also with total fat in breast milk.
Breast* ; Calcium ; Chromatography, Liquid ; Copper ; Dietary Supplements ; Fats ; Female ; Humans ; Infant* ; Iron ; Korea* ; Magnesium ; Manganese ; Micronutrients ; Milk ; Milk, Human* ; Minerals* ; Miners* ; Mothers ; Phosphorus ; Plasma ; Potassium ; Sodium ; Spectrum Analysis ; Trace Elements ; Vitamin A* ; Vitamins ; Zinc

Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular Ca²⁺ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with LPA₁ antagonists showed LPE induced intracellular Ca²⁺ increases in an LPA₁ GPCR-dependent manner. Furthermore, LPE increased intracellular Ca²⁺ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive IP₃ receptors, Ca²⁺ release from intracellular Ca²⁺ stores, and subsequent Ca²⁺ influx across plasma membranes, and LPA acted on LPA₁ and LPA₂ receptors to induce Ca²⁺ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.
Calcium Signaling* ; Calcium* ; Cell Membrane ; GTP-Binding Proteins ; Humans* ; Neuroblastoma* ; Ovarian Neoplasms

Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells. Of differentially expressed genes, plasminogen activator inhibitor (PAI)-2 was increased by annexin A5 siRNA confirmed by qRT-PCR and western blot. Treatment with auranofin decreased PAI-2 and increased annexin A5 expression as well as promoting apoptosis. Furthermore, auranofin-induced apoptosis was recovered by annexin A5 siRNA but it was promoted by PAI-2 siRNA. Interestingly, knockdown of annexin A5 rescued PAI-2 expression suppressed by auranofin. Taken together, our study suggests that induction of annexin A5 by auranofin may enhance apoptosis through suppression of PAI-2 expression in PC-3 cells.
Annexin A5* ; Antirheumatic Agents ; Apoptosis ; Auranofin* ; Blotting, Western ; Gene Expression ; Humans* ; Leukemia, Lymphocytic, Chronic, B-Cell ; Plasminogen Activator Inhibitor 2 ; Plasminogen Activators* ; Plasminogen* ; Prostate* ; Prostatic Neoplasms* ; RNA, Small Interfering ; Statistics as Topic

No abstract available.
Humans ; Surgeons* ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: Shift workers are increasing worldwide, and various negative health effects of shift work have been reported. This study aimed to evaluate the relationship between shift work and health behavior. METHODS: This cross-sectional study included a total of 11,680 Korean adults (6,061 men and 5,619 women) aged ≥20 years old who participated in the Fifth Korean National Health and Nutrition Examination Survey, 2010–2012. Multiple logistic regression analysis was performed to evaluate the association between shift work and health behavior after adjusting for covariates. RESULTS: In men, shift work was associated with an increased risk of inadequate sleep (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.00 to 1.40) compared to day work. In women, shift work was associated with an increased risk of smoking (OR, 1.73; 95% CI, 1.34 to 2.22) and inadequate sleep (OR, 1.24; 95% CI, 1.05 to 1.47) compared to day work. In an age-stratified subgroup analysis, female shift workers aged ≥50 years old demonstrated an increased risk of smoking (OR, 5.55; 95% CI, 3.60 to 8.55), alcohol consumption (OR, 2.22; 95% CI, 1.53 to 3.23), and inadequate sleep (OR, 1.50; 95% CI, 1.10 to 2.05) compared to female day workers. CONCLUSION: Shift work is associated with worse health behavior, and this is most evident in women aged ≥50 years. Targeted strategies to reduce the negative health effects of shift work should be implemented, with consideration of shift workers' demographic characteristics.
Adult ; Alcohol Drinking ; Alcoholism ; Cross-Sectional Studies ; Female ; Health Behavior* ; Humans ; Logistic Models ; Male ; Nutrition Surveys* ; Sleep Wake Disorders ; Smoke ; Smoking ; Work Schedule Tolerance