Hye Sun Gwak

Interaction between warfarin and Korean red ginseng in patients with cardiac valve replacement

BACKGROUND The objective of this study was to determine whether an interaction exists between warfarin and Korean red ginseng. METHODS A prospective, double-blind, randomized, two-period crossover study was conducted on 25 patients with cardiac valve replacement under warfarin therapy. Either Korean red ginseng 1 g or placebo (hop extract 0.25 g, caramel color 0.05 g, and red ginseng flavor 0.03 g) was concomitantly administered with warfarin. INR and warfarin concentrations were analyzed on the 3rd and 6th weeks of each study period. RESULTS The INR changes on the 3rd and 6th weeks of Korean red ginseng administration were -0.16±0.95 and -0.14±0.94 whereas those of placebo were -0.03±0.65 and 0.25±0.95; there were no statistically significant differences in mean INR changes. CONCLUSION Korean red ginseng could be used with close monitoring and under appropriate education in patients who take warfarin.

Pharmacokinetic Characteristics of Capsaicin-Loaded Nanoemulsions Fabricated with Alginate and Chitosan

Nanotechnologies are being employed to enhance the stability and oral bioavailability of lipophilic substances, such as capsaicin. This study aimed to examine the pharmacokinetic properties of the formulated capsaicin-loaded nanoemulsions. A pharmacokinetic study was carried out using double-layer nanoemulsions fabricated with alginate and chitosan polymers and triple-layer nanoemulsions fabricated with chitosan/alginate polymers. Capsaicin nanoemulsions and capsaicin control (oleoresin capsicum) were administered to the rat at a dose of 10 mg/kg. A statistically significant difference was found in the area under the curve from time zero to time infinity (AUCinf) among formulations (p < 0.01). In comparison to the control group, the relative bioavailability of formulated nanoemulsions was up to 131.7. The AUCinf increased in a nano-size-dependent manner; as nano size decreased, AUCinf increased. IN comparison to the double-layer nanoemulsions, the triple-layer nanoemulsion showed a significantly increased volume of distribution, resulting in the increased clearance and decreased AUCinf. It was concluded that the formulated nanoemulsions could significantly enhance the bioavailabilty of capsaicin.

Pharmacokinetic evaluation and modeling of formulated levodopa intranasal delivery systems

Levodopa (L-dopa), the metabolic precursor of dopamine, has primarily been used for the treatment of Parkinsons disease (PD) in combination with carbidopa (C-dopa). This study aims to investigate the feasibility of L-dopa nasal delivery systems prepared using maleic acid solution containing 2-hydroxypropyl-beta-cyclodextrin, and to develop pharmacokinetic models. Following oral or intravenous administration of L-dopa plus C-dopa and intranasal dosing of L-dopa in the presence and absence of C-dopa to the rat, the concentrations of L-dopa in plasma and brain were determined using HPLC. The pharmacokinetic profiles were analyzed using non-compartmental and compartmental modeling approaches. Simultaneous nonlinear regression was performed to improve the identifiability of model parameters. L-Dopa was rapidly absorbed into blood and brain. The absolute bioavailabilities of oral and nasal preparations containing C-dopa were 17.7 and 45.4%, respectively. C-dopa caused a 1.2-fold decrease in the elimination rate of L-dopa, indicating decreased metabolism. Although the half-life after nasal administration was relatively short (less than 30 min) in both blood and brain regardless of C-dopa addition, the systemic exposure was promising due to rapid absorption. In conclusion, the L-dopa nasal delivery system could be used as a good rescue therapy for PD patients who experience symptom fluctuation with oral L-dopa administration.

Association of vitamin D concentrations with adiposity indices among preadolescent children in Korea

Abstract Background and Objective: We aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) and anthropometric indicators of adiposity among Korean preadolescent children aged 7–9 years. Subjects and Methods: Children aged 7 to 9 from the Ewha Birth & Growth Cohort were followed up from July to August 2011. Serum 25(OH)D concentration was measured using radio immunoassay. We assessed the magnitude of cross-sectional association with vitamin D concentrations and indicators of adiposity [body mass index (BMI), waist circumference (WC), mid-arm circumference (MAC), body fat mass (BFM), percent body fat (PBF), and triceps skinfold thickness (TSF)] using multiple linear and logistic regression analyses adjusted for sex, age, birth order, maternal education, and fruit/fruit juice intake. Results: Thirty-two (16%) out of a total of 205 children showed an optimal level of serum 25(OH)D, but most children did not reach a sufficient level (<30 ng/mL) even in summer. The level of 25(OH)D was inversely associated with BMI (β=–0.10, p<0.01), WC (β=–0.28, p<0.01), and BFM (β=–0.12, p=0.02) after adjusting for confounding factors and showed marginal boundary with PBF (β=–0.20, p=0.06) and TSF (β=–0.11, p=0.08). Regarding the risk of overweight, a 13% protective effect per 1 ng/mL increase of 25(OH)D was shown even after adjusting for relevant confounding factors (adjusted odds ratio=0.87, 95% confidence interval 0.78–0.98). Conclusions: We found that the 25(OH)D concentrations were inversely associated with adiposity indices in preadolescent children. This study suggests that adequate vitamin D intake in growing children is crucial to maintain an optimal vitamin D level to prevent obesity and obesity-related health problems later in life.

Mendelian Randomization Analysis of the Effect of Maternal Homocysteine During Pregnancy, as Represented by Maternal MTHFR C677T Genotype, on Birth Weight

Background We used Mendelian randomization analysis to investigate the causal relationship between maternal homocysteine level, as represented by maternal methylenetetrahydrofolate reductase (MTHFR) C677T genotype, with the birth weight of offspring. Methods We recruited women at 24 to 28 weeks’ gestation who visited Ewha Womans University Hospital for prenatal care during the period from August 2001 to December 2003. A total of 473 newborns with a gestational age of at least 37 weeks were analyzed in this study. We excluded twin births and children of women with a history of gestational diabetes, gestational hypertension, or chronic renal disease. The association of maternal homocysteine concentration with the birth weight of infants was analyzed using 2-stage regression. Results MTHFR C677T genotype showed a dose–response association with homocysteine concentration for each additional T allele (Ptrend < 0.01). Birth weight decreased from 120 to 130 grams as maternal homocysteine level increased, while controlling for confounding factors; however, the association was of marginal significance (P = 0.06). Conclusions Our results suggest an adverse relationship between maternal homocysteine level and birth weight. A reduction in homocysteine levels might positively affect birth outcomes.

Association of pre-operative medication use with post-operative delirium in surgical oncology patients receiving comprehensive geriatric assessment

BackgroundOlder patients undergoing surgery tend to have a higher frequency of delirium. Delirium is strongly associated with poor surgical outcomes. This study evaluated the association between pre-operative medication use and post-operative delirium (POD) in surgical oncology patients receiving comprehensive geriatric assessment (CGA).MethodsA total of 475 patients who were scheduled for cancer surgery and received CGA from January 2014 to June 2015 were included. Pre-operative medication review through CGA was conducted on polypharmacy (≥5 medications), delirium-inducing medications (DIMs), fall-inducing medications (FIMs), and potentially inappropriate medications (PIMs). POD was confirmed by psychiatric consultation, and DSM-V criteria were used for diagnosing delirium. The model fit of the prediction model was assessed by computing the Hosmer-Lemeshow goodness-of-fit test. Effect size was measured using the Nagelkerke R2. Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC).ResultsTwo models were constructed for multivariate analysis based on univariate analysis; model I included dementia and DIM in addition to age and sex, and model II included PIM instead of DIM of model I. Every one year increase of age increased the risk of POD by about 1.1-fold. DIM was a significant factor for POD after adjusting for confounders (AOR 12.78, 95 % CI 2.83-57.74). PIM was also a significant factor for POD (AOR 5.53, 95 % CI 2.03-15.05). The Hosmer-Lemeshow test results revealed good fits for both models (χ2 = 3.842, p = 0.871 for model I and χ2 = 8.130, p = 0.421 for model II). The Nagelkerke R2 effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R2effect size of 0.174 and AUROC of 0.819.ConclusionsThese results suggest that pharmacists’ comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients.

Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease

PURPOSE The results of a prospective study of topical budesonide versus topical dexamethasone therapy for oral manifestations of chronic graft-versus-host disease (cGVHD) are presented. METHODS In a prospective single-center investigation, a cohort of patients who developed oral symptoms of cGVHD after allogeneic stem cell transplantation were assigned to topical treatment with 0.03% budesonide rinse (group A, n = 26) or 0.01% dexamethasone rinse (group B, n = 24). Diagnosis of oral cGVHD symptoms, clinical staging, and treatment response scoring were performed at baseline and one month later according to current National Institutes of Health consensus criteria. RESULTS At one-month follow-up, there was a significant decrease in the median oral cGVHD examination score in both groups (p < 0.001); the decrease in the median examination score was greater with budesonide versus dexamethasone therapy (2.5 points versus 1.0 point, p = 0.045). The rates of overall treatment response, including complete and partial responses, were 53.8% and 29.2% in groups A and B, respectively (p = 0.093). In addition, there was a significant decrease from baseline in the median self-rated oral pain severity score in group A (p < 0.001). CONCLUSION Patients who received topical budesonide or dexamethasone rinse to treat oral manifestations of cGVHD had decreased cGVHD severity and pain scores after 30 days compared with baseline scores, though no statistical differences were seen between groups.

The preventive effect of breast-feeding for longer than 6 months on early pubertal development among children aged 7–9 years in Korea

OBJECTIVE The present study was performed to investigate whether breast-feeding is associated with early pubertal development among children 7-9 years old in Korea. DESIGN Children were divided into those who did and did not receive breast-feeding for 6 months or longer in accordance with the recommendations of the WHO. Pubertal status was determined by clinical examination using Tanner staging. SETTING Prospective observational study. SUBJECTS We conducted a follow-up study of children aged 7-9 years in 2011 who had taken part in the Ewha Birth & Growth Cohort study. RESULTS Fifty (22.8%) of the total of 219 children were in early puberty, with the proportion being slightly higher for girls (24.1%) than boys (21.4%). Children who had entered early puberty were taller, weighed more and had a higher concentration of insulin-like growth factor 1. Moreover, the change in weight Z-score from birth to follow-up was significantly lower in children who were breast-fed than in those who were not (weight Z-score change: 0.32 (sd 1.59) v. 0.77 (sd 1.61), respectively, P=0.04). Comparison of breast-feeding by puberty status indicated a preventive association with early puberty in children who were breast-fed for 6 months or longer (OR=0.37; 95% CI 0.18, 0.74). This association remained significant after adjustment for relevant covariates. CONCLUSIONS These results demonstrate a beneficial association between breast-feeding and early pubertal development, especially in those breast-fed for 6 months or longer. The study suggests that interventions would need to start early in life to prevent early pubertal development.

Effects of bile salts on gastrointestinal absorption of pravastatin

This study aimed to examine the effects of bile salts and formulations on the absorption through gastrointestinal tract of pravastatin, which has low bioavailability. Pravastatin sodium physical mixtures and solid dispersions were prepared using various bile salts. The physicochemical characteristics and permeation profiles were investigated using pravastatin sodium-bile salt physical mixtures and solid dispersions. Pravastatin in the physical mixture did not achieve amorphous state, whereas that in the solid dispersion was completely converted to amorphous state. The permeation enhancement factors ranged between 1.13 and 11.9 with the addition of bile salts, and the permeation flux of pravastatin sodium greatly increased as the sodium cholate (NaC) concentration increased from 5 to 10 mM. Pravastatin sodium permeation fluxes [µg/(cm(2) h)] from solid dispersions (drug-NaC = 1:49) (20.8 ± 2.7) were much higher than those from physical mixtures (4.7 ± 3.1) and commercial tablets (3.5 ± 1.2) (p < 0.05). The dissolution rates of pravastatin sodium from solid dispersions in pH 1.2 were much lower than those from physical mixtures and commercial products, whereas more than 97% of pravastatin sodium was dissolved at 5 min in pH 6.8. On the basis of the results, it was concluded that pravastatin sodium solid dispersions containing bile salts could enhance drug absorption.

Effect of Urinary Bisphenol A on Androgenic Hormones and Insulin Resistance in Preadolescent Girls: A Pilot Study from the Ewha Birth & Growth Cohort

To assess the effect of urinary bisphenol A (BPA) on repeated measurements of androgenic hormones and metabolic indices, we used multivariate analysis of variance (MANOVA) adjusted for potential confounders at baseline. During July to August 2011, 80 preadolescent girls enrolled in the Ewha Birth & Growth Cohort study participated in a follow-up study and then forty-eight of them (60.0%) came back one year later. Baseline levels of estradiol and androstenedione were higher in the BPA group than in the non-BPA group. One year later, girls in the high BPA exposure group showed higher levels of androstenedione, testosterone, estradiol, and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index, than those in the other groups (p < 0.05). In MANOVA, estradiol and androstenedione showed significant differences among groups, while dehydroepiandrosterone, insulin, and HOMA-IR showed marginally significant differences. Exposure to BPA may affect endocrine metabolism in preadolescents. However, further investigation is required to elucidate the mechanisms linking BPA with regulation of androgenic hormones.