• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.153-164
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• 2024

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 10¹¹ colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

• 한국임상약학회지
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• 제26권4호
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• pp.312-317
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• 2016

Objective: Midazolam is mainly metabolized by cytochrome P450 (CYP) 3A. Inhibition or induction of CYP3A can affect the pharmacological activity of midazolam. The aims of this study were to develop a population pharmacokinetic (PK) model and evaluate the effect of CYP3A-mediated interactions among ketoconazole, rifampicin, and midazolam. Methods: Three-treatment, three-period, crossover study was conducted in 24 healthy male subjects. Each subject received 1 mg midazolam (control), 1 mg midazolam after pretreatment with 400 mg ketoconazole once daily for 4 days (CYP3A inhibition phase), and 2.5 mg midazolam after pretreatment with 600 mg rifampicin once daily for 10 days (CYP3A induction phase). The population PK analysis was performed using a nonlinear mixed effect model ($NONMEM^{(R)}$ 7.2) based on plasma midazolam concentrations. The PK model was developed, and the first-order conditional estimation with interaction was applied for the model run. A three-compartment model with first-order elimination described the PK. The influence of ketoconazole and rifampicin, CYP3A5 genotype, and demographic characteristics on PK parameters was examined. Goodness-of-fit (GOF) diagnostics and visual predictive checks, as well as bootstrap were used to evaluate the adequacy of the model fit and predictions. Results: Twenty-four subjects contributed to 900 midazolam concentrations. The final parameter estimates (% relative standard error, RSE) were as follows; clearance (CL), 31.8 L/h (6.0%); inter-compartmental clearance (Q) 2, 36.4 L/h (9.7%); Q3, 7.37 L/h (12.0%), volume of distribution (V) 1, 70.7 L (3.6%), V2, 32.9 L (8.8%); and V3, 44.4 L (6.7%). The midazolam CL decreased and increased to 32.5 and 199.9% in the inhibition and induction phases, respectively, compared to that in control phase. Conclusion: A PK model for midazolam co-treatment with ketoconazole and rifampicin was developed using data of healthy volunteers, and the subject's CYP3A status influenced the midazolam PK parameters. Therefore, a population PK model with enzyme-mediated drug interactions may be useful for quantitatively predicting PK alterations.

• 대한한의학회지
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• 제28권2호통권70호
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• pp.80-92
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• 2007

Objectives : Functional dyspepsia (FD) is one of the most common gastrointestinal diseases. Nevertheless, there are many unknown mechanisms of autonomic functioning in FD patients. This study was designed to investigate the relationship between FD and biosignals from heart rate variability (HRV) and Yangdorak diagnosis. Methods : 32 patients (22 female, 10 male; mean age 40) and 32 healthy volunteers (21 female, 11 malemean; age 38) participated in this study. First gastrointestinal symptoms rating scale (GSRS) was assessed by questionnaires in both groups to evaluate the types of gastrointestinal symptoms. Second, HRV and Yangdorak diagnosis were measured in both groups. Results : 1. The FD group in this study mainly had the complaint of 'bloating' symptoms. 2. There was statistically no significant difference between Yangdorak (total average and 24 acupoints) and HRV values except logarithmic low-frequency band (lnLF) and total power (TP) in frequency domain. 3. There was statistically no significant relationship between HRV and Yangdorak in either group. However, most Yangdorak values were positively related with some HRV values (low-frequency, low-frequency/high-frequency ratio and high-frequency, etc) in the control group. Conclusions : FD patients had relatively lesser sympathetic domain than healthy subjects, indicated by decreased lnLF and TP. Particularly, there were positive relationships and significant differences between Yangdorak and HRV in young healthy subjects. This suggests that biosignals from HRV may be a useful method that can differentiate FD from healthy state in those of young age.

• Clinical and Experimental Pediatrics
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• 제62권11호
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• pp.416-421
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• 2019

Background: The seropositivity rate of hepatitis B surface antigen (anti-HBs) antibodies is known to be ≥95% after hepatitis B virus vaccination during infancy. However, a low level or absence of anti-HBs in healthy children is discovered in many cases. Recent studies in adults reported that a reduced anti-HBs production rate is related to obesity. Purpose: To investigate whether body mass index (BMI) affects anti-HBs levels in healthy children following 3 serial dose vaccinations in infancy. Methods: We recruited 1,200 healthy volunteers aged 3, 5, 7, or 10 years from 4-day care centers and 4 elementary schools. All subjects completed a questionnaire including body weight, height, and vaccine type received. Levels of serum hepatitis B surface antigen (HBsAg) and anti-HBs in all subjects were analyzed using electrochemiluminescence immunoassay. The standardized scores (z score) for each sex and age were obtained using the lambda-mu-sigma method in the 2017 Korean National Growth Charts for children and adolescents. Results: Our subjects (n=1,200) comprised 750 males (62.5%) and 450 females (37.5%). The overall anti-HBs seropositivity rate was 57.9% (695 of 1,200). We identified significant differences in mean BMI values between seronegative and seropositive groups (17.45 vs. 16.62, respectively; P<0.001). The anti-HBs titer was significantly decreased as the BMI z score increased adjusting for age and sex (B=-15.725; standard error=5.494; P=0.004). The probability of anti-HBs seropositivity based on BMI z score was decreased to an OR of 0.820 after the control for confounding variables (95% confidence interval, 0.728-0.923; P=0.001). Conclusion: There was a significant association between anti-HBs titer and BMI z score after adjustment for age and sex. Our results indicate that BMI is a potential factor affecting anti-HBs titer in healthy children.

• Journal of Oral Medicine and Pain
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• 제40권1호
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• pp.10-16
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• 2015

Purpose: Pilocarpine has the effects on improvement of salivary flow and subjective symptoms for xerostomic patients. Because of unwanted side effects following its systemic administration, topical pilocarpine has been paid attention as an alternative. This study aimed to investigate effects of pilocarpine solution as mouthwash on salivary flow and adverse effects compared to systemic administration of 5 mg pilocarpine tablet in healthy subjects. Methods: The study was a double blind, placebo-controlled, crossover clinical trial. Five milligrams pilocarpine tablets, 4 mL of 2% pilocarpine solution and placebo solution were given to 12 healthy volunteers (6 males and 6 females) in a predetermined order with wash-out period of at least two days and unstimulated whole saliva was collected before and after administration of each drug. Blood pressure and pulse rate was also measured and subjective effect and potential side effects were evaluated by a self-administrated questionnaire. Results: Systemic (5 mg tablet) and topical (2% solution) use of pilocarpine significantly increased salivary flow rate in healthy subjects compared to placebo (p<0.001). In both the pilocarpine solution and tablet groups, salivary flow rates at 120 minutes after administration remained increased. Subjective effect on salivation was the largest in the pilocarpine tablet group, followed by the pilocarpine solution group (p<0.05). There was no significant difference in blood pressure and pulse rate after administration of all three drugs. Fewer side effects reported in the pilocarpine solution group than in the tablet group. Conclusions: Two percents pilocarpine solution as mouthwash increases salivary flow rate, definitely superior to placebo solution and comparable to pilocarpine tablet, with fewer side effects in healthy subjects. It indicates a possibility of pilocarpine solution as a useful alternative of pilocarpine tablets for the xerostomic patients with systemic diseases.

• The Journal of Korean Physical Therapy
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• 제25권6호
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• pp.374-378
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• 2013

Purpose: Human body have biological rhythmic pattern in a day, which is affected by internal and external environmental factors. We investigated whether respiratory function was fluctuated according to the influence of time-of-day (around at 9 am, 1 pm, and 6 pm) in health subjects, using pulmonary function test (PFT). Methods: Eighteen healthy volunteers (8 men, mean ages; $22.4{\pm}1.6$, mean heights; $166.61{\pm}9.60$, mean weight; $59.3{\pm}10.3$) were recruited. Pulmonary function test (PFT) was measured at three time points in day, around 9 am, 1 pm, and 6 pm in calm research room with condition of under 55dB noise level, using a spirometer (Vmax 229, SensorMecis, USA). Forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FVC/FEV1, and peak expiratory flow (PEF) were acquired. Results: In comparison of raw value of PFT among three time points, subjects showed generally better respiratory function at 9 am, than at other points, although no significance was found. In comparison of distribution of ranking for respiratory function in each individual, only PEF showed significant difference. In general, distributional ratio of subjects who showed best performance of respiratory function in a day was high. Conclusion: These findings showed that circadian rhythm by diurnal pattern was not detected on respiratory function throughout all day. But, best performance on respiratory function was observed mostly in the morning, although statistical significance did not exist.

• 한국임상약학회지
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• 제22권1호
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• pp.65-72
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• 2012

Antidepressants are frequently prescribed for a wide range of symptoms. Surveys in several countries have suggested that negative attitudes towards antidepressants are common. However, there has been limited research associated with the attitudes in Korea. Therefore, this quantitative descriptive study describing the perception and attitudes toward antidepressants was performed using healthy people and outpatients who are not taking antidepressants. The surveys by means of self-reporting questionnaires showed negative attitudes towards antidepressants (74.2%). But, 74.2% of above participants gave positive answers to take antidepressants when they are counseled by medical professionals. Higher rates of negative attitudes were found in younger age group ("it causes addiction") and healthy volunteers and urban area groups ("it causes physical harm"). Study participants without experiences in taking antidepressants showed more negative attitudes although the difference was not statistically significant. Based on the results, accurate and objective information about antidepressants needs to be provided by well-trained health professionals.

• 대한예방한의학회지
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• 제14권2호
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• pp.105-120
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• 2010

Objectives : This study aims to evaluate the effects of expiration-to-inspiration time ratio (E/I-ratio) on heart rate, which represents cardiac autonomic function, and cold-heat in the healthy people. Methods : 49 healthy young volunteers(male : female = 32 : 17) were recruited in the study. The participants completed the questionnaire for yin-yang pattern identification and then we measured the chest plethysmogram for respiration signal and the electrocardiogram for NN intervals during different E/I-ratio from 1 to 2. We compared heart rate variability including RMS-SD, VLF, LF and HF, and the trend-cycle factors decomposed from NN interval data by time series analysis among the respective E/I-ratio. We also confirmed the difference on the trend-cycle factors according to the score of the questionnaire for cold and heat pattern identification. Results : There were differences on the trend-cycle factors from NN interval data, but no significant difference on heart rate variability, among the respective E/I-ratio. We also found significant relationship between the trend-cycle factors and the heat pattern identification scores. Conclusions : The results indicate that cardiac autonomic function can be modulated by the E/I-ratio and the modulation will be slower and more tendencious than respiratory sinus arrhythmia.

• Journal of Nutrition and Health
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• 제37권4호
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• pp.281-290
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• 2004

The purpose of this project was to evaluate whether daily fruit juice consumption could reduce the DNA damage in healthy subjects. The study was performed using 67 healthy volunteers (29 smokers, 38 nonsmokers) who were supple-mented with 480 m1 of grape juice for 8 weeks. Eight weeks of grape juice consumption did not change any anthropometric parameters. Lymphocyte DNA damage before the study was significantly greater (p<0.05) in smoker than nonsmoker, but, grape juice consumption significantly reduced DNA damage in both smoker (26%) and nonsmoker (I7%) to the level where there was no difference remained between the two groups after the intervention trial. This preventive effect of grape juice against DNA damage was not affected by sex of the subjects in non-smokers. Plasma $\alpha$-carotene, Iyco-pene and ${\gamma}$-totopherol was significantly increased after the trial in smokers, while erythrocyte catalase was significan-tly increased in both smokers and nonsmokers. Total radical-trapping antioxidant potential (TRAP) level in all subjects was significantly reduced after the intervention, while GSH-Px activity was increased only in nonsmokers. These results suggests that daily consumption of grape juice may protect DNA damage in peripheral lymphocytes, and supports the hypothesis that grape juice might exert their effect partially via a decrease in oxidative damage to DNA in humans partly by improving their antioxidative defense system.

• 대한한의학회지
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• 제24권1호
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• pp.133-140
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• 2003

Objectives : Kochiae Fructus (dried fruits of Kochia scoparia L. Schrad,) is used in the treatment of skin diseases as internal or external medicine in Oriental Medicine, but there has not been experimental study of Kochiae Fructus as an external medicine. The purpose of this study was to investigate if it has certain effects on the skin or not. Methods : By a skin prick test method, we evaluated the effects of wet dressing with Kochiae Fructus decoction in different concentrations on histamine-induced itch, erythema and wheal responses, and compared them with the effects of calamine lotion and distilled water in 8 healthy volunteers aged 26-32. Results : The mean intensity and duration of itch were most decreased after wet dressing with a Kochiae Fructus decoction of 100mg/150ml. The time required for erythema to reach the maximal size was around 5 minutes in all groups, and the size of erythema was smallest on the skin taking wet dressing with the Kochiae Fructus decoction of highest concentration. The size of wheal was also smallest after wet dressing with the highest concentration Kochiae Fructus decoction. The effects of wet dressing with Kochiae Fructus decoction on skin were dependent on their concentrations. Conclusions : Kochiae Fructus suppressed the histamine-induced skin responses, which supports the ancient herbal literatures which describe that Kochiae Fructus has a certain effectiveness on some skin diseases.