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1.
J Breath Res ; 18(4)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38968933

ABSTRACT

Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221,P= 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis.


Subject(s)
Breath Tests , Methane , Non-alcoholic Fatty Liver Disease , Humans , Breath Tests/methods , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/diagnosis , Methane/analysis , Female , Male , Middle Aged , Republic of Korea/epidemiology , Adult , Body Mass Index , Hydrogen/analysis , Aged , Risk Factors , Exhalation
2.
Nat Commun ; 14(1): 3668, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37339951

ABSTRACT

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10-7 (odds ratio = 1.72) and 1.1 × 10-7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling.


Subject(s)
Fractures, Bone , Osteoporosis , Animals , Female , Mice , Bone Density/genetics , Fractures, Bone/genetics , Osteogenesis/genetics , Osteoporosis/genetics , Osteoporosis/metabolism , Zebrafish
3.
Int J Mol Sci ; 23(19)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36233190

ABSTRACT

Although many genome-wide association studies (GWASs) have evaluated the association with metabolic disorders, the current study is the first attempt to analyze the genetic risk factors for various metabolic disorders according to sex and age groups of the life course in Korean adults. A total population of 50,808 people were included in this GWAS. The genetic traits for eight metabolic phenotypes were investigated in peri-, and postmenopausal women compared to a younger group or men of corresponding age groups. The metabolic phenotypes include general obesity, abdominal obesity, hypertension, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, and metabolic syndrome. In the total participants, GWAS results for eight metabolic phenotypes found 101 significant loci. Of these, 15 loci were the first reported to be associated with the risk of metabolic disorder. Interestingly, some of the significant loci presented the association with the various phenotypes, which presented when there was a correlation between phenotypes. In addition, we analyzed divided by gender and age (young adult, peri-menopausal group, older adult), and specifically identified specific loci in peri-menopausal women. Meanwhile, several genetic factors associated with metabolic disorders were newly reported in our study. In particular, several genes were significantly associated with one of the metabolic phenotypes in only a single specific group. These findings suggest that menopausal transition rather than aging itself potentiates the influence of genetic risks on metabolic disorders. In addition, some genetic loci with low frequencies may play a role in the metabolic disturbances in a specific sex and age group. The genetic traits derived from our study may contribute to understanding the genetic risk factors for metabolic disorders in the Korean population.


Subject(s)
Diabetes Mellitus, Type 2 , Metabolic Syndrome , Asian People/genetics , Female , Genome-Wide Association Study , Humans , Lipoproteins, HDL/genetics , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/genetics , Obesity/genetics , Republic of Korea/epidemiology
4.
Nutrients ; 14(12)2022 Jun 18.
Article in English | MEDLINE | ID: mdl-35745268

ABSTRACT

Few studies have investigated the effects of calcium supplementation on cardiovascular outcomes in individuals with low calcium intake in real-world settings. This study examined the association between calcium supplementation and cardiovascular outcomes in the Korean population in a real-world setting. This large retrospective cohort study included patients aged ≥45 years first prescribed calcium supplements in 2010. Age- and sex-matched controls were recruited among those who had no prescription for calcium supplements. Longitudinal data were collected on 31 December 2018. Kaplan−Meier estimation and Cox proportional hazard regression analysis were performed. The cumulative incidence of acute myocardial infarction, ischemic stroke, and death was significantly higher in the calcium supplementation group than in the control group (p < 0.05 by log-rank test). The calcium supplementation group had a significantly higher risk of myocardial infarction, ischemic stroke, and death than the control group. Compared to the control group, the hazard ratios (95% confidence intervals) of the incidence of myocardial infarction, stroke, and death in the supplementation group were 1.14 (1.03−1.27), 1.12 (1.05−1.20), and 1.40 (1.32−1.50), respectively, after adjusting for confounding variables. Considering the associated cardiovascular risk, calcium supplementation for osteoporosis treatment should be administered cautiously.


Subject(s)
Cardiovascular Diseases , Ischemic Stroke , Myocardial Infarction , Stroke , Calcium , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Dietary Supplements , Humans , Myocardial Infarction/complications , National Health Programs , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Stroke/complications
5.
BMC Nephrol ; 23(1): 197, 2022 05 26.
Article in English | MEDLINE | ID: mdl-35619087

ABSTRACT

BACKGROUND: Chronic kidney disease(CKD) is a major public health issue and is highly prevalent in the general population. Leptin is an adipose tissue-derived endocrine factor that has been associated with several metabolic factors involved in cardiovascular diseases. Several studies have investigated the association between leptin and renal diseases so far. But the results are conflicting between the studies. The objective of our study was to verify the direct association of serum leptin level with CKD development. METHODS: This prospective cohort study included 2646 adult aged 40-70 without CKD in the Korean Genome and Epidemiology Study(KoGES) across South Korea from November 2005 to February 2012. The primary outcome was the development of CKD as defined by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). Multivariate stepwise logistic regression analysis was done to assess the independent associations, for with the incident of CKD as the dependent variable, in tertiles of leptin values. RESULTS: Among 1100 men and 1546 women with 2.8 mean years of follow-up, incidence of CKD was 18(1.63%) for men and 50(3.23%) for women. In the multivariate logistic regression models, individuals in the highest serum leptin tertile showed significant associations with risk of CKD after adjustment compared to the lowest tertiles in the population. The crude odds ratio for trend was 2.95(p = 0.004) for men. After adjusting for age, baseline eGFR variables showed correlation with statistical significance (OR for trend = 2.25, p = 0.037) for men. The same trends were also seen observed in all population and women also, but no statistical significance was found. CONCLUSIONS: Higher plasma leptin levels are associated with the incidence of CKD, independent of traditional factors such as age, baseline eGFR. Our results suggest that leptin may partly explain part of the reported association between obesity and kidney disease.


Subject(s)
Leptin , Renal Insufficiency, Chronic , Adult , Female , Humans , Incidence , Longitudinal Studies , Male , Prospective Studies , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology
6.
J Obes Metab Syndr ; 30(2): 81-92, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-34045368

ABSTRACT

Obesity is a prevalent and complex disease. The prevalence of obesity in Korea increased from 29.7% in 2010 to 35.7% in 2018, with the prevalence of abdominal obesity being 23.8% in 2018. Obesity contributes to medical costs and socioeconomic burden due to associated comorbidities. The treatment and management of obesity is changing based on new clinical evidence. The 2020 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea summarizes evidence-based recommendations and treatment guidelines.

7.
J Clin Biochem Nutr ; 67(3): 344-348, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33293778

ABSTRACT

Metabolic syndrome is well known to increase the risk of cardiovascular diseases. We have reported that phytochemicals rich black rice with giant embryo reduced fat mass and metabolic disorders in an animal model. However, such effects have not been evaluated in humans. Subjects with metabolic syndrome (n = 49, 38 male, 44.3 ± 6.1 years) were randomly assigned into two groups and ingested roasted black-rice with giant embryo (BR, n = 26, 20 male) or white-rice (WR, n = 23, 18 male) powders mixed with water for breakfast for three months. Subjects were evaluated for various metabolic parameters before and after intervention. All parameters were not significantly different between groups before starting the intervention. After three months of consumption of either BR or WR, changes of body weight in BR vs WR groups (-1.54 kg vs -1.29 kg, p = 0.649) as well as waist circumference (-1.63 cm vs -1.02 cm, p = 0.365) were not significantly different between groups. However, changes in highly-sensitive C reactive proteins in BR vs WR groups (-0.110 mg/dl vs 0.017 mg/dl, p = 0.003) had significant differences. Three months of meal replacement with BR had a significant reduction of highly-sensitive C reactive protein compared to those with WR in adults with metabolic syndrome.

8.
Nutrients ; 12(9)2020 Sep 18.
Article in English | MEDLINE | ID: mdl-32961901

ABSTRACT

The aim of this study was to investigate the longitudinal change in muscle mass over 10 years according to serum calcium levels and calcium intake. A total of 1497 men and 1845 women aged 50 years and older were included. Significant muscle loss (SML) was defined as a 5% or greater loss from baseline, while time-dependent development of SML was assessed according to quartiles for corrected calcium level and daily calcium intake using Cox regression models. The incidence of SML was 6.7 and 7.7 per 100-person-years among men and women, respectively. Groups with the lowest corrected calcium levels had more prominent SML than those with higher calcium levels, regardless of sex. The relationship between SML and calcium intake was significant only among women. The hazard ratio for SML per 1 mmol/L increase in corrected calcium level was 0.236 and 0.237 for men and women, respectively. In conclusion, low serum calcium levels may predict SML among adults aged ≥ 50 years, while low calcium intake may be a predictor for muscle loss among women. Therefore, encouraging dietary calcium intake among middle-aged and older adults for preservation of muscle mass should be considered.


Subject(s)
Aging/genetics , Aging/physiology , Asian People/genetics , Calcium/blood , Muscle, Skeletal/physiology , Sarcopenia/genetics , Adult , Calcium/administration & dosage , Calcium, Dietary/administration & dosage , Female , Genome , Humans , Male , Middle Aged
9.
Nutrients ; 12(5)2020 May 14.
Article in English | MEDLINE | ID: mdl-32422942

ABSTRACT

Functional dyspepsia (FD) is associated with small intestinal bacterial overgrowth (SIBO). Several animal studies have reported that ursodeoxycholic acid (UDCA) has antibacterial and anti-inflammatory effects in the intestine. We hypothesized that UDCA may be effective against dyspeptic symptoms and SIBO in patients with FD. We conducted this randomized controlled trial to investigate the effects of UDCA in FD patients with SIBO. Twenty-four patients diagnosed with FD and SIBO based on lactulose breath test (LBT) were randomly assigned to either a UDCA treatment group or an untreated group. The treatment group received 100 mg of UDCA three times per day for two months; the untreated group was monitored for two months without intervention. After two months in both groups, we reevaluated LBT and FD symptoms using the Nepean dyspepsia index-K. FD symptoms in the UDCA-treated group were significantly reduced after two months compared with baseline and FD symptom scores between the UDCA-treated and untreated groups showed statistically significant differences after two months. In addition, the total methane gas levels for 90 minutes in LBT were significantly decreased after two months compared with baseline in the UDCA-treated group. In this preliminary exploratory study, we found that two months of UDCA treatment resulted in FD symptom improvement and reduced methane values during 90 minutes on the LBT, suggesting that methane-producing SIBO were associated with symptoms of dyspepsia and that UDCA was helpful in these patients. These findings need to be validated via large-scale controlled and well-designed studies.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Blind Loop Syndrome/drug therapy , Dyspepsia/drug therapy , Gastrointestinal Agents/therapeutic use , Ursodeoxycholic Acid/therapeutic use , Adult , Blind Loop Syndrome/complications , Breath Tests , Dyspepsia/microbiology , Female , Humans , Intestine, Small/microbiology , Lactulose/analysis , Male , Methane/analysis , Middle Aged , Pilot Projects , Severity of Illness Index , Treatment Outcome
10.
J Obes Metab Syndr ; 29(2): 99-109, 2020 Jun 30.
Article in English | MEDLINE | ID: mdl-32378399

ABSTRACT

Obesity is a serious and growing worldwide health challenge associated with type 2 diabetes mellitus, cardiovascular disease, osteoarthritis, some cancers, sleep apnea, asthma, and nonalcoholic fatty liver. The Korean Society for the Study of Obesity recommends that pharmacotherapy should be considered when intensive lifestyle modifications fail to achieve a weight reduction in obese patients with a body mass index ≥25 kg/m2. Long-term medications for obesity have traditionally fallen into two major categories: centrally acting anorexiant medications and peripherally acting medications, such as orlistat. In this paper, we provide an overview of the anti-obesity medications currently available for the long-term and individualized treatment of obesity.

11.
Medicine (Baltimore) ; 99(11): e18963, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32176028

ABSTRACT

High levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are associated with increased diabetes risk. In the present study, we investigated the combined effects of ALT and GGT on the development of diabetes in a Korean population. A total of 9405 individuals (4020 women and 5385 men) without diabetes were enrolled in this study. From the baseline health screening to the follow-up examination, the development of diabetes, based on changes in ALT and GGT quartile levels, was analyzed. In addition, we analyzed the quartiles of ALT and GGT together to determine any synergistic effect from the fourth quartile of ALT and GGT on the development of diabetes. The development of diabetes gradually increased with an increase in the circulating levels of ALT and GGT. For the fourth quartile ALT and GGT, the hazard ratios of diabetes compared with the first quartile were 1.892 (95% confidence interval [CI]: 1.26-2.83, P = .002) and 3.526 (95% CI: 2.12-5.85, P < .001) after adjusting for confounders, respectively. Hazard ratios of diabetes after combining both fourth quartiles of ALT and GGT were 3.663 (95% CI: 2.42-5.52, P < .001), as compared with the first and second quartiles. Serum ALT and GGT levels are well associated with diabetes in Koreans after adjusting for confounders, and a combination of ALT and GGT levels can have a synergy in predicting the development of diabetes.


Subject(s)
Alanine Transaminase/blood , Diabetes Mellitus/enzymology , gamma-Glutamyltransferase/blood , Biomarkers/blood , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Republic of Korea/epidemiology , Risk Factors
12.
J Bone Metab ; 23(4): 191-197, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27965940

ABSTRACT

BACKGROUND: With aging, calcium efflux from bone is increased with age-related bone loss, and it can reduce bone mineral density (BMD). On the contrary, age-related calcium adoption into arterial wall progressively stiffens blood vessels. Theses process insinuates shift of calcium among different pools in body. However, their relationships have not been elucidated yet. So we investigated the correlation among calcium contents in different body pools, such as hair, bone, and blood vessels in women. METHODS: We analyzed 50 females retrospectively who measured Agatston coronary artery calcium score (CACS), BMD, and hair calcium concentration at a regular health check-up in a university hospital. CACS was achieved by coronary multidetector computed tomography, BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femur, and hair calcium level was checked by hair tissue mineral analysis. RESULTS: CACS inversely correlated with BMD (r=-0.280, P=0.049 with lumbar vertebrae 1-4, r=-0.310, P=0.028 with femur neck, r=-0.333, P=0.018 with femur total) and hair calcium concentration (r=-0.352, P=0.012). CONCLUSIONS: CACS has negative correlation with BMD and hair calcium level in women. Different body calcium pools such as bone, hair and blood vessel significantly correlated each other.

13.
PLoS One ; 10(8): e0135285, 2015.
Article in English | MEDLINE | ID: mdl-26258864

ABSTRACT

To identify novel susceptibility variants for osteoporosis in Korean postmenopausal women, we performed a genome-wide association analysis of 1180 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 405 individuals with osteoporosis and 722 normal controls of the Korean Association Resource cohort. A logistic regression analysis revealed 72 nsSNPs that showed a significant association with osteoporosis (p<0.05). The top 10 nsSNPs showing the lowest p-values (p = 5.2×10-4-8.5×10-3) were further studied to investigate their effects at the protein level. Based on the results of an in silico prediction of the protein's functional effect based on amino acid alterations and a sequence conservation evaluation of the amino acid residues at the positions of the nsSNPs among orthologues, we selected one nsSNP in the SQRDL gene (rs1044032, SQRDL I264T) as a meaningful genetic variant associated with postmenopausal osteoporosis. To assess whether the SQRDL I264T variant played a functional role in the pathogenesis of osteoporosis, we examined the in vitro effect of the nsSNP on bone remodeling. Overexpression of the SQRDL I264T variant in the preosteoblast MC3T3-E1 cells significantly increased alkaline phosphatase activity, mineralization, and the mRNA expression of osteoblastogenesis markers, Runx2, Sp7, and Bglap genes, whereas the SQRDL wild type had no effect or a negative effect on osteoblast differentiation. Overexpression of the SQRDL I264T variant did not affect osteoclast differentiation of the primary-cultured monocytes. The known effects of hydrogen sulfide (H2S) on bone remodeling may explain the findings of the current study, which demonstrated the functional role of the H2S-catalyzing enzyme SQRDL I264T variant in osteoblast differentiation. In conclusion, the results of the statistical and experimental analyses indicate that the SQRDL I264T nsSNP may be a significant susceptibility variant for osteoporosis in Korean postmenopausal women that is involved in osteoblast differentiation.


Subject(s)
Osteoblasts/metabolism , Osteoporosis, Postmenopausal/genetics , Oxidoreductases Acting on Sulfur Group Donors/genetics , Polymorphism, Single Nucleotide , Postmenopause/genetics , Quinone Reductases/genetics , Aged , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Biomarkers/metabolism , Bone Density , Calcification, Physiologic , Case-Control Studies , Cell Differentiation , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Female , Gene Expression , Genome-Wide Association Study , Genotype , Humans , Hydrogen Sulfide/pharmacology , Logistic Models , Middle Aged , Monocytes/metabolism , Monocytes/pathology , Osteoblasts/drug effects , Osteoblasts/pathology , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/pathology , Osteoporosis, Postmenopausal/epidemiology , Osteoporosis, Postmenopausal/metabolism , Osteoporosis, Postmenopausal/pathology , Oxidoreductases Acting on Sulfur Group Donors/metabolism , Postmenopause/metabolism , Primary Cell Culture , Quinone Reductases/metabolism , Republic of Korea/epidemiology , Sp7 Transcription Factor , Transcription Factors/genetics , Transcription Factors/metabolism
14.
Eur J Pharmacol ; 762: 11-7, 2015 Sep 05.
Article in English | MEDLINE | ID: mdl-26003276

ABSTRACT

Activation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in conditioned taste aversion (CTA) learning induced by lithium chloride. This study investigated if circadian activation of the HPA axis affects the lithium-induced CTA formation. The pairing of conditioned stimulus (sucrose) and unconditioned stimulus (lithium chloride) was performed at night (shortly after light-off) when the HPA activity shows its circadian increase. Intraperitoenal injection of lithium chloride (0.15M, 3ml/kg or 12ml/kg) at night induced CTA formation and the HPA axis activation and increased c-Fos expression in both the parabrachial nucleus (PBN) and the nucleus tractus of solitarius (NTS) in a dose dependent manner. However, intracerebroventricular lithium (0.6M, 5µl) at night failed to induce CTA or the HPA axis activation, although it increased c-Fos expression in the PBN and NTS. Results suggest that circadian activation of the HPA axis may affect central, but not peripheral, effect of lithium in CTA formation, and the lithium-induced c-Fos expression in brain regions may not be effective to induce CTA unless it is coupled with the HPA axis activation. It is concluded that the HPA axis activation may play an important role mediating not only peripheral but also central effect of lithium in CTA formation.


Subject(s)
Avoidance Learning/drug effects , Circadian Rhythm/drug effects , Conditioning, Psychological/drug effects , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/physiology , Lithium Chloride/pharmacology , Taste Perception/physiology , Animals , Avoidance Learning/physiology , Cyclic AMP Response Element Modulator/metabolism , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Male , Rats , Rats, Sprague-Dawley , Taste Perception/drug effects
15.
Xenobiotica ; 45(3): 256-63, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25268386

ABSTRACT

1. Recently, we demonstrated that sarpogrelate is a potent and selective CYP2D6 inhibitor in vitro. Here, we evaluated the effect of sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy subjects. 2. Nine healthy male subjects genotyped for CYP2D6*1/*1 or *1/*2 were included in an open-label, randomized, three treatment-period and crossover study. A single oral dose of metoprolol (100 mg) was administered with water (treatment A) and sarpogrelate (100 mg bid.; a total dose of 200 mg and treatment B), or after pretreatment of sarpogrelate for three days (100 mg tid.; treatment C). Plasma levels of metoprolol and α-hydroxymetoprolol were determined using a validated LC-MS/MS method. Changes in heart rate and blood pressure were monitored as pharmacodynamic responses to metoprolol. 3. Metoprolol was well tolerated in the three treatment groups. In treatment B and C groups, the AUCt of metoprolol increased by 53% (GMR, 1.53; 90% CI, 1.17-2.31) and by 51% (1.51; 1.17-2.31), respectively. Similar patterns were observed for the increase in Cmax of metoprolol by sarpogrelate. However, the pharmacodynamics of metoprolol did not differ significantly among the three treatment groups. 4. Greater systemic exposure to metoprolol after co-administration or pretreatment with sarpogrelate did not result in clinically relevant effects. Co-administration of both agents is well tolerated and can be employed without the need for dose adjustments.


Subject(s)
Asian People , Cytochrome P-450 CYP2D6 Inhibitors/pharmacology , Healthy Volunteers , Metoprolol/pharmacology , Metoprolol/pharmacokinetics , Succinates/pharmacology , Administration, Oral , Adult , Area Under Curve , Cytochrome P-450 CYP2D6 Inhibitors/administration & dosage , Cytochrome P-450 CYP2D6 Inhibitors/adverse effects , Cytochrome P-450 CYP2D6 Inhibitors/pharmacokinetics , Humans , Male , Metoprolol/administration & dosage , Metoprolol/adverse effects , Metoprolol/analogs & derivatives , Middle Aged , Republic of Korea , Succinates/administration & dosage , Succinates/adverse effects , Young Adult
16.
Eur J Pharmacol ; 730: 14-9, 2014 May 05.
Article in English | MEDLINE | ID: mdl-24582760

ABSTRACT

Lithium chloride at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos expression in the paraventricular nucleus and increases the plasma level of corticosterone with activation of the hypothalamic-pituitary-adrenal axis. This study was conducted to define the role of glucocorticoid in the acquisition and extinction of lithium-induced CTA. In experiment 1, Sprague-Dawley rats received dexamethasone (2mg/kg) or RU486 (20mg/kg) immediately after 5% sucrose access, and then an intraperitoneal injection of isotonic lithium chloride (12ml/kg) was followed with 30min interval. Rats had either 1 or 7 days of recovery period before the daily sucrose drinking tests. In experiment 2, rats were conditioned with the sucrose-lithium pairing, and then received dexamethasone or vehicle at 30min before each drinking test. In experiment 3, adrenalectomized (ADX or ADX+B) rats were subjected to sucrose drinking tests after the sucrose-lithium pairing. Dexamethasone, but not RU486, pretreatment blunted the formation of lithium-induced CTA memory. Dexamethasone prior to each drinking test suppressed sucrose consumption and prolonged the extinction of lithium-induced CTA. Sucrose consumption was significantly suppressed not only in ADX+B rats but also in ADX rats during the first drinking session; however, a significant decrease was found only in ADX rats on the fourth drinking session. These results reveal that glucocorticoid is not a necessary component in the acquisition, but an important player in the extinction, of lithium-induced CTA, and suggest that a pulse increase of glucocorticoid may hinder the extinction memory formation of lithium-induced CTA.


Subject(s)
Avoidance Learning/drug effects , Conditioning, Psychological/drug effects , Extinction, Psychological/drug effects , Glucocorticoids/pharmacology , Lithium/pharmacology , Taste/drug effects , Adrenalectomy , Animals , Dexamethasone/pharmacology , Drinking , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/physiology , Lithium Chloride/pharmacology , Male , Mifepristone/pharmacology , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-Dawley , Sucrose/pharmacology , Taste/physiology
17.
Drug Metab Dispos ; 42(1): 33-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24167220

ABSTRACT

The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6-mediated dextromethorphan O-demethylation with an IC50 (Ki) value of 3.05 µM (1.24 µM), in a competitive manner. M-1 also markedly inhibited CYP2D6 activity; its inhibitory effect with an IC50 (Ki) value of 0.201 µM (0.120 µM) was more potent than that of sarpogrelate, and was similarly potent as quinidine (Ki, 0.129 µM), a well-known typical CYP2D6 inhibitor. In addition, sarpogrelate and M-1 strongly inhibited both CYP2D6-catalyzed bufuralol 1'-hydroxylation and metoprolol α-hydroxylation activities. However, sarpogrelate and M-1 showed no apparent inhibition of the other following eight CYPs: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Upon 30-minute preincubation of human liver microsomes with sarpogrelate or M-1 in the presence of NADPH, no obvious shift in IC50 was observed in terms of inhibition of the nine CYP activities, suggesting that sarpogrelate and M-1 are not time-dependent inactivators. Sarpogrelate strongly inhibited the activity of CYP2D6 at clinically relevant concentrations in human liver microsomes. These observations suggest that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions.


Subject(s)
Cytochrome P-450 CYP2D6 Inhibitors , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Succinates/pharmacology , Cytochrome P-450 CYP2D6/metabolism , Dextromethorphan/pharmacology , Drug Interactions , Female , Humans , Male , Metabolic Clearance Rate/physiology , Microsomes, Liver/enzymology , Quinidine/pharmacology
18.
Psychoneuroendocrinology ; 38(6): 777-88, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23010142

ABSTRACT

This study was conducted to examine if fluoxetine, a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral effects of neonatal maternal separation in female rats. Sprague-Dawley pups were separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from PND 35 until the end of the whole experimental period. Rats were either subjected to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses during PND 43-45. Daily food intake and weight gain of both NH and MS pups were suppressed by fluoxetine, with greater effects in MS pups. MS experience increased immobility and decrease swimming in forced swim test. Swimming was increased, although immobility was not significantly decreased, in MS females by adolescence fluoxetine. However, adolescence fluoxetine increased immobility during forced swim test and decreased time spent in open arms during elevated plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females, and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest that decreased 5-HTergic activity in the raphe nucleus is implicated in the pathophysiology of depression-like behaviors, and increased 5-HTergic activities in the raphe-hippocampus axis may be a part of anti-depressant efficacy of fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may contribute to the increased anorectic efficacy of fluoxetine in MS females. Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may be related with fluoxetine-induced depression- and/or anxiety-like behaviors in NH females.


Subject(s)
Fluoxetine/pharmacology , Hippocampus/metabolism , Maternal Deprivation , Raphe Nuclei/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology , Serotonergic Neurons/drug effects , Animals , Animals, Newborn , Behavior, Animal/drug effects , Body Weight/drug effects , Corticosterone/blood , Corticotropin-Releasing Hormone/biosynthesis , Depression/drug therapy , Eating/drug effects , Feeding and Eating Disorders/drug therapy , Feeding and Eating Disorders/metabolism , Female , Fluoxetine/therapeutic use , Hippocampus/drug effects , Hypothalamus/drug effects , Hypothalamus/metabolism , Raphe Nuclei/drug effects , Rats , Serotonergic Neurons/metabolism , Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/biosynthesis , Selective Serotonin Reuptake Inhibitors/therapeutic use
19.
Maturitas ; 74(2): 148-53, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23218685

ABSTRACT

OBJECTIVE: The purpose of this study is to investigate the relationship between sex hormones and metabolic syndrome independent of age and BMI in Korean men. STUDY DESIGN: We conducted a cross-sectional study with data from a health promotion center during the period from March 2007 to February 2010. 2172 Korean men aged 21-79 were enrolled. Total testosterone, sex hormone-binding globulin (SHBG), high density lipoprotein (HDL) cholesterol, triglyceride (TG), and glucose were assessed with overnight fasting serum samples. MAIN OUTCOME MEASURES: Sex hormones were divided into quartiles; odds ratios for metabolic syndrome and each component were analyzed. RESULTS: Total testosterone showed negative associations with waist circumference (WC), fasting glucose, TG, blood pressure and body mass index (BMI), and a positive relationship with HDL cholesterol (P for trend <0.001, respectively). SHBG was negatively associated with WC, fasting glucose, TG, and BMI, and positively associated with total testosterone and age. Comparing with the highest quartile, odds ratios of lowest quartile of total testosterone and SHBG for metabolic syndrome were 3.01 (95% CI, 2.11-4.28) and 6.34 (95% CI, 2.29-17.58), respectively, after adjusting for age, smoking status, alcohol intake, exercise, and BMI. Total testosterone was significantly associated with each metabolic component and SHBG was associated with glucose and TG after adjustment for age, smoking status, alcohol intake, and BMI. Calculated free testosterone had no significant relationship with metabolic syndrome or its components. CONCLUSION: Total testosterone and SHBG are negatively associated with prevalence of metabolic syndrome independent of age and BMI in Korean men.


Subject(s)
Asian People , Metabolic Syndrome/blood , Sex Hormone-Binding Globulin/metabolism , Testosterone/blood , Adult , Age Factors , Analysis of Variance , Blood Glucose/metabolism , Blood Pressure , Body Mass Index , Cholesterol, HDL/blood , Confidence Intervals , Cross-Sectional Studies , Humans , Male , Metabolic Syndrome/physiopathology , Middle Aged , Odds Ratio , Republic of Korea , Triglycerides/blood , Waist Circumference
20.
Int J Vitam Nutr Res ; 83(3): 154-61, 2013.
Article in English | MEDLINE | ID: mdl-24846904

ABSTRACT

Calcium concentration in hair, representing intracellular calcium levels, is associated with systemic diseases such as coronary artery disease. To date, there are no previous studies which investigate the regulation of hair calcium levels. The aim of the study is to investigate whether hair calcium concentration is related to calcium intake and calcium content in bone - bone mineral density (BMD). An observational research study was conducted with 55 women over the age of 20 who visited a university hospital in Suwon, Korea. The average age of the women was 51.45. Depending on the concentration of hair calcium, participants were divided into quartiles to compare calcium intake and BMD. There was no difference in demographic, anthropometric, and biochemical characteristics between the highest quartile of hair calcium concentration and the rest of the quartiles. However, the highest quartile ingested significantly less calcium compared to the rest of the quartiles (p < 0.05). The highest quartile of hair calcium concentration also showed significantly lower BMD and T-score in the L1 - 4 vertebrae compared to the rest of the quartiles (p < 0.05). These results show that high hair calcium concentration was associated with low calcium intake and low BMD.


Subject(s)
Bone Density , Calcium, Dietary/administration & dosage , Calcium/analysis , Hair/chemistry , Adult , Aged , Female , Humans , Middle Aged , Republic of Korea , Spine
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