In the published version of this article, an error in the sponsor's identity was discovered in the acknowledgment section.

Objectives: ：Based on the fact that cognitive functions decline known as comorbid symptoms of depression can precede depression, this study seeks to observe the effects of depressive symptoms and anxiety symptoms on cognitive function in healthy subjects. Methods: ：To recruit 50 general populations to evaluate cognitive and clinical symptoms and to find out the effects of clinical symptoms on cognitive functions, Pearson correlation and multivariate regression were conducted. Correlation analysis of subdomain cognitive function was conducted for reliability analysis. Results: ：Trail making test-B that evaluates the execution function correlates with depressive symptoms (r=0.300, p=0.03) and age (r=0.323, p=0.02). Depressive symptoms (β=0.304, p=0.03) and age (β=0.335, p=0.01) were significantly related to Trail making test -B (Adjusted R2 =0.148). Subjective cognitive tests correlates with anxiety symptoms (r=0.434, p=0.002). In the correlation between cognitive functional items, Subjective cognitive tests was found to be correlated with other test except Spotter. Conclusions ：In this study, depressive symptoms contribute independently to executive functions in addition to demographic characteristics such as age and duration of education. Given that cognitive decline is a common long-term clinical outcome in depression, we expect active early intervention and evaluation of cognitive function to be helpful.

Objective: To detect early subclinical signs of autonomic dysfunction in the cardiovascular system and explore the mechanism of orthostatic hypotension (OH) in patients with multiple system atrophy (MSA). Methods: Eighteen male patients with possible MSA and 10 healthy men were recruited. The hemodynamic responses to head-up tilt and tilt-reversal were studied by an electrically-powered tilt table and a non-invasive cardiac output measurement (NICOM) system. Results: At supine, there was no signifi cant difference in blood pressure, heart rate (HR), stroke volume, cardiac output and total peripheral resistance between MSA patients and healthy controls. During tilting upright, OH developed in 5 MSA patients, with a 23.7±4.8 mmHg drop in systolic blood pressure. Patients with OH were older and exhibited higher scores in unifi ed Multiple System Atrophy Rating Scale part I than patients without OH. The stroke volume, cardiac output and total peripheral resistance did not differ between groups. The controls had the most signifi cant HR elevation (6.5±2.5 bpm) during tiltup, followed by patients without OH (2.8±1.6 bpm) and those with OH (-0.2±2.2 bpm). A similar trend of HR decrease was observed during return to supine posture. The process of tilt-reversal altered HR more signifi cantly than head-up tilt in controls (8.0±2.9 vs 6.5±2.5 bpm; P=0.031) and patients without OH (4.2±2.1 vs 2.8±1.6 bpm; P=0.032), but not in patients with OH (1.2±1.5 vs -0.2±2.2 bpm; P=0.380). Conclusions: The HR change during postural challenge showed signifi cant difference between MSA patients and healthy controls. Impaired HR responsiveness contributed to OH in MSA. Monitoring HR during the tilt table test may be a practical and useful method to detect early autonomic dysfunction in patients with MSA.

Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs) with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1) mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.
Adenoma* ; Aldosterone* ; Carcinogenesis ; Humans ; Prevalence

OBJECTIVES: It has been reported that first episode polarity affected the course and the prognosis of bipolar disorder. However, there is remarkable paucity of information regarding first episode polarity in bipolar disorder. We investigated the clinical characteristics related to the first episode polarity of bipolar patients who had been hospitalized. METHODS: Analyses were based on the medical documents of 520 bipolar patients who had been hospitalized in 4 hospitals. We examined clinical features of the current episode, demographics, past treatment history, suicidal attempt history, family history and comorbidity. Clinical characteristics were compared between manic onset and depressive onset patients. RESULTS: The mean age of the patients was 36.7 years old; they had 2.1 number of admission history and 6.6 years of illness duration. The patients beginning with depressive onset was 39.4%, and they had more diagnosis of bipolar II disorder, more number of suicidal attempts and reported more depressive mood during index admission than manic onset patients. CONCLUSION: Depressive onset is a common presentation in bipolar disorder. It is necessary to give more attention to depressive episode in bipolar disorder. Prospective study needs to explore the correlation of first-episode of polarity and course of the illness in the future.
Bipolar Disorder* ; Comorbidity ; Demography ; Diagnosis ; Humans ; Prognosis

Levofloxacin is a broad-spectrum antibiotic with activity against gram-positive and -negative bacteria. This study compared the pharmacokinetics (PK) and evaluated the bioequivalence of two levofloxacin 100-mg tablet formulations. An open, randomized, two-way crossover study was conducted in 28 healthy volunteers. The reference (Cravit Tab 100-mg, Jeil) or test (Levobacter Tab, Seoul) formulation was administered and serial blood samples were collected over 24 h for PK analysis. Levofloxacin plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation of levofloxacin concentration at various time points with the area under the concentration time-curve over the time interval from 0 extrapolated to infinity (AUCinf) was estimated to determine the best reflected time point. The average half-life, maximum plasma concentration (Cmax), and AUClast were comparable. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR test/reference) of AUClast and Cmax were 0.8200-1.0633 and 0.9474-1.0643 respectively. Both formulations were tolerated with no clinically relevant safety issues. Plasma levofloxacin concentrations at various time points correlated well with the AUCinf, and showed high correlation coefficients (r > 0.7, P < 0.001) for both drugs 8 and 12 h after administration. Both formulations showed similar PK profiles while levofloxacin plasma levels after administration indicated their bioequivalence. The Cmax and AUClast GMR 90% CIs were 0.80-1.25. Moreover, 12 h was the best time point to predict the AUCinf and therefore suitable for therapeutic drug monitoring.
Bacteria ; Cross-Over Studies ; Drug Monitoring ; Half-Life ; Healthy Volunteers ; Levofloxacin* ; Mass Spectrometry ; Pharmacokinetics ; Plasma ; Therapeutic Equivalency

Donepezil is a centrally acting, reversible acetylcholinesterase inhibitor that is widely used for treating Alzheimer's disease. This study aimed to compare the pharmacokinetics of Bastia(R), a test tablet formulation of donepezil hydrochloride 10 mg, with those of Aricept(R), the reference tablet formulation of donepezil hydrochloride 10 mg, in healthy Korean male volunteers. A randomized, single-dose, two-way crossover study was conducted in 32 subjects. Subjects received a single dose of either test or reference compound and the alternate drug after a 4-week washout period. Serial blood samples for pharmacokinetic analysis were collected prior to dosing and periodically for 288 h after dosing for measurement of the plasma concentrations of donepezil. A non-compartmental method was used to estimate the pharmacokinetic parameters. The maximum concentration (C(max)) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(288h)) for the two formulations were compared to evaluate bioequivalence. The C(max) of the test and reference drugs were 27.58+/-7.46 and 26.35+/-6.51 microg/L (mean+/-SD), respectively, while AUC(288h) was 1080.14+/-229.77 and 1043.07+/-242.28 microg.h/L (mean+/-SD), respectively. The geometric mean ratios (90% confidence interval) of the C(max) and AUC(288h) of the two tablets were 1.043 (0.990-1.099) and 1.039 (1.013-1.065). In conclusion, the newly formulated tablet of donepezil hydrochloride 10 mg is bioequivalent to the currently marketed 10 mg tablet.
Acetylcholinesterase ; Alzheimer Disease ; Cross-Over Studies ; Humans ; Male ; Pharmacokinetics ; Plasma ; Tablets ; Therapeutic Equivalency* ; Volunteers*

Tamsulosin is an effective therapeutic option for lower urinary tract symptoms, as it selectively blocks alpha1A- and alpha1D-adrenoceptors in the bladder and prostate. The purpose of this study was to evaluate the bioequivalence in the pharmacokinetics (PK) of two 0.2 mg tamsulosin formulations when administered as the reference formulation (Yuropa(R) sustained-release tablet) vs. the test formulation (Yutanal(R) capsule) in healthy male subjects. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 37 healthy volunteers. The 0.2 mg of tamsulosin as the test or the reference formulation were administered during each period, and serial blood samples were collected up to 36 hours after dosing for PK analyses. A non-compartmental analysis was used to estimate the PK parameters. Geometric mean ratios (GMR) and 90% confidence inter-vals (CIs) were calculated for the two formulations to compare the maximum concentration (Cmax) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast). The mean Cmax and AUClast for the test formulation were 6.19 microg/L and 71.30 microg.h/L, respectively, and 5.76 microg/L and 70.38 microg.h /L for the reference formulation, respectively. The GMRs (90% CIs) of the Cmax and AUClast between the two formulations were 1.09 (1.01-1.17) and 1.03 (0.96-1.10), respectively. Tamsulosin 0.2 mg as the test formulation exhibited bioequivalent PK profiles to those of the reference formulation. Therefore, the test formulation is expected to be an alternative to the reference formulation without concerns about differences in drug exposure.
Cross-Over Studies ; Healthy Volunteers ; Humans ; Lower Urinary Tract Symptoms ; Male ; Pharmacokinetics* ; Prostate ; Therapeutic Equivalency* ; Urinary Bladder

Olmesartan is an angiotensin receptor blocker (ARB) and is widely used in clinical practice to treat hypertension. To compare the pharmacokinetic (PK) parameters and tolerability of two oral formulations of olmesartan (test drug: OMETAN(R) 20 mg tablet, reference drug: OLMETEC(R) 20 mg tablet) and assess their bioequivalence, a randomized, single dose, two-treatment crossover clinical study was conducted. At each period, 40 subjects received the test drug or the reference drug. Blood samples were collected at pre-dose and up to 48 h after study drug administration of each period. Plasma concentrations of olmesartan were measured using liquid chromatography-tandem mass spectrometry. To evaluate PK profiles, maximum plasma concentration (C(max)) and area under the concentration-time curve from zero to last measurable time (AUC(last)) were estimated using a non-compartmental method. Tolerability was evaluated based on the incidence of adverse events, vital signs, electrocardiograms, and laboratory tests. A total of 39 subjects completed the study. The geometric mean ratio and 90% confidence intervals (CI) of test drug to reference drug were 1.027 (0.969-1.088) for C(max) and 1.014 (0.957-1.074) for AUC(last), respectively. There were no serious adverse events and both formulations of olmesartan were well tolerated. The OMETAN 20 mg tablet was judged to be bioequivalent to the OLMETEC 20 mg tablet.
Angiotensins ; Cross-Over Studies* ; Electrocardiography ; Humans ; Hypertension ; Incidence ; Male* ; Mass Spectrometry ; Pharmacokinetics* ; Plasma ; Tablets* ; Therapeutic Equivalency* ; Vital Signs ; Volunteers* ; Olmesartan Medoxomil*

Angiotensin converting enzyme (ACE) plays an important role in the physiology of vasculature, blood pressure and inflammation. ACE gene, known to have insertion/deletion (I/D) polymorphism, has been widely investigated in its relation with cardiovascular and neurodegenerative diseases and longevity. ACE gene polymorphism in an inflammation associated osteoarthritis (OA) patients is not known. Here we have investigated ACE gene polymorphism in 142 Korean primary knee OA patients and 135 healthy volunteers to establish any clinical correlates between ACE polymorphism and knee osteoarthritis. Clinical parameters such as disease onset age, Kellgren-Lawrence grade and Lequesne's functional index provided additional analysis of the relationship of ACE polymorphism and clinical features of OA. Early onset OA showed significantly higher allele frequency and carriage rate of I than late onset OA. Radiographically severe and functionally poor OA showed higher carriage rate of I allele than radiographically mild and functionally good OA, respectively. This study first reports ACE gene polymorphism to be a risk factor for early onset, severe form primary knee OA.
Adult ; Aged ; Female ; Human ; Male ; Middle Aged ; Osteoarthritis, Knee/*genetics ; Peptidyl-Dipeptidase A/blood/*genetics ; *Polymorphism (Genetics)