Elevated levels of urine isocitrate, hydroxymethylglutarate, and formiminoglutamate are associated with arterial stiffness in Korean adults.

Recent evidence suggests that cellular perturbations play an important role in the pathogenesis of cardiovascular diseases. Therefore, we analyzed the association between the levels of urinary metabolites and arterial stiffness. Our cross-sectional study included 330 Korean men and women. The brachial-ankle pulse wave velocity was measured as a marker of arterial stiffness. Urinary metabolites were evaluated using a high-performance liquid chromatograph-mass spectrometer. The brachial-ankle pulse wave velocity was found to be positively correlated with L-lactate, citrate, isocitrate, succinate, malate, hydroxymethylglutarate, α-ketoisovalerate, α-keto-ß-methylvalerate, methylmalonate, and formiminoglutamate among men. Whereas, among women, the brachial-ankle pulse wave velocity was positively correlated with cis-aconitate, isocitrate, hydroxymethylglutarate, and formiminoglutamate. In the multivariable regression models adjusted for conventional cardiovascular risk factors, three metabolite concentrations (urine isocitrate, hydroxymethylglutarate, and formiminoglutamate) were independently and positively associated with brachial-ankle pulse wave velocity. Increased urine isocitrate, hydroxymethylglutarate, and formiminoglutamate concentrations were associated with brachial-ankle pulse wave velocity and independent of conventional cardiovascular risk factors. Our findings suggest that metabolic disturbances in cells may be related to arterial stiffness.

Clinical effectiveness of early treatment with paliperidone palmitate in schizophrenia: A retrospective real-world study in South Korea.

AIM: Long-acting injectable antipsychotic agents (LAIs) including paliperidone palmitate (PP) have shown promising results in preventing relapse and rehospitalization in schizophrenia. This study aimed to ascertain the comparative real-world effectiveness between the early and late administration of PP and oral formulations of risperidone and paliperidone (ORPs) in patients experiencing a first episode or relapse of schizophrenia. METHODS: We identified patients with schizophrenia admitted to a psychiatric ward at least once and treated with ORPs or PP using the Korea National Insurance Claims Database. Patients were divided into three groups based on the clinical data: (1) patients treated with PP within 30 days of the initiation of treatment (early-PP), (2) patients treated with PP after 30 days of the initiation of therapy (late-PP) and (3) patients treated with only ORPs and not received PP (only-ORP). The primary outcomes were determined as psychiatric rehospitalization during the entire duration of treatment after the first discharge. RESULTS: A total of 3790 patients (1096 early-PP, 799 late-PP and 1895 only-ORP) were finally included in the analysis. The mean of number and total length of rehospitalization stays during the entire duration in early-PP group were significantly lower than those of late-PP group and only-ORP group (number: 2.32 stays/year, 3.24 stays/year and 4.23 stays/year, p < .001; total length: 50.34 days/year, 72.26 days/year and 105.14 days/year, p < .001). CONCLUSIONS: Early treatment with PP was associated with a greater reduction in psychiatric rehospitalization during the treatment period than late treatment with PP and ORP in schizophrenia.

Influence of cytochrome P450 2D6 polymorphism on hippocampal white matter and treatment response in schizophrenia.

Cytochrome P450 2D6 (CYP2D6) is expressed at high levels in the brain and plays a considerable role in the biotransformation and neurotransmission of dopamine. This raises the question of whether CYP2D6 variations and its impact on the brain can confer susceptibility to schizophrenia. We investigated the possible links among the CYP2D6 genotype, white matter (WM) integrity of the hippocampus, and the treatment response to antipsychotic drugs in Korean patients with schizophrenia (n = 106). Brain magnetic resonance imaging and genotyping for CYP2D6 were conducted at baseline. The severity of clinical symptoms and the treatment response were assessed using the Positive and Negative Syndrome Scale (PANSS). After genotyping, 43 participants were classified as intermediate metabolizers (IM), and the remainder (n = 63) were classified as extensive metabolizers (EM). IM participants showed significantly higher fractional anisotropy (FA) values in the right hippocampus compared to EM participants. Radial diffusivity (RD) values were significantly lower in the overlapping region of the right hippocampus in the IM group than in the EM group. After 4 weeks of antipsychotic treatment, the EM group showed more improvements in positive symptoms than the IM group. FAs and RDs in the CYP2D6-associated hippocampal WM region were significantly correlated with a reduction in the positive symptom subscale of the PANSS. Greater improvements in positive symptoms were negatively associated with FAs, and positively associated with RDs in the right hippocampal region. The findings suggest that CYP26D-associated hippocampal WM alterations could be a possible endophenotype for schizophrenia that accounts for individual differences in clinical features and treatment responses.

Pharmacokinetic equivalence of CT-P17 to high-concentration (100 mg/ml) reference adalimumab: A randomized phase I study in healthy subjects.

This study aimed to demonstrate pharmacokinetic (PK) equivalence of a single dose of the proposed adalimumab biosimilar CT-P17 to United States-licensed adalimumab (US-adalimumab) and European Union-approved adalimumab (EU-adalimumab). This double-blind, parallel-group, phase I trial (clinicaltrials.gov NCT03970824) was conducted at 10 hospitals (Republic of Korea), in which healthy subjects (1:1:1) were randomized to receive a single 40 mg (100 mg/ml) subcutaneous injection of CT-P17, US-adalimumab, or EU-adalimumab. Primary end points were PK equivalence in terms of: area under the concentration-time curve from time zero to infinity (AUC0-inf ); AUC from time zero to the last quantifiable concentration (AUC0-last ); and maximum serum concentration (Cmax ). PK equivalence was concluded if 90% confidence intervals (CIs) for percent ratios of geometric least squares means (GLSMs) for pairwise comparisons were within the equivalence margin of 80-125%. Additional PK end points, safety, and immunogenicity were evaluated. Of the 312 subjects who were randomized (103 CT-P17; 103 US-adalimumab; 106 EU-adalimumab), 308 subjects received study drug. AUC0-inf , AUC0-last , and Cmax were equivalent among CT-P17, US-adalimumab, and EU-adalimumab, because 90% CIs for the ratios of GLSMs were within the 80-125% equivalence margin for each pairwise comparison. Secondary PK end points, safety, and immunogenicity were similar between treatment groups. In conclusion, PK equivalence for single-dose administration of CT-P17, EU-adalimumab, and US-adalimumab was demonstrated in healthy adults. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previous reports for adalimumab biosimilars.

Bioequivalence of the pharmacokinetics between tofacitinib aspartate and tofacitinib citrate in healthy subjects.

Tofacitinib is an oral disease-modifying anti-rheumatic drug to selectively inhibit Janus kinases. Tofacitinib is a representative small molecule inhibitor that is used to treat many diseases including rheumatoid arthritis and various autoimmune conditions. Unlike biological agents, tofacitinib has several advantages, including the ability to be administered orally and a short half-life. This study aimed to evaluate the bioequivalence of the pharmacokinetics (PK) between tofacitinib aspartate 7.13 mg (test formulation) and tofacitinib citrate 8.08 mg (reference formulation; Xeljanz®) in healthy subjects. A randomized, open-label, single-dose, 2-sequence, 2-period, 2-treatment crossover trial was conducted in 41 healthy volunteers. A total of 5 mg of tofacitinib as the test or the reference formulation was administered, and serial blood samples were collected up to 14 hours after dosing for PK analyses. The plasma concentration of tofacitinib was determined by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental analysis was used to estimate the PK parameters. A total of 35 subjects completed the study and the study drug was well-tolerated. The mean maximum concentration (Cmax) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) for the test formulation were 52.67 ng/mL and 133.86 ng∙h/mL, respectively, and 50.61 ng/mL and 133.49 h∙ng/mL for the reference formulation, respectively. The geometric mean ratios (90% confidence intervals) of the Cmax and AUClast between the 2 formulations were 1.041 (0.944-1.148) and 1.003 (0.968-1.039), respectively. Tofacitinib aspartate exhibited bioequivalent PK profiles to those of the reference formulation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04278391.

Outcomes Assessment of Sustainable and Innovatively Simple Lifestyle Modification at the Workplace - Drinking Electrolyzed-Reduced Water (OASIS-ERW): A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress has been associated with many diseases as well as aging. Electrolyzed-reduced water (ERW) has been suggested to reduce oxidative stress and improve antioxidant potential. This study investigated the effects of drinking ERW on biomarkers of oxidative stress and health-related indices in healthy adults. We conducted a randomized, double-blind, placebo-controlled clinical trial on 65 participants, who were allocated into two groups. Of these, 61 received intervention (32 with ERW and 29 MW [mineral water]). All participants were instructed to drink 1.5 L/day of ERW or MW for eight weeks. Biomarkers of oxidative stress and health-related indices were assessed at baseline as well as after 4 weeks and 8 weeks of intervention. Of the primary outcome variables assessed, diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential showed a significant interaction between the groups and time, with d-ROMs levels significantly decreased at 8 weeks in ERW compared to those in MW. Among the secondary outcome variables, total, visceral, and subcutaneous fat mass significantly changed over time, with a significant association observed between the groups and time. Thus, daily ERW consumption may be a potential consideration for a sustainable and innovatively simple lifestyle modification at the workplace to reduce oxidative stress, increase antioxidant potential, and decrease fat mass.

Low levels of total and high-molecular-weight adiponectin may predict non-alcoholic fatty liver in Korean adults.

OBJECTIVES: While weight gain is known as a predictor of non-alcoholic fatty liver disease (NAFLD) incidence, it remains controversial whether adipokine levels predict the development of NAFLD. We aimed to investigate the relationship of total adiponectin, high-molecular-weight (HMW) adiponectin, and leptin with the development and improvement of non-alcoholic fatty liver (NAFL) independent of sex and weight change over a maximum of 8.5 years. METHODS: This prospective study enrolled 2735 participants in a hospital health check-up setting. Adipokine levels were measured at baseline. NAFL was assessed with liver ultrasonography, and the development or improvement of NAFL was determined by repeated ultrasonography at follow-ups. RESULTS: Cross-sectional analyses revealed that total and HMW adiponectin levels were inversely associated with NAFL prevalence. In longitudinal analyses, the incidence of NAFL was 5.6 per 100-person-years during the observation period. The hazard ratios (HRs) per 1 µg/mL increase in the levels of total and HMW adiponectin were 0.900 (0.836-0.969) and 0.846 (0.754-0.948), respectively. Sex-stratified analyses showed that total and HMW adiponectin levels were significantly related to NAFL incidence only in women. In the subgroup of minimal weight change, only HMW adiponectin was a significant predictor for NAFL. Leptin predicted NAFL in the subgroup with weight gain. The improvement of NAFL was influenced by weight change, but not by adipokine levels. CONCLUSIONS: Low levels of total and HMW adiponectin may predict the development of NAFL independent of pathophysiological factors including obesity and insulin resistance. This predictability was evident in women. Leptin was a significant predictor for NAFL in the subjects with weight gain.

Effect of eradicating hydrogen-forming small intestinal bacterial overgrowth with rifaximin on body weight change.

Hydrogen formed by small intestinal bacterial overgrowth in patients with non-constipated irritable bowel syndrome has an inverse relationship with obesity. However, the effect of eradicating small intestinal hydrogen-producing bacterial overgrowth on the body weight of these patients has not yet been reported. The aim of this study was to investigate body weight changes after eradicating small intestinal bacterial overgrowth with rifaximin treatment in patients with non-constipated irritable bowel syndrome.We reviewed the charts of patients with non-constipated irritable bowel syndrome who showed abdominal symptoms with documented lactulose hydrogen breath test results in order to diagnose small intestinal bacterial overgrowth. A total of 153 patients were enrolled in the study and divided into quartiles according to body mass index (BMI) and body weight.In the lowest body weight quartile, the BMI and body weight were significantly increased (0.4 kg/m, P = .038; 0.6 kg, P = .010, respectively) in patients with negative lactulose hydrogen breath tests after rifaximin treatment. However, there was no significant change in body weight in the other quartiles. Despite treatment with rifaximin for 12 weeks, there was no change in BMI or body weight in any group of patients with consistently positive lactulose hydrogen breath tests.Eradication of hydrogen formed by small intestinal bacterial overgrowth does not cause clinically significant changes in body weight.

Biological Aspects of Aggression and Violence in Schizophrenia.

Although the majority of patients with schizophrenia are not actually violent, an increased tendency toward violent behaviors is known to be associated with schizophrenia. There are several factors to consider when identifying the subgroup of patients with schizophrenia who may commit violent or aggressive acts. Comorbidity with substance abuse is the most important clinical indicator of increased aggressive behaviors and crime rates in patients with schizophrenia. Genetic studies have proposed that polymorphisms in the promoter region of the serotonin transporter gene and in the catechol-O-methyltransferase gene are related to aggression. Neuroimaging studies have suggested that fronto-limbic dysfunction may be related to aggression or violence. By identifying specific risk factors, a more efficient treatment plan to prevent violent behavior in schizophrenia will be possible. Management of comorbid substance use disorder may help prevent violent events and overall aggression. Currently, clozapine may be the only effective antipsychotic medication to repress aggressive behavior. With the current medical field moving toward tailored medicine, it is important to identify vulnerable schizophrenia populations and provide efficient treatment.

Bowel preparation for colonoscopy may decrease the levels of testosterone in Korean men.

Although colonoscopy is commonly conducted for medical check-ups in Korea, investigations for the influence of bowel preparation on various health conditions are insufficient. This cross-sectional study investigated whether bowel preparation has an influence on serum levels of testosterone. A total of 1114 men were divided into the bowel preparation group and control groups. The median total and free testosterone levels were significantly lower in the bowel preparation group (14.89 and 0.26 nmol/L, respectively) than in the control groups (15.72 and 0.28 nmol/L, respectively). The level of total testosterone significantly increased with age in the bowel preparation group (r = 0.103). The differences in the levels of total and free testosterone between the 2 groups were more prominent in younger men than in older men. In multivariate regression models, bowel preparation was independently associated with the levels of total and free testosterone. In these models, the interaction between age and bowel preparation was significant for the levels of total and free testosterone. In conclusion, bowel preparation may independently decrease the serum levels of total and free testosterone. The decline in testosterone was more evident in younger men than in older men.

Pharmacokinetic study of two extended-release formulations of cilostazol in healthy Korean subjects: A randomized, open-label, multiple-dose, two-period crossover study
.

OBJECTIVES: The aim of this study was to compare the pharmacokinetic characteristics and safety of two extended-release formulations of cilostazol after multiple oral doses in healthy Korean subjects. MATERIALS AND METHODS: A randomized, open-label, multiple-dose, two-period, crossover study was conducted in 30 healthy male subjects. In each treatment period, subjects received oral doses of 200 mg cilostazol SR (Pletaal SR Cap.) or cilostazol CR (Cilostan CR Tab.) once daily for 5 consecutive days, with a washout period of 9 days. Plasma concentrations of cilostazol and its metabolites were determined using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: 24 subjects completed the study. The maximum plasma concentrations (Cmax,ss, geometric mean (geometric coefficient of variation, CV%)) of cilostazol after cilostazol SR and cilostazol CR regimens were 1,532.7 (43.2%) ng/mL and 548.3 (58.9%) ng/mL, respectively, and the areas under the plasma concentration-time curves within dosing intervals (AUCτ, geometric mean (CV%)) were 17,060.7 (39.2%) h×ng/mL and 7,485.7 (55.0%) h×ng/mL, respectively. The geometric mean ratios (cilostazol SR/cilostazol CR) of the Cmax,ss and AUCτ values were 2.7954 (90% confidence interval: 2.3561 - 3.3166) and 2.2791 (90% confidence interval: 1.9770 - 2.6273), respectively. Both cilostazol SR and cilostazol CR were well tolerated in all subjects, and no serious adverse events occurred. The total incidence of headache, which is the most common adverse drug reaction, was significantly higher with cilostazol SR (63.0%) than cilostazol CR (25.9%). CONCLUSION: Cilostazol SR showed significantly higher Cmax and AUCτ of cilostazol than cilostazol CR after 5 days of multiple dosing of extended-release formulations of cilostazol.

A first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 (FAS-associated factor 1 inhibitor), a drug for Parkinson's disease, in healthy volunteers.

BACKGROUND: KM-819 is a novel FAS-associated factor 1 (FAF1) inhibitor, and a neuroprotective agent, under clinical development for the treatment of Parkinson's disease as a disease-modifying drug. METHODS: This first-in-human, single and multiple ascending dose study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of KM-819 in healthy volunteers. Additionally, the effect of age on safety and pharmacokinetics were assessed. The starting dose was determined considering the no observed adverse effect level based on preclinical studies, and the dose escalations in subsequent cohorts were decided based on safety, tolerability, and pharmacokinetic data from previous dose cohorts. RESULTS: After a single dose, the KM-819 plasma exposure showed a less than dose-proportional increase across a dose range of 10-400 mg. After repeated dosing, KM-819 plasma exposure increased in an approximately dose-proportional manner across the evaluated dose range (30-400 mg once daily for 7 days). The mean elimination half-life was 1.8 to 4.8 h with the lower KM-819 doses (≤30 mg), which increased to around 9 h with the higher doses (100-400 mg). When administered to the elderly population, KM-819 plasma exposure increased to 102% after a 200 mg once-daily dosing for 7 days. No clear treatment-related effects on the estimated pharmacodynamic variables were observed. Single or multiple doses of KM-819 were generally well tolerated. CONCLUSION: The data from this study can be used to guide rational drug dosing and choose therapeutic regimens in subsequent clinical studies.

A Randomized Clinical Trial of Synbiotics in Irritable Bowel Syndrome: Dose-Dependent Effects on Gastrointestinal Symptoms and Fatigue.

BACKGROUND: This double-blind, randomized controlled design study aimed to assess the dose-dependent effects of synbiotics on gastrointestinal symptoms of and fatigue in irritable bowel syndrome (IBS). METHODS: Thirty subjects with IBS were randomly assigned into the following three groups and received 2 capsules a day for 8 weeks: (1) high-dose (2 capsules of synbiotics); (2) low-dose (1 capsule of synbiotics and 1 capsule of placebo); and (3) placebo (2 capsules of placebo). At baseline and 8 weeks, they completed the study questionnaires. RESULTS: Two subjects in the high-dose group were lost to follow-up, leaving a total of 28 patients for the analysis. After 8 weeks, abdominal discomfort, abdominal bloating, frequency of formed stool, fatigue Visual Analog Scale (VAS), and Multidimensional Fatigue Inventory were significantly different among the groups (P=0.002, 0.006, 0.007, 0.028, and 0.041, respectively, by Kruskal-Wallis test). However, only abdominal discomfort, abdominal bloating, frequency of formed stool, and fatigue VAS were significantly improved in the high-dose group compared with those in the placebo group (P=0.002, 0.003, 0.002, and 0.013, respectively) by Mann-Whitney test with Bonferroni correction. No adverse drug reactions were reported. CONCLUSION: High-dose synbiotics were superior to placebo in improving bowel symptoms and fatigue of IBS patients, suggesting that synbiotic dosage plays an important role in the treatment of IBS.

Identification and characterization of in vitro inhibitors against UDP-glucuronosyltransferase 1A1 in uva-ursi extracts and evaluation of in vivo uva-ursi-drug interactions.

Uva-ursi leaf is widely used to treat symptoms of lower urinary tract infections. Here, we evaluated the in vitro inhibitory effects of uva-ursi extracts on 10 major human UDP-glucuronosyltransferases (UGT) isoforms. Of the 10 tested UGT isoforms, uva-ursi extracts exerted the strongest inhibitory effect on UGT1A1-mediated ß-estradiol 3-glucuronidation with the lowest IC50 value of 8.45 ±â€¯1.56 µg/mL. To identify the components of uva-ursi extracts showing strong inhibitory effects against UGT1A1, the inhibitory effects of nine major constituents of the extracts were assessed. Among the tested compounds, gallotannin exerted the most potent inhibition on UGT1A1, followed by 1,2,3,6-tetragalloylglucose; both demonstrated competitive inhibition, with Ki values of 1.68 ±â€¯0.150 µM and 3.55 ±â€¯0.418 µM. We found that gallotannin and 1,2,3,6-tetragalloylglucose also inhibited another UGT1A1-specific biotransformation, SN-38-glucuronidation, showing the same order of inhibition. Thus, in vitro UGT1A1 inhibitory potentials of uva-ursi extracts might primarily result from the inhibitory activities of gallotannin and 1,2,3,6-tetragalloylglucose present in the extracts. However, in rats, co-administration with uva-ursi extracts did not alter the in vivo marker for UGT1A1 activity, expressed as the molar ratio of AUCSN-38 glucuronide/AUCSN-38, because plasma concentrations of gallotannin and 1,2,3,6-tetragalloylglucose may be too low to inhibit the UGT1A1-mediated metabolism of SN-38 in vivo. The poor oral absorption of gallotannin and 1,2,3,6-tetragalloylglucose in uva-ursi extracts might cause the poor in vitro-in vivo correlation. These findings will be helpful for the safe and effective use of uva-ursi extracts in clinical practice.

Reliability and Validity of the Korean Version of the Multidimensional Fatigue Inventory (MFI-20): A Multicenter, Cross-Sectional Study.

Introduction: A nonspecific symptom, fatigue accompanies a variety of diseases, including cancer, and can have a grave impact on patients' quality of life. As for multidimensional instruments, one of the most widely used is the Multidimensional Fatigue Inventory (MFI). This study aims to verify the reliability and validity of the MFI Korean (MFI-K) version. Materials and Method: This study was performed at four university hospitals in the Republic of Korea. Among outpatients visiting the Department of Family Medicine, those complaining of fatigue or visiting a chronic care clinic were enrolled in this study. A total of 595 participants were included, and the mean age was 42.2 years. Results: The Cronbach's alpha coefficient of the MFI-K was 0.88. The MFI-K had good convergent validity. Most subscales of the MFI-K were significantly correlated with the Visual Analogue Scale (VAS) and Fatigue Severity Scale (FSS). In particular, general and physical fatigue had the greatest correlation with the VAS and FSS. Although the English version of MFI had five subscales, the factor analysis led to four subscales in the Korean version. Conclusion: This study demonstrated the clinical usefulness of MFI-K instrument, particularly in assessing the degree of fatigue and performing a multidimensional assessment of fatigue.

The relationship of alanine aminotransferase to metabolic syndrome in a Korean population.

BACKGROUND/AIMS: Although associations between serum alanine aminotransferase and metabolic syndrome are well-recognized in Western countries, only a limited number of prospective studies have been performed in Asian populations. The aim of the study was to cross-sectionally and longitudinally examine whether serum alanine aminotransferase levels are associated with metabolic syndrome and its associated components in a Korean population. MATERIALS AND METHODS: A total of 31,832 subjects who received health screenings were included in cross-sectional analyses; a subgroup of 4.070 subjects without metabolic syndrome at baseline was included in the longitudinal analyses. The metabolic syndrome definition was based on the National Cholesterol Education Program Third Adult Treatment Panel criteria with modification on waist circumference cut-off to be more appropriate for an Asian population. RESULTS: In the cross-sectional analyses, serum alanine aminotransferase is positively associated with metabolic syndrome and its components. In the longitudinal analyses, the prevalence of metabolic syndrome increased across serum alanine aminotransferase quartiles in a dose-dependent manner after extensive adjustments (hazard ratios were 1.000, 1.609, 2.601, and 3.015 for quartiles, 1 through quartile 4; P for trend<0.001). CONCLUSION: Our study confirmed a positive association between components of metabolic syndrome and elevated serum alanine aminotransferase in a Korean population.

Acid Inhibitory Effect of a Combination of Omeprazole and Sodium Bicarbonate (CDFR0209) Compared With Delayed-Release Omeprazole 40 mg Alone in Healthy Adult Male Subjects.

CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state.

Low Levels of Sex Hormone-Binding Globulin Constitute an Independent Risk Factor for Arterial Stiffness in Korean Women.

The association between sex hormone-binding globulin (SHBG) and arterial stiffness in women is not conclusive. In addition, obesity might also be involved in the relationship between SHBG and atherosclerosis. The aim of this study was to determine the relationship between SHBG and arterial stiffness in association with central obesity in women. This cross-sectional study included 381 women who participated in the health checkup programs in one hospital. The brachial-ankle pulse wave velocity (baPWV) was measured as a marker for arterial stiffness. A negative correlation was observed between SHBG levels and baPWV (rho = -0.281). The relationship was significant even after adjusting for potential confounders (beta = -0.087 in fully adjusted model). After considering the interaction between central obesity and SHBG levels, the significant association was evident only in obese women (P for interaction = 0.025). Adjustment for a 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores, instead of each cardiovascular risk factor individually, did not affect the significance of the relationship between SHBG levels and baPWV. Serum levels of SHBG were negatively associated with arterial stiffness independent of cardiovascular risk factors or 10-year ASCVD risk scores in Korean women. The relationship may be potentiated by central obesity.

Coronary Calcification Is Reversely Related with Bone and Hair Calcium: The Relationship among Different Calcium Pools in Body.

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.

Reference Intervals for Plasma Amyloid ß in Korean Adults Without Cognitive Impairment.

Amyloid ß (Aß) peptides are important components of plaques in patients with Alzheimer's disease (AD). Recent studies suggest that a low plasma ratio of Aß42 to Aß40 may precede the development of the sporadic form of AD. The aim of this study was to establish reference intervals for plasma Aß in Korean adults. A total of 370 apparently healthy individuals (181 males and 189 females aged 40-69 yr) without cognitive impairment were enrolled. Plasma concentrations of Aß40 and Aß42 were measured by using a human amyloid ß assay kit (Immuno-Biological Laboratories, Japan). Reference intervals were established according to the "CLSI guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory". There was no need to partition the data with respect to gender or age group. The 95th percentile reference intervals for Aß40 and Aß42 were 127-331 pg/mL and 2.31-19.84 pg/mL, respectively. The reference interval for the Aß42/Aß40 ratio was 0.011-0.092. Plasma Aß concentrations obtained in this study could be used as reference intervals for clinical purposes.