A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) α-piperidinopropiophenone (PIPP) and (2) α-piperidinopentiothiophenone (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.
Animals ; Dopamine Plasma Membrane Transport Proteins ; Gene Expression ; Mice ; Nitrogen ; Rats ; Reward

No abstract available.
Humans ; Surgeons* ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: Dyslipidemia is a major risk factor contributing to cardiovascular disease and its prevalence is steadily rising. Although screening tests are readily accessible, dyslipidemia remains undertreated. Evaluating health behavior patterns after diagnosis may help improve lifestyle interventions for the management of dyslipidemia. METHODS: Data from the fifth Korean National Health and Nutrition Examination Survey 2010–2012 were used. A total of 6,624 dyslipidemia patients over 20 years old were included according to National Cholesterol Education Program-Adult Treatment Panel III guidelines. Logistic regression analysis was completed using a weighted method to determine whether awareness of dyslipidemia was associated with health behavior. Health behavior was divided into two categories: behavioral factors (smoking, alcohol consumption, exercise) and nutritional factors (adequate intake of fiber, carbohydrate, fat, protein). RESULTS: There were no significant differences in health behavior among dyslipidemia patients according to awareness after adjustment for covariates, diabetes and hypertension. Awareness in women was associated with decreased smoking (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.32 to 0.94), but when adjusted for diabetes and hypertension the result was not significant (OR, 0.61; 95% CI, 0.35 to 1.06). The same pattern applied to intake of carbohydrate in men (OR, 1.28; 95% CI, 0.99 to 1.67) and protein in women (OR, 1.22; 95% CI, 0.98 to 1.50). In subgroup analysis, awareness of dyslipidemia in men without hypertension or diabetes was associated with adequate intake of carbohydrate (OR, 1.70; 95% CI, 1.06 to 2.72). CONCLUSION: Increasing awareness alone may not be enough to improve healthy behavior in patients with dyslipidemia. Efforts including patient education and counseling through a multi-team approach may be required.
Adult* ; Alcohol Drinking ; Cardiovascular Diseases ; Cholesterol ; Counseling ; Diagnosis ; Dyslipidemias* ; Education ; Female ; Health Behavior* ; Humans ; Hypertension ; Life Style ; Logistic Models ; Male ; Mass Screening ; Methods ; Nutrition Surveys ; Patient Education as Topic ; Prevalence ; Risk Factors ; Smoke ; Smoking

No abstract available.
Early Diagnosis* ; Hemangioma* ; POEMS Syndrome*

This retrospective study aimed to compare the clinical features of paramedullary lesions (PLs) and extramedullary lesions (ELs) of plasmacytomas at diagnosis, using positron emission tomography integrated with computed tomography, using glucose labeled with the positron-emitting radionuclide ¹⁸F (¹⁸F-FDG-PET/CT) in newly diagnosed multiple myeloma (NDMM), and to address their prognostic impact. Sixty-four patients with NDMM presenting ELs (n=22) and/or PLs (n=42) were included. Patients with ELs at initial presentation had unfavorable laboratory parameters of calcium and lactate dehydrogenase, a higher percentage of bone marrow plasma cells, and showed a trend toward advanced international staging system (ISS), compared to patients with PLs. Using X-ray imaging, high bone disease (HBD) was observed in 50% and 71% of patients with ELs and PLs, respectively. After a median follow-up of 29.2 months (range, 3.4–76.5 months) in survivors, patients with ELs had a significantly lower overall survival (OS) (p=0.033) than patients with PLs did, whereas the progression-free survival (PFS) did not differ significantly (p=0.818). However, the PFS after 1(st) progression was significantly worse in patients with ELs than in those with PLs (p=0.017). In the multivariate analyses, the negative impact of initial ELs on OS (p=0.033) was sustained. Our results demonstrated the different clinical features and outcomes of ELs and PLs in NDMM. Patients with initial ELs showed a shorter PFS after 1(st) progression, which translated into poor OS, providing insight into the different biological effect of ELs.
Bone Diseases ; Bone Marrow ; Calcium ; Diagnosis ; Disease-Free Survival ; Follow-Up Studies ; Glucose ; Humans ; L-Lactate Dehydrogenase ; Multiple Myeloma* ; Multivariate Analysis ; Plasma Cells ; Plasmacytoma ; Positron-Emission Tomography ; Retrospective Studies ; Survivors

The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers. Clinical trial registry at the U.S. National Institutes of Health (https://clinicaltrials.gov), number NCT02299687.
Area Under Curve ; Chromatography, Liquid ; Cytochrome P-450 CYP2C19* ; Genotype ; Healthy Volunteers* ; Hydrogen-Ion Concentration ; Methods ; National Institutes of Health (U.S.) ; Omeprazole* ; Phenotype ; Plasma ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Tandem Mass Spectrometry ; Volunteers

BACKGROUND: Behçet disease (BD) is a relapsing inflammatory disease with increased production of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs); however, the underlying molecular mechanisms are not well known. OBJECTIVE: To analyze whether the differential expression of transcription factors is involved in the increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production by PBMCs of BD patients compared to healthy controls (HCs). METHODS: Expression of transcription factors was examined by real-time reverse transcriptase-polymerase chain reaction and western blotting. Cytokine production by CD11b+ cells transfected with siRNAs against transcription factors was measured by enzyme-linked immunosorbent assay. RESULTS: In the absence of lipopolysaccharide stimulation, the transcript level of CCAAT-enhancer-binding proteins (C/EBP) β was increased in PBMCs from patients with active BD compared to that in PBMCs from patients with stable BD. The C/EBPδ transcript level was higher in PBMCs from patients with active BD than in those from HCs. The activating transcription factor 3 (ATF3) transcript level was increased in PBMCs from patients with stable BD compared to that in PBMCs from HCs. siRNAs targeting C/EBPβ and C/EBPδ significantly reduced the production of IL-6 and TNF-α in lipopolysaccharide-stimulated CD11b+ cells from patients with BD as well as from HCs. CONCLUSION: We found differential expression of C/EBPβ, C/EBPδ, and ATF3 in PBMCs from patients with BD depending on disease activity, indicating the involvement of these molecules in BD pathogenesis.
Activating Transcription Factor 3 ; Behcet Syndrome* ; Blotting, Western ; CCAAT-Enhancer-Binding Proteins ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Humans ; Interleukin-6 ; Interleukins ; RNA, Small Interfering ; Transcription Factors* ; Tumor Necrosis Factor-alpha

BACKGROUND: Alopecia areata (AA) is a T cell-mediated autoimmune disease that targets hair follicles and interrupts hair regrowth. The microenvironment of the effector T cells and their related cytokines may affect immunopathogenesis around the hair bulb/bulge. OBJECTIVE: To determine the contributory roles of the effector T cell subsets and related cytokines to the pathogenesis of AA. METHODS: We investigated the correlation between histopathological grades and four clinical prognostic factors in 331 patients with AA, and analyzed the topography of T cell infiltrates and related cytokines around the hair bulb/bulge according to histopathological grades through immunohistochemical and double immunofluorescence studies on a subset of AA specimens. RESULTS: First, the groups with more severe histopathological grades were associated with earlier onset, longer duration, more hair loss, as well as poorer therapeutic outcomes. Second, the pattern of CD4 and CD8 expression around the hair bulb/bulge varied by histopathological grade, with staining density decreasing in the following order: type 1>type 2>type 3. In addition, interferon-γ and transforming growth factor-β1 expression appeared denser in the peribulbar area. Interestingly, the denser CCR6⁺ cells (Th17 cells) showed more infiltration than CCR5⁺ cells (Th1 cells) around the hair bulb/bulge as histopathological grade worsened. CONCLUSION: The insidious destruction of bulge stem cells and hair bulb matrix stem cells results in more severe hair loss in patients with chronic AA, which is mediated by Th17 lymphocyte and cytotoxic T lymphocyte infiltration. Furthermore, Th17 lymphocytes may play an even more important role than cytotoxic T cells in the development of AA.
Alopecia Areata* ; Alopecia* ; Autoimmune Diseases ; Cytokines ; Fluorescent Antibody Technique ; Hair Follicle ; Hair* ; Humans ; Lymphocytes* ; Stem Cells ; T-Lymphocyte Subsets ; T-Lymphocytes ; Th17 Cells

PURPOSE: Although heart failure (HF) is recognized as a leading contributor to healthcare costs and a significant economic burden worldwide, studies of HF-related costs in South Korea are limited. This study aimed to estimate HF-related costs per Korean patient per year and per visit. MATERIALS AND METHODS: This retrospective cohort study analyzed data obtained from six hospitals in South Korea. Patients with HF who experienced ≥one hospitalization or ≥two outpatient visits between January 1, 2013 and December 31, 2013 were included. Patients were followed up for 1 year [in Korean won (KRW)]. RESULTS: Among a total of 500 patients (mean age, 66.1 years; male sex, 54.4%), the mean 1-year HF-related cost per patient was KRW 2,607,173, which included both, outpatient care (KRW 952,863) and inpatient care (KRW 1,654,309). During the post-index period, 22.2% of patients had at least one hospitalization, and their 1-year costs per patient (KRW 8,530,290) were higher than those of patients who had only visited a hospital over a 12-month period (77.8%; KRW 917,029). Among 111 hospitalized patients, the 1-year costs were 1.7-fold greater in patients (n=52) who were admitted to the hospital via the emergency department (ED) than in those (n=59) who were not (KRW 11,040,453 vs. KRW 6,317,942; p<0.001). CONCLUSION: The majority of healthcare costs for HF patients in South Korea was related to hospitalization, especially admissions via the ED. Appropriate treatment strategies including modification of risk factors to prevent or decrease hospitalization are needed to reduce the economic burden on HF patients.
Ambulatory Care ; Cohort Studies* ; Delivery of Health Care* ; Emergency Service, Hospital ; Health Care Costs* ; Heart Failure* ; Heart* ; Hospitalization ; Humans ; Inpatients ; Korea* ; Male ; Outpatients ; Retrospective Studies* ; Risk Factors

PURPOSE: Few studies have reported on predicting prognosis using myocardial perfusion single-photon emission computed tomography (SPECT) during coronary artery disease (CAD) treatment. Therefore, we aimed to assess the clinical implications of myocardial perfusion SPECT during follow-up for CAD treatment. MATERIALS AND METHODS: We enrolled 1153 patients who had abnormal results at index SPECT and underwent follow-up SPECT at intervals ≥6 months. Major adverse cardiac events (MACE) were compared in overall and 346 patient pairs after propensity-score (PS) matching. RESULTS: Abnormal SPECT was associated with a significantly higher risk of MACE in comparison with normal SPECT over the median of 6.3 years (32.3% vs. 19.8%; unadjusted p<0.001). After PS matching, abnormal SPECT posed a higher risk of MACE [32.1% vs. 19.1%; adjusted hazard ratio (HR)=1.73; 95% confidence interval (CI)=1.27–2.34; p<0.001] than normal SPECT. After PS matching, the risk of MACE was still higher in patients with abnormal follow-up SPECT in the revascularization group (30.2% vs. 17.9%; adjusted HR=1.73; 95% CI=1.15–2.59; p=0.008). Low ejection fraction [odds ratio (OR)=5.33; 95% CI=3.39–8.37; p<0.001] and medical treatment (OR=2.68; 95% CI=1.93–3.72; p<0.001) were independent clinical predictors of having an abnormal result on follow-up SPECT. CONCLUSION: Abnormal follow-up SPECT appears to be associated with a high risk of MACE during CAD treatment. Follow-up SPECT may play a potential role in identifying patients at high cardiovascular risk.
Coronary Artery Disease* ; Coronary Vessels* ; Follow-Up Studies* ; Humans ; Ischemia* ; Perfusion* ; Prognosis ; Tomography, Emission-Computed* ; Tomography, Emission-Computed, Single-Photon