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1.  Three-dimensional functional unit analysis of hemifacial microsomia mandible—a preliminary report 
The aim of this study was to present three-dimensional (3D) structural characteristics of the mandible in the hemifacial microsomia. The mandible has six distinct functional units, and its architecture is the sum of balanced growth of each functional unit and surrounding matrix.
In order to characterize the mandibular 3D architecture of hemifacial microsomia, we analyzed the mandibular functional units of four hemifacial microsomia patients using the 3D reconstructed computed tomography (CT) images. And we compared the functional unit size between affected and non-affected side.
The length of condyle and angle showed significant differences between affected and non-affected sides. However, the length of mandibular body showed insignificant differences. The size differences between affected and non-affected side were observed at the condyle, angle, and body in descending order.
This preliminary study suggests that the main etiopathogenic units are condyle and angle in the hemifacial microsomia mandible. Further investigation with the increased number of subjects will be helpful to establish treatment modality by etiopathogenic targeting of hemifacial microsomia.
PMCID: PMC4572049  PMID: 26413495
Hemifacial microsomia; Functional unit; Mandible; Three-dimensional; Computerized tomography
2.  Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay 
Biomolecules & Therapeutics  2015;23(5):486-492.
Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
PMCID: PMC4556210  PMID: 26336590
CYP; Human hepatocytes; Luminescent assay; Mesalazine; Mosapride citrate
3.  Cardiovascular Safety Pharmacology of Sibutramine 
Biomolecules & Therapeutics  2015;23(4):386-389.
Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
PMCID: PMC4489835  PMID: 26157557
Anorectic; Sibutramine; QT prolongation; Beagle dogs
4.  Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice 
Toxicological Research  2015;31(1):61-68.
The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency.
PMCID: PMC4395656  PMID: 25874034
Single oral dose toxicity; Mouse; Blue honeysuckle; Proximate analysis; Phytochemical analysis
5.  Fish Myogenic Regulatory Protein LUC7L: Characterization and Expression Analysis in Korean Rose Bitterling (Rhodeus uyekii) 
Development & Reproduction  2014;18(4):251-258.
Serine-arginine-rich nuclear protein LUC7L plays an important role in the regulation of myogenesis in mice. In the present study, we isolated and characterized the Korean rose bitterling Rhodeus uyekii Luc7l cDNA, designated RuLuc7l. The RuLuc7l cDNA is 1,688 bp long and encodes a 364-amino-acid polypeptide containing serine/arginine-rich region at the C-terminus. The deduced RuLuc7l protein has high amino acid identity (71-97%) with those of other species including human. Phylogenetic analysis revealed that RuLUC7L clustered with fish LUC7L proteins. The expression of RuLuc7l mRNA was high in the brain, kidney, and stomach of Korean rose bitterling. Expression of the RuLuc7l mRNA was detected from 1 day post-fertilization (dpf) and moderately increased until 21 dpf during the early development. Further investigations are required to elucidate the functional role of RuLUC7L in myogenesis in R. uyekii.
PMCID: PMC4415636  PMID: 25949195
Development; Korean rose bitterling; Luc7l; Myogenesis; Rhodeus uyekii
6.  Characterization, Expression Profile, and Promoter Analysis of the Rhodeus uyekii Vitellogenin Ao1 Gene 
The fish Vitellogenin (Vg) gene has been applied as a biomarker for exposure to estrogenic compounds in the aquatic environment. In this study, we cloned and characterized Vg cDNA from the Korean rose bitterling Rhodeus uyekii (Ru-Vg). The Ru-Vg cDNA encodes a 1424-amino-acid polypeptide that belongs to the VgAo1 family and contains a putative signal peptide, lipovitellin I, phosvitin, and lipovitellin II, but does not contain the vWFD domain or the C-terminal peptide. The deduced Ru-Vg protein has high amino acid identity (73.97%–32.17%) with fish Vg proteins. Pairwise alignment and phylogenetic analysis revealed that Ru-Vg is most closely related to Acheilognathus yamatsutae Vg. Ru-Vg transcripts were detected using quantitative polymerase chain reaction in all tissues tested, with the highest level of expression observed in the ovary. Ru-Vg mRNA was upregulated in R. uyekii hepatopancreas cells in response to treatment with 17β-estradiol (E2) or 17α-ethinylestradiol (EE2). Luciferase reporter expression, driven by the 5'-regulatory region of the Ru-Vg gene spanning from −1020 bp to the start codon was induced by the estrogen receptor and was synergistically activated by treatment with E2 or EE2. These results suggest that R. uyekii and the Ru-Vg gene may be useful as biomarkers for exposure to E2 or EE2.
PMCID: PMC4227248  PMID: 25329620
17β-Estradiol; 17α-Ethinylestradiol; Korean rose bitterling; promoter assay; Rhodeus uyekii; vitellogenin
7.  Molecular and Functional Analyses of the Fast Skeletal Myosin Light Chain2 Gene of the Korean Oily Bitterling, Acheilognathus koreensis 
We identified and characterized the primary structure of the Korean oily bitterling Acheilognathus koreensis fast skeletal myosin light chain 2 (Akmlc2f), gene. Encoded by seven exons spanning 3955 bp, the deduced 168-amino acid AkMLC2f polypeptide contained an EF-hand calcium-binding motif and showed strong homology (80%–98%) with the MLC2 proteins of Ictalurus punctatus and other species, including mammals. Akmlc2f mRNA was highly enriched in skeletal muscles, and was detectable in other tissues. The upstream regions of Akmlc2f included a TATA box, one copy of a putative MEF-2 binding site and several putative C/EBPβ binding sites. The functional activity of the promoter region of Akmlc2f was examined using luciferase and red fluorescent protein reporters. The Akmlc2f promoter-driven reporter expressions were detected and increased by the C/EBPβ transcription factor in HEK293T cells. The activity of the promoter of Akmlc2f was also confirmed in the developing zebrafish embryo. Although the detailed mechanism underlying the expression of Akmlc2f remains unknown, these results suggest the muscle-specific expression of Akmlc2f transcript and the functional activation of Akmlc2f promoter by C/EBPβ.
PMCID: PMC3759931  PMID: 23945561
Acheilognathus koreenis; C/EBPβ; expression; Korean oily bitterling; myosin light chain 2; promoter assay
8.  Vitamin D, and Kidney Disease 
Mineral metabolism abnormalities, such as low 1,25-dihydroxyvitamin D (1,25(OH)2D) and elevated parathyroid hormone (PTH), are common at even higher glomerular filtration rate than previously described. Levels of 25-hydroxyvitamin D (25(OH)D) show an inverse correlation with those of intact PTH and phosphorus. Studies of the general population found much higher all-cause and cardiovascular (CV) mortality for patients with lower levels of vitamin D; this finding suggests that low 25(OH)D level is a risk factor and predictive of CV events in patients without chronic kidney disease (CKD). 25(OH)D/1,25(OH)2D becomes deficient with progression of CKD. Additionally, studies of dialysis patients have found an association of vitamin D deficiency with increased mortality. Restoration of the physiology of vitamin D receptor activation should be essential therapy for CKD patients.
PMCID: PMC3186891  PMID: 21998600
renal insufficiency, chronic; vitamin D; deficiency
9.  Reliability of MRI Findings of Peroneal Tendinopathy in Patients with Lateral Chronic Ankle Instability 
Clinics in Orthopedic Surgery  2010;2(4):237-243.
Patients with chronic lateral ankle instability also have peroneal tendinopathy often. However, preoperative MRIs of these patients are vague in many cases. Our study was performed to see the reliability of MRI findings of peroneal tendinopathy in patients with chronic lateral ankle instability.
MRI images for 82 patients who had chronic lateral ankle instability, and had received surgical treatment between March 2006 and November 2009 were compared with impressions from operating rooms. The mean age of patients was 36.4 years (range, 15 to 64 years), 82 ankles were studied, and patients with rheumatoid diseases were excluded from the study.
Of the 82 cases, 26 were true positives, 38 true negatives, 13 false positives and 5 false negatives. Of 39 cases of peroneal tendinopathy diagnosed from MRI, 14 had peroneal tendon partial tears, 15 tenosynovitis, 3 dislocations, 17 low-lying muscle bellies, and 6 peroneus quartus muscles. Of 31 cases of peroneal tendinopathy observed in surgery 11 had peroneal tendon partial tears, 4 tenosynovitis, 5 dislocations, 12 low-lying muscle belliess, and 1 peroneus quartus muscle. Sensitivity and specificity of peroneal tendinopathy were 83.9% and 74.5%, respectively. Positive predictive value was 66.7%. Negative predictive value was 88.4%. Accuracy rate was 78.0%.
MRI is a useful diagnostic tool for detecting peroneal tendinopathy in patients with chronic lateral ankle instability. However, MRI is vague in many cases. Therefore, a thorough delicate physical examination and careful observation is needed.
PMCID: PMC2981781  PMID: 21119941
Peroneal tendinopathy; Chronic lateral ankle instability; MRI
10.  Early Vascular Access Blood Flow as a Predictor of Long-term Vascular Access Patency in Incident Hemodialysis Patients 
Journal of Korean Medical Science  2010;25(5):728-733.
The long-term clinical benefits of vascular access blood flow (VABF) measurements in hemodialysis (HD) patients have been controversial. We evaluated whether early VABF may predict long-term vascular access (VA) patency in incident HD patients. We enrolled 57 patients, of whom 27 were starting HD with arteriovenous fistulas (AVFs) and 30 with arteriovenous grafts (AVGs). The patients' VABF was measured monthly with the ultrasound dilution technique over the course of the first six months after the VA operation. During the 20.4-month observational period, a total of 40 VA events in 23 patients were documented. The new VA events included 13 cases of stenosis and 10 thrombotic events. The lowest quartile of average early VABF was related to the new VA events. After adjusting for covariates such as gender, age, hypertension, diabetes, VA type, hemoglobin levels, body mass index, parathyroid hormone, and calcium-phosphorus product levels, the hazard ratio of VABF (defined as <853 mL/min in AVF or <830 mL/min in AVG) to incident VA was 3.077 (95% confidence interval, 1.127-8.395; P=0.028). There were no significant relationships between early VABF parameters and VA thrombosis. It is concluded that early VABF may predict long-term VA patency, particularly VA stenosis.
PMCID: PMC2858832  PMID: 20436709
Renal Dialysis; Blood Flow Velocity; Vascular Patency; Indicator Dilution Techniques
11.  Mycotic Pulmonary Artery Aneurysm as an Unusual Complication of Thoracic Actinomycosis 
Korean Journal of Radiology  2004;5(1):68-71.
Although pulmonary artery aneurysms are a rare vascular anomaly, they are seen in a wide variety of conditions, such as congenital heart disease, infection, trauma, pulmonary hypertension, cystic medial necrosis and generalized vasculitis. To our knowledge, mycotic aneurysms caused by pulmonary actinomycosis have not been reported in the radiologic literature. Herein, a case of pulmonary actinomycosis complicated by mycotic aneurysm is presented. On CT scans, this case showed focal aneurysmal dilatation of a peripheral pulmonary artery within necrotizing pneumonia of the right lower lobe, which was successfully treated with transcatheter embolization using wire coils.
PMCID: PMC2698115  PMID: 15064561
Lung, Infection; Aneurysm, Mycotic; Aneurysm, Pulmonary; Pulmonary arteries, Abnormalities

Results 1-11 (11)