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Sang-Gon Lee - Top 30 Publications

RIPL peptide-conjugated nanostructured lipid carriers for enhanced intracellular drug delivery to hepsin-expressing cancer cells.

To facilitate selective and enhanced drug delivery to hepsin (Hpn)-expressing cancer cells, RIPL peptide (IPLVVPLRRRRRRRRC, 16-mer)-conjugated nanostructured lipid carriers (RIPL-NLCs) were developed.

Metabolic Syndrome and the Risk of New-Onset Atrial Fibrillation in Middle-Aged East Asian Men.

Although the prevalence of both atrial fibrillation (AF) and metabolic syndrome (MetS) has been increasing in East Asia, the association between them is uncertain.Methods and Results:A total of 24,741 middle-aged Korean men without baseline AF were enrolled in a health screening program from January 2003 to December 2008. Among them, 21,981 subjects were evaluated to determine the risk of AF based on baseline MetS status through December 2016. At every visit, the subjects were evaluated for AF using ECG. MetS was defined using the criteria of the International Diabetes Federation and was present in 2,529 subjects (11.5%). Mean (±standard deviation) age was 45.9±5.3 years. During a mean follow-up of 8.7 years, 168 subjects (0.8%) were diagnosed with AF. The age-adjusted and multivariate-adjusted hazard ratios (HR) for MetS with AF were 1.62 (P=0.02) and 1.57 (P=0.03), respectively. Among the components of MetS, central obesity (age-adjusted HR 1.62, P<0.01) and raised blood pressure (age-adjusted HR 1.43, P=0.02) were associated with an increased risk of AF.

Early Strut Coverage in Patients Receiving Drug-Eluting Stents and its Implications for Dual Antiplatelet Therapy: A Randomized Trial.

This study sought to measure early strut coverage in patients receiving drug-eluting stents (DESs) and to explore the feasibility of short-term dual antiplatelet therapy (DAPT) based on the degree of early strut coverage.

The impact of a dose of the angiotensin receptor blocker valsartan on post-myocardial infarction ventricular remodelling.

Although clinical guidelines advocate the use of the highest tolerated dose of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after acute myocardial infarction (MI), the optimal dosing or the risk-benefit profile of different doses have not been fully identified.

Harmonization of laboratory results by data adjustment in multicenter clinical trials.

In multicenter clinical trials, laboratory tests are performed in the laboratory of each center, mostly using different measuring methodologies. The purpose of this study was to evaluate coefficients of variation (CVs) of laboratory results produced by various measuring methods and to determine whether mathematical data adjustment could achieve harmonization between the methods.

Comparison of long-term mortality according to obesity in patients with successful percutaneous chronic total occlusion interventions using drug-eluting stents.

To evaluate the long-term mortality according to obesity in patients with chronic total occlusion (CTO) lesions after successful percutaneous coronary intervention (PCI).

Intramuscular hematoma with motor weakness after trigger point injection: A case report.

Although trigger point injection is known as an easy and low-risk procedure, it is contraindicated to patients with hemorrhagic disorders or who regularly take anticoagulants/antiplatelets. However, taking clopidogrel is not a defined contraindication to this low-risk procedure.

Evaluation of the impact of statin therapy on the obesity paradox in patients with acute myocardial infarction: A propensity score matching analysis from the Korea Acute Myocardial Infarction Registry.

The phenomenon of obesity paradox after acute myocardial infarction (AMI) has been reported under strong recommendation of statin therapy. However, the impact of statin therapy on this paradox has not been investigated. This study investigated the impact of statin therapy on 1-year mortality according to obesity after AMI. A total of 2745 AMI patients were included from the Korea Acute Myocardial Infarction Registry after 1:4 propensity score matching analysis (n = 549 for nonstatin group and n = 2196 for statin group). Primary and secondary outcomes were all-cause and cardiac death, respectively. During 1-year follow-up, the incidence of all-cause (8.4% vs 3.7%) and cardiac (6.2% vs 2.3%) death was higher in nonstatin group than in statin (P < .001, respectively). In nonstatin group, the incidence of all-cause (7.2% vs 9.0%) and cardiac (5.5% vs 6.5%) death did not differ significantly between obese and nonobese patients. However, in statin group, obese patients had lower 1-year rate of all-cause (1.7% vs 4.8%) and cardiac (1.2% vs 2.9%) death (P < .05, respectively), and lower cumulative rates by Kaplan-Meier analysis of all-cause and cardiac death compared with nonobese patients (log-rank P < .05, respectively). The overall risk of all-cause death was significantly lower in obese than in nonobese patients only in statin group (hazard ratio: 0.35; P = .001). After adjusting for confounding factors, obesity was independently associated with decreased risk of all-cause death in statin group. In conclusion, the greater benefit of statin therapy for survival in obese patients is further confirmation of the obesity paradox after AMI.

Prediabetes is not a risk factor for subclinical coronary atherosclerosis.

There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals.

Enhanced Transdermal Delivery by Combined Application of Dissolving Microneedle Patch on Serum-Treated Skin.

Dissolving microneedle (DMN), a transdermal drug delivery system in which drugs are encapsulated in a biodegradable polymeric microstructure, is designed to dissolve after skin penetration and release the encapsulated drugs into the body. However, because of limited loading capacity of drugs within microsized structures, only a small dosage can be delivered, which is often insufficient for patients. We propose a novel DMN application that combines topical and DMN application simultaneously to improve skin permeation efficiency. Drugs in pretreated topical formulation and encapsulated drugs in DMN patch are delivered into the skin through microchannels created by DMN application, thus greatly increasing the delivered dose. We used 4-n-butylresorcinol to treat human hyperpigmentation and found that sequential application of serum formulation and DMNs was successful. In skin distribution experiments using Alexa Fluor 488 and 568 dyes as model drugs, we confirmed that the pretreated serum formulation was delivered into the skin through microchannels created by the DMNs. In vitro skin permeation and retention experiments confirmed that this novel combined application delivered more 4-n-butylresorcinol into the skin than traditional DMN-only and serum-only applications. Moreover, this combined application showed a higher efficacy in reducing patients' melanin index and hyperpigmented regions compared with the serum-only application. As combined application of DMNs on serum-treated skin can overcome both dose limitations and safety concerns, this novel approach can advance developments in transdermal drug delivery.

Sigma-Metrics of Electrolyte Tests From a Recently Launched New-Generation Proficiency Testing Program of the Korean Association of Quality Assurance for Clinical Laboratory.

Characteristics of Earlier Versus Delayed Presentation of Very Late Drug-Eluting Stent Thrombosis: An Optical Coherence Tomographic Study.

The pathophysiology underlying very late drug-eluting stent (DES) thrombosis is not sufficiently understood. Using optical coherence tomography, we investigated characteristics of very late stent thrombosis (VLST) according to different onset times.

Combination Therapy of Rosuvastatin and Ezetimibe in Patients with High Cardiovascular Risk.

The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk.

Dexmedetomidine combined with midazolam vs. dexmedetomidine alone for sedation during spinal anesthesia.

Dexmedetomidine is a useful sedative agent for spinal anesthesia. However, it has been reported that dexmedetomidine decreases heart rate in a dose-dependent manner. In the current study, we compared the administration of a bolus dose of midazolam and bolus loading of dexmedetomidine over 10 min with the goal of identifying an additional method of sedation.

Formulation of controlled-release pelubiprofen tablet using Kollidon(®) SR.

To develop a matrix-type, controlled-release tablet formulation of pelubiprofen (PLB), a recently developed non-steroidal anti-inflammatory drug, polymeric excipients including hypromellose, hydroxypropylcellulose, Eudragit(®) RS PO, and Kollidon(®) SR were screened. A formulation containing 12.4% w/w Kollidon(®) SR (K2 tablet) was found to be the most promising and stable for 6 months in an accelerated stability test. PLB release from K2 tablet was limited at pH 1.2, but gradually increased at pH 6.8 with a surface-erosion, resulting in the best fit to Hixson-Crowell equation. Comparative human PK studies were performed using a randomized, 2-way crossover design. LC-MS/MS assay revealed that the plasma level of PLB-transOH, an active metabolite, was significantly higher than that of PLB. After multiple dosing of immediate-release tablet (R) and K2 tablet (T), the T/R ratios of AUC were 1.02 and 1.04 for PLB and PLB-transOH, respectively. Level A in vitro-in vivo correlation was established for the K2 tablet-administered group. PK profile of PLB-transOH was not influenced by food intake, while that of PLB was altered. We suggest that K2 tablet could be administered twice a day without being affected by food intake, thereby enhancing patient compliance.

A Randomized, Double-blind, Candesartan-controlled, Parallel Group Comparison Clinical Trial to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan in Patients with Mild to Moderate Essential Hypertension.

A new antihypertensive drug that selectively blocks angiotensin II receptor type 1, fimasartan, has a potent and rapidly acting antihypertensive effect. We investigated the antihypertensive effects of fimasartan 60 and 120 mg and its safety in comparison to 8 mg of candesartan.

Development of a solidified self-microemulsifying drug delivery system (S-SMEDDS) for atorvastatin calcium with improved dissolution and bioavailability.

To improve the dissolution and oral bioavailability (BA) of atorvastatin calcium (ATV), we previously introduced an optimized self-microemulsifying drug delivery system (SMEDDS) using Capmul(®) MCM (oil), Tween(®) 20 (surfactant), and tetraglycol (cosurfactant). In this study, various solid carriers were employed to develop a solidified SMEDDS (S-SMEDDS): mannitol (M) and lactose (L) as water-soluble carriers, and Sylysia(®) 350 (S) and Aerosil(®) 200 (A) as water-insoluble carriers. Maximum solidifying capacities (SCmax) of water-insoluble carriers were significantly greater than those of water-soluble carriers were. The resultant powders were free flowing with an angle of repose <40° and Carr's index 5-20%, regardless of the solid carrier types. S-SMEDDS with mannitol (S(M)-SMEDDS) or lactose (S(L)-SMEDDS) had a smaller droplet size and greater dissolution than S-SMEDDS with Sylysia(®) 350 (S(S)-SMEDDS) or Aerosil(®) 200 (S(A)-SMEDDS). Following oral administration of various formulations to rats at a dose equivalent to 25mg/kg of ATV, plasma drug levels were measured by LC-MS/MS. The relative BAs (RBAs) of SMEDDS, S(M)-SMEDDS, and S(S)-SMEDDS were 345%, 216%, and 160%, respectively, compared to that of ATV suspension. Additionally, at a reduced dose of ATV equivalent to 5mg/kg, the RBAs of S(M)-SMEDDS and S(S)-SMEDDS compared to that of SMEDDS were 101% and 65%, respectively. These results suggest that S(M)-SEMDDS offers great potential for the development of solid dosage forms with improved oral absorption of drugs with poor water solubility.

Enhanced topical delivery of tacrolimus by a carbomer hydrogel formulation with transcutol P.

Tacrolimus (TAC), a non-steroidal anti-inflammatory and immunosuppressive agent, is used for the treatment of atopic dermatitis (AD) and skin immune diseases. TAC-loaded topical hydrogel formulations composed of carbomer, carnosine, transcutol P (diethylene glycol monoethyl ether) and humectant were prepared. For comparison, TAC-loaded topical cream-type formulations were also prepared and commercially available TAC ointment was used as a reference. A drug release study in vitro revealed that the total amount of TAC released from hydrogels over 24 h was approximately 30 times greater than that for the reference formulation. Compared to the reference ointment and creams, carbomer gel formulations showed higher skin permeation and retention of TAC (significantly different at p < 0.05), especially those with more than 10% of transcutol P. Therefore, carbomer gel formulations with sufficient levels of transcutol P are good candidates for skin delivery of TAC and have potential as therapeutic agents for the treatment of AD or immune skin disorders.

Design of Multifunctional Liposomal Nanocarriers for Folate Receptor-Specific Intracellular Drug Delivery.

As a novel carrier for folate receptor (FR)-targeted intracellular delivery, we designed two types of targetable liposomal systems using Pep-1 peptide (Pep1) and folic acid as a cell-penetrating peptide (CPP) and target molecule, respectively. Folate-linked Pep1 (Fol-Pep1) was synthesized by solid phase peptide synthesis (SPPS) and verified using (1)H NMR and far-ultraviolet (UV) circular dichroism (CD). The chimeric ligand (Fol-Pep1)-modified liposome (cF-P-L) was prepared by coupling Fol-Pep1 to maleimide-derivatized liposomes at various ratios. The dual ligand (folate and Pep1)-modified liposome (dF/P-L) was prepared by separately attaching both ligands to the liposomal surface via a short (PEG2000) or long (PEG3400) linker. The physical and conformational characteristics including vesicle size, zeta potential, and the number of conjugated ligands were determined. Intracellular uptake specificities of various fluorescent probe-containing cF-P-L and dF/P-L systems were assessed using FR-positive HeLa and FR-negative HaCaT cells. Cellular uptake behavior was visualized by confocal laser scanning microscopy (CLSM). Internalization was time-dependent. Fol-Pep1 and Pep-1 cytotoxicities were negligible up to 25 μM in FR-positive and FR-negative cells. Empty cF-P-L and dF/P-L were nontoxic at the concentration used. The optimized dF3/P2(450/90) system carrying 450 PEG3400-linked folate and 90 PEG2000-linked Pep1 molecules could be a good candidate for FR-specific intracellular drug delivery.

Evaluation of the Bio-Rad Geenius HIV 1/2 Confirmation Assay as an Alternative to Western Blot in the Korean Population: A Multi-Center Study.

Recently updated recommendations for diagnosis of HIV infection suggest a new diagnostic algorithm including HIV-1/HIV-2 antibody differentiation immunoassay instead of western blot (WB) as a confirmatory testing. We evaluated Bio-Rad Geenius HIV1/2 confirmation assay as a simple and reliable alternative to WB in the Korean population with low HIV prevalence. The Geenius HIV1/2 was performed in a total of 192 serum specimens (140 reactive and 52 nonreactive specimens by ARCHITECT HIV Ag/Ab Combo assay) that were prospectively collected from five institutions. HIV-1 nucleic acid amplification test (NAT) was performed in negative or indeterminate specimens by Geenius HIV1/2 or WB. Among 140 reactive specimens by HIV Ag/Ab assay, 82 (58.6%) were positive for HIV-1 Ab by Geenius HIV1/2. Among 58 negative or indeterminate specimens by Geenius HIV1/2, four specimens (6.9%) were positive by HIV-1 NAT. The sensitivity and specificity of Geenius HIV1/2 were 95.3% and 100.0%, respectively. When we considered only WB, the sensitivity and specificity of Geenius HIV1/2 were 100.0% and 99.1%, respectively. Agreement between Geenius HIV1/2 and WB was excellent (weighted Kappa = 0.89). The Geenius HIV1/2 is simple and time-saving compared with WB. It has an excellent performance and can be a reliable alternative to WB. HIV-1 NAT should be performed in negative or indeterminate specimens by Geenius HIV1/2 to detect acute HIV infection as recommended in new HIV testing algorithms.

Late-acquired incomplete stent apposition after everolimus-eluting stent versus sirolimus-eluting stent implantation in patients with non-ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction.

Our aim was to evaluate the incidence and clinical outcomes of late-acquired incomplete stent apposition (LAISA) after implantation of first- and second-generation drug-eluting stents in patients with acute myocardial infarction (AMI).

A Case of Perimembranous Ventricular Septal Defect Associated with Sinus of Valsalva Aneurysm Mimicking Membranous Septal Aneurysm.

Sinus of Valsalva aneurysms are rare. Sinus of Valsalva aneurysms are frequently associated with ventricular septal defect (VSD) and aortic regurgitation. They often remain asymptomatic until abruptly presenting with acute chest pain and heart failure secondary to rupture. Here, we describe a case of 20-year-old man who presented with chest pain with a history of VSD. Initial work-up concluded that the patient had VSD associated membranous septal aneurysm. Four years later, the patient presented with symptoms of heart failure. Work-up showed that the ruptured sinus of Valsalva aneurysm was the cause of symptoms. Due to its close proximity to the aortic annulus, sinus of Valsalva aneurysm should be differentiated from membranous septal aneurysm.

A Secure Routing Protocol for Wireless Sensor Networks Considering Secure Data Aggregation.

The commonly unattended and hostile deployments of WSNs and their resource-constrained sensor devices have led to an increasing demand for secure energy-efficient protocols. Routing and data aggregation receive the most attention since they are among the daily network routines. With the awareness of such demand, we found that so far there has been no work that lays out a secure routing protocol as the foundation for a secure data aggregation protocol. We argue that the secure routing role would be rendered useless if the data aggregation scheme built on it is not secure. Conversely, the secure data aggregation protocol needs a secure underlying routing protocol as its foundation in order to be effectively optimal. As an attempt for the solution, we devise an energy-aware protocol based on LEACH and ESPDA that combines secure routing protocol and secure data aggregation protocol. We then evaluate its security effectiveness and its energy-efficiency aspects, knowing that there are always trade-off between both.

Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture design.

In this study, we developed and optimized a self-microemulsifying drug delivery system (SMEDDS) formulation for improving the dissolution and oral absorption of atorvastatin calcium (ATV), a poorly water-soluble drug. Solubility and emulsification tests were performed to select a suitable combination of oil, surfactant, and cosurfactant. A D-optimal mixture design was used to optimize the concentration of components used in the SMEDDS formulation for achieving excellent physicochemical characteristics, such as small droplet size and high dissolution. The optimized ATV-loaded SMEDDS formulation containing 7.16% Capmul MCM (oil), 48.25% Tween 20 (surfactant), and 44.59% Tetraglycol (cosurfactant) significantly enhanced the dissolution rate of ATV in different types of medium, including simulated intestinal fluid, simulated gastric fluid, and distilled water, compared with ATV suspension. Good agreement was observed between predicted and experimental values for mean droplet size and percentage of the drug released in 15 minutes. Further, pharmacokinetic studies in rats showed that the optimized SMEDDS formulation considerably enhanced the oral absorption of ATV, with 3.4-fold and 4.3-fold increases in the area under the concentration-time curve and time taken to reach peak plasma concentration, respectively, when compared with the ATV suspension. Thus, we successfully developed an optimized ATV-loaded SMEDDS formulation by using the D-optimal mixture design, that could potentially be used for improving the oral absorption of poorly water-soluble drugs.

Randomized Comparisons Between Different Stenting Approaches for Bifurcation Coronary Lesions With or Without Side Branch Stenosis.

This study sought to evaluate the optimal percutaneous coronary intervention techniques using drug-eluting stents for bifurcation coronary lesions.

Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease: 5-Year Outcomes of the PRECOMBAT Study.

In a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.

Optical coherence tomographic observation of in-stent neoatherosclerosis in lesions with more than 50% neointimal area stenosis after second-generation drug-eluting stent implantation.

Despite the enhanced properties of the second-generation drug-eluting stent (DES), its association with neoatherosclerosis has not been sufficiently evaluated. Therefore, we sought to evaluate and compare neoatherosclerosis in second-generation DESs to first-generation DESs.

Response to letter regarding article, "optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial".

Hydrogel-based ultra-moisturizing cream formulation for skin hydration and enhanced dermal drug delivery.

To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm(2)) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm(2)) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.

Security analysis and improvements of authentication and access control in the Internet of Things.

Internet of Things is a ubiquitous concept where physical objects are connected over the internet and are provided with unique identifiers to enable their self-identification to other devices and the ability to continuously generate data and transmit it over a network. Hence, the security of the network, data and sensor devices is a paramount concern in the IoT network as it grows very fast in terms of exchanged data and interconnected sensor nodes. This paper analyses the authentication and access control method using in the Internet of Things presented by Jing et al. (Authentication and Access Control in the Internet of Things. In Proceedings of the 2012 32nd International Conference on Distributed Computing Systems Workshops, Macau, China, 18-21 June 2012, pp. 588-592). According to our analysis, Jing et al.'s protocol is costly in the message exchange and the security assessment is not strong enough for such a protocol. Therefore, we propose improvements to the protocol to fill the discovered weakness gaps. The protocol enhancements facilitate many services to the users such as user anonymity, mutual authentication, and secure session key establishment. Finally, the performance and security analysis show that the improved protocol possesses many advantages against popular attacks, and achieves better efficiency at low communication cost.