[Show abstract][Hide abstract] ABSTRACT: In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients.
This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride.
A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c < 7% (P = 0.229), it was significantly associated in the group with HbA1c ≥ 7% (P = 0.010) after adjusting for covariates in multivariate analyses.
This study demonstrated an effect modification of glycemic level on the association between NAFLD and CACS. NAFLD was independently associated with CACS only in diabetes patients with higher HbA1c, after adjustment for confounders.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to examine the effect of laser-assisted zona thinning (LAZT) at one or four-points on the blastocyst formation and hatching process in mice with respect to female age.
Eight-cell or morula embryos collected from superovulated C57BL female mice with different ages (6-11 and 28-31 weeks) were treated with LAZT at one-point (LAZT1) or four-points (LAZT4). The zona pellucida was thinned to more than 70% of its initial thickness by making two holes of 15-20 µm.
In the young mice, LAZT resulted in a significant increase in early hatching and hatching rates compared to the control group (p<0.05). However, in the old mice, LAZT significantly increased blastocyst formation as well as early hatching and hatching compared to the controls (p<0.05). These effects were more remarkable in LAZT4 than in LAZT1 and in aged mice than in young ones.
These results show that multi-point LAZT leads to a significant improvement of blastocyst formation and hatching in mice compared to controls.
[Show abstract][Hide abstract] ABSTRACT: Exfoliated graphitic carbon nitride nanosheets (g-C3N4-NS) were applied for the first time to the preparation of an electrocatalyst for the oxygen reduction reaction (ORR). A less dense structure with increased surface area was observed for g-C3N4-NS compared to bulk g-C3N4 from detailed analyses including TEM, STEM, AFM with depth profiling, XRD, and UV-Vis spectroscopy. The pyrolysis of the prepared g-C3N4-NS with Co and carbon under inert environment provided enhanced accessibility to the N functionalities required for efficient interaction of Co and C with N for the formation of Co-N-C networks and produced hollow and interconnected Co-N-C-NS structure responsible for high durability. The Co-N-C-NS electrocatalyst exhibited superior catalytic activity and durability and further displayed fast and selective four electron transfer kinetics for the ORR, as evidenced by various electrochemical experiments. The hollow, interconnected structure of Co-N-C-NS with increased pyridinic and graphitic N species was proposed to play a key role in facilitating the desired ORR reaction.
[Show abstract][Hide abstract] ABSTRACT: To investigate the efficacy of topical 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) in a mouse model of experimental dry eye (EDE).
Eye drops consisting of 0.001% or 0.01% AICAR, 0.05% cyclosporine A (CsA), or balanced salt solution (BSS) were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interferon gamma-induced protein 10 (IP-10), and monokine induced by interferon-γ (MIG) were measured in the conjunctiva. In addition, Western blot, periodic acid-Schiff staining for evaluating goblet cell density, flow cytometry for counting the number of CD4+CXCR3+ T cells, and immunohistochemistry for detection of 4-hydroxy-2-nonenal (4HNE) were performed.
Mice treated with 0.01% AICAR showed a significant improvement in all clinical parameters compared with the EDE control, vehicle control, and 0.001% AICAR groups (P < 0.001). A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, IP-10, and MIG, the number of CD4+CXCR3+ T cells, and the number of 4HNE-positive cells were also observed in the 0.01% AICAR group (P < 0.001). Although 0.05% CsA also led to an improvement in clinical parameters and inflammatory molecule levels, its therapeutic effects were comparable or inferior to those of 0.01% AICAR.
Topical application of 0.01% AICAR can markedly improve clinical signs and decrease inflammation in the ocular surface of EDE, suggesting that AICAR eye drops may be used as a therapeutic agent for dry eye disease.
[Show abstract][Hide abstract] ABSTRACT: Many studies have proposed that putative ovarian stem cells (OSCs) derived from the ovarian surface epithelium (OSE) layer of adult mammalian ovaries can produce oocytes. Few studies have reported that ovaries of aged mammalian females including mice and women possess rare premeiotic germ cells that can generate oocytes. However, no studies have reported the changes of OSCs according to the age of the female. Therefore, this study evaluated pluripotent and germ cell marker expression in the intact ovary, scraped OSE, and postcultured OSE according to age in female mice.
C57BL/6 female mice of 2 age groups (6-8 and 28-31 weeks) were superovulated by injection with 5 IU equine chorionic gonadotropin (eCG). Both ovaries were removed after 48 hours and scrapped to obtain OSE. Gene expressions of pluripotent (Oct-4, Sox-2, Nanog) and germ cell markers (c-Kit, GDF-9, and VASA) were evaluated by RT-PCR. VASA and GDF-9 were immune-localized in oocyte-like structures.
Expressions of germ cell markers in the intact ovary were significantly decreased in aged females, whereas expressions of pluripotent markers were not detected, regardless of age. Scraped OSE expression of all pluripotent and germ cell markers, except for c-Kit, was similar between both age groups. Three week post-cultured OSE had significantly decreased expression of GDF-9 and VASA , but not c-Kit, in old mice, as compared to young mice; however there was no difference in the expression of other genes. The number of positively stained Oct-4 by immunohistochemistry in postcultured OSE was 2.5 times higher in young mice than aged mice. Oocyte-like structure was spontaneously produced in postcultured OSE. However, while that of young mice revealed a prominent nucleus, zona pellucida-like structure and cytoplasmic organelles, these features were not observed in old mice.
These results shows that aged female mice have putative OSCs in OSE, but their differentiation potential, as well as the number of OSCs differs from those of young mice.
[Show abstract][Hide abstract] ABSTRACT: Goals: The aim of this study was to prospectively assess the effects of the order of colonoscopic procedures and other possible factors on the adenoma detection rate (ADR). Background: There have been conflicting studies regarding the timing or order of a colonoscopy and its ability to detect adenomas. Study: Between March 2011 and July 2011, consecutive colonoscopies were prospectively performed by 7 board-certified staff endoscopists at the Seoul National University Hospital Healthcare System Gangnam Center. The primary outcome was the overall ADR according to the procedure order of the colonoscopies, and the secondary outcome was the identification of other possible factors influencing the ADR. Results: A total of 1908 colonoscopies were analyzed. The detection rate was 56.5% for all polyps and 37.3% for adenomas. The ADR increased as the performance order of the colonoscopy increased and was highest for the third procedure (43.4%). However, the ADR of the remaining procedures, including later procedures, was similar throughout the workday. In the multivariable analysis, the ADR was significantly associated with older age, male sex, high body mass index, personal history of colorectal polyps, long withdrawal time, and an experienced endoscopist. However, the colonoscopy procedure order was not significantly associated with the ADR. Conclusions: The ADR was stable according to the procedure order for the later procedures of the workday in a setting of moderate daily procedure volumes. The withdrawal time and experience level of the endoscopist were more important than the procedure order in detecting adenomas by colonoscopy. Copyright
Journal of Clinical Gastroenterology 10/2014; Publish Ahead of Print. DOI:10.1097/MCG.0000000000000258 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A novel Fe-N-C composite material with a hollow graphitized nanostructure is prepared by pyrolyzing iron-chelating, nitrogen-containing precursors adsorbed on carbon black spheres for use in the oxygen reduction reaction (ORR) of polymer electrolyte membrane fuel cells (PEMFCs). The resulting composite hybrid exhibits excellent electrocatalytic activity and a four-electron dominated ORR pathway in an alkaline solution. The efficient catalytic activity of the prepared Fe-N-C is mainly attributed to the effective incorporation of nitrogen and iron atoms into the graphitized matrices and high electrical conductivity due to the interconnected structure. Furthermore, the hybrid material shows superior catalytic durability in the alkaline medium even after 3000 cyclic voltammetry cycles, making it a good candidate for a cathodic electrocatalyst in PEMFCs.
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective. Various factors including age, sex, body mass index (BMI) and history of operation have been linked to the colonoscopic intubation time. The aims of this study were to identify the factors predicting cecal intubation time (CIT) and to evaluate the effect of the visceral adipose tissue (VAT) area on CIT. Material and methods. A total of 1386 consecutive subjects who underwent colonoscopy and abdominal CT on the same day for a health checkup at a single health care center in Korea from August to December 2011 were studied prospectively. Age, sex, BMI, height, waist circumference, history of operation, symptoms of irritable bowel syndrome, bowel preparation status, experience of colonoscopists, VAT amount on abdominal CT and time required to reach the cecum were analyzed. Results. The mean age of the subjects was 53.0 ± 9.6 years, and 63.5% were male. The median CIT was 271 s. Univariate analyses showed that female gender, old age, shorter height, lower BMI, prior history of surgery and lower VAT were associated with longer CIT. To adjust for confounding effects of the gender, we investigated the genders separately in multivariate analysis. Older age and lower VAT were associated with prolonged CIT. However, the significance of association of VAT on prolonged CIT disappeared in women. Conclusion. This study demonstrates that CIT is prolonged by lower VAT area in men. This is the first study to demonstrate a direct association between VAT area and CIT.
[Show abstract][Hide abstract] ABSTRACT: Background To facilitate selective drug delivery to hepsin (Hpn)-expressing cancer cells, the RIPL peptide (IPLVVPLRRRRRRRRC; 16mer; 2.1 kDa) was synthesized as a novel cell penetrating/homing peptide (CPHP) and conjugated to a liposomal carrier. Methods RIPL peptide-conjugated liposomes (RIPL-Lipo) were prepared by conjugating RIPL peptides to maleimide-derivatized liposomal vesicles via the thiol-maleimide reaction. Vesicle size and zeta potential were examined using a Zetasizer. Intracellular uptake specificity of the RIPL peptide, or RIPL-Lipo, was assessed by measuring mean fluorescence intensity (MFI) after treatment with a fluorescent marker in various cell lines: SK-OV-3, MCF-7, and LNCaP for Hpn(+); DU145, PC3, and HaCaT for Hpn(-). FITC-dextran was used as a model compound. Selective translocational behavior of RIPL-Lipo to LNCaP cells was visualized by fluorescence microscopy and confocal laser scanning microscopy. Cytotoxicities of the RIPL peptide and RIPL-Lipo were evaluated by WST-1 assay. Results RIPL peptides exhibited significant Hpn-selectivity. RIPL-Lipo systems were of positively charged nanodispersion (165 nm in average; 6-24 mV depending on RIPL conjugation ratio). RIPL-Lipo with the conjugation of 2300 peptide molecules revealed the greatest MFI in all cell lines tested. Cellular uptake of RIPL-Lipo increased by 20- to 70-fold in Hpn(+) cells, and 5- to 7-fold in Hpn(-) cells, compared to the uptake of FITC-dextran. Cytosolic internalization of RIPL-Lipo was time-dependent: bound instantly; internalized within 30 min; distributed throughout the cytoplasm after 1 h. Cytotoxicities of RIPL peptide (up to 50 μM) and RIPL-Lipo (up to 10%) were minor (cell viability >90%) in LNCaP and HaCaT cells. Conclusion By employing a novel CPHP, the RIPL-Lipo system was successfully developed for Hpn-specific drug delivery.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 08/2014; 87(3). DOI:10.1016/j.ejpb.2014.03.016 · 4.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To compare the diagnostic performance of the noncontrast MRI including DWI to the standard MRI for detecting hepatic malignancies in patients with chronic liver disease.
Materials and methods
We included 135 patients with 136 histologically-confirmed hepatocellular carcinomas (HCCs), 12 cholangiocarcinomas, and 34 benign lesions (≤ 2.0 cm), and 22 patients with cirrhosis but no focal liver lesion who underwent 3.0 T liver MRI. Noncontrast MRI set (T1- and T2-weighted images and DWI) and standard MRI set (gadoxetic acid-enhanced and noncontrast MRI) were analyzed independently by three observers to detect liver malignancies using receiver operating characteristic analysis.
The Az value of the noncontrast MRI (mean, 0.906) was not inferior to that of the combined MRI (mean, 0.924) for detecting malignancies by all observers (P > 0.05). For each observer, no significant difference was found in the sensitivity and specificity between the two MRI sets for detecting liver malignancies and distinguishing them from benign lesions (P > 0.05), whereas negative predictive value was higher with the combined MRI than with the noncontrast MRI (P = 0.0001). When using pooled data, the sensitivity of the combined MRI (mean 94.8%) was higher than that of the noncontrast MRI (mean, 91.7%) (P = 0.001), whereas specificity was equivalent (78.6% vs 77.5%).
Noncontrast MRI including DWI showed reasonable performance compared to the combined gadoxetic acid-enhanced and noncontrast MRI set for detecting HCC and cholangiocarcinoma and differentiating them from benign lesions in patients with chronic liver disease.
Magnetic Resonance Imaging 07/2014; 32(6). DOI:10.1016/j.mri.2013.12.021 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE. The purposes of this study were to assess the widths of the intercostal spaces of the right inferior human rib cage through which high-intensity focused ultrasound therapy would be applied for treating liver cancer and to elucidate the demographic factors associated with intercostal space width. SUBJECTS AND METHODS. From March 2013 to June 2013, the widths of the intercostal spaces and the ribs at six areas of the right inferior rib cage (area 1, lowest intercostal space on anterior axillary line and the adjacent upper rib; area 2, second-lowest intercostal space on anterior axillary line and the adjacent upper rib; areas 3 and 4, lowest and second-lowest spaces on midaxillary line; areas 5 and 6, lowest and second-lowest spaces on posterior axillary line) were sonographically measured in 466 patients (214 men, 252 women; mean age, 53.0 years) after an abdominal sonographic examination. Demographic factors and the presence or absence of chronic liver disease were evaluated by multivariate analysis to investigate which factors influence intercostal width. RESULTS. The width of the intercostal space was 19.7 ± 3.7 mm (range, 9-33 mm) at area 1, 18.3 ± 3.4 mm (range, 9-33 mm) at area 2, 17.4 ± 4.0 mm (range, 7-33 mm) at area 3, 15.4 ± 3.5 mm (range, 5-26 mm) at area 4, 17.2 ± 3.7 mm (range, 7-28 mm) at area 5, and 14.5 ± 3.6 mm (range, 4-26 mm) at area 6. The corresponding widths of the ribs were 15.2 ± 2.3 mm (range, 8-22 mm), 14.5 ± 2.3 mm (range, 9-22 mm), 13.2 ± 2.0 mm (range, 9-20), 14.3 ± 2.2 mm (range, 9-20 mm), 15.0 ± 2.2 mm (range, 10-22 mm), and 15.1 ± 2.3 mm (range, 8-21 mm). Only female sex was significantly associated with the narrower intercostal width at areas 1, 2, 3, and 5 (regression coefficient, 1.124-1.885; p = 0.01-0.04). CONCLUSION. There was substantial variation in the widths of the intercostal spaces of the right inferior rib cage such that the anterior and inferior aspects of the intercostal space were relatively wider. Women had significantly narrower intercostal spaces than men.
American Journal of Roentgenology 07/2014; 203(1):201-8. DOI:10.2214/AJR.13.11744 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the enhancement of the efficacy of systemic doxorubicin by pulsed high-intensity focused ultrasound (HIFU)-induced, localized mild hyperthermia. For the in vitro study, the intranuclear uptake of doxorubicin by squamous cell carcinoma (SCC)-7 cells incubated at different temperatures was compared. For the in vivo study, mice with SCC-7 tumors were assigned to either the control, conventional hyperthermia, HIFU hyperthermia, doxorubicin-alone, conventional hyperthermia + doxorubicin or HIFU hyperthermia + doxorubicin group. Conventional hyperthermia was induced by immersing the tumor in warm water (42.5°C), and HIFU hyperthermia was induced by HIFU after optimizing the parameters with direct temperature measurements (frequency = 1 MHz, pulse repetition frequency = 5 Hz, power = 12 W, duty cycle = 50%). In the in vitro study, fluorescence was more intense at 42°C than at 37°C and was time dependent. In the in vivo study, tumor growth in the HIFU hyperthermia + doxorubicin group was most prominently suppressed with the highest apoptotic index compared with all other groups (p < 0.05). Pulsed HIFU-induced localized mild hyperthermia enhanced the anti-cancer efficacy of systemic doxorubicin more than conventional mild hyperthermia.
Ultrasound in medicine & biology 07/2014; 40(7). DOI:10.1016/j.ultrasmedbio.2014.01.005 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE. MRI-guided high-intensity focused ultrasound (HIFU) ablation is increasingly adopted for treating symptomatic uterine fibroids. As a noninvasive therapy performed on an outpatient basis, it has been viewed by patients to have distinct advantages over other treatment options. However, its breadth of clinical application is still limited. To address this issue, various techniques have been implemented. CONCLUSION. In this article, we discuss techniques that contribute to widening patient selection for MRI-guided HIFU therapy of uterine fibroids.
American Journal of Roentgenology 02/2014; 202(2):443-51. DOI:10.2214/AJR.13.10753 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: The aim of this study is to examine the differential expression of stromal cell-derived factor-1α (SDF-1α)/CXCR4 and vascular endothelial growth factor (VEGF) in the third trimester placental bed of normotensive controls and preeclamptic patients. Methods: Placental bed tissues were collected from 15 patients with preeclampsia (PE) and 15 gestational-matched normotensive controls at the time of their cesarean delivery. Placental bed expressions of SDF-1α, CXCR4 and VEGF were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and immunohistochemical staining. Results: No statistical difference was found between the PE and the normotensive control group with respect to their age and parity, gravidity and body mass index. The placental bed expressions of SDF-1α/CXCR4 and VEGF were significantly decreased in the PE group compared with the normotensive control group. Conclusions: This study showed decreased expressions of SDF-1α/CXCR4 and VEGF in the third trimester placental bed of pregnancies with PE. This result suggests that decreased expressions of SDF-1α/CXCR4 and VEGF in the placental bed could be associated with the pathogenesis of PE.
Hypertension in Pregnancy 12/2013; 33(1). DOI:10.3109/10641955.2013.828068 · 1.19 Impact Factor