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1.  The Prevalence and Therapeutic Effect of Constipation in Pediatric Overactive Bladder 
Overactive bladder (OAB) is a manifestation of urgency, regardless of urge incontinence, due to involuntary bladder contraction during the storage period. There is a close association between constipation and OAB, but constipation cannot be readily diagnosed. The aims of this study were to evaluate the prevalence of constipation in OAB and the consequent therapeutic effects according to the diagnostic criteria for constipation.
We collected clinical data from 40 children (mean age, 71±22 months) with chief complaints of urgency, frequency, and incontinence. A voiding questionnaire and a 2-day voiding diary were collected, and urinalysis, the Bristol stool scale, and plain abdominal radiography were performed. Constipation was defined as conditions satisfying at least one of the following criteria: Rome III diagnostic criteria, Bristol stool scale types I/II, or a Leech score higher than 8 points as determined by plain radiography. Lower urinary tract symptoms, defecation symptoms, and the bladder volume of patients were examined, and the therapeutic outcomes by constipation diagnostic criteria were evaluated.
Of the 40 OAB patients, 25 had constipation. Among them, 6 had reduced functional bladder capacity (24%; P>0.05). Regarding treatment, in patients who satisfied only one diagnostic criterion, the symptoms improved in 76.9%, 76.9%, and 69.6% of patients meeting the Rome III criteria, Bristol stool scale, and Leech score, respectively (P<0.05). Among the 8 patients satisfying all three criteria, 75% responded to treatment (P<0.05).
The prevalence of constipation in OAB is high. Constipated patients recruited by use of the Rome III criteria, Bristol scale, and Leech score alone and together showed similar outcomes on OAB improvement after the treatment of constipation, which implies that each criterion has the same strength and can be applied comprehensively and generally.
PMCID: PMC3256305  PMID: 22259734
Overactive urinary bladder; Pediatrics; Constipation
3.  Mesoesophagus and other fascial structures of the abdominal and lower thoracic esophagus: a histological study using human embryos and fetuses 
Anatomy & Cell Biology  2014;47(4):227-235.
A term "mesoesophagus" has been often used by surgeons, but the morphology was not described well. To better understand the structures attaching the human abdominal and lower thoracic esophagus to the body wall, we examined serial or semiserial sections from 10 embryos and 9 fetuses. The esophagus was initially embedded in a large posterior mesenchymal tissue, which included the vertebral column and aorta. Below the tracheal bifurcation at the fifth week, the esophagus formed a mesentery-like structure, which we call the "mesoesophagus," that was sculpted by the enlarging lungs and pleural cavity. The pneumatoenteric recess of the pleuroperitoneal canal was observed in the lowest part of the mesoesophagus. At the seventh week, the mesoesophagus was divided into the upper long and lower short parts by the diaphragm. Near the esophageal hiatus, the pleural cavity provided 1 or 2 recesses in the upper side, while the fetal adrenal gland in the left side was attached to the lower side of the mesoesophagus. At the 10th and 18th week, the mesoesophagus remained along the lower thoracic esophagus, but the abdominal esophagus attached to the diaphragm instead of to the left adrenal. The mesoesophagus did not contain any blood vessels from the aorta and to the azygos vein. The posterior attachment of the abdominal esophagus seemed to develop to the major part of the phrenoesophageal membrane with modification from the increased mass of the left fetal adrenal. After postnatal degeneration of the fetal adrenal, the abdominal esophagus might again obtain a mesentery. Consequently, the mesoesophagus seemed to correspond to a small area containing the pulmonary ligament and aorta in adults.
PMCID: PMC4276896  PMID: 25548720
Esophagus; Mesoesophagus; Pneumatoenteric recess; Phrenoesophageal membrane; Human embryo
4.  Upper terminal of the inferior vena cava and development of the heart atriums: a study using human embryos 
Anatomy & Cell Biology  2014;47(4):236-243.
In the embryonic heart, the primitive atrium is considered to receive the bilateral sinus horns including the upper terminal of the inferior vena cava (IVC). To reveal topographical anatomy of the embryonic venous pole of the heart, we examined horizontal serial paraffin sections of 15 human embryos with crown-rump length 9-31 mm, corresponding to a gestational age of 6-7 weeks or Carnegie stage 14-16. The IVC was often fixed to the developing right pulmonary vein by a mesentery-like fibrous tissue. Rather than the terminal portion of the future superior vena cava, the IVC contributed to form a right-sided atrial lumen at the stage. The sinus venosus or its left horn communicated with the IVC in earlier specimens, but in later specimens, the left atrium extended caudally to separate the sinus and IVC. In contrast, the right atrium consistently extended far caudally, even below the sinus horn, along the IVC. A small (or large) attachment between the left (or right) atrium and IVC in adult hearts seemed to be derived from the left (or right) sinus valve. This hypothesis did not contradict with the incorporation theory of the sinus valves into the atrial wall. Variations in topographical anatomy around the IVC, especially of the sinus valves, might not always depend on the stages but partly in individual differences.
PMCID: PMC4276897  PMID: 25548721
Heart; Atrium; Inferior vena cava; Sinus venosus horn; Human embryo
5.  Reproducibility of Peripapillary Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography in Pseudophakic Eyes 
To assess the reproducibility of circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurement (measurement agreement) and its color-coded classification (classification agreement) by Cirrus spectral domain optical coherence tomography (OCT) in pseudophakic eyes.
Two-hundred five participants having glaucoma or glaucoma suspected eyes underwent two repeated Cirrus OCT scans to measure cpRNFL thickness (optic disc cube 200 × 200). After classifying participants into three different groups according to their lens status (clear media, cataract, and pseudophakic), values of intra-class coefficient (ICC), coefficient of variance, and test-retest variability were compared between groups for average retinal nerve fiber layer (RNFL) thicknesses and that corresponding to four quadrant maps. Linear weighted kappa coefficients were calculated as indicators of agreement of color code classification in each group.
ICC values were all excellent (generally defined as 0.75 to 1.00) for the average and quadrant RNFL thicknesses in all three groups. ICC values of the clear media group tended to be higher than those in the cataract and pseudophakic groups for all quadrants and average thickness. Especially in the superior and nasal quadrants, the ICC value of the cataract group was significantly lower than that of the clear media and pseudophakic groups. For average RNFL thickness, classification agreement (kappa) in three groups did not show a statistically significant difference. For quadrant maps, classification agreement (kappa) in the clear media group was higher than those in the other two groups.
Agreement of cpRNFL measurement and its color code classification between two repeated Cirrus OCT scans in pseudophakic eyes was as good as that in eyes with clear crystalline lens. More studies are required to ascertain the effect of lens status on the reproducibility of Cirrus OCT according to different stages of glaucoma patients.
PMCID: PMC3958629  PMID: 24688256
Optical coherence tomography; Pseudophakia; Reproducibility of results
6.  Difference of Diagnostic Rates and Analytical Methods in the Test Positions of Vestibular Evoked Myogenic Potentials 
Annals of Rehabilitation Medicine  2014;38(2):226-233.
To compare the differences of diagnostic rates, of the two widely used test positions, in measuring vestibular evoked myogenic potentials (VEMP) and selecting the most appropriate analytical method for diagnostic criteria for the patients with vertigo.
Thirty-two patients with vertigo were tested in two comparative testing positions: turning the head to the opposite side of the evaluating side and bowing while in seated position, and bowing while in supine positions. Abnormalities were determined by prolonged latency of p13 or n23, shortening of the interpeak latency, and absence of VEMP formation.
Using the three criteria above for determining abnormalities, both the seated and supine positions showed no significant differences in diagnostic rates, however, the concordance correlation of the two positions was low. When using only the prolonged latency of p13 or n23 in the two positions, diagnostic rates were not significantly different and their concordance correlation was high. On the other hand, using only the shortened interpeak latency in both positions showed no significant difference of diagnostic rates, and the degree of agreement between two positions was low.
Bowing while in seated position with the head turned in the opposite direction to the area being evaluated is found to be the best VEMP test position due to the consistent level of sternocleidomastoid muscle tension and the high level of compliance. Also, among other diagnostic analysis methods, using prolonged latency of p13 or n23 as the criterion is found to be the most appropriate method of analysis for the VEMP test.
PMCID: PMC4026609  PMID: 24855617
Vestibular evoked myogenic potentials (VEMP); Patient positioning; Data interpretation
7.  The Efficacy of Endoscopic Submucosal Dissection of Type I Gastric Carcinoid Tumors Compared with Conventional Endoscopic Mucosal Resection 
Background and Aims. Conventional endoscopic submucosal resection (EMR) of carcinoid tumors often involves the resection margin, which necessitates further intervention. Endoscopic submucosal dissection (ESD) is widely accepted for removing carcinoid tumors. We aimed to evaluate the clinical usefulness of ESD with that of EMR for resection of type I gastric carcinoid tumors. Patients and Methods. The study enrolled 62 patients (37 males, 25 females; median age, 50 years; range, 40–68 years) who were treated with EMR or ESD at three hospitals; the study group had 87 type I gastric carcinoid tumors with an estimated size of ≤10 mm. The complete resection rate and the complications associated with these two procedures were analyzed. Results. The overall ESD complete resection rate was higher than that of the EMR rate (94.9% versus 83.3%, P value = 0.174). A statistically lower vertical margin involvement rate was achieved when ESD was performed compared to when EMR was performed (2.6% versus 16.7%, P value = 0.038). The complication rate was not significantly different between the two groups. Conclusions. ESD showed a higher complete resection rate, particularly for the vertical margin, with a similar complication rate. We mildly recommend ESD rather than EMR for removing type I gastric carcinoid tumors.
PMCID: PMC3947882  PMID: 24693280
8.  Prospects for nucleic acid-based therapeutics against hepatitis C virus 
In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.
PMCID: PMC3870548  PMID: 24379620
Hepatitis C virus; Nucleic acid-based therapeutics; Ribozyme; Aptamer; siRNA; Antisense oligonucleotide
9.  Can Initial 18F-FDG PET-CT Imaging Give Information on Metastasis in Patients with Primary Renal Cell Carcinoma? 
The aim of this study was to investigate the relationship between the maximum standardized uptake values (SUVmax) of primary renal cancers with and without metastatic lesions, if any. We also studied the relationship between the size of primary renal cancers and their SUVmax, and tried to find a clinical value of 18F-FDG PET-CT for the initial evaluation of renal cell carcinoma (RCC).
The cases of 23 patients, 16 men and 7 women, who underwent PET-CT examination before operation were retrospectively reviewed. We measured the SUVmax of the primary renal cancers and those of any existing metastatic lesions, and the size of the primary renal cancers. We compared the SUVmax of primary RCCs with metastases and those without metastases, SUVmax of primary RCC and those of metastases, and studied the correlation between the size and SUVmax of primary RCCs.
The SUVmax of primary RCC of the 16 patients without metastasis ranged from 1.1 to 5.6 with a median value of 2.6. Those of the patients with metastasis ranged from 2.9 to 7.6 with a median of 5.0. The size of the all 23 primary renal cancers ranged from 1.7 cm to 13.5 cm, with a median of 4.5 cm, and their SUVmax ranged from 1.1 to 7.6, with a median of 2.9. There was a statistically significant difference between the SUVmax of the primary RCC with metastasis (5.3 ± 1.7) and those without metastasis (2.9 ± 1.0). There was a moderate positive correlation between the sizes and SUVmax of all 23 primary RCCs. However, there was no statistically significant correlation between the sizes and SUVmax of primary RCCs with metastatic lesions and the same for RCCs without metastasis. The cutoff value of SUVmax for predicting extra-renal lesion was 4.4 and that for size was 5.8 cm according to the receiver operating characteristic curves.
Those who have primary RCC with high SUVmax are suggested to have a likelihood of metastasis. Also, there was a moderate trend of increasing value of SUVmax of primary RCC as their size increases. Physicians should beware of missing extra-renal lesions elsewhere.
PMCID: PMC4028476  PMID: 24900155
Renal cell carcinoma; Initial staging; 18F-FDG; PET-CT; SUV; Metastasis
10.  Umbilical cord blood mesenchymal stem cells protect amyloid-β42 neurotoxicity via paracrine 
World Journal of Stem Cells  2012;4(11):110-116.
AIM: To understand the neuroprotective mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) against amyloid-β42 (Aβ42) exposed rat primary neurons.
METHODS: To evaluate the neuroprotective effect of hUCB-MSCs, the cells were co-cultured with Aβ42-exposed rat primary neuronal cells in a Transwell apparatus. To assess the involvement of soluble factors released from hUCB-MSCs in neuroprotection, an antibody-based array using co-cultured media was conducted. The neuroprotective roles of the identified hUCB-MSC proteins was assessed by treating recombinant proteins or specific small interfering RNAs (siRNAs) for each candidate protein in a co-culture system.
RESULTS: The hUCB-MSCs secreted elevated levels of decorin and progranulin when co-cultured with rat primary neuronal cells exposed to Aβ42. Treatment with recombinant decorin and progranulin protected from Aβ42-neurotoxicity in vitro. In addition, siRNA-mediated knock-down of decorin and progranulin production in hUCB-MSCs reduced the anti-apoptotic effects of hUCB-MSC in the co-culture system.
CONCLUSION: Decorin and progranulin may be involved in anti-apoptotic activity of hUCB-MSCs exposed to Aβ42.
PMCID: PMC3536832  PMID: 23293711
Human umbilical cord blood-derived mesenchymal stem cells; Decorin; Progranulin; Aβ42; Anti-apoptosis
11.  Incidence and clinical features of endoscopic ulcers developing after gastrectomy 
AIM: To determine the precise incidence and clinical features of endoscopic ulcers following gastrectomy.
METHODS: A consecutive series of patients who underwent endoscopic examination following gastrectomy between 2005 and 2010 was retrospectively analyzed. A total of 78 patients with endoscopic ulcers and 759 without ulcers following gastrectomy were enrolled. We analyzed differences in patient age, sex, size of the lesions, method of operation, indications for gastric resection, and infection rates of Helicobacter pylori (H. pylori) between the nonulcer and ulcer groups.
RESULTS: The incidence of endoscopic ulcers after gastrectomy was 9.3% and that of marginal ulcers was 8.6%. Ulcers were more common in patients with Billroth II anastomosis and pre-existing conditions for peptic ulcer disease (PUD). Infection rates of H. pyloridid not differ significantly between the two groups. The patients who underwent operations to treat PUD had lower initial levels of hemoglobin and higher rates of hospital admission.
CONCLUSION: H. pylori was not an important factor in ulcerogenesis following gastrectomy. For patients who underwent surgery for PUD, clinical course of marginal ulcers was more severe.
PMCID: PMC3391763  PMID: 22783050
Gastrectomy; Marginal ulcer; Helicobacter pylori
12.  Icariside II Induces Apoptosis in U937 Acute Myeloid Leukemia Cells: Role of Inactivation of STAT3-Related Signaling 
PLoS ONE  2012;7(4):e28706.
The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937.
Methodology/Principal Findings
Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-xL and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells.
Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.
PMCID: PMC3320887  PMID: 22493659
13.  Early congenital syphilis presenting with skin eruption alone: a case report 
Korean Journal of Pediatrics  2011;54(12):512-514.
Congenital syphilis is one of the most well-known congenital infections, yet it remains a worldwide public health problem. Congenital syphilis can involve any organ system and present with various symptoms. However, early diagnosis of congenital syphilis is difficult because more than half of the affected infants are asymptomatic, and the signs in symptomatic infants may be subtle and nonspecific. Here, we report a case of congenital syphilis with only a skin rash, which led to a delay in diagnosis. This case indicates that congenital syphilis should be considered throughout early childhood.
PMCID: PMC3274658  PMID: 22323908
Congenital syphilis; Skin rash
14.  Current status of endoscopic submucosal dissection for the management of early gastric cancer: A Korean perspective 
The early diagnosis of gastric cancer allows patients and physicians to pursue the option of endoscopic resection, which is significantly less invasive than conventional surgical resection. In Korea, the use of endoscopic submucosal dissection (ESD) has been increasing, and many reports on ESD have been published. In addition, Korean gastroenterologists from several hospitals performing ESD have conducted formal meetings to discuss useful information regarding ESD. Here, we discuss the Korean experience with ESD, including outcomes and prospects of endoscopic treatments.
PMCID: PMC3110919  PMID: 21677825
Early gastric cancer; Endoscopic submucosal dissection; Endoscopic mucosal resection
15.  The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms 
Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.
PMCID: PMC3057556  PMID: 21423636
16.  T4 stage and preoperative anemia as prognostic factors for the patients with colon cancer treated with adjuvant FOLFOX chemotherapy 
FOLFOX-based adjuvant chemotherapy is a benefit for high-risk stage II and stage III colon cancer after curative resection. But, the prognostic factor or predictive marker for the efficacy of FOLFOX remains unclear. This study was aimed to identify the prognostic value and cumulative impact of adjuvant FOLFOX on the stage II and III colon cancer patients.
A total of 196 stage II and III colon cancer patients were retrospectively enrolled in prospectively collected data. They underwent curative resection followed by FOLFOX4 adjuvant chemotherapy. The oncological outcomes included the 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate. Cox-regression analysis was performed to identify the prognostic value, and its cumulative impact was analyzed.
The 5-year DFS rate of the patients was 71.94% and the 5-year OS rate was 81.5%. The prognostic values for the 5-year DFS rate and 5-year OS rate were T4 stage and preoperative anemia in a multivariate analysis. Each patient group who had no prognostic value, single, or both factors revealed 95.35%, 69.06%, and 28.57% in the 5-year DFS rate, respectively (p < 0.0001). The 5-year OS rate also showed the significant differences in each group who had no prognostic value, single, or both factors revealed 100%, 79.3%, and 45.92%, respectively (p < 0.0001).
Our results showed similar efficacy to MOSAIC study in stage II and stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy after curative resection. Patients who had T4 stage and/or preoperative anemia showed worse prognosis than patients without any prognostic value. These findings suggest that FOLFOX could not be effective in the patients with T4 stage colon cancer accompanied by preoperative anemia.
PMCID: PMC4336700
Colon cancer; FOLFOX; T4 stage; Anemia
17.  Patient’s Factors at Entering Hospice Affecting Length of Survival in a Hospice Center 
In order to provide effective hospice care, adequate length of survival (LOS) in hospice is necessary. However the reported average LOS is much shorter. Analysis of LOS in hospice has not been reported from Korea. We evaluated the duration of LOS and the factors associated with LOS at our hospice center.
Materials and Methods
We retrospectively examined 446 patients who were admitted to our hospice unit between January 2010 and December 2012. We performed univariate and multivariate analysis for analysis of factors associated with LOS.
The median LOS was 9.5 days (range, 1 to 186 days). The LOS of 389 patients (86.8%) was< 1 month. At the time of admission to hospice, 112 patients (25.2%) were completely bedridden, 110 patients (24.8%) had mouth care only without intake, and 134 patients (30.1%) had decreased consciousness, from confusion to coma. The median time interval between the day of the last anticancer treatment and the day of hospice admission was 75 days. By analysis of the results of multivariate analysis, decreased intake and laboratory results showing increased total white blood cell (WBC), decreased platelet count, increased serum creatinine, increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) level were poor prognostic factors for survival in hospice.
Before hospice admission, careful evaluation of the patient’s performance, particularly the oral intake, and total WBC, platelet, creatinine, AST, ALT, and LDH level is essential, because these were strong predictors of shorter LOS. In the future, conduct of prospective controlled studies is warranted in order to confirm the relationship between potential prognostic factors and LOS in hospice.
PMCID: PMC4296857  PMID: 25345463
Hospice care; Survival analysis; Prognosis
18.  Laparoscopic repair of indirect inguinal hernia containing endometriosis, ovary, and fallopian tube in adult woman without genital anomalies 
Obstetrics & Gynecology Science  2014;57(6):557-559.
Indirect inguinal hernia containing an ovary is a rare condition, especially in adult women who do not have any other genital tract anomalies. In addition, inguinal hernia containing an ovary and endometriosis is exceedingly rare. In the present report, we describe a case of indirect inguinal hernia containing an ovary, fallopian tube, and endometriosis. Laparoscopic repair was performed successfully using polypropylene mesh for the treatment of the inguinal hernia.
PMCID: PMC4245355  PMID: 25469350
Endometriosis; Hernia, inguinal; Laparoscopic repair; Ovary
19.  Synergistic Effect of Interleukin-6 and Hyaluronic Acid on Cell Migration and ERK Activation in Human Keratinocytes 
Journal of Korean Medical Science  2014;29(Suppl 3):S210-S216.
Wound healing is initiated and progressed by complex integrated process of cellular, physiologic, and biochemical events, such as inflammation, cell migration and proliferation. Interleukin 6 (IL-6) is a multifunctional cytokine, and it could regulate the inflammatory response of wound healing process in a timely manner. Hyaluronic acid (HA) is an essential component of the extracellular matrix, and contributes significantly to cell proliferation and migration. The purpose of this study was to investigate the effects of IL-6 or/and HA on the cell migration process in human keratinocytes. Combining IL-6 and HA significantly increased the cell migration in scratch based wound healing assay. The phosphorylation of extracellular-signal-regulated kinase (ERK) was significantly increased after 1 hr of IL-6 and HA treatment, but the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was not. We also found that significant increase of the NF-κB translocation from cytoplasm into nucleus after 1 hr of IL-6 or/and HA treatments. This study firstly showed that synergistic effects of combining IL-6 and HA on the cell migration of wound healing by activation of ERK and NF-κB signaling. Further studies might be required to confirm the synergistic effects of HA and IL-6 in the animal model for the development of a novel therapeutic mixture for stimulation of wound healing process.
Graphical Abstract
PMCID: PMC4248007  PMID: 25473211
Interleukin-6; Hyaluronic Acid; Cell Movement; ERK; Phosphorylation; Wound Healing; Keratinocytes
20.  Imatinib Mesylate plus Hydroxyurea Chemotherapy for Cerebellar Meningioma in a Belgian Malinois Dog 
An 8-year-old intact male Belgian Malinois, weighing 37.2 kg, was referred for evaluation due to right side facial paresis, ataxia and a 2-month history of decreased cognitive ability. Physical and neurological examinations revealed mild depression, left-sided head tilt, right-sided facial paresis and ataxia. A well-demarcated, broad-based cerebellar mass and hyperostosis were found on CT imaging of the brain. Based on these CT findings, a cerebellar meningioma was strongly suspected. Hydroxyurea and prednisolone were administered; after 4 weeks, there was reduction in mass size as compared to initial CT results. However, the mass size was found to have grown 6 weeks after hydroxyurea treatment. We then prescribed a combination of imatinib mesylate and hydroxyurea. Two weeks following combination treatment, the mass size had reduced significantly. The mass continuously decreased in size until the patient died during anesthesia. Cerebellar transitional meningioma was confirmed by histopathologic examination. To the author’s knowledge, this is the first reported case of imatinib mesylate plus hydroxyurea therapy for the treatment of meningioma in veterinary medicine.
PMCID: PMC4272992  PMID: 25131949
canine; hydroxyurea; imatinib mesylate; meningioma; tyrosine kinase inhibitor
21.  Cutoff Value of Pharyngeal Residue in Prognosis Prediction After Neuromuscular Electrical Stimulation Therapy for Dysphagia in Subacute Stroke Patients 
Annals of Rehabilitation Medicine  2014;38(5):612-619.
To determine the cutoff value of the pharyngeal residue for predicting reduction of aspiration, by measuring the residue of valleculae and pyriformis sinuses through videofluoroscopic swallowing studies (VFSS) after treatment with neuromuscular electrical stimulator (VitalStim) in stroke patients with dysphagia.
VFSS was conducted on first-time stroke patients before and after the VitalStim therapy. The results were analyzed for comparison of the pharyngeal residue in the improved group and the non-improved group.
A total of 59 patients concluded the test, in which 42 patients improved well enough to change the dietary methods while 17 did not improve sufficiently. Remnant area to total area (R/T) ratios of the valleculae before treatment in the improved group were 0.120, 0.177, and 0.101 for solid, soft, and liquid foods, respectively, whereas the ratios for the non-improved group were 0.365, 0.396, and 0.281, respectively. The ratios of the pyriformis sinuses were 0.126, 0.159, and 0.121 for the improved group and 0.315, 0.338, and 0.244 for the non-improved group. The R/T ratios of valleculae and pyriformis sinus were significantly lower in the improved group than the non-improved group in all food types before treatment. The R/T ratio cutoff values were 0.267, 0.250, and 0.185 at valleculae and 0.228, 0.218, and 0.185 at pyriformis sinuses.
In dysphagia after stroke, less pharyngeal residue before treatment serves as a factor for predicting greater improvement after VitalStim treatment.
PMCID: PMC4221389  PMID: 25379490
Deglutition disorder; Dysphagia; Electric stimulation therapy; Pharyngeal residue; Cutoff value
22.  No influence of parental origin of intact X chromosome and/or Y chromosome sequences on three-year height response to growth hormone therapy in Turner syndrome 
Whether parental origin of the intact X chromosome and/or the presence of Y chromosome sequences (Yseq) play a role in three-year height response to growth hormone (GH) were investigated.
Paternal (Xp) or maternal (Xm) origin of X chromosome was assessed by microsatellite marker analysis and the presence of hidden Yseq was analyzed. The first-, second-, and third-year GH response was measured as a change in height z-score (Z_Ht) in Turner syndrome (TS) patients with 45,Xp (n=10), 45,Xm (n=15), and 45,X/46,X,+mar(Y) (Xm_Yseq) (n=8).
The mean baseline Z_Ht did not differ according to Xp or Xm origin, however the mean baseline Z_Ht was higher in the Xm_Yseq group than in Xm group, after adjusting for bone age delay and midparental Z_Ht (P=0.04). There was no difference in the height response to GH between the 3 groups. The height response to GH decreased progressively each year (P<0.001), such that the third-year increase in Z_Ht was not significant. This third-year decrease in treatment response was unaffected by Xp, Xm, and Xm_Yseq groups. Increasing GH dosage from the second to third-year of treatment positively correlated with the increase in Z_Ht (P=0.017).
There was no evidence of X-linked imprinted genes and/or Yseq affecting height response to 3 years of GH therapy. Increasing GH dosages may help attenuate the decrease in third-year GH response in TS patients with 45,X and/or 46,X/+mar(Y).
PMCID: PMC4208262  PMID: 25346916
Turner syndrome; Growth hormone; X chromosome; Y chromosome; Genomic imprinting
23.  Effect of Korean Red Ginseng supplementation on dry eye syndrome in glaucoma patients – A randomized, double-blind, placebo-controlled study 
Journal of Ginseng Research  2014;39(1):7-13.
Many patients with glaucoma have difficulty using antiglaucoma eye drops because of dry eye symptom. In this prospective, randomized, double-blind, placebo-controlled study, we evaluated the effect of Korean Red Ginseng on dry eye syndrome in patients with glaucoma treated with antiglaucoma eye drops.
Forty-nine participants were allocated to the Korean Red Ginseng (3 g/day; n = 24) or placebo (n = 25) groups for 8 weeks. Tear film stability, fluorescein corneal staining, conjunctival hyperemia, tear production, grade of meibomian gland dysfunction, and dry eye questionnaire (Ocular Surface Disease Index) were evaluated at baseline and on completion of the treatment.
Almost all patients displayed dry eye symptoms and signs at baseline. After the 8-week intervention, Korean Red Ginseng supplementation significantly improved the tear film stability and total Ocular Surface Disease Index score, as compared to placebo (p < 0.01).
Korean Red Ginseng supplementation may provide an additional treatment option for dry eye and patients with glaucoma using antiglaucoma eye drops.
PMCID: PMC4268561  PMID: 25535471
dry eye syndrome; glaucoma; Korean Red Ginseng; Panax ginseng
24.  Probucol plus cilostazol attenuate hypercholesterolemia-induced exacerbation in ischemic brain injury via anti-inflammatory effects 
Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immunoreactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects.
PMCID: PMC4121353  PMID: 25017431
cilostazol; focal cerebral ischemia; hypercholesterolemia; inflammatory chemokine; microglia; neuroinflammation; probucol
25.  An Important Role of α-Hemolysin in Extracellular Vesicles on the Development of Atopic Dermatitis Induced by Staphylococcus aureus 
PLoS ONE  2014;9(7):e100499.
Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.
PMCID: PMC4084635  PMID: 24992681

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