Publications by authors named "Min-Ho Choi"

119 Publications

Prevalence and Risk Factors of Intestinal Helminthiasis in Remote Mountainous Villages of Northern Lao PDR: A Cross-Sectional Study.

Korean J Parasitol 2021 Apr 22;59(2):131-138. Epub 2021 Apr 22.

Department of Tropical Medicine and Parasitology, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul 03080, Korea.

Helminth infections are prevalent in Lao People's Democratic Republic (Lao PDR). This study aimed at determining the prevalence and risk factors of intestinal helminthiasis in remote mountainous villages of northern Lao PDR. During the dry season in January 2017, a cross-sectional survey was conducted in 3 remote mountainous villages in Oudomxay province, Lao PDR. Villagers older than 18 years of age who agreed to submit stool samples or undergo an interview, were recruited. Stool samples from 198 individuals were examined by the Kato-Katz method, and a questionnaire surveyed 161 individuals among them. Univariable and multivariable logistic regression analyses were used to identify risk factors associated with the intestinal helminthiasis. An overall prevalence of intestinal helminthiasis was 75.8%. Hookworm infection was the most common (63.1%), followed by Opisthorchis viverrini/minute intestinal flukes (17.7%), Taenia spp. (15.2%), Trichuris trichiura (2.0%), Ascaris lumbricoides (1.5%), and Enterobius vermicularis (1.0%). Questionnaire analysis revealed sex (male) and absence of latrine to be significant risk factors for hookworm infection and consumption of raw meat for taeniasis. These results suggest that the mountainous area in northern Lao PDR has a different composition of helminth infections from other studies conducted in Lao PDR; a high prevalence of hookworm infection and taeniasis and low prevalence of T. trichiura and A. lumbricoides infections were observed. Also, liver flukes or intestinal flukes were similarly prevalent in the mountainous area.
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http://dx.doi.org/10.3347/kjp.2021.59.2.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106991PMC
April 2021

Preemptive intravenous iron therapy versus autologous whole blood therapy for early postoperative hemoglobin level in patients undergoing bimaxillary orthognathic surgery: a prospective randomized noninferiority trial.

BMC Oral Health 2021 01 7;21(1):16. Epub 2021 Jan 7.

Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Background: Previous studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery.

Methods: This was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was - 1 g/dL.

Results: Baseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group-whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = - 0.83 to 1.0). As the lower limit of the 95% CI (- 0.83) was higher than the prespecified noninferiority margin (δ = - 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group.

Conclusion: As collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery.

Trial Registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2<ype=my&rtype=my .
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http://dx.doi.org/10.1186/s12903-020-01359-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791750PMC
January 2021

A first nation-wide assessment of soil-transmitted helminthiasis in Fijian primary schools, and factors associated with the infection, using a lymphatic filariasis transmission assessment survey as surveillance platform.

PLoS Negl Trop Dis 2020 09 25;14(9):e0008511. Epub 2020 Sep 25.

Department of Tropical Medicine and Parasitology and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul, Korea.

Background: Soil-transmitted helminthiasis (STH) is endemic in Fiji but its prevalence is not known and likely to have changed after a decade of mass drug administration (MDA) for lymphatic filariasis (LF). By linking with LF transmission assessment surveys (LF-TAS), we undertook the first nation-wide assessment of STH in Fijian primary schools, as well as an analysis of factors associated with STH infections.

Methodology/principal Findings: A cross-sectional assessment for STH was conducted in all four Divisions of Fiji from 2014 to 2015. In the Western, Central, and Northern Divisions, schools were sub-sampled after LF-TAS, while, in the Eastern Division, schools were selected via simple random sampling. For the diagnosis of STH, stool samples were examined by coproscopy with a single Kato-Katz thick smear (KK) and the formol-ether-acetate concentration technique, except for the samples from the Eastern Division where only KK was used. Mean prevalence of any STH among class 1-2 students at the national level was 10.5% (95% CI: 6.9-15.5). Across the three Divisions via LF-TAS, the prevalence levels for ascariasis were 8.7% (95% CI: 4.3-16.6), hookworm 3.9% (95% CI: 2.3-6.6) and trichuriasis 0%. In the Eastern Division, ascariasis prevalence was 13.3% (95% CI: 6.4-25.6), and hookworm 0.7% (95% CI: 0.2-2.5), with one case of trichuriasis. Among class 3-8 students, ascariasis prevalence was lower. Lower risk of any STH was associated with wearing shoes (adjusted OR 0.54, 95% CI: 0.32-0.90) and having piped water from the Fiji Water Authority at home (adjusted OR 0.48, 95% CI: 0.25-0.92).

Conclusions: After a decade of community-based LF-MDA, STH in school-age children in Fiji is now close to 10%, but localities of endemicity remain. Preventive chemotherapy should be maintained in areas with elevated STH prevalence alongside targeted delivery of integrated WASH interventions. LF-TAS has provided an opportunity to develop future public health surveillance platforms.
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http://dx.doi.org/10.1371/journal.pntd.0008511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518615PMC
September 2020

Cu(In,Ga)Se Solar Cells Integrated with Subwavelength Structured Cover Glass Fabricated by One-Step Self-Masked Etching.

Micromachines (Basel) 2020 Sep 21;11(9). Epub 2020 Sep 21.

School of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology, Gwangju 61005, Korea.

We report an anti-reflective cover glass for Cu(In,Ga)Se (CIGS) thin film solar cells. Subwavelength structures (SWSs) were fabricated on top of a cover glass using one-step self-masked etching. The etching method resulted in dense whiskers with high aspect ratio. The produced structure exhibited excellent anti-reflective properties over a broad wavelength range, from the ultraviolet to the near infrared. Compared to a flat-surface glass, the average transmittance of the glass integrated with the SWSs improved from 92.4% to 95.2%. When the cover glass integrated with the SWSs was mounted onto the top of a CIGS device, the short-circuit current and the efficiency of the solar cell were enhanced by 4.38 and 6%, respectively, compared with a CIGS solar cell without cover glass.
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http://dx.doi.org/10.3390/mi11090877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570425PMC
September 2020

Prevalence of Toxocariasis and Its Risk Factors in Patients with Eosinophilia in Korea.

Korean J Parasitol 2020 Aug 26;58(4):413-419. Epub 2020 Aug 26.

Department of Tropical Medicine and Parasitology and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia.
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http://dx.doi.org/10.3347/kjp.2020.58.4.413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462808PMC
August 2020

Co-Culturing of Endothelial and Cancer Cells in a Nanofibrous Scaffold-Based Two-Layer System.

Int J Mol Sci 2020 Jun 10;21(11). Epub 2020 Jun 10.

Department of Pharmacology, School of Medicine, Ajou University, Suwon 16499, Korea.

Angiogenesis is critical for local tumor growth. This study aimed to develop a three-dimensional two-layer co-culture system to investigate effects of cancer cells on the growth of endothelial cells (ECs). Poly(ε-caprolactone) (PCL) nanofibrous membranes were generated via electrospinning of PCL in chloroform (C-PCL-M) and chloroform and dimethylformamide (C/DMF-PCL-M). We assembled a two-layer co-culture system using C-PCL-M and C/DMF-PCL-M for EC growth in the upper layer with co-cultured cancer cells in the lower layer. In the absence of vascular endothelial growth factor (VEGF), growth of bEND.3 ECs decreased on C/DMF-PCL-M but not on C-PCL-M with time. Growth of bEND.3 cells on C/DMF-PCL-M was enhanced through co-culturing of CT26 cancer cells and enhanced growth of bEND.3 cells was abrogated with anti-VEGF antibodies and sorafenib. However, EA.hy926 ECs displayed steady growth and proliferation on C/DMF-PCL-M, and their growth was not further increased through co-culturing of cancer cells. Moreover, chemical hypoxia in CT26 cancer cells upon treatment with CoCl enhanced the growth of co-cultured bEND.3 cells in the two-layer system. Thus, EC growth on the nanofibrous scaffold is dependent on the types of ECs and composition of nanofibers and this co-culture system can be used to analyze EC growth induced by cancer cells.
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http://dx.doi.org/10.3390/ijms21114128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312426PMC
June 2020

Case Report of Urinary Schistosomiasis in a Returned Traveler in Korea.

Korean J Parasitol 2020 Feb 29;58(1):51-55. Epub 2020 Feb 29.

Department of Tropical Medicine and Parasitology and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.

A 23-year-old Korean woman with a residence history in Kenya and Malawi for about 2 years presented with gross hematuria for 1 month. Blood tests were within normal range except eosinophilia. Asymmetrically diffuse wall thickening and calcification were observed at the urinary bladder on CT. Multiple erythematous nodular lesions were observed in the cystoscopy and transurethral resection was done. Numerous eggs of Schistosoma haematobium with granulomatous inflammation were observed in the submucosal layer of the bladder. The patient was diagnosed with schistosomiasis-related cystitis and treated with praziquantel (40 mg/kg/day) twice before and after transurethral resection. This case suggests that S. haematobium infection should be considered as a cause of hematuria in Korea when the patient had a history of traveling endemic areas of schistosomiasis.
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http://dx.doi.org/10.3347/kjp.2020.58.1.51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066443PMC
February 2020

An Imported Case of Disseminated Echinococcosis in Korea.

Korean J Parasitol 2019 Aug 31;57(4):429-434. Epub 2019 Aug 31.

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.

A complicated case of echinococcosis with multiple organ involvement is reported in a 53-year-old businessman who frequently traveled overseas, including China, Russia, and Kazakhstan from 2001 to 2007. The patient was first diagnosed with a large liver cyst during a screening abdomen ultrasonography in 2011, but he did not follow up on the lesion afterwards. Six years later, dizziness, dysarthria, and cough developed, and cystic lesions were found in the brain, liver and lungs. The clinical course was complicated when the patient went through multiple surgeries and inadequate treatment with a short duration of albendazole without a definite diagnosis. The patient visited our hospital for the first time in August 2018 due to worsening symptoms; he was finally diagnosed with echinococcosis using imaging and serologic criteria. He is now on prolonged albendazole treatment (400 mg twice a day) with gradual clinical and radiological improvement. A high index of suspicion is warranted to early diagnose echinococcosis in a patient with a travel history to endemic areas of echinococcosis.
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http://dx.doi.org/10.3347/kjp.2019.57.4.429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753304PMC
August 2019

Metformin Induces Apoptosis and Inhibits Proliferation through the AMP-Activated Protein Kinase and Insulin-like Growth Factor 1 Receptor Pathways in the Bile Duct Cancer Cells.

J Cancer 2019 5;10(7):1734-1744. Epub 2019 Apr 5.

Division of Gastroenterology, Department of Internal Medicine, Hallym University College of Medicine, Gyeonggi-Do, Korea.

: Metformin has been found to have antineoplastic activity in some cancer cells. This study was performed to determine whether metformin inhibits the proliferation of bile duct cancer cells by inducing apoptosis and its effects on the expression of gene-related proteins involved in cancer growth. : Human extrahepatic bile duct cancer cells (SNU-245 and SNU-1196) were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the effect of metformin on the cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay. Expression levels of various proteins, with or without specific small interfering ribonucleic acid-induced gene disruption, were measured by Western blot analysis. The migratory activity of the cancer cells was evaluated by wound healing assay. Metformin suppressed cell proliferation in bile duct cancer cells by inducing apoptosis. Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPK). Hyperglycemia impaired metformin-induced AMPK activation and enhanced phosphorylation of AMPK at serine-485 (AMPK). Metformin blocked the inhibitory effect of insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor substrate 1 (IRS-1) pathway on TSC-2, and hyperglycemia impaired metformin-induced inhibition of IGF-1R/IRS-1 pathway and modulated the invasiveness of bile duct cancer cells; however, this effect was impaired by hyperglycemia. : Metformin has antineoplastic effects in bile duct cancer, and hyperglycemic environment interrupts the effect of metformin. In addition, AMPK and IGF-1R play a key role in the proliferation of bile duct cancer cells.
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http://dx.doi.org/10.7150/jca.26380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547996PMC
April 2019

Connexin 43 plays an important role in the transformation of cholangiocytes with Clonochis sinensis excretory-secretory protein and N-nitrosodimethylamine.

PLoS Negl Trop Dis 2019 04 3;13(4):e0006843. Epub 2019 Apr 3.

Department of Parasitology and Tropical Medicine and Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Clonorchis sinensis is a group I bio-carcinogen responsible for cholangiocarcinoma (CHCA) in humans. However, the mechanism by which C. sinensis promotes carcinogenesis is unclear.

Methodology: Using the human cholangiocyte line H69, we investigated cell proliferation and gap junction protein expression after stimulation with the hepatotoxin N-nitrosodimethylamine (NDMA) and/or excretory-secretory products (ESP) of C. sinensis, which induce inflammation. NDMA and ESP treatment increased proliferation by 146% and the proportion of cells in the G2/M phase by 37%. Moreover, the expression of the cell proliferation-related proteins E2F1, Ki-67, and cancer related protein cytokeratin 19 and Cox-2 increased in response to combined treatment with NDMA and ESP. The gap-junction proteins connexin (Cx) 43 and Cx26 increased. In contrast, Cx32 expression decreased in cells treated with NDMA and ESP. Silencing of Cx43 reduced cell proliferation and significantly suppressed Cx26 and Cox-2 expression.

Conclusions: These results suggest that Cx43 is an important factor in CHCA induced by C. sinensis ESP and NDMA and further investigations targeting this pathway may allow prevention of this deadly disease.
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http://dx.doi.org/10.1371/journal.pntd.0006843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6464552PMC
April 2019

Learning Curve for Lumbar Decompressive Laminectomy in Biportal Endoscopic Spinal Surgery Using the Cumulative Summation Test for Learning Curve.

World Neurosurg 2019 Feb 4;122:e1007-e1013. Epub 2018 Nov 4.

Spine Center and Department of Orthopedic Surgery, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea. Electronic address:

Objective: The purpose of the present study was to determine the learning curve for biportal endoscopic spinal surgery (BESS) for decompressive laminectomy in lumbar spinal stenosis using a learning curve cumulative summation test (LC-CUSUM).

Methods: The surgeon was proficient in open and microscopic decompressive laminectomy in lumbar spinal stenosis but did not have any experience with BESS or other endoscopic surgery techniques. The learning curve of BESS was investigated using LC-CUSUM analysis. Procedure success was defined as an operative time <75 minutes, the mean operative time with microscopic decompression laminectomy.

Results: The present study included the first 60 patients who had undergone single-level decompressive laminectomy using BESS by a single orthopedic surgeon. The mean operative time for decompressive laminectomy by BESS was 83.8 ± 37.9 minutes. The mean operative time in the early learning period (≤30 cases) and late learning period (second 30 cases) was 105.3 ± 39.7 minutes and 62.4 ± 19.9 minutes, respectively. The overall complication rate was ∼10%. The LC-CUSUM signaled competency for surgery at the 58th operation, indicating that sufficient evidence had accumulated to prove that the surgeon was competent. Thus, a trainee with no experience with BESS had reached adequate performance at 58 cases.

Conclusions: The results of the present study have demonstrated that a substantial learning period could be needed before adequate performance can be achieved with lumbar decompressive laminectomy using BESS.
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http://dx.doi.org/10.1016/j.wneu.2018.10.197DOI Listing
February 2019

Effect of ilaprazole on the healing of endoscopic submucosal dissection-induced gastric ulcer: randomized-controlled, multicenter study.

Surg Endosc 2019 05 30;33(5):1376-1385. Epub 2018 Aug 30.

Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.

Background: The optimal treatment regimen or the duration of treatment for an endoscopic submucosal dissection (ESD)-induced gastric ulcer has not been established. The aim of this study was to assess the efficacy of novel proton-pump inhibitor, ilaprazole, for the treatment of ESD-induced gastric ulcer.

Methods: This was a prospective, open-label, randomized multicenter study. Between June 2015 and March 2018, a total of 176 patients (178 lesions) who underwent ESD for a gastric neoplasm were randomly allocated to receive the oral proton-pump inhibitor ilaprazole 20 mg or rabeprazole 20 mg daily for 8 weeks. The primary outcome was the ulcer healing rate at 4 and 8 weeks.

Results: A total of 155 (157 lesions) and 154 patients (156 lesions) were included in the modified intention-to-treat (mITT) and per-protocol analyses, respectively. There was no significant difference in the ulcer healing rate (ilaprazole vs. rabeprazole, 97.4% vs. 97.0 p = 0.78 at 4 weeks, 100% vs. 100%, p = 0.95 at 8 weeks in the mITT analysis) or stage of ulcer (scar stage, 25.6% vs. 17.7%, p = 0.25 at 4 weeks, 92.3% vs. 88.6%, p = 0.59 at 8 weeks in the mITT analysis) between the treatment groups. The quality of ulcer healing was not significantly different between the two groups. No independent predictive factor for higher-quality ulcer healing was found in the multivariate analysis.

Conclusions: According to this trial, ilaprazole and rabeprazole showed no significant difference in the healing of artificial gastric ulcers. Most of the ulcers achieved complete healing within 4-8 weeks.

Trial Registration: ClinicalTrial.gov NCT02638584.
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http://dx.doi.org/10.1007/s00464-018-6412-9DOI Listing
May 2019

What Is Most Important to the Endoscopist for Therapeutic Plan? Morphology Pathology: A Nationwide Multicenter Retrospective Study in Korea.

Am Surg 2018 May;84(5):644-651

Eulji University Hospital, Eulji University School of Medicine, Daejeon, Korea.

Histologic discrepancy may sometimes occur between biopsy and endoscopic resection. We investigated the discrepancy rate between the biopsy and the resection lesion in the Korean population. From January 2010 to October 2016, 268 patients with gastric endoscopic mucosal resection/endoscopic submucosal dissection history from nationwide hospitals were enrolled retrospectively. We compared the histologic discrepancy rates from the biopsy and the resection. The mean age was 63.2 years. Gastric adenomas occurred most frequently in the antrum. The pathology of the resected specimens classified 25 lesions (9.3%) as gastritis/hyperplasia, 146 lesions (54.5%) as low-grade dysplasia, 76 lesions (28.4%) as high-grade dysplasia (HGD), and 21 lesions (7.8%) as adenocarcinoma. The discrepancy rate between biopsy and resection was 23.1 per cent. Among the 44 cases of gastritis/hyperplasia, two cases (4.5%) were diagnosed as HGD and 11 cases (25.0%) were diagnosed as cancer after resection. Among the 182 cases of low-grade dysplasia, 33 cases (18.1%) were diagnosed as HGD and nine cases (5.0%) were diagnosed as cancer after resection. Gastritis/hyperplasia, ulceration, and lesions in the lower body location were significant factors related to the discrepancies. Especially, discrepancy occurred most frequently in gastritis/hyperplasia lesions with ulcer in the lower body. There was considerable histologic discrepancy between biopsy and resection. Ulcerative-type tumor morphology and biopsy diagnosis of gastritis/hyperplasia are suggestive factors predictive of discrepancy between biopsy and resection in terms of malignancy. Therefore, although the results of biopsy are gastritis/hyperplasia, suspicious tumorous lesions with ulcer should be indicative of active endoscopic resection for diagnosis and treatment.
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May 2018

Investigation of tissue cysts in the retina in a mouse model of ocular toxoplasmosis: distribution and interaction with glial cells.

Parasitol Res 2018 Aug 2;117(8):2597-2605. Epub 2018 Jun 2.

Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.

The conversion of tachyzoites into bradyzoites is a way for Toxoplasma gondii to establish a chronic and asymptomatic infection and achieve lifelong persistence in the host. The bradyzoites form tissue cysts in the retina, but not much is known about the horizontal distribution of the cysts or their interactions with glial cells in the retina. A chronic ocular toxoplasmosis model was induced by per oral administration of T. gondii Me49 strain cysts to BALB/c mice. Two months after the infection, retinas were flat-mounted and immunostained to detect cysts, ganglion cells, Müller cells, astrocytes, and microglial cells, followed by observation under fluorescence and confocal microscope. The horizontal distribution showed a rather clustered pattern, but the clusters were not restricted to certain location of the retina. Axial distribution was confined to the inner retina, mostly in ganglion cell layer or the inner plexiform layer. Both ganglion cells, a type of retinal neurons, and Müller cells, predominant retinal glial cells, could harbor cysts. The cysts were spatially separated from astrocytes, the most abundant glial cells in the ganglion cell layer, while close spatial distribution of microglial cells was observed in two thirds of retinal cysts. In this study, we demonstrated that the retinal cysts were not evenly distributed horizontally and were confined to the inner retina axially. Both neurons and one type of glial cells could harbor cysts, and topographic analysis of other glial cells suggests role of microglial cells in chronic ocular toxoplasmosis.
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http://dx.doi.org/10.1007/s00436-018-5950-3DOI Listing
August 2018

An Analysis of Infectious Disease Research Trends in Medical Journals From North Korea.

J Prev Med Public Health 2018 Mar;51(2):109-120

Seoul National University College of Medicine, Seoul, Korea.

Objectives: This study aimed to investigate the current status of infectious disease research in North Korea by analyzing recent trends in medical journals from North Korea in comparison with research from South Korea.

Methods: Three medical journals (Preventive Medicine, Basic Medicine, and Chosun Medicine) were analyzed from 2012 to 2016. Articles on tuberculosis (TB), malaria, and parasitic diseases were selected and classified by their subtopics and study areas. Two medical journals published in the South Korea were selected for a comparative analysis of research trends.

Results: Of the 2792 articles that were reviewed, 93 were extracted from North Korea journals. TB research in North Korea was largely focused on multi-drug resistant TB and extrapulmonary TB, whereas research in South Korea more frequently investigated non-tuberculous mycobacteria. Research on parasitic diseases in North Korea was focused on protozoan and intestinal nematodes, while the corresponding South Korea research investigated various species of parasites. Additionally, the studies conducted in North Korea were more likely to investigate the application of traditional medicine to diagnosis and treatment than those conducted in South Korea.

Conclusions: This study presents an analysis of research trends in preventive medicine in North Korea focusing on infectious diseases, in which clear differences were observed between South and North Korea. Trends in research topics suggest a high prevalence of certain parasitic diseases in North Korea that are no longer widespread in South Korea. The large proportion of studies examining traditional medicine implies a lack of affordable medicine in North Korea.
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http://dx.doi.org/10.3961/jpmph.17.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897231PMC
March 2018

Factors Associated with Rebleeding in Patients with Peptic Ulcer Bleeding: Analysis of the Korean Peptic Ulcer Bleeding (K-PUB) Study.

Gut Liver 2018 May;12(3):271-277

Department of Internal Medicine, National Medical Center, Seoul, Korea.

Background/aims: Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB.

Methods: The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding.

Results: In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations.

Conclusions: The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.
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http://dx.doi.org/10.5009/gnl17138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945258PMC
May 2018

Island-Wide Surveillance of Gastrointestinal Protozoan Infection on Fiji by Expanding Lymphatic Filariasis Transmission Assessment Surveys as an Access Platform.

Am J Trop Med Hyg 2018 04 1;98(4):1179-1185. Epub 2018 Feb 1.

Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

As part of lymphatic filariasis (LF) transmission assessment surveys (TAS) on Fiji, an island-wide assessment of gastrointestinal protozoan infection was performed by inspection of a concomitant stool sample collection to investigate the distribution of parasitic protozoa. All grade 1 and 2 students of 69 schools on the two main islands were targeted in two phases (one in the Western Division and the other in the Central and Northern Divisions, except Taveuni sub-Division of Northern), where fecal samples of 1,800 students were available for coproscopy using formalin-ether-acetate concentration. The overall prevalence of infection was 1.6%, having 2.2% in Western and 0.8% in Central/Northern Divisions ( = 0.094). The school-level prevalence of giardiasis ranged from 0% to 15.4%, and hotspot analysis using the Getis-Ord Gi* method detected spatial heterogeneity of giardiasis prevalence in schools around Lautoka (-score = 3.36, value < 0.05), an area affected by Cyclone Kofi in February 2014. Any protozoan infection prevalence was 4.9% in Western and 4.4% in Central/Northern Divisions ( = 0.825). Real-time polymerase chain reaction analysis to confirm the findings from a parasitological examination of a 10% stool archive in 95% ethanol from Western Division revealed an elevated prevalence of giardiasis up to 22.4%, the presence of , and the absence of . Obtaining stool samples alongside LF TAS is a convenient access platform for cosurveillance of gastrointestinal protozoan infection and has pinpointed hitherto unknown hotspots of giardiasis in urban city centers of Fiji. This calls for greater attention to apply tailored water, sanitation and hygiene measures for the control of these parasites.
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http://dx.doi.org/10.4269/ajtmh.17-0559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928820PMC
April 2018

Human Laryngeal Infection by .

Am J Trop Med Hyg 2018 Jan;98(1):7-8

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4269/ajtmh.17-0718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928746PMC
January 2018

Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples.

PLoS Negl Trop Dis 2017 Oct 9;11(10):e0005995. Epub 2017 Oct 9.

Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Korea.

Background: Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited.

Methodology/principle Findings: The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1-99.2) of sensitivity and 100% (95% CI, 92.9-100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%.

Conclusions: To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis.
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http://dx.doi.org/10.1371/journal.pntd.0005995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648269PMC
October 2017

Safety and efficacy of early feeding based on clinical assessment at 4 hours after ERCP: a prospective randomized controlled trial.

Gastrointest Endosc 2018 Apr 28;87(4):1040-1049.e1. Epub 2017 Sep 28.

Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, Republic of Korea.

Background And Aims: The optimal timing of refeeding after ERCP is unknown. Some practices keep the patient fasting for 24 hours after ERCP, whereas others resume feeding earlier. We aimed to evaluate the risk of post-ERCP pancreatitis (PEP) in patients who initiate early feeding, based on their clinical assessment, including serum amylase testing performed at 4 hours after ERCP.

Methods: Patients who were scheduled for ERCP were recruited. Patients without abdominal pain and tenderness and a serum amylase level within 1.5-fold the upper limit of normal at 4 hours after ERCP were randomly assigned to either the 4-hour fasting or 24-hour fasting group. Patients from the 4-hour fasting group started oral intake 4 hours after ERCP, whereas those from the 24-hour fasting group fasted for 24 hours after ERCP.

Results: Among the 276 enrolled, PEP was identified in 3 (2.2%) from the 4-hour fasting group and in 5 (3.6%) from the 24-hour fasting group, with a rate difference of -1.4% (1-sided 97.5% confidence interval, -∞ to 2.5%). Four-hour fasting was non-inferior to 24-hour fasting in terms of PEP incidence. The total medical costs for treatment-related ERCP were significantly lower in the 4-hour fasting group than in the 24-hour fasting group (1157.20 ± 311.90 vs 1311.20 ± 410.70 U.S. dollars; P = .032).

Conclusion: Early feeding in patients without abdominal pain and tenderness and a serum amylase level <1.5-fold the upper limit of normal at 4 hours after ERCP does not increase the incidence of PEP after ERCP and decreases medical costs. (Clinical trial registration number: KCT0002354.).
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http://dx.doi.org/10.1016/j.gie.2017.09.021DOI Listing
April 2018

Efficacy and safety of etomidate-based sedation compared with propofol-based sedation during ERCP in low-risk patients: a double-blind, randomized, noninferiority trial.

Gastrointest Endosc 2018 Jan 10;87(1):174-184. Epub 2017 Jun 10.

Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, Korea.

Background And Aims: Etomidate is a short-acting intravenous hypnotic with a safety profile that is superior to alternative drugs such as propofol. However, there is a lack of evidence on the safety of etomidate in ERCP. The objective of this study was to compare efficacy and safety profiles of etomidate and propofol for endoscopic sedation.

Methods: This single-center, randomized, double-blind, noninferiority trial included patients with American Society of Anesthesiologists (ASA) physical status I to II who had been scheduled for ERCP. All patients received .05 mg/kg midazolam intravenously as pretreatment before receiving etomidate or propofol. Either etomidate or propofol was then administered according to group allocation. The primary endpoint was an overall respiratory event. A noninferiority margin of 10% was assumed.

Results: Sixty-three and 64 patients were enrolled in the etomidate and propofol groups, respectively. Respiratory events were identified in 10 patients (15.6%) in the etomidate group and 16 patients (25.4%) on the propofol group, with a rate difference of -9.8% (1-sided 97.5% confidence interval, -∞ to 4.2%). The overall incidence of cardiovascular events tended to be higher in the etomidate group (67.2% vs 50.8%, P = .060). In particular, tachycardia (heart rate > 100 beats/min) was more common in the etomidate group than in the propofol group (64.1% vs 34.9%, P = .001). Transient hypotension tended to be less common in the etomidate group (6.3 vs 15.9%, P = .084).

Conclusions: Etomidate-based sedation during ERCP was noninferior to propofol-based sedation in terms of the overall incidence of respiratory events in patients with ASA physical status I to II. (International Clinical Trials Registry Platform number: KCT0001926.).
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http://dx.doi.org/10.1016/j.gie.2017.05.050DOI Listing
January 2018

Significance of Serology by Multi-Antigen ELISA for Tissue Helminthiases in Korea.

J Korean Med Sci 2017 Jul;32(7):1118-1123

Department of Parasitology and Tropical Medicine, Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul, Korea.

It is clinically important to differentiate tissue-invading helminthiasis. The purpose of this study was to assess the specific immunoglobulin G (IgG) antibody positive rates for clonorchiasis, paragonimiasis, cysticercosis, and sparganosis 4 helminthiases from 1996 to 2006 using multi-antigen enzyme-linked immunosorbent assay (ELISA) in Korea. Results of 6,017 samples, which were referred to our institute for serodiagnosis, were analyzed. The subjects with positive serum IgG antibodies were 1,502 (25.0%) for any of the 4 helminthiases. The overall positive numbers for clonorchiasis, paragonimiasis, cysticercosis, and sparganosis were 728 (12.1%), 166 (2.8%), 729 (12.1%), and 263 (4.4%), respectively. The positive serologic reaction to multi-antigens was determined in 309 (20.6%) of the 1,502 total seropositive subjects. Those with multi-antigen positivity were regarded as positive for the antigen of strongest reaction but cross-reaction to others with weak positive reaction. Annual seropositive rates for those 4 tissue helminthiases ranged from 12.1% to 35.7%. The highest rate was observed in age from 60 to 69 years old and prevalence of men (27.4%; 1,030/3,763) was significantly higher than of women (19.1%; 332/1,741). Hospital records of 165 ELISA positive patients were reviewed to confirm correlation with their clinical diagnosis. Paragonimiasis was highly correlated as 81.8% (9/11), cysticercosis 29.9% (20/67), clonorchiasis 29.0% (20/69), and sparganosis 11.1% (2/18). In conclusion, the multi-antigen ELISA using 4 helminth antigens is useful to differentiate suspected tissue-invading helminthiases, especially ELISA diagnosis of paragonimiasis is reliable. The seropositivity is still high among suspected patients in Korea.
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http://dx.doi.org/10.3346/jkms.2017.32.7.1118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461315PMC
July 2017

Disruption of outer blood-retinal barrier by Toxoplasma gondii-infected monocytes is mediated by paracrinely activated FAK signaling.

PLoS One 2017 13;12(4):e0175159. Epub 2017 Apr 13.

Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.

Ocular toxoplasmosis is mediated by monocytes infected with Toxoplasma gondii that are disseminated to target organs. Although infected monocytes can easily access to outer blood-retinal barrier due to leaky choroidal vasculatures, not much is known about the effect of T. gondii-infected monocytes on outer blood-retinal barrier. We prepared human monocytes, THP-1, infected with T. gondii and human retinal pigment epithelial cells, ARPE-19, grown on transwells as an in vitro model of outer blood-retinal barrier. Exposure to infected monocytes resulted in disruption of tight junction protein, ZO-1, and decrease in transepithelial electrical resistance of retinal pigment epithelium. Supernatants alone separated from infected monocytes also decreased transepithelial electrical resistance and disrupted tight junction protein. Further investigation revealed that the supernatants could activate focal adhesion kinase (FAK) signaling in retinal pigment epithelium and the disruption was attenuated by FAK inhibitor. The disrupted barrier was partly restored by blocking CXCL8, a FAK activating factor secreted by infected monocytes. In this study, we demonstrated that monocytes infected with T. gondii can disrupt outer blood-retinal barrier, which is mediated by paracrinely activated FAK signaling. FAK signaling can be a target of therapeutic approach to prevent negative influence of infected monocytes on outer blood-retinal barrier.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175159PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390985PMC
April 2017

Development of Urinary Bladder Pre-Neoplasia by Eggs and Chemical Carcinogen in Mice.

Korean J Parasitol 2017 Feb 28;55(1):21-29. Epub 2017 Feb 28.

Department of Parasitology and Tropical Medicine, Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.

is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of in urothelial epithelial cells of the eggs+BBN group at week 20. The qRT-PCR showed high expression of gene in eggs group at week 4 and eggs+BBN group at week 20. and showed contrasting expression in eggs+BBN group. Such inverse expression of and may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in and increase in and expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using eggs.
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http://dx.doi.org/10.3347/kjp.2017.55.1.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365267PMC
February 2017

Etomidate versus propofol sedation for complex upper endoscopic procedures: a prospective double-blinded randomized controlled trial.

Gastrointest Endosc 2017 Sep 8;86(3):452-461. Epub 2017 Mar 8.

Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, Korea.

Background And Aims: Although a growing body of evidence demonstrates that propofol-induced deep sedation can be effective and performed safely, cardiopulmonary adverse events have been observed frequently. Etomidate is a new emerging drug that provides hemodynamic and respiratory stability, even in high-risk patient groups. The objective of this study was to compare safety and efficacy profiles of etomidate and propofol for endoscopic sedation.

Methods: A total of 128 patients undergoing EUS were randomized to receive either etomidate or propofol blinded administered by a registered nurse. The primary outcome was the proportion of patients with any cardiopulmonary adverse events.

Results: Overall cardiopulmonary adverse events were identified in 22 patients (34.38%) of the etomidate group and 33 patients (51.56%) of the propofol group, without significant difference (P = .074). However, the incidence of oxygen desaturation (4/64 [6.25%] vs 20/64 [31.25%]; P =.001) and respiratory depression (5/64 [7.81%] vs 21/64 [32.81%]; P =.001) was significantly lower in the etomidate group than in the propofol group. The frequency of myoclonus was significantly higher in the etomidate group (22/64 [34.37%]) compared with the propofol group (8/64 [12.50%]) (P =.012). Repeated measure analysis of variance revealed significant effects of sedation group and time on systolic blood pressure (etomidate group greater than propofol group). Physician satisfaction was greater in the etomidate group than in the propofol group.

Conclusions: Etomidate administration resulted in fewer respiratory depression events and had a better sedative efficacy than propofol; however, it was more frequently associated with myoclonus and increased blood pressure during endoscopic procedures. (Clinical trial registration number: KCT0001701.).
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http://dx.doi.org/10.1016/j.gie.2017.02.033DOI Listing
September 2017

Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

Parasitol Int 2017 Aug 15;66(4):436-442. Epub 2016 Nov 15.

Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Electronic address:

Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (P<0.001). Kupffer cells expressed Th2-related cytokines (IL-10 and IL-13) during primary infection. In addition, serum levels of C. sinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system.
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http://dx.doi.org/10.1016/j.parint.2016.11.006DOI Listing
August 2017

C3H/He Mice as an Incompatible Cholangiocarcinoma Model by Clonorchis sinensis, Dicyclanil and N-Nitrosodimethylamine.

Korean J Parasitol 2016 Jun 30;54(3):281-9. Epub 2016 Jun 30.

Department of Parasitology and Tropical Medicine, Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.

Clonorchis sinensis is a Group-I bio-carcinogen, associated with cholangiocarcinoma (CCA). The hamster is the only experimental model of C. sinensis-mediated CCA, but we oblige another animal model. The present study intended to develop a C. sinensis (Cs) mediated CCA model using C3H/He mice, co-stimulated with N-nitrosodimethyl-amine (NDMA) and dicyclanil (DC). The mice were divided into 8 groups with different combinations of Cs, NDMA, and DC. Six months later the mice were sacrificed and subjected to gross and histopathological examination. The body weights were significantly reduced among the groups treated with 2 or more agents (eg. Cs+NDMA, Cs+DC, NDMA+DC, and Cs+NDMA+DC). In contrast, liver weight percentages to body weight were increased in above groups by 4.1% to 4.7%. A Change of the spleen weight was observed only in Cs+NDMA group. Though C. sinensis infection is evident from hyperplastic changes, only 1 worm was recovered. T wo mice, 1 from Cs and the other from Cs+DC group, showed mass forming lesions; 1 (281.2 mm(3)) from the Cs group was a hepatocellular adenoma and the other (280.6 mm(3)) from the Cs+DC group was a cystic mass (peliosis). Higher prevalence of gray-white nodules was observed in Cs group (42.9%) followed by Cs+NDMA+DC group (21.4%). The mice of the Cs+NDMA+DC group showed hyper-proliferation of the bile duct with fibrotic changes. No characteristic change for CCA was recognized in any of the groups. In conclusion, C3H/He mice produce no CCA but extensive fibrosis when they are challenged by Cs, NDMA, and DC together.
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http://dx.doi.org/10.3347/kjp.2016.54.3.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977786PMC
June 2016

Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation.

Oncol Lett 2016 Jul 13;12(1):250-256. Epub 2016 May 13.

Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi 445-170, Republic of Korea.

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) signaling plays an important role in tumor progression in patients with certain gastrointestinal tract cancers. In addition to lowering cholesterol in serum, statins have pleiotropic effects, including anti-oxidative, anti-inflammatory or anti-neoplastic effects. Therefore, the present study investigated whether statins could induce the apoptosis of colon cancer cells and regulate the expression of IGF-1R and its associated signaling pathways in the present study. It was demonstrated that simvastatin and pravastatin suppressed cell proliferation and induced cell death in human HT-29 cells, but simvastatin was more potent than pravastatin. Simvastatin induced apoptosis in a concentration-dependent manner. In addition, simvastatin suppressed the expression of IGF-1R and inhibited the activity of phosphorylated-extracellular signal-regulated kinase (ERK)1/2 and phosphorylated-Akt activated by IGF-1. Simvastatin and IGF-1 each stimulated the activity of phosphorylated ERK1/2. However, simvastatin inhibited cell proliferation and IGF-1 stimulated cell proliferation. Mevalonic acid and PD98059 reversed the ERK activation and apoptosis induced by treatment with simvastatin. It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF-1-induced ERK and Akt expression via the downregulation of IGF-1R expression and proapoptotic ERK activation. Simvastatin may be beneficial for the treatment of colon cancer. The present study suggested that statin may possess therapeutic potential for the treatment of colon cancer.
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http://dx.doi.org/10.3892/ol.2016.4569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906996PMC
July 2016

Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer.

Oncotarget 2016 Jul;7(29):46219-46229

Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Gyeonggi do, Korea.

Statin has been known not only as their cholesterol-lowering action but also on their pleiotropic effects including anti-inflammatory and anti-oxidant as well as anti-cancer effect. Nrf2 (NF-E2-related factor 2) is a transcription factor to activate cellular antioxidant response to oxidative stress. There are little known whether statins affect activation of Nrf2 and Nrf2 signaling pathway in colon cancer cells. We investigated whether simvastatin stimulates the expression of Nrf2 and nuclear translocation of Nrf2 and which signal pathway is involved in the expression of Nrf2 and antioxidant enzymes. We investigated the effect of simvastatin on the expression of Nrf2 and nuclear translocation of Nrf2 in two human colon cancer cell lines, HT-29 and HCT 116 through cell proliferation assay, Western blotting and immunocytochemical analysis. We evaluated which signal pathway such as ERK or PI3K pathway affect Nrf2 activation and whether simvastatin induces antioxidant enzymes (heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1), γ-glutamate-cysteine ligase catalytic subunit (GCLC)). We demonstrated simvastatin-induced dose-dependent up-regulation of Nrf2 expression and stimulated Nrf2 nuclear translocation in colon cancer cells. We also demonstrated that simvastatin-induced anti-oxidant enzymes (HO-1, NQO1, and GCLC) in HT-29 and HCT 116 cells. PI3K/Akt inhibitor (LY294002) and ERK inhibitor (PD98059) suppressed simvastatin-induced Nrf2 and HO-1 expression in both HT-29 and HCT 116 cells. This study shows that simvastatin induces the activation and nuclear translocation of Nrf2 and the expression of various anti-oxidant enzymes via ERK and PI3K/Akt pathway in colon cancer cells.
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http://dx.doi.org/10.18632/oncotarget.10078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216792PMC
July 2016

Meta-Analysis for Cyto-Pathological Outcomes in Endoscopic Ultrasonography-Guided Fine-Needle Aspiration With and Without the Stylet.

Dig Dis Sci 2016 08 24;61(8):2175-2184. Epub 2016 Mar 24.

Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7, Keunjaebong-gil, Hwaseong-si, Gyeonggi-do, 18450, Korea.

Background: Theoretically, use of the stylet during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) will prevent the tip of the needle from being blocked and the sample from being contaminated, improving the quality and diagnostic yield of specimens.

Aim: This meta-analysis aimed to evaluate any benefit from the use of a stylet during EUS-FNA.

Methods: MEDLINE, EMBASE, WEB of SCIENCE, and the Cochrane Central Register of Controlled Trials were searched for articles published through October 2015. A fixed-effects model was used to calculate the pooled effects when there is no heterogeneity and a random-effects model was used in situations with significant heterogeneity.

Results: Five prospective randomized controlled studies and two retrospective studies of a total of 5491 specimens (2504 specimens in the S+ group and 2987 specimens in the S- group) were included in this study. The pooled analysis demonstrated no significant differences in the adequate sample rate between the S+ group (2135/2504, 85.26 %) and S- group (2609/2987, 87.35 %) [odds ratio 0.94 (95 % confidence interval 0.79-1.11), p = 0.45]. Furthermore, the rate of cellularity > 50 %, the contamination rate, and the blood contamination rate were not significantly superior in the S+ group when compared with the S- group.

Conclusions: Whether the use of a stylet improves the proportion of adequate specimens or quality of the specimen is questionable. Our results suggest that the use of a stylet dose not guarantee any advantage during EUS-guided tissue sampling.
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http://dx.doi.org/10.1007/s10620-016-4130-5DOI Listing
August 2016