• Title/Summary/Keyword: crohn's disease

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A Novel Chronic Enteropathy Associated with SLCO2A1 Gene Mutation: Enterography Findings in a Multicenter Korean Registry

  • Boryeong Jeong;Seong Ho Park;Byong Duk Ye;Jihun Kim;Suk-Kyun Yang
    • Korean Journal of Radiology
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    • v.24 no.4
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    • pp.305-312
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    • 2023
  • Objective: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a recently recognized disease. We aimed to evaluate the enterographic findings of CEAS. Materials and Methods: Altogether, 14 patients with CEAS were confirmed based on known SLCO2A1 mutations. They were registered in a multicenter Korean registry between July 2018 and July 2021. Nine of the patients (37.2 ± 13 years; all female) who underwent surgery-naïve-state computed tomography enterography (CTE) or magnetic resonance enterography (MRE) were identified. Two experienced radiologists reviewed 25 and 2 sets of CTE and MRE examinations, respectively, regarding the small bowel findings. Results: In initial evaluation, eight patients showed a total of 37 areas with mural abnormalities in the ileum on CTE, including 1-4 segments in six and > 10 segments in two patients. One patient showed unremarkable CTE. The involved segments were 10-85 mm (median, 20 mm) in length, 3-14 mm (median, 7 mm) in mural thickness, circumferential in 86.5% (32/37), and showed stratified enhancement in the enteric and portal phases in 91.9% (34/37) and 81.8% (9/11), respectively. Perienteric infiltration and prominent vasa recta were noted in 2.7% (1/37) and 13.5% (5/37), respectively. Bowel strictures were identified in six patients (66.7%), with a maximum upstream diameter of 31-48 mm. Two patients underwent surgery for strictures immediately after the initial enterography. Follow-up CTE and MRE in the remaining patients showed minimal-to-mild changes in the extent and thickness of the mural involvement for 17-138 months (median, 47.5 months) after initial enterography. Two patients required surgery for bowel stricture at 19 and 38 months of follow-up, respectively. Conclusion: CEAS of the small bowel typically manifested on enterography in varying numbers and lengths of abnormal ileal segments that showed circumferential mural thickening with layered enhancement without perienteric abnormalities. The lesions caused bowel strictures that required surgery in some patients.

Anti-inflammatory and apoptosis improving effects of sulfasalazine and Cinnamomi cortex and Bupleuri radix mixture in TNBS-induced colitis mouse model (TNBS로 유발된 마우스 대장염모델에서 설파살라진, 육계와 시호 복합 추출물의 항염증 및 세포 자멸 개선효과)

  • Kim, Kyeong Jo;Shin, Mi-Rae;Kim, Soo Hyun;Kim, Su Ji;Lee, Ah Reum;Kwon, O Jun;Kil, Ki-Jung;Roh, Seong-Soo
    • Journal of Applied Biological Chemistry
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    • v.60 no.3
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    • pp.227-234
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    • 2017
  • Inflammatory bowel disease (IBD) is including Crohn's disease and ulcerative colitis. Sulfasalazine commonly used in IBD, possibly has various side effects after high dosage and long term intake. The present study aimed to investigate the sulfasalazine and combination with herbal medicine on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced in mice model. TNBS-induced mice were injected through a flexible catheter 4 cm in length 1.6 mg TNBS. Animals were divided into five groups (n=12): Normal group, TNBS control group, Sulfasalazine (30 mg/kg) group, Sulfasalazine (60 mg/kg) group, Sulfasalazine (30 mg/kg)+Cinnamomi cortex and Bupleuri radix mixture (30 mg/kg) (SCB) group. Administration groups were fed extract during 7 days. The inflammatory, and apoptotic protein levels were determined using western blotting. SCB treatment showed an outstanding effectiveness in counteracting the IBD, as assessed by reduction of body weight loss, down-regulation of pro-inflammatory proteins and cytokines, and by inhibition of proteins related to apoptosis. This is the first report that sulfasalazine and Cinnamomi cortex plus Bupleuri radix mixture improve the severity of experimental IBD through the inhibition of both inflammation and apoptosis. We confirm that the SCB treatment instead of sulfasalazine alone may be promising as an alternative therapeutic plan against IBD, without any evidence of adverse effects.

Management of Pediatric Small Bowel Intussusception: Spontaneous Reduction vs Operation (소아의 소장 중첩증의 치료 : 자연 정복 vs 수술적 치료)

  • Kim, Eun-Young;Jung, Kyu-Whan;Park, Tae-Jin;Park, Kwi-Won;Jung, Sung-Eun;Kim, Hyun-Young
    • Advances in pediatric surgery
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    • v.16 no.2
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    • pp.117-125
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    • 2010
  • Unreduced small bowel intussusception requires operative treatment although the rate of spontaneous reduction is 60 to 70 %. The aim of this study is to compare clinical characteristics and outcome between spontaneous reduction and operation group and to analyze factors related to decisions to treat small bowel intussusceptions. The records of 25 patients with small bowel intussusceptions treated in Seoul National University Children's Hospital from January 1999 to August 2009 were reviewed respectively. Spontaneous reduction group (n=12, 48 %) had signs and symptoms of vomiting, abdominal pain, currant jelly stool, abdominal distension, fever, increased CRP but no rebound tenderness. One of them had been diagnosed with Henoch-Schonlein purpura and no one displayed pathologic leading point by image study. Operation group (n=13, 52 %) consisted of patients who had primary surgery. Their signs and symptoms were similar to spontaneous reduction group. Seven of them had underlying diseases such as Crohn' disease, ALL, Lymphoma, Peutz-Jeghers syndrome (n=3), post-transplanted state of liver and 2 of them displayed Peutz-Jeghers polyp and Meckel's diverticulum as pathologic leading point by preoperative ultrasonography. Mean relieve interval (interval between onset of symptoms and reduction/operation) was 1.78 days in spontaneous reduction group and 2.25 days in operation group (p=0.341). Seven of operation group had manual reduction and 6 out of 7 received segmental resection of the small bowel. No one of them underwent manual reduction and all of them underwent segmental resection were found to have pathologic leading points [Peutz-Jeghers polyp (n=3), Meckel's diverticulum (n=2), lymphoma (n=1)] during operation. In conclusion, 48% of small bowel intussusceptions resolved spontaneously. Patients' symptoms and relieve intervals were not related to the operative decisions. We therefore recommend significant factors for determining treatment plan such as change of clinical symptoms, underlying disease or pathologic leading point by imaging.

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DNA Microarray Analysis of Methylprednisolone Inducible Genes in the PC12 Cells

  • Choi, Woo-Jin;Choi, Seung-Won;Kim, Seon-Hwan;Kim, Youn;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.15 no.3
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    • pp.261-263
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    • 2009
  • Methylprednisolone is a synthetic glucocorticoid which is usually taken intravenously for many neurosurgical diseases which cause edema including brain tumor, and trauma including spinal cord injury. Methylprednisolone reduces swelling and decreases the body's immune response. It is also used to treat many immune and allergic disorders, such as arthritis, lupus, psoriasis, asthma, ulcerative colitis, and Crohn's disease. To identify genes expressed during methylprednisolone treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up- or down-regulated genes) which are methylprednisolone differentially expressed in neurons. Lipocalin 3 is the gene most significantly increased among 772 up-regulated genes (more than 2 fold over-expression) and Aristaless 3 is the gene most dramatically decreased among 959 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Fgb, Thbd, Cfi, F3, Kngl, Serpinel, C3, Tnfrsf4 and Il8rb are involved stress-response gene, and Nfkbia, Casp7, Pik3rl, I11b, Unc5a, Tgfb2, Kitl and Fgf15 are strongly associated with development. Cell cycle associated genes (Mcm6, Ccnb2, Plk1, Ccnd1, E2f1, Cdc2a, Tgfa, Dusp6, Id3) and cell proliferation associated genes (Ccl2, Tnfsf13, Csf2, Kit, Pim1, Nr3c1, Chrm4, Fosl1, Spp1) are down-regulated more than 2 times by methylprednisolone treatment. Among the genes described above, 4 up-regulated genes are confirmed those expression by RT-PCR. We found that methylprednisolone is related to expression of many genes associated with stress response, development, cell cycle, and cell proliferation by DNA microarray analysis. However, We think further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by methylprednisolone. The resulting data will give the one of the good clues for understanding of methylprednisolone under molecular level in the neurons.

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Ulcerative Colitis is Associated with Novel Polymorphisms in the Promoter Region of MIP-3${\alpha}$/CCL20 Gene

  • Choi, Suck-Chei;Lee, Eun-Kyung;Lee, Sung-Ga;Chae, Soo-Cheon;Lee, Myeung-Su;Seo, Geom-Seog;Kim, Sang-Wook;Yeom, Joo-Jin;Jun, Chang-Duk
    • IMMUNE NETWORK
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    • v.5 no.4
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    • pp.205-214
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    • 2005
  • Background: We examined global gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with ulcerative colitis (DC), and tested whether the identified genes with the altered expression might be associated with susceptibility to UC. Methods: PBMCs from 8 UC and 8 normal healthy (NH) volunteers were collected, and total RNAs were subjected to the human 8.0K cDNA chip for the micro array analysis. Real time-PCR (RT-PCR) was performed to verify the results of micro array. One hundred forty UC patients and 300 NH controls were recruited for single nucleotide polymorphism (SNP) analysis. Results: Twenty-five immune function-related genes with over 2-fold expression were identified. Of these genes, two chemokines, namely, CXCL1 and CCL20, were selected because of their potential importance in the evocation of host innate and adaptive immunity. Four SNPs were identified in the promoter and coding regions of CXCL1, while there was no significant difference between all patients with UC and controls in their polymorphisms, except minor association at g.57A>G (rs2071425, p=0.02). On the other hand, among three novel and one known SNPs identified in the promoter region of CCL20, g. -1,706 G>A (p=0.000000055), g. -1,458 G>A (p=0.0048), and g. -962C>A (p=0.0006) were found to be significantly associated with the susceptibility of Uc. Conclusion: Altered gene expression in mononuclear cells may contribute to IBD pathogenesis. Although the findings need to be confirmed in other populations with larger numbers of patients, the current results demonstrated that polymorphisms in the promoter region of CCL20 are positively associated with the development of Uc.

Incidence of Active Tuberculosis within One Year after Tumor Necrosis Factor Inhibitor Treatment according to Latent Tuberculosis Infection Status in Patients with Inflammatory Bowel Disease

  • Kang, Jieun;Jeong, Dae Hyun;Han, Minkyu;Yang, Suk-Kyun;Byeon, Jeong-Sik;Ye, Byong Duk;Park, Sang Hyoung;Hwang, Sung Wook;Shim, Tae Sun;Jo, Kyung-Wook
    • Journal of Korean Medical Science
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    • v.33 no.47
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    • pp.292.1-292.10
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    • 2018
  • Background: We investigated the incidence of active tuberculosis among patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF) inhibitors, with or without latent tuberculosis infection (LTBI). Methods: The study was performed at a Korean tertiary referral center between January 2011 and June 2017. In total, 740 patients with IBD who underwent LTBI screening tests and were followed-up for ${\geq}1$ year after TNF inhibitor treatment initiation were enrolled. LTBI was detected on the basis of tuberculin skin test results, interferon-gamma release assay results, chest X-ray findings, and previous tuberculosis treatment history. The patients were classified into LTBI (n = 84) or non-LTBI (n = 656) group. The risk of developing tuberculosis in each group was assessed on the basis of standardized incidence ratio (SIR) and 95% confidence interval (CI) for active tuberculosis. Results: Mean patient age was 33.1 years, and patients with Crohn's disease were predominant (80.7%). Within 1 year after the initiation of TNF inhibitor treatment, 1 patient in the LTBI group (1/84; 1.2%) and 7 patients in the non-LTBI group (7/656; 1.1%) developed active tuberculosis. The overall 1-year incidence of tuberculosis among the patients was significantly higher than that among the general population (SIR, 14.0; 95% CI, 7.0-28.0), and SIR was not affected by LTBI status (LTBI group: 14.5, 95% CI, 2.0-102.6; non-LTBI group: 14.0, 95% CI, 6.7-29.4). Conclusion: Patients with IBD undergoing TNF inhibitor treatment showed a higher 1-year incidence of tuberculosis than the general population irrespective of LTBI status.

E-cadherin Expression in Colonic Epithelium of Various Colitis in Children (소아에서 발생한 대장의 염증성 질환에서 E-cadherin의 발현)

  • Lee, Na-Young;Park, Do-Youn;Park, Jae-Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.12 no.2
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    • pp.177-182
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    • 2009
  • Purpose: Colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. E-cadherin plays a key role in the establishment and maintenance of epithelial tissue structure and cell-cell adhesion. The purpose of this study is to evaluate E-cadherin expression in colonic epithelium of various colitis in children. Methods: The expressions of E-cadherin were examined in 39 cases of colonic mucosal biopsy specimen using immunohistochemical staining. When more than 50 percent of cells exhibited uniformly the same intensity and pattern of immunostaining as the adjacent normal mucosa, the antigen expression was considered normal. Abnormal expression was defined when less than 50 percent of cells stained, when cells showed a heterogeneously weak or altered distribution, or when complete absence of staining was observed. Results: Fifteen cases with non-specific colitis (38.5%), 7 cases of with Crohn's disease (17.9%), 5 cases of infectious colitis and milk protein sensitive proctocolitis (12.8%), 3 cases of ulcerative colitis (7.7%), 2 cases of Henoch-Schonlein purpura colitis (5.1%), one case of Behcet's disease and ischemic colitis (2.6%) were included in this study. E-cadherin expression was decreased in all kinds of colitis. Reduced expression of E-cadherin was observed in 77 percent of cases. E-cadherin was weaker or no expression in reparative epithelium and "ulcer associated cell lineage". Conclusion: Altered expression of E-cadherin occurs during mucosal inflammation in any kinds of colitis. These changes may be involved in promoting cell migration during epithelial restitution of the gastrointestinal mucosa.

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Right-Sided and Left-Sided Colon Cancers are Two Distinct Disease Entities: an Analysis of 200 Cases in Pakistan

  • Hussain, Mudassar;Waqas, Omer;Hassan, Usman;Loya, Asif;Akhtar, Noreen;Mushtaq, Sajid;Yusuf, Muhammad Aasim;Syed, Aamir Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.5
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    • pp.2545-2548
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    • 2016
  • Background: There is growing evidence that there are differences in histological and genetic characteristics along with clinical behavior between right- and left-sided colon carcinomas. We have compared various parameters of the two types and assessed associations of the results with prognosis in patients in Pakistan. Materials and Methods: We reviewed 200 cases from our institutional database; 100 cases of right-sided and 100 cases of left-sided colon cancer. Parameters including age, gender, TNM stage, histological features and clinical outcome were analyzed. Results: The patients with right-sided colon cancer were significantly older as compared to their counterparts with left-sided cancer. They presented with a lumbar mass rather than symptoms of obstruction and perforation as seen in left-sided colon cancers, and the histology showed higher percentage of poorly differentiated tumors with advanced pT stage. Moreover, Crohn's-like reactions, intra tumoral lymphocyte responses and other poor prognostic factors like lymph vascular invasion and perineural invasion were more common in right-sided cancers. Conclusions: We found that right- and left-sided colon cancers are different from each other in terms of clinical presentation, histology and clinical behavior. Right-sided colon cancers are more aggressive and are associated with poorer clinical outcome as compared to left sided colon cancers in our population.

Identification and Functional Characterization of Novel Genetic Variations in the OCTN1 Promoter

  • Park, Hyo Jin;Choi, Ji Ha
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.2
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    • pp.169-175
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    • 2014
  • Human organic cation/carnitine transporter 1 (OCTN1) plays an important role in the transport of drugs and endogenous substances. It is known that a missense variant of OCTN1 is significantly associated with Crohn's disease susceptibility. This study was performed to identify genetic variants of the OCTN1 promoter in Korean individuals and to determine their functional effects. First, the promoter region of OCTN1 was directly sequenced using genomic DNA samples from 48 healthy Koreans. OCTN1 promoter activity was then measured using a luciferase reporter assay in HCT-116 cells. Seven variants of the OCTN1 promoter were identified, two of which were novel. There were also four major OCTN1 promoter haplotypes. Three haplotypes (H1, H3, and H4) showed decreased transcriptional activity, which was reduced by 22.9%, 23.0%, and 44.6%, respectively (p<0.001), compared with the reference haplotype (H2). Transcription factor binding site analyses and gel shift assays revealed that NF-Y could bind to the region containing g.-1875T>A, a variant present in H3, and that the binding affinity of NF-Y was higher for the g.-1875T allele than for the g.-1875A allele. NF-Y could also repress OCTN1 transcription. These data suggest that three OCTN1 promoter haplotypes could regulate OCTN1 transcription. To our knowledge, this is the first study to identify functional variants of the OCTN1 promoter.

Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity - Neuroprotective effect of Boswellic acid -

  • Ebrahimpour, Saeedeh;Fazeli, Mehdi;Mehri, Soghra;Taherianfard, Mahnaz;Hosseinzadeh, Hossein
    • Journal of Pharmacopuncture
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    • v.20 no.1
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    • pp.10-17
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    • 2017
  • Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.