• YAKHAK HOEJI
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• v.42 no.1
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• pp.5-11
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• 1998

5-Aminosalicyl-L-aspartic acid (5-ASA-Asp) and 5-aminosalicyl-L-glutamic acid (5-ASA-Glu) were synthesized as new colon-specific prodrugs of 5-aminosalicylic acid (5-ASA), their apparent partition coefficients, and the extent of conversion in the homogenates of tissue and contents of various G.I. Tract segments of rats were evaluated. These prodrugs were stable in the homogenate of tissue and contents of stomach, proximal small intestine (PSI) or distal small intestine (DSI). Release of 5-ASA from 5-ASA-Asp after incubation with the cecal and colonic contents for 8hrs at $37^{\circ}C$ was 18%, and 8%, respectively. No significant conversion of prodrug was observed in the cecal and colonic contents of rats pretreated with kanamycin sulfate, which indicated that microbial enzymes were responsible for the cleavage of these prodrugs.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

• Journal of Pharmacopuncture
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• v.13 no.3
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• pp.47-62
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• 2010

Objectives: Colitis is an inflammatory bowel disease characterized by colonic mucosal inflammation and chronic relapsing events represents. The purpose of this study is to evaluate effects of pharmacopuncture of anti-inflammatory herbal compound (AiC) applied to the different acupoints in the acute colitis induced by trinitrobenzenesulphonic acid (TNBS) intracolonic injection in rats. Methods: In Male Sprague - Dawley rats, weighing 250~400g, TNBS (5 mg/kg) was infused intrarectally through a silicon rubber catheter into the anus under isoflurane anaesthesia. Acupoints of LI4 (Hapkok), ST25 (Cheonchu), ST36 (Joksamni), and BL25 (Daejangsu) were intramuscularly injected by AiC, respectively (injection volume & times: 0.2 ml / acupoint, twice times on the 2nd & 3rd day). Expressions of cFos protein in the periaqueductal gray (PAG), locus coeruleus (LC), nucleus of solitary tract (Sol), and the 6th lumbar spinal cord (L6 s.c.) were observed at 24 hr after TNBS induced colitis by immunohistochemistry. Results: The expression of c-Fos protein in the L6 s.c., Sol, LC and PAG increased 24 hr after TNBS injection into colorectum as compared to normal and 50% ethanol treated group. AiC to LI4 inhibited the expression of c-Fos protein in Sol and PAG but not L6 s.c. and LC. AiC to ST36 showed significant inhibition the c-Fos expression in L6 s.c., Sol and PAG. AiC to ST25 only showed the effects in L6 s.c. and PAG. AiC to BL25 inhibited significantly the expression of c-Fos protein all over the areas. To investigate whether or not endogenous opioids are involved, intrathecal injection of naltrexone (30ug/30ul) was applied before the 2nd pharmacopuncture treatment 24 hr after TNBS-induced colitis in rat. Naltrexone reversed the inhibition of c-Fos protein expression in the spinal cord and brainstem. Conclusions: These data show that pharmacopuncture of Aic potently inhibits signal pathways ascending hypersensitivity of colorectum after TNBS induced colitis and depends on the endogenous opioids according to acupoints.

• Journal of the korean academy of Pediatric Dentistry
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• v.41 no.1
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• pp.80-84
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• 2014

Intractable ulcerating enterocolitis is an uncommon inflammatory bowel disease syndrome of neonatal onset first described in 1991. Intractable ulcerating enterocolitis usually presents in the neonate with a mouth ulceration and the subsequent development of perianal disease and colitis. In this case report, an infant, 18 days from birth, with ulcerative lesion on hard palate for systemic differential diagnosis about oral lesion is referred from the department depiatrics. At that time, there is no abnormality, except oral lesion-like Aphthous ulcer. The patient was discharged from pediatrics, but returned to the hospital 3weeks later with blood diarrhea. As a result of endoscopy, there were large ulcerating lesions and the patient was diagnosed intractable ulcerating enterocolitis. Early recognition of Intractable ulcerating enterocolitis appears to be beneficial because colectomy, as opposed to immunosuppression, appears to be effective in controlling disease symptoms and progression. Most of the infants who were affected intractable ulcerating enterocolitis were normal at birth and oral manifestation appeared earlier than others. So, it is very meaningful for dentists to know about Intractable ulcerating enterocolitis.

• Korean Journal of Acupuncture
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• v.24 no.2
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• pp.217-230
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• 2007

Objectives : Ulcerative colitis or Crohn's disease has been recognized as Ha-ri (下痢) or Jang-Byok in Korean oriental medicine. A purpose of the present study is to investigate the anti-inflammatory effect of moxi-tar herbal acupuncture at LI4 (HapGok) on 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis in rats and further elucidate the possibility of herbal acupuncture on ulcerative colitis which is chronic inflammatory disease of the gastrointestinal tract. Methods : Sprague-Dawley rats, weighing $170{\sim}190$ g, were subjected to intrarectal injection of either saline (300 ${\mu}l$, 500 ${\mu}l$) for a control or 2,4,6-trinitrobenzene sulphonic acid (TNBS) (300 ${\mu}l$, 500 ${\mu}l$) for a colitis, Moxi-tar (20 mg/ml) were subcutaneously injected to the LI4 just after the secondary injection time of TNBS in rats. To study the effects of Moxi-tar acupuncture in LI4, body weight, RBC count, WBC count, total protein, Paw edema rate, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels were observed. Results: Moxi-tar acupuncture in LI4 on TNBS-induced colitis inhibited the body weight lose rate but not effect RBC, WBC count. In addition, it inhibited the reduction of total protein concentration, paw edema, rate of protein leakage into CMC-pouch fluid, IgG levels and IgM levels. Conclusions : It is suggested that moxi-tar herbal acupuncture at LI4 helps to recover TNBS-induced colitis and plays an important role for an treatment of the irritable bowel syndrome (IBS).

• Clinical and Experimental Pediatrics
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• v.57 no.5
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• pp.226-231
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• 2014

Purpose: Kikuchi-Fujimoto disease (KFD) is a benign disease, which is characterized by a cervical lymphadenopathy with fever, and it often mimics malignant lymphoma (ML). 2-[$^{18}F$]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ($^{18}F$-FDG PET/CT) is a powerful imaging modality for the diagnosis, staging and monitoring of ML, with the limitations including the nonspecific FDG uptake in infectious or inflammatory processes. This study compared clinical manifestations and PET/CT findings between KFD and ML patients. Methods: We retrospectively reviewed the medical records of 23 patients with KFD and 33 patients with ML, diagnosed histopathologically, between January 2000 and May 2013 at the Department of Pediatrics, Yeungnam University Medical Center. Among them, we analyzed the clinical manifestations, laboratory findings and characteristics, and the amount of $^{18}F$-FDG uptake between 8 KFD and 9 ML patients who had $^{18}F$-FDG PET/CT. Results: The $^{18}F$-FDG PET/CT maximum standardized uptake values ($SUV_{max}$) ranged from 8.3 to 22.5 (mean, 12.0) in KFDs, and from 5.8 to 34.3 (mean, 15.9) in MLs. There were no significant differences in $SUV_{max}$ between KFDs and MLs. $^{18}F$-FDG PET/CT with ML patients showed hot uptakes in the extranodal organs, such as bone marrow, small bowel, thymus, kidney, orbit and pleura. However, none of the KFD cases showed extranodal uptake (P<0.001). $^{18}F$-FDG PET/CT findings of KFD with nodal involvement only were indistinguishable from those of ML. Conclusion: Patients who had extranodal involvement on PET/CT were more likely to have malignancy than KFD.

• 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.

• Journal of Yeungnam Medical Science
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• v.20 no.1
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• pp.79-84
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• 2003

Pyoderma gangrenosum is uncommon neutrophilic dermatosis characterized by richness of the mature neutrophilic polynuclear dermal infiltrate. Pyoderma gangrenosum is associated with variable diseases, most commonly inflammatory bowel disease, hematological diseases, malignancies, but it is reported rarely in rheumatoid arthritis. We report a case of pyoderma gangrenosum in rheumoid arthritis patient. A 50-year-old woman admitted to our hospital due to painful pretibial ulcerative skin lesions. She had been treated as rheumatoid arthritis for 8 years. At admission, body temperature was $36.5^{\circ}C$ and other vital sign was unremarkable. Physical examination revealed right pretibial ulceration, multiple pustules on left pretibial area and both palms. Laboratory studies revealed WBC count 7,600/uL (neutrophils 60.3%, eosinophil 3.2%), hemoglobin 11.4 g/dL, platelet count 319,000/uL, ESR 65 mm/hour. Other lab findings were also unremarkable. Skin biopsy was done, which showed dense dermal infiltrate of neutrophils and wound culture were negative. By 8 weeks after systemic high dose corticosteroid (1 mg/kg/day), cyclosporine A (5 mg/kg/day), sulfasalazine 2 g therapy, symptoms and skin ulceration were being improved. Without skin relapse, she is followed up our hospital with low dose corticosteroid and sulfasalazine.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.5
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• pp.478-483
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• 2010

Bisphosphonates are synthetic analogue and have high affinity on bone remodeling site. Since they have a long half-reduction time, they accumulate at bone and act for a long time. They are widely used in osteo-porosis derived from imflammatory bowel disease or postmenopausal osteoporosis patient for bone mineral density improvement. In addition, they neutralize hypercalcemia owing to bone metastasis of malignancy. However, a jaw bone necrosis was recently reported in some patients who have taken bisphosphonates for a long time. It is called Bisphosphonate Related Osteonecrosis of Jaws (BRONJ). It can come spontaneous-ly, but more often after oral surgery including tooth extraction. In this case, a 80-year-old woman was treated with bisphosphonate (sodium alendronate) for 2 years to improve bone mineral density. She had her left lower second molar tooth extracted at local clinic. After extraction, she had inflammatory symptoms like a pain, a cheek swelling, and a discharge of pus. She was referred to our clinic for treatment. We treated meticulously from dressing to surgery. After following up about 1.5 years, the jaw lesion was successfully healed. So we report this case.

• Biomolecules & Therapeutics
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• v.11 no.3
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.