• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.265-274
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• 2001

Purpose : Proctitis is one of acute complications encountered when radiotherapy was appled to the pelvis. Radiation-induced proctitis represents similar microscopic findings that are observed in inflammatory bowel disease (IBD). Nitric oxide (NO) plays an important role in the inflammatory process and many data suggest a close relationship between NO production and gastrointestinal inflammation. This study was aimed to establish the optimal radiation dose for radiation-induced proctitis in rat and to find a relationship between radiation proctitis and NO production. Materials and methods : Female Wistar rats, weighing from 150 to 220 g, received various doses(10-30 Gy) of radiation to the rectum. On the 5th and 10th day after irradiation, rectal specimens were evaluated grossly and microscopically. In addition, the degree of NO production by irradiation dose was evaluated by study with NOS expression and nitrite production in the irradiated rectal tissue. To evaluate relationship between radiation proctitis and NO, we administered aminoguanidine, iNOS inhibitor and L-arginine, substrate of NOS to rats from 2 days before to 7 days after the irradiation. Results : There were obvious gross and hostological changes after 17.5 Gy or higher radiation dose but not with 15 Gy or less radiation dose. Twenty Gy or higher dose of radiation caused Grade 4 damage in most of rectal specimens which were more likely to be related to the late complications such as fibrosis, rectal bleeding and rectal obstruction. A single fraction of 17.5 Gy to the rat rectum is considered to be an optimal dose to produce commonly experienced proctitis in the clinic. The result demonstrated that severity of microscopic damage of rectal mucosa from irradiation significantly correlated with iNOS over-expression. However, administration of iNOS inhibitor or substrate of iNOS did not influence the degree of rectal damage. Conclusion : A single fraction of 17.5 Gy irradiation to the rat rectum considered to be an optimal dose for radiation induced proctitis model. These results indicated that an excess production of NO contributes to pathogenesis of radiation-induced proctitis in part but was not the direct cause of rectal damage.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.309-316
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• 2009

Purpose: F-18 FDG can be accumulated in the liver, bowel, kidney, urinary tract, and muscles physiologically. The aim of this study was to evaluate the clinical value of dual time point 18F-FDG PET /8 imaging for the differentiation of the colonic focal uptake lesions. Materials and Methods: One hundred thirty two patients (M:F = 77:55, Age 62.8$\pm$11.6 years) underwent $^{18}$F-FDG PET/CT at two time points, prospectively: early image at 50-60 min and delayed image at 4-4.5 hours after the intravenous injection of $^{18}$F-FDG. Focally increased uptake lesions on early images but disappeared or shifted on delayed images defined a physiological uptake. For the differential evaluation of persistent focal uptake lesions on delayed images, colonoscopy and histopathologic examination were performed. SUVmax changes between early and delayed images were also compared. Results: Among the 132 patients, 153 lesions of focal colonic uptake were detected on early images of $^{18}$F-FDG PET/CT. Of these, 72 (47.1%) lesions were able to judge with physiological uptake because the focal increased uptake disappeared from delayed image. Among 81 lesions which was showed persistent increased uptake in delayed image, 61 (75.3%) lesions were confirmed as the malignant tumor and 14 (17.3%) lesions were confirmed as the benign lesions including adenoma and inflammatory disease. Remaining 6 (7.4%) lesions were confirmed as the physiological uptake because there was no particular lesion in the colonoscopy. In the malignant lesions, the calculated dual time point change for SUVmax ($\Delta$%SUVmax) was 20.8$\pm$18.7%, indicating a significant increase in SUVmax between the two point (p<0.01). In contrast, the change in SUVmax for the non-malignant lesions including benign lesions and physiological uptake was -13.7%$\pm$24.2%. For the differentiation of the malignant and non-malignant focal colonic uptake lesions, $\Delta$%SUVmax was the most effective parameter, and the cut-off value using -5% provided the best sensitivity, specificity, and accuracy. Conclusion: The dual time point $^{18}$F-FDG PET/CT imaging with SUVmax change evaluation could be an important noninvasive method for the differentiation of malignant and benign focal colonic uptake lesions including physiologic uptake.

• Pediatric Infection and Vaccine
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• v.27 no.3
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• pp.158-170
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• 2020

Purpose: We evaluated the incidence and characteristics of Clostridioides difficile infection (CDI) in Korean children. Methods: Medical records of patients aged 2-18 years and diagnosed with CDI at a tertiary hospital between 2009 and 2018 were analyzed. The patients were classified into three CDI groups: community-acquired (CA), community onset-health care facility-associated (CO-HCFA), and healthcare facility onset (HO). Results: The incidence of CDI increased from 1.00 to 10.01 cases per 10,000 admissions from 2009 to 2018 (P<0.001). As compared to the CA group, the HO group had a higher frequency of operation and malignancy as predisposing factors (40.4% vs. 0.0%, P=0.001; and 27.7% vs. 0.0%, P=0.027, respectively), frequency and number of previous antibiotic use (97.9% vs. 31.3%, P<0.001; and 2 vs. 0, P<0.001, respectively), and median postdiagnosis hospital stay (13 vs. 5 days, P=0.008). The CO-HCFA group had a lower median age and higher frequency of malignancy than the CA group (5 vs. 13 years, P=0.012; and 30.8% vs. 0.0%, P=0.030, respectively). As compared to the HO group, the CA group had a higher frequency of abdominal pain and hematochezia (56.3% vs. 10.6%, P=0.001; and 50.0% vs. 10.6%, P=0.002, respectively), inflammatory bowel disease (68.8% vs. 2.1%, P=0.001), and intravenous metronidazole treatment (37.5% vs. 2.1%, P=0.001). Conclusions: With the increasing incidence of pediatric CDI, awareness regarding its epidemiology and clinical characteristics is important to manage nosocomial infections.