Nuclear Factor Erythroid 2-Related Factor 2/Kelch-Like ECH-Associated Protein 1 as a Predictor of Prognosis and Radiotherapy Resistance in Patients With Locally Advanced Rectal Cancer: A Prospective Analysis

Background@#The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/ Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). @*Methods@#In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. @*Results@#The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. @*Conclusion@#CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance.The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

Inflammatory bowel disease–associated intestinal fibrosis

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

Upregulation of Toll-like Receptor 2 in Dental Primary Afferents Following Pulp Injury

Pulpitis (toothache) is a painful inflammation of the dental pulp and is a prevalent problem throughout the world. This pulpal inflammation occurs in the cells inside the dental pulp, which have host defense mechanisms to combat oral microorganisms invading the pulp space of exposed teeth.This innate immunity has been well studied, with a focus on Toll-like receptors (TLRs). The function of TLR4, activated by Gram-negative bacteria, has been demonstrated in trigeminal ganglion (TG) neurons for dental pain. Although Gram-positive bacteria predominate in the teeth of patients with caries and pulpitis, the role of TLR2, which is activated by Gram-positive bacteria, is poorly understood in dental primary afferent (DPA) neurons that densely innervate the dental pulp. Using Fura-2 based Ca2+ imaging, we observed reproducible intracellular Ca2+ responses induced by Pam3 CSK 4 and Pam2 CSK 4 (TLR2-specific agonists) in TG neurons of adult wild-type (WT) mice. The response was completely abolished in TLR2 knock-out (KO) mice. Single-cell RT-PCR detected Tlr2 mRNA in DPA neurons labeled with fluorescent retrograde tracers from the upper molars. Using the mouse pulpitis model, real-time RT-PCR revealed that Tlr2 and inflammatory-related molecules were upregulated in injured TG, compared to non-injured TG, from WT mice, but not from TLR2 KO mice. TLR2 protein expression was also upregulated in injured DPA neurons, and the change was corresponded with a significant increase in calcitonin gene-related peptide (CGRP) expression. Our results provide a better molecular understanding of pulpitis by revealing the potential contribution of TLR2 to pulpal inflammatory pain.

The Effect of Housing Unaffordability on the Incidence of Depression in Korean Adults: Focusingon Korean Longitudinal Study of Aging

Background@#This study examined the effect of housing affordability on the incidence of depression in Korean adults aged 45 years and above usingthe Korean Longitudinal Study of Aging (KLoSA). @*Methods@#Five-year data from wave two to wave six of the KLoSA provided by the Ministry of Labor were used. In the first year of KLoSA in 2006, amongthose who did not suffer from depression, ones who had one or more of the survey data from the second to the sixth were analyzed. generalizedestimating equation (GEE) regression analysis and chi-square test were used as data processing methods. @*Results@#According to the 2010 data, out of 4,606 people, 3,558 (77.3%) were in the affordable group, and 1,048 (22.8%) in the experienced overburdengroup. The result of regression analysis with controlling general characteristics as covariates showed that the experienced overburden group had ahigher incidence of depression than the affordable group. A longitudinal analysis of housing affordability and incidence of depression for five yearsrevealed no significant difference in the incidence of depression. However, the overall share of overburden experience increased steadily. Acomparison of the incidence of depression between the affordable and experienced overburden groups in each year showed that the incidence ofdepression was statistically higher each year. @*Conclusion@#Housing affordability increases the incidence of depression, and eight years of data indicated depression in the experienced overburdengroup to be higher than the affordable group.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

OBJECTIVE@#To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC).@*METHODS@#The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting.@*RESULTS@#Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment.@*CONCLUSIONS@#The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

Objective To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC). Methods The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α PGE

Is Preoperative Chemotherapy Safe for Patients with Colorectal Liver Metastases Undergoing Metastasectomy?

PURPOSE: Controversies regarding preoperative versus postoperative chemotherapy for patients having hepatic metastases of colorectal primary made us elucidate the safety of chemotherapy. By examining the histopathologic changes in the liver following preoperative chemotherapy and analyzing the relation between surgical outcomes and preoperative chemotherapy, we were able to answer whether preoperative chemotherapy is safe. METHODS: We analyzed 38 patients who underwent chemotherapy before resection of hepatic metastasis from colorectal primary, retrospectively. Types of chemotherapy regimen were FL (5-FU+leucovorin), FOLFOX4 (oxaliplatin+5-FU+leucovorin), and FOLFIRI (irinotecan+5-FU+leucovorin). Results of liver function tests were compared before and after preoperative chemotherapy. One pathologist reviewed the degree of hepatic injury from resected specimens. Associations between the histological findings of hepatic injury and surgical outcomes and chemotherapeutic agents were examined. RESULTS: Histopathologic analysis revealed severe liver injury was present in 12 patients (31.6%). In further detail, moderate to severe sinusoidal dilatation was found in 3 patients (25%), steatosis of more than 30% was identified in 9 patients (75%), and steatohepatitis Kleiner score of > or =4 in 5 patients (41.7%). Preoperative chemotherapy did not affect the biochemical profiles of liver function. The overall perioperative complication rate was 5.3% (n=2). There was no difference in postoperative morbidity or mortality from reported results following hepatectomy. CONCLUSION: We found preoperative chemotherapy definitely induced histopathologic changes of hepatotoxicities. Even so, preoperative chemotherapy did not increase morbidity or mortality after hepatic metastasectomy. Preoperative chemotherapy seems to be safe in performing curative hepatic resection for the metastases.

Efficacy of Endoscopic Ultrasonography for Prediction of Tumor Depth in Gastric Cancer

PURPOSE: As the proportion of early gastric cancer (EGC) has recently been increased, minimally invasive treatment is currently accepted as main therapy for EGC. Accurate preoperative staging is very important in determining treatment options. To know the accuracy of endoscopic ultrasonography (EUS), we compared the depth of invasion of the tumor with preoperative EUS and postoperative pathologic findings. MATERIALS AND METHODS: We retrospectively analyzed 152 patients who underwent EUS before laparoscopic gastrectomy. The preoperative EUS results were compared with the pathological findings. RESULTS: The overall proportion of coincidence for depth of invasion between EUS and pathologic results was 41.4%. Univariate analysis showed that the rate of corrected prediction of EUS for tumor depth significantly decreased for the lesions more than 3cm in diameter (P=0.033), and those with a depressed morphology (P=0.035). In multivariate analysis, the depressed type (P=0.029, OR=2.873) and upper lesion (P=0.035, OR=2.151) was the significantly independent factors influencing the inaccurate prediction of EUS for tumor depth. CONCLUSIONS: When we decide the treatment modality considering the clinical depth of invasion by EUS, the possibility of discordance with pathologic results should be considered for the lesions located in the upper third of the stomach and with a depressed morphology.

Limitations of 99mTc-DMSA scan in diagnosing acute pyelonephritis in children / 소아과

PURPOSE: We aimed to prove the relative limitation of 99mTc-DMSA scintigraphy (DMSA) compared to computed tomography (CT) in diagnosing acute pyelonephritis (APN) in children. METHODS: Since September 2006, after a 64-channel CT was imported, 10 DMSA false-negative patients have been identified: these patients underwent a CT scan for acute abdomen or acute febrile symptoms and were diagnosed as having APN; however, their DMSA scans were clear. We focused on these 10 DMSA false-negative patients and analyzed their clinical findings and CT results. We used Philips Brilliance Power 64-channel CT scanner for the CT scan and Siemens Orbitor Nuclear Camera 60 Hz for the DMSA scan. RESULTS: The 10 DMSA false-negative patients were mostly males (80%) and infants (80%). They had fever for a mean of 1.1-day duration before admission and showed increase in acute reactants: leukocyte, erythrocyte sedimentation rate, and C-reactive protein. The CT findings of renal lesions were focal in 6 (60%) cases and diffuse in 4 (40%) cases, and most of the lesions were unilateral in 80% of patients. CT proved that 22 renal lesions were neglected by DMSA. Differential renal function test by DMSA was also of no use in the evaluation of renal lesions. CONCLUSION: In this study, DMSA scan showed limitation in finding renal cortical lesions of CT-proven APN patients. DMSA false-negative results seem to occur at early-phase disease of infantile age, but more prospective studies are needed to determine the reasons and their prevalence.

Effect of Chlorella intake on Cadmium metabolism in rats

This study was performed to investigate the effect of chlorella on cadmium (Cd) toxicity in Cd- administered rats. Sixty male Sprague-Dawley rats (14 week-old) were blocked into 6 groups. Cadmium chloride was given at levels of 0 or 325 mg (Cd: 0, 160 ppm), and chlorella powder at levels of 0, 3 and 5%. Cadmium was accumulated in blood and tissues (liver, kidney and small intestine) in the Cd-exposed groups, while the accumulation of Cd was decreased in the Cd-exposed chlorella groups. Fecal and urinary Cd excretions were remarkably increased in Cd-exposed chlorella groups. Thus, cadmium retention ratio and absorption rate were decreased in the Cd exposed chlorella groups. Urinary and serum creatinine, and creatinine clearance were not changed in experimental animals. In addition, metallothionein (MT) synthesis in tissues was increased by Cd administration. The Cd-exposed chlorella groups indicated lower MT concentration compared to the Cd-exposed groups. Moreover, glomerular filtration rate (GFR) was not changed by dietary chlorella and Cd administration. According to the results above, this study could suggest that Cd toxicity can be alleviated by increasing Cd excretion through feces. Therefore, when exposed to Cd, chlorella is an appropriate source which counteracts heavy metal poisoning, to decrease the damage of tissues by decreasing cadmium absorption.

Postprandial hypoglycemic effect of mulberry leaf in Goto-Kakizaki rats and counterpart control Wistar rats

Postprandial hypoglycemic effect of mulberry leaf (Morus alba L.) was compared in two animal models: Goto-Kakizaki (GK) rats, a spontaneous non-obese animal model for type II diabetes, and their counterpart control Wistar rats. First, the effect of a single oral administration of mulberry leaf aqueous extract (MLE) on postprandial glucose responses was determined using maltose or glucose as substrate. With maltose-loading, MLE reduced peak responses of blood glucose significantly in both GK and Wistar rats (P < 0.05), supporting the inhibition of alpha-glucosidase by MLE in the small intestine. With glucose-loading, MLE also significantly reduced blood glucose concentrations, measured at 30 min, in both animal models (P < 0.01), proposing the inhibition of glucose transport by MLE. Next, dried mulberry leaf powder (MLP) was administered for 8 weeks by inclusion in the diet. By MLP administration, fasting blood glucose was significantly reduced at weeks 4 and 5 (P < 0.05), but then returned to values that were similar to those of the control at the end of experimental period in GK rats. Insulin, HOMA-IR, C-reactive protein, and triglycerides tended to be decreased by MLP treatment in GK rats. All other biochemical parameters were not changed by MLP administration in GK rats. Collectively, these findings support that MLE has significant postprandial hypoglycemic effect in both non-obese diabetic and healthy animals, which may be beneficial as food supplement to manage postprandial blood glucose. Inhibitions of glucose transport as well as alpha-glucosidase in the small intestine were suggested as possible mechanisms related with the postprandial hypoglycemic effect of MLE.

Outcome and Prognosis in Critically Ill Children Receiving Continuous Renal Replacement Therapy

PURPOSE: Continuous renal replacement therapy(CRRT) has been the first choice for the treatment of acute renal failure in critically ill children not only in western countries but also in Korea. However, there are very few studies that have analyzed the outcome and prognosis of this modality in Korean children. We performed this study to evaluate the factors associated with the outcome and prognosis of patients treated with CRRT. METHODS: We retrospectively reviewed the medical records of 32 children who had received CRRT at Severance hospital from 2003 to 2006. The mean age was 7.5 years(range 4 days- 16 years) and the mean body weight was 25.8 kg (range 3.2-63 kg). RESULTS: Eleven(34.4%) of the 32 patients survived. Bone marrow transplantation and malignancy were the most common causes of death and underlying disease leading to the need for CRRT. Mean patient weight, age, duration of CRRT, number of organ failures, urine output, estimated glomerular filtration rate(eGFR), C-reactive protein, and blood urea level did not differ significantly between survivors and nonsurvivors. (1) Pediatric risk of mortality(PRISM) III score at CRRT initiation(9.8+/-5.3 vs. 26.7+/-7.6, P<0.0001), (2) maximum pressor number (2.1+/-1.2 vs. 3.0+/-1.0, P=0.038), and (3) the degree of fluid overload(5.2+/-6.0 vs. 15.0+/-8.9, P=0.002) were significantly lower in survivors than in nonsurvivors. Multivariate analysis revealed that fluid overload was the only independent factor reducing survival rate. CONCLUSION: CRRT was successfully applied to the treatment of acute renal failure in a wide range of critically ill children. To improve survival, we suggest the early initiation of CRRT to prevent the systemic worsening and progression of fluid overload in critically ill children with acute renal failure.

A Case of Hemolytic Uremic Syndrome in a Child with Ischemic Colitis

Hemolytic uremic syndrome(HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia and the most common pathogen is Escherichia coli (E. coli) O157:H7. Ischemic colitis, which rarely occurs in children, is due to the reduced local blood flow to the intestine, tissue necrosis and secondary bacterial infection. We describe a patient who was admitted with abdominal pain, vomiting and hematochezia, and diagnosed as ischemic colitis by barium enema. This patient showed hemolytic anemia, thrombocytopenia and progressive renal failure and was subsequently diagnosed as hemolytic uremic syndrome. After hemodialysis, the patient showed improvement of symptoms and resolution of renal failure and ischemic colitis.

Clinical Observation of Mesenteric Lymphadenitis in Children / 소아과

PURPOSE: Mesenteric lymphadenitis is classified into acute and chronic, specific and nonspecific types according to clinical aspect and causative disease. We under took this study to find out clinical aspects, associated diseases and hospital course of mesenteric lymphadenitis in children. METHODS: We examined 98 children aged from 18 months to 14 years who visited Dongsan Medical Center for abdominal pain between March 1998 and May 2002. Ultrasonography was performed and medical records were analysed. The specific group had a causative disease, and the chronic group had persistent clinical symptom over three months. RESULTS: Symptoms were chronic in 4% of the patients and acute in 96%. Most of the patients were in oen to five years of age. In the acute group, abdominal pain, vomiting, fever and diarrhea were shown commonly in order, and average WBC count was normal. Gastroduodenitis, tonsillitis, pneumonia and enterocolitis were accompanied in the acute specific group. Ultrasonograms of abdomens showed lymph node enlargement. In the acute group, symptoms were improved within one week. Lymph node enlargement was noted on follow up ultrasonograms in the chronic group. Gastrocolonoscopy of chronic group showed one case of H. pylori positive duodenitis, one case of ulcerative colitis, and two cases of Crohn's disease. CONCLUSION: There was no statistical significance in clinical aspect, laboratory findings and hospital course between the patients with specific etiology and nonspecific etiology. Symptoms improved within one week in patients in the acute group. If abdominal pain persists, additional examinations such as endoscopic biopsy, stool cultures, or small bowel studies should be performed to determine the underlying cause.

Endoscopic Findings of Children with Henoch-Schonlein Purpura

PURPOSE: This study was performed to analyze the endoscopic findings in Henoch-Schonlein purpura patients, and to compare the differences in endoscopic findings according to age and gastrointestinal symptoms. METHODS: We examined children with Henoch-Schonlein purpura aged 3 to 15 years between September 1996 and October 2002. The total number studied was 65, consisting of 41 boys and 24 girls. Endoscopy was performed and the results were analysed. RESULTS: Among 65 cases, 12 cases of duodenitis, nine cases of gastritis and duodenitis, six cases of duodenal erosion, five cases of gastritis, five cases of duodenal ulcer, two cases of gastric ulcer and one case of colonic erosion were noted. Endoscopic abnormality was found in 38 of 53 who had gastrointestinal symptoms, and in two of 12 who didn't have gastrointestinal symptoms. CONCLUSION: Most of the gastrointestinal symptoms in Henoch-Schonlein purpura patients were relieved without complication. But in some cases severe symptoms such as hematemesis, melena, and abdominal pain localized to epigastric area were developed when diagnosis was delayed. Prompt endoscopy will be helpful for diagnosis and therapy of Henoch-Schonlein purpura with gastrointestinal involvement.

A Case of Goltz Syndrome

Goltz syndrome(focal dermal hypoplasia) is a rare disorder characterized by ectodermal and mesodermal dysplasia described in 1962 by Goltz. In Korea, one case of Goltz syndrome was reported in 1994. The inheritance mode is mostly X-linked dominant. Skin abnormality is the most common manifestation including hypoplasia of the dermis. Skeletal involvement such as syndactyly, polydactyly, scoliosis, kyphosis and spina bifida occulta may be present, also ocular and dental abnormalities are reported. Radiologic findings are the osteopathy and striation of the long bone. We experienced a case of Goltz syndrome in a 9-year old female who was presented with right side hypotrophy, focal dermal hypoplasia, ocular(anidria, microcornea), dental(oligodontia, amelogenesis) and skeletal(syndactyly) abnormalities. Skin biopsy was performed and showed decreased expression of type I collagen gene with Northern blotting.

A Clinical Study of Children Who Showed Benign Hemophagocytic Histiocytes in Bone Marrow Examination

PURPOSE: The aim of this study is to find a method to diagnose and treat children who showed benign hemophagocytic histiocytes in bone marrow examination. METHODS: We analyzed the clinical data of thirty patients retrospectively who showed benign hemophagocytic histiocytes in bone marrow examination from January 1995 to November 2001 at Keimyung University Dong-san Hospital. Bone marrow histiocytes were classified into a few, some, and many according to the number of histiocytes comparing with the white cells. RESULTS: The age of thirty patients ranged from two months to 15 years. The median age was 5.6 years with male predominance(2.3 : 1). The most frequent clinical manifestation was fever; others were respiratory symptom, hepatosplenomegaly, lymphadenopathy and skin rash(in order of frequency). Common laboratory findings were leukopenia, thrombocytopenia, anemia and abnormal liver function test. Infection was present in 30 patients; causative organisms were documented in 15 patients, and bacterial infection was more common. Epstein Barr virus was the cause of infection in four patients. Bone marrow examination showed a few(20.0%), some(75.0%) and many(30.0%) hemophagocytic histiocytes. Combination immunochemotherapy including immunoglobulin, steroids and cyclosporine were helpful in 22 out of 30 patients. The mortality rate was high in young patients who showed some to many hemophagocytic histiocytes. CONCLUSION: Bone marrow examinations and early detection of histiocytes will be helpful in children who have fever, hepatosplenomegaly and abnormal liver function test. Immunochemotherapy were helpful and further investigation will be needed for the detection of the relationship between the bone marrow findings and prognosis.

Clinical Features of Spontaneous Neonatal Gastric Perforation

PURPOSE: Spontaneous neonatal gastric perforation is a rare neonatal event which is associated with high mortality. The aim of this retrospective study is to investigate the diagnosis and the treatment of neonatal spontaneous gastric perforation. METHODS: From January 1991 to December 2000, eight cases of neonatal gastric perforation were presented at Keimyung University Dongsan Medical Center. RESULTS: Among 8 neonates (7 males and 1 females), 2 were premature infants. 7 cases (87.5%) had symptoms onset in first 4 days of life. The most presenting signs were abdominal distension, vomiting, and respiratory difficulty. The most common X-ray finding was pneumoperitoneum (87.5%) and the most common site of perforation was greater curvature (75%). The combined congenital anomalies were malrotation of small intestine, teratoma, and partial duodenal obstruction. The predisposing causes may be associated with congenital intestinal anomaly, necrotizing enterocolitis, and too fast increased formula. All the cases underwent surgical repairs. The mortality rate was 37.5%, and the surgical procedure performed 24 hours after presumed disease onset represented poor outcome (mortality rate 67%). CONCLUSION: This report suggests that early diagnosis and early management before clinical deterioration of metabolic status may improve the prognosis for neonatal spontaneous gastric perforation patient.

Neonatal Systemic Candidiasis : Comparison of Clinical Manifestations between Fullterm and Preterm Infants / 대한주산의학회잡지

No abstract available.

A Case of Cri-du-chat Syndrome with Genitourinary Anomaly / 대한주산의학회잡지

No abstract available.