Effect of Probiotics on Symptoms in Korean Adults with Irritable Bowel Syndrome

Hong, Kyoung Sup,Kang, Hyoun Woo,Im, Jong Pil,Ji, Geun Eog,Kim, Sang Gyun,Jung, Hyun Chae,Song, In Sung,Kim, Joo Sung The Korean Society of Gastroenterology; the Korean 2009 Gut and Liver Vol.3 No.2

<P><B>Background/Aims</B></P><P>Irritable bowel syndrome (IBS) is a troublesome disease. Some strains of probiotics reportedly exert remarkable immunomodulatory effects, and so we designed a prospective double-blind randomized placebo-controlled clinical study to assess their effects in Korean adults with IBS.</P><P><B>Methods</B></P><P>IBS patients who met Rome III criteria were randomly assigned to receive composite probiotics or placebo. A total of 20 billion lyophilized bacteria were administered twice daily for 8 weeks. Primary outcome variables were symptom scores consisting of abdominal pain, flatulence, defecation discomfort, and sum of symptom scores. A visual analogue scale was used to quantify the severity. Secondary outcome variables consisted of the quality of life and bowel habits including defecation frequency and stool form.</P><P><B>Results</B></P><P>Thirty-six and 34 patients were randomized to the probiotics and placebo groups, respectively. Intention-to-treat analysis showed significant reductions in pain after 8 weeks of treatment: -31.9 and -17.7 in the probiotics and placebo groups, respectively (p=0.045). The reductions in abdominal pain, defecation discomfort, and sum of scores were more significant in 58 patients with a score of at least 3 on the baseline stool-form scale.</P><P><B>Conclusions</B></P><P>Composite probiotics containing <I>Bifidobacterium bifidum</I> BGN4, <I>Lactobacillus acidophilus</I> AD031, and other species are safe and effective, especially in patients who excrete normal or loose stools.</P>

[Preclinical experience in stem cell therapy for digestive tract diseases].

Jeon, Myung Shin,Hong, Soon Sun Korean Society of Gastroenterology 2011 대한소화기학회지 Vol.58 No.3

<P>Adult stem cells are multipotent and self-renewing cells that contain several functions; i) migration and homing potential: stem cells can migrate to injured and inflamed tissues. ii) differentiation potential: stem cells which migrated to injured tissues can be differentiated into multiple cell types for repairing and regenerating the tissues. iii) immunomodulatory properties: stem cells, especially mesenchymal stem cells can suppress immune system such as inflammation. All those characteristics might be useful for the treatment of the digestive tract diseases which are complex and encompass a broad spectrum of different pathogenesis. Preclinical stem cell therapy showed some promising results, especially in liver failure, pancreatitis, sepsis, and inflammatory bowel disease. If we can understand more about the mechanism of stem cell action, stem cell therapy can become a promising alternative treatment for refractory digestive disease in the near future. In this review, we summarized current preclinical experiences in diseases of the digestive tract using stem cells. (Korean J Gastroenterol 2011;58:133-138).</P>

장관 베체트병의 병인과 치료

이창균,김효종 Korean Society of Gastroenterology 2007 대한소화기학회지 Vol.50 No.1

<P>Intestinal Behçet's disease (BD) refers to colonic ulcerative lesions documented by objective measures in patients with BD. Although the causes of intestinal BD are unknown, genetic, environmental, and immunological factors have been suggested. Intestinal BD is common in BD patients from Far East, while it is uncommon in those from the Middle East. The reasons for such peculiar geographic distribution in intestinal BD are unknown, but may provide clues for the elucidation of putative etiological agents or genetic factors that might be associated with intestinal BD. Although the treatment of Crohn's disease has improved significantly during past decade, the treatment of intestinal BD is still problematic. Corticosteroids, sulfasalazine, immunomodulators, and colchicines have been used to treat intestinal BD with varying degree of success. Thalidomide and its analogues also appear to be applicable. Monoclonal antibodies to TNF-alpha have recently been focused as a novel therapeutic option for patients with intestinal BD.</P>

The Biology of Cancer Stem Cells and Its Clinical Implication in Hepatocellular Carcinoma

The Korean Society of Gastroenterology; the Korean 2012 Gut and Liver Vol.6 No.1

<P>Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options in its advanced state. The molecular mechanisms underlying HCC remain unclear because of the complexity of its multi-step development process. Cancer stem cells (CSCs) are defined as a small population of cells within a tumor that possess the capability for self-renewal and the generation of heterogeneous lineages of cancer cells. To date, there have been two theories concerning the mechanism of carcinogenesis, i.e., the stochastic (clonal evolution) model and the hierarchical (cancer stem cell-driven) model. The concept of the CSC has been established over the past decade, and the roles of CSCs in the carcinogenic processes of various cancers, including HCC, have been emphasized. Previous experimental and clinical evidence indicated the existence of liver CSCs; however, the potential mechanistic links between liver CSCs and the development of HCC in humans are not fully understood. Although definitive cell surface markers for liver CSCs have not yet been found, several putative markers have been identified, which allow the prospective isolation of CSCs from HCC. The identification and characterization of CSCs in HCC is essential for a better understanding of tumor initiation or progression in relation to signaling pathways. These markers could be used along with clinical parameters for the prediction of chemoresistance, radioresistance, metastasis and survival and may represent potential targets for the development of new molecular therapies against HCC. This review describes the current evidence for the existence and function of liver CSCs and discuss the clinical implications of CSCs in patients demonstrating resistance to conventional anti-cancer therapies, as well as clinical outcomes. Such data may provide a future perspective for targeted therapy in HCC.</P>

The Effect of Rosiglitazone on the Cell Proliferation and the Expressions of p27 and Skp2 in<i>Helicobacter pylori</i>Infected Human Gastric Epithelial Cells

Kim, Sung-Soo,Cho, Young-Seok,Kim, Hyung-Keun,Shin, Ok-Ran,Chae, Hiun-Suk,Choi, Myung-Gyu,Chung, In-Sik The Korean Society of Gastroenterology 2010 대한소화기학회지 Vol.55 No.4

<P>Background/Aims: Ligands for peroxisome proliferator-activated receptorgamma (PPARgamma), a member of the ligand-activated nuclear receptor superfamily, exhibit anti-tumoral effects and are associated with de novo synthesis of proteins involved in regulating the cell cycle and cell survival/death. Helicobacter pylori (H. pylori) is an etiologic agent for gastric adenocarcinoma, and raises the cell turnover of gastric epithelium. The aim of this study was to investigate the effect of PPARgamma ligand rosiglitazone on the cell proliferation and the expressions of p27 and Skp2 protein in H. pylori infected gastric epithelial cells. Methods: We examined the expression of PPARgamma by Western blot in H. pylori infected AGS human gastric epithelial cells. The effect of rosiglitazone on the survival of H. pylori infected AGS cells was assessed by cell viability assay. After the treatment of rosiglitazone in H. pylori infected AGS cells, the expressions of p27 and Skp2 were assessed by Western blot. Results: The expression of PPARgamma protein was increased in H. pylori infected AGS cells. Cell growth was inhibited and decreased in dose- and time- dependent manner in H. pylori infected AGS cells treated with rosiglitazone. A decrease in Skp2 expression and a reciprocal increase in p27 expression were found in dose- and time-dependent manner in H. pylori infected AGS cells treated with rosiglitazone. Conclusions: Rosiglitazone inhibited the growth of H. pylori infected AGS cells. Rosiglitazone attenuated Skp2 expression, thereby promoting p27 accumulation in H. pylori infected human gastric epithelial cells. Further studies will be needed to find the effects of accumulation on cell turnover in H. pylori infection and the role in the H. pylori-associated gastric carcinogenesis.</P>

Proliferation of Hepatic Oval Cells via Cyclooxygenase-2 and Extracellular Matrix Protein Signaling during Liver Regeneration Following 2-AAF/Partial Hepatectomy in Rats

Bae, Si Hyun,Oh, Seh Hoon,Yoon, Seung Kew,Park, Joung Ah,Kim, Gi Dae,Hur, Wonhee,Choi, Jong Young,Oh, Il Hoan,Yoon, Kun Ho The Korean Society of Gastroenterology; the Korean 2011 Gut and Liver Vol.5 No.3

<P><B>Background/Aims</B></P><P>In the 2-acetylaminofluorene (2-AAF)/70% partial hepatectomy (PHx) model, the mechanism underlying the differentiation of activated hepatic oval cells (HOCs) into hepatocytes and bile ductile cells is unclear. We investigated the role of cyclooxygenase-2 (COX-2) in HOCs and the relationship between COX-2 and extracellular matrix proteins in cellular proliferation.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction, immunohistochemical staining, and Western blotting were used to assess COX-2 expression. The co-localization of COX-2 with Thy1, c-Met, epithelial cell adhesion molecule, and α-smooth muscle actin was also examined. Additionally, we investigated whether connective tissue growth factor (CTGF), fibronectin (FN), extracellular signal-regulated kinase 1/2 (P-ERK1/2), and AKT were expressed in HOCs.</P><P><B>Results</B></P><P>The expression of COX-2, prostaglandin E2 receptors, and c-Met was upregulated in HOCs. However, HOCs treated with the COX-2 inhibitor NS398 showed decreased COX-2, CTGF, FN, and AKT expression, whereas P-ERK1/2 was unaffected. Additionally, NS398 inhibited HOC proliferation, but not the proliferation of HOCs cultured on FN-coated dishes. Furthermore, the proliferative response of HOCs treated with NS398 was reversed by hepatic growth factor treatment.</P><P><B>Conclusions</B></P><P>These results suggest that HOC proliferation is mediated through COX-2, extracellular FN expression, and AKT activation. Thus, COX-2 plays an important role in HOC proliferation following acute injury.</P>

Sequential Changes in Aberrant Crypt Foci and Lectin Expression in the Early and Late Stages of DMH-Induced Colon Carcinogenesis in Rats

Won, Hye Sung,Maeng, Lee So,Chae, Hiun Suk,Kim, Hyung Keun,Cho, Young Suk,Kang, Jin-Hyoung,Jang, Hong Seok,Ryu, Mi-Ryeong The Korean Society of Gastroenterology; the Korean 2012 Gut and Liver Vol.6 No.2

<P><B>Background/Aims</B></P><P>The purpose of this study was to investigate the malignant potential of aberrant crypt foci (ACF) by measuring the multiplicity of crypts and lectin expression in the early and late stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis.</P><P><B>Methods</B></P><P>Six-week-old Wistar rats were injected subcutaneously with DMH for 27 weeks. We classified ACF according to the number of crypts per ACF as a few crypts (≤3 crypts, FC ACF) or numerous crypts (≥4 crypts, NC ACF). Immunohistochemistry was used to evaluate lectin expression.</P><P><B>Results</B></P><P>In the early stage, FC ACF (590/1,902, 31.0%) occurred more frequently than NC ACF (35/449, 7.8%); whereas in the late stage, NC ACF (176/449, 39.2%) occurred more frequently than FC ACF (324/1,902, 17.0%). The number of ACF peaked at 15 to 20 weeks. The ratio of NC/FC ACF increased gradually during carcinogenesis. The expression of both UEA1 and PNA was higher in NC ACF than FC ACF. Lectin expression increased in the late stage compared with the early stage.</P><P><B>Conclusions</B></P><P>The expression of lectin was higher in NC ACF and ACF in the late stage. Therefore, ACF with higher multiplicities in the late stage may have more malignant potential in DMH-induced colon carcinogenesis.</P>

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

Seo, Pyoung Ju,Kim, Nayoung,Kim, Joo-Hyon,Lee, Byoung Hwan,Nam, Ryoung Hee,Lee, Hye Seung,Park, Ji Hyun,Lee, Mi Kyoung,Chang, Hyun,Jung, Hyun Chae,Song, In Sung The Korean Society of Gastroenterology; the Korean 2012 Gut and Liver Vol.6 No.2

<P><B>Background/Aims</B></P><P>Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages.</P><P><B>Methods</B></P><P>For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A<SUB>2</SUB> (cPLA<SUB>2</SUB>) levels were measured after 24 hours.</P><P><B>Results</B></P><P>The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA<SUB>2</SUB> expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05).</P><P><B>Conclusions</B></P><P>NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.</P>

The Optimal Selection of Radiotherapy Treatment for Hepatocellular Carcinoma

Lee, Ik Jae,Seong, Jinsil The Korean Society of Gastroenterology; the Korean 2012 Gut and Liver Vol.6 No.2

<P>The majority of patients who present with hepatocellular carcinoma (HCC) are already at an advanced stage, and the tumors are unresectable. Radiotherapy (RT) technology can safely provide focused high-dose irradiation to these patients. A wide spectrum of RT technologiesis currently available, including internal RT consisting of Yttrium-90 (<SUP>90</SUP>Y), Iodine-131 (<SUP>131</SUP>I) anti-ferritin antibody and Homium-199 (<SUP>199</SUP>Ho) and external RT, such as three-dimensional conformal RT, intensity-modulated RT, helical tomotherapy, stereotactic body RT, and image-guided RT. However, it may be difficult for physicians to understand all of the available options and to select the optimal RT treatment. Physicians frequently query radiation oncologists on the practical indications of RT for managing patients with HCC. According to the Korean Liver Cancer Study Group practice guidelines, RT is considered appropriate for unresectable, locally advanced HCC without extrahepatic metastasis, a Child-Pugh class A or B, and tumors that occupy less than two-thirds of the liver with level II evidence. In this review, we discuss the application of various RT modalities based on disease status and the detailed indications for RT according to the Barcelona Clinic Liver Cancer staging system.</P>

Change of Clostridium difficile Colitis during Recent 10 Years in Korea

Lee, Yune Jeong,Choi, Myung Gyu,Lim, Chul Hyun,Jung, Woong Ryong,Cho, Hyun Sun,Sung, Hye Young,Nam, Kwan Woo,Chang, Jae Hyuck,Cho, Yu Kyung,Park, Jae Myung,Kim, Sang Woo,Chung, In Sik The Korean Society of Gastroenterology 2010 대한소화기학회지 Vol.55 No.3

<P>Background/Aims: Our clinical experience and recent published literatures suggest that Clostridium difficile colitis (CDC) has become more common and potentially more pathogenic in recent years. The aim of study was to evaluate changes in the epidemiological features of CDC in hospitalized patients in Korea. Methods: We retrospectively reviewed all patients of CDC diagnosed at Kangnam St. Mary Hospital from 1998 to 2007. CDC was defined as having a positive C. difficile cytotoxicity assay, or endoscopic or pathologic evidence of CDC. Results: A total of 189 cases (male 73, female 116, mean age 63.3 years) of CDC were diagnosed during the study period. The prevalence of CDC increased from 1.9/10,000 patient admissions in 1998-1999 to 8.82/10,000 patient admissions in 2006-2007. One hundred sixty three indication for cases (86.2%) of patients identified a prior use of antibiotics in the 2 months preceding diagnosis. The most common antibiotic use was prophylactic use during perioperational period (33.3%) followed by pneumonia (23.3%). The overall response rate to initial antibiotics was 82.7%. One hundred seventy two (91%) patients were initially treated with metronidazole. The response rate was 84.3%. All patients with initial failure to metronidazole were successfully treated by vancomycin. The response rate of vancomycin as first treatment was 80%. Three deaths were associated with CDC despite the use of combination of metronidazole and vancomycin. Conclusions: The prevalence of CDC in hospitalized patients in Korea significantly increased from 1998 to 2007.</P>