Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon.

Little is known about the time course of aging on interstitial cells of Cajal (ICC) of colon. The aim of this study was to investigate the change of morphology, ICC, and neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the aged rat. The proximal colon of 344 Fischer rats at four different ages (6, 31, 74 wk, and 2 yr) were studied. The immunoreactivity of c-Kit, nNOS, anti-protein gene product 9.5, and synaptophysin were counted after immunohistochemistry. The c-kit, stem cell factor (ligand of Kit), and nNOS mRNA were measured by real-time PCR. c-Kit and nNOS protein were assessed by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The area of intramuscular fat deposition significantly increased with age after 31 wk. c-Kit-immunoreactive ICC and nNOS-immunoreactive neurons and nerve fibers significantly declined with age. mRNA and protein expression of c-kit and nNOS decreased with aging. The functional study showed that the spontaneous contractility was decreased in aged rat, whereas EFS responses in the presence of atropine and L-NG-Nitroarginine methyl ester were increased in aged rat. In conclusion, the decrease of proportion of proper smooth muscle, the density of ICC and nNOS-immunoreactive neuronal fibers, and the number of nNOS-immunoreactive neurons during the aging process may explain the aging-associated colonic dysmotility.

Gastroprotective effect of Cochinchina momordica seed extract in nonsteroidal anti-inflammatory drug-induced acute gastric damage in a rat model.

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Status of primary liver cancer found through routine health check-up.

This study aimed to investigate the status of primary liver cancers found through a routine health check-up. The data of subjects who were diagnosed with primary liver cancer for the first time through a routine health check-up during a period of 8-yr were analyzed. Primary liver cancers were detected for the first time in 34 subjects among 91,219 routine health check-up subjects. Only 11.8% of primary liver cancer subjects had been under previous surveillance. Of them, 55.8% were positive for HBsAg, 17.7% were positive for anti-HCV, and 8.8% were heavy alcohol comsumers. However, 17.7% of the subjects were neither heavy alcohol consumers nor positive for both HBsAg and anti-HCV. Of the subjects, 50.0% had a single nodular tumor, 23.5% had multi-nodular tumors, and 26.5% had an infiltrative tumor. A routine health check-up may provide beneficial opportunities to detect a liver cancer in a very early stage. It is beneficial to start surveillance in high-risk subjects for liver cancer or to detect any liver cancer in subjects without risk factors of chronic viral hepatitis or heavy alcohol consumption.

The Effect of Cochinchina momordica Seed Extract on Gastric Acid Secretion and Morphologic Change in Aged Rat Stomach.

BACKGROUND/AIMS: Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to assess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat. METHODS: Acid secretions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, respectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H(+)-K(+)-ATPase were determined. The area of connective tissue of lamina propria was measured. RESULTS: Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H(+)-K(+)-ATPase significantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of connective tissue. CONCLUSIONS: As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to comparable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach.

Prevalence and risk factors of Helicobacter pylori infection in Korea: nationwide multicenter study over 13 years.

BACKGROUND: The aim of this study was to evaluate the time trend of seropositivity of Helicobacter pylori (H. pylori) over the period of 13 years in an asymptomatic Korean population, and investigate associated risk factors. METHODS: This cross-sectional nationwide multicentre study surveyed anti-H. pylori IgG antibodies in 19,272 health check-up subjects (aged [greater than and equal to]16 years) in 2011. Risk factors for H. pylori infection were investigated using logistic regression. Seropositivity in asymptomatic subjects without H. pylori eradication was compared between the years 1998 and 2005. Birth cohort effects were also evaluated. RESULTS: After exclusion of subjects with a history of H. pylori eradication therapy (n = 3,712, 19.3%) and gastric symptoms (n = 4,764, 24.7%), the seroprevalence of H. pylori infection was 54.4% in 10,796 subjects. This was significantly lower than the seroprevalence of 59.6% in 2005 and that of 66.9% in 1998, and this decrease of seropositivity of H. pylori became widespread across all ages and in most areas of the country. This decreasing trend could be explained by cohort analysis. All younger birth cohorts had a lower seroprevalence of H. pylori than older birth cohorts at the same age. Decreased seroprevalence within the same birth cohorts also accounted for this phenomenon. Clinical risk factors of H. pylori infection were higher cholesterol level ([greater than and equal to] 240 mg/dl) (OR = 1.33; 95% CI = 1.14-1.54), male gender, older age, low income, and residence in a rural area. CONCLUSIONS: A decreasing trend of H. pylori seroprevalence due to a birth cohort effect requires further studies on its related human host factors as well as socio-economic and hygienic factors. In addition, the relationship between H. pylori infection and high cholesterol level needs more investigation regarding underlying pathogenesis.

Incidence and short-term mortality from perforated peptic ulcer in Korea: a population-based study.

BACKGROUND: Perforated peptic ulcer (PPU) is associated with serious health and economic outcomes. However, few studies have estimated the incidence and health outcomes of PPU using a nationally representative sample in Asia. We estimated age- and sex-specific incidence and short-term mortality from PPU among Koreans and investigated the risk factors for mortality associated with PPU development. METHODS: A retrospective population-based study was conducted from 2006 through 2007 using the Korean National Health Insurance claims database. A diagnostic algorithm was derived and validated to identify PPU patients, and PPU incidence rates and 30-day mortality rates were determined. RESULTS: From 2006 through 2007, the PPU incidence rate per 100 000 population was 4.4; incidence among men (7.53) was approximately 6 times that among women (1.24). Incidence significantly increased with advanced age, especially among women older than 50 years. Among 4258 PPU patients, 135 (3.15%) died within 30 days of the PPU event. The 30-day mortality rate increased with advanced age and reached almost 20% for patients older than 80 years. The 30-day mortality rate was 10% for women and 2% for men. Older age, being female, and higher comorbidity were independently associated with 30-day mortality rate among PPU patients in Korea. CONCLUSIONS: Special attention should be paid to elderly women with high comorbidity who develop PPU.

Incidence and 30-day mortality of peptic ulcer bleeding in Korea.

OBJECTIVES: To estimate the rates of peptic ulcer bleeding (PUB) incidence and the association of demographic factors with 30-day mortality after PUB. METHODS: Diagnostic algorithms for PUB were derived and validated on the basis of 115 true PUB patients at one tertiary hospital in 2005, followed by estimation of age-specific PUB incidence and 30-day mortality rates, using the Korean National Health Insurance claim database. A Cox proportional hazard model was used to determine the impact of demographic factors on the 30-day mortality rate ratio (MRR) after PUB. RESULTS: The diagnostic algorithm showed 89 and 88% positive predictive value and sensitivity, respectively. On the basis of this algorithm, the rate of PUB incidence was 22.1 per 100 000 during 2006-2007 and the age-specific incidence rate increased with advanced age. This incidence rate was more than three times higher among men than women. Among 21 107 PUB patients, the overall 30-day mortality rate was 2.15%, but it ranged from 0.83% for patients younger than 60 years to 7.65% for patients older than 80 years. The adjusted 30-day mortality rate ratio for patients older than 80 was 8.13 (95% confidence interval 6.10-10.8) compared with those younger than 60 and 7.09 (95% confidence interval 2.78-4.51) for patients with a high level of comorbidity compared with a low level of comorbidity. CONCLUSION: PUB incidence was higher among men and increased with advanced age. Increased 30-day mortality was observed in association with increasing age, after adjusting for comorbidity.

Predictive factors for improvement of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication: a three-year follow-up study in Korea.

BACKGROUND AND AIMS: To date, data on the effects of anti-Helicobacter therapy on the improvement of atrophic gastritis (AG) and intestinal metaplasia (IM) have been conflicting. This study was performed to investigate whether eradication of H. pylori could lead to the improvement of AG and IM, and the prognostic factors associated with the improvement of AG and IM. METHODS: Four hundred patients consisting of H. pylori-negative (n = 116) and H. pylori-positive (n = 284) groups were followed up 1 and 3 years after initial H. pylori tests. Serum levels of pepsinogen (PG), bacteria, environmental factors, and genetic polymorphisms were determined. RESULTS: The grade of corpus atrophy decreased at 1 and 3 years after successful eradication (p < .001 and p = .033, respectively). However, there was no significant change in the IM in the antrum and in the corpus. Prediction factors for the improvement of corpus AG by H. pylori eradication were baseline low PG I/II ratio (≤3), high salt intake, and corpus-predominant gastritis. IM improvement was also associated with spicy food intake and high baseline grade of IM, in addition to these factors. In addition, IL-1B-511 C/T and IL-6-572 C/G alleles were found to inhibit IM improvement. However, H. pylori-negative and noneradicated group did not show any significant change in AG or IM. CONCLUSION: Corpus AG was reversed by H. pylori eradication, and improvement of IM by H. pylori eradiation was more definite in patients with severe IM, low PG I/II ratio, and corpus-predominant gastritis, suggesting that H. pylori eradication is valuable even in severe cases.

The Role of CDX2 in Intestinal Metaplasia Evaluated Using Immunohistochemistry.

BACKGROUND/AIMS: Intestinal metaplasia (IM) has been regarded as a premalignant condition. This study evaluated the role of the transforming factor CDX2 according to the severity and type of IM. METHODS: This analysis was performed on 383 subjects with IM in the antrum and/or body, with diagnoses that were categorized as controls, dysplasias, and gastric cancers. The IM grades were classified into four groups as negative, mild, moderate or severe using the updated Sydney scoring system. The IM subtypes were categorized as type I, type II, and type III using high iron diamine and alcian blue (pH 2.5) staining. The CDX2 expression in the IM foci was evaluated using immunohistochemistry in specimens from the antrum and/or body. RESULTS: CDX2 expression increased according to IM severity (p=0.001) but was not associated with the IM subtype (p=0.881) in the antrum specimens. Similarly, CDX2 expression increased according to the IM grade (p=0.001) but was not associated with the IM subtype (p=0.755) in the body specimens. CDX2 expression was also increased according to baseline disease in the antrum, especially dysplastic and GC group (p=0.003), but not in the body (p=0.582). However, status of Helicobacter pylori infection was not associated with CDX2 expression in the antrum (p=0.692) and body (p=0.271). CONCLUSIONS: These results show that CDX2 expression is associated with the IM grade regardless of the IM subtype and that it was more frequent in the dysplasia group. These results suggest that CDX2 expression might play an important role in the progression of IM in various environments that can affect neoplastic change.

Analysis of direct medical care costs of peptic ulcer disease in a Korean tertiary medical center.

OBJECTIVES: There have been no reported data on the medical care cost of idiopathic peptic ulcer disease (PUD) compared with H. pylori (+) and/or NSAID (+) cases although H. pylori-negative idiopathic ulcers are increasing. The aim of this study was to investigate the direct medical care costs of PUD based on whether it was H. pylori infection/from NSAIDs or idiopathic. MATERIAL AND METHODS: One hundred and seventy three patients with PUD comprising H. pylori and/or NSAID use-associated PUD (n = 145) and idiopathic PUD (n = 28) were prospectively enrolled in this study. The direct medical care costs were analyzed retrospectively for the patients with PUD during a one-year follow-up period. RESULTS: The recurrence rate within one year was significantly higher in idiopathic PUD than H. pylori and/or NSAID-associated PUD (p = 0.002). Direct medical care costs of idiopathic PUD ($2483.8) were higher than in patients with H. pylori and/or NSAID-associated PUD ($1751.8) resulting from longer duration of medication and higher proportion of endoscopic hemostasis and hospitalization. CONCLUSIONS: More clinical research is needed to improve outcome and reduce recurrence rate and medical care costs of idiopathic PUD.

Risk factors for peptic ulcer bleeding in terms of Helicobacter pylori, NSAIDs, and antiplatelet agents.

OBJECTIVES: The role of the Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), and antiplatelet agents in the risk of peptic ulcer bleeding has not yet been established. This study was performed to identify the risk factors for peptic ulcer bleeding compared with non-bleeding peptic ulcer disease (PUD). MATERIAL AND METHODS: A total of 475 patients, 265 with bleeding PUD and 210 with non-bleeding PUD were consecutively recruited. H. pylori status was determined by histology, rapid urease test, and culture. Exposure to NSAIDs, aspirin, and antiplatelet agents (clopidogrel and ticlopidine) within 4 weeks was obtained. RESULTS: Compared with non-bleeding PUD, bleeding PUD had a higher proportion of male gender and current smoking, alcohol drinking, history of aspirin/antiplatelet use, and history of PUD. Whereas the proportion of H. pylori infection and history of H. pylori eradication in bleeding PUD were significantly lower than that in non-bleeding PUD. In multivariate analysis, male gender (OR 1.78, 95% CI 1.10-2.89), drinking alcohol (OR 2.08, 95% CI 1.29-3.14), aspirin/antiplatelet use (OR 2.35, 95% CI 1.45-3.82), and history of PUD (OR 2.46, 95% CI 1.36-4.46) remained independent risk factors for bleeding PUD. When H. pylori status and aspirin/antiplatelet agent use were combined, highest risk of bleeding peptic ulcers was found among H. pylori-negative patients with a history of aspirin/antiplatelet agent use (OR 3.03 95% CI 1.48-6.18) compared with H. pylori-positive patients with no history of aspirin/antiplatelet agent use. CONCLUSIONS: Patients with H. pylori-negative peptic ulcers who continuously took aspirin or antiplatelet agents had the highest peptic ulcer bleeding risk.

CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer.

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.

Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection.

BACKGROUND AND AIMS: The incidence of early colorectal cancer (ECC) has been increasing. The aim of this study was to evaluate the clinical outcome and prognosis of ECC treated by endoscopic mucosal resection (EMR). METHODS: A total of 129 ECC patients who were initially treated by EMR between April 2005 and August 2007 were enrolled. Clinicopathological characteristics and prognoses were evaluated retrospectively. RESULTS: En bloc resection was performed in 85% of ECC patients, and piecemeal resection was performed in 15% of patients. Clear lateral and deep margins were achieved in 86% of cases. Of the 129 patients, 64 were found to have intramucosal cancer and 65 had submucosal cancer. Clinical characteristics were not different between patients with intramucosal cancer and submucosal cancer; however, poor differentiation and the absence of background adenoma showed significant association with submucosal cancer. Seven patients with submucosal cancer underwent subsequent surgical resection; five had lymphovascular invasion or a positive resection margin, one had perforation, and one patient requested surgical resection. Of these seven patients, one had residual cancer and two had lymph node metastasis. All patients with intramucosal cancer had no recurrence during the follow-up period. Seven patients with submucosal cancer showed adverse outcomes within 3 years, such as residual/recurrence of primary cancer or lymph node metastasis; five showed lymphovascular invasion or a positive deep margin, and two had no histological risk factors. CONCLUSIONS: Our results suggest that intramucosal cancer shows good prognosis, and a cure could be expected after EMR; however, adverse outcomes can occur in submucosal cancer. Therefore, meticulous endoscopic follow up is needed in patients with submucosal cancer for at least 3 years after EMR.

Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, (13)C-urea breath test, and serology.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut-off value in the screening population. METHODS: A consecutive 515 patients undergoing a routine health check-up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, (13)C-urea breath test, and serology) were positive. A stool antigen test (EZ-STEP H. pylori) was performed for the detection of H. pylori. The optimal cut-off value was determined by the receiver-operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age. RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the (13)C-urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6-95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years. CONCLUSIONS: The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.

Metastatic hepatocellular carcinoma presenting as facial nerve palsy and facial pain.

Facial nerve palsy due to temporal bone metastasis of hepatocellular carcinoma (HCC) has rarely been reported. We experienced a rare case of temporal bone metastasis of HCC that initially presented as facial nerve palsy and was diagnosed by surgical biopsy. This patient also discovered for the first time that he had chronic hepatitis B and C infections due to this facial nerve palsy. Radiation therapy greatly relieved the facial pain and facial nerve palsy. This report suggests that hepatologists should consider metastatic HCC as a rare but possible cause of new-onset cranial neuropathy in patients with chronic viral hepatitis.

[Risk factors for development and recurrence of peptic ulcer disease].

BACKGROUND/AIMS: Peptic ulcer disease (PUD) is one of the common gastrointestinal diseases, and its medical management has been developed so much that the incidence of its serious complications, such as bleeding and perforation, are declining significantly. Its prevalence in Korea is not definitely decreased, probably due to increasing proportion of elderly patients and their rising usage of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin. This study was conducted to identify the risk factors for development and recurrence of peptic ulcer disease in Korea. METHODS: From 2003 to 2008, upper gastrointestinal endoscopy and detailed personal questionnaires were performed for patients who visited Department of Gastroenterology at Seoul National University Bundang Hospital. In total, 475 PUD patients and 335 non-ulcer dyspepsia patients were included. The results of questionnaires and repeated upper gastrointestinal endoscopy at initial diagnosis time and follow-up periods were analyzed. RESULTS: Multivariable analysis showed that male, H. pylori infection, NSAIDs use and smoking were risk factors for the development of PUD. The use of proton pump inhibitors (PPIs) and H2 receptor antagonists has significantly reduced the risk of PUD in patients who had taken NSAIDs and/or aspirin. H. pylori infection was found as the only risk factor for the recurrence of PUD. CONCLUSIONS: For the old patients who are taking drugs, such as NSAIDs and aspirin, concomitant use of PPIs or H2 receptor antagonists should be considered to protect from the development of PUD. H. pylori eradication has been confirmed again to be essential for the treatment of PUD patients infected with H. pylori.

Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons.

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging.

Enhancement of gastric ulcer healing and angiogenesis by cochinchina Momordica seed extract in rats.

Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis, a perennial vine. The antiulcer effect of an extract from cochinchina momordica seeds (SK-MS10) was evaluated in a rat model of acetic acid-induced gastric ulcers. Gastric ulcers were produced by subserosal injection of acetic acid. SK-MS10 (200 mg/kg) or vehicle was administered orally once per day for 14 days after the acetic acid injection. The stomach was removed and the ulcer size measured at day 7 and 14 of the treatment. Expression of vascular endothelial growth factor (VEGF) was assessed by real-time RT-PCR and Western blot analysis. In addition, the microvasculature density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. The treatment with SK-MS10 for 7 and 14 days significantly accelerated ulcer healing and increased the expression of mRNA (at day 7) as well as VEGF protein (at day 14) compared to the vehicle-treated rats. The MVD for factor VIII was also higher in the SK-MS10 treatment group compared to the vehicle-treated rats; however, these differences were not statistically significant. These results suggest that SK-MS10 treatment accelerates the healing of gastric ulcers via upregulation of VEGF and angiogenesis in an acetic acid rat model.