Yuji Naito

Vitamin E in gastric mucosal injury induced by ischemia-reperfusion

To clarify the relationship among vitamin E, oxygen radicals, and lipid peroxidation in ischemia-reperfusion, we produced an experimental model of gastric mucosal injury in rats by ischemia-reperfusion with clamping of the celiac artery and measurements of the area of gastric erosion, thiobarbituric acid (TBA)-reactive substances, and alpha-tocopherol in serum and gastric mucosa during ischemia-reperfusion. The area of gastric erosions and TBA-reactive substances in gastric mucosa were significantly increased after 30 and 60 min of reperfusion. The serum alpha-tocopherol-cholesterol ratio and gastric mucosal alpha-tocopherol were significantly decreased after 30 and 60 min of reperfusion. On the other hand, in vitamin E-deficient rats, gastric mucosal injury induced by ischemia-reperfusion was more severe than that in vitamin E-nondeficient rats. These results indicate that vitamin E is consumed in the process of lipid peroxidation induced by oxygen radicals in ischemia-reperfusion to prevent the development of tissue damage.

Therapeutic and Diagnostic Approaches in Colonoscopy

Colorectal cancer is a common gastrointestinal malignancy in the USA, Europe, and Japan. Most colorectal cancers are thought to arise from preexisting adenomas based on the concept of the adenoma-carcinoma sequence [1]. Chromoendoscopy, using Kudo and Tsuruta’s pit pat‐ tern classification, is an efficient tool for the differential diagnosis of colorectal polyps [2-4]. Re‐ cently, image-enhanced endoscopy (IEE) has been used for diagnosing gastrointestinal tumors [5-7]. Endoscopic therapy, including endoscopic mucosal resection (EMR) and endoscopic sub‐ mucosal dissection (ESD), is used worldwide to treat adenoma and early colorectal cancer [8-10]. In this chapter, we demonstrated the effectiveness of IEE and discuss strategies of thera‐ peutic endoscopy including EMR and ESD.

Dehydroepiandrosterone in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease (CLD) in many developed countries and results in a serious public health problem worldwide. NAFLD includes a wide spectrum of liver diseases, ranging from simple fatty liver, which is usually a benign and nonprogressive condition, to nonalcoholic steatohepatitis (NASH) which may progress to liver cirrhosis (LC), hepatic failure and hepatocellular carcinoma (HCC) in the absence of significant alcohol consumption (Ludwig et al., 1980, Matteoni et al. 1999). About a third of people with NAFLD will develop NASH, and about 20% of people with NASH will go on to liver fibrosis and cirrhosis, with its accompanying risk of liver failure and even HCC (Yasui et al. 2011). In Japan, current best estimates make the prevalence of NAFLD approximately 20% and of NASH 2% to 3% in the general population. Pathophysiology of primary NASH still hasn’t been completely clarified. According to the “two-hits” model of NASH pathogenesis proposed by Day and James (Day & James. 1999), excessive triglyceride accumulation is the most likely first step. The second step may relate to an increase in oxidative stress (Sumida et al. 2011a), which, in turn, triggers liver cell necrosis and activation of hepatic stellate cells, both leading to fibrosis and ultimately to the development of LC. Although the number of NASH cases in women is known to be higher than in men over 50 years of age, the mechanisms remain unknown (Hashimoto & Tokushige, 2011). According to our study produced by Japan Study Group of NAFLD (JSG-NAFLD) including nine hepatology centers in Japan (Sumida et al., 2011b), NASH patients with significant or advanced fibrosis (Brunt stage 2-4) was more prevalent in females than in males (Fig.1). Although plausible mechanisms have been proposed, including estrogen deficiency after menopause, iron accumulation generating hydroxylradicals via Fenton reaction (Sumida et al., 2009), and so on, precise mechanisms have not been clarified. Although several factors have been associated with more advanced NAFLD, the biological basis of the histological diversity of severity of NAFLD [i.e., why some patients develop simple fatty liver and others develop NASH with advanced fibrosis] remains unknown. More advanced NAFLD is characterized by insulin resistance, oxidative stress, and advanced fibrosis.