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ABSTRACT: Endoscopic ultrasonography (EUS) is useful to diagnose the depth of invasion because of obtaining tomographic image of gastric cancer. Stomach layer has a 5-layer structure. Gastric cancer is visualized as low echoic tumor image by EUS. Massive invasion of gastric cancer is viewed as low echoic and clear boundary image. Diffuse invasion is imaged unclear boundary echo and visualized thick layer with remaining layer structure. Invasion depth of gastric cancer by EUS is diagnosed according to level of wall destruction. When depressed type cancer has ulceration in cancer nest, echoic image is modified with fibrous tissue. The diagnostic criteria of depressed type cancer classified into EUS imaging of cancer in consideration for image modified by fibrous tissue accompanied ulceration.
Nippon rinsho. Japanese journal of clinical medicine 10/2012; 70(10):1752-7.
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ABSTRACT: Aim: We studied eosinophilic esophagitis (EE) to clarify the clinical and endoscopic features of a Japanese case series. Methods: Records of 10 patients diagnosed with EE at our hospital between May 2010 and December 2011 were examined for age, sex, symptoms, allergic disorder, endoscopic findings, and treatment received. Esophageal wall thickness was measured by endoscopic ultrasonography (EUS). Results: Patients were seven males and three females with a mean age of 48 years. Symptoms included dysphagia, heartburn, food impaction, and chest pain. Nine patients had a history of allergic diseases. Increased peripheral eosinophil count was observed in one patient whereas increased immunoglobulin E level was observed in eight patients. Endoscopic findings included longitudinal furrows in all patients, mucosal edema in nine patients, loss of vascular pattern in nine patients, white exudates in six patients, cobblestone-like appearance in five patients, and concentric rings in three patients. EUS revealed thickening of the esophageal wall in one patient. Histopathological examination revealed eosinophilic infiltration (≥15 eosinophils/high-powered field) in the esophageal epithelium of all patients. Treatment was required in six patients. Proton pump inhibitor (PPI) therapy was given as the first-line treatment but was ineffective in four patients and effective in two patients. Steroid therapy was given to three patients unresponsive to PPI therapy and was effective. Conclusions: EE was common among relatively young men and was associated with allergic diseases. Longitudinal furrows were observed as the most characteristic endoscopic finding. Esophageal wall thickening was not commonly observed by EUS.
Digestive Endoscopy 06/2012; · 1.19 Impact Factor
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ABSTRACT: The guideline for peptic ulcer treatment was reported by Japanese Society of Gastroenterology in 2009. In the guideline, 23 clinical questions were chosen for NSAIDs induced ulcer. Nine questions out of them were related to the prevention, eight were low dose aspirin, three were COX-2 inhibitors and three were the treatment. The recommendations were made for these questions according to evidence-based medicine. In the recommendations, the grade of recommendation, the evidence level of literatures and the applications to Japanese medical insurance were mentioned.
Nippon rinsho. Japanese journal of clinical medicine 06/2011; 69(6):1024-31.
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ABSTRACT: We retrospectively investigated the incidence of pancreatic ductal adenocarcinoma among patients with intraductal papillary mucinous neoplasms of the pancreas. Based on imaging in 195 such patients, we chose surgery as initial treatment for 54, and periodic evaluation over 6 to 192 months (mean, 52) for 141. In 6 of the 141 patients observed for intraductal papillary mucinous neoplasm (4.2%), pancreatic ductal adenocarcinoma developed. Further, careful monitoring for cancer occurrence in the remnant pancreas proved essential in the surgical resection group; 2 of 26 patients (7.7%) subsequently developed pancreatic ductal adenocarcinoma in the remnant pancreas, at 41 months and 137 months after surgery. Serial observation of patients with intraductal papillary mucinous neoplasms by contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography therefore is critical, whether or not surgical treatment initially was performed.
ISRN gastroenterology. 01/2011; 2011:940378.
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Toshihito Kosaka,
Junji Yoshino,
Kazuo Inui,
Takao Wakabayashi, Takashi Kobayashi,
Shinya Watanabe,
Shigekazu Hayashi,
Yoshifumi Hirokawa,
Taizo Shiraishi,
Takayuki Yamamoto,
Mayumi Tsuji,
Takahiko Katoh,
Masatoshi Watanabe
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ABSTRACT: Inflammatory bowel disease is a multifactorial disease. Oxidative stress has been thought to be one of etiologic factor for inflammatory bowel disease. The genes superoxide dismutase (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress. The purpose of the present case-control study with 134 patients with ulcerative colitis (UC) and 125 healthy controls was to determine whether polymorphisms of these genes, the NQO1 C609T and the SOD2 Ala-9Val, are associated with the risk of UC and influence the clinical characteristics. These polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphisms and direct sequencing. In patients showing steroid resistance, the number with the NQO1 T/T genotype was significantly higher than other genotypes (odds ratio 9.45, 95% confidence interval 2.46-41.6, p = 0.002). In the patients whose onset of UC was age 20 years or younger, more patients had SOD2 T/T genotype than the other genotypes (odds ratio 6.46, 95% confidence interval 0.82-51.0). No association between these polymorphisms and UC risk was apparent. The NQO1 C609T polymorphism may influence steroid resistance of UC patients, while the SOD2 Ala-9Val polymorphism may influence age of onset of UC. Oxidative stress may influence the clinical features of UC.
DNA and cell biology 09/2009; 28(12):625-31. · 2.28 Impact Factor
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ABSTRACT: We used endoscopic color Doppler ultrasonography to detect hemorrhagic gastric ulcer, and to determine whether this modality could show blood vessels present deep to ulcers and whether these vessels influenced clinical course. Subjects were 20 patients with hemorrhagic gastric ulcers which had visible vessels on the ulcer base endoscopically. In 11 of 20 patients (group P) color signals indicating blood flow were observed, in which a weak pulsatile wave was detected in five cases. In two operated cases the signals were confirmed as blood vessels histologically. The diameters of these vessels were over 0.35 mm. It was thought that in cases undetectable on endoscopic color Doppler ultrasonography (group N) the diameter of vessels was too narrow or the velocity of blood too slow. There were no differences in the clinical background of group P and group N. However, ulcer bleeding was more severe in group P cases (P<0.05). Many patients in whom blood flow was detected experienced repeated ulcer bleeding as well as ulcer recurrences. Patients with hemorrhagic ulcers and in whom ultrasonic imaging demonstrates blood flow should be managed with great care. (Dig Endosc 1999; 11: 231–235)
Digestive Endoscopy 12/2007; 11(3):231 - 235. · 1.19 Impact Factor
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ABSTRACT: This study was undertaken to clarify the importance of nutritional status in patients with acute cholecystitis, and also evaluate whether they benefited from enteral nutrition supplementation, including medium-chain triglycerides (MCT), during the convalescent stage. Patients with acute cholecystitis admitted to our hospital between April 1994 and March 2002 were classified into a poor nutrition group (n=40; total serum protein<5.0 g/dl) or a fair nutrition group (n=71; >5.0 g/dl). Patients with poor nutrition were significantly more elderly than those with fair nutrition, and had significantly higher serum C-reactive protein (CRP) concentrations. The two groups did not differ significantly with respect to other laboratory data, gender distribution, or medical treatment. We supplemented ordinary meals with enteral nutrition including MCT in 16 patients during the convalescent stage (MCT group). We compared their length of hospital stay and days required to recovery to pre-admission functional status for activities of daily living (ADL) with the same intervals in 16 patients without supplementation (non-MCT group) selected to match for age, gender, and fair or poor nutritional status from among 111 patients. Hospitalizations were significantly longer in the poor nutrition group (43.0+/-2.2 days) than in the fair nutrition group (27.0+/-8.2 days). Significantly more days were required to recover ADL status in the poor nutrition group (12.0+/-7.2 days) than in the fair group (9.4+/-5.2 days). Hospitalizations were significantly shorter in the MCT group (20.1+/-15 days) than in the non-MCT group (35.4+/-12.8 days). Significantly fewer days were required to recover ADL status in the MCT group (10.9+/-7 days) than in the non-MCT group (13.1+/-6.8 days). Administration of enteral nutrition including MCT during convalescence from acute cholecystitis thus appears to promote functional recovery shorten hospital stay.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 09/2007; 104(9):1352-8.
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Toshihito Kosaka,
Junji Yoshino,
Kazuo Inui,
Takao Wakabayashi,
Kazumu Okushima, Takashi Kobayashi,
Hironao Miyoshi,
Yuta Nakamura,
Shigekazu Hayashi,
Taizou Shiraishi,
Masatoshi Watanabe,
Takayuki Yamamoto,
Ai Nakahara,
Takahiko Katoh
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ABSTRACT: To examine the influence of lipoprotein lipase (LPL) gene polymorphism in ulcerative colitis (UC) patients.
Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind III and Pvu II polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing. Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.
In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR = 3.13, 95% CI = 0.95-10.33). Patients with H(+/-) or H(-/-) genotype for Hind III polymorphism also were more numerous than those with H(+/+) genotype (OR = 2.51, 95% CI = 0.85-7.45). In the group with H(+/+) genotype for Hind III polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H(+/-) or H(-/-) genotype (P < 0.01, OR = 6.46, 95% CI = 1.39-30.12). Hypertriglycemia was also more prevalent in patients with P(+/+) genotypes for Pvu II polymorphism (P < 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.
Ser447stop and Hind III LPL polymorphisms may influence age of onset of UC, while Hind III and Pvu II polymorphisms influence serum triglyceride in UC patients.
World Journal of Gastroenterology 10/2006; 12(39):6325-30. · 2.47 Impact Factor
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ABSTRACT: The study examined whether Shigyaku-san (Si-Ni-San) extract (TJ-35), a traditional Kampo medicine, prevents acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80). Rats treated with C48/80 (0.75 mg/kg body weight, i.p.) received TJ-35 (0.15, 0.35 or 0.75 g/kg body weight, p.o.) 0.5 h after the treatment at which time gastric mucosal lesions appeared. At 0.5 h after C48/80 treatment, the gastric mucosa of the treated rats had increased myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content. At 3 h after C48/80 treatment, the gastric mucosa of the treated rats showed progressive lesions and further increases in myeloperoxidase and xanthine oxidase activities and thiobarbituric acid reactive substances content and decreases in vitamin E, ascorbic acid and adherent mucus contents and Se-glutathione peroxidase activity. Post-administered TJ-35 attenuated all these changes found at 3 h after C48/80 treatment dose-dependently. These results indicate that TJ-35 prevents the progression of C48/80-induced acute gastric mucosal lesions in rats possibly by attenuating enhanced neutrophil infiltration, enhanced lipid peroxidation associated with decreased vitamin E and ascorbic acid contents and Se-glutathione peroxidase activity, and destruction of the defensive barrier in the gastric mucosa.
Phytotherapy Research 05/2006; 20(4):256-62. · 2.09 Impact Factor
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ABSTRACT: The effect of oral vitamin E administration on acute gastric mucosal lesion progression was examined in rats treated once with compound 48/80 (C48/80) (0.75 mg/kg, i.p.) in comparison with that of subcutaneously administered superoxide dismutase (SOD) plus catalase (CAT). Vitamin E (50, 100 or 250 mg/kg) administered at 0.5 h after C48/80 treatment reduced progressive gastric mucosal lesions at 3 h after the treatment dose-dependently, like SOD plus CAT administered at the same time point. The gastric mucosa of C48/80-treated rats had decreased Se-glutathione peroxidase activity and vitamin E, ascorbic acid, and hexosamine contents and increased myeloperoxidase and xanthine oxidase activities and thiobarbituric acid reactive substances content at 3 h after the treatment. Administered vitamin E attenuated all these changes found at 3 h after C48/80 treatment dose-dependently, like administered SOD plus CAT. C48/80-treated rats administered with vitamin E (100 or 250 mg/kg) had higher gastric mucosal vitamin E content than C48/80-untreated rats. Neither administered vitamin E nor SOD plus CAT had any effect on the increases in serum serotonin and histamine concentrations and the decrease in gastric mucosal blood flow found at 3 h after C48/80 treatment. In the gastric mucosa of C48/80-untreated rats administered with vitamin E, thiobarbituric acid reactive substances content decreased with an increase in vitamin E content. These results indicate that orally administered vitamin E prevents acute gastric mucosal lesion progression in C48/80-treated rats possibly by suppressing oxidative stress, neutrophil infiltration, and mucus depletion in the gastric mucosa like administered SOD plus CAT.
Biological & Pharmaceutical Bulletin 05/2006; 29(4):675-83. · 1.66 Impact Factor
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ABSTRACT: We have reported that teprenone (geranylgeranylacetone), an anti-ulcer drug, prevents acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80), a mast cell degranulator, possibly by suppressing mucus depletion, neutrophil infiltration, and oxidative stress in the gastric mucosa. Herein, we examined the preventive effect of gefarnate (geranyl farnesylacetate), an anti-ulcer drug, on acute gastric mucosal lesion progression in rats treated once with C48/80 (0.75 mg/kg, i.p.) in comparison with that of teprenone, because the chemical structure and anti-ulcer action of gefarnate are similar to those of teprenone. Gefarnate (50, 100 or 200 mg/kg) administered orally at 0.5 h after C48/80 treatment, at which time gastric mucosal lesions appeared, reduced progressive gastric mucosal lesions at 3 h dose-dependently. At 3 h after C48/80 treatment, the gastric mucosa had decreased adherent mucus and hexosamine contents and increased myeloperoxdiase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content. Post-administered gefarnate attenuated all these changes dose-dependently. These preventive effects of gefarnate were similar to those of teprenone at a dose of 200 mg/kg. Post-administered gefarnate did not affect the increases in serum serotonin and histamine concentrations and the decrease in gastric mucosal blood flow at 3 h after C48/80 treatment like teprenone. These results indicate that orally administered gefarnate prevents acute gastric mucosal lesion progression in C48/80-treated rats possibly by suppressing mucus depletion, neutrophil infiltration, and oxidative stress in the gastric mucosa like teprenone.
Biological & Pharmaceutical Bulletin 09/2005; 28(8):1424-30. · 1.66 Impact Factor
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ABSTRACT: The preventive effect of teprenone (6,10,14,18-teramethyl-5,9,13,17-nonadecatetaene-2-one), an anti-ulcer drug, on acute gastric mucosal lesion progression was examined in rats with a single intraperitoneal (i.p.) injection of compound 48/80 (0.75 mg/kg). Teprenone (20, 100 or 200 mg/kg), which was orally administered 0.5 h after compound 48/80 treatment at which time gastric mucosal lesions appeared, prevented gastric mucosal lesion development at 3 h after the treatment dose-dependently. Gastric mucosal tissues of compound 48/80-treated rats showed increases in myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content and decreases in Se-glutathione peroxidase activity and hexosamine and vitamin E contents at 3 h after the treatment. Post-administered teprenone attenuated all these changes dose-dependently. These results indicate that teprenone prevents acute gastric mucosal lesion progression in compound 48/80-treated rats possibly by suppressing gastric mucus depletion, neutrophil infiltration and oxidative stress in the gastric mucosal tissue.
European Journal of Pharmacology 04/2004; 487(1-3):223-32. · 2.52 Impact Factor
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ABSTRACT: The protective effect of teprenone, an anti-ulcer drug, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (0.75 mg/kg). Teprenone (50, 100, or 200 mg/kg) was orally administered 0.5 h before compound 48/80 treatment. Administered teprenone prevented gastric mucosal lesion development found at 3 h after compound 48/80 treatment dose-dependently, although no dose of teprenone affected the decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 3 h after the treatment. Increases in the activities of myeloperoxdiase (an index of neutrophil infiltration) and xanthine oxidase and the content of thiobarbituric acid reactive substances (an index of lipid peroxidation) and decreases in the contents of hexosamine (a marker of gastric mucus) and adherent mucus occurred in gastric mucosal tissues at 3 h after compound 48/80 treatment. Administered teprenone dose-dependently attenuated all these changes found at 3 h after compound 48/80 treatment. These results indicate that orally administered teprenone protects against compound 48/80-induced acute gastric mucosal lesions in rats possibly through its stimulatory action on gastric mucus synthesis and secretion and its inhibitory action on neutrophil infiltration and enhanced lipid peroxidation in the gastric mucosal tissue.
Journal of Pharmacological Sciences 12/2003; 93(3):337-46. · 2.08 Impact Factor
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ABSTRACT: The protective effect of ebselen, which possesses glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, against the progression of acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (0.75 mg/kg). Ebselen (50, 100 or 200 mg/kg) was orally administered 0.5 h after compound 48/80 treatment, at which time gastric mucosal lesions appeared. Post-administered ebselen suppressed gastric mucosal lesion progression at 3 h after compound 48/80 treatment dose-dependently, although no dose of ebselen affected the decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 3 h after the treatment. A decrease in Se-glutathione peroxidase activity and increases in myeloperoxidase and xanthine oxidase activities and the concentration of thiobarbituric acid reactive substances were found in gastric mucosal tissues at 0.5 h after compound 48/80 treatment, and these changes were further enhanced at 3 h. Post-administered ebselen attenuated all these changes found at 3 h after compound 48/80 treatment dose-dependently. The present results indicate that ebselen exerts a protective effect against the progression of compound 48/80-induced acute gastric mucosal lesions in rats, and they suggest that this protective effect of ebselen could be due to its glutathione peroxidase-like activity and its antioxidative and anti-inflammatory properties.
The Japanese Journal of Pharmacology 01/2003; 90(4):295-303.
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ABSTRACT: Omeprazole, a proton pump inhibitor is known to function not only as a proton pump inhibitor but also as an anti-inflammatory agent, an antioxidant or a stimulator of gastric mucus secretion. We have shown that the pathogenesis of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats involves neutrophil infiltration, lipid peroxidation, and mucin depletion, but not acid secretion, in the gastric mucosal tissue. Therefore, we examined whether omeprazole protects against acute gastric mucosal lesions induced by compound 48/80 in rats. Rats were injected with omeprazole (10 or 50 mgkg(-1), i.p.) at 0.5h before injection of compound 48/80 (0.75 mgkg(-1), i.p.). Omeprazole prevented gastric mucosal lesion development at 0.5 and 3h after compound 48/80 injection. Omeprazole attenuated decreased nonprotein sulfhydryl content and increased myeloperoxidase and xanthine oxidase (XO) activities and lipid peroxide (LPO) content in the gastric mucosa at 0.5h after compound 48/80 injection and increased myeloperoxidase and XO activities and LPO content, but not decreased hexosamine and adherent mucus contents, in the gastric mucosa at 3h. These results indicate that omeprazole protects against compound 48/80-induced acute gastric mucosal lesions in rats possibly through its anti-inflammatory and antioxidant actions.
Pharmacological Research 08/2002; 46(1):75-84. · 4.44 Impact Factor
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ABSTRACT: Actual age and biological age are not always proportional. To find out indices of aging, other than actual age, we investigated relationship between aging and four hepatic fibrosis markers: hyaluronates, type IV collagen, type IV collagen 7s and P III P. The subject of this study were 78 patients of inpatients and outpatients of our hospital. They were divided into four groups of very elderly (over 80-year-old), elderly (70-79-year-old), non-elderly (50-69-year-old), and non-elderly (20-49-year-old), and these four groups were compared. The results were as follows: regarding hyaluronates value were 86.3 +/- 46.7 ng/ml in the patients in the very elderly group, 58.9 +/- 37.4 ng/ml in the elderly group, 48.7 +/- 71.9 ng/ml in patients aged between 50 and 69 years old, and 22.6 +/- 26.1 ng/ml in patients aged between 20 and 49 years old. Regarding type IV collagen value were 134.6 +/- 27.8 ng/ml in the very elderly group, 131.1 +/- 46.5 ng/ml in the elderly group, 135.1 +/- 102.1 ng/ml in patients aged between 50 and 69 years old and 92.8 +/- 21.8 ng/ml in patients aged between 20 and 49 years old. Type IV collagen 7s value were 4.4 +/- 0.9 ng/ml in the very elderly group, 4.4 +/- 0.6 ng/ml in the elderly group, 4.8 +/- 1.6 ng/ml in patients of between 50 and 69 years old, and 4.3 +/- 0.6 ng/ml in patients between 20 and 49 years old. P III P value were 0.70 +/- 0.31 U/ml in the very elderly group, 0.64 +/- 0.34 U/ml in the elderly group, 0.59 +/- 0.43 U/ml in patients aged between 50 and 69 years old, and 0.46 +/- 0.14 U/ml in patients aged between 20 and 49 years old. The results indicated that three markers: hyaluronates, type IV collagen, P III P increased with the aging. Especially, hyaluronates were remarkably increased. Next, we studied 159 patients (78 patients added to 81 patients who visited our hospital for health checkup), and investigated the fluctuation of hyaluronate values by the aging. The results showed a definite increase of hyaluronate values with age. A correlation was recognized between ages and hyaluronate values (correlation coefficient: r = 0.64, p < 0.001). Furthermore we investigated effect on aging of various items including fibrosis markers, immunoglobulin or serum albumin by using multiple factor analysis, and found that hyaluronates influenced most strongly on aging (p < 0.0002, p < 0.00002). Thus, hyaluronates could be considered to be an index other than actual ages to evaluate progress of aging.
Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 03/2002; 39(2):176-80.
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ABSTRACT: Background: The normal gastric wall has been reported to appear to be a five-layered structure. The structure of the gastric wall using a 30 MHz endoscopic ultrasound probe and especially the identification of the muscularis mucosae (MM), has not been analyzed clearly.Methods: In a basic study, 11 sections of normal gastric wall with 26 horizontally inserted nylon sutures were immersed in water. The sections were scanned and the findings correlated using standard histology. In a clinical study, 15 early gastric cancers were examined by a 30 MHz endoscopic ultrasound probe.Results: In a basic study, layers deeper than the lower part of the submucosa could not be seen using ultrasonography. The first to fourth layers represented the mucosal layer except the MM, the fifth layer (high-echo layer) represented the boundary echo and a part of the MM, while the sixth layer (low-echo layer) represented the rest of the MM. The muscularis mucosae was seen clearly in all samples. In a clinical study the layers deeper than the submucosal layer could not be seen and the MM was visible in 87% of cases. The depth of invasion was estimated accurately in 90% of mucosal cancers and in 80% of submucosal cancers.Conclusion: A 30 MHz endoscopic ultrasound probe, which cannot image the entire gastric wall, can visualize the MM and may help to confirm the structure of gastric wall layers and improve the ability to determine the depth of invasion in gastric cancer.
Digestive Endoscopy 06/2000; 12(3):233 - 236. · 1.19 Impact Factor
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ABSTRACT: Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing-promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg−1× 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing-promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration and enhanced lipid peroxidation in the ulcerated gastric tissue.
Pharmacological Research.
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ABSTRACT: The preventive effect of ebselen, a seleno-organic compound, which is known to possess glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties, on the development of acute gastric mucosal lesions was examined in rats with a single injection of compound 48/80 (0.75 mg/kg, i.p.), a mast cell degranulator. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, prevented gastric mucosal lesion development at 3 h, but not gastric mucosal lesion formation at 0.5 h, after compound 48/80 injection, although any dose of pre-administered ebselen did not affect decreased gastric mucosal blood flow and increased serum serotonin and histamine concentrations found at 0.5 and 3 h after compound 48/80 injection. A decrease in Se-glutathione peroxidase activity and increases in the activities of myeloperoxidase, an index of tissue neutrophil infiltration, and xanthine oxidase and the concentration of thiobarbituric acid reactive substances, an index of lipid peroxidation, were found in gastric mucosal tissues at 0.5 h after compound 48/80 injection and these changes were further enhanced at 3 h. Pre-administration of ebselen (p.o.) at a dose of 50 or 100 mg/kg, but not 10 mg/kg, attenuated all these changes found at 3 h after compound 48/80 injection. These preventive effects of ebselen occurred in a dose-dependent manner. The present results indicate that pre-administered ebselen prevents the development of compound 48/80-induced acute gastric mucosal lesions in rats, and suggest that this preventive effect of ebselen could be due to its glutathione peroxidase-like activity and antioxidative and anti-inflammatory properties.
European Journal of Pharmacology.
