Endoscopic submucosal dissection (ESD) has the advantage over endoscopic mucosa resection, permitting removal of gastrointestinal neoplasms en bloc, but is associated with relatively high risk of complications. Indications for early gastric cancer (EGC) are expanded: mucosal cancer without ulcer findings irrespective of tumor size; mucosal cancer with ulcer findings ≤3 cm in diameter; and minute submucosal invasive cancer ≤3 cm in size. The indications for early esophageal cancer (EEC) are the tumors confined to the two-third layer of the lamina propria. The EEC lesions spreading more than three-quarter of circumference of the esophagus are at frequent risk of stenosis. The procedures include marking, submucosal injection, circumferential mucosal incision and exforiation of the lesion along the submucosal layer. Complete ESD can achieve a large one-piece resection, allowing precise histological assessment to prevent recurrence. Clinical outcomes of gastric and esophageal ESD have been promising, and the prognosis of EGC patients treated by ESD is likely to be excellent, though further longer follow-up studies are warranted. Notification of perforation risk is essential in particular for esophageal ESD. Bleeding during ESD can be managed with coagulation forceps, and postoperative bleeding may be reduced with routine use of the stronger acid suppressant, proton pump inhibitors.
Vascular complications, as a consequence of atherosclerosis, are main causes of morbidity and mortality in patients with diabetes mellitus. There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. In this study we investigated the effect of soybean hypocotyl extract (SHE), rich in isoflavones and saponins, on lipid peroxide (LPO) levels in liver, plasma and lipoproteins in GK diabetic rats, and its efficacy on the reduction of susceptibility of LDL and high density lipoprotein (HDL) to oxidation. The oxidative modification of LDL and HDL was determined with the lag time of copper ion-induced oxidation curve identified by the conjugated dienes. In SHE group which were fed diet containing 40 g/kg of SHE for 16 weeks, LPO levels in liver, plasma and HDL fraction were significantly decreased compared with the control group. The lag phage of LDL oxidation curve was prolonged noticeably by a mean of 27 min in SHE group as compared to the control group, indicating a reduced susceptibility to oxidation. The results suggest that intake of soybean hypocotyl extract might be useful for the prevention and treatment of diabetes mellitus and diabetes-associated diseases.
α-Lipoic acid (LA) is the one of the strongest antioxidants to be utilized in supplement, skin ointment and so on. The distorted five membered dithiolane ring of LA, which is necessary structure to work as a cofactor of enzyme, is considerably vulnerable to UV irradiation. LA is easily decomposed by photoirradiation resulting in the loss of its characteristic absorption band at 333 nm. The photodegradation of LA means loss of its physiological activity, so that protection of LA from UV light is eagerly desired. Thiol compounds can be regarded as a potential candidate. In order to pursue the possibility of the thiol compounds in prevention of LA degradation, we examined the photoirradiation of LA in the presence and absence of homocysteine.
Effects of soy isoflavones, genistein and daidzein, on the hepatic gene expression profile and indices for lipid metabolism were compared in rats. In the first experiment (Expt. 1), animals were fed diets containing 2 g/kg of either genistein or daidzein, or a control diet free of isoflavone for 14 days. In the second experiment (Expt. 2), rats were fed diets containing 1 or 2 g/kg of genistein, or an isoflavone-free diet for 16 days. Genistein at a dietary level of 2 g/kg reduced serum triacylglycerol concentrations in both experiments, and serum concentrations of cholesterol in Expt. 2. However, daidzein at 2 g/kg did not decrease serum lipid concentrations in Expt. 1. A DNA microarray analysis in Expt. 1 showed that genistein was stronger than daidzein in affecting gene expression in liver, targeting many genes involved in lipid and carbohydrate metabolism. Detailed analyses indicated that alterations in the expression of genes related to lipogenesis are primarily responsible for the serum lipid-lowering effect of genistein. This notion was supported by analyses of the activity of enzymes involved in lipogenesis in Expt. 2.
We estimated the intake of individual flavonoids in a cross sectional study and clarified the major sources contributing to the flavonoid levels in the middle-aged Japanese women by a 24-h weighed dietary record study. The subjects included in the study were 516 free-living women. Each subject completed a 24-h weighed dietary record and received a health check-up. We used the Functional Food Factor database for estimating the intake of 5 major flavonoid intakes, i.e. flavan-3-ols, isoflavones, flavonols, flavanones and flavones. The mean intake of flavan-3-ols, isoflavones, flavonols, flavanones and flavones was 1277, 216, 58, 31 and 15 μmol/d, respectively. The richest source of flavan-3-ols was green tea. The 3 major food sources of isoflavone were the processed soy foods and those of flavonol were the onion, moroheiya (nalta jute) and Japanese radish leaves. Grapefruit and citrus fruit juices were the major sources of flavanones, and tsurumurasaki (malabar spinach), green pepper and grapefruit were the main sources of flavone. Furthermore, analysis of sub-samples from middle-aged Japanese women indicated that there may be an association between flavonoid intake and the levels of oxidized LDL, which might be related to the incidence of cardiovascular diseases.
Oxidative stress is frequently considered as a central mechanism of hepatocellular injury in non-alcoholic steatohepatitis (NASH). The aim of this study was to investigate the effects of fermented green tea extracts (FGTE) on NASH. Rats were fed a choline-deficient high-fat diet for 4 weeks to nutritionally generate fatty livers. NASH was induced chemically by oxidative stress using repeated intraperitoneal injections of nitrite. Rats with NASH developed steatohepatitis and liver fibrosis after 6-week of such treatment. At 10 weeks, blood and liver samples were collected from anesthetized animals and assessed for extent of OS injury and effects of FGTE, by biochemical, histological and histochemical analyses. FGTE reduced serum levels of liver enzymes, lipid peroxidation and production of mitochondrial reactive oxygen species. In addition, FGTE showed inhibition of progressions of cirrhosis. Our findings suggest that our FGTE have strong radical scavenging activity and may be beneficial in the prevention of NASH progression.
Bilateral lesions in the Ventromedial nucleus of hypothalamus (VMH) cause hyperphagia and a preference for high lipid, high carbohydrate diet. Reversible lesion by procaine microinfusion produces a decrease in serum glucose and immunoreactive insulin levels. In the present study the effect of procaine microinfusion on feeding behavior and taste preference was observed. 5 h and 24 h food intake, water intake and weekly body weight of the rats was measured. Three bottle preference test was used to study the diet preferences. The 24 h food intake was found to be significantly more on 1st, 2nd and 3rd day (41 ± 6.03, 38.83 ± 6.17 and 33.66 ± 5.88 g/day, respectively) of procaine injection. There was also a significant increase in food intake at 0.25 h (4.166 ± 2.04 g) and 1 h (5 ± 0 g) as compared to saline group (0 ± 0 g at 0.25 h and 0.83 ± 2.04 g at 1 h). Post procaine water intake and body weight for seven days was not statistically significantly when compared to pre-lesion values. In the three bottles preference test, after procaine microinfusion there was a significantly increased preference for 20% sucrose and 0.15% saccharin than quinine and citric acid. The results suggest that bilateral procainization of VMH produces a transient increase in food intake and enhance preference for sweet tasting substances.
The essential oil of silver fir (Abies alba) is known to help respiratory system and have easing and soothing effect for muscle. In the present study, we investigated the chemical composition, cytotoxicity and its biological activities of silver fir (Abies alba) essential oil. The composition of the oil was analyzed by GC-MS and bornyl acetate (30.31%), camphene (19.81%), 3-carene (13.85%), tricyclene (12.90%), dl-limonene (7.50%), α-pinene (2.87%), caryophyllene (2.18%), β-phellandrene (2.13%), borneol (1.74%), bicyclo[2.2.1]hept-2-ene,2,3-dimethyl (1.64%) and α-terpinene (1.24%) were the major components in the oil. The results tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that the oil showed no cytotoxic effect, at concentrations of 1 and 5%, for as long as 24 and 3 h, respectively. The antiradical capacity was evaluated by measuring the scavenging activity of the essential oil on the 2,20-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethyl benzothiazoline-6-sulfonic acid (ABTS) radicals. The oil was able to reduce the both radicals dose-dependently, and the concentration required for 50% reduction (RC50) against DPPH radicals (2.7 ± 0.63%) was lower than ABTS radicals (8.5 ± 0.27%). The antibacterial activity of the oil was also evaluated using disc diffusion method against Staphylococcus aureus, Streptococcus mutans, Listeria monocytogenes, Acinetobacter baumannii, Escherichia coli, and Vibrio parahaemolyticcus. The oil exhibited no antibacterial activity against all the bacterial strains tested except S. aureus of mild activity.
In this study, we investigated the mechanistic role of the caspase cascade in extrinsic and intrinsic apoptosis induced by apigenin, which has been targeted as a candidate in the development of noncytotoxic anticancer medicines. Treatment with apigenin (1–100 μM) significantly inhibited the proliferation of MDA-MB-453 human breast cancer cells in a dose- and time-dependent manner with IC50 values of 59.44 and 35.15 μM at 24 and 72 h, respectively. This inhibition resulted in the induction of apoptosis and the release of cytochrome c in cells exposed to apigenin at its 72 h IC50. Subsequently, caspase-9, which acts in mitochondria-mediated apoptosis, was cleaved by apigenin. In addition, apigenin activated caspase-3, which functions downstream of caspase-9. The apigenin-induced activation of caspase-3 was accompanied by the cleavage of capases-6, -7, and -8. These results are supported by evidence showing that the activity patterns of caspases-3, -8, and -9 were similar. The present study supports the hypothesis that apigenin-induced apoptosis involves the activation of both the intrinsic and extrinsic apoptotic pathways.
This study was conducted to investigate whether or not a food substitute (Dr. BAANs®) containing three bioactive components L-arginine, ω-3 polyunsaturated fatty acid, and ribonucleic acid, supplied orally to 15 overweight patients, may have efficacy to prevent or improve the metabolic syndrome of these patients. To provide supporting data for this clinical study, the in vivo fatty acid metabolism of obese mice was analyzed using 125I labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA) in the tissues’ lipid pool. After 3 months of intervention, the results showed that there were improvements observed in liver functions, lipid profiles and metabolic syndrome marker. Significant differences were also found in the values of blood pressure, body weight, percentage of body fat, and body mass index. In the animal study, the tissue uptake of 125I-9MPA at 10 min after injection was higher in obese mice than in the control mice and the treatment with Dr. BAANs® in obese mice decreased the uptake significantly. The final product metabolite of p-iodophenylacetic acid in obese mice was increased significantly by the treatment. In conclusion, this food substitute may have a beneficial effect for the prevention or improvement of metabolic syndrome.
Our previous study has already clarified that partially decomposed alginate (Alg53) by Vibrio alginolyticus SUN53 has a competitive inhibitory effect on sucrase. The objective of this study is to evaluate the influence of Alg53 on the production of glucan from sucrose by glucosyltransferase and acid from glucose by Streptococcus sobrinus 6715. Glucosyltransferase was prepared from cultural medium of S. sobrinus using ultrafiltration and hydroxyapatite chromatography. In order to examine the inhibitory effect of Alg53 for production of glucan by GTase, partially purified GTase, sucrose and Alg53 solution were incubated at 37°C. The influence of Alg53 on the production of acid from glucose was evaluated by a degree of pH decline during the incubation for 60 min. The original Alg53 solution markedly inhibited to 21% of the synthesis of water-insoluble glucan from sucrose and that of 10-fold diluted of Alg53 solution was 23%. However, the production of water-soluble glucan from sucrose by GTase was hardly affected by Alg53. Furthermore, Alg53 suppressed dose-dependently pH decline by organic acid converted from glucose. These results suggest that Alg53 is expected as a functional food material which prevents or reduces dental caries.
Astaxanthin (Ax), a carotenoid ubiquitously distributed in microorganisms, fish, and crustaceans, has been known to be a potent antioxidant and hence exhibit various physiological effects. We attempted in these studies to evaluate clinical toxicity and efficacy of long-term administration of a new Ax product, by measuring biochemical and hematological blood parameters and by analyzing brain function (using CogHealth and P300 measures). Ax-rich Haematococcus pluvialis extracts equivalent to 4, 8, 20 mg of Ax dialcohol were administered to 73, 38, and 16 healthy adult volunteers, respectively, once daily for 4 weeks to evaluate safety. Ten subjects with age-related forgetfulness received an extract equivalent to 12 mg in a daily dosing regimen for 12 weeks to evaluate efficacy. As a result, no abnormality was observed and efficacy for age-related decline in cognitive and psychomotor functions was suggested.
In clinical trials for dietary supplements and functional foods, the study population tends to be a mixture of healthy subjects and those who are not so healthy but are not definitely diseased (called “borderline subjects”). For such heterogeneous populations, the t-test and ANCOVA method often fail to provide the desired treatment efficacy. We propose an alternative approach for the efficacy evaluation of dietary supplements and functional foods based on a change-point linear regression model. The model does not require the assumption of a constant treatment effect and provides clinically interpretable results. By employing the AIC-based profile likelihood method, inferences can be made easily using standard statistical software. The proposed method was applied to the Garcinia study data, and the merit of the method was demonstrated by comparing it with traditional methods.