Chronic inflammation has been thought as the major risk factor for various types of human cancer. The International Agency for Research on Cancer (IARC) has estimated that approximately one-fifth of cancer cases worldwide is attributable to infectious/inflammatory diseases. While we fundamentally understand that persistent inflammation plays a role in carcinogenesis, recent advances in the molecular study of the mechanisms have revealed that reactive oxygen and nitrogen species, harmful endogenous genotoxic substances, produced by inflammatory cells are largely involved in the carcinogenic process. In this article, we review the instances demonstrating the definite link between inflammation and cancer, and shed light on the molecular mechanisms proved to be responsible for the inflammation-based carcinogenesis.
We clarified that adequate oxygen stress induced by low dose irradiation activates not only chemical biological protective function, such as induction of the synthesis of superoxide dismutase, glutathione peroxidase, and heat shock protein 70, but also the biomembrane function, such as enhanced membrane fluidity and ATPase activity. It is possible that activation of these mechanisms alleviates in vivo oxidation injuries resulting in alleviation of pathologic condition, such as symptoms of hepatopathy and diabetes mellitus. Namely, adequate activation of the functions of the living body by low dose irradiation can contribute to suppressing aging and to preventing or reducing reactive oxygen species related diseases which are thought to involve peroxidation and have been regarded as the diseases for which radon spring water is an effective treatment. Clarification in detail of the mechanisms of these phenomena is required to understand the effects of low dose irradiation or radon inhalation on the functions of the living body, including adaptive response.
Partially hydrolyzed guar gum (PHGG) has a number of properties associated with dietary fiber. PHGG ingestion results in not only an increase in defecting frequency and softer stools in persons with constipation but also significantly improvement of diarrhea in patient with gastrointestinal intolerance. The lowering of fecal pH by intake of PHGG resulted in the growth of Lactobacillus spp. and Bifidobacterium spp., intestinal flora good for human health. Improvement of balance of intestinal microflora resulted in prevention from infection and colonization of Salmonella enteritidis. Further the ingestion of PHGG promoted absorption of mineral and lowered serum cholesterol and triglycerides in the rat and serum cholesterol in human by improving lipid metabolism without reduction of protein utilization. In addition, PHGG significantly reduced the level of plasma glucose, and thereby improved acute post-prandial plasma glucose and insulin response. All these observations suggest that the PHGG is prospective one of dietary fiber with various biological functions.
We report the first case-control study in Japan on the prevalence of non-steroidal anti-inflammatory drug (NSAID)-induced gastroduodenal ulcer and the prophylactic effect of co-administered anti-ulcer drugs in regular NSAID users. The NSAID users were 125 patients with rheumatoid arthritis (RA) and without gastrointestinal symptoms while regularly taking NSAIDs (>1 month). The NSAID non-users were125 age- and sex-matched healthy individuals seen between April 2001 and September 2003. Gastric ulcer prevalence was significantly higher among NSAID users than non-users and the odds ratio was 9.50 (95% CI: 2.21-40.8), while that of duodenal ulcers and reflux esophagitis was similar between users and non-users and the odds ratios were 1.11 (0.45-2.73) and 2.00 (0.68-5.85), respectively. The odds ratios for ulcers with concomitant treatment with a proton pump inhibitor or prostaglandin E1 analogue were 0.12 and 0.72 respectively, and were even lower than H2 receptor antagonist and mucosal-protective drug. In conclusion, gastric ulcer prevalence was significantly higher in Japanese RA patients using NSAIDs than in healthy non-users. Concomitant proton pump inhibitor or prostaglandin therapy was effective in preventing NSAID-induced ulcers.
We attempted to elucidate how Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a Chinese herbal medicine, attenuates the disruption of hepatic reactive oxygen species metabolism with the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats. TJ-15 (100, 250 or 500 mg/kg body weight) was orally administered to rats injected with CCl4 (1 ml/kg, i.p.) at 6 h after the toxicant treatment. Post-administered TJ-15 reduced progressive liver injury in CCl4-treated rats at 24 h after the toxicant treatment dose-dependently. The liver of rats treated with CCl4 alone showed increases in the concentration of thiobarbituric acid-reactive substances, an index of lipid peroxidation, and xanthine oxidase activity and decreases in reduced glutathione and ascorbic acid concentrations and superoxide dismutase, catalase, and glutathione reductase activities at 24 h after the toxicant treatment. The liver of CCl4-treated rats showed no change in Se-glutathione peroxidase activity and an increase in hepatic glucose-6-phosphate dehydrogenase activity at 24 h after the toxicant treatment. Post-administered TJ-15 attenuated the increases in hepatic thiobarbituric acid-reactive substances and xanthine oxidase activity and the decreases in hepatic reduced glutathione and ascorbic acid concentrations and superoxide dismutase, catalase, and glutathione reductase activities dose-dependently but did not affect the hepatic Se-glutathione peroxidase activity and the increased hepatic glucose-6-phosphate dehydrogenase activity. These results indicate that orally administered TJ-15 attenuates the disruption of hepatic reactive oxygen species metabolism with the progression of CCl4-induced acute liver injury in rats through its direct and indirect antioxidant actions. The results also suggest that this attenuating effect of TJ-15 could contribute to its preventive effect on the progression of CCl4-induced acute liver injury.
In a previous study, COLD-fX (CVT-E002), a proprietary extract of the root of North American ginseng (Panax quinuefolium), was found effective in the prevention of upper respiratory tract infections (URIs) in healthy adults. The underlying mechanisms of its action, however, were not determined. The present study was carried out to explore if the effects observed could be due to COLD-fX-mediated changes in the distribution of peripheral blood leukocytes, changes in the relative distribution of lymphocyte subsets or IgA levels in plasma. At the onset of an influenza season, a total of 323 subjects between 18 and 65 years with a history of more than 2 colds in the previous year, participated in a randomized double-blind placebo-controlled study. The participants were instructed to take 2 capsules/day of either COLD-fX or placebo for a period of 4 months. Two blood samples were collected from 42 (COLD-fX = 21; placebo = 21) of the 323 recruited volunteers. These samples were obtained before and after the treatment, and were used for determination of white blood cell differential counts, enumeration of lymphocyte subsets and measurement of plasma levels of immunoglobulin A (IgA). The distribution of colds over the 4 month period was found to be similar in both treatment and placebo groups. However although non-significant, the severity of the colds in the COLD-fX group was found to decrease over time. COLD-fX intervention increased the proportion of T-helper and natural killer (NK) cells, and decreased IgA levels in plasma to a greater extent than the placebo. It is possible, therefore, that these cells acted synergistically to reduce the severity and duration of URIs in the COLD-fX group. Further studies are warranted to determine the effects of daily supplementation of COLD-fX on the activities of T-helper and NK cells in plasma.
Heartburn is the main symptom of gastro-oesophageal reflux disease (GORD) which is a common disorder and is detrimental to health-related quality of life. The aim of the present study is to investigate the role of both Helicobacter pylori (H. pylori) infection and obesity to heartburn in a Japanese population. This was a cross-sectional study of 7386 (3789 male, mean age 52.5 yr), performed in 2002. Age, sex, smoking, drinking status, and presence/absence of heartburn were recorded. Body mass index (BMI) was calculated and anti-H. pylori antibodies were measured. For subjects aged 30-39 years and aged 50-59 years, heartburn reported by 7.8% and 9.1%, respectively, and antibodies to H. pylori were detected in 20.2% and 63.3%, respectively. Among younger individuals (≤39 years) with H. pylori infection, the adjusted odds ratio (OR) for having heartburn was 2.41, compared with those without infection. Overall, 21.3% were obese (BMI ≥25). Among middle-aged individuals (40-59 years) who were obese, the adjusted OR for having heartburn was 1.41, compared who were not obese. In conclusion, H. pylori infection and obesity are independently associated with increased risk of heartburn in the younger-aged and the middle-aged Japanese population, respectively.
We investigated the weight loss efficacy and safety of Citrus aurantium (CA, 1,000 mg/kg diet) along with usual levels of adrenergic stimulants in foods, i.e. caffeine (100 mg/kg diet) and/or tea catechins (500 mg/kg diet), in rats for 44 or 45 days. Even in combination with caffeine and tea catechins, the suppressive effect of CA against body fat accumulation was negligible, whereas no deleterious influences concerning cardiotoxicity were observed. Thus, although the efficacy of CA for weight loss seems to be questionable, no safety problems may occur even in people who habitually consume coffee and tea. However, it is noteworthy that the intake of CA markedly elevated the urinary excretion of adrenaline, and this was not affected by intake of caffeine and/or tea catechins at the usual levels. Therefore, the safety of CA intake with high levels of caffeine and tea catechins, especially in people at risk of heart disease, remains to be elucidated further.
Retracted publication: Marie Yeo, Tae Young Oh, Yong Seok Kim, Young Mi Won, Sung Whan Ahn, Jin Kim, Soon Ki Chung, Myung Hee Chung, Sung Uk Han and Ki-Baik Hahm: Journal of Clinical Biochemistry and Nutrition, 38(2), 77-93(2006). "Identification of Molecular Targets Associated with Augmented Gastric Mucosal Damages after Stress in the Presence of Helicobacter Pylori Using High Throughput Analysis of cDNA Microarray and Proteomics" (Received 11 October 2005, Accepted 22 November 2006)
This article was withdrawn by the request of the authors on September 22, 2006.
Wrong:Watanabe hyperlipidemic rabbits develop atherosclerosis after months of treatment with high fat-diet
Right:Watanabe hyperlipidemic rabbits develop atherosclerosis spontaneously under normal chow diet