It was found that uraemic toxin, p-cresol, was associated with constipation and that SYN treatment resulted in normalization of bowel habits and a decrease of serum p-cresol levels in HD patients. Therefore, SYN treatment may be anticipated to reduce the toxic effect of p-cresol in HD patients.

The faecal microbiota of 166 healthy Japanese newborns was analysed periodically from day 1 after birth until the age of 3 years by using the reverse transcription-quantitative PCR. Faecal pH and the organic acid concentration were also examined. Colonisation by both facultative anaerobes and strict anaerobes was confirmed in 95% of the meconium tested. Bifidobacterium-predominant microbiota was established subsequently in most of the infants by 3 months after birth. Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium catenulatum group and Bifidobacterium bifidum were the species mainly detected. Intergroup correlation analysis revealed that the bifidobacterial population levels, but not other strict anaerobe groups, were found to be negatively correlated with those of the Enterobacteriaceae from 7 days until 3 months after birth. Faecal pH was maintained at about 6 until 6 months after birth and reached 6.6 at 3 years after birth. The initial concentration of faecal organic acids (19 μM/g of faeces) just after birth increased until 3 years after birth to the level of 111 μM/g of faeces. Early start of feeding formula milk promoted colonisation by obligate anaerobes such as the Clostridium coccoides group, the Clostridium leptum subgroup, Prevotella, and Atopobium cluster during the 3 months after birth. Population levels of the bifidobacteria until 1 month after birth and those of the Bacteroides fragilis group until 6 months after birth were lower in infants delivered by Caesarean section than in those delivered normally. The results suggested that both earlier start of feeding of formula milk and the mode of infant delivery were found to be important in the development of intestinal microbiota in early infancy.

For conducting effective risk management in long-stay elderly people at a health service facility, we performed an open case-controlled study to evaluate the effect of the intake of probiotic-fermented milk containing Lactobacillus casei strain Shirota (LcS-fermented milk) on norovirus gastroenteritis occurring in the winter season during the intake period. A total of seventy-seven elderly people (mean age 84 years) were enrolled in the study. During a 1-month period, there was no significant difference in the incidence of norovirus gastroenteritis between the LcS-fermented milk-administered (n 39) and the non-administered (n 38) groups; however, the mean duration of fever of .378C after the onset of gastroenteritis was 1·5 (SD 1·7) d in the former and 2·9 (SD 2·3) d in the latter group, showing a significant shortening in the former group (P, 0·05). RT-quantitative PCR analysis targeting ribosomal RNA showed both Bifidobacterium and Lactobacillus to be significantly dominant, whereas Enterobacteriaceae decreased in faecal samples from the administered group (n 10, mean age 83 years), with a significant increase in faecal acetic acid concentration. Continuous intake of LcS-fermented milk could positively contribute to the alleviation of fever caused by norovirus gastroenteritis by correcting the imbalance of the intestinal microflora peculiar to the elderly, although such consumption could not protect them from the disease.

No abstract

Breast cancer is common in women all over the world, and exploration of chemopreventive approaches to this cancer is very important. Nimesulide, a selective inhibitor of cyclooxygenase-2 (COX-2), is a good candidate as a chemopreventive agent with low toxicity. We examined its effects on mammary tumor development in female Sprague-Dawley rats induced with the environmental carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rats at 7 weeks of age received intragastric intubations of PhIP (85 mg/kg body weight) 4 times weekly for 2 weeks and were maintained on control diet (high fat diet) or experimental diet (high fat diet supplemented with 400 ppm nimesulide) throughout the experiment. COX-2 protein was over-expressed in epithelial cancer cells and stromal cells of the PhIP-induced mammary carcinomas, but was weak or not apparent in normal mammary gland cells. The development of mammary carcinomas was clearly suppressed by administration of nimesulide. The carcinoma incidence was 51% as compared to 71% for the control diet group. The average multiplicity of carcinomas in the experimental diet group was 1.2 ± ± ± ±0.2 (P < < < <0.05), significantly smaller than the control diet group value (2.6 ± ± ± ±0.5). The size of carcinomas was also clearly decreased; 1.1 ± ± ± ±0.4 cm 3 /rat in experimental diet group (P < < < <0.05), 4.1 ± ± ± ±1.3 cm 3 /rat in the control diet group. The results therefore provide evidence that the selective COX-2 inhibitor, nimesulide, possesses chemopreventive activity against PhIPinduced mammary carcinogenesis in rats.Key words: Nimesulide -COX-2 inhibitor -Chemoprevention -Mammary gland cancer -PhIP Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to decrease prostanoid synthesis through inhibition of cyclooxygenase (COX) activity, 1) resulting in antiinflammatory effects. Two isoforms of cyclooxygenase-1 and -2 (COX-1 and COX-2) have been characterized in mammalian and avian species. COX-1 is constitutively expressed in most tissues to regulate prostaglandin (PG) production and maintain stable physiological conditions, including gastric cytoprotection and blood flow. In contrast, COX-2 is transiently induced by lipopolysaccharide, cytokines and growth factors, and has been indicated to produce large amount of prostanoids involved in inflammation and mitogenesis.2) COX-2 protein and mRNA are known to be expressed in not only inflammatory tissues, but also colorectal cancers in rats and humans.3, 4) Consistent with a causal role, regular use of aspirin has been shown to lower the risk of colon cancer in man. 5) Animal model studies have also demonstrated that NSAIDs, including aspirin and sulindac, can suppress colon carcinogenesis induced by azoxymethane (AOM) in rats.6, 7) In addition, NSAIDs have been shown to inhibit chemically induced mammary carcinogenesis in rats. 8, 9) Conventional NSAIDs such as aspirin, sulindac and indomethacin block both COX-1 and COX-2, resulting in unwanted side effects such as gastritis and gastric ulceration. However, selective CO...