Comparison of digestibility and breath hydrogen gas excretion of fructo-oligosaccharide,galactosyl-sucrose,and isomalto-oligosaccharide in healthy human subjects

OBJECTIVES: To clarify the difference of digestibility in the small intestine among fructo-oligosaccharide (FOS), galactosyl-sucrose (GS), and isomalto-oligosaccharide (IMO) using breath hydrogen test. DESIGN: The first step: screening test of breath hydrogen excretion and FOS tolerance test to select the subjects. The second step: breath hydrogen test of three kinds of oligosaccharides, carried out using precautionary regulations. The ingestion order was 10 g of FOS, GS, and IMO, with increases, at 1-week interval, up to 20 g, respectively. Breath gas was collected before, at 20 min intervals from 40 to 120 min after, and at 30 min intervals from 120 min to 7 h after ingestion of test substance. SETTING: Laboratory of Public Health Nutrition, Department of Nutrition and Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan. SUBJECTS: A total of nine males (average: age 25.7+/-3.5 y, weight 61.9+/-8.8 kg, height 170.0+/-6.0 cm) and 29 females (average: 23.1+/-7.2 y, 52.9+/-5.3 kg, 157.5+/-5.1 cm) from the University of Tokyo and Siebold University of Nagasaki. MAIN OUTCOME MEASURES: Breath hydrogen excretion from end-expiratory gas. RESULT:: Breath hydrogen of FOS was more remarkably excreted than that of GS; that of IMO was slight; and that of AUC (10 g) was significantly different. FOS was 9768+/-3253 ppm, GS was 3662+/-2632 ppm, and IMO was 831+/-1154 ppm. A dose dependence was observed at doses between 10 and 20 g of FOS and GS, and the initial time of 20 g was earlier than that of 10 g. CONCLUSIONS: FOS was not hydrolyzed, GS was slightly hydrolyzed, and IMO was readily hydrolyzed by small intestinal enzymes. H(2) gas reflected fermentability in the large intestine. SPONSORSHIP: Siebold University of Nagasaki.     

A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer

A 67-year-old female was admitted to our hospital in May, 2001 for examination. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy, and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and prolonged NC were obtained after these chemotherapies. However, pleural effusion and ascites appeared again, and we diagnosed progressive disease. As a third line chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week, with a 1-week break between the courses. Two weeks after the start of this therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is considered to be promising for advanced gastric cancers, as second or third line chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to be effective in improving QOL.     

Release of glutamate and GABA in the hippocampus under zinc deficiency

Zinc homeostasis in the brain is affected by dietary zinc deficiency, and its alteration may cause brain dysfunctions. On the basis of the previous evidence that hippocampal zinc was responsive to 12-week zinc deprivation, responsiveness of hippocampal zinc to dietary zinc deficiency was examined in rats fed a zinc-deficient diet for 4 weeks. Zinc concentration in the hippocampus was not decreased by zinc deprivation for 4 weeks. However, Timm's stain was extensively attenuated in the brain of the zinc-deficient rats. In the brain of the zinc-deficient rats, moreover, zinc concentration in the hippocampal extracellular fluid was approximately 30% of that of control rats. These results demonstrate that vesicular zinc is responsive to dietary zinc and may decrease easily under zinc deficiency. Zinc concentration in the hippocampal extracellular fluid during stimulation with high K(+) was significantly increased even in zinc-deficient rats, although the increased levels of zinc were lower than the basal levels of zinc in control rats. The basal glutamate concentration in the hippocampal extracellular fluid was not significantly different between the control and zinc-deficient rats. However, glutamate concentration in the hippocampal extracellular fluid during stimulation with high K(+) was more increased in the zinc-deficient rats than in the control rats. Gamma aminobutyric acid (GABA) concentration in the hippocampal extracellular fluid during stimulation with high K(+) was increased in the control rats, but not in the zinc-deficient rats. The present study suggests that the excitability of hippocampal glutamatergic neurons is enhanced by dietary zinc deficiency.     

Effects of phototherapy in neonates on circadian sleep-wake and saliva cortisol level rhythms

The influence of phototherapy treatment during the neonatal period on sleep-wake rhythm, and its long-term effects on biological rhythms, was evaluated in preterm and full-term infants. Forty-three infants treated with phototherapy during the neonatal period and 47 untreated infants were examined for entrainment of sleep-wake rhythms between 16 and 52 weeks and for sleep-wake and saliva cortisol rhythms at 2.5 years of age. The age of sleep-wake rhythm entrainment was not significantly different between the 2 groups. No correlations between duration of exposure to phototherapy and corrected age of entrainment of sleep-wake rhythm were observed. At follow-up, no significant differences in sleep-wake and saliva cortisol rhythms were observed between the 2 groups, indicating that circadian variations were similar to those in adults.     

Improved diabetic syndrome in C57BL/KsJ-db/db mice by oral administration of the Na(+)-glucose cotransporter inhibitor T-1095

1. The therapeutic effects of an orally active inhibitor of Na(+)-glucose cotransporter (SGLT), T-1095 (a derivative of phlorizin; 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glycopyranoside)) were examined in C57BL/KsJ-db/db (db/db) mice, a genetic animal model of obese type 2 diabetes. 2. The higher renal SGLT activity in db/db mice than normoglycaemic C57BL/KsJ-db/+m (db/+m) mice may support the rationale for using an SGLT inhibitor in the treatment regimen for type 2 diabetes. Both T-1095 and its metabolite, T-1095A, which had approximately 10 times more potency, effectively inhibited renal SGLT activity of these mice in vitro. 3. Single oral administration of T-1095 (10, 30, 100 mg kg(-1), p.o.) to db/db mice caused a dose-dependent reduction in blood glucose levels and a concomitant increase in glucose excretion into urine. In contrast, T-1095 only slightly affected blood glucose levels in db/+m mice. 4. Chronic administration of T-1095 (0.1% w w(-1) pellet chow, for 12 weeks) decreased blood glucose and haemoglobin A(1C) levels, and improved glucose intolerance in db/db mice. The age-related decrease in plasma insulin levels was markedly inhibited and there was a 2.5 fold increase of insulin content in the pancreas of T-1095-treated db/db mice. Food consumption was not changed, while impaired body weight gain was ameliorated by T-1095 treatment. 5. Both the development of albuminuria and the expansion of glomerular mesangial area in db/db mice were significantly suppressed by chronic T-1095 treatment, indicating the prevention of the progression of diabetic nephropathy. 6. These results demonstrate that the SGLT inhibitor T-1095 is able to improve the metabolic abnormalities and inhibit the development of diabetic complications in db/db mice. Thus, T-1095 can be used for therapy of type 2 diabetic patients.     

Zinc homeostasis in the brain of adult rats fed zinc-deficient diet

Zinc concentration and (65)Zn uptake in the brain of rats fed zinc-deficient diet for 12 weeks were examined, based on a previous finding of the impairment of learning behavior by the zinc deprivation. Zinc concentrations in the brain, except for the hippocampal formation, did not decrease significantly in zinc-deficient rats, whereas zinc concentration in the liver of the zinc-deficient rats was approximately half that of control rats. When zinc-deficient rats were subjected to brain autoradiography with (65)Zn, (65)Zn concentration in any brain region of zinc-deficient rats was significantly higher than in control rats 6 days after injection of (65)ZnCl(2). The increase rate of (65)Zn concentration in the brain by the zinc deprivation was approximately 150%, and was similar to those in the liver and serum, suggesting that dietary zinc deprivation may cause a scarcity of zinc in the brain, in addition to the peripheral tissues such as the liver. These results indicate that the adult brain is responsive to dietary zinc deprivation. In the brain of zinc-deficient rats, the increase rate of (65)Zn concentration in the hippocampal formation seemed to be low compared to those in other brain regions. The hippocampal formation may be the most responsive to dietary zinc deprivation in the adult brain. The present finding demonstrates that zinc homeostasis in the brain is altered by chronically dietary zinc deprivation.     

Neonatally administered diethylstilbestrol retards the development of the blood-testis barrier in the rat

Newborn rats were treated with 10 microg of diethylstilbestrol (DES) on alternate days from the 2nd to the 12th postnatal day, and the testes were sequentially examined up to 105 days of age by light, electron, and confocal laser microscopy. In control rats, spermatozoa and step 19 spermatids were observed in stage VIII seminiferous tubules at 56 days of age. Spermatogenic cells in DES-treated rats differentiated normally from birth until 21 days of age, after which differentiation continued only to the pachytene-spermatocyte stage. From this age onward, spermatogenic cells older than pachytene spermatocytes were not found until 56 days of age. After this point, the cells resumed differentiation and finally became spermatozoa by 91 days of age; that is, 35 days later than control rats. Electron and confocal laser microscopy showed that in the normal rat, the formation of the ectoplasmic specialization between adjoining Sertoli cells was observed as early as 20 days of age. In contrast, the specialization was not formed until 56 days of age in DES-treated rats. Furthermore, the delay in functional maturation of this structure as the blood-testis barrier was confirmed by intercellular tracer experiments. It is clear that neonatal administration of DES delayed the establishment of the blood-testis barrier for 4 weeks. Consequently, during this period, pachytene spermatocytes were exfoliated from the seminiferous epithelium without completion of meiosis.     

Establishment of an oral squamous cell carcinoma cell line (NOS-1) exhibiting amplification of the erbB-1 oncogene and point mutation of p53 tumor suppressor gene: its biological characteristics and animal model of local invasion by orthotopic transplantation of the cell line

We established a new cancer cell line, NOS-1, which was derived from a human oral primary squamous cell carcinoma. Geneticin treatment was adopted to eliminate contaminating fibroblasts and to enrich tumor cells in the early stage of the culture. The NOS-1 cells showed epithelial morphological features with light and electron microscopy, and immunohistochemical analysis confirmed their epithelial origin. Overexpression of mutant p53 protein, a p53 point mutation at codon 248 with transition from CGG to TGG, and amplification of the erbB-1 oncogene/epidermal growth factor receptor gene were also observed in NOS-1 cells. The NOS-1 cells formed tumors in nude mice when transplanted subcutaneously into their backs. Further, they were transplantable orthotopically in the tongues of nude mice, and the transplanted tumors in the tongue showed diffuse invasion without forming capsules. The NOS-1 cells were useful for elucidating the mechanism involving p53 inactivation and erbB-1 oncogene amplification, as well as treatment of oral cancer.