Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma.

Neoadjuvant treatment has become standard care for patients with resectable esophageal cancer. However, some patients cannot undergo surgery or curative resection because of disease progression during neoadjuvant treatment. The aim of this study is to identify the pretreatment characteristics of patients in whom neoadjuvant treatment failed. The study enrolled 231 patients who underwent chemotherapy with cisplatin and 5-fluorouracil (CF) as neoadjuvant therapy for T1N1-3 or T2-3 any-N esophageal squamous cell carcinoma (ESCC). Of these patients, 201 (87.0%) underwent curative resection (R0) and 30 (13.0%) could not undergo curative resection; 19 patients (8.2%) underwent incomplete resection (R1 or R2), and 11 patients (4.8%) could not undergo surgery because of disease progression. We compared clinical characteristics and survival between patients who underwent curative resection (curative group) and those who could not undergo curative resection (noncurative group) to determine the factors predicting noncurative treatment. The noncurative group had significantly worse disease-specific survival than the curative group (P < 0.001). All patients in the noncurative group had cT3 tumors. In 141 patients with cT3 tumors, those in the noncurative group were more likely to have higher serum SCC antigen concentration (P = 0.021), location of the main tumor in the upper to the middle third of the esophagus (P = 0.071), intramural metastases (P < 0.001), advanced N category (P = 0.016), and bulky lymph node metastases (P = 0.060). Multivariate logistic regression analysis identified location of the main tumor in the upper to the middle third of the esophagus (P = 0.047), intramural metastases (P = 0.002), and nodal metastases (N1, P = 0.014; N2, P = 0.015, respectively) as independent predictors of treatment failure in patients with cT3 tumors. Neoadjuvant CF therapy alone may not be effective for patients with cT3 tumors accompanied by these risk factors, and the efficacy of alternative strategies, such as triplet chemotherapy or chemoradiotherapy, should be evaluated.

14-3-3ζ-Mediated Stimulation of Oxidative Phosphorylation Exacerbates Oxidative Damage Under Hypothermic Oxygenated Conditions in Human Renal Tubular Cells (HK-2).

Cellular survival and death are at least partially regulated by the phosphorylation of proteins. A chaperon protein, 14-3-3ζ, regulates the activity of many proteins by covering the phosphorylation site within a 14-3-3 binding motif. Therefore, regulation of 14-3-3ζ activity may affect the fate of cells subjected to cold preservation and/or hypothermic oxygenated conditions. The present study assessed whether 14-3-3ζ protects cells from hypothermic oxygenation-induced injury and clarified its role in mitochondrial functions. Human renal tubular cell line HK-2 or 14-3-3ζ-overexpressed HK-2 (ζHK-2) cells were subjected to 72 hours of normoxic cold preservation in UW solution with or without antioxidants and hydroperoxides. Cellular death, adenosine triphosphate (ATP) content, and MTT catabolism were evaluated. Deferoxamine treatment reduced cellular death and augmented ATP content in both cell types. These indices were higher in ζHK-2, regardless of deferoxamine treatment. Exposure to hydroperoxides did not affect cellular death in either cell type, whereas hydroperoxide supplementation significantly reduced ATP content, except for low-dose hydrogen peroxide in HK-2 cells. MTT assay at normal state showed higher values in ζHK-2 cells, whereas it was impaired by hydroperoxides in both cell types. These results suggest that accumulation of hydroperoxides as a byproduct of the augmented oxidative phosphorylation by 14-3-3ζ overexpression causes mitochondrial dysfunction. In conclusion, despite possessing many potentially protective functions, 14-3-3ζ exacerbates cellular injury under hypothermic oxygenated conditions. 14-3-3ζ accelerates mitochondrial functions together with iron-dependent oxidative damage. Although further investigations are necessary, upregulation of 14-3-3ζ could be a method to maintain mitochondrial function under hypothermic oxygenated conditions, as shown in hypothermic machine preservation of renal grafts, when appropriate antioxidant treatment is administered.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

BACKGROUNDS: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. PATIENTS AND METHODS: A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. RESULTS: We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). CONCLUSIONS: We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.

Skimmed, sterilized, and concentrated bovine late colostrum promotes both prevention and recovery from intestinal tissue damage in mice.

Bovine colostrum is a rich source of tissue repair and growth factors, and inhibits gastrointestinal injury induced by the side effects of nonsteroidal antiinflammatory drugs (NSAID), such as indomethacin. Nonsteroidal antiinflammatory drugs are drugs with analgesic and antipyretic effects, but in higher doses they have inflammatory effects. The pathogenesis of small intestinal damage caused by NSAID is unclear. The present study was performed to investigate the antiinflammatory effects of skimmed, sterilized, and concentrated bovine late colostrum on intestinal injury induced by side effects of NSAID, and then to identify the active ingredient in the colostrum for intestinal tissue. In Japan, the sale of bovine colostrum within 5 d after parturition is prohibited by law. Therefore, we focused on bovine late colostrum obtained from healthy lactating cows 6 to 7 d after parturition. Proliferation of small intestine epithelial cells was stimulated in mice fed the colostrum for 1 wk. With regard to indomethacin-induced enteropathy, both prefeeding and postfeeding with colostrum facilitated growth of the intestinal villi, indicating preventive and healing effects. Furthermore, to identify the active ingredient in the colostrum responsible for this effect, the casein and whey fractions were prepared from the colostrum and fed to normal mice. Only the colostrum casein fraction stimulated intestinal villus elongation, whereas the whey fraction and mature milk casein showed no such effect. Taken together, these observations indicate that the skimmed, sterilized, and concentrated bovine late colostrum, especially the casein fraction, could be used to treat the injurious effects of NSAID in the intestine and could be effective for treatment of other ulcerative conditions in the bowel, suggesting that the colostrum has therapeutic potential for intestinal inflammation.

CO2 laser improves 45S5 bioglass interaction with dentin.

Bioglass 45S5 is a bioactive glass that can create a layer of calcium-phosphate crystals on mineralized hard tissues. In this study, 45S5 bioglass was mixed with phosphoric acid and irradiated with CO(2) laser and examined as a possible aid in the treatment of dentin hypersensitivity. The dentinal surface modified by the aforementioned technique was chemically and micro-morphologically examined with a field emission scanning electron microscope (FE-SEM) equipped with an energy-dispersive x-ray spectroscope (EDS), and the crystalline structures of the examined dentinal surfaces were examined by x-ray diffraction (XRD). Moreover, the mechanical properties of the newly formed layer were examined by nanoindentation. The results showed that 45S5 bioglass could occlude the dentinal tubule orifices with calcium-phosphate crystals. The application of CO(2) laser potentially improved the mechanical organization of these crystals.

Double-stranded RNA induces the synthesis of retinoic acid-inducible gene-I in vascular endothelial cells.

Viral infection induces various responses in vascular endothelial cells. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA), and treatment of cells with poly IC mimics the viral infection to the cells. Retinoic acid-inducible gene-I (RIG-I) is a protein belonging to the DExH-box family and designated as a putative RNA helicase. RIG-I is considered to play a role in antiviral responses through the regulation of gene expressions. In the present study, the authors treated human umbilical vein endothelial cells (HUVECs) with poly IC and found that poly IC induced the expression of RIG-I. The poly IC-induced RIG-I expression was inhibited by the preincubation of the cells with 2-aminopurine, an inhibitor of dsRNA-dependent protein kinase (PKR). Immunohistochemical examination revealed high levels of RIG-I immunoreactivity in vascular endothelial cells in the thalamus from rats inoculated with hantavirus. Induction of RIG-I by poly IC may be involved in the antiviral responses in endothelial cells.

Complete nucleotide sequences of attenuated and severe isolates of Leek yellow stripe virus from garlic in northern Japan: identification of three distinct virus types in garlic and leek world-wide.

We have determined the complete nucleotide sequence of three isolates (two severe and one attenuated) of the potyvirus Leek yellow stripe virus (LYSV), the main causal agent of the garlic mosaic disease that is prevalent in Aomori prefecture, northern Japan. They contained 10,296-10,297 nucleotides and encoded a deduced polyprotein of 3,215 amino acids. Sequence variation among the three isolates was 1.5% at both the nucleotide and amino acid levels. Surprisingly, the sequences of all three isolates were quite different from that of recently described garlic isolate of LYSV from China. Sequence similarities among the 5'-UTR and P1 regions were only 56-57% and 52-53%, respectively, raising the possibility that these isolates may actually be distinct virus species. Phylogenetic analyses using 5'-UTR, P1 protein and coat protein revealed that all LYSV isolates described to date can be divided into three groups; i.e., those from leek, those from garlic in northern Japan, and those from garlic in southern Japan, China, and other parts of the world. The garlic isolates from northern Japan were more closely related to LYSV isolates from leek than to garlic isolates from southern Japan and China, suggesting a different origin for the garlic cultivars now cultivated in northern Japan.

Effects of preoperative chemotherapy on metastatic lymph nodes in esophageal squamous cell carcinoma.

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.

High-rate methane fermentation of lipid-rich food wastes by a high-solids co-digestion process.

This paper presents an experimental study on anaerobic degradation of lipids-rich food wastes by using the high solids co-digestion process. The experiments were conducted under mesophilic (35 degrees C) and thermophilic (55 degrees C) condition, respectively, by using a semi-continuous flow completely mixed reactor. The influent TS level was controlled at around 10%, while the hydraulic retention time (HRT) was changed from 15 days to 7.5 days. The lipids (fats or oil and grease) content in the influent TS was changed from 8% to 40% by adding salad oil (vegetable) and lard (animal) to the food wastes. The result of this study showed that the food wastes containing high lipids content was effectively degraded by the high solids co-digestion process and over 85% of lipid was degraded to biogas with 60-65% of methane. In addition, thermophilic methane fermentation was more effective for reducing lipids and had more higher loading capacity compared with mesophilic condition.

Dietary sesame seeds elevate alpha- and gamma-tocotrienol concentrations in skin and adipose tissue of rats fed the tocotrienol-rich fraction extracted from palm oil.

The metabolism of tocotrienol remains unclear. We studied the distribution of tocotrienol in rats fed the tocotrienol-rich fraction extracted from palm oil. We have previously shown that dietary sesame seeds markedly elevate the tocopherol concentration in rats. In this study, we also examined the effect of dietary sesame seeds on the tocotrienol concentration. In experiment 1, rats (4-wk-old) were fed the diet with alpha-tocopherol alone or with alpha- and gamma-tocotrienols. In experiment 2, the effect of dietary sesame seeds on tocopherol and tocotrienol concentrations in rats fed the diet with tocopherol and tocotrienol was studied. The rats were fed the experimental diet for 8 wk in both experiments. alpha- and gamma-Tocotrienols accumulated in the adipose tissue and skin, but not in plasma or other tissues, of the rats fed tocotrienols. Dietary sesame seeds elevated (P < 0.05) tocotrienol concentrations in the adipose tissue and skin, but did not affect their concentrations in other tissues or in plasma. The gamma-tocopherol concentration in all tissues and plasma of rats fed gamma-tocopherol was extremely low but was elevated (P < 0.05) in many tissues by feeding sesame seeds. These data suggest that the transport and tissue uptake of vitamin E isoforms are different. Dietary sesame seeds elevate the concentrations of both tocopherols and tocotrienols.

The elevation of natural killer cell activity induced by laughter in a crossover designed study.

The elevation of natural killer cell activity (NKCA) by laughter was not confirmed due to incomplete methodology of previous studies although positive emotion is believed to be favorable for health. To verify NKCA elevation by laughter in a crossover design, we measured NKCA before and after watching films, presenting 75-min comic film and non-emotional control film at different days to the same 21 healthy male subjects. Electromyogram of left major zygomatic muscle was obtained during the films to quantify the magnitude of laughter as an index of emotional expression. As indices of emotional experience, the self-rated pleasantness of the comic film and mood state before and after film were measured using visual analogue scale and Profiles of Mood State (POMS), respectively. The comic film significantly elevated NKCA (26.5-29.4%, p<0.05), whereas the control film did not (27.1-24.8%, not significant). This is the first study to demonstrate NKCA elevation by laughter in a crossover designed study. To examine the contribution of experiential and expressive aspects of laughter to NKCA elevation, correlation of NKCA elevation with the self-rated pleasantness, mood scores before and after comic film and the magnitude of laughter was statistically tested. We found that NKCA elevation was negatively correlated with the scores of negative mood scales of POMS while NKCA elevation had no significant correlation with self-rated pleasantness and the magnitude of laughter. Further group analysis revealed that high scores of depression and anger-hostility suppressed NKCA elevation by laughter. We also found that NKCA before and after comic film had tendency of correlation with self-rated pleasantness of the comic film while NKCA had no correlation with the magnitude of laughter. These findings suggest that NKCA elevation and NKCA before and after comic film seem to be related with the experiential aspects of laughter rather than with the expressive aspects.

Seasonal rhinitis in a cat sensitized to Japanese cedar (Cryptomeria japonica) pollen.

A cat showing seasonal allergic symptoms of rhinitis was examined for reactivities to Japanese cedar (Cryptomeria japonica, CJ) pollen allergen by intradermal skin test (IDST), Prausnitz-Kustner (P-K) test, and lymphocyte blastogenic response. In IDST for 26 common allergens. the cat showed a positive reaction to CJ pollen allergen. P-K test using CJ pollen allergen also showed a positive reaction, indicating the presence of serum IgE specific to CJ pollen. In the lymphocyte blastogenic response, the stimulation index in the presence of CJ pollen allergen was 2.4. These data suggested that the seasonal rhinitis observed in the cat was caused by the sensitization to CJ pollen allergen.

Interleukin-2 carbohydrate recognition modulates CTLL-2 cell proliferation.

Interleukin-2 (IL-2) specifically recognizes high-mannose type glycans with five or six mannosyl residues. To determine whether the carbohydrate recognition activity of IL-2 contributes to its physiological activity, the inhibitory effects of high-mannose type glycans on IL-2-dependent CTLL-2 cell proliferation were investigated. Man(5)GlcNAc(2)Asn added to CTLL-2 cell cultures inhibited not only phosphorylation of tyrosine kinases but also IL-2-dependent cell proliferation. We found that a complex of IL-2, IL-2 receptor alpha, beta, gamma subunits, and tyrosine kinases was formed in rhIL-2-stimulated CTLL-2 cells. Among the components of this complex, only the IL-2 receptor alpha subunit was stained with Galanthus nivalis agglutinin which specifically recognizes high-mannose type glycans. This staining was diminished after digestion of the glycans with endo-beta-N-acetylglucosaminidase H or D, suggesting that at least a N-glycan containing Man(5)GlcNAc(2) is linked to the extracellular portion of the IL-2 receptor alpha subunit. Our findings indicate that IL-2 binds the IL-2 receptor alpha subunit through Man(5)GlcNAc(2) and a specific peptide sequence on the surface of CTLL-2 cells. When IL-2 binds to the IL-2Ralpha subunit, this may trigger formation of the high affinity complex of IL-2-IL-2Ralpha, -beta, and -gamma subunits, leading to cellular signaling.

[Evaluation of patients who received treatment (procedures) that involved minor surgical techniques at home].

We retrospectively examined the clinical records of 24 patients who underwent minor surgery under local anesthesia among 207 who were taken care of at home by our staff, from December 1986 to March 2001. There were 17 men and 7 women. Their mean age was 74 years and the range was 50 to 92 years old. The treatment consisted of central vein catheterization in 14 patients, skin suture in 6, subcutaneous implantation of port establishment and epidural catheterization in 3 patients each, treatment of anus, thorax centesis, skin tumor resection, and treatment of bed sores 2 patients each, wash of thorax, ovarian cyst centesis, and transcutaneous trachocentesis 1 patient each. A relationship of trust with the patient and the family and informed consent were thought as the most important aspects regarding treatment involving minor surgery provided at home.

Experimental sensitization with Japanese cedar pollen in dogs.

Japanese cedar pollinosis is a type I allergic disease mediated by immunoglobulin E (IgE) antibodies to Japanese cedar (Cryptomeria japonica) pollen antigen (CPAg). By using 22 dogs consisting of 20 dogs aged 3 months and 2 dogs aged 3 years, immunization was performed by subcutaneous injections of CPAg with aluminum hydroxide gel. Variable levels of CPAg-specific IgE antibody response were detected in 21 of the 22 immunized dogs two weeks after the second immunization. This study provided an experimental sensitization system with CPAg in dogs, which will be useful for further immunological studies on Japanese cedar pollinosis.

In vivo and in vitro tests showing sensitization to Japanese cedar (Cryptomeria japonica) pollen allergen in atopic dogs.

Using both in vivo and in vitro tests, dogs with atopic dermatitis were examined for sensitization with Japanese cedar (Cryptomeria japonica, CJ) pollen allergen. Ten dogs with clinical manifestation of atopic dermatitis were shown to be sensitized to CJ pollen based on the results of intradermal skin test and serum antigen-specific IgE test. In vitro lymphocyte stimulation test showed blastogenic response after stimulation with crude antigen of CJ pollen in all of the 5 cases examined. The peripheral leukocytes showed increased histamine release after stimulation with crude antigen of CJ pollen in 2 cases examined. These data indicate that a proportion of dogs with atopic dermatitis is sensitized to CJ pollen in a cell-mediated manner and show immediate phase reaction of type I hypersensitivity.

Inhibition by dietary tea polyphenols of chemical mediator release from rat peritoneal exudate cells.

Male Wistar rats were given purified diets containing safflower (SAF), perilla (PER), or palm (PAL) oils with or without 1% tea polyphenols (TP) for 3 weeks, and chemical mediator releasing activity from rat peritoneal exudate cells (PEC) was measured. Histamine releasing activity was not influenced by TP, while histamine release and intracellular histamine content were significantly increased in the PAL-fed group. On the contrary, leukotriene B4 (LTB4) release was significantly lower in rats fed PER than in those fed SAF and PAL, and TP significantly decreased the release in all fat groups. TP also significantly inhibited the release of LTB5, which was generated only in rats fed PER. TP significantly decreased the proportion of arachidonic acid (AA) in PEC in the SAF-fed group and that of eicosapentaenoic acid (EPA), the precursor of LTB5 in the PER-fed group, but did not influence that of AA in the PAL- and PER-fed group. These results suggest that ingestion of TP improves type I allergic symptom through the inhibition of LT release though the inhibition by TP could not be totally explained by the reduction of substrate fatty acid.

IgE-reactivity to major Japanese cedar (Cryptomeria japonica) pollen allergens (Cry j 1 and Cry j 2) by ELISA in dogs with atopic dermatitis.

The present study investigated IgE-reactivity to two major Japanese cedar (Cryptomeria japonica, C. japonica) pollen allergens (Cry j 1 and Cry j 2) in dogs with atopic dermatitis by use of a fluorometric ELISA. The serum samples from 27 dogs that showed IgE-sensitivity to crude C. japonica pollen allergen by ELISA were tested for specific IgE to the two major allergens. All 27 dogs had anti-Cry j 1 IgE, and 10 (37%) had anti-Cry j 2 IgE. Inhibition of binding of dog specific IgE to crude C. japonica pollen allergen was carried out by addition of Cry j 1. When serum samples containing anti-Cry j 1 IgE but no anti-Cry j 2 IgE were incubated with Cry j 1, specific IgE binding to crude C. japonica pollen allergen was almost abolished. These findings suggest that Cry j 1 is a major allergen in dogs.

[Antimicrobial susceptibility testing for Mycobacterium tuberculosis by the bioluminescence assay of mycobacterial ATP using filamentous cell treatment].

The antimicrobial susceptibility testing for Mycobacterium tuberculosis by the bioluminescence assay of adenosine triphosphate(ATP) derived from living mycobacteria was improved introducing filamentous cell treatment(FCT) reported for beta-lactam susceptibility test of Pseudomonas aeruginosa by Hattori. Before ATP extraction, bacterial cells were treated with the FCT reagent for 30 minutes at room temperature. Adenosine phosphate deaminase in the FCT reagent simultaneously digested the extracted ATP and released ATP in a liquid culture of M. tuberculosis H37Rv and the RLU level was decreased markedly. Using this improved ATP method, we determined the ATP contents of M. tuberculosis inoculated into Middle-brook 7H9 broth medium with or without drugs. In ethambutol(EB) susceptibility, the ATP method reported previously, showed false-resistance when judged within 7 days. To eliminate false-resistance in EB susceptibility we applied the modified ATP method with FCT treatment to strains determined EB susceptible by reference methods. Using this modified ATP method, we could judge EB susceptibility of 5 ATCC reference strains within 3 days, and these of 15 clinical isolates of M. tuberculosis within 5 days. And all the results obtained were coincident between the ATP method and the reference methods. The reproducibility of this modified ATP method was evaluated with six ATCC reference strains at the concentrations of 0.1 microgram/ml of isoniazid(INH), 2.0 micrograms/ml of rifampicin(RFP), 2.5 micrograms/ml of EB, 2.0 micrograms/ml of streptomycin(SM), and 5.0 micrograms/ml of kanamycin(KM). The test was repeated six times. Reduction of ATP contents were observed in susceptible strains but not in resistant ones within 3 days of cultivation and susceptibilities to drugs could be determined within 3 days at every time when combined FCT to the ATP method. And highly reproducible results were obtained. It is strongly suggested that this modified method is simple, rapid, highly reproducible and nonradiometric, and could be used for the assessment of drug susceptibility for M. tuberculosis.

Effects of various tocopherol-containing diets on tocopherol secretion into bile.

Gamma-tocopherol is abundant in common vegetable oil, but its concentration in plasma and liver is much lower than that of alpha-tocopherol. Discrimination between different forms of tocopherol is thought to take place via the hepatic alpha-tocopherol transfer protein (alpha-TTP). Gamma-tocopherol, with a low binding capacity to alpha-TTP, is thought to be excreted via the bile. Our previous studies showed that gamma-tocopherol administered with sesame seed exhibits significantly higher concentrations in the plasma and liver of rats than gamma-tocopherol alone. Thus, we attempted to confirm whether a much higher amount of gamma-tocopherol rather than alpha-tocopherol would be secreted in the bile, and whether sesame seed would suppress the secretion of gamma-tocopherol. In one experiment, we examined the concentrations of alpha- or gamma-tocopherol in the plasma, liver, and bile of rats fed diets containing 300 mg/kg of alpha-tocopherol, 300 mg/kg of gamma-tocopherol, or 300 mg/kg each of alpha-tocopherol + gamma-tocopherol, and in the other experiment, we compared the gamma-tocopherol concentrations of rats fed a diet of gamma-tocopherol alone to those of rats fed a gamma-tocopherol + sesame seed diet (each diet contained 300 mg/kg gamma-tocopherol). The bile collection was done over 6 h. The gamma-tocopherol concentration in the bile was markedly lower than that of alpha-tocopherol, paralleling the concentrations in the plasma and liver. Intake of alpha-tocopherol and gamma-tocopherol together further lowered the concentration of gamma-tocopherol in the bile as well as in the plasma and liver, compared to the intake of gamma-tocopherol alone. The gamma-tocopherol concentration in the bile, as well as in the plasma and liver, was markedly higher in the sesame seed-fed group than in the gamma-tocopherol alone group. We found that the concentrations of alpha- or gamma-tocopherol in the bile showed a good correlation with the concentrations of alpha- or gamma-tocopherol in the liver, though the concentrations in the bile were substantially lower than those in the liver. These findings suggest that secretion into the bile is not a major metabolic route of alpha- or gamma-tocopherol.