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For understanding the factors affecting bovine viral diarrhea virus (BVDV) transmission, this study investigated the distribution of BVDV and the epidemiological features of persistently infected (PI) cattle in Ibaraki Prefecture of Japan, and identified farm-level risk factors associated with BVDV infection, with a focus on within-farm transmission and PI animal detection. Among all 377 dairy farms, forty-four PI cattle were identified on 22 farms. Thirty-eight and six PI cattle were born on their current farms or purchased, respectively. Twenty-six PI cattle were born from pregnancies on their current farms, seven from pregnancies in summer pastures, and eight from pregnancies on other farms. The within-farm seroprevalence on farms with PI animals was significantly higher than that on farms without PI cattle. Of 333 farms holding homebred cattle without movement records, antibody-positivity in homebred cattle was observed on 194 farms; these cattle were likely infected by within-farm transmission. Herd size, summer pasturing, and BVDV infection status of the nearest dairy farm were risk factors associated with within-farm transmission. Likewise, herd size, summer pasturing, and the proportion of purchased cattle were related to PI animal occurrence. This study shows the risk of within-farm transmission and occurrence of PI animals after the introduction of BVDV via purchasing and summer pasturing, and illustrates the significant role of PI cattle in circulating BVDV. More effective measures for screening BVDV infection and PI animals, including intensive tests targeting moved cattle and newborn calves, and bulk milk surveillance, are required to control the spread of BVDV in Japan.

Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophage-like J774.1 cells and found that a monocatechol derivative SC1, (7α,7'α,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-β (IFN-β) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the β-glucuronidase inhibitor and enhanced by the catechol-O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-β/iNOS signaling through macrophage-mediated deconjugation.

Sesamin [(7α,7′α,8α,8′α)-3,4:3′,4′-bis(methylenedioxy)-7,9′:7′,9-diepoxylignane] is a major lignan in sesame seeds. Sesamin is converted to the catechol metabolite, SC1 [(7α,7′α,8α,8′α)-3′,4′-methylenedioxy-7,9′:7′,9-diepoxylignane-3,4-diol] with anti-inflammatory effects after oral administration. However, its molecular target remains unknown. Analysis using high-performance affinity nanobeads led to the identification of annexin A1 (ANX A1) as an SC1-binding protein. SC1 was found to bind to the annexin repeat 3 region of ANX A1 with a high-affinity constant (Kd = 2.77 μmol L−1). In U937 cells, SC1 exhibited an anti-inflammatory effect dependent on ANX A1. Furthermore, administration of sesamin or SC1 attenuated carbon tetrachloride-induced liver damage in mice and concurrently suppressed inflammatory responses dependent on ANX A1. The mechanism involved SC1-induced ANX A1 phosphorylation at serine 27 that facilitates extracellular ANX A1 release. Consequently, the ANX A1 released into the extracellular space suppressed the production of tumor necrosis factor α. This study demonstrates that ANX A1 acts as a pivotal target of sesamin metabolites to attenuate inflammatory responses.

Sesamin is a major lignan in sesame seeds and oil. We previously demonstrated that sesamin induces chromosomal aberrations (CA) in Chinese hamster lung (CHL/IU) cells in the presence of a metabolic activation system (S9 mix), although no genotoxicity was detected in vivo. To clarify the mechanism of CA induction by sesamin, we identified its principal active metabolite. A mono-catechol derivative, [2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabi-cyclo[3.3.0]octane (SC-1)], was previously identified in culture medium when sesamin was incubated with S9 mix. In the present study, we show that SC-1 induces CA in CHL/IU cells but not in human hepatoblastoma (HepG2) cells. SC-1 was unstable in culture medium. Addition of glutathione (GSH) to the incubation mixture decreased the rate of decomposition and also suppressed induction of CA in CHL/IU cells. These results indicate that SC-1 itself may not contribute to the induction of CA. Two GSH adducts of SC-1 were identified when SC-1 was incubated with GSH, suggesting that SC-1 was converted to the semiquinone/quinone form and then conjugated with GSH in the culture medium. Sodium sulfite (a quinone-responsive compound) also suppressed CA induction by SC-1. These findings strongly suggest that SC-1 is oxidized to semiquinone/quinone derivatives extracellularly in culture medium, that these derivatives are responsible for the induction of CA in CHL/IU cells, and therefore that the positive results obtained with sesamin in in vitro CA tests using CHL/IU cells may not be relevant to the assessment of in vivo activity.

Sesame lignans, which are biologically active compounds present in sesame seeds and oil, are known to have neuroprotective effects in several models of brain dysfunction. However, the effects of sesame lignans on age-related brain dysfunction are not clear and were thus investigated in the present study using a senescence-accelerated mouse (SAMP10). Two-month-old male SAMP10 mice were administrated a basal diet with 0% or 0.05% sesame lignans for two months, or with 0%, 0.02%, or 0.05% sesame lignans for 10 months and subjected to step-through passive avoidance tasks and forced swim tests. Reactive carbonyl species (RCs) were evaluated as markers of oxidative stress using a recently developed comprehensive analytical method. Both learning time in passive avoidance tasks and immobile time in forced swim tests became longer with aging (p &lt, 0.05). However, the administration of sesame lignans significantly ameliorated age-related effects in both tests (p &lt, 0.05). Age-related increases in RCs such as 4-hydroxy-2-nonenal in the cerebral cortex and liver were reduced in mice fed sesame lignans. These results suggest that sesame lignans can prevent age-related brain dysfunction via anti-oxidative activity.

Male C57BL/6J (B6) mice aged 24 weeks were provided two concentrations (1.5 or 3.0 g/L) of quercetin glycosides (QG) in drinking water over the subsequent 24 weeks. The objective was to determine if QG could improve motor function during early stages of aging. No sustained significant differences in body composition or food intake were noted to confirm the safety of QG treatment. Treated mice had significantly improved performance in grip strength and rotarod tests but not in treadmill performance. The functional benefits were reflected in muscle morphology with increased wet weights of a selected group of muscles (quadratus femoris, gastrocnemius, tibialis anterior, and soleus) in treated mice. Thus, it would appear that long-term oral treatment with QG can safely and effectively improve selected elements of motor performance and increase muscle mass during the early stages of aging.

We previously showed a prophylactic effect of Lactobacillus pentosus strain S-PT84 against oral candidiasis in mice. In the present study, we evaluated the protective effect of S-PT84 against Candida infection of the gastrointestinal tract. As the first step, we used an in vitro assay to compare the inhibitory effects of several lactobacilli (S-PT84 and Lactobacillus pentosus type strain JCM1558T, Lactobacillus gasseri type strain JCM1131T and Lactobacillus casei type strain JCM1134T) on mycelial growth of Candida albicans. S-PT84 directly adhered to Candida cells and showed the strongest growth-inhibitory activity among the tested Lactobacillus strains. In the second experiment, we used an in vivo assay to evaluate the effect of S-PT84 ingestion on severity score of stomach lesion and gastric inflammation in a mouse model of gastrointestinal candidiasis. The severity scores were significantly improved by oral administration of S-PT84 (6 mg/ 200 μL), consistent with decreased coverage of stomach lesions by patchy whitish plaques. The attenuation of stomach lesion severity by S-PT84 was more pronounced than that obtained with L. gasseri type strain JCM1131T, consistent with the results of the above in vitro study. Histological analysis also indicated that S-PT84 prevented the adhesion of C. albicans to the stomach surface and suppressed stomach inflammation caused by neutrophil infiltration. Furthermore, S-PT84 also suppressed the vascular permeability observed in Candida-infected stomach. These results suggest that oral administration of S-PT84 might be effective not only in inhibiting Candida infection but also in preventing gastric inflammation induced by Candida infection.

New Findings What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus. Abstract We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus.

The effect of S-PT84, a heat-killed preparation of Lactobacillus pentosus on growth of Candida albicans was examined in vitro and in vivo. The mycelial growth was effectively inhibited by S-PT84 and seemed to bind to the hyphae. We assessed the potential of S-PT84 for treatment of oral and gastric candidiasis using a murine model. When 2 mg of S-PT84 was administered three times into the oral cavity of orally Candida infected mice, the score of lesions on the tongue was improved on day 2. When 50 μl and 200 μl of S-PT84 (10 mg/ml) were administered three times into the oral cavity (0.5 mg × 3) and the stomach (2 mg × 3) of the same mouse model, the number of viable Candida cells in the stomach was reduced significantly on day 2. These findings suggest the possibility that S-PT84 has potential as a food ingredient supporting anti-Candida treatment, especially for Candida infection in the gastrointestinal tract.

Splenic sympathetic nerve activity (SNA) modulates cellular immune functions such as splenic natural killer cell activity. Lactobacillus pentosus strain S-PT84 enhances splenic natural killer cell activity. Here, we examined whether S-PT84 affects splenic natural killer activity through splenic SNA in BALB/c mice. Splenic SNA was significantly decreased following the administration of S-PT84. This phenomenon was inhibited by pretreatment with thioperamide (histamine H3 receptor antagonist), suggesting that S-PT84 directly affected splenic SNA. Thioperamide also inhibited the increase in splenic natural killer activity by S-PT84. Thus, the change in splenic natural killer activity by S-PT84 may be partially modulated through SNA.

Antioxidative effects of sesamin (a mixture of sesamin and episesamin) were evaluated in the liver, kidney and inferior vena cava of living rats using a radiofrequency ESR method. TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, was used as an in vivo redox probe, the half-life of which is believed to be correlated with the antioxidant status. The oral administration of sesamin (250 mg/kg rat weight) 3 h before ESR measurements shortened the half-life of TEMPOL in the liver by 10 - 15% as compared with the controls, but did not affect the other organs. This effect was maintained for at least 3 h after the administration, and then disappeared at 24 h, corresponding to the results of our preliminary pharmacokinetic studies. Changes in the reducing ability were observed only in the hepatic sites of the sesamin-treated rats. These findings suggest that sesamin exhibits effective antioxidant activity in the liver via modulation of the intracellular redox status related to TEMPOL reduction.

Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100 g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.

Induction of phase II antioxidant enzymes by activation of Nrf2/ARE (antioxidant response element) signaling has been considered as a promising strategy to combat with oxidative stress-related diseases. In the present study, we tested for potential effects of sesamin, a major lignan contained in sesame seeds, its stereoisomer episesamin, and their metabolites on Nrf2/ARE activation in rat pheochromocytoma PC12 cells. Luciferase reporter assays showed that primary metabolites of sesamin and episesamin, SC-1 and EC-1 were the most potent ARE activators among all tested compounds. SC-1 {(1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane} enhanced nuclear translocation of Nrf2 and up-regulated expression of phase II antioxidant enzymes including heme oxygenase-1 (HO-1). Treatment with SC-1 resulted in increased phosphorylation of p38 MAP kinase and transient increase in intracellular ROS levels. N-acetylcysteine (NAC) treatment abolished p38 phosphorylation as well as HO-1 induction caused by SC-1, indicating that ROS are upstream signals of p38 in Nrf2/ARE activation by SC-1. Furthermore, preconditioning with SC-1 attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Finally, treatment with a HO-1 inhibitor, Zn-protoporphyrin (ZnPP), and overexpression of a dominant-negative mutant of Nrf2 diminished SC-1-mediated neuroprotection. Our results demonstrate that SC-1 is capable of protecting against oxidative stress-induced neuronal cell death in part through induction of HO-1 via Nrf2/ARE activation, suggesting its potential to reduce oxidative stress and ameliorate oxidative stress-related neurodegenerative diseases.

Sesamin is a major lignan that is present in sesame seeds and oil. Sesamin is partially converted to its stereoisomer, episesamin, during the refining process of non-roasted sesame seed oil. We evaluated the genotoxicity of these substances through the following tests: a bacterial reverse mutation assay (Ames test), a chromosomal aberration test in cultured Chinese hamster lung cells (CHL/IU), a bone marrow micronucleus (MN) test in Crlj:CD1 (ICR) mice, and a comet assay using the liver of Sprague-Dawley (SD) rats. Episesamin showed negative results in the Ames test with and without S9 mix, in the in vitro chromosomal aberration test with and without S9 mix, and in the in vivo comet assay. Sesamin showed negative results in the Ames test with and without S9 mix. In the in vitro chromosomal aberration test, sesamin did not induce chromosomal aberrations in the absence of S9 mix, but induced structural abnormalities at cytotoxic concentrations in the presence of S9 mix. Oral administration of sesamin at doses up to 2.0 g/kg did not cause a significant increase in either the percentage of micronucleated polychromatic erythrocytes in the in vivo bone marrow MN test or in the % DNA in the comet tails in the in vivo comet assay of liver cells. These findings indicate that sesamin does not damage DNA in vivo and that sesamin and episesamin have no genotoxic activity.

Nosocomial infections caused by microbial opportunistic infections or microbial biofilms may occur during hospitalization and increase patient morbidity, mortality and health care costs. Artificial antibiotic agents were initially used to prevent infection; however, the high prevalence of nosocomial infections has resulted in their excessive use, which has led to microbial resistance to these agents. The increase in microbial resistance to antibiotics and the development of antibiotic agents may be the cause of the production of other microbial resistance. Thus, natural compounds that have no adverse side effects would be a preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose (1,5-AF), a natural plant compound derived from starch, has been found to have multifunctional properties, including antioxidant, antiplatelet aggregation by thrombin and anti-inflammatory activities. The results of the present study demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci on the hands as well as the growth of Staphylococcus epidermidis, which is a cause of opportunistic infections. Furthermore, 1,5-AF suppressed biofilm formation by the methicillin-resistant Staphylococcus aureus. In conclusion, 1,5-AF is a natural compound that may be effective in preventing nosocomial infections, without causing adverse side effects.

Noriyuki Kanzaki,1 Yoshiko Ono,1 Hiroshi Shibata,1 Toshio Moritani2 1Institute for Health Care Science, Suntory Wellness Ltd, Seika-cho, Soraku-gun, 2Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, Japan Background: The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain.Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16weeks in 100 Japanese subjects (age, 51.8±0.8years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200mg of glucosamine hydrochloride, 60mg of chondroitin sulfate, 45mg of type II collagen peptides, 90mg of quercetin glycosides, 10mg of imidazole peptides, and 5µg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions.Results: In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03m/s vs 0.05±0.02m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren–Lawrence (K–L) grade showed that normal walking speed at week 16 (1.36±0.05m/s vs 1.21±0.02m/s, P

Sesamin has anti-oxidative functions in vivo. Fatigue is caused in part by oxidative stress. We evaluated whether sesame lignans (sesamin/episesamin = 1/1, 10 mg) with vitamin E (55 mg of α-tocopherol) (SVE) could improve subjective statuses and anti-oxidative capacity in humans using questionnaires on fatigue, sleep and physical appearance, as well as low-density lipoprotein oxidation lag time. A placebo-controlled, double-blind, parallel-group study was conducted with subjects experiencing daily fatigue. After a run-in period, subjects were administered oral SVE or a placebo (P) for 8 weeks. A questionnaire regarding fatigue, sleep and physical appearance was conducted at 0, 4, and 8 weeks. Plasma low-density lipoprotein oxidation lag time was measured as an indicator of anti-oxidative capacity. The per-protocol analysis revealed significant improvements in fatigue status at 4 and 8 weeks compared to 0 weeks in both groups (p < 0.01), and sleep and physical appearance at 8 weeks compared to 0 weeks only in the SVE group (p < 0.01). There were no significant differences observed between the groups. According to the 72-subject subgroup analysis (aged 40 and over), the sleep and physical appearance significantly improved compared to the P group (p < 0.05), and fatigue status showed a tendency for improvement compared to the P group. Anti-oxidative capacity in the SVE group significantly increased compared to the P group (p < 0.01). No adverse events relating to SVE supplementation were confirmed. These results suggest SVE supplementation could safely alleviate daily fatigue and oxidative stress.

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radical-scavenging activities against the xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (NOARG), or a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.

During the past twenty years or so, four major lines of criticism-psychoanalytic, feminist, new historicism, cultural materialist-have emerged and made us aware that not only the poet but also the reader exists in history. The revision of poet's work is, therefore, to locate the modern reader in his/her own historical moment as well as the text itself. Any critical endeavour of reading Shakespeare takes dual process of activity. Namely, we are reading two different stories at once: the story that Shakespeare's audience enjoyed on the contemporary Elizabethan and Jacobean stage, and the story that we read/create between the lines and behind the scenes in our own historical location. This paper is one step to examine how such a play as The Taming of the Shrew, which advocates the system of patriarchal hegemony prevailed in every particle of Elizabethan society, can be localized in the modern reassessment of Shakespeare through gender-conscious reading. The critical reading of the play consists of three parts: Patruchio's story, Katherina's story, and Sly's story. The first two stories, Petruchio's and Katherina's, tell his/her own version of the taming of the shrew, demonstrating the procedure of which the gender/identity politics is negotiated to establish its ideologically righteous power system. The Sly's story, on the other hand, as an induction to the taming of the shrew plot created for the entertainment of the Lord and Sly, negates the whole process of battle for power as theatrical illusion.

After 12, 18, and 24 h of oral administration of carbon tetrachloride (as a 1:1 mixture with mineral oil: 4 ml/kg body weight) to rats, the activity of caspase-3-like protease in the liver increased significantly compared to that in the control group that was given mineral oil (4 ml/kg). In plasma, the activity of caspase-3 was barely detectable in the control rat, but increased significantly 24 h after drug administration along with a dramatic increase in glutamate oxaloacetate transaminase. These results indicate that carbon tetrachloride causes apoptosis in the liver by activating caspase-3, which is released to plasma by secondary necrosis. After 18 and 24 h of carbon tetrachloride administration, the liver concentration of hydrophilic vitamin C was decreased significantly, while that of hydrophobic vitamin E was not affected. The plasma concentration of vitamins C and E was not influenced significantly. These results suggest that carbon tetrachloride induces oxidative stress mainly in the aqueous phase of the liver cell.

Harold Pinter's Betrayal is a sister play to The Collection (1961) and Old Times (1970). All three plays deal with a husband and wife verifying what actually happened to their partner in the past. However, what makes Betrayal outstanding among them is its anti-clockwise scheme. The play opens with the ex-lovers meeting in one of their old pub haunts in order finally to bury their liaison. Then it moves progressively, through all stages of their affairs, backwards in time to the lovers' first moment of embrace nine years earlier. As the story develops, our conventional interest in what happens next is replaced by questions of how. By switching attention to behavioural motivation, Pinter focuses more precisely than ever before on the mechanics of exploitation, the politics of human relations. Betrayal is a story in which main characters betray one another in separate ways on different levels. Conversations are thus negotiations in which the characters try to achieve and maintain the controlling position among them, and to protect themselves from others' attempts to place them in a subordinate status. Every line expresses their continual struggle for alignment. In their communication what matters most is not whether the statement is true or not, but how the words spoken modify and adjust their present relationship. The events recollected and verified are also filtered through each character's own mode of communication. They remember the past as it should have happened. Their past experience is thus recalled in order to improve the present situation and for the benefit of the potential relationships.

Neptune's Triumph for the Return of Albion was composed as the Twelfth Night masque for the Court Christmas. Ben Jonson wrote the masque in answer to the request from Prince Charles and the Duke of Buckingham who had returned from a Spanish mission. Charles and Buckingham had made a secret journey to Spain to negotiate the prince's marriage with the Spanish Infanta and to bring her home to England. The Spanish match had been a favorite and ambitious project of King James. However, after long negotiations the prince and the duke returned home resentfully, and the Jacobean court was divided between James and Prince Charles concerning England's Continental policies. Jonson's masque dealt with the safe return of Prince Charles from his misson to Spain; and yet the subject-matter was to pay homage to King James's political wisdom and the consequent triumph for the victorious return of his son. Neptune and his court was dentified with James I and his court and the argument of the masque was presented as an ideal version of the recent political events. In fact, Charles's mission to Spain brought nothing fruitful to England; and much worse, King James was pushed into a new and hard course in foreign policy. Nevertheless, Jonson's loyalty to the State as the court poet urged him to rewrite English history and to create another myth of Jacobean England as the 'Fortunate Isles'. Jonson was convinced that the poet had obligation to serve the State and to sustain wise government by providing the monarch with good counsel. Yet Jonson was never ignorant of the fact that the masquewriter's function which the poet himself believed to be was not identical with the one that the court audience expected. Jonson's awareness of this gap was demonstrated in the comic dialogue between the 'Poet' and the 'Master-Cooke' of the masque. The main masque celebrated the ideal reign of James I by identifying it with the myth of Ocean God, Neptune. And, by the employment of the poet figure as masque-writer of the masque in progress on the stage, Jonson exposed that the masque world was an illusion, a fiction created by the poet. The meta-masque device introduced in Neptune's Triumph was thus a Jonsonian way of manifestation that the poet's invention alone could achieve the ideal transformation of the Monarchy.

Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7'β,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-1-2) and (7α,7'β,8α,8'α)-3,4:3',4'-bis(dihydroxy)-7,9':7',9-diepoxylignane (EC-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1m-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-1m-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-2m-1) and (7α,7'β,8α,8'α)-3,4-dihydroxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans.

The royal entry developed in the Renaissance Europe was a vehicle for the glorification of monarchical imagery. The coronation entry of James I and the pageants were devised to create a mythology for the new monarchy. The triumphal arches with emblems and allegorical figures erected along the processional route were the symbol of the expected wise government of the virtuous king. The accompanying pageants embodied the moral arguments that the arches signified. The introductory part of this paper will make a brief survey of the development of the royal entry in Europe. The second part will examine the function of the triumphal arches and the accompanying pageants at the time of James I's coronation. The focus of my examination here will be Ben Jonson's contribution to this royal entry. The last part will be concluded with the analysis of the decline of processions and the subsequent flourishing of the court masque in James's Court.

Sesamin, a major lignan in sesame seeds, exhibits various health benefits. Here, we investigated effects of sesamin, its stereoisomer episesamin, and their metabolites on neuronal differentiation in rat pheochromocytoma PC12 cells. Among all compounds tested, primary metabolites of sesamin and episesamin, SC-1 and EC-1 {S- and R-epimer of 2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3.3.0]octane}, were the most potent to induce neuronal differentiation. SC-1 alone induced neuronal differentiation through extracellular signal-regulated kinase (ERK) 1/2 activation that is essential for nerve growth factor (NGF)-induced neuronal differentiation, as shown by the suppression with MEK1/2 inhibitors, PD98059 and U0126. However, SC-1 did not increase phosphorylation of TrkA, a high-affinity NGF receptor, and a TrkA inhibitor, K252a, did not affect SC-1-induced neuronal differentiation. Furthermore, SC-1 potentiated neuronal differentiation in cells co-treated with NGF, which was associated with enhanced ERK1/2 activation and increased expression of neuronal differentiation markers. Interestingly, when treated with SC-1 and a high dose of NGF, formation of synaptic connections and synaptophysin accumulation at the neurite terminals were markedly enhanced. These results indicate that (1) SC-1 alone induces neuronal differentiation, (2) SC-1 potentiates neuronal differentiation in NGF-treated cells, (3) SC-1 enhances formation of synaptic connections in cells treated with a high dose of NGF, all of which are associated with ERK1/2 activation. It is therefore concluded that SC-1 may promote neuronal differentiation by tapping into the ERK1/2-MAPK (mitogen-activated protein kinase) signaling pathway downstream from the TrkA receptor in PC12 cells.

The first chemical synthesis of two metabolites ((1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane (SC-1) and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane (SC-2)) of sesamin was achieved by a simple two-step approach from sesamin. The approach consists of acetoxylation of the methylenedioxy moiety(ies) with lead(IV) tetraacetate and acid hydrolysis of the resulting hemiorthoester to SC-1 and SC-2.

We have previously reported that substantial amounts of tocotrienols were present in the skin of animals fed a diet containing a tocopherols and tocotrienols rich fraction (T-mix) extracted from palm oil, and further, that sesame lignans enhanced tocotrienol levels in the skin. The present studies were undertaken to determine whether dietary tocotrienols and those with sesamin could protect the skin from damage induced by UVB irradiation in hairless mice fed four diets: a vitamin E-free diet, a 50 mg/kg alpha-tocopherol diet, a 229 mg/kg T-mix (with 50 mg alpha-tocopherol) diet and a 229 mg/kg T-mix with 2 g/kg sesamin diet. In Experiment 1, mice were fed the diets for 6 wk, and half of the mice were exposed to 180 mJ/cm(2 )of UVB light once daily for 7 d. After the intensity of sunburn was scored, vitamin E and thiobarbituric acid reactive substances (TBARS) concentrations in the skin and liver were determined. In Experiment 2, hairless mice were initiated with a single application of 7, 12-dimethylbenz[a]anthracene (DMBA), then 1 wk later mice were fed the experimental diets and subjected to 180 mJ/cm(2) UVB irradiation twice weekly for 20 wk. Tumor incidences were counted once a week. Tocotrienols were detected in the skin of mice fed T-mix, but their concentrations were significantly lower than for alpha-tocopherol. Sesamin elevated tocotrienol contents in the skin. In spite of the high alpha-tocopherol contents, the effects of alpha-tocopherol on sunburn and incidence of tumor were slight. T-mix fed groups reduced the extent of sunburn and incidence of tumor, and further reduction of sunburn and incidence of tumor were observed in the T-mix with sesamin group. These results suggest that dietary tocotrienols protect the skin more strongly than alpha-tocopherol against damage induced by UVB and sesamin enhances tocotrienol effects.

This paper is an attempt to see how the satirist in John Marston's works is characterized. First of all, a brief survey will be made of English satire before Marston. Then I will examine how Marston presents the satirist in his verse satire and on the stage. In verse satire, Pigmalion and The Scourge of Villanie, the satirist, filled with righteous indignation, exposes the depraved world where the fools and villains prosper by pretending to be virtuous. In order to attack vice effectively, the satirist employs the most sharp-edged weapons: irony, sarcasm, caricature, and vituperation. He speaks harsh and unnecessarily obscene language to make human depravity as ugly as possible. As a result of this, he acquires unpleasant characteristics which make suspect his post of a heroic scourger of vice. But our attention is always diverted from the satirist to his satiric objects, because we hear only his voice and stand with him. So his moral flaw remains hidden in verse satire. On the stage, however, we escape the control of his rhetoric, and see the distance between what the satirist claims he is and what he really is. In Antonio and Mellida and What You Will, Marston makes explicit the satirist's ugliness, the features twisting with hate and envy at the sight of the prosperous fools and villains. Thus, the satirist becomes a caricature of the conventional satirist developed in verse satire. In The Malcontent, Marston again elaborates on the moral and sanative purpose of satire. The satirist's sharp-edged weapons serve as effective political instruments to control the depraved world. The satirist contributes to probe to the very source of infection in the state and cut it out of the body politic. The Fawn has quite a different type of the satirist. Disguised as a flatterer, the satirist lures men into foolishness by praising that folly and vice are worldly wisdom. Instead of raillery and diatribe, he employs a technique of exposing absurdity by intensification. As a result, the action of the play moves towards clarification through release.

We compared the dietary effects of dihomo-gamma-linolenic acid (DGLA) contained in the DGLA oil produced by a fungus with gamma-linolenic acid (GLA) on the fatty acid composition. Wistar rats were fed with three kinds of oil for two weeks as follows: (i) control group: corn oil; (ii) GLA group: borage oil; (iii) DGLA group: DGLA oil/safflower oil = 55:45. The DGLA concentrations in the liver, serum, and brain of the DGLA group were higher than those of the GLA oil group. We also examined the dose effect of DGLA. The DGLA levels in the liver, serum, and brain significantly increased with increasing dosage of DGLA in the diet. DGLA administration significantly increased the ratio of PGE1/PGE2 in the rat plasma. The mechanism for GLA administration to improve atopic eczema is thought to involve an increase in the concentration of DGLA metabolized from GLA, so these results suggest that the dietary effect of DGLA would be more dominant than GLA.