The purpose of the present study was to investigate the effects of stress on allergic reaction. We studied changes in the contact hypersensitivity reaction (CHR) of mice exposed to foot shock (FS) stress or psychological () stress induced by the communication box. CHR was elicited by applying antigen (2,4-dinitrofluorobenzene, DNFB) to the ear of the mice at 4 days after DNFB sensitization. In acute stress experiments, DNFB-sensitized mice were exposed for 2 h to FS or stress after contact challenge with DNFB. Acute FS stress significantly inhibited CHR immediately after the end of the stress period (3 h after DNFB-challenge), and a significant enhancement of the CHR was observed at 5 h after DNFB-challenge. The concentration of the serum corticosterone level of the mice exposed to acute FS stress significantly increased compared to the control mice, immediately after stress loading. Both CHR and serum corticosterone levels after acute stress loading were almost the same as those of the control groups. The temporary decrease of the inflammatory reaction at CHR caused by acute FS stress loading may have been correlated with serum corticosterone produced by the stress, and the increase of corticosterone may act as a trigger of enhancement of the CHR (delayed-type hypersensitivity). Chronic stress experiments were designed to expose mice to FS or stress 2 h daily after sensitization with DNFB. These chronic stresses caused a significant reduction in the body weight of mice. The temporary decrease effect on the CHR of chronic FS stress-loaded mice was similar to the acute FS stress-loaded mice. In contrast, no significant enhancement of the CHR (late phase) at 24 h and 48 h after challenge was observed. Although the changes in body weight suggested that mice were influenced by chronic stress, no significant difference from the control group for the CHR of mice exposed to chronic stress was found, as in the case of acute stress loading. The correlation between chronic stress and CHR remains to be ascertained.

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This study was conducted to determine whether dietary psyllium () can protect against the estrogenic activity of Bisphenol A (BPA) in a rat uterotrophic bioassay. Fifteen immature female rats were fed a commercial diet (blank diet), a blank diet containing 0.1% BPA (control diet), or a blank diet with 0.1% BPA and 5% ( diet) for 6 days. The uterine weight of the control group was significantly higher than of the blank group. The uterine weight and the uterine BPA levels of the group were significantly lower than the control group. Serum BPA concentrations and liver BPA levels of the group tended to decrease compared to the control group. However, BPA excretions in feces were significantly higher in the group than in the control group (p<0.01). These observations indicate that dietary feeding can protect against the estrogenic activity of BPA in rats.

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Phytoene synthase (

) is one of the key regulatory enzyme on the biosynthesis and accumulation of carotenoid in citrus fruits. The transcriptional diversity of is mainly attributed to the structural variation in promoter region among alleles. In aim to clarify how this transcriptional diversity is regulated among them, alleles responsible for carotenoid biosynthesis in the fruits are characterized and their promoter sequences were compared. Based on gene structure and expression pattern of homologues on the clementine mandarin genome sequence, alleles responsible for carotenoid biosynthesis are derived from a single locus in the scaffold 6. AG mapping population possessed four alleles derived from parent lines of A255 and G434, and their F₁ individuals with

PSY

-g2 allele tended to have low transcription level. From sequence comparison of their promoter regions, the cis-motif alternation from MYBPZM to RAV1AAT might be a candidate to influence the transcription level. Among the ancestral pedigree varieties of AG mapping population, the transcription level of correlated with genotypes of MYBPZM and RAV1AAT motifs in the promoter region of alleles, so that homozygous genotype of MYBPZM showed higher transcription level while heterozygous genotype of MYBPZM and RAV1AAT showed lower transcription level.

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Syntaxin is a component of t-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE), which is responsible for docking membrane vesicles at the target membrane and is highly conserved among eukaryotes. In the fission yeast Schizosaccharomyces pombe, the + gene encoding a syntaxin 1 homolog was originally isolated as a multicopy suppressor of the sporulation-deficient mutant, spo3, but little is known about the way 1 is involved in sporulation. Here we report the isolation of a sporulation-defective mutant,

psy

1-S1, generated by random PCR mutagenesis.

psy

1-S1 also exhibited temperature sensitivity in growth. In

psy

1-S1 cells, assembly of the forespore membrane (FSM) initiated near the spindle pole bodies during meiosis II, but subsequent expansion of the membrane was severely impaired. Overproduction of the cognate SNARE proteins, Syb1 and Sec9, suppressed both the temperature sensitivity and sporulation defects of

psy

1-S1. These results indicate that 1 plays an essential role in FSM formation coordinated by Syb1 and Sec9.

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The antinociceptive effect induced by exposure to socio-psychological () stress using a communication box was assessed by the formalin test in mice, compared with those by exposure to footshock (FS) stress and forced swimming (SW) stress. After the termination of stress exposure, whereas exposure to FS- and SW-stress resulted in the attenuation of the formalin-induced biphasic pain response over 15 min, no appreciable antinociceptive effect was found in the case of stress. When exposure to stress was started during the period of early or late phase of pain after the formalin injection, the antinociceptive effect was maintained for 5 - 15 min; however, further exposure to stress was not effective for producing antinociception. In the tail-pinch test, likewise, exposure to stress longer than 5 min rather decreased the intensity of antinociception. We conclude that stress in this tonic pain paradigm produces antinociception, but further continuous exposure to the emotional stress caused mice to become recuperative even in such a fear-inducing situation.

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The analgesic effect induced by exposure to psychological stress, using a communication box (psychological stress-induced analgesia, -SIA), was completely antagonized by 10 min pretreatment with 0.5, 1 and 2 mg/kg of nor-binaltorphimine and with 0.5 and 1 mg/kg of Mr2266, selective κ-opioid receptor antagonists, in the tail pinch method. Neither footshock (FS)- nor forced swimming (SW)-SIA was affected by these antagonists. The selective δ-opioid receptor antagonist naltrindole, at doses up to 20 mg/kg, had no appreciable effect on -SIA. Daily morphine treatment, 10 mg/kg, s.c., resulted in tolerance to the analgesic effect, and concurrent exposure to -stress suppressed the development of morphine tolerance. The substitution of treatment with U-50, 488H for -stress still resulted in analgesia on the initial day; and likewise, the suppression by U-50, 488H of the development of morphine tolerance was replicated by -stress. Pretreatment with nor-binaltorphimine antagonized the suppressive effect of -stress on the development of morphine tolerance without affecting the analgesic effect of morphine per se. These results provide further evidence that -SIA involves the mediation by κ-opioid receptor mechanisms.

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Free plant sterols cannot be dissolved in oil or water. Using free plant sterols and egg yolks, we developed a plant sterol-egg yolk lipoprotein complex () that can be dispersed in water and considered suitable for use in processed foods. The cholesterol-lowering activity of was equal to that of free plant sterols and plant sterol esters. Consumption of a freeze-dried -containing omelet reduced serum and hepatic cholesterol concentrations. The results suggest that has cholesterol-lowering activity equivalent to that of free plant sterols and plant sterol esters. Moreover, the cholesterol-lowering activity of was maintained in processed foods.

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Psychological () stress using the communication box produced a short-lasting antinociceptive effect which was less potent than that induced by physical stress such as footshock (FS) and forced swimming (SW) in mice. Naloxone completely antagonized -stress induced analgesia (SIA) when the analgesia was measured by the tail pinch (TP) method; however, the antagonist did not reverse the effect in the tail flick (TF) assay. On the other hand, FS-SIA was antagonized by naloxone in both methods, while naloxone failed to reverse SW-SIA in either TF or TP assessment. Daily exposure to psychological stress developed tolerance to the analgesia. One-way cross-tolerance between -SIA and morphine and the naloxone antagonism of -SIA by the tail pinch method lead to the suggestion that an endogenous opioid system may be involved in the underlying mechanism for its production. On the contrary, from the findings of cross-tolerance between SW- or FS-SIA and the lack of naloxone antagonism in the TF method, the involvement of a more complicated mechanism is suggested in -SIA. In both tests, U-50488H, a selective κ-agonist, produced profound analgesia; however, no appreciable antagonism of naloxone was found in the TF test, whereas the effect was completely blocked by naloxone in the TP test. From the similarity in naloxone antagonism of -stress and U-50488H induced an algesia, the participation of a common mechanism which may be mediated by κ-opioid receptors, is suggested in the production of -SIA.

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β-Carboline-3-carboxylic acid ethyl ester (β-CCE) dose-dependently potentiated psychological-stress induced analgesia (-SIA), and the effect was reversed by diazepam. Concurrent exposure to stress or concomitant treatment with β-CCE blocked the development of analgesic tolerance to morphine; the effect of stress was antagonized by diazepam, and that of β-CCE was reversed by Ro 15-1788. These results suggest that psychological factors which are mediated through benzodiazepine receptors are involved in the mechanism for blocking the development of analgesic tolerance to morphine by stress.

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The role of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH₂) in biological responses to stress exposure was examined in mice. Intraperitoneal or intracerebroventricular administration of Tyr-MIF-1 attenuated not only footshock (FS)- and forced swimming (SW)-stress-induced analgesia (SIA) but also socio-psychological ()-SIA that, when using the communication box, is produced without any direct physical nociceptions. Tyr-MIF-1 also disrupted the suppressive effect of concurrent exposure to FS- and -stress on the development of morphine antinociceptive tolerance. In elevated-plus-maze tests, mice treated with Tyr-MIF-1 tended to spend more time in the open arms compared with the control group, suggesting the anxiolytic properties of the peptide. Thus, the finding that Tyr-MIF-1 modulates these stress responses suggests that the peptide regulates an endogenous biological alert system responding to stress exposure, perhaps, counteracting the excessive response of the system. Furthermore, Tyr-MIF-1, in the case of -stress, through the attenuation of emotional factors such as fear and anxiety, may suppress -SIA and inhibition by -stress of the development of morphine tolerance.

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Besides the important role of emotional factors in the production of psychological-stress-induced analgesia (-SIA), recent attention to the participation of serotonergic (5-HTnergic)neurons in the fear and anxiety-evoking mechanism led us to examine the effects of 5-HTnergic ligands on -SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT_1A receptor partial agonist, dose-dependently suppressed the production of -SIA. Ritanserin, a 5-HT₂ receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25, 130, a 5-HT₃ receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited -SIA dose-dependently, while (±)pindolol, a 5-HT_1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of -stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25, 130, but not by (±)pindolol. These results suggest that 5-HT receptor (5-HT_1A, 5-HT₂ and 5-HT₃ but not 5-HT_1B)-mediated mechanisms play an important role in the production of -SIA.

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The site of action involved in the suppression by exposure to footshock (FS)- and psychological ()-stress of the development of antinociceptive tolerance to morphine has been investigated. Daily treatment with 10 mg/kg, s.c.; 3μg, i.t.; and 5μg, i.c.v. of morphine, regardless of the administration route, resulted in the development of tolerance. Daily exposure to FS- or -stress suppressed the development of tolerance to s.c. and i.t. administered morphine but not that to i.c.v. administered morphine. Pretreatment with 2 mg/kg, i.p. of nor-binaltorphimine (nor-BNI) abolished the suppressive effect of -stress on the development of tolerance to morphine given s.c. The suppression by -stress was also antagonized by 2μg, i.t. of nor-BNI and not by 2μg, i.c.v. of nor-BNI. Thus, the development of tolerance in the spinal cord due to interaction of morphine at μ-opioid receptors can be suppressed by exposure to these stresses, probably through the descending signals from the supraspinal area, and activation of κ-opioid receptors in the spinal cord could also participate in the suppression by -stress.

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Modulation of learning and memory acquisition, retention and retrieval in the one trial passive avoidance learning task in mice by three inescapable stresses, i.e., footshock (FS), psychological () and forced swimming (SW) were investigated. Pre-, post-training and pre-test FS-stress (2 mA, 0.2 Hz, 1 sec for 30 min) and pre-training -stress (communication box, 5 min) resulted in enhanced test latencies. On the contrary, SW-stress (20°C, 5 min) immediately or 1 hr after training impaired retention latencies that tended to recover after 2 hr post-training SW-stress, suggesting that at least 2 hr are required to consolidate newly acquired information. In contrast, pre-stress naloxone (Nx), which did not affect FSand -stress induced facilitatory effects, returned to control levels the impaired retention latencies induced by SW-stress. Taken collectively, these results imply the involvement of an opioid-dependent mechanism in the modulation of memory by SW-stress and non-opioid in the case of FS- and -stress. Furthermore, they suggest that different mechanisms are involved in stress-induced memory modifications and the production of stress-induced analgesia (SIA) since in the latter, FS and but not SW stress produce Nx-sensitive antinociception.

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Based on the data that diazepam, a benzodiazepine (BZP) receptor agonist, antagonized psychological ()-stress induced analgesia (SIA) without prominent action on footshock (FS)- and forced swimming (SW)-SIA and that BZP receptors are coupled with GABA receptors, we examined how the GABAergic system participates in the production of various SIAs. Muscimol, a GABA_A receptor agonist, at doses of 0.25 to 1.0 mg/kg, affected each SIA differently, suppressed -SIA at 0.25 mg/kg but tended to potentiate it at 1.0 mg/kg, potentiated SW-SIA dose-dependently and did not affect FS-SIA at the doses employed. Both bicuculline, a GABA_A receptor antagonist, 0.5 to 2.0 mg/kg, and picrotoxin, a Cl^- channel blocker, 0.25 to 1.0 mg/kg, dose-dependently suppressed -and FS-SIA. Meanwhile, the effects of both drugs on SW-SIA were less than those on - and FS-SIA, namely, bicuculine slightly inhibited it only at 2.0 mg/kg, and picrotoxin did not produce any appreciable effect even at the highest dose. Baclofen, a GABA_B receptor agonist, at 5.0 and 10.0 mg/kg had no influence on each SIA. On the contrary, CGP 35348, a GABA_B receptor antagonist at 20 to 100 mg/kg caused the dose-dependent blockade of FS-SIA, but affected neither - nor SW-SIA. The production of - and SW-SIA is attributable to the GABA_A receptors/Cl channel mediated mechanism alone, while that of FS-SIA involves both GABA_A and GABA_B receptor mediated systems. Thus, GABAergic systems play an important role in the production of each SIA; however, the participation of the receptor subtypes in the mechanism was different from each other.

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Exposure to footshock (2 mA, 1-sec duration, 0.2 Hz for 15 min; FS), forced swimming (water at 20°C for 3 min, SW) or psychological stress (using a communication box for 5 min, ) produced antinociceptive effects (stress-induced analgesia, S1A). Intracerebroventricular (i.c.v.) injection of glibenclamide (10-40 μg/mouse), an ATP-sensitive K⁺ (K_ATP) channel blocker, antagonized FS-SIA, while SW- and -SIA were unaffected by the compound. Cromakalim (0.1-10 μg/mouse, i.c.v.), a K_ATP-channel opener, did not affect FS-, SW- or -SIA. Thus, we provided evidence that central K_ATP channels participate in the production of FS-SIA but not production of SW or -SIA; and we suggest that glibenclamide, through closing of K_ATP channels, suppresses μ-opioid receptor functions, which subsequently leads to the inhibition of FS-SIA since antinociception is produced by the activation of μ-receptors.

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Subanalgesic dose, 0.01 to 0.25 mg/kg, of clonidine (CLO), an α₂-adrenoceptor agonist, potentiated forced swimming (SW) stress induced analgesia (SIA) and suppressed psychological ()-SIA in a dose dependent manner but did not affect foot-shock (FS)-SIA. Daily exposure to each stress rapidly developed tolerance, and the development was suppressed by daily concomitant subanalgesic dose of CLO in SW-SIA but not in FS- and -SIA. Meanwhile, SW-stress, applied after injection of CLO, 1 mg/kg, potentiated the analgesic effect of CLO and suppressed the development of tolerance to the effect. On the other hand, FS- and -stress did not affect CLO analgesia and failed to block the tolerance development. These results provide further evidence that α₂-adrenergic mechanism is involved in the production of SW-SIA.

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We examined how the ginseng extract (GE) acts on the antinociceptive effect induced by footshock (FS)-, psychological ()- and forced swimming (SW)-stress (stress-induced analgesia, SIA), and also on the suppression by FS- and -stress of the development of tolerance to morphine in mice. Neither an acute treatment nor 5 daily pretreatments with GE at 100 mg/kg, p.o. affected each SIA. Pretreatment with GE at 100 mg/kg, p.o. for 5 days followed by the treatment in combination with the exposure to stresses for another 5 days caused no appreciable changes in the development of tolerance to FS and SW-SIA, but suppressed the development of tolerance to -SIA. When mice were pretreated with GE for 5 days and given GE daily prior to morphine at 10 mg/kg/day, with stress exposure for another 5 days, the inhibitory effect of FS-stress on the development of tolerance to morphine was completely eliminated. The present results suggest that GE, by improving the general metabolism in the body, directs toward normalization of the adaptability which is impaired by stress exposure, while not compromising morphine antinociceptive activity or the SIA, another adaptability produced in confrontation to abnormal environmental stimuli. In addition, the differences in the mechanism underlying the FS- and -stress effect which we have previously demonstrated are also reconfirmed.

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