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Background: Although bronchial asthma is well known as an inflammatory disease that shows obvious circadian rhythms of airway narrowing, it remains to be elucidated whether the suprachiasmatic nucleus (SCN), a major circadian pacemaker, regulates inflammatory mediators relevant to asthma. Thus, we investigated the effects of electrolytic lesioning of the SCN on the antigen-induced immediate allergic response and the late allergic response (LAR) in male Brown Norway rats, i.e. in a model of allergic inflammation. Methods: The immediate allergic response, assessed by the histamine levels in plasma and bronchoalveolar lavage fluid (BALF), and the LAR, assessed by the eosinophilic infiltration into BALF and the lamina propria mucosae of the left main bronchus, were examined in three groups of 18 rats each, including (1) an unoperated control group, (2) a sham SCN-lesioned group, and (3) an SCN-lesioned group. Results: Both the plasma histamine levels and the number of eosinophils in bronchial tissues in the SCN-lesioned group were significantly lower than those in the other groups. The concentration of histamine and the number of eosinophils in the right BALF showed a similar pattern; however, no significant differences were found. Both plasma adrenaline and noradrenaline levels were highest during the LAR, whereas the corticosterone level was lowest in the SCN-lesioned group; again, no significant differences were obtained. Conclusions: These findings indicate that the SCN has a significant effect on the inflammatory mediators relevant to bronchial asthma. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To clarify the possibility of pharmacological mediation on classical conditioning-associated asthmatic response, the effect of diazepam on an odor-induced conditioned histamine release was investigated in ovalbumin (OA)-sensitized guinea pigs, i.e. a model of bronchial asthma. The animals received conditioning sessions in which an antigen (OA) as the unconditioned stimulus and an odor (dimethylsulfide) as the conditioned stimulus (CS) were simultaneously inhaled. After the animals were intraperitoneally injected with saline or diazepam (2.5 or 5 mg/kg), they underwent exposure to the CS and blood collecting. This procedure was repeated three times in order that the animals would have each kind of injection. The animals injected with saline showed significantly higher levels of plasma histamine following the exposure to the CS as a conditioning effect compared with the baselines (P<0.05), whereas the group injected with diazepam (5 mg/kg) did not indicate such elevations. The suppressing effect of diazepam on the conditioned histamine release was also confirmed by a multiple regression analysis (5 mg/kg) and an analysis of covariance (2.5 and 5 mg/kg), even after adjustments for several factors regarding immunological sensitization and conditionability. The present study suggests that diazepam attenuates a conditioned histamine release. [Copyright &y& Elsevier]

To clarify the contribution of stress to classical conditioning-associated asthmatic responses, the effect of fasting stress on conditioned histamine release was investigated in a guinea pig model of asthma. The animals were randomly divided into 2 groups for Experiment 1 and 2, and received a conditioning procedure in which ovalbumin (OA) as an unconditioned stimulus (US) and dimethylsulfide (DMS, sulfur smelling) as a conditioned stimulus (CS) were simultaneously inhaled after fasting for 16 h. Then, one group was given food as a reward for respiratory distress, and the other group was denied it for more than 3 h, while being placed in front of the feeding group. After this procedure was repeated 5 times, the plasma histamine levels in response to the CS were measured in half of each group in Experiment 1, and the respiratory resistance (Rrs) was assessed similarly in the other half of each group in Experiment 2. The same experiments were again performed after exchanging assignments of feeding group or fasting group in both experiments. The control groups in both experiments received the CS and the US 10 times separately in a random order under 16 h fasting conditions and were provided food after the exposures. After these pseudo-conditioning presentations, the plasma histamine levels or the Rrs in response to the CS were measured. In Experiment 1, the plasma histamine levels in the fasting stress group after the first conditioning sessions were significantly higher than those of the other groups. This difference was not observed when the groups were exchanged. In Experiment 2, the fasting stress group showed higher values in the Rrs compared to the other groups, irrespective of the first or second conditionings; however, they were not significant. The present study indicates that fasting stress after the conditioning procedures exacerbates the following conditioned histamine release, although the stress effect on bronchoconstriction was not confirmed. [Copyright &y& Elsevier]

To investigate the effect of abrupt or non-abrupt isolation stress on the classical conditioned histamine release, socially isolated or paired guinea pigs underwent conditioning procedures in which ovalbumin (OA) as an unconditioned stimulus (US) and dimethylsulfide (sulfur smelling) as a conditioned stimulus (CS) were simultaneously inhaled, and the plasma histamine levels after the exposure to the CS in a state of isolation or pairing were measured. The plasma histamine levels significantly increased from baseline in response to the CS (P<0.05), except in the animals which were abruptly isolated during the exposure to the CS. The guinea pigs which were isolated during either the conditioning procedures or the exposure to the CS displayed significantly lower levels of plasma histamine than did the paired animals during both periods (P<0.01, respectively). The plasma histamine levels in the guinea pigs which were isolated or paired during both periods were significantly higher than those of the control animals which had received the CS and the US separately (P<0.05 and P<0.01). A change of social relations, particularly isolation during the presentation of the CS, may have a suppressive effect on immediate asthmatic responses due to the conditioning mechanism. [Copyright &y& Elsevier]