モルモットの好酸球性気管支炎モデルにおける咳受容体感受性亢進とミクロオキニゲナーゼ代謝産物およびニューロペプチドの関与について

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1057号, 学位授与年月日：平成4年9月30日,学位授与年：199

Multifocal Osteonecrosis Secondary to Chronic Alcohol Ingestion

Multifocal osteonecrosis is a relatively rare disorder with an estimated incidence of around 3% among patients diagnosed as having osteonecrosis. Multifocal osteonecrosis is caused by the several conditions including corticosteroid treatment, coagulation disorders, connective tissue disorders including systemic lupus erythematosus (SLE), inflammatory bowel disease, renal transplantation, and underlying malignancies. Alcohol abuse is one of the risk factors for osteonecrosis, and alcohol-induced osteonecrosis is 5% among all the osteonecrosis. Furthermore, the overall incidence of alcohol-induced multifocal osteonecrosis was approximately 6% among all the osteonecrosis induced by the alcohol. Therefore, here, we report an extremely rare case of alcohol-induced multifocal osteonecrosis involving three joints (two knees and one hip) and review the related literature

Effects of pentazocine and concomitant clonidine on opioid receptors in the rat brain.

The changes in opioid receptors (Op-R) caused by repeated administration of pentazocine and the effect of concomitant clonidine were investigated. Binding of [3H] naloxone was markedly decreased in the absence of Na+, but was increased in the presence of Na+ in the diencephalon-mesencephalon of chronic pentazocine-treated rats. No significant changes were observed in the cerebral cortex of pentazocine-treated rats. The pentazocine-induced changes in Op-R were abolished by the concurrent use of clonidine, an alpha-adrenergic agonist, which has been shown to relieve the withdrawal symptoms of morphine. This result indicated that the behavioral action of clonidine can also be observed at the Op-R level.</p

The Influence of Schizophyllum commune on Asthma Severity

Background: The sensitization and exposure to fungal allergens have been reported to be associated with asthma. The aim of this study was to clarify the impact of sensitization to Schizophyllum commune (S. commune) on the severity and exacerbations of asthma. Methods: Ninety-two patients with asthma of various levels of severity [mild (n = 18), moderate (28), and severe (46)] and exacerbation severity [moderate (n = 43) and severe (6)] were retrospectively examined with regard to fungal sensitization such as specific IgE or intradermal skin reactions against S. commune and other common allergens. We also classified the patients into three groups: (1) three or more asthma attacks during the past year (F-BA) (n = 29),(2) one or two asthma attacks (NF-BA) (n = 20), and (3) no asthma attack (C-BA) (n = 43). Results: The positive rate of late cutaneous reactions to S. commune was higher in patients with severe asthma (41.2%) than with moderate (26.1%) or mild asthma (6.7%), and was significantly different among the three groups (P < 0.05). Although the ratio did not show a significant difference between the patients with severe (83.3%) or moderate (36.1%) exacerbation, it was higher in F-BA (60.9%) than in NF-BA (21.1%) and C-BA patients (10.0%), and it was significantly different among the three groups (P = 0.0002). Multivariate analysis identified positive results for late-phase skin reactions to S. commune and the age of the patients as an independent determinant of asthma severity, and the skin results and %FVC an independent determinant of exacerbation frequency. Conclusion: This study demonstrated that S. commune is an environmental fungus that appears to enhance both the severity of asthma and the exacerbation frequency. © 2011 Springer Science+Business Media, LLC

Two cases of Schizophyllum asthma: Is this a new clinical entity or a precursor of ABPM?

Background: There is a close link between fungal sensitization and asthma severity. Although Schizophyllum commune (S. commune, "suehirotake" in Japanese), one of the basidiomycetous (BM) fungi, is a fungus that can cause allergic bronchopulmonary mycosis (ABPM) and allergic fungal sinusitis (AFS), whether the fungus causes or sensitizes subjects to asthma is unclear. Methods: The bronchial provocation test using S. commune antigen was performed in two asthmatics who had demonstrated positive skin reactions to the S. commune antigen, and low dose of itraconazole (50 mg/day) was prescribed as an adjunctive therapy for 2 weeks. The allergological features and clinical manifestations of these patients are herein evaluated and discussed. Results: Case 1 was a 71-year-old female, and case 2 was a 69-year-old male. Both patients demonstrated positive reactions to the inhalation test. A diagnosis of AFS or ABPM was excluded in both patients because of the lack of a history of pulmonary infiltrates, central bronchiectasis, a history of expectoration of brown plugs or flecks, or sinusoidal findings. Although the efficacy of itraconazole in our cases was unclear, the elevated titer of the specific IgG-for S. commune in case 2 gradually decreased during the period of antifungal therapy. Conclusions: The two patients described herein were diagnosed to have bronchial asthma caused by S. commune; so-called Schizophyllum asthma. S. commune may also be a causative fungal antigen of bronchial asthma. © 2011 Elsevier Ltd. All rights reserved

Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone.

To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.</p

Mood Stabilizers and Antipsychotics for Acute Mania: Systematic Review and Meta-Analysis of Augmentation Therapy vs Monotherapy From the Perspective of Time to the Onset of Treatment Effects

Background: Existing meta-analytic evidence on bipolar mania treatment has revealed that augmentation therapy (AUG) with antipsychotics and mood stabilizers is more effective than monotherapy. However, the speed of the onset of treatment effects and subsequent changes in risk/benefit are unclear. Methods: We searched the Cochrane CENTRAL, MEDLINE, and EMBASE databases until January 2021. Our primary outcomes were response and tolerability. We set 3 time points: 1, 3, and 6 weeks after randomization. Results: Seventeen studies compared AUG therapy and MS monotherapy (comparison 1), and 8 studies compared AUG therapy and antipsychotics monotherapy (comparison 2). In comparison 1, AUG therapy resulted in significantly more responses than monotherapy, with an odds ratio of 1.45 (95% confidence interval [CI]: 1.17 to 1.80) at 3 weeks and 1.59 (95% CI: 1.28 to 1.99) at 6 weeks. Significant improvement was observed in the first week with a standardized mean difference of −0.25 (95% CI: −0.38 to −0.12). In comparison 2, AUG therapy was significantly more effective than monotherapy, with an odds ratio of 1.73 (95% CI: 1.25 to 2.40) at 3 weeks and 1.74 (95% CI: 1.11 to 2.73) at 6 weeks. Significant improvement was observed in the first week with an standardized mean difference of −0.23 (95% CI: −0.39 to −0.07). Regarding tolerability, there was no significant difference between AUG therapy and monotherapy at 3 and 6 weeks in both comparisons. Conclusions: Early AUG therapy should be considered, as it has shown efficacy from weeks 1 to 6, although attention to side effects is necessary for acute mania treatment