間質性肺疾患の治療のための臨床ビッグデータに基づくドラッグリパーパシング研究

京都大学0048新制・課程博士博士(薬科学)甲第22752号薬科博第126号新制||薬科||14(附属図書館)京都大学大学院薬学研究科薬科学専攻(主査)教授 金子 周司, 教授 土居 雅夫, 教授 竹島 浩学位規則第4条第1項該当Doctor of Pharmaceutical SciencesKyoto UniversityDFA

The Effect of Mangiferin Against Brain Damage Caused by Oxidative Stress and Inflammation Induced by Doxorubicin

Doxorubicin (DOX) is an anthracycline antibiotic used for anticancer therapy. However, this agent can cause various systemic side effects including cognitive impairments in chronic use. Brain damage due to DOX is caused by an increase of tumor necrosis factor-alpha (TNF-α) level in the brain. Increased TNF-α can further lead to chronic inflammation which can lead to neuronal deaths or neurodegenerative diseases. Mangiferin (MAG), a compound extracted from Mangifera indica, has been found neuroprotective activities, but its effect on DOX-induced brain damage is unknown. This study aims to determine the effect of MAG on brain damage induced by DOX. Male Sprague-Dawley rats were induced by DOX intraperitoneally. MAG was given orally at the doses of 30 and 60 mg/kg bw for 7 consecutive weeks. The parameters measured were inflammatory and oxidative stress markers in brain tissue. Coadministration of MAG with DOX reduced inflammation which was marked by the reduction of TNF-α mRNA expression, decreased TNF-α level and reduction of oxidative stress marked by increase of superoxide dismutase level and decrease of malondialdehyde level. In conclusion, MAG was shown to have a neuroprotective effect on brain damage induced by DOX, partly due to inhibition of inflammation and oxidative stress

Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia

ジスキネジア新治療法の発見 --副作用を減らす併用薬から新しい創薬標的へ--. 京都大学プレスリリース. 2021-04-16.Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevents the dyskinesia induced by dopamine D₂ receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, but not in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos⁺/preproenkephalin⁺ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect-pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404

Implementing online team-based learning in an interuniversity setting: A case study of a traditional medicine course

Background: Online team-based learning is a crucial teaching method to successfully increase students’ engagement during the pandemic. This study provides a report on online team-based learning during a traditional medicine course attended by undergraduate students from different higher education institutions in Indonesia and overseas. Methods: A questionnaire was administered to determine the active participation of team members and to carry out a course evaluation Results: The learning outcome was successfully achieved as 96% of the groups scored above the passing grade for the team-based projects. Students from various institutions had generally positive opinions on the course, especially on the course design, course material and the speakers, and the collaborative working with students from diverse backgrounds. Conclusion: Language barriers and technical difficulties were some factors that hindered the students from gaining full benefit from the course, and thus should be mitigated in the implementation of online team-based learning. Additionally, a well-designed pre-test and post-test survey should be conducted to aid the assessment of students’ comprehension of the course