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Intraocular deposits and cataracts after long-term rifabutin intake: A case report
Get PDFRATIONALE: Rifabutin is a broad-spectrum antibiotic known to cause deposits on the corneal endothelium and lens. We report a patient in whom cataracts developed and progressive pigment deposits were seen on the corneal endothelium, lens, and iridocorneal angle. PATIENT CONCERNS: The patient was a 45-year-old woman who had been received long-term treatment with a combination of various anti-mycobacterial drugs for multidrug-resistant tuberculosis starting in 2004. Rifabutin was started in 2009, and she was referred to our department in 2017 for detailed ophthalmological examination. DIAGNOSES: Both eyes showed pigmented deposits over the entire corneal endothelium, the entire periphery of the iridocorneal angle, and the anterior surface of the lens. Mild cataracts were also diagnosed bilaterally. Pigment deposits on the anterior surface of the lens and the cataracts in both eyes gradually progressed. These lesions were assumed to be associated with long term rifabutin intake. INTERVENTIONS: Rifabutin intake was discontinued after progression of intraocular deposits, cataracts, and ERG deterioration. OUTCOMES: Visual acuity improved, although cataracts, deposits, and ERG deterioration remained. LESSONS: Rifabutin may induce not only corneal endothelial deposits, but also cataracts and iridocorneal angle deposits
新たな高分解能CT肺線維化スコアを用いた肺癌患者における抗癌剤起因性薬剤性肺炎の発症予測について
No full textBackground and objective: Pre-existing interstitial lung disease (ILD) in lung cancer patients is considered a risk factor for anti-cancer drug-induced pneumonia; however, a method for evaluating ILD, including mild cases, has not yet been established. We aimed to elucidate whether the quantitative high-resolution computed tomography fibrosis score (HFS) is correlated with the risk of anti-cancer drug-induced pneumonia in lung cancer patients, even in those with mild pre-existing ILD. Methods: The retrospective single-institute study cohort comprised 214 lung cancer patients who underwent chemotherapy between April 2013 and March 2016. The HFS quantitatively evaluated the grade of pre-existing ILD. We extracted data regarding age, sex, smoking history, and coexisting factors that could affect the incidence of anti-cancer drug-induced pneumonia. Cox proportional hazard models were used to analyze the effects of the HFS and other factors on the risk of anti-cancer drug-induced pneumonia. Results: Pre-existing ILD was detected in 61 (29%) of 214 patients, while honeycombing and traction bronchiectasis were observed in only 15 (7.0%) and 10 (4.7%) patients, respectively. Anti-cancer drug-induced pneumonia developed in 19 (8.9%) patients. The risk of anti-cancer drug-induced pneumonia increased in proportion to the HFS (hazard ratio, 1.16 per point; 95% confidence interval, 1.09–1.22; p < 0.0001). Conclusions: The quantitative HFS was correlated with the risk of developing anti-cancer drug-induced pneumonia in lung cancer patients, even in the absence of honeycombing or traction bronchiectasis. The quantitative HFS may lead to better management of lung cancer patients with pre-existing ILD.長崎大学学位論文 学位記番号:博(医歯薬)甲第1255号 学位授与年月日:令和2年6月3日Author: Hiroshi Gyotoku, Hiroyuki Yamaguchi, Hiroshi Ishimoto, Shuntaro Sato, Hirokazu Taniguchi, Hiroaki Senju, Tomoyuki Kakugawa, Katsumi Nakatomi, Noriho Sakamoto, Minoru Fukuda, Yasushi Obase, Hiroshi Soda, Kazuto Ashizawa and Hiroshi MukaeCitation: Journal of Clinical Medicine, 9(4), 1045; 202
ネーザルハイフローはプロポフォール鎮静中の換気を改善する健康被験者でのランダム化クロスオーバー研究
No full textObjective: Hypoventilation and carbon dioxide (CO2) retention are common during sedation. The current study investigated the ventilation responses to nasal high flow (NHF) during sedation with propofol. Methods: NHF of 30 L/min and 60 L/min with room air was applied during wakefulness and sedation in 10 male volunteers. Ventilation was monitored by respiratory inductance plethysmography, transcutaneous partial pressure of CO2 (TcCO2), and SpO2. Results: During sedation, NHF of 30 L/min and 60 L/min reduced the TcCO2 by 2.9 ± 2.7 mmHg (p = 0.025) and by 3.6 ± 3.4 mmHg (p = 0.024) without affecting SpO2 and reduced the mean respiratory rate by 3 ± 3 breaths/min (p = 0.011) and by 4 ± 3 breaths/min (p = 0.003), respectively. Conclusion: During sedation with propofol, NHF without supplemental oxygen attenuated CO2 retention and reduced the respiratory rate. The findings show that NHF can improve ventilation during sedation, which may reduce the risk of complications related to hypoventilation.長崎大学学位論文 学位記番号:博(医歯薬)甲第1256号 学位授与年月日:令和2年6月3日Author: Gaku Mishima, Takuro Sanuki, James Revie, Max Pinkham, Toshihiro Watanabe, Shinji Kurata, Stanislav Tatkov, Takao AyuseCitation: Respiratory Physiology & Neurobiology, 277, 103429; 202
Algicidal hydroxylated C18 unsaturated fatty acids from the red alga Tricleocarpa jejuensis: Identification, synthesis and biological activity
No full textBioassay-guided separation of a methanol extract of Tricleocarpa jejuensis by monitoring algicidal activity against the red tide phytoplankton Chattonella antiqua led to the isolation of an active fraction consisting of a mixture of four isomeric compounds. The active compounds were identified as (E)-9-hydroxyoctadec-10-enoic acid (1), (E)-10-hydroxyoctadec-8-enoic acid (2), (E)-11-hydroxyoctadec-12-enoic acid (3) and (E)-12-hydroxyoctadec-10-enoic acid (4) by NMR, IR and mass spectral data. The structures were confirmed by comparison of the NMR and MS data with those of authentic samples of 1–4 obtained by unambiguous syntheses. Synthesized hydroxy acids 1–4 and related compounds were assessed for algicidal activity against C. antiqua and it was found that all of 1–4 had high activity (>80% mortality at 24 h) at a concentration of 20 μg/mL. A structure–activity relationship study using 11 related compounds revealed that the presence of the hydroxyl group is important for the activity and the double bond may be replaced with a triple bond
Characterization of tick-borne encephalitis virus isolated from a tick in central Hokkaido in 2017
Get PDFTick-borne encephalitis virus (TBEV) is a zoonotic virus in the genus Flavivirus, family Flaviviridae. TBEV is widely distributed in northern regions of the Eurasian continent, including Japan, and causes severe encephalitis in humans. Tick-borne encephalitis (TBE) was recently reported in central Hokkaido, and wild animals with anti-TBEV antibodies were detected over a wide area of Hokkaido, although TBEV was only isolated in southern Hokkaido. In this study, we conducted a survey of ticks to isolate TBEV in central Hokkaido. One strain, designated Sapporo-17-Io1, was isolated from ticks (Ixodes ovatus) collected in Sapporo city. Sequence analysis revealed that the isolated strain belonged to the Far Eastern subtype of TBEV and was classified in a different subcluster from Oshima 5-10, which had previously been isolated in southern Hokkaido. Sapporo-17-Io1 showed similar growth properties to those of Oshima 5-10 in cultured cells and mouse brains. The mortality rate of mice infected intracerebrally with each virus was similar, but the survival time of mice inoculated with Sapporo-17-Io1 was significantly longer than that of mice inoculated with Oshima 5-10. These results indicate that the neurovirulence of Sapporo-17-Io1 was lower than that of Oshima 5-10. Using an infectious cDNA clone, the replacement of genes encoding non-structural genes from Oshima 5-10 with those from Sapporo-17-Io1 attenuated the neuropathogenicity of the cloned viruses. This result indicated that the non-structural proteins determine the neurovirulence of these two strains. Our results provide important insights for evaluating epidemiological risk in TBE-endemic areas of Hokkaido
Anti-malarial activity of traditional Kampo medicine Coptis rhizome extract and its major active compounds
Get PDFBACKGROUND: Herbal medicine has been a rich source of new drugs exemplified by quinine and artemisinin. In this study, a variety of Japanese traditional herbal medicine ('Kampo') were examined for their potential anti-malarial activities. METHODS: A comprehensive screening methods were designed to identify novel anti-malarial drugs from a library of Kampo herbal extracts (n = 120) and related compounds (n = 96). The anti-malarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) strains of Plasmodium falciparum. The cytotoxicity was also evaluated using primary adult mouse brain cells. After being selected through the first in vitro assay, positive extracts and compounds were examined for possible in vivo anti-malarial activity. RESULTS: Out of 120 herbal extracts, Coptis rhizome showed the highest anti-malarial activity (IC50 1.9 µg/mL of 3D7 and 4.85 µg/mL of Dd2) with a high selectivity index (SI) > 263 (3D7) and > 103 (Dd2). Three major chlorinated compounds (coptisine, berberine, and palmatine) related to Coptis rhizome also showed anti-malarial activities with IC50 1.1, 2.6, and 6.0 µM (against 3D7) and 3.1, 6.3, and 11.8 µM (against Dd2), respectively. Among them, coptisine chloride exhibited the highest anti-malarial activity (IC50 1.1 µM against 3D7 and 3.1 µM against Dd2) with SI of 37.8 and 13.2, respectively. Finally, the herbal extract of Coptis rhizome and its major active compound coptisine chloride exhibited significant anti-malarial activity in mice infected with Plasmodium yoelii 17X strain with respect to its activity on parasite suppression consistently from day 3 to day 7 post-challenge. The effect ranged from 50.38 to 72.13% (P < 0.05) for Coptis rhizome and from 81 to 89% (P < 0.01) for coptisine chloride. CONCLUSION: Coptis rhizome and its major active compound coptisine chloride showed promising anti-malarial activity against chloroquine-sensitive (3D7) and -resistant (Dd2) strains in vitro as well as in vivo mouse malaria model. Thus, Kampo herbal medicine is a potential natural resource for novel anti-malarial agents
Intervention trial in school teachers for establishing breakfast consumption habits using cereal food －First report－
Get PDF長崎大学教育学部社会科学論叢 通巻 第82号（Bulletin of Faculty of Education, Nagasaki University: Social Science, Vol.82
Roles of Elm1 in antifungal susceptibility and virulence in Candida glabrata
Get PDFElm1 is a serine/threonine kinase involved in multiple cellular functions, including cytokinesis, morphogenesis, and drug resistance in Saccharomyces cerevisiae; however, its roles in pathogenic fungi have not been reported. In this study, we created ELM1-deletion, ELM1-reconstituted, ELM1-overexpression, and ELM1-kinase-dead strains in the clinically important fungal pathogen Candida glabrata and investigated the roles of Elm1 in cell morphology, stress response, and virulence. The elm1Δ strain showed elongated morphology and a thicker cell wall, with analyses of cell-wall components revealing that this strain exhibited significantly increased chitin content relative to that in the wild-type and ELM1-overexpression strains. Although the elm1Δ strain exhibited slower growth than the other two strains, as well as increased sensitivity to high temperature and cell-wall-damaging agents, it showed increased virulence in a Galleria mellonella-infection model. Moreover, loss of Elm1 resulted in increased adhesion to agar plates and epithelial cells, which represent important virulence factors in C. glabrata. Furthermore, RNA sequencing revealed that expression levels of 30 adhesion-like genes were elevated in the elm1Δ strain. Importantly, all these functions were mediated by the kinase activity of Elm1. To our knowledge, this is the first report describing the functional characterization of Elm1 in pathogenic fungi
A case study on teacher's decision making in multi-grade class.
Get PDF長崎大学教育学部紀要：教育科学 通巻 第84号（Bulletin of Faculty of Education, Nagasaki University: Educational Science, Vol.84
Co-delivery Systems of Multiple Drugs Using Nanotechnology for Future Cancer Therapy
Get PDFCancer treatments have improved significantly during the last decade but are not yet satisfactory. Combination therapy is often administered to improve efficacy and safety. Drug delivery systems can also improve efficacy and safety. To control the spatiotemporal distribution of drugs, nanotechnology involving liposomes, solid lipid nanoparticles, and polymeric micelles has been developed. Co-delivery systems of multiple drugs are a promising approach to combat cancer. Synergistic effects and reduced side effects are expected from the use of co-delivery systems. In this review, we summarize various co-delivery systems for multiple drugs, including small-molecule drugs, nucleic acids, genes, and proteins. Co-delivery of drugs with different properties is relatively difficult, but some researchers have succeeded in developing such co-delivery systems. Environment-responsive carrier designs can control the release of cargos. Although their preparation is more complicated than that of mono-delivery systems, co-delivery systems can simplify clinical procedures and improve patient QOL