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Okayasu Ichiro,Mizuki Tachi,Sanuki Takuro,Kurata Shinji,Ayuse Takao 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.2
Goreisan might be a medicine to cure the pain caused by thirst and dry mouth symptom of glossodynia. All registered patients were treated with Goreisan by taking 7.5 g / day (min 3) for 2 weeks. Self-filled Visual Analogue Scale (VAS) and tongue perception test by nomo-filament. Furthermore, daily self-filled VAS evaluation was required patients’ home for two weeks during Goreisan administration. There was 57% of patients (8/14) showed “improved” after administration of 2 weeks Goreisan administration based on the criteria of 20% reduction of VAS compared to baseline. Self-filled VAS score was significant low (p = 0.006) at 2 weeks evaluation at second visit and remained lower level through 4 week observation periods compared to baseline value. QST significantly increased after 2 weeks administration of Goreisan (p = 0.008) and remained higher level through 4 week observation periods compared to baseline value. There was significant reduction of daily self-filled VAS patients’ home at day 3 and day 13 ~ day 14. (p < 0.05). There is a weak positive and negative correla-tion between Barometric pressure (hPa) and self-filled VAS scale (cm) in each patients. The administration of Goreisan for two weeks lead to significant reduction of pain perception based on the evaluation of Self-filled pain scale (VAS) and tongue perception test (QST). There is correlation between barometric pressure and self-filled VAS scale. This fact might indicate that Goreisan would be the alternative treatment for glossodynia patients. Goreisan would be a successful alternative treat-ment modality forglossodynia patients.Trial registration Current Controlled trials was registered with the UMIN Clinical TrialsRegistry (identifier: UMIN000035965, 02.21.2019).
Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit
( Mahmoud Kandeel ),( Mizuki Yamamoto ),( Hideki Tani ),( Ayako Kobayashi ),( Jin Gohda ),( Yasushi Kawaguchi ),( Byoung Kwon Park ),( Hyung-joo Kwon ),( Jun-ichiro Inoue ),( Abdallah Alkattan ) 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.3
A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 μM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 μM). Peptide #2 inhibited the SARSCoV- 2 pseudovirus assay at IC50=1.49 μM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.
( Mahmoud Kandeel ),( Mizuki Yamamoto ),( Abdulla Al-taher ),( Aya Watanabe ),( Kentaro Oh-hashi ),( Byoung Kwon Park ),( Hyung-joo Kwon ),( Jun-ichiro Inoue ),( Mohammed Al-nazawi ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.4
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC<sub>50</sub> values of 12.6, 21.8, and 11.12 μM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 μM with no observed toxicity in Vero cells at 10 μM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.
Kenji Ohwada,Tatsuo Fukuda,Jun’ichiro Mizuki,Kazuma Hirota,Hikaru Terauchi,Satoshi Tsutsui,Alfred Q. R. Baron,Hidehiro Ohwa,Naohiko Yasuda 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.31
Pb(In_(1/2)Nb_(1/2))O_3 (PIN) can be antiferroelectric (AFE), ferroelectric (FE) or a relaxor depending upon the perovskite B-site randomness. In order to clarify the effect of B-site randomness, we studied the dynamics of ordered PIN without B-site randomness (O-PIN, AFE), which will give us a clear picture of the AFE/relaxor nature of the ground state due to B-site randomness. The quasielastic (QE) scattering shows a critical slowing down near the Γ-point and the transverse acoustic (TA) mode shows a softening trend at a finite wavenumber position (not at the Γ-point) towards the AFE phase transition temperature (T_N ∼ 450 K). On the other hand, the transverse optic (TO) mode shows a softening near the Γ-point toward low temperature with no clear anomaly at T_N. These results indicate that the AFE phase transition is associated with the TA mode and the origin of the QE scattering while a ferroelectric correlation exists behind the AFE ordering. The effect of B-site randomness is finally discussed on the basis of the results.
Sanuki, Takuro,Mishima, Gaku,Kurata, Shinji,Watanabe, Toshihiro,Kiriishi, Kensuke,Tachi, Mizuki,Ozaki, Yu,Okayasu, Ichiro,Kawai, Mari,Matsushita, Yuki,Miura, Keiichiro,Ayuse, Takao The Korean Dental Society of Anesthsiology 2015 Journal of Dental Anesthesia and Pain Medicine Vol.15 No.3
Background: We hypothesized that ketamine, when administered as the anesthetic induction agent, may prevent cardiovascular depression during high-dose remifentanil administration, unlike propofol. To test our hypothesis, we retrospectively compared the hemodynamic effects of ketamine, during high-dose remifentanil administration, with those of propofol. Methods: Thirty-eight patients who underwent oral surgery at the Nagasaki University Hospital between April 2014 and June 2015 were included in this study. Anesthesia was induced by the following procedure: First, high-dose remifentanil ($0.3-0.5{\mu}g/kg/min$) was administered 2-3 min before anesthesia induction;next, the anesthetic induction agent, either propofol (Group P) or ketamine (Group K), was administered. Mean arterial pressure (MAP) and the heart rate were recorded by the automated anesthesia recording system at four time points: immediately before the administration of high-dose remifentanil (T1);immediately before the administration of propofol or ketamine (T2);2.5 min (T3), and 5 min (T4) after the administration of the anesthetic induction agent. Results: In Group P, the MAP at T3 ($75.7{\pm}15.5mmHg$, P = 0.0015) and T4 ($68.3{\pm}12.5mmHg$, P < 0.001) were significantly lower than those at T1 ($94.0{\pm}12.4mmHg$). However, the MAP values in the K group were very similar (P = 0.133) at all time points. The heart rates in both Groups P (P = 0.254) and K (P = 0.859) remained unchanged over time. Conclusions: We showed that ketamine, when administered as the anesthetic induction agent during high-dose remifentanil administration, prevents cardiovascular depression.