Reactivities of Hydroxycinnamic Acid Derivatives Involving Caffeic Acid toward Electrogenerated Superoxide in N,N-Dimethylformamide

Reactivity of (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid (caffeic acid), classified as a hydroxycinnamic acid (HCA) derivative, toward electrogenerated superoxide radical anion (O2•−) was investigated through cyclic voltammetry, in situ electrolytic electron spin resonance spectrometry, and in situ electrolytic ultraviolet–visible spectrometry in N,N-dimethylformamide (DMF), aided by density functional theory (DFT) calculations. The quasi-reversible redox of dioxygen/O2•− is modified in the presence of caffeic acid, suggesting that O2•− is scavenged by caffeic acid through proton-coupled electron transfer. The reactivities of caffeic acid toward O2•− are mediated by the ortho-diphenol (catechol) moiety rather than by the acryloyl group, as experimentally confirmed in comparative analyses with other HCAs. The electrochemical and DFT results in DMF suggested that a concerted two-proton-coupled electron transfer mechanism proceeds via the catechol moiety. This mechanism embodies the superior kinetics of O2•− scavenging by caffeic acid

Electrochemical and Mechanistic Study of Oxidative Degradation of Favipiravir by Electrogenerated Superoxide through Proton-Coupled Electron Transfer

Electrochemical analyses aided by density functional theory calculations were used to investigate the oxidative degradation of pyrazine antiviral drugs, 3-hydroxypyrazine-2-carboxamide (T-1105) and 6-fluoro-3-hydroxypyrazine-2-carboxamide (favipiravir, T-705), by the electrogenerated superoxide radical anion (O2•–). T-1105 and T-705 are antiviral RNA nucleobase analogues that selectively inhibit the RNA-dependent RNA polymerase. They are expected as a drug candidate against various viral infections, including COVID-19. The pyrazine moiety was decomposed by O2•– through proton-coupled electron transfer (PCET). Our results show that its active form, pyrazine-ribofuranosyl-5′-triphosphate, is easily oxidized under inflamed organs by overproduced O2•– through the PCET mechanism in the immune system. This mechanistic study implies that the oxidative degradation of pyrazine derivatives will be prevented by controlling the PCET through simple modification of the pyrazine structure

Laparoscopic splenectomy for a large multilocular splenic cyst with elevated CA19-9: Report of a case

AbstractINTRODUCTIONBecause splenic cysts are rare, a definitive treatment regime for these cysts remains unclear. We report a case of a large multilocular splenic cyst with elevated carbohydrate antigen 19-9 (CA19-9) levels, which was successfully treated with laparoscopic splenectomy.PRESENTATION OF CASEA 22-year-old female was admitted to our hospital with severe left upper abdominal pain. Serum CA19-9 level was mildly elevated (65U/ml). Computed tomography revealed a 25-cm long spleen with multilocular cystic lesions, for which an emergency laparoscopic splenectomy was performed. Histological findings revealed that the lesion was a benign true cyst, and immunostaining analyses showed that the epithelium was CA19-9-positive.DISCUSSIONAlthough some spleen-preserving approaches have been reportedly used, splenic cyst recurrence usually occurs in true cyst cases, wherein the cyst is incompletely removed. Most reported cases of splenic cysts producing CA19-9 are true cysts.CONCLUSIONThe treatment approach should be decided on the basis of the type, shape, location, and even CA19-9 levels of the splenic cyst

Electrochemical and Mechanistic Study of Superoxide Scavenging by Pyrogallol in N,N-Dimethylformamide through Proton-Coupled Electron Transfer

Scavenging of electrogenerated superoxide radical anion (O2•−) by pyrogallol (PyH3) was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectrum in N,N-dimethylformamide with the aid of density functional theory (DFT) calculations. Quasi-reversible dioxygen/O2•− redox couple was modified by the presence of PyH3, suggesting that O2•− was scavenged by PyH3 through proton-coupled electron transfer (PCET) involving two proton transfer and one electron transfer. DFT calculation suggested that the pre-reactive formation of a hydrogen-bond (HB) complex and the subsequent concerted two-proton-coupled electron transfer characterized by catechol moiety in PyH3 is plausible mechanism that embodies the superior kinetics of the O2•− scavenging by PyH3 as shown in the electrochemical results. Furthermore, it was clarified that the three hydroxyl groups of PyH3 promote the formation of HB complex, in comparative analyses using related compounds, resulting in the promotion of the O2•− scavenging

Electrochemical and Mechanistic Study of Reactivities of α-, β-, γ-, and δ-Tocopherol toward Electrogenerated Superoxide in N,N-Dimethylformamide through Proton-Coupled Electron Transfer

Scavenging of superoxide radical anion (O2•−) by tocopherols (TOH) and related compounds was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectrum in N,N-dimethylformamide (DMF) with the aid of density functional theory (DFT) calculations. Quasi-reversible dioxygen/O2•− redox was modified by the presence of TOH, suggesting that the electrogenerated O2•− was scavenged by α-, β-, γ-TOH through proton-coupled electron transfer (PCET), but not by δ-TOH. The reactivities of α-, β-, γ-, and δ-TOH toward O2•− characterized by the methyl group on the 6-chromanol ring was experimentally confirmed, where the methyl group promotes the PCET mechanism. Furthermore, comparative analyses using some related compounds suggested that the para-oxygen-atom in the 6-chromanol ring is required for a successful electron transfer (ET) to O2•− through the PCET. The electrochemical and DFT results in dehydrated DMF suggested that the PCET mechanism involves the preceding proton transfer (PT) forming a hydroperoxyl radical, followed by a PCET (intermolecular ET–PT). The O2•− scavenging by TOH proceeds efficiently along the PCET mechanism involving one ET and two PTs

PICO-LON Project for WIMPs search

Highly segmented inorganic crystal has been shown to have good performance for dark matter search. The energy resolution of ultra thin and large area NaI(Tl) scintillator has been developed. The estimated sensitivity for spin-dependent excitation of 127I was discussed. The recent status of low background measurement at Oto Cosmo Observatory is reportedComment: 3 pages, 1 figure, Proceedings of TAUP200

発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験

Importance: Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset. Objective: To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design: A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019. Setting: Twenty-five neurology centers in Japan. Participants: Patients with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Interventions: Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks. Main outcomes and measures: The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups. Conclusions and relevance: Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate. Trial registration: UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov

Electrochemical and Computational Analysis of Superoxide/Hydroperoxyl Radical Trap by 5,5-Dimethyl-1-pyrroline N-oxide in N,N-dimethylformamide

Spin trap of electrogenerated superoxide radical anion (O2•−) and hydroperoxyl radical (HO2•)using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was investigated via cyclicvoltammetry and insitu electrolytic electron spin resonance (ESR) measurements in dehydrated N,Ndimethylformamide (DMF) aided by density functional theory calculations. In aprotic environments, DMPO gradually traps the electrogenerated O2•, however, its trap rate is considerably slow. Conversely, adding a small amount of proton source to O2•− to form HO2• changes the voltammetric behavior, rendering the detection of the spin adduct easy with ESR.These electrochemical and ESR results obtained in aprotic DMF well demonstrate the differences between O2•− trap and HO2• trap, since the effects of a proton derived from aqueoussolvent on O2•−/HO2• traps, such as superoxide spontaneous dismutation and pH of solution, are not involved. Accordingly, the obtained kinetic and thermodynamic results show the exactchemical reaction parameters for each of the O2•−/HO2• trap. Therefore, these results will beuseful for estimating an apparent O2•−/HO2• adduct-formation in aqueous ESR measurements