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Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. Objective: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). Methods: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. [ABSTRACT FROM AUTHOR]

Background: Enforcement of the 2018 Clinical Trials Act (CTA) in Japan resulted in strict and complicated regulations surrounding intervention studies. Few Japan-specific measures have been developed to promote intervention studies in Japan despite concerns about CTA's negative influence on such studies. Therefore, this study examined the changes in academic investigators' interest in conducting clinical studies before and after enforcement of the CTA to determine measures to promote specified clinical trials. Methods: We conducted a questionnaire survey with investigators belonging to the Institute of Biomedical Sciences, Tokushima University Graduate School, before and after enforcement of the CTA. Results: Investigators had lesser interest in intervention studies in the post-questionnaire survey (post) group than in the pre-questionnaire survey (pre) group. Their desire for "project management" was significantly higher in the post-group than in the pre-group. Their desire for "support for preparing documents when conducting specified clinical trials" was significantly higher in the group interested in conducting specified clinical trials than that in the not-interested group. Conclusion: We revealed that investigators were highly interested in "project management" and "support for preparing documents when conducting specified clinical trials" after enforcement of the CTA. Measures for these desires may promote specified clinical trials. [ABSTRACT FROM AUTHOR]

The lifetimes and spin-lattice relaxation time of photo-excited triplet electron of pentacene doped in p-terphenyl at room temperature have been investigated. Values of spin-lattice relaxation time previously reported in ESR studies are inconsistent with each other. In this paper, we determined these time constants based on proton signals enhanced by dynamic nuclear polarization using the electrons (Triplet-DNP). The combined analysis of dependences of proton signal intensities on the delay time of polarization transfer and laser pulse structure allows us to disentangle contributions of the lifetimes and spin-lattice relaxation time. The lifetimes of triplet sublevels with ms = 0 and ±1 were determined to be 22.3 and 88 µs, respectively. The spin-lattice relaxation time was found to be longer than 300 µs, hence the time evolution of the electron population in the triplet state is governed by the lifetimes. It was also found that the proton signal enhancement is limited at a high repetition rate by the partial cancellation of the electron spin polarization by the remaining population produced by the preceding laser pulses. [ABSTRACT FROM AUTHOR]

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ligand was designed and synthesized from readily accessible L-leucinol. The combination of a Cu salt with this chiral ligand precursor promoted the asymmetric conjugate addition of Et2Zn to 2-cyclohexen- 1-one at room temperature without the need for temperature control to afford the corresponding 1,4-adduct with up to 95% ee. [ABSTRACT FROM AUTHOR]

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ligand was designed and synthesized from readily accessible L-leucinol. The combination of a Cu salt with this chiral ligand precursor promoted the asymmetric conjugate addition of Et2Zn to 2-cyclo-hexen-1-one at room temperature without the need for temperature control to afford the corresponding 1,4-adduct with up to 95% ee. [ABSTRACT FROM AUTHOR]

Oxidative arylation of ethylene with benzene was examined by using a Pd(OAc)2/heteropoly acid/O2 system under mild conditions. The reaction of benzene with ethylene in the presence of catalytic amounts of Pd(OAc)2 combined with H4PMo11VO40·15H2O (or H3PMo12O40·30H2O), AcONa, and dibenzoylmethane under air at 90–120 °C produced oxidative coupling products, styrene and stilbene, in fair yields (up to 167 total turnovers). From the examination of the catalyst performance of Pd(OAc)2 combined with various heteropoly acids, it was found that the employment of heteropoly acids including molybdenum ion in their structure is very important to obtain high turnover numbers of Pd. [ABSTRACT FROM AUTHOR]