Prospective Five-Year Follow-Up of Patients with Schizophrenia Suspected with Parkinson’s Disease

Objective. It is difficult to distinguish patients with schizophrenia with neuroleptic-induced parkinsonism (NIP) from those with existing idiopathic Parkinson’s disease when their striatal dopamine transporter uptake is reduced. There is a possibility of misdiagnosis of Parkinson’s disease in patients with schizophrenia as schizophrenia with NIP, which leads to inappropriate treatment. This prospective study aimed at determining the underlying pathophysiology using detailed clinical and psychological assessments. Methods. We enrolled six patients with schizophrenia who had parkinsonism and were diagnosed with Parkinson’s disease according to the Movement Disorder Society Clinical Diagnostic Criteria, except for the fifth absolute exclusion criteria. Results. Five patients had been treated with neuroleptics for 20 years. One patient refused treatment for schizophrenia. All patients had impaired cognitive function at enrolment, olfactory dysfunction, and constipation. All patients were treated with dopaminergic therapy, and their parkinsonism substantially improved; one woman in her 40s experienced a wearing-off effect and dyskinesia. The uptake of dopamine transporter in the striatum decreased by 13%/year during the study period. Conclusion. Some patients with schizophrenia and parkinsonism benefit from dopaminergic therapy. Some of these patients may also exhibit Lewy pathology

The High Stability of Intermediate Radicals Enhances the Radical-Scavenging Activity of Aminochromanols

The hydroxyl radical-scavenging activity of the amino-substituted alpha-tocopherol analogues was much higher than that of alpha-tocopherol. Aminochromanoxyl radicals generated from 5- and 7-aminochromanol were successfully detected in aqueous solution at room temperature during ESR measurements. The stability of the aminochromanoxyl radicals leads to a significant enhancement of the radical-scavenging activity

Effect of Alkyl Group on Transnitrosation of N-Nitrosothiazolidine Thiocarboxamides

S-Nitrosoglutathione (GSNO) relaxes vascular smooth muscles, prevents platelet aggregation, and acts as a potential in vivo nitric oxide donor. 3-Nitroso-1,3-thiazolidine- 4-thiocarboxamide (1), a N-nitrosothioproline analogue, exhibited a high GSNO formation activity. In this study, two compounds (2 and 3) based on compound 1 were newly synthesized by introducing either one or two methyl groups onto a nitrogen atom on the thioamide substituent in 1. The pseudo-first-order rate constants (kobs) for the GSNO formation for the reaction between the compound and glutathione (GSH) followed the orde 1 > 2 ≈ 3. Thus, the introduction of a methyl group(s) onto the thioamide group led to a decrease in the transnitrosation activity. On the basis of density functional theoretical calculations, the transnitrosation for the N-nitrosothiazolidine thiocarboxamides was proposed to proceed via a bridged intermediate pathway. Specifically, the protonated compound 1 forms a bridged structure between the nitrogen atom in the nitroso group and two sulphur atoms–one in the ring and the other in the substituent. The bridged intermediate gives rise to a second intermediate, in which the nitroso group is bonded to the sulphur atom in the thioamide group. Finally, the nitroso group is transferred to GSH to form GSNO

Additional file 1: of Isolation and characterization of antimutagenic components of Glycyrrhiza aspera against N-methyl-N-nitrosourea

Fractionations of antimutagenic compounds from dichloromethane soluble fraction. (DOCX 3675 kb

Chlorine Atom Substitution Influences Radical Scavenging Activity of 6-Chromanol

Synthetic 6-chromanol derivatives were prepared with several chlorine substitutions, which conferred both electron-withdrawing inductive effects and electron-donating resonance effects. A trichlorinated compound (2), a dichlorinated compound (3), and three monochlorinated compounds (4, 5, and 6) were synthesized; compound 2, 3, and 6 were novel. The antioxidant activities of the compounds, evaluated in terms of their capacities to scavenge galvinoxyl radical, were associated with the number and positioning of chlorine atoms in the aromatic ring of 6-chromanol. The activity of compound 1 (2,2-dimethyl-6-chromanol) was slightly higher than the activities of compounds 2 (2,2-dimethyl-5,7-dichloro-6-chromanol) or 3 (2,2-dimethyl-5,7,8-trichloro-6-chromanol), in which the chlorine atoms were ortho to the phenolic hydroxyl group of 6-chromanol. The scavenging activity of compound 3 was slightly higher than that of 2, which contained an additional chlorine substituted in the 8 position. The activities of polychlorinated compounds 2 and 3 were higher than the activities of any of the monochlorinated compounds (4-6). Compound 6, in which a chlorine was substituted in the 8 position, exhibited the lowest activity. Substitution of a chlorine atom meta to the hydroxyl group of 6-chromanol (compounds 2 and 6) decreased galvinoxyl radical scavenging activity, owing to the electron-withdrawing inductive effect of chlorine. Positioning the chloro group ortho to the hydroxyl group (compounds 4 and 5) retained antioxidant activity because the intermediate radical was stabilized by the electron-donating resonance effect of chlorine in spite of the electron-withdrawing inductive effect of chlorine. Antioxidant activities of the synthesized compounds were evaluated for correlations with the O-H bond dissociation energies (BDEs) and the ionization potentials. The BDEs correlated with the second-order rate constant (k) in the reaction between galvinoxyl radical and the chlorinated 6-chromanol derivatives in acetonitrile. This indicated that the antioxidant mechanism of the synthesized compounds consisted of a one-step hydrogen atom transfer from the phenolic OH group rather than an electron transfer followed by a proton transfer. The synthesized compounds also exhibited hydroxyl radical scavenging capacities in aqueous solution

Solvent Effect on the Radical-Scavenging Mechanism of Ascorbic Acid and Its Derivatives

Ascorbic acid (AscH2) is a representative water-soluble antioxidant and shows diverse biological activities, such as antitumor and radioprotective activities. However, the mechanism of the radical-scavenging reaction of AscH2 has yet to be fully clarified. Recently, we have reported that a water-insoluble 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) frequently used as a reactivity model of reactive oxygen species was successfully solubilized in water using β-cyclodextrin (β-CD) (Chem. Commun. 2015, 51, DOI: 10.1039/c5cc02236c). This enables us to investigate the radical-scavenging mechanism of AscH2 and its derivatives both in aqueous and non-aqueous media using DPPH•.AscH2 efficiently scavenged DPPH• both in MeOH and aqueous buffer solutions. The decay of the absorbance at 516 nm due to DPPH• monitored by a stopped-flow technique in MeOH obeyed pseudo-first-order kinetics, when the concentration of AscH2 ([AscH2]) was maintained at more than a 10-fold excess of DPPH• concentration. The pseudo-first-order rate constants (kobs) increased with increasing [AscH2] to reach a constant value. On the other hand, the kobs values determined in a phosphate buffer (0.1 M, pH 7.4) from the decay of the absorbance at 527 nm due to β-CD-solubilized DPPH• (DPPH•/β-CD) linearly increased with increasing [AscH2]. Because the pKa value of AscH2 is reported to be 4.1, AscH2 undergoes deprotonation and exists in its anionic form, AscH–, in the phosphate buffer solution (0.1 M, pH 7.4). In such a case, AscH– scavenged DPPH• to produce Asc•– and DPPH-H via a hydrogen-atom transfer. On the other hand, little deprotonation of AscH2 occurs in MeOH. Thus, the saturation behavior of the kobs values in MeOH may reflect a pre-equilibrium between AscH2 and AscH–. The effects of aprotic solvents as well as pH in aqueous systems using AscH2 and its derivatives were also investigated to clarify the detailed radical-scavenging mechanism of AscH2.THE INTERNATIONAL CHEMICAL CONGRESS OF PACIFIC BASIN SOCIETIES 2015 (PACIFICHEM 2015

Radical-Scavenging Reactions of Ascorbic Acid and Its Analogue in the Presence of a Redox-Inactive Metal Ion

Ascorbic acid (AscH(2)) is an important naturally occurring, water-soluble antioxidant. However, the detailed radical-scavenging mechanism of AscH(2) has yet to be fully clarified. In this study, we investigated the radical-scavenging kinetics of AscH(2) and 5,6-isopropylidenen ascorbic acid (iAscH(2)) in the absence or presence of magnesium ion (Mg(2+)). AscH(2) efficiently scavenged galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl radicals (GO radical and DPPH radical, respectively) in deaerated methanol (MeOH) at 298 K. The pseudo-first-order rate constants (k(obs)) determined for these reactions increased with increasing AscH(2) concentration to reach constant values. The k(obs) values were significantly decreased in the presence of 0.1 M Mg(ClO(4))(2). Similar results were obtained for the reactions of iAscH(2) with these radicals in deaerated MeOH as well as in deaerated acetonitrile (MeCN). The detailed radical-scavenging mechanisms will be discussed based on the kinetic data obtained in this study.19th Annual Meeting of the Society for Free Radical Biology and Medicine (SFRBM 2012