α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

Feasibility of Performing Concurrent Coulometric Titrations Using a Multicompartment Electrolysis Cell

Feasibility of performing multiple coulometric titrations in a single course of electrolysis is presented. In these titrations, three pairs of cathode and anode compartments were connected with a network of electrodes and salt bridges. Passage of current through the cell caused concurrent electrolysis in cathode and anode compartments. Electrogenerated reagents produced in these compartments were used as titrants for quantifying the analyte samples. Endpoints of the titrations were determined from the visual color change of an indicator. The charge passing through the cell was monitored and Faraday’s laws of electrolysis were applied to assess the quantitative relation between the charge and analyte concentration. Experimentally determined coulombs required to titrate aqueous potassium hydrogen phthalate, MnO4–, OH–, and S2O32– were 0.100, 0.466, 0.103, and 0.0934 C, respectively. These results matched with estimated values of 0.0965, 0.482, 0.0965, and 0.0965 C, respectively. Agreement between the coulombs determined from experimental results and reaction stoichiometry suggests a feasible application of concurrent coulometric titrations. Efficacy of the method was tested for determining the active ingredients in household vinegar and vitamin C dietary supplement tablets. Quantities of acetic acid and ascorbic acid in these products were 5.1% and 980 mg, respectively, agreeing with the quantities determined from volumetric titrations (5.1% and 990 mg) and manufacturer’s label (5.0% and 1000 mg)

Feasibility of Performing Concurrent Coulometric Titrations Using a Multicompartment Electrolysis Cell

© 2019 American Chemical Society. Feasibility of performing multiple coulometric titrations in a single course of electrolysis is presented. In these titrations, three pairs of cathode and anode compartments were connected with a network of electrodes and salt bridges. Passage of current through the cell caused concurrent electrolysis in cathode and anode compartments. Electrogenerated reagents produced in these compartments were used as titrants for quantifying the analyte samples. Endpoints of the titrations were determined from the visual color change of an indicator. The charge passing through the cell was monitored and Faraday\u27s laws of electrolysis were applied to assess the quantitative relation between the charge and analyte concentration. Experimentally determined coulombs required to titrate aqueous potassium hydrogen phthalate, MnO 4- , OH - , and S 2 O 32- were 0.100, 0.466, 0.103, and 0.0934 C, respectively. These results matched with estimated values of 0.0965, 0.482, 0.0965, and 0.0965 C, respectively. Agreement between the coulombs determined from experimental results and reaction stoichiometry suggests a feasible application of concurrent coulometric titrations. Efficacy of the method was tested for determining the active ingredients in household vinegar and vitamin C dietary supplement tablets. Quantities of acetic acid and ascorbic acid in these products were 5.1% and 980 mg, respectively, agreeing with the quantities determined from volumetric titrations (5.1% and 990 mg) and manufacturer\u27s label (5.0% and 1000 mg)