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11 results on '"Manandhar, Erica"'

1. Correction to: Monitoring Dose Response of Cyanide Antidote Dimethyl Trisulfide in Rabbits Using Diffuse Optical Spectroscopy

Author

Lee, Jangwoen, Rockwood, Gary, Logue, Brian, Manandhar, Erica, Petrikovics, Ilona, Han, Changhoon, Bebarta, Vikhyat, Mahon, Sari B, Burney, Tanya, and Brenner, Matthew

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

The online version of the original article can be found at.

Published
2019

2. Monitoring Dose Response of Cyanide Antidote Dimethyl Trisulfide in Rabbits Using Diffuse Optical Spectroscopy

Author

Lee, Jangwoen, Rockwood, Gary, Logue, Brian, Manandhar, Erica, Petrikovics, Ilona, Han, Changhoon, Bebarta, Vik, Mahon, Sari B, Burney, Tanya, and Brenner, Matthew

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Vaccine Related, Biodefense, Prevention, Animals, Antidotes, Carbon Dioxide, Dose-Response Relationship, Drug, Electron Transport Complex IV, Hemoglobins, Oxidation-Reduction, Oxygen Consumption, Rabbits, Sodium Cyanide, Spectrum Analysis, Sulfides, Survival Analysis, Chemical and biological weapons, Cyanide toxicity reversal, Optical hemodynamic monitoring, Dimethyl trisulfide, Lethal cyanide poisoning, Diffuse optical spectroscopy, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

IntroductionCyanide (CN) poisoning is a serious chemical threat from accidental or intentional exposures. Current CN exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Dimethyl trisulfide (DMTS) is capable of reacting with CN to form the less toxic thiocyanate with high efficiency, even without the sulfurtransferase rhodanese. We investigated a soluble DMTS formulation with the potential to provide a continuous supply of substrate for CN detoxification which could be delivered via intramuscular (IM) injection in a mass casualty situation. We also used non-invasive technology, diffuse optical spectroscopy (DOS), to monitor physiologic changes associated with CN exposure and reversal.MethodsThirty-six New Zealand white rabbits were infused with a lethal dose of sodium cyanide solution (20 mg/60 ml normal saline). Animals were divided into three groups and treated with saline, low dose (20 mg), or high dose (150 mg) of DMTS intramuscularly. DOS continuously assessed changes in tissue hemoglobin concentrations and cytochrome c oxidase redox state status throughout the experiment.ResultsIM injection of DMTS increased the survival in lethal CN poisoning. DOS demonstrated that high-dose DMTS (150 mg) reversed the effects of CN exposure on cytochrome c oxidase, while low dose (20 mg) did not fully reverse effects, even in surviving animals.ConclusionsThis study demonstrated potential efficacy for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for CN detoxification via intramuscular injection in a moderate size animal model and showed that DOS was useful for optimizing the DMTS treatment.

Published
2018

11. Analysis of Novel Cyanide Antidote Dimethyl Trisulfide for Pharmacokinetic Studies, and Sulfur Mustard Metabolites for Identification of Biomarker of Inhaled Dose

Author

Manandhar, Erica

Subjects
antidote, chemical warfare agents, cyanide, dimethyl trisulfide, stir bar sorptive extraction, sulfur mustard, Chemistry, Medicinal-Pharmaceutical Chemistry
Abstract

Cyanide poisoning by accidental or intentional exposure poses a severe health risk. The current FDA approved antidotes for cyanide poisoning can be effective, but each suffers from specific major limitations. Dimethyl trisulfide (DMTS), a sulfur donor that detoxifies cyanide by converting it into thiocyanate, is a promising next generation cyanide antidote. Although a validated analytical method to analyze DMTS is not currently available from any matrix, one will be vital for the approval of DMTS as a therapeutic agent against cyanide poisoning. Hence, a stir bar sorptive extraction (SBSE) gas chromatography – mass spectrometry (GC-MS) method was developed and validated for the analysis of DMTS from rabbit whole blood. The limit of detection (LOD) using this method was 0.06 μM with dynamic range from 0.5 – 100 μM. The method described here allows further investigations of DMTS as a promising antidote for cyanide poisoning. Sulfur mustard (SM) is the most utilized chemical weapon in modern history. Although its exposure can result in wide range of toxic outcomes, airway injury leading to respiratory failure is the principal cause of mortality in victims. Therefore, current investigations are underway which focus on understanding the inhalation toxicity of SM in order to develop effective therapeutic interventions. A major challenge in inhalation studies is the quantification of actual respiratory dose. In this report, we identified biomarkers that have the potential for correlation to inhalation dose. Preliminary data for correlation of two biomarkers to dose are also presented. To our knowledge, there are no studies done in identifying SM biomarkers in inhalation exposure. Additionally, a rapid, simple, and direct GC-MS analysis technique for an important SM biomarker, sulfur mustard oxide (SMO), was developed and validated in swine plasma. The LOD of the method was 0.1 μM, with a linear range from 0.5 -100 μM. The availability of this method will allow easy and rapid diagnosis (within 15 min of exposure) of SM poisoning especially during the asymptomatic latency period (6-24 h post-exposure).

Published
2017

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