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Biogeneration of Volatile Organic Compounds in Microalgae-Based Systems
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Pricila Nass Pinheiro, Karem Rodrigues Vieira, Andriéli Borges Santos, Eduardo Jacob-Lopes, Leila Queiroz Zepka
Sulfur compounds are another group of potent odorous products that are liberated by many microalgae, compounds with human odor threshold concentrations sufficiently low to cause malodors (Achyuthan et al. 2017; Watson and Jüttner 2017). Dimethylsulfide (DMS), dimethyldisulfide (DMDS), and dimethyltrisulfide (DMTS) are the major components responsible for the strong offensive odor, generated by a diversity of biota, biochemical pathways, enzymes, and precursors (Graham et al. 2010; Watson and Jüttner 2017; Huang et al. 2018).
Cyanides: Toxicology, Clinical Presentation, and Medical Management
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Gary A. Rockwood, Gennady E. Platoff Jr., Harry Salem
Sulfur Donors. These enhance the endogenous sulfurtransferase mechanisms for the detoxification of CN to SCN. Sodium thiosulfate is often used in combination with other antidotes having different modes of antidotal action; for example, with sodium nitrite or 4-dimethylaminophenol (4-DMAP). As a generalization, sodium thiosulfate is used as a supplementary treatment on the basis that it is slow acting, possibly due to limited penetration into mitochondria. Recent reports have demonstrated that the sulfur donor dimethyl trisulfide (DMTS) shows promise of being more efficient than sodium thiosulfate in countering CN toxicity (Rockwood et al., 2016) using both KCN injection and HCN inhalation models of CN poisoning in mice (DeLeon et al., 2018). Importantly, DMTS does not require intravenous administration and is efficacious when administered intramuscularly. Sulfanegen, another sulfur donor, has also shown promise as a CN countermeasure (Patterson et al., 2016).
Evaluation of aqueous dimethyl trisulfide as an antidote to a highly lethal cyanide poisoning in a large swine model
Published in Clinical Toxicology, 2022
Tara B. Hendry-Hofer, Carter C. Severance, Subrata Bhadra, Patrick C. Ng, Kirsten Soules, Dennean S. Lippner, Diane M. Hildenberger, Melissa O. Rhoomes, Jessica N. Winborn, Brian A. Logue, Gary A. Rockwood, Vikhyat S. Bebarta
Although current FDA-approved therapies hydroxocobalamin (Cyanokit®) and sodium nitrite/sodium thiosulfate (Nithiodote®) are efficacious, they require intravenous administration [7,8]. Moreover, hydroxocobalamin requires reconstitution and both antidotes require slow intravenous infusion, limiting their usefulness when rapid administration of antidote to a large number of victims in a short period of time is necessary. Furthermore, these antidotes are expensive making it costly to maintain a stockpile in case of a mass exposure. Lastly, following administration of these antidotes, patients require careful monitoring for adverse effects such as hypotension, hypertension, cardiac arrhythmias, tachycardia, nausea, vomiting, and methemoglobinemia. With the high risk of a large-scale cyanide exposure resulting in multiple critically ill victims, an efficacious antidote with minimal side effects that is quick and easy to administer is needed. Intramuscular administration (IM) of dimethyl trisulfide (DMTS) has been evaluated in rodent and large animal models and found to be efficacious against lethal cyanide poisoning [9–11]. However, with the exception of the study done by Rice and colleagues [11], the majority of these studies have not evaluated long-term efficacy of DMTS. Additionally, these studies were done using a previous formulation of DMTS, whereas this study was completed using a new, novel, aqueous formulation of DMTS that has improved bioavailability and demonstrates efficacy at a much lower dose [10,12].
A novel aqueous dimethyl trisulfide formulation is effective at low doses against cyanide toxicity in non-anesthetized mice and rats
Published in Clinical Toxicology, 2022
D. S. Lippner, D. M. Hildenberger, M. O. Rhoomes, J. N. Winborn, H. Dixon, J. McDonough, G. A. Rockwood
Much work has been focused upon identifying an effective CN countermeasure that can be administered IM [28–33] since IM administration with certain types of autoinjectors can be rapidly performed by minimally trained personnel. Dimethyl trisulfide (DMTS) is a natural compound that is found to be generally safe by the FDA when consumed orally [34,35] and has been extensively studied as a CN medical countermeasure using various animal models [28,36–40]. While effective, the earlier, non-aqueous DMTS formulations exhibited some limitations with stability [37,41], or bioavailability [28,36]. The studies presented in this manuscript introduce a novel aqueous 10% DMTS formulation (developed by Southwest Research Institute, San Antonio, TX) that has recently demonstrated stability out to 24 months when stored in ampoules (unpublished data) and improved bioavailability profiles in rodents (described as a “proprietary formulation of DMTS”) [42], and determine whether this aqueous formulation exhibits efficacy in various rodent models at lower IM doses than previous formulations. Moreover, we exhibit the efficacy of this DMTS formulation when it is administered at a set delay in rats, which can better simulate real-life scenarios for CN countermeasure treatment.
Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity
Published in Clinical Toxicology, 2019
Tara B. Hendry-Hofer, Alyssa E. Witeof, Dennean S. Lippner, Patrick C. Ng, Sari B. Mahon, Matthew Brenner, Gary A. Rockwood, Vikhyat S. Bebarta
Nithiodote®, an FDA approved therapy for cyanide poisoning, contains sodium nitrite and sodium thiosulfate [3]. Sodium thiosulfate acts as a sulfur donor, converting cyanide to the less toxic, renally excreted compound thiocyante [4–6]. Thiosulfate relies on the sulfur transferase rhodanese, which is primarily found in the mitochondria of the liver and kidneys. Furthermore, thiosulfate is minimally lipophilic, limiting its ability to penetrate the cell and blood–brain barrier, a target organ of cyanide toxicity [4,7]. Dimethyl trisulfide (DMTS), like the FDA approved drug sodium thiosulfate, has been found to be therapeutic following cyanide poisoning [8]. Similar to sodium thiosulfate, DMTS, a sulfur-based molecule found in garlic, onion and other plants, acts as a sulfur donor making it an antagonist for cyanide, converting cyanide to the less toxic compound thiocyanate [9,10]. However, compared to thiosulfate, DMTS has been shown to clear cyanide with greater efficiency, making it a potentially ideal candidate drug for cyanide toxicity [8,9].