TY - JOUR AU - Orján, Erik Márk AU - Kormányos, Eszter Sára AU - Fűr, Gabriella AU - Dombi, Ágnes AU - Bálint, Emese Réka AU - Balla, Zsolt AU - Balog, Beáta Adél AU - Dágó, Ágnes AU - Totonji, Ahmad AU - Bátai, István Zoárd AU - Jurányi, Eszter Petra AU - Ditrói, Tamás AU - Al-omari, Ammar AU - Pozsgai, Gábor AU - Kormos, Viktória AU - Nagy, Péter AU - Pintér, Erika AU - Rakonczay, Zoltán AU - Kiss, Lóránd TI - The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 19 SN - 2045-2322 DO - 10.1038/s41598-023-43692-9 UR - https://m2.mtmt.hu/api/publication/34183455 ID - 34183455 N1 - * Megosztott szerzőség AB - Various organosulfur compounds, such as dimethyl trisulfide (DMTS), display anti-inflammatory properties. We aimed to examine the effects of DMTS on acute pancreatitis (AP) and its mechanism of action in both in vivo and in vitro studies. AP was induced in FVB/n mice or Wistar rats by caerulein, ethanol-palmitoleic acid, or L-ornithine-HCl. DMTS treatments were administered subcutaneously. AP severity was assessed by pancreatic histological scoring, pancreatic water content, and myeloperoxidase activity measurements. The behaviour of animals was followed. Pancreatic heat shock protein 72 (HSP72) expression, sulfide, and protein persulfidation were measured. In vitro acinar viability, intracellular Ca 2+ concentration, and reactive oxygen species production were determined. DMTS dose-dependently decreased the severity of AP. It declined the pancreatic infiltration of leukocytes and cellular damage in mice. DMTS upregulated the HSP72 expression during AP and elevated serum sulfide and low molecular weight persulfide levels. DMTS exhibited cytoprotection against hydrogen peroxide and AP-inducing agents. It has antioxidant properties and modulates physiological but not pathophysiological Ca 2+ signalling. Generally, DMTS ameliorated AP severity and protected pancreatic acinar cells. Our findings indicate that DMTS is a sulfur donor with anti-inflammatory and antioxidant effects, and organosulfur compounds require further investigation into this potentially lethal disease. LA - English DB - MTMT ER - TY - JOUR AU - Suzuki, Yuto AU - Taguchi, Kazuaki AU - Okamoto, Wataru AU - Enoki, Yuki AU - Komatsu, Teruyuki AU - Matsumoto, Kazuaki TI - Methemoglobin-albumin clusters for cyanide detoxification JF - TOXICOLOGY AND APPLIED PHARMACOLOGY J2 - TOXICOL APPL PHARM VL - 466 PY - 2023 SN - 0041-008X DO - 10.1016/j.taap.2023.116472 UR - https://m2.mtmt.hu/api/publication/34037024 ID - 34037024 LA - English DB - MTMT ER - TY - JOUR AU - Bátai, István Zoárd AU - Dombi, Ágnes AU - Borbély, Éva AU - Fehér, Ádám AU - Papp, Ferenc AU - Varga, Zoltán AU - Mócsai, Attila AU - Helyes, Zsuzsanna AU - Pintér, Erika AU - Pozsgai, Gábor TI - Investigation of the Role of the TRPA1 Ion Channel in Conveying the Effect of Dimethyl Trisulfide on Vascular and Histological Changes in Serum-Transfer Arthritis. JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 15 PY - 2022 IS - 6 PG - 15 SN - 1424-8247 DO - 10.3390/ph15060671 UR - https://m2.mtmt.hu/api/publication/32907493 ID - 32907493 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFIH), Hungary [OTKA FK 132454, OTKA KKP 129954]; Ministry for Innovation and Technology in Hungary Funding text: This research was funded by the National Research, Development, and Innovation Office (NKFIH), Hungary, under grant numbers OTKA FK 132454 and OTKA KKP 129954. The research also was financed by the Thematic Excellence Program 2020 (Institutional Excellence Subprogram) and Thematic Excellence Program 2021 Health Subprogram of the Ministry for Innovation and Technology in Hungary, within the framework of the second thematic program of the University of Pecs, within the framework of the EGA-16 project of Pecs University. AB - Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases. Its therapy is often challenging, even in the era of biologicals. Previously, we observed the anti-inflammatory effects of garlic-derived organic polysulfide dimethyl trisulfide (DMTS). Some of these effects were mediated by activation of the TRPA1 ion channel. TRPA1 was mostly expressed in a subset of nociceptor neurons. We decided to investigate the action of DMTS in K/BxN serum-transfer arthritis, which is a relevant model of RA. TRPA1 gene knockout (KO) and wild-type (WT) mice were used. The interaction of DMTS and TRPA1 was examined using a patch clamp in CHO cells. Arthritis was characterized by mechanical hyperalgesia, paw swelling, movement range of the ankle joint, hanging performance, plasma extravasation rate, myeloperoxidase activity, and histological changes in the tibiotarsal joint. DMTS activated TRPA1 channels dose-dependently. DMTS treatment reduced paw swelling and plasma extravasation in both TRPA1 WT and KO animals. DMTS-treated TRPA1 KO animals developed milder collagen deposition in the inflamed joints than WT ones. TRPA1 WT mice did not exhibit significant cartilage damage compared to ones administered a vehicle. We concluded that DMTS and related substances might evolve into novel complementary therapeutic aids for RA patients. LA - English DB - MTMT ER - TY - JOUR AU - Hendry-Hofer, T.B. AU - Severance, C.C. AU - Bhadra, S. AU - Ng, P.C. AU - Soules, K. AU - Lippner, D.S. AU - Hildenberger, D.M. AU - Rhoomes, M.O. AU - Winborn, J.N. AU - Logue, B.A. AU - Rockwood, G.A. AU - Bebarta, V.S. TI - Evaluation of aqueous dimethyl trisulfide as an antidote to a highly lethal cyanide poisoning in a large swine model JF - CLINICAL TOXICOLOGY J2 - CLIN TOXICOL VL - 60 PY - 2022 IS - 1 SP - 95 EP - 101 PG - 7 SN - 1556-3650 DO - 10.1080/15563650.2021.1935992 UR - https://m2.mtmt.hu/api/publication/32165914 ID - 32165914 N1 - Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, United States Brooke Army Medical Center, Ft Sam Houston, San Antonio, TX, United States Medical Toxicology Division, Biochemistry and Physiology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, United States Export Date: 31 August 2021 Correspondence Address: Hendry-Hofer, T.B.; Department of Emergency Medicine, 12801 E. 17th Ave, United States AB - Background: Cyanide is a rapid acting, lethal, metabolic poison and remains a significant threat. Current FDA-approved antidotes are not amenable or efficient enough for a mass casualty incident. Objective: The objective of this study is to evaluate short and long-term efficacy of intramuscular aqueous dimethyl trisulfide (DMTS) on survival and clinical outcomes in a swine model of cyanide exposure. Methods: Anesthetized swine were instrumented and acclimated until breathing spontaneously. Potassium cyanide infusion was initiated and continued until 5 min after the onset of apnea. Subsequently, animals were treated with intramuscular DMTS (n = 11) or saline control (n = 10). Laboratory values and DMTS blood concentrations were assessed at various time points and physiological parameters were monitored continuously until the end of the experiment unless death occurred. A subset of animals treated with DMTS (n = 5) were survived for 7 days to evaluate muscle integrity by repeat biopsy and neurobehavioral outcomes. Results: Physiological parameters and time to apnea were similar in both groups at baseline and at time of treatment. Survival in the DMTS-treated group was 90% and 30% in saline controls (p = 0.0034). DMTS-treated animals returned to breathing at 12.0 ± 10.4 min (mean ± SD) compared to 22.9 ± 7.0 min (mean ± SD) in the 3 surviving controls. Blood collected prior to euthanasia showed improved blood lactate concentrations in the DMTS treatment group; 5.47 ± 2.65 mmol/L vs. 9.39 ± 4.51 mmol/L (mean ± SD) in controls (p = 0.0310). Low concentrations of DMTS were detected in the blood, gradually increasing over time with no elimination phase observed. There was no mortality, histological evidence of muscle trauma, or observed adverse neurobehavioral outcomes, in DMTS-treated animals survived to 7 days. Conclusion: Intramuscular administration of aqueous DMTS improves survival following cyanide poisoning with no observed long-term effects on muscle integrity at the injection site or adverse neurobehavioral outcomes. © 2021 Informa UK Limited, trading as Taylor & Francis Group. LA - English DB - MTMT ER - TY - CHAP AU - Achiaa, Atwereboannah A. AU - Wu, W.-P. AU - Nanor, E. TI - Prediction of Drug Permeability to the Blood-Brain Barrier using Deep Learning PB - Association for Computing Machinery (ACM) SN - 9781450387651 PY - 2021 SP - 104 EP - 109 PG - 6 DO - 10.1145/3476779.3476797 UR - https://m2.mtmt.hu/api/publication/32598556 ID - 32598556 N1 - Export Date: 17 January 2022 Correspondence Address: Wu, W.-P.; University of Electronic Science and Technology of ChinaChina; email: wei-ping.wu@uestc.edu.cn AB - In our quest to design new drugs, conventional means of designing drugs characterized by experiments is a time and resource demanding process. It involves exploring many molecular combinations, to find potential drugs to target indications. Machine Learning (ML) techniques upon their fantastic achievement in many application domains such as Computer vision and Natural Language Processing etc., are recently, being utilized in the research of drugs. With the surge in compound databases, ML and Deep Learning (DL) have shown great promise in various fields of drug discovery including pharmaceutics, biotechnology and physical chemistry. It is not incredible that these techniques are being incorporated in BBB studies. Predicting the permeability of drug compounds to the Blood-Brain Barrier (BBB) is indispensable for Central Nervous System (CNS) drug discovery, thus this work leverages two DL models in distinguishing between drugs that are BBB permeable and those that are not. The first architecture is a Fully-Connected Neural Network (FCNN) and the second is based on Convolutional Neural Network (CNN). Both algorithms were evaluated using two distinct CNS drug datasets. Our DL models generalize well, on both datasets and achieve competitive advantage over other ML and in silico techniques used in drug Blood-Brain Barrier Permeability (BBBP) prediction studies. The best performing model was the FCNN achieving AUROC of 99.5% on the first benchmark dataset. © 2021 ACM. LA - English DB - MTMT ER - TY - THES AU - Bhadra, S TI - Advanced analytical techniques for the analysis of therapeutics of toxic inhalation agents and pharmacokinetic investigation PY - 2021 SP - 104 UR - https://m2.mtmt.hu/api/publication/34037019 ID - 34037019 LA - English DB - MTMT ER - TY - JOUR AU - Dombi, Ágnes AU - Sánta, Csenge AU - Bátai, István Zoárd AU - Kormos, Viktória AU - Kecskés, Angéla AU - Tékus, Valéria AU - Pohóczky, Krisztina AU - Bölcskei, Kata AU - Pintér, Erika AU - Pozsgai, Gábor TI - Dimethyl Trisulfide Diminishes Traumatic Neuropathic Pain Acting on TRPA1 Receptors in Mice JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 7 PG - 16 SN - 1661-6596 DO - 10.3390/ijms22073363 UR - https://m2.mtmt.hu/api/publication/31933041 ID - 31933041 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office, Hungary [OTKA FK 132454]; University of Pecs Faculty of Pharmacy [GYTK-KA-2020-01]; New National Excellence Program of the Ministry for Innovation and Technologies from the source of the National Research, Development and Innovation Fund [UNKP-20-4-II-PTE-465]; Hungarian Academy of Sciences; [EFOP-3.6.2-16-2017-00006]; [GINOP-2.3.2.-15-2016-00050]; [KTIA_NAP-20017-1-2.1.-NKP-2017-00002 20765-3/2018/FEKUTSTRAT] Funding text: OTKA FK 132454 from the National Research, Development and Innovation Office, Hungary; EFOP-3.6.2-16-2017-00006, GINOP-2.3.2.-15-2016-00050, KTIA_NAP-20017-1-2.1.-NKP-2017-00002 20765-3/2018/FEKUTSTRAT. K.P. was supported by GYTK-KA-2020-01, University of Pecs Faculty of Pharmacy and the New National Excellence Program of the Ministry for Innovation and Technologies from the source of the National Research, Development and Innovation Fund UNKP-20-4-II-PTE-465. A.K. was sponsored by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. AB - Pharmacotherapy of neuropathic pain is still challenging. Our earlier work indicated an analgesic effect of dimethyl trisulfide (DMTS), which was mediated by somatostatin released from nociceptor nerve endings acting on SST4 receptors. Somatostatin release occurred due to TRPA1 ion channel activation. In the present study, we investigated the effect of DMTS in neuropathic pain evoked by partial ligation of the sciatic nerve in mice. Expression of the mRNA of Trpa1 in murine dorsal-root-ganglion neurons was detected by RNAscope. Involvement of TRPA1 ion channels and SST4 receptors was tested with gene-deleted animals. Macrophage activity at the site of the nerve lesion was determined by lucigenin bioluminescence. Density and activation of microglia in the spinal cord dorsal horn was verified by immunohistochemistry and image analysis. Trpa1 mRNA is expressed in peptidergic and non-peptidergic neurons in the dorsal root ganglion. DMTS ameliorated neuropathic pain in Trpa1 and Sstr4 WT mice, but not in KO ones. DMTS had no effect on macrophage activity around the damaged nerve. Microglial density in the dorsal horn was reduced by DMTS independently from TRPA1. No effect on microglial activation was detected. DMTS might offer a novel therapeutic opportunity in the complementary treatment of neuropathic pain. LA - English DB - MTMT ER - TY - JOUR AU - Aruwa, Christiana Eleojo AU - Mukaila, Yusuf Ola AU - Ajao, Abdulwakeel Ayokun-Nun AU - Sabiu, Saheed TI - An Appraisal of Antidotes' Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements JF - MOLECULES J2 - MOLECULES VL - 25 PY - 2020 IS - 7 PG - 27 SN - 1420-3049 DO - 10.3390/molecules25071516 UR - https://m2.mtmt.hu/api/publication/31493742 ID - 31493742 N1 - Department of Biotechnology and Food Technology, Durban University of Technology, P.O. Box 1334, Durban, 4000, South Africa Department of Botany, Obafemi Awolowo University, Ile-Ife, 220005, Nigeria Department of Botany and Plant Biotechnology, University of Johannesburg, P.O. Box 524, Auckland Park APK, 2006, South Africa Export Date: 15 February 2021 CODEN: MOLEF Correspondence Address: Sabiu, S.; Department of Biotechnology and Food Technology, P.O. Box 1334, South Africa; email: sabius@dut.ac.za AB - Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette's cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes' effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist in vitro and in vivo with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote's short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities' approval. LA - English DB - MTMT ER - TY - THES AU - Bátai, István Zoárd TI - A HIDROGÉN-SZULFID ÉS POLISZULFID VEGYÜLETEK TRPA1 MEDIÁLTA HATÁSAI AKUT ÉS KRÓNIKUS GYULLADÁS ÁLLATMODELLJEIBEN PY - 2020 UR - https://m2.mtmt.hu/api/publication/31661870 ID - 31661870 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Chung, Yu-Han AU - Lin, Chia-Wei AU - Huang, Hsin-Yu AU - Chen, Shu-Ling AU - Huang, Hei-Jen AU - Sun, Ying-Chieh AU - Lee, Guan-Chiun AU - Lee-Chen, Guey-Jen AU - Chang, Ya-Ching AU - Hsieh-Li, Hsiu Mei TI - Targeting Inflammation, PHA-767491 Shows a Broad Spectrum in Protein Aggregation Diseases JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 70 PY - 2020 IS - 7 SP - 1140 EP - 1152 PG - 13 SN - 0895-8696 DO - 10.1007/s12031-020-01521-y UR - https://m2.mtmt.hu/api/publication/31493743 ID - 31493743 N1 - Department of Life Science, National Taiwan Normal University, Taipei, Taiwan Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan Department of Pharmacy, Taiwan Adventist Hospital, Taipei, Taiwan Cited By :2 Export Date: 15 February 2021 CODEN: JMNEE Correspondence Address: Hsieh-Li, H.M.; Department of Life Science, Taiwan; email: hmhsieh@ntnu.edu.tw Correspondence Address: Chang, Y.-C.; Department of Pharmacy, Taiwan; email: 147943@tahsda.org.tw AB - Many protein aggregation diseases (PAD) affect the nervous system. Deposits of aggregated disease-specific proteins are found within or around the neuronal cells of neurodegenerative diseases. Although the main protein component is disease-specific, oligomeric aggregates are presumed to be the key agents causing the neurotoxicity. Evidence has shown that protein aggregates cause a chronic inflammatory reaction in the brain, resulting in neurodegeneration. Therefore, strategies targeting anti-inflammation could be beneficial to the therapeutics of PAD. PHA-767491 was originally identified as an inhibitor of CDC7/CDK9 and was found to reduce TDP-43 phosphorylation and prevent neurodegeneration in TDP-43 transgenic animals. We recently identified PHA-767491 as a GSK-3 beta inhibitor. In this study, we established mouse hippocampal primary culture with tau-hyperphosphorylation through the activation of GSK-3 beta using Wortmannin and GF109203X. We found that PHA-767491 significantly improved the neurite outgrowth of hippocampal primary neurons against the neurotoxicity induced by GSK-3 beta. We further showed that PHA-767491 had neuroprotective ability in hippocampal primary culture under oligomeric A beta treatment. In addition, PHA-767491 attenuated the neuroinflammation in mouse cerebellar slice culture with human TBP-109Q agitation. Further study of SCA17 transgenic mice carrying human TBP-109Q showed that PHA-767491 ameliorated the gait ataxia and the inflammatory response both centrally and peripherally. Our findings suggest that PHA-767491 has a broad spectrum of activity in the treatment of different PAD and that this activity could be based on the anti-inflammation mechanism. LA - English DB - MTMT ER - TY - JOUR AU - Warnakula, I.K. AU - Ebrahimpour, A. AU - Li, S.Y. AU - Gaspe, Ralalage R.D. AU - Hewa-Rahinduwage, C.C. AU - Kiss, M. AU - Rios, C.T. AU - Kelley, K.D. AU - Whiteman, A.C. AU - Thompson, D.E. AU - Rockwood, G.A. AU - Petrikovics, I. TI - Evaluation of the long-term storage stability of the cyanide antidote: Dimethyl trisulfide and degradation product identification JF - ACS OMEGA J2 - ACS OMEGA VL - 5 PY - 2020 IS - 42 SP - 27171 EP - 27179 PG - 9 SN - 2470-1343 DO - 10.1021/acsomega.0c03208 UR - https://m2.mtmt.hu/api/publication/31873888 ID - 31873888 N1 - Department of Chemistry, Sam Houston State University, Huntsville, TX 77341, United States Department of Forensic Science, Sam Houston State University, Huntsville, TX 77341, United States Analytical Toxicology Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, United States Cited By :1 Export Date: 15 February 2021 Correspondence Address: Petrikovics, I.; Department of Chemistry, United States; email: ixp004@shsu.edu Department of Chemistry, Sam Houston State University, Huntsville, TX 77341, United States Department of Forensic Science, Sam Houston State University, Huntsville, TX 77341, United States Analytical Toxicology Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, United States Cited By :3 Export Date: 14 August 2021 Correspondence Address: Petrikovics, I.; Department of Chemistry, United States; email: ixp004@shsu.edu AB - This study reports the long-term storage stability of a formulation of the cyanide (CN) antidote dimethyl trisulfide (DMTS). The F3-formulated DMTS was stored in glass ampules at 4, 22, and 37 °C. Over a period of one year, nine ampules (n = 3 at each temperature) were analyzed by high-performance liquid chromatography (HPLC)−UV/vis at daily time intervals in the first week, weekly time intervals in the first month, and monthly thereafter for a period of one year to determine the DMTS content. No measurable loss of DMTS was found at 4 and 22 °C, and good stability was noted up to five months for samples stored at 37 °C. At 37 °C, a 10% (M/M) decrease of DMTS was discovered at the sixth month and only 30% (M/M) of DMTS remained by the end of the study; discoloration of the formulation and the growth of new peaks in the HPLC chromatogram were also observed. To identify the unknown peaks at 37 °C, controlled oxidation studies were performed on DMTS using two strong oxidizing agents: meta-chloroperoxybenzoic acid (mCPBA) and hydrogen peroxide (H2O2). Dimethyl tetrasulfide and dimethyl pentasulfide were observed as products using both of the oxidizing agents. Dimethyl disulfide was also observed as a product of degradation, which was further oxidized to S-methyl methanethiosulfonate only when mCPBA was used. HPLC−UV/vis and gas chromatography−mass spectrometry/solid phase microextraction analysis revealed good agreement between the degradation products of the stability study at 37 °C and those of disproportionation reactions. Furthermore, at 4 and 22 °C, chromatograms were remarkably stable over the one-year study period, indicating that the F3-formulated DMTS shows excellent long-term storage stability at T ≤ 22 °C. © 2020 American Chemical Society LA - English DB - MTMT ER - TY - JOUR AU - Bhadra, Subrata AU - Zhang, Zhiling AU - Zhou, Wenhui AU - Ochieng, Fredrick AU - Rockwood, Gary A. AU - Lippner, Dennean AU - Logue, Brian A. TI - Analysis of potential cyanide antidote, dimethyl trisulfide, in whole blood by dynamic headspace gas chromatography-mass spectroscopy JF - JOURNAL OF CHROMATOGRAPHY A J2 - J CHROMATOGR A VL - 1591 PY - 2019 SP - 71 EP - 78 PG - 8 SN - 0021-9673 DO - 10.1016/j.chroma.2019.01.058 UR - https://m2.mtmt.hu/api/publication/30914375 ID - 30914375 N1 - Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007, United States Analytical Toxicology Division, United States Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving GroundMD 21010, United States Cited By :3 Export Date: 15 February 2021 CODEN: JCRAE Correspondence Address: Logue, B.A.; Department of Chemistry and Biochemistry, United States; email: brian.logue@sdstate.edu AB - Cyanide is a rapidly acting and highly toxic chemical. It inhibits cytochrome c oxidase in the mitochondrial electron transport chain, resulting in cellular hypoxia, cytotoxic anoxia and potentially death. In order to overcome challenges associated with current cyanide antidotes, dimethyl trisulfide (DMTS), which converts cyanide to less toxic thiocyanate in vivo, has gained much attention recently as a promising next-generation cyanide antidote. While there are three analysis methods available for DMTS, they each have significant disadvantages. Hence, in this study, a dynamic headspace (DHS) gas chromatography-mass spectroscopy method was developed for the analysis of DMTS from rabbit whole blood. The method is extremely simple, involving only acidification of a blood sample, addition of an internal standard (DMTS-d(6)) and DHS-GC-MS analysis. The method produced a limit of detection of 0.04 mu M for DMTS with dynamic range from 0.2 to 50 mu M. Inter- and intraassay accuracy (100 +/- 15% and 100 +/- 9%, respectively), and precision (<10% and <9% relative standard deviation, respectively) were good. The validated method performed well during pharmacokinetic analysis of DMTS from the blood of rats treated with DMTS, producing excellent pharmacokinetic parameters for the treatment of cyanide exposure. The method produced significant advantages over current methods for analysis of DMTS and should be considered as a "gold standard" method for further development of DMTS as a potential next-generation cyanide countermeasure. (C) 2019 Elsevier B.V. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Hendry-Hofer, Tara B. AU - Witeof, Alyssa E. AU - Lippner, Dennean S. AU - Ng, Patrick C. AU - Mahon, Sari B. AU - Brenner, Matthew AU - Rockwood, Gary A. AU - Bebarta, Vikhyat S. TI - Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity JF - CLINICAL TOXICOLOGY J2 - CLIN TOXICOL VL - 57 PY - 2019 IS - 4 SP - 265 EP - 270 PG - 6 SN - 1556-3650 DO - 10.1080/15563650.2018.1511800 UR - https://m2.mtmt.hu/api/publication/30914374 ID - 30914374 N1 - Department of Emergency Medicine and Toxicology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Medical Toxicology Division, Biochemistry and Physiology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, M.D, United States Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, United States Beckman Laser Institute, University of California, Irvine, CA, United States Colonel, USAF Reserve, Office of the Chief Scientist, San Antonio, TX, United States Cited By :2 Export Date: 15 February 2021 Correspondence Address: Hendry-Hofer, T.B.; University of Colorado, Campus Box B-215, 12401 E. 17th Avenue, United States; email: Tara.Hendry-Hofer@ucdenver.edu Department of Emergency Medicine and Toxicology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States Medical Toxicology Division, Biochemistry and Physiology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, M.D, United States Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, United States Beckman Laser Institute, University of California, Irvine, CA, United States Colonel, USAF Reserve, Office of the Chief Scientist, San Antonio, TX, United States Cited By :4 Export Date: 14 August 2021 Correspondence Address: Hendry-Hofer, T.B.; University of Colorado, Campus Box B-215, 12401 E. 17th Avenue, United States; email: Tara.Hendry-Hofer@ucdenver.edu AB - Background: Cyanide is a deadly compound used as a terrorist agent. Current FDA approved antidotes require intravenous administration, limiting their utility in a mass casualty scenario. Dimethyl trisulfide (DMTS), a sulfur-based molecule, binds cyanide converting it to the less toxic by-product thiocyanate. Studies evaluating efficacy in rodents have been performed, but a large, clinically relevant animal model has not been reported. Objective: This study evaluates the efficacy of intramuscular DMTS on survival and clinical outcomes in a swine model of acute, severe cyanide toxicity. Methods: Anesthetized swine were instrumented for continuous monitoring of hemodynamics. Prior to potassium cyanide infusion animals were acclimated and breathing spontaneously. At 5-minutes post-apnea animals were treated with DMTS or saline. Vital signs, hemodynamics, and laboratory values were evaluated at various time points. Results: Baseline values and time to apnea were similar in both groups. Survival in the DMTS treated group was 83.3% and 0% in saline controls (p = .005). The DMTS group returned to breathing at a mean time of 19.3 +/- 10 min after antidote, control animals did not return to breathing (CI difference 8.8, 29.8). At the end of the experiment or time of death, mean lactate was 9.41 mmol/L vs. 4.35 mmol/L (CI difference -10.94,0.82) in the saline and DMTS groups, respectively and pH was 7.20 vs. 7.37 (CI difference -0.04, 0.38). No adverse effects were observed at the injection site. Conclusion: Intramuscular administration of DMTS improves survival and clinical outcomes in our large animal swine model of acute cyanide toxicity. LA - English DB - MTMT ER - TY - JOUR AU - Petrikovics, Ilona AU - Kiss, Lóránd AU - Chou, Ching-En AU - Ebrahimpour, Afshin AU - Kovacs, Kristof AU - Kiss, Marton AU - Logue, Brian AU - Chan, Adriano AU - Manage, Ananda B. W. AU - Budai, Marianna AU - Boss, Gerry R. AU - Rockwood, Gary A. TI - Antidotal efficacies of the cyanide antidote candidate dimethyl trisulfide alone and in combination with cobinamide derivatives JF - TOXICOLOGY MECHANISMS AND METHODS J2 - TOXICOL MECH METHOD VL - 29 PY - 2019 IS - 6 SP - 438 EP - 444 PG - 7 SN - 1537-6516 DO - 10.1080/15376516.2019.1585504 UR - https://m2.mtmt.hu/api/publication/30913189 ID - 30913189 N1 - Department of Chemistry, Sam Houston State University, Huntsville, TX, United States Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, United States Department of Medicine, University of California, San Diego, CA, United States Department of Mathematics and Statistics, Sam Houston State University, Huntsville, TX, United States US Army Medical Research Institute of Chemical Defense, APG, MD, United States Cited By :1 Export Date: 15 February 2021 CODEN: TMMOC Correspondence Address: Petrikovics, I.; Department of Chemistry, 1003 Bowers Blvd, United States; email: ixp004@shsu.edu AB - Formulation optimization and antidotal combination therapy are the two important tools to enhance the antidotal protection of the cyanide (CN) antidote dimethyl trisulfide (DMTS). The focus of this study is to demonstrate how the formulation with polysorbate 80 (Poly80), an excipient used in pharmaceutical technology, and the combinations with other CN antidotes having different mechanisms of action enhance the antidotal efficacy of the unformulated (neat) DMTS. The LD50 for CN was determined by the statistical Dixon up-and-down method on mice. Antidotal efficacy was expressed as antidotal potency ratio (APR). CN was injected subcutaneously one minute prior to the antidotes' injection intramuscularly. The APR values of 1.17 (dose: 25 mg/kg bodyweight) and 1.45 (dose: 50 mg/kg bodyweight) of the neat DMTS were significantly enhanced by the Poly80 formulation at both investigated doses to 2.03 and 2.33, respectively. The combination partners for the Poly80 formulated DMTS (DMTS-Poly80; 25 and 50 mg/kg bodyweight) were 4-nitrocobinamide (4NCbi) (20 mg/kg bodyweight) and aquohydroxocobinamide (AHCbi; 50, 100, and 250 mg/kg bodyweight). When DMTS-Poly80 (25 and 50 mg/kg bodyweight; APR = 2.03 and 2.33, respectively) was combined with 4NCbi (20 mg/kg bodyweight; APR = 1.35), significant increase in the APR values were noted at both DMTS doses (APR = 2.38 and 3.12, respectively). AHCbi enhanced the APR of DMTS-Poly80 (100 mg/kg bodyweight; APR = 3.29) significantly only at the dose of 250 mg/kg bodyweight (APR = 5.86). These studies provided evidence for the importance of the formulation with Poly80 and the combinations with cobinamide derivatives with different mechanisms of action for DMTS as a CN antidote candidate. LA - English DB - MTMT ER - TY - JOUR AU - Bátai, István Zoárd AU - Horváth, Ádám István AU - Pintér, Erika AU - Helyes, Zsuzsanna AU - Pozsgai, Gábor TI - Role of transient receptor potential ankyrin 1 ion channel and somatostatin sst4 receptor in the antinociceptive and anti-inflammatory effects of sodium polysulfide and dimethyl trisulfide JF - FRONTIERS IN ENDOCRINOLOGY J2 - FRONT ENDOCRINOL VL - 9 PY - 2018 PG - 12 SN - 1664-2392 DO - 10.3389/fendo.2018.00055 UR - https://m2.mtmt.hu/api/publication/3347234 ID - 3347234 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIH, Hungary [OTKA PD 112171, OTKA NN 114458]; European Regional Development Fund [GINOP-2.3.2-15-2016-00048 STAY ALIVE, EFOP-3.6.2-16-2017-00006 LIVE LONGER]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences Funding text: This study was funded by the following grants of the National Research, Development and Innovation Office-NKFIH, Hungary: OTKA PD 112171, OTKA NN 114458. This work was funded by the grants GINOP-2.3.2-15-2016-00048 STAY ALIVE and EFOP-3.6.2-16-2017-00006 LIVE LONGER from the European Regional Development Fund. This project was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (GP). LA - English DB - MTMT ER - TY - JOUR AU - Kiss, M. AU - Petrikovics, I. AU - Thompson, D.E. TI - Methemoglobin Forming Effect of Dimethyl Trisulfide in Mice JF - HEMOGLOBIN J2 - HEMOGLOBIN VL - 42 PY - 2018 IS - 5-6 SP - 315 EP - 319 PG - 5 SN - 0363-0269 DO - 10.1080/03630269.2018.1553182 UR - https://m2.mtmt.hu/api/publication/30648162 ID - 30648162 N1 - Export Date: 27 April 2019 CODEN: HEMOD Export Date: 8 May 2019 CODEN: HEMOD Correspondence Address: Thompson, D.E.; Associate Professor of Chemistry, Sam Houston State University, P.O. Box: 2117, United States; email: david.thompson@shsu.edu Export Date: 11 December 2020 CODEN: HEMOD Correspondence Address: Thompson, D.E.; Associate Professor of Chemistry, Sam Houston State University, P.O. Box: 2117, United States; email: david.thompson@shsu.edu Export Date: 15 February 2021 CODEN: HEMOD Correspondence Address: Thompson, D.E.; Associate Professor of Chemistry, P.O. Box: 2117, United States; email: david.thompson@shsu.edu Cited By :1 Export Date: 14 August 2021 CODEN: HEMOD Correspondence Address: Thompson, D.E.; Associate Professor of Chemistry, P.O. Box: 2117, United States; email: david.thompson@shsu.edu LA - English DB - MTMT ER - TY - JOUR AU - Sato, K. TI - Consideration for future in vitro bbb models — technical development to investigate the drug delivery to the CNS JF - FOLIA PHARMACOLOGICA JAPONICA J2 - FOLIA PHARMACOL JPN VL - 152 PY - 2018 IS - 6 SP - 287 EP - 294 PG - 8 SN - 0015-5691 DO - 10.1254/fpj.152.287 UR - https://m2.mtmt.hu/api/publication/30750988 ID - 30750988 LA - Japanese DB - MTMT ER -