@article{MTMT:34183455, title = {The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis}, url = {https://m2.mtmt.hu/api/publication/34183455}, author = {Orján, Erik Márk and Kormányos, Eszter Sára and Fűr, Gabriella and Dombi, Ágnes and Bálint, Emese Réka and Balla, Zsolt and Balog, Beáta Adél and Dágó, Ágnes and Totonji, Ahmad and Bátai, István Zoárd and Jurányi, Eszter Petra and Ditrói, Tamás and Al-omari, Ammar and Pozsgai, Gábor and Kormos, Viktória and Nagy, Péter and Pintér, Erika and Rakonczay, Zoltán and Kiss, Lóránd}, doi = {10.1038/s41598-023-43692-9}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34183455}, issn = {2045-2322}, abstract = {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.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Orján, Erik Márk/0000-0003-4176-0834; Balog, Beáta Adél/0009-0008-3568-4090; Jurányi, Eszter Petra/0000-0002-0563-4876; Nagy, Péter/0000-0003-3393-235X; Pintér, Erika/0000-0001-9898-632X; Rakonczay, Zoltán/0000-0002-1499-3416} } @article{MTMT:34037024, title = {Methemoglobin-albumin clusters for cyanide detoxification}, url = {https://m2.mtmt.hu/api/publication/34037024}, author = {Suzuki, Yuto and Taguchi, Kazuaki and Okamoto, Wataru and Enoki, Yuki and Komatsu, Teruyuki and Matsumoto, Kazuaki}, doi = {10.1016/j.taap.2023.116472}, journal-iso = {TOXICOL APPL PHARM}, journal = {TOXICOLOGY AND APPLIED PHARMACOLOGY}, volume = {466}, unique-id = {34037024}, issn = {0041-008X}, year = {2023}, eissn = {1096-0333} } @article{MTMT:32907493, title = {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.}, url = {https://m2.mtmt.hu/api/publication/32907493}, author = {Bátai, István Zoárd and Dombi, Ágnes and Borbély, Éva and Fehér, Ádám and Papp, Ferenc and Varga, Zoltán and Mócsai, Attila and Helyes, Zsuzsanna and Pintér, Erika and Pozsgai, Gábor}, doi = {10.3390/ph15060671}, journal-iso = {PHARMACEUTICALS-BASE}, journal = {PHARMACEUTICALS}, volume = {15}, unique-id = {32907493}, abstract = {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.}, keywords = {PLASMA EXTRAVASATION; patch clamp; dimethyl trisulfide; fibroblast-like synoviocyte; K/BxN serum-transfer arthritis; TRPA1 ion channel; cartilage destruction}, year = {2022}, eissn = {1424-8247}, orcid-numbers = {Borbély, Éva/0000-0002-1234-4391; Fehér, Ádám/0000-0002-3638-5067; Mócsai, Attila/0000-0002-0512-1157; Pintér, Erika/0000-0001-9898-632X} } @article{MTMT:32165914, title = {Evaluation of aqueous dimethyl trisulfide as an antidote to a highly lethal cyanide poisoning in a large swine model}, url = {https://m2.mtmt.hu/api/publication/32165914}, author = {Hendry-Hofer, T.B. and Severance, C.C. and Bhadra, S. and Ng, P.C. and Soules, K. and Lippner, D.S. and Hildenberger, D.M. and Rhoomes, M.O. and Winborn, J.N. and Logue, B.A. and Rockwood, G.A. and Bebarta, V.S.}, doi = {10.1080/15563650.2021.1935992}, journal-iso = {CLIN TOXICOL}, journal = {CLINICAL TOXICOLOGY}, volume = {60}, unique-id = {32165914}, issn = {1556-3650}, abstract = {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.}, keywords = {SWINE; CYANIDE; antidote; dimethyl trisulfide}, year = {2022}, eissn = {1556-9519}, pages = {95-101} } @inproceedings{MTMT:32598556, title = {Prediction of Drug Permeability to the Blood-Brain Barrier using Deep Learning}, url = {https://m2.mtmt.hu/api/publication/32598556}, author = {Achiaa, Atwereboannah A. and Wu, W.-P. and Nanor, E.}, doi = {10.1145/3476779.3476797}, unique-id = {32598556}, abstract = {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.}, keywords = {Brain; BLOOD; COMPETITION; neurophysiology; Central Nervous System; Forecasting; Blood-Brain Barrier; machine learning; physical chemistry; DRUG DISCOVERY; DRUG DISCOVERY; Learning algorithms; Machine-learning; Natural language processing systems; blood-brain barrier permeability; blood-brain barrier permeability; Convolutional neural networks; Central nervous systems; Learning models; Deep learning; Deep learning; Deep learning; Potential drug; Drug permeabilities; Fully connected neural network}, year = {2021}, pages = {104-109} } @mastersthesis{MTMT:34037019, title = {Advanced analytical techniques for the analysis of therapeutics of toxic inhalation agents and pharmacokinetic investigation}, url = {https://m2.mtmt.hu/api/publication/34037019}, author = {Bhadra, S}, unique-id = {34037019}, year = {2021} } @article{MTMT:31933041, title = {Dimethyl Trisulfide Diminishes Traumatic Neuropathic Pain Acting on TRPA1 Receptors in Mice}, url = {https://m2.mtmt.hu/api/publication/31933041}, author = {Dombi, Ágnes and Sánta, Csenge and Bátai, István Zoárd and Kormos, Viktória and Kecskés, Angéla and Tékus, Valéria and Pohóczky, Krisztina and Bölcskei, Kata and Pintér, Erika and Pozsgai, Gábor}, doi = {10.3390/ijms22073363}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {31933041}, issn = {1661-6596}, abstract = {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.}, keywords = {SOMATOSTATIN; Neuropathic pain; microglia; TRPA1; sciatic nerve; dimethyl trisulfide; RNAscope; SST4; partial ligation}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Pohóczky, Krisztina/0000-0003-0385-5162; Pintér, Erika/0000-0001-9898-632X} } @article{MTMT:31493742, title = {An Appraisal of Antidotes' Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements}, url = {https://m2.mtmt.hu/api/publication/31493742}, author = {Aruwa, Christiana Eleojo and Mukaila, Yusuf Ola and Ajao, Abdulwakeel Ayokun-Nun and Sabiu, Saheed}, doi = {10.3390/molecules25071516}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {25}, unique-id = {31493742}, issn = {1420-3049}, abstract = {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.}, keywords = {Antidotes; SECONDARY METABOLITES; SNAKEBITES; phyto-antidotes; poisons; snake envenomation}, year = {2020}, eissn = {1420-3049}, orcid-numbers = {Aruwa, Christiana Eleojo/0000-0003-4979-8968; Sabiu, Saheed/0000-0001-7209-9220} } @mastersthesis{MTMT:31661870, title = {A HIDROGÉN-SZULFID ÉS POLISZULFID VEGYÜLETEK TRPA1 MEDIÁLTA HATÁSAI AKUT ÉS KRÓNIKUS GYULLADÁS ÁLLATMODELLJEIBEN}, url = {https://m2.mtmt.hu/api/publication/31661870}, author = {Bátai, István Zoárd}, unique-id = {31661870}, year = {2020} } @article{MTMT:31493743, title = {Targeting Inflammation, PHA-767491 Shows a Broad Spectrum in Protein Aggregation Diseases}, url = {https://m2.mtmt.hu/api/publication/31493743}, author = {Chung, Yu-Han and Lin, Chia-Wei and Huang, Hsin-Yu and Chen, Shu-Ling and Huang, Hei-Jen and Sun, Ying-Chieh and Lee, Guan-Chiun and Lee-Chen, Guey-Jen and Chang, Ya-Ching and Hsieh-Li, Hsiu Mei}, doi = {10.1007/s12031-020-01521-y}, journal-iso = {J MOL NEUROSCI}, journal = {JOURNAL OF MOLECULAR NEUROSCIENCE}, volume = {70}, unique-id = {31493743}, issn = {0895-8696}, abstract = {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.}, keywords = {Inflammation; PHA-767491; GSK-3 beta inhibitor; Protein aggregation diseases}, year = {2020}, eissn = {1559-1166}, pages = {1140-1152} } @article{MTMT:31873888, title = {Evaluation of the long-term storage stability of the cyanide antidote: Dimethyl trisulfide and degradation product identification}, url = {https://m2.mtmt.hu/api/publication/31873888}, author = {Warnakula, I.K. and Ebrahimpour, A. and Li, S.Y. and Gaspe, Ralalage R.D. and Hewa-Rahinduwage, C.C. and Kiss, M. and Rios, C.T. and Kelley, K.D. and Whiteman, A.C. and Thompson, D.E. and Rockwood, G.A. and Petrikovics, I.}, doi = {10.1021/acsomega.0c03208}, journal-iso = {ACS OMEGA}, journal = {ACS OMEGA}, volume = {5}, unique-id = {31873888}, issn = {2470-1343}, abstract = {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}, year = {2020}, eissn = {2470-1343}, pages = {27171-27179} } @article{MTMT:30914375, title = {Analysis of potential cyanide antidote, dimethyl trisulfide, in whole blood by dynamic headspace gas chromatography-mass spectroscopy}, url = {https://m2.mtmt.hu/api/publication/30914375}, author = {Bhadra, Subrata and Zhang, Zhiling and Zhou, Wenhui and Ochieng, Fredrick and Rockwood, Gary A. and Lippner, Dennean and Logue, Brian A.}, doi = {10.1016/j.chroma.2019.01.058}, journal-iso = {J CHROMATOGR A}, journal = {JOURNAL OF CHROMATOGRAPHY A}, volume = {1591}, unique-id = {30914375}, issn = {0021-9673}, abstract = {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.}, keywords = {Method validation; dimethyl trisulfide; Dynamic headspace; Cyanide countermeasure}, year = {2019}, eissn = {1873-3778}, pages = {71-78} } @article{MTMT:30914374, title = {Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity}, url = {https://m2.mtmt.hu/api/publication/30914374}, author = {Hendry-Hofer, Tara B. and Witeof, Alyssa E. and Lippner, Dennean S. and Ng, Patrick C. and Mahon, Sari B. and Brenner, Matthew and Rockwood, Gary A. and Bebarta, Vikhyat S.}, doi = {10.1080/15563650.2018.1511800}, journal-iso = {CLIN TOXICOL}, journal = {CLINICAL TOXICOLOGY}, volume = {57}, unique-id = {30914374}, issn = {1556-3650}, abstract = {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.}, keywords = {SWINE; terrorism; Intramuscular; dimethyl trisulfide; KCN; DMTS; Cyanide poisoning}, year = {2019}, eissn = {1556-9519}, pages = {265-270} } @article{MTMT:30913189, title = {Antidotal efficacies of the cyanide antidote candidate dimethyl trisulfide alone and in combination with cobinamide derivatives}, url = {https://m2.mtmt.hu/api/publication/30913189}, author = {Petrikovics, Ilona and Kiss, Lóránd and Chou, Ching-En and Ebrahimpour, Afshin and Kovacs, Kristof and Kiss, Marton and Logue, Brian and Chan, Adriano and Manage, Ananda B. W. and Budai, Marianna and Boss, Gerry R. and Rockwood, Gary A.}, doi = {10.1080/15376516.2019.1585504}, journal-iso = {TOXICOL MECH METHOD}, journal = {TOXICOLOGY MECHANISMS AND METHODS}, volume = {29}, unique-id = {30913189}, issn = {1537-6516}, abstract = {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.}, keywords = {combination therapy; dimethyl trisulfide; intramuscular antidote injection; subcutaneous cyanide exposure; cobinamide}, year = {2019}, eissn = {1537-6524}, pages = {438-444}, orcid-numbers = {Kiss, Marton/0000-0001-7010-6511} } @article{MTMT:3347234, title = {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}, url = {https://m2.mtmt.hu/api/publication/3347234}, author = {Bátai, István Zoárd and Horváth, Ádám István and Pintér, Erika and Helyes, Zsuzsanna and Pozsgai, Gábor}, doi = {10.3389/fendo.2018.00055}, journal-iso = {FRONT ENDOCRINOL}, journal = {FRONTIERS IN ENDOCRINOLOGY}, volume = {9}, unique-id = {3347234}, issn = {1664-2392}, year = {2018}, eissn = {1664-2392}, orcid-numbers = {Pintér, Erika/0000-0001-9898-632X} } @article{MTMT:30648162, title = {Methemoglobin Forming Effect of Dimethyl Trisulfide in Mice}, url = {https://m2.mtmt.hu/api/publication/30648162}, author = {Kiss, M. and Petrikovics, I. and Thompson, D.E.}, doi = {10.1080/03630269.2018.1553182}, journal-iso = {HEMOGLOBIN}, journal = {HEMOGLOBIN}, volume = {42}, unique-id = {30648162}, issn = {0363-0269}, year = {2018}, eissn = {1532-432X}, pages = {315-319} } @article{MTMT:30750988, title = {Consideration for future in vitro bbb models — technical development to investigate the drug delivery to the CNS}, url = {https://m2.mtmt.hu/api/publication/30750988}, author = {Sato, K.}, doi = {10.1254/fpj.152.287}, journal-iso = {FOLIA PHARMACOL JPN}, journal = {FOLIA PHARMACOLOGICA JAPONICA}, volume = {152}, unique-id = {30750988}, issn = {0015-5691}, keywords = {Brain; Brain; Animals; Humans; SWINE; CATTLE; ARTICLE; BOVINE; human; animal; Cell Differentiation; PIG; Central Nervous System; Homeostasis; Blood-Brain Barrier; drug delivery system; drug delivery system; Drug Delivery Systems; blood vessel; blood brain barrier; brain development; induced pluripotent stem cell; Induced pluripotent stem cells; central nervous system agents; central nervous system agents}, year = {2018}, eissn = {1347-8397}, pages = {287-294} }