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Polymers Nov 2021In the context of imminent threats concerning biological and chemical warfare agents, the aim of this study was the development of a new method for biological and...
In the context of imminent threats concerning biological and chemical warfare agents, the aim of this study was the development of a new method for biological and chemical decontamination, employing non-toxic, film-forming, water-based biodegradable solutions, using a nano sized reagent together with bentonite as trapping agents for the biological and chemical contaminants. Bentonite-supported nanoparticles of Cu, TiO, and Ag were successfully synthesized and dispersed in a polyvinyl alcohol ()/glycerol () aqueous solution. The decontamination effectiveness of the proposed solutions was evaluated by qualitative and quantitative analytical techniques on various micro-organisms, with sulfur mustard () and dimethyl methylphosphonate () as contaminants. The results indicate that the peelable active nanocomposite films can be successfully used on contaminated surfaces to neutralize and entrap the hazardous materials and their degradation products. Mechanical and thermal characterization of the polymeric films was also performed to validate the decontamination solution's potential as peelable-film generating materials. The removal efficacy from the contaminated surfaces for the tested micro-organisms varied between 93% and 97%, while for the chemical agent , the highest decontamination factor obtained was 90.89%. was almost completely removed from the contaminated surfaces, and a decontamination factor of 99.97% was obtained.
PubMed: 34833298
DOI: 10.3390/polym13223999 -
Journal of Chromatography. B,... Dec 2021Sulfur mustard reacts with blood proteins, such as hemoglobin, to form stable adducts that can be used as long-lived biomarkers of exposure. These adducts can be...
Development of an immobilized-trypsin reactor coupled to liquid chromatography and tandem mass spectrometry for the analysis of human hemoglobin adducts with sulfur mustard.
Sulfur mustard reacts with blood proteins, such as hemoglobin, to form stable adducts that can be used as long-lived biomarkers of exposure. These adducts can be analyzed by liquid chromatography coupled to tandem mass-spectrometry (LC-MS/MS) after an enzymatic digestion step. The objective of this study was to develop trypsin-based immobilized enzyme reactors (IMERs) in order to obtain a faster digestion of hemoglobin than the conventional in-solution digestion. Trypsin IMERs were synthetized by grafting the enzyme on a CNBr-Sepharose gel and the influence of several parameters on the digestion yields, such as the transfer volume between the injection loop and the IMER, the temperature and the digestion time was studied. The repeatability of the digestion on three laboratory-made IMERs was demonstrated for pure hemoglobin and hemoglobin previously exposed to different concentrations of sulfur mustard (RSD inferior to 13% and 21% respectively) and was better than that obtained for in-solution digestions (RSD inferior to 28% and up to 53% respectively). A preferential adduction of sulfur mustard on the histidine residues of hemoglobin was confirmed, for both in-solution and IMER digestion results. On a quantitative point of view, the performances of in-solution and IMER digestions were similar, with the theoretical possibility to detect peptides resulting from the in vitro incubation of hemoglobin in pure water with sulfur mustard at 7.5 ng⋅mL. However, digestion on IMER proved to be more repeatable and 32 times faster than in-solution digestion, and a given IMER could be reused at least 60 times.
Topics: Chromatography, Liquid; Digestion; Enzymes, Immobilized; Hemoglobins; Humans; Mustard Gas; Tandem Mass Spectrometry; Trypsin
PubMed: 34781109
DOI: 10.1016/j.jchromb.2021.123031 -
The American Journal of Emergency... Jan 2022This study aims to assess the prognosis of inpatients with COVID-19 infection who have a history of sulfur mustard exposure.
OBJECTIVE
This study aims to assess the prognosis of inpatients with COVID-19 infection who have a history of sulfur mustard exposure.
METHODS
We started a cohort study in October 2020 and ended in May 2021 on inpatients with COVID-19 infection who had been admitted to university healthcare centers. The analytic sample included 960 inpatients having COVID-19 infection (192 with; and 768 without sulfur mustard exposure). The exposed patients were male war veterans, and the unexposed patients were male individually age-matched people. All patients had a positive RT-PCR test and a positive chest CT for COVID-19. The outcome was death within 28 days of admission, and the predictors were clinical features recorded at patients' bedsides.
RESULTS
There was a significantly higher prevalence for asthma (p = 0.026) and pulmonary disease other than asthma (p < 0.001) in patients with the exposure. Sulfur mustard exposure was associated with increased risk for mortality of COVID-19 [hazard ratio (95% CI) = 1.92 (1.14,3.24), p = 0.013]. Early intubation signified a poor prognosis [hazard = 7.34 (4.65,11.58), p < 0.001]. However, individuals with higher PaO2 [hazard = 0.97 (0.95,0.98), p < 0.001], or people undergoing O2 therapy early upon admission [hazard = 0.58 (0.38,0.89), p = 0.011] showed lower risks for mortality. Individuals with asthma were at higher risk for mortality [hazard = 3.76 (1.69,8.36), p = 0.001].
CONCLUSION
Individuals with COVID-19 infection and sulfur mustard exposure should be considered high-risk patients and that, healthcare settings should be ready to provide critical care for them, including O therapy. They are more likely to have asthma or other pulmonary diseases.
Topics: Asthma; COVID-19; Chemical Warfare Agents; Cohort Studies; Hospitalization; Hospitals, University; Humans; Inpatients; Iran; Male; Middle Aged; Mustard Gas; Survival Analysis; Tomography, X-Ray Computed; Veterans
PubMed: 34739867
DOI: 10.1016/j.ajem.2021.09.053 -
Frontiers in Microbiology 2021Polyhydroxyalkanoates (PHAs) are intracellularly synthesized by bacteria as carbonosomes that exhibit biodegradable thermoplastics and elastomeric properties. The use of...
Polyhydroxyalkanoates (PHAs) are intracellularly synthesized by bacteria as carbonosomes that exhibit biodegradable thermoplastics and elastomeric properties. The use of cheaper edible oils as a source of carbon assists in the reduction of the production cost of such biopolyesters. In this work, different edible oils, such as groundnut oil (GNO), mustard oil, sesame oil, and soybean oil (SBO) were used to check their effect on PHA production from EO1 (MK049902). EO1 was used in a two-stage production system. In the first stage, bacterial growth was favored and, in the second, PHA was synthesized. GNO was found as the best carbon source for PHA production. The use of 2% (v/v) GNO, rich in saturated fatty acids, allowed PHA content of 58.41% and dry cell weight (DCW) of 10.5g/L at pH7 and temperature 35°C for 72h. Groundnut has a high potential for oil production and for the diversification of co-products with some potential of value aggregation. Such a perennial and sustainable species will almost certainly meet the criteria for becoming a significant commercial oilseed crop. Fourier transform infrared spectroscopy (FTIR) spectra showed strong characteristic bands at 1,282, 1,725, 2,935, 2,999, and 3,137cm for the PHA polymer. Gas chromatography-mass spectrometry (GC-MS) detects the presence of PHA copolymers.
PubMed: 34721317
DOI: 10.3389/fmicb.2021.711588 -
Iranian Journal of Allergy, Asthma, and... Sep 2021The mitochondrion has a substantial role in innate immunity and inflammasome signaling pathways. Sulfur mustard (SM) induces toxicity in cytoplasmic organelles. We aimed...
The mitochondrion has a substantial role in innate immunity and inflammasome signaling pathways. Sulfur mustard (SM) induces toxicity in cytoplasmic organelles. We aimed to evaluate the potential therapeutic effect of curcumin on the toxicity of SM analog through measuring gene expression levels of mitochondrial dynamics followed by induction of the inflammasome signaling pathway. After the treatment of pulmonary epithelial cell line (A549) by 2-chloroethyl ethyl sulfide (CEES) (2500 mM) for 48h, the transcriptional activity of mitochondrial fission and fusion genes such as dynamin-related protein 1 (Drp1), mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and Dominant optic atrophy (Opa1) and inflammasome pathway genes including absent in melanoma 2 (AIM2), NLR family containing protein 3 (NLRP3), and Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) was measured. Furthermore, the inhibitory effect of curcumin (160 mM) concurrent with SM analog on the expression level of mitochondria and inflammasome genes was investigated. CEES was able to over-express the fission, fusion (Drp1 ~ 8, Fis1 4.5, Mfn2 15, and Opa1 16-fold) and inflammasome genes (AIM2, NLRP3, 8 and 6-fold, respectively), whereas Mfn1 was significantly decreased (0.5-fold) and a not statistically significant decrease was observed in the ASC gene. Curcumin could modulate the effect of CEES, mitigate the expression of fission, fusion, and inflammasome genes exceedingly. However, a major increase in the repairer fusion gene (Mfn1, 6-fold) and complete suppression of the ASC gene were the outcomes of using the curcumin. In conclusion, we suggest curcumin alleviates the disturbance of mitochondrial dynamics and downregulates the inflammasome genes exposed to the CEES.
Topics: Biomarkers; Cell Line; Curcumin; Gene Expression Regulation; Homeostasis; Humans; Inflammasomes; Mitochondria; Mitochondrial Dynamics; Mustard Gas; Signal Transduction
PubMed: 34664820
DOI: 10.18502/ijaai.v20i5.7411 -
PloS One 2021Sulfur mustard (SM) is a cytotoxic, vesicating, chemical warfare agent, first used in 1917; corneas are particularly vulnerable to SM exposure. They may develop...
Sulfur mustard (SM) is a cytotoxic, vesicating, chemical warfare agent, first used in 1917; corneas are particularly vulnerable to SM exposure. They may develop inflammation, ulceration, neovascularization (NV), impaired vision, and partial/complete blindness depending upon the concentration of SM, exposure duration, and bio-physiological conditions of the eyes. Comprehensive in vivo studies have established ocular structural alterations, opacity, NV, and inflammation upon short durations (<4 min) of SM exposure. In this study, detailed analyses of histopathological alterations in corneal structure, keratocytes, inflammatory cells, blood vessels, and expressions of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and cytokines were performed in New Zealand white rabbits, in a time-dependent manner till 28 days, post longer durations (5 and 7 min) of ocular SM exposure to establish quantifiable endpoints of injury and healing. Results indicated that SM exposure led to duration-dependent increases in corneal thickness, opacity, ulceration, epithelial-stromal separation, and epithelial degradation. Significant increases in NV, keratocyte death, blood vessels, and inflammatory markers (COX-2, MMP-9, VEGF, and interleukin-8) were also observed for both exposure durations compared to the controls. Collectively, these findings would benefit in temporal delineation of mechanisms underlying SM-induced corneal toxicity and provide models for testing therapeutic interventions.
Topics: Animals; Biomarkers; Blood Vessels; Cell Survival; Chemical Warfare Agents; Cornea; Corneal Injuries; Corneal Keratocytes; Cyclooxygenase 2; Interleukin-8; Matrix Metalloproteinase 9; Mustard Gas; Rabbits
PubMed: 34637469
DOI: 10.1371/journal.pone.0258503 -
Frontiers in Plant Science 2021Environmental concerns related to synthetic pesticides and the emphasis on the adoption of an integrated pest management concept as a cardinal principle have...
Environmental concerns related to synthetic pesticides and the emphasis on the adoption of an integrated pest management concept as a cardinal principle have strengthened the focus of global research and development on botanical pesticides. A scientific understanding of the mode of action of biomolecules over a range of pests is key to the successful development of biopesticides. The present investigation focuses on the protein-ligand interactions of allyl isothiocyanate (AITC), a major constituent of black mustard ( essential oil (MEO) against two pests, namely, (Mi) and f. sp. (Fol), that cause severe yield losses in agricultural crops, especially in vegetables. bioassay results of MEO against Mi exhibited an exposure time dependent on the lethal concentration causing 50% mortality (LC) values of 47.7, 30.3, and 20.4 μg ml at 24, 48, and 72 h of exposure, respectively. The study revealed short-term nematostatic activity at lower concentrations, with nematicidal activity at higher concentrations upon prolonged exposure. Black mustard essential oil displayed excellent Fol mycelial growth inhibition, with an effective concentration to cause 50% inhibition (EC) value of 6.42 μg ml. In order to decipher the mechanism of action of MEO, its major component, AITC (87.6%), which was identified by gas chromatography-mass spectrometry (GC-MS), was subjected to docking and simulation studies against seven and eight putative target proteins of Mi and Fol, respectively. Allyl isothiocyanate exhibited the highest binding affinity with the binding sites of acetyl cholinesterase (AChE), followed by odorant response gene-1 (ODR1) and neuropeptide G-protein coupled receptor (nGPCR) in Mi, suggesting the possible suppression of neurotransmission and chemosensing functions. Among the target proteins of Fol, AITC was the most effective protein in blocking chitin synthase (CS), followed by 2,3-dihydroxy benzoic acid decarboxylase (6m53) and trypsinase (1try), thus inferring these as the principal molecular targets of fungal growth. Taken together, the study establishes the potential of MEO as a novel biopesticide lead, which will be utilized further to manage the Mi-Fol disease complex.
PubMed: 34512695
DOI: 10.3389/fpls.2021.714730 -
Ecotoxicology and Environmental Safety Dec 2021As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of...
As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of sulfur mustard (HD), a persistent chemical warfare agent that has been widely disposed since World War II and continuously leaks into aquatic environments. Herein, we report the first systematic investigation of CPO-catalyzed degradation of HD and the potential application of CPO in destroying chemical weapons under mild conditions. The related Michaelis-Menten parameters (K=0.17 mM, V=0.06 mM s (R =0.935), and k= 2717 s) indicated nearly a prominent enzymatic efficiency. Under optimal conditions, 80% of HD was transformed to bis(2-chloroethyl) sulfoxide as identified by mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Other metabolites were also generated during the decontamination process. A plausible oxidation mechanism was proposed based on the degradation products, NMR titration experiments, and molecular dynamics simulations. CPO also promoted the degradation of other chemical weapon agents, namely, Lewisite (L) and venomous agent X (VX), thereby exhibiting a broad substrate scope. The high potential of the developed system for the decontamination of aquatic environments was demonstrated by the successful hatching of zebrafish embryos after HD degradation and the survival of zebrafish (Danio rerio, AB strain) larvae after the degradation of Agent Yellow (L+HD).
Topics: Animals; Catalysis; Chloride Peroxidase; Mustard Gas; Oxidative Stress; Zebrafish
PubMed: 34500382
DOI: 10.1016/j.ecoenv.2021.112715 -
Toxicological Sciences : An Official... Oct 2021Sulfur mustard (SM) has been widely used as a chemical warfare agent including most recently in Syria. Mice exposed to SM exhibit an increase in pro-inflammatory...
Sulfur mustard (SM) has been widely used as a chemical warfare agent including most recently in Syria. Mice exposed to SM exhibit an increase in pro-inflammatory cytokines followed by immune cell infiltration in the lung, however, the mechanisms leading to these inflammatory responses has not been completely elucidated. Mast cells are one of the first responding innate immune cells found at the mucosal surfaces of the lung and have been reported to be activated by SM in the skin. Therefore, we hypothesized that nitrogen mustard (NM: a surrogate for SM) exposure promotes activation of mast cells causing chronic respiratory inflammation. To assess the role of mast cells in NM-mediated pulmonary toxicity, we compared the effects of NM exposure between C57BL/6 and B6.Cg-KitW-sh/HNihrJaeBsmJ (KitW-sh; mast cell deficient) mice. Lung injury was observed in C57BL/6J mice following NM exposure (0.125 mg/kg) at 72 h, which was significantly abrogated in KitW-sh mice. Although both strains exhibited damage from NM, C57BL/6J mice had higher inflammatory cell infiltration and more elevated prostaglandin D2 (PGD2) present in bronchoalveolar lavage fluid compared with KitW-sh mice. Additionally, we utilized murine bone marrow-derived mast cells to assess NM-induced early and late activation. Although NM exposure did not result in mast cell degranulation, we observed an upregulation in PGD2 and IL-6 levels following exposure to NM. Results suggest that mast cells play a prominent role in lung injury induced by NM and may contribute to the acute and potentially long-term lung injury observed caused by SM.
Topics: Animals; Chemical Warfare Agents; Cytokines; Lipids; Lung; Mast Cells; Mechlorethamine; Mice; Mice, Inbred C57BL; Mustard Gas
PubMed: 34453837
DOI: 10.1093/toxsci/kfab107 -
Inhalation Toxicology 2021To develop a novel inhalation exposure system capable of delivering a controlled inhaled HD dose through an endotracheal tube to anesthetized rats to investigate the...
OBJECTIVE
To develop a novel inhalation exposure system capable of delivering a controlled inhaled HD dose through an endotracheal tube to anesthetized rats to investigate the lung pathophysiology and evaluate potential medical countermeasures.
MATERIALS AND METHODS
Target HD vapor exposures were generated by a temperature-controlled vapor generator, while concentration was monitored near real-time by gas chromatography. Animal breathing parameters were monitored real-time by in-line EMKA/SciReq pulmonary analysis system. Individual exposures were halted when the target inhaled doses were achieved. Animals were observed daily for clinical observations and lethality with scheduled termination at 28 days post-exposure. Upon scheduled or unscheduled death, animals underwent a gross necropsy and lung and trachea were collected for histopathology.
RESULTS
Controlled HD concentrations ranged from 60 to 320 mg/m. Delivered inhaled doses range from 0.3 to 3.20 mg/kg with administered doses within 3% of the target. The 28-day inhaled LD is 0.80 mg/kg (95% CI = 0.42-1.18 mg/kg). Post exposure respiratory abnormalities were observed across all dose levels though the higher dose levels had earlier onset and higher frequency of occurrence. Histopathologic alterations were not qualitatively altered in accordance with dose but instead showed a relationship to an animals' time of death, with early deaths demonstrating acute damage and later deaths displaying signs of repair.
DISCUSSION/CONCLUSION
This novel exposure system administers targeted HD inhaled doses to generate a small animal model that can be used to evaluate physiological toxicities of inhaled HD on the lungs and for evaluation of potential medical countermeasure treatments.
Topics: Animals; Disease Models, Animal; Inhalation Exposure; Lung Diseases; Male; Medical Countermeasures; Mustard Gas; Rats; Rats, Sprague-Dawley
PubMed: 34396872
DOI: 10.1080/08958378.2021.1951401