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American Journal of Respiratory Cell... May 2023Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern...
Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as acute respiratory distress syndrome. In survivors, long-term effects such as the development of respiratory ailments are reported for the organoarsenical sulfur mustard; however, no long-term pulmonary effects are documented for lewisite and DPCA. No animal models exist to explore the relationship between skin exposure to vesicants and constrictive bronchiolitis. We developed and characterized a mouse model to study the long-term effects of cutaneous exposure on the lungs after exposure to a sublethal dose of organoarsenicals. We exposed mice to lewisite, DPCA, or a less toxic surrogate organoarsenic chemical, phenyl arsine oxide, on the skin. The surviving mice were followed for 20 weeks after skin exposure to arsenicals. Lung microcomputed tomography, lung function, and histology demonstrated increased airway resistance, increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and peribronchial lymphocyte infiltration in mice exposed to arsenical on skin.
Topics: Humans; Animals; Mice; X-Ray Microtomography; Skin; Chemical Warfare Agents; Bronchiolitis Obliterans; Mustard Gas; Arsenicals
PubMed: 36780670
DOI: 10.1165/rcmb.2022-0321MA -
Annals of the New York Academy of... Nov 2020Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog of sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and...
Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog of sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and coagulation and altered levels of plasma microRNAs (miRNAs). Rats were exposed to aerosolized CEES and euthanized 12 h later for collection of tissue and plasma. Profiling of miRNAs in plasma, using a TaqMan-based RT-PCR array, revealed 14 differentially expressed miRNAs. Target gene prediction and pathway analysis revealed miRNA-mediated regulation of organismal injury, inflammation, and respiratory diseases. miR-140-5p, a marker of ALI, was downregulated in the plasma, lung, liver, and kidney of CEES-exposed rats, with a concomitant increase in the expression of the inflammation markers IL-6 and IL-1α and the coagulation marker tissue factor (F3). Exposure of rat airway epithelial cells (RL-65) to CEES (0.5 mM) caused cell death and a decrease in miR-140-5p both in cells and media supernatant. This was accompanied by an increase in cellular mRNA levels of IL-6, IL-1α, and F3, as well as FGF9 and EGR2, putative targets of miR-140. Knockdown of miR-140 by specific oligos in RL-65 cells mimicked the in vivo CEES-mediated effects, leading to significantly increased mRNA levels of IL-6, IL-1α, F3, FGF9, and EGR2. Our study identifies miR-140-5p as a mediator of CEES-induced ALI, which could potentially be targeted for therapy.
Topics: Acute Lung Injury; Animals; Blood Coagulation; Chemical Warfare Agents; Early Growth Response Protein 2; Fibroblast Growth Factor 9; Inflammation; Interleukin-1alpha; Interleukin-6; Male; MicroRNAs; Mustard Gas; Rats; Rats, Sprague-Dawley
PubMed: 32602122
DOI: 10.1111/nyas.14416 -
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, Physical Therapy Education Sep 2023The aim of this study was to adapt and validate the Belongingness Scale-Clinical Placement Experience (BES-CPE) for Doctor of Physical Therapy (DPT) students in the...
INTRODUCTION
The aim of this study was to adapt and validate the Belongingness Scale-Clinical Placement Experience (BES-CPE) for Doctor of Physical Therapy (DPT) students in the United States.
REVIEW OF LITERATURE
Belongingness is vital to one's mental, emotional, and physical health. Research has shown that belongingness is positively correlated with students' academic performance and achievement. An absence of belongingness may hinder students' full participation in clinical experiences and compromise clinical achievement.
SUBJECTS
Respondents were current or former DPT students at least 18 years of age who had either completed the midterm evaluation of their final terminal full-time clinical education experience (TCE) in their DPT program or were no more than 1 year from the completion of their final TCE.
METHODS
The BES-CPE was adapted for DPT students, and the scale was completed electronically by those who met the inclusion criteria. Principal component analysis with promax rotation and Cronbach's α were used to determine construct validity and reliability.
RESULTS
One hundred fifty-nine respondents completed all items on the BES-CPE and demographic survey. A 3-component structure was identified (esteem, connectedness, and efficacy), which was aligned to the original BES-CPE scale. One item was discarded, and the final version of the BES-CPE for DPT students is a 33-item scale with satisfactory internal consistency.
DISCUSSION AND CONCLUSION
This study adapted and provided evidence for validity of the first known scale to measure belongingness in DPT students during their clinical education experiences (CEEs) in the United States. The 33-item BES-CPE provided valid and reliable measures of belongingness in DPT students during CEEs that can be used to provide a better understanding of the student experience in the clinical learning environment.
Topics: Humans; United States; Reproducibility of Results; Students; Physical Therapy Modalities; Mustard Gas; Alkanesulfonic Acids
PubMed: 38478813
DOI: 10.1097/JTE.0000000000000292 -
International Journal of Molecular... May 2021Photosynthetic organisms commonly develop the strategy to keep the reaction center chlorophyll of photosystem I, P700, oxidized for preventing the generation of reactive...
Photosynthetic organisms commonly develop the strategy to keep the reaction center chlorophyll of photosystem I, P700, oxidized for preventing the generation of reactive oxygen species in excess light conditions. In photosynthesis of C plants, CO concentration is kept at higher levels around ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) by the cooperation of the mesophyll and bundle sheath cells, which enables them to assimilate CO at higher rates to survive under drought stress. However, the regulatory mechanism of photosynthetic electron transport for P700 oxidation is still poorly understood in C plants. Here, we assessed gas exchange, chlorophyll fluorescence, electrochromic shift, and near infrared absorbance in intact leaves of maize (a NADP-malic enzyme C subtype species) in comparison with mustard, a C plant. Instead of the alternative electron sink due to photorespiration in the C plant, photosynthetic linear electron flow was strongly suppressed between photosystems I and II, dependent on the difference of proton concentration across the thylakoid membrane (ΔpH) in response to the suppression of CO assimilation in maize. Linear relationships among CO assimilation rate, linear electron flow, P700 oxidation, ΔpH, and the oxidation rate of ferredoxin suggested that the increase of ΔpH for P700 oxidation was caused by the regulation of proton conductance of chloroplast ATP synthase but not by promoting cyclic electron flow. At the scale of intact leaves, the ratio of PSI to PSII was estimated almost 1:1 in both C and C plants. Overall, the photosynthetic electron transport was regulated for P700 oxidation in maize through the same strategies as in C plants only except for the capacity of photorespiration despite the structural and metabolic differences in photosynthesis between C and C plants.
Topics: Carbon Dioxide; Darkness; Electron Transport; Ferredoxins; Kinetics; Models, Biological; Oxidation-Reduction; Photosynthesis; Photosystem I Protein Complex; Photosystem II Protein Complex; Plant Leaves; Protons; Quantum Theory; Zea mays
PubMed: 34063101
DOI: 10.3390/ijms22094894 -
Acta Pharmacologica Sinica Dec 2021Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no...
Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no effective therapeutic treatments or antidotes available currently to counteract its toxic effects. Our previous study shows that bone marrow-derived mesenchymal stromal cells (BMSCs) could exert therapeutic effects against SM-induced lung injury. In this study, we explored the therapeutic potential of BMSC-derived exosomes (BMSC-Exs) against ALI and the underlying mechanisms. ALI was induced in mice by injection of SM (30 mg/kg, sc) at their medial and dorsal surfaces. BMSC-Exs (20 μg/kg in 200 μL PBS, iv) were injected for a 5-day period after SM exposure. We showed that BMSC-Exs administration caused a protective effect against pulmonary edema. Using a lung epithelial cell barrier model, BMSC-Exs (10, 20, 40 μg) dose-dependently inhibited SM-induced cell apoptosis and promoted the recovery of epithelial barrier function by facilitating the expression and relocalization of junction proteins (E-cadherin, claudin-1, occludin, and ZO-1). We further demonstrated that BMSC-Exs protected against apoptosis and promoted the restoration of barrier function against SM through upregulating G protein-coupled receptor family C group 5 type A (GPRC5A), a retinoic acid target gene predominately expressed in the epithelial cells of the lung. Knockdown of GPRC5A reduced the antiapoptotic and barrier regeneration abilities of BMSC-Exs and diminished their therapeutic effects in vitro and in vivo. BMSC-Exs-caused upregulation of GPRC5A promoted the expression of Bcl-2 and junction proteins via regulating the YAP pathway. In summary, BMSC-Exs treatment exerts protective effects against SM-induced ALI by promoting alveolar epithelial barrier repair and may be an alternative approach to stem cell-based therapy.
Topics: Acute Lung Injury; Animals; Apoptosis; Cell Line; Epithelial Cells; Exosomes; Gene Knockout Techniques; Lung; Male; Mesenchymal Stem Cells; Mice, Inbred ICR; Mice, Knockout; Mustard Gas; Receptors, G-Protein-Coupled; Signal Transduction; YAP-Signaling Proteins; Mice
PubMed: 33654219
DOI: 10.1038/s41401-021-00625-4 -
Archives of Toxicology Oct 2021Creatine kinase (CK) catalyzes the formation of phosphocreatine from adenosine triphosphate (ATP) and creatine. The highly reactive free cysteine residue in the active...
Creatine kinase (CK) catalyzes the formation of phosphocreatine from adenosine triphosphate (ATP) and creatine. The highly reactive free cysteine residue in the active site of the enzyme (Cys) is considered essential for the enzymatic activity. In previous studies we demonstrated that Cys is targeted by the alkylating chemical warfare agent sulfur mustard (SM) yielding a thioether with a hydroxyethylthioethyl (HETE)-moiety. In the present study, the effect of SM on rabbit muscle CK (rmCK) activity was investigated with special focus on the alkylation of Cys and of reactive methionine (Met) residues. For investigation of SM-alkylated amino acids in rmCK, micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry measurements were performed using the Orbitrap technology. The treatment of rmCK with SM resulted in a decrease of enzyme activity. However, this decrease did only weakly correlate to the modification of Cys but was conclusive for the formation of Met-HETE and Met-HETE. In contrast, the activity of mutants of rmCK produced by side-directed mutagenesis that contained substitutions of the respective Met residues (MetAla, MetLeu, and MetAla/MetLeu) was highly resistant against SM. Our results point to a critical role of the surface exposed Met and Met residues for CK activity.
Topics: Alkylation; Animals; Chemical Warfare Agents; Chromatography, Liquid; Creatine Kinase, MM Form; Cysteine; Methionine; Mustard Gas; Rabbits; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 34396457
DOI: 10.1007/s00204-021-03137-6 -
Archives of Toxicology Apr 2020Sulfur mustard (SM) is a highly toxic war chemical that causes significant morbidity and mortality and lacks any effective therapy. Rats exposed to aerosolized CEES...
Sulfur mustard (SM) is a highly toxic war chemical that causes significant morbidity and mortality and lacks any effective therapy. Rats exposed to aerosolized CEES (2-chloroethyl ethyl sulfide; 10% in ethanol), an analog of SM, developed acute respiratory distress syndrome (ARDS), which is characterized by increased inflammation, hypoxemia and impaired gas exchange. We observed elevated levels of extracellular nucleic acids (eNA) in the bronchoalveolar lavage fluid (BALF) of CEES-exposed animals. eNA can induce inflammation, coagulation and barrier dysfunction. Treatment with hexadimethrine bromide (HDMBr; 10 mg/kg), an eNA neutralizing agent, 2 h post-exposure, reduced lung injury, inhibited disruption of alveolar-capillary barrier, improved blood oxygenation (PaO/FiO ratio), thus reversing ARDS symptoms. HDMBr treatment also reduced lung inflammation in the CEES-exposed animals by decreasing IL-6, IL-1A, CXCL-1 and CCL-2 mRNA levels in lung tissues and HMGB1 protein in BALF. Furthermore, HDMBr treatment also reduced levels of lung tissue factor and plasminogen activator inhibitor-1 indicating reduction in clot formation and increased fibrinolysis. Fibrin was reduced in BALF of the HDMBr-treated animals. This was further confirmed by histology that revealed diminished airway fibrin, epithelial sloughing and hyaline membrane in the lungs of HDMBr-treated animals. HDMBr completely rescued the CEES-associated mortality 12 h post-exposure when the survival rate in CEES-only group was just 50%. Experimental eNA treatment of cells caused increased inflammation that was reversed by HDMBr. These results demonstrate a role of eNA in the pathogenesis of CEES/SM-induced injury and that its neutralization can serve as a potential therapeutic approach in treating SM toxicity.
Topics: Animals; Chemical Warfare Agents; Lung; Lung Injury; Male; Mustard Gas; Nucleic Acids; Rats; Toxicity Tests
PubMed: 32157350
DOI: 10.1007/s00204-020-02699-1 -
Evidence-based Complementary and... 2023Sims is an aromatic rhizomatous herb of family Zingiberaceae which is endemic to Peninsular India. This study first reports the phytochemical profile and pesticidal...
Sims is an aromatic rhizomatous herb of family Zingiberaceae which is endemic to Peninsular India. This study first reports the phytochemical profile and pesticidal potential of oleoresins obtained from the aerial and rhizome parts of Sims. The oleoresins were prepared by the cold percolation method and were analyzed by a gas chromatography-mass spectrometry (GC-MS) method. Both the oleoresins varied greatly in composition, the major compounds identified in aerial part oleoresin (GSAO) were methyl linoleate, methyl palmitate, and phytol, while the major compounds present in rhizome part oleoresin (GSRO) were -sitosterol, 8 (17),12-labdadiene-15, 16-dial, methyl linoleate, and methyl palmitate. In order to evaluate the biological activities, the oleoresins were tested under laboratory conditions for nematicidal action and inhibition of egg hatching potential against root knot nematode, where GSRO was more effective. Insecticidal activity was performed against mustard aphid, and castor hairy caterpillar, . In case of mustard aphid, GSRO (LC = 154.8 ppm) was more effective than GSAO (LC = 263.0 ppm), while GSAO (LC = 346.7.0 ppm) was more effective against castor hairy caterpillar than GSRO (LC = 398.1 ppm). The herbicidal activity was performed in the receptor species subsp. , and the oleoresins showed different intensities for seed germination inhibition and coleoptile and radical length inhibition. Molecular docking studies were conducted to screen the activities and through molecular docking, it was found that the major oleoresins components were able to interact with the binding pocket of HPPD and AChE with -sitosterol showing the best binding affinity.
PubMed: 36636605
DOI: 10.1155/2023/5936513 -
Marine Environmental Research Oct 2020Sulphur mustard (HD) was the most widely produced chemical warfare agent (CWA) in the history of chemical warfare (CW). Simultaneously, the loads of HD account as by far...
Sulphur mustard (HD) was the most widely produced chemical warfare agent (CWA) in the history of chemical warfare (CW). Simultaneously, the loads of HD account as by far the largest fraction of the sea-dumped CW. Nowadays its presence in the marine ecosystems recognized as a serious threat for marine users and maritime industries. Although, during over a decade of research much has been done to assess the environmental threats linked with underwater chemical munitions. There are, however, essential gaps in scientific knowledge including scarce information about the aquatic toxicity thresholds of HD and its degradation products. Standardized biotests were performed according to the Organisation for Economic Co-operation and Development (OECD) Test No. 202: Daphnia sp. Acute Immobilisation Test guidelines. Obtained results provide a solid foundation for comparison and categorisation of threats of HD and its degradation products. With the D. magna LC aquatic acute toxicity threshold at as low as 224 ± 12 μg × L, 1,2,5-trithiepane is very toxic, being one of the most toxic CWA degradation products that have been investigated up to date. It exhibits stronger effects than 1,4,5-oxadithiepane and diluted HD that turn out to be toxic. In total, the toxicity of 7 compounds has been estimated. Whenever possible, toxicity thresholds were compared with previously existing data originating from different biotests and mathematical modelling.
Topics: Animals; Chemical Warfare Agents; Daphnia; Ecosystem; Lethal Dose 50; Mustard Gas; Toxicity Tests, Acute; Water Pollutants, Chemical
PubMed: 32853855
DOI: 10.1016/j.marenvres.2020.105077