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ACS Omega May 2023Developing an accurate chemical warfare agent (CWA) vapor generator is critical for homeland security because it enables real-time monitoring of target agent...
Development of a Rapid and Accurate Vapor Generation System for Real-Time Monitoring of a Chemical Warfare Agent (CWA) by Coupling Fourier Transform Infrared (FT-IR) Spectroscopy.
Developing an accurate chemical warfare agent (CWA) vapor generator is critical for homeland security because it enables real-time monitoring of target agent concentration for testing and evaluation. We designed and built an elaborate CWA vapor generator that offers reliable long-term stability and real-time monitoring capabilities by coupling it with Fourier transform infrared (FT-IR) spectroscopy. We evaluated the reliability and stability of the vapor generator using a gas chromatography-flame ion detector (GC-FID) and conducted a comparison between the experimental and theoretical results of sulfur mustard (HD, bis-2-chloroethylsulfide), a real CWA, at concentrations ranging from 1 to 5 ppm. Our FT-IR-coupled vapor generation system showed real-time monitoring ability, which enables rapid and accurate evaluation of chemical detectors. The vapor generation system was able to generate CWA vapor continuously for over 8 h, demonstrating its long-term vapor generation capability. In addition, we vaporized another representative CWA, viz., GB (Sarin, propan-2-yl ethylphosphonofluoridate), and conducted real-time monitoring of GB vapor concentration with high accuracy. This versatile vapor generator approach can enable the rapid and accurate evaluation of CWAs for homeland security against chemical threats and can be used in constructing a versatile real-time monitoring vapor generation system for CWAs.
PubMed: 37251177
DOI: 10.1021/acsomega.3c01301 -
Experimental Eye Research Jun 2023The vesicant sulfur mustard (SM) is a chemical warfare agent that causes acute and chronic injury to the cornea and proximal anterior segment structures. Despite...
The vesicant sulfur mustard (SM) is a chemical warfare agent that causes acute and chronic injury to the cornea and proximal anterior segment structures. Despite clinical evidence of SM-exposure causing unexplained retinal deficits, there have been no animal studies conducted to examine the retinal toxicity of this vesciant. The cardinal hallmark of retinal response to stressors or injury is the activation of reactive gliosis, a cellular process largely governed by Müller glia. Previously we showed that corneal exposure to sodium hydroxide elicits rapid induction of reactive gliosis and results in retinal degeneration in a dose-related manner. Based on this evidence, we hypothesized that the vesicant nitrogen mustard (NM), an analog of SM, may also elicit reactive gliosis. To test this idea, we developed a mouse model of NM ocular injury and investigated corneal and retinal effects focusing on citrullination, a posttranslational modification (PTM) of proteins. This PTM was recently linked to alkali injury and has also been shown to occur in retinal degenerative conditions. Here, we demonstrate that corneal exposure to 1% NM causes a synchronous activation of citrullination in both the cornea and retina with hypercitrullination becoming apparent temporally and manifesting with altered cellular expression characteristics. A key finding is that ocular citrullination occurs acutely as early as 1-h post-injury in both the cornea and retina, which underscores a need for expeditious interception of this acute corneal and retinal response. Moreover, exploiting dose response and temporal studies, we uncoupled NM-induced retinal citrullination from its induction of retinal gliosis. Our findings demonstrate that hypercitrullination is a common corneo-retinal mechanism that sensitizes the eye to NM injury and suggests that counteracting hypercitrullination may provide a suitable countermeasure to vesicant injury.
Topics: Animals; Mice; Mechlorethamine; Irritants; Gliosis; Cornea; Eye Injuries; Retina; Mustard Gas; Retinal Diseases
PubMed: 37080381
DOI: 10.1016/j.exer.2023.109485 -
Experimental Eye Research May 2023Sulfur mustard (SM) is a chemical warfare agent (CWA) that causes severe eye pain, photophobia, excessive lacrimation, corneal and ocular surface defects, and blindness....
Sulfur mustard (SM) is a chemical warfare agent (CWA) that causes severe eye pain, photophobia, excessive lacrimation, corneal and ocular surface defects, and blindness. However, SM's effects on retinal cells are relatively meager. This study investigated the role of SM toxicity on Müller glial cells responsible for cellular architecture, inner blood-retinal barrier maintenance, neurotransmitter recycling, neuronal survival, and retinal homeostasis. Müller glial cells (MIO-M1) were exposed to SM analog, nitrogen mustard (NM), at varying concentrations (50-500 μM) for 3 h, 24 h, and 72 h. Müller cell gliosis was evaluated using morphological, cellular, and biochemical methods. Real-time cellular integrity and morphological evaluation were performed using the xCELLigence real-time monitoring system. Cellular viability and toxicity were measured using TUNEL and PrestoBlue assays. Müller glia hyperactivity was calculated based on glial fibrillary acidic protein (GFAP) and vimentin immunostaining. Intracellular oxidative stress was measured using DCFDA and DHE cell-based assays. Inflammatory markers and antioxidant enzyme levels were determined by quantitative real-time PCR (qRT-PCR). AO/Br and DAPI staining further evaluated DNA damage, apoptosis, necrosis, and cell death. Inflammasome-associated Caspase-1, ASC, and NLRP3 were studied to identify mechanistic insights into NM toxicity in Müller glial cells. The cellular and morphological evaluation revealed the Müller glia hyperactivity after NM exposure in a dose- and time-dependent manner. NM exposure caused significant oxidative stress and enhanced cell death at 72 h. A significant increase in antioxidant indices was observed at the lower concentrations of NM. Mechanistically, we found that NM-treated MIO-M1 cells increased caspase-1 levels that activated NLRP3 inflammasome-induced production of IL-1β and IL-18, and elevated Gasdermin D (GSDMD) expression, a crucial component actuating pyroptosis. In conclusion, NM-induced Müller cell gliosis via increased oxidative stress results in caspase-1-dependent activation of the NLRP3 inflammasome and cell death driven primarily by pyroptosis.
Topics: Humans; Ependymoglial Cells; Gliosis; Mustard Gas; Antioxidants; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Caspases
PubMed: 37023936
DOI: 10.1016/j.exer.2023.109461 -
The Journal of the Royal College of... Jun 2023The fruit fly, , is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and...
The fruit fly, , is a simple and powerful model organism. It has played a critical role over more than a century, for example in establishing the field of genetics, and in foundational insights into the molecular basis of development. From the 1930s until today, researchers at the University of Edinburgh have used to tackle questions in basic and biomedical science. Here the history of the initial decades of this research is explored, beginning with the introduction of research to Edinburgh by Francis Albert Eley Crew, in the newly established Institute of Animal Genetics. This period of research includes the discovery that chemicals can cause genetic mutation. This was demonstrated by research of the effects of mustard gas on flies by Charlotte Auerbach and colleagues, guided by the future Nobel laureate Hermann Muller. research was also formative in Conrad Hal Waddington's conceptual thinking about developmental biology, including in his vision of the epigenetic landscape. This holistic, systems-level view of the control of development was far before its time and has continued to be influential to this day in our conceptualisation of developmental biology and in the increasingly important field of systems biology. Waddington's experiments with in Edinburgh also gave rise to the evolutionary concept of genetic assimilation, in which an environmentally induced phenotype subsequently becomes genetically encoded.
Topics: Animals; Drosophila; Drosophila melanogaster; Phenotype; Biological Evolution; Mutation
PubMed: 36927337
DOI: 10.1177/14782715231162675 -
International Journal of Fertility &... Feb 2023War toxin, mustard gas, alkylating agent results in male infertility via inducing reactive oxygen species (ROS) production and DNA mutagenesis. SIRT1 and SIRT3 are...
OBJECTIVE
War toxin, mustard gas, alkylating agent results in male infertility via inducing reactive oxygen species (ROS) production and DNA mutagenesis. SIRT1 and SIRT3 are multifunctional enzymes that involve in the DNA repair, oxidative stress responses. This study aim is to assess the correlation between serum levels of SIRT1, SIRT3 and both rs3758391T>C and rs185277566C>G gene polymorphisms with infertility in the war zones of Kermanshah province, Iran.
MATERIALS AND METHODS
In this case-control study based on the semen analysis, samples were divided into two groups infertile (n=100) and fertile (n=100). High-performance liquid chromatography (HPLC) method was used to determine the malondialdehyde level, and also a sperm chromatin dispersion (SCD) test was used to evaluate the DNA fragmentation rate. Using the colorimetric assays, superoxide dismutase (SOD) activity was measured. SIRT1 and SIRT3 protein levels were determined by using ELISA. The genetic variants of SIRT1 rs3758391T>C, and SIRT3 rs185277566C>G, were detected by polymerase chain reaction-restriction fragment length (PCR-RFLP) technique.
RESULTS
Malondialdehyde (MDA) level and the percentage of DNA fragmentation were higher in infertile samples, but serum levels of SIRT1 and SIRT3, and SOD activity was lower in infertile compared to fertile samples (P<0.001). The TC+CC genotypes and the C allele from SIRT1 rs3758391T>C polymorphism, and CG+GG genotypes and the G allele from SIRT3 rs185277566C>G polymorphism could increase risk of infertility (P<0.05).
CONCLUSION
The results of this study suggest that war toxins through the impact on genotypes, decreasing levels of SIRT1 and SIRT3 and increasing levels of oxidative stress, lead to defects in the concentration, motility and morphology of sperms and thus, infertility in men.
PubMed: 36906829
DOI: 10.22074/ijfs.2022.553494.1304 -
Antibiotics (Basel, Switzerland) Feb 2023Organic selenocyanates (RSeCN) are among the most reactive and biologically active Se species, often exhibiting a pronounced cytotoxic activity against mammalian cells...
Organic selenocyanates (RSeCN) are among the most reactive and biologically active Se species, often exhibiting a pronounced cytotoxic activity against mammalian cells and microorganisms. Various aromatic selenocyanates have been synthesized and, similar to some of the most Reactive Sulfur Species (RSS), such as allicin, found to be active against a range of bacteria, including , and , and fungi, including , , , and , even via the gas phase. The highest antimicrobial activity has been observed for benzyl selenocyanate, which inhibited the growth of all bacteria considerably, even at the lowest tested concentration of 50 µM. Notably, neither the analogues thiocyanate (BTC) nor isothiocyanate (BITC) show any of these activities, rendering this selenium motif rather special in activity and mode of action. Eventually, these findings advocate a range of potential applications of organic selenocyanates in medicine and agriculture.
PubMed: 36830201
DOI: 10.3390/antibiotics12020290 -
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 -
Experimental Eye Research Mar 2023Sulfur mustard (SM) remains a highly dangerous chemical weapon capable of producing mass casualties through liquid or vapor exposure. The cornea is highly sensitive to...
Sulfur mustard (SM) remains a highly dangerous chemical weapon capable of producing mass casualties through liquid or vapor exposure. The cornea is highly sensitive to SM toxicity and exposure to low vapor doses can cause incapacitating acute injuries. At higher doses, corneas fail to fully heal and subsequently develop a constellation of symptoms known as mustard gas keratopathy (MGK) that causes reduced quality of life and impaired or lost vision. Despite a century of research, there are no specific treatments for acute or persistent ocular SM injuries. Here I summarize toxicological, clinical and pathophysiological mechanisms of SM vapor injury in the cornea, describe a preclinical model of ocular SM vapor exposure for reproducible therapeutic studies, and propose new approaches to improve evaluation of therapeutic effects. I also describe recent findings illustrating the delayed development of a transient but severe recurrent corneal lesion that, in turn, triggers the emergence of secondary keratopathies characteristic of the chronic form of MGK. Development of this recurrent lesion is SM dose-dependent, although the severity of the recurrent lesion appears SM dose-independent. Similar recurrent lesions have been reported in multiple species, including humans. Given the mechanistic relationship between the recurrent lesion and chronic, secondary keratopathies, I hypothesize that preventing the development of the recurrent lesion represents a novel and potentially valuable therapeutic approach for treatment of severe corneal SM injuries. Although ocular exposure to SM vapor continues to be a challenging therapeutic target, establishing consistent and reproducible models of corneal injury that enhance mechanistic and pathophysiological understanding will help satisfy regulatory requirements and accelerate the development of effective therapies.
Topics: Humans; Mustard Gas; Chemical Warfare Agents; Quality of Life; Corneal Diseases; Corneal Injuries
PubMed: 36731603
DOI: 10.1016/j.exer.2023.109395 -
Cornea Jun 2023Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to... (Review)
Review
PURPOSE
Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries.
METHODS
Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye."
RESULTS
Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging.
CONCLUSIONS
MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.
Topics: Humans; Mustard Gas; Chemical Warfare Agents; Cornea; Corneal Diseases; Eye Injuries
PubMed: 36729713
DOI: 10.1097/ICO.0000000000003182 -
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