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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 280: 121553, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-35792481

RESUMO

Phosgene (carbonyl chloride, COCl2) is a widely used colorless gas in organic synthesis. However, its high toxicity sets a severe potential damage of public safety. As the fluorescence method has the advantages of simple operation and real-time detection of phosgene, it is extremely important to develop a fluorescent phosgene probe for public health and safety. This study aimed to present a simple Eu3+ complex (1) with 2-hydroxyl-1H-benzimidazole moiety as a novel phosgene probe. Probe 1 exhibited characteristic emission of Eu3+ in CH3CN solution, which was specifically quenched after encountering phosgene. The change in the solution color from light red to dark could be easily distinguished with the naked eye under a 365 nm ultraviolet lamp. Finally, the test paper with probe 1 was fabricated for effortless, selective, and visual detection of phosgene gas.


Assuntos
Fosgênio , Európio , Corantes Fluorescentes
2.
J Mol Model ; 28(7): 195, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727345

RESUMO

A fluorescent probe Pi with the excited-state intramolecular proton transfer (ESIPT) properties was synthesized and used to detect the phosgene in solution and gas phases. However, the detection mechanism of the fluorescent probe needs to be further studied. Herein, the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods were adopted to explore the molecular structures and electronic spectra properties of probe and its product Pio after reacting with phosgene. Through analysis for molecular structure parameters and infrared vibrations accompanied with the hydrogen bond of Pi, it is confirmed that the intramolecular hydrogen bond of Pi is enhanced under light excitation, which illustrates the occurrence of ESIPT reaction combined with the scanned potential energy curves. It can be seen from the simulated spectra that Pi shows double fluorescence through ESIPT process, while the fluorescent product Pio exhibits the single fluorescence due to the disappearance of intramolecular hydrogen bond. Through the study on the structure and optical properties of Pi and Pio, it can be helpful to deeply understand the intrinsic mechanism of the detection of phosgene by the Pi molecule probe, which also supplies a reference to the further study about the fluorescence probe.


Assuntos
Fosgênio , Prótons , Corantes Fluorescentes/química , Modelos Moleculares , Teoria Quântica
3.
Anal Bioanal Chem ; 414(17): 4953-4962, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35567611

RESUMO

The improper use of phosgene, either as a chemical warfare agent or a leak during chemical production, causes significant risks to human life and property. Therefore, it is particularly important to develop a rapid and highly selective method for the detection of phosgene. In this article, a highly selective fluorescent sensor ONB with a BODIPY unit as a fluorophore and o-aminophenol as a reactive site was constructed for the selective and rapid detection of phosgene in solution. The ONB-containing nanofibers were sprayed onto a non-woven fabric by electrostatic spinning and cut into test films, which can be used well for the detection of gaseous phosgene. While, there were no reported bio-imaging applications for phosgene detection. In this work, nasal mucosa and lung samples from the mice exposed to gaseous phosgene after dropping the ONB solution through the nasal cavity achieved bio-imaging applications successfully.


Assuntos
Substâncias para a Guerra Química , Fosgênio , Animais , Compostos de Boro , Substâncias para a Guerra Química/toxicidade , Gases/química , Pulmão , Camundongos , Mucosa Nasal , Fosgênio/química , Fosgênio/toxicidade
4.
Comput Intell Neurosci ; 2022: 2743878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619760

RESUMO

Mesenchymal stem cells (MSCs) have promising potential in the treatment of various diseases, such as the therapeutic effect of bone marrow-derived MSCs for phosgene-induced acute lung injury (P-ALI). However, MSC-related therapeutics are limited due to poor cell survival, requiring appropriate MSC delivery systems to maximise therapeutic capacity. Biomaterial RGD-hydrogel is a potential cell delivery vehicle as it can mimic the natural extracellular matrix and provide cell adhesion support. The application of RGD-hydrogel in the MSC treatment of respiratory diseases is scarce. This study reports that RGD-hydrogel has good biocompatibility and can increase the secretion of Angiopoietin-1, hepatocyte growth factor, epidermal growth factor, vascular endothelial cell growth factor, and interleukin-10 in vitro MSCs. The hydrogel-encapsulated MSCs could further alleviate P-ALI and show better cell survival in vivo. Overall, RGD-hydrogel could improve the MSC treatment of P-ALI by modulating cell survival and reparative activities. It is exciting to see more and more ways to unlock the therapeutic potential of MSCs.


Assuntos
Lesão Pulmonar Aguda , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fosgênio , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/terapia , Animais , Medula Óssea/metabolismo , Hidrogéis/efeitos adversos , Hidrogéis/metabolismo , Células-Tronco Mesenquimais/metabolismo , Oligopeptídeos/efeitos adversos , Oligopeptídeos/metabolismo , Fosgênio/metabolismo , Fosgênio/toxicidade , Ratos
5.
Chem Commun (Camb) ; 58(34): 5296-5299, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35403642

RESUMO

Herein, an aggregation-induced emission (AIE)-based sensor, 4-(1,2,2-triphenylvinyl)benzoxime (TPE-phos), has been rationally designed for phosgene detection. The sensor has a tetraphenylethylene unit combined with an oxime moiety. TPE-phos undergoes nitrile formation after the oxime group reacts with phosgene, which will give a significant "light-up" fluorescence due to the AIE effect within seconds.


Assuntos
Fosgênio , Corantes , Oximas , Espectrometria de Fluorescência
6.
Environ Int ; 162: 107152, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35231840

RESUMO

We report on the concentration ranges and combustion source-related emission profiles of organic and inorganic species released during 34 major industrial fires in the UK. These episodic events tend to be acute in nature and demand a rapid public health risk assessment to indicate the likely impact on exposed populations. The objective of this paper is to improve our understanding of the nature, composition and potential health impacts of emissions from major incident fires and so support the risk assessment process. Real world monitoring data was obtained from portable Fourier Transform Infrared (FTIR) monitoring (Gasmet DX-4030/40) carried out as part of the UK's Air Quality in Major Incidents service. The measured substances include carbon monoxide, sulphur dioxide, nitrogen dioxide, ammonia, hydrogen chloride, hydrogen bromide, hydrogen fluoride, hydrogen cyanide, formaldehyde, 1,3-butadiene, benzene, toluene, xylenes, ethyl benzene, acrolein, phosgene, arsine, phosphine and methyl isocyanate. We evaluate the reported concentrations against Acute Exposure Guideline Values (AEGLs) and Emergency Response Planning Guidelines (ERPGs), as well as against UK, EU and WHO short-term ambient guideline values. Most exceedances of AEGL or ERPG guideline values were at levels likely only to cause discomfort to exposed populations (hydrogen cyanide, hydrogen chloride, hydrogen fluoride and formaldehyde), though for several substances the exceedances could have potentially given rise to more serious health effects (acrolein, phosphine, phosgene and methyl isocyanate). In the latter cases, the observed high concentrations are likely to be due to cross-interference from other substances that absorb in the mid-range of the infrared spectrum, particularly when the ground level plume is very concentrated.


Assuntos
Poluentes Atmosféricos , Incêndios , Fosgênio , Acroleína , Poluentes Atmosféricos/análise , Benzeno/análise , Monitoramento Ambiental , Formaldeído , Humanos , Ácido Clorídrico , Hidrogênio
7.
J Cell Mol Med ; 26(10): 2831-2840, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35355403

RESUMO

Phosgene gas leakage can cause life-threatening acute lung injury (ALI), which is characterized by inflammation, increased vascular permeability, pulmonary oedema and oxidative stress. Although the downregulation of neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) is known to be associated with inflammation and oxidative damage, its functions in phosgene-induced ALI remain unclear. In this study, rats with phosgene-induced ALI were intravenously injected with NEDD4-overexpressing lentiviruses to determine the functions of NEDD4 in this inflammatory condition. NEDD4 expression was decreased in the lung parenchyma of phosgene-exposed control rats, whereas its expression level was high in the NEDD4-overexpressing rats. Phosgene exposure increased the wet-to-dry lung weight ratio, but NEDD4 abrogated this effect. NEDD4 overexpression attenuated phosgene-induced lung inflammation, lowering the high lung injury score (based on total protein, inflammatory cells and inflammatory factors in bronchoalveolar lavage fluid) and also reduced phosgene-induced oxidative stress and cell apoptosis. Finally, NEDD4 was found to interact with Notch1, enhancing its ubiquitination and thereby its degradation, thus attenuating the inflammatory responses to ALI. Therefore, we demonstrated that NEDD4 plays a protective role in alleviating phosgene-induced ALI, suggesting that enhancing the effect of NEDD4 may be a new approach for treating phosgene-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Ubiquitina-Proteína Ligases Nedd4 , Fosgênio , Receptor Notch1 , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Inflamação/metabolismo , Pulmão/metabolismo , Ubiquitina-Proteína Ligases Nedd4/genética , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Fosgênio/toxicidade , Ratos , Ratos Sprague-Dawley , Receptor Notch1/genética , Receptor Notch1/metabolismo
8.
Acta Chim Slov ; 69(1): 125-132, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35298020

RESUMO

The use of a cellulose detection film as a carrier for a colorimetric sensor to detect phosgene and allied compounds to be evaluated primarily visually is studied. For the case study, a benzimidazole-rhodamine dye and an acetyl cellulose film were selected. The detection complex was modified using cyclic ether 18-crown-6 to achieve more desirable analytic properties. The chromatic properties of detection film was verified using reflectance colorimetry in the visible light spectrum. The employed detection agent demonstrated high sensibility to phosgene vapours, but acid gases, acyl chlorides, base organic solvents, and in higher concentrations, even some organophosphorus substances interfered. The detection film application was adjusted to the in-situ preparation of simple detection devices (a spray or a marker) as well as to manufacture detection strips with beforehand excluded polymer film.


Assuntos
Éteres de Coroa , Fosgênio , Celulose , Colorimetria , Éter
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 269: 120789, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968834

RESUMO

As a colorless, highly toxic and widely used chemical reagent, phosgene poses a potentially serious threat to public health and environmental safety. Therefore, there is an urgent need to develop a simple and sensitive method for detecting phosgene. In this work, a ratiometric fluorescent probe (NED) for phosgene was developed by utilizing 4-substituted 1,8-naphthimide unit as the fluorophore and ethylenediamine as the recognition moiety. The probe NED undergoes intramolecular cyclization reaction with phosgene, resulting in a remarkable ratiometric fluorescence response. The probe NED displays high sensitivity (LOD = 4.9 nM), excellent ratiometric fluorescence signal, and high selectivity toward phosgene over other relevant analytes. In addition, paper test strip capable of visually detecting gaseous phosgene has also been fabricated.


Assuntos
Fosgênio , Ciclização , Corantes Fluorescentes , Gases , Espectrometria de Fluorescência
10.
Talanta ; 236: 122826, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635216

RESUMO

A new fluorescent probe for ratiometric detection of phosgene is reported. This probe was constructed with classic 1,8-naphthalimide and 2-(2-aminophenyl)benzimidazole by Ullmann coupling reaction. After exposure to phosgene, yellow fluorescence weakened while blue fluorescence enhanced significantly. There was a ratiometric response between 542 nm and 490 nm. The detection limit (LOD) was 6.7 nM and the response time was within 200 s in CHCl3. Meaningfully, a new chromophore, benzo [4,5]imidazo[1,2-c]quinazolin-6(5H)-one, was formed after 2-(2-aminophenyl)benzimidazole unit reacted with phosgene, and the ratiometric response was achieved by two chromophores in which the mechanism was confirmed by 1H NMR spectra, HRMS and theoretical calculation. Furthermore, test papers and nanofibers were fabricated with the probe, which could sensitive detection of phosgene within 10 min and 1 min respectively.


Assuntos
Fosgênio , Corantes Fluorescentes , Naftalimidas , Espectrometria de Fluorescência
11.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 39(10): 733-737, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34727652

RESUMO

Objective: To investigate the changes in kidney and its mechanism during the development of acute phosgene exposure in rats. Methods: Rats were randomized into 2 groups: control and phosgene group (including 1, 3, 6, 12 and 24 h after exposed to phosgene) , 6 rats in each group. Rats in control group were exposed to air for 5 min, while rats in phosgene group were exposed to 8.33 mg/L phosgene for 5 min. The blood samples were collected at 1, 3, 6, 12 and 24 h after phosgene exposure. The blood creatinine (Cr) , urea nitrogen (BUN) and blood gas analysis were detected. HE staining and immunohistochemical staining were performed to observe the expression levels of 8-hydroxy deoxyguanosine and myeloperoxidase. Results: The arterial partial pressure of oxygen and oxygenation index of rats in the phosgene group were significantly lower than those in the control group at 3, 6 and 12 h after exposure (P<0.01) . The lowest points were reached at 6 h, which were (58.67±7.89) mmHg and (202.30±27.20) mmHg, respectively. The Cr and BUN of rats in the phosgene group were significantly higher than those in the control group at 3, 6, 12, and 24 h, and the renal organ coefficients were significantly higher than those in the control group at 3, 6 and 12 h (P<0.01) . HE staining showed that there were more erythrocytes in the glomeruli of rats in the phosgene group, the volume of renal tubular epithelial cells increased, and the cytoplasm was loose and lightly stained. The damage was most obvious at 6 h. The results of immunohistochemical staining showed that the positive expressions of 8-hydroxy deoxyguanosine and myeloperoxidase in the kidney tissue of the phosgene group increased. Conclusion: Hypoxemia and oxidative stress caused by phosgene poisoning may be the cause of renal damage in rats.


Assuntos
Fosgênio , Animais , Nitrogênio da Ureia Sanguínea , Creatinina , Rim , Oxigênio , Fosgênio/toxicidade , Ratos
12.
Chem Biol Interact ; 350: 109654, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34634268

RESUMO

Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents occurred not only due to their use as chemical warfare agents but also because of occupational hazards. Therefore, a clear understanding of these agents and their mode of action is essential to develop effective decontamination and therapeutic strategies. The blister agents have been categorised on the basis of their chemistry and the biological interactions that entail post contamination. These compounds have been known to majorly cause blisters/bullae along with alkylation of the contaminated DNA. However, due to the high toxicity and restricted use, very little research has been conducted and a lot remains to be clearly understood about these compounds. Various decontamination solutions and detection technologies have been developed, which have proven to be effective for their timely mitigation. But a major hurdle seems to be the lack of proper understanding of the toxicological mechanism of action of these compounds. Current review is about the detailed and updated information on physical, chemical and biological aspects of various blister agents. It also illustrates the mechanism of their action, toxicological effects, detection technologies and possible decontamination strategies.


Assuntos
Vesícula/induzido quimicamente , Substâncias para a Guerra Química/química , Substâncias para a Guerra Química/toxicidade , Descontaminação/métodos , Alquilantes/química , Alquilantes/toxicidade , Arsenicais/efeitos adversos , Arsenicais/química , Vesícula/terapia , Substâncias para a Guerra Química/classificação , Olho/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Modelos Biológicos , Compostos de Mostarda/química , Compostos de Mostarda/toxicidade , Oximas/química , Oximas/toxicidade , Fosgênio/química , Fosgênio/toxicidade , Pele/efeitos dos fármacos
13.
Int J Mol Sci ; 22(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34681591

RESUMO

Phosgene (COCl2) was once used as a classic suffocation poison and currently plays an essential role in industrial production. Due to its high toxicity, the problem of poisoning caused by leakage during production, storage, and use cannot be ignored. Phosgene mainly acts on the lungs, causing long-lasting respiratory depression, refractory pulmonary edema, and other related lung injuries, which may cause acute respiratory distress syndrome or even death in severe cases. Due to the high mortality, poor prognosis, and frequent sequelae, targeted therapies for phosgene exposure are needed. However, there is currently no specific antidote for phosgene poisoning. This paper reviews the literature on the mechanism and treatment strategies to explore new ideas for the treatment of phosgene poisoning.


Assuntos
Lesão Pulmonar Aguda/terapia , Fosgênio/toxicidade , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Antioxidantes/uso terapêutico , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Oxigenação por Membrana Extracorpórea , Glucocorticoides/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Estresse Oxidativo/efeitos dos fármacos , Prognóstico , Espécies Reativas de Oxigênio/metabolismo
14.
J Biochem Mol Toxicol ; 35(9): e22851, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34331784

RESUMO

Phosgene may induce acute lung injury (ALI) when a person is exposed to it. Mesenchymal stem cells (MSCs) were affirmed to have therapeutic effects on phosgene-induced ALI. In a previous study, ALI exosomes have been confirmed to promote the proliferation and migration of MSCs. However, the mechanism of this phenomenon is still unclear. MicroRNAs (miRNAs) are essential in the physiological process of cells. In this study, lung-derived exosomes were isolated from phosgene-exposed and normal rats, respectively, through ultracentrifugation and cultured MSCs with these exosomes. We found that rno-miR-34c-3p was downregulated in MSCs cocultured with ALI exosomes. MiR-34c-3p inhibitor promoted the proliferation and migration of MSCs. Moreover, the dual-luciferase reporter assay demonstrated that miR-34c-3p regulated Janus kinase 1 (JAK1) expression. The miR-34c-3p inhibitor also significantly activated the JAK1/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, ALI exosomes decrease the miR-34c-3p expression levels, influencing MSCs via the JAK1/STAT3 signaling pathway.


Assuntos
Exossomos/metabolismo , Lesão Pulmonar/metabolismo , Pulmão/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Fosgênio/toxicidade , Animais , Técnicas de Cocultura , Exossomos/patologia , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Ratos , Ratos Sprague-Dawley
15.
Artigo em Chinês | MEDLINE | ID: mdl-33691364

RESUMO

Objective: To investigate the effect of heat shock protein 60 (HSP60) overexpression on the ability of bone marrow mesenchymal stem cells (MSCs) and its therapeutic effect on rats with phosgene induced acute lung injury. Methods: HSP60 was transfected into MSCs by adenovirus. Western blot was used to measure the expressions of HSP60 before and after transfection. CCK-8 assay was used to detect the activity of MSCs, flow cytometry was used to detect the apoptotic ability of MSCs, and Transwell assay was used to observe the migration ability of MSCs. Sixty SPF grade male SD rats were randomly divided into control group, phosgene exposure group (inhalation of phosgene for 5 min) , MSCs group (phosgene exposure, MSCs treatment group) and transfected MSCs group (phosgene exposure, overexpression of HSP60 MSCs treatment group) . The pathological changes of lung were observed by lung pathological section, lung wet dry ratio, the degree of pulmonary edema, the total cell count and total protein content of alveolar lavage fluid, the inflammatory changes of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF and serum were observed. The data were analyzed by Graphpad Prism 8.0 software. Paired comparisons were performed by non paired t-test. One way ANOVA was used for comparison between groups. Results: The proliferation ability of MSCs transfected with HSP60[A= (0.69±0.05) ] was significantly higher than that of MSCs not transfected with HSP60[A= (0.27±0.02) ] (P<0.05) . Compared with the phosgene exposure group, the pulmonary edema and inflammatory factor infiltration of MSCs group and MSCs transfected group were reduced. However, compared with MSCs group, the degree of pulmonary edema in MSCs transfected group was significantly improved, the levels of inflammatory factors IL-6 and TNF-α were significantly decreased, and the total protein content and total cell count in bronchoalveolar lavage fluid were less (P<0.05) . Conclusion: MSCs transfected with HSP60 can enhance the ability of proliferation, anti apoptosis, migration and the curative effect in rats with phosgene induced acute lung injury.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Fosgênio , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Medula Óssea , Líquido da Lavagem Broncoalveolar , Chaperonina 60 , Pulmão , Masculino , Fosgênio/toxicidade , Ratos , Ratos Sprague-Dawley
16.
Toxicol Mech Methods ; 31(4): 293-307, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33588685

RESUMO

Phosgene is a gas crucial to industrial chemical processes with widespread production (∼1 million tons/year in the USA, 8.5 million tons/year worldwide). Phosgene's high toxicity and physical properties resulted in its use as a chemical warfare agent during the First World War with a designation of CG ('Choky Gas'). The industrial availability of phosgene makes it a compound of concern as a weapon of mass destruction by terrorist organizations. The hydrophobicity of phosgene exacerbates its toxicity often resulting in a delayed toxidrome as the upper airways are moderately irritated; by the time symptoms appear, significant damage has occurred. As the standard of care for phosgene intoxication is supportive therapy, a pressing need for effective therapeutics and treatment regimens exists. Proposed toxicity mechanisms for phosgene based on human and animal exposures are discussed. Whereas intermediary components in the phosgene intoxication pathways are under continued discussion, generation of reactive oxygen species and oxidative stress is a common factor. As animal models are required for the study of phosgene and for FDA approval via the Animal Rule; the status of existing models and their adherence to Haber's Rule is discussed. Finally, we review the continued search for efficacious therapeutics for phosgene intoxication; and present a rapid post-exposure response that places exogenous human heat shock protein 72, in the form of a cell-penetrating fusion protein (Fv-HSP72), into lung tissues to combat apoptosis resulting from oxidative stress. Despite significant progress, additional work is required to advance effective therapeutics for acute phosgene exposure.


Assuntos
Contramedidas Médicas , Animais , Substâncias para a Guerra Química/toxicidade , Humanos , Pulmão/efeitos dos fármacos , Modelos Animais , Fosgênio/toxicidade
17.
Toxicology ; 450: 152682, 2021 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-33484734

RESUMO

Phosgene (carbonyl dichloride) gas is an indispensable high-production-volume chemical intermediate used worldwide in numerous industrial processes. Published evidence of human exposures due to accidents and warfare (World War I) has been reported; however, these reports often lack specificity because of the uncharacterized exposure intensities of phosgene and/or related irritants. These may include liquid or solid congeners of phosgene, including di- and triphosgene and/or the respiratory tract irritant chlorine which are often collectively reported under the umbrella of phosgene exposure without any appreciation of their differences in causing acute lung injury (ALI). Among these irritants, phosgene gas is somewhat unique because of its poor water solubility. This prevents any appreciable retention of the gas in the upper airways and related trigeminal sensations of irritation. By contrast, in the pulmonary compartment, amphiphilic surfactant might scavenge this lipophilic gas. The interaction of phosgene and the surfactant may affect basic physiological functions controlled by Starling's and Laplace's laws, which can be followed by cardiogenic pulmonary edema. The phenotypic manifestations are dependent on the concentration × exposure duration (C × t); the higher the C × t is, the less time that is required for edema to appear. It is hypothesized that this type of edema is caused by cardiovascular and colloid osmotic imbalances to initial neurogenic events but not because of the injury itself. Thus, hemodynamic etiologies appear to cause imbalances in extravasated fluids and solute accumulation in the pulmonary interstitium, which is not drained away by the lymphatic channels of the lung. The most salient associated findings are hemoconcentration and hypoproteinemia. The involved intertwined pathophysiological processes coordinating pulmonary ventilation and cardiopulmonary perfusion under such conditions are complex. Pulmonary arterial catheter measurements on phosgene-exposed dogs provided evidence of 'cor pulmonale', a form of acute right heart failure produced by a sudden increase in resistance to blood flow in the pulmonary circulation about 20 h postexposure. The objective of this review is to critically analyze evidence from experimental inhalation studies in rats and dogs, and evidence from accidental human exposures to better understand the primary and secondary events causing cardiopulmonary dysfunction and an ensuing life-threatening lung edema. Mechanism-based diagnostic and therapeutic approaches are also considered for this form of cardiogenic edema.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Substâncias para a Guerra Química/efeitos adversos , Substâncias para a Guerra Química/toxicidade , Fosgênio/administração & dosagem , Fosgênio/toxicidade , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/terapia , Administração por Inalação , Animais , Humanos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Pressão Propulsora Pulmonar/fisiologia , Respiração Artificial/métodos
18.
Chemistry ; 27(27): 7525-7532, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33496974

RESUMO

Lactams are cyclic amides that are indispensable as drugs and as drug candidates. Conventional lactamization includes acid-mediated and coupling-agent-mediated approaches that suffer from narrow substrate scope, much waste, and/or high cost. Inexpensive, less-wasteful approaches mediated by highly electrophilic reagents are attractive, but there is an imminent risk of side reactions. Herein, a methods using highly electrophilic triphosgene in a microflow reactor that accomplishes rapid (0.5-10 s), mild, inexpensive, and less-wasteful lactamization are described. Methods A and B, which use N-methylmorpholine and N-methylimidazole, respectively, were developed. Various lactams and a cyclic peptide containing acid- and/or heat-labile functional groups were synthesized in good to high yields without the need for tedious purification. Undesired reactions were successfully suppressed, and the risk of handling triphosgene was minimized by the use of microflow technology.


Assuntos
Amidas , Peptídeos , Ácidos Carboxílicos , Lactamas , Fosgênio/análogos & derivados
19.
Biomed Res Int ; 2021: 6278526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506021

RESUMO

Phosgene exposure can cause acute lung injury (ALI), for which there is no currently available effective treatment. Mesenchymal stem cells (MSCs) which have been proven to have therapeutic potential and be helpful in the treatment of various diseases, but the mechanisms underlying the function of MSCs against phosgene-induced ALI are still poorly explored. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in the lung tissues from rats of three groups-air control (group A), phosgene-exposed (group B), and phosgene + MSCs (group C). The results showed that 389 mRNAs, 198 lncRNAs, and 56 circRNAs were differently expressed between groups A and B; 130 mRNAs, 107 lncRNAs, and 35 circRNAs between groups A and C; and 41 mRNAs, 88 lncRNAs, and 18 circRNAs between groups B and C. GO and KEGG analyses indicated that the differentially expressed RNAs were mainly involved in signal transduction, immune system processes, and cancers. In addition, we used a database to predict target microRNAs (miRNAs) interacting with circRNAs and the R network software package to construct a circRNA-targeted miRNA gene network map. Our study showed new insights into changes in the RNA expression in ALI, contributing to explore the mechanisms underlying the therapeutic potential of MSCs in phosgene-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Pulmão , Fosgênio/efeitos adversos , Transcriptoma , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Modelos Animais de Doenças , Pulmão/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Células-Tronco Mesenquimais/fisiologia , RNA/análise , RNA/genética , RNA/metabolismo , Ratos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
20.
Nucl Med Biol ; 92: 138-148, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32546396

RESUMO

Carbon-11-labeled phosgene ([11C]phosgene, [11C]COCl2) is a useful labeling agent that connects two heteroatoms by inserting [11C]carbonyl (11C=O) function in carbamates, ureas, and carbonates, which are components of biologically important heterocyclic compounds and functional groups in drugs as a linker of fragments with in vivo stability. Development of 11C-labeled PET tracers has been performed using [11C]phosgene as a labeling agent. However, [11C]phosgene has not been frequently used for 11C-labeling because preparation of [11C]phosgene required dedicated synthesis apparatus (not commercially available) and had problems in reproducibility and reliability. In our laboratory, an improved method for synthesizing [11C]phosgene using a carbon tetrachloride detection tube kit in environmental air analysis and the automated synthesis system for preparing [11C]phosgene have been developed in 2009. This apparatus has been used for routine synthesis of 11C-labeled tracers 1-4 times/week. Using [11C]phosgene we have developed and produced many PET radiotracers containing [11C]urea and [11C]carbamate moieties. In this review, we report the performance of our method for preparing [11C]phosgene, including automated synthesis apparatus developed in house, and the application of [11C]phosgene for development and production of 11C-labeled PET tracers.


Assuntos
Radioisótopos de Carbono , Fosgênio/síntese química , Tomografia por Emissão de Pósitrons/métodos , Animais , Humanos , Fosgênio/química , Traçadores Radioativos
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