Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.

We assessed the mechanisms by which nonencapsulated heme, released in the plasma of mice after exposure to chlorine (Cl2) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult male and female C57BL/6 mice to Cl2 (500 ppm for 30 min), returned them to room air, and injected them intramuscularly with either human hemopexin (hHPX; 5 µg/g BW in 50-µL saline) or vehicle at 1 h post-exposure. Upon return to room air, Cl2-exposed mice, injected with vehicle, developed respiratory acidosis, increased concentrations of plasma proteins in the alveolar space, lung mitochondrial DNA injury, increased levels of free plasma heme, and major alterations of their lung proteome. hHPX injection mice mitigated the onset and development of lung and mitochondrial injury and the increase of plasma heme, reversed the Cl2-induced changes in 83 of 237 proteins in the lung proteome at 24 h post-exposure, and improved survival at 15 days post-exposure. Systems biology analysis of the lung global proteomics data showed that hHPX reversed changes in a number of key pathways including elF2 signaling, verified by Western blotting measurements. Recombinant human hemopexin, generated in tobacco plants, injected at 1 h post-Cl2 exposure, was equally effective in reversing acute lung and mtDNA injury. The results of this study offer new insights as to the mechanisms by which exposure to Cl2 results in acute lung injury and the therapeutic effects of hemopexin.NEW & NOTEWORTHY Herein, we demonstrate that exposure of mice to chlorine gas causes significant changes in the lung proteome 24 h post-exposure. Systems biology analysis of the proteomic data is consistent with damage to mitochondria and activation of eIF2, the master regulator of transcription and protein translation. Post-exposure injection of hemopexin, which scavenges free heme, attenuated mtDNA injury, eIF2α phosphorylation, decreased lung injury, and increased survival.

Chlorine gas hazardous material incident in Karachi, Pakistan: A clinical experience from an emergency department of a tertiary care hospital.

OBJECTIVE: To determine the clinical characteristics, management and outcomes of patients presenting with chlorine gas exposure in an emergency setting. METHODS: The single-centre, retrospective cross-sectional study was conducted at the emergency department of Aga Khan University Hospital, Karachi, and comprised data of all patients who presented on March 06, 2020, due to acute chlorine gas exposure after a specific industrial accident. Demographic and clinical data was recorded from the medical record files. The association between risk factors and complications was explored. Data was analysed using SPSS 20. RESULTS: There were 51 male patients with a mean age of 33.10±8.37 years. The most commonly affected organ system was respiratory 49(96%), with 43(84.3) having shortness of breath. Eye irritation was found in 44(86.3%) cases and the central nervous system was involved in 14(27.4%). Most of the patients were admitted from the emergency department 36(70%). Regarding treatment, 1(1.9%) patient each required invasive and non-invasive mechanical ventilation. Complications included toxic pneumonitis 3(5.9%) and pneumomediastinum 1(1.7%). No correlation was found between smoking and complications (p>0.05). CONCLUSIONS: Most patients showed complete resolution of symptoms after receiving supportive treatment, while complications were rare and there was no mortality.

Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis.

To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl2-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl2, Cl2+Fer-1, Cl2+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell-cell communication analysis identified several important receptor-ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p < 0.05). This study revealed novel molecular features of Cl2-induced ALI. PTX may be a potential specific drug by inhibiting the process of ferroptosis in epithelial and endothelial cells.

Tinción dental por cloro / Chlorine`s dental stain

Las manchas dentales son motivo frecuente de preocupación por parte de las familias. Aunque en general se trata de patologías estéticas, algunos casos precisan tratamiento adecuado y eficaz. Por este motivo, es importante conocer las posibles etiologías con el fin de poder prevenirlas y tratarlas si es necesario. Las manchas dentales más frecuentes son las manchas cromógenas, manchas postraumáticas y las secundarias a caries dentales. Sin embargo, existen también otros motivos menos comunes a tener en cuenta, como la afectación dental por cloro. Esta patología es de especial interés, ya que puede pasar desapercibida si no realizamos una buena historia clínica (AU)

Dental stains are a common cause of concern for families. Although in general it is about aesthetic pathologies, it is important to know the possible causes that can lead to an adequate and effective treatment, as well as future prevention.The most frequent stains are black stains, post-trauma stains and dental caries. However, there are also other less common reasons to take into account, such as dental damage caused by chlorine. This pathology is of special interest, since it can go unnoticed if we do not take a good clinical history. (AU)

Lessons Learned From a Chlorine Gas Leakage in Dezful City, Iran.

Dezful is the capital of Dezful County, a city in Khuzestan Province, Iran. On August 12, 2017, after a chlorine gas leakage in Dezful, more than 475 people were affected by chlorine gas, and they all suffered from respiratory complications. A lot of problems were encountered in the preparation of the relief forces and organization of the blueprint on how to respond to the incident, such as lack of knowledge on establishment of danger zone, lack of warning system, lack of proper triage and absence of decontamination plans, lack of special chemical safety outfit and respiratory equipment for rescuers, lack of instructions for proper handling, lack of knowledge in dealing with this type of disaster, and inappropriate evacuation skills and failure to cordon off and insure the location of the incident. Although the initial measures to arrest this crisis was performed based on the health system's instructions of the country with regard to all the possible risks, lack of a comprehensive inter-organizational program and prevention plans, lack of control plans, lack of adequate preparation and response to chemical poisoning, lack of foresight, lack of a risk plan, and lack of an intervention plan for these incidents were the reasons for the damages and problems encountered after the crisis.

Health effects of exposure to chlorination by-products in swimming pools.

Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since some have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming pools (water ingestion, skin absorption, and inhalation) contribute to the individual exposome. Some CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated pools as customers, particularly children, may also be affected has been a matter of debate. In this article, we discuss the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports, and recreational attendance) and identify the main recommendations and unmet needs for research in this area.

Low-dose chlorine exposure impairs lung function, inflammation and oxidative stress in mice.

AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1ß, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1ß and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1ß, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1ß and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.

Changes in spirometric parameters after protective interventions among workers at a chlorine production plant in Iran.

OBJECTIVES: This study was conducted to assess changes in spirometric parameters after protective interventions among workers at a chlorine production plant in Semnan, Iran during 2012-2016. METHODS: This quasi-experimental study included 100 workers at a chlorine production plant in Semnan during 2012-2016. Spirometric parameters (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], FEV1/FVC, peak expiratory flow [PEF], and PEF occurring in the middle 50% of the patient's exhaled volume [PEF 25-75%]) were measured in all workers before the initial intervention in 2012. Protective interventions were then implemented for 4 consecutive years and the parameters were measured annually. A multivariable linear regression model was used to assess the factors affecting spirometric parameters before and after the protective interventions in SPSS version 24. RESULTS: The mean values of all spirometric parameters significantly increased after the protective interventions (p<0.05). Multivariable linear regression showed that age (ß=-0.40), body mass index (BMI) (ß=0.71; 95% confidence interval [CI], 0.11 to 1.31), and type of mask (ß=-7.88; 95% CI, -15.96 to -0.46) had significant effects on the mean difference in FVC. Similarly, age (ß=-0.35; 95% CI, -0.70 to -0.01), BMI (ß=0.80; 95% CI, 0.20 to 1.41) and type of mask (ß=-8.88; 95% CI, -16.98 to -0.79) had significant associations with the mean difference in FEV1. The type of mask (ß=-12.81; 95% CI, -25.01 to -0.60) had a significant effect on the mean difference in PEF. CONCLUSIONS: All spirometric parameters significantly increased in workers after protective interventions were implemented. Therefore, protective interventions to prevent respiratory disorders in workers exposed to chlorine gas are suggested.

Successful use of extracorporeal membrane oxygenation in acute respiratory distress syndrome following accidental chlorine gas inhalation at a swimming pool.

While there is evidence to support the use of extracorporeal membrane oxygenation in acute respiratory distress syndrome due to a variety of causes, its use in chlorine gas-induced acute respiratory distress syndrome has not been described in the English medical literature. We present a young girl who had severe acute respiratory distress syndrome following exposure to chlorine gas during the disinfection process at a swimming pool. She failed conventional management and underwent venovenous extracorporeal membrane oxygenation. Despite multiple infections and a pneumothorax, she eventually recovered. Chlorine gas was the first agent of chemical warfare which caused a massive death toll during the First World War. Even today, the chemical is produced in large quantities and the threat of a large-scale leak is ever-present from industrial accidents or terrorist attacks. The criteria to assess and manage chlorine gas-induced acute respiratory distress syndrome are likely to be the same as for other causes of acute respiratory distress syndrome and extracorporeal membrane oxygenation can be used successfully.

The influence of chlorine in indoor swimming pools on the composition of breathing phase of professional swimmers.

OBJECTIVES: Swimming is one of the most popular forms of physical activity. Pool water is cleaned with chlorine, which - in combination with compounds contained in water - could form chloramines and trichloromethane in the swimmer's lungs. The aim of the present study was to examine the effect of swimming training in an indoor pool on the composition of swimmers' respiratory phase metabolomics, and develop a system to provide basic information about its impact on the swimmer's airway mucosa metabolism, which could help to assess the risk of secondary respiratory tract diseases i.e. sport results, condition, and health including lung acute and chronic diseases). DESIGN: A group of competitive swimmers participated in the study and samples of their respiratory phase before training, immediately after training, and 2 h after training were assessed. METHODS: Sixteen male national and international-level competitive swimmers participated in this study. Respiratory phase analysis of the indoor swimming pool swimmers was performed. Gas chromatography combined with mass spectrometry (GCMS) was used in the measurements. All collected data were transferred to numerical analysis for trends of tracking and mapping. The breathing phase was collected on special porous material and analyzed using GCMS headspace. RESULTS: The obtained samples of exhaled air were composed of significantly different metabolomics when compared before, during and after exercise training. This suggests that exposition to indoor chlorine causes changes in the airway mucosa. CONCLUSION: This phenomenon may be explained by occurrence of a chlorine-initiated bio-reaction in the swimmers' lungs. The obtained results indicate that chromatographic exhaled gas analysis is a sensitive method of pulmonary metabolomic changes assessment. Presented analysis of swimmers exhaled air indicates, that indoor swimming may be responsible for airway irritation caused by volatile chlorine compounds and their influence on lung metabolism.

Metabolic Insights into the Anion-Anion Antagonism in Sweet Basil: Effects of Different Nitrate/Chloride Ratios in the Nutrient Solution.

Sweet basil (Ocimum basilicum L.) is a highly versatile and globally popular culinary herb, and a rich source of aromatic and bioactive compounds. Particularly for leafy vegetables, nutrient management allows a more efficient and sustainable improvement of crop yield and quality. In this work, we investigated the effects of balanced modulation of the concentration of two antagonist anions (nitrate and chlorine) in basil. Specifically, we evaluated the changes in yield and leaf metabolic profiles in response to four different NO3-:Cl- ratios in two consecutive harvests, using a full factorial design. Our work indicated that the variation of the nitrate-chloride ratio exerts a large effect on both metabolomic profile and yield in basil, which cannot be fully explained only by an anion-anion antagonist outcome. The metabolomic reprogramming involved different biochemical classes of compounds, with distinctive traits as a function of the different nutrient ratios. Such changes involved not only a response to nutrients availability, but also to redox imbalance and oxidative stress. A network of signaling compounds, including NO and phytohormones, underlined the modeling of metabolomic signatures. Our work highlighted the potential and the magnitude of the effect of nutrient solution management in basil and provided an advancement towards understanding the metabolic response to anion antagonism in plants.

Antibiogram and beta-lactamase genes among cefotaxime resistant E. coli from wastewater treatment plant.

BACKGROUND: The World Health Organization (WHO) recently classified Enterobacteriaceae resistance to third-generation cephalosporin into the group of pathogens with critical criteria for future research. METHODS: A study to assess the antibiogram and beta-lactamase genes among the cefotaxime resistant E. coli (CREc) from a South African wastewater treatment plant (WWTP) was conducted using standard phenotypic and molecular biology characterization methods. RESULTS: Approximate total E. coli (TEc) concentration (log10 CFU/mL) ranged between 5.7 and 6.8 among which cefotaxime resistant E. coli were between 1.8 and 4.8 (log10 CFU/mL) for cefotaxime antibiotic concentration of 4 and 8 mg/L in the influent samples. Effluent samples, heavily influenced by the chlorination had only 0.3 log10 CFU/mL of TEc. Fifty-one cefotaxime resistant isolates were selected out of an overall of 75 isolates, and subjected to a new round of testing, with a follow up of 36 and 48 isolates for both colistin and gentamicin, respectively as guided by initial results. Selected CREc exhibited resistance to amoxicillin-clavulanic acid (35.3%; n = 51), colistin sulphate (76.5%; n = 36), ciprofloxacin (47.1%; n = 51), gentamicin (87.5%; n = 48) and intermediate-resistance to meropenem (11.8%; n = 51). Extended spectrum-beta-lactamase genes detected, viz.: blaCTX-M (52.6%; n = 38) and blaTEM (84.2%; n = 38) and concurrent blaCTX-M + blaTEM (36.8%; n = 38), but no blaSHV was detected. Carbapenem resistance genes, blaKPC-2 (15.8%; n = 38), blaOXA-1 (57.9%; n = 38), blaNDM-1 (15.8%; n = 38) were also detected. Approximately, 10.5 - 36.8% (n = 38) co-occurrence of two or more beta-lactamase genes was detected in some isolates. Out of the selected number (n = 30), 7(23.3%) were enterotoxigenic E. coli (ETEC), 14 (46.7%) were Enteroaggregative E. coli (EAEC), but no enteropathogenic E. coli (EPEC) was detected. CONCLUSION: Resistance to cefotaxime and the presence of a wide range of beta-lactamase genes exposed the potential risks associated with these pathogens via occupational and domestic exposure during the reuse of treated wastewater.

The introduction of gas warfare and its medical response in world war one.

The introduction of gas warfare in World War One was impactful, as it both expanded the breadth of warfare and fueled the invention of techniques required to treat these new injuries. Gas injuries were responsible for 91,000 of 1.3 million deaths in World War One. Gassed soldiers had wounds which the world had never seen. They presented in large scale to medical tents and base hospitals across Europe. As gas casualties poured in, doctors and nurses had to treat these conditions in the best way they knew. Gas warfare changed how war was performed and how casualties of this attack were treated. The techniques learned from treating the multitudes of men with gas burns led to advances in the field of burn care, which have helped to improve mortality and reduce morbidity in hospitals across the world.

Occupational and work-related respiratory disease attributed to cleaning products.

OBJECTIVES: Exposure to cleaning products has been associated with adverse respiratory outcomes. This study aimed to investigate the medically reported incidence, trends in incidence and occupational determinants of work-related respiratory disorders attributed to cleaning agents and to explore the role of 'Quantitative Structure Activity Relationships' (QSAR) in corroborating the identification of chemical respiratory sensitisers. METHODS: Respiratory diagnoses attributed to cleaning agents were extracted from The Health and Occupation Research (THOR) surveillance network, 1989-2017. Incidence, trends in incidence and incidence rate ratios by occupation were investigated. Agents were classified by chemical type and QSAR hazard indices were determined for specific organic chemicals. RESULTS: Approximately 6% (779 cases) of the (non-asbestos) THOR respiratory cases were attributed to cleaning agents. Diagnoses were predominantly asthma (58%) and inhalation accidents (27%) with frequently reported chemical categories being aldehydes (30%) and chlorine/its releasers (26%). No significant trend in asthma incidence (1999-2017) was observed (annual average change of -1.1% (95% CI -4.4 to 2.4)). This contrasted with a statistically significant annual decline in asthma incidence (-6.8% (95% CI -8.0 to -5.6)) for non-cleaning agents. There was a large variation in risk between occupations. 7 of the 15 organic chemicals specifically identified had a QSAR generated hazard index consistent with being a respiratory sensitiser. CONCLUSION: Specific occupations appear to be at increased risk of adverse respiratory outcomes attributed to cleaning agents. While exposure to agents such as glutaraldehyde have been addressed, other exposures, such as to chlorine, remain important. Chemical features of the cleaning agents helped distinguish between sensitising and irritant agents.

Exhaled nitric oxide as a marker of chlorine exposure in young asthmatic swimmers.

BACKGROUND: Swimming is recommended for people with asthma. However, the inevitable exposure to chlorine and its disinfectant byproducts in indoor swimming pools could be responsible for bronchial inflammation and asthma development. Fractional exhaled nitric oxide (FeNO) is a noninvasive marker of airway inflammation that predicts asthma exacerbations. OBJECTIVES: To evaluate pretraining and posttraining FeNO levels in young swimmers with asthma attending an indoor chlorinated pool compared with a set of healthy swimmers and to examine the potential risk of exposure to chlorine as a factor associated with bronchial inflammation. METHODS: A total of 146 children (8-18 years old) constantly attending an indoor chlorinated swimming pool were enrolled. Spirometry and FeNO measurements were performed 30 minutes after their arrival at the pool and immediately after exercise. Pre-exercise and postexercise spirometric and FeNO levels were assessed in a random subgroup of 14 swimmers (10 with asthma and 4 without) who performed cardiopulmonary exercise testing. RESULTS: Asthma was detected in 23 swimmers. In swimmers with asthma, preswimming FeNO values were significantly elevated compared with swimmers without asthma and their FeNO values measured before cardiopulmonary exercise testing. Postexercise FeNO values were significantly decreased by approximately one-third in healthy children and children with asthma in all sporting backgrounds. However, postswimming FeNO values remained significantly higher in swimmers with asthma compared with those without asthma. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio values showed no significant difference before and after 2 types of activity. CONCLUSION: Elevated FeNO levels before and after swimming were recorded in swimmers with asthma not observed in a different exercise field. The presence of chlorine in the indoor swimming pool seems to explain this finding.

Impact of low dose chlorine inhalation in healthy humans: a pilot study

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Influence of chlorinated water on the development of allergic diseases - An overview.

Indoor swimming pools can be used all year round and serve for one of the most popular sport pursued for recreation. The positive effect of swimming arises in particular from the involvement of all the muscles of the body, decreasing the burden on the joints, as well as functional improvement of both the lungs and heart. Chlorine is typically used to disinfect swimming pool water and as a result the changes that take place lead to the formation of by-products, such as monochloramines (NH2Cl), dichloramines (NH2Cl2) i trichloramines (NH2Cl3), trihalogenometans (THM) or haloacetic acid (HAA). The highest concentration of these substances is just above the water surface and they may cause irritation of skin, eyes and mucosa of the respiratory tract. The toxic effect of high chlorine concentration and its side-products on the respiratory system is known, but the effect of low concentrations of these compounds is still not fully determined. Recent studies suggest that development of allergic diseases among swimmers may be increased by epithelial disorders driven by airway barrier dysfunction caused by chlorine irritation. Swimming in chlorinated water may be linked to symptoms of bronchial hyperreactivity, asthma and rhinitis especially in children, elite swimmers and employees of indoor swimming pools. Hypersensivity pneumonitis related to the use of swimming pools may manifest as a swimming pool or sauna user lung, most commonly caused by water polluting pathogens. The article summarizes recent data concerning the influence of chlorinated water on the development of allergic diseases.

Inhalation Injury and Toxic Industrial Chemical Exposure.

Toxic industrial chemicals include chlorine, phosgene, hydrogen sulfide, and ammonia have variable effects on the respiratory tract, and maybe seen alone or in combination, secondary to inhalation injury. Other considerations include the effects of cyanide, carbon monoxide, and fire suppressants. This Clinical Practice Guideline (CPG) will provide the reader with a brief overview of these important topics and general management strategies for each as well as for inhalation injury. Chlorine, phosgene, hydrogen sulfide, and ammonia are either of intermediate or high water solubility leading to immediate reactions with mucous membranes of the face, throat, and lungs and rapid symptoms onset after exposure. The exception to rapid symptom onset is phosgene which may take up to a day to develop severe acute respiratory distress syndrome. Management of these patients includes early airway management, lung-protective ventilator strategies, aggressive pulmonary toilet, and avoidance of volume overload.