Mitigation potential of global ammonia emissions and related health impacts in the trade network.

Ammonia (NH3) emissions, mainly from agricultural sources, generate substantial health damage due to the adverse effects on air quality. NH3 emission reduction strategies are still far from being effective. In particular, a growing trade network in this era of globalization offers untapped emission mitigation potential that has been overlooked. Here we show that about one-fourth of global agricultural NH3 emissions in 2012 are trade-related. Globally they induce 61 thousand PM2.5-related premature mortalities, with 25 thousand deaths associated with crop cultivation and 36 thousand deaths with livestock production. The trade-related health damage network is regionally integrated and can be characterized by three trading communities. Thus, effective cooperation within trade-dependent communities will achieve considerable NH3 emission reductions allowed by technological advancements and trade structure adjustments. Identification of regional communities from network analysis offers a new perspective on addressing NH3 emissions and is also applicable to agricultural greenhouse gas emissions mitigation.

Estructura organizacional del policlínico Julián Grimau para la respuesta médica ante emergencias químicas por amoníaco / Organizational structure of Julián Grimau polyclinic for medical response to chemical emergencies by ammonia

Introducción: El amoníaco constituye riesgo de emergencia química en el Policlínico Docente Julián Grimau del municipio Arroyo Naranjo, lo que hace necesario asumir una estructura organizacional que viabilice la respuesta médica frente a este tipo de eventos. Objetivo: Diseñar una propuesta de estructura organizacional del policlínico Julián Grimau para la respuesta médica ante emergencias químicas por amoníaco. Métodos: Se realizó una investigación en sistemas y servicios de salud, entre septiembre de 2017 y diciembre de 2018, en el Policlínico Docente Julián Grimau. Se analizaron documentos relacionados con las acciones médicas en las emergencias químicas en la atención primaria de salud. Se empleó el método sistémico estructural-funcional para diseñar la estructura organizacional, y el informante clave para su concreción. Resultados: Se propone una estructura organizacional de la respuesta médica a emergencias químicas por amoníaco en el Policlínico Docente Julián Grimau que se conformó por nueve áreas: punto de recepción (1), tratamiento especial (2), clasificación (3), tratamiento de urgencia al intoxicado grave (4), tratamiento de urgencia al intoxicado leve (5), aseguramiento al diagnóstico (6), aseguramiento médico material (7), el área de fallecidos (8) y asintomáticos (9). Conclusiones: La estructura organizacional de la respuesta médica a emergencias químicas por amoníaco en el Policlínico Docente Julián Grimau quedó conformada en áreas con sustento en los principios clínicos, evolutivos y de tratamiento del paciente intoxicado agudo, donde se aprovechan las potencialidades orgánicas y funcionales de la institución. Se caracteriza por ser sistémica, flexible, objetiva, participativa, oportuna, adecuada y selectiva(AU)

Introduction: At Julián Grimau Teaching Polyclinic in Arroyo Naranjo municipality, ammonia is a risk of chemical emergency. Hence, it is necessary for the medical response to these situations to implement an organizational structure. Objective: Design a proposal of organizational structure in Julián Grimau Polyclinic for the medical response to chemical emergency by ammonia. Methods: A research was carried out on health systems and services, from September 2017 to December 2018, in Julián Grimau Teaching Polyclinic. A documentary analysis related to medical actions in chemical emergencies was conducted in primary health care's level. In addition, the following methods were used: structural-functional system for the design of the organizational structure and the key informant for its concretion. Result: It is proposed an organizational structure of the medical response to chemical emergencies by ammonia in the Polyclinic, that was formed by nine areas: reception point (1), special treatment (2), classification (3), emergency treatment to severe poisoned patient (4), emergency treatment to slightly poisoned patient (5), logistics for the diagnosis (6), medical-material logistics (7), deceased´s area (8), and asymptomatic patients (9). Conclusions: The organizational structure of the medical response to chemical emergencies by ammonia in Julián Grimau Teaching Polyclinic was formed of areas secured by principles of clinical, evolutive and of acute poisoned patient´s treatment where the organic and functional potentials of the institution are seized. Hence, this proposal is flexible, objective, participatory, timely, adequate and selective(AU)

Geospatial correlation between COVID-19 health misinformation and poisoning with household cleaners in the Greater Boston Area.

INTRODUCTION: Calls to poison control about exposure to household cleaners have increased during the COVID-19 pandemic. This dynamic may reflect increased exposure from public health efforts as well as health misinformation shared on social media. METHODS: We analyzed the dynamics of calls to the Regional Center for Poison Control and Prevention serving Massachusetts and Rhode Island (MARI PCC) and tweets discussing treating COVID-19 with house cleaners from January 20, 2020 to May 5, 2020. We obtained publicly available tweets discussing the use of household cleaners to "cure COVID" from the same time period with geographic co-ordinates indicating that they were emitted from the Greater Boston Area. RESULTS: Our main finding is that public health efforts were followed by a sustained increase in calls after March 15, 2020 (10 ± 2 calls per day before to 15 ± 2.5 after) while misinformation on social media was associated with intermittent spikes in calls. Overall, calls significantly increased during the study period by 34% as compared to the previous 8 years, mostly reporting unintentional ingestions with no serious effects. The daily volume of tweets and retweets was significantly correlated with daily call rates to MARI PCC for the surrounding 7-10 days. CONCLUSIONS: Health misinformation on social media about using household cleaning agents to treat COVID-19 and public health efforts lead to different dynamics in PCC calls. Public health efforts were followed by a sustained increase in calls after March 15, 2020 while misinformation on social media was followed by intermittent spikes in calls. This analysis is the first to link the geospatial dynamics of social media and public health interventions to poison center calls about exposure to household cleaners.

Acute ammonia poisoning in dolly varden char (Salvelinus malma) and effect of methionine sulfoximine.

Ammonia is toxic to most bony fishes. However, little information is available on the toxicology mechanisms induced by ammonia and the means to mitigate the effects by various fishes. In this study, four groups of experiments were designed and carried out to test the response of dolly varden char to ammonia toxicity and their mitigation through methionine sulfoximine (MSO). NaCl group was injected with NaCl, NH3 group was injected with ammonium acetate, NH3+MSO group was injected with ammonium acetate and MSO, MSO group was injected with MSO. Results showed that ammonia toxicity could lead to blood deterioration (elevation in white blood cell and blood ammonia), free amino acid imbalance (elevation in glutamine, glutamate, arginine and ornithine, coupled with reduction of citrulline and aspartate), ammonia metabolism enzyme activity inhibition (reduction in carbamyl phosphate synthetase, ornithine transcarbamylase and arginase), oxidative stress (reduction in superoxide dismutase, catalase and glutathione peroxidase) and immunosuppression (reduction in lysozyme, 50% hemolytic complement, total immunoglobulin and phagocytic index), but the MSO can eliminate fatal effect of oxidative damage. In addition, ammonia poisoning could induce down-regulation of antioxidant enzymes coding genes (SOD, CAT and GPx) and up-regulation of inflammatory cytokine genes (TNFα, IL-1ß and IL-8) transcription, suggesting that immunosuppression and inflammation may relate to oxidative stress in fish.

Ammonia toxicity in the yellow catfish (Pelteobagrus fulvidraco): The mechanistic insight from physiological detoxification to poisoning.

Ammonia is toxic to fishes. Different fish have different defense strategies against ammonia, so the mechanism of ammonia poisoning is different. In this study, yellow catfish were exposed to three levels of ammonia (0, 5.70 and 57.00 mg L-1) for 96 h. The results showed that ammonia poisoning could lead to free amino acid imbalance (ornithine and citrulline contents declined; arginine content elevated), urea cycle enzymes deficiency (carbamyl phosphate synthetase and arginase contents declined), oxidative stress (superoxide dismutase, catalase and glutathione peroxidase activities declined), immunosuppression (lysozyme activity, 50% hemolytic complement and total immunoglobulin contents and phagocytic index declined) and cytokines release (TNF, IL 1 and IL 8 contents elevated). In addition, ammonia poisoning could induce up-regulation of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, CAT and GPx), cytokines (TNFα, IL 1 and IL 8) and apoptosis (p53, Bax, cytochrome c, Caspase 3 and Caspase 9) genes transcription. This study suggesting that the urea cycle and glutamine synthesis both were involved in the ammonia detoxification of yellow catfish, and the immunosuppression, inflammation and apoptotic induced by ammonia poisoning in yellow catfish are related to oxidative stress.

miR-187-5p/apaf-1 axis was involved in oxidative stress-mediated apoptosis caused by ammonia via mitochondrial pathway in chicken livers.

Ammonia (NH3), a toxic gas, is an important cause of atmospheric haze and one of the main pollutants in air environment of poultry houses, threatening the health of human beings and poultry. However, little is known about the effect of NH3 on liver apoptotic damage. This study aimed to investigate the mechanism of oxidative stress-mediated apoptosis caused by NH3 in chicken livers and whether miR-187-5p/apaf-1 axis was involved in this mechanism. Here we duplicated NH3 poisoning model of chickens for fattening to study the ultrastructure of chicken livers, apoptosis rate, oxidative stress indexes, miR-187-5p, and apoptosis-related genes. Obvious apoptotic characteristics of liver tissues exposed to excess NH3 were observed, and the apoptosis rate increased. Excess NH3 decreased the activities of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px), and increased the content of malondialdehyde (MDA), suggesting that oxidative stress occurred. miR-187-5p decreased, and apoptotic protease activating factor-1 (apaf-1) increased, indicating that excess NH3 dysregulated miR-187-5p/apaf-1 axis. The expression of tumor protein p53 (p53), Bcl-2 associated X protein (Bax), Bcl-2 homologous antagonist/killer (Bak), Cytochrome-c (Cyt-c), Caspase-9, Caspase-8, and Caspase-3 was promoted, and the expression of B-cell lymphoma-2 (Bcl-2) was inhibited, resulting in apoptosis. Moreover, oxidative stress indexes, miR-187-5p, and apoptosis-related genes changed in dose- and time-dependent manner. Altogether, miR-187-5p/apaf-1 axis participated in oxidative stress-mediated apoptosis caused by NH3 via mitochondrial pathway in the livers of chickens for fattening. This study may provide new ideas to study the mechanism of liver apoptotic damage induced by NH3 exposure.

[Application of extracorporeal membrane oxygenation technique in patients with acute respiratory failure caused by ammonia poisoning].

OBJECTIVE: Acute severe ammonia inhalation can seriously affect oxygenation and ventilation function of patients, and even cause acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) technology is increasingly used in treating patients with ARDS caused by infection, cardiogenic shock, trauma, and drowning with achieved certain effects, but its usage for ARDS caused by ammonia is rarely reported. On July 7, 2018, a case of ARDS caused by ammonia inhalation was admitted to the emergency ICU of the First Affiliated Hospital of Zhengzhou University. After admission, the patient was treated with ECMO immediately on the basis of anti-infection, anti-oxidation, suctioning and nebulization treatments. After 8 days, he was weaned from ECMO and transferred to a general ward for continued rehabilitation. After 23 days, his condition improved and was discharged without complaining of any discomfort during the follow-up till March 2019. The successful experience was summarized in order to provide reference for the treatment of such patients in the future.

Effects of branched-chain amino acids on muscles under hyperammonemic conditions.

The aim was to determine the effects of enhanced availability of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) on ammonia detoxification to glutamine (GLN) and protein metabolism in two types of skeletal muscle under hyperammonemic conditions. Isolated soleus (SOL, slow-twitch) and extensor digitorum longus (EDL, fast-twitch) muscles from the left leg of white rats were incubated in a medium with 1 mM ammonia (NH3 group), BCAAs at four times the concentration of the controls (BCAA group) or high levels of both ammonia and BCAA (NH3 + BCAA group). The muscles from the right leg were incubated in basal medium and served as paired controls. L-[1-14C]leucine was used to estimate protein synthesis and leucine oxidation, and 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. We observed decreased protein synthesis and glutamate and α-ketoglutarate (α-KG) levels and increased leucine oxidation, GLN levels, and GLN release into medium in muscles in NH3 group. Increased leucine oxidation, release of branched-chain keto acids and GLN into incubation medium, and protein synthesis in EDL were observed in muscles in the BCAA group. The addition of BCAAs to medium eliminated the adverse effects of ammonia on protein synthesis and adjusted the decrease in α-KG found in the NH3 group. We conclude that (i) high levels of ammonia impair protein synthesis, activate BCAA catabolism, enhance GLN synthesis, and decrease glutamate and α-KG levels and (ii) increased BCAA availability enhances GLN release from muscles and attenuates the adverse effects of ammonia on protein synthesis and decrease in α-KG.

Cough and expiration reflexes elicited by inhaled irritant gases are intensified in ovalbumin-sensitized mice.

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO2; 200 and 400 ppm) or ammonia (NH3; 0.1% and 0.2%) was drawn into the chamber at a constant flow rate for 8 min. Ova sensitization and sham sensitization with vehicle (Veh) were performed over a 25-day period in separate groups of mice. Our results showed that 1) both SO2 and NH3 inhalation challenges increased CR and ER frequencies in a concentration-dependent manner before Ova sensitization; 2) the baseline CR frequency was significantly elevated after Ova sensitization, accompanied by pronounced airway inflammation; and 3) Ova sensitization also markedly augmented the responses of CR and ER to both SO2 and NH3 inhalation challenges; in sharp contrast, the cough responses did not change after sham sensitization in the Veh group. In conclusion, Ova sensitization caused distinct and lingering increases in baseline cough frequency, and also intensified both CR and ER responses to inhaled irritant gases, which probably resulted from an allergic inflammation-induced hypersensitivity of airway sensory nerves.

Relationship between oxidative stress and brain swelling in goldfish (Carassius auratus) exposed to high environmental ammonia.

Buildups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). We investigated brain swelling and its possible relationship to oxidative stress in the brain and liver of goldfish acutely exposed to high external ammonia (HEA; 5 mmol/l NH4Cl) at two different acclimation temperatures (14°C, 4°C). Exposure to HEA at 14°C for 72h resulted in increased internal ammonia and glutamine concentrations in the brain, and it caused cellular oxidative damage in the brain and liver. However, oxidative damage was most pronounced in brain, in which there was a twofold increase in thiobarbituric acid-reactive substances, a threefold increase in protein carbonylation, and a 20% increase in water volume (indicative of brain swelling). Increased activities of catalase, glutathione peroxidase, and glutathione reductase in the brain suggested that goldfish upregulate their antioxidant capacity to partially offset oxidative stress during hyperammonemia at 14°C. Notably, acclimation to colder (4°C) water completely attenuated the oxidative stress response to HEA in both tissues, and there was no change in brain water volume despite similar increases in internal ammonia. We suggest that ammonia-induced oxidative stress may be responsible for the swelling of goldfish brain during HEA, but further studies are needed to establish a mechanistic link between reactive oxygen species production and brain swelling. Nevertheless, a high capacity to withstand oxidative stress in response to variations in internal ammonia likely explains why goldfish are more resilient to this stressor than most other vertebrates.

Ammonia toxicity induces glutamine accumulation, oxidative stress and immunosuppression in juvenile yellow catfish Pelteobagrus fulvidraco.

A study was carried to test the response of yellow catfish for 28 days under two ammonia concentrations. Weight gain of fish exposure to high and low ammonia abruptly increased at day 3. There were no significant changes in fish physiological indexes and immune responses at different times during 28-day exposure to low ammonia. Fish physiological indexes and immune responses in the treatment of high ammonia were lower than those of fish in the treatment of low ammonia. When fish were exposed to high ammonia, the ammonia concentration in the brain increased by 19-fold on day 1. By comparison, liver ammonia concentration reached its highest level much earlier at hour 12. In spite of a significant increase in brain and liver glutamine concentration, there was no significant change in glutamate level throughout the 28-day period. The total superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) activities in the brain gradually decreased from hour 0 to day 28. Liver SOD, GPX and GR activities reached the highest levels at hour 12, and then gradually decreased. Thiobarbituric acid reactive substance brain and liver content gradually increased throughout the 28-day period. Lysozyme, acid phosphatase and alkaline phosphatase activities in the liver reached exceptionally low levels after day 14. This study indicated that glutamine accumulation in the brain was not the major cause of ammonia poisoning, the toxic reactive oxygen species is not fully counter acted by the antioxidant enzymes and immunosuppression is a process of gradual accumulation of immunosuppressive factors.

Mass chemical casualties: treatment of 41 patients with burns by anhydrous ammonia.

BACKGROUND: This article reports a chemical burn incident that occurred on 31 August 2013 in Shanghai. We describe situations at the scene, emergency management, triage, evacuation, and follow-up of the victims. METHOD: The scene of the incident and information on the 41 victims of this industrial chemical incident were investigated. The emergency management, triage, evacuation, and hospitalization data of the patients were summarized. RESULTS: At the time of the incident, 58 employees were working in a closed refrigerator workshop, 41 of whom sustained burns following the leakage of anhydrous ammonia. Ten victims died of severe inhalation injury at the scene, and another five victims died during the process of evacuation to the nearest hospital. After receiving information on the incident, a contingency plan for the burn disaster was launched immediately, and a first-aid group and an emergency and triage group were dispatched by the Changhai Hospital to the scene to aid the medical organization, emergency management, triage, and evacuation. All casualties were first rushed to the nearest hospital by ambulance. The six most serious patients with inhalation injuries were evacuated to the Changhai Hospital and admitted to the burn intensive care unit (BICU) for further treatment, one of whom died of respiratory failure and pulmonary infection. CONCLUSION: This mass casualty incident of anhydrous ammonia leakage caused potential devastating effects to the society, especially to the victims and their families. Early first-aid organization, emergency management, triage, and evacuation were of paramount importance, especially rapid evaluation of the severity of inhalation injury, and subsequent corresponding medical treatment. The prognosis of ammonia burns was poor and the sequelae were severe. Management and treatment lessons were drawn from this mass casualty chemical burn incident.

[Impact of atmospheric ammonia on livestock animals--a minireview]. / Wirkung von atmosphärischem Ammo- niak auf Nutztiere--eine Kurzübersicht.

Ammonia is one of the most important trace gases in the air of livestock buildings. Due to its physical and chemical properties and in dependance on the exposure conditions ammonia belongs to the irritant gases with a capability to have a negative impact on the respiratoy mucosa, the eyes and the skin of animals and men. The observed effects are ranging from performance losses over reductions of the mucociliary clearance to disturbences of the epithelial homeostasis including airway inflammations. Furthermore, some livestock species have shown in choice tests their affinity to a low ammoniated environment, where exposure concentrations were considerable lower than the threshold limit values fixed in animal welfare regulations. It can be expected that ammonia will continously be of relevance in future. Therefore, this article gives a short literature-based overview about the biological impact of ammonia on poultry, pigs and cattle.

Enhancement of Hsp70 synthesis protects common carp, Cyprinus carpio L., against lethal ammonia toxicity.

Exposure to TEX-OE®, a patented extract of the prickly pear cactus (Opuntia ficus indica) containing chaperone-stimulating factor, was shown to protect common carp, Cyprinus carpio L., fingerlings against acute ammonia stress. Survival was enhanced twofold from 50% to 95% after exposure to 5.92 mg L(-1) NH(3) , a level determined in the ammonia challenge bioassay as the 1-h LD50 concentration for this species. Survival of TEX-OE®-pre-exposed fish was enhanced by 20% over non-exposed controls during lethal ammonia challenge (14.21 mg L(-1) NH(3) ). Increase in the levels of gill and muscle Hsp70 was evident in TEX-OE®-pre-exposed fish but not in the unexposed controls, indicating that application of TEX-OE® accelerated carp endogenous Hsp70 synthesis during ammonia perturbation. Protection against ammonia was correlated with Hsp70 accretion.

The inhibitory effect of environmental ammonia on Danio rerio LPS induced acute phase response.

Ammonia is a toxic by-product of amino acid catabolism and a common environmental pollutant that has been associated with increased disease susceptibility in fish although the mechanism is not well understood. We addressed the hypothesis that elevated environmental ammonia acts by impairing the acute phase response (APR). Specifically, we determined the impact of sub-lethal acute (24 h) and chronic (14 d) ammonia exposure on acute phase protein gene expression in zebrafish (Danio rerio) in response to a challenge with bacterial lipopolysaccharide (LPS: i.p. 10 µg/g after 24h). A panel of LPS-responsive genes (SAA, HAMP, LECT2, Hp and IL1ß) were identified and evaluated by real-time quantitative PCR. Ammonia was found to impair induction of SAA, HAMP and LECT2 by 50-90%. Both short (15 min, 1h and 24h) and long-term (14 days) exposure to high environmental ammonia concentrations significantly elevated whole-body cortisol levels compared with control fish. Our results reveal for the first time that exposure to high environmental levels of ammonia suppresses the innate immune response in fish. We hypothesize that high environmental ammonia-mediated elevation of cortisol levels in zebrafish may be playing a key role in this immunosuppression, while the mechanisms involved remains to be elucidated.

Ammonia intoxication on workplace--case report and a review of literature.

In December 2003 in Rijeka, Croatia, a work accident happened when in the meat industry 'Vir" a forklift damaged the ammonia pipe. Two butchers were acutely poisoned. The objective is to warn of the danger of ammonia and of the need to improve preventive programs of occupational medicine. The method of comparing the two injured workers, i.e. their spirometric values, was used. The results showed progressive diminishing of patients' respiratory abilities, in the patient with lungs transplanted VC 32%, FVC 33%, FEV1 16% and FEF75% = 6% in 2006, the year when he died. In the patient that survived, the values in 2008 were VC 43.5%, FVC 27.2%, FEV1% 56.7% and FEF75% = 6%. The patients' CT showed diffused fibrosing and bronchiectasiae. Obliterating bronchiolitis developed in both patients. The second patient is the lung transplantation candidate. The first patient developed post transplantation cytomegalovirus pneumonia so he fought CMV antigenemia and infection till the end.

Ammonia toxicity and its prevention in inherited defects of the urea cycle.

The urea cycle is the final pathway for removal of surplus nitrogen from the body, and the major route in humans for detoxification of ammonia. The full complement of enzymes is expressed only in liver. Inherited deficiencies of urea cycle enzymes lead to hyperammonaemia, which causes brain damage. Severe defects present with hyperammonaemic crises in neonates. Equally devastating episodes may occur in previously asymptomatic adults with mild defects, most often X-linked ornithine transcarbamylase (OTC) deficiency. Several mechanisms probably contribute to pathogenesis. Treatment aims to reduce plasma ammonia quickly, reduce production of waste nitrogen, dispose of waste nitrogen using alternative pathways to the urea cycle and replace arginine. These therapies have increased survival and probably improve the neurological outcome. Arginine, sodium benzoate, sodium phenylbutyrate and, less often, sodium phenylacetate are used. Long-term correction is achieved by liver transplantation. Gene therapy for OTC deficiency is effective in animals, and work is ongoing to improve persistence and safety.