Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis. METHODS: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated. RESULTS: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions. CONCLUSIONS: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis. CLINICAL TRIAL REGISTRATION: NCT02250729.

Phenotypical evidence of effective amelioration of ammonium-inhibited plant (root) growth by exogenous low urea.

Ammonium and nitrate are major soil inorganic-nitrogen sources for plant growth, but many species cultivated with even low millimolar NH4+ as a sole N form display a growth retardation. To date, critical biological components and applicable approaches involved in the effective enhancement of NH4+ tolerance remain to be thoroughly explored. Here, we report phenotypical traits of urea-dependent improvement of NH4+-suppressed plant/root growth. Urea at 0.1 mM was sufficient to remarkably stimulate NH4+ (3 mM)-fed cotton growth, showing a 2.5∼4-fold increase in shoot- and root-biomass and total root-length, 20 % higher GS activity, 18 % less NH4+-accumulation in roots, and a comparable plant total-N content compared to the control, implying a novel role for urea in cotton NH4+detoxification. A similar phenomenon was observed in tobacco and rice. Moreover, comparisons between twelve NH4+-grown Arabidopsis accessions revealed a great degree of natural variation in their root-growth response to low urea, with WAR and Blh-1 exhibiting the most significant increase in primary- and lateral-root length and numbers, and Sav-0 and Edi-0 being the most insensitive. Such phenotypical evidence suggests a common ability of plants to accommodate NH4+-stress by responding to exogenous urea, providing a novel aspect for further understanding the process of urea-dependent plant NH4+ tolerance.

Bioprospecting of indigenous marine microalgae with ammonium tolerance from aquaculture ponds for microalgae cultivation with ammonium-rich wastewaters.

We isolated fifty-two strains from the marine aquaculture ponds in Malaysia that were evaluated for their lipid production and ammonium tolerance and four isolates were selected as new ammonium tolerant microalgae with high-lipid production: TRG10-p102 Oocystis heteromucosa (Chlorophyceae); TRG10-p103 and TRG10-p105 Thalassiosira weissflogii (Bacillariophyceae); and TRG10-p201 Amphora coffeiformis (Bacillariophyceae). Eicosapentenoic acid (EPA) in three diatom strain was between 2.6 and 18.6 % of total fatty acids, which were higher than in O. heteromucosa. Only A. coffeiformi possessed arachidonic acid. Oocystis heteromucosa naturally grew at high ammonium concentrations (1.4-10 mM), whereas the growth of the other strains, T. weissflogii and A. coffeiformi, were visibly inhibited at high ammonium concentrations (>1.4 mM-NH4). However, two strains of T. weissflogii were able to grow at up to 10 mM-NH4 by gradually acclimating to higher ammonium concentrations. The ammonium tolerant strains, especially T. weissflogii which have high EPA contents, were identified as a valuable candidate for biomass production utilizing NH4-N media, such as ammonium-rich wastewater.

Internal ammonium excess induces ROS-mediated reactions and causes carbon scarcity in rice.

BACKGROUND: Overuse of nitrogen fertilizers is often a major practice to ensure sufficient nitrogen demand of high-yielding rice, leading to persistent NH4+ excess in the plant. However, this excessive portion of nitrogen nutrient does not correspond to further increase in grain yields. For finding out the main constraints related to this phenomenon, the performance of NH4+ excess in rice plant needs to be clearly addressed beyond the well-defined root growth adjustment. The present work isolates an acute NH4+ excess condition in rice plant from causing any measurable growth change and analyses the initial performance of such internal NH4+ excess. RESULTS: We demonstrate that the acute internal NH4+ excess in rice plant accompanies readily with a burst of reactive oxygen species (ROS) and initiates the downstream reactions. At the headstream of carbon production, photon caption genes and the activity of primary CO2 fixation enzymes (Rubisco) are evidently suppressed, indicating a reduction in photosynthetic carbon income. Next, the vigorous induction of glutathione transferase (GST) genes and enzyme activities along with the rise of glutathione (GSH) production suggest the activation of GSH cycling for ROS cleavage. Third, as indicated by strong induction of glycolysis / glycogen breakdown related genes in shoots, carbohydrate metabolisms are redirected to enhance the production of energy and carbon skeletons for the cost of ROS scavenging. As the result of the development of these defensive reactions, a carbon scarcity would accumulatively occur and lead to a growth inhibition. Finally, a sucrose feeding cancels the ROS burst, restores the activity of Rubisco and alleviates the demand for the activation of GSH cycling. CONCLUSION: Our results demonstrate that acute NH4+ excess accompanies with a spontaneous ROS burst and causes carbon scarcity in rice plant. Therefore, under overuse of N fertilizers carbon scarcity is probably a major constraint in rice plant that limits the performance of nitrogen.

Evaluating the response of anaerobic ammonium-oxidizing bacteria to heavy metal spill in freshwater sediment.

Anaerobic ammonium-oxidizing (anammox) bacteria can play an important role in nitrogen elimination in the environment. However, the effect of heavy metals on anammox bacteria in aquatic ecosystem remains largely unknown. The present study investigated the variability of anammox bacterial community in a freshwater reservoir after a severe heavy metal spill. The richness (Chao1 richness estimator = 2-18), diversity (Shannon index = 0.26-2.04) and community structure of anammox bacteria changed considerably with sampling date, while anammox bacterial abundance (from 1.38 × 105 to 3.09 × 105 anammox bacterial 16S rRNA gene copies per gram dry sediment) was less responsive to metal spill. Anammox bacterial communities were mainly composed of Brocadia- and Anammoxoglobus-like bacteria as well as novel phylotype, however, there relative abundance varied among sampling dates. This work could add the knowledge of the response of anammox bacteria to heavy metal contamination.

The effect of seasonal and human pressure on macrobenthic fauna in the Caroni Swamp Ramsar Site, Trinidad and Tobago / Efecto de la presión estacional y humana en la fauna macrobentónica del sitio Ramsar pantano Caroní, Trinidad y Tobago

Abstract Human pressures have placed many tropical estuaries in developing countries under increased levels of stress. The Caroni Swamp Ramsar Site, the largest mangrove swamp along the west coast of Trinidad, has been subjected to high levels of anthropogenic impacts including hydrological alteration and pollution from land-based sources since the 1920's. While most of these impacts have been well documented, limited information exists on the macrobenthic communities in the swamp. This study addresses the paucity of information. The macrobenthic fauna in the main waterways of Caroni Swamp was sampled at 12 locations using a Van Veen 0.025 m2 grab, once in the dry (April) and wet (August) season of 2015 with a total of 144 samples. The samples were sorted, counted and species were identified to the lowest possible taxonomic level. A total of 55 taxa were identified with polychaetes being the most abundant taxa. The ecological status of the macrobenthos was assessed using AZTI's Marine Biotic Index (AMBI) and the multivariate-AMBI (M-AMBI). Physicochemical parameters were measured with a YSI multiparameter metre. Chemical analyses were also conducted on nitrates, nitrites, ammonia and reactive phosphates using standard methods. Overall, AMBI characterised the Caroni Swamp as "slightly disturbed" with a macrobenthic community of "poor" ecological status according to M-AMBI. Generally, the quality of the environment improves from the dry season to the wet season. However, seasonal variations in AMBI and M-AMBI were found to be site specific as some showed improvement in ecological status and macrozoobenthos quality while others showed degradation from the dry season to the wet season. The stations to the North of the swamp showed improvement from the dry season to the wet season while the opposite was observed in the more Southern stations. One notable characteristic of the swamp was the high levels of pollutants, particularly ammonia, recorded in one of its major waterways, the Caroni River. This is in contrast to the other waterways within the swamp which experience much lower levels of pollutant input from land-based sources. The assessment of the Caroni Swamp using AMBI and M-AMBI may be useful for informing management strategies to conserve the wetland and improve environmental quality. Rev. Biol. Trop. 66(3): 1101-1117. Epub 2018 September 01.

Resumen Los estuarios tropicales de países en desarrollo han experimentado un aumento en los niveles de estrés debido a la presión humana. El sitio Ramsar pantano Caroní, el manglar más grande de la costa oeste de Trinidad, ha estado sujeto a altos niveles de impacto antropogénico, incluyendo alteraciones hidrológicas y contaminación de fuentes terrestres desde la década de 1920. Aunque la mayoría de estos impactos han sido bien documentados, existe información limitada sobre las comunidades macrobentónicas en el pantano. Este estudio aborda esta escasez de información. Se muestreó la fauna macrobentónica en el canal principal del pantano Caroní en 12 localidades utilizando una draga Van Veen de 0.025 m2, una vez durante la época seca (Abril) y la época lluviosa (Agosto) 2015, con un total de 144 muestras. Las muestras fueron ordenadas, contadas y las especies se identificaron al menor nivel taxonómico posible. Se identificaron un total de 55 taxa, siendo los poliquetos el taxa más abundante. El estatus ecológico del macrobentos se evaluó utilizando el Índice Marino Biótico de AZTI (AMBI) y el AMBI-multivariado (M-AMBI). Los parámetros fisicoquímicos se midieron con un multiparámetro YSI. Los análisis químicos también se realizaron para nitratos, nitritos, amonio y fostatos activos utilizando métodos estándar. En conjunto, el índice AMBI caracterizó el pantano Caroní como "levemente alterado" con una comunidad macrobentónica de categoría "pobre" de acuerdo al M-AMBI. Generalmente, la calidad de los ambientes incrementa desde la época seca hasta la época lluviosa. Sin embargo, las variaciones estacionales en los índices AMBI y M-AMBI fueron específicas a la localidad, mostrando algunas un incremento en el estatus ecológico y calidad del macrozoobentos, mientras que otros mostraron una degradación de la época seca a la época lluviosa. Las estaciones al norte del pantano mostraron una mejora de la época seca a la época lluviosa, mientras que se presentó lo contrario en las estaciones más al sur. Una característica notable del pantano fueron los altos niveles de contaminantes, particularmente amonio, registrado en uno de los canales principales del río Caroní. Esto contrasta con los otros canales del pantano que experimentan niveles menores de aporte de contaminantes de fuentes terrestres. La evaluación del pantano Caroní utilizando los índíces AMBI y M-AMBI puede ser una base útil de información para las estrategias de manejo y conservación del humedal y mejorar su calidad ambiental.

Fine particulate matter constituents and blood pressure in patients with chronic obstructive pulmonary disease: A panel study in Shanghai, China.

OBJECTIVE: The evidence is limited about the potentially different health effects of various chemical constituents of fine particulate matter (PM2.5). We thus assessed the acute effects of various chemical constituents of PM2.5 on blood pressure (BP). METHODS: We performed a longitudinal panel study with six repeated visits in 28 urban residents with chronic obstructive pulmonary disease in Shanghai, China from May to July, 2014. Twelve (43%) of them took antihypertensive medications. We measured resting BP by using a mercury sphygmomanometer and monitored real-time concentrations of PM2.5 constituents at a nearby site. Based on the linear mixed-effects model, we evaluated the effects of 10 major constituents in PM2.5 on BP, using a single-constituent model and a constituent-residual model after accounting for the multicollinearity. RESULTS: We obtained a total of 168 pairs of effective BP measurements during the study period. There are moderate or high correlations among various PM2.5 constituents. An interquartile range increase of PM2.5 (19.1µg/m3) was associated with increments of 1.90mmHg [95% confidence interval (CI): 0.66, 3.13] in systolic BP, 0.68mmHg (95%CI: -0.02, 1.37) in diastolic BP and 1.23mmHg (95%CI: 0.19, 2.29) in pulse pressure. Some constituents of PM2.5, including organic carbon, elemental carbon, nitrate and ammonium, were robustly associated with elevated BP after controlling for total PM2.5 mass and accounting for multi-collinearity. Two constituents (magnesium and calcium) were associated with decreased BP. CONCLUSIONS: Organic carbon, elemental carbon, nitrate and ammonium may be mainly responsible for elevated BP from a short-term exposure to PM2.5.

Ammonia encephalopathy and awake craniotomy for brain language mapping: Cause of failed awake craniotomy / Encefalopatía por amonio y cirugía con el paciente despierto para mapeo del lenguaje; causa de fracaso de craneotomía despierta

We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l -carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration (AU)

Se presenta el caso de un paciente con un glioma insulofrontotemporal izquierdo, tratado con levetiracetam, valproato y clobazam. Se realizó una primera cirugía bajo anestesia general para la exéresis del lóbulo temporal tumoral, y 8 días después se sometió a una cirugía con el paciente despierto para mapeo del lenguaje, bajo sedación consciente con remifentanilo y anestesia local. A la llegada a quirófano, el paciente se encontraba cansado y con cierta bradipsiquia; tras parar la infusión de remifentanilo, y antes de abrir la duramadre, el paciente presentó una disminución del nivel de consciencia con privación respiratoria que requirió intubación endotraqueal y la finalización de la cirugía. En el periodo posoperatorio se apreció bradipsiquia moderada, cansancio y temblor de manos. Fueron detectados niveles altos de amonio en sangre, y la clínica mejoró tras la administración de L-carnitina y la suspensión del valproato. La encefalopatía por amonio, aunque con mínima sintomatología, debería ser considerada en pacientes tratados con valproato que van a ser sometidos a una cirugía bajo sedación, donde se requiere que el paciente colabore (AU)

Mortality and cancer incidence in ammonium perfluorooctanoate production workers.

OBJECTIVE: To evaluate mortality and cancer incidence in a cohort of ammonium perfluorooctanoate (APFO) exposed workers. METHODS: We linked a combined cohort (n=9027) of employees from APFO and non-APFO production facilities in Minnesota to the National Death Index and to cancer registries of Minnesota and Wisconsin. Industrial hygiene data and expert evaluation were used to create a task-based job exposure matrix to estimate APFO exposure. Standardised mortality ratios were estimated using Minnesota population rates. HRs and 95% CIs for time-dependent cumulative APFO exposure were estimated with an extended Cox model. A priori outcomes of interest included cancers of the liver, pancreas, testes, kidney, prostate and breast, and mortality from cardiovascular, cerebrovascular and chronic renal diseases. RESULTS: Mortality rates in the APFO-exposed cohort were at or below the expected, compared with Minnesota. The HR for dying from the cancer and non-cancer outcomes of interest did not show an association with APFO exposure. Similarly, there was little evidence that the incident cancers were associated with APFO exposure. Compared to the non-exposed population, modestly elevated, but quite imprecise HRs were observed in the higher-exposure quartiles for bladder cancer (HR=1.66, 95% CI 0.86 to 3.18) and pancreatic cancer (HR=1.36, 95% CI 0.59 to 3.11). No association was observed between APFO exposure and kidney, prostate or breast cancers. CONCLUSIONS: This analysis did not support an association between occupational APFO exposure and the evaluated health endpoints, however, the study had limited power to evaluate some conditions of interest.

Short-term associations of cause-specific emergency hospitalizations and particulate matter chemical components in Hong Kong.

Despite an increasing number of recent studies, the overall epidemiologic evidence associating specific particulate matter chemical components with health outcomes has been mixed. The links between components and hospitalizations have rarely been examined in Asia. We estimated associations between exposures to 18 chemical components of particulate matter with aerodynamic diameter less than 10 µm (PM10) and daily emergency cardiorespiratory hospitalizations in Hong Kong, China, between 2001 and 2007. Carbonaceous particulate matter, sulfate, nitrate, and ammonium accounted for two-thirds of the PM10 mass. After adjustment for time-varying confounders, a 3.4-µg/m(3) increment in 2-day moving average of same-day and previous-day nitrate concentrations was associated with the largest increase of 1.32% (95% confidence interval: 0.73, 1.92) in cardiovascular hospitalizations; elevation in manganese level (0.02 µg/m(3)) was linked to a 0.91% (95% confidence interval: 0.19, 1.64) increase in respiratory hospitalizations. Upon further adjustment for gaseous copollutants, nitrate, sodium ion, chloride ion, magnesium, and nickel remained significantly associated with cardiovascular hospitalizations, whereas sodium ion, aluminum, and magnesium, components abundantly found in coarser PM10, were associated with respiratory hospitalizations. Most positive links were seen during the cold season. These findings lend support to the growing body of literature concerning the health associations of particulate matter composition and provide important insight into the differential health risks of components found in fine and coarse modes of PM10.

Short-term alteration of nitrogen supply prior to harvest affects quality in hydroponic-cultivated spinach (Spinacia oleracea).

BACKGROUND: Quality-associated problems, such as excessive in planta accumulation of oxalate, often arise in soillessly cultivated spinach (Spinacia oleracea). Maintaining a higher level of ammonium (NH4⁺) compared to nitrate (NO3⁻) during the growth period can effectively decrease the oxalate content in hydroponically cultivated vegetables. However, long-term exposure to high concentrations of NH4⁺ induces toxicity in plants, and thus decreases the biomass production. Short-term application of NH4⁺ before harvesting in soilless cultivation may provide an alternative strategy to decrease oxalate accumulation in spinach, and minimise the yield reduction caused by NH4⁺ toxicity. RESULT: The plants were pre-cultured in 8 mmol L⁻¹ NO3⁻ nutrient solution. Next, 6 days before harvest, the plants were transferred to a nutrient solution containing 4 mmol L⁻¹ NO3⁻ and 4 mmol L⁻¹ NH4⁺. This new mix clearly reduced oxalate accumulation, increased levels of several antioxidant compounds, and enhanced antioxidant capacity in the edible parts of spinach plants, but it did not affect biomass production. However, when the 8 mmol L⁻¹ NO3⁻ was shifted to either nitrogen-free, 4 mmol L⁻¹ NH4⁺ or 8 mmol L⁻¹ NH4⁺ treatments, although some of the quality indexes were improved, yields were significantly reduced. CONCLUSIONS: Short-term alteration of nitrogen supply prior to harvest significantly affects quality and biomass of spinach plants, and we strongly recommend to simultaneously use NO3⁻ and NH4⁺ in hydroponic cultivation, which improves vegetable quality without decreasing biomass production.

Asthma among workers in healthcare settings: role of disinfection with quaternary ammonium compounds.

INTRODUCTION: An increased incidence of asthma has been reported among healthcare workers. The role of quaternary ammonium compounds (QACs), commonly used in cleaning/disinfection products, has not been clearly defined. The aim of this study was to analyse associations between asthma and occupational exposure to disinfectants, especially QACs. METHODS: The study was performed on a stratified random sample of the various healthcare departments of 7 healthcare settings. The study included: questionnaire, physical examination and specific IgE assays. Occupational exposure assessment was performed by means of a work questionnaire, workplace studies and a review of products ingredients. Data were analysed by logistic regression. RESULTS: Response rate was 77%; 543 workers (89% female) participated; 37.1% were registered nurses (RNs), 16.4% auxiliary nurses (ANs), 17.3% cleaners; 32.8% were atopic. 335 participants were exposed to QACs. Nursing professionals reported a significantly higher risk of reported physician-diagnosed asthma and, for RNs, of nasal symptoms at work than administrative staff working in healthcare sector. This risk was particularly marked during disinfection tasks and when exposure to QACs. Exposure to QACs increased significantly the risk of reported physician-diagnosed asthma and nasal symptoms at work (adjusted OR = 7.5 and 3.2, respectively). No significant association was found with other exposures such as latex glove use, chlorinated products/bleach or glutaraldehyde. CONCLUSION: RNs and ANs presented a higher risk of reported asthma than administrative staff. The highest risk was associated with tasks involving dilution of disinfection products by manual mixing, suggesting possible exposure to repeated peaks of concentrated products known to be strong respiratory irritants. Workplace interventions should be conducted to more clearly determine QAC exposure and improve disinfection procedures.

Safety assessment of ammonium hectorites as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 4 ammonium hectorite compounds used in cosmetics: disteardimonium hectorite, dihydrogenated tallow benzylmonium hectorite, stearalkonium hectorite, and quaternium-18 hectorite. These ingredients function in cosmetics mainly as nonsurfactant suspending agents. The Panel reviewed available animal and human data and concluded that these ammonium hectorite compounds were safe as cosmetic ingredients in the practices of use and concentration as given in this safety assessment.

Human and mouse embryonic development, metabolism and gene expression are altered by an ammonium gradient in vitro.

Ammonium is generated in culture media by the spontaneous deamination of amino acids at 37 °C and through the metabolism of amino acids by human embryos. The appearance of ammonium is a time-dependent phenomenon and can compromise embryo physiology, development and viability. In this study, the effects of a gradient of ammonium on the development, metabolism and transcriptome of human and mouse embryos were investigated. Pronucleate oocytes were cultured in the presence of an ammonium gradient that mimicked the spontaneous deamination of Eagle's amino acids together with 1 mM glutamine. All embryos were cultured in sequential media G1/G2 at 5% O2, 6% CO2 and 89% N2. Human embryo metabolism was assessed through a non-invasive fluorometric analysis of pyruvate consumption. Transcriptome analysis was performed on the resultant blastocysts from both species using a microarray technology. Embryo development prior to compaction was negatively affected by the presence of low levels of ammonium in both species. Human embryo metabolism was significantly inhibited after just 24 and 48 h of culture. Transcriptome analysis of blastocysts from both species revealed significantly altered gene expression profiles, both decreased and increased. Functional annotation of the altered genes revealed the following over represented biological processes: metabolism, cell growth and/or maintenance, transcription, cell communication, transport, development and transcription regulation. These data emphasize the enhanced sensitivity of the cleavage-stage embryo to its environment and highlight the requirement to renew culture media at frequent intervals in order to alleviate the in vitro induced effects of ammonium build-up in the environment surrounding the embryo.