Toxicology letters
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Although the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of atropine dosing was undertaken in 34 patients who had been enrolled in a clinical study assessing obidoxime effectiveness in OP-poisoning. All patients were severely intoxicated (suicidal attempts) and required artificial ventilation. ⋯ Elimination half-life of S-hyoscyamine was 1.5 h, showing occasionally a second slow elimination phase with t(½)=12 h. Malignant arrhythmias were observed in some 10% of our cases, which occurred late and often in the absence of relevant glandular cholinergic signs, when the S-hyoscyamine concentration was below 2.5 nmol L⁻¹. Arrhythmias mostly resolved on reinstitution of atropine.
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An important factor for successful therapy of poisoning with organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Unfortunately, clinically used oximes, e.g. obidoxime and pralidoxime, are of limited effectiveness in poisoning with different OP nerve agents requiring the search for alternative oximes, e.g. ⋯ In soman or tabun exposed human intercostal muscle HI 6 (50 and 100 μM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition, HI 6 up to 1000 μM had no effect on soman blocked muscle force indicating that this oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial therapeutic effect on nerve agent blocked neuromuscular transmission.
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Comparative Study
Mainstream smoke of the waterpipe: does this environmental matrix reveal as significant source of toxic compounds?
In recent years the number of waterpipe smokers has increased substantially worldwide. Here we report on the concentrations of tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) in waterpipe smoke and the analysis of selected biomarkers indicative for the body burden in waterpipe users. We further identify high amounts of unburned humectants (glycerol and propylene glycol) in the waterpipe smoke as main part of the so-called "tar" fraction. ⋯ This finding explained the low levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol detected in the urine of waterpipe smokers. Finally, the levels of benzo[a]pyrene were three times higher in waterpipe smoke compared to the reference cigarette. Altogether, the data presented in this study point to the health hazards associated with the consumption of waterpipes.
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Female sex hormones (FSHs) exert profound regulatory effects on the course of lung inflammation due to allergic and non-allergic immune responses. As pollution is one of the pivotal factors to induce lung dysfunction, in this study we investigated the modulatory role of FSHs on lung inflammation after a formaldehyde (FA) exposure. For this purpose, lung and systemic inflammatory responses were evaluated in terms of leukocytes countings in bronchoalveolar lavage (BAL), peripheral blood and bone marrow lavage from 7-day ovariectomized (OVx) and Sham-OVx rats subjected to FA inhalation for 3 consecutive days. ⋯ In addition, OVx rats upon FA exposure significantly increased both, the ability of mast cell degranulation and serum corticosterone levels. In conclusion, it was found that FSHs act by distinct control mechanisms on FA-induced lung inflammation and tracheal hyperresponsiveness, since at low circulating levels of FSHs (such as those after OVx) there is some resistance to the development of a lung inflammatory response, but the cholinergic tracheal responsiveness is exacerbated. Our data also help to understand the involvement of FSHs on mast cells activity after pollutants exposure and add information regarding the role of FSHs on the mechanisms related to endothelium-leukocyte interactions.
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An increase in creatinine > 3 μmol/L/h has been suggested to predict death in patients with paraquat self-poisoning and the value of other plasma biomarkers of acute kidney injury has not been assessed. The aim of this study was to validate the predictive value of serial creatinine concentrations and to study the utility of cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as predictors of outcome in patients with acute paraquat poisoning. The rate of change of creatinine (dCr/dt) and cystatin C (dCyC/dt) concentrations were compared between survivors and deaths. ⋯ NGAL did not separate survivors from deaths. Death due to acute paraquat poisoning is associated with changes in creatinine and cystatin concentrations. Further validation of these measurements is needed before they can be adopted in guiding intensive treatments.