Toxicology letters
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Aside from nerve agents, various highly toxic pesticides belong to the group of organophosphorus (OP) compounds, thereby causing a large number of intoxications every year. Unfortunately, there are still shortcomings in the current treatment for OP poisoning and research on novel therapeutic options is restricted in several aspects. In this study we investigated the suitability of organotypic cocultures for pharmacological in vitro studies involving OP compounds. ⋯ The application of nerve agents led to an almost complete loss of muscle activity. However, cell cultures regained equivalent muscular function to the control situation three and seven days after intoxication. In summary, the tested in vitro system could be a promising tool for the investigation of long term effects and therapeutic options for OP poisoning.
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Sulfur mustard (SM) is a chemical warfare agent (CWA) that was first used in World War I and in several military conflicts afterwards. The threat by SM is still present even today due to remaining stockpiles, old and abandoned remainders all over the world as well as to its ease of synthesis. CWA are banned by the Chemical Weapons Convention (CWC) interdicting their development, production, transport, stockpiling and use and are subjected to controlled destruction. ⋯ SM-exposure was verified for all three patients using bioanalytical GC MS and LC MS/MS based methods applied to urine and plasma. Urinary biotransformation products of the β-lyase pathway were detected until 5 days after poisoning whereas albumin-SM adducts could be found until day 29 underlining the beneficial role of adduct detection for post-exposure verification. In addition, we provide general recommendations for management and therapy in case of SM poisoning.
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In organotypic spinal cord-skeletal muscle co-cultures, motoneurons are driven by locomotor commands and induce contractions in surrounding muscle fibres. Using these co-cultures, it has been shown that effects of organophosphorus compounds on neuromuscular synapses can be determined in vitro. In the present study we aimed to extend this in vitro tool for pharmacologic testing of botulinum toxin B. ⋯ Administration of the glycine- and GABA(A)-receptor antagonists strychnine (1μM) and bicuculline (100μM) did not alter intrinsic muscle activity. In contrast, application of a non-depolarizing muscle relaxant rocuronium bromide reduced the muscle activity in a dose-dependent manner. Our findings suggest that glutamatergic synapses in the spinal cord are more sensitive to botulinum toxin B than synaptic contacts between spinal motoneurons and muscle fibres.
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Comparative Study
Evaluation of the antigenicity of hydrolyzed cow's milk protein formulas using the mouse basophil activation test.
Hypoallergenic infant formulas are widely used for infants with cow's milk allergy. The aim of this study was to assess the utility of the mouse basophil activation test (BAT) in the evaluation of residual antigenicity in these formulas. Whole blood samples derived from β-lactoglobulin- or casein-immunized mice were incubated with one of the following formulas: conventional, partially hydrolyzed, or extensively hydrolyzed. ⋯ Although the partially hydrolyzed formula also induced basophilic activation and systemic anaphylaxis, the magnitude of these effects was smaller than that observed with the conventional formula. Compared to CD200R1, the observed trend in CD200R3 expression resembled the results obtained from systemic anaphylaxis test more closely. These findings show that mouse BAT, in particular using CD200R3, is highly useful for the evaluation of antigenicity of milk formulas.