Blood Donors on Medication - an Approach to Minimize Drug Burden for Recipients of Blood Products and to Limit Deferral of Donors.

BACKGROUND: Blood products derived from donors on medication can contain drugs which might pose a risk for the recipients or influence the quality of the product itself. MATERIAL AND METHODS: To judge the eligibility of blood donors on medication, 4 drug classes have been formed with respect to their pharmacological properties, and blood products have been divided in accordance with their single-donor plasma contents. RESULTS: For drugs with dose-dependent pharmacodynamics, no deferral periods are necessary for donation of blood products containing less than 50 ml single-donor plasma for application to adults.

Assessment of alterations in barrier functionality and induction of proinflammatory and cytotoxic effects after sulfur mustard exposure of an in vitro coculture model of the human alveolo-capillary barrier.

Acute lung injury after sulfur mustard (SM) inhalation is characterized by massive, localized hemorrhage and alveolar edema, which implies severe disruption of the vascular and distal airway barrier. In this study, we tested a recently established in vitro coculture model of the alveolo-capillary barrier for its applicability to investigate acute toxic effects of SM at the human respiratory unit. The epithelial compartment of cocultures was exposed to varying concentrations of SM (0-1000 microM; t = 30 min).

Testing of antidotes for organophosphorus compounds: experimental procedures and clinical reality.

According to current knowledge, inhibition of acetylcholinesterase (AChE) is a very important toxic action of organphosphorus compounds (OP). Hence, it is obvious to follow the AChE activity in order to quantify the degree of inhibition and to assess possible reactivation. Red blood cell (RBC)-AChE provides an easily accessible source to follow the AChE status also in humans.

Development of antidotes: problems and strategies.

Antidotes against chemical warfare agents are "orphan drugs" given that these poisonings are rare. Therefore, they are of limited interest to the pharmaceutical industry. For this reason, and recognizing the increasing threat of terrorist or asymmetrical use of chemical warfare agents, the responsibility for research into medical countermeasures against these weapons is of primary interest to armies.

Simulation of cholinesterase status at different scenarios of nerve agent exposure.

The ongoing threat of homicidal use of organophosphorus-type chemical warfare agents ("nerve agents") during military conflicts and by terrorists underlines the necessity for effective medical countermeasures. Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. From obvious ethical reasons only animal experiments can be used to evaluate new oximes as nerve agent antidotes.

Estimation of oxime efficacy in nerve agent poisoning: a kinetic approach.

Standard treatment of poisoning by organophosphorus compounds (OP) includes the administration of an anti-muscarinic, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime).

Correlation between red blood cell acetylcholinesterase activity and neuromuscular transmission in organophosphate poisoning.

Assessment of effectiveness of oximes in severely organophosphate poisoned patients is hampered by sedation, artificial ventilation and other therapeutic measures as well as varying individual clinical courses due to, e.g. differences in type and amount of poison ingested or time elapsed before treatment starts.

Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

Background: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause.

Methods: We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals.

Medical aspects of sulphur mustard poisoning.

Sulphur mustard is one of the major chemical warfare agents developed and used during World War I. Large stockpiles are still present in several countries. It is relatively easy to produce and might be used as a terroristic weapon.

Diagnostic aspects of organophosphate poisoning.

Organophosphate (OP)-type chemical warfare agents (nerve agents) present a constant threat to the population. Sensitive and specific methods for the detection and verification of exposure to nerve agents are required for diagnosis, therapeutic monitoring, health surveillance and forensic purposes. Determination of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in blood remains a mainstay for the fast initial screening but lacks sensitivity and specificity.

Effects of oximes on muscle force and acetylcholinesterase activity in isolated mouse hemidiaphragms exposed to paraoxon.

Toxicity of organophosphates (OP) is caused by inhibition of acetylcholinesterase (AChE), resulting in accumulation of acetylcholine. While cholinolytics such as atropine are able to counteract muscarinic symptoms, they are unable to restore the impaired neuromuscular transmission (NMT). Here, oximes as potential reactivators of inhibited AChE may be effective.

Evaluation of oxime efficacy in nerve agent poisoning: development of a kinetic-based dynamic model.

The widespread use of organophosphorus compounds (OP) as pesticides and the repeated misuse of highly toxic OP as chemical warfare agents (nerve agents) emphasize the necessity for the development of effective medical countermeasures. Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. From obvious ethical reasons only animal experiments can be used to evaluate new oximes as nerve agent antidotes.

Ketamine reduces cholinergic modulated GABA release from rat striatal slices.

Striatal GABA release has been shown to be enhanced under pathological conditions of cholinergic overstimulation, e.g. inhibition of acetylcholine esterase.

Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes.

The wide-spread use of organophosphorus compounds (OP) as pesticides and the availability of highly toxic OP-type chemical warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE, EC 3.1.

The effect of acetylcholinesterase-inhibition on depolarization-induced GABA release from rat striatal slices.

The severity of poisoning after intoxication with the acetylcholinesterase (AChE) inhibitor soman has been shown to be positively correlated with GABA release in rat striatum. Since most of the neurons in striatum and striatal projection regions use GABA as transmitter, it is still unclear, whether an increase of extracellular GABA in this region results from enhanced activation of these projections or is due to the local effect of AChE inhibition. In this study, the modulation of depolarization-induced increase in GABA concentration by soman was determined in the superfusate of rat striatal slices.