A simple acetylcholinesterase inhibition assay for the quantification of the nerve agent VX: Application in a Franz cell model with rat skin and various decontaminants.

The medical community continues to regard organophosphate nerve agent poisoning as a significant concern. Due to the lack of therapeutic options for the nicotinic signs and symptoms for certain agents (e.g.

Concentration-dependent effects of the nerve agents cyclosarin and VX on cytochrome P450 in a HepaRG cell-based liver model.

The exposure to highly toxic organophosphorus (OP) compounds, including pesticides and nerve agents, is an ongoing medical challenge. OP can induce the uncontrolled overstimulation of the cholinergic system through inhibition of the enzyme acetylcholinesterase (AChE). The cytochrome P450 (CYP) enzymes in the liver play a predominant role in the metabolism of xenobiotics and are involved in the oxidative biotransformation of most clinical drugs.

Optimization of long-term incubation of precision-cut kidney slices.

Precision-cut kidney slices (PCKS) provide a powerful model to close the gap between and research. Publications by various authors favor different incubation conditions, media, and antibiotics, that have not yet been compared in a standardized manner. After preparation, rat-PCKS were incubated in a total of nine combinations of incubation media and antibiotics for four days.

The influence of the model pesticides parathion and paraoxon on human cytochrome P450 and associated oxygenases in HepaRG cells.

Introduction: Intentional and unintentional organophosphorus pesticide exposure is a public health concern. Organothiophosphate compounds require metabolic bioactivation by the cytochrome P450 system to their corresponding oxon analogues to act as potent inhibitors of acetylcholinesterase. It is known that interactions between cytochrome P450 and pesticides include the inhibition of major xenobiotic metabolizing cytochrome P450 enzymes and changes on the genetic level.

The use of bispyridinium non-oxime analogues for the restoration of nerve agent impaired neuromuscular transmission in rat hemidiaphragms - Structure optimization.

Organophosphate pesticide poisoning challenges health care systems worldwide. Furthermore, nerve agents remain a continuous threat. The treatment options for organophosphate poisoning have virtually been unchanged for decades, relying on symptomatic treatment and the use of oximes to indirectly restore neuromuscular function.

Toxicokinetic analysis of the highly toxic nerve agent VX in commercially available multi-organ-chips - Ways to overcome compound absorption.

Organ-on-a-chip technology is considered a next-generation platform in pharmacology and toxicology. Nevertheless, this novel technology still faces several challenges concerning the respective materials which are used for these microfluidic devices. Currently available organ-chips are most often based on polydimethylsiloxane (PDMS).

Restoration of nerve agent impaired neuromuscular transmission in rat diaphragm by bispyridinium non-oximes - Structure-activity relationships.

Organophosphate (OP) poisoning is currently treated with atropine, oximes and benzodiazepines. The nicotinic signs, i.e.

A pharmacologically pre-contracted smooth muscle bowel model for the study of highly-potent opioid receptor agonists and antagonists.

Isolated organ models are a versatile tool for pharmacological and toxicological research. Small bowel has been used to assess the inhibition of smooth muscle contraction by opioids. In the present study, we set out to establish a pharmacologically stimulated rat bowel model.

Diagnostics and treatment of nerve agent poisoning-current status and future developments.

Although 193 states have committed to the Chemical Weapons Convention and 98% of the declared chemical weapons stockpiles have been destroyed so far, nerve agent poisoning remains a lingering threat. The recent dissemination of sarin in Syria, the assassination of Kim Jong-Nam in Malaysia, and the assault on Sergei Skripal in the United Kingdom underline the need for effective treatment. The current therapeutic options of a muscarinic receptor antagonist, an oxime, and an anticonvulsant have been unchanged for decades.

The arrhythmogenic potential of nerve agents and a cardiac safety profile of antidotes - A proof-of-concept study using human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM).

The global use of organophosphorus compounds (OP) for pest control and nerve agents being used in military conflicts and for assassinations renders intoxications by these agents a public health concern. OP-poisoned patients often suffer from dysrhythmias which may ultimately result in death. In this study, human-induced pluripotent stem cells derived cardiomyocytes were exposed to OP compounds in a microelectrode array system (MEA).

Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats.

Background: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.

Results of physical inspection before races and race-related characteristics and their association with musculoskeletal injuries in Thoroughbreds during races.

Objective: To estimate the relative risk of injury among horses deemed to be at increased risk of injury on the basis of prerace physical inspection findings and to examine the association of injury during races with race-related characteristics.

Design: Cohort study.

Animals: 2,187 Thoroughbred horses that started 3,227 races in Kentucky.

Systemic responses to SFHS-infusion in hemorrhaged dogs.

Anesthetized mongrel (weight range: 16-27 Kg) dogs were prepared for monitoring hemodynamics, blood flow distribution, plasma colloid osmotic pressure and renal functional parameters at various intervals. Removal of 35 ml/Kg blood resulted in marked drop and only partial spontaneous recovery in systemic and pulmonary arterial pressures, cardiac output and organ blood flows (> 50% flow-decrements occurred in kidney, spleen, heart, gut and pancreas); plasma colloid osmotic pressure as well as urine output and creatinine clearance also fell. Group I (n = 6) of dogs was transfused after 45 minutes of hypovolemia with their own anticoagulated blood, while Group II (n = 6) received an equal volume of unmodified 6% stromafree hemoglobin solution (SFHS).

Transmission of enteritis in the Syrian hamster.

Twenty-six of 39 Syrian hamsters obtained by this laboratory from a pet supplier had enteritis and showed signs of "wet tail." An enteritis was reproduced in healthy hamsters by oral inoculation of homogenized ilea and jejuna from the diseased hamsters. The most characteristic pathologicfeatures were a variably enlarged distal jejunum and ileum and granulomatous lesions in the ileal subserosal wall.

A survey of naturally occurring diseases of the Syrian hamster.

Questionnaires on research activities, mortality rates observed in various age groups, extent of examination of dead hamsters, and natural disease conditions and their relative importance were returned by 24 of 43 organisations surveyed in the United States. The average preweaning mortality rate due to all causes was 11-9%. Comparative data from 6 organisations that raised 87 880 hamsters in the calendar year 1971 indicated that 97-5% of total preweaning mortality was due to cannibalism.