Suicidal ingestion of organophosphorus (OP) or carbamate (CM) compounds challenges health care systems worldwide, particularly in Southeast Asia. The diagnosis and treatment of OP or CM poisoning is traditionally based on the clinical appearance of the typical cholinergic toxidrome, e.g. miosis, salivation and bradycardia. Yet, clinical signs might be inconclusive or even misleading. A current case report highlights the importance of enzymatic assays to provide rapid information and support clinicians in diagnosis and rational clinical decision making. Furthermore, the differentiation between OP and CM poisoning seems important, as an oxime therapy will most probably not provide benefit in CM poisoning, but-as every pharmaceutical product-it might result in adverse effects. The early identification of the causing agent and the amount taken up in the body are helpful in planning of the therapeutic regimen including experimental strategies, e.g. the use of human blood products to facilitate scavenging of the toxic agent. Furthermore, the analysis of biotransformation products and antidote levels provides additional insights into the pathophysiology of OP or CM poisoning. In conclusion, cholinesterase activities and modern analytical methods help to provide a more effective treatment and a thorough understanding of individual cases of OP or CM poisoning.

Yükselmiş U, Özçetin M, Çağ Y, Yıldızdaş D, Yılmaz HL. The role of plasmapheresis in organophosphate poisoning: Case reports of three pediatric patients. Turk J Pediatr 2017; 59: 491-496. The aim of the study was to assess the impact of plasmapheresis treatment in the management of three pediatric patients with organophosphate poisoning who did not respond to standard treatment. The treatment of signs and symptoms, and supportive treatment has been evaluated in this paper. Patients were initially given atropine infusion and 0.05 mg/kg atropine with five-minute intervals. Despite pralidoxime loading and three consecutively infusions clinical symptoms did not respond to the treatment and plasma pseudocholinesterase levels did not decrease. At this point, plasmapheresis was used on three consecutive days. Accordingly, the clinical signs improved and mechanical ventilation was no longer necessary. Patients were discharged on the sixteenth day after their admission to the hospital. Plasmapheresis may be an option for the patients who do not respond to atropine and pralidoxime treatment in organophosphate poisoning.

Between late 2010 to early 2011, an increased mortality in gulls was observed along the northern coast of Portugal, with individuals exhibiting neurologic disorders consistent with an eventual anticholinesterase pesticide poisoning event. To clarify if this mortality was related to organophosphate (OP) and/or carbamate (CB) poisoning, chemical and spontaneous cholinesterase (ChE) reactivation was tested in the brain of the yellow-legged gull (Larus michahellis). Initial brain ChE activity in L. michahellis was 40.92 ± 5.23 U/mg of protein (average ± SE). Following chemical and spontaneous reactivation, ChE activity increased in average 70.38 ± 48.59% and 131.95 ± 92.64%, respectively. ChE reactivation was found to decrease at increasing concentrations of the oxime pyridine-2-aldoxime methochloride and dilution factor, underscoring the importance of first optimizing the assay conditions prior to its use on bird species. These results suggest that birds analysed could have been exposed to OP and CB pesticide compounds and that in most cases CB exposure appeared to be the main cause of birds poisoning. These results are an important contribution to environmental monitoring as it demonstrates the suitability of L. michaellis as sentinel species of OP and CB pesticides within an urban environment.

Accidental self-poisoning or deliberate use in suicidal intent of organophosphorus pesticides (OPP), which are widely used in agriculture, represent a health problem worldwide. Symptoms of poisoning are characterized by acute cholinergic crisis caused by inhibition of acetylcholinesterase. A 75-year-old male patient ingested 20ml of an OPP solution containing 10% methamidophos in suicidal intent. In the course of poisoning typical clinical symptoms of cholinergic crisis (miosis, bradycardia, hypotension, hypersalivation and impairment of neurologic status) were evident. Butyryl (plasma) cholinesterase (BChE) and red blood cell acetylcholinesterase (RBC-AChE) revealed decreased activities, thus specific treatment with the enzyme reactivator obidoxime was started. Inhibitory activity of the patient\'s plasma indicated significant amounts of persisting methamidophos in the circulation and was still found on day 4 after ingestion. Due to missing spontaneous breathing on day 6, obidoxime was administered again. Afterwards a significant increase of RBC-AChE activity was found. The patient was extubated on day 10 and a restitution ad integrum was achieved. In conclusion, obidoxime is a potent reactivator of OPP-inhibited AChE. A repetitive and prolonged administration of obidoxime should be considered in cases of severe methamidophos poisoning and should be tailored with an advanced analytical biomonitoring.

Alzheimer\'s disease (AD) is characterized by an extensive loss of cholinergic neurons, and their cortical projections, from the basal forebrain area. The resulting reduction in cholinergic activity is associated with decreased levels of the neurotransmitter acetylcholine (ACh), decreased activity of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased butyrylcholinesterase (BChE) activity. In the present study, we investigated whether the BCHE, ACHE, and CHAT genes were associated with AD and the possibility of a synergistic effect with APOE-epsilon4 in a Sardinian sample. AD patients (n = 158), exclusively of Sardinian ancestry, were recruited from the Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology, Department of Neurosciences, University of Cagliari. Patients were diagnosed according to DSM-IV, and National Institute of Neurologic and Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) criteria for possible or probable AD. Cognitive screening was performed by means of Mini-Mental State Examination (MMSE). Healthy controls (n = 118) of Sardinian ancestry were recruited from religious and sport associations. All patients and control subjects gave informed consent for participation in the study. Single nucleotide polymorphism (SNP) analysis was performed by PCR/RFLP or the TaqMan 5\' exonuclease method. Our study confirms the association between APOE epsilon4 allele and AD (P < 0.000). No significant differences were observed in allele and genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype analysis of ACHE SNPs did not reveal a significant association between ACHE and AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not constitute a major genetic risk factor for susceptibility to AD in a Sardinian population.

暂无摘要。

To counter the threat of organophosphate nerve agents, military personnel may be issued auto-injectors containing pralidoxime chloride. This drug helps to dephosphorylate the nerve agent-acetylcholinesterase complex and, thus, regenerate the enzyme. In non-poisoned persons, pralidoxime chloride is rapidly excreted by the kidneys and is fairly well tolerated. We present the first reported case of an accidental injection of an Air Force aviator by an auto-injector. The patient recovered well with no specific treatment needed. The pharmacology and toxicology of pralidoxime chloride are discussed.

A couple showing signs of cholinergic crisis was admitted to the hospital. Analyses with high-performance liquid chromatography and gas chromatography-mass spectrometry conducted on serum, urine, and stomach contents that were collected few hours after first symptoms showed the presence of aldicarb, which is the most potent carbamate insecticide on the market. A murder attempt was suspected because the patients showed the first signs some minutes after drinking coffee upon returning home and no commercial products containing aldicarb were found in the house. Because of the reversibility of inhibition of acetylcholinesterase, the patients recovered after treatment with atropine and toxogonin. They left the hospital after 12 days. To our knowledge, the serum concentrations of aldicarb reported in this paper are the highest reported for a nonfatal case.

Aldicarb is the most potent of the commercially available carbamate pesticides and is an unusual source of acute human poisonings. We present the case of a 43-year-old man exposed to aldicarb who developed severe cholinergic symptoms and progressive weakness requiring intubation for 5 days. Both his red blood cell cholinesterase and plasma pseudocholinesterase levels were depressed for a minimum of 44 hours. He demonstrated neuromuscular improvement concurrent with pralidoxime administration. The pertinent medical literature on aldicarb poisoning is reviewed.

暂无摘要。