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oxime, poisoning, organophosphate

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https://www.readbyqxmd.com/read/27896325/utilization-of-plasmapheresis-for-organophosphate-intoxication-a-case-report
#1
Nezihat Rana Disel, Ayca Acikalin, Zeynep Kekec, Ahmet Sebe
Organophosphate (OP) compounds are extremely toxic chemicals that may be absorbed via skin, conjunctiva, gastrointestinal and respiratory systems. Treatment of OP poisoning is a critical and aggressive process which includes decontamination, antidote administration (atropin and oximes), mechanical ventilation support and extracorporeal elimination procedures if needed. Here we present a young female patient who was unintentionally poisoned by an OP (trichlorfon) after using it to moisture her skin. The importance of this patient is the dermal disease that makes her unprotective to dermal exposure of chemicals and application of plasmapheresis to treat her poisoning...
June 2016: Turkish Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27830420/organophosphate-hydrolyzing-enzymes-as-first-line-of-defence-against-nerve-agent-poisoning-perspectives-and-the-road-ahead
#2
REVIEW
A R Satvik Iyengar, Abhay H Pande
Nerve agents (NAs) are extremely neurotoxic synthetic organophosphate (OP) compounds exploited as weapons of mass destruction in terrorist attacks and chemical warfare. Considering the current world scenario, there is a persistent threat of NA-exposure to military personals and civilians. Various prophylactic and post-exposure treatments (such as atropine and oximes) available currently for NA-poisoning are inadequate and unsatisfactory and suffer from severe limitations. Hence, developing safe and effective treatment(s) against NA-poisoning is a critical necessity...
December 2016: Protein Journal
https://www.readbyqxmd.com/read/27396356/in-vitro-characterization-of-pralidoxime-transport-and-acetylcholinesterase-reactivation-across-mdck-cells-and-stem-cell-derived-human-brain-microvascular-endothelial-cells-bc1-hbmecs
#3
Erin Gallagher, Il Minn, Janice E Chambers, Peter C Searson
BACKGROUND: Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. METHODS: To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs)...
2016: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/27371941/limitations-in-current-acetylcholinesterase-structure-based-design-of-oxime-antidotes-for-organophosphate-poisoning
#4
Andrey Kovalevsky, Donald K Blumenthal, Xiaolin Cheng, Palmer Taylor, Zoran Radić
Acetylcholinesterase (AChE; EC 3.1.1.7), an essential enzyme of cholinergic neurotransmission in vertebrates, is a primary target in acute nerve agent and organophosphate (OP) pesticide intoxication. Catalytically inactive OP-AChE conjugates formed between the active-center serine and phosphorus of OPs can, in principle, be reactivated by nucleophilic oxime antidotes. Antidote efficacy is limited by the structural diversity of OP-AChE conjugates resulting from differences in the structure of the conjugated OP, the different active-center volumes they occupy when conjugated to the active-center serine of AChE, and the distinct chemical characteristics of both OPs and oximes documented in numerous X-ray structures of OP-conjugated AChEs...
August 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27212759/a-study-of-effectiveness-of-fresh-frozen-plasma-in-organophosphorous-compound-poisoning-in-reducing-length-of-intensive-care-unit-stay-and-in-reducing-need-for-tracheostomy
#5
V P Dayananda, B Bhaskara, G N P Pateel
BACKGROUND: The main stay of treatment in organophophosphorous [OP] poisoning is with atropine, oximes and supportive therapy. Despite the therapy, no improvement in mortality and morbidity. Fresh frozen plasma [FFP] a source of serum cholinesterase act as bio-scavenger to neutralise organophosphate toxins to improve the patients out come. METHODS: The prospective study was conducted in 80 patients with acute OP poisoning. Patients with moderate to severe grade of OP poisoning with serum cholinesterase level <1000 IU/L were included in the study...
May 2016: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/27191504/structures-of-paraoxon-inhibited-human-acetylcholinesterase-reveal-perturbations-of-the-acyl-loop-and-the-dimer-interface
#6
Matthew C Franklin, Michael J Rudolph, Christopher Ginter, Michael S Cassidy, Jonah Cheung
Irreversible inhibition of the essential nervous system enzyme acetylcholinesterase by organophosphate nerve agents and pesticides may quickly lead to death. Oxime reactivators currently used as antidotes are generally less effective against pesticide exposure than nerve agent exposure, and pesticide exposure constitutes the majority of cases of organophosphate poisoning in the world. The current lack of published structural data specific to human acetylcholinesterase organophosphate-inhibited and oxime-bound states hinders development of effective medical treatments...
September 2016: Proteins
https://www.readbyqxmd.com/read/27138243/synthesis-and-in-vitro-reactivation-screening-of-imidazolium-aldoximes-as-reactivators-of-sarin-and-vx-inhibited-human-acetylcholinesterase-hache
#7
Rahul Sharma, Bhanushree Gupta, Arvind Kumar Sahu, Jyotiranjan Acharya, Manmohan L Satnami, Kallol K Ghosh
Post-treatment of organophosphate (OP) poisoning involves the application of oxime reactivator as an antidote. Structurally different oximes are widely studied to examine their kinetic and mechanistic behavior against OP-inhibited cholinesterase enzyme. A series of structurally related 1,3-disubstituted-2-[(hydroxyiminomethyl)alkyl]imidazolium halides (5a-5e, 9a-9c) were synthesized and further evaluated for their in-vitro reactivation ability to reactivate sarin- and VX-inhibited human acetylcholinesterase (hAChE)...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27129421/novel-bifunctional-hybrid-small-molecule-scavengers-for-mitigating-nerve-agents-toxicity
#8
Gabriel Amitai, Rellie Gez, Lily Raveh, Nira Bar-Ner, Ettie Grauer, Shira Chapman
The antidotal treatment of organophosphates (OP) nerve agents (NA) poisoning is based on anticholinergics (e.g. atropine) combined with oxime reactivators (e.g. 2PAM) of acetylcholinesterase (AChE). This treatment is symptomatic and does not degrade the OP. New small-molecule OP scavengers were developed as bifunctional hybrids. Their molecular design was based on combining a nucleophile that directly degrades OP with a moiety that reactivates OP-inhibited AChE. The OP degrading moiety is either benzhydroxamic acid (BHA) or 4-pyridinehydroxamic acid (4PHA) coupled via (CH2)n, (n = 1 or 3) to 2PAM...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27125761/oximes-in-organophosphate-poisoning-60-years-of-hope-and-despair
#9
Franz Worek, Horst Thiermann, Timo Wille
The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27125569/mechanistic-studies-of-new-oximes-reactivators-of-human-butiryl-cholinesterase-inhibited-by-cyclosarin-and-sarin
#10
Willian E Amaral de Lima, Ander Francisco, Elaine F F da Cunha, Zoran Radic, Palmer Taylor, Tanos C C França, Teodorico C Ramalho
Butyryl cholinesterase (BChE) has been seen as a key enzyme in the search for new strategies in the treatment of poisoning by organophosphates (OPs), since human BChE (HssBChE), complexed with the appropriate oxime, can be a suitable scavenger and deactivator for OPs in the blood stream. However, the efficacy of HssBChE is limited by its strict stoichiometric scavenging, slow reactivation and propensity for aging. The improvement of the reactivation rate by new and more efficient oximes could contribute to mitigate this problem and increase the HssBChE efficiency as scavenger...
April 29, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27102179/efficacy-of-recommended-prehospital-human-equivalent-doses-of-atropine-and-pralidoxime-against-the-toxic-effects-of-carbamate-poisoning-in-the-hartley-guinea-pig
#11
Matthew K Brittain, Kevin G McGarry, Robert A Moyer, Michael C Babin, David A Jett, Gennady E Platoff, David T Yeung
PURPOSE: Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning (muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride [2-PAM Cl]) could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates...
May 2016: International Journal of Toxicology
https://www.readbyqxmd.com/read/27101948/oxime-mediated-in-vitro-reactivation-kinetic-analysis-of-organophosphates-inhibited-human-and-electric-eel-acetylcholinesterase
#12
Arvind Kumar Sahu, Rahul Sharma, Bhanushree Gupta, Kamil Musilek, Kamil Kuca, Jyotiranjan Acharya, Kallol K Ghosh
Organophosphate (OP)-based pesticides and nerve agents are highly toxic compounds which interrupt the catalytic mechanism of acetylcholinesterase (AChE) by phosphorylating the hydroxyl moiety of serine residue. The inhibited enzyme can be reactivated by the nucleophilic action of oxime reactivators. To analyze the effect of different AChE sources on reactivation efficacy of reactivators, several in vivo studies have carried out using variety of AChE sources like pig, rat and monkey. Investigations on species differences provide a better insight for the development of new reactivators...
June 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/26899146/emergence-of-catalytic-bioscavengers-against-organophosphorus-agents
#13
Patrick Masson, Sofya V Lushchekina
Bioscavengers are an effective alternative approach for pre- and post-exposure treatments of nerve agent (NA) poisoning. Bioscavengers are natural or recombinant enzymes, reactive proteins, and antibodies that neutralize NAs before they reach their physiological targets. They are administered by injection (protein or gene delivery vector) and react with NAs in the bloodstream. Other ways of delivery can be used: inhalation for pulmonary delivery, topical creams for skin protection, etc. Operational bioscavengers must be producible at low cost, not susceptible to induce immune response and adverse effects, and stable in the bloodstream, upon storage, and under field conditions...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/26751814/intranasal-delivery-of-obidoxime-to-the-brain-prevents-mortality-and-cns-damage-from-organophosphate-poisoning
#14
Jishnu K S Krishnan, Peethambaran Arun, Abhilash P Appu, Nivetha Vijayakumar, Taíza H Figueiredo, Maria F M Braga, Sudikshya Baskota, Cara H Olsen, Natalia Farkas, John Dagata, William H Frey, John R Moffett, Aryan M A Namboodiri
Intranasal delivery is an emerging method for bypassing the blood brain barrier (BBB) and targeting therapeutics to the CNS. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the BBB. Therefore, they cannot effectively counteract the central neuropathologies caused by cholinergic over-activation when administered peripherally. For these reasons we examined intranasal administration of oximes in an animal model of severe organophosphate poisoning to determine their effectiveness in reducing mortality and seizure-induced neuronal degeneration...
March 2016: Neurotoxicology
https://www.readbyqxmd.com/read/26735571/extrapyramidal-effects-of-acute-organophosphate-poisoning
#15
Kent K Reji, Vivek Mathew, Anand Zachariah, Anil Kumar B Patil, Samuel George Hansdak, Ravikar Ralph, John Victor Peter
BACKGROUND: There is limited information on extrapyramidal symptoms in acute organophosphate (OP) poisoning. We describe the course and outcome of severely poisoned patients who develop extrapyramidal manifestations. METHODS: In this prospective observational study, spanning 8 months (Apr-Nov 2013) adult patients (>18 years) admitted with OP poisoning were enrolled. Patients on anti-psychotic therapy, those refusing consent or presenting with co-ingestions were excluded...
March 2016: Clinical Toxicology
https://www.readbyqxmd.com/read/26564198/brain-cholinesterase-reactivation-as-a-marker-of-exposure-to-anticholinesterase-pesticides-a-case-study-in-a-population-of-yellow-legged-gull-larus-michahellis-naumann-1840-along-the-northern-coast-of-portugal
#16
Cátia S A Santos, Marta S Monteiro, Amadeu M V M Soares, Susana Loureiro
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...
January 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/26386953/development-and-validation-of-a-fia-uv-vis-method-for-pk-a-determination-of-oxime-based-acetylcholinesterase-reactivators
#17
Karel Musil, Veronika Florianova, Pavel Bucek, Vlastimil Dohnal, Kamil Kuca, Kamil Musilek
Acetylcholinesterase reactivators (oximes) are compounds used for antidotal treatment in case of organophosphorus poisoning. The dissociation constants (pK(a1)) of ten standard or promising acetylcholinesterase reactivators were determined by ultraviolet absorption spectrometry. Two methods of spectra measurement (UV-vis spectrometry, FIA/UV-vis) were applied and compared. The soft and hard models for calculation of pK(a1) values were performed. The pK(a1) values were recommended in the range 7.00-8.35, where at least 10% of oximate anion is available for organophosphate reactivation...
January 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/26274808/bispyridinium-compounds-inhibit-both-muscle-and-neuronal-nicotinic-acetylcholine-receptors-in-human-cell-lines
#18
Avi Ring, Bjorn Oddvar Strom, Simon R Turner, Christopher M Timperley, Michael Bird, A Christopher Green, John E Chad, Franz Worek, John E H Tattersall
Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects of acetylcholine accumulation and oximes to reactivate acetylcholinesterase (the effectiveness of which depends on the specific anticholinesterase), but does not directly address the nicotinic effects of poisoning. Bispyridinium molecules which act as noncompetitive antagonists at nicotinic acetylcholine receptors have been identified as promising compounds and one has been shown to improve survival following organophosphorus poisoning in guinea-pigs...
2015: PloS One
https://www.readbyqxmd.com/read/25701203/quaternary-and-tertiary-aldoxime-antidotes-for-organophosphate-exposure-in-a-zebrafish-model-system
#19
Hayden R Schmidt, Zoran Radić, Palmer Taylor, Erica A Fradinger
The zebrafish is rapidly becoming an important model system for screening of new therapeutics. Here we evaluated the zebrafish as a potential pharmacological model for screening novel oxime antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE). The ki values determined for chlorpyrifos oxon (CPO) and dichlorvos (DDVP) showed that CPO was a more potent inhibitor of both human and zebrafish AChE, but overall zebrafish AChE was less sensitive to OP inhibition. In contrast, aldoxime antidotes, the quaternary ammonium 2-PAM and tertiary amine RS-194B, showed generally similar overall reactivation kinetics, kr, in both zebrafish and human AChE...
April 15, 2015: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/25672037/acute-organophosphorus-poisoning-complicated-by-acute-coronary-syndrome
#20
Madhu Pankaj, Kavita Krishna
We report a case of 30 year old alcoholic male admitted with vomiting, drowsiness, limb weakness and fasciculations after alleged history of consumption of 30 ml of chlorpyriphos insecticide. He had low serum cholinesterase levels. With standard treatment for organophosphorus poisoning (OPP), he improved gradually until day 5, when he developed neck and limb weakness and respiratory distress. This intermediate syndrome was treated with oximes, atropine and artificial ventilation. During treatment, his ECG showed fresh changes of ST elevation...
July 2014: Journal of the Association of Physicians of India
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