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opc poisoning

Francine S Katz, Stevan Pecic, Laura Schneider, Zhengxiang Zhu, Ashley Hastings, Michal Luzac, Joanne Macdonald, Donald W Landry, Milan N Stojanovic
Organophosphate compounds (OPCs) are commonly used as pesticides and were developed as nerve agents for chemical warfare. Exposure to OPCs results in toxicity due to their covalent binding and inhibition of acetylcholinesterase (AChE). Treatment for toxicity due to OPC exposure has been largely focused on the reactivation of AChE by oxime-based compounds via direct nucleophilic attack on the phosphorous center. However, due to the disadvantages to existing oxime-based reactivators for treatment of OPC poisoning, we considered non-oxime mechanisms of reactivation...
March 31, 2018: Toxicology Letters
S Sichler, G Höfner, S Rappenglück, T Wein, K V Niessen, T Seeger, F Worek, H Thiermann, F F Paintner, K T Wanner
The bispyridinium compound MB327 has been shown previously to have a positive pharmacological effect against poisoning with organophosphorous compounds (OPCs). The mechanism by which it exerts its therapeutic effect seems to be directly mediated by the nicotinic acetylcholine receptor (nAChR). In the present study, the development of mass spectrometry based binding assays (MS Binding Assays) for characterization of the binding site of MB327 at the nAChR from Torpedo californica is described. MS Binding Assays follow the principle of radioligand binding assays, but do not, in contrast to the latter, require a radiolabeled reporter ligand, as the readout is in this case based on mass spectrometric detection...
November 13, 2017: Toxicology Letters
Getnet Mequanint Adinew, Assefa Belay Asrie, Eshetie Melese Birru
BACKGROUND: Despite the apparent benefits of organophosphate compounds (OPCs) acute organophosphate (OP) pesticide poison is an increasing problem worldwide. In a country like Ethiopia, where agriculture is a major component of the economy, these compounds are readily available to the general public. There is paucity of evidence from Ethiopia showing the pattern of organophosphate poisoning (OPP) in healthcare facilities. The objective of this study was to evaluate retrospectively the pattern of acute OPP at the University of Gondar Teaching Hospital in northwest Ethiopia, during September 2010 through December 2014 was conducted...
April 4, 2017: BMC Research Notes
K V Niessen, S Muschik, F Langguth, S Rappenglück, T Seeger, H Thiermann, F Worek
Organophosphorus compounds (OPC), i.e. nerve agents or pesticides, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). Inhibited AChE results in accumulation of acetylcholine in the synaptic cleft and thus the desensitisation of the nicotinic acetylcholine receptor (nAChR) in the postsynaptic membrane is provoked. Direct targeting of nAChR to reduce receptor desensitisation might be an alternative therapeutic approach. For drug discovery, functional properties of potent therapeutic candidates need to be investigated in addition to affinity properties...
April 15, 2016: Toxicology Letters
Teng Ma, Xiyan Wu, Qiyan Cai, Yun Wang, Lan Xiao, Yanping Tian, Hongli Li
Lead (Pb) poisoning has always been a serious health concern, as it permanently damages the central nervous system. Chronic Pb accumulation in the human body disturbs oligodendrocytes (OLs) differentiation, resulting in dysmyelination, but the molecular mechanism remains unknown. In this study, Pb at 1 μM inhibits OLs precursor cells (OPCs) differentiation via decreasing the expression of Olig 2, CNPase proteins in vitro. Moreover, Pb treatment inhibits the sodium/calcium exchanger 3 (NCX3) mRNA expression, one of the major means of calcium (Ca(2+)) extrusion at the plasma membrane during OPCs differentiation...
2015: International Journal of Molecular Sciences
Syed M Nurulain, Shreesh Ojha, Kornelia Tekes, Mohammad Shafiullah, Huba Kalasz, Abdu Adem
There are a great number of reports with assertions that oxidative stress is produced by organophosphorus compound (OPC) poisoning and is a cofactor of mortality and morbidity in OPC toxicity. In addition, antioxidants have been suggested as adjuncts to standard therapy. However, there is no substantial evidence for the benefit of the use of antioxidants in survival after acute intoxication of OPCs. The present study was conducted to assess the effectiveness of three non-enzymatic antioxidants (NEAOs), N-acetylcysteine (NAC), glutathione (GSH), and ascorbic acid (AA), in acute intoxication of adult male Wister rats with paraoxon...
2015: Oxidative Medicine and Cellular Longevity
Pinaki Dutta, Shruthi S Kamath, Ashish Bhalla, V N Shah, Anand Srinivasan, Prakamya Gupta, Surjit Singh
BACKGROUND: Organophosphate compound (OPC) poisoning is common in the developing countries such as India. The acute and later effects of OPC poisoning on pituitary and target gland hormones is largely unknown. MATERIALS AND METHODS: This prospective study was conducted at Postgraduate Institute of Medical Education and Research between January 2012 and March 2013. Fourteen patients (8 males, age 18-50 years) with acute OPC poisoning were included in the study based on the history and clinical features, documented decreased in plasma cholinesterase activity or presence of the OPC in gastric lavage/blood samples...
January 2015: Indian Journal of Endocrinology and Metabolism
V Ashok Murthy, Y J Visweswara Reddy
The aim of this prospective study design is to understand the audiological parameters in central and peripheral auditory pathway in organophosphorus compound (OPC) poisoning, within the setting of Tertiary care/Medical College Hospital we studied Distortion Product Oto Acoustic Emission (DPOAE) and brain evoked response audiometry (BERA) in 25 patients with OPC poisoning with respiratory failure and 75 patients without respiratory failure. The results showed that DPOAE was absent in 17 patients with respiratory failure and 51 patients without respiratory failure...
January 2014: Indian Journal of Otolaryngology and Head and Neck Surgery
Syed M Nurulain, Tekes Kornelia, Syed Naimul Hassan Naqvi, Charu Sharma, Shreesh Ojha, Abdu Adem
Oxime-type acetylcholinesterase reactivators (oxime-AChER) are used as an adjunct in the treatment for organophosphorus anticholinesterase poisoning. Because of the widespread usage and exposure of organophosphorus compounds (OPCs), its poisoning and fatalities is obvious in pregnant women, embryos and fetuses. OPCs irreversibly inhibit acetylcholinesterase (AChE) at nerve synapses. Furthermore, the role of AChE other than neurotransmission termination has been defined in the literature. The growing evidences show that cholinergic mechanisms are involved during growth and development of other organ systems...
March 2014: Archives of Toxicology
Dietrich E Lorke, Syed M Nurulain, Mohamed Y Hasan, Kamil Kuča, Georg A Petroianu
Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone...
October 2014: Journal of Applied Toxicology: JAT
Marina Schäfer, Franziska Koppe, Bernhard Stenger, Christoph Brochhausen, Annette Schmidt, Dirk Steinritz, Horst Thiermann, Charles James Kirkpatrick, Christine Pohl
Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system...
December 5, 2013: Chemico-biological Interactions
Syed Muhammad Nurulain
Organophosphorus compounds (OPCs) have a wide variety of applications and are a serious threat for self-poisoning, unintentional misuse, terrorist attack, occupational hazard and warfare attack. The present standard treatment has been reported to be unsatisfactory. Many novel approaches are being used and tested for acute organophosphorus (OP) poison treatment. The bioscavenger concept captured high attention among the scientific community during the last few decades. Other approaches like alkalinisation of blood plasma/serum and use of weak inhibitors against strong inhibitors, though it showed promising results, did not get such wide attention...
July 2012: JPMA. the Journal of the Pakistan Medical Association
Milan Jokanović
During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with organophosphorus compounds. Their mechanism of action is reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus agents. Organophosphorus compounds (OPC) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OPC can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions...
2012: Current Topics in Medicinal Chemistry
Georg A Petroianu, Syed M Nurulain, Mohamed Shafiullah, Mohamed Y Hasan, Kamil Kuča, Dietrich E Lorke
Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0...
September 2013: Journal of Applied Toxicology: JAT
Mohammed Joynal Abedin, Abdullah Abu Sayeed, Ariful Basher, Richard J Maude, Gofranul Hoque, M A Faiz
Severe organophosphate compound (OPC) poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine the best therapy. A study was therefore undertaken to determine the optimal dosing regimen for atropine in the treatment of OPC poisoning. An open-label randomized clinical trial was conducted in Chittagong Medical College Hospital, Chittagong, Bangladesh, on 156 hospitalized individuals with OPC poisoning from June to September 2006...
June 2012: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
Harald John, Marc-Michael Blum
Pralidoxime (2-PAM) belongs to the class of monopyridinium oximes with reactivating potency on cholinesterases inhibited by phosphylating organophosphorus compounds (OPC), for example, pesticides and nerve agents. 2-PAM represents an established antidote for the therapy of anticholinesterase poisoning since the late 1950s. Quite high therapeutic concentrations in human plasma (about 13 µg/ml) lead to concentrations in urine being about 100 times higher allowing the use of less sensitive analytical techniques that were used especially in the early years after 2-PAM was introduced...
March 2012: Drug Testing and Analysis
F R Chowdhury, A U Rahman, F R Mohammed, A Chowdhury, H A M N Ahasan, M A Bakar
This retrospective study was carried out in the Medicine Department of Khulna Medical College, the biggest tertiary hospital in the southern part of Bangladesh to observe the trends of poisoning in southern part of Bangladesh over four years including age and sex variation, mode of poisoning, type of poison used and outcome of poisoning. The hospital medical records of all patients, aged 10 years and above with history of acute poisoning from January, 2003 to December, 2006 were enrolled. Patients were categorized into four age group including Group (Gr...
August 2011: Bangladesh Medical Research Council Bulletin
A Barelli, P M Soave, M Del Vicario, R Barelli
Organophosphorus compounds (OPCs) are widely used in agriculture as pesticides and occasionally in industrial settings. They have also been developed as warfare nerve agents. OPCs poisoning from intentional, accidental, and occupational exposure is a major public health problem, especially across the rural developing world. The main toxic mechanism of OPCs is the inhibition of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), resulting in accumulation of acetylcholine (ACh) at the synapse with cholinergic crisis and possible death...
December 2011: Minerva Anestesiologica
Supreeti Biswas, Kanchan Kumar Mondal, Debasish Som, Subesha Basu Roy, Swaraj Haldar
Indiscriminate use of organophosphorus compounds (OPC) increases the potential threat of self-poisoning and death. To make a conclusive diagnosis on academic interest a retrospective record-based study was undertaken. Postautopsy studies were carried out on 100 victims of OPC poisoning by collecting data from following 3 sources: Medicolegal autopsy reports, inquest reports, and inpatient case sheets. Mode of ingestion of OPC was to commit suicide. Incidence was more in 20 to 30 years age group, in females and in urban area...
September 2010: Journal of the Indian Medical Association
Harald John, Florian Eyer, Thomas Zilker, Horst Thiermann
S-hyoscyamine (S-hyo) is a toxic tropane alkaloid from plants of the solanacea family, which is extracted for pharmaceutical purposes thereby undergoing racemization (atropine). Merely the S-hyo enantiomer acts as an antagonist of muscarinic receptors (MR). Nevertheless, racemic atropine is clinically administered in e.g. ophthalmology and for symptomatic therapy of acute poisoning with organophosphorus compounds (OPCs, e.g. pesticides, nerve agents). However, very limited data are available of comparative pharmacokinetics of S- and R-enantiomers in humans or other species...
November 8, 2010: Analytica Chimica Acta
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