Effect of diphenhydramine on myocardial injury caused by organophosphate poisoning.

BACKGROUND: The aim of this experimental study was to investigate whether diphenhydramine could prevent or diminish myocardial injury caused by organophosphate poisoning as defined by histologic findings and cardiac troponin I (cTnI) levels. METHODS: Twenty-four Sprague-Dawley rats were divided into equal three groups. Group 1 did not receive any agent during the experiment. Group 2 received 0.8 g/kg fenthion subcutaneously followed by normal saline (3 ml/kg) intramuscularly 30 minutes later. Group 3 received 0.8 g/kg fenthion subcutaneously, followed by diphenhydramine 30 mg/kg (in 3 ml/kg) intramuscularly 30 minutes later. All rats underwent laparotomy and thoracotomy while under anesthesia at 24 hours. RESULTS: Treatment with diphenhydramine significantly decreased the blood cTnI levels. Additionally, diphenhydramine significantly reduced myocardial injury, including edema, inflammation, vacuolization and necrosis, as determined by pathologic scoring. CONCLUSION: Organophosphate poisoning can cause myocardial injury as determined by measurement of I cTnI levels. Our study demonstrates that this injury can be attenutated by the administration of diphenydramine.

Effect of interleukin-10 on tissue damage caused by organophosphate poisoning.

Organophosphate poisoning is a common cause of severe morbidity and mortality among patients admitted to emergency departments. Tissue damages as a consequence of organophosphate poisoning are frequently reported, but preventing this potentially severe complication has not been the subject of much research. We tested whether interleukin-10, a cytoprotective agent, could prevent or diminish pathological signs of tissue damages caused by organophosphate poisoning. Thirty rats were divided into three equal groups (n = 10). Group 1 (sham) did not receive any agent during the experiment. Group 2 (control) received 0.8 g/kg of fenthion intraperitoneally, followed by 6 ml/kg of intraperitoneal normal saline 30 min and 3 hr later. Group 3 (treatment) received 0.8 g/kg of fenthion intraperitoneally, followed by 2 microg/kg of interleukin-10 intraperitoneally 30 min and 3 hr later. All rats were killed under anaesthesia after 6 hr and tissue samples were obtained from liver, kidneys and lungs. Even organophosphate poisonings do not cause significant clinical problems; several degrees of damages could be observed in liver, kidneys and lungs. These damages could be reduced by interleukin-10 treatment.

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. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. FINDINGS: Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. INTERPRETATION: Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.

Electromyography in relation to end-plate acetylcholinesterase in rats poisoned by different organophosphates.

Organophosphate (OP) poisoning produces various forms of acute, subacute, or delayed neurotoxicity. We investigated in vivo the relationship between clinical, histochemical and electromyographic (EMG) parameters in rats at various stages of poisoning by paraoxon or fenthion. Paraoxon is acutely toxic, whereas fenthion produces more sustained AChE inhibition. Fenthion has been involved in a subacute type of OP-related neurotoxicity in patients, the so-called intermediate syndrome. The animals underwent serial EMGs, with single and repetitive nerve stimulation, and concomitant contralateral muscle biopsies to determine the end-plate acetylcholinesterase (AChE) activity. Repetitive activity (RA) after single nerve stimulation and decrements on repetitive nerve stimulation (RNS) were the major EMG findings in either type of poisoning, occurring in the initial and later stages of the poisoning, respectively. RA was highly correlated to fasciculations in acute, but not in prolonged intoxication. Amplitude decrements provoked by RNS occurred only in weak rats with severe end-plate AChE inhibition. The smallest amplitude occurred either at the second response with gradual improvement in the subsequent responses (decrement-increment phenomenon), or the amplitude decrease progressed up to the last response (decrement phenomenon). The decrement-increment phenomenon preceded the decrement phenomenon and occurred at a slightly less severe degree of AChE inhibition. Various types of impairment of neuromuscular transmission coexist, probably to a different extent at distinct stages of anticholinesterase poisoning.

Acute and subacute organophosphate poisoning in the rat.

The intermediate syndrome in organophosphate poisoning is clinically characterized by weakness in the territory of cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep tendon reflexes. It occurs between the acute cholinergic crisis and the usual onset of organophosphate-induced delayed neurotoxicity. The weakness has been ascribed to muscle fiber necrosis. Fenthion has been the most common cause. This study assesses the occurrence of the necrotizing myopathy in rats in relation to the clinical course and the acetylcholinesterase (AChE) inhibition after poisoning with organophosphates representative for each of the major types of organophosphate-related neurotoxicity. Marked differences are noted in the duration of cholinergic symptoms and of AChE inhibition after either paraoxon and mipafox, or fenthion poisoning. The necrotizing myopathy begins shortly after the initial decline in AChE activity with all organophosphates studied. Maximal muscle involvement occurs within the first 2 days of the poisoning with all organophosphates studied. The myopathy is not aggravated by a further decline in AChE activity in fenthion poisoning. Our data argues against the monophasic necrotizing myopathy being the cause of the intermediate syndrome, and is suggestive of persistent AChE inhibition being involved.

Analysis of fenthion in postmortem samples by HPLC with diode-array detection and GC-MS using solid-phase extraction.

Fenthion (O,O-dimethyl-O-[3-methyl-4-(methylthio)-phenyl]-thiophos-phate ) is an organophosphate insecticide. A specific method to quantitate fenthion in postmortem matrices with solid-phase extraction combined with high-performance liquid chromatography-diode-array detection (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS) is presented. Fenitrothion (O,O-dimethyl-O-[3-methyl-4-nitrophenyl]-thiophosphate) is selected as the internal standard. For sample cleanup, a simple but selective solid-phase extraction is chosen after comparison with traditional liquid-liquid extraction procedures. Homogenized and appropriately diluted aqueous samples are applied, and the analytes are desorbed with 5 mL of dichloromethane. Aliquots of the extract are used for HPLC-DAD and GC-MS analysis, Liquid and GC conditions are as follows: gradient elution with a mixture of methanol and water (10:90 to 90:10, v/v) containing 0.0125M NaOH on an Aluspher RP-Select B column monitoring at 250 nm, and temperature programming from 60 to 300 degrees C on a dimethylpolysiloxane column in the SCAN mode, respectively. This method is applied to a suicidal case involving unsuspected acute intoxication with fenthion (concentration in blood, 3.8 micrograms/mL).

Parasuicide by self-injection of an organophosphate insecticide.

Parasuicide by ingestion of organophosphate (OP) insecticides is common in Sri Lanka, but the use of the parateral route to self administer the poison is extremely rare. We report a patient who deliberately injected herself intramuscularly with an OP compound with suicidal intent. The clinical manifestations of OP poisoning were unpredictable and posed a therapeutic problem.

Extrapyramidal manifestations complicating organophosphorus insecticide poisoning.

Six patients who developed extrapyramidal manifestations following poisoning with the organophosphorus (OP) insecticide fenthion are reported. The extrapyramidal features, in order of frequency, were dystonia, rest tremor, cog-wheel rigidity, and choreo-athetosis. The delay in onset of these signs, following poisoning, varied from 4 to 40 days, and they disappeared spontaneously in about 1 to 4 weeks in those who survived. The human extrapyramidal system is rich in cholinergic neurons and acetylcholinesterase (AChE). Inhibition of AChE by fenthion, which has ready access to central neurons on account of its lipid solubility, is postulated as the mechanism underlying the extrapyramidal manifestations.

Severe fenthion intoxications due to ingestion and inhalation with survival outcome.

Two cases of severe fenthion intoxication are presented. The first is a case of a psychiatric patient who attempted suicide with ingestion of the compound, and the second case was of a child exposed to the chemical agent by air spraying. Both patients were treated in the intensive care unit with atropine and pralidoxime and finally survived. Fenthion blood levels on admission were 2.7 and 0.95 microg/mL, respectively. Different concentrations of pralidoxime were added to the first patient's poisoned serum in order to assess in vitro the effect of pralidoxime on cholinesterase reactivation. The clinical and toxicological data of the poisonings are discussed, as well as the potential therapeutic use of pralidoxime in organophosphate intoxication.

Case histories of bald eagles and other raptors killed by organophosphorus insecticides topically applied to livestock.

Since 1982 when secondary poisoning of a red-tailed hawk (Buteo jamaicensis) was documented following the recommended use of famphur applied topically to cattle, the Patuxent Wildlife Research Center has tested dead birds of prey for poisoning by famphur and other pour-on organophosphorus (OP) insecticides. Brain cholinesterase (ChE) activity was first determined, then if ChE was depressed greater than or equal to 50%, stomach and/or crop contents were evaluated for anti-ChE compounds. This report presents the circumstances surrounding the OP-caused deaths of eight bald eagles (Haliaeetus leucocephalus), two red-tailed hawks, and one great horned owl (Bubo virginianus) between March 1984 and March 1985. OP poisoning of raptors by pour-on insecticides in the United States is widespread, but its magnitude is unknown.

Evaluation of hazards involved in treating cattle with pour-on organophosphate insecticides.

Eighteen veterinarians regularly practicing organophosphate pour-on treatment of cattle for grub infestations were examined in the course of the 1975-1976 application season for symptoms and signs as well as enzymologic and chemical evidence of organophosphate absorption. Some subjects reported headache, nausea, and irritation of the face and throat during chemical applications in poorly ventilated buildings. Organophosphate absorption was not sufficient to depress blood cholinesterase activities, and only occasionally generated measurable amounts of alkyl phosphate meatbolites in urine of exposed veterinarians.

Selected neurotoxins.

The small animal practitioner is faced with an infinite number of potential toxins in our modern environment. Unapproved usage of drugs and insecticides requires the practitioner to keep informed about the development of new toxic syndromes. Recreational drug toxicosis in animals is still seen with some frequency in clinical practice and should not be overlooked, even when the owner denies the possible exposure. In this article, we have discussed a few of the more common and newer neurotoxicities seen in clinical practice today. Neurologic toxicities are complex, but treatment can be rewarding if early diagnosis is made and aggressive therapy is instituted. The practitioner will find it worthwhile to establish contact with a toxicologist or poison information center for additional support when necessary.

The neurophysiologic examination in organophosphate ester poisoning. Case report and review of the literature.

A 65-year-old woman who has been admitted after organophosphate-induced poisoning (Fenthion), develops pareses as a result of neuromuscular junctional dysfunction 7 days post-exposure. These findings are consistent with an intermediate syndrome, which may appear within 24 to 96 hours of exposure and subsides after 5 to 18 days. Delayed polyneuropathy develops within 1 to 3 weeks and abates after 6 to 12 months. A distal axonopathy can be demonstrated. Several authors have attempted EMG monitoring of pesticide-workers in agricultural and industrial settings. The electrophysiologic examination is an important diagnostic adjunct in the development and course of muscle paresis following organophosphate-ester poising.

Possible fenthion toxicity in magpies (Pica pica).

Unusual mortality in magpies (Pica pica) is described. Dead or sick birds were discovered in proximity to cattle in Alberta feedlots. Subsequent examinations indicated magpies were being exposed to fenthion, an organophosphate used on cattle for control of warble larvae and lice. The possibility of toxicity with fenthion is suggested.

Observation on a human intentional poisoning case by the organophosphorus insecticide fenthion.

A case of acute poisoning by oral ingestion of fenthion is reported. Plasma cholinesterase activity and fenthion whole blood concentration were thoroughly evaluated during the therapeutic intervention that consisted in administration of atropine, toxogonine and fresh plasma. Correlation studies between clinical signs, cholinesterase activity and fenthion levels revealed that pChE activity was not as helpful as the patient's clinical status in determining when the atropine infusion could be stopped. Moreover pChE was also useless in signaling sudden relapses. It is concluded, based on this case, that supportive care combined with antidotal therapy remains the cornerstone of treatment specially in severe acute poisoning cases.

[Chronic organophosphorus intoxication and aging in rats].

Possible acceleration of aging due to the administration of organophosphorus pesticide (OP) was studied. Fenthion (6 mg/kg/day) was subcutaneously administered dorsally to rats over a period of 12 weeks. The amounts of fluorescent lipid peroxidation products (FLPP) and superoxide dismutase (SOD) activity were measured in various tissues. Microscopic examination was added only in the lens. The amount of FLPP in the retina-choroid, lens, kidney and heart of the rats was found to be increased (lens; p less than 0.01, kidney; p less than 0.05). The activity of SOD in the retina-choroid, optic nerve, liver and heart increased temporarily, but eventually returned to control levels. The lens preparations at the end of the 12-week administration period showed irregular bow configuration and epithelial nuclear dislocation in the bow area. FLPP are fluorescent products produced by peroxide lipids and their amounts increase with aging. Increase in the amounts of these products and microscopic findings for the lens were indications of the progress of aging. There is thus the possibility that the inducement of SOD production may decrease with aging. It was concluded that the organophosphorus pesticide may accelerate the aging of rats.

[Sensitivity of the females of Ixodes persulcatus and Dermacentor silvarum (Ixodidae) to baytex and the possibility of their overcoming poisoning with this substance]. / Chuvstvietl'nost' samok Ixodes persulcatus i Dermacentor Silvarum (Ixodidae) k baiteksu i vozmozhnost' predoleniia otravleniia.

Females of I. persulcatus and D. silvarum are very sensitive to baytex, the value of LD50 for both species are similar. The development of injury after exposure to baytex proceeds very quickly and the subsequent stages of injury development correspond to those caused by DDT (Uspensky and Levikov, 1974). The overcoming of baytex poisoning during the sucking of the host's blood is possible only at the initial stage of the injury. The simulatneous feeding on the same rabbit of ticks treated with baytex and control ones has shown a system effect of baytex on the second group of ticks.