Dizocilpine improves beneficial effects of cholinergic antagonists in anticholinesterase-treated mice. (1/15)

Mice were administered anticholinesterase pesticides dichlorvos (DDVP) or methomyl (MET). Both DDVP and MET induced dose-dependent seizures and lethality in mice. The muscarinic antagonist atropine (ATR, 1.8 mg/kg) did not prevent seizures but diminished the lethality induced by DDVP or MET. The nicotinic antagonist mecamylamine (MEC, 1 mg/kg) affected neither DDVP-induced seizures nor DDVP- and MET-induced lethality, but diminished MET-induced seizures. At a higher dose (10 mg/kg), MEC attenuated seizures produced by MET, but not DDVP, and decreased lethality of both anticholinesterases. The N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801, 1 mg/kg) prevented DDVP-, but not MET-induced seizures. MK-801 did not affect DDVP- or MET-induced lethality. Concurrent administration of ATR and MK-801 prevented the occurrence of DDVP- but not MET-induced seizures. MK-801 coadministered with ATR enhanced its protective effect against DDVP- or MET-induced lethality in mice. Coinjection of MEC (at both doses studied) and MK-801 completely prevented seizures produced by both acetylcholinesterase (AChE) inhibitors. Coadministration of MEC (1 mg/kg) and MK-801 protected mice against DDVP or MET lethality. MK-801 administered along with MEC at 10 mg/kg enhanced antilethal effects of the nicotinic antagonist in DDVP- or MET-treated mice. With respect to the mechanism underlying anticholinesterase-induced neurotoxicity, muscarinic and nicotinic, as well as NMDA receptors, seem to play major roles. The results suggest that combined treatment with cholinergic and NMDA antagonists might be beneficial in anticholinesterase-induced poisonings.  (+info)

Methomyl-induced severe acute pancreatitis: possible etiological association. (2/15)

CONTEXT: N-methyl carbamate insecticides are widely used in homes, gardens and agriculture. They share the capacity to inhibit cholinesterase enzymes with organophosphates and therefore share similar symptomatology during acute and chronic exposures. One of the serious effects of organophosphate and carbamate intoxication is the development of acute pancreatitis and subsequent intrapancreatic fluid formation. CASE REPORT: An 18-year old Caucasian man was admitted to our Intensive Care Unit with cholinergic crisis symptomatology, after the ingestion of an unknown amount of a carbamate insecticide (methomyl). Pseudocholinesterase levels were 2 kU/L on the day of admission (reference range: 5.4-13.2 kU/L). Two days after admission, an abdominal CT scan revealed blurring of the peripancreatic fat planes, inflammation and swelling of the pancreas, and a substantial amount of ascitic fluid in the left anterior pararenal space and pelvis. Paracentesis and analysis of the ascitic fluid demonstrated findings diagnostic of pancreatic ascites. There had been no other evident predisposing factors for acute pancreatitis, other than methomyl intoxication. Eleven days after admission, pseudocholinesterase levels returned to normal, while a new abdominal CT scan revealed the formation of intrapancreatic fluid collection. The patient was discharged in good physical condition two weeks after admission. A follow up abdominal CT scan performed one month later showed a significant reduction in the size of the intrapancreatic fluid. DISCUSSION: Acute pancreatitis is not uncommon after organophosphate intoxication and carbamates share the same risk as organophosphorus pesticides. The development of acute pancreatitis and subsequent intrapancreatic fluid collection after methomyl intoxication has not previously been reported. This is the first case reported of acute pancreatitis and pancreatic ascite formation after anticholinesterase insecticide ingestion.  (+info)

Chronic neuropsychological sequelae of cholinesterase inhibitors in the absence of structural brain damage: two cases of acute poisoning. (3/15)

Here we describe two cases of carbamate poisoning. Patients AMF and PVM were accidentally poisoned by cholinesterase inhibitors. The medical diagnosis in both cases was overcholinergic syndrome, as demonstrated by exposure to cholinesterase inhibitors. The widespread use of cholinesterase inhibitors, especially as pesticides, produces a great number of human poisoning events annually. The main known neurotoxic effect of these substances is cholinesterase inhibition, which causes cholinergic overstimulation. Once AMF and PVM had recovered from acute intoxication, they were subjected to extensive neuropsychological evaluation 3 and 12 months after the poisoning event. These assessments point to a cognitive deficit in attention, memory, perceptual, and motor domains 3 months after intoxication. One year later these sequelae remained, even though the brain magnetic resonance imaging (MRI) and computed tomography (CT) scans were interpreted as being within normal limits. We present these cases as examples of neuropsychological profiles of long-term sequelae related to acute poisoning by cholinesterase inhibitor pesticides and show the usefulness of neuropsychological assessment in detecting central nervous system dysfunction in the absence of biochemical or structural markers.  (+info)

A method to determine precise benchmark doses for carbamate anticholinesterases. (4/15)

In determining benchmark doses for risk assessment and regulation of carbamate anticholinesterase pesticides like formetanate, oxamyl, and methomyl, one needs to quantitate low levels of cholinesterase inhibition. For improved accuracy while using fewer subjects, we developed an assay based on the recognized ability of carbamates to protect cholinesterase from irreversible inactivation. This assay measures enzyme that survives diisopropylfluorophosphate exposure in vitro and then reactivates by decarbamylation after small molecules are removed with size-exclusion centrifugation. The 99% silencing of unprotected cholinesterase yields a low background. Comparisons of recovered activity with initial activity (representing carbamate-free enzyme) use each sample as its own control. As a result, carbamate-protection assays can demonstrate a statistically significant 2-3% inhibition of brain cholinesterase in a single experimental group of modest size. When applied to brain samples from formetanate-treated rats, such an assay predicted a benchmark dose of 0.19 mg/kg for 10% inhibition (BMD10), with a lower 95% confidence limit of 0.15 mg/kg (BMDL10). Protection assays should enable precise determinations of benchmark doses for other carbamates, as well as accurate assessment of in vivo inhibition half-lives under low-dose scenarios.  (+info)

Influence of parasitism by Chelonus insularis Cresson (Hymenoptera: Braconidae) on the susceptibility of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) to insecticides. (5/15)

The egg-larval parasitoid Chelonus insularis Cresson is a key parasitoid of the fall armyworm Spodoptera frugiperda (J. E. Smith) during the second field generation in the upper Magdalena River Basin, Colombia. In spite of selection pressure, the higher susceptibility of the second generation fall armyworm larvae to insecticides, compared with that of the first generation, suggests that the parasitism may be responsible for the apparent difference in susceptibility. Parasitized and non-parasitized 2nd-instar larvae of the fall armyworm were tested for susceptibility to chlorpyriphos, methomyl, cypermethrin, and Bacillus thuringiensis in the laboratory, using the leaf dip test. Parasitized larvae were up to 3.93 times more susceptible to chlorpyriphos, 3.71 times to methomyl, and 14.11 times to cypermethrin than non-parasitized larvae. The least effect of parasitism on susceptibility was found for B. thuringiensis. We discuss the negative influence of synthetic insecticide on the parasitoid population dynamics and its impact on insecticide resistance.  (+info)

Plasma and brain cholinesterase in methomyl-intoxicated free-ranging pigeons (Columba livia f. domestica). (6/15)

A mortality event caused by exposure to the carbamate insecticide methomyl was diagnosed in several hundred pigeons fed treated corn kernels in a city park. A cholinesterase inhibitor insecticide was initially suspected based on clinical signs and a significant inhibition (P < 0.05) of brain cholinesterase (ChE) activity compared with normal values for the species. However, brain ChE activity was within the normal range in birds subsequently submitted in an advanced stage of autolysis. Two groups of 10 healthy pigeons were allocated into a control group and an experimental group, which was offered corn samples retrieved from the incident site. Within minutes of ingesting the contaminated corn, the birds became immobile, had transient wing fluttering, and developed profuse salivation immediately followed by death. Plasma ChE activity at death had declined by more than 95% of preexposure levels (0.04 +/- 0.02 vs. 1.56 +/- 0.23 micromol/min per milliliter). Brain activity in the sagittal brain sections that were immediately frozen after death was inhibited by > or =50% of control birds (13.5 +/- 2.2 vs. 27.5 +/- 1.8 micromol/min per gram). However, the sagittal sections left for 1.5 days at ambient temperature of 25 degrees C had normal or higher activity, an effect that was attributed to a combination of spontaneous reactivation and dehydration. After incubation of both plasma and brain homogenates for 1 hr at 37 degrees C, ChE activity recovered by 2- and 1.46-fold, respectively. An organophosphorus and carbamate screen conducted by 2 independent laboratories identified and quantified methomyl in treated kernels at 400 ppm. These results indicate that spontaneous reactivation and dehydration can mask previous reductions in ChE activity.  (+info)

Molluscicidal activity of methomyl and cardenolide extracts from Calotropis procera and Adenium arabicum against the land snail Monacha cantiana. (7/15)

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Expression in yeast of the T-urf13 protein from Texas male-sterile maize mitochondria confers sensitivity to methomyl and to Texas-cytoplasm-specific fungal toxins. (8/15)

The mitochondrial gene T-urf13 from maize (Zea mays L.) with Texas male-sterile (T) cytoplasm codes for a unique 13 kd polypeptide, T-URF13, which is implicated in cytoplasmic male sterility and sensitivity to the insecticide methomyl and to host-specific fungal toxins produced by Helminthosporium maydis race T (HmT toxin) and Phyllosticta maydis (Pm toxin). A chimeric gene coding for T-URF13 fused to the mitochondrial targeting peptide from the Neurospora crassa ATP synthase subunit 9 precursor was constructed. Expression of this gene in the yeast Saccharomyces cerevisiae yielded a polypeptide that was translocated into the membrane fraction of mitochondria and processed to give a protein the same size as maize T-URF13. Methomyl, HmT toxin and Pm toxin inhibited growth of yeast cells expressing the gene fusion on medium containing glycerol as sole carbon source and stimulated respiration with NADH as substrate by isolated mitochondria from these cells. These effects were not observed in yeast cells expressing T-URF13 without a targeting peptide. The results show that T-URF13 is sufficient to confer sensitivity to methomyl and the fungal toxins in a heterologous eukaryotic system, and suggest that mitochondrial localization of T-URF13 is critical for these functions.  (+info)

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