Suspected intermediate syndrome in a dog after organophosphate poisoning.

OBJECTIVE: To discuss the clinical presentation and successful treatment of a suspected case of intermediate syndrome due to organophosphate (OP) poisoning in a dog. CASE SUMMARY: Two dogs presented with acute cholinergic signs after ingesting an OP insecticide containing 50% acephate. Clinical signs consistent with acute cholinergic crisis resolved in both dogs within 24 hours postingestion. One dog developed an onset of neurological signs consistent with intermediate syndrome approximately 24 hours postingestion. This patient's clinical signs resolved with the use of pralidoxime chloride. NEW OR UNIQUE INFORMATION PROVIDED: OP poisoning most commonly presents as an acute cholinergic crisis, with rare instances of animals developing intermediate syndrome. Few reports of successful treatment and recovery from intermediate syndrome exist in the veterinary literature, particularly with instances in which 2 dogs within the same exposure setting were treated for acute cholinergic signs and only 1 progressed to an intermediate syndrome. This report also highlights the importance of early intervention with pralidoxime chloride prior to the onset of aging.

Prevalence, clinical manifestations, laboratory findings, treatment, and outcome of intermediate syndrome in anticholinesterase pesticide intoxication of dogs: A retrospective study.

Organophosphates and carbamates are important anticholinesterase intoxicants of humans and dogs. Intermediate syndrome (IMS) typically occurs 7-96 h following a toxicity-associated acute cholinergic crisis (ACC), and manifests clinically as weakness of the proximal limb, respiratory, and neck flexor muscles. The aim of this study was to describe the prevalence, clinical findings, and outcome of IMS in dogs. The medical records of a veterinary teaching hospital were searched for dogs diagnosed with ACC, IMS, or both, between 2017 and 2021. Case files were retrospectively reviewed. Six historical IMS cases were additionally reviewed. Thirty-two dogs were diagnosed with anticholinesterase intoxication during the search period, of which 23 (72 %) were only diagnosed with ACC, seven (22 %) progressed from ACC to IMS, and two (6 %) were only diagnosed with IMS. Duration of hospitalisation was longer in the IMS group compared to the ACC only group (P = 0.005). When all dogs with IMS (n = 15, including the six historical cases) were considered, survival was 100 %, including four (27 %) that required positive pressure mechanical ventilation following respiratory failure. Serum butyrylcholine esterase activity, a marker of cholinesterase activity, was below reference interval when first measured in 14 (93 %) of dogs; however, was not a useful as a recovery marker. IMS should be suspected in dogs demonstrating respiratory, neck, and proximal limb muscle paresis or paralysis, especially following clinical signs consistent with ACC. Absence of clinical signs consistent with ACC or butyrylcholine esterase activity within the reference interval does not exclude IMS as a differential.

Use of bone marrow for detection of toxic chemicals for the elucidation of poisoning in forensic veterinary medicine / Uso de medula óssea para detecção de produtos químicos tóxicos para a elucidação de intoxicação em patologia veterinária forense

In forensic toxicology, the detection of toxic chemicals from human bone marrow is often used in cases with an extended post mortem interval; however, in veterinary medicine, this practice is not used. Therefore, this study was performed to investigate the suitability of bone marrow for toxicological analysis in dogs and cats. Six animals with suspected poisoning were selected; the carcasses were sent for necropsy, and the organs were collected and preserved in buffered formalin and processed routinely for histological examination. In addition, bone marrow samples from the femur, humerus, and tibia were collected for toxicological analysis by liquid chromatography coupled to mass spectrometry detection (LC-MS). This analysis confirmed the presence of aldicarb, aldicarb sulfone, asulam, carbendazim, chlorpyrifos, dichlorvos, thifensulfuron methyl and trifloxysulfuron-sodium and associated with clinical symptoms and anatomo-histopathological alterations it was recognized the poisonings. It is expected that this study will promote the toxicological investigation of bone marrow and open avenues for the use of this tissue as an option for the detection of toxic chemicals in cases of forensic pathology.(AU)

Na toxicologia forense, a detecção de substâncias químicas tóxicas provenientes da medula óssea humana é frequentemente usada em casos com intervalo post mortem prolongado; no entanto, na medicina veterinária, essa prática não é utilizada. Portanto, este estudo foi realizado para investigar a utilização da medula óssea nas análises toxicológicas em cães e gatos. Seis animais com suspeita de intoxicação foram selecionados; as carcaças foram enviadas para necropsia e os órgãos foram coletados e preservados em formalina tamponada e processados rotineiramente para exame histológico. Amostras de medula óssea de fêmur, úmero e tíbia foram coletadas para análise toxicológica por cromatografia líquida acoplada à espectrometria de massa-massa (LC-MS). A análise por LC-MS confirmou a presença dos agrotóxicos aldicarbe, aldicarbe sulfona, asulam, carbendazim, clorpirifós, diclorvós, tifensulfuron metil e trifloxisulfuron-sódico, e em associação com sinais clínicos e achados anatomo-histopatológicos comprovou-se as intoxicações. Espera-se que este estudo promova a utilização da medula óssea como uma opção na investigação toxicológica para a detecção de produtos químicos tóxicos em casos de patologia forense.(AU)

Clinical manifestations, laboratory findings, treatment and outcome of acute organophosphate or carbamate intoxication in 102 dogs: A retrospective study.

Organophosphates (OP) and carbamates are commonly used insecticides and important intoxication sources of humans and animals. Nevertheless, large scale studies of these intoxications in dogs are unavailable. The medical records of dogs presented to a veterinary hospital were reviewed retrospectively. The study included 102 dogs definitely diagnosed with acute OP or carbamate intoxication. The most common presenting clinical signs included muscle tremor, hypersalivation, miosis, weakness, vomiting and diarrhea. Hypersalivation, muscle tremor and tachypnea were significantly (P < 0.05) associated with survival to discharge; while weakness, mental dullness, anorexia, pale mucous membranes and paddling were significantly associated with death. Common laboratory abnormalities included decreased butyrylcholine esterase activity, acidemia, increased total plasma protein, leukocytosis, hypochloridemia, hyperbilirubinemia, increased creatinine and alanine transaminase (ALT), aspartate transaminase (AST) and creatine kinase activities, and prolonged activated partial thromboplastin time (aPTT). Compared to the survivors, the non-survivors showed significantly: higher frequencies of thrombocytopenia, hypocarbemia, prolonged prothrombin time (PT), hypernatremia, hyperkalemia, hypocholesterolemia, hypoproteinemia, hypertriglyceridemia, increased ALT activity and increased urea concentration; lower median concentrations of venous blood bicarbonate, serum chloride and total CO2; and higher medians of PT, serum total bilirubin and urea concentrations, and ALT and AST activities. Intoxicated dogs were commonly treated with diphenhydramine, atropine-sulfate, antibiotics, diazepam and pralidoxime, while some (19.2%) required general anesthesia and mechanical ventilation. The survival rate of dogs treated by gastric lavage was higher (P = 0.041) compared to that of the remaining dogs. Development of respiratory failure and mechanical ventilation requirement were significantly associated (P < 0.001) with death. The mortality rate was 17%.

Acetylcholinesterase activity in the brain of wild birds in Korea-2014 to 2016.

Acetylcholinesterase (AChE) activity level can be used as a diagnostic marker for anticholinesterase pesticide poisoning. In this study, we aimed to establish a baseline level of normal brain AChE activity in wild birds. AChE activity was measured in the brains of 87dead wild birds (26 species). The level of AChE activity ranged from 6.40 to 15.9 µmol/min/g of brain tissue in normal wild birds. However, the brain tissue AChE activity level in wild birds exposed to organophosphate (OP) pesticide was 48.0%-96.3% of that in the normal birds. These results may serve as reference values to facilitate routine diagnosis and monitoring of OP-poisoned wild birds.

Geographical characteristics influencing the risk of poisoning in pet dogs: Results of a large population-based epidemiological study in Italy.

Pets can act as sentinels for human health and thus surveillance of pet dogs has the potential to improve awareness of emerging risks for animal and public health. The aim of this study was to investigate factors associated with the risk of canine poisoning. In a large population-based epidemiological investigation in Italy performed from January 2015 to January 2016 and April 2016 to April 2017, descriptive statistics were acquired and analysed to determine variables associated with poisoning events in pet dogs. Results were validated in a test population and forecast analysis of risk was performed. The cumulative incidence of poisoning events was low (10.2/1000 dogs/year). Anticoagulant rodenticides, organophosphate pesticides, metaldehyde and strychnine were the most frequent causes of intoxications. Territory characteristics significantly modulated both the frequency and the nature of the involved substances. The seashore area was associated with poisoning by rodenticides (odds ratio, OR, 1.81, 95% confidence interval, CI, 1.54-2.13) and metaldehyde (OR 1.61, 95% CI 1.16-2.28). The hill country area was associated with poisoning by organophosphate pesticides (OR 1.73, 95% CI 1.38-2.15), metaldehyde (OR 2.26, 95% CI 1.53-3.25) and strychnine (OR 1.86, 95% CI, 1.34-2.57). The mountain area was associated with strychnine poisoning (OR 3.79, 95% CI 2.84-5.06). The prospective cumulative incidence of poisoning over 10 years was 9.74% (95% CI 9.57-9.91). These results may be useful for predicting the risk of poisoning and for estimating the risk index related to specific toxic compounds in specific territories. This study suggests that poisoning events in dogs may represent a problem of public health with the potential to affect wildlife and human beings.

HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants.

The high toxicity of organophosphorus compounds originates from covalent inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OPs focuses on the use of bioscavengers against the parent organophosphate. Our previous research showed that AChE mutagenesis can enable aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates, while dramatically slowing down rates of OP-conjugate dealkylation (aging). Herein, we demonstrate an efficient HI-6-assisted VX detoxification, both ex vivo in human blood and in vivo in mice by hAChE mutants modified at the choline binding site (Y337A and Y337A/F338A). The catalytic scavenging of VX in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms.

Determination of organophosphorus pesticides in stomach contents of postmortem animals by QuEChERS and gas chromatography.

The quick, easy, cheap, effective, rugged and safe (QuEChERS) method for sample preparation was applied to determine seven organophosphorus pesticides (OPs) in stomach contents of poisoned postmortem animals. The pesticides consisted of diazinon, edifenphos, ethyl p-nitrophenyl phenylphosphonothioate, fenitrothion, monocrotophos, parathion and phosphamindon, and tested samples included stomach contents from postmortem animals of cattle, goat, dog, cat, birds, deer and rabbit. The pesticides were spiked into the samples which were found to be negative through previous pesticide poisoning analysis, and the pesticides were extracted and cleaned up based on the QuEChERS process and then they were analyzed using gas chromatography (GC)-flame photometric detector (FPD) or GC-nitrogen-phosphorus detector (NPD) with a DB-5 column. Limits of detection ranged from 0.27 to 0.41 mg/kg for the seven pesticides. The mean recoveries ranged from 80 to 99% in GC-FPD and 83 to 90% in GC-NPD. The coefficients of variation were <10% for all analytes and sample matrix combinations except for phosphamidon and edifenphos in dog stomach contents. This study demonstrated that the method using QuEChERS and GC-FPD and/or GC-NPD is very effective to analyze the OPs in the stomach contents of postmortem animals.

Uso inadequado de organofosforados: uma prática de risco para bovinos no Sul do Rio Grande do Sul / Misuse of organophosphate: potential risk to cattle in Southern Brazil

Com o objetivo de determinar as causas para o súbito aumento no número de surtos de intoxicação por organofosforados foram analisados nove surtos da intoxicação diagnosticados em bovinos no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD/UFPel) entre novembro de 2013 e fevereiro de 2014. Em todos os surtos os animais foram tratados com concentrações entre duas e 151 vezes maiores que a concentração recomendada de diazinon para banho carrapaticida utilizado nas diferentes propriedades. Contribuíram, ainda, para o grande número de casos de intoxicação a via de adminstração pour on não recomendada para os produtos utilizados e o intenso calor registrado na época de ocorrência dos surtos.

In order to determine the cause of the sudden increase in the number of outbreaks of organophosphate poisoning, nine outbreaks diagnosed in cattle were analyzed at the Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas (LRD/UFPel) between November 2013 and February 2014. In all outbreaks the animals were treated with concentration from two to 151 times higher than the concentration recommended of diazinon for tick treatment. The incorrect route of application, and the intense heat recorded at the time of the outbreaks also contributed to the large number of poisoning.

Molecular mechanisms of reduced nerve toxicity by titanium dioxide nanoparticles in the phoxim-exposed brain of Bombyx mori.

Bombyx mori (B. mori), silkworm, is one of the most important economic insects in the world, while phoxim, an organophosphorus (OP) pesticide, impact its economic benefits seriously. Phoxim exposure can damage the brain, fatbody, midgut and haemolymph of B. mori. However the metabolism of proteins and carbohydrates in phoxim-exposed B. mori can be improved by Titanium dioxide nanoparticles (TiO2 NPs). In this study, we explored whether TiO2 NPs treatment can reduce the phoxim-induced brain damage of the 5th larval instar of B. mori. We observed that TiO2 NPs pretreatments significantly reduced the mortality of phoxim-exposed larva and relieved severe brain damage and oxidative stress under phoxim exposure in the brain. The treatments also relieved the phoxim-induced increases in the contents of acetylcholine (Ach), glutamate (Glu) and nitric oxide (NO) and the phoxim-induced decreases in the contents of norepinephrine (NE), Dopamine (DA), and 5-hydroxytryptamine (5-HT), and reduced the inhibition of acetylcholinesterase (AChE), Na+/K+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase activities and the activation of total nitric oxide synthase (TNOS) in the brain. Furthermore, digital gene expression profile (DGE) analysis and real time quantitative PCR (qRT-PCR) assay revealed that TiO2 NPs pretreatment inhibited the up-regulated expression of ace1, cytochrome c, caspase-9, caspase-3, Bm109 and down-regulated expression of BmIap caused by phoxim; these genes are involved in nerve conduction, oxidative stress and apoptosis. TiO2 NPs pretreatment also inhibited the down-regulated expression of H+ transporting ATP synthase and vacuolar ATP synthase under phoxim exposure, which are involved in ion transport and energy metabolism. These results indicate that TiO2 NPs pretreatment reduced the phoxim-induced nerve toxicity in the brain of B. mori.

Intoxicação aguda por triclorfon em caprinos tratados com a dose terapêutica / Acute poisoning by trichlorfon in goats given a therapeutic dose

O presente estudo descreve um surto de intoxicação por triclorfon em caprinos, que receberam pela via oral, a dosagem terapêutica do princípio ativo em questão (100mg/kg), provenientes da Universidade Estadual de Maringá, campus de Umuarama, PR. Cinquenta e três ovinos foram tratados com a mesma formulação/solução e não se observou nenhum efeito colateral nos animais referente ao tratamento com triclorfon. Das 20 cabras medicadas, cerca de 40 minutos após a administração do triclorfon, oito apresentaram os clássicos sinais clínicos de ataxia, decúbito externo-lateral, sialorreia, tremores, constrição das pupilas, dispneia com ruídos, micção e defecação involuntária, paresia espástica, timpanismo e lacrimejamento. Quase que imediatamente após a detecção destes sinais, as oito cabras foram medicadas com sulfato de atropina 1% 0,5mg/kg mais fluidoterapia. Cinco destes animais tiveram de receber nova dosagem de sulfato de atropina uma hora após a primeira aplicação, em função de alguns sinais clínicos, como tremores musculares, ainda estarem presentes. De 48 a 72 horas após a administração do triclorfon, três destes cinco animais vieram a óbito. Na necropsia, foi possível observar mucosas cianóticas, congestão de fígado, baço e rins, vasos mesentéricos congestos, vesícula biliar repleta, enfisema pulmonar, parênquima pulmonar avermelhado. Os resultados encontrados neste trabalho chamam atenção que o surto aconteceu em cabras adultas, que apresentavam boas condições clínicas e acima de tudo, receberam a dosagem terapêutica recomendada em bula pelo fabricante. Talvez isso possa indicar alguma sensibilidade mais elevada desta espécie animal à dosagem recomendada em bula do triclorfon (100mg/kg) para caprinos.

The present study describes an outbreak of trichlorfon poisoning in goats from the State University of Maringá, campus Umuarama/PR that received orally the therapeutic dose of the active ingredient in question (100mg/kg). Fifty-three sheep had been treated with the same formulation/solution and no side effects were observed in any of these sheep medicated with triclorfon. But from 20 goats medicated with trichlorfon, eight goats showed, about 40 minutes after its administration, the classic clinical signs of ataxia, external lateral decubitus, drooling, tremors, constricted pupils, noisy dyspnea, involuntary urination and defecation, spastic paresis, bloat and tearing. Almost immediately after the detection of these signals, eight goats were medicated with 1% atropine sulfate (0.5mg/kg and fluid). Five of these goats received a second dose of atropine sulfate one hour after the first application because of some clinical signs such as muscle tremor still being present. Forty-eight to 72 hours after administration of trichlorfon, three of those five goats died. At necropsy we observed cyanotic mucous membranes, congestion of liver, spleen, kidneys and mesenteric vessels, filled gallbladder, emphysema, and reddish lungs. The results of this study call attention to the outbreak that occurred in adult goats in good clinical conditions and, above all, that they received the therapeutic dosage recommended on the manufacture label. This suggests a higher sensitivity of the species to the recommended dose of trichlorfon (100mg/kg) for goats.