Pine needle abortions in cattle due to consumption of Pinus ponderosa in Argentina: Case reports.

Two outbreaks of pine needle abortions in cattle are here reported for the first time in Argentina. The cases occurred in Chubut and Neuquén provinces in the Patagonia region, causing 29.6% and 9% of abortions in each herd respectively. In both outbreaks, the dams were in the last third of gestation, and, due to a period of cold, snow and lack of available forage, they gained access to Pinus ponderosa and Pinus contorta forests. No pathological lesions, serological, molecular, or microbiological evidence of infectious causes were observed in any of the six fetuses analyzed. Microhistological analysis of feces confirmed higher presence of fragments of Pinus spp. needles in the diet of affected dams than in that of non-affected ones (12.2 vs 3.0%). Moreover, toxicological analysis showed higher tetrahydroagathic acid in the sera of affected dams than in that of non-affected ones (10.05 vs 2.81 ppm). In addition, this acid was detected in different fetal fluids (3.6-8.1 ppm) of the six fetuses analyzed. Interestingly, isocupressic acid was detected only in needles of P. ponderosa, and its content was lower than that found in other areas of the world (0.31 and 0.5% in Chubut and Neuquén respectively). These results confirm that the consumption of P. ponderosa by dams could have been the cause of these abortion outbreaks, a fact that should be considered as differential diagnosis in abortions of cattle, especially in silvopastoral systems of Argentina.

Acute death as a result of poisoning tropical (Bos taurus indicus) but not temperate (Bos taurus taurus) cattle after oral dosing with Lupinus leucophyllus (velvet lupine).

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Indigofera cryptantha-induced pigmenturia in cattle in South Africa.

Two field cases of reddish-black pigmenturia occurred where cattle grazed on an established Cenchrus ciliaris (blue buffalo grass) pasture in South Africa. The pasture was noticeably invaded by Indigofera cryptantha, which was heavily grazed. Apart from the discolored urine, no other clinical abnormalities were detected. Urinalysis revealed hemoglobinuria, proteinuria and an alkaline pH. When the animals were immediately removed from the infested pasture, they made an uneventful recovery. However, a bull died when one of the herds could not be removed from the I. cryptantha-infested pasture. Macroscopically, the kidneys were dark red in color and the urinary bladder contained the dark pigmented urine. Microscopically, the renal tubules contained eosinophilic, granular pigment casts in the lumen. In addition, many renal tubular epithelial cells were attenuated with granular cytoplasm and were detached from the basement membranes. Chemical analysis was performed on dried, milled plant material and two urine samples collected during the field investigations. Qualitative UPLC-UV-qTOF/MS analysis revealed the presence of indican (indoxyl-ß-glucoside) in the stems, leaves and pods of I. cryptantha and indoxyl sulfate was identified, and confirmed with an analytical standard, in the urine samples. It is proposed that following ingestion of I. cryptantha, indican will be hydrolysed in the liver to indoxyl and conjugated with sulfate. Indoxyl sulfate will then be excreted in relatively high concentrations in the urine. In the alkaline urine, two indoxyl molecules might dimerize to form leucoindigo with subsequent oxidation to indigo, thus, contributing to the dark pigmentation of the urine. It is also possible that indoxyl sulfate contributed to the renal failure and death of the bull. Although I. suffruticosa-induced hemoglobinuria has been described in Brazil, this is the first report of I. cryptantha-induced pigmenturia in cattle in South Africa.

Death of Socrates: a likely case of poison hemlock (Conium maculatum) poisoning.

INTRODUCTION: The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others. THE EVIDENCE: Socrates' death has almost always been attributed to his drinking an extract of poison hemlock, Conium maculatum, despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains. EVALUATION: Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato. CONCLUSIONS: Seen in this way, the death of Socrates can be accepted as a limited case report of Conium maculatum poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.

Ruminant metabolism of zygacine, the major toxic alkaloid in foothill death camas (Zigadenuspaniculatus).

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.

Plants Causing Toxic Myopathies.

Boxelder and sycamore maple contain hypoglycin A (HGA), the toxic metabolite of which, MCPA-CoA, inhibits fatty acid ß-oxidation, causing seasonal pasture myopathy (SPM) or atypical myopathy (AM), respectively. White snakeroot and rayless goldenrod contain multiple benzofuran ketones (BFKs). The identity/toxicity of BFKs appear variable, possibly involving interactions between toxins/toxic metabolites, but ultimately inhibit cellular energy metabolism. Unthrifty horses grazing sparse pastures during the fall appear predisposed to these plant-associated, frequently fatal, toxic myopathies. Toxidromes are characterized by varying degrees of rhabdomyolysis and cardiac myonecrosis, with plant toxins remaining toxic in hay and being excreted in milk.

Deliberate Self-Poisoning with Plants in Southeastern France, a Poison Center 20-Year Report.

INTRODUCTION: In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe plant self-intoxication using the experiences of the southeastern France poison control center (PCC) between 2002 and 2021. RESULTS: During those 20 years, 262 deliberate plants poisonings were reported involving 35 various plants. In most of the cases, poisoning was caused by Nerium oleander (n = 186, 71%), followed by the Datura genus (4.2%), Ricinus communis (3.8%), Taxus baccata (1.9%), Digitalis purpurea (1.2%), Aconitum nape (1.9%), Myristica fragans (1.5%), and Pyracantha coccine (1.2%). Through the 262 plants poisonings, 19 patients among the 186 Nerium oleander poisonings received Digifab as an antidote and 1 patient received physostigmine among the 11 Datura poisonings. Only four deaths were reported for this review, each involving Nerium oleander. DISCUSSION: The first involved species was Nerium oleander (71% of all plants poisonings), then Datura sp and Ricinus communis. It is explained by this native local species' important repartition. Most patients must be admitted to an emergency department for adapted medical care; however, only 41 of them described severe poisonings symptoms. Even fewer needed an antidote, only 20 patients. There is no protocol for the use of a specific treatment, and it might be interesting to develop one for this purpose. MATERIAL AND METHODS: This retrospective review was realized with files managed by the southeastern France PCC based in Marseille from 2002 to 2021. Our department covers the complete French Mediterranean coast, Corsica, and tropical islands (Reunion Island, Mayotte). For every patient, toxicity was evaluated using the Poison Severity Score (PSS).

DNA barcoding as new diagnostic tool to lethal plant poisoning in herbivorous mammals.

Reliable identification of plant species in the digestive tract of a deceased animal often represents the major key to diagnose a lethal intoxication with poisonous plants in veterinary pathology. In many cases, identification of the species is challenging or even impossible because the diagnostic morphological features have been degraded, and because the interpretation of such features requires a considerable expertise in plant anatomy and biodiversity. The use of DNA barcoding markers can support or even replace classical morphological assessment. While these markers have been widely used for plant taxonomy, their forensic application to clarify causes of animal poisoning is novel. In addition, we use specific single-nucleotide polymorphisms as fingerprints. This allows for a clear decision even in cases, where the conventionally used statistical e-values remain ambiguous. In the current work, we explore the feasibility of this strategy in a couple of exemplary cases, either in concert with anatomical diagnostics, or in cases where visual species identification is not possible, or where chemical toxin detection methods are not well established, complex, time consuming and expensive.

[One case of acute poisoning with stramonium].

This paper reported 1 case of poisoning caused by stramonium. Cases of Datura poisoning have been reported nationwide, Its effect on the central nervous system of patients is characterized by first excitation and then inhibition, clinical manifestations include decreased gland secretion, dilated pupils, and tachycardia, etc. Its poisoning mechanism is anticholinergic effect, the effect on Peripheral nervous system is to inhibit Parasympathetic nervous system. Hemoperfusion combined with neostigmine anticholinergic therapy at the early stage of poisoning can effectively improve the clinical symptoms of patients in a short time.

Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Emerging Plant Intoxications in Domestic Animals: A European Perspective.

Exposure to phytotoxins that are present in imported ornamental or native plants is an important cause of animal disease. Factors such as animal behaviors (especially indoor pets), climate change, and an increase in the global market for household and ornamental plants led to the appearance of new, previously unreported plant poisonings in Europe. This has resulted in an increase in the incidence of rarely reported intoxications. This review presents some of the emerging and well-established plant species that are responsible for poisoning episodes in companion animals and livestock in Europe. The main plant species are described, and the mechanism of action of the primary active agents and their clinical effects are presented. Data reflecting the real incidence of emerging poisoning cases from plant toxins are scarce to nonexistent in most European countries due to a lack of a centralized reporting/poison control system. The diversity of plant species and phytotoxins, as well as the emerging nature of certain plant poisonings, warrant a continuous update of knowledge by veterinarians and animal owners. The taxonomy and active agents present in these plants should be communicated to ensure awareness of the risks these toxins pose for domestic animals.

Poisonous Plants of the Genus Pimelea: A Menace for the Australian Livestock Industry.

Pimelea is a genus of about 140 plant species, some of which are well-known for causing animal poisoning resulting in significant economic losses to the Australian livestock industry. The main poisonous species/subspecies include Pimelea simplex (subsp. simplex and subsp. continua), P. trichostachya and P. elongata (generally referred to as Pimelea). These plants contain a diterpenoid orthoester toxin, called simplexin. Pimelea poisoning is known to cause the death of cattle (Bos taurus and B. indicus) or weaken surviving animals. Pimelea species are well-adapted native plants, and their diaspores (single seeded fruits) possess variable degrees of dormancy. Hence, the diaspores do not generally germinate in the same recruitment event, which makes management difficult, necessitating the development of integrated management strategies based on infestation circumstances (e.g., size and density). For example, the integration of herbicides with physical control techniques, competitive pasture establishment and tactical grazing could be effective in some situations. However, such options have not been widely adopted at the field level to mitigate ongoing management challenges. This systematic review provides a valuable synthesis of the current knowledge on the biology, ecology, and management of poisonous Pimelea species with a focus on the Australian livestock industry while identifying potential avenues for future research.

Anti-ricin toxin human neutralizing antibodies and DMAbs protection against ricin toxin poisoning.

DNA-encoded monoclonal antibodies (DMAbs) and in vivo expression of antibody therapeutics presents an innovative alternative to conventional delivery methods. Therefore, in order to prevent the lethal dose of ricin toxin (RT) and to avoid human anti-mouse antibody (HAMA) reaction, we developed the human neutralizing antibody 4-4E against RT and constructed DMAb-4-4E. The human neutralizing antibody 4-4E could neutralize RT in vitro and in vivo, while the mice in RT group all died. Using intramuscular electroporation (IM EP), antibodies were rapidly expressed in vivo within 7 days and were enriched in intestine and gastrocnemius muscle mostly. Besides, we found that DMAbs have shown a broad protective efficacy of RT poisoning prophylaxis. Driven by plasmids for IgG expression, mice were survived and the blood glucose level of mice in DMAb-IgG group returned to normal at 72 h post RT challenge, and the RT group died within 48 h. Furthermore, hindrance of protein disulfide isomerase (PDI) and accumulation of RT in endosomes were found in IgG-protected cells, revealing the possible mechanism of neutralization details. These data support the further study of RT-neutralizing monoclonal antibodies (mAbs) in the development.

Toxicity of House Plants to Pet Animals.

Cases of ingestion of indoor poisonous plants are relatively common among animals and lead to both acute cases of poisoning and long-term exposure to harmful substances and chronic damage to the animal's health. Plants produce a large number of secondary metabolites, which serve to protect the plant from attacks by insects, parasitic plants, fungi or, for example, during reproduction. However, these metabolites can be toxic if ingested by animals or humans. Toxicologically effective components found in plants are mainly alkaloids, glycosides, saponins, terpenes and others. This review article describes in detail the most common and popular indoor poisonous plants grown in Europe, the mechanisms of action of their active substances and clinical signs of the respective poisonings. This manuscript is supplemented with rich photographic documentation of these plants not found in similar articles, and also includes a description of the treatment of individual types of poisoning.

DART-HRMS allows the detection of toxic alkaloids in animal autopsy specimens and guides the selection of confirmatory methods in accidental plant poisoning.

BACKGROUND: In cases of suspected animal poisonings or intoxications, there is the need for high-throughput, rapid and accurate analytical tools capable of giving rapid answers and, thus, speeding up the early stages of investigations. Conventional analyses are very precise, but do not meet the need for rapid answers capable of orienting the decisions and the choice of appropriate countermeasures. In this context, the use of ambient mass spectrometry (AMS) screening methods in toxicology laboratories could satisfy the requests of forensic toxicology veterinarians in a timely manner. RESULTS: As a proof of principle, direct analysis in real time high resolution mass spectrometry (DART-HRMS) was applied to a veterinary forensic case in which 12 of a group of 27 sheep and goats died with an acute neurological onset. Because of evidence in the rumen contents, the veterinarians hypothesized an accidental intoxication after ingestion of vegetable materials. The DART-HRMS results showed abundant signals of the alkaloids calycanthine, folicanthidine and calycanthidine, both in the rumen content and at the liver level. The DART-HRMS phytochemical fingerprinting of detached Chimonanthus praecox seeds was also compared with those acquired from the autopsy specimens. Liver, rumen content and seed extracts were then subjected to LC-HRMS/MS analysis to gather additional insights and confirm the putative assignment of calycanthine anticipated by DART-HRMS. HPLC-HRMS/MS confirmed the presence of calycanthine in both rumen contents and liver specimens and allowed its quantification, ranging from 21.3 to 46.9 mg kg-1 in the latter. This is the first report detailing the quantification of calycanthine in liver after a deadly intoxication event. SIGNIFICANCE AND NOVELTY: Our study illustrates the potential of DART-HRMS to offer a rapid and complementary alternative to guide the selection of confirmatory chromatography-MSn strategies in the analysis of autopsy specimens from animals with suspected alkaloid intoxication. This method offers the consequent saving of time and resources over those needed for other methods.

Acute necrotic hepatotoxicity caused by Melanthera latifolia (Asteraceae) in cattle.

This study aims to report a spontaneous and experimental intoxication in cattle by Melanthera latifolia (Asteraceae) for the first time, and to describe its epidemiological, clinical, and pathological findings. An outbreak of acute toxic hepatopathy in cattle occurred from December of 2021 to January of 2022 in a beef cattle farm from Rio Grande do Sul state, Southern Brazil, and resulted in 94 deaths from a herd of 430 animals. At necropsy, lesions consisted of enhanced lobular pattern of the liver, transmural gallbladder edema, and hemorrhages on the surface of multiple organs. The main microscopic lesion was marked hepatocellular necrosis in the centrilobular region associated with hemorrhage and infiltration of neutrophils. During the outbreak, multiple specimens of M. latifolia were noted in the paddocks where affected cattle were grazing and many showed signs of consumption. No other known acute hepatotoxic plants were found. Two 12-month-old steers were experimentally intoxicated with a single oral dose of the fresh plant (flowers, leaves, and less fibrous stalks). One bovine ingested a dose of 10 g/kg and was euthanized after 48 h, and the other ingested 15 g/kg and was euthanized 17 h later. Clinical signs, macroscopic, and microscopic lesions in both animals were similar to those observed in the spontaneous cases. Thus, this study demonstrates that M. latifolia was the cause of the outbreak of acute toxic hepatopathy with significant mortality in cattle. M. latifolia nor any plant of the genus Melantherahad ever been reported as toxic.

Lantana camara poisoning in cattle that took refuge during a storm in a forest invaded by this plant.

An outbreak of poisoning by Lantana camara occurred in cattle when a herd sought refuge in a Eucalyptus forest heavily infested by this plant. The animals showed apathy, elevated serum activities of hepatic enzymes, severe photosensitivity, jaundice, hepatomegaly and nephrosis. After a clinical manifestation period of 2-15 days, 74 out of 170 heifers died. The main histological changes were random hepatocellular necrosis, cholestasis, biliary proliferation and, in one animal, centrilobular necrosis. Immunostaining for Caspase 3 detected scattered apoptotic hepatocytes.