Clinical and pathological comparison of Astragalus lentiginosus and Ipomoea carnea poisoning in goats.

The indolizidine alkaloid swainsonine, found in some Astragalus and Oxytropis (i.e., locoweed) species, is a potent cellular glycosidase inhibitor that often poisons livestock. Other toxic genera such as some Ipomoea species also contain swainsonine as well as calystegines which are similar polyhydroxy alkaloids. The toxicity of calystegines is poorly characterized; however, they are also potent glycoside inhibitors capable of intestinal and cellular glycoside dysfunction. The objective of this study was to directly compare A. lentiginosus and I. carnea poisoning in goats to better characterize the role of the calystegines. Three groups of four goats each were treated with ground alfalfa (control), I. carnea or A. lentiginosus to obtain daily doses of 0.0, 1.5, and 1.5 mg swainsonine/kg bw per day, respectively, for 45 days. Animals were observed daily and weekly body weights, serum enzyme activities, and serum swainsonine concentrations were determined. At day 45 all animals were euthanized and necropsied. Goats treated with A. lentiginosus and I. carnea developed clinical disease characterized by mild intention tremors and proprioceptive deficits. Goats treated with A. lentiginosus developed clinical disease sooner and with greater consistency. No differences in body weight, serum swainsonine concentrations and serum enzyme activity were observed between goats treated with A. lentiginosus and I. carnea. Additionally, there were no differences in the microscopic and histochemical studies of the visceral and neurologic lesions observed between goats treated with A. lentiginosus and I. carnea. These findings suggest that I. carnea-induced clinical signs and lesions are due to swainsonine and that calystegines contribute little or nothing to toxicity in goats in the presence of swainsonine.

Widespread anatoxin-a detection in benthic cyanobacterial mats throughout a river network.

Benthic algae fuel summer food webs in many sunlit rivers, and are hotspots for primary and secondary production and biogeochemical cycling. Concerningly, riverine benthic algal assemblages can become dominated by toxic cyanobacteria, threatening water quality and public health. In the Eel River in Northern California, over a dozen dog deaths have been attributed to cyanotoxin poisonings since 2000. During the summers of 2013-2015, we documented spatial and temporal patterns of cyanotoxin concentrations in the watershed, showing widespread distribution of anatoxin-a in benthic cyanobacterial mats. Solid phase adsorption toxin tracking (SPATT) samplers were deployed weekly to record dissolved microcystin and anatoxin-a levels at 10 sites throughout the watershed, and 187 Anabaena-dominated or Phormidium-dominated cyanobacterial mat samples were collected from 27 locations to measure intracellular anatoxin-a (ATX) and microcystins (MCY). Anatoxin-a levels were higher than microcystin for both SPATT (mean MCY = 0.8 and ATX = 4.8 ng g resin-1 day-1) and cyanobacterial mat samples (mean MCY = 0.074 and ATX = 1.89 µg g-1 DW). Of the benthic mats sampled, 58.9% had detectable anatoxin-a (max = 70.93 µg g-1 DW), while 37.6% had detectable microcystins (max = 2.29 µg g-1 DW). SPATT cyanotoxin levels peaked in mid-summer in warm mainstem reaches of the watershed. This is one of the first documentations of widespread anatoxin-a occurrence in benthic cyanobacterial mats in a North American watershed.

Protection by a transdermal patch containing eserine and pralidoxime chloride for prophylaxis against (±)-Anatoxin A poisoning in rats.

The prophylactic and neuroprotective impact of a transdermal patch containing eserine and pralidoxime chloride (2-PAM) against (±)-Anatoxin A poisoning was investigated using Wistar strain albino rats. Rats were smooth-shaved on the dorsal side, attached with a drug-in-adhesive matrix type prophylactic transdermal patch for 72 h and challenged with subcutaneous injection of three doses (1.0, 1.5 and 2.0×LD50) of (±)-Anatoxin A. The LD50 value of (±)-Anatoxin A was determined to be 1.25mg/kg, and at this particular dose (1.0×LD50) of toxin induced severe clinical symptom including extreme seizures in rats, resulting acute brain injuries in discrete brain regions, leading to 100% mortality within 5 min. The anticonvulsant effect, antiarrythmic effect, nerve conduction study, clinical observations and mortality, neuroprotective effect as well as skin histopathology of the prophylactic transdermal patch against (±)-Anatoxin A poisoning were investigated systematically. It was found that seizures, tachycardia, nerve damage, clinical symptoms, brain injuries and mortality induced by such lethal toxin were effectively prevented by the prophylactic patch treatment up to certain LD50 level. Hence, it could be a choice of potential therapeutic regimen against such lethal poisoning.

Acute dermal irritation, sensitization, and acute toxicity studies of a transdermal patch for prophylaxis against ({+/-}) anatoxin-a poisoning.

The skin irritating, sensitizing, and acute dermal toxicity potential of a novel combinational prophylactic transdermal patch, mainly composed of eserine and pralidoxime chloride as active pharmaceutical ingredients, against (±) anatoxin-a poisoning were investigated in rabbits, guinea pigs, and rats in compliance with the Organisation for Economic Cooperation and Development guidelines. In primary skin irritation test, rabbits were dermally attached with the therapeutically active transdermal patch or with a placebo patch for 72 hours. The transdermal patches did not induce any adverse reactions such as erythema and edema on intact skin sites. The active patch was classified as a practically nonirritating material based on the score in the primary irritation index. In the Buehler test, guinea pigs were sensitized by the active or placebo transdermal patches attached for 24 hours. The patches did not induce any sensitization reactions in contrast to a severe sensitization reaction that occurred in the positive control. Therefore, the active patch and placebo patch were both graded as weak in sensitization score and rate. Acute dermal toxicity test in rats did not produce any overt signs of toxicity following a 14-day treatment period. Taken together, these findings suggest that the transdermal patch does not cause skin irritation, skin sensitization, or dermal toxic effects following dermal application.

Treatment and diagnosis of a dog with fulminant neurological deterioration due to anatoxin--a intoxication.

OBJECTIVE: To describe the clinical features, treatment, diagnostic work-up, and outcome of a dog with acute neurologic signs subsequent to algal toxin exposure. CASE SUMMARY: A Golden Retriever was presented for evaluation of acute onset of paraparesis after swimming in a man-made pond in early June and ingesting algae from a nearby bucket. The dog was anxious, had mild ptyalism, and when excited, developed generalized self-limiting tremors that progressed to generalized fasciculations and lateral recumbency. The dog was treated with activated charcoal and crystalloid fluids. Two hours after the presentation, the dog acutely decompensated and was ultimately euthanized. Gastric contents, bucket contents, pond water, bile, and urine were positive for anatoxin-a. NEW OR UNIQUE INFORMATION PROVIDED: Anatoxin-a intoxication is rarely confirmed in dogs but should be considered as a differential diagnosis in any dog with acute neurologic signs. We report the first successful detection of anatoxin-a in urine and bile of a dog exposed to blue green algae. This new test provides an enhanced diagnostic tool in suspect cases and has possible therapeutic implications in dogs.

Cyanobacterial poisoning in livestock, wild mammals and birds--an overview.

Poisoning of livestock by toxic cyanobacteria was first reported in the 19th century, and throughout the 20th century cyanobacteria-related poisonings of livestock and wildlife in all continents have been described. Some mass mortality events involving unrelated fauna in prehistoric times have also been attributed to cyanotoxin poisoning; if correct, this serves as a reminder that toxic cyanobacteria blooms predate anthropogenic manipulation of the environment, though there is probably general agreement that human intervention has led to increases in the frequency and extent of cyanobacteria blooms. Many of the early reports of cyanobacteria poisoning were anecdotal and circumstantial, albeit with good descriptions of the appearance and behaviour of cyanobacteria blooms that preceded or coincided with illness and death in exposed animals. Early necropsy findings of hepatotoxicity were subsequently confirmed by experimental investigations. More recent reports supplement clinical and post-mortem findings with investigative chemistry techniques to identify cyanotoxins in stomach contents and tissue fluids.

Diagnosis of anatoxin-a poisoning in dogs from North America.

Anatoxin-a, a toxin produced by several genera of blue-green algae, is considered a potent neurotoxin. Ingestion of water contaminated with the toxin results in acute neurological signs and often death. This report describes fatal cases of anatoxin-a ingestion in 6 dogs, with confirmation of anatoxin-a exposure by liquid chromatography/tandem mass spectrometry (LC-MS/MS/MS). In 1 outbreak, 3 dogs developed seizures and died within an hour after swimming in a river in California, while the other outbreak involved 3 dogs that died within 1 hour after swimming in a pond in Ontario. Anatoxin-a poisoning is rarely reported in dogs as a cause of acute neurological signs and death. However, increased occurrences of blue-green algae blooms in North America make this neurotoxin an important consideration in the diagnosis of sudden death associated with environmental water exposure. This brief communication reports on the isolation and detection of anatoxin-a from environmental water sources and the stomach contents of North American dogs dying of acute neurotoxicosis. This demonstrates the first documented cases of anatoxin-a poisoning in dogs in North America and the importance of LC-MS/MS/MS in identifying neurotoxins responsible for sudden death in cases of suspected blue-green algae toxicosis; especially those cases showing no gross or histological lesions.

Systemic toxicity from ocular homatropine.

Toxidromes are well known to emergency physicians. An unclear or incomplete history and subtle findings on physical examination make the diagnosis of poisonings challenging. This article reports a patient who had an acute onset of visual hallucinations, pressured speech, and mania. Although she denied taking any medications, she was ultimately diagnosed as having anticholinergic toxicity. On further questioning of family members, it was discovered that she was being treated for anterior uveitis with 5% homatropine. This case illustrates the potential role of ocular medications in systemic toxicity. Patients often do not consider eyedrops to be medications, and their use may be overlooked in the medical history. It also is important to educate patients and medical staff in methods to minimize systemic toxicity when using ocular medication.

Tropane alkaloids and toxicity of Convolvulus arvensis.

Horses in a few, localized northern Colorado pastures exhibited weight loss and colic. At post mortem, intestinal fibrosis and vascular sclerosis of the small intestine was identified. The pastures where the affected horses grazed were overrun by field bindweed (Convolvulus arvensis). Bindweed from the pasture was found to contain the tropane alkaloids tropine, pseudotropine, and tropinone and the pyrrolidine alkaloids cuscohygrine and hygrine. Laboratory mice readily ate C. arvensis and exhibited a variety of abnormal clinical signs depending on the amount eaten. Similar alkaloids have been found in other Convolvulus species and cuscohygrine and calystegines (polyhydroxytropanes) have been previously reported from C. arvensis roots. This is the first report of simple tropane alkaloids in C. arvensis, a world wide problem weed. Pseudotropine, the major alkaloid, is known to affect motility and might represent a causative agent for the observed cases of equine intestinal fibrosis.

Positive diagnosis of self-medication with homatropine eye drops.

A 25-year-old man with a variety of unusual ocular symptoms was fully investigated and no abnormality discovered. The suspicion of self-medication with a mydriatic was confirmed when homatropine was isolated in his tears. We describe a method for collecting tears which allowed biochemical confirmation at leisure.

Serial serum drug concentrations and prolonged anticholinergic toxicity after benztropine (Cogentin) overdose.

A 38-year-old man overdosed on benztropine mesylate (Cogentin; Merck Sharpe & Dohme, West Point, PA) and developed anticholinergic poisoning syndrome, which lasted nine days. Serial serum benztropine concentrations were obtained during his hospitalization. Fluctuating benztropine levels suggested that his lengthy intoxication may have been secondary to prolonged, intermittent absorption rather than from slow plasma clearance. This is believed to be the first report of serial serum benztropine concentrations after overdose.

[Endocrinological and neurophysiological modifications in a case of atropinic delusional state]. / Modifications endocriniennes et neurophysiologiques dans un cas de délire atropinique.

In this case report, we observed a delirium probably owing to toxic effects of homatropine eye drops. We reproduced this syndrome and we reversed it with physostigmine salicylate as an antidote. We observed a decrease of cortisol at 9.00 a.m. and impairment of regional cerebral blood flow with increase in the previous right side. The unusual susceptibility of this patient to the anticholinergic effect of homatropine is perhaps related to a preexisting mild cognitive defect possibly related to a cholinergic neurotransmitter deficit.

Benztropine-induced acute dystonic reaction.

We report an unusual case of benztropine-induced acute dystonia and dyskinesia without findings of acute anticholinergic toxicity in a 20-month-old child. Laboratory analysis of blood, urine, and gastric contents demonstrated the presence of an atropinic compound and diphenhydramine only, suggesting the association of benztropine and acute dystonia. Effects of benztropine on neuronal uptake of dopamine may represent a possible mechanism for this unusual adverse effect.