Liquid chromatography-tandem mass spectrometry (LC-MS/MS) determination of cantharidin in biological specimens and application to postmortem interval estimation in cantharidin poisoning.

A rapid, sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination and quantification of cantharidin in rats liver and kidney. After grinding with methanol, the supernatant was determined by LC-MS/MS using an Thermo Accucore C18 column (100 mm×2.1 mm, 2.6 µm) with a gradient elution of 0.1% formic acid and 0.1% acetonitrile, and in the subsequent analysis using selected reaction monitoring mode, three ion transitions were monitored for analyte. The limit of detection (LOD) was 0.741 ng/ml and the limit of quantitation (LOQ) was 2.471 ng/ml. Good linearity (R2 = 0.9998) was observed for the analyte over the linear range (5-400 ng/ml). The LC-MS/MS method was applied to the analysis of rats liver and kidney in different postmortem intervals (6 h, 12 h, 24 h, 48 h, 72 h and 168 h after death) after a single dose (4 mg/kg) of cantharidin administration by gavage. At 72 h after death, the cantharidin concentration in livers and kidneys were significantly higher than that in other postmortem intervals. Linear regression equations between postmortem interval and lg postmortem cantharidin concentration in rats liver and kidney were Y = 0.007455*X + 1.332(R2 = 0.863) and Y = 0.002689*X + 1.433 (R2 = 0.115) respectively. The animal experiment demonstrated LC-MS/MS method can be used to determine the postmortem cantharidin concentration in rats liver and kidney and the determination of cantharidin in the rats liver after death has potential value for postmortem interval estimation in cantharidin poisoning.

[A Potentially Fatal Aphrodisiac: Cantharidin Poisoning]. / Um Afrodisíaco Potencialmente Fatal: Intoxicação por Cantaridina.

Cantharidin is a toxin extracted from coleoptera beetles, commonly known as 'Spanish fly'. Traditionally it was used as an aphrodisiac, a vesicant or as an abortifacient. Intoxication by this substance has been widely reported, generally associated with gastrointestinal complications, such as digestive hemorrhage, and genitourinary disorders, such as hematuria and acute kidney injury. The authors describe the case of a 51-year old male patient who developed severe cantharidin poisoning after ingesting a preparation ('tea formulation') containing the substance. The patient reported a burning sensation in his oral cavity, diarrhea and hematuria, having sustained acute kidney injury and atypical neurological symptoms. Due to the lack of an antidote, the available treatment options are reduced to supportive measures. This case strengthens the need for a thorough medical history to ascertain the use of 'natural' products and medicinal herbs (i.e. of unregulated origin), and the importance of educating the community to their potential toxicity.

A cantaridina é uma toxina extraída de coleópteros, comummente conhecidos como 'Spanish fly'. Historicamente utilizada como afrodisíaco, vesicante e abortivo. A intoxicação por este agente encontra-se amplamente descrita, tipicamente com envolvimento das mucosas gastrointestinal, com hemorragia digestiva, e genitourinária, com hematúria e lesão renal aguda. Os autores apresentam o caso de um doente do sexo masculino, com 51 anos que desenvolveu um quadro de intoxicação aguda por cantaridina, após ingestão de uma preparação ('chá') desta substância, com ardor na cavidade oral, diarreia, disúria, hematúria, lesão renal aguda e com um quadro neurológico atípico. A toxicidade pela cantaridina é sistémica, contudo, o envolvimento neurológico é raro. Dada ausência de um antídoto, preconiza-se a terapêutica de suporte. Este caso reforça a importância de uma anamnese detalhada, incluindo a utilização de produtos 'naturais' ou de ervanária (i.e. de origem não controlada), e da necessidade de alertar os doentes para a sua potencial toxicidade.

Cantharides poisoning: A retrospective analysis from 1996 to 2016 in China.

Cantharides poisoning may cause serious adverse reactions or even death.We attempt to retrieval articles automatically and manually with the key words of "cantharides" and " poisoning " or " side effects ", then summarized and analyzed the cases of cantharides poisoning from 1996 to 2016 in China, to provide some reference for clinical drug use and forensic identification. Finally, 91 cases were conformance to require; general data, clinical data, prognosis, autopsy results were analyzed.We found that the health education of cantharides in primary doctors and people is lackable, the case fatality rate was 18.68% . The death patients of cantharides poisoning had cardiomyocyte necrosis and neuronal apoptosis in the histopathological examination of autopsy , but the toxicological mechanism was unclear. There may be redistribution of cantharidin in vivo after death. Collectively, we hope that an anthropological database for cantharides poisoning established by multicenter cooperation, include medical institutions and forensic identified centers, and conduct more further studies on its cardiotoxicity and neurotoxicity.

The "Madness" of Friedrich Hölderlin: an iatrogenic intoxication.

The German poet Hölderlin, assumed to have suffered from schizophrenia, in fact has been the victim of a combined calomel and cantharidine intoxication administered by his physician Autenrieth. This new theory explains much better his behavioural changes and also his neurological and other concomitant symptoms; it can be tested by analysing a very few of his hairs for the presence of these compounds.

Poisoning by toxic animals in China--18 autopsy case studies and a comprehensive literature review.

Although exposure to animal venom and poison, such as snakebites, bee stings, and contact, with toads, is a common problem, reported deaths are rare. The present report discusses 18 fatal cases in China. Causes of death were grouped into 6 categories, including 1 case of tetrodotoxin poisoning, 1 case of gallbladder poisoning, 3 cases of snake venom toxicity, 4 cases of melittin toxicity, 4 cases of cantharidin poisoning and 5 cases of venenum bufonis poisoning. The epidemiology of each venom-induced death, the mechanism of exposure to venom, and the target organs and tissues affected by these toxic animals were here systematically reviewed. Such details are important to even suspected cases of venom damage. The associated problems related to forensic medicine, such as manner of death and possible attribution to the toxic effects of various animals, are also discussed herein.

Possible cantharidin poisoning of a great bustard (Otis tarda).

A possible cantharidin intoxication of a great bustard (Otis tarda) was described. This wild bird died by a traumatism, but also presented diarrhoea, congestion of the gastrointestinal tract and kidneys and had ingested several blister beetles of the species Berberomeloe majalis. The analysis of the stomach content by GC-MS revealed the presence of cantharidin at a concentration of 1.37 µg/g of wet weight, a similar level than in other birds poisoned in captivity.

[Simon Bolivar and the cantharides]. / Simón Bolívar y las cantáridas.

Simon Bolivar, The Liberator, did not trust medical care and if he ever requested a doctor, it seems to have been mainly politically motivated. Unfortunately his fears seem to have been correct as his death was accelerated by Dr. Revenand, a man whose medical title is yet under discussion, who applied an extract of cantharides, a beetle known as "the Spanish fly", employed generally as an aphrodisiac, over Bolivar's neck region. According to popular belief of the time, cantharidin, the insect's active principle, reduced "the excess of humours", such as cerebrospinal fluid, plasma, "pituita" and others. Cantharidin has severe adverse effects and was for sure the origin of great suffering for many unfortunate patients in the past.

[A technique for investigating the component of cantharidin blisters by flow cytometry].

OBJECTIVE: Cantharidimide cause blister. The effect of blister on immunoregulation was investigated. METHODS: Cantharidimide was placed on the skin, 48h later, the blister was analyzed by flow cytometry. RESULTS: The blister contained 1 x 10(6) - 1 x 10(7) cells per ml, most of which were neutrophils, macrophages, dendritic cells (DC), and IL-12 secreted by Thl cells. CONCLUSION: There are high concent of DC in the blister, which is differential and induce the secretion of Th1, the activation of T cell. The blister modulate the biological response of patients and is helpful for treatment with infective disease.

Simón Bolívar y las cantáridas / Simon Bolivar and the cantharides

Simon Bolivar, The Liberator, did not trust medical care and if he ever requested a doctor, it seems to have been mainly politically motivated. Unfortunately his fears seem to have been correct as his death was accelerated by Dr. Revenand, a man whose medical title is yet under discussion, who applied an extract of cantharides, a beetle known as "the Spanish fly", employed generally as an aphrodisiac, over Bolivar's neck region. According to popular belief of the time, cantharidin, the insect's active principle, reduced "the excess of humours", such as cerebrospinal fluid, plasma, "pituita" and others. Cantharidin has severe adverse effects and was for sure the origin of great suffering for many unfortunate patients in the past.

Cantharidin revisited: a blistering defense of an ancient medicine.

Cantharidin, a vesicant produced by beetles in the order Coleoptera, has a long history in both folk and traditional medicine. In dermatology, topical cantharidin has long been used to treat warts and molluscum. In 1962, cantharidin lost Food and Drug Administration (FDA) approval owing to the failure of its manufacturers to submit data attesting to cantharidin's efficacy. However, it is expected that the FDA will soon include cantharidin on its "Bulk Substances List," which would permit physicians or pharmacists to compound cantharidin to be used in the office for individual patients. A comprehensive discussion of the origins, folk uses, current FDA status, current dermatologic uses, and effects of cantharidin poisoning has been compiled herein. No cases of systemic intoxication or scarring have been reported with the proper use of cantharidin by a physician. Cantharidin is a safe and valuable medication and should be readded to the dermatologic therapeutic armamentarium.

Cantharidin poisoning due to "Blister beetle" ingestion.

Cantharidin, the active ingredient of "Spanish Fly", is contained in a number of insects collectively called blister beetles and is a well known toxin and vesicant. We report on a case of ingestion of Mylabris dicincta ("Blister beetle") in Zimbabwe by a 4 year old girl. The ingested beetles were probably mistaken for the edible Eulepida mashona. She presented with many of the classic signs and symptoms of cantharidin poisoning including haematuria and abdominal pains. This was recognised only after consultation with the drug information centre. She was managed conservatively, recovered and was discharged after 9 days. A overview of the clinical effects of cantharidin toxicity and its treatment is presented.

Clinical features of blister beetle poisoning in equids: 70 cases (1983-1996).

OBJECTIVE: To document clinical signs and gross pathologic changes associated with naturally acquired cantharidiasis (blister beetle poisoning) in equids. DESIGN: Retrospective study. ANIMALS: 70 equids with laboratory-confirmed blister beetle poisoning. PROCEDURE: Medical records were reviewed to obtain history, physical examination findings, feeding practices, and diagnostic test and necropsy results. RESULTS: 32 horses and 2 donkeys died from exposure to cantharidin, whereas 36 horses survived. Diet content varied, but alfalfa hay was the common component. Onset of signs of disease was rapid. Most equids had signs of gastrointestinal tract distress. Six horses had nonspecific neurologic signs. All equids dying from cantharidiasis were in shock terminally, with duration of clinical signs ranging from 3 to 18 hours. Six horses that died had no gross lesions, whereas 14 had mild to moderate erythema of gastric, small intestinal, or colonic mucosa. Only 2 horses had gastric or duodenal ulceration, and 2 had hemorrhage of the urinary bladder mucosa. One horse had cardiac muscle necrosis. Clinicopathologic data available on 10 horses included hypocalcemia, hypomagnesemia, and azotemia. Cantharidin concentrations in urine or pooled gastric-cecal contents did not always correlate with severity of disease. CLINICAL IMPLICATIONS: Blister beetle poisoning is not universally fatal in equids. Clinical signs are related to the amount of cantharidin ingested. Every horse that survived was treated aggressively. In fatal poisonings, gross lesions may be minimal or inapparent, and diagnosis must be confirmed by chemical detection of cantharidin in urine, blood, or stomach or cecal contents.

Poisoning from "Spanish fly" (cantharidin).

Cantharidin, known popularly as Spanish fly, has been used for millennia as a sexual stimulant. The chemical is derived from blister beetles and is notable for its vesicant properties. While most commonly available preparations of Spanish fly contain cantharidin in negligible amounts, if at all, the chemical is available illicitly in concentrations capable of causing severe toxicity. Symptoms of cantharidin poisoning include burning of the mouth, dysphagia, nausea, hematemesis, gross hematuria, and dysuria. Mucosal erosion and hemorrhage is seen in the upper gastrointestinal (GI) tract. Renal dysfunction is common and related to acute tubular necrosis and glomerular destruction. Priapism, seizures, and cardiac abnormalities are less commonly seen. We report four cases of cantharidin poisoning presenting to our emergency department with complaints of dysuria and dark urine. Three patients had abdominal pain, one had flank pain, and the one woman had vaginal bleeding. Three had hematuria and two had occult rectal bleeding. Low-grade disseminated intravascular coagulation, not previously associated with cantharidin poisoning, was noted in two patients. Management of cantharidin poisoning is supportive. Given the widespread availability of Spanish fly, its reputation as an aphrodisiac, and the fact that ingestion is frequently unwitting, cantharidin poisoning may be a more common cause of morbidity than is generally recognized. Cantharidin poisoning should be suspected in any patient presenting with unexplained hematuria or with GI hemorrhage associated with diffuse injury of the upper GI tract.

Mortality in chickens associated with blister beetle consumption.

Mortality in young chickens was associated with blister beetle consumption. Two species of these insects, Cyaneolytta sp. and Cylindrothorax sp., were found in the chickens' crops, and erosive lesions in the gastrointestinal tract were compatible with blister beetle poisoning (cantharidiasis).

[Acute poisoning caused by cantharidin ingestion for aphrodisiac purposes. A clinical case]. / Intossicazione acuta per ingestione di cantaridina a scopo afrodisiaco. Caso clinico.

We report a case of a man who died after ingestion of cantharidin as aphrodisiac. After evaluating the toxicology, we examined the development and therapeutic possibilities of handling the poisoning including charcoal hemoperfusion.

Renal and neuromuscular respiratory failure--is this a syndrome associated with cantharidin poisoning?

OBJECTIVE: To describe the clinical and laboratory features of patients with renal and neuromuscular respiratory failure due to suspected cantharidin poisoning. DESIGN: Retrospective record review of cases with neuromuscular respiratory failure. SETTING: Intensive Care Unit (ICU), Hillbrow Hospital, Johannesburg. PATIENTS: Out of a total of 47 patients with neuromuscular respiratory failure admitted to the ICU between January 1983 and December 1990, 10 with suspected cantharidin poisoning were selected and studied further. OUTCOME MEASURES: Description of clinical features, laboratory data, treatment and prognosis. RESULTS: In 10 of the 47 patients, the cause of renal and neuromuscular respiratory failure that which precipitated the need for ICU admission was suspected to be cantharidin poisoning. This was based on the history and clinical and laboratory features. In 4 cases trace amounts of cantharidin were detected in blood and/or urine, strengthening the diagnosis. There were 8 males and 2 females. All had evidence of renal injury and 9 had gastro-intestinal symptoms. All presented with fixed dilated pupils, varying cranial nerve palsies and muscle weakness, usually ascending and progressive, necessitating admission to the ICU. All but 1 of the patients were mechanically ventilated, 5 required significant inotropic support of the blood pressure, and 6 dialysed. Four patients died soon after admission and the remainder survived with relatively complete return of neurological function. CONCLUSION: This study highlights the possibility that cantharidin poisoning may be a cause of a 'Guillain-Barrè-like' syndrome.