[Ergotism-a weed from Mesopotamia became an epidemic pathogen in Europe]. / Der Ergotismus ­ ein Ackerunkraut aus Mesopotamien wurde in Europa zum noch immer aktuellen Epidemie-Erreger.

In Mesopotamian wheat fields rye grew as weed and after certain developments rye reached Europe and there became a cultivable plant and the dominant grain in certain regions. With the rye also its parasite, the Claviceps purpurea, reached Europe. This ascomycete infects particular rye grains and in its developmental cycle grows to sclerotia bigger than each grain. These forms, the so-called ergots, contain the poisonous ergotalcaloids. After their intake they produce two characteristic forms of ergotism.The clinical picture of the Ergotismus gangraenosus already before the knowledge of its origin, was known as "Ignis sacer", "Anthony's Fire" and "Cold Gangrene". In this non-febrile affection mostly of the limbs, the muscles were decomposed without bleeding and without pain and thereafter the bones detached. Sooner or later the patients died.The other form, Ergotismus convulsivus, mostly described in the German literature as "Kriebelkrankheit" (Crawly disease), begins with the sensation of running ants upon the limbs and continues with painful contractions of hands and feet. In many cases there is a loss of mind and language. Finally, death occurs.The intake of ergotalcaloids predominantly with products of rye flour and meal but also during processing the harvested rye are discussed as well as the "Carry-over" by meat and milk. It is stressed that the compliance with the legal Austrian and EU regulations for the maximum contents of sclerotia and ergotalcaloids resp. in products for human and animal nourishments only can be guaranteed by continuing the technics of separating the sclerotia and their parts.

Acute Ischemia of Lower Extremities Caused by Ergotamine Toxicity due to Pharmacologic Interaction With Cobicistat in an HIV-Positive Patient.

Ergotism is an uncommon condition that affects patients with exposure to ergot alkaloids causing ischemia of extremities. We report the case of lower extremities ischemia caused by ergot toxicity in a human immunodeficiency virus (HIV) positive individual due to the interaction between ergot alkaloid and Cobicistat. In addition, we present a brief review of medical, and pharmacological aspects of this condition. To our knowledge, this is the second reported case describing this interaction.

Three New Ergot Alkaloids from the Fruiting Bodies of Xylaria nigripes (Kl.) Sacc.

Three new ergot alkaloids, xylanigripones A - C (1 - 3) together with three known compounds, agroclavine (4), 8,9-didehydro-10-hydroxy-6,8-dimethylergolin (5), and (6S)-agroclavine N-oxide (6) were isolated from the fungus Xylaria nigripes (Kl.) Sacc. Their structures were elucidated by comprehensive spectroscopic analyses and high-resolution mass spectrometry as well as by comparison with the literature. The absolute configuration was determined by Density Functional Theory (DFT) calculation methods. In addition, all of the compounds were evaluated for bioactivity via a cytotoxicity assay, an acetylcholinesterase inhibition assay and a cholesterol ester transfer protein inhibition assay.

[Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy]. / Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case.

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

Ergotism: a change of persepective.

Clinical ergotism is a rare disorder, and clinical and therapeutic implications have continued to attract attention. The Holy Fire or St. Anthony's Fire was the primary vascular manifestation, causing burning pain and gangrene in the feet and hands related to the arterial spasm properties of ergot. The chronic use of ergotamine and migraine has also been associated with ergotism. Severe vasospasm and acute peripheral ischemia of the extremities can develop. However, in modern times, the spectrum of poisoning by alkaloids has broadened to include antiviral therapies in patients with HIV and abuse of stimulants. These changes have made taking an accurate medical history and conducting an accurate detailed differential diagnosis more essential. The purpose of this review is to highlight the importance of ergotism as a cause of peripheral vascular ischemia and analyze changes associated with this poisoning.

Human and cattle ergotism since 1900: symptoms, outbreaks, and regulations.

Ergotism in humans and cattle are caused by several species of Claviceps that infect rye and other cereal grains. Symptoms in humans vary greatly and are generally classified as convulsive, gangrenous, or gastrointestinal (enteric). Cattle are particularly susceptible to both gangrenous and hyperthermic ergotism (also called summer syndrome). The prevalence of ergotism has decreased as knowledge of the fungus has increased, mainly through implementation of regulations and advances in milling procedures. However, outbreaks in humans have recently occurred in lower socioeconomic populations of Ethiopia (1977 and 2001) and India (1975) with devastating results. Prominent outbreaks in cattle have occurred in Australia (1987), the United States (1996), South Africa (1996-1997), and Brazil (1999) and, as opposed to human cases, they do not appear to be bound by economic development. This review provides a detailed summary of all major ergot epidemics since 1900 in both humans and cattle. Special attention is devoted to the ergotism symptoms and to the regulations surrounding the control of ergot in the food supply.

[Ergotism and HIV]. / Ergotismo y HIV.

Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.

Holy medicine: Patron saints of wounds due to animal bites.

The cult (system of religious beliefs and rituals) of saints in Western Europe appeared in the 3rd century CE and gained momentum from the 4th to the 6th centuries. Its importance for European society in late antiquity and the early Middle Ages was undeniable; holy medicine was the only hope for sick people because the number of physicians was insufficient, and usually physicians were helpless in the face of most of the ailments that plagued society at that time. The number of saints had increased over the years, and people sought medical help from them through prayer and other religious practices. Some saints "specialized" in the treatment of various wounds, including skin diseases. Our research revealed many saints who were patrons of wounds and skin. They can be collected in three groups: patron saints against snakebites and dog bites; patron saints of the treatment of wounds, ulcers, burns, and frostbite; and patron saints against spreadable diseases such as ergotism, leprosy, and scabies. The large number of saints who were patrons against snakebites and dog bites shows the relevance and importance of the problem. In our research, we tried to find out whether the cult of saints led to the development of hospitals for the treatment of skin diseases like ergotism in the hospital of Brother St. Anthony or only in miracles of healing emphasizing the power of faith in the cure of diseases.

Ergot alkaloids in sclerotia collected in Japan: synthetic profiles and induction of apoptosis by Clavine-type compounds.

The genus Claviceps (Clavicipitaceae) is famous for producing ergot alkaloids (EAs) in sclerotia. EAs can cause ergotism, resulting in convulsions and necrosis when ingested, making these compounds a serious concern for food safety. Agroclavine (2), a typical Clavine-type EA, is a causative agent of ergotism and is listed as a compound to be monitored by the European Food Safety Authority. Clavine-type EAs are known to cause cytotoxicity, but the mechanism has not been elucidated. We performed annexin V and PI double-staining followed by flow cytometric analysis to detect apoptosis in HepG2 and PANC-1 cells after exposure to Clavine-type EAs. Clavine-type EAs reduced cell viability and induced apoptosis in both cell lines. We then performed LC-MS analysis of EAs from 41 sclerotia samples of Claviceps collected in Japan. 24 out of 41 sclerotia extracts include peptide-type EAs (ergosine/inine: 4/4', ergotamine: 5, ergocornine/inine: 6/6', α-ergocryptine/inine: 8/8', and ergocristine/inine: 9/9') and 19 sclerotia extracts among 24 sclerotia detected peptide type EAs include Clavine-type EAs (pyroclavine: 1, agroclavine: 2, festuclavine: 3) by LC-MS. We then performed a metabolomic analysis of the EAs in the sclerotia using principal component analysis (PCA). The PCA score plots calculated for EAs suggested the existence of four groups with different EA production patterns. One of the groups was formed by the contribution of Clavine-type EAs. These results suggest that Clavine-type EAs are a family of compounds requiring attention in food safety and livestock production in Japan.

[Splenic infarction. Ergotism induced by ritonavir?]. / Infarto esplénico. ¿Ergotismo inducido por ritonavir?

Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.

An unusual mimicker of a sepsis outbreak: ergot intoxication.

Methylergonovine (MEV) is a semi-synthetic ergot alkaloid used in the prevention and control of postpartum hemorrhage. This report describes 12 newborns born on the same day in a local country hospital in Turkey and developed sepsis-like symptoms and encephalopathy within the first 6 h of life due to accidental administration of MEV instead of vitamin K in the delivery room. The major features of MEV poisoning were lethargy (41.7%), seizure (75.0%), feeding intolerance (66.6%), hypoventilation (58.3%), irritability (25%), and peripheral circulatory abnormalities (58.3%). As a conclusion, clinical findings of ergot toxicity in newborns cannot be distinguished from infectious disease or neonatal encephalopathy.

[Ergotism secondary to ergotamine-ritonavir association. Report of three cases]. / Ergotismo secundario a la asociación ergotamina-ritonavir. A propósito de 3 casos.

Ergotism is a complication of the acute intoxication or chronic abuse of ergot derivatives. It may be manifested by a vasomotor syndrome with peripheral vascular disease frequently involving extremities. We report three patients infected with human immunodeficiency virus (HIV), in antiretroviral treatment (ART) that included a protease inhibitor as ritonavir, and had received self-medicated ergotamine. They developed symptoms of peripheral vascular disease and the physical examination showed no arterial pulses in the affected vessels. Arterial Doppler confirmed signs of diffuse arterial spasm in all of them. An arteriography was performed to the second patient and it showed obliteration of the distal sector of the ulnar and radial arteries. Ergotism secondary to ergotamine-ritonavir association was diagnosed. Patients were treated discontinuing the administration of involved drugs, arterial vasodilators and prophylactic anticoagulation, with marked improvement of symptoms.

The endocrine disruptive effects of ergopeptine alkaloids on pregnant mares.

During equine gestation, ergopeptine alkaloid exposure is not uncommon, and pregnant mares are particularly sensitive to the endocrine disruptive effects of these compounds on lactogenesis and steroidogenesis. Agalactia, prolonged gestation, abortion, dystocia, and placental and fetal abnormalities are all clinical manifestations of changes in the endocrine milieu induced by the ingestion of ergopeptine alkaloid-contaminated feedstuffs by mares during late gestation. An understanding of the endocrine disruptive effects of gestational exposure to ergopeptine alkaloids is necessary for the diagnosis of potential exposures to these compounds and for effective prophylaxis and therapy.

[Dancing manias. Between culture and medicine]. / Manie taneczne. Miedzy kultura a medycyna.

Dancing mania is a clinical and cultural phenomenon which occurred in Western Europe between 13th and 18th centuries. The term dancing mania is derived from the Greek words choros, a dance, and mania, a madness. An Italian variant was known as tarantism as victims were believed to have been bitten by tarantula spider. Although symptoms of dancing manias were well documented in contemporary writings the exact aetiology of dancing plaques is still unclear. Several causes for dancing mania have been postulated: demonic possession, the bite of tarantula, ergot poisoning, epilepsy, mass hysterias, exotics religious cults. The article contains a review of hypothesis of epidemic dances included both medical and psychological factors.

[The Piscine Probatica, a painted canvas of the Hotel-Dieu of Rheims, documentation of an epidemic at the end of the 15th century]. / La piscine probatique, une toile peinte de l'hötel-Dieu de Reims Témoignage d'une épidémie de la fin du XVème siècle d'Ignis Plaga.

The Piscina Probatica theme is the highly distinctive iconography in an impressive painted canvas from the ancient Rheims hôtel-Dieu, dating back to the late 15th or early 16th century. In the first place, it is interesting to note that the actual site of the pool has been located, so that archaeological findings bring confirmation to testament scriptures. Through the choice of the painted-canvas medium, and thanks to his great pictorial skill, the anonymous Rheims artist has given us a document of exceptional value, concerning the signs and symptoms of an illness which wrought havoc in the Rheims area in his own lifetime, namely ignis plaga or "mal des ardents". Other great artists of the same period, such as J. Bosch, have testified to the horror of the illness. As a matter-of-fact, the illness has been fully documented, from the 17th century onwards, and the medical expert H.A. Tessier, also acting as an agricultural expert, has demonstrated that ergotized rye is responsible for the fatal condition known as ergotism, and for the heavy toll it has levied on human lives in the course of centuries.

Ergotism and Saint Anthony's fire.

It has been widely accepted that ergot is a fungal disease caused by infection with the parasitic Claviceps purpurea leading to the development of typical black kernels n the plant. Ingestion of infected rye grains containing ergot alkaloids-usually in the form of contaminated rye bread-causes poisoning, also known as ergotism. The negative impacts of ergot contamination of grain on the health of humans and animals were first documented in ancient times. The history of ergotism shows the influence of food on human health. Although ergot has been known for ages, until the 18th century, its nature was not recognized. It was a part of the rye plant and it was used in traditional medicine. The diet was based was mostly on rye that led to neurologic disorders and gangrene. In the Middle Ages, in regions where rye was a dietary staple, many cases of a peculiar epidemic were recorded. Two names are usually used to describe it: "Saint Anthony's fire" and "holy fire," although there are many more appellations. The history of ergotism is a very important part of history of dermatology. The saint who people prayed to for protection against the disease was Anthony the Great (251-356). Monks of the Order of Saint Anthony played a particular role in treating ergotism by natural methods and specialized in treating skin diseases. Ergot alkaloids still pose a risk to human and animal safety if they appear in food.

Ergotism with acute limb ischemia, provoked by HIV protease inhibitors interaction with ergotamine, rescued by multisite transluminal balloon angioplasty.

Acute limb ischemia induced by arterial vasospasm remains an exceptional situation, favoured by the use of arterial vasoconstrictors. The risk of these substances is largely underestimated in the general population, especially with the co-administration of strong cytochrome inhibitors like human immunodeficiency virus (HIV) protease inhibitors. A 33-year-old woman, who used to take dihydroergotamine for orthostatic hypotension, was prescribed a post-exposure HIV prophylaxis including lopinavir and ritonavir. One day later, she presented an acute bilateral limb ischemia with a sudden pain in both calves, initially while walking and then at rest with bilateral ischemic toes. Angiography confirmed diffuse arterial vasospasm of the lower limb arteries. A first-line therapy with isosorbide dinitrate and amlodipine was ineffective, with rapid clinical worsening. A combination of intra-arterial injections and intra-venous infusions of vasodilators, transluminal balloon angioplasty and bilateral 4-Compartment fasciotomies permitted rapid improvement and finally resulted in both lower limbs rescue. This case and literature review illustrate ergotism due to ergotamine overdose after taking HIV protease inhibitors. It also demonstrates the benefit of an interventional procedure besides medical therapy with vasodilators in severe arterial vasospasm. All along the lower limb arterial tree, transluminal balloon angioplasty restored the blood flow, without vasospasm recurrence. CONCLUSION: In case of ergotism with acute lower limbs ischemia, combining medical vasodilator therapy with interventional procedure can restore the arterial blood flow, thus allowing to save lower limbs.