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.

[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.

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.

Vasoactive Effects of Acute Ergot Exposure in Sheep.

Ergotism is a common and increasing problem in Saskatchewan's livestock. Chronic exposure to low concentrations of ergot alkaloids is known to cause severe arterial vasoconstriction and gangrene through the activation of adrenergic and serotonergic receptors on vascular smooth muscles. The acute vascular effects of a single oral dose with high-level exposure to ergot alkaloids remain unknown and are examined in this study. This study had two main objectives; the first was to evaluate the role of α1-adrenergic receptors in mediating the acute vasocontractile response after single-dose exposure in sheep. The second was to examine whether terazosin (TE) could abolish the vascular contractile effects of ergot alkaloids. Twelve adult female sheep were randomly placed into control and exposure groups (n = 6/group). Ergot sclerotia were collected and finely ground. The concentrations of six ergot alkaloids (ergocornine, ergocristine, ergocryptine, ergometrine, ergosine, and ergotamine) were determined using HPLC/MS at Prairie Diagnostic Services Inc., (Saskatoon, SK, Canada). Each ewe within the treatment group received a single oral treatment of ground ergot sclerotia at a dose of 600 µg/kg BW (total ergot) while each ewe in the control group received water. Animals were euthanized 12 h after the treatment, and the pedal artery (dorsal metatarsal III artery) from the left hind limb from each animal was carefully dissected and mounted in an isolated tissue bath. The vascular contractile response to phenylephrine (PE) (α1-adrenergic agonist) was compared between the two groups before and after TE (α1-adrenergic antagonist) treatment. Acute exposure to ergot alkaloids resulted in a 38% increase in vascular sensitivity to PE compared to control (Ctl EC50 = 1.74 × 10-6 M; Exp EC50 = 1.079 × 10-6 M, p = 0.046). TE treatment resulted in a significant dose-dependent increase in EC50 in both exposure and control groups (p < 0.05 for all treatments). Surprisingly, TE effect was significantly more pronounced in the ergot exposed group compared to the control group at two of the three concentrations of TE (TE 30 nM, p = 0.36; TE 100 nM, p < 0.001; TE 300 nM, p < 0.001). Similar to chronic exposure, acute exposure to ergot alkaloids results in increased vascular sensitivity to PE. TE is a more potent dose-dependent antagonist for the PE contractile response in sheep exposed to ergot compared to the control group. This study may indicate that the dry gangrene seen in sheep, and likely other species, might be related to the activation of α1-adrenergic receptor. This effect may be reversed using TE, especially at early stages of the disease before cell death occurs. This study may also indicate that acute-single dose exposure scenario may be useful in the study of vascular effects of ergot alkaloids.

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.

Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers.

Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. Angus steers (n = 36) were allocated randomly in a 2 × 2 factorial arrangement of treatments including endophyte-infected (E+) or endophyte-free (E-) tall fescue seed, with (P+) or without (P-) isoflavones. Steers were provided a basal diet with fescue seed for 21 days, while isoflavones were orally administered daily. Following the trial, blood and rumen fluid were collected for metabolite analysis. Metabolites were extracted and then analyzed by UPLC-MS. The MAVEN program was implemented to identify metabolites for MetaboAnalyst 4.0 and SAS 9.4 statistical analysis. Seven differentially abundant metabolites were identified in serum by isoflavone treatment, and eleven metabolites in the rumen due to seed type (p < 0.05). Pathways affected by treatments were related to amino acid and nucleic acid metabolism in both rumen fluid and serum (p < 0.05). Therefore, metabolism was altered by fescue seed in the rumen; however, isoflavones altered metabolism systemically to potentially mitigate detrimental effects of seed and improve animal performance.

Ergotism, a relatively unknown mimic of vasculitis: A case report and review of literature / Ergotismo: un imitador poco conocido de vasculitis. Reporte de caso y revisión de la literatura

ABSTRACT Introduction: Ergotism is a vasospasm that affects visceral and peripheral muscle arteries. Classically, symmetrical involvement of lower limb arteries is described, and is often associated with a history of chronic consumption of ergotamine derived medications (Cafergot). Case report: A 22 year-old healthy man with infectious mononucleosis syndrome, who presented with a sudden onset of paraesthesias in the lower limbs, as well as livedo reticularis. The initial diagnosis was a medium-sized vessel vasculitis (polyarteritis nodosa). The symptoms were preceded by the administration of Cafergot for headache treatment, and resolved spontaneously. The magnetic resonance angiography (MRA) of the lower limbs showed occlusion of peroneal arteries, with filiform distal flow. Other infectious, autoimmune and cardiovascular origins were ruled out. Discussion: Ergotism is an important differential diagnosis in the study of the patient with vasculitis, especially in acute onset presentations. Its treatment is the suspension of the causal drug, with vasodilator and surgical vascular procedures, if necessary. Conclusions: Ergotism is an imitator of vasculitis, especially in young patients with a history of difficult to control migraine. The concomitant administration of CYP3A4 inhibitors (mainly, protease inhibitors and macrolides) enhances the toxic effects of ergot.

RESUMEN Introducción: El ergotismo es un vasoespasmo que afecta las arterias musculares periféricas y viscerales. Clásicamente se describe la afectación simétrica de las arterias de las extremidades inferiores, a menudo asociada con el consumo crónico de medicamentos derivados de ergotamina (Cafergot®). Caso clínico: Varón sano de 22 anos con síndrome de mononucleosis, presentó parestesias en las extremidades inferiores y livedo reticularis de forma súbita, el diagnóstico inicial fue una vasculitis de mediano vaso (poliarteritis nodosa). Los síntomas fueron precedidos por la administración de Cafergot® para el tratamiento de cefalea, y se resolvieron espontáneamente. La angiografía por resonancia magnética (ARM) de las extremidades inferiores mostró oclusión de las arterias peroneas, con flujo distal filiforme. Se descartaron otras etiologías infecciosas, autoinmunes y cardiovasculares. Discusión: Los ergotismos son un diagnóstico diferencial importante en el estudio del paciente con vasculitis, especialmente en presentaciones de inicio agudo. Su tratamiento es la suspensión del fármaco causal, vasodilatadores y procedimientos vasculares quirúrgicos, si es necesario. Conclusiones: El ergotismo es un imitador de vasculitis, especialmente en pacientes jóvenes con antecedentes de migrana de difícil control. La administración concomitante de inhibidores del CYP3A4 (principalmente, inhibidores de proteasa y macrólidos) potencia los efectos tóxicos del ergot.

Use of Integrative Interactomics for Improvement of Farm Animal Health and Welfare: An Example with Fescue Toxicosis.

Rapid scientific advances are increasing our understanding of the way complex biological interactions integrate to maintain homeostatic balance and how seemingly small, localized perturbations can lead to systemic effects. The 'omics movement, alongside increased throughput resulting from statistical and computational advances, has transformed our understanding of disease mechanisms and the multi-dimensional interaction between environmental stressors and host physiology through data integration into multi-dimensional analyses, i.e., integrative interactomics. This review focuses on the use of high-throughput technologies in farm animal research, including health- and toxicology-related papers. Although limited, we highlight recent animal agriculture-centered reports from the integrative multi-'omics movement. We provide an example with fescue toxicosis, an economically costly disease affecting grazing livestock, and describe how integrative interactomics can be applied to a disease with a complex pathophysiology in the pursuit of novel treatment and management approaches. We outline how 'omics techniques have been used thus far to understand fescue toxicosis pathophysiology, lay out a framework for the fescue toxicosis integrome, identify some challenges we foresee, and offer possible means for addressing these challenges. Finally, we briefly discuss how the example with fescue toxicosis could be used for other agriculturally important animal health and welfare problems.

One holy man, one eponym, three distinct diseases. St. Anthony's fire revisited.

The use of eponyms adds a valuable historical context to the art of medicine, and shall hence be encouraged, nevertheless their use must always reflect an appropriate historical and medical terminology. A bizarre narration concerns the widespread term "St. Anthony's fire", which has been used for denoting not less than three distinct diseases. In this article we underscore that at least three distinct diseases, one toxic (i.e., ergotism) and two infectious (i.e., erysipelas and herpes zoster) have been called, in different times and countries, with the same eponym term of "St. Anthony's fire", whilst some other diseases may have also been comprised under this "umbrella" definition. It is possible, for example, that even some cases of plague may have been misclassified as "St. Anthony's fire". This article also deals with the importance of this topic in the history of art. Several important artists in different periods, in particular painters, were inspired from the history of St. Anthony, who is generally represented in association with fire (representing the burning pain of the diseases), pig (symbolizing the fat of pigs used in the past for relieving skin symptoms), and different "temptations" (devils, food, gold, jewelry, etc.). A literary masterwork is also cited and discussed.

Neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state, Brazil / Enfermidades neurológicas em bovinos causadas por plantas e micotoxinas no estado de Santa Catarina

This study described the epidemiological and clinical-pathological aspects of 25 outbreaks of neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state. Six of them were due to Sida carpinifolia poisoning, five to Solanum fastigiatum, five to Phalaris angusta, three to Claviceps paspali, three to Claviceps purpurea, and three outbreaks were of unknown etiology. The clinical signs observed in the affected cattle were mild to severe and characterized by generalized muscle tremors, incoordination, hypermetria, wide-based stance, intentional head tremors, dull staring eyes, and frequent ear twitching, with convulsions in some cases. At necropsy, lesions were observed only for P. angusta poisoning, characterized by gray-greenish discoloration in thalamus and midbrain. Microscopically, rarefaction and/or disappearance of Purkinje neurons with substitution by Bergmann cells were observed for S. carpinifolia and S. fastigiatum poisoning. For P. angusta poisoning, thin granular brown-yellowish pigment was observed in the cytoplasm of some neurons. Gross and microscopic findings were not observed in three outbreaks of tremorgenic disease of unknown etiology. Experiments conducted with leaves, flowers and seeds of Ipomoea indivisa and Ipomoea triloba, as well as with maize and soybean residues contaminated with Ipomoea spp. did not reproduced clinical signs.(AU)

Descrevem-se os aspectos epidemiológicos e clinico-patológicos de 25 surtos de enfermidade neurológica em bovinos no estado de Santa Catarina causadas por plantas e micotoxinas. Destes, seis corresponderam a intoxicação por Sida carpinifolia, cinco por Solanum fastigiatum, cinco por Phalaris angusta, três por Claviceps paspali, três por Claviceps purpurea e três surtos de etiologia não definida. Os sinais clínicos observados nos bovinos afetados eram de intensidade leve a acentuada e caracterizados por tremores musculares generalizados, incoordenação, hipermetria, aumento da base de sustentação, balanço contínuo de cabeça, olhar atento e movimentos frequentes de orelhas, e em alguns surtos convulsões. Por meio de necropsia foram observadas alterações somente na intoxicação por P. angusta as quais caracterizaram por coloração cinza-esverdeada no tálamo e mesencéfalo. Na histologia, rarefação e/ou desaparecimento de neurônios de Purkinje com substituição por células de Bergmann foram observadas na intoxicação por S. carpinifolia e S. fastigiatum. Na intoxicação por P. angusta foi observado no citoplasma de alguns neurônios do tronco encefálico com pigmentação finamente granular marrom-amarelada. Nos três surtos de enfermidade tremorgênica com etiologia não definida não foram observadas lesões macroscópicas e microscópicas. Experimentos com folhas, flores e sementes de Ipomoea indivisa e Ipomoea triloba e resíduos de milho e soja contaminados com sementes destas duas plantas não produziram alterações clínicas.(AU)

Sobre el mal de los ardientes o del fuego de San Antonio / Saint Anthony's fire illness

Resumen El ergotismo es el resultado de la intoxicación con alcaloides derivados del ergot. Durante la edad media y hasta el siglo XIX fue el responsable de grandes epidemias en Europa por el consumo de granos contaminados con el cornezuelo del centeno provocando manifestaciones isquémicas características y afección del sistema nervioso. El ergotismo como se conoció en el Medioevo ha desaparecido, pero aún hoy en día se reportan casos en el marco de uso terapéutico de ergotamínicos. Se pretenden describir algunos de sus aspectos históricos y clínicos distintivos.

Abstract Ergotism is the result of intoxication with alkaloids derived from ergot. During the middle ages and until the nineteenth century it was responsible for major epidemics in Europe for the consumption of grains contaminated with ergot, causing characteristic ischemic manifestations and nervous system involvement. Ergotism as it was known in the Middle Ages has disappeared, but even today cases are reported in the therapeutic use of ergotamine. Some of its distinctive historical and clinical aspects are intended to be described.

Neuropatía úptica isquémica anterior unilateral asociada con ergotismo / Anterior unilateral ischemic optic neuropathy associated to ergotism

Case report of a patient with ergotism. ergotism is a complication of acute intoxication of chronic abuse of ergot derivates. Ergot is a fungus that grows on rye and less commonly on other grases such as wheat. Ergotism is a severe reaction to ergocontaminated food (such as rye bread). Ergot refers to a group of fungi of the genus Claviceps. It is a condition that develops of longterm ingestion of ergotamines. In excess, ergotamine can cause symptos such as hallucinations, severe gastrointestinal upset, a type-of dry gangrene and a pain-ful sensation in the extremities. Our patient is presented with anterior unilateral ischemic optic neuropathy. The studies performed and the clinical evaluatiion, are presented, and the treatment the same as the follow-up, are described in the article.

Headache in an HIV-Positive Patient: Dangerous Interaction.

Ergotism is an ischaemic complication due to vasoconstriction throughout the body due to ingestion of ergotamine. A 34-year-old Hispanic man with HIV infection treated with saquinavir, ritonavir and abacavir/lamivudine presented to the emergency department complaining of left foot pain 1 week prior to admission. The affected extremity was cold with absence of pedal and tibial pulses. Arterial Doppler revealed absent arterial flow from the popliteal artery later confirmed by arteriography. Medication reconciliation revealed a recent prescription for migraine headache containing ergotamine. Drug was discontinued and the patient was started on cilostazol, enoxaparin and nitroglycerin patches on the affected limb. Complete resolution of symptoms and arteriography findings occurred 2 days after therapy began.

Insuficiencia arterial aguda severa vinculada a ergotismo / Severe acute arterial insufficiency linked to ergotism / Insuficiência arterial aguda severa vinculada a ergotismo

El ergotismo es un síndrome clínico poco frecuente pero potencialmente letal vinculado a la intoxicación aguda o crónica con el uso de alcaloides del ergot en el tratamiento de la migraña. Se caracteriza por un vasoespasmo severo generalizado que puede generar isquemia periférica o visceral y conducir a disfunción orgánica múltiple y muerte. Existen numerosos fármacos de metabolismo hepático que pueden alterar la metabolización de la ergotamina pudiendo alcanzar concentraciones tóxicas incluso a bajas dosis. Presentamos el caso de un paciente infectado con virus de la inmunodeficiencia humana bajo tratamiento antirretroviral que incluía inhibidores de la proteasa y que se había automedicado con ergotamina. El paciente presentó posteriormente sintomatología sensitivo motora deficitaria de miembros superiores e inferiores, acompañada de elementos de hipoperfusión distal severa. Se solicitó Doppler arterial que evidenció vasoespasmo de ejes arteriales de miembros. Se realizó diagnóstico de ergotismo secundario a la asociación de ergotamina - ritonavir, ingresando a cuidados intensivos. Se inició tratamiento en base a suspensión de ambos fármacos, vasodilatación arterial con nitroprusiato y antiagregación con ácido acetilsalicílico. En relación con este caso se presenta una revisión del mecanismo de toxicidad de la ergotamina, sus interacciones farmacológicas, así como diagnóstico y tratamiento disponibles para esta patología. (AU)

Ergotism is a rare but potentially lethal clinical syndrome linked to acute or chronic poisoning with the use of ergot alkaloids in the treatment of migraine. It is characterized by a severe generalized vasospasm that can generate peripheral or visceral ischemia and lead to multiple organ dysfunction and death. There are numerous drugs of hepatic metabolism that can alter the metabolism of ergotamine and can reach toxic concentrations even at low doses. We present the case of a patient infected with human immunodeficiency virus under antiretroviral treatment that included protease inhibitors and who had self-administered with ergotamine. The patient subsequently presented motor sensory deficit symptoms of upper and lower limbs, accompanied by elements of severe distal hypoperfusion. Arterial Doppler was requested, which showed vasospasm of the arterial axis of the limbs. A diagnosis of ergotism secondary to the ergotamine-ritonavir association was made, entering intensive care. Treatment was started based on suspension of both drugs, arterial vasodilatation with nitroprusside and antiaggregation with acetylsalicylic acid. In relation to this case, we present a review of the ergotamine toxicity mechanism, its pharmacological interactions, as well as the diagnosis and treatment available for this pathology. (AU)

O ergotismo é uma síndrome clínica pouco frequente, porém potencialmente letal vinculado à intoxicação aguda ou crônica pelo uso de alcalóides do Ergot no tratamento da enxaqueca. Caracteriza-se por um vaso espasmo severo generalizado que pode gerar isquemia periférica ou visceral e levar a disfunção orgânica múltipla e morte. Existem múltiplos fármacos de metabolismo hepático que podem alterar a metabolização da ergotamina podendo alcançar concentrações tóxicas inclusive em doses baixas. Apresentamos o caso de um paciente infectado com vírus da imunodeficiência humana recebendo tratamento antirretroviral que incluía inibidores da protease e que se automedicou com ergotamina. O paciente apresentou posteriormente sintomatologia sensitiva motora deficitária de membros superiores e inferiores, acompanhada de elementos de hipoperfusao distal severa. Solicitou-se Doppler arterial que mostrou vaso espasmo dos eixos arteriais de membros. Realizou-se diagnóstico de ergotismo secundário à associação ergotamina - ritonavir, e transferiu-se o paciente a cuidados intensivos. Iniciou-se tratamento com a suspensão de ambos os fármacos, vasodilatação arterial com nitroprussiato e antiagregaçao com ácido acetilsalicílico. Apresenta-se uma revisão do mecanismo de toxicidade da ergotamina, suas interações farmacológicas, seu diagnóstico e os tratamentos disponíveis para esta patologia. (AU)

ANNIVERSARY REVIEW: 50 years since the discovery of bromocriptine.

Ergotism is the long-term ergot poisoning by ingestion of rye or other grains infected with the fungus Claviceps purpurea and more recently by excessive intake of ergot drugs. It has either neuropsychiatric or vascular manifestations. In the Middle Ages, the gangrenous poisoning was known as St. Anthony's fire, after the order of the Monks of St. Anthony who were particularly skilled at treating the condition. In 1917, Prof. Arthur Stoll returned home to Switzerland from Germany, to lead the development of a new pharmaceutical department at Sandoz Chemical Company. Stoll, using the special methods of extraction learned from his work with his mentor Willstetter, started his industrial research work with ergot. He succeeded in isolating, from the ergot of rye, ergotamine as an active principle of an old popular remedy for excessive post-partum bleeding. The success of this discovery occurred in 1918 and was translated into a pharmaceutical product in 1921 under the trade name Gynergen. In subsequent work, Stoll and his team were leaders in identifying the structure of the many other alkaloids and amines produced by Claviceps purpurea This was the cultural background and scientific foundation on which bromocriptine was discovered.

Claviceps purpurea e Bipolaris sp. como causa de ergotismo em bovinos no estado de Santa Catarina / Claviceps purpurea e Bipolaris sp. as a cause of ergotism in cattle in Santa Catarina State

Claviceps purpurea é o fungo associado ao ergotismo. Esta é uma enfermidade causada pela ingestão de escleródios chamados de ergot, que contém alcalóides que atuam em receptores adrenérgicos, dopaminérgicos e seratoninérgicos causando efeito direto em vasos sanguíneos, musculatura lisa e sistema nervoso central e autônomo. Descrevem-se dados epidemiológicos, sinais clínicos e lesões de uma enfermidade de bovinos caracterizada por hipertermia, taquicardia, taquipneia e ulcerações na coroa do casco de bovinos. Entre 2000 e 2014 foram diagnosticados 13 surtos, três da forma distérmica, sete da forma gangrenosa e três da forma convulsiva. Porém, em cinco destes sete surtos, nos locais onde esses animais pastoreavam havia alta incidência de inflorescências de Sporobolus indicus conhecido como "capim-mourão", infectadas por um fungo com coloração enegrecida, identificado como Bipolaris sp. A enfermidade foi reproduzida experimentalmente em cinco bovinos com a administração destas inflorescências. Os bovinos em experimentação receberam inflorescências de S. indicus respectivamente nas doses diárias de 0,1g/kg, 0,2g/kg, 0,2g/kg, 0,26g/kg e 0,34g/kg por um período de 4, 7, 9 e 30 dias. Após três a sete dias de ingestão das inflorescências infectadas, quatro dos cinco bovinos apresentaram diarreia e manifestaram taquicardia, taquipneia e hipertermia em algum período durante a ingestão. Estes sinais coincidiram com os dias mais quentes deste período. Um bovino manifestou hiperemia na coroa do casco e perda de pêlos da extremidade da cauda. Baseado na reprodução experimental é possível afirmar que o capim Sporobolus indicus infectado pelo fungo Bipolaris sp é capaz de causar diarreia, hipertermia, taquicardia, taquipneia, hiperemia na coroa do casco e perda de pêlos da extremidade da cauda.(AU)

Claviceps purpurea is the fungus associated with ergotism. Ergotism is a disease caused by the ingestion of esclerodios called ergot, which contains alkaloids that act on dopaminergic and adrenergic receptors, causing seratoninergic effect on blood vessels, smooth muscles and central nervous and autonomic system. The present study describes epidemiological data, clinical signs and lesions of a bovine cattle disease characterized by hyperthermia, tachycardia, tachypnea and injuries in the coronary band of the hooves. Initially the cause was attributed to the fungus Claviceps purpurea. Between 2000 and 2014, 13 outbreaks were described, being three of distermic form, seven of gangrenous and three of the convulsive form. However, in five out of the seven of the gangrenous form outbreaks, it has been observed a high incidence of smut grass (Sporobolus indicus) inflorescences infected by a blackened fungus, classified as Bipolaris sp., in the places where the bovine grazed. The disease was reproduced experimentally by administration of inflorescences of smut grass contaminated by Bipolaris sp. Five bovine received daily doses of 0.1g/kg, 0.2g/kg, 0.2g/kg, 0.26g/kg and 0.34g/kg during 4, 7, 9, 30 and 30 days respectively. After three to seven days of eating contaminated inflorescences four cattle had diarrhea, tachycardia, tachypnea and intermittent hyperthermia. These clinical signs happened on the warmest days and during the warmest temperatures of the day. A bovine showed hyperemia in the coronary band of the hoof and loss of tail tip hair. According to data obtained during the experimental reproduction, smut grass contaminated by Bipolaris sp. can cause hyperthermia, tachycardia, tachypnea, injuries in the coronary band of the hoof and loss of the tail tip hair in bovine cattle.(AU)

Isquemia de miembros inferiores secundaria a ergotamina. Reporte de casos y revisión de literatura / Lower limb ischaemia secondary to ergotamine. Case reports and a review of the literature

El ergotismo es en la actualidad un trastorno raro, asociado a la administración iatrogénica de ergotamina en pacientes que padecen de cefaleas migrañosas. La intensidad del vasoespasmo que presenta esta entidad clínica en la mayoría de los casos resulta en isquemia aguda de las extremidades. Presentamos 2 casos de isquemia aguda de las extremidades, en pacientes de sexo femenino, de mediana edad, con signos y síntomas que amenazaban la viabilidad de los miembros inferiores. El estudio por ultrasonido y la arteriografía (en el caso 1) confirmaron la presencia de espasmo arterial bilateral difuso. Inmediatamente se procedió a interrumpir la administración de ergotamina y se instauró terapia vasodilatadora. Los síntomas de las pacientes empezaron a mejorar a las 48-72 h de iniciado el tratamiento (AU)

Ergotism is a rare disorder associated with the iatrogenic administration of ergotamine in patients with migraine headaches. The intense vasospasm that occurs in this clinical condition results in acute limb ischaemia in the majority of cases. Two cases are presented of acute limb ischaemia in middle age female patients with signs and symptoms that threatened the viability of lower limbs. Duplex ultrasound and arteriography (in the first case) confirmed the presence of a bilateral diffuse arterial spasm. Ergotamine treatment was discontinued immediately and vasodilator therapy was administered. The patient's symptoms began to improve 48-72 h after starting therapy (AU)