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.

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.

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.

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.

Ruminal tryptophan-utilizing bacteria degrade ergovaline from tall fescue seed extract.

The objectives of this study were to evaluate degradation of ergovaline in a tall fescue [ (Schreb.) Darbysh.] seed extract by rumen microbiota ex vivo and to identify specific bacteria capable of ergovaline degradation in vitro. Rumen cell suspensions were prepared by harvesting rumen fluid from fistulated wether goats ( = 3), straining, and differential centrifugation. Suspensions were dispensed into anaerobic tubes with added Trypticase with or without extract (∼10 µg kg ergovaline). Suspensions were incubated for 48 h at 39°C. Samples were collected at 0, 24, and 48 h for ergovaline analysis and enumeration of hyper-ammonia producing (HAB) and tryptophan-utilizing bacteria. Ergovaline values were analyzed by repeated measures using the mixed procedure of SAS. Enumeration data were log transformed for statistical analysis. When suspensions were incubated with extract, 11 to 15% of ergovaline disappearance was observed over 48 h ( = 0.02). After 24 h, suspensions with added extract had 10-fold less HAB than controls ( = 0.04), but treatments were similar by 48 h ( = 1.00). However, after 24 h and 48 h, suspensions with extract had 10-fold more tryptophan-utilizing bacteria ( < 0.01) that were later isolated and identified by their 16S RNA gene sequence as . The isolates and other known rumen pure cultures ( JB1, B159, HD4, B, F, MD1, SR) were evaluated for the ability to degrade ergovaline in vitro. Pure culture cell suspensions were incubated as described above and samples were taken at 0 and 48 h for ergovaline analysis. Data were analyzed using the ANOVA procedure of SAS. All HAB, including the isolates, tested degraded ergovaline (54 to 75%; < 0.05). B14 was also able to degrade ergovaline but to a lesser capacity (12%; < 0.05), but all other bacteria tested did not degrade ergovaline. The results of this study indicate which rumen bacteria may play an important role in ergovaline degradation and that microbiological strategies for controlling their activity could have ramifications for fescue toxicosis and other forms of ergotism in ruminants.

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.