Pharmaceutical

Communication

Biosci. Biotech. Res. Comm. 11(3): 356-362 (2018)

Clinical uses and toxicity of Ergot,

Claviceps purpurea

An evidence-based comprehensive retrospective review

(2003-2017)

Raghad Al-Omari

, Atheer Al-Enazi

, Rizwan Ahmad*

, Niyaz Ahmad

, Atta Abbas Naqvi

and Adeeb Shehzad

College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia

Natural Products and Alternative Medicines, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal

University, Dammam, Saudi Arabia

Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University,

Dammam, Saudi Arabia

Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University,

Dammam, Saudi Arabia

Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering,

National University of Sciences and Technology, Islamabad, Pakistan

ABSTRACT

Ergot alkaloids produced by the fungusClavicepsparasitizing on cereals presents a high toxicity risk for animals

and humans due to presence of its alkaloid content. Ergot-alkaloid toxicity occurs via their medicinal use however

human poisoning from ergot plant is rare. The aim of this review is to determine the toxicity of ergot plant or ergot-

amine derivatives in humans. Databases such as Google scholar, PubMed, Scopus, Web of Science alongwith related

books and theses as well as the library resources from Imam Abdulrahman Bin Faisal University were used whereas

the Key words searched included; Ergot, Egotism, Ergotamine poisoning, Ergotamine interaction with HIV therapy,

Ergotamine overdose, and report cases of ergotism. The relevant literature search suggests many toxicity cases and

side effects associated with the use of ergot-alkaloids. More commonly it develops a condition known as ergotism i.e.

a disease or toxic condition produced by eating ergot grains or rye or chronic use of ergot drug. The characteristic

356

ARTICLE INFORMATION:

*Corresponding Author: rizvistar_36@yahoo.com

Received 1

July, 2018

Accepted after revision 21

Sep, 2018

BBRC Print ISSN: 0974-6455

Online ISSN: 2321-4007 CODEN: USA BBRCBA

Thomson Reuters ISI ESC / Clarivate Analytics USA and

Crossref Indexed Journal

NAAS Journal Score 2018: 4.31 SJIF 2017: 4.196

Online Contents Available at: http//www.bbrc.in/

DOI: 10.21786/bbrc/11.3/2

Raghad Al-Omari et al.

features of ergotism consist of painful and cold extremities. Furthermore, a notable and severe interaction of ergot-

alkaloids was found in HIV patients using ergotamine and antiretroviral drugs together. Ergotamine which is one of

ergot preparation has poisonous effect when taken in over dose and it interacts with antiretroviral drugs also.

KEY WORDS: EGOTISM; MIGRAINE HEADACHE; POSTPARTUM HEMORRHAGE; ARTERIAL SPASM; CYANOSIS

INTRODUCTION

The ergot fungus (Claviceps purpurea) is family of sec-

ondary metabolites and is a common seed pathogen

of grasses and cereals. Ergot is a parasitic fungus that

belongs to the genus Claviceps and forms dark sclerotia

on various grasses and grains. After maturing, the scle-

rotia fall to the ground and remain partially buried for

the resting stage of ergot formation. This period occurs

during cold or winter weather, (Ehrlich et al., 2013).

Ergot plant has medicinal uses to treat some diseases;

even though, Ergot contain alkaloids which can cause

severe toxicity in mammals when ingested and thus the

fungal infection might provide protection for the host

plant against mammalian herbivores, (Panaccione et al.,

2012). Ergot alkaloids are natural products having nitro-

gen indole alkaloids. There are three group of ergot; I.

peptides (ergopeptines), II. Clavines and III. Lysergic acid

amides, (Gerhards et al., 2014).

There are more than fourty known ergot and usu-

ally six of them may cause toxicity by interaction with

neurotransmitters. These are ergotamine, ergocornine,

ergocryptine, ergocristine, ergosine and ergometrine,

(Mulac et al., 2011). Ergot alkaloids have pharmacological

and toxicological effect on several receptor systems in the

human body. Ergot become activated in the body to some

receptors and show cytotoxic affects and induces apopto-

sis in human primary cells, (Mulac et al., 2013).

Ergotism occurs when either the fungus is ingested

via the contamination of grain, for example, rye or by

the medicinal use of drugs derived from ergotamine

compounds. Ergot toxicity called Ergotism previously

known as Holy Fire, in some cases may lead to death,

(Floss, 1976). There are two forms of Ergotism; gangre-

nous and convulsive and both can occur in the same

individual. Gangrenous named as Saint Anthony’s, usu-

ally characterized by pain in one limb particularly the

calf and leg, in amed, swollen, and violet hand and foot

whereas in severe cases the limb will separate from the

knee with hemorrhage and may need a knee amputa-

tion. The other form of ergotism i.e. convulsive form

is accompanied with heaviness and numbness in limbs

with paresthesia well as diarrhea without vomiting. In

humans, ergot is used pharmacologically to inhibit lac-

tation, postpartum hemorrhage, and induce labor, (Lee

and Coll, 2009). Previously ergot was used in the treat-

ment of Parkinsonism and other endocrine and neuro-

logicaldisorders, (Tesh, 2015).

In addition, ergot induces cytotoxic and apoptotic

effect shows anti-cancer effect and thus used as a can-

cer therapy. In a study on two cancer lines (Hep-G2

and HT-29) ergot showed a high grade apoptotic effect,

(Mulac et al., 2013). Furthermore, ergot alkaloids have

an important widespread use in migraine headaches and

5-hydroxytryptamine (5-HT) receptors acts as binding site

for these ergot derivatives such as Ergotamine, Dihydro-

ergotamine, and Methysergide. They work as agonist of

5-HT1B, 5-HT1D, and 5-HT1F receptors to treat for treat-

ment as well as prophylaxis for migraine headache with a

high ef cacy, (Dholf et al., 2012). Though in human, ergot

complications i.e. ergotism appears rarely with symptoms

such as tachycardia, hypertension and arterial spasm, still

it is important to be taken care as ergot acts as a strong

vasoconstrictor and may cause severe adverse effects at

cardiac and limbs level, (Adam et al., 2014).

Current review aims to highlight the more impor-

tant and recently reported cases regarding ergotism in

humans with major symptoms observed, as associated

with the use of ergot-alkaloids. The literature will be

searched to extract out the factors behind ergotism and

to report the possible measure in order to tackle such

reasons. The study owes importance as it will compare

the therapeutic and toxic pro le for ergot and to con-

clude an overall scenario of how to use ergot-alkaloids

for therapeutic purposes and to avoid ergotism.

MATERIAL AND METHODS

Various databases searched were: Google scholar, Sci-

ence direct, Research gate, Web of Science, PubMed,

Science Finder, Scopus and Journals such as; Journal

of Ethnopharmacology, Frontier in Ethnopharmacology,

Thieme journals, Clinical Toxicology journal, Journal of

Agricultural and Food Chemistry, Journals of Toxicol-

ogy, Canadian Medical Association Journal, JSM foot

and ankle journal, Toxicology and Industrial Health

(SAGE journals) and The Royal College of Physician of

Edinburgh were searched. In addition, books and the-

ses and online as well as hard resources from library of

Imam Abdulrahman Bin Faisal University Damam, Saudi

Arabia was also searched.

Key words were also searched:

Ergot, Ergot alkaloids, reported case of Ergot toxicity,

adverse effects of ergot; ergotism, ergotamine toxicity,

BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS A COMPREHENSIVE REVIEW OF ERGOT 357

Raghad Al-Omari et al.

clinical cases observed for ergot alkaloids, uses of ergot

alkaloids, interactions of ergot alkaloids.

The literature was searched for retrospective  fteen

years i.e. 2003-2017. All the clinical cases regarding ergot

toxicity or ergotism were gathered and  ltered as per the

inclusion and exclusion criteria as mentioned below;

Inclusion criteria

The clinical cases reported in humans associated with

the use of ergot or ergot alkaloids in any of its form

used, were included. The toxicity resulted due to over-

dose, long term use as well as any adverse effect and

drug interaction of ergot and ergot derivatives with HIV

drugs were also included in the study.

Exclusion criteria

Clinical cases regarding ergot toxicity, reported in ani-

mals or in vivo studies (cell lines) as well as in vitro stud-

ies were excluded from the study. Any clinical report with

minor side effects or adverse effects was also excluded.

Similarly, any interaction with conventional medicine

other than ergotism was excluded from the study.

Search result

The number of clinical cases, after an in-depth and

extensive review as well as the cases which met the

inclusion/exclusion criteria was found to be ten. These

cases are reported in detail in the forthcoming section of

literature review;

LITERATURE REVIEW

The ten cases  ltered as per eligibility criteria are

explained in detail as below. These cases are reported

here-in an ascending year wise order;

A. Clinical case reported in 2003

i. Overdose of Ergot preparation

A 36-years old man was diagnosed with HIV and lym-

phoma eight years ago and he was taking triple antivi-

ral therapy. He developed bilateral claudication and foot

cyanosis. History revealed that the patient was taking

2 mg of ergotamine tartrate due to migraine headache.

The overdose of ergot-alkaloid developed paresthesia,

and coolness in feet without pain. The left foot was

cyanotic and he was administered with heparin IV and

oral nifedipine. The symptoms resolved within one week

of the therapy, (Badwin and Ceraldi, 2003).

B. Clinical case reported in 2005

ii. Ergot toxicity in neonate

An infant born at 41 weeks gestation period was acci-

dentally administered with methylergonovine (I.M.)

instead of naloxone for respiratory depression. Soon

after administration he suffered from capillary re ll,

low oxygen saturation, his hand and feet became warm

and pink and after sometime his color became grey with

development of hypercarbia (partial pressure of carbon

dioxide). The infant was put on mechanical ventilation

and treated with nitroprusside infusion. The condition

recovered with 10 days of hospital treatment, (Bangh

et al., 2005).

C. Clinical case reported in 2009

iii. Ergotamine with caffeine

A 28-year old patient reported to hospital with pain in

both legs. Upon history it was revealed that the patient

used ergotamine tartrate (1 mg) with caffeine (100 mg)

for 3 days, due to a bi temporal headache a week ago.

Thus he developed the symptoms of severe leg pains,

especially below the ankle with cold and purple legs.

Hands were also cold but without any pain. The patient

was treated with I.V crystalline  uids and nitroprus-

side as well as oral nifedipine (every 8 h). Papaverine

was also administered as the patient had arterial spasm

whereas Enoxaparine was administered in order to

inhibit any thrombus formation, (Musikatavorn et al.,

2009).

D. Clinical case reported in 2009

iv. Ergotamine with Anti-HIV

A 31-year female patient on anti-HIV therapy used

ergotamine for migraine headache. Soon after she start

to complain about pain in lower extremity and her both

legs were cold particularly the left leg. In addition, a

palpable popliteal artery with peripheral pulses was also

observed. This condition is termed as Ergotism. The sign

and symptoms resolved gradually with the use of Nifedi-

pine (30 mg) and Enoxiparine was used as treatment for

Ergotism, (Cagatay et al., 2009).

E. Clinical case reported in 2010

v. Ergotamine used with clarithromycin (Antibiotic)

An eighteen year ole female patient reported with a pain

in emergency which started 2 days ago. The symptoms

she presented were; cool cyanotic lower extremities,

tender on palpitation, pain at rest, a thin iliac to pop-

liteal region and blood  ow with increased velocity. The

history revealed that the patient was using ergotamine

since 3 year for migraine whereas at the same time she

used clarithromycin for upper respiratory tract infection.

Heparin was administered in order to prevent possible

thrombotic complications and infusion of bupivacaine

was given. The symptoms resolved within a month,

(Demir et al., 2010).

358 A COMPREHENSIVE REVIEW OF ERGOT BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS

Raghad Al-Omari et al.

F. Clinical case reported in 2010

vi. Ergotamine interaction with anti-HIV drugs produces

paresthesia

A 29-year old patient using antiretroviral therapy for

HIV traveled Egypt and developed a severe migraine. A

local physician prescribed him ergotamine tartrate for

two weeks. Soon after its use, he developed sever pain

in left upper extremities, pale and cool wooden hand

with paresthesia, absent arterial pulse and axillary artery

stenosis, and he was facing dif culty in writing. Heparin

was started as therapy to inhibit any coagulation. Pros-

tacyclin IV and topical Nitroglycerine was used as ther-

apy. The symptoms resolved within six days, (Frohlich

et al., 2010).

G. Clinical case reported in 2012

vii. Neonate and methylergonovine

A female neonate, 10 minutes after her delivery, was

given methylergonovine instead of vitamin-K. after 30

minutes, she developed respiratory depression with cya-

nosis in extremities. Naloxone IM was administered to

recover the symptoms, (Sullivan et al., 2012).

H. Clinical cases reported in 2014

viii. Ergotamine with azithromycin (Antibiotic)

A 35-year old women reported with severe pain and pal-

lor in left foot, into emergency room. She was using

ergotamine since long time due to migraine, and in

addition she used azithromycin for four days (as she

was heavy smoker). Upon examination, vasospasm and

acute arterial embolism was observed due to interac-

tion between azithromycin and ergotamine. For treat-

ment purpose, ergotamine was stopped and Heparin was

administered for a week. The symptoms resolved gradu-

ally,( Adam et al., 2014).

I. Clinical cases reported in 2016

ix. Ergotamine use with caffeine

A 33-year old women presented with critical limb

ischemia, foot camping pain and a decreased walking

distance for 36 hours. Two days ago she used ergot-

amine tartrate (1 mg) and caffeine (100 mg) for migraine

headache. She was treated with vasodilator (PG-E1 I.V.),

pentoxifylline, heparin and sildena l for every 8 hours.

The patient recovered partially within 4 days, however

for full recovery she was further prescribed with aspirin,

sildena l and cilostazol, (Eduardo et al., 2016). Ergot-

amine overdose develops cerebral ergotism

A 49-year old patient with a history of HIV infection

treated with ritonavir used ergotamine (3g) for migraine.

He developed cerebral ergotism with an ischemic attack

after 20 minutes. The Cervical Doppler ultrasound

revealed a narrowing in both internal carotid arteries.

The treatment plan consist of; stopping ergotamine, and

changing the antiretroviral regimen, aspirin (325 mg)

was administered and bed rest suggested. The patient

became asymptomatic after a week. (Gaye-Saavedra

et al., 2016) The cases reported for Ergot are presented in

detail in Table 1, as below;

DISCUSSION

Ergot, with the most prominent member in group i.e.

Claviceps purpurea, grows on rye and other grasses. It is

considered as a poisonous plant that produce ergotism

in humans and sever toxicity in mammals. The improper

use or overdose of ergot may lead to various severe

complications, discussed as below.

Ergot develops psychological effects;

convulsive,

spasmodic or nervous ergotism i.e. chronic serious stage

of ergotism called “convulsive stage”, can occur due to

patchy damage of mid brain and cerebral hemisphere

which leads to degeneration in the posterior column of

spinal cord. The patient in such cases suffers from opistho-

tonos strong muscle spasm, tonic or clonic spasm of limbs,

battened tongue, dilated pupils, mania, dementia, glau-

coma, and delirium. In addition, the patient may develop

status epilepticus/multiple convulsions with less or lack

of sleep and  nally coma and death, (Lee and Coll, 2009).

Ergonovine evoke coronary artery spasm (CAS);

earlier, ergonovine (i.v.) was considered as a useful test

for CAD diagnosis however, recently it has been reported

that it may provoke variant angina in patients. It effects

vascular smooth muscles via alpha adrenergic agonist

activity and leads to vasoconstriction. Similarly, in CNS

it blocks the baroreceptors and prevents response of

re ex bradycardia. Thus it is considered an unsafe drug

in CAD patients because ergonovine may develop severe

hypertension, myocardial infarction, seizures, intracer-

ebral hemorrhage and death, (Curry and Pepine, 1977).

Acute coronary syndrome with myocardial bridg-

ing;

Ergotamine may induce vasoconstriction in coro-

nary, cerebral and pulmonary arteries and leads to

change in ECG pattern. A case of ergotamine overdose

was reported in 2003, for a 48-year aged women with

migraine headache, whereby she developed recurrent

chest pain with a complaint since last 10 days. The ECG

showed T-wave inversion and elevated ST-segment.

This shows that ergotamine may cause serious cardiac

adverse effects such as; arrhythmias, coronary vasos-

pasm and death, (Shimony et al., 2006).

Induces serotonin syndrome;

it can be a mild to

life-threatening syndrome. Dihydroergotamine, binds

to serotonin receptors in the dorsal horn of spinal

cord, result in serotonergic hyper-stimulation and may

BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS A COMPREHENSIVE REVIEW OF ERGOT 359

Raghad Al-Omari et al.

Table 1. Clinical cases reported for ergot

Case No. Age Gender Clinical manifestation Cause Treatment plan

1 36 Male

-Paresthesia and coldness of left foot

-Loss of sensation

Ergotamine tartrate for

migraine

-Heparin-IV

-Nifedipine orally

2 41 weeks Male infant

-Warm pink hands and feet

-Low oxygen saturation

-Hypercarbia-Oliguria

- Methylergonovine IM - Nitroprusside infusion

-Furosemide

3 28 Male

-Painful ,cold, and purple left legs especially below ankle

-Arteries spasm

-Ergotamine tartrate for bi

temporal headache

-Crystalloid  uids(IV)

-Sodium nitroprusside (IV)

-Nifedipine orally

-Papaverine for arteries spasm

-Enoxaparin to prevent thrombus formation

4 31 Female

-Pain, cold lower left extremity

-Palpable popliteal artery

-Ergotamine for migraine +D-

DI with anti-HIV

-Nifedipine

-Enoxaparin

5 18 Female

-Cool cyanotic lower extremities

-Tender on palpitation

-Thin arteries with increased blood  ow velocity

-Ergotamine for migraine

-Heparin

-Infusion of bupivacaine

6 29 Male

-Painful cold left upper extremities

-Pale wooden hands

Paresthesia

-Writing dif culties

Ergotamine tartrate for

migraine for 2 weeks + D-DI

with anti-HIV

-Heparin

-Prostacyclin IV

-Nitroglycerin(dermal application)

7 10 min Female

-Respiratory depression

-Cyanosis in her extremities

Unintentional use of

methylergonovine

Naloxone IM

8 35 Female

-Pain and pallor in the left foot

-Vasospasm and acute arterial embolism

Ergotamine for migraine Heparin for 7 days

9 33 Female

-Critical limbs ischemia

-Foot camping pain

-Decreased walking distance

Ergotamine tartrate for

migraine+

D-DI with ritonavir

- Prostaglandin E1(IV)

- Pentoxifylline

- heparin

- sildena l every(8h)

10 49 Male

-Cerebral ergotism

-Ischemia

Ergotamine overdose +D-DI

with ritonavir

325mg aspirin+ bed rest

360 A COMPREHENSIVE REVIEW OF ERGOT BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS

Raghad Al-Omari et al.

develop “convulsive ergotism” characterized with symp-

toms of behavioral changes and mental disturbances,

agitation, sweating, fever, and hallucination etc. (Eadie,

2003).

Ergotamine and its interaction with macrolide anti-

biotics;

the combination of ergotamine with erythromycin

is considered and reported as a dangerous combination.

The reason behind is; macrolides have hepatic circula-

tion with ergotamine whereby it causes severe vascular

spasm and transient renal ischemia. And this is due to

macrolide inhibition of cytochrome P-450 metabolism

leading to an increase serum ergotamine concentration.

(Ghali et al., 1993) A clinical case reported in 2010 about

a woman with sore throat and migraine. She was pre-

scribed with erythromycin (500 mg) and ergotamine (100

mg) and soon after the combined use of these drugs she

developed pain and paresthesia in both feet as well as

numbness in hands. (Tseng et al., 2010) Though ergot may

have unwanted side effects or adverse effects as observed

above, however it is also a well-known fact that ergot

possess potential advantages as discussed below.

Bromocriptine as treatment of AML:

acute amyloid

leukemia is a type of cancer that affect the blood and

bone marrow. Bromocriptine is a hydrogenated ergot

derivatives with dopamine agonist activity, a novel

therapy as Anti-AML, induce apoptosis for AML cells.

(Lara-Castillo et al., 2016).

Bromocriptine as a treatment of breast cancer:

there

is a role of dopamine in development of cancer whereas

bromocriptine via down regulation of prolactin, result in

decrease and suppress the proliferation of MCT-7 cells

and induce apoptosis. It also shows effectiveness in idi-

opathic granulomatous mastitis (IGM) associated with

hyperprolactinemia. (Majid et al., 2015).

Ergot still the best as compared to triptans:

ergot

is still a drug of choice in migraine. It has more good

activity as compared to triptans as a powerful vaso-

constrictor because it works longer and better for pro-

long attacks than some triptans. Ergotamine is still very

useful and is used in many countries to relief migraine

headache. Rectal ergotamine reported higher ef cacy as

compared to triptans with rectal ergotamine activity of

(73%), while triptan rectally was (63%). (Marcelo et al.,

2003).

Reduce postpartum hemorrhage:

Ergotamine IM/IV,

as prophylactic agent, shows a good reduction in post-

partum hemorrhage when coadminstered with analgesic

to reduce the pain. An optimum result predicted with

intramuscular injection of ergotamine oxytocin combi-

nation called (Syntometrine) at the end of second stage

of labor. (Liabsuetrakul, 2007).

Ergot toxicity is due to cytochrome P-450:

Ergot-

amine is metabolized via CYP enzyme and interaction

with enzyme inhibitors drugs can increase its level in the

body which will lead to toxicity such as in the case of

antiviral and antibacterial drugs. Grapefruit also has been

reported to increase the level of ergotamine, thus it shows

that toxicity as resulted may not be due to ergotamine

itself, but due to interaction with drugs inhibiting the

enzymes. (Badwin and Ceraldi, 2003) Current review con-

sist of clinical cases reported due to use of ergot. It was

observed that the misuse or use without proper medical

guidance may result a condition known as ergotism. The

major symptoms for ergotism includes; vasospasm, arte-

rial embolism, pain and coldness in feet especially the left

one, respiratory depression particularly in neonates, par-

esthesia and decreased walking distance. The treatment

applied for these conditions mostly included vasodilators

and Heparin and almost all of the cases observed were

due to ergotamine overdose or drug-drug interaction

with protease inhibitors. In few of the cases an interac-

tion among ergot alkaloids and other drugs, especially

antivirals and azithromycin, was observed when they are

administered together. Furthermore, in most of the cases

it affected elder people i.e. age of 30 or likewise, however

it can affect infants when it’s given by medical mistake.

Regarding gender it effects both female and male equally

however it was observed that patients with HIV disease

are more prone to ergotism due to severe interaction. Two

cases were observed where toxicity of ergot resulted due

to overdose of ergotamine.

Plants remains the well-known sources of treating

many ailments mostly working as antioxidant, antidia-

betic and antiglycation, (Ahmad et al., 2013 & 2014) and

the people mostly possesses sound knowledge regard-

ing the use and treatment of most of the plants (Ahmad

et al., 2017).

However, in most of the cases the poisoning or toxicity

cases are not known to common peoples. Herein, we men-

tioned ten poisoning cases for ergot where the general

and common symptoms observed in elder patients, due to

toxicity were; painful and coldness lower extremity espe-

cially the left foot, ischemia and purple legs whereas, the

symptoms of affected infants were; respiratory depression

and pinkish skin. In some cases the lab tests showed nor-

mal hemoglobin, white blood cells with a normal temper-

ature (37-37.7C) measured orally. The common treatment

used in such toxicity cases was; aspirin, low molecular

heparin given IV, and nifedipine orally.

CONCLUSION

Finally, ergot plant has medicinal uses as well as toxic

effects. Current review has found poisoning cases which

were mostly due to overdose, mistakenly administered

or interaction with anti-HIV drugs for ergot alkaloids.

Any disease condition using ergot with proper dose,

time and under sound medical supervision whereby the

BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS A COMPREHENSIVE REVIEW OF ERGOT 361

Raghad Al-Omari et al.

interaction with other drugs is taken under considera-

tion, may result a proper therapeutic outcome for ergot.

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362 A COMPREHENSIVE REVIEW OF ERGOT BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS