NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
CALOTROPIS PROCERA AND CALOTROPIS GIGANTEA
69
Another segment of a rabbit's duodenum was held suspended in a bath and the
tincture was added and produced a marked increase in the tone of the intestine.
At B and C atropine solution was added, which failed to antogonise its action and
could not produce relaxation of the intestine. (Pl. X, Fig. j.)
The volume of a loop of an intestine (small) was taken with the help of an
oncometer. This remained practically unaffected under the effect of the drug.
(Pl. VIII, Fig. e).
Conclusion.—Tincture calotropis increases the tone of the intestines both in an
isolated segment and when intact. It causes a persistent contraction and decreases
peristaltic movements.
After paralysing the vagal nerve endings the tincture produces a marked in-
crease in tone, an action which atropine failed to antagonize. This shows that the
increase in tone is not brought about by stimulation of the vagal nerve endings, but
most probably by the action of the drug on the musculature of the intestines.
CIRCULATORY APPARATUS.—Blood Pressure.—The blood pressure was recorded
in the right carotid artery of a dog weighing 17 kgms. under chloretone anaesthesia.
Injection of tincture calotropis 0.25 to 0.4 c. c. in the dog produced a well-
marked and persistent rise of blood pressure varying from 70 m.m. to 140 m. m. of
mercury. The blood pressure remained high for about 4 to 10 minutes after which
it returned to its normal level, but never went below normal.
In an atropinized dog with both the vagi cut, the rise in blood pressure is more
marked. (PI. IX, Fig. h and PI. X, Fig. i.)
Heart.—The action of the drug on the heart was studied in a bitch weighing
11 kgms. under paraldehyde anaesthesia. The tracings of auricle and ventricle
were recorded with the help of a myocardio-graph and artificial respiration was
continued throughout the experiment. Tincture calotropis 0.3 c. c. injected into
the femoral vein produced a marked and persistent increase in the force of beats,
both of auricles and ventricles. The increased ventricular contractions were more
marked, (PI. XI, Fig. a).
The volume of the heart in an atropinized dog was recorded with the help of
cardio-meter. Tincture calotropis injected intravenously showed a marked
increase in the volume of the heart. (PI. XII, Fig. b).
70 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
Frogs. heart.—A rana frog was pithed, and perfused with heart in tact, through
the inferior vena cava with frog's Ringer solution. The tracings of the ventri-
cles were recorded with a heart lever.
Explanation of tracings is illustrated in PI. XIV, Fig. d. During systole the
lever makes an upstroke, and a down stroke during diastole.
A. Normal tracing of the frog's heart with Ringer's solution.
B. The heart was perfused with 0.25 per cent. solution of tincture calotropis in
frog Ringer's solution. This produced a slowing of the rhythm and an increase
in the amplitude.
C. The rhythm was slower still and amplitude increased toward systole.
The systolic contraction was increased and the dilatation during diastole was
greater.
D. The rhythm had become very slow and the diastole was much prolonged.
The toxic action of the drug has set in.
E. The toxic action was more pronounced. The action of the heart was very
slow, irregular and intermittent, heart block was present and ultimately the heart
stopped in systole.
Conclusion.—The action of calotropis on the mammalian heart is to increase the
force of the systolic contractions and to cause a persistent increase in the amplitude
of contraction and relaxation of auricles and systolic contraction of ventricles.
Thus it increases the output of the blood and raises the blood pressure. In the
frog's heart it produces an increase in the force of beats and marked slowing of the
rhythm. In toxic doses the heart becomes infrequent, irregular and intermittent.
The bronchioles were constricted and there was a marked fall in the blood
pressure under the effect of arecoline. Tincture calotropis 0. 4 c. c. injected intra-
venously produced an increase in the intrathoracic pressure with a rise of blood
pressure. This was due to the dilatation of the already constricted bronchioles
(under the effect of arecoline) and consequent increase of the volume of the lungs,
(PI. XIII, Fig. c.)
Uterus.—An isolated strip of rabbits' uterus was suspended in a bath con-
taining 100 c. c. of Tyrodes' solution at 37° C. Tinct ure calotropis 0. 1 c. c. added
into the bath at the arrow mark (PI. XV, Fig. e) produced a strong contraction
of the uterine strip with incomplete relaxation following. The stimulating action
occurs in all animals, whether pregnant or not, and the action is attributed to
direct effect upon musculature.
PLATE XIII.
(c) Showing the action of tincture calotropis on the
intrathoracic pressure of a dog weighing 11 kgms.
under chloretone anæsthesia. The bronchiols were
already constricted under the effect of arecoline.
PLATE XIV.
(d) Showing a frog's heart intact perfused with 0.25%
solution of tincture calotropis in Frogs' Ringer solution. During systole the lever makes an
upstroke and downstroke during diastole.
CALOTROPIS PROCERA AND CALOTROPIS GIGANTEA
71
TOXICOLOGY.
The milky juice of the plant is very acrid and is used for criminal purposes as
an abortifacient and as an infanticide in human beings (5). When applied on the
raw surface or over a freshly cut skin, it is absorbed and produces an acute
inflammatory swelling of the surrounding tissues and may produce general poison-
ing. The milky juice is sometimes used in mallacious poisoning of cattle.
The following experiments were undertaken to study the toxic action of the
drug :—
I.
Subject.—A healthy dog weighing 8 kgms.
2-30 P.M. pulse 92 per minute.
2-35 „ The following was given by stomach tube :—
Alcoholic saturated solution of Calotropis juice
.
.
.
.
40 m.
Aqua
2 oz.
2-40 P.M. The dog walks about, cries and is restless. Pulse 105 per minute.
2-50 „ Nausea, attempts at emesis and vomited twice. Pulse 105 per minute.
3-0 „ Vomiting continued. The animal arches the neck, lowers the head and
makes several attempts at emesis but only vomits a white foamy liquid. Pulse
90 per minute.
3-5 P.M. Passed semiliquid faeces. Pulse 83 per minute.
3-15 „ The animal looks depressed. Dribbling of saliva from the mouth.
Occasional attempts to vomit. Pulse 75 per minute.
3-25 P.M. The animal prefers to lie down and shows a great desire for water,
which however is quickly rejected on drinking. Pulse 68 per minute.
3-35 P.M. Dribbling of saliva continued and the animal remained lying for most
of the time. Pulse 65 per minute. The animal looks very much exhausted.
3-45 P.M. The dog keeps lying down and pulse 90 per minute.
4-15 „ The dog lost control over the hind limbs. Pulse very much accele-
rated, weak and almost imperceptible. The animal died after a few convulsive
movements at 4-18 P.M.
Post-mortem report—Acute gastro-enteritis with excoriations of the mucous
membranes.
Congestion and fatty degeneration of the liver.
72 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
II.
To another dog weighing 8 kgms. alcoholic saturated solution of the juice
15 m. in 4 dr. of distilled water was administered subcutaneously. The animal
showed the following symptoms :—
After half an hour's time the dog became restless, jumped and cried.
Respirations accelerated and laboured and profuse salivation from the mouth.
Pulse infrequent, later irregular and intermittent. The animal died an hour
and three minutes after the injection.
Post-mortem revealed an enteritis of the small intestines, fatty degeneration
of the liver and endo-carditis close to the apex in the left ventricle.
III.
The third dog weighing 9 kgms. was injected with 15 min. of alcoholic
saturated solution of the juice in 4 dr. of sterilized distilled water intra-peritoneally.
The animal uttered a few cries, walked round, dribbling of saliva from the mouth
and fell down. The pulse was weak and imperceptible and soon the heart stopped
beating. The animal took a few gasps and died 7 minutes after the injection.
IV.
Donkey male c. b. mouse-coloured 10 years.
The alcoholic saturated solution of the juice 1 dr. injected subcutaneously.
The animal showed the following symptoms:—
After 15 minutes there was perspiration all over the body particularly over
the scrotum, neck and ears.
Respiration accelerated. Later the animal became restless, bathed in per-
spiration, lost control over the hind limbs and fell down. The animal tried to get
up but could not do so and strikes its head against the ground. Respiration
infrequent, pulse weak and frequent, neighing frequently. The animal kept
lying down, respiration deep and occasional, pulse very weak and almost imper-
ceptible. The donkey died an hour and eight minutes after the injection.
Post-mortem. Liver highly congested, small intestines inflamed and kidneys
congested.
A dun horse 7 years old was admitted as an in-patient on the 4th June 1931.
The animal had a contusion of the off shoulder. The owner treated him by
applying calotropis juice over the shoulder after scarification, which produced
symptoms of poisoning. There developed a huge painful swelling on the shoulder,
PLATE XV.
(e) Showing the action of the drug on an isolated strip of a
rabbit's uterus. Note the marked contraction under
the effect of the drug.
(f) Showing the toxic action of the drug on a dog weighing 12 kgms. under chloretone anæsthesia. Note the sudden fall
in the blood pressure due to stoppage of the heart under the toxic effect of the drug.
CALOTROPIS PROCERA AND CAL0TROPIS G1GANTEA
73
breast„ forearm, neck and extending upto the head. The animal was restless and
could not bear weight on the off fore leg. The swollen parts pit on pressure and
the prescapular lymph gland was enlarged and swollen.
Respiration and pulse accelerated. Temperature ranged between 102° F. and
103.4° F.
The restlessness increased and the nervous symptoms developed, the animal
striking his head against the ground and remained lying most of the time. There
was trembling of the muscles and the animal was in a great distress. Died on the
8th June 1931.
To study the toxic action of the drug further, the respiration and blood
pressure were recorded in a dog. The alcoholic saturated solution of the juice
0.5 c. c. injected into the femoral vein first raised the blood pressure and then
brought it down to zero. The heart stopped beating and the respirations became
irregular and intermittent but they continued even after the heart stopped. (PI. XV,
Fig.f.)
The juice is very irritant and corrosive poison. It produces an acute gastro-
enteritis when given by mouth. When applied on a scarified skin over a large
area or over a raw surface, it produces an extensive, painful swelling. It acts
particularly on the small intestines, liver and heart after absorption. There is
a very little danger of its poisoning when applied on an indolent ulcer or over
chronic yoke and saddle galls. This is due to the fact that in indolent and long
standing ulcers a lot of fibrous tissue is formed, which checks its absorption and
thus the action remains localised to the part where it is applied.
Antidotes. In cases of poisoning by calotropis, demulcent and mucilaginous
drinks such as milk, rice gruel, etc., should be given and morphine and atropine
administered to allay the pain. If the poisoning is due to absorption from the
skin, the local treatment consists in applying cold water to the swollen part,
followed by Glycerine Belladonna or some such soothing preparations. If the
juice is sticking to the part, it should be well washed and the juice thoroughly
removed before any other application is made to the part. If there is a danger
of heart failure diffusible stimulants and heart tonics such as ether or camphor
are indicated.
Discussion. Tinctures of the drug were prepared both by percolation and
maceration, according to the directions of the British Pharmacopea, but those
prepared by maceration were found pharmacologically more active and a tincture
prepared in this way was used throughout the experiments in order to maintain
uniformity.
74 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
The alcoholic saturated solution of the juice, being highly poisonous, is never
used in ordinary experiments. This is used only when toxic action of the drug is
being studied; as the juice is the common cause of poisoning. The decoction has
been found to have slight pharmacological activity.
DOSES.
Tincture calotropis increases the tone of the stomach and intestines. Both
pharmacologically and in toxic doses the drug appears to have a selective action
on the liver and small intestines, whatever channel of administration is used.
The action on the intestines is not by way of the vagal nerve as it persits even
after paralysis of the vagal nerve endings with atropine, while the contraction
produced by tincture calotropis cannot be antagonized by atropine. The drug
appears to act on the musculature of the intestines.
It causes a slowing of the pulse and at the same time increases the force of the
heart and raises blood pressure.
Doses.—(per mouth) Root-bark powder.
Tincture of calotropis root-bark.
Subcutaneous injection in a
drachm of sterlised distilled
water.
Intravenous injection diluted
in 2 c. c. of distilled water.
Dog .
Horse and cattle .
Dog .
.
.
Horse and cattle .
Dog .
.
.
Dog .
2 to 8 gr.
1 to 3 dr.
5 to 15 m.
2 to 3 dr.
2 to 8 m.
2—5 m.
(The biggest doses of the tincture given subcutaneously produced localised
swelling.)
My thanks are due to W. Taylor, Esq., M.R.C.V.S., D.V.H., I.V.S.,
Principal, Punjab Veterinary College, Lahore, for his kind advice in connection
with this work.
REFERENCES.
1. Kirtikar, K. R. and Basu, B. D. Indian Medicinal Plants, Part 2.
2. G. Watt. Dictionary of the Economic Products of India, 1889. Vol 2.
3. Warden. Pharm. Journal Aug. 22nd, 1885.
4. Hill, E. G., and Sarkar, A. R. Journal of Chemical Society. (T. 1915, pp. 1437—1442).
5. J. P. Modi. Text-book of Medical Jurisprudence and Toxicology.
PRELIMINARY NOTE ON THE USE OF GOAT TISSUE VACCINE
ALONE FOR THE CONTROL OF OUTBREAKS OF RINDERPEST.
BY
P. J. KERR, I.V.S.,
Director, Civil Veterinary Department, Bengal
AND
M. B. MENON,
Veterinary Investigation Officer, Bengal.
(Received for publication on the 5th February 1934.)
INTRODUCTION BY P. J. KERR, I.V.S.
A brief introduction is necessary to this note on the use of goat tissue vaccine
for the control of outbreaks of rinderpest. On the advice of Dr. Edwards, Late
Director, Imperial Institute of Veterinary Research, Muktesar, goat virus has been
used in Bengal for immunisation of cattle by the Serum Simultaneous method since
1929. The behaviour of the controls used in these operations led us to believe that
goat virus alone might possibly be used with safety. Experiments on a small scale
were carried out to demonstrate this point, with most encouraging results, but had
to be closed down for want of funds and staff.
It was not known to me that Menon had already experimented with goat virus
alone on a small scale in 1927-28. This work was referred to by Major Stirling in
his report, 1932. In the meantime this work was taken up independently in the
Central Provinces by Major Stirling and in Mysore by Major Simpson. The results
of these officers amply demonstrated the safety of this method for plains cattle
which had not been subject to the risk of natural infection. It appeared to me
that the next step was to test the application of this method in the face of the
disease and also its safety for buffaloes, if full benefit of the method were to be
obtained.
In my opinion there are several objections to the wholesale immunisation of
cattle against rinderpest.
(1) An effective campaign on these lines is not possible with the veterinary staff
employed in India.
( 75 )
76 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
(2) The immunisation of all the scrub cattle in India is not desirable, were it
possible.
(3) It is only in face of an outbreak that all susceptible animals must be immu-
nised, as, good or bad, they can act as a source of infection and spread the disease.
(4) To apply virus alone inoculation in the absence of the disease is liable to
bring the method into disrepute, as ignorant owners are apt to opine that we have
introduced the disease for our own purposes should any serious reactions occur.
Before putting the goat virus alone method in face of the disease into practice on
an extended scale I went to Muktesar to discuss the various aspects of the matter
with Mr. Ware, the Director of the Institute, and Mr. Haddow the Serologist. I
learnt that the latter would shortly be prepared to issue goat tissue virus instead
of goat blood virus. For the purposes of this note I have adopted the name of goat
tissue vaccine for the former product, tissue vaccine for short.
On the appointment of Mr. Menon to Bengal as Veterinary Investigation Officer,
I decided to utilise his long experience and special knowledge of rinderpest work at
the Institute, and to concentrate on this problem of the use of virus alone to control
outbreaks of rinderpest.
GOAT VIRUS ALONE IN FACE OF THE DISEASE.
In the first instance goat blood virus was used. The seed virus being obtained
from Muktesar from which the virus for injection was freshly prepared in the field.
1774 inoculations were performed in this way with very encouraging
results:—
Cattle
.
.
.
.1765
Buffaloes . .
.
.
9
Reactions.
:
58=3.3%
:
4=44%
Deaths.
10=0.57%
Nil
In each case the outbreaks were controlled but in the course of this work it was
evident that this method would not be suitable for general application in place of
serum, if goat blood virus were used.
1. The technique of this method was beyond the ability of the average Veterinary
Assistant Surgeon to carry out singlehanded,
2. It necessitated the presence of a more experienced officer particularly with
regard to the interpretation of the reaction in the virus producing goats.
3. There was unavoidable delay of 3-4 days after arriving at the seat of outbreak
while the virus was under preparation,
GOAT TISSUE VACCINE FOR CONTROL OF OUTBREAKS OF RINDERPEST
77
4. There were difficulties in regard to sterilisation of the appliances and instru-
ments under field conditions.
It was also impracticable to maintain at headquarters a large stock of freshly
prepared blood virus to issue in place of serum.
GOAT TISSUE CACCINE IN FACE OF THE DISEASE.
We decided to continue the work using goat tissue vaccine. The advantages of
tissue vaccine are :—
1. It is easy to prepare at headquarters, preserve in sealed ampoules, and keep
in cold storage till required.
2. These ampoules are handy for packing and despatch by post.
3. The vaccine can be ready for injection one hour after receipt.
4. One goat produces 2,000 to 2,500 doses as compared with some 500 doses of
blood virus (Small Bengal goats).
5. It retains its potency in cold storage at 45° F for 30 days after preparation
and for 7 days at room temperature after removal from cold storage, under cold
weather conditions. (Maximum temperature 85°F.)
Several preliminary tests had to be carried out to ascertain the above facts as
to viability of the vaccine. The tests of the viability of the vaccine in cold storage
were carried out at the Bengal Veterinary College during October, 1933. Then
owing to lack of facilities to carry on this work there, the subsequent tests had to
be postponed until a temporary vaccine depot had been established elsewhere.
These tests were eventually carried out during the X'mas holidays at Barrackpore.
The spleens of the viability experimental animal were ampouled and issued to
selected officers in the district for the control of outbreaks of rinderpest, in place of
serum. From the establishment of the Barrackpore depot at the beginning of
December the regular preparation of vaccine was commenced.
In all some 10,764 animals while subject to natural infection have been
inoculated with most satisfactory results. The outbreaks were stopped. Buffaloes
were inoculated together with the cattle.
Cattle .
Buffaloes .
. 10,119
. 645
10764
reactions
„
.
167=1.6%
52=8%
219=2.0 %
deaths .
„
.
51=0.5 %
Nil.
51=0.47 %
78 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [IV, I.
The seats of outbreak were inspected by responsible officers 5 to 6 days, and 10
to 11 days after the inoculation to ascertain results. Animals were judged to be
reactors if they showed clinical symptoms of fever. We personally inspected as
many inoculated animals as possible and our observations tally for the most part
with those of other officers. Taking into considerations the large number of animals
inoculated, and the readiness of owners to report unfavourably upon any new
method of treatment we feel that the reporting is reliable. Any error being against
rather than for the new method.
Over 3,000 animals in controlled herds were done under our personal supervision
and subsequent inspection. In these no hearsay evidence was taken and the results
were more favourable than generally reported by other officers.
The selected localities for trial of this method were as widely separated in the
province as the incidence of disease permitted. We were also handicapped to some
extent, till X'mas, by our uncertainty as to the viability of virus after issue from
cold storage. It had been demonstrated potent up to 4 days, but this was not long
enough for its use in the more remote districts to reach which a parcel takes three
days by post.
The need for the careful application of this method in each district of the
province has been appreciated as the incidence of reaction is far from uniform, and
susceptibility may be higher in submontane tracts from the mixture of hill blood.
It was not possible to take the temperatures of all animals inoculated, and
some few were done while in the incubation period of the disease. These have,
however, been included in our main calculation of results, but subsequently
abstracted.
It was not possible either to take temperatures of all reactors reported. It
was expected that buffaloes would show a higher percentage of reactions and this
was found to be the case. In one instance all the male buffaloes inoculated showed
a strong reaction, while the females reacted normally. This must be put down to
the fact that all the males were put to work immediately after injection and kept
at work until they went sick. No fatality occurred. In order to modify the
reaction in buffaloes, if possible, the dose was reduced to ½ c.c. after this experience.
To test the immunity conferred by giving ½ c.c. doses, two buffaloes were
tested four weeks after immunisation by giving them 1 c.c. of fresh bull virus
obtained from a natural case of rinderpest. No reaction whatever was shown.
Similarly the immunity conferred by giving cattle 1 c.c. of tissue vaccine was tested
by giving 1 c.c. of fresh bull virus taken from the same animal. No reaction