32
REPORT OF THE IMPERIAL INSTITUTE OF VETERINARY RESEARCH,.
with the length of postponement: with a four-day postponement, the serum control is
apt to be too late to prevent fatality; with the three-day postponement, the reaction is
still too severe; with the two-day and one-day delays there is a well observed and conti-
nued pyrexia, much better developed with the two-day than with the one-day delay
(Chart V). Bleeding is timed to start 7 days after the commencement of apyrexia; that
is, from the 20th to 30th day after the virus inoculation, according to the severity of
pyrexia. The animals are then bled three times on alternate days, at the rates of 6, 7,
and 8 c.c. respectively per lb. body weight; next, they are rested for 9 or 10 days, and
the bleedings repeated. The buffaloes are subjected to four series of bleedings in this
way in all, and then discontinued. Meanwhile, the methods of feeding the animals while
they are drained in this manner are subjected to careful observation, so that they retain
good body condition. While " fat" condition has not been found to be a quality that
improves animals as serum producers, it is distinctly advantageous to maintain the body
weight without marked decrease throughout the bleeding period. In the system of feeding
the producers are fed two concentrate rations, one of a mixture of rape-cake, gram, and
bran, calculated to replace protein loss, and given at a fixed rate according to body
weight throughout the bleeding period, and one composed of a mixture of barley and
maize to provide " energy," which is varied according to the cooling effects of the
weather at the time.
Action of certain inorganic salts in increasing the antibody content of serum. Work
upon this problem was initiated after the appearance of an article by MADSEN (Journal of
State Medicine, 1923. Feb. Vol. 31, No. 2, pp. 51-73) reporting the experience gained
over some years in the State Serum Institute, Copenhagen, upon the effects of repeated
injections of minute quantities of certain inorganic salts into the blood stream in stimu-
lating the " secretion" of specific antibodies. From the charts published it would
appear that the potency of anti-diphtheria serum, obtained from horses, undergoes a
gradual increase, when they are subjected after a hyperimmunizing dose of toxin to
daily intravenous injection of manganese chloride, and that this increase is similar in
nature to that which follows the injection of the specific antigen in that it attains a
maximum on the 8th or 9th days after the commencement of salt injections and then
declines. Further, the maximum " secretion " following upon the administration of a
single dose of the inorganic salt would seem to be demonstrable in the blood serum
withdrawn two hours after injection, declining in the serum withdrawn later. More-
over, tables are published indicating a very neat relationship between efficacy in stimu-
lating secretion and position of the various kations in the different groups of the
Periodic System of classification of chemical elements, when a large range of these elements
are tested in regard to their power of stimulating the production of antibodies in the form
of specific agglutinins in rabbits. Following upon the economic advantages claimed
to have been achieved by the manganese treatment of horses destined for the production
of anti-diphtheria serum at the Copenhagen institute, steps were taken at once to exploit
the possibilities of applying the system to the production of anti-rinderpest serum. In-
vestigations have been carried out almost continuously at Muktesar upon the subject,
and the results now available so far as they can be interpreted in their present state show
that while it has not greatly succeeded, the system, or some modification of the system
described by MADSEN, is capable sometimes of yielding encouraging results when applied
in experimental conditions.
The earlier investigations included tests upon hill bulls or buffaloes subjected to the
routine procedure of " hyperimmunization " then followed, and treated according to
MADSEN'S indications with uniform daily dosages of gram-molecular solutions of the
chlorides of certain kations (manganese, zinc, magnesium, barium, copper), and also
pilocarpine. Although the stimulation produced was not very marked or consistent in
its occurrence in the various experiments, the effects produced by zinc and magnesium
seemed at least to rival those produced by manganese, as is evidenced by the following
curves (Chart VI) showing the test results upon sera from " hyperimmunized " bulls
treated with daily injections of zinc and magnesium (in Expts. Nos. 1 and 2,
respectively).
Trials with beryllium chloride, which had been indicated as having the highest efficacy
in MADSEN'S tables, proved that this salt was too toxic after intravenous injection to
repeat with it satisfactorily upon cattle the process of non-specific stimulation; the ani-
mals succumbed in large proportion with lesions of myocarditis.
After a single intravenous injection of a salt the result usually seen was that the potency
of the serum obtained increased towards the second hour after injection and then declined,
but it also seemed from control tests that an increase in antibody content could sometimes
be demonstrated as the result of the repeated bleeding alone.