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Arthur R. Cushny: Pharmacological Laboratory, University College, London
Arthur R. Cushny: Pharmacological Laboratory, University College, London
ARTHUR R. CUSHNY
with very viscid yellowish black or black bile, and the interior
shows a number of red spots of the size of a pin’s head. The
urinary bladder and heart may also show these petechia. The
first three stomachs present nothing abnormal, but the fourth has
red hamorrhagic spots. The folds are thickened by the submu-
cous exudation of gelatinous fluid. The intestine is inflamed
around the openings of the bile ducts and the lower bowel may be
congested from straining.
The disease is of great economic importance, for in Nova
Scotia it is calculated it has been the cause of the loss of several
thousand head of stock, and in the East London district of South
Africa, Dixon2 states that it has rendered horse-breeding impossi-
ble as the mares contract the disease after two years or more
grazing. A number of investigations have been carried out as
to its causation more especially in Canada where its limitation
to the district immediately around the town of Pictou has been
especially remarked. It seems to be generally believed in this
neighborhood that the disease is of recent origin and it has been
associated popularly with the introduction of Senecio jacobaa or
ragwort (Stinking Willie) in the ballast of a ship from Scotland
about fif1y years ago. The disease certainly rose a few years
afterwards and occurred more particularly on the farms on which
the plant was prevalent. But investigations carried out in 1882
under government auspices failed to connect the disease with the
weed, and cirrhosis of the liver was therefore put on the list of
contagious diseases, animals affected with it were slaughtered
and the buildings in which they had been kept were disinfected.
The pathology of the disease was studied by Osler, Wyatt
Johnston and especially exhaustively by Adami,3 who states that
the main lesion is an extreme ondition of cirrhosis of the liver,
“the fibrous tissue not only being along the vessels between the
lobules, but extending in between the individual cells, the organ
being enlarged and having a smooth or more rarely a finely granu-
lar surface.” In the animals examined by him in Canada there
became ill after about eighteen days and died on the twenty-
eighth and thirtieth day of the experiment. The symptoms
were typical of Winton disease. Post mortem the peritoneal
cavity contained straw colored fluid and the gall-bladder was
full of dark fluid of the consistency of treacle. The connective
tissue of the liver was much increased especially around the
portal canal and smaller interlobular branches of the portal
vein; from these bands of finer fibres extended between the liver
cells sometimes isolating them completely. Areas of congested
portal capillaries were found irregularly in the sections. The
liver cells were distorted in shape and atrophied. The capsule
of the liver was thickened and trabecula passed from it into the
tissue.
In South Africa, Chase6 found that the inoculation of the bile,
blood and stomach contents of an animal dead of Molteno dis-
ease had no effect upon healthy cattle. After Gilruth’s results
in New Zealand appeared, the &necio burchellii of South Africa
fell under suspicion and Chase found that about 4 oz. of this
plant given on four successive days to an ox caused his death with
the usual symptoms and the typical post mortem appearances on
the fifth day. He does not state whether the plant was given
green or dry.
Dixon notes (1906) that the Senecio latifolius grows abundantly
in the area in which the hepatic cirrhosis is observed in the East
London district, South Africa.
In Canada Pethick7 carried out an admirably planned investi-
gation of the subject in 1903; sixteen head of cattle were kept in
a new stable and fed on hay from Pictou, while sixteen controls,
kept in an old stable in which several cattle had previously died
of the disease, received hay from Quebec, where the disease is
unknown. These sixteen controls remained healthy for twenty-
three months, though they were placed in contact with the dis-
eased animals and in some cases were inoculated with the blood
or ascitic fluid of animals that had died of the disease; when
‘bc. cit.
Department of Agriculture, Canada. Health of Animals: Special Report on
Pictou Cattle Disease, Ottawa, 1906.
ACTION OF SENECIO ALKALOIDS 535
SENECIFOLINE NITRATE
a
+ . .;
tube.
In the rat the symptoms were very similar, setting in with
loss of appetite (but with no diarrhoeic stool), after which increas-
ing weakness and deepening stupor and coma followed; the res-
piration became slow and finally ceased, the heart beating for
some minutes longer. The senecifoline nitrate was always in-
jected hypodermically, and great variation was found in the
quantity which proved fatal in different animals. Thus in one
rat 0.044 gm. per kg. proved fatal in three days, while others sur-
vived 0.135, 0.16 and even 0.22 gm. per kg. The interval between
the injection and death again showed great variation, some
rats dying within twenty-four hours of the injection, while others
survived five to six days. The amount of alkaloid injected did
not seem to bear any definite relation to the time of survival. In
rabbits the symptoms resembled those in cats, and the fatal
dose was not ascertained in them.
ACTION OF SENECIO ALKALOIDS 541
11. III. Ate some meat, but sits still, weak and apathetic; saliva-
tion, tears and snuffles.
14. III. Eats fairly well, but salivates a good deal in doing so.
No jaundice. Some conjunctivitis. Weight, 875 gms.
16. III. Did not eat yesterday or today. Very thin but fairly
active. Weight, 820 gms.
17. III. Did not eat meat but drank some milk. Weight, 790
gms.
18. III. Found dead in the morning. Weight, 770 gms.
26th (weight, 205 gms.), 29th (205 gms.), 32d (209 gms.), 35th
(195 gms.), and 40th day of the experiment and was then found to
weigh 168 gins., having lost about a third of its original weight.
The animal was now very weak, with labored respiration, and ate
very little. The coat was very rough, the hairs standing up
erect and separate. It was found dead on the morning of the
41st day of the experiment. The abdominal vessels were found
congested, and in the upper part of the small intestine small
haemorrhages, some of which were quite recent, were seen. The
stomach seemed normal and had no halmorrhages. The liver
weighed 8 gms., did not appear congested, and macroscopically
nothing abnormal was seen in it. Some hepatization and several
small abscesses were found in the lungs. Microscopically the
cells of the kidney tubules were found so swollen as to close the
lumen entirely. The liver showed large areas of necrosis and,
between these, groups of lobules in which the liver cells stained
badly, while the connective tissue was increased in amount and deli-
cate strands extended between the individual cells. Some ham-
orrbages had occurred in the liver and the whole organ was much
congested.
SENECIFOLIDINE NITRATE