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SORBITOL (SIONON) FOR DIABETICS
1257 in such numbers as to be packed closely together in the manner Courrier pictures in his book. It is possible that copulation takes place in only some of the animals before hibernation, or that the spermatozoa perish; at all events, one can demonstrate spermatozoa in the uterus in only a proportion of the
animals. The hibernating bat appears to me to be a good object for the study of exogenous influence on the rupture of the follicle. Can one produce a rupture of the follicle by means of a change in temperature ? As far as I have been able to discover in zoological literature, this question has hitherto been answered in the negative. Benecke observed in the case of bats, kept during the winter at room temperature, simply an enlargement of the follicle, but no rupture. My observations were different. After the bats had been sleeping for a while in the cellar, they were brought into the laboratory where the temperature was 18°-20° C. The animals woke up at night and took After 14 days I was able to discover an some food. early pregnancy with a living fcetus ! This discovery was made on Dec. 23rd. The change in temperature had therefore sufficed, even in winter, to bring about a rupture of the follicle. The ovum had travelled into the uterus and was there fertilised by a spermatozoon. Rupture of the follicle was therefore influenced by the exogenous stimulus. It thus appears to me to have been proved, and this is clinically important, that external climatic influences may cause rupture of the follicle. Doubtless here also hormonic factorsi.e., the anterior pituitary lobe-play the decisive part, since I was also successful in bringing about the rupture of a follicle in a bat in midwinter by means of prolan. Here again the ovum wandered into the uterus, was fertilised and a living foetus resulted. The highly important sex hormone, the gonadotropic anterior pituitary lobe hormone-i.e., prolan-is therefore able to bring about follicular rupture in hibernating animals in winter, an occurrence which does not take place naturally until the spring. I conclude from these experiments that climatic influence on ovarian function is dependent on the
(2) The gonadotropic anterior pituitary lobe hormone-i.e., prolan-is capable of producing rupture of the follicle in bats during winter ; here also a
normal pregnancy with a living foetus is produced. (3) By means of folliculin and prolan we can produce in the bat during winter all the phases of the generative process ; oestral reaction of the vaginal mucous membrane, conversion of the enlarged follicle into a corpus luteum, hyperluteinisation, pregnancy.
SORBITOL (SIONON) FOR DIABETICS BY W. W. PAYNE, M.B. Lond. BIOCHEMIST TO THE HOSPITAL FOR SICK ORMOND-STREET
R. D.
CHILDREN, GREAT
LAWRENCE, M.D.Aberd., F.R.C.P.Lond.
JUNIOR PHYSICIAN IN CHARGE OF THE DIABETIC DEPARTMENT, KING’S COLLEGE HOSPITAL, LONDON ; AND
R. A.
MCCANCE, M.D., Ph.D. Camb., M.R.C.P. Lond.
ASSISTANT CHEMICAL PATHOLOGIST TO
KING’S COLLEGE HOSPITAL
SIONON is the trade name for D-sorbitol, CtH, (OH)6, polyhydric alcohol which is closely related to the hexoses. It does not reduce Fehling’s solution, nor does it yield an osazone. It hasbeen put on the market as a substitute for sugar in diabetes. The substance is a light white powder, easily soluble in warm water, and having a sufficiently pleasant sweet taste which is not destroyed by cooking. The effect of sionon on the blood-sugar has been studied on two cases of juvenile diabetes. Two methods have been used. In the first 25 g. of dextrose were given to the fasting subject and the a
TABLE I.
(CASE 1)
pituitary (anterior lobe). In further experiments the influence exercised by the follicular hormone (folliculin) as well as by the gonadotropic anterior pituitary lobe hormone (prolan) It was possible to on hibernating bats was tested. a means of folliculin cornification of the produce by cells such as in and of we find mice superficial layers rats during oestrus. Whether this cornification occurs physiologically in bats during the warm season I
cannot say. Circumstances did not allow me to continue the investigations in the spring. If prolan is injected into the bats, the enlarged follicle, already physiologically present, can be converted into a corpus luteum. More than this, I was able to produce, by. the introduction of large doses of prolan, a series of 4-6 lutein bodies in the ovary-i.e., the same ovary contained several corpora lutea. Although the ovary in winter contains only one, at most two, enlarged follicles, there were here 4-6 newly formed corpora lutea as a result of " hyperprolanisation." They appeared to be very well vascularised and must therefore be regarded as capable of functioning. SUMMARY
(1) The exogenous stimulus of warmth produces rupture of the follicle in bats during winter. The ovum wanders through the tube into the uterus and is there fertilised by a spermatozoon. A normal pregnancy occurs with a living foetus.
blood-sugar estimated at half-hour intervals for three hours. A similar quantity of sorbitol was given under similar conditions a few days later. Figs. 1 and 2 and Table I. show these results. The rise in the blood-sugar after sorbitol is slight compared with that of dextrose. TABLE II.
(CASE 3).-One Mild Diabetic Case
Glucose (45 g.). Blood-sugar. Before 0-100
Sionon (50 g.).
......
A
hr. after
1 11 2 hrs. 3
11
....
....
....
...
0.181 0-266 0-186
—
0-164 -
......
......
......
......
obtained with
0.184 0-178 0-153
a mild elderly rise in the slight reducing value of the blood was obtained, but much less than with glucose (Table II.). This slight rise is not understood. In the second method sorbitol was added to the diet and the change in the blood-sugar was examined.
A similar result
diabetic, in whom
was
a
z3
1258 In Case 1 25 g. and in Case 2 40 g. a day given. Examination of Table III. shows that there was only a slight difference in the general level of the blood-sugar. In both cases, however, this was in an upward direction, so it may be concluded that there is a small effect on the bloodwere
sugar level. The urinary acetone excretion as shown by Rothera’s test was also noted in order to see if there was any antiketogenic action. The differences were not marked, but again c;, in both cases less acetone was passed when c: sorbitol was being given. An examination of the acetone excretion in Table I. shows a similar result, especially in Case 1 ; here the fasting acetonuria is practically abolished by sorbitol. Thirdly, the immediate effect of sionon in relieving insulin hypoglycsemia was observed. In Table IV., both from the blood-sugar figures and the feelings of the patients, it is clear that sionon had no effect, whereas glucose produced a quick
change. most important and to increase the glycogen in the liver of starved rats. Glucose and all other available carbohydrate quickly does so, as is shown in Table V.
And
fourthly,
and
probably
decisive, sionon failed
TABLE
III.—Effect of Adding
Sionon to the Diet
sionon is not absorbed and acts as a foreign sugar in the intestine. To our mind this limits the amount, of sionon that can safely be used to be a maximum of 50 g. a day, and this should be given in divided doses.
TABLE V.-Liver
Glycogen !irt Rats
three hours
after
2 g. Sionon or Glucose Average from four rats.
CASE 1
Sionon. Glucose. Tap water. 0-114 per cent... 0-124 per cent... 0-980 per cent.
CONCLUSIONS
Sionon (D-sorbitol) can safely be used as a sweetening agent for diabetics as it does not enter directly into carbohydrate metabolism. The probability of intestinal irritation must limit the dose. Also its price makes it a luxury, which can usually be more economically provided by the use of ordinary sugars and slightly more insulin.
Clinical
and
Laboratory Notes
A NOTE ON THE USE OF
ACETYLCHOLINE IN PARALYTIC ILEUS BY KENNETH HERITAGE,
M.S. Lond., F.R.C.S. Eng.
SURGICAL FIRST ASSISTANT, LONDON HOSPITAL
My experience of the use of acetylcholine egtenda the last three years, during which period I have used it in about 20 cases. My attention was first attracted to its use by.the papers of Lawrence Abel and Wolf and I have since had opportunity of confirming their findings, particularly in so far as they apply to paralytic ileus associated with and due to general or local peritonitis. The immediately post-operative or " active " ileus is best treated by rest and morphia, but at varying intervals after the second day a very grave condition is liable to arise, characterised by constant abdominal pain, vomiting, progressive abdominal distension, rising pulse-rate, and collapse. An enema as a rule gives a " coloured result only or is retained, and in the absence of relief to a stomach-tube the patient’s condition gets rapidly worse and the imminence of a fatal outcome is apparent. My practice is to giveover
TABLE
IV.-Effect of Sionon
Case 1. B.-s. per cent..... 0-067 20 g. sionon given. B.-s. hr. later.. 0-058
Hypoglyemmia Remarks.
Case 2. ....
....
0-079
0-077
....
Symptoms.
....
Symptoms persist.
20 g.
glucose given. .. 0-125 B.-s.i hr. later
in
....
0-174
....
Symptoms gone.
B.-s. = Blood-sugar.
The condition of the small intestine in the rats fed with sionon was interesting. Intense hyperaemia and dilatation was present, which from our experience with other similar " sugars " makes it probable that
"
animals. The hibernating bat appears to me to be a good object for the study of exogenous influence on the rupture of the follicle. Can one produce a rupture of the follicle by means of a change in temperature ? As far as I have been able to discover in zoological literature, this question has hitherto been answered in the negative. Benecke observed in the case of bats, kept during the winter at room temperature, simply an enlargement of the follicle, but no rupture. My observations were different. After the bats had been sleeping for a while in the cellar, they were brought into the laboratory where the temperature was 18°-20° C. The animals woke up at night and took After 14 days I was able to discover an some food. early pregnancy with a living fcetus ! This discovery was made on Dec. 23rd. The change in temperature had therefore sufficed, even in winter, to bring about a rupture of the follicle. The ovum had travelled into the uterus and was there fertilised by a spermatozoon. Rupture of the follicle was therefore influenced by the exogenous stimulus. It thus appears to me to have been proved, and this is clinically important, that external climatic influences may cause rupture of the follicle. Doubtless here also hormonic factorsi.e., the anterior pituitary lobe-play the decisive part, since I was also successful in bringing about the rupture of a follicle in a bat in midwinter by means of prolan. Here again the ovum wandered into the uterus, was fertilised and a living foetus resulted. The highly important sex hormone, the gonadotropic anterior pituitary lobe hormone-i.e., prolan-is therefore able to bring about follicular rupture in hibernating animals in winter, an occurrence which does not take place naturally until the spring. I conclude from these experiments that climatic influence on ovarian function is dependent on the
(2) The gonadotropic anterior pituitary lobe hormone-i.e., prolan-is capable of producing rupture of the follicle in bats during winter ; here also a
normal pregnancy with a living foetus is produced. (3) By means of folliculin and prolan we can produce in the bat during winter all the phases of the generative process ; oestral reaction of the vaginal mucous membrane, conversion of the enlarged follicle into a corpus luteum, hyperluteinisation, pregnancy.
SORBITOL (SIONON) FOR DIABETICS BY W. W. PAYNE, M.B. Lond. BIOCHEMIST TO THE HOSPITAL FOR SICK ORMOND-STREET
R. D.
CHILDREN, GREAT
LAWRENCE, M.D.Aberd., F.R.C.P.Lond.
JUNIOR PHYSICIAN IN CHARGE OF THE DIABETIC DEPARTMENT, KING’S COLLEGE HOSPITAL, LONDON ; AND
R. A.
MCCANCE, M.D., Ph.D. Camb., M.R.C.P. Lond.
ASSISTANT CHEMICAL PATHOLOGIST TO
KING’S COLLEGE HOSPITAL
SIONON is the trade name for D-sorbitol, CtH, (OH)6, polyhydric alcohol which is closely related to the hexoses. It does not reduce Fehling’s solution, nor does it yield an osazone. It hasbeen put on the market as a substitute for sugar in diabetes. The substance is a light white powder, easily soluble in warm water, and having a sufficiently pleasant sweet taste which is not destroyed by cooking. The effect of sionon on the blood-sugar has been studied on two cases of juvenile diabetes. Two methods have been used. In the first 25 g. of dextrose were given to the fasting subject and the a
TABLE I.
(CASE 1)
pituitary (anterior lobe). In further experiments the influence exercised by the follicular hormone (folliculin) as well as by the gonadotropic anterior pituitary lobe hormone (prolan) It was possible to on hibernating bats was tested. a means of folliculin cornification of the produce by cells such as in and of we find mice superficial layers rats during oestrus. Whether this cornification occurs physiologically in bats during the warm season I
cannot say. Circumstances did not allow me to continue the investigations in the spring. If prolan is injected into the bats, the enlarged follicle, already physiologically present, can be converted into a corpus luteum. More than this, I was able to produce, by. the introduction of large doses of prolan, a series of 4-6 lutein bodies in the ovary-i.e., the same ovary contained several corpora lutea. Although the ovary in winter contains only one, at most two, enlarged follicles, there were here 4-6 newly formed corpora lutea as a result of " hyperprolanisation." They appeared to be very well vascularised and must therefore be regarded as capable of functioning. SUMMARY
(1) The exogenous stimulus of warmth produces rupture of the follicle in bats during winter. The ovum wanders through the tube into the uterus and is there fertilised by a spermatozoon. A normal pregnancy occurs with a living foetus.
blood-sugar estimated at half-hour intervals for three hours. A similar quantity of sorbitol was given under similar conditions a few days later. Figs. 1 and 2 and Table I. show these results. The rise in the blood-sugar after sorbitol is slight compared with that of dextrose. TABLE II.
(CASE 3).-One Mild Diabetic Case
Glucose (45 g.). Blood-sugar. Before 0-100
Sionon (50 g.).
......
A
hr. after
1 11 2 hrs. 3
11
....
....
....
...
0.181 0-266 0-186
—
0-164 -
......
......
......
......
obtained with
0.184 0-178 0-153
a mild elderly rise in the slight reducing value of the blood was obtained, but much less than with glucose (Table II.). This slight rise is not understood. In the second method sorbitol was added to the diet and the change in the blood-sugar was examined.
A similar result
diabetic, in whom
was
a
z3
1258 In Case 1 25 g. and in Case 2 40 g. a day given. Examination of Table III. shows that there was only a slight difference in the general level of the blood-sugar. In both cases, however, this was in an upward direction, so it may be concluded that there is a small effect on the bloodwere
sugar level. The urinary acetone excretion as shown by Rothera’s test was also noted in order to see if there was any antiketogenic action. The differences were not marked, but again c;, in both cases less acetone was passed when c: sorbitol was being given. An examination of the acetone excretion in Table I. shows a similar result, especially in Case 1 ; here the fasting acetonuria is practically abolished by sorbitol. Thirdly, the immediate effect of sionon in relieving insulin hypoglycsemia was observed. In Table IV., both from the blood-sugar figures and the feelings of the patients, it is clear that sionon had no effect, whereas glucose produced a quick
change. most important and to increase the glycogen in the liver of starved rats. Glucose and all other available carbohydrate quickly does so, as is shown in Table V.
And
fourthly,
and
probably
decisive, sionon failed
TABLE
III.—Effect of Adding
Sionon to the Diet
sionon is not absorbed and acts as a foreign sugar in the intestine. To our mind this limits the amount, of sionon that can safely be used to be a maximum of 50 g. a day, and this should be given in divided doses.
TABLE V.-Liver
Glycogen !irt Rats
three hours
after
2 g. Sionon or Glucose Average from four rats.
CASE 1
Sionon. Glucose. Tap water. 0-114 per cent... 0-124 per cent... 0-980 per cent.
CONCLUSIONS
Sionon (D-sorbitol) can safely be used as a sweetening agent for diabetics as it does not enter directly into carbohydrate metabolism. The probability of intestinal irritation must limit the dose. Also its price makes it a luxury, which can usually be more economically provided by the use of ordinary sugars and slightly more insulin.
Clinical
and
Laboratory Notes
A NOTE ON THE USE OF
ACETYLCHOLINE IN PARALYTIC ILEUS BY KENNETH HERITAGE,
M.S. Lond., F.R.C.S. Eng.
SURGICAL FIRST ASSISTANT, LONDON HOSPITAL
My experience of the use of acetylcholine egtenda the last three years, during which period I have used it in about 20 cases. My attention was first attracted to its use by.the papers of Lawrence Abel and Wolf and I have since had opportunity of confirming their findings, particularly in so far as they apply to paralytic ileus associated with and due to general or local peritonitis. The immediately post-operative or " active " ileus is best treated by rest and morphia, but at varying intervals after the second day a very grave condition is liable to arise, characterised by constant abdominal pain, vomiting, progressive abdominal distension, rising pulse-rate, and collapse. An enema as a rule gives a " coloured result only or is retained, and in the absence of relief to a stomach-tube the patient’s condition gets rapidly worse and the imminence of a fatal outcome is apparent. My practice is to giveover
TABLE
IV.-Effect of Sionon
Case 1. B.-s. per cent..... 0-067 20 g. sionon given. B.-s. hr. later.. 0-058
Hypoglyemmia Remarks.
Case 2. ....
....
0-079
0-077
....
Symptoms.
....
Symptoms persist.
20 g.
glucose given. .. 0-125 B.-s.i hr. later
in
....
0-174
....
Symptoms gone.
B.-s. = Blood-sugar.
The condition of the small intestine in the rats fed with sionon was interesting. Intense hyperaemia and dilatation was present, which from our experience with other similar " sugars " makes it probable that
"