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The effect of 15(R)-15-methyl prostaglandin E2 on basal and meal stimulated serum gastrin in duodenal ulcer patients
PROSTAGLANDINS
THE
EFFECT
MEAL
OF
15(R)-1%METHYL
STIMULATED
GUIDO Div.
N. J.
SERUM
TYTGAT,
Amsterdom,
The
GASTRIN
K.
Gostroenterology,
PROSTAGLANDIN IN
E2 ON
DUODENAL
BASAL
ULCER
AND
PATIENTS.
HUIBREGTSE
Univ.
Amsterdam,
Wilhelmino
Gosthuis,
Netherlands.
ABSTRACT Basol
ond meol-stimulated
serum gastrin
100 mcg 15(R)-&methyl
prostaglandin
measured
with
in 40 patients
active
ond at the end of a 4 week placebo
(PI).
study.
Neither
release rote
wos there
by PG
(68.4%
be exploined
a blunting
PG
compared
by changes
did
prior
with
disease
observed.
to 33.3%
PI)
in bosal or meol-stimuloted
the
serum gastrin
The enhanced
during
q i d or
throughout
meal-stimulated
of
form were
ot the start
100 mcg PG
not change
of the
intake
in encapsulated ulcer
period
levels
OS has been previously
during
or without
duodenal
treatment
Basol serum gostrin
with E2 (PG)
healing
con therefore
not
serum gostrin.
INTRODUCTION Orally
administered
prostaglandin to inhibit patients
duodenol
the serum gastrin
documented
attributed of
this
at least
study
with
active
trin
release
period
with
placebo
release
ulcer
level
inhibitory
was to extend as well
of gastrin
in
to a meal,
by measuring
at the beginning
100 mcg 15(R)-15-methyl
human volunteers it
on gastric
findings
15(S)-l5-methyl
E2 have been shown
Because of this
reduction
these
ulcer,
(l-3).
action
to this
E2,
prostaglandin
disease
in response
in part
duodenol
prostaglandin
I6 dimethyl
the postprondiol with
the well
15(R)-l5-methyl
E2 and 16,
has been suggested acid
in gostrin in a larger bosal
and in
depression
secretion release.
may be The
purpose
group of patients
and meal-stimulated
OS at the end of o 4 weeks prostaglandin
of that
E2 (PG)
gostreotment
q i d or
(PI).
METHODS Subiects Forty
patients
yrs) with
(32
active
moles,
duodenal
mean age 44.7, ulcer
SUPPLEMENT TO VOL. 21
were
and 8 females,
mean oge 45.4
studied.
53
PROSTAGLANDINS
Medications All
patients
PI.
PG
were
treated
was given
for
Basal and meal-stimulated Fasting lated
serum gastrin serum gastrin
60 min before test
was obtained was obtained
after
of 609
lipids
bread,
and 575
Statistical
The
14,
27 and 35.
iust
followed
prior
at -20
by intake
to the meal, a total
and was centrifuged
frozen
log butter,
which
259
corresponds
C until
cheese,
to 409
Meal-stimu-
Blood was obtained
of six
after The
IOOg minced 439
determi-
I h of
analysis.
protein,
of the
(min 0) and
Serum test
meal
beef
meat
carbohydrate,
calories.
methods
The fasting I.
100 mcg q i d or
was measured by radioimmunoassay.
and 2OOml of milk, 279
I,
I and 27.
of the meal for
to clot
The serum was kept
concentration
consisted
capsules
immediately
-6O),
the start
Blood was allowed
gastrin
at Day at Day
(100 mcg PG or PI),
at 30 min intervals sampling.
PG
serum gastrin
the meal (min
medication
nations.
28 days with
I hour before meals and at bedtime.
serum gastrin
meal-stimulated
ces from
min 0.
The
values
were
serum gastrin t-test
transformed values
to differences
were
was used to test
for
transformed differences
from
Day
to differenbetween
PG
and PI. RESULTS Fasting
Serum
The average
Gastrin fasting
at Day
I,
pg/ml.
Corresponding
27,
14,
100 2 43,
significant
86 t
average 30.
The I50
at Day
54
over
(p =
time
between
27 between
83 + 33 and 84 + 20
the
PG
PG
treated
pa?ients
There
were
and PI treated
patients
were
83 +
no statistically
group.
each treatment
group versus
At
Day
group
I,
the
a plateau from
were
PG
PG rise
at min 90.
but begin
min 0 reveal at min I20
no statistically
and PI treated
time
for
Day
has increasing
is reached
make an initial the two groups
There the
32,
the placebo%eated
of the differences
.06).
for
96 7
for
until
PI group
analysis
cal significance min
mean values
of the
(m + SD)
Gastrin
27 respectively.
values
for
between
Serum
I shows
I and Day ge values
values
values
85 + 35,
38 and 90 +_ 40 pg/ml.
differences
Meal-stimulated Figure
serum gastrin
20 and 35 were
borderline
(p =
significant
The avera-
to decline .06)
at min
statistiand at
differences
groups.
SUPPLEMENT TO VOL. 21
PROSTAGLANDINS
Figure I,
Average
PG or PI treated
meal stimulated patients.
SEM after
vals at Day
I were respectively
12.5,
10.0,
7.5,
11.6,
9.0,
Duodenal
6.9, Ulcer
8.3 6.0,
serum gastrin at Day
12.5,
I and Day 27 for
PG and PI for the various time inter10.2,
and at Day 27 16.2,
14.3, 12.0,
13.3, 14.1,
12.9, 12.8,
and 12.4, 13.4,
and
8.2.
healing
rate
68.4% of PG treated patients were endoscopically healed within .28 days as compared to 33.3% in the PI treated group (p = 0.028).
SUPPLEMENT TO VOL. 21
55
PROSTAGLANDINS
DISCUSSION Previous
studies
inhibit
(l-3)
Using
a larger
were
unable
group
group.
after
were
prior
was performed treatment study
at the start These
results
ulcer
which
were
the test
medication.
gastrin
during
less than
conclusion
from
of
this
in
the PG
using
study
and PI treatment
particularly
that
after
instead
study,
in design
such
duodenal
was infused
administration
the mean rise
of in serum
the meal was not significantly form of
the duodenal
prostaglandin
in basal or meal-stimulated
those
the latter
of active
meal which
the capsule
is that
with
with
by differences
inactive
which
27) of the
the discrepancy
test
serum gastrin
medication
of 60 min after in
period
15(R)-l&methyl
differences
also
when
we
detected
or PI test
in part, with
instead
hour
placebo
disease,
were
in meal-stimulated
a different
30
However,
the three
after
properties
with
the stomach,
ulcer
are at variance
at least
studied
into
duodenal
I) and at the end (Day Perhaps
analogues
differences
between
detected
number of patients
directly
No
of the PG
(Day
E2 methyl
in humans.
active
levels
et al (3).
may be explained,
as the smaller
rise
with
differences
by Peterson
prostaglandin
these findings.
administration
period.
obtained
of patients
serum gastrin
Neither
levels
that
serum gastrin
to confirm
the basal fasting
The
suggested
the postprandial
E2 cannot gastrin
the PG
ulcer
medication.
healing
be related
to
levels.
ACKNOWLEDGEMENTS The
generous
help of the
supply Upjohn
of 15(R)-1%methylprostaglandin Company,
Kalamazoo,
E2 and the
Michigan,
technical
is gratefully
acknowledged. LIST I)
OF
REFERENCES
Konturek, and A. given
2)
orally meal
Ippoliti,
A.F.,
acid
of
16,
J.I.
Peterson, of
Ulcer
56
W.,
M.
15(R)-l5-Methyl
Secretion,
Isenberg,
488,
Dig.
Feldman,
Dis.
Oleksy,
responses 70:
Maxal,
683,
E.
to pentagastrin
and
1976
and J.H.
Walsh.
E2 on meal-stimulated
in duodenal
Sito,
E2 analogues
ulcer
The gastric
patients.
1976
I.
Prostaglandin
serum gastrin
patients.
Y.
Prostaglandin
J.
prostaglandin
of gastric
and serum gastrin 70: -
Swierczek,
Gastroenterology
l6-Dimethyl
secretion
J.
of methylated
inhibition
in man.
Gastroenterology
3)
Kwiecien,
Comparison
in the
peptone effect
N.
S. J., Robert.
Taylor,
and Pancreatic Sci:
and M.
Bremer.
E2 on meal -stimulated 24: -
381,
Polypeptide
The
effect
Gastric
acid
in Duodenal
I979
SUPPLEMENT TO VOL. 21
THE
EFFECT
MEAL
OF
15(R)-1%METHYL
STIMULATED
GUIDO Div.
N. J.
SERUM
TYTGAT,
Amsterdom,
The
GASTRIN
K.
Gostroenterology,
PROSTAGLANDIN IN
E2 ON
DUODENAL
BASAL
ULCER
AND
PATIENTS.
HUIBREGTSE
Univ.
Amsterdam,
Wilhelmino
Gosthuis,
Netherlands.
ABSTRACT Basol
ond meol-stimulated
serum gastrin
100 mcg 15(R)-&methyl
prostaglandin
measured
with
in 40 patients
active
ond at the end of a 4 week placebo
(PI).
study.
Neither
release rote
wos there
by PG
(68.4%
be exploined
a blunting
PG
compared
by changes
did
prior
with
disease
observed.
to 33.3%
PI)
in bosal or meol-stimuloted
the
serum gastrin
The enhanced
during
q i d or
throughout
meal-stimulated
of
form were
ot the start
100 mcg PG
not change
of the
intake
in encapsulated ulcer
period
levels
OS has been previously
during
or without
duodenal
treatment
Basol serum gostrin
with E2 (PG)
healing
con therefore
not
serum gostrin.
INTRODUCTION Orally
administered
prostaglandin to inhibit patients
duodenol
the serum gastrin
documented
attributed of
this
at least
study
with
active
trin
release
period
with
placebo
release
ulcer
level
inhibitory
was to extend as well
of gastrin
in
to a meal,
by measuring
at the beginning
100 mcg 15(R)-15-methyl
human volunteers it
on gastric
findings
15(S)-l5-methyl
E2 have been shown
Because of this
reduction
these
ulcer,
(l-3).
action
to this
E2,
prostaglandin
disease
in response
in part
duodenol
prostaglandin
I6 dimethyl
the postprondiol with
the well
15(R)-l5-methyl
E2 and 16,
has been suggested acid
in gostrin in a larger bosal
and in
depression
secretion release.
may be The
purpose
group of patients
and meal-stimulated
OS at the end of o 4 weeks prostaglandin
of that
E2 (PG)
gostreotment
q i d or
(PI).
METHODS Subiects Forty
patients
yrs) with
(32
active
moles,
duodenal
mean age 44.7, ulcer
SUPPLEMENT TO VOL. 21
were
and 8 females,
mean oge 45.4
studied.
53
PROSTAGLANDINS
Medications All
patients
PI.
PG
were
treated
was given
for
Basal and meal-stimulated Fasting lated
serum gastrin serum gastrin
60 min before test
was obtained was obtained
after
of 609
lipids
bread,
and 575
Statistical
The
14,
27 and 35.
iust
followed
prior
at -20
by intake
to the meal, a total
and was centrifuged
frozen
log butter,
which
259
corresponds
C until
cheese,
to 409
Meal-stimu-
Blood was obtained
of six
after The
IOOg minced 439
determi-
I h of
analysis.
protein,
of the
(min 0) and
Serum test
meal
beef
meat
carbohydrate,
calories.
methods
The fasting I.
100 mcg q i d or
was measured by radioimmunoassay.
and 2OOml of milk, 279
I,
I and 27.
of the meal for
to clot
The serum was kept
concentration
consisted
capsules
immediately
-6O),
the start
Blood was allowed
gastrin
at Day at Day
(100 mcg PG or PI),
at 30 min intervals sampling.
PG
serum gastrin
the meal (min
medication
nations.
28 days with
I hour before meals and at bedtime.
serum gastrin
meal-stimulated
ces from
min 0.
The
values
were
serum gastrin t-test
transformed values
to differences
were
was used to test
for
transformed differences
from
Day
to differenbetween
PG
and PI. RESULTS Fasting
Serum
The average
Gastrin fasting
at Day
I,
pg/ml.
Corresponding
27,
14,
100 2 43,
significant
86 t
average 30.
The I50
at Day
54
over
(p =
time
between
27 between
83 + 33 and 84 + 20
the
PG
PG
treated
pa?ients
There
were
and PI treated
patients
were
83 +
no statistically
group.
each treatment
group versus
At
Day
group
I,
the
a plateau from
were
PG
PG rise
at min 90.
but begin
min 0 reveal at min I20
no statistically
and PI treated
time
for
Day
has increasing
is reached
make an initial the two groups
There the
32,
the placebo%eated
of the differences
.06).
for
96 7
for
until
PI group
analysis
cal significance min
mean values
of the
(m + SD)
Gastrin
27 respectively.
values
for
between
Serum
I shows
I and Day ge values
values
values
85 + 35,
38 and 90 +_ 40 pg/ml.
differences
Meal-stimulated Figure
serum gastrin
20 and 35 were
borderline
(p =
significant
The avera-
to decline .06)
at min
statistiand at
differences
groups.
SUPPLEMENT TO VOL. 21
PROSTAGLANDINS
Figure I,
Average
PG or PI treated
meal stimulated patients.
SEM after
vals at Day
I were respectively
12.5,
10.0,
7.5,
11.6,
9.0,
Duodenal
6.9, Ulcer
8.3 6.0,
serum gastrin at Day
12.5,
I and Day 27 for
PG and PI for the various time inter10.2,
and at Day 27 16.2,
14.3, 12.0,
13.3, 14.1,
12.9, 12.8,
and 12.4, 13.4,
and
8.2.
healing
rate
68.4% of PG treated patients were endoscopically healed within .28 days as compared to 33.3% in the PI treated group (p = 0.028).
SUPPLEMENT TO VOL. 21
55
PROSTAGLANDINS
DISCUSSION Previous
studies
inhibit
(l-3)
Using
a larger
were
unable
group
group.
after
were
prior
was performed treatment study
at the start These
results
ulcer
which
were
the test
medication.
gastrin
during
less than
conclusion
from
of
this
in
the PG
using
study
and PI treatment
particularly
that
after
instead
study,
in design
such
duodenal
was infused
administration
the mean rise
of in serum
the meal was not significantly form of
the duodenal
prostaglandin
in basal or meal-stimulated
those
the latter
of active
meal which
the capsule
is that
with
with
by differences
inactive
which
27) of the
the discrepancy
test
serum gastrin
medication
of 60 min after in
period
15(R)-l&methyl
differences
also
when
we
detected
or PI test
in part, with
instead
hour
placebo
disease,
were
in meal-stimulated
a different
30
However,
the three
after
properties
with
the stomach,
ulcer
are at variance
at least
studied
into
duodenal
I) and at the end (Day Perhaps
analogues
differences
between
detected
number of patients
directly
No
of the PG
(Day
E2 methyl
in humans.
active
levels
et al (3).
may be explained,
as the smaller
rise
with
differences
by Peterson
prostaglandin
these findings.
administration
period.
obtained
of patients
serum gastrin
Neither
levels
that
serum gastrin
to confirm
the basal fasting
The
suggested
the postprandial
E2 cannot gastrin
the PG
ulcer
medication.
healing
be related
to
levels.
ACKNOWLEDGEMENTS The
generous
help of the
supply Upjohn
of 15(R)-1%methylprostaglandin Company,
Kalamazoo,
E2 and the
Michigan,
technical
is gratefully
acknowledged. LIST I)
OF
REFERENCES
Konturek, and A. given
2)
orally meal
Ippoliti,
A.F.,
acid
of
16,
J.I.
Peterson, of
Ulcer
56
W.,
M.
15(R)-l5-Methyl
Secretion,
Isenberg,
488,
Dig.
Feldman,
Dis.
Oleksy,
responses 70:
Maxal,
683,
E.
to pentagastrin
and
1976
and J.H.
Walsh.
E2 on meal-stimulated
in duodenal
Sito,
E2 analogues
ulcer
The gastric
patients.
1976
I.
Prostaglandin
serum gastrin
patients.
Y.
Prostaglandin
J.
prostaglandin
of gastric
and serum gastrin 70: -
Swierczek,
Gastroenterology
l6-Dimethyl
secretion
J.
of methylated
inhibition
in man.
Gastroenterology
3)
Kwiecien,
Comparison
in the
peptone effect
N.
S. J., Robert.
Taylor,
and Pancreatic Sci:
and M.
Bremer.
E2 on meal -stimulated 24: -
381,
Polypeptide
The
effect
Gastric
acid
in Duodenal
I979
SUPPLEMENT TO VOL. 21