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have recently demonstrated (Walker et al., 1977, Clinical
Science and Molecular Medicine, 53, 431-438) that the renal
tubular reabsorption of phosphate responds acutely to low-dose
infusions of bovine PTH in man. During these studies it was
apparent that changes in calcium reabsorption were small or
occasionally undetectable. We have therefore studied changes in
renal calcium reabsorption by using a combination of PTH
infusions with oral calcium loading.
A 12 h infusion of bovine PTH at a dose of 0.2 i.u. h-I kg-'
produced no discernible change in calcium excretion (Ca,) in a
fasting healthy individual. However, a small but significant fall
in Ca, was observed in six normal fasting subjects in response
to a 30 min infusion of 30 i.u. (=approximately 0.8 i.u. h-I kg-I).
In two normal fasting subjects an oral load of 20 mmol of
calcium including 5 pCi of 47Caresulted in a rapid rise in plasma
activity and a marked and sustained increase in C%. When the
experiment was repeated during an infusion of PTH at a dose of
0.2 i.u. h-' kg-I plasma activity increased as before while Ca,
remained unaltered. Repeated oral doses of calcium (30 mmol) in
a normal subject being infused with PTH at the rate of 0.4 i.u.
h-I kg-' produced a steady fall in fractional calcium excretion
and a simultaneous rise in plasma calcium during a 12 h study.
A similar response was observed in a patient with moderately
severe hyperparathyroidism after a single oral calcium load.
These results suggest that infusion of PTH at near-physiological doses has acute effects on the tubular reabsorption of
calcium. Such effects are not apparent in the fasting state where
presumably calcium reabsorption is operating at close to its
maximum rate.
9P
3 days in BGJ medium containing 15% heat-inactivated horse
serum. All P G were tested at doses of up to 3 x lo-' M. Of the
major PG, PGE, was the most potent, the minimum resorbing
doses being lo-' M. PGE, was about half as potent as PGE,. AU
other major prostaglandins (PGA,, PGD,, PGD, and PGF,,)
were devoid of activity at doses below lo-' M. The metabolites
of PGE, (15-keto-PGE2, 13,14-dihydro-PGE2 and 13,14dihydro-15-keto-PGE2) were also tested for bone-resorbing
activity. 13,14-Dihydro-PGE2 was five times less active than
PGE, itself, whilst the other metabolites were virtually devoid of
activity. The PGE, precursor, arachidonic acid, had no bone-resorbing activity even at doses up to 3 x lo-+ M.
This study confirms that the most potent bone-resorbing P G
so far tested is PGE,, and, furthermore, any metabolism of
PGE, leads to a marked decrease in activity. Independent
observations show that PGI, (prostacyclin) only slightly
elevates cyclic AMP levels in osteogenic sarcoma cells, which
suggests that the unstable prostanoids (PG endoperoxides,
thromboxane A, or PGI,) are unlikely to play an important role
in bone resorption under physiological or pathological conditions.
30. EFFECT O F INTRAVENOUS GLUCOSE AND
AMINO ACID SOLUTIONS ON AMINO ACID
DYNAMICS IN PATIENTS IMMEDIATELY AFTER
SEVERE SURGICAL STRESS
S . J. D. O'KEEFE', L. L. MOLDAWER,
R. M. SALAHand G. L.
BLACKBURN
NutritionlMetabolic Laboratory, New England Deaconess
Hospital, Harvard Medical School, Boston, Massachusetts,
USA.
Loss of body nitrogen following after stress is well documented.
This may be reduced by infusion of either glucose with insulin or
amino acid solutions alone, so-called protein-sparing therapies.
Eight well-nourished patients over the age of 45 years were
studied after major elective abdominal surgery. Amino acid
dynamics in uiuo were traced by our method of constant
infusion of ~-[l-'~Clleucine
(1974, Lancet, ii, 1035). The study
was begun 12 h after surgery once haemodynamic stability was
established. For the initial 10 h a 0.45% sodium chloride solution (NS) was infused at 90 mllh followed by 10 h of either
(group A: n = 5) a 5% amino acid solution (AA) or (group B:
n = 3) a 10% glucose solution containing 10 units of insulin11
(GI). Rate of incorporation of leucine into albumin (Alb.1.R.)
and globulin (Glob.1.R.) was measured once plasma isotopic
steady state ha6 been achieved. Plasma proteins were separated
by standard acidlalcohol techniques. (Table 1 shows leucine
results.)
I Present address: Liver Unit, Kings College Hospital,
London.
29. STIMULATION
O F BONE RESORPTION BY
VARIOUS PROSTAGLANDINS IN TISSUE CULTURE
K.J. IBBOTSON,
D. ATKINSand T. J. MARTIN
Department of Chemical Pathology, University of Shefield
Medical School, Shefield
Bone resorption in tissue culture can be stimulated by a variety
of agents including parathyroid hormone, 1,25-dihydroxychole:alciferol and vitamin A..More recently it has been shown that
several prostaglandins (PG) have bone-resorbing activity, and
that PGE, is the most potent of the P G types tested. Other evidence suggests that a PG (possibly PGE,) may be involved in
the development of the hypercalcaemia associated with some
types of cancer. As part of a study of mechanisms of tumourinduced bone resorption, we have investigated in detail the
relative potencies of a variety of PG and P G metabolites as
bone-resorbing agents.
Bone resorption was assessed by the release of calcium from
whole calvaria obtained from 5-7 day-old mice and cultured for
TABLE1. Resultsf o r leucine
Mean values f SD are shown.
Dynamics
bmollh)
Incorporation
b m o l h-' g-I of N)
Flux
Synthesis
Breakdown
Oxidation
Intake
Alb.1.R.
3691
f1808
3307
f1756
3691
f1808
390
+59
0
NS
0
14.5
f11.4
AA
6492
f3240
5113
f2369
3688
f293 1
1379
f 1086
2805
f513
13.9
f13.4
2476
f1295
2203
f 1125
2476
f1295
273
f171
0
k 36.2
.01
1741
2780
1584
f710
1741
f780
157
+70
0
0
3.7
f0.6
Glob.1.R.
A
NS
28.6
f13.5
B
GI
*P=
(0.005
56.2