Download Human Pepsins: Partial Amino-Acid Composition and N

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93 A RANWMISED CONROLLED TRIAL OF ELEMENTAL DIET
VERSUS PREDNISOLONE IN TREA'IME OF NEW AND RECURRENT
CROHN'S DISEASE
do
.*-
do
JB m,"
JJ PAYNE-JAMES;' KR PALMEX,"PJ KW;'
.I_
ML CLARK,
IUG FARTHING, JJ MISIEWIW and DBA SILK (;:' introduced)
Departments of Gastroenterology, St Bartholomew's
Hospital, London, Central Middlesex Hospital, London
and Western General Infirmary,Minburgh
Traditional medical treatment of Crohn's disease (CD)
consists of corticosteroid therapy. Elemental diet (ED)
has been shown to be equally effective as corticosteroids
for inducing remission in new presentations of CD. This
may be due to improved nutritional intake with ED. The
efficacy of ED in relapses of CD has not been tested.
We have randomised 30 adults (18 new (N), 12 recurrent
disease (R)) according to nutritional and disease status
to receive ED (Vivonex TEN) 2 l/day for 28 days, n=16) or
prednisolone (P, 0.75 mg/kg/day for 2 weeks with subsequent dose reduction, n=14) to assess (i) practicality
of ED as primary treatment (ii) the efficacy of ED in N
and R CD and (iii) any differences in protein energy
intake with ED or P.
-isease activity index (DAI), ESR, albumin (Alb) and Hb
were assessed at entry and weekly for 4 weeks. Inspite
of hospitalisation 7 patients (3 N, 4 R) were unable to
tolerate ED. 'Ihey were excluded from further analysis.
Results:
-EN)
Elemental diet (n=9) Prednisolone (n=14)
0 Weeks
4 Weeks
0 Weeks
4 Weeks
4.9 1.1 ) 2.2 (0.6b: 5.5 (0.6) 1.8(0.7 );:'
DAI
E R
52(i4) '
22(11);*:'
48(ii) '
ig(ti);? '
34.9( 1.6) 38.5( 1.O)
Alb
34.7( 1.5) 38.3(0.8)
ll.Z(O.5)
12.4(0.4)
Hb
12.3(0.6)
12.6(0.5)
:2'
0 vs 4 weeks p<O.O5
When tolerated, ED and P produced similar improvements in
DAI and ESR at 4 weeks. Nutritional intake was the same
in both groups.
These results confirm ED to be equal to P for treatment
of Crohn's disease and suggest (i) the effect is not due
to difference in nutritional intake, (ii) ED is a viable
alternative to prednisolone in s m e patients with Crohn's
disease.
94
HUMAN PEPSINS: PARTIAL AMINO-ACID COMPOSITION AND
N-TERMINAL AMINO-ACID SEQUENCES
J.N. KEEN,*+ J.B.C. FINDLAY*+ K. PEEK,+ N.B. ROBERTS
AND W.H. TAYLOR
Departments of Biochemistry, University of Leeds,*
LS2 gJT, and Chemical Pathology, Royal Liverpool Hospital,
Liverpool L7 ~ X W
(+introduced
The amino-acid composition and sequence o f human
pepsins A and C,(named also pepsins 3 and 5, from their
position on electrophoresis of gastric juice), are known.
The amino-acid structure of pepsin 1 , the ulcerassociated pepsin, is not known, nor is that of pepsins
3A and 3C, which are components of pepsin 3.
After acid hydrolysis,thepartial amino-acid
compositions of pepsins 1 , 3 and 5 have been determined
and can be conveniently expressed as percentages by mass
of determined glycine. The known data from pepsins A and
C can be expressed similarly. The ratios for the
individual amino-acids of pepsin 1:pepsin 3 ranged from
0.84 to 1.08, for pepsin 1: pepsin A from 0.84 to 1.17
(except cystine 0.60), for pepsin 1: pepsin 5 from 0.34
to 2.22 and f o r pepsin 1: pepsin C 0.52 to 1.66. The
amino-acid composition of pepsin 1 is thus more similar
to that of pepsin 3 than to pepsin 5.
The N-terminal sequences of pepsins 1 , 3A, 3, 3C and
5 have been determined by automated solid phase Edman
degradation on the "Leedsffapparatus (Findlay, J.B.C.,
Pappin, D.J.C. and Keen, J.N. in press). Our HPIEC
preparations of pepsin 3 and pepsin 5 have the same Nterminal sequence as pepsins A and C respectively, f o r
the first 24 and 30 residues respectively, except that
residue 1 has not been identified in both. For pepsins
1 , 3A and 3C, the first 30 residues are identical with
pepsin A, except that residue 28 in pepsin 1, and 22 in
3A have not been identified.
The protein component of pepsin 1 is thus similar to
pepsin 3 in amino-acid composition and N-terminal
sequence, raising the possibility that pepsin 1 ,
containing about 50% carbohydrate by weight, may be a
carbohydrate/pepsin3 complex. How such a hypothesis
might account f o r the unusual collagenolytic and mucolytic properties of pepsin 1 requires further
investigation.
95
ANALYSIS OF DUODENAL BILE CONFIRMS HEIGHTENED FREE
PADICAL ACTIVITY IN PRIMARY BILIARY CIRRHOSIS (PBC)
Pi4 KAY, Pi.1 GUYAN, H KLASS, TW WARNES and JM BRAGANZA
Department of Gastroenterology, Royal Infirmary,
danchester, M13 9WL, England
In PBC the brunt of the early attack is borne by
epithelial cells lining medium sized bile ducts,
suggesting that a toxic biliary constituent(s) initiates
tne trouble. Free radical oxidation products are a
plausible candidate for this role, since some are known
to alter the structure, and thereby, the immunogenicity
of globulin, whilst others interfere with membrane
fluidity and could thii.: lead to intrahepatic cholestasis.
We examined the hypothesis in the first instance by
analysing serum for the % "molar ratio" of the free
radical oxidation isomer (9,11 LA') to linoleic acid
(9,12 LA) in 11 PBC patients and 20 controls: the
levels in the patients were significantly higher
(mean SE 6.63 0.62% v 2.14 L 0.18%, ~(0.001).
Confirmation that the liver was the source of heightened
free radical activity was obtained by analysing duodenal
bile collected in the first 10 min after an intravenous
injection of secretin. In 7 controls this fraction
contained 34 L 5.75 unol of 9,12 LA and 1.62 + 0.31 unol
of 9,11 LA', giving a % molar ratio of 4.75 '-0.74%.
In
8 ratients with LudJi: grade 1-111 PBC the corresponding
values were elevated - 104 + 27 umol (p<0.05), 6.59 +
2.12 umol (p t O . 0 5 ) and 6.9g L 1.80% (NS). CholestasTs
in patients with grade IV disease resulted in very low
lipid outputs (8.00 + 3.21 umol of 9.12 LA; 0.76 + 0.17
unol of 9.11 LA) but-the molar ratio was very hi&,
12.0
There was no overall correlation
+ 3.09% (p<O.O>).
between molar ratio in bile/serum and histology grade but
patients with grade I disease tended to have lower ratios
Thus increased hepatic free radical activity is a feature
of PBC, including the pre-cirrhotic stages.
96
PLACEBO-CONTROLLED DOUBLE-BLIND TRIAL OF ANTIOXIDANT
SUPPLEMENTS IN PATIENTS WITH RECURRENT PANCREATITIS
S
UDEN, C MAIN, LP HUNT, L NATHAN and JM BRAGANZA
Departments of Gastroenterolozy, Computation and Pharmacy,
r?oyal Infirmary, Manchester, ill3 9WL; and Department of
Psychology, Hope Hospital, Salford, M6 8ND, England
Oxidant stress seems to play a pivotal role in the pathogenesis of pancreatitis: hence antioxidant supplements
could be beneficial in patients with (non-gallstone)
recurrent pancreatitis. We tested this notion in a doseseeking study, spanning five years, in 20 patients and
then examined the successful combination in a 20-week
double-blind placebo-controlled switchover trial in a
further 20 patients with frequent attacks (acute five,
chronic 1 5 ) . The combination, which was chosen on the
basis of published dietary (European Journal of Clinical
Nutrition 1988; 42: 561) and biochemical studies (Trace
Elements in Medicine 1988; 5: 79), provdided daily doses
of 600 pg organic selenium. 9000 IU !-carotene, 0.54 g
vitamin C, 270 IU vitamin E and 2 g methionine. Patients
kept diaries to gauge overall pain on a 10 cm visual
analogue scale (VAS). Before entry, at crossover and at
the end of the trial, they completed VAS pain descriptor