17~
Medical Research Society
sampling method used. The modified 13C-UBT is not only easier and
cheaper to perform than previous breath tests, but being non-invasive and
avoiding the Inherent sampling error of biopsy based methods. may also be
a better 'gold standard' for the detection of H.pylori. This new test is ideal for
epidemiologicaland clinical studies requiring serial assessments of H.pylori
status.
FUUXLCNSHIP
~ m m m SERUM ~ D I A S E
PCTIVITYAND SEVERITYOF LIVER FAlLuRE IN F"IENBWIM
AUWOLLC AND
BILIARY CIRRHOSIS.
60
THE
PD Duane, C3N Fleystre and I% msowsky. Uepartment of
Medicine, St. James's University Hospital, Leeds IS9
No significant change was observed in the PMOPDE in the 4
patients with Pugh's scores of 5.
However, significant
abnormalities were observed in meankSEM) values for
PMWPDE, 0.76k0.09 cf. 0.21 50.01 (ps0.002), PMUATP,
0.9720.12 cf. 0.4320.04 (p=0.005) and PDWATP, 1.44k0.10 cf.
2.0220.1 4 (p=0.006) in the 6 patients with Pugh's scores 26.
Thus, no significant change in the PMWPDE is observed in the
hepatic 31P MR spectra in patients with well compensated
alcoholic cirrhosis who 'are abstinent from alcohol whereas
significant spectral abnormalities are observed in abstinent
cirrhotics with evidence of hepatic decompensation.
7TF, U.K.
The activity of serum carnosinase is inversely related
of Typ2 I1 fibre atrophy in patients with
to the d-ee
alcoholic skeletal rmSCle myopathy. It is not Clear if
this is a reflection of the severity of their
associated liver disease, as low activity of this
enzyme has been reported in patients with other forms
of chronic liver disease. In this study, the relationship between serum carnosinase activity and the
clinical grade of their liver failure, as measured by
the ChilcFpush score, is assessed in patients with
alcoholic (ALC) and primary biliary (WC) cirrkosis.
serum carnosinase activity (mum)was significantly
decreased in the cirrhotic group, 53.7 f 4.8 (58) (mean
f SE (n)) ccanpared with controls, 135 2 40.9 (45);
ptO.OO1. The activity in patients with A K , 48.8 k 8.1
(27) was similar to those with PBC, 57.8 k 5.7 (31);
When the patients were divided into their
p>O.3.
respective Child-PLqh classes, serum carnosinase
activity for class C, 28.6
2.7
(18). was
significantly lowei t h a n class A, 83.5
10.8 (18)
(pCO.001)or Class B, 52.4
6.1 ( 2 2 ) (-0.01).
Only 5
patients (28%) in class A and 14 patients (64%) in
class B, whereas all 18 patients in class C had serum
carnosinase activities >2sD below the mean for control
subjects (pt0.001). A significant inverse correlation
was found between sennn carnosinase activity and the
child-Pugh score (r = -0.560, n = 58, FO.001).
These findings show that serum carnosinase activity is
decreased in patients with cirrhosis am3 is inversely
related to the severity of their hepatic failure.
61
HEPATIC PHOSPHORUS-31 MAGNETIC RESONANCE
SPECTROSCOPY C'P MRS) IN PATIENTS WITH ALCOHOLIC
CIRRHOSIS
DK MENON*, M HARRIS+, J SARGENTONI*, IJ COX* and
MY MORGAN+
*NMR Unit, Hammersmith Hospital, London W12 OHS and
+Medical Unit, Royal Free Hospital and School of Medicine,
London NW3 2QG, England
There is no clear consensus about the hepatic spectroscopic
appearances in patients with alcoholic cirrhosis. However, the
populations studied, to date, have been heterogeneous with little
attempt made to control for the severity of the liver injury or the
drinking behaviour. Hepatic "P MRS was undertaken in 10
patients (5M:5F) of mean(range) age 44.3(32-57) years with
biopsy proven alcoholic cirrhosis and Pugh's scores varying from
5 to 13. All patients had been abstinent from alcohol for a
minimum of two months to control for the drinking variable.
Spectroscopic reference data were obtained from 7 healthy
volunteers. Peak area ratios for phosphomonoester (PME),
phosphodiesters (PDE) and PATP ware calculated from localised
hepatic 31P spectra obtained using 2-dimensional chemical shift
imaging with a repetition time of 5s and pulse angle 45'.
62
TRANSPORT IN RABBIT CAECUM: EFFECT OF LOW SODIUM
SoumONs
SPL Travis, AG Taylor and DP Jewel1
University Laboratory of Physiology and Gastrointestinal Unit,
Radcliffe Infirmary, Oxford
Rabbit caecum is a moderately tight epithelium exhibiting
electrogenic Na transport with low amiloride sensitivity (Claus et
al Am J Physiol 1989; 256: G1090-9). Decreasing serosal and
mucosal Na simultaneously reduces the short circuit current
(SCC) in rabbit caecum , but the polarity of this effect is unknown.
Stripped muwsal segments of rabbit caecum were mounted
in Ringer's solution (Na 140mM, Ca 1.2mM, pH 7.4) in Ussing
chambers and SCC monitored before and after ion replacement
(choline substitution, n = 5-9 for all studies). Lowering Na
bilaterally to 21mM decreased SCC by 48 t 4.7% (se) (pcO.OOl),
relative to paired controls. Mucosal Na lOmM, 21mM, 50mM and
lOOmM decreased SCC by 40 t 3.4% (pcO.OOl), 25 t 1.2%
(pcO.OOl), 16 t 1.7% (pcO.01) and 3 ? 1.8 % (ns)
respectively. Serosal Na IOrnM and 2imM decreased SCC by 19 f
2.5% (pcO.01) and 13 f 3.1% (pcO.01). Possible mechanisms
underlying the inhibition of SCC induced by low serosal Na were
investigated. The inhibitory effect of low serosal Na was not
altered when serosal Ca was varied in the range 0.1 - 1.2mM.
Serosal addition of amiloride 10-3M. or frusemide lO-4M, had no
influence on the SCC at 140mM serosal Na, nor on the decrease in
SCC induced by 10mM serosal Na.
Separate effects on SCC of decreasing muwsal and serosal Na
have been demonstrated in isolated rabbit caecum. The mechanism
by which low serosal Na reduces SCC remains uncerlain.
63
AMINOGUANIDINE INCREASES INTESTINAL
PROTEIN AND NUCLEIC ACID CONCENTRATION IN
THE MALNOURISHED RAT.
VICTOR R PREEDY
AND TIMOTHY J PETERS
Department of Clinical Biochemistry, King's
College School of Medicine, Bessemer Road,
London, SE5 9PJ, U.K.
It has been suggested that the dialnine
oxidase inhibitor aminoguanidine (AMG) has
the potential to increase tissue nitrogen
retention in catabolic states (Baylin, et
al., Experientia, 31, 562-567, 1975).
In
this
study,
we
determined
whether
aminoguanidine
has an anabolic effect on
the rat small intestine.
Medical Research Society
18P
Male rats (approx 0.1 kg body weight) were
either a) dietary-restricted (50% of food
eaten by
libitum-fed rats); b) dietaryrestricted + AMG (60 mgjkg body weightiday,
in drinking water); c) fed ad libitum; d)
fed ad libitum plus AMG.
After 3 weeks, intestinal protein, RNA and
DNA concentrations in dietary-restricted
control rats were 66.952.6, 4.1120.32 and
3.5920.20 mg/g wet weight, respectively. In
AMG-treated
dietary-restricted
rats,
corresponding values were 74.021.3 (P<O.O5),
4.8220.14 (P<O.O5) and 4.20+0.10 (P<O.O5).
In fed rats, neither protein, RNA nor DNA
were significantly altered by AMG treatment.
Similar analysis was also carried out on the
liver, but in both fed and dietaryrestricted rats hepatic protein, RNA and DNA
was unresponsive to AMG treatment.
Thus,
aminoguanidine has an apparent trophic
effect
on
the
small
intestine
of
malnourished rats, but the mechanism for
these selective changes are not known.
64 DIETARY CYSTEINE SUFFICIENCY INFLUENCES THE
HEPATIC RESPONSE TO TNF
R' GRIMBLE. 'AA
JACKSON, ' C PERSAUD and 2I BREMNER
of IBD. We have previously shown increased
production of ILp by PBMNC from patients with
active IBD. This study investigated production
of IL6 and TNFa by PBMNC from patients with
ulcerative colitis (UC) and Crohn's disease
(CD). PBMNC were cultured with or without
lipopolysaccharide (LPS) for 24h and total
amount of cytokine determined by ELISA.
Results: Expressed as mean (SEM) of IL6 or TNFa
in pg per 0.5X106 PBMNC. Compared to controls,
there was greater spontaneous (endotoxin free)
production of IL6 by PBMNC from UC (p=0.004)
and CD (p=O.O29). For others, differences did
not reach statistical sianificance.
.
IL6
LPS (uq/ml)O
0.01
0.1
10
Normal
0.6
5500
7187
8406
( 1930L
(15831
(0.4)
(1687)
(n=8)
UC
20.5
10300
11300
S350
(6488)
(5787)
( 29831
(6.6)
(n=6)
CD
42.4
11860
13620
14680
(1304)
(1811)
( 17321
jn=5)
(21.6)
TNV"
....LPS (uq/ml)O
0.01
0.1
10
Normal
8.5
1514
1557
2579
(n=lO)
(3.6)
(294
(319)
(976)
uc
26.9
2408
3172
5590
(n=8)
(8.9)
(718)
(1054)
(2404)
CD
4.8
1450
2687
3235
(n=7)
(1.2)
(777)
(769)
(519)
There is enhanced spontaneous synthesis of IL6
by PBMNC in active IBD.
.
:Human Nutrition Department, Southampton University and
The Rowett Research Institute
Inflammatory stimuli bring about cytokine and free
radical production. Cytokines may enhance antioxidant
defenses. Some components of antioxidant defenses such
as glutathione (GSH) and metallothionein (MTI) are rich
in cysteine (CYS). Dietary cysteine sufficiency may
therefore limit responsiveness to cytokines. Theeffect
of TNF (100pglkg i.p.) 24h after injection, on hepatic
zinc, GSH and MTI concentrations and on serum
caeruloplasmin (CR) was examined in weanling rats fed
for 1 week on a low protein diet containing caseine
(CAS) (80g/kg) supplemented with isonitrogenous amounts
of CYS (8g/kg) or alanine (ALA, 6g/kg). Responses were
compared with those of rats receiving a CAS (200g/kg)
diet containing CYS (8glkg). Controls (C) for each
dietary group were injected with saline i.p. and pair
fed to the intake of animals receiving TNF.
8% CAS ALA
8% CAS CYS
20% CAS CYS
LIVER
C
TNF
C
TNF
C
TNFb
Wt(g)
9.0
9.6a
6.9'
7.2'
43.2
29.3'
31.3'
21.7'
31.
9'$c
Zn ( p g l g ) 42.3
163
155
120
55
10Bb
MTI ( p g l g ) 151
GSH (mglg) 23.9
29.0b
5.4'
8.gbc
19.8'
25.8
CR (U/1)
179
357b
274'
519bC
150
329
Sig. diff. from C value: a=p<0.05; b=p<O.Ol and from
corresponding 20% CAS CYS value c=pcO.O5
MTI concentrations were unaffected by either dietary
change or TNF treatment. Protein deficiency had
paradoxical effects. While it impaired the increase in
liver weight and zinc and GSH concentrations, it
enhanced the response of caeruloplasmin. Cysteine
supplementation normalised all of these responses.
Cysteine sufficiency may therefore be important in the
maintenance of hepatic antioxidant defenses in
conditions involving cytokine production.
66 VARIABLE
EXPRESSION
OF
FAMILIAL
APOLIPOPROTEIN B-100 (FDB) IN THREE FAMILIES
DEFECTIVE
NB MYANT, JJ GALLAGHER, BL KNIGHT, P TALMUD* and SE
HUMPHRIES*. Introduced by AJ REES
MRC Lipoprotein Team, Hammersmith Hospital and *Charing
Cros_s Sunley Research Centre, London, England
FDB is a lipoprotein disorder caused by a rare mutation
resulting in the substitution of glutamine for arginine at
position 3500 in apoB-100, the protein of low-density
lipoprotein (LDL). The mutation decreases the affinity of
LDL for LDL receptors, giving rise to increased plasma
LDL cholesterol levels in most heterozygotes. We have
studied the phenotypic expression of the FDB mutation in
three families comprising a total of 20 heterozygotes. In
two heterozygotes, rhe age-adjusted plasma LDL level was
normal and there were no clinical abnormalities; in the
remaining 18, including a 2-year-old girl, the plasma LDL
level was raised (mean 6.1 r 0.26 mol/l, m a . 9.2
mmol/l). Five had had a myocardial infarct at ages 31,
46, 52, 53 and 65, and three had tendon xanthomas. Thus,
carriers of a single FDB allele may have normal plasma
cholesterol levels and no clinical signs, or they may have
all the signs of classical heterozygous familial hypercholesterolaemia (FH). FH as a sole or contributory cause
of hypercholesterolaemia was excluded in all three
families by showing that (a) skin fibroblasts from the
three index subjects exhibited normal LDL-receptor
function and that (b) in each family, hypercholesterolaemia failed to segregate with a haplotype of two
polymorphic sites within the receptor gene.
67
SULPHASALAZINE AND LYMPHOPROLIFERATIVERESPONSES
IN RHEUMATOID ARTHRITIS
65 PRODUCTION OF INTERLEUKIN 6 (IL6) AND
TUMOUR NECROSIS FACTOR a (TNFa) BY PERIPHERAL
BLOOD MONONUCLEAR CELLS (PBMNC) FROM PATIENTS
WITH ACTIVE INFLAMMATORY BOWEL DISEASE (IBD)
Y R MAHTDP
KURLAC
L. GPLLAC-HER
? and H4WEY
Department
of
Therapeutics,
Hospital, Nottingham NGI 2UH
CJ
University
Cytokines may be involved in the pathogenesis
A SAMANTA, C WEBB, K GRINDULIS and PJ SHELDON
Leicester Royal Infirmary, Leicester, LE1 5WW
Clinical and immunological parameters in 37 patients
with rheumatoid arthritis (RA) receiving sulphasalazine
(SASP) were evaluated, to determine whether any quantitative o r qualitative changes observed in their
peripheral blood lymphocytes correlated with the clinical
response.