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PATHOGENESIS OF ATOPIC ALLERGY
661 GLUCOSE CONCENTRATION IN AMNIOTIC FLUID
TRYPTOPHAN METABOLISM, ORAL CONTRACEPTIVES, AND PYRIDOXINE
FROM ANENCEPHALIC PREGNANCIES
SIR,-Pettit
et
al.’ found low
glucose
concentrations in the
amniotic fluid, collected between 15 and 24 weeks of gestation, in
pregnancies
where the fetus
was
anencephalic.
Because
amniotic-fluid glucose concentrations decrease with advancing pregnancy, we looked at two periods in our study-25-35 weeks and 36-43 weeks. We measured glucose levels in anencephalic samples and in amniotic fluid from pregnancies with a normal outcome; diabetic mothers were excluded from the control group because glucose levels are high in such cases. AMNIOTIC-FLUID GLUCOSE VALUES
SIR,-You stated’ that oral contraceptives (o.c.) induced hepatic tryptophan pyrrolase activity, and Dr Badawy and Dr Evans (Feb. 25, p. 448) discussed the possible role of this enzyme in regulating the brain 5-hydroxytryptamine (5-H.T.) pathway. However, data from this laboratory suggests care should be exercised in the interpretation of previous observations. It is widely believed that giving oestrogen results in pyrrolase induction, which causes a decreased availability of tryptophan for brain 5-H.T. synthesis.l-9 It has been suggested that this mechanism may be linked with the mood change that can occur in women on oral contraceptives. 1.6, 10, 11 The main evidence for pyrrolase induction is the increased urinary excretion of the kynurenine-pathway metabolites, xanthurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid in women taking oral contraceptives.2,6,12,13 PLASMA HALF-LIFE
(T-1), PLASMA CLEARANCE, VOLUME OF
(VD), AND AREA UNDER PLASMA-TRYPTOPHAN CURVE (A.U.C.) AFTER TRYPTOPHAN (50 mg/kg)
DISTRIBUTION
Our results confirm those of Pettit et al. However, since pregnancy is often accompanied by hydramnios it could be that the decrease in the glucose level is related to the hydramnios rather than a hormonal mechanism, as suggested. In our series amniotic-fluid glucose levels were lower in hydramnios cases, but the decrease was much more striking in anencephalic gestations (see table). Determination of glucose in amniotic fluid could be a complementary test to the alphafetoprotein test in the detection of malformation of neural tube. S. GUIBAUD M. BONNET F. KHALIL Departments of Biochemistry A. COMBET and Obstetrics and Gynæcology, J. M. THOULON Hôpital Croix-Rousse 69317 Lyon, France. M. DUMONT
anencephalic
PATHOGENESIS OF ATOPIC ALLERGY
S!R,—The suggestion by Dr Strannegard and colleagues (Feb. 18, p. 385) that "atopic disease is caused by or associated with a lymphocyte defect" accords with our observations. Patients with atopic asthma,2 which often has definite associations with allergy, and with atopic eczema (unpublished), where the allergic connection may seem to be non-existent, have low T-lymphocyte levels in their peripheral blood. This is particularly apparent when the counting is done after incubation in
a
system from which fetal calf serum has been omit-
Values are mean +
s.E.
We examined14 the metabolism of oral tryptophan (50 in 14 women taking oral contraceptives and 10 women on no drugs. The contraceptive users excreted increased
mg/kg)
amounts of 3-hydroxykynurenine and xanthurenic acid after tryptophan. Since renal excretion and the volume of distribution of tryptophan was similar in both groups (see table), tryptophan was probably removed from the circulation by uptake and metabolism by pyrrolase. The similarity of plasma half-life, plasma clearance, and area under the plasma-tryptophan curve in the two groups (see, table) suggests strongly that pyrrolase activity was the same. Mason and Gullekson" found that oestrogen sulphate esters interfere competitively with the activity of some pyridoxalphosphate-dependent enzymes, and Rose and colleagues16 suggested that this was more likely to occur with supernatant kynureninase rather than mitochondrial aminotransferase. Such changes would lead to increased accumulation and excretion of 3-hydroxykynurenine and xanthurenic acid; consistent with this hypothesis is the observation that the abnormal
excretion of these metabolites both in women on oral contraceptives and in pregnant women becomes normal after they take pyridoxine.2,s,i3,l We have found14 that contraceptive users have normal 5-hydroxyindole acetic acid and indole acetic acid excretion,
ted.3
Strannegard et al. found evidence for the defect of T-lymphocytes in atopic eczema being primary. A likely pathway after this might involve mechanisms causing an overproduction of IgE and the release of histamines and other vasoactive
pharmacological mediators that could be blamed for some features of the rash.
Departments of Dermatology and Chemical Pathology, P. W. M. COPEMAN N. A. BYROM Westminster Hospital, London SW1P 2AR 1.
Pettit, B. R., King, G. S., Blau, K. Lancet, 1977, ii,
1288.
2. Byrom, N. A., Caballero, F., Campbell, M. A., Chooi, M., Lane, A. M., Hugh-Jones, K., Timlin, D. M., Hobbs, J. R. Clin. exp. Immun. (in the Press). 3. Byrom, N. A., Campbell, M. A., Staughton, R. C. D., Timlin, D. M. Lancet, 1977, ii, 1132.
1. Lancet, 1977, ii, 1333. Rose, D. P. Clin. Sci. 1966, 31, 265. 3. Rose, D. P., Braidman, I. P.Am.J. clin.Nutr. 1971, 24, 673. 4. Rose, D. P.J. clin. Path. 1972, 25, 17. 5. Winston, F. Am.J. Psychiat. 1973, 130, 1217. 6. Adams, P. W., and others. Lancet, 1973, i, 897. 7. Grant, E. C. G. Hemicrania, 1975, 6, 2. 2.
8. Wynn, V. Lancet, 1975, i, 561. 9. Malik-Ahmadi, P., Behrmann, P. J. Dis. nerv. System, 1976,37,406. 10. Herzberg, B. N., Johnson, A. L., Brown, S. Br. med.J. 1970, iv, 142. 11. Herzberg, B. N., Coppen, A. Br.J. Psychiat. 1970, 116, 161. 12. Leklem, J. E., and others.Am.J. clin. Nutr. 1975, 28, 146. 13. Luhby, A. L., and others. ibid. 1971, 24, 684. 14. Green, A. R., Bloomfield, M. R., Woods, H. F., Seed, M. Br. J. clin. Phar-
mac. 1978, 5, 233. 15. Mason, M., Gullekson, E. H.J. biol. Chem. 1960, 235, 1312. 16. Rose, D. P., Strong, R., Adams, P. W., Harding, P. E. Clin. Sci. 1972, 465. 17. Wachstein, M., Gudaitis, A.J. lab. clin. Med. 1975, 42, 98.
42,
TRYPTOPHAN METABOLISM, ORAL CONTRACEPTIVES, AND PYRIDOXINE
FROM ANENCEPHALIC PREGNANCIES
SIR,-Pettit
et
al.’ found low
glucose
concentrations in the
amniotic fluid, collected between 15 and 24 weeks of gestation, in
pregnancies
where the fetus
was
anencephalic.
Because
amniotic-fluid glucose concentrations decrease with advancing pregnancy, we looked at two periods in our study-25-35 weeks and 36-43 weeks. We measured glucose levels in anencephalic samples and in amniotic fluid from pregnancies with a normal outcome; diabetic mothers were excluded from the control group because glucose levels are high in such cases. AMNIOTIC-FLUID GLUCOSE VALUES
SIR,-You stated’ that oral contraceptives (o.c.) induced hepatic tryptophan pyrrolase activity, and Dr Badawy and Dr Evans (Feb. 25, p. 448) discussed the possible role of this enzyme in regulating the brain 5-hydroxytryptamine (5-H.T.) pathway. However, data from this laboratory suggests care should be exercised in the interpretation of previous observations. It is widely believed that giving oestrogen results in pyrrolase induction, which causes a decreased availability of tryptophan for brain 5-H.T. synthesis.l-9 It has been suggested that this mechanism may be linked with the mood change that can occur in women on oral contraceptives. 1.6, 10, 11 The main evidence for pyrrolase induction is the increased urinary excretion of the kynurenine-pathway metabolites, xanthurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid in women taking oral contraceptives.2,6,12,13 PLASMA HALF-LIFE
(T-1), PLASMA CLEARANCE, VOLUME OF
(VD), AND AREA UNDER PLASMA-TRYPTOPHAN CURVE (A.U.C.) AFTER TRYPTOPHAN (50 mg/kg)
DISTRIBUTION
Our results confirm those of Pettit et al. However, since pregnancy is often accompanied by hydramnios it could be that the decrease in the glucose level is related to the hydramnios rather than a hormonal mechanism, as suggested. In our series amniotic-fluid glucose levels were lower in hydramnios cases, but the decrease was much more striking in anencephalic gestations (see table). Determination of glucose in amniotic fluid could be a complementary test to the alphafetoprotein test in the detection of malformation of neural tube. S. GUIBAUD M. BONNET F. KHALIL Departments of Biochemistry A. COMBET and Obstetrics and Gynæcology, J. M. THOULON Hôpital Croix-Rousse 69317 Lyon, France. M. DUMONT
anencephalic
PATHOGENESIS OF ATOPIC ALLERGY
S!R,—The suggestion by Dr Strannegard and colleagues (Feb. 18, p. 385) that "atopic disease is caused by or associated with a lymphocyte defect" accords with our observations. Patients with atopic asthma,2 which often has definite associations with allergy, and with atopic eczema (unpublished), where the allergic connection may seem to be non-existent, have low T-lymphocyte levels in their peripheral blood. This is particularly apparent when the counting is done after incubation in
a
system from which fetal calf serum has been omit-
Values are mean +
s.E.
We examined14 the metabolism of oral tryptophan (50 in 14 women taking oral contraceptives and 10 women on no drugs. The contraceptive users excreted increased
mg/kg)
amounts of 3-hydroxykynurenine and xanthurenic acid after tryptophan. Since renal excretion and the volume of distribution of tryptophan was similar in both groups (see table), tryptophan was probably removed from the circulation by uptake and metabolism by pyrrolase. The similarity of plasma half-life, plasma clearance, and area under the plasma-tryptophan curve in the two groups (see, table) suggests strongly that pyrrolase activity was the same. Mason and Gullekson" found that oestrogen sulphate esters interfere competitively with the activity of some pyridoxalphosphate-dependent enzymes, and Rose and colleagues16 suggested that this was more likely to occur with supernatant kynureninase rather than mitochondrial aminotransferase. Such changes would lead to increased accumulation and excretion of 3-hydroxykynurenine and xanthurenic acid; consistent with this hypothesis is the observation that the abnormal
excretion of these metabolites both in women on oral contraceptives and in pregnant women becomes normal after they take pyridoxine.2,s,i3,l We have found14 that contraceptive users have normal 5-hydroxyindole acetic acid and indole acetic acid excretion,
ted.3
Strannegard et al. found evidence for the defect of T-lymphocytes in atopic eczema being primary. A likely pathway after this might involve mechanisms causing an overproduction of IgE and the release of histamines and other vasoactive
pharmacological mediators that could be blamed for some features of the rash.
Departments of Dermatology and Chemical Pathology, P. W. M. COPEMAN N. A. BYROM Westminster Hospital, London SW1P 2AR 1.
Pettit, B. R., King, G. S., Blau, K. Lancet, 1977, ii,
1288.
2. Byrom, N. A., Caballero, F., Campbell, M. A., Chooi, M., Lane, A. M., Hugh-Jones, K., Timlin, D. M., Hobbs, J. R. Clin. exp. Immun. (in the Press). 3. Byrom, N. A., Campbell, M. A., Staughton, R. C. D., Timlin, D. M. Lancet, 1977, ii, 1132.
1. Lancet, 1977, ii, 1333. Rose, D. P. Clin. Sci. 1966, 31, 265. 3. Rose, D. P., Braidman, I. P.Am.J. clin.Nutr. 1971, 24, 673. 4. Rose, D. P.J. clin. Path. 1972, 25, 17. 5. Winston, F. Am.J. Psychiat. 1973, 130, 1217. 6. Adams, P. W., and others. Lancet, 1973, i, 897. 7. Grant, E. C. G. Hemicrania, 1975, 6, 2. 2.
8. Wynn, V. Lancet, 1975, i, 561. 9. Malik-Ahmadi, P., Behrmann, P. J. Dis. nerv. System, 1976,37,406. 10. Herzberg, B. N., Johnson, A. L., Brown, S. Br. med.J. 1970, iv, 142. 11. Herzberg, B. N., Coppen, A. Br.J. Psychiat. 1970, 116, 161. 12. Leklem, J. E., and others.Am.J. clin. Nutr. 1975, 28, 146. 13. Luhby, A. L., and others. ibid. 1971, 24, 684. 14. Green, A. R., Bloomfield, M. R., Woods, H. F., Seed, M. Br. J. clin. Phar-
mac. 1978, 5, 233. 15. Mason, M., Gullekson, E. H.J. biol. Chem. 1960, 235, 1312. 16. Rose, D. P., Strong, R., Adams, P. W., Harding, P. E. Clin. Sci. 1972, 465. 17. Wachstein, M., Gudaitis, A.J. lab. clin. Med. 1975, 42, 98.
42,