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December 1959, Vol 98, No. 6 >
Article | December 1959

Studies on Glucuronide Formation in Newborn Infants and Older Children:  Measurement of p-Aminophenol Glucuronide Levels in the Serum After an Oral Dose of Acetanilid FREE

MARKUS F. VEST, M.D.; RICHARD R. STREIFF, M.D.
[+] Author Affiliations

Submitted for publication Jan. 15, 1959.


AMA Am J Dis Child. 1959;98(6):688-693. doi:10.1001/archpedi.1959.02070020690003.
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The work of Schmid,1 Billing, Cole, and Lathe,2 and Talafant3 demonstrated that bilirubin has to be conjugated with glucuronic acid before excretion in the bile is possible. It appears that the ability of the liver to form glucuronides is not completely developed in the newborn infant, and this seems to lead to the accumulation of bilirubin in the serum after birth (Vest,4a Shirley and Hsia5). On the other hand, an increased destruction of red cells immediately after birth, which for a long time was incriminated as a cause of icterus neonatorum, was not borne out by more recent investigations (Findlay, Higgins and Stanier,6 Fashena,7 Vest4b).

In a previous investigation8 we demonstrated that acetanilid, a substance of which approximately 80% is excreted in the urine of adults in a conjugated form, appears only slowly in the urine of the newborn and within

REFERENCES

1 +
Schmid, R.:  Direct-Reacting Bilirubin, Bilirubin Glucuronide, in Serum, Bile, and Urine , Science 124:76, 1956;.
2 +
Billing, B. H.; Cole, P. G., and Lathe, G. H.:  The Excretion of Bilirubin as a Diglucuronide Giving the Direct van den Bergh Reaction , Biochem. J. 65:774, 1957;.
3 +
Talafant, E.:  Properties and Composition of the Bile Pigment Giving a Direct Diazo Reaction , Nature, London 178:312, 1956;.
4 +
Vest, M.: Physiologie und Pathologie des Neugeborenenicterus , Basel, S. Karger, 1959;.
5 +
Shirley, G. D., and Hsia, D. Y. Y.:  The Development of Enzyme Systems During Early Infancy , Pediatrics 22:785, 1958;.
6 +
Findlay, L.; Higgins, G., and Stanier, M. W.:  Icterus Neonatorum: Its Incidence and Cause , Arch. Dis. Childhood 22:65, 1947;.
7 +
Fashena, G. J.:  Mechanism of Hyperbilirubinemia in the Newborn Infant , Am. J. Dis. Child. 76:196, 1948;.
8 +
Vest, M.:  Insufficient Glucuronide Formation in the Newborn and Its Relationship to the Pathogenesis of Icterus Neonatorum , Arch. Dis. Childhood 33:473, 1958;.
9 +
Brodie, B. B., and Axelrod, J.:  The Estimation of Acetanilide and Its Metabolic Products, Aniline, N-Acetyl-p-aminophenol and p-aminophenol (Free and Total Conjugated) in Biological Fluid and Tissues , J. Pharmacol. & Exper. Therap. 94: 22, 1948;.
10 +
Axelrod, J.; Schmid, R., and Hammaker, L.:  A Biochemical Lesion in Congenital, Non-Obstructive, Non-Haemolytic Jaundice , Nature, London 180:1426, 1957;.
11 +
Jendrassik, L., and Gróf, P.:  Vereinfachte photometrische Methoden zur Bestimmung des Blutbilirubins , Biochem. Ztschr. 297:81, 1938;.
12 +
Evelyn, K. A., and Malloy, H. T.:  Microdetermination of Oxyhemoglobin, Methemoglobin and Sulfhemoglobin in a Single Sample of Blood , J. Biol. Chem. 126:655, 1938;.
13 +
Brodie, B. B., and Axelrod, J.:  The Fate of Acetanilide in Man , J. Pharmacol. Exper. Therap. 94:29, 1948;.
14 +
Smith, H. W.: The Kidney: Structure and Function in Health and Disease , New York, Oxford University Press, 1951;, p. 502.
15 +
Schmid, R.; Hammaker, L., and Axelrod, J.:  The Enzymatic Formation of Bilirubin Glucuronide , Arch. Biochem. & Biophys. 70:285, 1957;.
16 +
Grodsky, G. M., and Carbone, J. V.:  The Synthesis of Bilirubin Glucuronide by Tissue Homogenates , J. Biol. Chem. 226:449, 1957;.
17 +
Karunairatnam, M. C.; Kerr, L. M. H., and Levvy, G. A.:  The Glucuronide-Synthesizing System in the Mouse and Its Relationship to β-Glucuronidase , Biochem. J. 45:496, 1949;.
18 +
Hartiala, K. J. V., and Pulkkinen, M.:  Studies on Detoxication Mechanisms: IV. Glucuronide Synthesis in Foetal Rabbit , Ann. med. exper. et. biol. Fenniae 33:246, 1955;.
19 +
Brown, A. K.; Zuelzer, W. W., and Burnett, H. H.:  Studies on the Neonatal Development of the Glucuronide Conjugating System , J. Clin. Invest. 37:332, 1958;.
20 +
Flinn, F. B., and Brodie, B. B.:  The Effect on the Pain Threshold of N-Acetyl-p-Aminophenol, a Product Derived in the Body from Acetanilide , J. Pharmacol. & Exper. Therap. 94: 76, 1948;.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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References

1 +
Schmid, R.:  Direct-Reacting Bilirubin, Bilirubin Glucuronide, in Serum, Bile, and Urine , Science 124:76, 1956;.
2 +
Billing, B. H.; Cole, P. G., and Lathe, G. H.:  The Excretion of Bilirubin as a Diglucuronide Giving the Direct van den Bergh Reaction , Biochem. J. 65:774, 1957;.
3 +
Talafant, E.:  Properties and Composition of the Bile Pigment Giving a Direct Diazo Reaction , Nature, London 178:312, 1956;.
4 +
Vest, M.: Physiologie und Pathologie des Neugeborenenicterus , Basel, S. Karger, 1959;.
5 +
Shirley, G. D., and Hsia, D. Y. Y.:  The Development of Enzyme Systems During Early Infancy , Pediatrics 22:785, 1958;.
6 +
Findlay, L.; Higgins, G., and Stanier, M. W.:  Icterus Neonatorum: Its Incidence and Cause , Arch. Dis. Childhood 22:65, 1947;.
7 +
Fashena, G. J.:  Mechanism of Hyperbilirubinemia in the Newborn Infant , Am. J. Dis. Child. 76:196, 1948;.
8 +
Vest, M.:  Insufficient Glucuronide Formation in the Newborn and Its Relationship to the Pathogenesis of Icterus Neonatorum , Arch. Dis. Childhood 33:473, 1958;.
9 +
Brodie, B. B., and Axelrod, J.:  The Estimation of Acetanilide and Its Metabolic Products, Aniline, N-Acetyl-p-aminophenol and p-aminophenol (Free and Total Conjugated) in Biological Fluid and Tissues , J. Pharmacol. & Exper. Therap. 94: 22, 1948;.
10 +
Axelrod, J.; Schmid, R., and Hammaker, L.:  A Biochemical Lesion in Congenital, Non-Obstructive, Non-Haemolytic Jaundice , Nature, London 180:1426, 1957;.
11 +
Jendrassik, L., and Gróf, P.:  Vereinfachte photometrische Methoden zur Bestimmung des Blutbilirubins , Biochem. Ztschr. 297:81, 1938;.
12 +
Evelyn, K. A., and Malloy, H. T.:  Microdetermination of Oxyhemoglobin, Methemoglobin and Sulfhemoglobin in a Single Sample of Blood , J. Biol. Chem. 126:655, 1938;.
13 +
Brodie, B. B., and Axelrod, J.:  The Fate of Acetanilide in Man , J. Pharmacol. Exper. Therap. 94:29, 1948;.
14 +
Smith, H. W.: The Kidney: Structure and Function in Health and Disease , New York, Oxford University Press, 1951;, p. 502.
15 +
Schmid, R.; Hammaker, L., and Axelrod, J.:  The Enzymatic Formation of Bilirubin Glucuronide , Arch. Biochem. & Biophys. 70:285, 1957;.
16 +
Grodsky, G. M., and Carbone, J. V.:  The Synthesis of Bilirubin Glucuronide by Tissue Homogenates , J. Biol. Chem. 226:449, 1957;.
17 +
Karunairatnam, M. C.; Kerr, L. M. H., and Levvy, G. A.:  The Glucuronide-Synthesizing System in the Mouse and Its Relationship to β-Glucuronidase , Biochem. J. 45:496, 1949;.
18 +
Hartiala, K. J. V., and Pulkkinen, M.:  Studies on Detoxication Mechanisms: IV. Glucuronide Synthesis in Foetal Rabbit , Ann. med. exper. et. biol. Fenniae 33:246, 1955;.
19 +
Brown, A. K.; Zuelzer, W. W., and Burnett, H. H.:  Studies on the Neonatal Development of the Glucuronide Conjugating System , J. Clin. Invest. 37:332, 1958;.
20 +
Flinn, F. B., and Brodie, B. B.:  The Effect on the Pain Threshold of N-Acetyl-p-Aminophenol, a Product Derived in the Body from Acetanilide , J. Pharmacol. & Exper. Therap. 94: 76, 1948;.

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