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The digestion of carbohydrates during postnatal development
Vol. 50. No.4
GASTROENTEROLOGY
Copyright © 1966 by The Williams & Wilkins Co.
Printed in U.S.A.
EDITORIALS THE DIGESTION OF CARBOHYDRATES DURING POSTNATAL DEVELOPMENT The purpose of this communication is to discuss those recent advances in the developmental biochemistry of carbohydrate metabolism which have particular significance to gastroenterology. Holzel's description of siblings who had intolerance to lactose generated a great deal of interest in the study of intestinal disaccharidases. 1 There have been several excellent reviews of the clinical abnormalities associated with different types of disaccharidase deficiencies in man ;2. 3 therefore we will concentrate on the problems concerned with changes of disaccharidase activities in mammals during development, the factors which affect these changes, and the digestion of carbohydrates in the intestine of suckling animals. This is not intended as a comprehensive report but rather reflects our present convictions as to the importance of developmental phenomena in the study of digestion and absorption. The activity of intestinal disaccharidases of suckling mammals differs from that of the adult. ,B-Galactosidase and ,B-glucosidase activities are elevated in the suckling animal and decrease during the weaning period; the a-glucosidases (maltase, isomaltase, invertase, trehelase, and palatinase) are virtually absent in the suckling period, but increased activities occur during the weaning period. Th.is pattern of enAddress request for reprints to: Dr. P. Sunshine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California 94304. These investigations reported were supported in part by the John A. Hartford Foundation and by Research Grant A-03501 from the National Institute of Arthritis and Metabolic Diseases, United States Public Health Service. Dr. Koldovsky is on leave of absence from the Laboratory of Developmental Nutrition, Institute of Physiology of Czechoslovak Academy of Science, Praha-Podoli, Czechoslovakia. 596
zymatic development has been described in the intestine of the rat, dog, cow, rabbit, mouse, and pig, but not in man. Invertase has been found in the intestine of 2- to 3month-old human fetuses and reaches comparable adult levels of activity by the 35th to 36th week of intrauterine life. 4 • 5 Heilskov found no ,B-galactosidase activity in the human fetal intestine until the fifth month of gestation, but noted that the activity of this enzyme increased during the second half of intrauterine growth.6 Workers at the Prague laboratory, using o-nitrophenol ,B-galactoside as a substrate, detected ,B-galactosidase activity in the intestine of IO-week-old human fetuses (unpublished data). Using lactose as a substrate, Doell, Kretchmer, and Sunshine have likewise found ,B-galactosidase activity in the intestine of 3-month-old human fetuses and, by 36 weeks of age, the activity is comparable to that found in adults (unpublished data). Auricchio et al} studying the development of intestinal disaccharidases, have detected lactase (substrate lactose) in 2- to 3-monthold human fetuses. They have observed that the increase in activity of the ,B-galactosidases, lactase and cellobiase, occurs at a later date in the intrauterine growth period than do the activities of the a-glucosidases. Although there have been reports of lactase deficiency occurring in some adults, there is no evidence of change in activities of intestinal disaccharidases during later life. The only mammals that have been described with complete absence of intestinal disaccharidases are two species of sea lions. 7 The relationship of this finding to digestion is discussed below. Both diet and a maturing adrenal cortex have been considered as potential regulators of the changes in the developmental pattern of these sugar-splitting enzymes. In the rat, where most of the variations of dietary
April 1966
EDITORIALS
intake have been studied, the mother's milk is the only source of calories for the suckling animal. Consequently, lactose is the main dietary carbohydrate. About the 14th postnatal day, the rat begins to consume some of the solid food present in his environment, and by the 30th postnatal day, the intake of milk ceases and the young rat is fuBy weaned. During the 14th to 21st day pancreatic amylase,S intestinal invertase,9-11 maltase, isomaltase, and trehelase l l increase in activity and reach adult levels by the 30th postnatal day. When the carbohydrate in the diet changes from lactose to polysaccharides 13galactosidase and f3-glucosidase activities decrease,12-14 while amylase and a-glucosidases increase.9-11 The association of dietary change and enzymatic activity levels was studied under varied experimental conditions to see if alteration of disaccharide supply could affect the normal enzymatic development in the intestine. It was observed in preliminary experiments that when a pregnant rabbit was mastectomized, no lactose was detected in the mother's blood during later gestation, and no change was noted in the usual prenatal increase of f3-galactosidase in the intestines of her offspring.12 Likewise if rats were weaned on a standard diet to which lactose was added, the usual decrease of f3-galactosidase activity seen between the 14th and 21st day of the animal life was not aItered.15 Only if the suckling rat is weaned, in the presence of the mother rat, on a diet where lactose is the only source of carbohydrate and is present in the same concentration as it is in rat's milk, is the usual decrease in 13galactosidase activity delayed. 13 A control group of animals, weaned in the same manner, but having isocaloric amounts of glucose and galactose present in the diet instead of lactose, showed the usual decrease of intestinal f3-galactosidase as those rats weaned on a standard diet. 13 Interestingly, the newborn guinea pig, which has a very low level of intestinal 13galactosidase activity, shows little decrease in this activity during development. 16. 17 In this species weaning begins soon after birth. Accordingly, the intake of milk is of
597
minor importance in nutrition and this animal's intake can be correlated weB with low intestinal f3-galactosidase activity. Furthermore, the lactating sea lion has no lactose in her milk, and her pups have no intestinal lactase. Thus far, no intestinal disaccharidases have been demonstrated in these species. 7 Adrenal cortical hormones have a profound effect on the development of intestinal disaccharidases. Injections of corticosterone or hydrocortisone (0.5 mg per 100 g of body weight per day) over a period of several days will precociously induce an increase in the activities of pancreatic amylases and intestinal invertase. 9 A single injection of hydrocortisone produces a transient induction of invertase activity, which then disappears, only to return at the usual time in development.9 The normal decrease of f3-galactosidase and increase of invertase activities observed between the 14th to 21st postnatal days can be delayed if adrenalectomy is performed on the 15th postnatal day.1s Administration of corticosterone or aldosterone abolishes the effect of adrenalectomy on the developmental pattern of these enzymes. IS Digestion of disaccharides has been investigated primarily using the substrates lactose and sucrose. When sea lions are fed sucrose, no elevation of blood glucose is noted, and a severe diarrhea ensues. This correlates well with their lack of intestinal disaccharidases. 7 Likewise, sucrose disappears from the lumen of the small intestine of 3-week-old piglets at a much faster rate than it does in l-week-old piglets. This finding is well correlated with the difference in invertase activity of piglets of these two age groups.19 The problem of lactose digestion is more complex than that of sucrose. In the sea lion no lactase is present and, therefore, no lactose is digested.7 In most animals that have been studied, there appears to be more than one enzyme with f3-galactosidase activity present. These enzymes differ in pH optimum, substrate specificity, and cellular localization. In the rat, guinea pig, and mouse,12. 13. 16. 17 the hydrolytic activity is greatest with the f3-galactosidase whose pH
598
EDITORIALS
optimum is 3.5, while in the rabbit the greatest activity is with the enzyme whose pH optimum is 5.8. 12 , 16, 17 Furthermore, the ,8-galactosidase activity located in the brush border (microvilli) of the suckling rat jejunum differs from the ,8-galactosidase activity located in the rest of the cell. 20 This observation has not as yet been described for other enzymes of the intestinal mucosa. Whether these are different enzymes or merely different stages of development of the same enzyme has not been elucidated. The presence of a ,8-galactosidase in the brush border of the intestine of suckling rats has been demonstrated by Doell et al. 21 using immunochemical techniques. Using everted intestinal sacs it has been shown that greater digestion of lactose occurred in suckling rabbits22 and rats 23 than in weaned animals. In all age groups of both species, only trace amounts of lactose appear on the serosal side of the sac. It thus appears that the activity of disaccharidases determined in an intestinal homogenate correlates well with the animal's ability to digest lactose, but other factors such as substrate specificity and availability of intestinal sites for hydrolysis, may also play an important role in the digestion of carbohydrates in the suckling animal. Some of the biochemical changes which occur in the small intestine during development and the factors which effect changes have been discussed. Further investigation and clarification of these changes as well as correlation of the developmental changes which occur in the human would be of significant benefit in understanding some of the gastroenterological problems encountered in infancy and childhood. O. Koldovsky, M.D., P. Sunshine, M.D., and N. Kretchmer, M.D., Ph.D. Department of Pediatrics Stanford University School of Medicine Palo Alto, California REFERENCES 1. Holzel, A., V. Schwarz, and K. W. Sutcliffe. 1959. Defective lactose absorption causing malnutrition in infancy. Lancet 1: 1126-1128. 2. Durand, P . [ed.]. 1964. Disorders due to in-
testinal defective carbohydrate digestion and
Vol. 50, No.4
absorption, p. 190. II Pensiero Scientifico, Rome. 3. Haemmerli, U. P., H. Kistler, R. Ammann, T. Marthaler, G. Semenza, S. Auricchio, and A. Prader. 1965. Acquired milk intolerance in the adult caused by lactose malabsorption due to a selective deficiency of intestinal lactase activity. Amer. J. Med. 38: 7-30. 4. Fomina, L. S. 1960. The activities of some enzymes in the intestine and other organs of human foetus [in Russian] Vop. Med. Khim. 6: 176-183. 5. Auricchio, S., A. Rubino, and G. Miirset. 1965. Intestinal glycosidase activities in the human embryo, fetus, and newborn. Pediatrics 35: 944-954. 6. H eilskov, N. S. C. 1952. Studies on animal
lactase . II. Distribution in some of the glands of the digestive tract. Acta Physiol. Scand. 24: 84-89. 7. Sunshine, P ., and N. Kretchmer. 1964. Absence of intestinal disaccharidases in two species of sea lions. Science 144 : 850-851. 8. Prochazka, P., P. Hahn, O. Koldovsky, M. Nohynek, and J. Rokos. 1964. The activity of a-amylase in homogenates of the pancreas of rats during early postnatal development. Physiol. Bohemoslov. 13: 288291. 9. Doell, R. G., and N. Kretchmer. 1964. In-
10.
11.
12.
13.
testinal invertase : Precocious development of activity after injection of hydrocortisone. Science 143: 42-44. Yezuitova, N. N., N. M. Timofeeva, O. Koldovsky, Y. A. Nurx, and A. M. Ugolev. 1964. The postnatal development of enzymatic activity of the mucosal surface of the small intestine of rats (invertase, peptidase, lipase). Proc. Acad. Sci. USSR 154: 990-992. Rubino, A., F . Zimbalatti, and S. Auricchio. 1964. Intestinal disaccharidase activity in adult and suckling rats. Biochim. Biophys. Acta 92: 305-311. Doell, R. G., and N. Kretchmer, 1962. Studies of small intestine during development. 1. Distribution and activity of ,a-galactosidase. Biochim. Biophys. Acta (12 : 353-362. Koldovsky, 0., and F. Chytil. 1965. Postnatal development of ,a-galactosidase activity in the small intestine of the rat. Effect of adrenalectomy and diet. Biochem. J. 94:
266-270. 14. Koldovsky, 0., V. Jirsova, and A. Heringova. 1965. ,a-Glucosidase activity in homogenates
of ileum and jejunum of rats of different ages. Physiol. Bohemoslov. 14: 228-232. 15. Alvarez, A., and J. Sas. 1961. fl-Galactosidase
April 1966
EDITORIALS
changes in the developing intestinal tract of the rat. Nature (London) 190 : 826-827. 16. DeGroot, A. P., and P. Hoogendoorn. 1957. The detrimental effect of lactose. II. Quantitative lactase determinations in various mammals. Neth. Milk Dairy J. 11: 290-303. 17. Koldovsky, 0., A. Heringova, V. Jirsova, F. Chytil, and J. Hoskova. 1966. Postnatal development of the ,,-galactosidase activity in the jejunum and ileum of mice, rabbits and guinea pigs. Canad. J. Biochem. Physiol. In press. 18. Koldovsky, 0., A. Heringova, and V. Jirsova. 1965. The effect of corticosterone and aldosterone on ,,-galactosidase activity in adrenalectomized infant rats. Nature (London) 206: 300---301. 19. Kidder, D. E., M. J. Manners, M. R. McCrea, and A. D. Osborne. 1964. Alimentary absorption of sugars by the piglet (Abstr.), p. 497.
In D. P . Cuthbertson, . C. F . Mills, and R. Passmore [ed.] Proceedings of the sixth inter-
599
national congress of nutrition. E. & S. Livingston Ltd., Edinburgh. 20. Koldovsky, 0., R. Noack, G. Schenk, V. Jirsova, A. Heringova, H. Brana, F. Chytil, and M. Fridrich. 1965. Activity of ,,-galactosidase in homogenates and isolated microvilli fraction of jejunal mucosa from suckling rats. Biochem. J. 96: 492--494. 21. Doell, R. G., G. Rosen, and N. Kretchmer. 1965. Immunochemical studies of intestinal disaccharidases during normal and precocious development. Proc. Nat. Acad. Sci. USA 54: 1268-1273. 22. Sterk, V. V., and N. Kretchmer. 1964. Studies
of the small intestine during development. IV. Digestion of lactose as related to lactosuria in the rabbit. Pediatrics 34: 609-614. 23. Koldovsky, 0., H. Muzycenkova, P. Hahn, A. Heringova, and V. Jirsova. 1965. Concerning the transport of lactose across the intestinal wall of infant rats. Canad. J. Physiol. Pharmacol. 43: 469-471.
GASTROENTEROLOGY
Copyright © 1966 by The Williams & Wilkins Co.
Printed in U.S.A.
EDITORIALS THE DIGESTION OF CARBOHYDRATES DURING POSTNATAL DEVELOPMENT The purpose of this communication is to discuss those recent advances in the developmental biochemistry of carbohydrate metabolism which have particular significance to gastroenterology. Holzel's description of siblings who had intolerance to lactose generated a great deal of interest in the study of intestinal disaccharidases. 1 There have been several excellent reviews of the clinical abnormalities associated with different types of disaccharidase deficiencies in man ;2. 3 therefore we will concentrate on the problems concerned with changes of disaccharidase activities in mammals during development, the factors which affect these changes, and the digestion of carbohydrates in the intestine of suckling animals. This is not intended as a comprehensive report but rather reflects our present convictions as to the importance of developmental phenomena in the study of digestion and absorption. The activity of intestinal disaccharidases of suckling mammals differs from that of the adult. ,B-Galactosidase and ,B-glucosidase activities are elevated in the suckling animal and decrease during the weaning period; the a-glucosidases (maltase, isomaltase, invertase, trehelase, and palatinase) are virtually absent in the suckling period, but increased activities occur during the weaning period. Th.is pattern of enAddress request for reprints to: Dr. P. Sunshine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California 94304. These investigations reported were supported in part by the John A. Hartford Foundation and by Research Grant A-03501 from the National Institute of Arthritis and Metabolic Diseases, United States Public Health Service. Dr. Koldovsky is on leave of absence from the Laboratory of Developmental Nutrition, Institute of Physiology of Czechoslovak Academy of Science, Praha-Podoli, Czechoslovakia. 596
zymatic development has been described in the intestine of the rat, dog, cow, rabbit, mouse, and pig, but not in man. Invertase has been found in the intestine of 2- to 3month-old human fetuses and reaches comparable adult levels of activity by the 35th to 36th week of intrauterine life. 4 • 5 Heilskov found no ,B-galactosidase activity in the human fetal intestine until the fifth month of gestation, but noted that the activity of this enzyme increased during the second half of intrauterine growth.6 Workers at the Prague laboratory, using o-nitrophenol ,B-galactoside as a substrate, detected ,B-galactosidase activity in the intestine of IO-week-old human fetuses (unpublished data). Using lactose as a substrate, Doell, Kretchmer, and Sunshine have likewise found ,B-galactosidase activity in the intestine of 3-month-old human fetuses and, by 36 weeks of age, the activity is comparable to that found in adults (unpublished data). Auricchio et al} studying the development of intestinal disaccharidases, have detected lactase (substrate lactose) in 2- to 3-monthold human fetuses. They have observed that the increase in activity of the ,B-galactosidases, lactase and cellobiase, occurs at a later date in the intrauterine growth period than do the activities of the a-glucosidases. Although there have been reports of lactase deficiency occurring in some adults, there is no evidence of change in activities of intestinal disaccharidases during later life. The only mammals that have been described with complete absence of intestinal disaccharidases are two species of sea lions. 7 The relationship of this finding to digestion is discussed below. Both diet and a maturing adrenal cortex have been considered as potential regulators of the changes in the developmental pattern of these sugar-splitting enzymes. In the rat, where most of the variations of dietary
April 1966
EDITORIALS
intake have been studied, the mother's milk is the only source of calories for the suckling animal. Consequently, lactose is the main dietary carbohydrate. About the 14th postnatal day, the rat begins to consume some of the solid food present in his environment, and by the 30th postnatal day, the intake of milk ceases and the young rat is fuBy weaned. During the 14th to 21st day pancreatic amylase,S intestinal invertase,9-11 maltase, isomaltase, and trehelase l l increase in activity and reach adult levels by the 30th postnatal day. When the carbohydrate in the diet changes from lactose to polysaccharides 13galactosidase and f3-glucosidase activities decrease,12-14 while amylase and a-glucosidases increase.9-11 The association of dietary change and enzymatic activity levels was studied under varied experimental conditions to see if alteration of disaccharide supply could affect the normal enzymatic development in the intestine. It was observed in preliminary experiments that when a pregnant rabbit was mastectomized, no lactose was detected in the mother's blood during later gestation, and no change was noted in the usual prenatal increase of f3-galactosidase in the intestines of her offspring.12 Likewise if rats were weaned on a standard diet to which lactose was added, the usual decrease of f3-galactosidase activity seen between the 14th and 21st day of the animal life was not aItered.15 Only if the suckling rat is weaned, in the presence of the mother rat, on a diet where lactose is the only source of carbohydrate and is present in the same concentration as it is in rat's milk, is the usual decrease in 13galactosidase activity delayed. 13 A control group of animals, weaned in the same manner, but having isocaloric amounts of glucose and galactose present in the diet instead of lactose, showed the usual decrease of intestinal f3-galactosidase as those rats weaned on a standard diet. 13 Interestingly, the newborn guinea pig, which has a very low level of intestinal 13galactosidase activity, shows little decrease in this activity during development. 16. 17 In this species weaning begins soon after birth. Accordingly, the intake of milk is of
597
minor importance in nutrition and this animal's intake can be correlated weB with low intestinal f3-galactosidase activity. Furthermore, the lactating sea lion has no lactose in her milk, and her pups have no intestinal lactase. Thus far, no intestinal disaccharidases have been demonstrated in these species. 7 Adrenal cortical hormones have a profound effect on the development of intestinal disaccharidases. Injections of corticosterone or hydrocortisone (0.5 mg per 100 g of body weight per day) over a period of several days will precociously induce an increase in the activities of pancreatic amylases and intestinal invertase. 9 A single injection of hydrocortisone produces a transient induction of invertase activity, which then disappears, only to return at the usual time in development.9 The normal decrease of f3-galactosidase and increase of invertase activities observed between the 14th to 21st postnatal days can be delayed if adrenalectomy is performed on the 15th postnatal day.1s Administration of corticosterone or aldosterone abolishes the effect of adrenalectomy on the developmental pattern of these enzymes. IS Digestion of disaccharides has been investigated primarily using the substrates lactose and sucrose. When sea lions are fed sucrose, no elevation of blood glucose is noted, and a severe diarrhea ensues. This correlates well with their lack of intestinal disaccharidases. 7 Likewise, sucrose disappears from the lumen of the small intestine of 3-week-old piglets at a much faster rate than it does in l-week-old piglets. This finding is well correlated with the difference in invertase activity of piglets of these two age groups.19 The problem of lactose digestion is more complex than that of sucrose. In the sea lion no lactase is present and, therefore, no lactose is digested.7 In most animals that have been studied, there appears to be more than one enzyme with f3-galactosidase activity present. These enzymes differ in pH optimum, substrate specificity, and cellular localization. In the rat, guinea pig, and mouse,12. 13. 16. 17 the hydrolytic activity is greatest with the f3-galactosidase whose pH
598
EDITORIALS
optimum is 3.5, while in the rabbit the greatest activity is with the enzyme whose pH optimum is 5.8. 12 , 16, 17 Furthermore, the ,8-galactosidase activity located in the brush border (microvilli) of the suckling rat jejunum differs from the ,8-galactosidase activity located in the rest of the cell. 20 This observation has not as yet been described for other enzymes of the intestinal mucosa. Whether these are different enzymes or merely different stages of development of the same enzyme has not been elucidated. The presence of a ,8-galactosidase in the brush border of the intestine of suckling rats has been demonstrated by Doell et al. 21 using immunochemical techniques. Using everted intestinal sacs it has been shown that greater digestion of lactose occurred in suckling rabbits22 and rats 23 than in weaned animals. In all age groups of both species, only trace amounts of lactose appear on the serosal side of the sac. It thus appears that the activity of disaccharidases determined in an intestinal homogenate correlates well with the animal's ability to digest lactose, but other factors such as substrate specificity and availability of intestinal sites for hydrolysis, may also play an important role in the digestion of carbohydrates in the suckling animal. Some of the biochemical changes which occur in the small intestine during development and the factors which effect changes have been discussed. Further investigation and clarification of these changes as well as correlation of the developmental changes which occur in the human would be of significant benefit in understanding some of the gastroenterological problems encountered in infancy and childhood. O. Koldovsky, M.D., P. Sunshine, M.D., and N. Kretchmer, M.D., Ph.D. Department of Pediatrics Stanford University School of Medicine Palo Alto, California REFERENCES 1. Holzel, A., V. Schwarz, and K. W. Sutcliffe. 1959. Defective lactose absorption causing malnutrition in infancy. Lancet 1: 1126-1128. 2. Durand, P . [ed.]. 1964. Disorders due to in-
testinal defective carbohydrate digestion and
Vol. 50, No.4
absorption, p. 190. II Pensiero Scientifico, Rome. 3. Haemmerli, U. P., H. Kistler, R. Ammann, T. Marthaler, G. Semenza, S. Auricchio, and A. Prader. 1965. Acquired milk intolerance in the adult caused by lactose malabsorption due to a selective deficiency of intestinal lactase activity. Amer. J. Med. 38: 7-30. 4. Fomina, L. S. 1960. The activities of some enzymes in the intestine and other organs of human foetus [in Russian] Vop. Med. Khim. 6: 176-183. 5. Auricchio, S., A. Rubino, and G. Miirset. 1965. Intestinal glycosidase activities in the human embryo, fetus, and newborn. Pediatrics 35: 944-954. 6. H eilskov, N. S. C. 1952. Studies on animal
lactase . II. Distribution in some of the glands of the digestive tract. Acta Physiol. Scand. 24: 84-89. 7. Sunshine, P ., and N. Kretchmer. 1964. Absence of intestinal disaccharidases in two species of sea lions. Science 144 : 850-851. 8. Prochazka, P., P. Hahn, O. Koldovsky, M. Nohynek, and J. Rokos. 1964. The activity of a-amylase in homogenates of the pancreas of rats during early postnatal development. Physiol. Bohemoslov. 13: 288291. 9. Doell, R. G., and N. Kretchmer. 1964. In-
10.
11.
12.
13.
testinal invertase : Precocious development of activity after injection of hydrocortisone. Science 143: 42-44. Yezuitova, N. N., N. M. Timofeeva, O. Koldovsky, Y. A. Nurx, and A. M. Ugolev. 1964. The postnatal development of enzymatic activity of the mucosal surface of the small intestine of rats (invertase, peptidase, lipase). Proc. Acad. Sci. USSR 154: 990-992. Rubino, A., F . Zimbalatti, and S. Auricchio. 1964. Intestinal disaccharidase activity in adult and suckling rats. Biochim. Biophys. Acta 92: 305-311. Doell, R. G., and N. Kretchmer, 1962. Studies of small intestine during development. 1. Distribution and activity of ,a-galactosidase. Biochim. Biophys. Acta (12 : 353-362. Koldovsky, 0., and F. Chytil. 1965. Postnatal development of ,a-galactosidase activity in the small intestine of the rat. Effect of adrenalectomy and diet. Biochem. J. 94:
266-270. 14. Koldovsky, 0., V. Jirsova, and A. Heringova. 1965. ,a-Glucosidase activity in homogenates
of ileum and jejunum of rats of different ages. Physiol. Bohemoslov. 14: 228-232. 15. Alvarez, A., and J. Sas. 1961. fl-Galactosidase
April 1966
EDITORIALS
changes in the developing intestinal tract of the rat. Nature (London) 190 : 826-827. 16. DeGroot, A. P., and P. Hoogendoorn. 1957. The detrimental effect of lactose. II. Quantitative lactase determinations in various mammals. Neth. Milk Dairy J. 11: 290-303. 17. Koldovsky, 0., A. Heringova, V. Jirsova, F. Chytil, and J. Hoskova. 1966. Postnatal development of the ,,-galactosidase activity in the jejunum and ileum of mice, rabbits and guinea pigs. Canad. J. Biochem. Physiol. In press. 18. Koldovsky, 0., A. Heringova, and V. Jirsova. 1965. The effect of corticosterone and aldosterone on ,,-galactosidase activity in adrenalectomized infant rats. Nature (London) 206: 300---301. 19. Kidder, D. E., M. J. Manners, M. R. McCrea, and A. D. Osborne. 1964. Alimentary absorption of sugars by the piglet (Abstr.), p. 497.
In D. P . Cuthbertson, . C. F . Mills, and R. Passmore [ed.] Proceedings of the sixth inter-
599
national congress of nutrition. E. & S. Livingston Ltd., Edinburgh. 20. Koldovsky, 0., R. Noack, G. Schenk, V. Jirsova, A. Heringova, H. Brana, F. Chytil, and M. Fridrich. 1965. Activity of ,,-galactosidase in homogenates and isolated microvilli fraction of jejunal mucosa from suckling rats. Biochem. J. 96: 492--494. 21. Doell, R. G., G. Rosen, and N. Kretchmer. 1965. Immunochemical studies of intestinal disaccharidases during normal and precocious development. Proc. Nat. Acad. Sci. USA 54: 1268-1273. 22. Sterk, V. V., and N. Kretchmer. 1964. Studies
of the small intestine during development. IV. Digestion of lactose as related to lactosuria in the rabbit. Pediatrics 34: 609-614. 23. Koldovsky, 0., H. Muzycenkova, P. Hahn, A. Heringova, and V. Jirsova. 1965. Concerning the transport of lactose across the intestinal wall of infant rats. Canad. J. Physiol. Pharmacol. 43: 469-471.