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Biomedical subjects

P E Hartmann

Publications and source records attributed to P E Hartmann.

At least 37 records · Page 2Linked to original sources

Maintenance of villus height and crypt depth, and enhancement of disaccharide digestion and monosaccharide absorption, in piglets fed on cows' whole milk after weaning.

The aims of the present study were (a) to maintain the structure and function of the small intestine of the piglet after weaning, and (b) to compare the capacity in vivo of sucking and weaned piglets to digest oral boluses of lactose and sucrose and absorb their monosaccharide products. Piglets were fed on cows' whole milk ad libitum every 2 h for 5 d after weaning. Physiological doses of lactose plus fructose (treatment LAC+FRU) and sucrose plus galactose (treatment SUC+GAL) were administered on day 27 of lactation and on the fifth day after weaning, after which time piglets were killed. Villus height and crypt depth were maintained (P > 0.05) by feeding cows' milk after weaning. The areas under the curves (AUC) for galactose and glucose, adjusted for live weight and plasma volume, increased (P < 0.05) after weaning. Despite the enhancement of gut function after weaning, the galactose index (GalI:AUC for galactose ingested as lactose divided by the AUC for the same dose of galactose ingested as the monosaccharide) and fructose index (FruI: AUC for fructose ingested as sucrose divided by the AUC for the same dose of fructose ingested as the monosaccharide), which are indices of digestive and absorptive efficiency, both decreased after weaning. This apparent anomaly may be reconciled by increased growth, and hence surface area, of the small intestine between weaning and slaughter such that 'total' digestion and absorption most probably increased despite apparent decreases in GalI and FruI. Positive correlations (P < 0.05) between villus height and GalI are consistent with the maximum activity of lactase occurring more apically along the villus. Significant linear relationships (P < 0.05) were recorded between villus height at the proximal jejunum and adjusted AUC for galactose and glucose following treatment LAC+FRU, and between villus height at the proximal jejunum and adjusted glucose AUC following treatment SUC+GAL. These relationships suggest that maximum digestion and absorption occurs at increasing distances along the crypt:villus axis in the weaned pig.

Animals↗

Frequency and degree of milk removal and the short-term control of human milk synthesis.

The effect of the temporal spacing and degree of milk removal by either expression or breastfeed on short-term (hour to hour) rates of milk synthesis was investigated. For four expressing mothers (three of whom had given birth prematurely), the relationship between milk produced at an expression and the time since the last expression showed that proportionally less milk is produced after intervals of 6-18 h than after intervals of less than 6 h (P < 0.0002). For five breastfeeding and four expressing mothers (three of whom had given birth prematurely), rates of milk synthesis (ranging from 0 to 56 ml/h) were linear between breastfeeds and expressions (intervals ranging from < 1 h to 6 h). Changes in rate of milk synthesis were not directly associated with the frequency of breastfeeds but rather with the degree of emptying of the breast (P < 0.05). These results indicate the importance of degree, rather than frequency, of breast emptying in the short-term control of human milk synthesis.

Adult↗

Blood and milk prolactin and the rate of milk synthesis in women.

In women, the concentration of prolactin in the plasma increases in response to nipple stimulation. This response has led to the assumption that prolactin influences the rate of milk synthesis. To investigate this hypothesis we have measured 24 h milk production, the short-term (between breastfeeds) rates of milk synthesis and the concentration of prolactin in the blood and breastmilk, from 1 to 6 months of lactation in eleven women. Over the long term, the 24 h milk production remained constant (means +/- S.E.M.): 708 +/- 54.7 g/24 h (n = 11) and 742 +/- 79.4 g/24 h (n = 9) at 1 and 6 months, respectively. The average short-term rate of milk synthesis (calculated from the increase in breast volume between breastfeeds; means +/- S.E.M.) did not change: 23 +/- 3.5 ml/h (n = 23) and 23 +/- 3.4 ml/h (n = 21) at 1 and 6 months, respectively. However, significant variation in the short-term rate of milk synthesis (from < 5.8 to 90 ml/h) was found both between breasts, measured concurrently (coefficient of variation, c.v. = 72%), and within the same breast, measured over consecutive breastfeeds (c.v. = 85%). The basal and suckling-stimulated concentrations of prolactin in the plasma (means +/- S.E.M.) declined from 1 to 6 months (basal, from 119 +/- 93 to 59 +/- 29 micrograms/1; peak, from 286 +/- 109 to 91 +/- 44 micrograms/l). In contrast, the concentration of prolactin in milk was much lower than in plasma, and decreased only slightly from 1 to 6 months of lactation (fore-milk, from 26.4 +/- 10 to 23.3 +/- 9.8 micrograms/l; hind-milk, from 18.9 +/- 5.1 to 13.2 +/- 6.3 micrograms/l). The concentration of prolactin in the milk was related to the degree of fullness of the breast, such that the concentration was highest when the breast was full. We found no relationship between the concentration of prolactin in the plasma and the rate of milk synthesis in either the short or long term. However, the relationship between the concentration of prolactin in milk and the degree of fullness of the breast suggests that the internalization of prolactin, after binding to its receptor, may be restricted when the alveolus is distended with milk.

Adult↗

Assessment of mammary gland metabolism in the sow. I. Development of methods for the measurement of cellular metabolites in milk and colostrum.

We have modified deproteinization methods and a number of spectrophotometric and bioluminescent methods in order to measure the concentrations of cellular metabolites in small volumes (< 0.3 ml) of sows' colostrum and milk. For the majority of the assays, recoveries ranged from 92 to 105%. The binding of ATP and UTP to a calcium phosphate-citrate-caseinate complex in milk, and the decrease in ATP (92%/h) and UTP (18.1%/h) concentrations during in vitro incubation of the whey fraction suggested that it was unlikely ATP and UTP (both < 1 microM) could exist free in sows' milk. The mean concentrations (range) of cellular metabolites in milk (6-11 d post partum) were: glucose, 669 microM (220-1367); glucose 6-phosphate, 63.0 microM (27.6-101.4); glucose 1-phosphate, 18.3 microM (13.1-24.8); UDPglucose, 296 microM (170-494); UDPgalactose, 635 microM (230-945); lactose, 162 mM (124-187); UDP, 105 microM (85-130); UMP, 1760 microM (1326-2587); inorganic phosphate, 13.5 mM (1.4-29.3); ATP, < 0.5 microM; ADP, 53.6 microM (10.5-171.25); AMP, 215 microM (61.6-491.6); cAMP, 22.3 microM (3.5-61.6); galactose, 198 microM (118-474) and fructose, 226 microM (172-283). Differences in the concentrations of glucose, glucose 6-phosphate, glucose 1-phosphate, UDPgalactose and cAMP between fore and hind milk samples indicated postsecretory changes in the concentrations of certain metabolites. Changes in the concentrations of metabolites during in vitro incubation of milk and of colostrum suggested that these postsecretory changes were probably due to the actions of enzymes present in mammary secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Assessment of mammary gland metabolism in the sow. II. Cellular metabolites in the mammary secretion and plasma during lactogenesis II.

The concentrations of lactose, glucose, glucose 6-phosphate, glucose 1-phosphate, UDPglucose, UDPgalactose, UDP, UMP, inorganic phosphate, ADP and AMP (metabolites involved in the lactose synthesis pathway), and cAMP, galactose and fructose were measured in the mammary secretion from sucked (n = 9) and unsucked (n = 4) mammary glands of nine sows during the first 5 d post partum. The concentrations of lactose, glucose, galactose and fructose were also measured in plasma during this time. The progressive increase in the concentration of lactose, and changes in the concentrations of cellular metabolites in the mammary secretion from sucked glands were consistent with an increase in the metabolic activity of those glands during lactogenesis II. In contrast, unsucked glands showed a progressive decrease in the concentration of lactose, while the concentrations of cellular metabolites in the milk generally remained unchanged. These results indicated that there was no increase in the metabolic activity of unsucked glands (no increase in lactose synthesis or utilization of glucose and ATP) and that the rate of lactose synthesis prior to milk removal was limited by the availability of glucose and/or UDPgalactose. Therefore, the removal of colostrum from the mammary gland was necessary for an increase in the rate of lactose synthesis (and probably de novo fatty acid synthesis) and implies that autocrine mechanisms are operating to control the rate of milk synthesis during lactogenesis in the sow. The low concentration of glucose in colostrum compared with that in plasma is discussed in view of the paracellular pathway.

Animals↗

Assessment of mammary gland metabolism in the sow. III. Cellular metabolites in the mammary secretion and plasma following weaning.

The concentrations of lactose, glucose, glucose 6-phosphate, glucose 1-phosphate, UDPglucose, UDPgalactose, UDP, UMP, inorganic phosphate, ADP and AMP (metabolites involved in the lactose synthesis pathway), and cAMP, galactose and sodium were measured in the mammary secretion from four or five mammary glands on each of six sows during the first 5 d post weaning. The concentrations of lactose, glucose and galactose were also measured in plasma during this time. Following weaning, the rapid increase in the concentrations of glucose 6-phosphate and UDPgalactose suggested that the rate of lactose synthesis was regulated by the inhibition of hexokinase and/or lactose synthase, while the decrease in glucose and AMP indicated a subsequent decline in glucose and ATP utilization. The rapid increase in glucose 6-phosphate which plays a pivotal role as a substrate for both lactose and de novo fatty acid synthesis, and the rapid decrease in AMP which reflects ATP utilization, were good markers of decreased metabolic activity. These rapid changes in the metabolic activity of the mammary glands were not observed in a second weaning study when two piglets were removed from selected mammary glands for periods up to 5 h during established lactation. Since concentrations of lactogenic hormones remain elevated following partial weaning, but fall following total weaning (Rojkittikhun et al. 1991), these differences in mammary gland metabolism indicate that endocrine rather than autocrine mechanisms are controlling lactose and fat synthesis during the initial stages of total weaning.

Animals↗

The responses of blood galactose to oral doses of lactose, galactose plus glucose and milk to piglets.

The capacity of intestinal lactase (EC 3.2.1.23) of piglets to hydrolyse lactose in vivo was investigated by measuring the response of blood galactose to doses of lactose, galactose plus glucose and both whole and skimmed milk. Following the administration of oral doses of lactose dissolved in water to piglets from 2 to 18 d of age the adjusted galactose area under the curve (AUC) was between 1.12 and 1.36 arbitrary units, while following a dose of galactose plus glucose dissolved in water it was between 1.56 and 1.98 arbitrary units. Whereas these results suggest that the rate of digestion of lactose appeared to limit the amount of galactose reaching the peripheral blood after a dose of lactose dissolved in water, there was no significant correlation between the capacity of piglets to hydrolyse physiological amounts of lactose and the age of the piglets (2- to 18-d-old piglets; r 0.11). Following oral doses of sow's milk containing either lactose, or galactose plus glucose, the adjusted galactose AUC values were 0.94 and 1.00 arbitrary units respectively, in 10-d-old piglets. Thus, the limitation to the digestion of lactose observed when it was present in water was not evident for lactose in sow's milk. Since there was no significant difference between the adjusted galactose AUC following a dose of whole milk (0.95 arbitrary units) and that following a dose of skimmed milk (1.03 arbitrary units), the presence of fat in sow's milk did not appear to affect the utilization of lactose by the sucking piglets.

Animals↗

Infant demand and milk supply. Part 1: Infant demand and milk production in lactating women.

This first part of a two-part commentary examines evidence for the notion that human milk production is at least in part controlled by the infant's appetite. The studies that we review, of milk production by breastfeeding and expressing mothers, strongly support this hypothesis. Therefore, in established lactation and with a demand feeding regime, a mother's milk production is likely to be a reflection of her infant's appetite, rather than her ability to produce milk, which may in fact be several-fold higher. However, previous studies of human milk production have not provided a clear insight into how the lactating breast matches milk production to infant demand.

Appetite↗

Infant demand and milk supply. Part 2: The short-term control of milk synthesis in lactating women.

In this second part of our two-part commentary, milk production and milk synthesis are defined and the methods that may be used in their measurement are briefly reviewed. In particular, the rationale for the development of breast volume measurement techniques is described. We review our studies which have employed breast volume measurement techniques and propose a model for the short-term control of milk synthesis in lactating women. According to this model, the breast responds to the degree to which the infant empties the breast at each breastfeed. The frequency of milk removal may not directly affect the rate of milk synthesis except as a function of the mother's ability to store milk.

Appetite↗

The response in the blood of piglets to oral doses of galactose and glucose and intravenous administration of galactose.

The kinetics of the response in the blood of piglets to physiological oral intakes of galactose and glucose, and intravenous administration of galactose are described. Following the intravenous administration of galactose to 2- and 10-d-old piglets (n 7), the half-life was 7.98 (SD 0.75) and 7.99 (SD 1.89) min respectively, and efficient elimination rate was 9.09 (SD 2.15) and 8.75 (SD 0.79)% per min respectively. The turnover of galactose in the piglets was 100.3 micrograms/min per kg body weight. These observations demonstrate that galactose was rapidly removed from the blood of the piglets. While the dosing and sampling procedures stimulated hyperglycaemia, they had no effect on the concentration of galactose in the peripheral plasma. The galactose area under the curve (adjusted to the plasma volume of the animal) following a dose of either galactose or galactose plus glucose was 1.75 (SD 0.15) and 1.95 (SD 0.14) arbitrary units respectively in 2-d-old piglets and 1.96 (SD 0.26) and 1.98 (SD 0.10) arbitrary units respectively in 10-d-old piglets. Since the presence of glucose did not lower the adjusted area under the curve for galactose in the peripheral blood, the effect of glucose on the metabolism of galactose in piglets was more like that reported for rats than that for man, guinea-pigs or mice. It is suggested that the galactose moiety of lactose may make an important contribution to the replenishment of liver glycogen in the neonatal piglet.

Administration, Oral↗

Metabolites of lactose synthesis in milk from diabetic and nondiabetic women during lactogenesis II.

The concentrations of lactose, glucose, glucose 6-phosphate (G6P), glucose 1-phosphate (G1P), UDPglucose (UDPglc), UDPgalactose (UDPgal), and inorganic phosphate (P(i)) (metabolites in the lactose synthesis pathway) were measured in mammary secretion from nondiabetic (ND) and insulin-dependent diabetic (IDD) mothers during the first 10 days postpartum to determine their relationship with the amount of lactose synthesized and their association with the delay in lactose synthesis in IDD mothers. For all mothers the concentrations of all metabolites were low initially, and in ND mothers the first increases occurred as follows: lactose--day 2; glucose, G6P and P(i)--day 3; G1P and UDPglc--day 4; and UDPgal--day 6. The first increases for IDD mothers occurred 1-4 days later than for ND mothers. The concentrations of glucose, G6P, G1P, UDPglc, and P(i) were related to the amount of lactose synthesized. Since the rate of lactose synthesis and concentrations of other metabolites were less than half-maximal while the concentration of glucose was low, and since there was a delay in the increase in mammary gland concentrations of glucose in IDD mothers, it is concluded that glucose availability has the potential to play a role in the regulation of the rate of lactose synthesis at lactogenesis II.

Animals↗

Concentration of citrate in the mammary secretion of sows during lactogenesis II and established lactation.

The functional significance of citrate in the mammary secretion of six sows was investigated during the second stage of lactogenesis (lactogenesis II) and established lactation. The changes in the concentrations of progesterone and lactose in the maternal blood, and lactose, Na and K in the mammary secretion, suggested that lactogenesis II began during the final day of pregnancy. The concentration of citrate in the mammary secretion of the sows during lactogenesis II was high and varied from 5.4 (SEM 0.5) mM at day 0.5 post partum to 6.8 (SEM 0.4) mM at day 1.5 post partum. There was a decline of approximately 30% in the concentration of citrate in the milk of sows during the first week of lactation. These findings suggest that, in contrast to all other species studied previously, milk citrate is not a harbinger of lactogenesis II in the sow. However, the changes in the concentration of citrate in the mammary secretions of sows may reflect changes in the rate of de novo synthesis of fatty acids that take place in the mammary glands of sows during lactogenesis II and established lactation.

Animals↗

The short-term synthesis and infant-regulated removal of milk in lactating women.

We studied how short-term milk synthesis responds to milk removal by observing breast volume before and after each breastfeed over 24 h periods within the homes of seven lactating mothers, using the Computerized Breast Measurement system. Short-term rates of milk synthesis varied markedly between the breasts of individual mothers, varied markedly between interfeed intervals for individual breasts and, for six of the thirteen breasts studied, were positively related to the degree to which the breast was emptied (r2 ranging from 0.32 to 0.95). In addition, the infants rarely emptied the breasts of available milk (mean +/- S.D. of degree of emptying postfeed = 76 +/- 20%, n = 147) and, within women, storage capacity of a breast was related to the demand for milk from that breast (r2 = 0.91, P < 0.0001). It was concluded that the infants were self-regulating their milk intake. Furthermore, the storage capacity of the breast, variations in the short-term rates of milk synthesis and responsiveness of milk synthesis to the degree of breast emptying provided mechanisms whereby maternal milk supply could be directly linked to infant demand. Our findings are discussed with reference to the autocrine control of milk synthesis.

Breast↗

Degree of breast emptying explains changes in the fat content, but not fatty acid composition, of human milk.

We compared within and between breastfeed changes in milk fat to short-term rates of milk synthesis and degree of breast emptying (measured using the Computerized Breast Measurement system) over two 24 h periods for five lactating mothers. The fat content (f) of fore and hind milk samples increased more steeply as the breast was progressively emptied by the infant (degree of emptying, d, range 0-1; f = 21.59 + 9.38d + 70.99d2; P < 0.0001; r2 = 0.68; n = 154). For the nine individual breasts, between 41-95% of the variance of the fat content of milk was explained by degree of breast emptying. We argue that this relationship explains differences in the circadian rhythm of the fat content of milk and allows the accurate calculation of the average fat content of milk consumed by infants (37-66 g/l for the nine individual breasts). The fatty acid composition of the fore and hind milk samples was determined for four of the mothers. We observed within and between breastfeed variability in the relative proportions of the seven major fatty acids of milk fat and these changes are discussed with reference to the control of fat synthesis in the human mammary gland.

Breast↗

Calcium, phosphate and citrate in human milk at initiation of lactation.

The onset of copious milk secretion (lactogenesis II) in women occurs between 1 and 3 d after birth, and during this period the composition of breast milk changes. During the first 5 d of lactation we measured the concentrations of total, diffusible and ionized Ca (Catot, Cad, Ca2+), diffusible phosphate (Pid), diffusible citrate (Citd) and lactose in the breast milk. On day 1 after birth the concentrations (mean +/- SEM) were Catot, 5.71 +/- 0.30 mM; Cad, 2.66 +/- 0.19 mM; Ca2+, 2.90 +/- 0.18 mM; Pid, 0.26 +/- 0.16 mM; Citd, 0.25 +/- 0.03 mM and lactose, 76 +/- 11 mM. Between day 1 and day 4 the concentration of Catot increased 1.7-fold to 9.56 +/- 0.39 mM, Cad increased 1.8-fold to 4.75 +/- 0.26 mM, Ca2+ decreased by 20% to 2.33 +/- 0.13 mM, Pid increased 6.6-fold to 1.69 +/- 0.11 mM, Citd increased 20-fold to 5.06 +/- 0.21 mM, and lactose increased 2.3-fold to 173 +/- 4 mM. A high correlation has been found between [Cad] and [Citd] in the milk of both ruminant and non-ruminant species, which show a wide range in concentrations of [Cad] and [Citd], and the data fit a simple physicochemical model of ion equilibria in the aqueous phase of milk. The results of the present study confirm the relationship between [Cad] and [Citd] in human milk, even during lactogenesis II when the composition of the milk is changing very rapidly.

Adult↗

Collection of fore and hind milk from the sow and the changes in milk composition during suckling.

A new sampling method for the collection of fore and hind milk from the sow has been developed which resembles normal milk removal by the piglet, yet overcomes the difficulties of collecting milk that is available for only a short time (10-20 s) at each let-down. Samples of hind milk were collected immediately after the completion of a successful sucking, while the fore milk was collected at the beginning of the next natural let-down. Modification of existing assays for fat, protein and lactose was required to provide rapid analysis of the small volumes (less than 0.5 ml) of milk collected using this procedure, and these methods were validated by comparison with reference methods. Total solids and the concentration of fat in whole milk, and protein and lactose in skim milk, were measured in fore and hind milk collected from 4, 20, 12 and 12 sows respectively, 6-11 d post partum. For fore milk, the results (mean +/- SD (n)) were: total solids, 199.9 +/- 9.9 g/l (8); fat, 96.7 +/- 13.9 g/l (41), protein, 47.7 +/- 4.5 g/l (27) and lactose, 58.3 +/- 4.0 g/l (27). In hind milk, there was a significant increase in the concentration of fat (15.3 g/l, P less than 0.001, n = 41) which was reflected by a significant increase in total solids (14.7 g/l, P less than 0.001, n = 8) and calculated energy (511 kJ/l, P less than 0.001, n = 27), but there was no significant difference in the concentration of either protein or lactose. This increase in milk fat during milk let-down is in contrast to the results of most previous studies in the sow and is discussed in terms of the possible mechanisms that may cause the concentration of fat to increase as milk is removed from the mammary gland.

Animals↗

The determination of short-term breast volume changes and the rate of synthesis of human milk using computerized breast measurement.

The feasibility of using sequential breast volume measurements as a method of studying short-term rates of milk synthesis in women has been established. We have developed a rapid Computerized Breast Measurement system for the determination of breast volume, based upon the Shape Measurement System. A circle encompassing all the breast tissue is drawn in black face paint on the subject's skin. Six patterns of sixty-four horizontal light stripes are projected onto the breast and chest wall surface. A CCD camera relays video images to a computer, which produces a model of the chest by active triangulation. The volume of the breast and the chest wall segment enclosed by the circle is then calculated. The precision of the method was dependent upon the subject repositioning carefully. The coefficient of variation of replicate measurements was 1.6%. The accuracy of the method was established by comparing the change in breast volume before and after a breast-feed with the amount of milk removed by the infant as determined by test weighing. There was a close relationship between the removal of milk by the infant (x) and the change in breast volume (y), (r = 0.93, n = 73, y = 1.10x - 3.25). The rates of milk synthesis between breast-feeds, for six women determined on one to eight occasions, varied from 11 to 58 ml/h. The results show that the amount of milk available in the breast is not necessarily an important determinant of the amount of milk removed by the infant at a breast-feed.

Breast↗