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Biomedical subjects

M Vestergaard

Publications and source records attributed to M Vestergaard.

At least 19 recordsLinked to original sources
PubMed2006

Serum from heifer calves treated with bovine growth hormone affects the rate of proliferation of C2C12 myogenic cells dependent on the plane of nutrition: the role of insulin-like growth factor-I and IGF-binding proteins-2 and -3.

The present in vitro experiments were carried out in order to study whether variations in the bovine growth hormone (bGH)/insulin-like growth factor (IGF)-I axis induced by plane of nutrition and bGH treatment of heifer calves caused variations in serum-induced proliferation of C2C12 myoblasts. Serum was obtained from two groups each of six heifer calves (195 +/- 8 kg) before (d -1) and after treatment with 15 mg/day of bGH for 6 days (d 6) fed either a low (GHL) or a high plane (GHH) of nutrition. Preceding the experiment all 12 heifer calves were fed at the low plane of nutrition. At d 6, serum concentrations of insulin and IGF-I were increased while that of IGF-binding proteins (IGFBP)-2 was decreased in GHH, but unchanged in GHL calves. Serum-induced proliferation of C2C12 myoblasts, was elevated at d 6 by GHH treatment. Especially human IGFBP-3 but also bovine IGFBP-2 added to cell cultures inhibited the rate of proliferation of C2C12 myoblasts stimulated by human IGF-I. The present results showed that GH treatment causes changes in the GH/IGF axis, which leads to changes in serum-induced growth of C2C12 muscle cells dependent on the plane of nutrition that mimic in vivo effects of GH treatment, which indicate an endocrine contribution of the IGF system. However, drawbacks of this suggestion are discussed.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Leptin does not act directly on mammary epithelial cells in prepubertal dairy heifers.

The mammary gland of prepubertal dairy heifers consists of parenchyma expanding into the stroma, a matrix of connective and adipose tissue. High planes of nutrition increase stromal mass, but inhibit growth of parenchyma. The parenchyma consists of epithelial cells proliferating in response to growth factors such as insulin like growth factor-I (IGF-I). These observations have led to the hypothesis that elevated planes of nutrition increase leptin production, which in turn inhibits IGF-I-mediated epithelial cell proliferation. To assess this possibility, heifers were offered planes of nutrition sustaining average daily gains of 715 g/d (normal; NP) or 1,202 g/d (high; HP) from 42 d of age until slaughter at 240 kg. At slaughter, HP heifers had 2-fold greater plasma leptin concentration and 3-fold greater leptin mRNA abundance in mammary stroma and parenchyma. To assess the causal nature between leptin and parenchymal development, the induction of signaling events and functional responses in the MAC-T cell line and in primary mammary epithelial cells by leptin was examined. Leptin did not induce phosphorylation of signal transducers and activators of transcription (STAT)3, STAT5, extracellular signal-regulated kinase (ERK1/2), or AKT/Protein kinase B. Consistent with its inability to signal, leptin did not alter basal- or IGF-I-stimulated thymidine incorporation or increase suppressors of cytokine signaling 3 (SOCS3) expression in these cells. Transcripts corresponding to the short leptin receptor form were present in mammary tissue, but those corresponding to the long signaling form were not detected in either mammary tissue or cells. In conclusion, elevated planes of nutrition increase leptin synthesis in mammary stroma, but leptin does not act directly on bovine mammary epithelial cells.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Cell turnover and activity in mammary tissue during lactation and the dry period in dairy cows.

Milk yield of the dairy cow follows a pattern termed the lactation curve. We have investigated the cellular background for this pattern. Seven mammary biopsies were obtained from each of 10 cows: at the end of lactation (d 347, equal to d 77 before next parturition); during the dry period at d 48 (4 d after dry off); 16 d before parturition; and during lactation at d 14, 42, 88, and 172. The fraction of proliferating (staining positive for Ki-67) alveolar cells was higher during the dry period (8.6%) than during lactation (0.5%). The fraction of apoptotic (staining positive by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) alveolar cells was higher immediately after dry off (0.37%) and in early lactation (0.76%) than during other periods (0.15%). The enzyme activities of fatty acid synthetase, acetyl CoA-carboxylase, and galactosyl transferase were approximately 12-, 11-, and 4-fold higher, respectively, during lactation than during the dry period. In conclusion, mammary cell proliferation is substantial in a period near parturition but otherwise low, and apoptosis is elevated at dry off and in early lactation. The increase in apoptosis in early lactation may be due to discarding nonfunctional or senescent cells or to removal of a surplus of newly synthesized cells. The activity of selected enzymes central for milk synthesis is probably not limiting for milk production.

Animals↗
PubMed2005

Compliance with European guidelines for diagnostic mammography in a decentralized health-care setting.

PURPOSE: To evaluate the compliance of Danish mammography clinics with requirements concerning organization, activity volume, and assessment procedures from two European guidelines for quality assurance in diagnostic mammography (EUSOMA and EUREF). MATERIAL AND METHODS: We used individual records on all diagnostic mammographies performed in Denmark in 2000, and questionnaires given to Danish mammography clinics in 2000, 2002, and 2004. RESULTS: The study showed a marked centralization of the diagnostic activity from 2000 to 2004 to a smaller number of public breast assessment centers with full multidisciplinary breast assessment. However, a relatively large number of these centers did not comply with the activity volume requirement of 2000 mammograms per clinic per year. The number of private diagnostic mammography clinics performing basic diagnostic mammography has remained fairly stable in the period 2000 to 2004. Compared with public breast assessment centers, the private diagnostic mammography clinics had a lower compliance with activity volume requirements. CONCLUSION: A marked proportion of Danish public breast assessment centers operate with less than optimal activity volume, suggesting that further centralization would be appropriate. The situation in private diagnostic mammography clinics may cause concern, as our study showed that the majority of these clinics did not meet the activity volume requirements.

Ambulatory Care Facilities↗
PubMed2004

Additional dietary zinc for weaning piglets is associated with elevated concentrations of serum IGF-I.

Two experiments were performed in order to study how weaning and post-weaning dietary zinc level affect serum IGF-I. Further, whether the growth-enhancing effect of 2500 ppm of dietary zinc (Zn2500) and/or 175 ppm of dietary copper (Cu175) in post-weaning diets is associated with elevated serum IGF-I levels in piglets was studied. Experiment 1 included 54 piglets (six litters of nine piglets). One piglet from every litter was assigned to a control group (blood sampled 1 day before weaning). At weaning the remaining eight piglets from every litter were allocated randomly to four dietary treatments with increasing zinc inclusions (Zn100, Zn250, Zn1000, Zn2500). In exp. 2, 48 piglets (six litters of eight piglets) were allocated to four dietary treatments (Zn100, Zn100Cu175, Zn2500, Zn2500Cu175). All piglets in exp. 1 were blood sampled at -1, 1-2, 5-6 or 14-15 days after weaning and in exp. 2 blood samples were taken from all pigs 5-7 days after weaning. Feed intake was recorded per pen (two piglets) and weight gain was recorded for every piglet. Just after weaning feed intake was very low, piglets lost weight and serum IGF-I decreased in exp. 1. However, the piglets fed 2500 ppm of zinc reached pre-weaning levels of serum IGF-I at 14-15 days post-weaning, whereas piglets receiving lower zinc levels showed no changes in serum IGF-I. In exp. 2, additional dietary zinc in weaning diets for piglets was found to be associated with increased feed intake, improved growth rate and increased serum IGF-I. High levels of dietary copper did not affect any of these measurements. Zinc-induced rise in serum IGF-I was partly due to increased feed intake. After correcting for differences in feed intake, zinc significantly increased serum IGF-I. However, to completely separate effects of feed intake from effects of zinc status, pair-feeding should be considered in future studies.

Administration, Oral↗
PubMed2004

Effect of energy density in the diet and milking frequency on plasma metabolites and hormones in early lactation dairy cows.

The effects of energy density in the diet [low = 0.86 SFU/kg dry matter (DM) or high = 1.06 SFU/kg DM] and daily milking frequency (two or three times) in early lactation on plasma concentrations of metabolites and hormones were evaluated in 40 Holstein dairy cows arranged in a 2 x 2 factorial block design. The four treatment combinations were L2, L3, H2 and H3, and the experimental period comprised the first 8 weeks of lactation. Plasma glucose, insulin and insulin-like growth factor (IGF)-I concentrations were on average 8 (3.43 versus 3.19 mmol/l), 114 (41.6 versus 19.4 pmol/l) and 60% (91.9 versus 57.4 ng/ml) higher, whereas beta-hydroxybutyrate (BOHB), plasma urea nitrogen (PUN) and growth hormone (GH) concentrations were on average 18 (0.73 versus 0.89 mmol/l), 14 (7.18 versus 8.35 mmol/l), and 63% (1.0 versus 2.6 ng/ml) lower for cows fed diet H than for cows fed diet L. Cows milked three times daily had a 6% (3.20 versus 3.42 mmol/l) lower plasma glucose concentration and a 19% (0.88 versus 0.74 mmol/l) higher plasma concentration of BOHB compared with cows milked two times daily. Plasma non-esterified fatty acid (NEFA) concentration was not affected by either treatment. Overall, it is concluded that increasing the daily milking frequency creates a higher metabolic imbalance in early lactation. Cows in early lactation will benefit from receiving a high energy density diet and thereby avoid a too high metabolic imbalance when mobilizing body tissue in support of milk production.

3-Hydroxybutyric Acid↗
PubMed2003

Pre-eclampsia and febrile convulsions.

An association between pre-eclampsia and febrile convulsions has been reported, but the association may not be causal. We compared the risk of febrile convulsions in 14 974 children who had been exposed to pre-eclampsia in fetal life with that of 39 210 unexposed children. Children exposed to pre-eclampsia had a slightly increased risk of febrile convulsions, but the association was apparently caused by a shorter gestation in pre-eclamptic women.

Child, Preschool↗
PubMed2003

Effects of growth hormone and feeding level on endocrine measurements, hormone receptors, muscle growth and performance of prepubertal heifers.

Prepubertal Friesian heifer calves (n = 24, initial BW = 195 +/- 5 kg) were assigned to a 2 x 2 factorial block design and used to evaluate the effects of daily GH treatment (0 or 15 mg/d) at either a low or a high feeding level in a 5-wk treatment period on endocrine measurements, hormone receptors, muscle growth, and overall performance. In the pretreatment period, a low feeding level was employed for all calves. During the treatment period, animals at the low feeding level had free access to a roughage-based mixture, whereas animals at the high feeding level had free access to a concentrate mixture and were offered 2 kg/d of the roughage-based mixture. Blood samples were collected weekly starting 3 wk before treatment. Longissimus (LM) and supraspinatus (SS) muscles were obtained at slaughter. Metabolizable energy intake was 81% higher, digestible CP intake was 140% higher, and ADG was 115% higher (all P < 0.001) at the high vs. low feeding level. Feed (DMI, ME, and protein) intake was not affected by GH treatment, but ADG was 18% higher (P < 0.13) in GH-treated than in control heifers at both feeding levels. Although of different magnitudes, the muscle anabolic effects of GH treatment and high vs. low feeding level were additive, and both treatments increased carcass weights (P < 0.02 and P < 0.001, respectively), LM (P < 0.05 and P < 0.001), and SS (P < 0.06 and P < 0.003). The anabolic effect of GH treatment was similar in both muscles, whereas the effect of feeding level was most pronounced in LM. Overall, GH treatment increased plasma GH, IGF-I (both P < 0.001), and IGFBP-3 (P < 0.02); however, GH treatment increased total IGF-I, free IGF-I, and IGFBP-3, and decreased IGFBP-2 mainly at the high feeding level (GH x feeding level interaction; P < 0.02, 0.01, 0.03, and 0.10, respectively). The high feeding level increased insulin, free and total IGF-I, and IGFBP-3 (all P < 0.001), but decreased GH and IGFBP-2 (both P < 0.001). High feeding increased type-1 IGF receptor density (P < 0.02), mainly in LM, in accordance with the largest anabolic response in this muscle, whereas GH treatment had no effect on type-1 IGF receptors. The results suggest that in skeletal muscle, the anabolic effects of exogenous GH are related to endocrine changes in the GH-IGF axis, whereas the effects of feeding level also seem to rely on IGF receptor density in the muscles.

Animals↗
PubMed2003

Milk production, nutrient utilization, and endocrine responses to increased postruminal lysine and methionine supply in dairy cows.

The effect of increased postruminal supply of lysine and methionine was investigated in a production trial involving 64 dairy cows in early lactation. Within each of two basal rations, based on either corn silage or grass silage, rations were either naturally deficient in lysine or fortified with 24 g of lysine in a rumen-protected form and naturally deficient in methionine or fortified with 12 g of methionine in a rumen-protected form. The data were analyzed separately for the four lysine and the four methionine treatment groups. Milk production, body weight gain, and plasma concentrations of insulin-like growth factor-I, bovine somatotropin, insulin, glucose, nonesterified fatty acids, and urea were monitored over a 12-wk period. Supplementation with protected methionine led to increases in milk fat and protein contents of 2.4 and 1.8 g/kg of milk, respectively. Supplementation with protected lysine or methionine numerically increased protein yield comparable to values reported in the literature, but the treatment effects were not statistically significant. Efficiency of utilization of absorbed amino acids for milk protein synthesis and efficiency of utilization of metabolizable energy for milk production were not significantly altered in response to increased postruminal lysine and methionine flow, but a numerically increased efficiency of utilization of total amino acids was observed. No significant effect of lysine or methionine supplementation was observed on endocrine parameters nor on plasma metabolite concentrations. However, across treatment groups, high milk yield was correlated with low plasma insulin-like growth factor-I concentrations (r = -0.44) and partially with low plasma nonesterified fatty acids concentration and insulin levels (r = -0.26), while body weight gain was negatively correlated (r = -0.33) with elevated plasma bovine somatotropin concentrations.

Animal Feed↗
PubMed2002

Febrile convulsions and sudden infant death syndrome.

It has been suggested that sudden infant death syndrome (SIDS) and febrile convulsions are related aetiologically. We compared the risk of SIDS in 9877 siblings of children who had had febrile convulsions with that of 20 177 siblings of children who had never had febrile convulsions. We found no support for the shared susceptibility hypothesis.

Child, Preschool↗
PubMed2001

Effects of a four-day hyperinsulinemic-euglycemic clamp in early and mid-lactation dairy cows on plasma concentrations of metabolites, hormones, and binding proteins.

The effects of insulin, using a 4 d hyperinsulinemic-euglycemic clamp, on plasma concentrations of hormone, metabolites, and binding proteins were evaluated in four Holstein dairy cows during wk 4 and 17 of lactation. Insulin was infused at 1 microg/kg/hr for 96 hr during the clamp period. Compared with the pre-clamp period, plasma insulin concentrations increased 7-fold and 4-fold during the clamp periods in early and mid-lactation, respectively. The total amount of glucose infused was higher (P < 0.05) during the clamp in early lactation. The clamp decreased plasma concentrations of non-esterified fatty acids (P < 0.001) during early lactation while differences in mid-lactation were minor. The clamp also decreased plasma concentration of beta-hydroxybutyrate (P < 0.001), plasma urea nitrogen (P < 0.001), and true protein (P < 0.01) although the patterns of decline differed between early and mid-lactation. Growth hormone (GH) concentrations decreased (P < 0.001) and insulin-like growth factor-1 (IGF-1) increased (P < 0.01) during the clamp period suggesting a direct effect of insulin on the un-coupling of the GH/IGF-1 axis. Levels of IGF binding protein-2 (IGFBP-2) decreased (P < 0.01) during the clamp period. The relative proportion of IGFBP-2 decreased (P < 0.001) and that of IGFBP-3 increased (P < 0.001) during the clamp period. There were no interactions between the clamp period and stage of lactation on GH, IGF-1, or IGFBPs. Overall, most plasma variables measured were affected in the same way during the two clamps, but the pattern of change often varied with stage of lactation.

3-Hydroxybutyric Acid↗
PubMed2000

Involvement of growth factors in the regulation of pubertal mammary growth in cattle.

Pubertal mammary growth in heifers is dependent on interactions of many hormones and growth factors of which some are stimulatory while others are inhibitory. Although estrogen and growth hormone (GH) are of primary importance, more recent studies have suggested a role for both systemic and mammary tissue-specific growth factors. Growth factors may act as mediators of estrogen and GH or through specific effects of their own. These growth factors include insulin (INS), IGFs (IGF-I and IGF-II), epidermal growth factor (EGF), FGFs (FGF-1 and FGF-2), TGFs (TGF-alpha and TGF-beta's, amphiregulin (AR), platelets derived growth factor (PDGF), and mammary derived growth factor-1 (MDGF-1). Using mammary epithelial cells derived from prepubertal heifers and cultured in three-dimensional collagen gels as an in vitro model, we have investigated the mitogenic effects of a number of different growth factors (IGF-I, des(1-3) IGF-I, IGF-II, INS, EGF, TGF-alpha, AR, FGF-1, FGF-2, and TGF-beta 1). As expected, IGF-I, des(1-3)IGF-I, IGF-II and INS all stimulated proliferation of mammary cells with des(1-3)IGF-I being the most potent and INS the least potent. The mitogenic effect of IGF-I could be inhibited by both IGFBP-2 and IGFBP-3 showing that these binding proteins modulate the bioactivity of IGF-I in the mammary gland at the cellular level. Regulation of IGF availability by IGFBPs in the extracellular environment therefore is critical for IGF action in the mammary gland. Proliferation of mammary epithelial cells was also stimulated by growth factors of the EGF family, i.e. EGF, TGF-alpha and AR, however, not as much as growth factors from the IGF family. Members of the fibroblast growth factor family showed various mitogenic activities. FGF-1 stimulated DNA synthesis while FGF-2 in concentrations above 10 ng/ml inhibited DNA synthesis. TGF-beta 1 at very low concentrations stimulated proliferation slightly whereas higher concentrations strongly inhibited proliferation of mammary epithelial cells and inhibited mitogenesis induced by growth factors of both the EGF- and IGF family. This shows that TGF-beta 1 is a very potent regulator of pubertal mammary growth.

Animals↗
PubMed2000

High body weight gain and reduced bovine mammary growth: physiological basis and implications for milk yield potential.

Available evidence concerning the relationship between growth rate, mammary growth and milk yield in heifers leads to these conclusions: 1) Increased growth rate due to high feeding level before puberty onset can lead to reduced pubertal mammary growth and reduced milk yield potential. 2) Increased growth rate due to high feeding level after puberty and during pregnancy have no effect on mammary growth and milk yield. 3) Higher body weight gain due to higher genetic potential for growth is positively related to milk yield. The negative effect of high feeding level before puberty occurs in all breeds, but the level of feeding causing reduced yield varies. Variation in responses between experiments suggests that feeding regimes that support high growth rates without negative effect on yield can be developed. A breakthrough most likely will originate from increased knowledge of the physiological relationship between nutrition and mammary development. Our investigations suggest that blood growth hormone (GH) is important for mammary development, and that the negative effect of high feeding level on mammary development may be due to reduced blood GH. GH, however, does not bind to mammary tissue. Experiments with exogenous GH suggest that GH acts on mammary tissue via IGF-I, but IGF-I is increased by high feeding level - not decreased as GH. This paradoxical relationship cannot be explained by changes in circulating IGF binding proteins. However, the sensitivity of mammary tissue to IGF-I is reduced by high feeding level, probably due to the action of locally produced binding proteins and/or growth factors.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Nutritional and somatotropin regulation of the mitogenic response of mammary cells to mammary tissue extracts.

Our objective was to investigate the mitogenic response of primary mammary epithelial cells to extracts of mammary parenchyma from 24 prepubertal Friesian heifers treated with placebo or growth hormone at either a low or a high feeding level. The mitogenic responses to mammary extracts were tested by using primary mammary epithelial organoids obtained from prepubertal heifers cultured for 4 to 5 d in collagen gels in serum-free medium supplemented to 5% concentration of the mammary extracts. Cell proliferation was determined using [methyl-3H]thymidine incorporation as a measure of DNA synthesis. High feeding level reduced DNA synthesis in response to mammary extracts. At low feeding level, growth hormone treatment decreased DNA synthesis in response to mammary extracts whereas, at high feeding level, growth hormone increased DNA synthesis in response to mammary extracts. These results suggest that locally produced growth factors are involved in the regulation of mammary development when mammary growth is modulated by feeding level and growth hormone treatment.

Animal Feed↗
PubMed2000

Local IGF-I axis in peripubertal ruminant mammary development.

The regulation of mammary growth and development in heifers is accomplished by complex interactions of hormones, growth factors, and extracellular matrix molecules. Many of these growth stimulators are believed to be locally produced in the mammary gland and to be affected by developmental and nutritional status. Although estrogen and growth hormone are considered critical to pubertal mammogenesis, results summarized in this review suggest that IGF-I and IGF binding proteins are especially important locally-produced growth regulators in peripubertal ruminants. This assertion is supported by studies of ovariectomized heifers, in which increased stromal IGFBP-3 and reduced IGF-I correspond with a failure of udder development. Similarly, reduced mammary development with overfeeding coincides with reduced mitogenic activity of mammary tissue extracts and altered concentrations of IGF-I and IGFBPs. In vitro studies convincingly demonstrate that much of the mitogenic activity of mammary extracts or serum can be attributed to IGF-I and that alterations in IGFBP-3 modulate its effectiveness. Thus by analogy to second messenger mechanisms of action for protein hormones, local mammary-derived growth factors likely explain many of the effects attributed to the classic mammogenic hormones.

Animals↗
PubMed2000

Regulation of local synthesis of insulin-like growth factor-I and binding proteins in mammary tissue.

Our objective was to investigate the mammary expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins in prepubertal heifers and regulation of IGF-I by bovine somatotropin (bST) and feeding level. Twenty-four prepubertal Friesian heifers were divided into six blocks according to genotype and starting date for the experiments. Within blocks, heifers were assigned to daily bST treatment (0 or 15 mg/d) at low or high feeding level (0.55 kg/d or 1.1 kg/d average daily gain, respectively) for 5 wk so that the mean body weight and standard error was approximately equal for all four treatment groups. At high feeding level, content of IGF-I protein in mammary tissue extracts was increased 46% by somatotropin compared with placebo. Somatotropin tended to increase abundance of IGF-binding protein-3 (40 to 43 kD) in mammary extracts. High feeding level increased abundance of a 24-kD binding protein and reduced abundance of IGF-binding protein-2 (32 kD) in mammary extracts. High feeding level reduced abundance of IGF-binding protein-1 mRNA in mammary tissue, but there was no significant effect of feeding level or somatotropin on mRNA levels of other IGF-binding proteins. These results suggest that effects of somatotropin treatment and feeding level on the prepubertal mammary gland are mediated in part by alterations in local synthesis of IGF-I and IGF-binding proteins.

Animals↗
PubMed1999

Growth hormone and mammary development.

Classic studies in rodents conducted in the 1950s showed that growth hormone (GH) is essential for mammary development both in the pubertal phase and during pregnancy. Since then, a considerable number of experiments have been carried out in ruminants to investigate the role of GH for regulation of normal mammary development and to examine the possibility of enhancing mammary growth by administration of GH. The available evidence demonstrates that GH treatment stimulates mammary growth before puberty, but the data do not convincingly support the idea that the effect is translated into increased milk yield. GH treatment during late pregnancy seems to stimulate both mammary growth and milk yield during lactation. The limited data concerning the effect of GH on mammary growth during lactation indicate that mammary growth is unaffected by GH treatment in early lactation, whereas GH seems to increase the amount of mammary parenchyma in mid-lactation. The mechanism of action of GH remains a puzzle, but the effect of exogenous GH most likely involves insulin-like growth factor-I (IGF-I). Full understanding of the role of endogenous GH for regulation of normal mammary development requires more knowledge about the interaction between GH and IGF-I and the interplay between the GH-IGF-I axis and locally produced factors, including receptors, binding proteins, and growth factors.

Animals↗