| 1. |
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| 2. |
- Korotkova, Marina, 1954, et al.
(author)
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Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats.
- 2004
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In: The British journal of nutrition. - 0007-1145. ; 92:4, s. 643-8
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Journal article (peer-reviewed)abstract
- PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6+n-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0.4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6+n-3 group than in the other groups. Cortical bone thickness in the n-6+n-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning.
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| 3. |
- Korotkova, Marina, 1954
(author)
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Essential fatty acids in the perinatal period. Short and long term effects in a rat model
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Nutritional factors during a sensitive perinatal period may lead to developmental adaptations proposed to program for pathological conditions later in life. An adequate supply of essential fatty acids (EFA) during pregnancy and lactation is crucial for optimal fetal and postnatal development. In animals and man, variations in the levels of EFA and in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) affect growth, development of the neuroendocrine and the immune systems of the offspring and might also have additional effects later in life via, for instance, leptin-associated mechanisms. The major aim of the study was to investigate whether variation in the type of dietary EFA during pregnancy and lactation in rats could modulate neonatal leptin levels and induce developmental adaptations that may persist into adulthood.A deficiency of both n-6 and n-3 EFA in the maternal diet resulted in decreased serum leptin levels in the offspring associated with reduction of both the amount of inguinal white adipose tissue (WAT) and the leptin mRNA expression in inguinal WAT. In addition, deficiency of EFA in the maternal diet affected also the milk leptin levels, which were higher in the EFA deficient dams than in the controls at 3 weeks of lactation. The serum leptin levels during the first week of age was two-fold less in the pups of dams fed the diet enriched in n-3 PUFA (n-3 diet) compared to the those fed the diet containing nine-fold more n-6 PUFA than n-3 PUFA (n-6/n-3 diet). Further increase in the dietary intake of n-6 PUFA (n-6 diet) did not elevate the leptin levels in the pups compared to the n-6/n-3 group. Both the lower adipose tissue mass and smaller adipocyte size could explain the lower serum leptin levels in the n-3 group. The data demonstrate that the total intake and the ratio of the n-3 and n-6 PUFA in the mother's diet modulated neonatal leptin levels. Furthermore, the maternal n-6/n-3 diet promoted increase in body weight, inguinal WAT mass and adipocyte size and suppressed leptin mRNA levels in WAT in the offspring. In order to study the long-term effects of the dietary intake of n-6 in relation to n-3 PUFA during the perinatal period, all offsprings were weaned onto an ordinary chow and followed up until 30 weeks of age. At postnatal week 28 the food intake and the mean body weight were significantly higher in the offsprings of the dams fed the n-6/n-3 diet during pregnancy and lactation compared to the other two diet groups. The fasting plasma insulin concentration was elevated in both the adult male and female rats of the n-6/n-3 group, but the systolic blood pressure was only increased in the adult male rats. The data suggest that the ratio of the n-6 to n-3 PUFA in the mother's diet have important long-term effects in the offspring. Variations in the dietary intake of PUFA during pregnancy and lactation seem to be important for development and programming, influencing the health of the offspring in adult life.
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| 4. |
- Korotkova, Marina, 1954, et al.
(author)
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Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids.
- 2005
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In: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 288:3
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Journal article (peer-reviewed)abstract
- Epidemiological studies in humans have shown that perinatal nutrition affects health later in life. We have previously shown that the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) in the maternal diet affects serum leptin levels and growth of the suckling pups. The aim of the present study was to investigate the long-term effects of various ratios of the dietary n-6 and n-3 PUFA during the perinatal period on serum leptin, insulin, and triacylglycerol, as well as body growth in the adult offspring. During late gestation and throughout lactation, rats were fed an isocaloric diet containing 7 wt% fat, either as linseed oil (n-3 diet), soybean oil (n-6/n-3 diet), or sunflower oil (n-6 diet). At 3 wk of age, the n-6/n-3 PUFA ratios in the serum phospholipids of the offspring were 2.5, 8.3, and 17.5, respectively. After weaning, all pups were given a standard chow. At the 28th postnatal wk, mean body weight and fasting insulin levels were significantly increased in the rats fed the n-6/n-3 diet perinatally compared with the other groups. The systolic blood pressure and serum triacylglycerol levels were only increased in adult male rats of the same group. These data suggest that the balance between n-6 and n-3 PUFA during perinatal development affects several metabolic parameters in adulthood, especially in the male animals.
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| 5. |
- Korotkova, Marina, 1954, et al.
(author)
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Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet
- 2002
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In: J Lipid Res. ; 43:10, s. 1743-9
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Journal article (peer-reviewed)abstract
- The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal development. We have previously shown that leptin levels in suckling rats are reduced by maternal PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and (n-6) PUFA on the leptin content in rat milk and serum leptin levels in suckling pups. For the last 10 days of gestation and throughout lactation, the rats were fed an isocaloric diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet), or soybean oil (n-6/n-3 diet). Body weight, body length, inguinal fat pad weight, and adipocyte size of the pups receiving the n-3 diet were significantly lower during the whole suckling period compared with n-6/n-3 fed pups. Body and fat pad weights of the n-6 fed pups were in between the other two groups at week one, but not different from the n-6/n-3 group at week 3. Feeding dams the n-3 diet resulted in decreased serum leptin levels in the suckling pups compared with pups in the n-6/n-3 group. The mean serum leptin levels of the n-6 pups were between the other two groups but not different from either group. There were no differences in the milk leptin content between the groups. These results show that the balance between the n-6 and n-3 PUFA in the maternal diet rather than amount of n-6 or n-3 PUFA per se could be important for adipose tissue growth and for maintaining adequate serum leptin levels in the offspring.
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| 6. |
- Korotkova, Marina, 1954, et al.
(author)
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Maternal dietary intake of essential fatty acids affects adipose tissue growth and leptin mRNA expression in suckling rat pups
- 2002
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 52:1, s. 78-84
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Journal article (peer-reviewed)abstract
- We have previously shown that maternal intake of essential fatty acids during late gestation and lactation affects the level of serum leptin in pups. The aim of the present study was to investigate the effect of dietary essential fatty acids on leptin content in the milk of rat dams and leptin expression in white adipose tissue of pups during the suckling period. During late gestation and throughout lactation, rats were fed a control or an essential fatty acid-deficient (EFAD) diet. Milk of the EFAD dams contained more saturated and less polyunsaturated fatty acids compared with the control dams. Milk leptin levels were higher in the EFAD dams than in the control dams at 3 wk of lactation. The weight of inguinal white adipose tissue depots and the serum leptin levels of the EFAD pups were significantly lower than in the control pups during the whole suckling period. In addition, semiquantitative reverse transcriptase-PCR analysis of leptin mRNA levels in inguinal white adipose tissue showed a reduction in the EFAD pups compared with the control pups at 3 wk of age. We conclude that maternal dietary essential fatty acid intake affects serum leptin levels in pups by regulating both the amount of adipose tissue and the leptin mRNA expression.
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| 7. |
- Korotkova, Marina, 1954, et al.
(author)
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Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups.
- 2001
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In: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 42:3, s. 359-365
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Journal article (peer-reviewed)abstract
- Dietary lipid quantity and quality have recently been shown to affect serum leptin levels in adult rats. Moreover, suckling pups from dams fed a high fat diet had increased serum leptin levels. The aim of the present study was to analyze the influence of essential fatty acid (EFA) deficiency on serum leptin levels in dams and their pups during the suckling period. For the last 10 days of gestation and throughout lactation, pregnant rats were fed a control or an EFA-deficient (EFAD) diet. The levels of leptin and EFA in the serum of the dams and pups were analyzed 1, 2, and 3 weeks after delivery. In parallel, serum levels of glucose and corticosterone were analyzed in the pups. Low serum leptin levels were found in the control lactating dams during the entire lactation period compared with the age-matched nonlactating animals. The leptin concentrations in the lactating dams fed the EFAD diet were lower compared with those fed the control diet. The serum leptin levels of suckling pups from dams on the EFAD diet were markedly decreased compared with controls (P < 0.05). The reduced serum leptin levels could not be explained by nutritional restriction as evaluated by serum levels of glucose and corticosterone. These results indicate the importance of the EFA composition of the maternal diet for serum leptin levels in both dams and pups. EFA deficiency in lactating dams may cause long-term effects on the pups through dysregulation of leptin and leptin-dependent functions. -- Korotkova, M., B. Gabrielsson, L. A. Hanson, and B. Strandvik. Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups. J. Lipid Res. 2001. 42: 359--365.
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| 8. |
- Korotkova, Marina, 1954, et al.
(author)
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Modulation of neonatal immunological tolerance to ovalbumin by maternal essential fatty acid intake
- 2004
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In: Pediatr Allergy Immunol. - 0905-6157. ; 15:2, s. 112-22
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Journal article (peer-reviewed)abstract
- The present study examines whether dietary essential fatty acid (EFA) intake influences the induction of oral tolerance to ovalbumin (OA) in neonatal and adult rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet supplemented (S) with EFA (7% soybean oil), or a diet deficient (D) in EFA (7% hydrogenated lard). The rat offspring were subsequently exposed to OA either via the milk at 10-16 days (neonatal rats), or as adults via the drinking water at 7-9 wk of age. Oral administration of OA to the adult rats lead to suppression of the delayed-type hypersensitivity (DTH) reactivity and IgG antibody response against OA, which was not influenced by their diets. In the offspring of the dams fed the D diet antigen exposure via the milk resulted in suppression of the serum antibody levels and DTH reaction against OA indicating induction of oral tolerance. Higher transforming growth factor beta (TGF-beta) mRNA levels in the draining lymph nodes suggested this to be mediated by regulatory T cells. In contrast, OA exposure of the dams fed the S diet did not result in a suppressed OA response of their offspring. Thus, the quality of FA ingested by the mother may have effects on the development of immunological tolerance to dietary antigens in the offspring. Our results might have importance for the understanding of the increase in allergy related to the Western type of diet.
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| 9. |
- Korotkova, Marina, 1954, et al.
(author)
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Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats.
- 2005
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In: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1686:3, s. 248-54
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Journal article (peer-reviewed)abstract
- Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, rats were fed a control or an EFA-deficient (EFAD) diet. At 3 weeks of age the offspring were weaned onto an ordinary chow and followed until adult age. The mean body weight of adult rats receiving the EFAD diet during the perinatal period was significantly increased from 12 weeks of age compared to the controls (P<0.05). Analysis by peripheral quantitative computerized tomography (pQCT) at 44 weeks of age showed that the trabecular volumetric bone mineral density (BMD) of the femur was significantly decreased (P<0.05) but the cortical bone mineral content, cortical area, and cortical thickness were increased (P<0.05) in the EFAD group of rats. The length of the femur was not affected. In conclusion, neonatal EFA deficiency was in adult rats associated with increased body weight and significant changes in both cortical and trabecular bone. The results indicate that regulatory mechanisms related to bone mass seemed to be programmed by EFA in the perinatal period. The nature of this modulation needs to be identified.
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| 10. |
- Korotkova, Marina, 1954, et al.
(author)
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The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin
- 2004
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In: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 137:2, s. 237-44
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Journal article (peer-reviewed)abstract
- Prevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet) or soybean oil (n-6/n-3 diet). At 10-16 days of age the rat offspring were subsequently exposed, or not, to OA via the milk. The offspring were weaned onto the same diets as the mothers and immunized with OA and the bystander antigen human serum albumin (HSA). In the offspring on the n-3 diet exposure to OA via the milk resulted in lower delayed type hypersensitivity reaction (DTH) and antibody responses against both OA and HSA, compared to those in the offspring not exposed to OA, indicating the induction of oral tolerance. In the offspring on the n-6 diet, the exposure to OA led to depressed specific immune responses against only OA, not HSA. In the offspring on the n-6/n-3 diet oral exposure to OA did not influence immune responses against OA, or HSA. The results indicate that the dietary ratio of n-6/n-3 FA is important for the induction of neonatal oral tolerance. Thus nonoptimal feeding may have effects on the development of immunological tolerance to dietary antigen ingested by the mother. The ratio of n-6/n-3 FA in the diet may be considered in the context of increased prevalence of allergy.
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| 11. |
- Mullazehi, Mohammed, 1966-, et al.
(author)
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Anti-type II collagen-IC-induced production of IL-1β and TNF-α, stimulate production of matrix met-alloproteinases from monocytes/rheumatoid arthritis synovial fibroblast co-cultures
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Other publication (other academic/artistic)abstract
- Objective: To establish an in vitro model that might explain the association between early joint destruction and the appearance of collagen type II (CII) antibodies in early Rheumatoid Arthritis (RA) patients. This RA pannus tissue model utilizes immune complexes (IC) containing CII-antibodies as stimulus and monocytes and synovial fibroblastsas responder cells. Methods: Peripheral blood mononuclear cells (PBMC) and RA synovial fibroblasts (RASF) were stimulated with IC individually as well in co-cultures. Monocytes were depleted to define the responder cells, and TNF-α and IL-1β were neutralized to study the effect on MMP production. TNF-α, IL-1β, MMP-1, MMP-8 and MMP-13 were measured in cell culture super-natants using ELISA.Results: Anti-CII-containing IC induced production of TNF-α, IL-1β and MMP-1 in PBMC cultures, and TNF-α, IL-1β, MMP-1 and MMP-8 in PBMC/fibroblast co-cultures, in a dose-dependent manner. IC-induced MMP-1 responses were stronger and more associated with induced produc-tion of IL-1β as compared to MMP-8 responses. Baseline production of IL-1β and MMP-1 increased significantly in co-cultures as compared to indi-vidual cultures, whereas this was not the effect for TNF-α and MMP-8. Monocyte depletion decreased TNF-α, IL-1β and MMP-1 production, while the effect on MMP-8 production was variable. Cytokine neutralization re-vealed that IL-1β was a stronger inducer of MMP-1 than was TNF-α.Conclusion:Synergistic actions between RASF and PBMC result in enhanced anti-CII IC-induced production of IL-1β and MMP-1. IL-1β and MMP-1 are regu-lated in parallel as anti-CII IC-induced IL-1β supports the production of MMP-1. MMP-8 seems to be regulated by other means. Anti-CII IC-induced TNF-α seems to be inferior to IL-1β concerning MMP-1 induction. The fact that IC stimulated synovial macrophages and fibroblasts to produce MMP, which are the first enzymes to cleave the interstitial collagens may explain the anti-CII-associated joint destruction apparent in early RA.
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| 12. |
- Ravi Sharma, Dulal, 1987, et al.
(author)
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Human Milk: Its Components and Their Immunobiologic Functions
- 2015
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In: Mucosal Immunology: Fourth Edition. Volume 2. - : Elsevier. - 9780124158474 ; , s. 2307-2341
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Book chapter (other academic/artistic)abstract
- Whereas a neonate is born is sterile, immediate exposure to its mother's mucosal surfaces allows it to acquire microflora, which plays an important role in defense against potential pathogens. This initial stimulus helps the immature immune system of the newborn to develop the capacity to respond with specific immunologic tolerance while avoiding the development of allergic and autoimmune disease. Breast-feeding provides nutritional and developmental, along with anti-infectious, advantages to the infant. The significant protection conferred by breast-feeding against varied infections such as acute and prolonged diarrhea, neonatal septicemia, respiratory tract infections, acute and recurrent otitis media, and urinary tract infections is observed worldwide. Human breast milk contains numerous components, including antibodies, cytokines, hormones, enzymes, and major proteins with multiple activities (microbicidal, tumoricidal, anti-inflammatory, autoimmune, etc.). Breast-feeding can strikingly reduce infant mortality, as well as the fertility of the breast-feeding mother. In this manner, breast-feeding provides significant benefits for lactating mothers and their offspring, in addition to society as a whole. © 2015 Elsevier Inc. All rights reserved.
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| 13. |
- Stern, N., et al.
(author)
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Subchronic toxicity of baltic herring oil and its fractions in the rat (III) bone tissue composition and dimension, and ratio of n-6/n-3 fatty acids in serum phospholipids
- 2005
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In: Basic Clin Pharmacol Toxicol. - : Wiley. - 1742-7835 .- 1742-7843. ; 96:6, s. 453-64
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Journal article (peer-reviewed)abstract
- Changes in total bone mineral density determined by the bone-ash method were recently demonstrated in rats, exposed to Herring oil from the contaminated southern part of the Baltic Sea. In the present study more detailed analysis of bone structure and biomechanics was performed and obtained results were evaluated in the context of dietary factors, such as polyunsaturated fatty acids, vitamin D and vitamin A. Baltic Sea herring oil was fractionated into one relatively pollutant-free fraction (F1), and two fractions with pronounced enrichment of pollutants (F2 and F3). Female Sprague-Dawley rats were fed diets supplemented with Baltic Herring oil, its fractions, Nordic Sea capelin oil or soy oil. Femur was scanned with peripheral quantitative computed tomography (pQCT) and also tested by a mechanical compression analysis. Polyunsaturated fatty acids, vitamin A and D were analysed in serum. Rats fed the high dose of herring oil exhibited shorter femur length with decreased diaphyseal cortical bone mineral density, as well as lowered metaphyseal cross-sectional area compared to the soy oil group. Rats fed the high dose of F1 diet had increased cortical and decreased trabecular area, and higher total and trabecular bone mineral density. Rats fed the low dose of F2 diet showed similar changes associated with increased maximum load and energy absorption in compression test of the femoral metaphysis. In summary, our findings in changes of bone geometry and density could not be linked to any isolated exposure parameter, suggesting synergistic or antagonistic effects of several components of the test diets.
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