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Biomedical subjects

V E Baracos

Publications and source records attributed to V E Baracos.

At least 19 recordsLinked to original sources
PubMed2005

Effects of bovine somatotropin on beta-casein mRNA levels in mammary tissue of lactating cows.

Bovine somatotropin (bST) increases milk production in lactating cows through its effect on nutrient partition and maintenance of mammary cell function. A positive relationship between bST treatment and abundance of beta-casein mRNA in mammary tissues from lactating cows was hypothesized. In mammary tissue isolated from 14 midlactation Holstein cows, beta-casein mRNA was 35.4% higher among 7 cows receiving continuous bST infusions at 29 mg/d for 63 d compared with tissue from 7 untreated control cows. To investigate whether increased beta-casein mRNA resulted from a direct effect of bST on the mammary gland, explants of mammary tissue from other lactating cows that had not received bST were incubated with bST and prolactin in 2 experiments. Mammary explant cultures taken from 2 lactating cows that had not been milked for 48 h were supplemented with either prolactin or bST. Both prolactin and bST stimulated higher levels of beta-casein mRNA in the mammary explants compared with their non-supplemented counterparts. Explant cultures from 4 additional lactating cows were prepared from rear quarter mammary tissue subjected to milking intervals of 6 h for right rear quarters or 20 h for left rear quarters. Both bST- and prolactin-mediated increases in beta-casein mRNA were dependent on milking intervals. That is, levels of beta-casein mRNA were increased by bST or prolactin supplementation in explants isolated from the mammary quarters biopsied 20 h after milking but not for those biopsied at 6 h after milking. Results are consistent with a potential role for bST in up-regulating or sparing beta-casein mRNA levels in lactating bovine mammary tissue in a manner similar to prolactin.

Animals↗
PubMed2003

Selective protein loss in lactating sows is associated with reduced litter growth and ovarian function.

This study was designed to test the degree of protein loss that may be sustained by lactating sows before milk biosynthesis and ovarian function will be impaired. First-parity Camborough x Canabrid sows were allocated to receive isocaloric diets (61 +/- 2.0 MJ of ME/d) and one of three levels of protein intake in lactation: 1) 878 g of CP and 50 g of lysine/d (n = 8), 2) 647 g of CP and 35 g of lysine/d (n = 7), or 3) 491 g of CP and 24 g of lysine/d (n = 10). Every 5 d during a 23-d lactation, sow live weight, backfat depth, and litter weight were recorded, and a preprandial blood sample was collected. Milk samples were collected on d 10 and 20 of lactation. Sows were slaughtered on the day of weaning, and liver and ovarian variables were measured. Lower dietary protein intakes elicited progressively larger live weight losses during lactation (-13, -17, and -28 +/- 2.3 kg; P < 0.001), but similar and minimal backfat losses (-1.3 +/- 0.29 mm). Approximately 7, 9, and 16% of the calculated body protein mass at parturition was mobilized by d 23. Lactation performance did not differ among treatments until d 20, at which time approximately 5, 6, and 12% of the calculated protein mass at parturition had been lost. The milk protein concentration on d 20 of lactation reflected the amount of body protein lost, and was lowest (P < 0.05) in sows that lost the most protein. After d 20, piglet growth rate decreased (P < 0.05) in a manner related to the amount of body protein lost. At weaning, ovarian function was suppressed in sows that had mobilized the most body protein; they had fewer medium-sized follicles (> 4 mm; P < 0.05), their follicles contained less (P < 0.01) follicular fluid, and had lower estradiol (P < 0.05) and IGF-I (P < 0.10) contents. Culture media containing 10% pooled follicular fluid (vol/vol) from high-protein-loss sows were less able to support nuclear and cytoplasmic maturation of oocytes in vitro, evidenced by more oocytes arrested at metaphase I (P < 0.05) and showing limited cumulus cell expansion (P < 0.06). Plasma insulin and IGF-I concentrations did not seem to be related to the observed differences in animal performance. Our data suggest that no decline in lactational performance or ovarian function when a sow loses approximately 9 to 12% of its parturition protein mass. However, progressively larger decreases in animal performance are associated with a loss of larger amounts of body protein mass at parturition.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Parturition body size and body protein loss during lactation influence performance during lactation and ovarian function at weaning in first-parity sows.

We investigated the effect of body protein mass at parturition and different degrees of body protein loss in lactation on sow performance. In a 2 x 2 factorial arrangement, 77 Genex gilts were fed to achieve either a standard or high body mass at parturition and to lose either a moderate (MPL) or high (HPL) amount of protein in lactation. Pregnant gilts were fed either 24.4 MJ of ME, 266 g of CP, and 11 g of lysine/d or 34.0 MJ of ME, 436 g of CP, and 20 g of lysine/d resulting in divergent (P < 0.01) live weights (165 vs. 193 kg) and calculated protein masses (24.3 vs. 30.0 kg) and slightly different backfat depths (20.0 vs. 22.8 mm; P < 0.05) at parturition. Diets fed during lactation were formulated to deliver 731 g of CP and 37 g of lysine/d or 416 g of CP and 22 g of lysine/d to induce differential body protein mobilization. Sows were slaughtered at weaning (d 26), and the weight of the organs and the lean, fat, and bone in five primal cuts was measured. The external diameter of the eight largest follicles on each ovary was recorded, and the follicular fluid from these follicles was collected, weighed, and analyzed for estradiol. Losses in lactational live weight (26 vs. 20 kg; P < 0.01) and calculated protein mass (17.8 vs. 10.7%; P < 0.001) were greater, and the carcass lean mass at weaning was 10% lighter (P < 0.05) in HPL sows. Backfat (5.1 +/- 0.8 mm; P = 0.29) and calculated fat mass (25.8 +/- 1.5%; P = 0.84) losses did not differ between treatments. Both sow body mass (P < 0.05) and lactation protein loss (P < 0.01) affected litter growth rate. Litter growth rate decreased (P < 0.05) at the end of lactation in HPL sows once these sows had lost 10 to 12% of their calculated protein mass. Ovarian follicular development was most advanced in high body mass sows that lost the least protein; these sows had the heaviest (P < 0.05) uterine weight and highest (P < 0.05) follicular fluid estradiol concentration. Follicular development was least advanced in standard body mass sows that lost the most protein. These sows had the lowest (P < 0.05) muscle:bone ratio at weaning and likely lost the largest proportion of their muscle mass compared with the other treatments. In conclusion, ovarian function at weaning and litter performance was higher in high body mass sows and in sows that lost the least protein in lactation, suggesting that a larger lean mass may delay the onset of a decrease in performance in sows that lose protein in lactation.

Adipose Tissue↗
PubMed2002

Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation.

Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12+/-1 g day(-1)) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20 : 4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20 : 4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils.

Adult↗
PubMed2002

Elevated rate of collagen solubilization and postmortem degradation in muscles of lambs with high growth rates: possible relationship with activity of matrix metalloproteinases.

The extracellular matrix, composed mainly of collagen, is considered responsible for the residual toughness of meat. Matrix metalloproteinases (MMP) responsible for the degradation of connective tissue are found in most tissues, but their participation in meat aging has not been tested. We recently showed that skeletal muscle has multiple MMP activities, as well as regulators and tissue inhibitors of metalloproteinases. Here we present the first observations of physiologic and postmortem variation of MMP activities in muscle. Growing lambs were offered two levels of intake: hay + concentrate for lambs with high growth rate (average daily gain > 250 g) and hay only for those with low growth rate (average daily gain < 25 g). At slaughter and at 21 d of postmortem aging of longissimus and semimembranosus muscles, we studied collagen content, collagen solubility, free hydroxyproline (OH-pro), and levels of latent and active forms of a matrix metalloproteinase (MMP-2) by gelatin zymography. Our results demonstrate the presence of an active isoform of MMP-2 in lamb muscle. Its level was higher (+90%, P < 0.01) in lambs that expressed a high growth rate. Activity of MMP-2 was also present at 21 d postmortem, at levels similar to those detected at slaughter. At slaughter and at 21 d, all muscles contained latent MMP-2 and the quantity of proenzyme was greater than that present in the activated form. The levels of free OH-pro in muscles of lambs with high growth rate increased significantly (P < 0.001) over 21 d from 3.75 to 5.08% of total collagen, and this was significantly related to the level of active MMP-2 at slaughter. By contrast, the amount of free OH-pro in muscles of lambs with low growth rate was not different at 21 d (1.63% of total OH-pro) than it had been at slaughter (1.84% of total OH-pro). These results suggest that collagen degradation all the way to free amino acids occurs postmortem in muscle and that there are active MMP simultaneously present that may account for this catabolism. The growth rate of animals at slaughter influences collagen turnover in vivo, as well as postmortem collagen degradation.

Animals↗
PubMed2001

Management of muscle wasting in cancer-associated cachexia: understanding gained from experimental studies.

BACKGROUND: Cancer-associated cachexia is a syndrome of progressive wasting of body energy (adipose) and protein (skeletal muscle) reserves. Cachexia occurs in a majority of advanced cancer patients. Extensive loss of muscle mass is one factor likely to be associated with fatigue in cancer patients. METHODS: Research with animal models of cancer-associated cachexia that have focused on the processes of muscle protein synthesis and degradation are reviewed in this article. Modulation of the production or action of anabolic and catabolic factors known to regulate muscle protein synthesis and degradation have been employed to identify causal factors in muscle wasting. RESULTS: Impaired muscle protein synthesis and activation of catabolism participate in cancer-associated muscle atrophy. The relative roles of multiple factors, including a low level of physical activity, poor nutritional status, and secretion of catabolic mediators of host or tumor origin, are discussed herein. A diversity of putative mediators has been identified, and a number of common themes are beginning to emerge. CONCLUSIONS: Multiple distinct catabolic profiles exist in animal models of cancer-associated muscle wasting. The presence of these catabolic phenotypes in cancer patients must be determined, and the application of successful treatments will depend on our ability to determine which categories of patients experience the greatest benefit.

Animals↗
PubMed2001

Nutrition and athletic performance.

This supplement is based on presentations made at the "First International Congress on Nutrition and Athletic Performance" held at the Shaw Conference Centre, Edmonton, Alberta, Canada, August 8-11, 2001. This conference was stimulated by an increasing awareness of the potential benefits and risks of diet modification and supplementation for elite athletic performance. This supplement summarizes recent findings and commentary on new research directions in nutrition and athletic performance by 22 invited plenary speakers from around the world.

Humans↗
PubMed2001

Coordinate expression of matrix-degrading proteinases and their activators and inhibitors in bovine skeletal muscle.

Matrix metalloproteinases (MMP) responsible for degradation of connective tissue are found in most tissues. The MMP are regulated at the levels of transcription, zymogen activation by plasmin or membrane-type- (MT) MMP, and control of enzyme activity by tissue inhibitors of metalloproteinases (TIMP). Whole bovine skeletal muscle showed multiple MMP activities on gelatin zymography and also expressed mRNA encoding MMP-1, -2, -9, -14, and -16, tissue inhibitors of metalloproteinase (TIMP)-1, -2, and -3 and plasminogen activator and its receptor. Purified intramuscular fibroblasts and myogenic cell culture derived from satellite cells expressed most or all of these elements. Statistical analysis (n = 35) revealed a strong positive correlation among the mRNA levels of several elements of the MMP system, including MMP-2, MMP-14, TIMP-1, -2, and -3 (r = 0.614 to 0.930, P < 0.0001). Our results provide an extensive profile of an extracellular proteolytic cascade involving MMP in skeletal muscle and suggest that 1) the activation cascades of muscle MMP may be initiated by both plasmin and membrane-type MMP; 2) a group of genes involved in the same "arm" of zymogen activation are coexpressed in this tissue; and 3) skeletal muscle cells, in addition to the intramuscular fibroblasts, express an extensive complement of MMP and related proteins.

Animals↗
PubMed2000

Regulation of skeletal-muscle-protein turnover in cancer-associated cachexia.

Cancer is frequently associated with anorexia, weight loss, negative nitrogen balance, and skeletal-muscle wasting. Depletion of skeletal-muscle mass is critical to overall survival of the patient, can prolong rehabilitation to normal function after recovery, and decreases quality of life in a palliative-care setting. The biochemical and physiologic bases of cancer-associated muscle wasting have been most fully investigated in animal models. These studies provide evidence for suppressed protein synthesis and activated proteolysis in cancer-associated muscle wasting and indicate a need for both anabolic and anticatabolic therapies. Several humoral factors of host or tumor origin are implicated in altered muscle-protein metabolism, including cytokines, metabolites of arachidonic acid, and a proteolysis-inducing glycoprotein; their interrelationships are less well characterized. Several catabolic mediators may share common downstream mechanisms because they ultimately activate the ATP-, ubiquitin-, and proteasome-dependent intracellular proteolytic system. Although important gaps in our current understanding remain, data available from animal studies can be used as a basis to develop relevant studies in human subjects.

Animals↗
PubMed2000

Anabolic and catabolic mediators of intestinal protein turnover: a new experimental approach.

Studies on regulation of protein turnover in skeletal muscle have revealed the important contributions of protein synthesis and catabolism to tissue protein balance, and have identified a host of specific anabolic and catabolic stimuli and biochemical mechanisms that regulate these processes. This knowledge is critical to current efforts designed to promote anabolism and limit atrophy. Of the tissues with a potentially large contribution to whole-body amino acid metabolism, protein turnover of the intestine stands out as being poorly understood. The intestine is subject to complexities in regulation of its metabolism that are not apparent for other tissues. The study of intestinal protein turnover also entails some important technical challenges. We recently developed an in-situ experimental system for study of intestinal mucosal protein synthesis with the following unique features: multiple observations within an animal; controlled delivery of nutritional stimuli to the apical side, basolateral side, or both; and luminal delivery of tracer in a flooding dose for determination of protein synthesis. We have begun to use the system to test the specific roles of individual luminal nutrients in regulation of mucosal protein synthesis. We have also used protease gene expression as an index of potential regulation of catabolic pathways.

Animals↗
PubMed2000

Cytokines and endotoxin induce cytokine receptors in skeletal muscle.

Proinflammatory cytokines are important factors in the regulation of diverse aspects of skeletal muscle function; however, the muscle cytokine receptors mediating these functions are uncharacterized. Binding kinetics (dissociation constant = 39+/-4.7 x 10(-9) M, maximal binding = 3.5+/-0.23 x 10(-12) mol/mg membrane protein) of muscle tumor necrosis factor (TNF) receptors were obtained. Skeletal muscle was found to express mRNAs encoding interleukin-1 type I and II receptors, interleukin-6 receptor (IL-6R), and interferon-gamma receptor by RT-PCR, but these receptors were below limits of detection of ligand-binding assay (> or =1 fmol binding sites/mg protein). Twenty-four hours after intraperitoneal administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA were increased in skeletal muscle (P<0.05). In cultured L6 cells, the expression of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-alpha, and all six cytokine receptor mRNA were induced by a mixture of TNF-alpha, IFN-gamma, and endotoxin (P<0.05). This suggests that the low level of cytokine receptor expression is complemented by a capacity for receptor induction, providing a clear mechanism for amplification of cytokine responses at the muscle level.

Animals↗
PubMed2000

The activity of transcription factor Stat5 responds to prolactin, growth hormone, and IGF-I in rat and bovine mammary explant culture.

Signal transducer and activator of transcription-5 (Stat5) is known to play a critical role in prolactin-induced beta-casein gene transcription in rodents. In nonmammary cells, Stat5 is activated by multiple hormones and cytokines, including growth hormone. We hypothesized that Stat5 may serve as a common point in the signal transduction pathways of hormones that promote milk protein gene expression in bovine mammary cells, which are regulated by GH and IGF-I in addition to prolactin. Assays for Stat5 DNA binding activity and protein were validated in mammary explant culture. The Stat5 protein abundance was not changed by any of the short-term hormonal treatments used in our study, suggesting that short-term regulation of Stat5 is predominantly at the level of protein activation. Both rat and bovine explant culture showed a rapid stimulation of Stat5 DNA binding activity by prolactin, GH, and IGF-I at the high concentrations typically used in explant cultures as well as at levels within physiologic ranges. Growth hormone stimulated Stat5 activity at a lower concentration in bovine than in rat cultures, but in both species the presence of GH increased the response of Stat5 activity to prolactin. These results suggest that transcription factor Stat5 may represent part of a common route by which different extracellular signals converge and are transduced intracellularly to coordinately regulate cell function in the mammary gland.

Animals↗
PubMed2000

Physiological levels of Stat5 DNA binding activity and protein in bovine mammary gland.

Signal transducer and activator of transcription (Stat)5 has been implicated in the signal transduction pathways of several factors that are lactogenic or galactopoeitic in mammary cells, including prolactin, GH, and IGF-I. Data from cell or explant culture support the concept that Stat5 may represent part of a common route by which different extracellular signals converge and are transduced into the cell. There are few data on Stat5 activity and level in vivo, and we set out to determine whether physiological stimuli of milk synthesis, including GH, GH-releasing factor, and milking frequency, would be associated with alterations in Stat5 activity or protein. We measured Stat5 DNA binding activity using electrophoretic mobility shift assay and Stat5 protein by Western blot in bovine mammary tissue obtained by biopsy or slaughter. Stat5 activity was absent in nonlactating, nonpregnant cows and was present in late pregnancy and throughout lactation. Stat5 activity varied considerably among cows at similar stages of lactation. Mammary Stat5 activity and protein were determined in hormone-treated lactating cows and mammary quarters of cows milked at different frequencies. Infusion of GH and GH-releasing factor for 2 mo significantly raised levels of milk production and depressed mammary Stat5 activity without influencing Stat5 protein abundance. Mammary Stat5 was also influenced by milking frequency; once-daily milking reduced milk production, Stat5 activity, and protein abundance compared with twice-daily milking. Analysis of mammary Stat5 in relation to milk protein concentration in pooled data from lactating cows indicated that Stat5 activity was correlated (r = 0.505, P < 0.05) with average milk protein concentration and not related to milk protein yield (P > 0.05). These results show that both Stat5 protein and Stat5 activity are modulated by different physiological signals in vivo and suggest that Stat5 lies within in the zone where signal transduction cascades from a variety of factors are convergent. Further work is required to clarify the role of Stat5 in relation to other factors in regulation of milk protein gene expression.

Animals↗
PubMed1999

Luminal amino acids acutely decrease intestinal mucosal protein synthesis and protease mRNA in piglets.

Because parenteral feeding is associated with negative N balance and reduced rates of protein synthesis in intestinal mucosa, we hypothesized that luminal exposure to specific amino acids or energy fuels would stimulate intestinal protein synthesis. We studied the acute effects of luminal nutrients on mucosal protein synthesis in the absence of systemic influences. Multiple jejunal segments constructed in piglets deprived of food overnight (n = 6) were randomly assigned to luminal perfusion with saline, 30 mmol/L amino acid mixture with or without 50 mmol/L glucose, or 30 mmol/L glutamine for 90 min. Protein synthesis was then measured by luminal perfusion with L-[2,6-(3)H]-phenylalanine. Energy substrates (glucose, short-chain fatty acids or beta-hydroxybutyrate) had no effect on mucosal protein synthesis. Relative to saline, a 30 mmol/L amino acid mixture or 30 mmol/L glutamine suppressed mucosal protein synthesis by 20-25% (P < 0.05). On the basis of these surprising results, we speculated that a coordinate reduction of proteolytic processes would be required to maintain positive intestinal N balance. Although intestinal protein catabolism cannot be assessed directly, the 30 mmol/L amino acid mixture acutely suppressed mucosal levels of mRNA encoding ubiquitin, 14-kDa ubiquitin conjugating enzyme and the C9 subunit of the proteasome by 20-30% (P < 0.05), demonstrating the sensitivity of components of the ATP-ubiquitin proteolytic pathway to acute regulation by nutrients. The suppression of protein synthesis by luminal amino acids in the absorptive state might lower intestinal utilization of amino acids to ensure efficient allocation of absorbed nutrients to nonintestinal tissues.

Amino Acids↗