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Biomedical subjects

R G Campbell

Publications and source records attributed to R G Campbell.

At least 19 recordsLinked to original sources

The effect of dietary protein intake on glutamine and glutamate nitrogen metabolism in humans.

The response of glutamine and glutamate kinetics were studied in five healthy young adult men on diets containing deficient (0.1), adequate (0.8), or surfeit (2.2 g.kg-1.d-1) amounts of protein. Glutamate, glutamine, and phenylalanine kinetics were measured in the postabsorptive state at the end of each diet period. Urinary urea and ammonia excretion correlated with protein intake (the sum of the two was 2.1 +/- 0.2, 5.7 +/- 0.3, and 11.9 +/- 1.2 g N g.kg-1.d-1 for the respective 0.1, 0.8, and 2.2 g.kg-1.d-1 protein intakes). Glutamate and glutamine concentrations varied inversely with protein intake. Phenylalanine concentrations and phenylalanine flux did not change significantly with the changing protein intake. Both glutamate and glutamine fluxes varied inversely with protein intake (glutamate flux was 177 +/- 15, 120 +/- 10, and 125 +/- 11 mumol.kg-1.h-1 and glutamine flux was 373 +/- 29, 343 +/- 26, and 318 +/- 15 mumol.kg-1.h-1 at the respective 0.1, 0.8, and 2.2 g.kg-1.d-1 protein intakes). These changes in glutamine or glutamate flux in response to alterations in dietary protein intake were attributable to changes in de novo production.

Adult

Growth hormone increases whole-body protein turnover in growing pigs.

Ten pigs with an average initial live weight of 65 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone (pGH; .1 mg.kg-1.d-1) for a 13-d period on N retention and whole-body protein turnover. Feed intake was restricted to both the control (treated with excipient) and pGH-treated groups to ensure that animals in each group consumed equal amounts. Whole-body protein turnover was estimated from the excretion of 15N in urinary urea and ammonia after a single oral dose of [15N]glycine. Nitrogen balance and whole-body N flux were increased by 35 to 40% with pGH treatment (P less than .001). Protein synthesis and breakdown were increased by 56 and 59% (P less than .001), respectively, in pGH-treated pigs relative to controls. These higher rates of protein turnover seemed to lower slightly the efficiency of the metabolic process for protein deposition. However, the absolute increment in protein synthesis rate was greater than that for breakdown, leading to the increased net N retention. Thus, pGH treatment improved the utilization of dietary amino acids for protein deposition.

Animals

Developmental changes in growth hormone, insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in plasma of young growing pigs.

The relationship between plasma concentrations of normally secreted GH and insulin-like growth factor-I (IGF-I) was investigated in pigs after weaning. Frequent blood sampling for between 12 and 24 h showed that plasma GH was pulsatile in pigs of 10, 20 and 35 kg liveweight. Pulses were brief in duration, low in amplitude and variable in frequency. Basal and average daily plasma concentrations of GH changed significantly with development, increasing by about 50% between 10 and 20 kg liveweight. Concentrations of IGF-I in plasma showed little or no evidence of diurnal periodicity and were not increased by GH pulses. Average daily concentrations of both IGF-I and IGF-II in plasma progressively increased between 10 and 35 kg liveweight, as did the total desaturated IGF-binding protein (IGFBP) activity of plasma. A strong positive correlation was observed between the total concentration of IGFs (IGF-I plus IGF-II) in the circulation and plasma IGFBP activity. The developmental rise in IGFBP activity of plasma was associated with increased labelling with 125I-labelled human IGF-II in ligand blots of binding proteins of apparent molecular masses greater than 200, 50, 43 and 29 kDa. One class of binding proteins of 34.5 kDa decreased with development. This study of young growing pigs shows that normally secreted endogenous GH exerts no significant immediate control over plasma IGF-I concentrations, and that plasma levels of IGF-I and IGF-II increase with maturation in this species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of exogenous porcine somatotropin administration between 30 and 60 kilograms on longissimus muscle fiber morphology and meat tenderness of pigs grown to 90 kilograms.

Twenty-four barrows were used to investigate the effects of exogenous porcine somatotropin (pST) administration (0 and 100 micrograms.kg-1.d-1) between 30 and 60 kg on longissimus muscle morphology and meat tenderness of pigs grown to 90 kg. Administration of pST was by daily i.m. injection. Pigs were fed a fortified diet in restricted amounts between 30 and 60 kg and had ad libitum access to this diet from 60 to 90 kg. Excipient pigs had fewer alpha R fibers and more alpha W fibers than pST-treated pigs (P less than .05). Administration of pST increased (P less than .05) muscle fiber area for all three fiber types at both the 60 kg (34%) and 90 kg (29%) slaughter weights. Furthermore, pST administration increased shear-force (30% at 60 kg; 19% at 90 kg) of the longissimus muscle, indicating that pST administration reduced meat tenderness. All the pST-treated pigs exhibited the "giant fiber syndrome" and a high proportion (62%) of pST-treated pigs exhibited pale, soft, exudative muscle. Whether the giant fiber anomaly resulted from increased muscle protein accretion rate or fiber degeneration is unknown. Results indicated that the stimulatory effects of pST on muscle growth are sustained following cessation of hormone treatment. However, the incidence of pale, soft, exudative muscle in 62% of the pST-treated pigs indicates that pST potentially has undesirable side effects.

Animals

Interrelationships between exogenous porcine somatotropin (PST) administration and dietary protein and energy intake on protein deposition capacity and energy metabolism of pigs.

Exogenous porcine somatotropin (PST) administration stimulates protein deposition and inhibits lipogenesis, resulting in dose-related improvements in growth performance and reduction of carcass fat content. However, the associated impacts of this technology on dietary nutrient requirements and energy partitioning between maintenance, protein, and fat remain unclear. Studies with pigs between 25 and 60 kg body weight indicate that, because of unknown improvements in amino acid utilization and(or) in the energy available for protein synthesis, only marginal increases in dietary protein percentage are required to support 20 to 25% improvements in protein deposition induced by PST administration. In contrast, an increased dietary protein concentration is required to support maximal protein deposition in pigs 60 to 100 kg. Exogenous PST administration increased the maintenance energy requirement and altered the relationship between energy intake and protein deposition, although the magnitude of these changes and the consequent effects on expression of dietary protein (amino acid) requirements was influenced by gender. Albeit limited, information suggests that PST alters nutrient demand at the tissue level. Information of this type will form the basis for rational decisions concerning the method for expression of dietary nutrient requirements (% vs g/d) for PST-treated pigs. Further quantitative information is required on the effects of PST dosage on the relationship of protein deposition to energy intake and on any underlying changes in amino acid utilization and metabolism.

Animals

Effect of epinephrine on amino acid and energy metabolism in humans.

Epinephrine was infused for 8.5 h into five normal, healthy, young adult men on four different occasions at 0, 0.5, 1, and 2 micrograms/min to elevate circulating levels of epinephrine into the high physiological range as seen in stress and trauma. Energy expenditure, heart rate, and blood pressure were measured at hourly intervals. [1-13C]leucine, [ring-2H5]phenylalanine, and [2-15N]glutamine were infused during the last 3.5 h to follow essential amino acid and glutamine kinetics. This design was adapted to study the effects of epinephrine on energy and protein metabolism after acute and temporary metabolic responses to epinephrine had occurred. Plasma glucose was significantly increased by approximately 20 mg/dl from 83 mg/dl (saline infusion) at all levels of epinephrine infusion. Amino acid levels were depressed with epinephrine infusion, with the largest drop occurring for the essential amino acids (-27% at the 2.0-micrograms/min dose). Energy expenditure was increased with epinephrine infusion in a dose-dependent fashion (+17% increase at 2.0 micrograms/min infusion). These effects were sustained for the duration of 8.5 h epinephrine infusion. There was no significant change in leucine or phenylalanine flux, indicative of protein breakdown, or in leucine oxidation. Glutamine flux was significantly (but modestly, +7%) increased at only the 2.0-micrograms/min infusion rate. Changes in kinetics that altered amino acid levels were not apparent by 7 h of epinephrine infusion (the beginning of the plateau period for the tracer infusion study). Although epinephrine can produce long-term elevations of metabolic rate, its effects on protein metabolism are minimal beyond acute changes affecting amino acid levels.

Adult

Growth hormone increases insulin-like growth factor-I (IGF-I) and decreases IGF-II in plasma of growing pigs.

Insulin-like growth factor-I (IGF-I) and IGF-II have been measured in plasma obtained from male and female pigs of two strains during daily administration of pituitary-derived porcine GH (pGH; 100 micrograms/kg) from 60 to 90 kg body weight. Each plasma sample was first chromatographed to separate the IGF from binding proteins in order to obtain reliable measurements. IGF-I concentrations showed no differences between strains, but were higher in untreated males (497 +/- 43 (S.E.M.) micrograms/l) than females (299 +/- 15 micrograms/l). GH-treated animals had two-fold higher concentrations of IGF-I. IGF-II concentrations were not significantly different between sexes or strains, but were decreased in pigs treated with pGH (299 +/- 28 micrograms/1) compared with controls (431 +/- 32 micrograms/l). Binding protein concentrations, measured as interference in the IGF-I and IGF-II assays, were not different between sexes or strains, but were increased in pGH-treated animals. Taken together, these results indicate that in addition to the expected increase in IGF-I concentrations, exogenous administration of pGH to pigs leads to an increase in IGF-binding protein and a depression in IGF-II concentrations.

Animals

Interaction of dietary protein content and exogenous porcine growth hormone administration on protein and lipid accretion rates in growing pigs.

Sixty-six intact male pigs were used to investigate the relationships between exogenous porcine growth (pGH) administration (0, excipient-treated, and .09 mg recombinant pGH.kg-1.d-1) and dietary protein content (8.3, 11.4, 14.5, 17.6, 20.7 and 23.8%) on protein and lipid accretion rates over the live weight range of 30 to 60 kg. Feed intakes were restricted (1.84 kg.pig-1.d-1) and pGH was administered daily by i.m. injection. Rate of protein deposition increased with increasing dietary protein up to 17.6 and 20.7%, respectively, for control and pGH-treated pigs; both growth and protein deposition were enhanced by pGH on the four higher protein diets but remained unaffected by pGH administration to pigs given the two lowest protein diets. Plasma IGF-I concentration was elevated by pGH administration in pigs given the four higher protein diets but unaffected by pGH with the two lowest protein diets. Rate of fat deposition was depressed on all dietary protein treatments by pGH administration; carcass fat content of control and pGH-treated pigs declined with each increase in dietary protein up to 17.6 and 23.8%, respectively. The results demonstrate that pGH acts independently on protein and lipid metabolism.

Adipose Tissue

Effect of sex and exogenous porcine somatotropin on longissimus muscle fiber characteristics of growing pigs.

Thirty-seven pigs with an initial live weight of 60 kg were used to investigate the effects of daily exogenous porcine somatotropin (pST) administration at two dose levels (0 and 100 micrograms.kg-1.d-1) for a 31-d period on muscle fiber characteristics and meat tenderness of boars, gilts and barrows. Excipient boars and gilts had more alpha W and fewer alpha R fibers than did those receiving pST. The percentage of muscle fiber type for barrows was not affected by pST treatment. The administration of pST resulted in an increase in muscle fiber size for all three fiber types in all three sexes, but these changes were of greater magnitude in barrows (31.8%) and gilts (27.8%) than in boars (9.3%). Somatotropin negated the intrinsic sex effect differences in fiber area of the pigs. There was no difference in tenderness among excipient boars, barrows and gilts; however, with the inclusion of pST, shear force decreased in boars and gilts and increased in barrows. A high proportion of the pST-treated pigs contained giant fibers in the longissimus muscle. Furthermore, a small proportion of the pST-treated pigs exhibited pale, soft, exudative muscle. Whether the giant fiber anomalies occurred through increased muscle activity or from fibers undergoing degenerative changes was not determined.

Animals

Effects of gender and genotype on the response of growing pigs to exogenous administration of porcine growth hormone.

Sixty crossbred pigs (Large White x Landrace) were used in a 2 x 2 x 2 factorial experiment to investigate the effects of gender (intact males vs females) and strain (A vs B) on the response to exogenous porcine growth hormone (pGH) administration (0 [excipient-treated] vs .1 mg pGH.kg live weight-1.d-1). All pigs had ad libitum access to their diet; pGH was administered daily from 60 to 90 kg live weight. All aspects of growth performance and body composition were affected to different degrees by gender and pGH. Strain A pigs had a higher capacity for protein accretion, superior growth performance and contained less fat in the eviscerated carcass and empty body compared with Strain B pigs. Within each strain, intact males ate more feed, had a higher rate of protein deposition and exhibited faster and leaner growth than females. Exogenous pGH administration increased average protein deposition and growth rate by 84 and 34%, respectively, and reduced average feed intake, fat deposition rate, feed:gain and carcass fat content by 14, 59, 37 and 33%, respectively. The magnitude of the changes in growth performance, tissue accretion rates and body composition elicited by pGH were independent of strain. However, within each strain the improvement in feed:gain and reduction in carcass fat measurements elicited by pGH were proportionately larger for females than for intact males.

Animals

Genetic engineering of livestock.

Genetic engineering of livestock is expected to have a major effect on the agricultural industry. However, accurate assessment of the consequences of transgene expression is impossible without multigenerational studies. A systematic study of the beneficial and adverse consequences of long-term elevations in the plasma levels of bovine growth hormone (bGH) was conducted on two lines of transgenic pigs. Two successive generations of pigs expressing the bGH gene showed significant improvements in both daily weight gain and feed efficiency and exhibited changes in carcass composition that included a marked reduction in subcutaneous fat. However, long-term elevation of bGH was generally detrimental to health: the pigs had a high incidence of gastric ulcers, arthritis, cardiomegaly, dermatitis, and renal disease. The ability to produce pigs exhibiting only the beneficial, growth-promoting effects of growth hormone by a transgenic approach may require better control of transgene expression, a different genetic background, or a modified husbandry regimen.

Agriculture

Stimulation of protein turnover by carbohydrate overfeeding in men.

The effect of carbohydrate overfeeding on protein metabolism was studied in 11 healthy men. Total urinary nitrogen output during 10 days of carbohydrate overfeeding (1,600 extra kcal/day) decreased 27% relative to nitrogen excretion during 10 days of weight maintenance, indicating protein accretion during over-feeding. However, postabsorptive nitrogen excretion did not change, which means that the positive nitrogen balance associated with overfeeding results from enhanced postprandial nitrogen retention. Overfeeding reduced postabsorptive glucose concentrations 4 +/- 1% and increased glucose production rate 14 +/- 2% and glucose clearance 17 +/- 4%. Overfeeding increased plasma concentrations of insulin, glucagon, and 3,5,3'-triiodothyronine approximately 20%. Alanine and branched-chain amino acid concentrations were increased after overfeeding, but serine, threonine, and asparagine concentrations were reduced. Postabsorptive leucine flux, which is an index of proteolysis, was measured using L-[1-13C]leucine as a tracer. Overfeeding increased leucine flux 13 +/- 2% compared with values after 10 days on a weight-maintenance diet. If it is assumed that overfeeding did not alter the fraction of 13CO2 not recovered in breath, there was no change in the portion of leucine flux that was oxidized. Thus the difference between flux and oxidation, which is a theoretical index of protein synthesis, increased 12 +/- 3% after overfeeding. These data suggest that excess caloric intake, without an increase in protein intake, stimulates post-absorptive proteolysis and protein synthesis.

Adult

Failure of chronic beta-adrenergic blockade to inhibit overfeeding-induced thermogenesis in humans.

The effect of the beta-adrenergic antagonist propranolol on the increase in resting metabolic rate (RMR) induced by overfeeding was examined to determine whether increased beta-adrenergic activity contributes to this response. Six male subjects who were overfed with carbohydrate (1,600 excess kcal/day) for 10 days without drug treatment (control group) had increases (compared with values after 10 days of weight maintenance) in RMR after 6 days [0.24 +/- 0.06 kcal/min (22%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. Eight male subjects were given a weight-maintenance diet for 10 days with oral propranolol treatment (40-60 mg every 6 h) over the last 7 days of this period. Five of these subjects were then overfed for 10 days, and three remained on the weight-maintenance diet; propranolol treatment continued until the end of the study. Propranolol significantly reduced RMR (mean 9%) before the onset of overfeeding but did not prevent increases in RMR after 6 days [0.18 +/- 0.05 kcal/min (16%)] and 10 days of overfeeding [0.17 +/- 0.03 kcal/min (15%)]. In the subjects who remained on the weight-maintenance diet throughout the study, there was no reversal of propranolol's initial reduction of RMR that would have falsely elevated the overfeeding effect. These data provide further evidence that the increase in RMR induced by overfeeding in humans is not mediated by increased beta-adrenergic activity.

Adult

Interrelationships between sex and exogenous growth hormone administration on performance, body composition and protein and fat accretion of growing pigs.

Forty-five pigs with an average initial live weight of 60 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone administration at two dose levels (pGH; 0, excipient buffer injected, and 100 micrograms.kg-1.d-1) for a 31-d period on the performance and body composition of boars, gilts and barrows allowed to consume feed ad libitum. Excipient boars consumed less feed, exhibited faster and more efficient growth (P less than .01) and produced less fat and more protein and water (P less than .01) in the empty body compared with excipient barrows, which in turn contained more fat and less water (P less than .05) in the empty body than did excipient gilts. These differences were largely eliminated by pGH administration, which induced differential effects in growth performance and body composition in boars, gilts and barrows. Growth hormone administration improved growth rate by 13, 22 and 16% and feed conversion efficiency by 19, 34 and 32% in boars, gilts and barrows, respectively. The reduction of body fat content (g/kg) elicited by pGH was 22, 36 and 33% for boars, gilts and barrows, respectively, with a corresponding increase (P less than .01) of body protein and water content. The magnitude of the pGH responses was greatest for gilts and barrows compared with boars, negating intrinsic sex-effect differences in growth performance and body composition of pigs. Pigs used in this study and treated with pGH exhibited a rate of protein deposition (approximately 225 g/d) far greater than previously reported, and as such redefine the genetic capacity for lean tissue growth by the pig.

Adipose Tissue

Interrelationships of exogenous porcine growth hormone administration and feed intake level affecting various tissue levels of iron, copper, zinc and bone calcium of growing pigs.

Trace mineral status was evaluated in a 2 x 3 factorial treatment array with a total of 34 barrows growing from 25 to 55 kg live weight. Treatments included three levels of feed intake (100, 80 and 60% of ad libitum intake) and exogenous pituitary growth hormone (pGH) therapy (0 and 100 micrograms/kg BW daily). Blood was collected prior to slaughter for the determination of hematocrit and serum trace metal concentrations; tissues (liver, heart, kidney, bone and muscle) were obtained when pigs were slaughtered at 55 kg. Hematocrits and serum Fe were lower in pGH-treated pigs than in controls at all levels of feed intake. Serum Cu was increased by feed restriction but was not altered by pGH therapy. The concentration of serum Zn was not affected by either treatment. Concentrations of hepatic Fe and Cu were lower in pGH-treated pigs than in controls but were higher in feed-restricted pigs than in ad libitum-fed pigs. However, the total amounts of hepatic Fe and Cu were similar in pGH-treated pigs to concentrations in controls. The concentration of hepatic Zn was not influenced by either pGH treatment or feed intake. Femur weights were marginally greater in pGH-treated pigs, probably due to elevated water content. Iron concentration in bone was higher in pGH-treated pigs than in control pigs, whereas Ca, Cu and Zn were not influenced by pGH treatment or feed restriction. Feed intake and pGH treatment did not influence the concentrations of Fe, Cu or Zn in muscle. These findings indicate that pGH therapy affects the metabolism of Fe but has little impact on the overall composition of body ash.

Animal Feed

Effects of exogenous porcine growth hormone administration between 30 and 60 kilograms on the subsequent and overall performance of pigs grown to 90 kilograms.

Twenty-eight barrows were used to investigate the effects of exogenous porcine growth hormone (pGH) administration (0 and 100 micrograms.kg-1.d-1) between 30 and 60 kg on the subsequent and overall performance and carcass composition of pigs grown to 90 kg. The pGH was administered by daily i.m. injection and all pigs were fed one diet. Control animals were pair-fed to the intake noted for pGH-treated pigs between 30 and 60 kg and all pigs were fed ad libitum from 60 to 90 kg. Pigs administered pGH had an improved rate (36%) and efficiency (28%) of gain and an improved protein accretion rate (46%) compared to excipient-treated pigs. Pigs previously treated with pGH continued to exhibit superior (P less than .01) rate and efficiency of gain, and the gain was associated with enhanced protein accretion during the quiescent (postinjection) period compared with excipient counterparts. Administration of pGH between 30 and 60 kg reduced carcass fat and increased carcass protein and water at 90 kg, although fat accretion rate was comparable to that of control pigs. Results indicate that, to varying degrees, the stimulatory effects of pGH on growth performance are sustained following cessation of hormone treatment.

Animals

Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.

Because intravenous infusion of beta-hydroxybutyrate (beta-OHB) has been reported to decrease urinary nitrogen excretion, we investigated in vivo metabolism of leucine, an essential amino acid, using L-[1-13C]leucine as a tracer during beta-OHB infusion. Leucine flux during beta-OHB infusion did not differ from leucine flux during normal saline infusion in nine normal subjects, whereas leucine oxidation decreased 18-41% (mean = 30%) from 18.1 +/- 1.1 mumol.kg-1.h-1 (P less than 0.01), and incorporation of leucine into skeletal muscle protein increased 5-17% (mean = 10%) from 0.048 + 0.003%/h (P less than 0.02). Since blood pH during beta-OHB infusion was higher than the pH during saline infusion, we performed separate experiments to study the effect of increased blood pH on leucine kinetics by infusing sodium bicarbonate intravenously. Blood pH during sodium bicarbonate infusion was similar to that observed during the beta-OHB infusion, but bicarbonate infusion had no effect on leucine flux or leucine oxidation. We conclude that beta-OHB decreases leucine oxidation and promotes protein synthesis in human beings.

3-Hydroxybutyric Acid

Effect of feed intake and exogenous porcine somatotropin on longissimus muscle fiber characteristics of pigs weighing 55 kilograms live weight.

Thirty two barrows were used in a 2 x 3 factorial arrangement to evaluate the effects of porcine somatotropin (pST) administration (USDA-pGH-B1; 0 and 100 micrograms.kg BW-1.d-1) and feed intake (FI; ad libitum [A], 1.64 [R1:80% of A] and 1.38 [R2:60% of A] kg/d) on longissimus (LM) muscle fiber characteristics of pigs growing from 25 to 55 kg live weight. The administration of pST resulted in an increase (P less than .05) in muscle fiber size (all three fiber types) and shear-force (17.1%). The percentage of muscle fiber types was not affected by pST treatment. Feeding of the diet at restricted levels (R1 and R2) resulted in smaller (P less than .05) beta R and alpha W fibers compared with feeding ad libitum. Pigs with ad libitum access to their diet had fewer alpha R fibers and more alpha W fibers in the LM compared with those fed at R1 and R2 levels. Restricted feed intake (R1 and R2) resulted in lower (P less than .05) shear-force values compared with ad libitum feeding. The present study indicates that pST administration of young barrows results in an increase in muscle hypertrophy. Restricted FI reduces both transformation from alpha R to alpha W fibers and muscle fiber hypertrophy.

Animals