Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial.

OBJECTIVES: Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX. METHODS: In this double-blind randomised controlled phase III study, 755 MTX-naïve patients with active RA were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX. The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score. RESULTS: 249, 249 and 250 patients were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX, respectively. At week 52, treatment with rituximab 2×1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage (mean change in total modified Sharp score 0.359 vs 1.079; p=0.0004) and an improvement in clinical outcomes (ACR50 65% vs 42%; p<0.0001); rituximab 2×500 mg + MTX improved clinical outcomes (ACR50 59% vs 42%; p<0.0001) compared with MTX alone but did not significantly reduce the progression of joint damage. Safety outcomes were similar between treatment groups. CONCLUSIONS: Treatment with rituximab 2×1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA. ClinicalTrials.gov identifier NCT00299104.

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

OBJECTIVES: This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. METHODS: Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. RESULTS: At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. CONCLUSIONS: Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

Energy metabolism in lactating beef heifers.

To obtain measurements of energy balance in lactating beef cows, respiration calorimetry and digestion trials were conducted using seven lactating (613 kg BW) and three nonlactating (598 kg BW) Hereford x Angus heifers fed a pelleted 75% alfalfa:25% concentrate diet. Five measurements of energy balance were obtained at 6- to 7-wk intervals beginning 6 to 10 wk postpartum in lactating heifers and at 6-wk intervals in nonlactating heifers. Milk yield was measured using a combination of weigh-suckle-weigh and machine milking to adapt heifers to milking by machine without the use of oxytocin. Heifers were milked only by machine during measurements of energy balance. Weekly milk yield averages ranged from 8.2 kg/d at wk 5 postpartum to 3.2 kg/d at wk 32 postpartum. When scaled to BW(.75), the regression of NE1 on ME intake and the regression of ME intake on NE1 were remarkably similar to previously published regressions for measurements obtained from lactating Holstein-Friesian cows. The average daily maintenance energy requirement from these regressions was 503 kJ ME/kg BW(.75), a value similar to the average value reported previously for lactating Holstein-Friesian cows (488 kJ/kg (BW.75)). This is in contrast to numerous published comparisons of the maintenance requirements of cattle breed types in the nonlactating state and current NRC standards for estimating maintenance energy requirements of beef and dairy cattle. The results of the present study suggest that when expressed on the basis of BW(.75) the efficiency of utilization of incremental ME above maintenance for milk and tissue energy (i.e., NE1) is similar among lactating Hereford x Angus heifers and lactating Holstein-Friesian cows. The breeds differ in terms of their propensity for milk yield and the resulting partition of ME between milk synthesis and tissue energy retention.

Randomised controlled trial of combined diphtheria, tetanus, whole-cell pertussis vaccine administered in the same syringe and separately with Haemophilus influenzae type b vaccine at two, three and four months of age.

An open randomised controlled multicentre study compared the immunogenicity and reactogenicity of three vaccines given by injection at two, three and four months of age. Children (89) received Haemophilus influenzae type b (Hib) vaccine (SmithKline Beecham Biologicals [SB]) administered in the same syringe with combined diphtheria-tetanus-whole-cell pertussis (DTPw) vaccine (Evans); 75 received Hib vaccine (SB) administered as a separate injection with DTPw vaccine; 66 received Hib vaccine (Pasteur Merieux [PM]) administered as a separate injection with DTPw vaccine. All subjects in both groups receiving Hib (SB) vaccine had levels of antibodies to the Hib polysaccharide polyribosylribitol phosphate (PRP) greater than 0.15 microgram ml-1 as did 97% of those receiving Hib (PM) vaccine 1 month after administration of the final vaccine dose. Subjects in all three groups demonstrated an immunological response to pertussis, diphtheria and tetanus antigens. The geometric mean titres of the group given Hib (SB) and DTPw vaccine mixed in the same syringe were lower than the other groups. There were no apparent differences between the treatment groups in the incidence of local or systemic reactions, or serious adverse events. This study has confirmed that it is possible to halve the number of injections necessary to offer protection, with advantages to parents, children, doctors and nurses, using a combined DTPwHib vaccine and in accordance with the UK's accelerated primary immunisation schedule at two, three and four months of age.

Components of growth in Holstein heifers fed either alfalfa or corn silage diets to produce two daily gains.

Growth components were compared in an experiment with a 2 x 2 factorial design. Eight replicates of Holstein heifers were fed diets based on either alfalfa or corn silage for daily gain of either 725 or 950 g from 181 to 334 kg of body weight (BW). Mean daily gains from corn diets were greater than gains from alfalfa diets for BW, udder, empty body, fat, fat-free matter, protein, H2O, C, and energy but were less than gains from alfalfa for gut contents and ash. High daily gain produced higher mean values for all of these variables than did lower daily gain. The percentage of protein in fat-free matter was not affected by either main effect. The percentage of fat in empty body gain was increased as daily gain increased. Energy concentration of fat-free matter that was gained was not affected by either diet or daily gain. Energy concentration of empty body gain increased as daily gain increased. The percentage of gut contents in daily BW gain was higher for heifers fed the alfalfa diet than for those fed the corn diet. Energy concentration in daily BW gain was affected by diet and daily gain. Variations of fat and gut contents in daily BW gain must be considered when requirements or expected growth are described.

Comparison of milk and blood lipids in Jersey and Holstein cows fed total mixed rations with or without whole cottonseed.

Lipids in milk and blood were examined in Holstein and Jersey cows (8 lactating and 4 dry) fed two TMR containing either 10% whole cottonseed or a control concentrate mixture of corn, cottonseed hulls, and cottonseed meal in a switchback experiment. Milk from Jersey cows contained more total lipid than did milk from Holstein cows (4.4 vs. 3.5 g/dl), had a higher proportion of lipid as triglyceride (97.3% vs. 96.7%), and had a lower proportion of lipid as phospholipid (0.8% vs. 1.0%). Milk from the group fed cottonseed contained fewer medium-chain fatty acids (24.4% vs. 29.4%) and more C18 fatty acids (35.9% vs. 25.8%) than did milk from the control group. Total blood lipids were 234 mg/dl for Holsteins and 168 mg/dl for Jerseys. Total blood lipids were higher for dry cows fed cottonseed (100 vs. 72 mg/dl), particularly Jersey cows. As determined by gravimetric or TLC analysis, milk fat percentages of cows fed cottonseed were not different from those of cows fed control rations. However, as determined by infrared instrumentation, milk fat appeared to be lower (4.3%) for cows fed cottonseed than that (4.6%) for control cows. Changes in milk fatty acids that were related to diets might explain the difference between infrared and gravimetric determinations of milk fat.

A study to assess the immunogenicity, reactogenicity and safety of hepatitis A vaccine administered subcutaneously to patients with congenital coagulation disorders.

The objective was to compare the immunogenicity, reactogenicity and safety of an inactivated hepatitis A vaccine administered subcutaneously to patients with congenital coagulation disorders. Subjects, 97 patients with congenital coagulation disorders (67 men aged > 16 and 30 children aged ≤ 16 years), received hepatitis A vaccine administered at 1440 ELISA (enzyme linked immunosorbent assay) units (ELU) to the adult group and at 720 ELU to the child group at 0 and 6 months by the subcutaneous route. The vaccine was well tolerated, with the incidence of adverse events decreasing with subsequent administration of vaccine. Overall, 90% of subjects seroconverted 1 month after the booster (95% confidence interval 76-97%), with 100% seroconversion occurring in the child group compared with 85% in the adult group. There was a corresponding progressive rise in geometric mean titres in each group and no significant difference in the geometric mean titres was found between the two groups. Of the subjects, 29% were HIV positive, 3% of children compared with 40% of adults. A lower rate of seroconversion was observed in subjects with low CD4 counts. Administration of two doses of an inactivated hepatitis A vaccine at 1440 ELU in adults and 720 ELU in children is safe and highly immunogenic when given by the subcutaneous route.

Effects of mesenteric vein L-alanine infusion on liver metabolism of organic acids by beef heifers fed diets differing in forage: concentrate ratio.

Effects of diet forage:concentrate ratio and mesenteric vein L-alanine infusion on net VFA metabolism by portal-drained viscera (PDV) and liver were determined in four multicatheterized Hereford x Angus heifers (443 kg BW) fed in equal meals every 2 h pelleted, isonitrogenous diets containing 75% alfalfa or 75% corn:soybean meal (SBM) in a balanced single reversal of diets with 6 wk for adaptation. In addition, effects of L-alanine infusion on net metabolism of individual amino acids (AA) by PDV and liver was determined when heifers were fed 75% corn:SBM. Four measurements of blood flow (p-aminohippurate dilution) and net flux of VFA and AA (venous-arterial difference times blood flow) were obtained at 30-min intervals immediately before beginning and ending a 24-h mesenteric vein infusion of L-alanine at 75 mmol/h. Net PDV absorption of acetate (P < .02), propionate (P < .02), and total VFA (P < .02) was lower when 75% corn:SBM was fed, reflecting increased carbohydrate digestion postruminally and only partially balanced by increases in net PDV glucose absorption reported previously. In addition, net PDV absorption of n-butyrate was lower when 75% alfalfa was fed. Excluding acetate, net liver removal of VFA was 83 to 108% of their net PDV release. L-Alanine infusion did not affect net PDV or liver flux of VFA but decreased net total splanchnic (PDV plus liver) release of propionate (P < .07) and n-butyrate (P < .03) and decreased (P < .10) net PDV release and liver removal of glycine. In spite of the increase in liver L-alanine removal, the ratio of glucose release to precursor removal remained remarkably constant across the liver when L-alanine was infused, emphasizing the tight control of liver glucose release and the dynamic interplay of precursor supply and removal in the maintenance of liver carbon balance.

Utilization of energy and nitrogen by yearling Holstein cattle fed direct-cut alfalfa or orchardgrass ensiled with formic acid plus formaldehyde.

First-growth orchardgrass and alfalfa were harvested at two stages of maturity, treated with formic acid plus formaldehyde, and ensiled as direct-cut silage during 1978 and 1979. The 1978 silages were fed to eight yearling Holstein heifers (average BW 273 kg), and the 1979 silages were fed to eight yearling Holstein steers (average BW 264 kg) in replicated 4 x 4 Latin square experiments to measure total energy and N balance using the Beltsville open-circuit respiration calorimeters. Silage was offered daily at 70 g of DM/kg.75 BW, a rate that was essentially ad libitum for late-maturity orchardgrass, but restricted for the other three silages within each experiment. Cattle fed alfalfa used ME for growth with greater efficiency (55%) than did cattle fed orchardgrass (40%). Cattle fed orchardgrass achieved the same tissue N retention at a lower total N intake than did cattle fed alfalfa. Differences in tissue N retention were accounted for by differences in N intake insoluble in autoclaved ruminal fluid, but soluble in acid detergent, a fraction termed available N. At equal intake of ME and available N, cattle fed alfalfa gained more tissue energy than those fed orchardgrass and gained tissue protein similarly to cattle fed orchardgrass. Fractions composing digestible OM were different between forage types but similar within forage type between maturities at harvest. More efficient use of ME for growth by animals fed alfalfa compared with orchardgrass may be related to differences in digestible OM composition, load of digestive tract content, and composition of absorbed nutrients.

Effects of mesenteric vein n-butyrate infusion on liver metabolism by beef steers.

Effects of a 3-d mesenteric vein n-butyrate infusion (25 mmol/h) on net metabolism of nutrients by portal-drained viscera (PDV) and liver were measured in six Hereford x Angus steers. Steers were fed a pelleted 75% concentrate: 25% alfalfa diet at 135 kcal of ME/kg BW.75. Six measurements of blood flow and net metabolism of nutrients were obtained at hourly intervals immediately before beginning and ending n-butyrate infusion. Measurements were obtained during two trials, with three steers (457 kg BW, 28 mo of age in Trial 1; 478 kg BW, 19 mo of age in Trial 2) in each trial. The infusion of n-butyrate increased (P less than .01) net PDV release of n-butyrate. Infusion increased net liver removal of n-butyrate (P less than .01) and L-lactate (P less than .02) and release of beta-hydroxybutyrate (BOHB; P less than .02) and increased (P less than .03) liver extraction ratio for alanine. Net total splanchnic (PDV plus liver) release of n-butyrate (P less than .03) and BOHB (P less than .01) were increased, and net total splanchnic release of L-lactate (P less than .05) and propionate (P less than .07) were decreased by n-butyrate infusion. The infusion of n-butyrate decreased (P less than .01) net PDV release and liver removal of propionate in five of six steers. Infusion had no effect (P greater than .10) on insulin and glucagon concentration or net flux. In a companion in vitro study, L-lactate metabolism to glucose and CO2 by calf hepatocytes was decreased (P less than .08) by n-butyrate addition (2.5 mM). Effects of n-butyrate on liver L-lactate and alanine metabolism suggest that pyruvate carboxylase activity was increased, but our study failed to show a consistent effect of n-butyrate infusion on liver glucose production.

Clinical trial with inactivated hepatitis A vaccine and recommendations for its use.

OBJECTIVE: To compare the reactogenicity and immunogenicity of an inactivated hepatitis A vaccine in two different immunisation schedules. DESIGN: Randomised trial. SETTING: One London teaching hospital. SUBJECTS: 104 healthy adult volunteers (71 men, 33 women aged 19-60). INTERVENTIONS: Hepatitis A vaccine to group 1 (54 volunteers) at 0, 1, and 2 months and to group 2 (50) at 0, 1, and 6 months. MAIN OUTCOME MEASURES: Symptoms at and after each dose; liver function, hepatitis A virus specific serum immune response; and responses in saliva and parotid fluid in immunised volunteers and subjects with natural immunity. RESULTS: The vaccine was well tolerated; 97% (96/99) and 100% of those immunised developed serum antibody after one and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose and were significantly higher in men but not women in group 2 after the third dose (ratio between geometric mean titres 0.265, 95% confidence interval 0.18 to 0.39; p less than 0.001). At one year this group-sex interaction was absent; geometric mean titres for both sexes were significantly higher in group 2 (ratio 0.330, 0.227 to 0.478; p less than 0.0001). Antibody responses were not significantly different between the groups at two years. Compared with naturally infected subjects immunised volunteers developed poor or undetectable virus specific IgG and IgA responses in saliva and parotid fluid. CONCLUSIONS: The vaccine was safe and highly immunogenic, and the differences in the immune responses in saliva and parotid fluid are unlikely to affect its efficacy.

Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net hormone metabolism by portal-drained viscera and liver.

Effects of growth hormone-releasing factor (GRF) and intake on arterial concentrations and net visceral metabolism of hormones were measured in six growing Hereford x Angus steers using a split-plot design with 4-wk injection periods within 8-wk intake periods. Steers were fed a 75% concentrate diet at two intakes and were injected s.c. twice daily with saline or GRF (10 micrograms/kg of BW). Arterial concentrations of growth hormone (GH) were measured on d 1 and d 8 to 10 of injections. Eleven measurements, obtained at 30-min intervals, of arterial concentration and net flux of hormones across portal-drained viscera (PDV) and liver were obtained on d 8 to 10 of injections (six hourly measurements were used for insulin-like growth factor-I [IGF-I] and somatostatin). The area under the GH curve and average and peak GH concentrations were increased (P less than .01) by GRF and were greater (P less than .10) at low than at high intake. Liver removal of GH was not affected by GRF or intake. Arterial IGF-I concentration was increased (P less than .05) by GRF and not affected by intake. Treatments did not affect IGF-I flux across the liver. Arterial insulin concentration was greater (P less than .05) at high than at low intake, in part because of greater (P less than .01) PDV release. Increased (P less than .10) arterial insulin concentration in GRF-treated steers was not attributable to significant changes in PDV or liver net flux. Arterial glucagon concentration was greater (P less than .01) at high than at low intake, in part because of greater (P less than .05) PDV glucagon release and decreased (P less than .10) liver extraction ratio. Effects of intake on arterial concentration of insulin and glucagon were in part due to changes in visceral metabolism, but GRF did not affect PDV or liver hormone metabolism.

Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net nutrient metabolism by portal-drained viscera and liver.

Effects of growth hormone-releasing factor (GRF) and intake on net nutrient metabolism by portal-drained viscera (PDV) and liver were measured in six growing Hereford x Angus steers fed a 75% concentrate diet at two intakes in a split-plot design with 4-wk saline or GRF injection periods within 8-wk intake periods. Daily rations were fed as 12 equal meals delivered every 2 h. Steers were injected s.c. for 21 d with either saline or 10 micrograms/kg of (1-29)NH2 human GRF at 12-h intervals. Six hourly measurements of net nutrient flux (venous-arterial concentration different [VA] x blood flow) across PDV and liver were obtained 8 to 10 d after injections began. Energy and N balances were measured using respiration calorimetry during the last week of injections. Greater intake increased blood flow (P less than .01) and net visceral release or removal of most nutrients (P less than .10). Exceptions included a decrease (P less than .10) in net PDV glucose release with greater intake in saline-treated steers and a decrease (P less than .01) in net liver removal of lactate with greater intake. Treatment of steers with GRF decreased net liver removal of alpha-amino N (AAN; P less than .05) and ammonia N (NH3N; P less than .10) and release of urea N (UN; P less than .05), increased liver release of glutamate (P less than .05), and decreased net PDV release of NH3 N (P less than .10). Decreased liver extraction ratio for AAN in GRF-treated steers (P less than .01) implies a direct effect of GRF treatment on liver metabolism separate from changes in liver AAN supply. Proportions of body N retention not accounted for by net total splanchnic AAN release increased with GRF treatment. This suggests a change in peripheral utilization of dietary AAN supply or an increase in total splanchnic N retention.

Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: whole-body energy and nitrogen metabolism.

Effects of growth hormone-releasing factor (GRF) on energy and N metabolism in six growing Hereford x Angus steers were measured using a split-plot design with 4-wk injection periods within 8-wk intake periods. Steers were fed a 75% concentrate pelleted diet at two intakes (low: 50 g/BW.75 and high: 90 g/BW.75 as fed) and injected s.c. with saline or 10 micrograms/kg of BW of human GRF(1-29)NH2 twice daily for 3 wk. Measurements of energy and N balance were obtained during wk 3 of treatments. Diet DM digestibility (%) was decreased by greater intake (P less than .05) and increased by GRF (P less than .06). Treatment with GRF increased (P less than .01) N retention by decreasing (P less than .05) fecal and urinary excretion: N retention averaged 10.0 and 20.8 g/d at low intake and 25.9 and 46.7 g/d at high intake for control- and GRF-treated steers, respectively. Increased ME (P less than .05) in GRF-treated steers also resulted from decreased fecal (P less than .05) and urinary (P less than .07) energy excretion but was countered by increased (P less than .06) heat energy (HE). Tissue energy (TE), partial efficiency of ME use for TE retention, and estimated maintenance energy were not affected (P greater than .10) by GRF treatment. In summary, GRF treatment altered the partition of TE by increasing protein retention (108 and 80% for low and high intake, respectively) at the expense of fat retention.

Composition of formaldehyde- and formic acid-treated alfalfa and orchardgrass silages harvested at two maturities and their effects on intake and growth by Holstein heifers.

Alfalfa and orchardgrass herbages were each harvested at two maturities (May 22 to 25 vs June 5 to 7) in primary growth and directly ensiled with 5 kg of a mixture of 30% formic acid and 25% formaldehyde per metric ton of fresh herbage in upright conventional silos. Alfalfa silage contained less NDF (71%) and more N (150%) and hot-water-insoluble N (117%) than orchardgrass silage did. Major differences between silages were that orchardgrass contained 20.4 percentage units more NDF and 1.10 percentage units less N than alfalfa. The NDF increased 104% and total N decreased to 86% with advancing maturity. Twenty-eight yearling Holstein heifers (223 kg BW) were given ad libitum access to the four silages with trace mineral salt, and growth rate was measured in a 119-d period. Daily DE intake was 297 kcal/kg.75 BW for heifers fed alfalfa silage compared with 202 kcal/kg.75 BW for heifers fed orchardgrass silage. Daily gain was 992 g for heifers fed alfalfa compared with 661 g for heifers fed orchardgrass. Gross efficiency, or gain per unit of DE, was similar for heifers fed orchardgrass and alfalfa. Rate of gain was primarily a function of ad libitum intake of DE. Heifers fed alfalfa had greater plasma essential amino acid concentrations (122%) than those fed orchardgrass did. Late alfalfa produced greater ADG than orchardgrass harvested 2 wk earlier.

Voluntary intake, growth rate, and tissue retention by Holstein steers fed formaldehyde- and formic acid-treated alfalfa and orchardgrass silages.

Alfalfa and orchardgrass herbages of similar digestibility were harvested at early and late maturity from primary growth and conserved as direct-cut silage using formic acid and formaldehyde simultaneously. Major compositional differences between the silages were lower NDF (principally hemicellulose) and a greater N content in alfalfa than in orchardgrass. An initial group of eight steers was slaughtered with a mean BW of 222 kg, and each of the four silages was fed to comparable groups of eight Holstein steers. Ad libitum DMI per unit of metabolic BW for alfalfa silages was 128% of that for orchardgrass silages. The ADG of steers fed alfalfa silages was 132% of that of steers fed orchardgrass silages. Despite greater ad libitum intake, total gut fill, as a percentage of BW, on alfalfa silages was 77% of that on orchardgrass silages. Daily empty BW gain of steers fed alfalfa silages was 158% of that of steers fed orchardgrass silages. Daily energy retention of steers fed alfalfa silages was 180% of that of steers fed orchardgrass silages. Steers fed alfalfa silages retained 140% more protein than steers fed orchardgrass silages did, but steers fed alfalfa silages retained only 71% as much protein energy relative to their total energy retention compared with steers fed orchardgrass silages. Differences in composition of daily energy retained were almost totally a result of differences in the total daily energy retention. Late alfalfa silage produced a greater daily gain than orchardgrass silage cut 2 wk earlier because greater intake compensated for lower digestibility.

Effects of mesenteric vein L-alanine infusion on liver metabolism in beef heifers fed on diets differing in forage:concentrate ratio.

Effects of 24 h mesenteric vein infusion of L-alanine (75 mmol/h) and diet forage:concentrate ratio on net nutrient metabolism by portal-drained viscera (PDV) and liver were measured in four Hereford-Angus heifers. Heifers were fed on diets containing approximately 750 g lucerne (Medicago sativa) or 750 g concentrate/kg every 2 h at similar metabolizable energy intakes in a balanced single reversal design with 6 weeks for diet adaptation. Measurements of blood flow and net metabolism of nutrients were obtained at 30 min intervals starting immediately before (four measurements) and after (five measurements) beginning, immediately before ending (four measurements) and 1.5 h after ending (three measurements) alanine infusion. Only values obtained immediately before beginning and ending alanine infusion were compared statistically. Net total splanchnic (PDV plus liver) release of glucose was greater when heifers were fed on the 750 g concentrate/kg v. 750 g lucerne/kg diet due to greater net PDV absorption. Net PDV absorption of ammonia-nitrogen, beta-hydroxybutyrate (BOHB) and lactate, and net liver and total splanchnic release of urea-N (UN) were greater when heifers were fed on the 750 g lucerne/kg v. 750 g concentrate/kg diet. Infusion of alanine increased net liver removal of alanine and alpha-amino-N, net liver release of UN and net total splanchnic release of alanine, UN and lactate. Infusion of alanine decreased net liver release of BOHB and removal of lactate. Mesenteric vein infusion of alanine altered the net availability of precursors for liver glucose synthesis, but did not affect net glucose release by liver in these beef heifers.

Net energy for lactation of calcium salts of long-chain fatty acids for cows fed silage-based diets.

The NEL of calcium salts of long-chain fatty acids from palm oil was determined in mature Holstein cows. Twelve lactating (fed for ad libitum intake) and six nonlactating (restricted to near maintenance intake) Holstein cows were fed 0 or 2.95% fat supplement in diets formulated to contain 16 or 20% CP in a 2 x 2 factorial arrangement of treatments in a single reversal design within protein level. The fat supplement was substituted for ground corn and minerals. Two 6-d total collection balance trials were conducted during which cows were in open circuit respiration chambers. Intake of OM was lower for lactating cows fed the fat supplement (18.1 vs. 19.1 kg/d), but energy intake did not differ (93.2 Mcal/d). Total long-chain fatty acid intake was increased from 477 to 820 g/d with fat feeding. Apparent digestibility of long-chain fatty acids was increased 11.1 percentage units with increased dietary CP for lactating cows with no difference in fatty acid digestibility for the dry cows. Milk yield was higher (34.3 vs. 32.0 kg/d) with fat feeding, but milk energy yield did not differ (22.6 Mcal/d). The NEL of the fat supplement was estimated from the incremental differences in energy values within cows, assuming NEL of corn replaced by fat to be 1.96 Mcal/kg DM, and was determined to be 6.52 Mcal/kg DM (SE = 1.74). The efficiency of the use of metabolizable energy for lactation from dietary fat was 77.2%. The energy in calcium salts of long-chain fatty acids is utilized efficiently for lactation in mature cows.

Effects of diet forage-to-concentrate ratio and intake on energy metabolism in growing beef heifers: net nutrient metabolism by visceral tissues.

Effects of diet forage-to-concentrate ratio and intake on metabolism of nutrients by portal-drained viscera (PDV), liver and kidneys were measured in seven growing beef heifers. Isonitrogenous pelleted diets containing approximately 75% alfalfa or 75% concentrate were fed every 2 h at two metabolizable energy intakes. Greater intake increased net PDV removal of glucose and urea nitrogen and net PDV release of NH3N, alpha-amino nitrogen (AAN), alanine and lactate. Lower net PDV release of NH3N, liver removal of NH3N and AAN and liver release of urea nitrogen accompanied lower N intake and digestion in heifers fed the 75% concentrate vs. the 75% alfalfa diet. Lower net PDV glucose removal resulted in greater total splanchnic glucose release when heifers were fed the 75% concentrate vs. the 75% alfalfa diet. In addition, net PDV, liver and total splanchnic release of beta-hydroxybutyrate (BOHB) were lower when heifers were fed the 75% concentrate vs. the 75% alfalfa diet. Greater tissue energy retention in heifers fed the 75% concentrate vs. the 75% alfalfa diet at equal metabolizable energy intake accompanied differences in net PDV metabolism of glucose, NH3N and BOHB and liver metabolism of nitrogenous compounds, BOHB and lactate.

Effects of diet forage-to-concentrate ratio and intake on energy metabolism in growing beef heifers: whole body energy and nitrogen balance and visceral heat production.

Effects of diet forage-to-concentrate ratio and intake on balances of energy and nitrogen and portal-drained viscera (PDV), liver and kidney blood flow and O2 consumption were measured in seven growing beef heifers. Isonitrogenous pelleted diets containing approximately 75% alfalfa or 75% concentrate were fed daily as 12 equal meals every 2 h at two isoenergetic metabolizable energy intakes. A split-plot design was used, with 4 wk for adaptation to diet followed by 3-wk intake periods within 6-wk diet periods. Heifers consumed and digested less dry matter, energy and nitrogen when fed the 75% concentrate vs. 75% alfalfa diet at equal metabolizable energy. Heifers fed the 75% concentrate diet produced less heat energy and retained more tissue energy than when fed the 75% alfalfa diet. Blood flow for PDV, liver and kidneys increased with intake and was greater when heifers were fed the 75% alfalfa vs. 75% concentrate diet. Increased PDV and liver O2 uptake accounted for 44 and 72% of heat increment for the 75% concentrate and 75% alfalfa diets, respectively. Greater PDV uptake of O2 accounted for 72% of the decrease in tissue energy of heifers fed the 75% alfalfa vs. 75% concentrate diet at equal metabolizable energy.