Effect of protein supplementation and forage allowance on the growth and reproduction of beef heifers grazing stockpiled tall fescue.

Stockpiled tall fescue can provide adequate winter forage for beef cattle, although unsupplemented replacement heifers may display marginal performance before breeding. The objective of this study was to determine if protein supplementation and/or additional forage improves growth and reproductive performance of replacement heifers grazing stockpiled fescue. Cattle averaging 272 ± 1.59 kg were stratified by BW and then randomly assigned to 1 of 4 plots within a pasture replication. Treatment combinations were assigned in a 2 × 2 factorial arrangement and included 1) a conservative forage allocation ("normal," targeting 85% forage use) and mineral supplement (normal forage allocation with mineral supplement [FM]), 2) normal forage allocation with protein tub (FT), 3) more liberal forage allocation ("extra," targeting 70% forage use) and mineral supplement (extra forage allocation with mineral supplement [EM]), and 4) "extra forage allocation with protein tub (ET). Treatments were administered for 8 wk from early November to early January. Heifers were fed fescue hay for 1 wk before breeding in late January. Heifers were synchronized with the 7-d CO-Synch + controlled internal drug release device protocol and inseminated in late January. Heifers were checked for pregnancy by ultrasonography at 35 and 90 d after AI. Main and interaction effects between the 2 treatments were determined. Total supplement intake was greater for protein tub than mineral supplement (0.36 vs. 0.11 kg·heifer·d, respectively; < 0.0001), and the additional dietary protein in the tub groups resulted in greater serum urea N concentrations ( < 0.0001; 8.15 vs. 10.4 mg/dL for mineral and protein tub, respectively). Forage utilization efficiency was greater for normal than extra forage allocation (74.7 vs. 65.8%, respectively; < 0.0001). Main effects of both treatments on ADG were significant ( < 0.0001; 0.28, 0.43, 0.43, and 0.51 kg·heifer·d for FM, FT, EM, and ET, respectively). There was an interaction effect of the 2 treatments on change in BCS ( < 0.05; 0.12, 0.10, 0.18, and 0.31 for FM, FT, EM, and ET, respectively). Reproductive tract scores, pelvic area, and AI pregnancy rates were not different between treatments ( > 0.05). Overall, feeding a protein supplement or providing extra forage increased gain and interacted to increase BCS but did not have an effect on reproductive performance. Supplementing with protein and providing extra forage are strategies that can increase gain in heifers, which could aid heifers in reaching puberty before estrous synchronization.

Exploring the influence of ancient and historic megaherbivore extirpations on the global methane budget.

Globally, large-bodied wild mammals are in peril. Because "megamammals" have a disproportionate influence on vegetation, trophic interactions, and ecosystem function, declining populations are of considerable conservation concern. However, this is not new; trophic downgrading occurred in the past, including the African rinderpest epizootic of the 1890s, the massive Great Plains bison kill-off in the 1860s, and the terminal Pleistocene extinction of megafauna. Examining the consequences of these earlier events yields insights into contemporary ecosystem function. Here, we focus on changes in methane emissions, produced as a byproduct of enteric fermentation by herbivores. Although methane is ∼ 200 times less abundant than carbon dioxide in the atmosphere, the greater efficiency of methane in trapping radiation leads to a significant role in radiative forcing of climate. Using global datasets of late Quaternary mammals, domestic livestock, and human population from the United Nations as well as literature sources, we develop a series of allometric regressions relating mammal body mass to population density and CH4 production, which allows estimation of methane production by wild and domestic herbivores for each historic or ancient time period. We find the extirpation of megaherbivores reduced global enteric emissions between 2.2-69.6 Tg CH4 y(-1) during the various time periods, representing a decrease of 0.8-34.8% of the overall inputs to tropospheric input. Our analyses suggest that large-bodied mammals have a greater influence on methane emissions than previously appreciated and, further, that changes in the source pool from herbivores can influence global biogeochemical cycles and, potentially, climate.

Induction of heat-shock protein 72 in rat skeletal muscle does not increase tolerance to ischemia-reperfusion injury.

Ischemia-reperfusion injury is implicated in the failure of free flap and replant surgeries and is associated with the pathogenesis of a wide variety of clinical diseases including stroke, myocardial infarction, spinal injury, and compartment syndromes. We used a skeletal muscle flap model to test if the induction of heat-shock protein 72 (HSP72) by mild hyperthermia provides tolerance against ischemia-reperfusion injury. Immunocytochemistry and Western blot analysis verified increased production of HSP72 in the gracilis muscle of globally heated rats. Neutrophil accumulation in the microvasculature and postischemic muscle survival after ischemia-reperfusion were unaltered by preischemic hyperthermia, indicating HSP72 induction is not sufficient to provide resistance against severe injury in skeletal muscle.

Compatibility of filgrastim with selected antimicrobial drugs during simulated Y-site administration.

The compatibility of filgrastim with imipenem-cilastatin, ceftazidime, fluconazole, gentamicin, tobramycin, and amikacin was studied. Filgrastim 40 micrograms/mL or filgrastim 10 micrograms/mL (with human albumin) was combined with (1) imipenem-cilastatin 5 mg/mL (in terms of imipenem content), (2) ceftazidime 10 mg/mL (as the sodium salt), (3) fluconazole 2 mg/ mL, (4) gentamicin 1.6 mg/ mL (as the sulfate), (5) tobramycin 1.6 mg/mL (as the sulfate), or (6) amikacin 5 mg/ mL (as the sulfate). Equal volumes (5 mL) of the test-agent solutions were added in pairs to glass containers (simulating Y-site administration) in triplicate. Samples were analyzed for filgrastim activity, drug concentration, pH, and visible physical changes during storage at approximately 25 degrees C for up to four hours. Filgrastim activity was measured by the in vitro bioassay, and antimicrobial drug concentrations were measured by stability-indicating high-performance liquid chromatography or fluorescence polarization immunoassay. Filgrastim retained its activity, except for the combination of filgrastim at the lower concentration with gentamicin or at the higher concentration with imipenem-cilastatin. Antimicrobial drug concentrations did not change significantly during the study. No precipitation, color change, or haze was noted in any mixture. Changes in pH were negligible except for an increase in the mixture of filgrastim at either concentration with ceftazidime. In most cases, filgrastim retained its activity in the presence of a variety of antimicrobial drugs for up to four hours; in all cases, the antimicrobial drugs remained stable.

Hyperbaric oxygen and cyclosporine as a combined treatment regimen to prevent skin allograft rejection in immunohistoincompatible mice.

Several previous studies reported various immunosuppressive effects of hyperbaric oxygen on nonspecific and specific cell-mediated reactions. A highly immunogenic skin allograft mouse model was used to evaluate the clinical relevance of the previously described immunosuppressive effects of hyperbaric oxygen. A 1.5 x 2.0-cm full-thickness skin allograft was cross-grafted between paired immunohistoincompatible mouse strains (N = 40, C57BL/6 and BALB/c female mice) that were randomly assigned to four groups receiving (1) no treatment (controls), (2) cyclosporine 1 mg per kilogram intraperitoneally daily, (3) cyclosporine plus a low-dose hyperbaric oxygen treatment (two treatments per day, once a week), and (4) cyclosporine plus a high-dose hyperbaric oxygen treatment (two treatments per day, three times a week) following surgery (N = 32). Allograft samples were taken from each group at day 9 after cross-grafting (N = 8). Skin allograft rejection was significantly delayed in all treatment groups compared to controls. No difference was found between animals who received cyclosporine only and the combined treatment regimen including low-dose hyperbaric oxygen. High-dose hyperbaric oxygen treatment in combination with cyclosporine substantially prolonged skin allograft survival compared to other treatments. These findings were histologically confirmed. We conclude that hyperbaric oxygen treatment as an adjunct to standard immunosuppressive therapy may only be advantageous if frequently applied.

Skin allograft rejection and hyperbaric oxygen treatment in immune-histoincompatible mice.

The effect of hyperbaric oxygen (HBO) as an immunosuppressive agent was evaluated by using a highly immunogenic skin allograft mouse model. Immune-histoincompatible female C57BL/6 and BALB/c mice (N = 30) were randomly assigned to three groups receiving no treatment (control group), low dose HBO treatment (two treatments once a week), and intermediate HBO treatment (two treatments 3 times/wk) 1 wk before and 2 wk after transplantation of a 1.5 x 2 cm full thickness skin allograft from the back. Rejection was observed a Day 7 and was completed 14 days after surgery in controls. Low dose and intermediate HBO treatment delayed skin allograft rejection, which was histologically confirmed.

"Give me a fish and I eat today: teach me to fish and I eat for a lifetime". The Newcastle Programme.

The development of a new occupational therapy course at the University of Newcastle has proved an exciting challenge to the authors. A common core year with other health professionals introduces students to the concepts of holistic health. Students develop problem solving skills and an attitude to therapy which encourages them to focus on each client as an individual, living and working within their specific environment. The reductionist view of intervention does not seem to be compatible with the self directed, problem based approach to learning. New patterns of fieldwork to support and consolidate theoretical input have been developed. Staff have learnt a new approach to education which is satisfying and rewarding. We believe students will graduate with skills which will allow them to meet the challenge of a new century.

Cytotoxic effects of dihydroorotase inhibitors upon human CCRF-CEM leukemia.

6-L-Thiodihydroorotate (TDHO) and 2-oxo-1,2,3,6-tetrahydropyrimidine-4,6-dicarboxylate (HDDP) are potent inhibitors of mammalian dihydroorotase in vitro (R. I. Christopherson, K. J. Schmalzl, E. Szabados, R. J. Goodridge, M. C. Harsanyi, M. E. Sant, E. M. Algar, J. E. Anderson, A. Armstrong, S. C. Sharma, W. A. Bubb, and S. D. Lyons, Biochemistry, 28: 463-470, 1989). Using human CCRF-CEM leukemia cells growing in culture, TDHO and HDDP as the free acids have 50% inhibitory concentration (IC50) values of 32 microM and greater than 1000 microM, respectively, whereas for TDHO methyl ester, the IC50 value is 25 microM, and for HDDP dimethyl ester, the IC50 value is 21 microM. These IC50 values were not affected by addition of dihydroorotate, uridine, or deoxycytidine to the culture medium. TDHO methyl ester (25 microM) had only slight inhibitory effects upon the dihydroorotase reaction of de novo pyrimidine biosynthesis in growing leukemia cells, cells arrested in G2 + M phases of the cell cycle. At 250 microM TDHO methyl ester, analysis of cell extracts by high-performance liquid chromatography showed that after 4 h carbamyl aspartate had accumulated from undetectable levels to 760 microM, whereas UTP decreased from 580 to 110 microM and CTP from 350 to 86 microM, indicating inhibition of dihydroorotase in growing leukemia cells. IMP accumulated from 63 to 350 microM, total guanylates increased while adenylates decreased, and the adenylate energy charge decreased from 0.91 to 0.69 after 4 h. The cellular concentration of 5-phosphoribosyl 1-pyrophosphate increased from 180 to 290 microM due to sparing from pyrimidine nucleotide biosynthesis resulting in complementary stimulation of the de novo purine pathway. HDDP dimethyl ester at concentrations of up to 250 microM had no discernable effect upon pyrimidine or purine nucleotide biosynthesis. At 25 microM HDDP-dimethyl ester, cells arrested in G2 + M phases initially, with accumulation of cells in G1/G0 at later times. These data suggest that the primary mechanisms of growth inhibition for TDHO and HDDP involve inhibition of cell cycle progression from late G2 or M phase to G1 phase and that blockade of the pyrimidine pathway by TDHO is a secondary effect found at higher concentrations.

Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemia.

The glutamine antagonists, acivicin (NSC 163501), azaserine (NSC 742), and 6-diazo-5-oxo-L-norleucine (DON) (NSC 7365), are potent inhibitors of many glutamine-dependent amidotransferases in vitro. Experiments performed with mouse L1210 leukemia growing in culture show that each antagonist has different sites of inhibition in nucleotide biosynthesis. Acivicin is a potent inhibitor of CTP and GMP synthetases and partially inhibits N-formylglycineamidine ribotide (FGAM) synthetase of purine biosynthesis. DON inhibits FGAM synthetase, CTP synthetase, and glucosamine-6-phosphate isomerase. Azaserine inhibits FGAM synthetase and glucosamine-6-phosphate isomerase. Large accumulations of FGAR and its di- and triphosphate derivatives were observed for all three antagonists which could interfere with the biosynthesis of nucleic acids, providing another mechanism of cytotoxicity. Acivicin, azaserine, and DON are not potent inhibitors of carbamyl phosphate synthetase II (glutamine-hydrolyzing) and amidophosphoribosyltransferase in leukemia cells growing in culture although there are reports of such inhibitions in vitro. Blockade of de novo purine biosynthesis by these three antagonists results in a "complementary stimulation" of de novo pyrimidine biosynthesis.

A clinical comparison of AH8165 and pancuronium as muscle relaxants in patients undergoing cardiac surgery.

The non-depolarizing muscle relaxant AH8165 has been compared at two doses (0.5 and 1.0 mg/kg) with pancuronium (0.1 mg/kg) during induction of anaesthesia for patients having major cardiac surgery. After barbiturate-opiate premedication and thiopentone induction, administration of pancuronium was followed by no significant alteration in heart rate or arterial pressure. Both doses of AH8165 werr followed by significant tachycardia, and the higher dose by arterial hypotension. The lower dose of AH8165 was unsatisfactory for tracheal intubation, but the AH8165 1 mg/kg gave intubating conditions similar to those with pancuronium 0.1 mg/kg.