Immunotherapy of the nonobese diabetic mouse: treatment with an antibody to T-helper lymphocytes

Spontaneous diabetes mellitus was blocked in nonobese diabetic mice by treatment with a monoclonal antibody against the L3T4 determinant present on the surface of T-helper lymphocytes. Sustained treatment with the monoclonal antibody led to cessation of the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Moreover, the mice remained normoglycemic after the antibody therapy was stopped. These studies indicate that immunotherapy with monoclonal antibodies to the lymphocyte subset may not only halt the progression of diabetes, but may lead to long-term reversal of the disease after therapy has ended.     

Influence of slow-release urea on nitrogen balance and portal-drained visceral nutrient flux in beef steers

Two experiments were conducted to evaluate the effects of slow-release urea (SRU) versus feed-grade urea on portal-drained visceral (PDV) nutrient flux, nutrient digestibility, and total N balance in beef steers. Multi-catheterized steers were used to determine effects of intraruminal dosing (Exp. 1; n = 4; 319 +/- 5 kg of BW) or feeding (Exp. 2; n = 10; 4 Holstein steers 236 +/- 43 kg of BW and 6 Angus steers 367 +/- 46 kg of BW) SRU or urea on PDV nutrient flux and blood variables for 10 h after dosing. Intraruminal dosing of SRU (Exp. 1) prevented the rapid increase in ruminal ammonia concentrations that occurred with urea dosing (treatment x time P = 0.001). Although apparent total tract digestibilities of DM, OM, NDF, and ADF were not affected by treatment (P > 0.53, Exp. 2), SRU increased fecal N excretion (49.6 vs. 45.6 g/d; P = 0.04) and reduced apparent total tract N digestibility (61.7 vs. 66.0%; P = 0.003). Transfer of urea from the blood to the gastrointestinal tract occurred for both treatments in Exp. 1 and 2 at all time points with the exception for 0.5 h after dosing of urea in Exp. 1, when urea was actually transferred from the gastrointestinal tract to the blood. In both Exp. 1 and 2, both urea and SRU treatments increased arterial urea concentrations from 0.5 to 6 h after feeding, but arterial urea concentrations were consistently less with SRU (treatment x time P < 0.001, Exp. 1; P = 0.007, Exp. 2). Net portal ammonia release remained relatively consistent across the entire sampling period with SRU treatment, whereas urea treatment increased portal ammonia release in Exp. 1 and tended to have a similar effect in Exp. 2 (treatment x time P = 0.003 and P = 0.11, respectively). Urea treatment also increased hepatic ammonia uptake within 0.5 h (treatment x time P = 0.02, Exp. 1); however, increased total splanchnic release of ammonia for the 2 h after urea treatment dosing suggests that PDV ammonia flux may have exceeded hepatic capacity for removal. Slow-release urea reduces the rapidity of ammonia-N release and may reduce shifts in N metabolism associated with disposal of ammonia. However, SRU increased fecal N excretion and increased urea transfer to the gastrointestinal tract, possibly by reduced SRU hydrolysis or effects on digestion patterns. Despite this, the ability of SRU to protect against the negative effects of urea feeding may be efficacious in some feeding applications.     

Expression of mRNA for proglucagon and glucagon-like peptide-2 (GLP-2) receptor in the ruminant gastrointestinal tract and the influence of energy intake

Glucagon-like peptide-2 (GLP-2) is a potent trophic gut hormone, yet its function in ruminants is relatively unknown. Experiment 1 was conducted as a pilot study to establish the presence of GLP-2 in ruminants and to ascertain whether it was responsive to increased nutrition, as in non-ruminants. Concentrations of intact GLP-2 in the blood and gut epithelial mRNA expression of proglucagon (GCG) and the GLP-2 receptor (GLP2R) were measured in 4 ruminally, duodenally, and ileally cannulated steers. Steers were fed to meet 0.75 × NE_M for 21 d, and then increased to 1.75 × NE_M requirement for another 29 d. Blood samples and ruminal, duodenal, and ileal epithelium biopsies were collected at low intake (Days −6 and −3), acute high intake (Days 1 and 3), and chronic high intake (Days 7 and 29) periods. Experiment 2 investigated the mRNA expression pattern of GCG and GLP2R in epithelial tissue obtained from the forestomachs (rumen, omasum, and abomasum) and intestines (duodenum, jejunum, ileum, and colon) of 18 forage-fed Angus steers (260 kg BW). In Experiments 1 and 2, real-time polymerase chain reaction showed that expression of GCG and GLP2R mRNA was detectable in forestomach tissues, but expression was greater (P < 0.001) in small intestinal and colon tissue. High energy intake tended (P = 0.07) to increase plasma GLP-2 during the acute period and was paralleled by a 78% increase (P = 0.07) in ileal GCG mRNA expression. After this initial adaptation, duodenal GCG mRNA expression increased (P = 0.08) during the chronic high intake period. Duodenal GLP2R mRNA expression was not affected by energy intake, but ileal GLP2R expression was increased after 29 d of high energy intake compared to both the low and acute high intake periods (P = 0.001 and P = 0.01, respectively). These data demonstrate that cattle express GCG and GLP2R mRNA primarily in small intestinal and colon tissues. Increased nutrient intake increases ileal GCG mRNA and plasma GLP-2, suggesting that GLP-2 may play a role in the trophic response of the ruminant gastrointestinal tract to increased feed intake.     

Effects of slow-release urea on ruminal digesta characteristics and growth performance in beef steers

Two experiments were conducted to evaluate the effects of slow-release urea (SRU) versus feed-grade urea on ruminal metabolite characteristics in steers and DMI, gain, and G:F in growing beef steers. Experiment 1 used 12 ruminally cannulated steers (529 +/- 16 kg of BW) to monitor the behavior of SRU in the ruminal environment. Compared with feed-grade urea, SRU decreased ruminal ammonia concentration (P = 0.02) and tended to increase ruminal urease activity (P = 0.06) without affecting ruminal VFA molar proportions or total concentrations (P > 0.20). After 35 d of feeding, the in situ degradation rate of SRU was not different between animals fed urea or SRU (P = 0.48). Experiment 2 used 180 Angus-cross steers (330 +/- 2.3 kg) fed corn silage-based diets supplemented with urea or SRU for 56 d to evaluate the effects on feed intake, gain, and G:F. The design was a randomized complete block with a 2 x 4 + 1 factorial arrangement of treatments. Treatments included no supplemental urea (control) or urea or SRU at 0.4, 0.8, 1.2, or 1.6% of diet DM. Over the entire 56 d experiment, there were interactions of urea source x concentration for gain (P = 0.04) and G:F (P = 0.01) because SRU reduced ADG and G:F at the 0.4 and 1.6% supplementation concentrations but was equivalent to urea at the 0.8 and 1.2% supplementation concentrations; these effects were due to urea source x concentration interactions for gain (P = 0.06) and G:F (P = 0.05) during d 29 to 56 of the experiment. The SRU reduced DMI during d 29 to 56 (P = 0.01) but not during d 0 to 28, so that over the entire experiment there was no difference in DMI for urea source (P = 0.19). These collective results demonstrate that SRU releases N slowly in the rumen with no apparent adaptation within 35 d. Supplementation of SRU may limit N availability at low (0.4%) concentrations but is equivalent to urea at 0.8 and 1.2% concentrations.