Evaluation of ceftiofur crystalline free acid sterile suspension for control of metritis in high-risk lactating dairy cows.

Two studies were conducted to determine if clinical metritis could be prevented or decreased in at-risk lactating dairy cows by a single treatment with Excede Sterile Suspension (ceftiofur crystalline free acid sterile suspension [CCFA-SS]) administered within 24 hours after an abnormal calving. Study 1 was a preliminary study and study 2 was a clinical trial (designed to confirm the results of study 1). In both studies, abnormal calving was defined as cows that had dystocia (required assistance), twins, abortion, retained fetal membranes for 12 hours or more, or any combination thereof. A randomized block design with cows blocked on order-of-entry within dairy without regard to parity was used in both studies. In study 1, cows that had abnormal calving from six commercial dairies were randomly assigned to either untreated control (N = 122) or 6.6 mg ceftiofur equivalents/kg of body weight sc in the base of the ear (CCFA-SS, N = 121), within 24 hours after calving. Cows with normal calving during the enrollment period received no treatment and were included for observational purposes (N = 122). Health observations and rectal temperatures were recorded daily, and physical examinations were conducted on Days 1 ± 1, 7 ± 2, 14 ± 2, and 21 ± 2, and uterine swabs (for bacterial culture) were collected from a subsample of cows on Days 3 or 4, 7 ± 2, 14 ± 2, and 21 ± 2. These observations were made by treatment-blinded personnel. In study 2, cows with abnormal calving from 12 commercial dairies were assigned to receive either saline (control, N = 247) or CCFA-SS (N = 247) within 24 hours after calving. Health observations and rectal temperatures were recorded daily, and physical examinations were conducted on Days 0 to 2, 7 ± 1, and 14. In study 1, the incidence of metritis on Day 14 ± 2 was 20.2% versus 36.8% for CCFA-SS and control, respectively, with an odds ratio of 2.30 (P < 0.05). In study 2, incidences of metritis on Day 14 were 28.7% versus 43.5% for CCFA-SS and saline, respectively, with an odds ratio of 1.92 (P < 0.05). Rectal temperatures on Days 1 and 2 and the average for the first 6 days were lower (P < 0.05) for CCFA-SS compared with control cows for both studies. Treatment of cows with a single dose of CCFA-SS within 24 hours after abnormal calving reduced the incidence of subsequent metritis in lactating dairy cows.

Evaluation of two doses of ceftiofur crystalline free acid sterile suspension for treatment of metritis in lactating dairy cows.

The objectives of this study were to evaluate efficacy of a 2-dose regimen of ceftiofur crystalline free acid sterile suspension (CCFA-SS) for treatment of acute metritis in lactating dairy cows under field conditions and to provide additional safety and injection site tolerance data for injections at the base of the ear. Cows at 15 dairies with rectal temperature ≥ 39.5°C and fetid uterine discharge ≤ 10 d postcalving were randomly assigned by blocks of 2, based on order of entry and without regard to parity, to treatment with saline (1.5 mL/45.5 kg of body weight, n=509) or CCFA-SS (6.6 mg of ceftiofur equivalents/kg of body weight, n=514). Treatments were administered by subcutaneous injection in the posterior aspect of the ear where it attaches to the head; the first dose was administered on study d 0 and the second dose was administered in the contra lateral ear on study d 3. Rectal temperatures were recorded on study d 1 to 4 and 5 or 6 and cows were clinically evaluated daily from study d 1 to 13. Cows that exhibited increased adverse clinical signs of poor health or complications associated with metritis were categorized as a treatment failure and administered escape therapy. Each cow received a veterinary physical examination on study d 5 or 6 to determine if she should be removed from the study and on study d 14 to determine clinical cure or failure to cure. Clinical cure was defined as rectal temperature <39.5°C and non-fetid and purulent or mucopurulent discharge on study d 14 and no escape therapy administered. The injection procedure was scored after each injection (study d 0 and 3) and injection sites and ear carriage were scored on study d 5 or 6, 14, and 57±3. Of the 1,023 cows enrolled, 7 were completely censored due to protocol deviations and 34 were removed for protocol deviations or medical conditions not related to metritis. Clinical cure rate was higher for CCFA-SS than for saline (74.3 vs. 55.3%) and rectal temperatures for each of study d 1 to 5 or 6 were lower for CCFA-SS than saline. Injection procedure indices showed that CCFA-SS could be practically and safely administered using commercial dairy facilities. Although injection site scores were higher for CCFA-SS than saline at study d 5 or 6 and 14, ≥98.6% of ears were normal on d 57±3. Thus, a 2-dose treatment with CCFA-SS given 72h apart increased metritis clinical cure rate and was well tolerated in dairy cows.

Effect of acarbose on milk yield and composition in early-lactation dairy cattle fed a ration to induce subacute ruminal acidosis.

Subacute ruminal acidosis reduces lactation performance in dairy cattle and most often occurs in animals fed a high concentrate:forage ration with large amounts of readily fermentable starch, which results in increased production of volatile fatty acids and lactic acid and a reduction in ruminal pH. Acarbose is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. In cattle, acarbose acts as an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of volatile fatty acid production and maintaining rumen pH at higher levels. The ability of acarbose to reverse the reduced feed intake and milk fat percentage and yield associated with a high concentrate:forage ration with a high risk of inducing subacute ruminal acidosis was evaluated in 2 experiments with lactating dairy cattle. In 2 preliminary experiments, the effects of a 70:30 concentrate:forage ration on ruminal pH and lactation were evaluated. Ruminal pH was monitored in 5 Holstein steers with ruminal cannulas every 10 min for 5 d. Ruminal pH was <5.5 for at least 4 h in 79% of the animal days. In dairy cows, the 70:30 concentrate:forage ration decreased feed intake 5%, milk fat percentage 7%, and milk fat yield 8% compared with a 50:50 concentrate:forage ration but did not affect milk yield. Early lactating dairy cattle were offered the 70:30 concentrate:forage ration with 0 or 0.75 g/d of acarbose added in a crossover design in 2 experiments. In the first experiment, acarbose increased dry matter feed intake (23.1 vs. 21.6 kg/d) and 3.5% fat-corrected milk yield (33.7 vs. 31.7 kg/d) because of an increase in percentage milk fat (3.33 vs. 3.04%) compared with control cows. In the second experiment, cows were fasted for 3 h before the morning feeding to induce consumption of a large meal to mimic conditions that might be associated with unplanned delayed feeding. In this experiment, acarbose also increased feed intake (22.5 vs. 21.8 kg/d) and 3.5% fat-corrected milk yield (36.9 vs. 33.9 kg/d) due to increased percentage milk fat (3.14 vs. 2.66%) compared with controls. Thus, acarbose reversed the decreased feed intake and low milk fat percentage and yield associated with feeding a high concentrate:forage ration shown to induce subacute ruminal acidosis in Holstein steers.

Effect of acarbose on acute acidosis.

A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level. It is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. The ability of acarbose to reduce the incidence of acidosis and the comparative efficacies of acarbose, sodium bicarbonate, and monensin were tested in 3 acute acidosis challenge experiments in cattle. Rumen-cannulated Holstein steers were challenged with a mixture of 48.4% cornstarch, 48.4% ground corn, 2.1% sodium caseinate, and 1.1% urea with or without test substance. The challenge was administered at a rate of 12.5 g/kg of body weight (BW) as a slurry through the cannula directly into the rumen. Ruminal pH was monitored at 10-min intervals throughout the study. Animals were removed from study and rumen contents replaced if they exhibited acute acidosis as defined as pH <4.5. If acidosis was not observed within 24 h, animals were subjected to a second challenge. Ruminal fluid samples were taken for measurement of VFA and lactate concentrations at various intervals after the challenge. In experiment 1, the carbohydrate challenge induced acidosis in 4 of 4 control animals and 0 of 4 animals treated with 2.14 or 21.4 mg of acarbose/kg of BW in the challenge based on the criterion of pH <4.5. In experiment 2, the carbohydrate challenge induced acidosis in 4 of 7 control animals and 1 of 7 animals when 1.07 mg of acarbose/kg of BW was included in the challenge. In experiment 3, acidosis was induced in 7 of 7 animals in the control, 1% sodium bicarbonate, and 12 mg of monensin/kg of dry matter intake groups and in 3 of 8 steers administered 1.07 mg of acarbose/kg of BW in the challenge. Increases in lactate concentrations and decreases in total VFA associated with acute acidosis were mitigated by acarbose. Thus, acarbose, an amylase and glucosidase inhibitor, prevented or reduced the incidence of acidosis in an acute challenge model in steers and was more effective than monensin or sodium bicarbonate.

Effects of recombinant bovine somatotropin (rbST) and season on plasma and milk insulin-like growth factors I (IGF-I) and II (IGF-II) in lactating dairy cows.

During two studies, effects of recombinant bovine somatotropin (rbST) on plasma and milk IGF's in cows adapted to summer (S; 12 cows) or winter (W; 12 cows) conditions were evaluated. Each study consisted of on-farm periods (30 days) followed by climatology chamber periods (CC; 30 days). Cows were given daily injections of rbST, Sometribove, USAN (25mg/day; 6 cows each study) or saline (control; 6 cows each study). During on-farm periods, blood and milk (am and pm) samples were collected once weekly. During CC periods, blood samples were collected every 2 days and milk samples (am and pm) were collected daily. Plasma IGF-I and IGF-II were increased in cows treated with rbST. A pronounced seasonal pattern in basal and rbST-stimulated plasma IGF-I but not IGF-II was detected. Higher basal and rbST-stimulated plasma IGF-I concentrations in S occurred despite large decreases in feed intake and energy balance. Milk IGF-I and IGF-II was not affected by rbST treatment or season. Although milk IGF-I and IGF-II concentrations were unaffected by rbST treatment, total IGF-output increased due to increased milk yield. The observed seasonal patterns in plasma IGF-I may be indicative of seasonal differences in the coupling of the somatotropin-IGF axis. In particular, we failed to detect an uncoupling of the somatotropin-IGF-I axis in S despite an induced negative energy balance during thermal stress.

Effects of sustained release bovine somatotropin (sometribove) on animal health in commercial dairy herds.

The health of dairy cows given bovine somatotropin (bST) for one lactation was evaluated in 28 commercial herds located in four regions of the United States. At least six herds were in a region and at least one herd/region contained fewer than 60 cows. Cows (n = 1213) were assigned randomly to control or bST groups and were treated beginning in wk 9 to 10 of lactation and every 14 d until dry-off or d 400 of lactation. Management was according to site practices. Cows were observed for health-related signs by farm personnel daily and by the herd veterinarian biweekly. Average 305-d test-day milk yields were 932 kg greater for bST-treated cows. Pregnancy rates, days open, twinning, cystic ovaries, or abortions were unaffected by treatments. Supplementation of cows with bST had no effect on total mastitis cases, total days of mastitis, duration of mastitis, or the odds ratio of a cow to develop mastitis. Cows supplemented with bST used more medications for health events other than mastitis. This usage was associated primarily with treatments for disorders of the foot and hock. Supplemented cows had a slight increase in foot disorders. There was no effect of supplementation with bST on culling from the herd or removal from study. Overall, the results confirm that label directions for bST are adequate for safe use under field conditions. All clinical signs observed in this study occur normally in dairy herds and were managed in cows supplemented with bST.

Growth performance, endocrine, and metabolite responses of finishing hogs to porcine prolactin.

Prolactin, a member of the somatotropin-prolactin-placental lactogen gene family, increases feed intake and rate of weight gain in several species. To determine whether prolactin affects growth performance and carcass composition in swine, recombinant porcine prolactin (rpPRL) was administered to finishing hogs. Doses of 0, 2, 4, 8, and 16 mg of rpPRL/d and 4 mg of recombinant porcine somatotropin (rpST)/d were administered to groups of seven barrows and seven gilts initially weighing 75.0 +/- .2 kg for a 28-d period. Recombinant pPRL did not alter feed intake or growth rate or affect carcass composition. In addition, most growth-related blood variables did not change, although plasma IGF-I was increased in the 8 and 16 mg of rpPRL treatment groups. At slaughter, mammary development was apparent in rpPRL-treated gilts and was characterized by distended alveolar and ductal lumina and presence of secretory material. In rPST-treated hogs, feed intake was decreased 28% (P < .01), gain/feed was increased more in barrows than in gilts (59 vs 39%, treatment x sex interaction, P = .035), and growth rate was increased 22%, but in barrows only (treatment x sex interaction P = .005). Compared with those in control hogs, circulating concentrations of IGF-I, insulin, and glucose were 175, 311, and 22% higher, respectively, and of blood urea nitrogen were 62% lower in rpST-treated hogs (P < .05). These results suggest that rpPRL, at the doses administered, does not increase feed intake in finishing hogs in contrast to rats and other species.

Effects of exogenous somatotropin on whole-body glycemic response to insulin in young preruminant and ruminant lambs.

The purpose of this study was to determine the effects of exogenous recombinant bovine somatotropin (bST) treatment on whole-body glycemic responsiveness and sensitivity to exogenous insulin in preruminant and ruminant lambs. Twelve milk-fed (MF) and 12 ruminating (RUM) wether lambs weighing 20 +/- 0.6 kg were assigned to one of four treatment groups: MF control, MF plus bST, RUM control, and RUM plus bST. Lambs received a daily subcutaneous injection of 160 micrograms of sometribove (recombinant methionyl bST) bST/kg live weight or the equivalent volume of sterile water (control) for 10 d. The MF lambs had higher plasma insulin and nonessential fatty acids and lower acetate concentrations than RUM lambs (all P < 0.05). Plasma insulin-like growth factor concentrations were similar in both. The administration of bST raised plasma insulin-like growth factor-1 (P < 0.001) and insulin (P < 0.05) in MF and RUM lambs, but with greater effect in MF lambs (P < 0.01 and P < 0.1, respectively). Six successive dose-incremented insulin challenges (50, 100, 200, 300, 500, and 700 mU/kg body weight) were performed two per day on Days 8, 9, and 10 of treatment. Dose-response curves for absolute decline in glucose concentration from preinjection baseline to nadir were used to characterize whole-body responsiveness and sensitivity (ED50) to insulin. Somatotropin treatment increased insulin ED50 values 64 and 70% (P < 0.07) in RUM and MF lambs, respectively, suggesting that sensitivity to insulin was reduced. Insulin ED50 values were 40% higher in MF than in RUM lambs (P < 0.05). Insulin clearance rates increased with each dose increment to 300 mU/kg body weight (P = 0.001) and were 50% lower in bST-treated MF lambs than in all other treatment groups (P < 0.05). Results suggest that somatotropin modulates the insulin control of glucose homeostasis similarly in preruminant and ruminant lambs by decreasing sensitivity but not maximum responsiveness.

Performance, clinical chemistry, and carcass responses of finishing lambs to formulated sometribove (methionyl bovine somatotropin).

Formulated zinc methionyl bST (sometribove, 50, 100, or 150 mg) was administered as a single treatment once every 2 wk or as two equal treatments once/week to evaluate the efficacy of prolonged release delivery of bovine somatotropin (bST) in finishing lambs. Feed conversion during the 6-wk treatment period was improved 9 and 19% in lambs that received treatments once and twice/2 wk, respectively (P < .05), and the responses to differing doses were similar within a dosing frequency (P > .05). Carcass muscle:fat ratio indicators generally were affected in a dose-related manner and were independent of frequency of administration. For example, fat thickness was 17, 30, and 42% lower than control in lambs that received 50, 100, and 150 mg of formulated sometribove/2 wk, respectively (P < .05). Percentages of muscle were higher and of fat were lower with increasing dose of formulated sometribove, but weight of only fat was significantly affected (P < .05). Clinical chemistry indices of metabolic effects of bST (e.g., circulating bST, IGF-I, insulin, glucose, and urinary nitrogen concentrations) were affected in directions similar to those observed with bST administered by daily injection. The results of this study demonstrate the growth performance and carcass composition advantages of a formulation designed to deliver bST over a 2-wk period.

Performance, clinical chemistry, and carcass responses of finishing lambs to recombinant bovine somatotropin and bovine placental lactogen.

Bovine placental lactogen (PL) is a partial somatotropin agonist in the cow and decreases urea nitrogen, indicating increased nitrogen retention. In the present study, the somatogenic effects of bovine PL (bPL; 4 and 8 mg/d) were compared with those of bovine somatotropin (bST; 4 and 8 mg/d) in finishing lambs. Measures of comparison included growth performance, carcass composition, and growth-related clinical chemistry traits. Although feed efficiency during the first 3 wk of treatment with bPL was improved by 14% (P < .05), feed efficiency for the full 6-wk treatment period did not differ from that of control lambs. Responsiveness to bPL may have been attenuated by high titer antibodies present after 2 wk of treatment. However, bPL also did not influence growth-related clinical chemistry traits during short-term (7 d) treatment, strongly suggesting that bPL was ineffective in finishing lambs at the doses tested. In contrast, bST improved 6-wk feed efficiency by an average of 17% (P < .05) and decreased feed intake by an average of 12% (P < .05). In addition, measures of carcass composition including longissimus muscle area, specific gravity of the rack, kidney and pelvic fat, and fat thickness demonstrated that bST, but not bPL, treatment decreased carcass fatness and increased carcass leanness. Treatment with bST, but not with bPL, affected IGF-I, insulin, glucose, and urea nitrogen in a dose-related manner. Thus, daily injections of bPL did not affect either performance or carcass quality, whereas performance and carcass responses of finishing lambs to bST were consistent with those reported by others.

Comparison of performance, clinical chemistry, and carcass characteristics of finishing lambs treated with recombinant ovine or bovine somatotropins.

The variation in growth and carcass composition responses of lambs to somatotropin (ST) treatment may depend on the source of ST used as well as on other experimental conditions. In the present experiment, growth, carcass composition, and clinical chemistry responses to recombinantly produced ovine ST (oST) and two bovine ST (N-methionyl-bST[M-bST] and N-alanyl-bST[A-bST] were compared. Lambs weighing 42 kg were assigned to treatment groups of control (no injection) or 4 mg/d of M-bST, A-bST, or oST administered by s.c. injection for 6 wk. Growth rate was increased by an average of 30% and feed efficiency was improved by an average of 22% by ST treatment compared with control, and responses did not differ among ST. The IGF-I, insulin, and glucose concentrations were increased by 107, 700, and 53% compared with control, respectively, and did not differ among ST treatment groups. Urea nitrogen responses to A-bST and oST were transiently greater than those to M-bST. Although quality grade was not affected by treatment, an average .8-kg increase in weight of retail cuts was calculated from yield grade. Carcasses of ST-treated lambs were calculated to have 1.3 kg more muscle and 1.9 kg less fat. Although fat and muscle were affected more by oST than by M-bST on a percentage basis, they did not differ among treatment groups on a total weight basis. Thus, both bST variants and oST improved growth performance and carcass leanness. Decreased responses of some carcass variables to M-bST treatment may have been related to the presence of antibodies that were indicated by an increased number of positive responders in a relative bST binding assay.

Food intake and body temperature responses of rats to recombinant human interleukin-1 beta and a tripeptide interleukin-1 beta antagonist.

Food intake and body temperature are two of many factors affected by IL-1 beta, a cytokine which is produced in response to tissue injury and inflammatory processes. In the present experiment, a tripeptide IL-1 beta antagonist which blocked IL-1 beta-induced hyperalgesia was tested for the ability to block IL-1 beta-induced effects on food intake and body temperature. Food intake was decreased 4-22 h after intraperitoneal (IP) administration of 1.25, 1.88, or 2.50 micrograms IL-1 beta/rat, and 0-22 h food intake was decreased by 1.88 and 2.50 micrograms IL-1 beta/rat. The effect of 1.25 micrograms IL-1 beta/rat on food intake measured 4 and 22 h after (IP) injection was blocked by coadministration of 5 mg tripeptide IL-1 beta antagonist. However, 25 mg tripeptide IL-1 beta antagonist/rat plus 1.25 micrograms IL-1 beta/rat decreased 0-22 h food intake more than IL-1 beta alone. Administration (IP) of 1.25 micrograms IL-1 beta/rat increased body temperature 1 degrees C 4 h later, and 5 and 25 mg tripeptide IL-1 beta antagonist/rat blocked this increase. Although food intake remained decreased after IL-1 beta administration alone or with 25 mg tripeptide IL-1 beta antagonist/rat for 22 h, body temperature returned to normal under these conditions. Thus, a tripeptide IL-1 beta antagonist shown to block IL-1 beta-induced hyperalgesia also blocked food intake and body temperature responses to IL-1 beta, although the effective doses of IL-1 beta and the tripeptide IL-1 beta antagonist differ by 4,000-fold when both are administered peripherally.

Impact of somatotropins on nutrient requirements in domestic animals.

Somatotropins increase nitrogen retention, decrease carcass fat and increase lean/fat ratio in growing ruminants and swine. However, responses are much more variable in growing ruminants. Maintenance requirements in both ruminants and swine are increased slightly with somatotropin treatment in conjunction with increased lean mass. This is associated with increases in partial efficiency of protein accretion, resulting in increased efficiency of growth. Additional information is required to accurately assess effects of somatotropin on nutrient requirements for growing ruminants and swine. Future studies should target degradable and nondegradable protein requirements for growing ruminants and the impact of somatotropin on these requirements; definition of dose, pattern and formulation of somatotropin for both ruminants and swine and interaction of somatotropin with other factors affecting feed intake in swine and ruminants.

Abomasal casein infusion and exogenous somatotropin enhance nitrogen utilization by growing lambs.

Growing Dorset wether lambs (23 kg initial body weight) were used to determine whether the magnitude of nitrogen retention response to daily administration of exogenous somatotropin is limited by post-ruminal amino acid availability in growing ruminants. Eight lambs surgically fitted with abomasal cannulae were fed a total mixed ration of 85% of ad libitum intake. All lambs received a continuous abomasal infusion of 2 L of water or casein and twice daily subcutaneous injections of 0 or 100 micrograms recombinant bovine somatotropin (rbST)/kg body wt for 15 d per treatment in a 2 x 2 single reversal design. The casein solution was infused at a rate (4 to 5 g nitrogen/d) to achieve 25% of nitrogen intake observed with ad libitum feeding prior to initiation of treatments. Each lamb received all four treatments. Nitrogen balance was determined on d 8 to 14 of each treatment. Casein infusion increased nitrogen balance 43.4% (P less than 0.001), and rbST increased nitrogen balance 33.5% (P less than 0.001), without significant interaction (P less than 0.88). Combined effects of casein and rbST were additive, resulting in an 89% increase in nitrogen balance when compared with water plus excipient treatment. Results suggest that the quantity or composition of absorbed amino acids, or both, limit nitrogen retention by growing lambs, and that rbST increases the efficiency of utilization of absorbed amino acids for protein deposition.

Finishing lamb performance responses to bovine and porcine somatotropins administered by Alzet pumps.

Daily injection of ovine and bovine somatotropin (oST and bST, respectively) has been shown to improve performance and carcass quality of finishing lambs. To evaluate responses to continuously released bST and porcine ST (pST), which have 99 and 91% sequence homology with oST, respectively, finishing lambs were implanted with 2-wk Alzet pumps containing bST or pST, which was released at rates of 2 or 4 mg/d. Six-week growth rate and feed efficiency responses to bST were greater than those to pST (P less than .05). Overall feed efficiency was improved 15% and growth rate was increased 16% in lambs treated with 4 mg/d of bST compared with control lambs and neither trait was affected in pST-treated lambs. Performance responses were reflected by changes in circulating glucose, blood urea nitrogen, and insulin-like growth factor I (IGF-I) concentrations. Scatchard analysis of sera with relative binding of greater than 30% revealed that average binding capacities and affinities of pST-treated lambs were 7.0 mg/liter and 6.0 x 10(9) liters/mol, respectively, and of bST-treated lambs were .8 mg/liter and 1.3 x 10(9) liters/mol, respectively. In addition, lambs with high-capacity pST antibodies had lower 6-wk IGF-I concentrations than those of controls, suggesting that these antibodies may have been attenuating responsiveness to pST. It is concluded that continuously released bST, but not pST, improves performance of finishing lambs.

Full amino acid sequence of centrally administered NPY required for maximal food intake response.

Central administration of NPY (1-36) potently increases food intake and it has been hypothesized that biological activities of NPY are related to its ability to form an alpha-helix, represented by the fragment NPY (14-31). In this experiment the necessity of N-terminal fragments for increasing food intake was evaluated. Two-h fasted male rats were administered 0, 0.2, 1.0 or 5.0 nmol NPY (1-36) or NPY fragments in 5 microliters saline ICV and intake of lab chow pellets was measured for 22 h. Fragments containing all or part of the polyproline-like helix [NPY (1-8)] antiparallel to the alpha-helix dose-relatedly increased food intake for 4 hours after injection. Five nmol NPY (1-36) and NPY (2-36) increased 4-hour food intake 486 and 219%, respectively (p less than 0.05). Fragments excluding the first 8 amino acids but including all of the alpha-helix also increased food intake, but the response was much reduced. Five nmol NPY (9-36) and NPY (14-36) increased 4-hour food intake 128% (p = 0.02) and 62% (NS), respectively. When all or part of the alpha-helix was excluded, no activity was detected, i.e., NPY (21-36) and NPY (32-36). Substitution of dPro for lPro in position 2 increased potency but not efficacy of NPY since food intake was increased at the 0.2 and 1.0 but not 5.0 nmol doses and the percent increase was not more than to 5 nmol NPY (1-36). Thus the maximum food intake response to NPY requires both C-terminal and N-terminal fragments as well as the alpha-helix.

Responses of Beijing black hogs to porcine somatotropin.

Somatotropin treatment of U.S-breed finishing hogs improves feed efficiency, growth rate and carcass lean-to-fat ratio. Because Chinese-bred hogs have poorer feed efficiency, growth rate and lean-to-fat ratio than U.S. bred hogs, the characteristics affected by porcine somatotropin (PST) may respond differently to treatment. In the present experiment, Beijing Black finishing hogs (a composite of a local Chinese, Berkshire and Yorkshire breeds) were treated with PST for 28 d from average initial to final weights of 67.8 to 96.6 kg. In hogs individually fed as much as they would eat four times a day (n = 12/treatment group, six gilts and six barrows), feed efficiency was improved by 22.4 and 29.9% by 2 and 4 mg/d PST, respectively (P less than .01), primarily due to increased growth rate (22.1 and 32.6% greater than control, respectively, P less than .01); feed intake was not affected. Performance of group-housed and group-fed hogs (six/pen, four pens/treatment) administered 2 mg/d PST for 28 d (average initial and final weights of 66.5 +/- 1.7 and 94.0 +/- 2.4 kg, respectively) was similar (22.7% improved feed efficiency, P less than .01; 25% increased growth rate, P less than .01). At slaughter, last rib backfat thickness was decreased an average of 19.2% for hogs treated with 2 and 4 mg/d PST (P less than .01). Percentage of total muscle, obtained by physical separation of the half-carcass, was increased an average of 13.5% (P less than .01), whereas percentage of total fat was decreased 21.8% (P less than .01) in PST-treated hogs. The pH, water-holding capacity and meat color scores of longissimus muscle from PST-treated hogs did not differ from those of control hogs. Growth rate, feed efficiency and muscle weight responses to PST treatment were at least as large as those for U.S. breeds.

Mechanisms controlling feed intake in ruminants: a review.

The purpose of this paper is to review our understanding of the involvement of central and peripheral factors in the control of feed intake in ruminants. The regulation of body weight under various states of energy need depends on an animal's ability to control feed intake to meet these needs. In the central nervous system (CNS), the ventromedial and lateral hypothalamus appear to be the areas involved in satiety and hunger, respectively; other important areas are the paraventricular nucleus and rostral brain areas. Intracerebroventricular injection of neurotransmitters, alpha- and beta-adrenergic agonists, 5-hydroxytryptamine and gamma aminobutyric acid (GABA) agonists, has stimulated feeding in ruminants; intravenous administration of benzodiazepines stimulated feed intake in sheep and cattle, possibly by increasing GABA levels in the brain. Neuropeptides of the opioid and cholecystokinin families have reciprocal hunger-stimulating and satiety-eliciting effects when administered centrally in sheep. Further, concentrations of these neuropeptides in specific areas of the hypothalamus have been shown to change with the state of hunger-satiety of sheep. In the periphery, none of the hormones associated with the pituitary, adrenal gland, pancreas or gastrointestinal tract has been shown to have significant effects on the control of feed intake. In addition, the physical properties of the ingested feed in the gastrointestinal tract, while possibly influencing the rate or pattern of feeding, do not appear to be primary factors in the control of feed intake under many feeding conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid peptides and the control of feeding in sheep.

Opioid peptides, particularly beta-endorphin, methionine- (MEK) and leucine-enkephalin, and dynorphin, are involved in the regulation of food intake in mammals. The precursor molecules of these peptides undergo differential processing in brain areas producing regional concentration differences in opioids. Intraregional concentration changes also accompany alterations in feeding states. For example, MEK concentrations decrease in the basomedial hypothalamus, amygdala, and olfactory bulb in fed sheep compared with fasted sheep. Moreover, these changes are species specific. In sheep, beta-endorphin decreases in the dorsomedial and posterior hypothalami after feeding, but in the rat it is increased in the ventromedial hypothalamus and decreased in the posterior hypothalamus. In addition, immunohistochemical localization of cell bodies shows interspecies differences in concentrations. For example, dynorphin is found predominantly in the suprachiasmatic area in sheep, but in the paraventricular nucleus in the rat. These observations indicate that regulation of food intake may be differentially controlled in these species. In sheep, kappa agonists increase food intake, whereas stimulation of delta receptors inhibits feeding. Further clarification of the receptors involved in food intake will necessitate studies with more specific agonists.

Circadian rhythm of feeding induced changes in hypothalamic Met-enkephalin concentrations.

Accumulating evidence suggests that opioid peptides play an important role in the hunger component of the control of food intake. The enkephalins, one of the opioid peptide families, stimulate feeding when injected into specific hypothalamic areas and endogenous concentrations change with the fed/fasted condition of rats and sheep and with phase of circadian cycle. To demonstrate a possible circadian rhythm in feeding-induced changes in Met-enkephalin (MEK), 54 male rats initially weighing 255 +/- 3 g were adapted to a 12-hr fast during the light (light-fasted) or dark (dark-fasted) phase of the circadian cycle, then sacrificed before (non-fed) or after (fed) being allowed to eat a meal. In non-fed compared with fed rats, MEK concentrations were higher in the paraventricular nucleus (PVN, 170 vs. 109 pg/mg tissue, p less than 0.05) and ventromedial hypothalamus (VMH, 209 vs. 161 pg/mg tissue, p less than 0.05) in the dark (light-fasted) but not light (dark-fasted), even though rats ate a larger meal in the light (8.6 vs. 5.0 g, p less than 0.01). In rats fed the same amount of food in the light (dark-fasted) as ad lib fed rats in the dark (light-fasted), MEK concentrations did not differ in the PVN or VMH, suggesting that circadian rhythm is more important than meal size. Rats gavaged with an amount of milk equal in calories to dark ad lib-fed rats (light-fasted) had MEK concentrations not different from light-fasted non-fed rats (216 vs. 209 pg/mg tissue, NS) suggesting that feeding behavior, pregastric stimuli and/or form of diet is important for influencing MEK concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)