Developmental alterations in the regulation of glucagon and insulin secretion in Holstein calves

Twenty-one Holstein bull calves were randomly assigned at birth to 3 groups. Two groups (each of 7 calves) were raised as follows: fed a milk diet alone or fed milk with grain supplementation after 2 weeks of age; studies were done when calves reached 4 weeks of age. The 3rd group was fed on milk with grain supplementation until weaning after which the calves were maintained on grain and pasture. These calves (older calves) were studied at 12 weeks of age. Either propionate (0.28 mmol/kg) or glucose (0.56 mmol/kg) was injected IV in a random order. Samples of blood were obtained from the calves before and immediately after injections were done and at 2, 5, 10, 15, 30, 45, and 60 minutes after secretagogue injection. Plasma was examined for glucose by a glucose oxidase procedure and for immunoreactive insulin (IRI) and glucagon (IRG) by radioimmunoassay. The IRI response to the injection of glucose was greater in older calves (P less than 0.02). Patterns of IRI secretion, as determined by heterogeneity of regression, showed age differences for both secretagogues (P less than 0.05). Base-line IRG was greater in milk/grain-fed calves than in milk-fed calves (P less than 0.05). Mean IRG response to propionate injection was higher (P less than 0.05) in milk/grain-fed calves than in milk-fed calves. Plasma glucose concentration increased in older calves, but decreased in milk-fed calves after propionate injection. The data indicate that maturation in the ruminant is accompanied by altered regulation of insulin and glucagon secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nutrient intake on the development of the somatotropic axis and its responsiveness to GH in Holstein bull calves

We investigated the effect of increasing nutrient intake on the responsiveness of the GH/IGF-I system in calves fed a high-protein milk replacer. Fifty-four Holstein bull calves were fed one of three levels (low, medium, and high; n = 18 per treatment) of a 30% crude protein, 20% fat milk replacer to achieve target rates of gain of 0.50, 0.95, or 1.40 kg/d, respectively, for low, medium, and high. Six calves per treatment were slaughtered at approximately 65, 85, and 105 kg BW. Additionally, six calves were slaughtered at 1 d of age to provide baseline data. Plasma aliquots from blood samples collected weekly were analyzed for IGF-I, insulin, glucose, NEFA, and plasma urea nitrogen (PUN). Plasma IGF-I and insulin, measured weekly, increased (P < 0.001) with greater nutrient intake from wk 2 of life to slaughter. Plasma glucose and NEFA also increased (P < 0.05) with nutrient intake. In addition, each calf underwent a GH challenge beginning 4 d before the scheduled slaughter. Plasma from blood collected before the first GH injection and 14 and 24 h after the third injection was analyzed for IGF-I and PUN. Response to challenge, calculated as the absolute difference between the prechallenge and 14-h postchallenge plasma IGF-I concentrations, was significant in calves on all three treatments. Plasma urea nitrogen was not different among treatments as measured weekly but decreased (P < 0.001) following GH challenge in all calves. Results of ribonuclease protection assays showed increased expression of hepatic mRNA for GH receptor 1A and IGF-I with increased intake. The amounts of GH receptor and IGF-I mRNA in muscle and adipose, however, were not affected by intake. In summary, plasma IGF-I was elevated in calves with increased nutrient intake, and the elevations in plasma IGF-I following short-term administration of GH were significant in all calves by 65 kg BW. Data demonstrate that in well-managed milk-fed calves the somatotropic (GH/IGF-I) axis is functionally coordinated and sensitive to nutrient intake and GH.     

Orally administered clonidine as a secretagogue of growth hormone and as a thymotrophic agent in dogs of various ages

The growth hormone (GH) secretagogue activity of variable dosages of clonidine (16.5, 50, 150, and 450 micrograms/kg of body weight), given orally mixed with the daily food ration, was evaluated in young and old dogs. Significant (P less than 0.05) increase in plasma GH concentration was detected at all dosages tested in young dogs and in response to all but the lowest dose tested in the old dogs fed the clonidine-containing diet. Old dogs had plasma GH concentration that exceeded that of young dogs when higher doses of clonidine were used. A clonidine (100 micrograms/kg)-supplemented diet was fed to middle-aged dogs twice daily for 30 days. Significant (P less than 0.01) increase of plasma GH concentration was observed on the first day of the feeding trial, but was undetectable by day 30. After feeding the clonidine-enhanced diet for 30 days, the effects on thymic morphology were variable, and there was no effect on plasma thymulin titer. Clonidine-fed dogs had significantly increased lymphocyte blastogenic responsiveness to mitogens, compared with that of control dogs, when evaluated as stimulation index.     

Relation of growth hormone response to growth hormone-releasing hormone to estimation of milk production via deuterium oxide dilution in beef cattle

Current methods of estimating milk production in beef cows can be time-consuming, labor-intensive, and subject to high variability. The weigh-suckle-weigh (WSW) method requires repeated separation of offspring from their dams. Machine milking requires that animals be acclimated to the equipment prior to the estimation. The objective of Exp. 1 was to validate a deuterium oxide (D2O) dilution method of estimating milk production in cattle. In Exp. 1, Holstein calves (n = 5) averaging 29+/-2 d of age and 52.6+/-2.5 kg (+/- SE) were used as the model. Blood was collected for baseline D2O measurements followed by an injection of 300 mg D2O/kg BW. Syringes were weighed before and after the injection to gravimetrically determine the dose. Another blood sample was collected after D2O was allowed to equilibrate with body water for 2 h, and on each of the next five consecutive days, prior to feeding. Actual milk intake was measured by disappearance (i.e., amount of milk replacer offered to the calf minus the amount refused). Deuterium oxide in plasma was measured by mass spectrometry and milk intake was computed from the disappearance curve of D2O in blood plasma for each calf. Accumulated milk intake estimated by D2O dilution was highly correlated (y = 0.9x + 0.6; R2 = 0.99; P < 0.001) with actual milk intake. The objectives of Exp. 2 were to determine whether 1) D2O dilution was comparable to a standard measure of milk production in beef heifers and 2) growth hormone (GH) response to GH-releasing hormone (GHRH) in heifers at weaning is predictive of subsequent milk production. Deuterium oxide dilution and WSW were compared using 14 first-calf Angus heifers and their calves. Deuterium oxide dilution was used to estimate milk production of 40 first-calf Angus heifers that had been challenged with GHRH at weaning. Results indicate that the D2O dilution method is correlated (R2 = 0.89; P = 0.04) to the WSW estimation of milk production. Growth hormone response to GHRH in weanling heifers is positively related (R2 = 0.22; P = 0.03) to their subsequent milk production. Deuterium oxide dilution in calves offers an additional approach to the estimation of milk production of the dam in typical beef cattle production settings.     

Effect of spiramycin and tulathromycin on abomasal emptying rate in milk-fed calves

Impaired abomasal motility is common in cattle with abomasal disorders. The macrolide erythromycin has been demonstrated to be an effective prokinetic agent in healthy calves and in adult cattle with abomasal volvulus or left displaced abomasum. We hypothesized that 2 structurally related macrolides, spiramycin and tulathromycin, would also be effective prokinetic agents in cattle. Six milk-fed, male, Holstein-Friesian calves were administered each of the following 4 treatments: spiramycin, 75 000 IU/kg BW, IM, this dose approximates 25 mg/kg BW, IM; tulathromycin, 2.5 mg/kg BW, SC; 2 mL of 0.9% NaCl (negative control); and erythromycin, 8.8 mg/kg BW, IM (positive control). Calves were fed 2 L of cow’s milk containing acetaminophen (50 mg/kg body weight) 30 min after each treatment was administered and jugular venous blood samples were obtained periodically after the start of sucking. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration. Spiramycin, tulathromycin, and the positive control erythromycin increased abomasal emptying rate compared to the negative control. We conclude that the labeled antimicrobial dose of spiramycin and tulathromycin increases the abomasal emptying rate in healthy milk-fed calves. Additional studies investigating whether spiramycin and tulathromycin exert a prokinetic effect in adult cattle with abomasal hypomotility appear indicated.     

Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in clinically normal milk-fed calves

OBJECTIVE: To characterize the change of pH in the abomasal lumen throughout a 24-hour period, to determine whether pH of the abomasal body differs from pH of the pyloric antrum, and to determine whether oral administration of cimetidine and ranitidine alters pH of the abomasal lumen in milk-fed calves. ANIMALS: 5 male dairy calves (4 Holsteins-Friesian, 1 Ayrshire), 5 to 15 days old. PROCEDURE: Cannulas were surgically positioned in the abomasal body and pyloric antrum of each calf. Calves received the following treatments in a randomized crossover design: milk replacer (60 ml/kg of body weight, q 12 h [untreated control calves]), milk replacer and cimetidine (50 or 100 mg/kg, q 8 h), or milk replacer and ranitidine (10 or 50 mg/kg, q 8 h). The pH of the abomasal body and pyloric antrum was measured for 24 hours, using miniature glass pH electrodes. RESULTS: Suckling of milk replacer immediately increased abomasal luminal pH from 1.4 to 6.0, followed by a gradual decrease to preprandial values by 6 hours. Preprandial and postprandial pH values were not significantly different between the abomasal body and pyloric antrum, indicating lack of pH compartmentalization in the abomasum of milk-fed calves. Administration of cimetidine and ranitidine caused a significant dose-dependent increase in mean 24-hour abomasal luminal pH. CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal acid secretion in milk-fed calves is mediated in part by histamine type-2 receptors. Cimetidine and ranitidine may be efficacious in the treatment of abomasal ulcers in milk-fed calves.     

Determination of effective dosage of GH-releasing factor for blood GH responses in mithun (Bos frontalis)

A study was undertaken to determine the effective dosage of GH-releasing hormone (GRF) required to produce blood GH response in mithun (Bos frontalis), a semi-wild ruminant species. For the purpose, 12 mithuns averaging 11.5 months of age and 146 kg body weight (BW) were randomly assigned to receive GRF (n = 12), administered at 0 (normal saline), 5, 10 and 20 mug per 100 kg BW. Blood samples were collected prior to and after GRF administration at -60, -45, -30, -15, -10, -5, 0 min and 5, 10, 15, 30 and thereafter, at 15-min interval up to 8 h post-GRF were assayed for plasma GH. For all the dosages, the pre-treatment GH concentrations and corresponding area under GH response curve (AUC) were similar (p > 0.05). The post-GRF plasma GH responses to different dosages of GRF viz. 5, 10 and 20 mug per 100 kg BW and corresponding AUCs were higher (p < 0.05) than those recorded in normal saline-treated controls. The GH responses to 10 and 20 mug GRF per 100 kg BW and corresponding AUCs were higher (p < 0.05) than those registered in mithuns administered with 5 mug GRF per 100 kg BW. Interestingly, post-GRF concentration of plasma GH and AUCs were not different for 10 and 20 mug GRF per 100 kg BW dosages. In all animals treated with GRF, a peak of GH was registered within 10 to 20 min post-GRF. Following 5 mug GRF per 100 kg BW, GH concentrations were maintained at higher level for 90 min post-GRF and thereafter became similar to that of controls and it was 435 min for 10 and 20 mug GRF per 100 kg BW dosages. In conclusion, our results suggest that 10 mug GRF per 100 kg BW is the dosage, which can be used for augmentation of mithun production.     

Evaluation of commercial oral replacement formulas in healthy neonatal calves

Effects of 5 commercial oral replacement formulas on hematologic and plasma biochemical values, body weight, and prevalence of diarrhea were studied in healthy neonatal calves. Products were fed according to manufacturers' recommendations beginning at 3 to 7 days of age for 3 days. Whole milk, diluted 1:1 with commercial formulas, was fed for 3 days thereafter. There were no consistently significant (P greater than 0.05) effects of commercial product feeding with time or by treatment, as compared with those in whole milk-fed controls, on the hematologic or biochemical values of PCV, leukocyte count, platelet count, or plasma K, Cl, glucose, and lactic acid concentrations. Plasma Na concentrations decreased significantly (P less than 0.05) with age in all groups. After 2 weeks, milk-fed calves had gained 2.09 +/- 0.96 kg, and calves fed all but 2 hypertonic energy-dense products 1 and 5 had significant (P less than 0.05) weight losses (up to 2.95 +/- 1.34 kg). Transition to a diet of whole milk and commercial product at one half each of their standard doses resulted in a significant (P less than 0.05) occurrence of diarrhea. Seemingly, such formulas should not be fed to healthy calves on a long term basis. The product with the lowest osmolal and caloric content was associated with the greatest weight loss.     

Comparative pharmacokinetics of chlortetracycline in milk-fed versus conventionally fed calves

Plasma and tissue concentration and pharmacokinetics of chlortetracycline (CTC) was determined in milk-fed and conventionally fed Holstein calves. A two-compartment open model was used after a single intravenous dose (11 mgn CTC/kg body weight). There were no significant differences between dietary treatments. The drug was rapidly distributed from plasma into the peripheral compartment but was slowly eliminated, with detectable concentration of CTC continuing for 72 h after dosing. A single-compartment model was used after a single oral dose (22 mg CTC/kg body weight). All but four of the kinetic parameters were significantly different for the two dietary treatments. Milk-fed calves had a larger area under the plasma level curve, a larger fraction of the dose absorbed, a smaller volume of distribution and a smaller overall body clearance rate. Estimated recovery of CTC in the urine of the milk-fed calves was greater, regardless of route of administration. The concentration of CTC in tissues following an oral dose was greatest in kidney, followed by liver, heart, skeletal muscle, spleen and brain. Tissue depletion of CTC closely paralleled the decline in plasma concentration.     

Plasma growth hormone concentrations in female mithun (Bos frontalis) of different ages: relations with age and body weight

The role of growth hormone (GH) in postnatal somatic growth is well established. Its basal level and relation to growth performance in different age group mithun (Bos frontalis), a semiwild ruminant has not been characterized until now. To estimate the normal blood GH level and also to assess the influence of age and body weight (BW) on blood GH level in captive mithuns, a total of 65 female mithuns was divided into six age groups (group I, 0-6 months; group II, >6-12 months; group III, >1-2 years; group IV, >2-2.5 years; group V, >2.5-3.0 years and group VI, >3.0 years). Blood samples collected weekly for six consecutive weeks were assayed for GH. GH was also estimated in the samples collected from six growing mithuns at -60, -45, -30, -15, -10, -5 and 0 min prior to GH-releasing hormone (GHRH) administration for calculation of basal GH level and at 5, 10, 15, 30 min and thereafter at 15-min interval up to 8 h post-GHRH to assess blood GH response following GHRH administration in growing mithuns. For calculation of basal plasma GH in adult mithuns, GH was measured in blood samples collected at 30-min interval for 24 h from four animals. BW of all animals was recorded on two consecutive days per week and average of weekly BW was considered for growth rate calculation. It was found that both mean GH and GH per 100 kg BW between the age groups differ (p < 0.01). With increasing age and BW, GH and GH per 100 kg BW both decreased (p < 0.01). The age group with higher plasma GH and GH per 100 kg BW showed higher growth rates (r = 0.83 and 0.97 respectively). Interestingly, mean plasma GH for six consecutive weeks in all the groups showed much greater GH concentration (group I, 86.6 +/- 9.7 ng/ml to group VI 33.2 +/- 5 ng/ml) than reported in other species. Mean basal plasma GH calculated in growing and adult mithuns was 29.6 +/- 4.01 ng/ml and around 25 +/- 3.6 ng/ml respectively. The GH peak (444 +/- 21.3 ng/ml) was registered at 15 min post-GHRH administration in growing mithuns. In conclusion, age and BW influence plasma GH and GH per 100 kg BW but the latter is a better indicator of growth. The basal plasma GH and GH response to GHRH administration is six to eight and four to five times higher in mithun than in other species reported so far. An accurate assessment of the relationship between GH profiles and protein metabolism, proper receptor level study for GH action at the cellular level and the interaction of GH with other growth factors awaits better understanding of higher GH in this unique species.     

GH secretory responses to ghrelin and GHRH in growing and lactating dairy cattle

Release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus. A novel peripheral release-regulating hormone, ghrelin, was recently identified. In this study, differences of the GH secretory response to ghrelin and GHRH in growing and lactating dairy cattle were investigated and an alteration of plasma ghrelin levels was observed. The same amounts of ghrelin and GHRH (0.3 nmol/kg) were intravenously injected to suckling and weanling calves, early and mid-lactating cows and non-lactating cows. Plasma ghrelin levels were also determined in dairy cattle in various physiological conditions. The peak values of ghrelin-induced GH secretion were increased in early lactating cows compared to those in non-lactating cows. The relative responsiveness of GH secretion to ghrelin was also increased compared with that to GHRH in early lactating cows. GH secretory responses to GHRH were blunted in mature cows with and without lactation. Conversely, GHRH-induced GH secretory response was greater than that to ghrelin in calves, and also greater in calves than in mature cows. Plasma ghrelin concentrations were elevated in early lactating cows compared to those in non-lactating cows. Plasma GH concentrations were higher in suckling calves and early lactating cows compared with those in non-lactating cows. These results suggest that GHRH is an effective inducer of GH release in growing calves, and that the relative importance of ghrelin in contributing to the rise in plasma GH increases in early lactating cows.     

Tumor necrosis factor as a potential mediator of acute metabolic and hormonal responses to endotoxemia in calves

The effects of coliform endotoxin (E) and recombinant bovine tumor necrosis factor alpha (TNF) were compared with respect to clinical signs of disease and changes in plasma metabolite and pituitary and pancreatic hormone concentrations in calves. In addition, changes in plasma TNF concentration during each challenge exposure were quantitated by use of radioimmunoassay. Healthy Holstein bull calves with mean body weight of 90 kg were each given, in order, on different days, saline solution (5.0 ml, IV, day 1, n = 4), E (type 055:B5, 1.0 micrograms/kg of body weight IV, day 2, n = 4) and TNF (5.0 micrograms/kg IV, day 9, n = 3). Jugular venous blood samples, rectal temperature reading, and PCV were obtained at hourly intervals before (2 hours) and after challenge exposure. The PCV increased (P less than 0.05) after E and TNF administrations for the first 5 hours, then returned to normal in calves given E, but decreased and remained low in calves given TNF through 24 hours. Plasma triglyceride and nonesterified free fatty acids concentrations were increased through 10 hours (P less than 0.05) after E administration, whereas triglyceride and nonesterified free fatty acids concentrations were not significantly affected by TNF administration. Increase in blood glucose concentration at 1 hour after administration of E and TNF was followed by prolonged hypoglycemia that lasted through 6 hours. Changes in plasma insulin concentration paralleled the observed changes in glucose concentration, initially increased at 2 hours after E and TNF (P less than 0.05) administrations, but then tended to decrease below control values thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of sulphanilamide and its three acetyl metabolites in dairy cows and calves

An intravenous low dosage of sulphanilamide (SAA) (14.0 mg/kg) to 6 pre-ruminant calves revealed a biphasic SAA plasma disposition with a mean elimination half-life of 4.1 h. The main metabolite in plasma was N4-acetylsulphanilamide (N4), which 4 hours after injection exceeded the parent SAA plasma concentration. Urinary recovery of SAA was 10 to 16% of the dose; of N4, it was at least 69%. Traces of the N1-acetyl (N1) metabolite and the doubly acetylated derivative (N1N4) were present in urine. The renal clearances of the N1 and N4 metabolites showed a tubular secretion pattern, which was at least 2 to 6 times higher than that of SAA. A single high oral SAA dose of 200 mg/kg to 3 dairy cows resulted in extensive metabolism of SAA into N4, N1, and N1N4 metabolites; their mean maximum plasma concentrations were 64, 48, 0.72 and 24 micrograms/ml, respectively. The mean disposition half-life of SAA in plasma and milk was 10 h. In milk the metabolite concentrations exceeded those in plasma; the N4 and N1N4 metabolite concentrations in milk exceeded that of SAA. The mean maximum concentrations of SAA, N4, N1, and N1N4 in milk were 52, 89, 2.3, and 98 micrograms/ml, respectively. For SAA and its metabolites, the binding to plasma and milk proteins was determined. No glucuronide or sulphate conjugates of SAA and its acetyl metabolites could be found in plasma, milk, or urine. Based on the sensitivity of the bioassay (0.2 micrograms SAA/ml), a withholding time of 5 days was suggested for milk following single oral SAA dosage of 200 mg/kg.     

Effects of intravenous ghrelin injection on plasma growth hormone,insulin and glucose concentrations in calves at weaning

Ghrelin action, which stimulates growth hormone (GH) secretion, may alter during the weaning period in calves. Our objective was to compare the effects of intravenous ghrelin injection on plasma GH, insulin and glucose concentrations in calves around the weaning period. Four Holstein bull calves were fed whole milk and allowed free access to solid feeds, and weaned at 7 weeks of age. Measurements were performed at weeks 1, 2, 4, 6, 7, 9, 11 and 13, when calves were intravenously injected with ghrelin (1.0 μg/kg body weight (BW)) through a catheter, and jugular blood samples were obtained temporally relative to the injection time. Estimated digestible energy intake per metabolic BW transiently decreased at week 7 because of low solid intake immediately after weaning, and thereafter gradually increased. Plasma insulin and glucose concentrations were not affected by ghrelin injection at all ages. In contrast, plasma GH concentrations increased with ghrelin injection at all ages. The incremental area of GH at week 7 was greatest and significantly higher compared with weeks 2, 4, 6 and 9. This result suggests that nutrient insufficiency immediately after weaning enhances GH responsiveness to ghrelin.     

Efficacy evaluations of the use of oral tilmicosin in pneumonic calves

The therapeutic effect of oral tilmicosin was compared with enrofloxacin, and the efficacy of three doses of the drug was examined in two fully randomized blinded field trials. Pneumonic milk-fed calves between 3 days and 2.5 months of age were allocated into two groups in trial 1 (50 animals) and into three groups in trial 2 (69 calves). In the first trial, the animals were treated with 25 mg/kg/day tilmicosin or 2.5 mg/kg/day enrofloxacin in milk for 5 days. In the second trial, the calves received either 25 mg/kg/day tilmicosin for 5 days or 3 days, or else 12.5 mg/kg tilmicosin for 5 days. All calves were clinically examined for 10 days. In the first trial, oral tilmicosin at a dose of 25 mg/kg/day for 5 days proved to be effective for the treatment of endemic pasteurellosis of milk-fed calves. The efficacy was the same as that of enrofloxacin. All three doses in the second trial were effective and were statistically equivalent to the original dose tested.     

Relative bioavailability of microgranulated sulfadimidine in veal calves

The kinetics of free and microgranulated sulfadimidine were compared in milk-fed calves dosed orally (180 mg/kg) in a crossover study. Microgranulation results in delayed absorption of sulfadimidine and poor bioavailability, with the area under the plasma concentration-time curve ( AUC (O-oo)) reduced from 7400 to 3781 μg·h/mL, and maximum plasma concentration ( C _max) reduced from 188.1 ± 39.0 to 84.41 ± 22.6 μg/mL. It is concluded that sulfadimidine microgranulated with long chain fatty acids is not suitable for use in milk-fed calves; the gastrointestinal transit time is too rapid to allow full release of the drug, markedly limiting its bioavailability. In adult animals, or in the young of other animal species in which digesta transit time is slower than in calves, the bioavailability of microgranulated sulfadimidine may be much greater.     

Role for des-acyl ghrelin in the responsiveness of plasma hormones and metabolites to ghrelin in Holstein steers

Gastric-derived peptide hormone ghrelin is known for its potent growth hormone (GH) stimulatory effects. The acyl-modification on N-terminal Ser(3) residue is reported to be important to stimulate the ghrelin receptor, GH secretagogue-receptor type1a (GHS-R1a). However, major portion of circulating ghrelin lacks in acylation, and some biological properties of des-acyl ghrelin have been reported in monogastric animals. In the present study, the responsiveness of plasma hormones and metabolites to ghrelin in steers was characterized, and role for des-acyl ghrelin in these changes was investigated. The repeated intravenous administrations of bovine ghrelin (1.0 microg/kg BW) every 2h for 8h to Holstein steers significantly increased the plasma acylated ghrelin, total ghrelin, GH, insulin and NEFA levels. The GH responses in peak values and area under the curves (AUCs) were attenuated by repeated injections of ghrelin, however, the responses of plasma total ghrelin were similar. Plasma insulin AUC decreased after fourth injection of ghrelin while plasma NEFA AUCs gradually increased by repeated injections of ghrelin. Pretreatment of des-acyl ghrelin (10.0 microg/kg BW) 5 min prior to the single injection of ghrelin (1.0 microg/kg BW) did not affect the ghrelin-induced hormonal changes. Moreover, the responses of plasma GH to bovine and porcine ghrelin, which differ in C-terminal amino acid residues, were similar in calves. These data show that (1) GH release was attenuated by repeated administration of ghrelin, (2) ghrelin regulates glucose and fatty acid metabolism probably via different pathway, and (3) des-acyl ghrelin is unlikely the antagonist for ghrelin to induce endocrine effects in Holstein steers.     

Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves

The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3‐week‐old) and ruminating (6‐month‐old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high‐pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration–time profile of the central compartment was best described by a two‐compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age‐related differences in plasma concentration–time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.     

Pre-pubertal measurements of the somatotrophic axis as predictors of milk production in Holstein-Friesian dairy cows

This study investigated possible relationships between measurements of the somatotrophic axis in pre-pubertal dairy calves and subsequent milk yields. Endogenous growth hormone (GH) release was measured through a fed and fasted period in fifty 6-month-old Holstein-Friesian heifers and they were then challenged with growth hormone-releasing factor (GRF) to assess their GH release pattern. Insulin-like growth factor-I (IGF-I), insulin and glucose concentrations were measured in relation to time of feeding. Cows were subsequently monitored through their first three lactations to record peak and 305-day milk yields. In the first lactation, milk energy output for the first 120 days of lactation was also calculated. The mean 305-day milk yield increased from 7417 +/- 191 kg in the first lactation (n=37) to 8749 +/- 252 kg in the third (n=25). There were no significant relationships between any measures of GH secretion and peak or 305-day yield in any lactation. A highly significant positive relationship was established between the GH peak measured 10 min post-GRF challenge and 120-day milk energy values in the first lactation. This relationship was, however, only present in the sub-population of 12 cows culled after one or two lactations and was absent in the 25 animals remaining for the third lactation. There were no significant relationships between pre-pubertal IGF-I and fed or fasted insulin or glucose concentrations and any subsequent measurement of yield. The usefulness of GH secretagogue challenges in calves as a predictive test for future milk production is thus limited but may have some bearing on nutrient partitioning and longevity.     

Pharmacokinetics of oral meloxicam in ruminant and preruminant calves

The pharmacokinetics of oral meloxicam has been studied in ruminant, but not preruminant calves. Oral meloxicam was administered at 0.5 mg/kg to six ruminant calves via gavage (RG); to six preruminant calves via gavage (PRG); and to six preruminant calves via suckling in milk replacer (PRF). Plasma drug concentrations, determined over 120-h postadministration, were analyzed by compartmental and noncompartmental methods. The rate of drug absorption was faster (P<0.01) in PRF (0.237±0.0478/h) than RG calves (0.0815±0.0188/h), while absorption in PRG calves (0.153±0.128/h) was not different from other groups. C(max) was lower (P=0.03) in PRF (1.27±0.430 μg/mL) than in PRG calves (2.20±0.467 μg/mL), while C(max) of RG calves (1.95±0.955 μg/mL) was not different from other groups. V/F was higher in PRF calves (365±57 mL/kg) than either PRG (177±63 mL/kg, P<0.01) or RG (232±83 mL/kg, P=0.01) calves. These observations were likely due to differences in bioavailability, physiological maturity, and timing of the drug delivery into different compartments of the ruminant gastrointestinal tract. Results suggest that an adjustment in meloxicam dose may be necessary when administered with milk replacer.