Use of a low dose synthetic ACTH challenge test in normal and prednisone-treated dogs

The utility of a low dose (1 microgram/kg) synthetic ACTH challenge test in detecting moderate reductions in adrenocortical sensitivity in dogs was examined. First, the adrenocortical responses to an intravenous bolus of either 1 microgram/kg or 0.25 mg per dog of synthetic ACTH were compared in two groups of normal dogs. While plasma cortisol concentrations were similar in both groups 60 minutes after ACTH injection, dogs given 0.25 mg ACTH showed continued elevations in plasma cortisol concentrations at 90 and 120 minutes after ACTH injection. Later, the dogs previously tested with the 1 microgram/kg ACTH challenge were given a single intramuscular dose of prednisone (2.2 mg/kg) and retested with 1 microgram/kg of ACTH one week later. Plasma cortisol levels were significantly reduced after ACTH injection in dogs previously given prednisone demonstrating that a single intramuscular prednisone dose causes detectable adrenocortical suppression one week after administration. The 1 microgram/kg synthetic ACTH challenge test provides a sensitive means for evaluating adrenocortical suppression in dogs.     

Adrenocorticotropic hormone and cortisol in calves after corticotropin-releasing hormone.

The aim for this study was to analyze responsiveness of the hypothalamo-pituitary-adrenocortical axis to exogenous bovine corticotropin-releasing hormone (bCRH) in calves. Two dose-response studies were carried out, using either bCRH alone (dose rates of 0, .01, .03, and .1 microg bCRH/kg live weight) or in combination with arginine-vasopressin (bCRH:AVP, 0:0, .1:.05, .5:.25, and 1:.5 microg kg live weight). The bCRH was administered i.v. to calves (n = 5 to 7 per dose) housed individually or in groups. Serial blood samples were obtained from before to 300 min after injection and analyzed for plasma ACTH and cortisol concentrations. The lowest bCRH dose that produced a response in all calves was .1 microg/kg. In the experiment using bCRH with AVP, increasing the bCRH dose from .1 to 1 microg/kg resulted in an increase in peak ACTH concentration (321 vs. 2,003 pg/mL) but did not significantly affect the peak cortisol concentration (37 vs. 40 ng/mL). The time to reach the peak cortisol concentration increased with the dose of bCRH with AVP (from 38 to 111 min). The ACTH and cortisol concentrations determined at any time between 20 and 90 min after bCRH injection were correlated to the integrated responses calculated as areas under the ACTH and the cortisol curves (r between .61 and .99, P<.05). In comparison with results from studies in humans, pigs, and sheep, our data showed that the pituitary of calves seems less sensitive to CRH than that of other mammals, despite a greater capacity to produce ACTH. Moreover, the calf's adrenals seem to have a lower capacity to produce cortisol than adrenals of other mammals. As in other species, it seems that AVP enhances the release of ACTH and cortisol. For CRH challenge to be used in calves, we suggest injecting at least .1 microg of bCRH/kg live weight either with or without AVP and taking several blood samples before injection and between 20 and 90 min after injection.     

Passive immunization with antiserum to adrenocorticotropin increases weight gain in normal female rats.

Passive immunization against ACTH was used to test the hypothesis that growth in female rats is constrained by physiological concentrations of glucocorticoids. When animals were stressed by 15-min exposure to ether before blood sampling by cardiac puncture, serum concentrations of corticosterone were lower (P less than .05) in immunized rats than in stressed controls. The maximum effect was apparent 2 h after injection of ACTH antiserum, and no effect was apparent 6 h after injection. To examine the effects of ACTH immunization on growth, rats received daily injections of either saline, sheep immunoglobulin G, or ACTH antiserum, 2 h before the afternoon peak in plasma concentrations of corticosterone. After 7 d of treatment, rats treated with ACTH antiserum had gained 37% more body weight than saline-injected controls, and this effect was accompanied by a 59% reduction in peak plasma concentrations of corticosterone. Immunoglobulin G purified from normal sheep serum had no effect on weight gain. It is concluded that growth rate in normal female rats can be stimulated through the suppression of adrenal activity.     

Enhancement of the adrenocortical response to metyrapone by L-dopa in the chicken (Gallus domesticus)

1. Eight-week-old chickens were treated with a single intravenous injection of saline, L-dopa (20 mg/kg body weight), metyrapone (60 mg/kg) or a combined dose of L-dopa and metyrapone. Serum corticosterone was measured by radioimmunoassay at 30, 60 and 90 min after the treatment. 2. L-dopa did not alter the corticosterone concentration during the experiment, whereas metyrapone increased it at 60 and 90 min. 3. When L-dopa and metyrapone were given together there was a gradual increase in corticosterone and the hormone concentrations were significantly greater than control values at all times. 4. It was concluded that L-dopa is not a potent stimulator of adrenocortical cells in chickens, but it enhances the response to metyrapone. This may be achieved through the release of endogenous ACTH by stimulating central dopamine receptors.     

Effects of frequency of treatment with recombinant equine somatotropin on selected biological responses in geldings

Two experiments compared the efficacies of different treatment frequencies for recombinant equine somatotropin (eST). In Experiment 1, five geldings received daily injections of eST at 20 microg/kg of body weight, and five received every-other-day injections at 40 microg/kg of body weight, for a total of 30 days. Plasma glucose (P=0.0001), insulin (P=0.0135), and non-esterified fatty acid (NEFA, P=0.0001) concentrations increased, and plasma urea nitrogen (PUN) concentrations decreased (P=0.0001), in both groups, and only minor differences (P<0.05) occurred between the two groups. Insulin-like growth factor-I (IGF-I) concentrations increased (P=0.0001) in both groups over time, and were higher (P<0.05) after day 2 in geldings treated daily. Endogenous somatotropin (ST) response to secretagogue was inhibited (P<0.05) in geldings receiving daily injections relative to those receiving every-other-day injections. In Experiment 2, 16 geldings were allotted to four groups of four. A control group received daily saline injections, and the other three groups received eST at 20 microg/kg of body weight daily as a single injection, two injections (every 12h), or four injections (every 6h), for a total of 14 days. Plasma IGF-I and insulin concentrations increased (P<0.05) in all groups receiving eST, with the responses being proportional to injection frequency. In contrast, PUN concentrations decreased (P<0.05) in all groups equally. In conclusion, the efficacy of daily versus every-other-day injections of eST depends upon the response to be measured, and for IGF-I concentrations, the every-other-day regimen was not acceptable. Injection frequencies greater than once daily were more efficacious for IGF-I and insulin concentrations, but not for PUN concentrations. Thus, the optimum injection regimen for any new application for eST cannot simply be inferred from other biological responses, and will need to be determined empirically.     

Effects of single intravenously administered doses of dexamethasone on response to the adrenocorticotropic hormone stimulation test in dogs

The effects of single IV administered doses of dexamethasone on response to the adrenocorticotropic hormone (ACTH) stimulation test (baseline plasma ACTH, pre-ACTH cortisol, and post-ACTH cortisol concentrations) performed 1, 2, and 3 days (experiment 1) or 3, 7, 10, and 14 days (experiment 2) after dexamethasone treatment were evaluated in healthy Beagles. In experiment 1, ACTH stimulation tests were carried out after administration of 0, 0.01, 0.1, 1, and 5 mg of dexamethasone/kg of body weight. Dosages greater than or equal to 0.1 mg of dexamethasone/kg decreased pre-ACTH plasma cortisol concentration on subsequent days, whereas dosages greater than or equal to 1 mg/kg also decreased plasma ACTH concentration. Treatment with 1 or 5 mg of dexamethasone/kg suppressed (P less than 0.05) post-ACTH plasma cortisol concentration (on day 3 after 1 mg of dexamethasone/kg; on days 1, 2, and 3 after 5 mg of dexamethasone/kg). In experiment 2, IV administration of 1 mg of dexamethasone/kg was associated only with low (P less than 0.05) post-ACTH plasma cortisol concentration in dogs on day 3. In experiment 2, pre-ACTH plasma cortisol and ACTH concentrations in dogs on days 3, 7, 10, and 14 and post-ACTH plasma cortisol concentration on days 7, 10, and 14 were not affected by dexamethasone administration. The results suggest that, in dogs, a single IV administered dosage of greater than or equal to 0.1 mg of dexamethasone/kg can alter the results of the ACTH stimulation test for at least 3 days. The suppressive effect of dexamethasone is dose dependent and is not apparent 7 days after treatment with 1 mg of dexamethasone/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intra-abdominal versus intramuscular application of two ampicillin preparations in cows

Plasma ampicillin concentrations were determined in a cross-over trial involving five cows after single intramuscular or intra-abdominal administration of sodium ampicillin (10 mg/kg) and ampicillin anhydrate (40 mg/kg). After injection of sodium-ampicillin, high plasma concentrations were reached within 10 min; Cmax following intramuscular injection was 9.1 micrograms/ml and after intra-abdominal injection 7.5 micrograms/ml. Urine concentrations of ampicillin were low after 24 h (1-1.5 micrograms/ml). No significant changes in blood leucocyte numbers, plasma zinc, iron or fibrinogen levels occurred. After injection of ampicillin anhydrate 1 h elapsed before maximum plasma levels were obtained; Cmax was 5.4 micrograms/ml after intramuscular and 6.7 micrograms/ml after intra-abdominal administration. Urine concentrations were very high (238-303 micrograms/ml) after 24 h and stayed above 1 microgram/ml for 6 days. After administration of ampicillin anhydrate a significant increase in blood neutrophils (P less than 0.01) and a significant increase in plasma fibrinogen was measured after intramuscular and intra-abdominal injection (P less than 0.05). A significant decrease in plasma zinc concentration after intra-abdominal injection occurred (P less than 0.05). In abdominal surgery in cows in which contamination cannot be prevented, and practical objections inhibit preoperative administration, intramuscular or intra-abdominal administration during surgery of sodium ampicillin seems justified. Ampicillin anhydrate should not be used intra-abdominally.     

Technical note: effect of corticotropin-releasing hormone on adrenocorticotropic hormone and cortisol in steers

The objective of this study was to determine an appropriate exogenous dose of bovine corticotropin-releasing hormone (bCRH) to stimulate the physiological effects of the hypothalamic-pituitary-adrenal axis in steers as a method to test the sensitivity of the pituitary and adrenal gland. Twenty 14-mo-old Holstein-Friesian steers were blocked by weight (443.7+/-2.5 kg) and randomly allotted to receive either saline (control) or bCRH (0.1, 0.3, 1.0, or 1.5 microg/kg BW). Animals were housed in a slatted-floor facility (n = 5 per pen). Indwelling jugular catheters, for both the administration of bCRH and blood collection, were fitted on d -1 of the experiment. Saline and bCRH were administered i.v. at time 0. Serial blood samples were collected at -15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, and 180 min relative to time 0. Following administration of 0.1 microg of bCRH/kg BW, the peak ACTH response was not significantly different from pretreatment baseline concentrations (mean concentrations as measured at -15 and 0 min before bCRH administration). Mean ACTH concentrations from 0 to 180 min following 0.1 microg of bCRH/kg BW were not significantly different (P = 0.177) from controls. Administration of 0.3, 1.0, and 1.5 microg of bCRH/kg BW increased (P < 0.05) peak ACTH above pretreatment concentrations, and mean ACTH from 0 to 180 min for these treatments were greater (P < 0.05) than for controls. Peak cortisol responses to all bCRH treatments were greater (P < 0.05) than those to pretreatment concentrations. Mean cortisol concentrations from 0 to 180 min were greater (P < 0.05) in all bCRH-treated steers than in controls, but there were no significant differences among the bCRH treatments. The ratio of mean cortisol to mean ACTH for all bCRH doses tested differed (P < 0.05) from control values, indicating reactivity of the adrenals. In conclusion, bCRH challenge may be a useful method for testing the sensitivity of the hypothalamic-pituitary-adrenal axis in steers subjected to stressful husbandry conditions, and a minimum dose of 0.3 microg of bCRH/kg BW is required to stimulate physiological effects of stressor hormones.     

Use of adrenocorticotropin challenges to indicate chronic stress responses of laying hens in several housing alternatives

The use of adrenocorticotropin (ACTH) challenges was tested as an indicator of the level of physiological stress response of laying hens in several housing alternatives. Single Comb White Leghorn (SCWL) hens were challenged with intravenous ACTH injections (either .33, 1.0 or 3.0 IU/kg body weight). Plasma corticosterone (CORT) concentrations taken at intervals from 10 to 180 min following ACTH challenges revealed CORT response curves which peaked within 30 min at 34-, 54- and 60-fold increases over pre-challenge CORT levels with doses of .33, 1.0 and 3.0 IU/kg ACTH, respectively. Peak CORT levels for 1.0 and 3.0 IU/kg of ACTH did not differ; however, CORT levels for 1.0 IU/kg ACTH were significantly elevated above the peak for .33 IU/kg ACTH. Laying hens housed in cage and floor management alternatives were challenged with .33 and 1.0 IU/kg of ACTH after 10 months of lay. Cage management treatments were 3, 4 or 5 hens per cage and floor treatments with hens kept at 2 densities. Significant differences in the ACTH-induced CORT response between management alternatives could be detected following injection of .33 IU/kg ACTH, but not with the higher ACTH dose (1.0 IU/kg). These studies demonstrated that the CORT response to the lower dose of ACTH seemed to be more effective in assessing management differences, but further clarification may be necessary before ACTH challenges can be accurately used to evaluate physiological stress responses of laying hens housed in different conditions.     

Plasma cortisol and progesterone responses to low doses of adrenocorticotropic hormone in ovariectmized lactating cows

The objective of this study was to describe the responses of the plasma progesterone and cortisol concentrations in ovariectomized lactating cows to low doses of adrenocorticotropic hormone (ACTH). The estrous cycles in 3 lactating cows were synchronized, and the cows were ovariectomized in the luteal phase. ACTH challenge tests were conducted at doses of 3, 6, 12 and 25 IU. Blood samples were collected at 30 min intervals, and the plasma progesterone and cortisol concentrations were analyzed by EIA. A concomitant rise in plasma progesterone and plasma cortisol was observed in cows treated with 12 IU or higher doses of ACTH. Significant increments in the plasma cortisol concentrations were observed at all doses of ACTH. The means (+/- SE) of the peak plasma progesterone concentrations after the 3, 6, 12 and 25 IU ACTH challenge tests were 0.6 +/- 0.1, 1.3 +/- 0.4, 1.5 +/- 0.3 and 2.4 +/- 0.3 ng/ml, respectively. The means of the peak plasma cortisol concentrations in the 3 cows after the ACTH challenge were 14.0 +/- 1.5, 17.0 +/- 2.5, 23.3 +/- 3.0, and 33.3 +/- 7.0 ng/ml, respectively. The effects of the doses, time after treatment, and their interaction on the plasma progesterone concentrations after the ACTH challenge were significant (P<0.01). Likewise, the effects of the doses, time after treatment, and their interaction on the plasma cortisol concentrations after the ACTH challenge were significant (P<0.01). The mean AUC values for the plasma progesterone and cortisol concentrations after the ACTH treatments were also significantly affected by the dose of ACTH (P<0.01 and P<0.05, respectively). A significantly positive correlation was obtained between the peak plasma progesterone and cortisol concentrations after different doses of ACTH (r=0.7, P<0.05). The results suggest that lactating dairy cows are capable of secreting a significant amount of adrenal progesterone, reaching up to the minimal concentration necessary to cause suppression of estrus in response to 12 IU ACTH (P<0.01). The concomitant plasma cortisol concentration was 23.3 ng/ml.     

Effect of dose and route of administration of ACTH 1–24 on plasma Cortisol concentrations in ewes

Doses of 0.005-1.0 mg of ACTH1-24 given intravenously, intramuscularly or as an intramuscular depot injection caused increases in cortisol concentrations within 15 min in the plasma of ewes. There was, however, considerable animal-to-animal variation in maximum concentrations achieved. A curvilinear dose-response relationship to ACTH1-24 was obtained which was similar for each route of administration when expressed in terms of maximum cortisol concentrations. However, for a given dose, more prolonged release of cortisol occurred after i.m. injection compared to i.v., with maximum concentrations occurring 6 h after the depot formulation injection. Five repeated daily doses of 1.0 mg depot ACTH1-24 resulted in no diminution of cortisol response indicating considerable synthesizing capacity of the adrenals in clinically normal ewes. Comparison of cortisol concentrations after an acute stressor (shearing) suggests that doses of ACTH1-24 greater than 0.25 mg are excessive for simulation of stress-induced adrenal activity.     

Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle

The disposition of florfenicol after single intravenous and intramuscular doses of 20 mg of florfenicol/kg of body weight (b.w.) to feeder calves was investigated. Serum florfenicol concentrations were determined by a sensitive high performance liquid chromatographic method with a limit of quantitation of 0.025 μg/ml. The extent of serum protein binding of florfenicol was only 13.2% at a serum florfenicol concentration of 3.0 μg/ml. Serum concentration-time data after intravenous administration were best described by a triexponential equation. Total body clearance and steady state volume of distribution were 3.75 ml/min/kg b.w. and 761 ml/kg b.w., respectively. The terminal half-life after intravenous administration was 159 min. The absolute systemic availability after intramuscular administration was 78.5% (range: 59.3–106%) and the harmonic mean of the terminal half-life was 1098 minutes, indicating slow release of the florfenicol from the formulation at the intramuscular injection site.     

Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats

Plasma cortisol responses of 19 healthy cats to synthetic ACTH and dexamethasone sodium phosphate (DSP) were evaluated. After administration of 0.125 mg (n = 5) or 0.25 mg (n = 6) of synthetic ACTH, IM, mean plasma cortisol concentrations increased significantly (P less than 0.05) at 15 minutes, reached a peak at 30 minutes, and decreased progressively to base-line values by 120 minutes. There was no significant difference (P greater than 0.05) between responses resulting from the 2 dosage rates. After administration of 1 mg of DSP/kg of body weight, IV (n = 7), mean plasma cortisol concentrations decreased at postadministration hour (PAH) 1, and were significantly lower than control cortisol concentrations at PAH 4, 6, 8, 10, and 12 (P less than 0.01). Administration of 0.1 mg of DSP/kg, IV (n = 8) or 0.01 mg of DSP/kg, IV (n = 14) induced results that were similar, but less consistent than those after the 1 mg of DSP/kg dosage. Mean plasma cortisol concentrations returned to base-line values by PAH 24. There was not a significant difference between the 3 doses (P greater than 0.05) at most times. Measurement of endogenous ACTH in 16 healthy cats revealed plasma ACTH of less than 20 to 61 pg/ml. Seemingly, administration of synthetic ACTH consistently induced a significant (P less than 0.05) adrenocortical response in healthy cats. On the basis of time-response studies, post-ACTH stimulation cortisol samples should be collected at 30 minutes after ACTH administration to ensure detection of peak adrenocortical response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and intramuscular bioavailability of cefuroxime sodium in goats

The pharmacokinetics of cefuroxime sodium, 20 and 40 mg kg(-1), were studied after i.v. and intramuscular injections in goats. Following single i.v. injections the serum concentration time curves of cefuroxime sodium were best fitted to a two-compartment open model. The drug was rapidly distributed with half-lives of distribution (t(1/2 alpha)) of 0.250 hours and 0.266 hours, and rapidly eliminated with half-lives of elimination (t(1/2 beta)) of 1.482 hours and 1.416 hours, respectively, following single i.v. injections of 20 and 40 mg kg(-1)body weight. After single intramuscular injections of cefuroxime sodium at the same doses, the mean absorption time (MAT) values were 1.379 and 1.716 hours and the peak serum concentration, C(max), was 12.965 and 38.50 microg ml(-1), attained after 0.515 and 0.608 hours (t(max)), respectively. The elimination half-lives (t(1/2el)) were 2.088 and 2.114 hours and the mean residence times (MRT) were 3.198 and 3.237 hours for 20 and 40 mg kg(-1)body weight, respectively. After both i.v. and intramuscular injections of cefuroxime sodium, the concentrations of cefuroxime in urine were much higher than that in serum. Urinary drug concentrations decreased gradually to reach their lowest levels at 24 and 48 hours post-injection, respectively. The systemic bioavailability of cefuroxime sodium in goats after intramuscular injections of 20 and 40 mg kg(-1)body weight was 88.4 per cent and 103.5 per cent, respectively. In vitro protein binding of cefuroxime sodium in goat's serum was low, ranging from 13.3 per cent to 21.6 per cent with an average of 17.0 per cent.     

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half-lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76+/-9.65% for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25+/-0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio.     

Effect of daily injections of ACTH on growth and on the adrenal and lymphoid tissues of two strains of immature fowls.

1. The effects of daily injections of ACTH (30 IU/kg) or physiological saline on growth and on adrenal and lymphoid tissues of Rhode Island Red (RIR) and Light Sussex (LS) chickens were compared at 1, 2 and 3 weeks of age. 2. Saline injections retarded skeletal growth in both strains during the 1st week but only affected weight gain in LS birds. 3. Injections of ACTH depressed growth rate, caused adrenal enlargement and deplenished adrenal cholesterol to the same extent in both strains. 4. ACTH caused a greater reduction in bursal size in RIR than in LS birds. Spleen size was reduced by ACTH only in RIR birds. 5. At 2 and 3 weeks the plasma concentrations of corticosterone of RIR birds were greater than those of LS birds. Plasma corticosterone concentrations were within the normal range 24 h after the last injection of ACTH in both strains. 6. Plasma concentrations of growth hormone was unaffected by ACTH treatment in RIR birds, but it was increased in LS birds after 3 weeks of treatment.     

Effect of administration of adrenocorticotropic hormone on plasma concentrations of testosterone, luteinizing hormone, follicle stimulating hormone and cortisol in stallions

In boars and rabbits, administration of adrenocorticotropic hormone (ACTH) results in a testis-dependent, short-term increase in concentrations of testosterone in peripheral plasma. This experiment was designed to assess the short-term effects of a single ACTH injection on plasma concentrations of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and cortisol in stallions. Eight light horse and two pony stallions were paired by age and weight and then one of each pair was randomly assigned to the treatment (ACTH, .2 IU/kg of body weight) or control (vehicle) group. Injection of ACTH increased (P<.01) plasma concentrations of cortisol by approximately twofold in the first 60 minutes; control stallions showed no change (P>.10) in concentrations of cortisol during the blood sampling period. Control stallions exhibited a midday increase (P>.05) in concentrations of testosterone similar to that reported previously; ACTH treatment prevented or delayed this increase such that concentrations of testosterone in treated stallions were lower (P<.05) than in controls 4 to 5 hours after injection of ACTH. Treatment with ACTH had no effect (P<.10) on plasma concentrations of LH or FSH up to 12 hours after injection.     

The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine

The effects of GHRP-2 (also named KP102), a new growth hormone-releasing peptide, on the release of growth hormone (GH) and growth performance were examined in swine. The single intravenous (i. v.) injection of GHRP-2 at doses of 2, 10, 30 and 100 microg/kg body weight (BW) to cross-bred castrated male swine stimulated GH release in a dose-dependent manner, with a return to the baseline by 120 min. The peak GH concentrations and GH areas under the response curves (GH AUCs) for 180 min after the injections of GHRP-2 were higher (P < 0.05) than those after the injection of saline. The GH responses to repeated i.v. injections of GHRP-2 (30 microg/kg BW) at 2-h intervals for 6 h were decreased after each injection. The chronic subcutaneous (s.c.) administration of GHRP-2 (30 microg/kg BW) once daily for 30 days consistently stimulated GH release. The GH AUCs for 300 min after the injections on d 1, 10 and 30 of treatment in GHRP-2-treated swine were higher than those in saline-treated swine. However, chronic administration of GHRP-2 caused a partial attenuation of GH response between d 1 and 10 of treatment. The chronic s.c. administration of GHRP-2 also increased average daily gain for the entire treatment period by 22.35% (P < 0.05) and feed efficiency (feed/gain) by 20.64% (P < 0.01) over the saline control values, but did not significantly affect daily feed intake. These results indicate that GHRP-2 stimulates GH release and enhancing growth performance in swine.     

Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism.

OBJECTIVE: To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism. DESIGN: Cohort study. ANIMALS: 6 clinically normal dogs and 7 dogs with hyperadrenocorticism. PROCEDURE: Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration. RESULTS: In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin. CLINICAL IMPLICATIONS: Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.     

Insulin-glucose interactions characterised in newly hatched broiler chicks

1. A study was conducted to identify the specificity of insulin-glucose interactions in newly hatched broiler chicks. 2. Plasma insulin concentrations in fed chicks at one day post-hatch were lower than those at later ages and tended to increase up to d 7, while the concentrations from 1 to 7 d of age were lower than those in chickens of 10 to 28 d of age. 3. Plasma glucose concentrations were lowered for 60 min by injection of insulin at 10 and 40 microg/kg body weight (BW) in both 1- and 21-d-old chicks, showing that the hypoglycaemic effect of exogenous insulin is of larger magnitude but shorter duration in 1-d-old chicks. 4. The decrease in plasma glucose concentration at 60 min after insulin injection (10 and 40 microg/kg BW) was larger in 1- to 7-d-old chicks than in 14- to 21-d-old chickens. 5. These results indicate that newly hatched broiler chicks are under the control of specific insulin-glucose interactions characterised by low plasma insulin concentrations with high sensitivity to insulin.