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1.
The study was performed to determine whether orally administered KP102 (also known as GHRP-2) stimulates GH release in adult goats, and how the orally administered KP102 passes through the digestive tract and stimulates GH release in ruminant animals. Five mg/kg body weight (BW) of KP102 dissolved in 9 ml of saline were administered into the oral cavity, rumen, omasum and duodenum of adult goats, and GH release after administration of KP102 was examined. The GH levels were significantly elevated at 20 min after administration of KP102 into the oral cavity, and plasma concentrations of GH remained significantly elevated until 60 min (P < 0.05). The GH levels after administration of KP102 into the abomasum were variable. However, the GH level tended to increase within 30 min after administration, and were significantly higher than those of controls after 120 to 150 min (P < 0.05). The GH levels after administration of KP102 into the duodenum were significantly elevated at 40 min after administration, and plasma concentrations of GH remained significantly elevated until 140 min (P < 0.05). The administration of KP102 into the rumen failed to stimulate GH release. The GH response curves (AUC) produced after administration of KP102 into the abomasum or duodenum were 2.2-fold greater than those for after administration into the oral cavity (P < 0.05). The oral administration of 5 mg/kg BW of KP102 in the powder state, not dissolved in 9 ml of saline, failed to stimulate GH release. These results suggested that orally administered KP102 dissolved in saline transiently stimulates GH release in adult goats, and this phenomenon might be due to small amounts of the peptides entering directly into the abomasum with liquid bypassing the rumen.  相似文献   

2.
The experiments were conducted to determine the effects of the administration of growth hormone-releasing peptide-2 (GHRP-2, also named KP102), both orally by gavage and in feed, on the release of growth hormone (GH) in swine and to investigate whether attenuation of the GH response occurs after short-term treatment with the peptide in feed. In the first experiment, saline or GHRP-2 at doses of 1, 4.5 and 9 mg/kg body weight (BW) was dissolved in 15 ml saline and administered orally as a bolus by gavage to cross-bred castrated male swine (n = 6). Orally administered GHRP-2 stimulated dose-related increases in peak concentrations of GH, with a return to basal by 120 min. After administering GHRP-2 orally, peak concentrations of GH and areas under the GH response curves (GH AUCs) for 180 min were higher (P < 0.05) than those in saline controls. In Experiment 2, GHRP-2 at doses of 0 (served as control), 1, 4.5 and 9 mg/kg BW was mixed in 150 g of feed and offered to cross-bred castrated male swine (n = 6) at 0900 hr and 1700 hr daily for a 3-d period. Administration of 1 mg/kg BW GHRP-2 to swine in feed failed to stimulate the release of GH, but GHRP-2 at doses of 4.5 and 9 mg/kg BW significantly (P < 0.05) increased plasma concentrations of GH after initial and final treatments at 0900 hr on Days 1 and 3 of treatment, respectively. Peak concentrations of GH and GH AUCs for 180 min after the initial and final treatments in the 4.5 and 9 mg/kg BW GHRP-2-treated swine were higher (P < 0.05) than those in controls. After 3 d of treatment with GHRP-2 in feed at doses of 4.5 and 9 mg/kg BW, GH responses to the peptide were maintained. The results of the present study indicate that the administration of GHRP-2 orally by gavage and in feed stimulates the release of GH in swine, and that the GH-releasing effect of the peptide does not become desensitized after short-term administration in feed.  相似文献   

3.
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.  相似文献   

4.
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.  相似文献   

5.
This study was conducted to investigate the arginine‐vasopressin (AVP)‐ and oxytocin‐induced changes in plasma adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin and glucagon levels and their metabolite concentrations in goats. In this study, five goats were intravenously injected with either AVP (0.3 nmol/kg body weight (BW)) or oxytocin (0.7 IU/kg BW). AVP injection significantly increased ACTH and GH secretions compared to controls, although insulin and glucagon concentrations were not altered. The incremental areas (ICAs) of the ACTH and GH concentrations were higher in the AVP group than in the saline group. Oxytocin injections increased insulin and glucagon secretions, while ACTH level was not altered. GH levels became elevated 30 min after the oxytocin injection. The ICAs of insulin and glucagon after oxytocin was injected were higher than those of the control. Results indicate that AVP is a potent stimulant of ACTH and GH secretions, while oxytocin uses different pathways to regulate insulin and glucagon secretions in goats.  相似文献   

6.
The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on the secretion of growth hormone (GH) in goats. The GH‐releasing response to an intravenous (i.v.) injection of GH‐releasing hormone (GHRH, 0.25 μg/kg body weight (BW)) was examined after treatments to augment central DA using carbidopa (carbi, 1 mg/kg BW) and L‐dopa (1 mg/kg BW) in male and female goats under a 16‐h photoperiod (16 h light, 8 h dark) condition. GHRH significantly and rapidly stimulated the release of GH after its i.v. administration to goats (P < 0.05). The carbi and L‐dopa treatments completely suppressed GH‐releasing responses to GHRH in both male and female goats (P < 0.05). The prolactin (PRL)‐releasing response to an i.v. injection of thyrotropin‐releasing hormone (TRH, 1 μg/kg BW) was additionally examined in male goats in this study to confirm modifications to central DA concentrations. The treatments with carbi and L‐dopa significantly reduced TRH‐induced PRL release in goats (P < 0.05). These results demonstrated that hypothalamic DA was involved in the regulatory mechanisms of GH, as well as PRL secretion in goats.  相似文献   

7.
The effects of intravenous infusion of mimosine or 2,3-dihydroxypyridine (2,3-DHP) and the effects of oral dose level of mimosine on fiber shedding in Angora goats were determined. In one experiment, 20 mature Angora wethers (36+/-1.9 kg BW) were infused for 2 d with 79, 102, or 135 mg/(kg BW.d) of mimosine, 90 mg/(kg BW.d) of 2,3-DHP, or saline. At 7 d after infusion began, fiber shedding was observed in all goats receiving mimosine but not in any goats infused with 2,3-DHP or saline. Fiber shedding varied among goats; in some goats, fiber shedding was complete and occurred without hand-plucking, whereas in others fiber was retained by nonshed fibers but could be removed by hand-plucking. Nonshed fibers were larger in diameter and more likely to be medullated (P < .05) compared with hand-plucked fibers. Mean plasma mimosine concentration at 24 and 48 h after infusion began was 79 and 98 micromol/L (P < .05), respectively, and greater (P < .05) for mimosine infused at 135 than at 102 mg/(kg BW.d) (89, 68, and 108 micromol/L for mimosine infused at 79, 102, and 135 mg/[kg BW.d], respectively; SE 9.5). In another experiment, oral dosing of eight Angora bucks (23+/-.5 kg BW) with 400 or 600 mg/kg BW of mimosine rapidly increased plasma mimosine concentration, which reached approximately 100 and 160 micromol/L at 5 h after dosing; however, periods of time during which plasma mimosine concentrations were comparable to those in the first experiment were considerably shorter. Oral mimosine dosing did not induce fiber shedding in 7 d. After 31 d, fiber was retained by nonshed fibers but could be removed by hand-plucking or could only be partially removed with difficulty by hand-plucking. There were no toxic effects of mimosine or 2,3-DHP administration; only minor, short-term inhibitions of feed intake by mimosine were noted in some goats. In conclusion, mimosine holds promise as a safe means to remove fiber of Angora goats; further research is necessary to characterize the seasonality of follicle activity and to develop convenient means of mimosine delivery.  相似文献   

8.
The effect of energy balance on the growth hormone (GH) secretory responsiveness to growth hormone-releasing hormone (GHRH) has not been determined in ruminant animals. Therefore, we examined the effects of intravenous injections of 0, 3.3, and 6.6 μg ghrelin/kg body weight (BW), with and without GHRH at 0.25 μg/kg BW, on GH secretory responsiveness in both the fed and fasted sheep. The injections were carried out at 48 h (Fasting state) and 3 h (Satiety state) after feeding. Blood samples were taken every 10 minutes, from 30 minutes before to 120 minutes after the injection. Low (3.3 μg/kg BW) and high (6.6 μg/kg BW) doses of ghrelin stimulated GH secretion significantly (P < .05) greater in the Satiety state than in the Fasting state. Growth hormone-releasing hormone plus both doses of ghrelin stimulated GH secretion significantly (P < .05) greater in the Satiety state than in the Fasting state. Ghrelin and GHRH exerted a synergistic effect in the Satiety state, but not in the Fasting state. Plasma ghrelin levels were maintained significantly (P < .05) greater in the Fasting state than in the Satiety state except the temporal increases after ghrelin administration. Plasma free fatty acid (FFA) concentrations were significantly (P < .01) greater in the Fasting state than in the Satiety state. In conclusion, the present study has demonstrated for the first time that ghrelin differentially modulates GH secretory response to GHRH according to feeding states in ruminant animals.  相似文献   

9.
Pharmacokinetics and bioavailability of enrofloxacin were determined after single intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight (BW) to 5 healthy adult Angora goats. Plasma enrofloxacin concentrations were measured by high performance liquid chromatography. Pharmacokinetics were best described by a 2-compartment open model. The elimination half-life and volume of distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 h and Vd(ss),1.2 to 1.5 L/kg, respectively). Enrofloxacin was rapidly (t1/2a, 0.25 h) and almost completely absorbed (F, 90%) after IM administration. Mean plasma concentrations of enrofloxacin at 24 h after IV and IM administration (0.07 and 0.09 microg/mL, respectively) were higher than the minimal inhibitory concentration (MIC) values for most pathogens. In conclusion, once-daily IV and IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in treatment of infectious diseases caused by sensitive pathogens.  相似文献   

10.
This study was conducted to investigate the nutrition-dependent changes in insulin-like growth factor (IGF)-1 and IGF-binding proteins (IGFBPs) with growth hormone releasing peptide-2 (D-Ala-D-betaNal-Ala-Trp-D-Phe-Lys-NH(2); GHRP-2 or KP102) treatment in growing Holstein steers. Eight 13 month-old Holstein steers were grouped on two levels of feed intake (high intake (HI); 2.43% body weight or low intake (LI); 1.22%) and each group was daily injected with KP102 (12.5 microg/kg body weight/day) or saline solution into the jugular vein during 6-day period. The concentration of plasma GH showed an increase after an i.v. bolus injection of KP102 on Day 1 and Day 6 in both the LI and HI groups. Plasma IGF-1 began to increase 10 hr following an i.v. bolus injection of KP102, but this was only observed in the HI group (P < 0.05). Also, the plasma IGF-1 in the HI group with daily injections was significantly greater than the LI group from Day 1 of KP102 administration (P < 0.05). It reached maximum values of 125.1 +/- 7.6 ng/ml after Day 2, and returned to pre-injection levels after Day 4, however, no change in plasma IGF-1 was observed in LI with administration of KP102. During 6 days of treatment, plasma 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 were significantly higher in KP102 treated steers but only in the HI group (P < 0.05). Plasma 34 kDa IGFBP-2 decreased in the HI group and did not show any change following an injection of KP102. In conclusion, the effect of stimulated endogenous GH with KP102 administration increased plasma IGF-1, 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 levels in the HI group of growing Holstein steers, but not in the LI one. Thus, we strongly believe that the plasma IGF-1 and IGFBPs response to KP102 treatment is modulated by the nutritional status of growing Holstein steers and the increased plasma IGF-1 concentration with KP102 treatment may be regulated by plasma 38-43 kDa IGFBP-3 and 24 kDa IGFBP-4 in Holstein steers.  相似文献   

11.
Genetic variations in plasma GH concentrations before and following thyrotropin-releasing hormone (TRH) stimulation and in IGF-I concentrations were studied in 11-mo-old Polish Friesian cattle (104 heifers and 110 bulls). A possible association between stimulated GH release, IGF-I, and the polymorphism in the GH gene causing substitution of leucine-Leu to valine-Val at amino acid position 127 of the protein was also investigated. The GH concentrations were determined in serial plasma samples collected every 15 min from 15 min before to 135 min after intravenous administration of 0.15 microg TRH/kg live weight. The analysis was performed on three variables: baseline (mean of samples at -15 and 0 min), peak (sample at 15 min after injection) and rate (peak minus sample at 60 min, divided by 45 min). The IGF-I concentrations were measured in plasma samples taken before the TRH stimulation. Additionally, first lactation records from the 75 cows earlier tested for GH release and IGF-I were used to study a possible association of milk production traits with GH genotypes. The data were analyzed by multivariate mixed linear models. The heritability of IGF-I reached a higher value (0.35) than variables baseline, peak, and rate (0.02, 0.14, and 0.14, respectively). The GH variables were positively genetically correlated with each other (0.22 to 0.93), whereas they had negative genetic correlations with IGF-I (-0.26). The Val/Val genotypes reached the highest peak value compared with other GH genotypes (P > 0.01), whereas the Leu/Leu genotypes had the highest IGF-I concentrations (P < or = 0.05). Moreover, the Leu/Val heterozygotes were superior to others in milk and protein yields, whereas the Leu/Leu homozygotes reached the highest fat yield (P > or = 0.01). We conclude that GH peak, GH rate, and IGF-I are heritable traits in young dairy cattle and are affected by the Leu/Val polymorphism in the GH gene.  相似文献   

12.
Ghrelin is a gut peptide which participates in growth regulation through its somatotropic, lipogenic and orexigenic effects. Synergism of ghrelin and growth hormone-releasing hormone (GHRH) on growth hormone (GH) secretion has been reported in humans and rats, but not in domestic animals in vivo. In this study, effects of a combination of ghrelin and GHRH on plasma GH and other metabolic parameters, and changes in plasma active and total ghrelin levels were studied in Holstein bull calves before and after weaning. Six calves were intravenously injected with vehicle (0.1% BSA-saline), ghrelin (1 microg/kg BW), GHRH (0.25 microg/kg BW) or a combination of ghrelin plus GHRH at the age of 5 weeks and 10 weeks (weaning at 6 weeks of age). Ghrelin stimulated GH release with similar potency as GHRH and their combined administration synergistically stimulated GH release in preweaning calves. After weaning, GH responses to ghrelin and GHRH became greater compared with the values of preweaning calves, but a synergistic effect of ghrelin and GHRH was not observed. The GH areas under the concentration curves for 2h post-injection were greater in weaned than in preweaning calves (P<0.05) if ghrelin or GHRH were injected alone, but were similar if ghrelin and GHRH were injected together. Basal plasma active and total ghrelin levels did not change around weaning, but transiently increased after ghrelin injection. Basal plasma insulin, glucose and non-esterified fatty acid levels were reduced after weaning, but no changes by treatments were observed. In conclusion, ghrelin and GHRH synergistically stimulated GH release in preweaning calves, but this effect was lost after weaning.  相似文献   

13.
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.  相似文献   

14.
We found previously that porcine growth hormone (pGH) causes an increase in growth rate with a concurrent improvement in carcass composition in pigs. The somatomedin, insulin-like growth factor 1 (IGF-1), is though to play a major role in mediating some of the anabolic actions of GH, while the glucocorticoid hormones are potential counter-regulators of these effects. The present study was conducted to determine the temporal and dose-response relationship between GH administration and serum IGF-1 and cortisol concentrations in pigs. Twelve Yorkshire barrows, fitted with femoral artery catheters, were injected (im) with either 0, 10, 100 or 1,000 micrograms/kg pGH. Blood sampling began 40 min prior to pGH injection and was continued for 37 h. Serum GH, IGF-1 and cortisol concentrations were determined by radioimmunoassay. In control animals, serum GH concentrations ranged from 1.6 to 5.7 ng/ml over 37 h. In the animals treated with increasing doses of pGH, peak serum GH concentrations reached 28, 112 and 286 ng/ml and levels remained elevated for 4, 12 and 24 h, respectively. Serum IGF-1 concentrations were elevated by pGH after a lag time of 4 to 6 h. When the IGF-1 concentrations were integrated over time, the response appeared to be dose-dependent, with an ED50 of 710 micrograms/kg body weight (BW). Data for serum cortisol concentrations showed a great deal of individual variation. A transient increase in cortisol was observed, but only in the group treated with 1,000 micrograms pGH/kg BW. Cortisol levels returned to baseline 2 h after pGH injection.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.  相似文献   

16.
The effects of growth hormone-releasing factor (GHRF) injections to sows during late gestation were investigated in two experiments. In the first one, four treatments were applied to eight catheterized sows according to two 4 x 4 Latin squares: oral administration of 2 mg of pyridostigmine, a cholinesterase inhibitor, per kilogram of BW (PYR group); i.m. injection of 50 micrograms of GHRF/kg BW (GHRF group); a combination of the pyridostigmine and GHRF treatments (PYR+GHRF); or i.m. injection of glucose (control). Pyridostigmine slightly increased the plasma concentration of growth hormone (GH). Growth hormone responses to GHRF and PYR+GHRF treatments were similar, with significantly elevated GH concentrations from 5 to 240 min after GHRF injection. In the second experiment, 36 sows were allocated to two treatments at 102 d of gestation. Until farrowing, they were injected twice daily with 50 micrograms of GHRF/kg BW (GHRF group) or isotonic glucose (control). The DM, N, fat, and energy content of 24 pigs per group was determined at weaning at 22 d. Six pigs per litter had ad libitum access to feed until slaughter at 100 kg BW and their carcasses were evaluated. Treatment with GHRF increased pregnancy duration (114.8 vs 113.6 d, P less than .05), weight of pigs at 13 d (3.69 vs 3.54 kg, P less than .05) and at weaning (5.74 vs 5.48 kg, P less than .05), and improved pig survival (86 vs 71%, P less than .05). Lipid (on a DM basis) and energy contents of the pigs slaughtered at weaning were significantly higher in the GHRF group than in the control group (14.4 vs 12.5% and 2,178 vs 2,029 kcal/kg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
The pharmacokinetic properties and bioavailability of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug nimesulide were investigated in female goats following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 4 mg/kg BW. Blood samples were collected by jugular venipuncture at predetermined times after drug administration. Plasma concentrations of nimesulide were determined by a validated high-performance liquid chromatography method. Plasma concentration-time data were subjected to compartmental analysis and pharmacokinetic parameters for nimesulide after i.v. and i.m. administration were calculated according to two- and one-compartment open models respectively. Following i.v. administration, a rapid distribution phase was followed by the slower elimination phase. The half-lives during the distribution phase (t1/2alpha) and terminal elimination phase (t1/2beta) were 0.11+/-0.10 and 7.99+/-2.23 h respectively. The steady-state volume of distribution (Vd(ss)), total body clearance (ClB) and mean residence time (MRT) of nimesulide were 0.64+/-0.13 L/kg, 0.06+/-0.02 L/h/kg and 11.72+/-3.42 h respectively. After i.m. administration, maximum plasma concentration (Cmax) of nimesulide was 2.83+/-1.11 microg/mL attained at 3.6+/-0.89 h (tmax). Plasma drug levels were detectable up to 72 h. Following i.m. injection, the t1/2beta and MRT of nimesulide were 1.63 and 1.73 times longer, respectively, than the i.v. administration. The bioavailability of nimesulide was 68.25% after i.m. administration at 4 mg/kg BW. These pharmacokinetic data suggest that nimesulide given intramuscularly may be useful in the treatment of inflammatory disease conditions in goats.  相似文献   

18.
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.  相似文献   

19.
We assessed the interaction of GH gene polymorphisms (AA, AB and BB genotypes) with body weight and measures of endocrine function in Japanese black calves at 10 months of age. The average body weight for the BB genotype (281+/-5 kg) was significantly lower (P=0.0017, ANOVA) than those for the AA (324+/-9 kg) and AB (317+/-7 kg) genotypes. Plasma concentrations of insulin and IGF-I were greater for the AA genotype than for the AB genotype, and AB and BB genotypes, respectively. There were significant differences in the triglyceride and cholesterol concentrations among the GH genotypes. The area under the basal GH concentration was significantly greater (P=0.0314) for the AA genotype than for the two other genotypes. The incremental area over the basal GH concentrations in response to intravenous GHRH injection (0.4 microg/kg BW) was significantly smaller (P=0.0005) for the BB genotype than for the two other genotypes. In addition, linear regression analysis between GH incremental area induced by GHRH and body weight demonstrated that there was a positive linear correlation (r=0.6496, P<0.002) for incremental areas less than 600 ng min/ml, but a negative correlation (r=0.6473, P<0.05) for incremental areas over 600 ng min/ml. These findings indicate that the GH genotypes of the animals could be associated with difference in the GH response in Japanese black cattle at 10 months of age. We also observed a relationship between genotype and animal performances, but other studies on more animals in different conditions must be realized to make a definite conclusion.  相似文献   

20.
Objective-To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Procedures-Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Results-Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Conclusions and Clinical Relevance-Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.  相似文献   

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