Effects of long-term consumption of sewage solids on blood, milk and tissue elemental composition of breeding ewes

Fine-wool ewes received for 2 yr a complete pelleted basal diet (11% protein) or the basal diet fortified with 3.5% cottonseed meal (CSM; 12% protein) or gamma-irradiated (1 megarad) dried solids (SS; 12% protein) from primary (undigested) sewage (Las Cruces, New Mexico, municipal sewage). Five ewes fed each diet were sampled to determine Ag, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb and Zn in blood, milk and tissues. Tissues and blood were sampled at slaughter 40 d after weaning of lambs. Mean whole blood mineral concentrations were similar (P less than .05) among treatments 3 d postpartum; however, at 42 d after lambing (mean +/- SE) both basal- (54 +/- 2 micrograms/ml) and sewage-fed (54 +/- 2 micrograms/ml) ewes had elevated (P less than .05) blood Ca compared with ewes fed CSM (46 +/- 2 micrograms/ml). No biologically important differences were detected in the concentrations of elements in milk. Ewes fed SS had lower (P less than .05) blood Fe than animals in the other groups. Sewage-fed ewes also had higher (P less than .05) liver Fe (1,092 +/- 100 micrograms/g) than basal-fed ewes (626 +/- 100 micrograms/g); whereas Fe in CSM-fed ewes (873 +/- 100 micrograms/g) was similar to both. Basal-fed animals had 1.1- to 1.3 times more (P less than .05) liver Mg and two- to threefold higher liver Na than CSM or SS. Livers from SS-fed ewes had higher concentrations (P less than .05) of Cd (1.5- to 1.6-times) and Pb (1.4- to 1.9-times) than livers from CSM- or basal-fed ewes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of probenecid in sheep

Six Merino ewes were given 1 g (27 g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half-life was 1.55 h and apparent volume of distribution at the steady state (Vdss) 0.18 l/kg. Body clearance (ClB) and renal clearance (ClR) were 0.12 l/h/kg and 0.03 l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 micrograms/ml, respectively, at 15 min; 76, 36, and 34 micrograms/ml at 1 h; and 43, 23 and 34 micrograms/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly. Urine output was correlated positively (P less than 0.05) with kel and ClB. Urine pH increased significantly (P less than 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration.     

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.     

Influence of macronutrients and polyethylene glycol on intake of a quebracho tannin diet by sheep and goats

We determined if supplemental macronutrients or polyethylene glycol (PEG) influenced intake of a tannin diet. Sheep (lambs 5 mo age, 36 kg) and goats (kids 7 mo age, 32 kg) were fed supplements high in either energy or protein or offered a choice between the two supplements before and after receiving a meal containing 15% quebracho tannin. The effect of PEG, a compound that attenuates the negative effects of tannins, was assessed by offering PEG while animals consumed the tannin diet for 4 h/d. Intake of the tannin diet was influenced by both macronutrients and PEG. Animals that chose their own supplements or that received the high-protein supplement, consumed more of the tannin diet than animals fed the high-energy supplement: 34 and 36 vs 31 g/kg(0.75) (lambs) and 41 and 39 vs 34 g/kg(0.75) (kids), respectively (P < 0.05). Animals supplemented with PEG ate much more of the tannin diet than unsupplemented animals: 70 vs 39 g/kg(0.75) (lambs) and 63 vs 34 g/kg(0.75) (kids), respectively (P < 0.001). Sheep and goats consumed more tannin food when given PEG than when supplemented with macronutrients (51 and 38 g/kg(0.75), P < 0.001). Sheep and goats offered a choice between supplements consumed more CP than animals fed the high-energy supplement and more ME than animals fed the high-protein supplement (P < 0.05). In so doing, they selected a combination of foods that yielded a more balanced intake of macronutrients, while achieving high levels of intake of the tannin food. Sheep and goats can be used as an environmentally safe and economically sound means to reduce the abundance of tannin-rich vegetation. Macronutrients and PEG enhance use of tannin-containing plants, which may increase production of alternate forages and create a more diverse mix of species in a plant community.     

Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two-way cross-over design. Blood samples were taken serially over a 72-h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post-treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5-0.75 h up to 32 h post-administration, with a Cmax for the zwitterion suspension of 1.21 +/- 0.13 micrograms/ml and AUC of 18.55 +/- 1.45 micrograms.h/ml, respectively, which were significantly higher (P less than 0.01) than the Cmax (0.67 +/- 0.12 micrograms/ml) and AUC (8.57 +/- 0.91 micrograms.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a Cmax (2.91 +/- 0.10 micrograms/ml) and AUC (51.67 +/- 1.95 micrograms.h/ml) for ABZSO2, which were significantly higher (P less than 0.01) than those obtained for the trisamine solution (Cmax = 1.67 +/- 0.11 micrograms/ml and AUC = 22.77 +/- 1.09 micrograms.h/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 was significantly longer (P less than 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acceptance and digestibility of some selected browse feeds with varying tannin content as supplements in sheep nutrition in west Africa

In 1994 and 1995 leaves from 10 selected West African trees and shrubs with varying tannin content were tested to determine their suitability as an alternative and supplementary browse feed for West African dwarf sheep to improve productivity in small-scale holdings in Benin. Dry matter intake per kg metabolic body weight (DM g/kg W0.75) varied between the different browse feeds and between the different trials and ranged from zero (Leucaena leucocephala) up to 26.7 DM g/kg W0.75 (Margaritaria discoidea). The digestibility of the organic matter varied between 58.9% (L. leucocephala) and 68.2% (Mallotus oppositifolius). Agelaea obliqua showed the highest levels of total phenols (10.2%), tannin phenols (8.8%) and extractable condensed tannins (8.0%). Leaves from various browse feeds are a good and protein-rich supplementary fodder in addition to the grass Panicum maximum. However, feeding of A. obliqua and Cnestis ferruginea should be avoided due to toxic components.     

Biotin requirements of broiler breeders fed diets of different protein content and effect of insufficient biotin on the viability of progeny

Production of eggs or normal chicks was depressed when practical diets containing 168 g or 137 g of crude protein (CP)/kg were not supplemented with synthetic biotin. Overall egg production and hatchability of fertile eggs was significantly (P less than 0.05) higher with the diets containing 137 g CP/kg. Biotin requirement was higher with the diet containing 168 g CP/kg and was estimated to be about 100 micrograms of available biotin/kg, equivalent to a daily intake of 16 micrograms for food-restricted hens. Biotin concentrations in egg yolk and chick plasma were related to maternal intake and increased with maternal age. The minimum yolk biotin concentration indicative of adequate maternal status was about 550 micrograms/g. Chicks from young hens fed insufficient biotin had the poorest biotin status at hatching and their growth potential and viability were reduced.     

Effect of growth hormone-releasing factor infusion on somatotropin, prolactin, thyroxine, insulin, insulin-like growth factor I and blood metabolites in control and somatostatin-immunized growing pigs.

The aim of this study was to characterize the effects of prolonged infusion of growth hormone-releasing factor (1-29)NH2 (GRF) on plasma concentrations of hormones and metabolites when administered to control pigs and pigs immunized against somatostatin (SRIF). In the first experiment, eight purebred Yorkshire boars averaging 113 +/- 2 kg BW were immunized against SRIF conjugated to bovine serum albumin (BSA) (n = 4) or BSA alone (n = 4). Somatotropin (ST) response to four rates of GRF infusion (0, 1.66, 5 and 15 ng/min/kg BW) for 6 hr was evaluated using a double balanced 4 x 4 Latin square design. During the 4 hr before infusion, SRIF-immunized animals tended (P = 0.06) to have a higher ST release (613 vs 316 ng.min/ml, SE = 232) than controls. During infusion, GRF elicited a dose-dependent increase in ST release in both squares; the ST response was not better in SRIF-immunized animals than in controls (P greater than 0.05) (1435 vs 880 ng.min/ml; SE = 597). In the second experiment, ten purebred Yorkshire boars (5 controls and 5 SRIF-immunized animals) averaging 69 +/- 2 kg BW were continuously infused with GRF at the rate of 15 ng/min/kg BW for six consecutive d. Under GRF infusion, ST concentrations increased (P less than 0.05) from 805 to 4768 ng.min/ml (SE = 507) from day 1 to day 6 in both SRIF-immunized and control animals. Prolactin levels increased (P less than 0.05) with GRF infusion; pattern of increase was different (P less than .01) overtime in control and SRIF-immunized animals. Thyroxine levels increased from 2.53 to 3.45 micrograms/dl (SE = 0.16) after six d of infusion. Insulin-like growth factor I was higher (P less than 0.05) before (139 vs 90 ng/ml; SE = 11) and during (222 vs 185 ng/ml; SE = 11) GRF infusion in SRIF-immunized animals. A transient increase (P less than 0.05) in glucose and insulin was observed in both groups. Immunization against SRIF had no effect on blood metabolites; however, GRF infusion increased free fatty acids from 157 to 204 microEq/l (SE = 11) and decreased blood urea nitrogen from 4.1 to 3.5 mmol/l (SE = 0.2) from day 1 to day 6, respectively. In summary, active immunization against SRIF in growing pigs increased ST and IGF-I concentrations. Infusion of GRF continuously raised ST levels with days of infusion without any sign of decrease responsiveness.     

Phmacodynamics and pharmacokinetics of carprofen, a non-steroidal anti-inflammatory drug, in healthy cows and cows with Escherichia coli endotoxin-induced mastitis

The pharmacodynamics of carprofen and its pharmacokinetics in plasma and milk of healthy cows and cows with endotoxin-induced mastitis were studied after a single intravenous dose of 0.7 mg/kg body weight. Carprofen was administered to five clinically healthy cows and to the same cows 3 weeks later, 2 h after intramammary infusion of endotoxin. Mastitis developed in all endotoxin-infused quarters. The pharmacokinetic characteristics of carprofen in healthy cows were a small volume of distribution (0.09 l/kg), a relatively low systemic clearance (2.4 ml/h kg), and a long elimination half-life (30.7 h). In the mastitic cows, systemic clearance (1.4 ml/h kg) was significantly lower (P less than 0.01), and elimination half-life (43.0 h) was significantly longer (P less than 0.01) than in the normal animals. Concentrations of carprofen in milk from healthy quarters were below the limit of detection for the assay (0.022 micrograms/ml). In milk from mastitic quarters, concentrations of carprofen increased up to 0.164 micrograms/ml during the first 12 h after induction of mastitis, but were less than 0.022 micrograms/ml at 24 to 48 h. Compared with the untreated mastitic controls, carprofen treatment significantly reduced heart rate (P less than 0.01), rectal temperature (P less than 0.001), quarter swelling (P less than 0.01) and other parameters measured. Local and systemic adverse reactions to carprofen were not observed.     

Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin

The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroid function in relation to reproductive efficiency in postpartum buffaloes (Bubalus bubalis) during summer and winter

Thyroid function was studied by estimating of plasma-protein-bound iodine (PBI), in buffaloes, from 0 to 57 days postpartum. PBI values (microgram/100 ml) were lowest on day 1 postpartum, followed by a gradual increase by day 57. The values were consistently lower (P less than 0.01) during summer (3.79 +/- 0.13 micrograms/100 ml), as compared to winter (5.06 +/- 0.27). A lower value (P less than 0.01) was obtained in animals requiring less than 30 days (3.53 +/- 0.45) or more than 30 days (4.88 +/- 0.27) for uterine involution. The values were 4.56 +/- 0.13, 5.03 +/- 0.68 and 2.72 +/- 0.50 in animals requiring less than 25, 25-50 and more than 50 days for initiation of follicular development (P less than 0.01). Similarly the values were 4.95 +/- 0.38, 3.95 +/- 0.45 and 4.03 +/- 0.59 in buffaloes having postpartum oestrus intervals less than 45, 45-90, and more than 90 days (P less than 0.01). Higher values (P less than 0.05) were obtained in conceiving (4.55 +/- 0.41), as compared to non-conceiving animals (4.21 +/- 0.31). It can be concluded that the thyroid function is depressed during summer and in poorly reproducing buffaloes.     

Secretion of tumor necrosis factor by endotoxin-treated equine mammary exudate macrophages: effect of dexamethasone and pentoxifylline.

Secretion of tumor necrosis factor (TNF) by equine mammary exudate macrophages (MEM phi) exposed to bacterial lipopolysaccharide (LPS) was dose-dependent and was maximal (216.5 +/- 51.9 U/ml) at 100 micrograms LPS/ml, the highest concentration tested. All concentrations of dexamethasone tested (10(-8) to 10(-4) M) significantly (P less than or equal to 0.05) inhibited TNF production by MEM phi when the agent was added 1 hour before LPS. Pretreatment with pentoxifylline at concentrations greater than 3 micrograms/ml also significantly (P less than or equal to 0.05) reduced secretion of TNF by MEM phi. The inhibitory effect of dexamethasone (10(-4) M) was observed when the agent was added to MEM phi from 30 minutes before until 4 hours after LPS. Pentoxifylline (100 micrograms/ml) significantly (P less than or equal to 0.05) suppressed TNF when added from 2 hours before until 2 hours after LPS; however, when pentoxifylline addition was delayed until 8 hours post-LPS, TNF production was enhanced. These apparent inhibitory effects of dexamethasone and pentoxifylline were not due to reduced macrophage viability or to interfering effects of the agents at the level of the TNF bioassay.     

Plasma concentrations of oxytetracycline in swine after administration of the drug intramuscularly and orally in feed

Four pigs were used in a 2 X 2 crossover study to determine plasma oxytetracycline (OTC) concentration and OTC pharmacokinetic variables after IM administration of 2 OTC preparations--long acting OTC and a 100-mg of OTC/ml solution (OTC-LA and OTC-100, respectively)--at a dosage of 20 mg/kg of body weight. In a second study, 3 additional pigs were given ad libitum access to feed containing pure OTC (0.55 g/kg of feed). The mean (+/- SD) peak plasma OTC concentration after OTC-LA administration was 6.0 +/- 2.2 micrograms/ml at 30 minutes; the mean peak plasma OTC concentration after OTC-100 administration was 6.7 +/- 3.4 micrograms/ml at 90 minutes. Mean plasma OTC concentration after oral OTC administration in feed peaked at 0.4 micrograms/ml 48 hours after access to OTC-medicated feed and decreased to 0.25 micrograms/ml by the end of that study. Mean plasma OTC concentration was maintained at greater than 0.5 micrograms/ml for less than 48 hours after OTC-LA administration and for less than 36 hours after OTC-100 administration. Mean plasma OTC concentration decreased to less than 0.2 micrograms/ml by 72 hours after IM administration of either product. Calculation of area under the plasma OTC concentration-time curve (AUC) did not reveal significant difference between the 2 OTC formulations. There also was not significant difference (between OTC-LA and OTC-100) in the value of the disappearance rate constant after administration of either OTC formulation. The data did not indicate significant pharmacologic advantage of OTC-LA, compared with OTC-100, when either formulation was administered IM at a dosage of 20 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and body fluid and endometrial concentrations of cephapirin in mares

Six healthy adult horse mares were each given a single injection of sodium cephapirin (20 mg/kg of body weight, IV), and serum cephapirin concentrations were measured serially over a 6-hour period. The mean elimination rate constant was 0.78 hour-1 and the elimination half-life was 0.92 hours. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.17 L/kg and 598 ml/hour/kg, respectively. Each mare was then given 4 consecutive IM injections of sodium cephapirin (400 mg/ml) at a dosage level of 20 mg/kg. Cephapirin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 14.8 micrograms/ml 25 minutes after the 4th injection. The highest mean synovial and peritoneal concentrations were 4.6 micrograms/ml and 5.0 micrograms/ml, respectively, 2 hours after the 4th injection. The highest mean endometrial concentration was 2.2 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 7,421 micrograms/ml. Cephapirin did not readily penetrate the CSF. When cephapirin was given IM at the same dose, but in a less concentrated solution (250 mg/ml), serum concentrations peaked at 25.0 micrograms/ml 20 minutes after injection, but the area under the serum concentration-time curve was not significantly different (P greater than 0.05). The bioavailability of the drug was greater than or equal to 95% after IM injection.     

Effect of aztreonam upon human polymorphonuclear leukocyte functions.

Aztreonam (SQ 26,776), a new synthetic monobactam with an excellent antibacterial spectrum was analyzed in vitro. In this paper, the effect of aztreonam on the phagocytic process of human neutrophils isolated from fifteen healthy volunteers was studied. Chemotaxis was not modified with aztreonam at any of the doses used (10, 20, 40, 60, 80 and 100 micrograms/ml). On the other hand, this antibiotic at 100 micrograms/ml significantly increases (P less than 0.05) Candida albicans ingestion as well as their digestion by neutrophils at 10 and 100 micrograms/ml.     

The influence of level of feeding on growth and serum insulin-like growth factor I and insulin-like growth factor-binding proteins in growing beef cattle supplemented with somatotropin

The objective of this study was to determine the effects of level of feeding on growth, feed efficiency (gain:feed; G:F), body composition (BC), and serum concentrations of somatotropin (ST), IGF-I, and IGF-binding proteins (BP) in growing beef cattle supplemented with bovine (b) ST. In each of two consecutive years, 40 growing beef cattle were blocked by weight (average BW: yr 1 = 316 kg, yr 2 = 305 kg) and used in a 2 x 2 factorial arrangement with main effects of bST (0 or 33 microg x kg BW(-1) x d(-1)) and level of feed intake (ad libitum [AL] or 0.75 AL). Relative to uninjected cattle, treatment with bST increased ADG 9.6% (1.14 vs 1.25 kg/d; P < 0.05) and increased G:F 8.1% (12.3 vs 13.3 gain [g]:feed [kg]; P < 0.05), whereas ADG in AL animals was 39% greater than that in 0.75 AL animals (1.39 vs 1.00 kg/d; P < 0.05). There was a tendency (P = 0.10) for a bST x level of feeding interaction, such that the increase in ADG with bST was greater in AL cattle than in 0.75 AL cattle (10.6 vs 7.8%; P = 0.10). Serum concentrations of ST were greater in 0.75 AL cattle than in AL cattle (13.0 vs 8.6 ng/mL; P < 0.05) and in bST-treated cattle than in uninjected cattle (16.3 vs 5.2 ng/mL; P < 0.05). Due to a bST x level of feeding interaction (P < 0.01), the magnitude of the increase in serum ST to exogenous bST was greater (P < 0.01) in 0.75 AL cattle than in AL cattle. Relative to uninjected cattle, treatment with bST increased (P < 0.05) serum concentrations of IGF-I and IGFBP-3 and reduced (P < 0.05) concentrations of IGFBP-2. Similarly, AL cattle had greater (P < 0.05) serum concentrations of IGF-I and IGFBP-3 and reduced (P < 0.05) IGFBP-2 compared with 0.75 AL cattle. In summary, treatment with bST increased growth rate and G:F and stimulated serum IGF-I and IGFBP-3 while reducing IGFBP-2. Feeding at 0.75 ad libitum intake reduced the magnitude of response for each of these variables. Thus, limit-feeding may reduce the effect of exogenous bST on growth rate by blunting bST-induced increases in IGF-I and IGFBP-3 and bST-induced decreases in IGFBP-2.     

Alterations in epinephrine-induced arrhythmogenesis after xylazine and subsequent yohimbine administration in isoflurane-anesthetized dogs

Effects of xylazine (1.1 mg/kg of body weight, IV bolus, plus 1.1 mg/kg/h infusion) and subsequent yohimbine (0.125 mg/kg, IV bolus) administration on the arrhythmogenic dose of epinephrine (ADE) in isoflurane (1.8% end-tidal)-anesthetized dogs were evaluated. The ADE was defined as the total dose of epinephrine that induced greater than or equal to 4 premature ventricular contractions within 15 seconds during a 3-minute infusion period or within 1 minute after the end of infusion. Total ADE values during isoflurane anesthesia, after xylazine administration, and after yohimbine injection were 36.6 +/- 8.45 micrograms/kg, 24.1 +/- 6.10 micrograms/kg, and 45.7 +/- 6.19 micrograms/kg, respectively. Intravenous xylazine administration significantly (P less than 0.05) increased blood pressure and decreased heart rate, whereas yohimbine administration induced a significant (P less than 0.05) decrease in blood pressure. induced a significant (P less than 0.05) decrease in blood pressure. After yohimbine administration, the ADE significantly (P less than 0.05) increased above that after isoflurane plus xylazine administration. After yohimbine administration, blood pressure measured immediately before epinephrine-induced arrhythmia was significantly (P less than 0.05) less than the value recorded during isoflurane plus xylazine anesthesia. Heart rate was unchanged among treatments immediately before epinephrine-induced arrhythmia. Seemingly, yohimbine possessed a protective action against catecholamine-induced arrhythmias in dogs anesthetized with isoflurane and xylazine.     

Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model. Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3-day-old foals. The mean elimination rate constant for clavulanate was significantly less (P less than 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3-day-old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 0.01), in 3-day-old foals than in 28-day-old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3-day-old foals were 100% and 88.3%, respectively, and in 28-day-old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 micrograms/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC less than or equal to 16 micrograms/ml), it should be administered i.v. four times daily.     

Pharmacokinetics of cefotaxime in the domestic cat

Cefotaxime was administered as single IV or IM dose for the purpose of examining its pharmacokinetics in healthy cats. The mean predicted plasma concentration of cefotaxime in 6 cats at 0 time after a single IV dosage of 10 mg/kg of body weight was 88.9 micrograms/ml. The mean plasma concentrations decreased to 10.8 micrograms/ml at 2 hours, 3.7 micrograms/ml at 3 hours, and 0.5 microgram/ml at 6 hours. The half-life was 0.98 +/- 0.25 hour (mean +/- SD), and the total body clearance was determined to be 2.76 +/- 1.25 ml/min/kg. After a single IM injection of 10 mg/kg of body weight, the mean maximum observed plasma concentration was 36.2 micrograms/ml at 0.75 hour. The mean absorption half-life was 0.24 hour. In 2 animals, the bioavailability of an IM injection was 98.2% and 93.0%.     

Exogenous human growth hormone-releasing factor and ovine somatotropin improve growth performance and composition of gain in lambs

The objectives of this study were 1) to compare intermittent subcutaneous administration of human growth hormone-releasing factor (hGRF) at two doses with a similar regimen of ovine somatotropin (oST) for effects on growth and composition of gain in growing lambs and 2) to determine whether increasing the dietary amino acid availability enhances response to oST or hGRF. Eighty crossbred ewe and wether lambs (25.5 kg live weight) were assigned randomly in pairs to receive four daily injections of excipient, 40 micrograms oST/kg BW, 5 micrograms hGRF/kg BW or 10 micrograms hGRF/kg BW for 42 (n = 80) or 56 (n = 40) d. Doses were adjusted weekly for BW. Mean plasma oST concentrations increased from 2.03 ng/ml prior to treatment to 20.64, 4.80 and 5.45 ng/ml with oST, 5 and 10 micrograms/kg hGRF doses, respectively. Lambs did not become refractory to hGRF. Cumulative gain increased approximately 18% with 7 wk of treatment with oST and the low dose of hGRF (both P less than .01), and feed efficiency improved 21% with oST and 18% with both doses of hGRF (both P less than .05). Carcass lipid accretion rate decreased 22% to 30% (P less than .001), and carcass protein accretion rate increased 30% to 36% (P less than .001) with hGRF and oST treatment, respectively. Addition of fishmeal to the diet at 4% to replace an equal amount of soy protein improved gain 8.5%; it improved efficiency 14.2% (P less than .05) across all treatments, and it significantly enhanced the effects of oST on feed efficiency (interaction P less than .12) and hind leg muscle weights.