Pharmacokinetic and pharmacodynamic integration of enrofloxacin against Salmonella Enteritidis after administering to broiler chicken by per-oral and intravenous routes.

It is crucial to optimize the dose of fluoroquinolones to avoid antibiotic resistance and to attain clinical success. We undertook this study to optimize the dose of enrofloxacin against Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) in chicken by assessing its pharmacokinetic/pharmacodynamic (PK/PD) indices. The antibacterial activities of enrofloxacin against S. Enteritidis were evaluated. After administering 10 mg/kg body weight (b.w.) of enrofloxacin to broiler chickens of both sexes by intravenous (IV) and peroral (PO) routes, blood samples were drawn at different intervals and enrofloxacin concentrations in plasma were determined. PK/PD indices were calculated by integrating the PK and PD data. The elimination half-lives (T1/2), time required to reach peak concentration (Tmax), peak concentration (Cmax), and area under curve (AUC) after administering enrofloxacin by PO and IV routes were 25.84 ± 1.40 h, 0.65 ± 0.12 h, 3.82 ± 0.59 µg/mL, and 20.84 ± 5.0 µg·h/mL, and 12.84 ± 1.4 h, 0.22 ± 0.1 h, 6.74 ± 0.03 µg/mL, and 21.13 ± 0.9 µg.h/mL, respectively. The bioavailability of enrofloxacin was 98.6% ± 8.9% after PO administration. The MICs of enrofloxacin were 0.0625-1 µg/mL against S. Enteritidis strains, and the MIC50 was 0.50 µg/mL. The Cmax/MIC50 were 7.64 ± 0.2 and 13.48 ± 0.7 and the 24 h AUC/MIC50 were 41.68 ± 0.1 and 42.26 ± 0.3 after administering the drug through PO and IV routes, respectively. The data in this study indicate that the application of 50 mg/kg b.w. of enrofloxacin to chicken through PO and IV routes with a dosing interval of 24 h can effectively cure S. Enteritidis infection, indicating the need for a 5-fold increase in the recommended dosage of enrofloxacin in chicken.

Therapeutic effect of ginsenoside Rg1 on mastitis experimentally induced by lipopolysaccharide in lactating goats.

Escherichia coli is a cause of subclinical and clinical mastitis in dairy cattle and goats, and sometimes causes severe clinical disease that may result in death of the animal. Previous investigation showed that ginsenoside Rg1 extracted from Panax ginseng C.A. Meyer (Araliaceae) has an anti-inflammatory effect on the sepsis induced by E. coli lipopolysaccharide via competitive binding to toll-like receptor 4. We hypothesized that intravenous injection of Rg1 had therapeutic effect on mastitis experimentally induced by intramammary infusion of lipopolysaccharide in lactating goats. In this study, 9 lactating goats were randomly assigned to 1 of the 3 groups: (1) lipopolysaccharide intramammary infusion + saline intravenous injection, (2) lipopolysaccharide intramammary infusion + Rg1 intravenous injection, and (3) saline intramammary administration + saline intravenous injection. Because no adverse clinical signs were observed after intramammary infusion of saline and intravenous injection of Rg1 in a preliminary experiment, and available qualified goats were limited in this study, this treatment was not included in this study. One udder half of each goat received intramammary infusion of lipopolysaccharide (50 µg/kg of body weight; groups 1 and 2) or saline solution (group 3), and the other half was infused with 2 mL of saline solution at h 0. Afterward, intravenous injections of saline solution (groups 1 and 3) or Rg1 (2.5 mg/kg of body weight; group 2) were administered at h 2 and 4 post-lipopolysaccharide challenge. Blood and milk samples were collected 3, 6, 9, 12, 15, 18, 21, 24, 48, and 72 h post-lipopolysaccharide challenge, and clinical signs were monitored hourly after lipopolysaccharide challenge within the first 10 h and at the same time points as blood samples. The results showed that Rg1 treatment downregulated rectal temperature, udder skin temperature, udder girth, milk somatic cell count, and N-acetyl-ß-d-glucosaminidase and upregulated milk production, lactose, and recovered blood components, such as white blood cells, neutrophils, lymphocytes, total proteins, albumin, and globulin. Considering the positive therapeutic effect on lipopolysaccharide-induced mastitis in goats presented in this study as well as the anti-inflammatory activity found previously, the botanical Rg1 deserves further study as a therapeutic agent in the treatment of E. coli mastitis in dairy animals.

Pharmacokinetics of sanguinarine, chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration.

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half-life (t1/2 ) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (Cmax ) of DHSA (2.49 ± 1.4 µg/L) was higher that of SA (1.89 ± 0.8 µg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h-1 ·kg-1 ) with a t1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.

Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.

OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.

Pharmacokinetics, bioavailability and PK/PD relationship of cefquinome for Escherichia coli in Beagle dogs.

The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration-time curve of cefquinome was analyzed using a two-compartmental model, and the mean values of t1/2α (h), t1/2ß (h), Vss (L/kg), ClB (L/kg/h) and AUC (µg·h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one-compartmental model with first-order absorption. The mean values of t1/2Kel , t1/2Ka , tmax (h), Cmax (µg/mL) and AUC (µg·h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC90 (0.125 µg/mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study.

Treatment of experimentally induced osteoarthritis in horses using an intravenous combination of sodium pentosan polysulfate, N-acetyl glucosamine, and sodium hyaluronan.

OBJECTIVE: To assess the effects of sodium pentosan polysulfate (PPS), N-acetyl glucosamine (NAG), and sodium hyaluronan (HA) in horses with induced osteoarthritis (OA). STUDY DESIGN: Experimental. ANIMALS: Adult Standard bred horses (n = 16). METHODS: OA was induced arthroscopically in 1 intercarpal joint; 8 horses were administered 3 mg/kg PPS, 4.8 mg/kg NAG, and 0.12 mg/kg HA (PGH), intravenously (IV), weekly and 8 horses were administered an equivalent volume of saline IV until study completion (day 70). Horses underwent a standardized treadmill exercise program. Clinical and radiographic findings and synovial fluid analysis were evaluated throughout the study. Macroscopic, histologic, histochemical, and biochemical findings were evaluated after necropsy. Comparisons of interest included OA and non-OA joints of saline treated horses and OA joints of PGH treated horses and OA joints of saline treated horses. Results were statistically analyzed with significance set at P < .05. RESULTS: OA caused increases in clinical assessment scores, synovial fluid variables, radiographic, macroscopic, and histologic cartilage scores, synovial fluid and cartilage chondroitin sulfate 846-epitope and glycosaminoglycan concentration. Total radiographic scores, total macroscopic joint pathology and macroscopic cartilage pathology scores were significantly reduced in horses treated with PGH compared with saline treated horses. Synovial fluid total protein concentration and white blood cell count were higher in OA joints of PGH treated horses compared with saline treated horses. There were no other significant differences between treatment groups. CONCLUSIONS: Improvements in macroscopic variables were not supported by other outcomes. Further evidence is needed before PGH can be recommended as a therapeutic option for osteoarthritis in horses.

Effect of intravenously injected zinc on tissue zinc and metallothionein gene expression of broilers.

1. The effect of intravenously injected zinc (Zn) on tissue Zn concentrations and pancreas metallothionein (MT) gene expression in broilers was investigated to detect differences in the tissue utilisation of Zn from different Zn sources. 2. A total of 432 male chickens were randomly allotted on d 22 post-hatch to one of nine treatments in a completely randomised design. Chickens were injected with either a 0.9% (w/v) NaCl solution (control) or a saline solution supplemented with Zn sulphate or one of three organic Zn chelates with weak (Zn-AA W), moderate (Zn-Pro M) or strong (Zn-Pro S) chelation strengths at two injected Zn dosages calculated according to two Zn absorbability levels (6 and 12%). 3. Bone and pancreas Zn concentrations, pancreas MT mRNA levels and MT concentrations increased on d 6 and 12 after Zn injections as the injected Zn dosages increased. Chickens injected with the Zn-Pro S had lower bone Zn concentration than those injected with the Zn-Pro M or Zn-AA W on d 6 after injections. However, no differences among Zn sources were observed in bone Zn concentration on d 12 after injections, pancreas Zn concentrations, pancreas MT mRNA levels and MT concentrations on both d 6 and d 12 after injections. 4. It was concluded that the injected Zn-Pro S was the least favourable for bone Zn utilisation of broilers. The pancreas Zn concentration and pancreas MT gene expressions might not be sensitive enough to detect differences in the tissue utilisation of injected Zn in broilers between organic and inorganic Zn sources or among organic Zn sources.

Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares.

Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg/kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (beta-haemolytic streptococci) ranged from 0.25-2 and 1.5-3.0 microg/mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg/kg respectively. After i.v. treatment with EFX at 5 mg/kg, endometrial concentrations of EFX and CFX above the MIC value were detected for 36-48 and 22-43 h posttreatment for Gram-negative and -positive isolates respectively. Concentrations above MIC were maintained for much shorter periods at the lower (2.5 mg/kg) treatment dose. Based on these results, a conventional dose (5 mg/kg) of EFX given prebreeding followed by two further doses at 36-48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis.

Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep.

Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79-1.75×MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against "deep" infections caused by bacteria with MICs<1 µg/mL or "shallow" infections caused by bacteria with MICs<0.1 µg/mL. Intramuscular administration could be safely considered effective against both "deep" and "shallow" infections when the MICs of the targeted pathogens are lower than 1 µg/mL.

Oral bioavailability of quercetin from different quercetin glycosides in dogs.

Although the flavonol quercetin is used as a supplement in commercial dog food, data on quercetin bioavailability in dogs are not available. Thus, we investigated quercetin bioavailability (measured as area under the concentration-time curve) in nine adult beagle dogs at an oral dose of 10 mg/kg body weight (b.w.). The major fraction (>80 %) of flavonols circulating in blood plasma were conjugated metabolites of quercetin. The absolute bioavailability of quercetin (i.e. the fraction that reaches the systemic circulation) was only about 4 %. We also compared the oral bioavailability between the aglycone quercetin and its more often used glucorhamnoside (rutin) and 3-O-glucoside (isoquercitrin) at an equimolar dose of 30 mumol/kg b.w. (corresponding to 10 mg quercetin/kg). Quercetin and isoquercitrin were mainly absorbed in the small intestine with isoquercitrin being one and a half times more bioavailable than quercetin. Maximal plasma concentration after isoquercitrin treatment was 0.89 (sem 0.07) mumol/l. Although quercetin absorption from rutin was delayed, relative bioavailability was not lower than from the aglycone itself. The latter observation is in clear contrast to findings in human subjects, pigs or rats and might indicate that rutin is a better source of quercetin in dogs than in other species. However, potential in vivo quercetin effects beyond the gastrointestinal tract are limited by the intensive metabolism as well as by the rather low bioavailability of this flavonol.

The bioavailability and disposition kinetics of genistein in cats.

The absorption and disposition kinetics of the soy isoflavone genistein were determined in cats (n = 6). An oral dose of 100 mg/kg was administered, which has previously been demonstrated to be the minimum oral estrogenic dose, and was administered intravenously at a dose of 20 mg/kg, being the largest practical dose that could be safely administered. Plasma free, and total (conjugated + free) genistein concentrations were determined by HPLC following organic extraction. Noncompartmental analysis revealed a half-life of 21.67 +/- 7.9 h (free) and 9.95 +/- 2.7 h (conjugated), volume of distribution 31.94 +/- 10.38 L/kg (free) and 11.82 +/- 3.96 L/kg (conjugated) following intravenous administration. Following oral administration the half-lives were determined to be 17 +/- 4.8 h (free) and 8.56 +/- 4.65 h (conjugated), with tmax = 4.4 +/- 0.6 h (free) and 4.42 +/- 0.99 h (conjugated), and Cmax = 0.276 +/- 0.1 microg/mL (free) and 6.24 +/- 6.58 microg/mL (conjugated). Oral bioavailabilities were 1.379 +/- 0.9% (free) and 29.85 +/- 22.61% (conjugated). The ratio of total:free genistein ranged from 25.9 to 5.5. Poor oral absorption and efficient conjugation explain the low bioavailability of free genistein. Accumulation of genistein in peripheral lipophilic compartments may occur.

Effects of chromium propionate on response to an intravenous glucose tolerance test in growing Holstein heifers.

To test the effect of chromium propionate on glucose utilization in growing dairy heifers, 0, 5, 10, or 15 mg of chromium/d were fed to 20 Holstein heifers of 11 to 14 mo of age, in a replicated Latin square. A 2-wk adaptation period was followed by 4 periods of 2 wk each with a 2-wk flush out period between treatments. Treatments were allotted to periods in a design balanced for potential carryover effects. Chromium propionate was fed in 0.25 kg/d of ground corn individually. After 14 d on each treatment, animals were fitted with an indwelling jugular catheter, and an intravenous glucose tolerance test was conducted the following morning. Body weights increased throughout the experiment, but weights and condition scores were unaffected by treatment. Chromium supplementation increased basal glucose and decreased basal insulin and nonesterified fatty acids (NEFA) in serum in a dose-dependent, quadratic manner. Chromium increased glucose clearance rate as measured by half-life, time to nadir, and area under the curve. Over all periods, insulin concentrations tended to be lower in treated animals whereas clearance rates were unchanged. Serum NEFA levels were negatively correlated with glucose, such that treated animals with increased glucose had lower NEFA overall. There was an apparent long-term effect of chromium, because heifers in period 4 on the control diet had reduced insulin concentrations than those in the other control periods. Chromium propionate may increase glucose utilization in growing dairy heifers.

Clinical efficacy of intravenous administration of marbofloxacin in a Staphylococcus aureus infection in tissue cages in ponies.

Tissue cages (TC), implanted subcutaneously in the neck in eight ponies, were inoculated with Staphylococcus aureus (S. aureus) to determine the clinical efficacy of marbofloxacin in the treatment of this infection. From 21 h after inoculation, marbofloxacin (6 mg/kg) was administered intravenously (i.v.) once daily for 7 days. Samples of the tissue cage fluid (TCF) were taken to determine marbofloxacin concentrations (days 1, 3 and 7), using high-pressure liquid chromatography, and numbers of viable bacteria [colony forming units (CFU)] (days 1, 3, 7, 14 and 21). Statistical analysis was used to compare CFU before and after treatment. Clinical signs and CFU were used to evaluate the efficacy of treatment. Although, there was a slight decrease in CFU in all TC initially, the infection was not eliminated by marbofloxacin treatment in any of the ponies and abscesses formed. As the MIC (0.25 microg/mL) did not change during treatment and the concentration of marbofloxacin during treatment (mean concentration in TCF was 0.89 microg/mL on day 1, 0.80 microg/mL on day 3 and 2.77 microg/mL on day 7) was above MIC, we consider that the treatment failure might be attributable to the formation of a biofilm by S. aureus. Based on the present results, i.v. administration of marbofloxacin alone is not suitable for the elimination of S. aureus infections from secluded sites.

Chronic lung inflammation affects plasma amino acid concentrations in pigs.

Metabolic changes associated with inflammatory processes and immune response can modify protein and AA requirements. Improved knowledge of these processes will provide opportunities for nutritional intervention to sustain growth and animal defense at the same time. The objective of the study was to identify AA whose metabolism is affected by chronic lung inflammation. Six pairs of littermate piglets were selected at 28 d of age on the basis of their BW. After catheterization of the jugular vein, one littermate received complete Freund's adjuvant (CFA) intravenously, whereas its littermate was injected with a sterile saline solution (CON). Piglets within a litter were pair-fed in order to avoid confounding effects of feed intake and inflammation on plasma AA concentrations. Blood samples were taken after an overnight fast and 2 h after the morning meal for 9 d. Rectal temperature, food consumption, weight gain, plasma haptoglobin, and AA concentrations were measured. The CFA injection decreased food intake, and increased body temperature and plasma haptoglobin concentration. Plasma tryptophan, glutamine, proline, glycine, tyrosine, ornithine, total AA concentrations, and the ratio of tryptophan to large neutral AA were less in CFA than in CON (P < 0.05), independent of time and meal. In contrast, plasma histidine concentration was higher (P < 0.05) in CFA than in CON pigs. Plasma serine, arginine, alanine, asparagine, and total AA concentrations were lower in CFA than in CON pigs only in the fed state (P < 0.05). Among essential AA, only plasma tryptophan concentration was lower (P < 0.01) in CFA than in CON pigs in both fasted and fed state. These results show that chronic lung inflammation affects individual AA differently and suggest that the utilization of some AA increased during chronic lung inflammation in pigs. Activation of tryptophan catabolism enzyme indoleamine 2,3-dioxygenase seems a relevant hypothesis to explain the increased tryptophan utilization, although its incorporation in acute-phase proteins and the existence of other catabolic pathways cannot be excluded.

Evaluation of a single dose versus a divided dose regimen of danofloxacin in treatment of Actinobacillus pleuropneumoniae infection in pigs.

A single versus a divided dose regimen of danofloxacin was evaluated in treatment of porcine Actinobacillus pleuropneumoniae infection using clinical observations combined with biochemical infection markers: C-reactive protein, zinc and ascorbic acid. Twenty hours after experimental infection, the 18 pigs received danofloxacin intravenously as a single dose of 2.5mg/kg or four doses of 0.6 mg/kg administered at 24h intervals. These dosage regimens resulted in similar AUCs of the plasma danofloxacin vs time curve. The maximum concentration was 3.5-fold higher using the single dose regimen, while the time with concentrations above the MIC was 2.5-fold longer using the fractionated regimen. Using the single dose regimen, temperature was normalised 32 h post-infection. In contrast, normalisation was delayed until 44 h post-infection using four low doses and a relapse with elevated temperatures at 52 and 68 h was observed. No other significant differences between the treatments were found, neither regarding clinical, haematological nor biochemical observations. The use of the more convenient single dose regimen was appropriate, as it was at least equivalent to the fractionated regimen.

Effect of L-NAME on pulmonary arterial pressure, plasma nitric oxide and pulmonary hypertension syndrome morbidity in broilers.

1. Experiments were conducted to evaluate the effect of a synthetic inhibitor of nitric oxide (NO) synthase (L-NAME) on pulmonary arterial pressure (PAP) and pulmonary hypertension syndrome (PHS) morbidity in broilers. 2. In Experiment 1, broilers were infused intravenously with L-NAME, and the mean pulmonary arterial pressure (mean PAP) and plasma NO were measured at 0, 1, 2 and 4 h after the start of infusion. The mean PAP increased and plasma NO was reduced at 1 to 2 h in broilers treated with L-NAME. 3. In Experiment 2, 180 Arbor Acres broilers were evenly divided into three groups: a control group (group C), and two groups exposed to low environmental temperatures and fed a 3, 3, 5-triiodothyronine (T3) supplemented diet alone (group A) or also including 100 ppm L-NAME (group B). 4. The PHS morbidity of group A was higher than for group C but lower than for group B. Plasma endothelin-1 was higher in broilers in groups A and B than in group C. Plasma NO was not significantly lower in broilers of group B when compared with those in group A. 5. The right/total ventricular weight ratio (RV/TV) and mean PAP were higher in groups A and B than in group C, and the RV/TV ratio increased one week earlier in group B than in group A. 6. These results suggest that L-NAME increases broiler PAP by inhibiting the endogenous synthesis of NO, leading to pulmonary hypertension, right ventricular hypertrophy and the increased morbidity of PHS in broilers.

Serum ascorbic acid concentrations in previously unsupplemented greyhounds after administration of a single dose of ascorbic acid intravenously or per os.

Plasma vitamin C concentrations (mean + SD) were measured after a large (1 g) dose of vitamin C was administered orally or intravenously to each of four trained greyhounds in a randomized cross-over design. Concentrations increased (p<0.05) for 2 h but returned to baseline by 6 h after supplementation. Peak concentrations were greater (p<0.01) after intravenous than oral administration (6.1+/-1.2 vs. 0.54+/-0.23 mg/dl). This suggests that vitamin C must be administered many times daily to maintain plasma concentrations above normal.

Influence of lipoic acid on lipid metabolism and beta-adrenergic response to intravenous or oral administration of clenbuterol in broiler chickens.

The effects of lipoic acid (LA) on muscle growth, metabolic response and hepatic respiration in broilers treated with or without clenbuterol (CLE) were examined. In 4-week-old chickens, dietary LA administration (100 mg x kg(-1)) enhanced the beta-adrenergic response of plasma nonesterified fatty acid with an intravenous injection of CLE (50 microg x kg(-1), estimated from the response area for 120 min (-7,860 vs. 874 micromol x L(-1) min in control and LA-treated groups, respectively; P < 0.05). When chickens received long-term oral administration of CLE (0.25 mg x kg(-1)) for 30 d, LA interfered with the repartitioning action of CLE, decreased abdominal fat weight (P < 0.05) and increased protein concentration of the breast muscle (P < 0.05), in 7-week-old chickens. In addition, the LA supplementation alone increased both plasma nonesterified fatty acid (P < 0.05) and triacylglycerol (P < 0.05), whereas these effects were not associated with CLE administration. These findings suggest that the dietary LA level used stimulates rapid lipolytic response of plasma nonesterified fatty acid to CLE injection and fatty acid turnover between adipose tissue and the liver, but does not facilitate the repartitioning action of CLE during long-term treatment in broilers.

Suspected tolazoline toxicosis in a llama.

Clinical signs of tolazoline toxicosis developed in a 4-year-old llama that received 2 doses of tolazoline hydrochloride to reverse xylazine-induced sedation. The full first dose (4.3 mg/kg [2.0 mg/lb] of body weight) was erroneously injected i.v., and the second dose was administered half i.v., half i.m. 45 minutes later, because the llama became weak and recumbent. Signs of anxiety, hyperesthesia, profuse salivation, and tachypnea were the first detectable clinical signs of tolazoline toxicosis. Convulsions, hypotension, gastrointestinal tract hypermotility, and diarrhea also developed. The llama was treated successfully with i.v. administration of diazepam, phenylephrine, and lactated Ringer's solution supplemented with potassium chloride and oxygen administered via nasal insufflation. We suggest that the maximum dose of tolazoline administered at any one time to llamas not exceed 2 mg/kg (0.91 mg/lb). Furthermore, tolazoline should be administered slowly i.v. or i.m. to reduce the risk of adverse reactions.

Comparison of sedative effects of romifidine following intravenous, intramuscular, and sublingual administration to horses.

OBJECTIVE: To compare sedative effects of romifidine following IV, IM, or sublingual (SL) administration in horses. ANIMALS: 30 horses that required sedation for routine tooth rasping. PROCEDURE: Horses (n = 10/group) were given romifidine (120 microg/kg) IV, IM, or SL. Heart rate, respiratory rate, head height, distance between the ear tips, thickness of the upper lip, response to auditory stimulation, response to tactile stimulation, and degree of ataxia were recorded every 15 minutes for 180 minutes. Tooth rasping was performed 60 minutes after administration of romifidine, and overall adequacy of sedation was assessed. RESULTS: IV and IM administration of romifidine induced significant sedation, but SL administration did not induce significant sedative effects. Scores for overall adequacy of sedation after IV and IM sedation were not significantly different from each other but were significantly different from scores for horses given romifidine SL. Sedative and other effects varied among groups during the first 60 minutes after drug administration; thereafter, effects of IV and IM administration were similar. CONCLUSIONS AND CLINICAL RELEVANCE: Onset of action was fastest and degree of sedation was greater after IV, compared with IM, administration of romifidine, but duration of action was longer after IM administration. Sublingual administration did not result in clinically important sedative effects.