Pharmacokinetics of combined administration of iron dextran with meloxicam or flunixin meglumine in piglets.

Objective: The objective was to evaluate the pharmacokinetics of compounding non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam or flunixin meglumine with iron dextran (ID) in piglets. Animal: Forty piglets (8 d of age) were randomly allocated into 5 groups (8 piglets/group) and received 1 intramuscular injection in the neck of the following treatments: flunixin meglumine (2.2 mg/kg) administered alone (F) or mixed with ID (F+ID); or meloxicam (0.4 mg/kg) administered alone (M) or mixed with ID (M+ID); or ID alone. Procedure: Blood samples were collected via indwelling jugular catheters at pre-dose, and 10, 20, 30, 45, and 60 min, and 2, 4, 8, 12, 24, 36, 48, and 72 h post-treatment to determine plasma NSAIDs concentrations using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters for plasma meloxicam and flunixin meglumine concentration-time profiles were determined for each piglet using noncompartmental analysis approaches. Statistical analyses were performed using SAS software with significance set at P < 0.05. Results: The AUC0-tlast, AUC0-∞, Cmax, and relative bioavailability values in the M+ID and F+ID groups were lower than corresponding M and F groups. The M+ID group elimination half-life was lower, whereas λz and tmax values were greater than the corresponding M group. Conclusion: Relative bioavailability of meloxicam and flunixin meglumine were reduced when compounded with ID in the same bottle and administered to piglets. Clinical relevance: Further research is warranted to evaluate if decreased NSAID exposure when compounded with ID alters analgesic efficacy or drug residue depletion.

Objectif: L'objectif était d'évaluer la pharmacocinétique de la combinaison d'anti-inflammatoires non stéroïdiens (NSAID) méloxicam ou flunixine méglumine avec du fer dextran (ID) chez les porcelets. Animal: Quarante porcelets (âgés de 8 jours) ont été répartis au hasard en cinq groupes (8 porcelets/groupe) et ont reçu une injection intramusculaire dans le cou des traitements suivants : flunixine méglumine (2,2 mg/kg) administrée seule (F) ou mélangée avec ID (F+ID); soit du méloxicam (0,4 mg/kg) administré seul (M) ou en mélange avec ID (M+ID); ou du ID seul. Procédure: Des échantillons de sang ont été prélevés via des cathéters jugulaires à demeure à la pré-dose, et 10, 20, 30, 45 et 60 min, et 2, 4, 8, 12, 24, 36, 48 et 72 h après le traitement pour déterminer la concentration plasmatique de NSAID par chromatographie liquide-spectrométrie de masse en tandem. Les paramètres pharmacocinétiques des profils concentration-temps du méloxicam et de la flunixine méglumine plasmatiques ont été déterminés pour chaque porcelet à l'aide d'approches d'analyse non compartimentale. Les analyses statistiques ont été effectuées à l'aide du logiciel SAS avec un seuil de signification fixé à P < 0,05. Résultats: Les valeurs AUC0­tlast, AUC0­∞, Cmax et de biodisponibilité relative dans les groupes M+ID et F+ID étaient inférieures à celles des groupes M et F correspondants. La demi-vie d'élimination du groupe M+ID était plus faible, tandis que les valeurs λz et tmax étaient supérieures à celles du groupe M correspondant. Conclusion: La biodisponibilité relative du méloxicam et de la méglumine de flunixine était réduite lorsqu'ils étaient combinés avec ID dans le même flacon et administrés aux porcelets. Pertinence clinique: Des recherches supplémentaires sont nécessaires pour évaluer si une diminution de l'exposition aux NSAID lorsqu'elle est associée à une ID modifie l'efficacité analgésique ou l'épuisement des résidus de médicaments.(Traduit par Dr Serge Messier).

The effect of transdermal flunixin meglumine on blood cortisol levels in dairy calves after cautery disbudding with local anesthesia.

The objective of this study was to evaluate the effect of the nonsteroidal anti-inflammatory drug transdermal flunixin meglumine (Finadyne Transdermal) on plasma cortisol, average daily weight gain, and standing and lying behavior of calves, when given at the time of disbudding combined with local anesthesia. A sedative was not used to minimize pharmacological interactions. Seventy-one female Holstein Friesian calves aged 13 ± 2 d, with an average weight of 48.9 ± 4.26 kg were enrolled in the study. All calves were randomly assigned to one of 3 treatment groups: (1) control group (CON, n = 27), (2) 1-flunixin group (1-FLU, n = 26) with a single administration of transdermal flunixin meglumine at disbudding, and (3) 2-flunixin group (2-FLU, n = 24) with 2 administrations of transdermal flunixin meglumine, the first treatment at disbudding and the second 6 h after disbudding. Although the CON group received a placebo, 1-FLU and 2-FLU received flunixin meglumine transdermally. To account for plasma cortisol changes due to manipulation and handling of the calves, a sham disbudding procedure was performed one week before disbudding took place. Sham disbudding was conducted by using a cold cautery dehorner applied to each horn bud for 10 s. Disbudding was performed in a similar way by using a hot cautery dehorner. Plasma samples were collected to measure the stress biomarker cortisol at 7 different time points. Body weights were measured 4 times in 2 wk. Standing and lying behavior was assessed via 3-dimensional accelerometer. During sham disbudding and disbudding mean plasma cortisol concentrations were 6.09 ± 2.5 ng/mL and 5.16 ± 2.8 ng/mL, respectively. Treatment tended to have an effect on plasma cortisol concentrations during sham disbudding and had an effect on plasma cortisol concentrations during disbudding. Plasma cortisol concentrations were affected by treatment 2 h after disbudding in comparison to CON group. Furthermore, there was a significant effect on plasma cortisol concentrations 6 h after disbudding in contrast to CON. A return to baseline plasma cortisol levels (initial concentrations) was not achieved in CON during disbudding. There was no statistical difference between average daily weight gain and the treatment procedure. Total lying time was not affected by treatment after disbudding. In conclusion, transdermal flunixin meglumine given at the time of disbudding combined with local anesthesia decreased concentrations of the stress biomarker cortisol, but a second dose 6 h after disbudding had no further effect on plasma cortisol levels.

Therapeutic plasma exchange to mitigate flunixin meglumine overdose in a cria.

OBJECTIVE: To describe the use of therapeutic plasma exchange (TPE) in the treatment of flunixin meglumine overdose in a cria. CASE SUMMARY: A 3-day-old alpaca cria was diagnosed with ureteral obstruction and agenesis resulting in severe bilateral hydronephrosis. During hospitalization, the cria inadvertently received a flunixin meglumine overdose of >65 mg/kg. Here, we report the use of lipid emulsion and TPE to mitigate flunixin meglumine toxicosis. TPE appeared to prevent any flunixin-induced kidney or gastrointestinal injury, even in a patient with congenital defects of the urinary tract. NEW INFORMATION PROVIDED: This is the first report of the use of TPE in a cria.

Effects of Intravenous Flunixin Meglumine, Phenylbutazone, and Acupuncture on Ocular Pain Scores in the Horse: A Pilot Study.

In this controlled, blinded, randomized block pilot study, the main objective was to evaluate the effectiveness of intravenous flunixin meglumine, phenylbutazone, and acupuncture on ocular pain relief using a multifactorial pain scale in the horse. Four experimental horses underwent corneal epithelial debridement in four sessions, when a randomly selected treatment or a control was used. All horses were pain scored before corneal wounding, then at 18 time points, when 11 parameters were allocated. Differences in the area under the curve of pain scores between the treatment groups were analyzed using a paired t-test. Corneal pain was significantly reduced by the third postoperative day (P = .03) when all 11 parameters were considered. Five ocular signs showed significant differences between treatments and proved to be good indicators of ocular pain. The other parameters (heart rate, corneal touch threshold, respond to palpation, and three behavioral parameters) were determined to be irrelevant when evaluating the degree of pain. When considering the five ocular signs, the lowest pain score was attributed to the flunixin meglumine group (1114), followed by the electroacupuncture group (1356), the phenylbutazone group (1397), and the control group (1580). There were significantly lower pain scores (P = .01) in the flunixin meglumine group when compared with those recorded in the control group during the first 46 hours. Flunixin meglumine was the most effective treatment at reducing ocular pain in the horse. In the future, a reduction in the number of pain score parameters and more precisely defined image evaluation criteria could be used.

Pharmacopuncture Analgesia Using Flunixin Meglumine Injection into the Acupoint GV1 (Ho Hai) After Elective Castration in Horses.

The study evaluated the effect of a 1/10 dose of flunixin meglumine administered into the governing vessel 1 (GV1) acupoint in horses that underwent castration. Twenty animals received 0.02 mg/kg detomidine intravenously, followed by 2.2 mg/kg ketamine and 0.1 mg/kg diazepam by the same route, and also a local anesthesia with 30 mL lidocaine. As postoperative analgesia, the animals received 1.1 mg/kg flunixin meglumine IV (FIV) or 0.11 mg/kg flunixin meglumine into the GV1 acupoint (FGV). Behavioral parameters were assessed 12 hours before the procedure (baseline) and at 4, 6, 12, and 24 hours after surgery; physiological parameters were measured at baseline and at 2, 4, 6, 8, 10, 12, 16, and 24 hours after surgery. The groups did not differ regarding pain scores. Heart rate was higher in the FIV group than in the FGV group 2 hours after surgery (46 ± 5.2 bpm vs. 37 ± 8.2 bpm); gut sounds decreased at 2, 4, and 6 hours in both groups. The temperature showed a decrease after 2 hours compared with baseline in the FGV group, and the systolic blood pressure was higher in the FGV group than in the FIV group at 8 hours (158 ± 18.1 mmHg vs. 134 ± 14.5 mmHg), 10 hours (157 ± 15.5 mm Hg vs. 130 ± 11.5 mmHg), and 12 hours (151 ± 18.7 mmHg vs. 134 ± 15.8 mmHg). Pharmacopuncture was as effective as conventional dose and route of flunixin meglumine in horses that underwent elective castration under those conditions.

Royal jelly protection on flunixin meglumine-induced spermiotoxicity and testicular degeneration in mice.

Current study was designed to investigate the protective effects of royal jelly on Flunixin me- glumine (FM)-induced spermiotoxicity related to sperm concentration, abnormal spermatozoa count and histopathological changes in mice testis. The subjects were divided into five groups according to FM and/or royal jelly intake: Control group; group 1, FM alone (25 mg/kg, im); group 2, combination of FM (25 mg/kg, im) and royal jelly (200 mg/kg, oral); group 3, FM alone (50 mg/kg, im); and group 4, combination of FM (50 mg/kg, im) and royal jelly (200 mg/kg, oral). The animals were fed once daily for 15 days and they were sacrificed last day. Epididymal sperm concentration and abnormal spermatozoa count were noted. Testicular histological findings were evaluated. On purpose, organization of each animal was graded according to Johnsen's scoring to assess the spermatogenesis relying on seminiferous tubule cross-section scores. Comparing to controls, FM administration caused a decrease in sperm concentration (p⟨0.05), an increase in total abnormal spermatozoa rates (p⟨0.05) and more degenerative changes in testes in mice. Royal jelly supplementation ameliorated both sperm concentration and abnormal spermato- zoa (p⟨0.05) comparing to the control group. In conclusion, we suggested that royal jelly might have protective effects in the FM-induced reductions in epididymal sperm concentration and in- crease in abnormal spermatozoa rate.

The binding of orally dosed hydrophobic active pharmaceutical ingredients to casein micelles in milk.

Casein proteins (αS1-, αS2-, ß- and κ-casein) account for 80% of the total protein content in bovine milk and form casein micelles (average diameter = 130 nm, approximately 1015 micelles/mL). The affinity of native casein micelles with the 3 hydrophobic active pharmaceutical ingredients (API), meloxicam [351.4 g/mol; log P = 3.43; acid dissociation constant (pKa) = 4.08], flunixin (296.2 g/mol; log P = 4.1; pKa = 5.82), and thiabendazole (201.2 g/mol; log P = 2.92; pKa = 4.64), was evaluated in bovine milk collected from dosed Holstein cows. Native casein micelles were separated from raw bovine milk by mild techniques such as ultracentrifugation, diafiltration, isoelectric point precipitation (pH 4.6), and size exclusion chromatography. Acetonitrile extraction of hydrophobic API was then done, followed by quantification using HPLC-UV. For the API or metabolites meloxicam, 5-hyroxy flunixin and 5-hydroxy thiabendazole, 31 ± 3.90, 31 ± 1.3, and 28 ± 0.5% of the content in milk was associated with casein micelles, respectively. Less than ∼5.0% of the recovered hydrophobic API were found in the milk fat fraction, and the remaining ∼65% were associated with the whey/serum fraction. A separate in vitro study showed that 66 ± 6.4% of meloxicam, 29 ± 0.58% of flunixin, 34 ± 0.21% of the metabolite 5-hyroxy flunixin, 50 ± 4.5% of thiabendazole, and 33 ± 3.8% of metabolite 5-hydroxy thiabendazole was found partitioned into casein micelles. Our study supports the hypothesis that casein micelles are native carriers for hydrophobic compounds in bovine milk.

Comparative therapeutic effect of steroidal and non-steroidal anti-inflammatory drugs on pro-inflammatory cytokine production in water buffalo calves (Bubalus bubalis) naturally infected with bronchopneumonia: a randomized clinical trial.

In the current study, we compared the therapeutic effects of a non-steroidal and a steroidal anti-inflammatory drug on the production of pro-inflammatory cytokines, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α) in the blood of water buffalo (Bubalus bubalis) calves naturally infected by bronchopneumonia. Twenty-seven buffalo calves (7 ± 2-month-old, 163 ± 12 kg) reared in smallholder farms in El-Dakahlia province in Egypt were identified to have bronchopneumonia and randomly allocated into three equal groups. Ten clinically healthy buffalo calves with negative bronchoalveolar lavage results were served as negative control. Diseased calves were treated with tulathromycin alone, a combination of tulathromycin with dexamethasone (steroidal anti-inflammatory drug) or tulathromycin with flunixin meglumine (non-steroidal anti-inflammatory drug). The results revealed significant elevations (P < 0.05) in the production of selected cytokines in all diseased calves in comparison with healthy animals. Six days post-treatment, a significant inhibition (P < 0.05) in the production of all assessed cytokines was observed in the blood of all treated calves. Interestingly, the serum concentrations of IL-1ß and IL-12p40 were returned to the normal levels in pneumonic calves treated with the combination therapy of tulathromycin and flunixin meglumine. A strong significant positive correlation (P < 0.05) was detected between clinical sum scoring and IL-12p40 and TNF-α concentrations. The obtained results indicate the selectively potent anti-inflammatory effect of flunixin meglumine on the production of pro-inflammatory cytokines in pneumonic buffalo calves and highlight the efficacy of flunixin meglumine in the treatment of bronchopneumonia in buffalo calves when used in combination with tulathromycin.

Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish.

Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days post-fertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and 0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each was recorded and analysed using novel tracking software that measures time spent active in 25 larvae at one time. Subsequently, the efficacy of aspirin, lidocaine, morphine and flunixin as analgesics after exposure to 0.1% acetic acid was tested. Larvae exposed to 0.1% and 0.25% acetic acid spent less time active, whereas those exposed to 0.01% acetic acid and 0.1-5% citric acid showed an increase in swimming activity. Administration of 2.5 mg l-1 aspirin, 5 mg l-1 lidocaine and 48 mg l-1 morphine prevented the behavioural changes induced by acetic acid. These results suggest that larvae respond to a noxious challenge in a similar way to adult zebrafish and other vertebrates and that the effect of nociception on activity can be ameliorated by using analgesics. Therefore, adopting larval zebrafish could represent a direct replacement of a protected adult fish with a non-protected form in pain- and nociception-related research.

Protective Role of Curcumin and Flunixin Against Acetic Acid-Induced Inflammatory Bowel Disease via Modulating Inflammatory Mediators and Cytokine Profile in Rats.

Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study is to evaluate the effect of flunixin and curcumin in experimentally induced ulcerative colitis in rats. Animals were randomly divided into four groups, each consisting of 12 animals: normal control group, acetic acid group, curcumin-treated group, and flunixin-treated group. Induction of colitis by intracolonic administration of 4% acetic acid produced severe macroscopic inflammation in the colon, 14 days after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, edema, and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), colonic alkaline phosphatase (ALP), and myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxide formation and depleted reduced glutathione concentrations in colonic tissues. After induction of colitis, treatment with curcumin (50 mg/kg daily, p.o.) and flunixin (2.5 mg/kg daily, s.c.) decreased serum LDH, ALP, interleukin (IL)-1ß, and tumor necrosis factor-α levels, as well as colonic MPO and lipid peroxide levels, whereas increased colonic prostaglandin E2 and IL-10 concentrations were observed. Moreover, effective doses of curcumin and flunixin were effective in restoring the histopathological changes induced by acetic acid administration. The findings of the present study provide evidence that flunixin may be beneficial in patients with inflammatory bowel disease.

Effects of tail docking on behavior of confined feedlot cattle.

Tail tip injuries occur in some feedlot cattle housed in slatted-floor facilities typically found in the midwestern United States. The practice of tail docking cattle on entry into these feedlot facilities was initiated to prevent tail injuries. Tail docking is a welfare concern from the standpoint that an important method of fly avoidance is removed and the tail docking procedure is painful and often excludes local anesthesia or extended analgesia. The primary objective of this study was to describe the behavioral responses of feedlot cattle following tail docking. Thirty-six heifers were randomly assigned to 1 of 2 treatment groups: docked (DK) or control (CN). All calves received an epidural following surgical preparation of the sacrococcygeal area and postoperative intravenous flunixin meglumine. A portion of the tail of DK calves was removed using pruning shears. An elastrator band was placed near the tail tip for hemostasis and tail tips were sprayed with fly spray. IceQube accelerometers collected step counts, motion index, lying time, lying bouts, and lying bout duration during d -4 through 13. Direct observations of cattle behavior were performed on d 0, 1, and 2. Step counts of DK calves were increased (P < 0.05) on d 0, 2, 3, 4, 6, 9, 10, and 13, and motion index of DK calves was also increased (P < 0.05) on d 0, 3, 4, 9, 10, 11, and 13. Docked cattle performed rear foot stomp behavior more (P < 0.001) than CN on d 0, 1, and 2. Forty-eight hours after tail docking, DK calves had increased lying bouts per hour (1.7 vs. 0.9 on d 0; P < 0.001; 1.1 vs. 0.8 on d 1; P < 0.01) but reduced lying bout durations (12.6 vs. 47.1 min on d 0; P < 0.001; 22.6 vs. 44.7 min on d 1; P < 0.001). On d 0, DK calves twitched tails more (P < 0.05) and ruminated less (P < 0.001). Despite provision of perioperative and postoperative analgesia, we identified altered behavior in DK cattle that may reflect a compromised welfare state for tail-docked feedlot cattle. We recommend that alternative strategies to reduce tail tip injury be explored.

Treatment of naturally occurring bovine respiratory disease in juvenile calves with a single administration of a florfenicol plus flunixin meglumine formulation.

The efficacy and safety of a florfenicol plus flunixin meglumine formulation in the treatment of respiratory disease was evaluated in calves less than six weeks of age, compared with a positive control group treated with a well-established florfenicol formulation. A total of 210 calves, selected from nine sites in Belgium, France and Spain, showing severe signs of respiratory disease, were randomly assigned to treatment with either florfenicol plus flunixin meglumine (Resflor; MSD Animal Health) or florfenicol (Nuflor; MSD Animal Health), both administered subcutaneously once. Animals were clinically observed daily for 10 days following treatment initiation. The predominant respiratory pathogens were Pasteurella multocida, Mycoplasma bovis, Mannheimia haemolytica and Histophilus somni. All isolates were subject to in vitro sensitivity testing and found susceptible to florfenicol. In both groups, rectal temperature dropped and clinical index (depression and respiratory signs) significantly improved after treatment. Specifically, for the change in rectal temperature from pretreatment to six hours post-treatment, the florfenicol-flunixin formulation was found significantly superior to florfenicol. Moreover, the florfenicol-flunixin formulation alleviated the clinical signs of disease more rapidly, and was demonstrated to be non-inferior to florfenicol on days 4 and 10. The use of the product combining florfenicol and flunixin in calves is safe and efficacious in the treatment of outbreaks of bovine respiratory disease.

Effects of local anesthesia and flunixin meglumine on the acute cortisol response, behavior, and performance of young dairy calves undergoing surgical castration.

This study assessed the effects of flunixin meglumine (FM) and a local anesthetic block (LA) on postcastration performance, plasma cortisol concentration, and behavior in dairy calves. Thirty 2- to 3-mo-old Holstein-Friesian bull calves were allocated to 5 treatments: castration with LA (2% lidocaine injected into the testes and subcutaneously), castration with FM (1.1mg/kg, i.v.), castration with LA+FM, castration without drugs (CC), and sham castration (SC). Castration was performed using a Newberry knife and Henderson castrating tool. Feed intake and body weight gain were recorded for 10d postcastration. Plasma cortisol concentration and behavior frequency and duration were monitored for 8h postcastration. Variables with repeated measures were analyzed using PROC MIXED (SAS Institute Inc., Cary, NC); one-way ANOVA was used for nonrepeated measures. No differences in feed intake or body weight gain were detected among groups. Calves in the CC, LA, and FM groups had transient (<60, <60, and <45 min, respectively) increases in plasma cortisol concentration after castration, with a second increase at 120 min in the LA group, whereas cortisol concentration remained at baseline in the LA+FM and SC groups. Mean cortisol concentrations were lower for calves in the LA+FM and SC groups than in the CC group. The area under the plasma cortisol concentration curve during the first 3h postcastration was greater in CC- and LA-treated calves than in SC controls. Castration without drugs was associated with higher frequencies of crouching and statue standing and less oral activity compared with SC controls. Administering LA alone before castration was associated with higher frequencies of head turning, statue standing, and postural changes, and less feeding behavior compared with SC controls. More leg lifting to groom was seen in LA+FM-treated calves than in SC controls. Calves administered FM alone before castration exhibited less crouching than CC calves, fewer postural shifts, and more feeding behavior than LA-treated calves. In summary, FM alone tended to shorten the duration of cortisol response and reduce crouching after surgical castration. Combining LA+FM eliminated the cortisol response to castration but was associated with more leg lifting behavior. Treatment with LA alone did not mitigate the cortisol response and was associated with several behavioral differences compared with SC, FM-treated, or FM+LA-treated calves. Results suggest that LA alone did not effectively control discomfort in young dairy calves castrated using the Henderson castration tool.

Septic flexor tendonitis and suspensory desmitis in an alpaca.

CASE DESCRIPTION: A 2-year-old male Suri alpaca was referred for evaluation of severe right forelimb lameness of 2 weeks' duration following a traumatic episode. CLINICAL FINDINGS: Examination of the distal aspect of the metacarpus revealed 4 wounds exuding purulent material. On weight bearing, the metacarpophalangeal joint was severely hyperextended with the palmar surface touching the ground. Ultrasonography of the palmar surface of the metacarpus revealed desmitis of the proximal suspensory ligament, a large core lesion of the deep digital flexor tendon at mid-metacarpus, and complete loss of fiber pattern within the deep digital flexor tendon and lateral aspect of the superficial digital flexor tendon distally. TREATMENT AND OUTCOME: The alpaca was treated systemically with antimicrobials and anti-inflammatory drugs and underwent repeated antimicrobial intraosseous regional limb perfusion. A bandage and splint were applied to stabilize the affected forelimb in an anatomically correct position, and the alpaca underwent prolonged stall confinement. At the time of hospital discharge 5 days after initial evaluation, clinical evidence of infection at the wound sites was absent. Three months following treatment, the alpaca was moving freely in a small paddock and had moderate hyperextension of the metacarpophalangeal joint. CLINICAL RELEVANCE: Treatment of septic flexor tendonitis and suspensory desmitis with antimicrobial intraosseous regional limb perfusion in combination with systemic treatment with antimicrobials and orthopedic support resulted in an excellent outcome in this alpaca. Antimicrobial intraosseous regional limb perfusion is simple to perform and has the potential to be beneficial in the treatment of infections in the distal portion of a limb in camelids.

GABAergic regulation of auditory sensory gating in low- and high-anxiety rats submitted to a fear conditioning procedure.

The inferior colliculus (IC) is primarily involved in the processing of acoustic stimuli, being in a position to send auditory information to motor centers that participate in behaviors such as prey catching and predators' avoidance. The role of the central nucleus of the IC (CIC) on fear and anxiety has been suggested on the basis that rats are able to engage in tasks to decrease the aversiveness of CIC stimulation, increased Fos immunolabeling during diverse aversive states and increased CIC auditory evoked potentials (AEP) induced by conditioned fear stimuli. Additionally, it was shown that brainstem AEP, represented by wave V, for which the main generator is the IC, is increased during experimentally-induced anxiety. Rats segregated according to their low or high emotional reactivity have been used as an important tool in the study of fear and anxiety. The IC contains a high density of GABA receptors. Since the efficacy of an anxiolytic compound is a function of the animal's anxiety level, it is possible that GABA-benzodiazepine (Bzp) agents affect LA and HA animals differently. In this study we investigated the GABA-Bzp influence on the modulation of AEP in rats with low- (LA) or high-anxiety (HA) levels, as assessed by the elevated plus-maze test (EPM). GABA-Bzp modulation on the unconditioned AEP response was analyzed by using intra-CIC injections (0.2 µl) of the GABA-Bzp agonists muscimol (121 ng) and diazepam (30 µg), or the GABA inhibitors bicuculline (10 ng) and semicarbazide (7 µg). In a second experiment, we evaluate the effects of contextual aversive conditioning on AEP using foot-shocks as unconditioned stimuli. On the unconditioned fear paradigm GABA inhibition increased AEP in LA rats and decreases this measure in HA counterparts. Muscimol was effective in reducing AEP in both LA and HA rats. Contextual fear stimuli increased the magnitude of AEP. In spite of no effect obtained with diazepam in LA rats the drug inhibited AEP in HA animals. The specificity of the regulatory mechanisms mediated by GABA-Bzp for the ascending neurocircuits responsible for the acquisition of aversive information in LA and HA animals shed light on the processing of sensory information underlying the generation of defensive reactions.

Effects of enrofloxacin, flunixin meglumine and dexamethasone on disseminated intravascular coagulation, cytokine levels and adenosine deaminase activity in endotoxaemia in rats.

The aim of this study was to determine the effects of drugs used in the treatment of endotoxaemia on disseminated intravascular coagulation, cytokine levels and adenosine deaminase activities in endotoxaemic rats. Rats were divided into seven groups. Lipopolysaccharide (LPS) was injected into all groups, including the positive control group. The other six groups received the following drugs: enrofloxacin (ENR), flunixin meglumine (FM), low-dose dexamethasone (DEX), high-dose DEX, ENR + FM + low-dose DEX, and ENR + FM + high-dose DEX. After the treatments, serum and plasma samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 hours (h). A coagulometer was used to determine the levels of coagulation values, while ELISA was used to assay serum cytokines and adenosine deaminase (ADA). Low-dose DEX alone and combined treatments depressed the levels of cytokines and ADA (from 371 to 70 IU/L at 6 h) significantly and inhibited the decrease of coagulation values (antithrombin from 67 to 140% at 6 h, fibrinogen from 54 to 252 mg/dL at 6 h). In summary, FM + high-dose DEX may be the preferred treatment of endotoxaemia because of its highest effectiveness. FM plus high-dose DEX may be a new therapy for endotoxaemic domestic animals.

Effects of ring castration with local anesthesia and analgesia in Holstein calves at 3 months of age on welfare indicators.

Forty-seven Holstein calves (130 +/- 3.43 kg of BW and 95 +/- 1.5 d of age) were randomly assigned to 2 treatments [intact (INT), n = 23; or castrated (CAS), n = 24] to evaluate the effect of ring castration at 3 mo of age on welfare indicators. Castration was performed with local anesthesia (2% lidocaine, 3 mL in each testis and 2 mL in the scrotum) and analgesia (flunixin meglumine, intramuscularly, 3 mg/kg of BW). No local anesthesia or analgesia was used with INT calves. Serum cortisol concentration was determined at -120, 0, 30, 60, 90, and 180 min with respect to castration. At d 0, 1, 3, 7, 14, 21, 28, 35, 42, and 49, serum haptoglobin concentration was determined, rectal body and scrotal temperatures were measured, lesions at the castration site were scored, and the activity and behavior of 18 calves (9 INT and 9 CAS) were recorded continuously for 24 h. Weekly BW and concentrate and straw DMI were recorded. To evaluate humoral immunity, at 14 d after castration, ovalbumin was injected subcutaneously and serum antibody titers against ovalbumin before the injection and at d 35 were determined. At d 49 after castration, calves were intravenously injected with ACTH, and at 0, 1, 2, and 4 h thereafter, serum cortisol and testosterone concentrations were determined. Average daily gain was greater (P < 0.001) in INT than CAS calves (1.36 vs. 1.16 +/- 0.038 kg/d, respectively). Area under the curve of cortisol at castration day was reduced (P < 0.05) in CAS calves compared with INT calves (18 vs. 33 +/- 5.2 nmol/L per hour, respectively). The main scrotal lesion score observed in CAS calves throughout the study was 0, corresponding to no visible swelling, inflammation, or infection. However, scrotal lesion scores classified as 1 (swelling) were greater (P < 0.01) at 21 and 28 d after castration than at 1, 3, 7, and 14 d. Abnormal standing occurred more frequently (P < 0.001) in CAS than INT calves (2.6 vs. 0.5 +/- 0.03%, respectively) from 3 to 14 d after castration. Head turning tended (P = 0.06) to be greater at d 14 of the study in CAS than INT calves (3.0 vs. 2.6 +/- 0.04%, respectively). At d 49, 100% of CAS calves had no testes and no serum testosterone was detected. In summary, ring castration of Holstein calves performed at 3 mo of age with local anesthesia and analgesia decreased ADG and affected some behavioral traits during the first 14 d after castration. However, intake, serum cortisol and haptoglobin concentrations, rectal temperature, and humoral immunity were not altered.

Effects of drugs used in endotoxic shock on oxidative stress and organ damage markers.

The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

Effects of flunixin meglumine on pyrexia and bioenergetic variables in postparturient dairy cows.

Study objectives were to determine whether a nonsteroidal antiinflammatory drug would reduce parturition-induced inflammation and fever and consequently improve appetite, bioenergetic parameters, and production variables in transitioning dairy cows. Multiparous cows (n = 26) were randomly assigned to 1 of 2 treatments beginning at parturition: 1) flunixin meglumine (FM; 2.2 mg/kg of BW; Banamine, 50 mg/mL, Schering-Plough Animal Health, Kenilworth, NJ), or 2) saline (control) at 2.0 mL/45.5 kg of BW. All treatments were administrated i.v. daily for the first 3 d in milk (DIM). Individual milk yield and dry matter intake (DMI) were recorded daily for the first 35 DIM. Rectal temperature was measured daily at 0700 and 1600 h for the first 7 DIM. Milk composition was determined on 2, 7, 14, 21, 28, and 35 DIM and blood plasma was collected on 1, 2, 3, 4, 7, 14, 21, 28, and 35 DIM. Body weight and body condition score were determined on -7, 1, 7, 14, 21, 28, and 35 DIM. Flunixin meglumine treatment slightly increased rectal temperature (38.99 vs. 38.76 degrees C) during the first 7 DIM and reduced overall DMI (22.04 vs. 19.48 kg/d), but there were no treatment differences in overall milk yield (35.2 kg/d), 3.5% fat-corrected milk (37.6 kg/d), energy-corrected milk (37.7 kg/d), DMI (2.97% of BW), or overall energy balance (-2.32 Mcal/d). There were no treatment differences in milk fat (3.91%), protein (3.32%), or lactose (4.57%). Treatment had no effect on plasma glucose (66.5 mg/dL) or nonesterified fatty acids (553 microEq/L), but plasma urea nitrogen tended to be less in FM-treated cows (16.4 vs. 14.5 mg/dL). Daily FM administration to cows for the first 3 d after parturition slightly increased rectal temperatures by 0.23 degrees C, reduced feed intake, and did not improve production or energetic variables during the first 35 DIM in transition dairy cows.

Outcome of medical and surgical treatment of cecal impaction in horses: 114 cases (1994-2004).

OBJECTIVE: To determine short- and long-term outcomes, including recurrence rates, for horses with cecal impaction treated medically or surgically. DESIGN: Retrospective case series. ANIMALS: 114 horses. PROCEDURES: Medical records were reviewed for information on signalment, history, clinical findings, treatment (medical vs surgical), and short-term outcome. Information on longterm outcome was obtained through a mail survey and telephone interview with owners. RESULTS: 54 horses were treated medically, 49 horses were treated surgically, and 11 horses were euthanized after initial examination without further treatment. Horses treated surgically were significantly more likely to have signs of moderate or severe pain than were horses treated medically. Forty-four of the 54 (81%) horses treated medically were discharged from the hospital. Twelve of the 49 horses treated surgically were euthanized at surgery because of cecal rupture. Thirty-five of the 37 (95%) horses that were allowed to recover from surgery were discharged from the hospital. In 34 horses treated surgically, typhlotomy without a bypass procedure was performed. Long-term (>or= 1 year) follow-up information was available for 19 horses treated medically and 28 horses treated surgically. Eighteen (95%) and 25 (89%) of the horses, respectively, were alive at least 1 year after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that medical and surgical treatment were both associated with favorable outcomes in horses with cecal impactions. In this population, typhlotomy alone without cecal bypass was associated with a low recurrence rate. The long-term prognosis for horses that were discharged from the hospital was good.