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.

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 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.

Abdominal radiography in monitoring the resolution of sand accumulations from the large colon of horses treated medically.

This retrospective study consisted of 14 horses (age 6 weeks-12 years) with radiographically evident sand accumulations cranioventrally in the abdomen and clinical signs suggestive of sand enteropathy. The horses were treated medically and resolution of sand was monitored radiographically. Routine treatment consisted of psyllium mucilloid, combined with magnesium sulphate and/or mineral oilif needed. Initially, the number, size and shape of the sand accumulations showed large variation and the response to therapy was not predictable based on the initial appearance of the accumulation. In 2 foals, some of the sand was passed and the rest was mixed with other intestinal contents within 2-4 days. Even large accumulations disappeared in 2-4 days with psyllium alone or combined with mineral oil in 4 horses. In another 4 horses, the size of the accumulations decreased but varying amounts remained approximately at the same site, despite treatment for 1-4 weeks, and all these horses also had either gastric or large colon impaction. Three horses had a limited response to psyllium treatment, but the accumulation resolved with repeated doses of magnesium sulphate, with or without mineral oil. One horse did not respond to prolonged laxative treatment but the accumulation resolved on pasture. Clinical improvement was not necessarily related to the resolution of sand. Radiography of the cranioventral abdomen was found to be a useful means for monitoring the resolution of sand and confirming the effect of medical treatment in removing sand from the large colon in the horse.

Nutritional support for treatment of hepatic lipidosis in a llama.

A 3-year-old female llama that was 3 months into her first lactation and 10 weeks pregnant was evaluated for anorexia of 24 hours' duration. On physical examination, the llama was in lateral recumbency, bradycardic, tachypneic, and hyperthermic. Palpation per rectum confirmed the presence of a possible dry fecal mass in the spiral colon. A tissue biopsy specimen of the liver was obtained, and histologic examination revealed moderate diffuse lipid accumulation within the hepatocytes. Lactated Ringer's solution was administered for rehydration, and partial parenteral nutrition was then initiated. Hepatic lipidosis is a disease characterized by abnormal accumulation of lipid in the liver and is associated with high mortality in camelids. Anorexia associated with hepatic lipidosis promotes further lipid mobilization and fatty infiltration of the liver. Partial parenteral nutrition with enteral supplementation may be used to maintain adequate energy intake and minimize further lipid mobilization. The distinctive metabolism of camelids may require higher amino acid supplementation relative to nonprotein calories in parenteral solutions than those traditionally provided to other species. Treatment with insulin may be effective

Failure of dietary bentonite clay, Silent Herder mineral supplement, or parenteral Banamine to alleviate locoweed toxicosis in rats.

To evaluate treatments purportedly beneficial for livestock grazing locoweeds (LW), growing rats were fed diets containing 10 or 20% whole-plant Oxytropis sericea (LW) with and without Silent Herder mineral mix (1.5% of diet) or bentonite clay (1.5% of diet). Pregnant female rats fed 10% LW were treated i.m. with Banamine (a prostaglandins suppressor) or saline. The LW contained swainsonine (430 micrograms/g DM) and elicited toxicosis within 10 d at intake of 2 mg/kg BW. In Trial 1, 96 immature male Sprague-Dawley rats (BW approximately 100 g) were fed commercial rat feed (CRF) with and without LW, as follows: 100% CRF, free choice; 100% CRF, restricted intake to equal average intake of rats consuming 10 and 20% LW; 90% CRF+10% LW free choice; and 80% CRF+20% LW free choice. Diets with LW contained either no supplement or supplemental mineral mixture (Silent Herder, 1.5% of diet) or added bentonite clay (1.5% of diet). Twelve rats received each of eight dietary regimens through 28 d. Locoweed depressed (P < .05) feed intake and BW gain, increased (P < .05) relative size of liver, kidneys, heart, spleen, and testes, and altered blood serum components (P < .05) indicating toxicosis. Dietary provision of Silent Herder or bentonite failed to benefit rats that ingested approximately 4 or 8 mg of swainsonine/kg BW daily through 28 d. In Trial 2, 68 young adult female Sprague-Dawley rats (approximately 230 g BW) were mated and directly assigned to three diets (100% CRF, free choice, 100% CRF, intake restricted slightly below average intake of diet by rats consuming LW, or 90% CRF+10% LW free choice) and two treatments (i.m. saline or i.m. Banamine at .25 mg/kg BW daily for 10 d) in a 3 x 2 factorial arrangement. Approximately half (31 of 68) of the impregnated rats were killed at d 10, when Banamine was discontinued, but diets were continued until the remaining females gave birth. Ingested LW provided approximately 2 mg swainsonine/kg BW daily and elicited toxicosis in 10 d, but LW failed to affect numbers of live concepti at d 10 (P > .5) or numbers of offspring at parturition (P > .10). Banamine did not alleviate LW toxicosis of dams (P > .10). Provision of Silent Herder or bentonite in the diet or Banamine i.m. had no benefit for rats fed toxic locoweed.

Comparison of detomidine, butorphanol, flunixin meglumine and xylazine in clinical cases of equine colic.

Detomidine hydrochloride, butorphanol tartrate, flunixin meglumine and xylazine hydrochloride were evaluated in a blind multi-centre clinical trial in 152 horses with abdominal pain. The drugs were administered as follows: detomidine 20 or 40 micrograms/kg bodyweight (bwt); butorphanol 0.1 mg/kg bwt; flunixin meglumine 1.0 mg/kg bwt; xylazine hydrochloride 0.5 mg/kg bwt. Each centre compared responses to the two doses of detomidine with those to one of the other analgesics. The drugs were administered intravenously (i.v.) after clinical assessment of the degree of sweating, kicking, pawing, head and body movement, attitude, lip curling, stretching to urinate, pulse rate, respiratory rate and rectal temperature. Similar assessments were repeated at 15 min intervals for at least 1 h. The investigators ranked the response to treatment from 'not satisfactory' to 'highly satisfactory'. Significant differences in sweating, kicking, pawing, head and body movement, attitude, pulse rate and respiratory rate were noted between the horses receiving butorphanol and either dose of detomidine. The investigators' subjective evaluation of the analgesic and sedative effects of either dose of detomidine were significantly better than for butorphanol. Analgesia was rated as highly satisfactory or satisfactory in 93.3 per cent and 6.7 per cent of the horses receiving 40 micrograms/kg bwt of detomidine, 73.3 per cent and 26.7 per cent of the horses receiving 20 micrograms/kg bwt of detomidine, and none of the horses receiving butorphanol. There were no differences in the incidence of side effects with the two compounds. Significant differences were noted in kicking, pawing, head and body movement and attitude between the horses receiving flunixin meglumine and either dose of detomidine. Flunixin meglumine provided significantly less analgesia than either dose of detomidine. Analgesia was rated as highly satisfactory or satisfactory in 73.7 per cent and 21.0 per cent of the horses receiving 40 micrograms/kg bwt of detomidine, 42.9 per cent and 21.4 per cent of the horses receiving 20 micrograms/kg bwt of detomidine, and 6.3 per cent and 37.5 per cent of the horses receiving xylazine. Sedation was considered to be at least satisfactory in 84.2 per cent of the horses receiving 40 micrograms/kg of detomidine, 71.5 per cent of the horses receiving 20 micrograms/kg of detomidine and 53.3 per cent of the horses receiving xylazine.

Flunixin meglumine: a non-narcotic analgesic.

The N-methyl-d-glucamine salt of flunixin (flunixin meglumine) is a potent non-narcotic analgesic agent after parenteral administration in mice, rats and monkeys. It is significantly more potent than pentazocine, meperidine and codeine in the rat yeast paw test after subcutaneous administration in saline. Activity on intramuscular administration is comparable to that after subcutaneous administration and is enhanced when dissolved in buffered saline as compared to nonbuffered saline. In addition, flunixin meglumine also had oral activity and differs from indomethacin in having more analgesic activity per unit of anti-inflammatory activity. In mice, flunixin meglumine is equipotent to pentazocine and more potent than meperidine and codeine in the abdominal constriction test. In primates, flunixin meglumine at 10 mg/kg i.m., produced a degree of analgesic efficacy comparable to that of a clinically effective dose of morphine (0.3 mg/kg). In contrast to codeine, tolerance to the analgesic action of flunixin meglumine was not observed. Furthermore, flunixin meglumine retained its activity in rats made tolerant to codeine. Unlike narcotics, the analgesic effect of flunixin meglumine is not antagonized by naloxone after acute administration in rats. These results indicate that flunixin meglumine is a parenterally and orally effective analgesic in animals and is unlikely to have narcotic or drug dependence liability.