Dose-response relationship for the antipyretic effect of meloxicam in an endotoxin model in cats

The antipyretic efficacy of meloxicam was evaluated in a feline endotoxin model using a replicated change-over design. Twelve adult cats of both sexes were allocated at random to three experimental groups. At 30 min prior to the intravenous (i.v.) endotoxin challenge (0.5 µg/kg body weight(b.w.)), 2 animals in each group received an i.v. injection of 0.1, 0.3 or 0.5 mg meloxicam/kg b.w. and the two remaining animals in each group received physiological saline. In a second phase, 21 days later, the meloxicam/placebo treatment was exchanged within each group. The rectal temperature and scores for general demeanour were determined at 30-min intervals from before dosing to 300 min after the endotoxin challenge. Haematological parameters were analysed before and 60 min after administration of endotoxin. The results indicated a significant dose-dependent antipyretic response to meloxicam after endotoxin challenge. The antipyretic response in the medium- and high-dose meloxicam groups did not differ significantly, but both were significantly different from the low-dosage group. The individual effects of endotoxin on general demeanour were rather variable but meloxicam tended to have a beneficial effect. Endotoxin induced a reduction in the white blood cell count but this was not influenced by meloxicam. It was concluded that the pyretic endotoxin model is very suitable for studying new NSAIDs in cats and that the optimum single dose of meloxicam in this model was 0.3 mg/kg b.w.Abbreviations AUC area under the curve - b.w. body weight - i.v. intravenous - LPS lipopolysaccharide - MCV mean corpuscular volume - NSAID non-steroidal anti-inflammatory drug - WBC white blood cell count     

A comparison of the analgesic effects of butorphanol with those of meloxicam after elective ovariohysterectomy in dogs

This study was designed to compare the analgesic effects of butorphanol with those of meloxicam following ovariohysterectomy. Fifteen dogs were premedicated with 0.05 mg/kg body weight (BW) of acepromazine by intramuscular (IM) injection, plus 0.2 mg/kg BW of meloxicam by subcutaneous (SC) injection. Fifteen dogs were premedicated with 0.05 mg/kg BW of Acepromazine, IM, plus 0.2 mg/kg BW of butorphanol, IM. Anesthesia was induced with thiopental, and dogs were maintained on halothane. All pain measurements were performed by 1 experienced individual, blinded to treatment. Pain scores and visual analogue scales (VAS) were performed at 2, 3, 4, 6, 8, 12, and 24 hours postpremedication. An analgesiometer was used to determine the pressure required to produce an active avoidance response to pressure applied at the incision line. Pain scores, VAS, and analgesiometer scores were analyzed by using a generalized estimating equations method. A significance level of P < 0.05 was considered significant. Animals that received meloxicam demonstrated significantly lower pain scores and VAS than did animals that received butorphanol in the first 12 hours after surgery. Results of this study suggest that meloxicam will produce better postoperative analgesia than will butorphanol. Mucosal bleeding times were performed on cooperative animals in the study group (11 butorphanol, 13 meloxicam). Bleeding times were performed prior to premedication, 6 hours following premedication, and 24 hours after premedication. The 6- and 24-hour readings were compared with baseline bleeding times by using a paired t-test with a Bonferroni correction (a significance level of P < 0.025). Bleeding times did not change significantly over time.     

Clinical efficacy of meloxicam (Metacam) and flunixin (Finadyne) as adjuncts to antibacterial treatment of respiratory disease in fattening cattle

The clinical efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (Metacam 20 mg/ml) and flunixin meglumine (Finadyne), as adjuncts to antibacterial therapy in the treatment of acute febrile respiratory disease in cattle was compared. The randomised blind, positive controlled study was conducted under feedlot conditions in Mexico. Overall, 201 female cattle (weighing 220-250 kg) diagnosed with bronchopneumonia at the feedlot were recruited into the study. On Day 0 all animals were treated with 20 mg oxytetracycline/kg body-weight (Bivatop 200) by subcutaneous injection, in conjunction with either meloxicam (0.5 mg/kg subcutaneously, Metacam 20 mg/ml, n = 100), or flunixin meglumine (2.2 mg/kg intravenously, Finadyne, n = 101). According to label instructions, meloxicam was administered as a single dose, whereas flunixin meglumine could be administered daily for up to 3 consecutive days depending on the rectal temperature (with re-administration, if rectal temperature > or = 40.0 degrees C). Rectal temperature, respiratory rate, appetite, dyspnoea, coughing, nasal discharge and general condition were recorded on Days 0 (prior to treatment), 1, 2, 3 and 7 using a weighted numerical score. Scores were summed to generate a 'Clinical Sum Score' (CSS, range 7 to 24 points). Individual animal body weights were measured on Days 0 and 7. Nasal swabs were collected from 10 animals per treatment group on Day 0 for microbiological culture. Clinical parameters and the mean CSS showed no significant differences between treatment groups with mean CSS on Days 0 and 7 of 16.18 and 10.55 in the meloxicam group and 16.41 and 10.88 in the flunixin meglumine group. However, a significantly lower mean rectal temperature was measured in the meloxicam group on Day 2 (p < or = 0.01). No significant differences in mean body weights were found between groups. Repeated administration of flunixin meglumine was performed in 45% of the animals. No suspected adverse drug events related to treatments were reported. It is concluded that a single subcutaneous dose of meloxicam was as clinically effective as up to 3 consecutive daily intravenous doses of flunixin meglumine when used as an adjunctive therapy to antibacterial therapy in the treatment of acute febrile respiratory disease in feedlot cattle.     

The effects of subcutaneous injections of sodium selenate on blood composition and milk yield in dairy cows.

Three groups of four lactating cows received a subcutaneous injection of 0 . 05, 0 . 10 and 0 . 15 mg Se/kg body weighty respectively administered as sodium selenate. A fourth group was injected with saline. In all the cows injected with sodium selenate, the concentration of Se in blood increased rapidly and was significantly higher than in control cows for two days in the group receiving the lowest dose and for 182 days (the duration of the experiment) in the two other groups. The activity of glutathione peroxidase in blood increased slowly in all cows injected with sodium selenate and was significantly greater than in control cows after 15, 22 and 29 days respectively, and remained significantly greater for 63, 91 and 182 days respectively. In a second experiment a single subcutaneous injection of 0 . 15 mg Se/kg body weight had no effect on the mean milk yield of 37 animals (19 . 1 kg/day) compared with the milk yield of a similar group of control animals (19 . 1 kg/day) during 70 days. The concentration of Se in milk was significantly higher on the first (168 microgram/litre) and second (69 microgram/litre) day after injection than in control animals (mean 26 microgram/litre).     

Efficacy of tulathromycin in the treatment of respiratory disease in pigs caused by Actinobacillus pleuropneumoniae

The efficacy of a single dose of tulathromycin, a novel triamilide antimicrobial of the macrolide class, given at 2.5 mg/kg or 5 mg/kg bodyweight, or three daily doses of ceftiofur, given at 3 mg/kg bodyweight, was evaluated in pigs with respiratory disease induced experimentally with Actinobacillus pleuropneumoniae. On day 0, 100 pigs with clinical signs of respiratory disease were randomly assigned to groups of 25 pigs, which were treated with either saline, one of the doses of tulathromycin, or ceftiofur. The pigs' rectal temperatures and clinical scores for respiratory signs and general attitude were recorded daily until day 10. Animals withdrawn from the study for welfare reasons were recorded. On day 10, the animals remaining in the study were weighed, euthanased and examined postmortem. Three of the animals treated with saline and one of those treated with 2.5 mg/kg tulathromycin were withdrawn from the study, but none of those treated with 5 mg/kg tulathromycin or ceftiofur were withdrawn. The least squares mean bodyweight gains of the pigs treated with the antimicrobial agents were significantly (P<0.05) higher than that of the saline-treated group, and the least squares mean percentages of the total lung involvement and incidence of respiratory disease associated with A. pleuropneumoniae were significantly (P<0.05) lower, but there were no significant differences between the three groups of pigs treated with the antimicrobial agents.     

Effects of meloxicam on the haemostatic profile of dogs undergoing orthopaedic surgery

The buccal mucosal bleeding time (BMBT), prothrombin time (PT), activated partial thromboplastin time (APTT) and intraoperative bleeding score (IBS) of 38 dogs that underwent orthopaedic surgical procedures and received meloxicam orally and/or parenterally were measured. Fourteen of the dogs (group A) received a single subcutaneous dose of 0.2 mg/kg meloxicam at premedication, 18 dogs (group B) received 0.1 mg/kg meloxicam orally daily for five days followed by a single subcutaneous dose of 0.2 mg/kg meloxicam preoperatively, and six dogs (group C) received 0.5 ml of normal saline subcutaneously at premedication. No statistically significant differences among the groups were detected in relation to the mean (SD) values of BMBT, PT and IBS before and after the surgery, or in the values of APTT in group A. In group B there was a small but significant increase in APTT after the surgery, but all the measurements were within the normal range for dogs.     

Investigation on the clinical efficacy and safety of meloxicam (Metacam) in the treatment of non-infectious locomotor disorders in pigs

The clinical efficacy and safety of meloxicam (Metacam 20 mg/ml) in the treatment of non-infectious locomotor disorders in pigs was investigated in a randomised double-blind, placebo controlled, multi-centre field study. A total of 220 pigs were examined, 211 pigs were suitable for evaluation. Treatment was performed on Day 1 with meloxicam (0.4 mg meloxicam/kg) or placebo by intramuscular injection. If necessary, treatment was optionally repeated on Day 2. Clinical examinations were conducted daily from Day 1 (immediately prior to initiation of therapy) to Day 4. The primary parameter, mean "Clinical Lameness Score" (CLS, a sum of the scores of "Lameness at Rest" and "Lameness at Walk"; range 2 to 11) improved from 6.8 and 6.3 on Day 1, to 3.5 and 4.7 on Day 4 in the meloxicam and placebo groups respectively (p < 0.001). At the final examination mean changes from baseline for CLS (Day 1) were 3.25 for meloxicam treated animals and 1.7 for placebo treated animals (p < 0.001). Behaviour score and feed intake improved during the study period with statistically significant differences in favour of meloxicam at all time points after initiation of therapy. Significantly fewer pigs received a second treatment in the meloxicam group than in the placebo group, 46% versus 73% (p < 0.001). A 'very good' or 'good' clinical efficacy assessment was recorded in 83% of the meloxicam cases compared to 42% of the placebo controls at the final examination (p < 0.001). No adverse events were reported due to the use of meloxicam. Furthermore safety of meloxicam in pregnant sows was demonstrated. It is concluded that intramuscular injection of meloxicam (Metacam) at a dosage of 0.4 mg/kg is efficacious and safe for the treatment of non-infectious locomotor disorders in pigs.     

Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs

OBJECTIVE: To compare preoperative administration of meloxicam and butorphanol to perioperative administration of butorphanol alone for control of postoperative signs of pain in dogs. ANIMALS: 40 client-owned dogs scheduled for surgical repair of a cranial cruciate ligament rupture. PROCEDURE: Group-1 dogs received butorphanol (0.2 mg/kg, IV) and meloxicam (0.2 mg/kg, IV) just prior to surgery. Group-2 dogs received butorphanol just prior to surgery (0.2 mg/kg, IV) and at incision closure (0.1 mg/kg, IV). Pain assessment began 1 to 2 hours before surgery and from extubation until 24 hours after surgery by obtaining the following measurements: the visual analog scale (VAS) score, cumulative pain score (CPS), adjusted cumulative pain score, modified cumulative pain score, and the adjusted modified cumulative pain score (AMCPS). Serum cortisol concentration was measured between 12 to 24 and between 1 to 2 hours prior to surgery, and at 30 minutes, and 1, 2, 4, 8, 18, and 24 hours after extubation. RESULTS: No significant differences between treatment groups were observed in CPS or VAS score. At 8, 9, 10, and 11 hours after extubation, meloxicam-butorphanol-treated dogs had a significantly lower AMCPS, compared with butorphanol-alone-treated dogs. Total serum cortisol concentration (area under the curve) during the measurement period was significantly lower in meloxicam-butorphanol-treated dogs, compared with butorphanol-alone treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative single dose administration of meloxicam-butorphanol is equivalent to or slightly better than the administration of 2 perioperative doses of butorphanol for the control of postoperative signs of pain in dogs.     

Demonstration of the metaphylactic use of gamithromycin against bacterial pathogens associated with bovine respiratory disease in a multicentre farm trial

On five commercial cattle rearing sites across Europe, a total of 802 young cattle at high risk of developing bovine respiratory disease (BRD) associated with the bacterial pathogens Mannheimia haemolytica or Pasteurella multocida and/or Mycoplasma bovis were enrolled into a multicentre, controlled field trial. Half were treated with a single dose of gamithromycin at 6 mg/kg bodyweight by subcutaneous injection and half received an injection of a saline placebo as the control. All animals were observed daily for 14 days for signs of BRD as defined by set criteria. The proportion of metaphylactic preventive treatment successes, defined as animals surviving to day 14 without signs of BRD, in the gamithromycin-treated group (86 per cent) was significantly (P=0.0012) higher than in the saline-treated controls (61 per cent). Morbidity among the treated animals was reduced by 64 per cent compared with the controls.     

Efficacy of ivermectin against inhibited larvae of Ostertagia ostertagi

The efficacy of ivermectin against inhibited early 4th-stage larvae of ostertagia ostertagi and other nematodes of the abomasum and intestinal tract was determined in naturally infected yearling beef cattle. The time when large numbers of inhibited larvae were acquired was determined by monthly slaughter of monitor cattle, beginning in January. In April, 12 animals were removed from pasture and maintained free of further helminth exposure until slaughter (21 days). At 9 days after the cattle were removed from pasture, ivermectin was administered to the principals by subcutaneous injection (200 micrograms/kg); the other 6 animals were given subcutaneous injections of the ivermectin vehicle. both groups were klled and necropsied at 12 days after treatment. Mean numbers of O ostertagi in the 6 controls were: adults, 41,906; developing 4th stage, 73,813; and early 4th stage, 334,965. The mean proportion of early 4th-stage larvae was 73.7%. In the 6 principals (treated with ivermectin), the following reductions were observed: O ostertagi adults, 100%; developing 4th stage, 99.8%; and early 4th stage, 99,9%. Small numbers of dead and degenerated O ostertagi of all developmental stages were recovered from abomasal washings before fixation; few viable worms were recovered.     

Comparison of oral and subcutaneous administration of buprenorphine and meloxicam for preemptive analgesia in cats undergoing ovariohysterectomy

OBJECTIVE: To compare the effectiveness of preoperative PO and SC administration of buprenorphine and meloxicam for prevention of postoperative pain-associated behaviors in cats undergoing ovariohysterectomy. DESIGN: Randomized controlled study. ANIMALS: 51 female cats (4 to 60 months old; weight range, 1.41 to 4.73 kg [3.1 to 10.4 lb]). PROCEDURE: Cats received 1 of 5 treatments at the time of anesthetic induction: buprenorphine PO (0.01 mg/kg [0.0045 mg/lb]; n = 10), buprenorphine SC (0.01 mg/kg; 10), meloxicam SC (0.3 mg/kg 10.14 mg/lb]; 10), meloxicam PO (0.3 mg/kg; 10), or 0.3 mL of sterile saline (0.9% NaCI) solution SC (control group; 11). Sedation scores and visual analog scale and interactive visual analog scale (IVAS) pain-associated behavior scores were assigned to each cat 2 hours before and at intervals until 20 hours after surgery. RESULTS: Cats receiving meloxicam PO or SC had significantly lower IVAS scores (2.91 and 2.02, respectively), compared with IVAS scores for cats receiving buprenorphine PO (755). Pain-associated behavior scores for cats administered buprenorphine or meloxicam PO or SC preoperatively did not differ significantly from control group scores. Rescue analgesia was not required by any of the cats receiving meloxicam, whereas 3 of 10 cats receiving buprenorphine PO, 2 of 10 cats receiving buprenorphine SC, and 1 of 11 cats receiving the control treatment required rescue analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of pain-associated behavior scores, cats receiving meloxicam PO or SC before ovariohysterectomy appeared to have less pain after surgery than those receiving buprenorphine PO preoperatively.     

Effects of meloxicam on severity of lameness and other clinical signs of osteoarthritis in dogs

OBJECTIVE: To evaluate effects of meloxicam on severity of lameness and other clinical signs in dogs with osteoarthritis (OA). DESIGN: Randomized, controlled, multicenter clinical trial. ANIMALS: 217 client-owned dogs with clinical and radiographic signs of OA. PROCEDURE: Dogs were randomly assigned to be treated with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1 mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general clinical score was assigned by investigators on days 1 (ie, prior to initiation of treatment), 8, and 15 on the basis of severity of lameness, extent of weight bearing, and severity of signs during palpation of the affected joint. Owners and investigators provided overall evaluations on days 8 and 15. RESULTS: Dogs treated with meloxicam had significantly greater improvements in general clinical scores, compared with baseline scores, on days 8 and 15 than did dogs treated with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in which owners and investigators considered treatment to be successful were significantly higher than percentages of control dogs in which treatment was considered to be successful. No abnormalities in hematologic and serum biochemical test results were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that compared with administration of a placebo, administration of meloxicam for 14 days significantly improved the clinical condition of dogs with OA without causing adverse effects.     

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.     

Influence of rearing conditions and respiratory disease on haptoglobin levels in the pig at slaughter

Associations between serum concentrations of haptoglobin, pathological lung lesions indicative of Mycoplasma hyopneumoniae (EP) or Actinobacillus pleuropneumoniae (PL) infection at slaughter and previous rearing environment were investigated in 510 pigs (90-100 kg live weight) from 17 farms in England. Haptoglobin concentrations were significantly higher in pigs showing pathological signs of EP infection compared to those without signs of this disease (EP positive median 0.43 mg ml(-1) vs. EP negative median 0.26 mg ml(-1), p<0.01). However, there were no significant associations between serum haptoglobin concentrations and pathological signs of PL. The presence of solid partitions compared with barred or similar open partitions was associated with a decrease of 0.44 mg ml(-1) farm mean haptoglobin concentration, whilst an increase in pen size of 10 m(2) was associated with a decrease of 0.08 mg ml(-1) farm mean haptoglobin concentration. The findings indicate that pathological signs of EP were associated with increased serum haptoglobin at slaughter, which in turn was influenced by components of the farm environment.     

Clinical efficacy of flunixin,carprofen and ketoprofen as adjuncts to the antibacterial treatment of bovine respiratory disease

Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease. Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea. They were allocated randomly to four treatment groups. All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection). During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen. There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing. There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin.     

Comparison of carprofen and meloxicam for 72 hours following ovariohysterectomy in dogs

OBJECTIVE: To compare the peri- and post-operative (72 hours) analgesic effects of injectable and orally administered carprofen and meloxicam for ovariohysterectomy in dogs. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-three dogs undergoing elective ovariohysterectomy. MATERIALS AND METHODS: Dogs were randomly assigned to receive pre-operative carprofen, meloxicam or sterile saline by subcutaneous injection. Pre-anaesthetic medication was intramuscular acepromazine (0.02 mg kg(-1)) and methadone (0.2 mg kg(-1)). Anaesthesia was induced with either thiopentone or propofol injected to effect, and maintained with isoflurane in oxygen. Visual analogue scores (VAS) for pain and sedation were recorded at 1, 2, 3, 4 and 6 hours following tracheal extubation. Oral medication with the same treatment was continued post-operatively for 3 days, with VAS scores for pain being recorded before, and 2 hours after treatment on each day. Differences between group age, body mass, duration of general anaesthesia, time from treatment injection to tracheal extubation and time from treatment injection to first oral treatment were analysed using one-way analysis of variance and Kruskal-Wallis test. Visual analogue scores for pain and sedation were analysed using a re-randomization method. The significance level was set at p < 0.05. RESULTS: Meloxicam-treated subjects had lower mean VAS than the control group at 2 and 6 hours following tracheal extubation. Control group VAS were more varied than meloxicam scores (at 6 hours) and carprofen scores (at 3 and 6 hours). On the first post-operative day, pre- to post-treatment VAS scores decreased significantly after meloxicam. On day 3, scores in the meloxicam-treated group were significantly lower than control values after treatment. Changes in pre- to post-treatment VAS were greater in animals receiving either meloxicam or carprofen compared with those given saline. CONCLUSIONS AND CLINICAL RELEVANCE: Both carprofen and meloxicam provided satisfactory analgesia for 72 hours following ovariohysterectomy in dogs.     

Effects of meloxicam on reproduction parameters in dairy cattle

This study was carried out in dairy cattle with the NSAID meloxicam to investigate possible drug effects on different reproductive parameters as well as on the progeny. Forty-one cows received intravenous injection of either meloxicam (Metacam^® 20 mg/mL solution for injection) or placebo at a dose volume of 7.5 mL/100 kg, corresponding to a dose of 1.5 mg meloxicam/kg, i.e. three times the recommended therapeutic dose. Treatment was performed in each phase of reproduction, i.e. once prior to breeding, twice shortly after breeding, once at the beginning of the second and third trimester of gestation and once at the end of the third trimester of gestation. Offspring of the cows were weighed and clinically examined for vitality at birth and after 28 days. No relevant difference between the meloxicam and control group was found in the reproductive performance of the cows or in the body weight development or vitality of the calves.     

Treatment of experimentally induced pneumonic pasteurellosis of young calves with tilmicosin.

Twenty four (24) healthy male Holstein calves (< 70 kg) were each experimentally infected by intrabronchial inoculation of 4.0 x 10(9) viable cells of Pasteurella haemolytica-AI (B122) at Time = 0 h. At 1 h following inoculation animals received either: 1) Sham treatment with sterile 0.85% saline SC (n = 12); or 2) a single injection of 10 mg tilmicosin per kg body weight (n = 12). Calves that were non-infected and tilmicosin-treated were also included for determining tilmicosin concentrations in serum and lung tissue at 1, 2, 4, 6, 8, 24, 48, and 72 h (n = 3-per time). In the infected calves, response to therapy was monitored clinically. Serum samples were collected for determination of tilmicosin concentrations using HPLC. Any animal becoming seriously ill was humanely killed. Complete necropsy examinations were performed on all animals and included gross pathologic changes, bacteriologic analysis, histopathology, and determination of pulmonary concentrations of tilmicosin. Tilmicosin treated animals responded significantly better to therapy than saline-treated control calves. Clinical assessment of calves during the study indicated that tilmicosin-treated calves had significantly improved by T = 8 h compared to satine-treated animals (P < 0.05). At necropsy tilmicosin-treated calves had significantly less severe gross and histological lesions (P < 0.05) of the pulmonary tissue. Of the 12 saline-treated calves, 92% (11/12) had Pasteurella haemolytica-A1 in lung tissue, while of the tilmicosin-treated calves 0% (0/12) cultured positive for P. haemolytica. Mean (+/- standard error) serum tilmicosin concentrations in infected calves peaked at 1 h post-injection (1.10 +/- 0.06 micrograms/mL) and rapidly decreased to 0.20 +/- 0.03 microgram/mL, well below the MIC of 0.50 microgram/mL for P. haemolytica-A1 (B122), by 12 h. These serum concentrations were very similar to serum concentrations of tilmicosin in non-infected tilmicosin-treated calves. Lung tissue concentrations of the antibiotic were comparatively high, even at 72 h post-infection (6.50 +/- 0.75 ppm). Lung tissue concentrations at 72 h were significantly higher in experimentally infected calves than in non-infected tilmicosin-treated animals (P < 0.05). These data demonstrate that tilmicosin was effective in treating experimentally-induced pneumonic pasteurellosis as determined by alleviation of clinical signs, pathological findings at post mortem, and presence of viable bacteria from the lung. Concentrations substantially above MIC for P. haemolytica were present in lung tissue even at 72 h following a single subcutaneous injection of 10 mg tilmicosin per kg body weight.     

Development of a lameness model in sheep for assessing efficacy of analgesics

Objective To develop a lameness model to assess the efficacy of analgesics for alleviating pain, swelling and systemic signs of inflammation in sheep. Procedures The response to subcutaneous injection of 0.1 or 0.2 mL turpentine in a forelimb pastern (n = 4 ewes per dose) was examined at 0, 3, 6, 24, 48 and 72 h. In a second experiment, responses were measured at 0, 2, 4, 6, 8, 10, 12 and 24 h in ewes receiving 0.1 mL turpentine ± meloxicam 1 mg/kg IV at 0 h (n = 6 per group). Responses measured included forceplate pressure, skin temperature, limb circumference, nociception, leucocyte count, neutrophil : lymphocyte ratio, haptoglobin and daily feed intake. Results Turpentine injection caused a decrease in weight borne on the treated limb, increased skin temperature, increased sensitivity at the injection site and leucocytosis by 2 h and increased limb circumference by 4 h. Weight borne and sensitivity of the injected limb returned to control levels after around 24 h, whereas tissue swelling, elevated skin temperature and elevated haptoglobin levels persisted for at least 72 h. Treatment with meloxicam improved weight borne by and tolerance to pressure exerted on the turpentine‐injected limb. Conclusions The local and systemic signs of inflammation and pain, temporary reduction in function of the affected limb and partial amelioration of some of these changes by the dose of meloxicam used here suggest that injection of turpentine in the lower forelimb provides a suitable model for examining the efficacy of analgesics for alleviation of pain and inflammation in sheep.     

High doses of methylprednisolone are required for the treatment of collagenase-induced intracerebral hemorrhage in rats

Methylprednisolone (MP) was evaluated for the treatment of intracerebral hemorrhage in a Sprague-Dawley rat model of cerebral hematoma induced by subcortical injection of collagenase. At 1 and 24 h after the injection, MP was administered intraperitoneally (IP) at a concentration of 10, 35, or 100 mg/kg. Control groups received saline IP at 1 and 24 h after the intracerebral injection of collagenase (positive controls) or saline (negative controls). Motor behaviour 24 h before and 24 h and 48 h after the intracerebral injection was evaluated by means of a neurologic exam and a rotarod treadmill test. The animals were euthanized at 48 h; brain water content was determined in half of the rats, and histopathological studies were done in the other half. Compared with the positive controls, the animals with collagenase-induced hematoma performed significantly better on the neurologic exam after treatment with 100 mg/kg of MP and on the rotarod test after treatment with 35 or 100 mg/kg of MP. The hematoma volume was significantly smaller (P < 0.002) after all doses of MP; however, the smallest volume was seen with 100 mg/kg. There were significantly fewer neutrophils (P < 0.01) within the hematoma in the MP-treated animals (maximum reduction with 100 mg/kg) than in the positive controls, but the numbers of reactive astrocytes did not differ significantly between the treatment groups. The number of necrotic neurons in the penumbra did not differ between the treatment groups; however, there were significantly fewer (P < 0.005) in the cerebral cortex in the group treated with 100 mg/kg of MP compared with the positive controls. These results suggest that high doses of MP administered shortly after occurrence of a cerebral hematoma are beneficial for the treatment of intracerebral hemorrhage.