In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

INADVERTENT INTRATHECAL ADMINISTRATION OF DIATRIZOATE MEGLUMINE AND DIATRIZOATE SODIUM DURING MYELOGRAPHY IN A DOG

A dog undergoing diagnostic myelography inadvertently received 0.5 ml diatrizoate meglumine (66%) and (10%) diatrizoate sodium via intrathecal injection. This resulted in post-operative seizures requiring extended sedation of the patient. The clinical course and management of this patient are presented. Complications associated with the inappropriate administration of a hyperosmolar contrast agent into the subarachnoid space and the results of similar accidents in humans are also discussed. The dog in the report recovered with no evidence of long trem neurological dam     

A Leopard Seal from Hout Bay,South Africa

The catch per unit effort of Oreochromis mossambicus, Clarias gariepinus and Cyprinus carpio at different localities at Hartbeespoort Dam was investigated. Catches of the three species were between three and ten times higher on the southern shore of the lake than on the northern shore. The gradient of each locality was found to be the most important variable determining catch. Gill-net catches of O. mossambicus from littoral and limnetic stations indicated equal abundance of the species in these two habitats. The implications of the results for improved predictions of fish yield from lakes, and for management are discussed.     

Stalked Barnacles Conchoderma Auritum on an Elephant Seal: Occurrence of Elephant Seals on South African Coast

For most of the year, Meyer’s parrots in the Okavango Delta do not form large feeding flocks, and groups larger than two or three are probably the result of opportunistic aggregation at favoured food items after dispersion from communal roosts. Communal roosting likely does not facilitate flocking unless the food resources are close to the roost site, but may function in anti-predator defence. Meyer’s parrots appear to be dependent on riverine forest, Acacia-Combretum marginal woodland and mopane woodland for roost sites in the Okavango Delta. They aggregated more during the breeding season due to their specialist nutritional requirements, and female dependence on food provisioning by the male parrots. Meyer’s parrots may be sedentary in the Okavango Delta, but the possibility of limited local movements in other areas (especially the Zimbabwean highlands) should be investigated.     

Pharmacokinetic studies of levofloxacin after oral administration in healthy and febrile cow calves

The present experiment was designed to study the pharmacokinetics of levofloxacin in six healthy cross bred female cow calves (4 to 6 months age) weighing between 40 to 80 kg. Plasma from blood was separated by centrifugation at 10,000 rpm. Quantitative estimation of levofloxacin was done by UV-VIS spectrophotometer at 286 nm. The mean maximum plasma concentration (Cp_max ) of levofloxacin in febrile calves (5.28?±?0.32 µg/ml) did not differ significantly as compared with healthy calves (4.50?±?0.22 µg/ml) after single dose (20 mg/kg) oral administration. The mean therapeutic plasma concentration ( Cp_ther ) of levofloxacin was maintained for longer period in febrile calves (10 h) as compared to healthy calves ( 8 h). The mean maximum urine concentration (Cu_max) in febrile (40.86?±?2.19 µg/ml) also did not differ significantly as compared with healthy calves (39.38?±?2.43 µg/ml). No significant difference in various pharmacokinetic parameters of plasma was observed in healthy calves ( β?=?0.23?±?0.01/h ; t1/2 β?=?3.00?±?0.17 h and MRT?=?4.66?±?0.14 h ) and febrile calves ( β?=?0.23?±?0.01/ h; t1/2 β?=?3.05?±?0.16 h and MRT?=?5.04?±?0.14 h ) . The mean value of β, and t ½ β calculated in urine also did not differ between healthy and febrile calves. However, the value of MRT(3.79?±?0.07 h) and Cl_B(1.65?±?0.09 ml/kg/min) calculated in urine of febrile calves significantly(p?B?=?2.09?±?0.13 ml/kg/min). Based on kinetic profile levofloxacin may be given orally at the dose rate of 1.49 mg/kg B.W.at 8 h intervals in febrile calves.     

Comparison of two doses of recombinant human bone morphogenetic protein in absorbable collagen sponges for bone healing in dogs

OBJECTIVE: To determine the effects of 2 doses of recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge (rhBMP-2/ACS) on bone healing in dogs. ANIMALS: 27 adult dogs. PROCEDURES: Dogs underwent a mid-diaphyseal (1-mm) tibial osteotomy (stabilized with external skeletal fixation) and received an ACS containing 0.28 mg (0.2 mg/mL) or 0.56 mg (0.4 mg/mL) of rhBMP-2 or no treatment (control dogs). All dogs were examined daily; bone healing was assessed via radiography and subjective lameness evaluation every 2 weeks. After euthanasia at 8 weeks, tibiae were evaluated biomechanically and histologically. RESULTS: Control dogs required antimicrobial treatment for pin-site-related complications more frequently than did rhBMP-2/ACS-treated dogs. At 4 and 6 weeks, weight bearing was greater in dogs treated with rhBMP-2/ACS (0.2 mg/mL) than in control dogs, albeit not significantly. Compared with control treatment, both doses of rhBMP-2/ACS accelerated osteotomy healing at 4, 6, and 8 weeks, and the 0.2 mg/mL dose enhanced healing at 2 weeks; healing at 6 weeks was greater for the lower-dose treatment than for the higher-dose treatment. Histologically, healing at 8 weeks was significantly improved for both rhBMP-2/ACS treatments, compared with control treatment. Among groups, biomechanical variables did not differ, although less osteotomy-site failures occurred in rhBMP-2/ACS-treated groups. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs that underwent tibial osteotomy, rhBMP-2/ACS (0.2 mg/mL) appeared to accelerate bone healing and reduce lameness (compared with control treatment) and apparently augmented bone healing more than rhBMP-2/ACS (0.4 mg/mL). Compared with control dogs, rhBMP-2/ACS-treated dogs required antimicrobial treatments less frequently.     

Poisoning in ostriches following ingestion of toxic plants - field observations

Data from post-mortem and field studies were obtained that discussed poisoning in ostriches following ingestion of toxic plants. From the notes, all plants studied caused death in ostriches and there was systemic organ damage. Poisoning from Sarcostemma viminale (Melktou) resulted in beak patting, muscular tremors and head flopping, followed by collapse and violent kicking before death. Ingestion of Combretum oatesii (Red wings) seeds from plants in free grazing pastures resulted in vomiting, restlessness, eyelid flicking, collapse and kicking movements. Dichapetalum cymosum (Gifblaar) killed an ostrich after episodes of shaking legs, rapid respiration and bradycardia and hyperaemia of the lungs, liver and kidneys. Poisoning from Senecio sceleratus (Ragwort) caused skin haemorrhages and bleeding in tracheal mucous membranes, the pericardium, diaphragm and interperitoneal membrane. Consumption of drupes from Melia azedarach (Syringa berry) caused muscle tremors, kicking movements and respiratory distress. Lantana camara (Cherry pie) poisoning resulted in extremely inflamed eyes with copious yellow exudates extending down their beaks and onto their necks. Bentonite was administered by gavage at a dose of 5 g/kg. Poisoning in these cases is usually associated with the farmer allowing his/her birds to roam free-range in paddocks in which toxic plants are growing. Toxic plants should be removed from grass cut for hay. The author is willing to send photographs of all poisonous plants if requested by a reader.     

Assessment of antibiotic use in farm animals in Rwanda

The irrational use of antibiotics in humans and animals is highly related to the emergence and increase of antibiotic-resistant bacteria worldwide. A cross-sectional survey aimed at evaluating the current level of practices regarding antibiotic use in farm animals in Rwanda was carried out countrywide. Interviews were conducted on 229 farmers rearing different types of animals. The study has revealed that almost all respondent farmers could name at least one antibiotic used in farm animals and peni-streptomycin was named by most of them (95.6%). The use of antibiotics in farm animals was observed in the majority of respondents (97.4%). It was found that 44.4 and 26.5% of respondents reported that they used antibiotics for disease prevention and growth promotion, respectively. The use of non-prescribed antibiotics in animals was also reported by more than the half of respondent farmers (55.6%). The majority of farmers had a moderate level of practices regarding antibiotic use in farm animals (73.5%), very few had a high level (26%) and only one respondent had a low level. The high level of practices in regard to antibiotic use in animals was associated with the location of the farm, the type of reared animals, and the rearing system. The results of this study give an insight into antibiotics usage practices in farm animals in Rwanda. The generated information can guide sensitizations and promotions of the prudent use of antibiotics among farmers in order to limit the increase of antibiotic resistance in the country.     

Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses

OBJECTIVES: To measure serum polymyxin B concentration after single and repeated IV infusions in horses. ANIMALS: 5 healthy horses. PROCEDURES: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. RESULTS: In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and 1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. CONCLUSIONS AND CLINICAL RELEVANCE: Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.     

Determinants and Utility of the Anion Gap in Predicting Hyperlactatemia in Cattle

The objectives of this study were to investigate the determinants of the anion gap (AG) in cattle and to evaluate the utility of AG in detecting hyperlactatemia in sick neonatal calves and adult cattle. The AG was calculated as AG = ([Na+] + [K+]) - ([Cl^-] + [HCO₃]), with all values in mEq/L. The AG of healthy neonatal calves (n = 16) was 29.6 ± 6.2 mEq/L (mean ± SD), and the blood L-lactate concentration ranged from 0.5 to 1.2 mM/L. The AG was significantly (P > .05) correlated with serum phosphate (r = .66) and creatinine (r = .51) concentrations. The AG of neonatal calves with experimentally induced diarrhea (n = 16) was 28.6 ± 5.6 mEq/L, and the blood L-lactate concentration ranged from 1.1 to 2.9 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .67), serum phosphate concentration (r = .63), creatinine concentration (r = .76), and blood pH (r = -.61). The AG of adult cattle with abomasal volvulus (n = 41) was 20.5 ± 7.8 mEq/L, and the blood L-lactate concentration ranged from 0.6 to 15.6 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .60), serum phosphate concentration (r = .71), creatinine concentration (r = .65), albumin concentration (r = .47), total protein concentration (r = .54), blood pyruvate concentration (r = .67), and blood pH (r = -.41) but not plasma β-OH butyrate concentration. The results indicate that the AG in cattle is only moderately correlated with blood L-lactate concentration and is similarly correlated with serum phosphate and creatinine concentrations in neonatal calves and adult cattle, as well as with serum albumin and total protein concentrations in adult cattle. Anion gap determination is of limited usefulness in predicting blood L-lactate concentration in sick cattle, whereas the correlation between AG and serum creatinine concentration in sick cattle suggests that an increased AG should alert the clinician to the potential presence of uremic anions.