Barbiturate ingestion in three adult captive tigers (Panthera tigris) and concomitant fatal botulism of one.

Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay neutralisation test, confirming that this male had had concomitant barbiturate toxicity and botulism, and had succumbed to aspiration bronchopneumonia secondary to pharyngeal, laryngeal and oesophageal paralysis and oesophageal

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism.

In a safety study, Cape Griffon vultures (Gyps coprotheres) were dosed with ketoprofen at single doses of ~1 mg/kg (n = 5) and 5 mg/kg (n = 11). No toxicity was reported in the 1 mg/kg group, with the AUC(inf), V(z) and Cl being 10.42 µg/ml h, 0.37 l/kg and 0.10 l/h kg, respectively. Toxicity occurred in the 5 mg/kg group, with 7 of the 11 birds dying. Clinical signs of toxicity included depression, loss of appetite and apparent coma. Animals died within 48 h of dosing. The AUC(inf), V(z) and Cl in the birds that survived were 52.26 µg/ml h, 0.45 l/kg and 0.10 l/h kg, respectively. The AUC(inf), V(z) and Cl in the birds those died were 207.90 µg/ml h, 0.26 l/kg and 0.02 l/h kg, respectively. Based on the increase in the AUC(inf) and C(max) in the birds that died, we surmise that toxicity resulted from saturation of the metabolic process. While the exact metabolic pathway remains unknown in these vultures, we believe that toxicity may be due to pharmacogenomic differences in the cytochrome P450 pathway.

Chapter 5 - Detection of antimycolic acid antibodies by liposomal biosensors.

Antibodies to mycolic acid (MA) antigens can be detected as surrogate markers of active tuberculosis (TB) with evanescent field biosensors where the lipid antigens are encapsulated in liposomes. Standard immunoassay such as ELISA, where the lipid antigen is not encapsulated, but directly adsorbed to the well-bottoms of microtiter plates, does not yield the required sensitivity and specificity for accurate diagnosis of TB. One reason for this is the cross-reactivity of natural anticholesterol antibodies with MAs. MAs are the major cell wall lipids of mycobacteria. Mycobacterial MA has immunomodulatory properties and elicits specific antibodies in TB patients. Liposomes were optimized for their use as carriers both for the presentation of immobilized purified mycobacterial MA on sensor surfaces, and as a soluble inhibitor of antibody binding in inhibition assays. By using an inhibition assay in the biosensor, the interference by anticholesterol antibodies is reduced. Here, we describe the MA carrying capacity of liposomes with and without cholesterol as a stabilizing agent, optimized concentration and size of liposomes for use in the biosensor assay, comparison of the methods for wave-guide and surface plasmon resonance biosensors and how the cholesteroid nature of MA can be demonstrated by the biosensor when Amphotericin B is allowed to bind to MA in liposomes.

Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge.

BACKGROUND: Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma. OBJECTIVES: This pilot study examined the effect of roflumilast on allergen-induced airway hyperresponsiveness (AHR) to histamine challenge and asthmatic response to allergen challenge. METHODS: In a randomized, double-blind, 2-period, crossover trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1 s (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1)

Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy.

In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group), receiving a once-off carprofen 4 mg/kg injection (Carprofen group) or receiving both morphine and carprofen (MorphCarp group). The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.

Effect of Lactobacillus acidophilus supplementation of milk replacer on preweaning performance of calves.

Forty Holstein-Friesian calves were used to evaluate the effect on young calves of daily dietary supplementation with Lactobacillus acidophilus. Calves were randomly assigned at 2 d of age to one of two treatments; 1) milk replacer with no additives or 2) milk replacer supplemented with 1 ml (5 x 10(7)) of viable L. acidophilus bacteria at each of two feedings per day. Milk replacer was reconstituted to 12% DM and fed at 10% of BW/d for the duration of the 6-wk trial. A commercial starter pellet was offered for ad libitum intake from 7 d of age. Treatment had no effect on actual BW at any stage or on total BW gain; however, average daily gain during wk 2 was affected by L. acidophilus supplementation. Calves receiving L. acidophilus maintained initial BW, and the control calves lost BW until 2 wk of age, at an average rate of 112 g/d. Starter intake, total DMI, feed efficiency, and occurrence of diarrhea were unaffected by treatment. Therefore, L. acidophilus supplementation for calves fed milk replacer may be beneficial during the first 2 wk of life.

The in vitro activity of amoxycillin with clavulanic acid against clinically significant bacteria. A multicentre study.

A multicentre study to evaluate the activity of amoxycillin when combined with clavulanic acid against clinical bacterial isolates was performed in South Africa. Minimum inhibitory concentrations for amoxycillin alone and in combination with clavulanic acid were determined by agar dilution. The majority of amoxycillin-resistant Klebsiella and Escherichia coli strains became sensitive to amoxycillin in the presence of low concentrations of clavulanic acid. Beta-lactamase-producing strains of Staphylococcus aureus showed increased susceptibility to amoxycillin in the presence of clavulanic acid. Minimum bactericidal concentrations indicated that amoxycillin retains bactericidal activity in the presence of clavulanic acid. Enterobacter and Serratia species and Pseudomonas aeruginosa remained amoxycillin-resistant in the presence of clavulanic acid.

Infective complications in renal allograft recipients.

Infective complications were analysed in 74 patients who underwent renal transplantation. Bacterial infections were seen in 69%, viral infections in 48% and fungal infections in 17% of these patients. The urinary tract was involved in 56% of patients, the lungs in 24% and the upper respiratory tract in 17%. Less common were cellulitis (7%), CNS infections (4%), and other sites of infection.