Recombinant 47-kilodalton cytosol factor restores NADPH oxidase in chronic granulomatous disease

A 47-kilodalton neutrophil cytosol factor (NCF-47k), required for activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase superoxide (O2-.) production, is absent in most patients with autosomal recessive chronic granulomatous disease (AR-CGD). NCF-47k cDNAs were cloned from an expression library. The largest clone predicted a 41.9-kD protein that contained an arginine and serine-rich COOH-terminal domain with potential protein kinase C phosphorylation sites. A 33-amino acid segment of NCF-47k shared 49% identity with ras p21 guanosine triphosphatase activating protein. Recombinant NCF-47k restored O2-. -producing activity to AR-CGD neutrophil cytosol in a cell-free assay. Production of active recombinant NCF-47k will enable functional regions of this molecule to be mapped.     

The toxicity of cyclopiazonic acid in weaned pigs

Five- to six-week-old crossbred pigs weighing 5 to 14 kg were given purified cyclopiazonic acid at dosages of 10, 1.0, 0.1, and 0.01 mg/kg body weight orally for 14 days. Clinical signs observed by day 7 in pigs given 10 mg/kg body weight were weakness, inactivity, anorexia, rough hair coats, and reduced body weights. These pigs also developed diarrhea during week 2 of the experiment. The pigs given 1.0 mg/kg body weight had rough hair coats and were moderately inactive during the second week of the experiment. At necropsy, lesions were observed only in pigs given 10 and 1.0 mg/kg body weight of cyclopiazonic acid. Lesions were gastric ulcers, mucosal hyperemia, and hemorrhage throughout the small and large intestine in pigs given 10 mg/kg body weight of cyclopiazonic acid. The pigs also had yellow, fibrononecrotic material in the lumen of the small intestine and pale livers. One pig given 1.0 mg/kg body weight had gastric ulceration. Microscopic lesions in pigs given 10 mg/kg body weight were necrotizing gastroenteritis, focal hepatocellular necrosis, hepatic peripheral lobular fatty change, and focal renal tubular nephrosis with focal suppurative tubulointerstitial nephritis. Pigs given 1.0 mg/kg body weight of cyclopiazonic acid had necrotizing gastritis and villous blunting in the jejunum and ileum.     

Topical anaesthesia alleviates short-term pain of castration and tail docking in lambs

Objective To investigate the effect of a topical anaesthetic formulation on pain alleviation, wound healing and systemic levels of local anaesthetic actives in lambs undergoing castration and tail docking. Design Three placebo-controlled and/or randomised experiments were conducted using three groups of Merino lambs (n = 62, 68 and 19) undergoing routine castration and tail docking. Procedure Surgical castration, with either surgical or hot-iron tail docking, was performed with and without the application of topical anaesthetic (Tri-Solfen®) or placebo. The effects of this procedure were compared with those of rubber ring castration and tail docking, and of the handled but unmarked controls. Wound pain was assessed using calibrated Von-Frey monofilaments over a 4-h period, pain-related behaviour was assessed over 5 h, wound healing was assessed at 14 and 28 days, and the plasma levels of lignocaine and bupivacaine were determined. Results Rapid and up to 4 h primary hyperalgesia developed following surgical castration and tail docking in the untreated and placebo-treated lambs. It was absent in the castration wounds, and significantly reduced in the tail-docking wounds, of the treated lambs. Hot-iron docking was associated with mild and transient secondary hyperalgesia, which was abolished by the topical anaesthesia. There was a significant reduction in pain-related behaviours in treated lambs, which were not significantly different in their behaviour to the sham-operation handled controls. Plasma lignocaine and bupivacaine levels were below the toxic thresholds in all tested lambs. Conclusion Topical anaesthesia alleviates wound pain and significantly reduces pain-related behaviours in lambs undergoing surgical castration plus surgical or hot-iron tail docking, without a negative effect on wound healing or a risk of systemic toxicity.     

Topical vapocoolant spray reduces nociceptive response to ear notching in neonatal piglets

Objective

To evaluate the efficacy of a vapocoolant spray (VS) to provide local anaesthesia for piglets during ear notching.

The effect of dietary polyunsaturated fatty acids (PUFA) on infection with the nematodes Ostertagia ostertagi and Cooperia oncophora in calves

Diet-induced changes in the polyunsaturated fatty acid (PUFA) content of immune cells influences the immune phenotype that develops following infection. The aim of this study was to examine the effect of manipulating dietary PUFA supply on tissue fatty acids composition and immunity to a mixed infection with an abomasal and an intestinal nematode parasite in calves. Calves (n=24) were allocated into two treatment groups and fed 25 g/day of either fish oil (n-3 group) or a binary mixture of palm/rapeseed oil (normal group) as a supplement in milk replacer. Within each treatment group eight calves were infected with 2000 L3 Ostertagia ostertagi and Cooperia oncophora, three times per week for 8 weeks, the remaining calves were pair-fed uninfected controls. Faecal egg counts (FEC) were carried out twice weekly. At slaughter, the whole gut was removed intact for worm counts and tissue samples were taken for fatty acid analysis. Samples of abomasum, duodenum and mid-gut were also collected for immunohistological analysis. FEC were not significantly influenced by oil supplement but tended to remain higher in the palm/rapeseed oil-fed group (normal infected). The number of intestinal immature worms was significantly (p<0.05) higher in the n-3 group. Mucosal mast cell (MMC) and eosinophil numbers were significantly increased (p<0.05) by infection and were significantly lower (p<0.05) in the intestinal tissue of the fish oil supplemented and infected group (n-3 infected group). These results suggest that feeding an n-3 PUFA-rich supplement (fish oil) can influence cellular mediators of immunity to nematode infection. This is the first report of the establishment of patency and the subsequent development of immunity to a mixed infection with O. ostertagi and C. oncophora in calves undergoing early rumen development. The trend in the FEC, MMC and eosinophil numbers in the n-3 group suggests that decreasing the dietary n-6/n-3 PUFA ratio may be a worthwhile immunonutritional strategy for potentiating the immune response to nematode parasite infection in the calf.     

Effect of short term intravenous infusion of noradrenaline on energy metabolism in shorn and unshorn pregnant sheep

The effect of a three hour intravenous noradrenaline (NA) infusion, at a dose of 0.8 micrograms min-1 kg-1 bodyweight, on energy metabolism was studied in five pairs of shorn and unshorn pregnant ewes. The concentration of oxygen and carbon dioxide in blood was significantly higher in shorn animals during saline infusion, but this difference between shorn and unshorn groups was removed by NA infusion. Significant increases in the plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFA), 3-hydroxybutyrate and glycerol occurred in both shorn and unshorn animals during NA infusion. There was a 48 per cent larger rise in the plasma NEFA concentration during NA infusion in the unshorn group, suggesting that the lipolytic effect of exogenous NA is greater in these animals. NA infusion had no effect on the plasma concentration of thyroid hormones in both groups of ewes, while growth hormone levels fell and cortisol increased in all animals. The plasma insulin concentration was significantly reduced during NA treatment in the unshorn group, but was unchanged in shorn animals. These results may be a consequence of sympathetic activity already being elevated in shorn ewes due to chronic exposure to an environmental temperature below the thermoneutral zone.     

Effects of extracorporeal shock wave therapy on desmitis of the accessory ligament of the deep digital flexor tendon in the horse

Objective: To evaluate the effects of extracorporeal shock wave therapy (ESWT) on collagenase‐induced lesions in the accessory ligament of the deep digital flexor tendon (ALDDFT) of horses. Study Design: Paired, blinded controlled study. Animals: Eight Thoroughbred horses (3 mares, 5 geldings; mean±SD weight, 464±26 kg, mean age, 8±1.7 years). Methods: Lesions were created in both ALDDFTs of all horses by injection of 2 × 10³ IU of collagenase type I. Percent lesion and structure (fiber alignment and echogenicity) were quantified with ultrasonographic imaging 3, 6, and 9 weeks after collagenase injection. After ultrasound examinations, ESWT (1000 shocks at 0.15 mJ/mm²) was applied to 1 ALDDFT in each horse. ALDDFT were harvested 15 weeks after collagenase injection and the microstructure, mRNA levels of collagen types I and III, and collagen and glycosaminoglycan content were evaluated. Results: There were no differences in percent lesion, echogenicity, or fiber alignment between control‐ and ESWT‐treated ligaments at each evaluation time; however, compared with 3‐week values, there was a significant increase in percent lesion and echogenicity for EWST treated ligaments at 6 weeks and significant decrease in both variables for treated and control ligaments at 12 weeks. Fiber alignment improved significantly at 9 weeks in controls and at 12 weeks in treated and control ligaments. Collagen type I mRNA levels were significantly higher in the ESWT treatment group compared with the control group 15 weeks after collagenase injection though differences in other mRNA levels, microstructure, and composition were not significant. Conclusions: Our results do not support an effect of ESWT on collagenase‐induced lesions in the equine ALDDFT.