Effects of thromboxane synthetase inhibition on immune complex glomerulonephritis.

To determine the role of thromboxane A2 in the pathogenesis of experimentally induced immune complex glomerulonephritis, 12 concanavalin A-immunized Beagles were infused with 1 mg of concanavalin A via each renal artery and treated twice daily for 8 days with either 30 mg of CGS 12970/kg, PO, a specific thromboxane synthetase inhibitor, or placebo. The effect of treatment was assessed by measuring endogenous creatinine clearance and urine protein and eicosanoid excretion, and by evaluating changes in glomerular morphometric characteristics. On postinfusion day 8, urine protein, thromboxane B2, and 11-dehydro-thromboxane B2 excretion, glomerular epithelial crescent formation, and glomerular cell proliferation in the CGS 12970-treated dogs were significantly decreased when compared with values in the placebo-treated group. Differences were not observed in endogenous creatinine clearance, urine prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, or glomerular polymorphonuclear leukocyte infiltration between groups in this study. These findings suggest thromboxane A2 has a role in the development of immune complex glomerulonephritis and that thromboxane synthetase inhibition may be beneficial in attenuating some of the functional and histological changes associated with immune complex glomerulonephritis.     

Production of Lambs After the Transfer of Fresh and Cryopreserved in vitro Produced Embryos from Prepubertal Lamb Oocytes and Unsorted and Sex-sorted Frozen-thawed Spermatozoa

Cumulus-oocyte complexes from hormone-stimulated 3-4-week-old (n=43) and 6-7-week-old (n=12) prepubertal lambs were matured in vitro and incubated with unsorted, or X- or Y-spermatozoa separated with a high-speed cell sorter (SX MoFlo)frozen-thawed. Presumptive zygotes were then cultured to the blastocyst stage, and transferred to recipients fresh or after cryopreservation (frozen). Oocyte cleavage was higher (p <0.05) with unsorted (515/926, 55.6%) than X- or Y-spermatozoa (261/672, 38.8% and 229/651, 35.2%, respectively) and blastocyst formation (% zygotes) by Day 9 of in vitro culture was lower (p <0.05) for X- (102/261, 39.1%) than unsorted spermatozoa (249/515, 48.3%), but did not differ between Y-spermatozoa (103/229, 45.0%) and unsorted spermatozoa, or between X- and Y-spermatozoa (p >0.05). For fresh embryos, survival to term was 50.0% (3/6) for unsorted, 0.0% (0/6) for X- and 16.7% (1/6) for Y-spermatozoa-derived embryos (p >0.05), and for frozen embryos was 4.0% (2/50) for unsorted, 9.1% (2/22) for X- and 2.9% (1/34) Y-spermatozoa-derived embryos (p >0.05). Of the two lambs born from X-spermatozoa-derived embryos, one was female (50%), and from the two Y-spermatozoa-derived lambs, both were male (100%), demonstrating that lambs can be produced after the transfer of fresh and cryopreserved IVP embryos derived from prepubertal lamb oocytes and frozen-thawed sex-sorted sperm.     

Development and evaluation of a rapid absorbed enzyme immunoassay test for the diagnosis of Johne''s disease in cattle

An absorbed enzyme immunoassay (EIA) test for Johne's disease in cattle was developed in which absorption of cross-reacting antibodies occurred as a rapid reaction in solution rather than overnight with whole organisms and a subsequent centrifugation step. Total test time was reduced to less than 2 h with a minimum of manipulations. The test was evaluated in cattle herds from Johne's disease-endemic and Johne's disease-free regions of Australia. Specificity was 99.8%. Calculations of sensitivity were affected by the history of the herd under test. However, the EIA detected in excess of 80% of animals before onset of clinical disease and 65% of faecal shedders were EIA positive on, or before, first detection of Mycobacterium paratuberculosis in their faeces. The test should aid epidemiological studies and be a useful tool in the management and control of Johne's disease.     

Effects of a specific thromboxane synthetase inhibitor on thromboxane generation and excretion in healthy dogs

A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1-indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion.     

Investigations of an enteric infection of cockatoos caused by an enterovirus-like agent

An enteric infection in cockatoos associated with a 30 nm diameter enterovirus-like agent seen in faeces and intestinal epithelial cells is described. The disease is characterised by intractable, profuse, mucoid diarrhoea, weight loss, dehydration and death. Lesions in the intestine consist of villous atrophy, villous fusion, enterocyte hyperplasia and, in some cases, chronic inflammation. Affected birds so far examined have concurrent psittacine beak and feather disease.     

Pharmaceutical evaluation of compounded trilostane products

Compounded trilostane capsules (15 mg, 45 mg, or 100 mg) were purchased from eight pharmacies and assayed for content and dissolution characteristics. Capsules made in-house containing either inert material or 15 mg of the licensed product and proprietary capsules (30 mg and 60 mg) served as controls. Findings were compared with regulatory specifications for the licensed product. Altogether, 96 batches of compounded trilostane and 16 control batches underwent analysis. In total, 36 of 96 (38%) compounded batches were below the acceptance criteria for content. The average percentage label claim (% LC) for each batch ranged from 39% to 152.6% (mean, 97.0%). The range of average % LC for the controls was 96.1-99.6% (mean, 97.7%). The variance in content of the purchased compounded products was substantially greater than for the controls (234.65 versus 1.27; P<0.0001). All control batches exceeded the acceptance criteria for dissolution, but 19 of 96 batches (20%) of purchased compounded products did not. Mean percent dissolution for the purchased compounded products was lower than for controls (75.96% versus 85.12%; P=0.013). These findings indicate that trilostane content of compounded capsules may vary from the prescribed strength, and dissolution characteristics may not match those of the licensed product. The use of compounded trilostane products may therefore negatively impact the management of dogs with hyperadrenocorticism.