Streptozotocin causes pancreatic beta cell failure via early and sustained biochemical and cellular alterations.

The morphological and biochemical changes that occur in the early phase of streptozotocin (STZ)-induced beta cell failure have not been characterized. The pancreas and plasma of rats treated with STZ were processed for morphological and biochemical parameters 1-24 h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3 h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1 h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24 h after STZ treatment. The number of insulin-positive cells decreased significantly (p<0.05) at 24 h after STZ treatment with a concomitant increase in the number of glucagon-immunoreactive cells. Electron microscopy showed coalescing of beta cell granules 18 h after STZ treatment. A near to complete degranulation of beta cells settled at 21 h after STZ administration. The pancreatic tissue and plasma levels of adrenaline and noradrenaline increased significantly (p<0.004: pancreatic tissue; p<0.04: plasma) 3 h after STZ treatment and remained high after a reduction at 6 h post STZ treatment. The pancreatic tissue and plasma levels of 5-HIAA decreased significantly (p<0.002 pancreatic tissue; p<0.04: plasma) 1 h after STZ treatment and remained low after a reduction at 6-9 h post STZ treatment. STZ elicited significant dose-dependent increases in insulin secretion from the isolated pancreas. The early changes in catecholamine level may be used in screening and follow-up studies on diabetes mellitus.

Effect of alpha-tocopherol supplementation on the ultrastructural abnormalities of peripheral nerves in experimental diabetes.

Ultrastructural observations were made on myelinated fibers in the tibial nerves in order to investigate the beneficial effects of alpha-tocopherol administration in streptozotocin-diabetic rats. Male Wistar rats, aged 12 weeks and weighing between 250 g to 300 g were studied. Six onset control rats were used to obtain the baseline parameters for this strain and age. Further 3 groups--untreated diabetic animals, diabetic animals treated with alpha-tocopherol, and age-matched controls--were studied over a 3-month period. In the diabetic animal, administration of alpha-tocopherol resulted in a significant increase (p < 0.05) in total plasma vitamin E levels when compared with other groups. Myelinated fiber cross-sectional area (p < 0.05), axonal area (p < 0.01) and myelin sheath area (p < 0.05) were significantly less in the tibial nerve of diabetic animals than in age-matched controls, but not different from those of onset controls. In the alpha-tocopherol treated diabetic animals, the values for these parameters were intermediate without showing significant difference when compared with age-matched controls and untreated diabetics. The "g" ratio (axon to fiber area) did not differ between any experimental groups. The number of large myelinated fibers were less in the untreated diabetic animals, but in the alpha-tocopherol-treated diabetics, the values were significantly higher (p < 0.05) than with untreated diabetics and were similar to those of age-matched controls. In conclusion, this ultrastructural study reiterated the fact that structural abnormalities of myelinated fibers occur in experimental diabetes and that alpha-tocopherol administration may be useful in preventing the development of these abnormalities.

Pharmacokinetics of enrofloxacin after intravenous, intramuscular and oral administration in houbara bustard (Chlamydotis undulata macqueenii).

The in-vitro activity of enrofloxacin against 117 strains of bacteria isolated from bustards was determined. Minimum inhibitory concentrations for 72% of the Proteus spp., E. coli, Salmonella spp. and Klebsiella spp. (n = 61) and for 48% of the Streptococci spp. and Staphylococci spp. (n = 31) were < or = 0.5 microg/mL. The minimum inhibitory concentration (MIC) of 76% of Pseudomonas spp. (n = 25) was < or = 2 microg/mL. Fourteen strains were resistant to concentrations > or = 128 microg/mL. The elimination half-lives (t1/2 elim beta) (mean +/- SEM) of 10 mg/kg enrofloxacin in eight houbara bustards (Chlamydotis undulata) were 6.80 +/- 0.79, 6.39 +/- 1.49 and 5.63 +/- 0.54 h after oral (p.o.), intramuscular (i.m.) and intravenous (i.v.) administration, respectively. Enrofloxacin was rapidly absorbed from the bustard gastro-intestinal tract and maximum plasma concentrations of 1.84 +/- 0.16 microg/mL were achieved after 0.66 +/- 0.05 h. Maximum plasma concentration after i.m. administration of 10 mg/kg was 2.75 +/- 0.11 microg/mL at 1.72 +/- 0.19 h. Maximum plasma concentration after i.m. administration of 15 mg/kg in two birds was 4.86 microg/mL. Bioavailability was 97.3 +/- 13.7% and 62.7 +/- 11.1% after i.m. and oral administration, respectively. Plasma concentrations of enrofloxacin > or = 0.5 microg/mL were maintained for at least 12 h for all routes at 10 mg/kg and for 24 h after i.m. administration at 15 mg/kg. Plasma enrofloxacin concentrations were monitored during the first 3 days of treatment in five houbara bustards and kori bustards (Ardeotis kori) with bacterial infections receiving a single daily i.m. injection of 10 mg/kg for 3 days. The mean plasma enrofloxacin concentrations in the clinical cases at 27 and 51 h (3.69 and 3.86 microg/mL) and at 48 h (0.70 microg/mL) were significantly higher compared with the 3 h and 24 h time intervals from clinically normal birds. The maximum plasma concentration (Cmax)/MIC ratio was ranked i.v. (10/mg/kg) > i.m. (15 mg/kg) > i.m. (10 mg/kg) > oral (10 mg/kg), but it was only higher than 8:1 for i.v. and i.m. administrations of enrofloxacin at 10 mg/kg and 15 mg/kg, respectively, against a low MIC (0.5 microg/mL). A dosage regimen of 10 mg/kg repeated every 12 h, or 15 mg/kg repeated every 24 h, would be expected to give blood concentrations above 0. 5 microg/mL and hence provide therapeutic response in the bustard against a wide range of bacterial infections.