Clinical signs and biochemical changes in calves caused by injection of ivermectin.

Eight-month-old Jersey bull calves given ivermectin intravenously or subcutaneously showed signs of depression, ataxia, difficulty in breathing, tachycardia, salivation, diarrhoea, miosis, and an increase in pseudocholinesterase activity. The clinical signs were severe in calves given the drug intravenously. The findings suggest that the cholinergic nervous system may be involved in some of the adverse effects of ivermectin observed in calves.

Effect of trenbolone and testosterone on the plasma elimination rates of sulfamethazine, trimethoprim, and antipyrine in female dwarf goats.

Plasma elimination rates of sulfamethazine (100 mg/kg of body weight, IV), trimethoprim (20 mg/kg, IV), and antipyrine (35 mg/kg, IV) were studied in adult female dwarf goats (n = 5) before and after implantation with trenbolone acetate (5 mg/kg). Pretreatment with trenbolone caused a significant decrease in the elimination rate of the drugs tested: for sulfamethazine, 5 times; for antipyrine, 3 times; and for trimethoprim, 2 times. After treatment with testosterone (1 mg/kg, SC, twice weekly for 2.5 weeks), female goats (n = 5) had a similar decrease in the elimination rate of sulfamethazine. Other induced effects included a change in social behavior, a lower voice, and the development of a typical billy goat-like odor. Plasma creatinine concentrations after androgen administration were significantly higher than those before androgen administration; changes were not observed in plasma urea values. Because of the differences observed, we believe that more attention should be paid to the effects of androgenic agents on drug kinetic properties, with particular reference to studies on clinical efficacy, side effects, and drug residues in food products.

The vitamin D3 metabolite-type activity of Solanum malacoxylon.

1. Administration of an aqueous extract of the dried leaves of Solanum malacoxylon (DLSM) to rats causes a rapid hyperphosphataemia and a decrease in plasma alkaline phosphatase activity; the two effects are typical of 1,25(OH)2D3, the hormonally active metabolite of vitamin D3. 2. DLSM, like both vitamin D3 and parathyroid hormone, increases plasma calcium and citrate levels in rats. The effect of DLSM in influencing plasma citrate, and the role of this important metabolite in mineral metabolism is discussed. 3. A decrease of plasma magnesium levels occurs in rats following treatment with DLSM. This decrease, which is associated with a renal loss of this cation, is remarkably similar to that produced by hypervitaminosis D3. 4. Prolonged administration of DLSM to vitamin D deficient rats causes a polyuria, hypercalciuria, hyperphosphaturia, hypermagnesuria, an increase in urinary total hydroxyproline, an increase in plasma total hexosamines, and a corresponding decrease in the bone total hexosamines. These effects, some of which can also be produced by hyperparathyroidism, or following the administration of parathyroid extract (PTE), large doses of vitamin D3, or 1,25(OH)2D3, suggest that DLSM, like the latter compounds, is capable of causing bone mineral mobilization, and the dissolution of bone organic matrix.

The effect of the active principle of Solanum malacoxylon on rabbits and the inhibition of its action by actinomycin D.

The oral administration of an aqueous extract of 2.5 g of the dried leaves of Solanum malacoxylon (DLSM) produced a rapid hyperphosphataemia, which becomes apparent 4 to 8 h after treatment, in the rabbit. This effect was not accompanied by any significant change in plasma calcium, mangesium, total protein, albumin, urea and creatinine concentration. The urinary excretion of calcium, magnesium, and inorganic phosphate was markedly increased 24 and 48 h after treatment with the extract and was not accompanied by any significant change in the urinary excretion of hydroxyproline. The hyperphosphataemic effect of the DLSM extract was inhibited by Actinomycin D. It appeared that DLSM does not cause bone resorption in normal rabbits maintained on a diet containing adequate levels of calcium and phosphorus. The increased urinary excretion of calcium magnesium and inorganic phosphate after treatment with DLSM extract appeared to be due to increased intestinal absorption. The absence of any significant change in plasma urea and creatinine concentration after treatment with DLSM extract, and the inhibition of the hyperphosphataemic effect by Actinomycin D, indicated that this was a characteristic response of the rabbit to the active principle, and that it was not due to renal damage. The inhibition of the hyperphosphataemic effect of DLSM by Actinomyein D showed that its action involves the transcription of DNA to RNA and protein synthesis.

The effect of the administration of Solanum malacoxylon on the chick.

Replacement of the drinking water of chicks maintained on a normal mixed protein diet with an aqueous extract containing the equivalent of 5 g of the dried leaves of Solanum malacoxylon (DLSM) per 100 ml for one month produces a hypercalcaemia (23-49 per cent), hypomagnesamia (28-37 per cent), hypophosphataemia (26-34 per cent), hypouricaemia (29-34 per cent) and a decrease in plasma alkaline phosphatase activity (54-98 per cent). The ash content of the defatted, dried tibiae and the body weight of the DLSM treated chicks were also significantly lower (37-7 per cent and 17-79 per cent respectively) than the corresponding values for the untreated birds. The results obtained are similar to those reported for hypervitaminosis D3 in the chick.