Studies were conducted to ascertain in vitro effects and effects of percutaneous application (in vivo) of dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) on cholinesterase activities in bovine erythrocytes and plasma. Treatment in vitro of erythrocytes and plasma with DDVP resulted in concentration- and time-dependent inhibition of erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (ChE) activities. Mean (+/- SD) DDVP concentrations required to cause 50% enzyme inhibition were 15.7 +/- 3.3 muM and 43.1 +/- 5.7 muM for AChE and ChE, respectively; however, these values required to achieve this inhibition were markedly decreased with increasing incubation time. The inhibited AChE activity failed to be reactivated after incubation of erythrocytes with 2-pyridine aldoxime methiodide (2-PAM); however, limited reactivation of inhibited AChE and ChE activities was observed with excess concentration of 2-PAM. Percutaneous application of a DDVP-containing livestock spray on cattle also caused a marked decrease in the in vivo activities of AChE and ChE; however, the inhibited enzyme activities were reactivated rapidly after incubation with 2-PAM.

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 effect of glucocorticoids on early follicular growth in sows undergoing normal estrous cycles was evaluated by administration of dexamethasone during the middle of the luteal phase. Plasma specimens were obtained for measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and estradiol-17 beta concentrations. Fifteen sows were used. Control sows (n = 5) were given physiologic saline solution twice daily from day 9 to day 14 of the estrous cycle. Sows of the second group (n = 5) were given dexamethasone (30 microgram/kg of body weight, IM) similarly, and those of the third group (n = 5) were given dexamethasone plus gonadotropin-releasing hormone (GnRH+ 50 microgram at 6-hour intervals, IV). Plasma specimens, obtained twice daily from day 8 through day 26, indicated that progesterone production and luteal regression were not inhibited by any of the 3 treatment regimens. Although preovulatory plasma estradiol concentration increased in control sows, such was not observed in the sows treated with dexamethasone or dexamethasone plus GnRH (P less than 0.01). Ovulation, with formation of corpora lutea, occurred in gilts given saline solution. Dexamethasone administration resulted in persistence of 19 to 41 follicles/ovary (2 to 4 mm in diameter), and dexamethasone-plus-GnRH treatment resulted in 6 to 18 follicles/ovary (5 to 6 mm in diameter). Plasma was obtained at 15-minute intervals for 12 hours to compare the effect of treatmenton hormone concentrations on day 12 of the estrous cycle with the values on day 8. Glucocorticoid administration had no significant effect on mean concentration, final concentration excluding those hormone concentrations that constituted part of a pulse (referred to as base line), number of pulses, pulse amplitude, and area under the pulse for either gonadotropin. Addition of GnRH to dexamethasone treatment significantly (P less than 0.01) increased all plasma LH values, but only base-line concentration of FSH. For estradiol, pulse amplitude and mean pulse area were increased (P less than 0.05), and although the frequency of pulses was not significantly altered, base-line concentration in glucocorticoid-treated sows was significantly reduced, compared with that of control sows. In sows treated with GnRH plus dexamethasone, the pulse frequency of estradiol was significantly (P less than 0.01) increased, but pulse area and amplitude were similar to those of sows given saline solution. Dexamethasone treatment was associated with an increase in mean and base-line concentrations of progesterone. The results suggest that high midcycle glucocorticoid concentrations (1) do not inhibit luteal function or regression, (2) have little influence on LH and FSH secretion during the middle of the luteal phase, (3) alter the pattern of estradiol secretion, (4) are associated with the persistence of small ovarian follicles, and (5) result in the development of fewer but larger follicular structures when GnRH is administered concurrently.