Species variation in drug response is a well recognized pharmacological phenomenon. Strain variations within a given species, however, have been characterized to a much lesser degree. These problems assume importance not only when attempting to extrapolate results of animal experiments to man, but also in basic biological research.Law et a2( 1) have shown variations in beta-glucuronidase activity in various strains of mice. Jay(2) has also shown strain differences in mice with regard to hexobarbital sleeping time. The experiments of Yaffe(3) indicate that strain variation in drug response in mice is a genetic factor which is manifest soon after birth. Strain variation in drug response and hepatic drug metabolism in rats have been reported by Quinn et aZ(4). However, to our knowledge, no studies on strain differences in drug response have been reported using rabbits, a species commonly employed in research.We have attempted to determine whether the activity of several hepatic microsomal drug metabolizing enzyme systems varies in different rabbit strains. Studies were carried out on strains of rabbits commonly employed in research as well as on wild rabbits. We have also attempted to determine whether the stimulation of the hepatic drug metabolizing enzyme activity by phenobarbital dif-*This research was supported by a grant from Nat. Inst. Health ). fered in these strains. MateriaZs and methods. Dutch, New Zealand, English, and California strains were studied as representatives of commonly employed research animals. In addition, wild Jack rabbits were obtained from the Durant Animal Co., Ft. Sumner, New Mexico and wild Cottontails were obtained from the Earl Johnson Farms, Rago, Kansas. Rabbits were maintained on regular Purina Lab Chow and water ad libitum during the experiment, and constant conditions were maintained as nearly as possible. In all cases young adult bucks were employed.To study the effect of pre-treatment with phenobarbital, rabbits were injected intraperitoneally twice daily with 1 5 mg/kg phenobarbital sodium dissolved in normal saline. Injections were made for 3 days, on the 4th day the animals were not injected, and on the fifth day the animals were sacrificed and livers removed. Control animals were injected with normal saline on the same schedule. The livers were placed immediately on ice, blotted, weighed, and ground in the cold with a Potter homogenizer (teflon pestle) in 2 volumes of ice cold 1.15.h KCl solution. This homogenate was then centrifuged at 1-3 "C (International portable refrigerated centrifuge, model PR-2) at 9,0001 g for 30 minutes.The following metabolic pathways were studied: Side-chain oxidation of hexobarbital by guest on July 24, 2015 ebm.sagepub.com Downloaded from
The three-phase bone scan is finding increasing utility in acute and chronic pain syndromes in sports medicine settings. This useful technique may have significant clinical application in assessing the increasing numbers of patients with exercise induced lower leg or medial tibial pain. The authors present a case of exertional lower leg pain or medial tibial pain in which three-phase bone imaging exhibited a dramatic increase in early flow after a simple derived exercise stress. The three-phase bone scan should play a key role in the assessment of exercise pain, and may be enhanced by the addition of simple exercise intervention.
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