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Biomedical subjects

L R Beck

Publications and source records attributed to L R Beck.

At least 37 records · Page 2Linked to original sources

New long-acting injectable microcapsule contraceptive system.

A new long-acting, injectable contraceptive which provides continuous controlled release of the steroid norethisterone (NET) for a precise period of 6 months following a single intramuscular injection is described. The prototype system consists of microcapsules made of the biodegradable polymer d, l-polylactic acid, in which micronized crystals of NET are homogeneously dispersed. NET is slowly released from the microcapsules following intramuscular injection at a rate of 0.90 microgram NET/day/mg of microcapsule by diffusion of the steroid from the polymer matrix. Three different doses of a standard preparation of microcapsules were tested in normally cycling female babbons (4 to 5 baboons/group). Following injection of either 300, 200, or 100 mg of microcapsules containing 75, 50, or 25 mg of NET, blood samples were collected at selected intervals and analyzed for NET, estrogen, and progesterone by radioimmunoassay. All three doses provided continuous NET release for 6 months following injection. The NET serum profiles for the different doses are parallel, and ovulation was inhibited in all baboons for 6 months following treatment.

Animals↗

The baboon as a primate model for the study of endometrium.

A series of transcervical uterine biopsy specimens were obtained at various stages of the menstrual cycle from a colony of 11 normally cycling female baboons, Papio anubis and Papio cynocephalus. Morphologically, baboon endometrium appeared to be similar to human endometrium. Alkaline phosphatase activity was maximal throughout the preovulatory phase and during the late postovulatory period. During the preovulatory phase acid phosphatase was not demonstrable but increased after ovulation to reach maximal activity prior to menstruation. While differences exist between human and baboon endometria, the overall morphologic and histochemical changes are similar. In addition, the baboon's endometrium is readily accessible by transcervical uterine biopsy, thus making these animals valuable primate models for study of human reproductive problems.

Acid Phosphatase↗

A new long-acting injectable microcapsule system for the administration of progesterone.

A long-acting injectable microcapsule system for the controlled-release systemic administration of progesterone (P4) is described. The system consists of microcapsules made of the biodegradable polymer, d,l-polylactic acid, which contain crystalline P4. Following injection, P4 is released from the microcapsules by diffusion and biodegradation of the polymer matrix. The rate of P4 release from the prototype microcapsule system in vivo is 1.3 microgram of P4/day/mg of microcapsules, and the duration of release is 30 days. Vaginal estrous cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following a single injection of P4 microcapsules. The effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent. The utility of the system as a once-a-month injectable contraceptive is established in the baboon model.

Animals↗

The effects of oxytocin on fetal scalp temperature.

During a study of fetal temperature, it was found that there was a significantly higher temperature among infants whose mothers received oxytocin than among a comparable control group. These data indicate that normal-appearing oxytocin-induced contractions may reduce uterine blood flow and thereby raise the intrauterine fetal temperature.

Female↗

In vivo evaluation of cholesterol as a matrix for the controlled-release of progesterone.

Twelve adult, female baboons were used to test the rate and duration of progesterone (P4) release from cholesterol (C) pellets implanted subcutaneously. Four different preparations were tested (3 baboons per group). Each group was treated with pellets containing a different sized distribution and P4-cholesterol ratio (P4:C). Group 1 = 0.25--0.5 mm, 59% P4:41% C; Group 2 = 0.25--0.5 mm, 65% P4:35% C; Group 3 = 0.5 -1.0 mm, 59% P4:41% C; and Group 4 = 0.5 -1.0 mm, 65% P4:35% C. All baboons received the identical quantity of P4 (500 mg). Following treatment, blood samples were obtained at selected intervals, and the levels of progesterone were determined by radioimmunoassay. Serum-progesterone clearance curves were parallel for each experimental group. The rate of release of progesterone calculated from the serum clearance curves for groups 1--4 were: 42; 55; 29; and 38 mg P4/week. The mean duration of release for experimental groups 1--4 were 12, 9, 17, and 13 weeks respectively. The continuous progesterone treatment inhibited normal baboon ovarian function during the period of progesterone release.

Animals↗

Radioimmunological study of rat uterine extract.

A radioassay was used to demonstrate the high affinitiy of a crude rat uterine extract for tritiated estradiol-17B. Although no other chemical procedures were employed to further characterize the extract, it may contain the estrogen binding protein isolated by others. The isolate was antigenic in rabbits and administration of immune serum to female rats significantly lowered the in vitro retention of tritiated estradiol-17B in the rat uterus. It is thought that this immune serum could be successfully used to study the estrogen binding activity of rat uterus.

Animals↗

Demonstration of postovulatory sphincter action by the isthmus of the rabbit oviduct.

Doughnut-shaped, carbon-impregnated rubber microtransducers calibrated to measure changes in diameter are used to demonstrate the occurrence of a sphincter action in the isthmus of the rabbit oviduct following human chorionic gonadotropin (HCG)-induced ovulation. The postovulatory constricture of the isthmus is temporal and coincides with the period when ova are retained in the oviduct. The mean change in diameter of transducers positioned within the lumen of the isthmus in rabbits treated with HCG are significantly different from mean changes observed in nontreated control rabbits when tested at 8-hour intervals over a 104-hour period. The difference is due to a statistically significant decrease in transducer diameter which occurs between 16 and 56 hours post-HCG injection. Treatment with exogenous estrogen in combination with HCG enhances both the magnitude and duration of this constricture. Significant differences occur between 8 and 104 hours. Pretreatment with progesterone prior to HCG-induced ovulation completely blocks the constricture of the isthmus. Both oviducts exhibit identical responses following HCG-induced ovulation. Sphincter action is not confirmed to a small localized segment of the isthmus but occurs over a wide area.

Animals↗

Effect of ethynodiol diacetate and mestranol on serum folic acid and vitamin B12 levels and on tryptophan metabolism in baboons.

The effect of an oral contraceptive agent on serum folate and vitamin B12 levels and on some aspects of tryptophan metabolism in the baboon has been investigated. Folate levels were not affected by this treatment. Vitamin B12 levels were lowered during oral contraceptive treatment (P smaller than 0.1) and increased during a 30-day period of pyridoxine supplementation (P smaller than 0.01). Trends indicating deterioration of glucose tolerance and abnormal tryptophan metabolism were also observed. Definite conclusions concerning the effect of oral contraceptive agents on nutritive parameters could not be made. This is in keeping with the vast volume of literature published on the effects of oral contraceptive agents in humans and other species. It is concluded that perhaps, due to the biologically variable responses to oral contraceptive agents by individuals of any species, studies of serum levels of vitamins and other superficial biochemical parameters. Further, we conclude that the baboon could be a useful model for the study of endocrine influences on nutritive parameters, first because endocrine parameters resemble those of humans and second, because experimental protocols can be rigidly adhered to.

Animal Nutritional Physiological Phenomena↗

Diurnal and menstrual cycle variations in serum vitamin B-12 and folacin activity in baboons.

Serum levels of vitamin B-12 and folacin were determined every 6 hours over a 24-hour period in five baboons and every other day throughout complete menstrual cycles in seven baboons. All baboons were normally cycling females exhibiting serum estrogen, progestin, and luteinizing hormone levels during the follicular, ovulatory and, luteal phases, respectively, of their menstrual cycles of 217.9 plus or minus 115.6, 420.3 plus or minus 113.9, 207.3 plus or minus 88.6 pg/ml; 1.71 plus or minus 0.84, 2.72 plus or minus 1.50, 5.92 plus or minus 4.38 ng/ml; 2.85 plus or minus 2.3, 38.4 plus or minus 20.5, 6.0 plus or minus 6.6 mg/ml. Serum vitamin B-12 levels did not vary significantly over a 24-hour period although higher mean levels were observed at 1200 and 1800 hours, whereas the lowest mean levels were observed at 2400 and 0600 hours. Folacin activity varied significantly (P smaller than 0.01) over a 24-hour period with the mean level at 1800 hours significantly higher (P smaller than 0.01) than that at all other times. The overall means and standard deviations for vitamin B-12 and folacin, respectively, during this study were 742.2 plus or minus 785.6 pg/ml and 14.48 plus or minus 6.74 ng/ml. Serum levels of vitamin B-12 and folacin did not vary significantly between the follicular or luteal phases or show any significant correlation with the day of the menstrual cycle when analyzed by linear regression procedures. The overall means and standard deviations for vitamin B-12 and folacin, respectively, during the menstrual cycle study were 438.5 plus or minus 137.9 pg/ml and 14.8 plus or minus 4.27 ng/ml.

Animals↗