Melvin R. Sikov

Release of progesterone from polyethylene devices in vitro and in experimental animals

Abstract Low density polyethylene, homogeneously loaded with 2% progesterone and 12% barium sulfate, was tested as a matrix from which to fabricate biochemically active intrauterine devices. The effect of environment on hormone release from these devices was examined by measuring their progesterone content following various periods of residence in pig and rat uteri, in the peritoneal cavities of rats and in a continuous flow of synthetic tissue fluids. Results of a 4-week study showed that progesterone release rates, while initially high, attained a relatively constant value of 14 μg/day/cm 2 after the sixth day. The release pattern in utero was closely simulated by those in the continuous-flow system and in the rat peritoneal cavity. Both systems are thus inexpensive alternatives to large animals for the testing of progesterone release from future devices.

Measurement of Temperature Rise in Prenatal Rats During Exposure of the Exteriorized Uterus to Ultrasound

We have found that ultrasound produces intensitydepen- dent increases in embryotoxicity after exposure of the rat conceptus within the exteriorized uterus. To estimate the range where thermal mechanismspertain,implanted thermocouples and adigital thermometer were used to measure fetal and maternal temperatures under the same exposure conditions. Results with protracted exposures to focused beams were analyzed by calculating polynomial equations from the data for individual animals and developing families of curves describing tem- perature-time relationships for progressively greater intensities at two frequencies used in our bioeffects studies. Ancillary experiments examined heat dissipation by circulating blood. In experiments with plane beams, intensities were increased at S-minute intervals and separate polynomials were fit to each segment. The composite step-function curves indicated that patterns of temperature rise in the fetus were similar at 0.8 and 2.4 MHz, but the rises were greater at the higher fre- quency. Temperature rises in maternal tissues were frequency depen- dent and were great enough to account for effects observed in dams ex- posed at high intensities. The data with both focused and plane beams are generally consistent with the shapes of our embryotoxicity response curves and implicate thermal mechanisms in many of the effects.

STUDIES OF DUPLEX (COPPER-COATED) WIRES FOR USE IN INTRAUTERINE DEVICES

An investigation to develop and study duplex wire for use in IUDs was initiated by the observation that copper wires wound on IUDs occasionally fragmented after prolonged in vivo use. The duplex wires consist of an exposed active copper surface plated onto an inert inner core to maintain structural continuity. Data demonstrated that the dissolution rates as well as surface changes and biological effects are independent of whether stainless steel, Inconnel or Tophet-M was used as the core. Small IUDs can be wound with a duplex wire in a manner identical to that presently used with pure copper to resist fragmentation and to provide contraceptive effects.

Effects of d-norgestrel-releasing intracervical devices in the nonhuman primate, Erythrocebus patas

Primates (Erythrocebus patas) were implanted with intracervical devices which slowly released d-norgestrel at either of two rates: 38 +/- 12 microgram/day (high dose, 4 animals) or 14 +/- 10 microgram/day (low dose, 3 animals). An additional 8 animals received placebo devices or were untreated controls. All animals were studied for 3 months of exposure, at which time they were necropsied and evaluated. The uterus in all of the high dose primates had endometrial stromal and epithelial hyperplasia and, in two primates, suppurative endometritis. Similar, but less severe, uterine changes were present in animals of the low dose group. Systemic effects included evidence of diminished menstrual cycling and an absence of corpora lutea at both dose levels. Our results indicate that local application of these levels of d-norgestrel for contraception produces effects similar to those from systemically administered d-norgestrel.

Ultrasound: Its potential use for the termination of pregnancy

Abstract The literature on the general biological effects of ultrasound energy is briefly reviewed. The effects of high intensities of focused ultrasound, which have been shown to produce necrosis of well-defined volumes of tissue, are emphasized. The available studies on the effects of ultrasound on prenatal development are also described. Although ultrasonic diagnostic techniques are generally considered to be harmless, it appears that exposures of sufficient magnitude are embryocidal. Two potential techniques by which ultrasound may be used for pregnancy termination are proposed. In one approach an ultrasound-producing probe would be placed in the uterine cervix; the uterine lumen may act as a wave-guide to direct the energy to the implantation site. In the alternate approach high intensity focused ultrasound would be directed through the abdominal wall to the site of implantation, which would be previously and concurrently visualized by real-time ultrasonic imaging techniques.

Age effects on zinc metabolism in the rat

Abstract 1. 1. Newborn rats eliminated injected 65 Zn more slowly than did weanlings or adults. 2. 2. The largest fraction of 65 Zn was found in the skeleton of newborn and weanling rats and in the muscle of adults. 3. 3. Dialysis of liver homogenates against EDTA resulted in a more rapid removal of 65 Zn from neonatal than from weanling or adult liver.