Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin.

High-dose aspirin therapy for rheumatoid arthritis is frequently associated with severe gastrointestinal injury. To explore the possibility of reversing such damage, we conducted a double-blind, multicenter study with misoprostol, a prostaglandin E1 analog, which has demonstrated mucosal protective, gastric antisecretory, and ulcer healing properties. We also studied possible interference of misoprostol with continuing aspirin treatment in the management of patients with rheumatoid arthritis.

Correlation of aromatic hydroxylation of 11 beta-substituted estrogens with morphological transformation in vitro but not with in vivo tumor induction by these hormones.

In estrogen-induced cancer, catechol formation from administered steroids has been postulated to be a necessary event for estrogen activation and subsequent damage to cellular macromolecules. In the present study, this hypothesis has been tested using two homologous series of structurally related estrogens: estradiol, 11 beta-methylestradiol, 11 beta-ethylestradiol, 11 beta-methyl-17 alpha-ethinylestradiol, 11 beta-ethyl-17 alpha-ethinylestradiol, 11 beta-methoxy-17 alpha-ethinylestradiol, and 17 alpha-ethinylestradiol. In the Syrian hamster renal carcinoma model, only 11 beta-methylestradiol and 17 alpha-ethinylestradiol were weak carcinogens (2 of 20 and 2 of 24 hamsters with tumors, respectively).

Relationship between progesterone suppression and pregnancy in rats.

Four luteolytic agents were administered to groups of pregnant rats to examine the quantitative relationship between serum progesterone levels and the maintenance of pregnancy. Each agent inhibited progesterone in a dose-dependent manner, however only three, azastene, thiosemicarbazone and dihydrotestosterone, adversely affected pregnancy. A statistical analysis of the data suggests that, regardless of the mechanism of action of a particular luteolytic agent, a treatment-induced depression of serum progesterone to concentrations less than 45% of that of the controls on day 11 of pregnancy is incompatible with pregnancy maintenance.

The biological properties of aspartame. III. Examination for endocrine-like activities.

A series of studies with aspartame were run in mice, rats and rabbits using standard procedures to characterize possible estrogenic, androgenic, progestational and glucocorticoid activities. Aspartame was administered orally at levels (ca 300 mg/kg/day) substantially in excess of expected maximal human intake when used as a sweetening agent. No significant hormone-mimetic response was observed in the endocrine target organs evaluated.

Biological properties of aspartame. I. Evaluation of central nervous system effects.

Aspartame was administered intragastrically to rodents at doses between 10 and 550 times the expected daily human intake to evaluate the effects on central nervous system function. No biologically meaningful effects were observed in either rats or mice following acute administration by the intragastric route. Aspartame administered as 9% of the diet (about 11 g/kg/day) for thirteen weeks to weanling rats altered the learning behavior of male rats.

The biological properties of aspartame. IV. Effects on reproduction and lactation.

Intragastric administration of approximately 300 mg/kg/day of aspartame (APM) to female rats for seven days and to female hamsters for five days after mating did not affect postcoital fertility as measured by the number of implantation sites and normal appearing fetuses. In additional studies, the effect of APM fed at 1 to 14% in the diet to lactating rats and their litters of suckling young was studied using a pair-feeding experimental design. Levels of APM up to 4% in the diet (about 7 g/kg/day) did not affect food consumption, body weights, serum prolactin, serum gonadotropins, the mammary gland histology of the dams or the growth and survival rates of their pups.

The biological properties of aspartame. II. Actions involving the gastrointestinal system.

Aspartame (APM) was investigated in several pharmacological tests to delineate any effects on the gastrointestinal system. The compound did not affect food consumption at one hour following a single intragastric dose of 200 mg/kg in rats. There was no evidence of inhibition or stimulation of the gastric juice secretion rate, the concentration of gastric acid, acid output or proteolytic activity following an intragastric dose of 250 mg/kg in five-hour pylorus-ligated rats.

The biological properties of aspartame. V. Effects on a variety of physiological parameters related to inflammation and metabolism.

Aspartame (APM), L-aspartyl-L-phenylalanine methyl ester, is a low calorie sweetening agent 180 times sweeter than sucrose. As part of a series of studies designed to determine the potential effects of ingestion of excesses of APM on a wide spectrum of physiological processes, experiments were conducted in which high multiples (mg/kg basis) of the projected maximum daily human intake (20 mg/kg) were administered intragastrically to laboratory rats. Doses up to 16 times the maximum intake had no effect on inflammation parameters including carrageenin-induced paw edema, connective tissue formation and adjuvant arthritis.

The effect of a copper intrauterine device during the early stages of pregnancy in the rabbit.

Copper wire intrauterine devices (CuIUD) were surgically inserted into mature female rabbits 15 days prior to artificial insemination. Gold wire intrauterine devices and sham surgery served as controls. Animals were autopsied 48, 72, 96, 120, 144, and 192 hours after artificial insemination.

The effect of a copper intrauterine device on the uterine histology and progestational response in pregnant and immature rabbits.

A copper wire intrauterine device (GuIUD) was inserted into mature female rabbits 14 days prior to artificial insemination (AI), and its effect on the histology of the pregnant uterus was studied 48 to 192 hours after AI. In a related study, estrogen-primed immature femal rabbits were fitted with a device consisting of 321 mm of copper wire wound around a 17-mm plastic carrier and treated subcutaneously for 5 days with 0.1 mg of progesterone daily.

Uterine copper distribution in monkeys implanted with copper-carrying intrauterine devices.

Chemical and histochemical analyses were carried out on uteri of four monkeys in which plastic IUDs or Cu-IUDs had been implanted for 36 to 43 days. The mean uterine copper content of the plastic-treated animals was 1.1 mug/gm (mean of two), while this value for the Cu-IUD treated monkeys was 1.