Relative role of caloric restriction and exercise training upon susceptibility to isoproterenol-induced myocardial infarction in male rats.

To determine the relative effect of body weight and physical inactivity on susceptibility to drug-induced myocardial infarction, randomly selected groups of 100-day-old male Sprague-Dawley rats were subjected to a 10-wk program of exercise training and (or) to caloric restriction followed by two subcutaneous injections of L-isoproterenol. Two groups of rats were fed a restricted diet consisting of minimum calories to maintain body weight and were either exercised (R-Ex) or remained sedentary (R-C), one group was fed ad libitum and subjected to exercise (Ex), and one group remained sedentary (C), but was provided only enough food to maintain body weight in a range similar to Ex rats. Initially, there was no difference between group body weights, but Ex and C rats exhibited a significantly greater final body weight. All Ex, R-Ex, and R-C rats survived the isoproterenol injections, but 50% of C rats died. Group C rats exhibited significantly greater activity of total plasma lactate dehydrogenase (LDH), whereas R-Ex rats had the lowest total LDH activity (p less than 0.05). R-Ex and R-C rats had a significantly lower activity of plasma LDH-1, the heart isozyme, than did the heavier Ex and C rats. More specifically, R-C rats exhibited a significantly decreased amount of plasma LDH-1 activity when compared with Ex rats, indicating that smaller, untrained rats had less myocardial damage than the heavier, exercise-trained rats. These data suggest that either exercise or maintenance of body weight is beneficial toward prevention of the drug-induced myocardial infarction, but when weight maintenance is combined with exercise additional protection is provided.

Cocaine/polydrug use in pregnancy: two-year follow-up.

The impact of cocaine on pregnancy and neonatal outcome has been well documented over the past few years, but little information regarding long-term outcome of the passively exposed infants has been available. In the present study, the 2-year growth and developmental outcome for three groups of infants is presented: group 1 infants exposed to cocaine and usually marijuana and/or alcohol (n = 106), group 2 infants exposed to marijuana and/or alcohol but no cocaine (n = 45), and group 3 infants exposed to no drugs during pregnancy. All three groups were similar in racial and demographic characteristics and received prenatal care through a comprehensive drug treatment and follow-up program for addicted pregnant women and their infants. The group 1 infants demonstrated significant decreases in birth weight, length, and head circumference, but by a year of age had caught up in mean length and weight compared with control infants. The group 2 infants exhibited only decreased head circumference at birth. Head size in the two drug-exposed groups remained significantly smaller than in control infants through 2 years of age. On the Bayley Scales of Infant Development, mean developmental scores of the two groups of drug-exposed infants did not vary significantly from the control group, although an increased proportion of group 1 and 2 infants scored greater than two standard deviations below the standardized mean score on both the Mental Developmental Index and the Psychomotor Developmental Index compared with the control infants. Cocaine exposure was found to be the single best predictor of head circumference.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of maternal and foetal adrenal activity in the development of the rat mammary gland near term.

The essential role of adrenal corticosteroids in the initiation of mammary gland secretory activity near term in the rat has been investigated. Mammary gland DNA and RNA were estimated as a quantitative indication of the extent of mammary gland development. Maternal adrenalectomy or hypophysectomy resulted in a decrease in the mammary gland RNA:DNA ratio. Treatment of adrenalectomized animals with cortisol acetate completely restored the RNA:DNA ratio to the control level. Treatment of hypophysectomized animals with cortisol acetate resulted in an increase in the RNA:DNA ratio but did not restore the ratio to the control level. Removal of the pups had no effect on the RNA:DNA ratio. The findings are discussed in relation to the foetal and maternal contribution to the level of glucocorticoids in the circulation and with respect to changes in mammary gland sensitivity to lactogenic stimulation near term.

Three-year outcome of children exposed prenatally to drugs.

OBJECTIVE: To evaluate the 3-year behavioral and developmental outcome of children prenatally exposed to maternal substances of abuse. METHOD: Ninety-three children exposed prenatally to cocaine and other drugs taken by the mother during pregnancy (Group 1), 24 polydrug/noncocaine exposed children (Group 2), and 25 nonexposed children (Group 3) were evaluated at 3 years of age as part of a longitudinal prospective study of the impact of intrauterine substance exposure on long-term outcome. The Stanford-Binet Intelligence Scale: Fourth Edition(SBIS) was administered by examiners blinded to the exposure background of the children, and a pediatrician performed a complete medical evaluation on all the children. The children's primary caregiver completed the Achenbach Child Behavior Checklist. Stepwise multiple regression procedures were used to determine the factors that best predicted 3-year growth, intelligence, and behavior. RESULTS: Groups 1 and 2 differed from Group 3 on head circumference. Group 1 scored lower than Group 3 on SBIS Verbal Reasoning. Group 2 scored Slower than Group 3 on SBIS Abstract/Visual Reasoning. Cocaine exposure predicted poor verbal reasoning. Marijuana exposure predicted poor abstract/visual reasoning. Examiner rating predicted intellectual outcome and caregiver ratings. Caregivers rated exposed children as more aggressive than nonexposed. CONCLUSION: Contrary to information in the popular media, not all substance-exposed children suffer the same poor prognosis. In fact, generalizations about the fate of drug-exposed children must await additional research into the outcome of the broader population of drug-exposed children, examining the roles of maternal and environmental factors across a variety of geographic locations and socioeconomic levels.

Effects of thyroxine and exercise on the glandular and plasma levels of corticosterone in the male rat.

The results presented here demonstrates that the thyroid gland is essential for normal corticosterone production. They further show that exercise stimulates this production whether the thyroid gland is present or not. The release or metabolism of corticosterone seems dependent upon an intact thyroid gland since plasma levels of corticosterone are decreased during exercise if the thyroid is absent. The administration of thyroxine is not sufficient to renew these levels.

Inhibition of experimental lactational mammary gland growth in the rat with exogenous estrogen and progesterone.

PIP: To determine if the combination of estrogen and progesterone during pregnancy inhibits only the secretory capacity of the mammary gland or if it also inhibits the mitotic activity associated with lactogenesis, 113 virgin female Sprague-Dawley rats were ovariectomized and injected daily for 20 days with 2 mcg of 17beta-estradiol-3 benzoate and 6 mg of progesterone (EP). Then in 4 groups daily, injections were given of either cortisol (C), prolactin (L), growth hormone (G), or a combination of all 3 hormones, for 3 days following the last injection of EP. In another series of 4 groups, the injections of EP were continued along with the above 3 hormones. The structural and functional status of the mammary glands were estimated by measurement of DNA, RNA, and nitrogen content. Details of methods used are given. Only the group treated with C showed the maximum lactational activity with significant elevations in DNA, RNA, and nitrogen content of the mammary glands. When EP was given along with C, G, and L, all hormonally induced increases in DNA, RNA, and nitrogen were inhibited. Results were thought to indicate that, in the rat, levels of EP during normal pregnancy hold milk secretion in abeyance until parturition and also block the particular type of mitotic growth phase associated with early lactation.^ieng

Adrenocortical function in response to myocardial necrosis in exercise-trained rats.

Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone was determined in exercise-trained rats. Virgin, male rats, 100 days of age, were trained for an 11-wk period by treadmill running. Following the training program, rats were subjected to two subcutaneous injections of l-isoproterenol 24 h apart and killed 24 h after the second injection. All exercise-trained rats survived isoproterenol treatment, while 44% of the control rats died. Plasma corticosterone concentrations were elevated only in exercise-trained rats treated with isoproterenol. Control rats treated with isoproterenol had plasma corticosterone concentrations similar to that in control and exercise-treated rats given placebo injections. Exercise training reduced adrenocortical responsiveness to ACTH in vitro, but isoproterenol treatment increased in vitro responsiveness to ACTH in exercise-trained and control rats. Total unstimulated corticosterone secretion rates in vitro were similar. The reason for better rat survival in exercise-trained rats is unknown; however, improved energy metabolism, depressed aldosterone secretion, or both are suggested as reasons for the better survival of exercise-trained rats.

Temporal patterns of cocaine use in pregnancy. Perinatal outcome.

Seventy-five cocaine-using women enrolled in a comprehensive perinatal care program were divided into two groups: those who used cocaine in only the first trimester of pregnancy (group 1 [N = 23]) and those who used cocaine throughout pregnancy (group 2 [N = 52]). Perinatal outcomes of these pregnancies were compared with perinatal outcomes of a matched group of obstetric patients with no history or evidence of substance abuse (group 3 [N = 40]). Group 2 women had an increased rate of preterm delivery and low-birth-weight infants as well as an increased rate of intrauterine growth retardation. Group 1 women had rates of these complications similar to the drug-free group. Mean birth weight, length, and head circumference for term infants were reduced in only the group 2 infants. However, both groups of cocaine-exposed infants demonstrated significant impairment of orientation, motor, and state regulation behaviors on the Neonatal Behavioral Assessment Scale.

Cocaine and pregnancy: clinical and toxicological implications for the neonate.

Recent studies show that the rate of cocaine use by pregnant women in the United States is much higher than realized hitherto, and an increasing number of infants are being born to cocaine-using mothers. In an ongoing research project to study the effects of cocaine on pregnancy outcome, we studied 70 infants born to cocaine-using women. These infants were matched to a drug-free comparison group selected from the population of the same hospital: children of pregnant women of a similar racial and socioeconomic distribution, but with no history or evidence of licit or illicit drug use during pregnancy. Cocaine-exposed infants had lower birth weight, shorter gestation, and a smaller head circumference than control infants. Cocaine-exposed infants also had neurobehavioral abnormalities at initial evaluation and a higher rate of perinatal complications. Toxicological evaluation of urines of neonates born to cocaine-using women showed that benzoylecgonine, a primary metabolite of cocaine, persisted in the urines for as long as 120 h after delivery. We discuss the role of the immature fetal and neonatal system in the clinical and toxicological outcome of the infant, and emphasize that further long-term studies of this will be needed.

Adrenocortical function in aging exercise-trained rats.

Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone were determined in exercise-trained rats. Rats, 100, 200, and 300 days of age, were trained for a 10-wk period by treadmill running. Following the training program, rats were subjected to an acute bout of swimming. Acute swimming elevated plasma corticosterone concentrations in all age groups. At 170 days of age, the plasma corticosterone concentration following swimming was higher in exercise-trained rats than in controls. The opposite was true of acutely swum rats at 270 and 370 days of age. Acute swimming elevated the in vitro adrenal gland response to adrenocorticotropic hormone stimulation in control rats at all ages and in trained rats at 170 days of age. The in vivo relationship of epinephrine and the pituitary adrenal system is suggested as a mechanism which could have caused this response. The relationship of secretion rates to plasma corticosterone concentrations indicated that extra-adrenal mechanisms, such as decreased turnover, were also responsible for the elevated plasma corticosterone levels observed in response to acute swimming.