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Biomedical subjects

R W Moore

Publications and source records attributed to R W Moore.

At least 55 records · Page 3Linked to original sources
PubMed1992

In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Effects on androgenic status.

When administered in overtly toxic doses to postpubescent rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces a variety of adverse effects on the male reproductive system including a decrease in plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could potentially impair male reproductive function by disrupting the development of sex organs and/or causing incomplete sexual differentiation of the central nervous system. To determine whether TCDD can reduce androgen concentrations perinatally and/or impair androgen-dependent perinatal development, pregnant Holtzman rats were treated with 1.0 micrograms TCDD/kg or vehicle on Day 15 of gestation. Plasma testosterone concentrations in fetal males were significantly reduced by TCDD on Gestation Days 18 through 21. The surge in plasma testosterone concentrations shortly after birth was also significantly reduced, as was anogenital distance, an androgen-dependent parameter. To further investigate the effects of perinatal TCDD exposure on the male reproductive system, rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated from birth through sexual maturation. This report describes their growth, physical development, and androgenic status (i.e., androgen concentrations and androgen-dependent structures and functions); effects on spermatogenesis, testicular histology, sexual behavior, and fertility are reported separately. There was little evidence that TCDD caused maternal toxicity. Signs of overt toxicity in offspring were limited to an 8% reduction in live births (highest dose only) and to decreases in body weight gain and feed consumption (two highest doses only) which disappeared by early adulthood. With respect to androgenic status, maternal TCDD doses as low as 0.16 micrograms/kg produced significant dose-related decreases in the anogenital distance of 1- and 4-day-old males, delays in testicular descent, and decreases in seminal vesicle and ventral prostate weights. The reductions in organ weights were observed when rats were at the juvenile, pubertal, postpubertal, and mature stages of sexual development. Plasma testosterone and 5 alpha-dihydrotestosterone concentrations tended to be reduced at these times (though not significantly), while plasma luteinizing hormone concentrations were generally unaffected. Collectively, these results demonstrate that perinatal TCDD exposure alters the androgenic status of male rats from the fetal stage into adulthood, and that TCDD can affect androgenic status without causing overt toxicity. In rats, the male reproductive system appears to be more sensitive to the toxic effects of in utero and lactational TCDD exposure than any other organ or organ system studied thus far.

Animals↗
PubMed1992

In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 2. Effects on sexual behavior and the regulation of luteinizing hormone secretion in adulthood.

When administered to postpubescent male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could impair sexual differentiation of the central nervous system (CNS) and thereby alter male reproductive function. To examine this possibility, sexually dimorphic functions were assessed in male rats born to dams given TCDD (0.064, 0.16, 0.40, and 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation. Masculine sexual behavior was assessed at approximately 60, 75, and 115 days of age. When TCDD-exposed males were caged with receptive control females their mount, intromission, and ejaculation latencies were far longer than normal; these effects were dose-related and were statistically significant at maternal doses as low as 0.16, 0.064, and 0.16 micrograms TCDD/kg, respectively. The numbers of mounts and intromissions to ejaculation were slightly increased by TCDD, while copulatory rates [(mounts+intromissions)/min] were significantly decreased at the three highest maternal doses. Except for a modest increase at the higher doses, TCDD had little effect on the postejaculatory interval. Following assessment of their masculine sexual behavior, the males were castrated and 6 weeks later tested for feminine sexual behavior (lordosis). After being primed with estradiol benzoate and treated with progesterone, males displayed dose-related increases in lordosis quotient and lordosis intensity in response to being mounted by another male. These effects were statistically significant at maternal doses as low as 0.16 and 0.40 micrograms TCDD/kg, respectively. To determine if perinatal TCDD exposure alters the sexually dimorphic regulation of luteinizing hormone (LH) secretion, the LH secretory responsiveness of the hypothalamic/pituitary axis to ovarian steroids was assessed. In unexposed, gonadectomized female rats primed with estradiol benzoate, progesterone injection produced a surge in plasma LH concentrations, whereas in similarly treated control males, plasma LH concentrations were unaffected by progesterone. In castrated, estradiol benzoate-primed male rats that were perinatally exposed to TCDD, progesterone treatment produced dose-related increases in plasma LH concentrations that were statistically significant at the two highest maternal doses. We conclude that in utero and lactational exposure to small amounts of TCDD demasculinizes and feminizes male rats. These effects cannot be accounted for by TCDD-induced hypophagia, modest reductions in adult plasma androgen concentrations, possible nonspecific changes in motor activity, or possible reductions in penile sensitivity to sexual stimulation. The altered sexual behaviors and LH secretion were observed when nearly all TCDD had been excreted (as evidenced by uninduced hepatic ethoxyresorufin-O-deethylase activity).(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1992

In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability.

When administered in overtly toxic doses to postweanling male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day-old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm reserves caused by perinatal TCDD exposure since rats produce and ejaculate far more sperm than are required for normal fertility. The TCDD-induced reduction in spermatogenesis cannot be accounted for by concurrent effects on plasma follicle-stimulating hormone or androgen concentrations or by undernutrition. To investigate the nature of the spermatogenic lesion, leptotene spermatocyte to Sertoli cell ratios were determined.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1992

Immune responses and increased training of the elite athlete.

Ten elite male runners (age, 29.8 +/- 1.7 yr; maximum oxygen consumption, 65.3 +/- 4.9 ml.kg-1.min-1; 10-km times, 31 min 43 s +/- 1 min 46 s) deliberately increased training schedules by an average of 38% for 3 wk. Resting heart rate and maximal oxygen intake were unchanged, but the heart rate response to acute exercise was decreased. Following heavy training, blood samples taken at rest showed trends to a decreased helper/suppressor cell ratio, an increased phytohemagglutinin (PHA)- and concanavalin (ConA)-stimulated lymphocyte proliferation, and a decreased production of immunoglobulins IgG and IgM. Whereas PHA-stimulated lymphocyte proliferation was initially unchanged by acute exercise, after 3 wk of heavy training the same acute exercise caused an 18% suppression of proliferation. Acute exercise following heavy training did not alter pokeweed-stimulated IgG or IgM synthesis. There was no correlation between changes in lymphocyte subpopulations, helper/suppressor ratios, and mitogen-induced cellular proliferation. The immune system of endurance-trained athletes at rest seemed to tolerate the stress of heavy training, but superimposition of a bout of acute exercise on the chronic stress of heavy training resulted in immunosuppression, which was transient and most likely not of clinical significance.

Adult↗
PubMed1992

Amount of smoking independently predicts carotid artery atherosclerosis severity.

BACKGROUND AND PURPOSE: Cigarette smoking is correlated with extracranial carotid artery plaque thickness. Our aim in the present study was to determine whether the level of prior cigarette use is a significant predictor of carotid artery plaque thickness when age, history of hypertension, and history of diabetes are controlled. METHODS: We studied a continuous sample of 790 patients with a history of smoking referred for diagnostic ultrasound imaging of the carotid arteries. Subjects (mean age 61 years) had an average of 51 pack-years of cigarette use. History of hypertension was present in 44% and history of diabetes in 18%. RESULTS: Right and left maximum carotid artery plaque thicknesses were averaged for each patient; the average of this value for all 790 subjects was 1.9 mm. In bivariate analysis, age (p less than 0.0001), pack-years (p less than 0.0001), history of hypertension (p = 0.0003), and history of diabetes (p = 0.037) were each positively associated with carotid artery plaque thickness. In multiple regression analysis, age (p less than 0.0001), pack-years (p = 0.0005), and history of hypertension (p = 0.0044) were statistically significant independent predictors of carotid artery plaque thickness, but history of diabetes (p = 0.2451) was not. CONCLUSIONS: In smokers, the level of cigarette use is associated with an acceleration of carotid artery atherosclerosis development. This effect is independent of age, hypertension, and diabetes. These results support smoking abatement as an important element to stroke prevention in clinical practice.

Adolescent↗
PubMed1991

2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits steroidogenesis in the rat testis by inhibiting the mobilization of cholesterol to cytochrome P450scc.

Testosterone synthesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats is decreased because pregnenolone production by the testis is inhibited. This inhibition can only be caused by a reduction in the activity of the mitochondrial enzyme which converts cholesterol into pregnenolone (cytochrome P450scc), and/or by an impairment in the multistep process by which luteinizing hormone (LH) stimulates the mobilization of cholesterol to this enzyme. Seven days after rats were treated with 100 micrograms TCDD/kg, testicular cytochrome P450scc activity (assayed with 20 alpha-hydroxycholesterol as substrate) was decreased to 45% of control. If this decrease were responsible for the inhibition of testicular steroidogenesis in vivo, substrate pools for cytochrome P450scc in the testis would be increased. Yet TCDD decreased the amount of cholesterol that was readily available to cytochrome P450scc in isolated testis mitochondria (the reactive cholesterol pool), even when steroidogenesis was maximally stimulated in vivo with the LH analogue human chorionic gonadotropin (hCG). These decreases in substrate pools were not due to a reduction in mitochondrial capacity for reactive cholesterol. We conclude that the 55% decrease in cytochrome P450scc activity is not severe enough to inhibit testicular steroidogenesis in vivo. Instead, TCDD must act by inhibiting the LH-stimulated mobilization of cholesterol to cytochrome P450scc. This conclusion is supported by two observations. First, when pregnenolone formation was blocked by treating rats with the cytochrome P450scc inhibitor aminoglutethimide, TCDD greatly reduced the rate at which hCG caused reactive cholesterol to accumulate in testis mitochondria in vivo. Second, TCDD inhibited both testosterone synthesis and the mobilization of cholesterol to cytochrome P450scc within 1 day. The steroidogenic inhibition does not appear to be due to an LH receptor defect, because TCDD inhibited dibutyryl cAMP- and hCG-stimulated steroid secretion by isolated perfused testes to comparable extents. We conclude that TCDD inhibits testicular steroidogenesis predominantly if not exclusively by inhibiting the mobilization of cholesterol to cytochrome P450scc, and that this inhibition occurs subsequent to cAMP formation.

Animals↗
PubMed1991

The influence of the hospital financial officer.

The power and influence of financial officers in large, independent hospitals was examined through their involvement in decisions. Chief financial officers (CFOs) find their role as members of the management team relatively ambiguous and probably underutilized.

Decision Making, Organizational↗
PubMed1990

2,3,7,8-tetrachlorodibenzo-p-dioxin increases the potency of androgens and estrogens as feedback inhibitors of luteinizing hormone secretion in male rats.

Tetrachlorodibenzo-p-dioxin (TCDD) decreases plasma androgen concentrations in male rats, without increasing plasma luteinizing hormone (LH) concentrations. If plasma LH concentrations had increased appropriately, plasma androgen concentrations in these animals would have returned to normal. The mechanism by which TCDD prevents the compensatory increase in plasma LH concentrations was therefore investigated. TCDD was found to have no effect on the plasma disappearance of iv administered LH. Therefore, the failure of plasma LH concentrations to rise was not due to increased clearance of LH from the circulation, but rather to an effect of TCDD on LH synthesis and/or secretion by the pituitary. In the absence of gonadal steroids (i.e., in castrated rats) TCDD did not prevent the compensatory increase in plasma LH concentrations from occurring. This was shown by 20-fold increases in plasma LH concentrations in both control and TCDD-treated rats 1 week after castration. Thus, (1) the presence of gonadal steroids is required for TCDD to prevent the compensatory increase in plasma LH concentrations, and (2) TCDD does not impair LH secretion by acting, itself, as an androgen or estrogen. TCDD treatment also did not affect pituitary LH content in castrated, testosterone-implanted rats. The above findings demonstrate that TCDD does not decrease the maximum rate at which the pituitary can synthesize and secrete LH. Rather, TCDD alters the feedback regulation of LH secretion when gonadal steroids are present. To determine if TCDD affects the potency of testosterone and its metabolites 5 alpha-dihydrotestosterone and 17 beta-estradiol as feedback inhibitors of LH secretion, rats were dosed with TCDD, castrated, and implanted with sustained-release capsules containing graded amounts of each steroid. Seven days later, the potencies of all three hormones as feedback inhibitors of LH secretion were increased by TCDD, with little effect on their plasma concentrations. The TCDD dose dependence for the increased effectiveness of testosterone as a feedback inhibitor of LH secretion (ED50 10 micrograms/kg) was similar to that reported for the imbalance between plasma LH and androgen concentrations (ED50 15 micrograms/kg). Also, time courses for both responses were similar; each was detected within 1 day of TCDD dosing and each was fully developed after 7 days. We conclude that the mechanism by which TCDD prevents the compensatory increase in plasma LH concentrations in male rats is by increasing the potencies of androgens (and estrogens) as feedback inhibitors of LH secretion.

Animals↗
PubMed1990

Androgenic deficiency in male rats treated with perfluorodecanoic acid.

Effects of perfluorodecanoic acid (PFDA, 20-80 mg/kg, ip) on the androgenic status of sexually mature male rats were investigated 7 days after treatment. PFDA decreased plasma androgen concentrations in a dose-dependent fashion with an ED50 of approximately 30 mg/kg. The highest dose of PFDA decreased plasma testosterone and 5 alpha-dihydrotestosterone concentrations to 12 and 18%, respectively, of ad libitum-fed control (ALC) values. Secondary to the decreased plasma androgen concentrations were dose-related decreases in the weights and epithelial heights of accessory sex organs. Results from pair-fed control (PFC) rats show that hypophagia in PFDA-treated rats was not a major cause of the low plasma androgen concentrations. When rats were castrated and implanted with testosterone-containing capsules, PFDA-treated and ALC rats had similar plasma testosterone concentrations and secondary sex organ weights. Therefore, the androgenic deficiency in intact PFDA-treated rats does not result from increased plasma clearance of androgens. Rather, PFDA must cause the androgenic deficiency by decreasing the secretion of testosterone from the testis. The decrease in testosterone secretion does not appear to result from a decrease in plasma luteinizing hormone (LH) concentrations, because plasma LH concentrations were not significantly altered by PFDA treatment. This finding suggests that PFDA treatment decreases testicular responsiveness to LH stimulation. The observation that PFDA treatment reduced the secretion of testosterone by testes stimulated in vitro with the LH analog human chorionic gonadotropin demonstrates that this is the case. In addition, since plasma LH concentrations did not increase in response to the low plasma androgen concentrations in PFDA-treated rats, we suggest that PFDA disrupts the normal feedback relationship which exists between plasma androgen and LH concentrations.

Animals↗
PubMed1990

Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation.

The mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment decreases testosterone (T) secretion without significantly altering plasma luteinizing hormone (LH) concentrations was investigated. Testes from sexually mature Sprague-Dawley rats dosed 7 days earlier with 100 micrograms TCDD/kg secreted 30-75% less T than did testes from control rats when perfused in vitro with the LH analog human chorionic gonadotropin (hCG). This decrease confirms that testicular responsiveness to LH, the hormone which regulates T secretion in vivo, is impaired by TCDD treatment. Because TCDD also reduced intratesticular T content, the decrease in T secretion is due to an inhibition of T synthesis rather than to a failure of the secretion process. These effects of TCDD are not secondary to undernutrition, because perfused testes from feed-restricted control rats were fully hCG responsive. TCDD treatment neither increased the hCG-stimulated secretion of any T precursor nor significantly decreased the efficiency with which testes converted the pregnenolone (PREG) they synthesized into T (PREG is the initial steroidogenic intermediate). In addition, TCDD did not inhibit T secretion when steroidogenesis was supported by exogenous PREG at approximately the in vivo rate. We conclude that TCDD does not inhibit the conversion of PREG to T. The inhibition of T biosynthesis must instead result from an inhibition of PREG formation. The finding that TCDD treatment substantially decreased the rate at which hCG-perfused testes secreted PREG and its metabolites (a decrease seen across all hCG concentrations) confirms this conclusion. This inhibition of LH/hCG-stimulated PREG formation by TCDD must be due to a reduction in the activity of the enzyme which converts cholesterol to PREG (cytochrome P450scc), and/or an impairment in the multistep process responsible for mobilizing cholesterol to this enzyme.

Animals↗
PubMed1990

Altered regulation of pituitary gonadotropin-releasing hormone (GnRH) receptor number and pituitary responsiveness to GnRH in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases the potency of androgens as feedback inhibitors of luteinizing hormone (LH) secretion. Our objectives were to determine if this increase is due to pituitary or hypothalamic dysfunction (or both), and to investigate the mechanism by which TCDD produces this effect. Seven days after dosing, TCDD inhibited the compensatory increases in (i) pituitary gonadotropin-releasing hormone (GnRH) receptor number, (ii) LH secretory responsiveness of the pituitary to GnRH, and (iii) plasma LH concentrations which should have occurred in response to TCDD-induced decreases in plasma testosterone concentrations. TCDD did not inhibit these compensatory responses in the absence of testicular hormones, while treatment of castrated rats with testosterone restored the ability of TCDD to prevent these increases. These findings demonstrate that TCDD alters the androgenic regulation of pituitary GnRH receptor number and pituitary responsiveness to GnRH stimulation. The pituitary is therefore a target organ for TCDD; whether a hypothalamic defect is also involved in the altered regulation of LH secretion was not resolved. The compensatory increases in pituitary GnRH receptor number and plasma LH concentration elicited by low plasma testosterone concentrations were inhibited by similar doses of TCDD (ED50 20 micrograms TCDD/kg for both responses). We concluded that TCDD increases the potency of androgens as feedback inhibitors of LH secretion by increasing their potency as regulators of both pituitary GnRH receptor number and GnRH responsiveness. This is the first demonstration that TCDD treatment (i) affects pituitary responsiveness to a hormone secreted by a peripheral organ (testosterone), and (ii) alters the regulation of pituitary responsiveness to a hypothalamic hormone (GnRH).

Androgens↗
PubMed1990

Thickness of carotid artery atherosclerotic plaque and ischemic risk.

Noninvasive duplex scanning of carotid artery atherosclerotic plaque was performed in 286 consecutive patients referred to a cerebrovascular diagnostic laboratory. The presence and thickness of such plaque in the region of the carotid bifurcation were examined for association with the degree of vessel stenosis, age, sex, smoking history, history of prior transient ischemic attack or stroke, and systemic manifestations of atherosclerotic disease. Atherosclerotic plaque thickness was positively correlated with degree of vessel stenosis (P less than 0.0001). Both parameters were independent predictors of cerebrovascular events but plaque thickness was a better predictor of prior transient ischemic attacks (P less than 0.05), and vessel stenosis was a better predictor of prior stroke (P less than 0.005). Patient age (P less than 0.001) and pack-years of cigarette use (P less than 0.001) were independent positive predictors of carotid atherosclerotic plaque thickness. The greatest effect of smoking and atherosclerotic plaque thickness was seen in heavy smokers younger than age 55. Both carotid artery plaque thickness and pack-years of smoking were significant independent predictors of other systemic manifestations of atherosclerotic disease (P less than 0.05). Such noninvasive scanning of carotid artery atherosclerotic plaque demonstrates the significant role of age and smoking in the progression of disease. It also suggests a significant role for carotid atherosclerotic artery plaque in the pathophysiology of cerebrovascular events, especially transient ischemic attacks, even prior to the production of a flow-limiting stenosis. Finally, noninvasive screening of carotid artery plaque may provide a useful marker for the patient at risk for systemic atherosclerotic disease and identify the patient for whom maximal atherosclerotic risk factor modification is needed.

Adult↗
PubMed1989

Plasma concentrations of pituitary hormones in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats.

Experiments were conducted to test the hypothesis that acute TCDD toxicity is associated with pituitary hypofunction. Sexually mature male Sprague-Dawley rats were given graded doses of TCDD (0-100 micrograms/kg) and evaluated 7 days later. Despite pronounced hypophagia and body weight loss, plasma concentrations of growth hormone (GH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were not significantly affected by any dose of TCDD. Only prolactin (PRL) concentrations were reduced, while, as previously reported, thyroid-stimulating hormone concentrations were elevated. Also, plasma LH, PRL, and adrenocorticotropic hormone (ACTH) concentrations were not significantly affected 1, 2, 3, 4, 5, or 7 days after a single dose of TCDD (50 micrograms/kg). We conclude that (1) pituitary hypofunction is not a major cause of the initial stages of acute TCDD toxicity, (2) growth retardation in TCDD-treated rats is not the result of a deficiency of GH, (3) alterations in plasma corticosterone concentrations are due to altered responsiveness of the adrenal to ACTH stimulation rather than to changes in plasma ACTH concentrations, and (4) that impaired spermatogenesis is not associated with a decrease in plasma FSH concentrations. In addition, the lack of a consistent effect on plasma PRL concentrations suggests that alterations in plasma PRL concentrations do not play a critical role in the toxicity of TCDD. Finally, because TCDD treatment causes a serious androgenic deficiency without increasing the rates at which androgens are catabolized or excreted, the fact that plasma LH concentrations were unaffected indicates that TCDD treatment must reduce the responsiveness of the testis to LH stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Toe scratches cause scabby hip syndrome lesions.

Scabs and scratches in the hip region of chicken carcasses have become the single most common cause of downgrading and required trimming at processing in some areas of the United States. Repeatable correlations with microbiological agents, environment, and nutrition have not been observed. The present report provides evidence that scabs and scratches, present at processing, are the result of injuries inflicted by toenails of birds as they climb on one another. Onychectomy (removal of approximately two-thirds of the distal phalanx) of all four digits of each foot prior to chick placement resulted in 3.7 and 4.8-fold reduction in subjective lesion scores and 7 to 10-fold increases in the percentage of USDA Grade A carcasses at a commercial processing plant.

Animals↗
PubMed1988

Response of broiler chickens to dietary supplementation with roxarsone and bacitracin methylene disalicylate in diets containing narasin.

Six trials were conducted at different locations to examine the response of broiler chickens to roxarsone and bacitracin in the form of bacitracin methylene disalicylate (BMD) in the presence of the anticoccidal narasin. All diets contained narasin (80 mg/kg) and were fortified with a factorial arrangement of roxarsone (0 to 50 mg/kg) and BMD (0 or 55 mg/kg). Broilers were grown to market weights with narasin and roxarsone removed from the diets for the final 5 days. Addition of both roxarsone and BMD resulted in significant (P less than .05) improvements in body weight and feed utilization. Response to roxarsone for feed utilization was influenced to some extent by the presence or absence of BMD. Although the response to roxarsone was always positive, the degree of response was lessened by the presence of BMD. This resulted in a significant (P less than .10) interaction between roxarsone and BMD for feed utilization but not for body weight.

Animal Feed↗
PubMed1987

Altered regulation of adrenal steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

A single treatment of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (50 micrograms/kg) produced two distinct effects on adrenal steroidogenesis in rats 13 days post-treatment. In unstressed rats, the very low corticosterone levels early in the light phase (AM) increased 4-fold relative to ad libitum-fed control (ALC) rats, but the peak level of corticosterone that is seen late in the light phase (PM) decreased up to 40% relative to ALC rats. The AM stimulation was also observed in rats pair-fed to compensate for the diminished feed intake of TCDD-treated animals, indicating that the change results from nutritional deprivation. The PM suppression, however, was not observed in pair-fed rats. In rats given a lower dose of TCDD (15 micrograms/kg), there was no AM stimulation, whereas the suppression of the PM diurnal peak of corticosterone was retained. Plasma adrenocorticotropin (ACTH) levels and adrenal size were not changed by these treatments, indicating that TCDD affects adrenal responsiveness. TCDD did not, however, have a significant effect on corticosterone secretion in rats receiving high doses of ACTH. In control animals, the availability of cholesterol to cytochrome P-450scc limits the rate of steroidogenesis. While the specific content of the cytochrome was unaffected by TCDD, cholesterol turnover by this enzyme appeared to be affected following TCDD treatment, as evidenced by small increases in the mitochondrial levels of free cholesterol, reactive cholesterol, and in the proportion of P-450scc complexed with cholesterol relative to both ad libitum- and pair-fed controls. This accumulation of mitochondrial cholesterol following TCDD treatment is consistent with an inhibition of cholesterol metabolism at cytochrome P-450scc in vivo that is removed upon isolation of the mitochondria. These TCDD-induced increases were enhanced substantially in ACTH-stimulated rats, probably because ACTH enhances cholesterol influx into the mitochondria. Normally, substrate availability is rate limiting in cholesterol side-chain cleavage, and the AM stimulation of steroidogenesis by TCDD may result from such increased cholesterol transfer. The inhibition of cholesterol side-chain cleavage resulting from TCDD treatment may, however, only become rate limiting for corticosterone synthesis when cholesterol transfer is more substantially activated, as for peak PM secretion.

Adrenal Cortex Hormones↗
PubMed1986

Hypercholesterolemia and the regulation of adrenal steroidogenesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

Plasma and adrenal cholesterol disposition have been examined to gain further insight into the mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment decreases the diurnal peak in plasma corticosterone concentrations. TCDD induces an increase in plasma cholesterol concentration that is nearly complete on Day 2, at least 2 days before the most pronounced increase in adrenal cholesterol concentration (Days 4-6). This adrenal increase involves both free cholesterol and cholesterol esters, in contrast to the response to dietary hypercholesterolemia where only cholesterol esters increase. Although adrenocorticotropin (ACTH) does not increase adrenal mitochondrial cholesterol in normal rats (cholesterol turnover is faster than cholesterol uptake), this response changes between Days 6 and 9 after TCDD treatment such that ACTH then stimulates accumulation of mitochondrial cholesterol. This additional cholesterol is fully available to cytochrome P-450SCC, as judged both by active cholesterol metabolism in isolated mitochondria and by increased cholesterol-P-450SCC complex formation. The accompanying in vivo suppression of the peak plasma corticosterone concentration suggests a TCDD-induced inhibition of cholesterol side-chain cleavage (SCC). Consistent with this hypothesis, similar effects on adrenal mitochondrial cholesterol were produced by in vivo administration of the cholesterol side-chain cleavage inhibitor, aminoglutethimide, to ACTH-stimulated rats. Although the putative TCDD-induced inhibitory factor is apparently readily lost from mitochondria during preparation, inhibition may be retained in isolated cells. TCDD, therefore, affects adrenal cholesterol regulation by at least two mechanisms. Adrenal cholesterol content increases in part as a consequence of elevated plasma cholesterol, and cholesterol side-chain cleavage becomes partially inhibited in vivo.

Adrenal Glands↗