Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta)

Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non-Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance.     

Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta).

Experiments were conducted measuring the gastrointestinal absorption and elimination of a single dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead was followed for 23 days. Infant monkeys eliminated less and absorbed more orally administered lead. Adult animals excreted more absorbed lead in feces, while urinary excretion between adults and infants was similar. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in significantly greater body burden of lead-210 in infant animals. Blood lead values were increased in the infant animals, and were inversely correlated with body burden and percent absorption of ingested lead.     

The effect of subdermal testosterone filled polydimethylsiloxane implants on spermatogenesis in rhesus monkeys (Macaca mulata).

Previously it was reported that testosterone-filled polydimethyl silicone (PDS) implants induced azoospermia in male rabbits without chronically altering plasma testosterone concentration or the weight or secretory activity of accessory sex glands. Assayable serum luteinizing hormone (LH) and testicular testosterone secretion were completely suppressed. Testosterone emanating from the PDS capsule maintained libido but failed to support spermatogeneis in the rabbits. To test results in subhuman primates, 40 rhesus monkeys were used. Testosterone PDS capsules were prepared so that in groups of 6 each monkey received a daily dose of 0, 9.4, 16, 34, 67, or 150 mcg/pound of body weight. Capsules were implanted sc. After 70 days, animals were sacrificed. Body weights did not change significantly in any treatment group. Seminal vesicle weights increased significantly (p .01) with increased testosterone dosage. prostate gland weights also increased somewhat. Plasma testosterone concentrations were similar to control values with lower doses but increased significantly (p .01) in monkeys receiving the higher doses. Median doses failed to suppress immunoreactive LH concentrations in serum. However, it is thought that immunoreactive LH, as measured by methods used, may not always reflect biologically active LH. The testosterone synthesizing apparatus was not completely inhibited as it had been in rabbits and as shown by in vitro perfusion of tests. Failure to achieve azoospermia in 4 of 6 monkeys receiving 34 mcg of testosterone per pound of body weight per day suggested that species differences exist in the feedback of testosterone regulating LH release. However, spermatogenesis was depressed 5 times below normal in these monkeys. Data suggest that the dose of testosterone needed to induce azoospermia in rhesus monkeys is highly variable and that the effective dose is so narrow that it prevents the use of this testicular androgen as the sole constitutent of a contraceptive formulation for rhesus monkeys. Assuming that the same applies to humans, present results indicate the need for a contraceptive formulation containing not only a potent androgen but also an effective inhibitor of pituitary gonadotropin secretion.     

Initial heterosexual behavior of adolescent rhesus monkeys (Macaca mulatta)

This report describes the first heterosexual encounters of twelve 3-year-old rhesus monkeys, six of each sex. The subjects were all laboratory-born, and were reared in wire cages for the first 8 months of life, accompanied only by their mothers. After these animals were weaned, each was placed in a cage with another animal of the same age and sex. The pairs formed in this way remained intact until the animals were 2 years old. When heterosexual dyads were formed, some of the subjects attacked and bit the animal with which they had been paired, while the members of other pairs established almost immediate rapport as evidenced by mutual grooming and adequate sexual behavior. The initial sexual interactions of most pairs were uncoordinated, but all eventually demonstrated qualitatively species-typical patterns of sexual behavior. Despite their immaturity, two of these pairs succeeded in producing offspring, both of which were healthy.This research was supported by USPHS grants MH-22253 to G. Mitchell, HD-04335 to L. Chapman, and RR-00169 to California Primate Research Center.     

Isoflavone and Protein Constituents of Lactic Acid-Fermented Soy Milk Combine to Prevent Dyslipidemia in Rats Fed a High Cholesterol Diet

A high cholesterol diet induces dyslipidemia. This study investigated whether isoflavone aglycones in lactic acid-fermented soy milk (LFS) improve lipid metabolism in rats fed a high cholesterol diet. Male Sprague-Dawley rats aged seven weeks were fed an AIN-93G diet, a 1% cholesterol diet (a high cholesterol diet), a high-cholesterol diet containing 4% isoflavone extract of LFS (LFS extract diet), a high-cholesterol diet containing 19.4% ethanol-washed LFS (ethanol-washed LFS diet, isoflavone-poor diet), or a high cholesterol diet containing 23.2% intact LFS (intact LFS diet) for five weeks. The plasma total cholesterol (TC) level was increased in the rats fed the LFS extract diet compared with those fed the high cholesterol diet. The TC level was decreased by the intact LFS and ethanol-washed LFS diets. The cholesterol-lowering effect was stronger in the rats fed the intact LFS diet than those fed the ethanol-washed LFS diet. The plasma triglyceride (TG) level was unchanged in the rats fed the LFS extract diet, but it decreased in rats fed the intact LFS and ethanol-washed LFS diets. Although, compared with the high cholesterol diet, the LFS extract and ethanol-washed LFS diets did not reduce hepatic cholesterol and TG, both levels were remarkably lowered by the intact LFS diet. These results suggest that the improvement in lipid metabolism of rats fed a high-cholesterol diet containing LFS isoflavone aglycones is not due to an independent effect but due to a cooperative effect with soy protein.     

Effect of vaginally administered (Ala(8,13,18))-magainin II amide on the morphology of implantation stage endometrium in the rhesus monkey (Macaca mulatta).

Intravaginal administration of an anti-microbial agent, (Ala^8,13,18)-magainin II amide, during blastocyst implantation inhibits pregnancy establishment in a dose-related manner in the rhesus monkey (Macaca mulatta). In the present study, mated female rhesus monkeys were vaginally inserted with tampons containing vehicle (Group 1; N = 5) and test agent (magainin, 0.5 mg/animal; Group 2; N = 6) on cycle day 20. Endometrial tissue samples were collected on Cycle Day 24 from all monkeys and processed for morphometric and ultrastructural analysis. Concentrations of estradiol-17β, progesterone, and chorionic gonadotrophin in peripheral circulation were determined, which revealed that two monkeys in Group 1 were pregnant while no animals were pregnant in Group 2. Endometrial morphology, however, revealed histologic evidence of pregnancy in three out of the six magainin-treated animals. It appears that intra-vaginal administration of magainin II amide had a marginal effect on the implantation stage endometrium and the initiation of the implantation process in the rhesus monkey.     

Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized,Double-Blind,Placebo-Controlled Study)

Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33; 18–70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130–200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.