Martin J. J. Ronis

The health implications of soy infant formula

Soy formula (SF) has been fed to millions of infants worldwide. It has been shown to promote growth and development as well as milk-based formula (MF). Controversy has developed over the adequacy and safety of SF. Most concerns are based on in vivo and in vitro data that raise the possibility of estrogenic effects of isoflavones contained in SF. There are few studies of children who were fed SF, and thus insufficient data are available to judge if SF feeding results in clinically significant developmental effects and if there are any long-term health consequences (adverse or beneficial). However, the Arkansas Childrens Nutrition Center is conducting a prospective longitudinal study comparing growth, development, and health of breastfed children with formula-fed (SF and MF) children from birth through age 6 y. After 5 y of study, children in all 3 groups (n > 300) are growing and developing within normal limits, and there are no indications of adverse effects in the soy-fed children. Neonatal pig studies comparing SF, MF, and breast milk (BM) have shown diet-specific gene expression profiles in various target tissues. Therefore, although SF differed significantly from BM, MF also differed from BM, and SF differed from MF. Nonetheless, these animals grew and developed normally, and SF piglets had several health benefits (eg, increased bone quality) and no observable adverse effects. Thus, to date, our results suggest that SF supports normal growth and may have advantages in promoting bone development.

Effects of tributyltin on the Phase I testosterone metabolism and steroid titres of the clam Ruditapes decussata

Abstract The effects of tributyltin (TBT) on the cytochrome P450 monooxygenase system of the clam Ruditapes decussata have been evaluated. Digestive gland microsomes were observed to catalyze the oxidative metabolism of testosterone. The metabolites detected were androstenedione, dihydrotestosterone, dihydroandrostenedione, 6β-, 6α-, 2α- and 2β-hydroxytestosterone, estrone and 17β-estradiol. The effect of 0.1 and 1.0 mM TBT in the incubation mixture lead to a significant reduction in the total metabolism rate (28–39%) and changes in the metabolite profile, viz. a significant decrease in the formation of androstenedione (51–54%) and a stimulation in the formation of hydroxylated metabolites. To fully understand and validate the in vitro data, clams were exposed to different concentrations of TBT in water (0.1, 0.45 and 2.27 μg l−1 of TBT as Sn) for 7 days. When digestive gland microsomes of control and exposed organisms were assayed for their ability to metabolize testosterone, important changes were observed in the pattern of the metabolites formed. There was a significant increase in the formation of 6α-hydroxytestosterone and a dose-dependent decrease in the aromatization of testosterone to estrone and estradiol. Moreover, investigation of steroid concentrations by radioimmunoassay revealed an increase in testosterone in the tissue of TBT-exposed clams. These observations indicate a significant interaction of TBT with androgen metabolism in the clam Ruditapes decussata which may contribute to the masculinization of clam physiology.

Carbohydrate-Responsive Gene Expression in the Adipose Tissue of Rats

Although obesity is often associated with high-fat diets, it can develop from a variety of meal patterns. Excessive intake of simple carbohydrates is one consistent eating behavior leading to obesity. However, the impact of overconsumption of diets with high carbohydrate to fat ratios (C/F) on body composition and global adipose tissue gene expression remains unclear. We used total enteral nutrition to evaluate the effects of caloric intake and C/F on body weight gain and development of obesity. Female Sprague Dawley rats were fed diets with either low C/F or high C/F (HC) (reflecting a 19.5-fold increase in C/F) at two levels of caloric intake: 187 or 220 kcal/kg(3/4) x d (15% excess) for 4 wk. At the end of the study period, rats fed HC diets had about 20% higher body weight at either caloric intake compared with rats fed low C/F diets (P < 0.05). Body composition (assessed by nuclear magnetic resonance, computerized tomography, and adipose tissue weights) revealed higher percent fat mass (P < 0.05) in HC rats. Obesity was associated with increased serum resistin, leptin, fasting hyperinsulinemia, and insulin resistance after an oral glucose challenge (P < 0.05). Microarray analyses of adipose tissues revealed HC diets led to changes in 270 and 464 transcripts at 187 and 220 kcal/kg(3/4) x d intakes. Genes regulating glucose transport, glycolysis, fatty acid and triglyceride biosynthesis, desaturation and elongation, adipogenesis, and adipokines were affected by HC diets. These results suggest that C/F and interactions with excessive caloric intake per se may regulate body composition and play important roles in the development of obesity and metabolic syndrome.

Pulsatile blood alcohol and CYP2E1 induction during chronic alcohol infusions in rats.

Adult male Sprague-Dawley rats were treated with alcohol for 35 days using a total enteral nutrition model. Intragastric cannulae were inserted into rats and they were infused with a diet designed to promote normal growth in male rats. Alcohol was infused at 35% of total calories for 35 days. Urine and blood alcohol concentrations were determined and found to be pulsatile during continuous alcohol infusion, having values between near zero and greater than 500 mg/dl. Twenty-four-hour urine alcohol concentrations were found to be excellent indicators of blood alcohol concentrations (BACs). Cytochrome P450 CYP2E1 was induced in a two-step manner. Step one occurred at BACs below 250 mg/dl and was characterized by significant (p < or = 0.05) elevations in activities and apoprotein levels with no changes in steady-state mRNA. Step two occurred with BACs greater than 300 mg/dl and resulted in significant (p < or = 0.05) elevations in steady-state mRNA levels. We propose that the pulsatile BACs are caused by an ethanol concentration-dependent regulation of an ethanol metabolizing system, perhaps CYP2E1.

Effects of tributyltin on the cytochrome P450 monooxygenase system and sex steroid metabolism in the clam Ruditapes decussata

Abstract The effects of tributyltin (TBT) on the cytochrome P450 monooxygenase system of the clam Ruditapes decussata have been evaluated. Digestive gland microsomes were observed to catalyze the oxidative metabolism of testosterone. The metabolites detected were androstenedione, dihydrotestosterone, dihydroandrostenedione, 6β-, 6α-, 2α-, and 2β-hydroxytestosterone, estrone and 17β-estradiol. The effect of 0.1 and 1 mM TBT in the incubation mixture led to a significant reduction in the total metabolic rate and changes in the metabolite profile. Clams were also exposed to different concentrations of TBT in water (0.1, 0.45, 2.27 μgl−1 of TBT as Sn) for seven days. A significant increase in testosterone levels was found in the TBT exposed organisms. When digestive gland microsomes of control and exposed organisms were assayed for their ability to metabolize testosterone, a dose-responsive decrease in aromatization of testosterone to estrone and estradiol was observed (p

Whey Protein Hydrolysate but not Whole Whey Protein Protects Against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats

Effects of intact and processed bovine milk proteins on development of chemically induced mammary tumors in female rats were compared. AIN-93G diets were made with 20% casein (CAS), casein hydrolysate (CASH), intact whey protein (IWP), or whey protein hydrolysate (WPH). Pregnant Sprague-Dawley rats were fed the diets starting at Gestational Day 4. Offspring were fed the same diet. At 50 days, female offspring (44–49/group) were gavaged with sesame oil containing 80 mg/kg of the mammary carcinogen dimethylbenzanthracene (DMBA) and euthanized 62 days posttreatment. Rats fed WPH had an adenocarcinoma incidence of 17% compared to the rats fed CAS, CASH, and IWP diets (34%, 33%, and 36% respectively) (P < 0.001). Median palpable tumor latency for rats fed WPH was greater (61 days, P < 0.001) compared to CAS (44 days), CASH (42 days) and IWP (45 days). Tumor multiplicity was also lower (1.5 vs. 3.0, P < 0.05) in rats fed WPH than in CAS and CASH fed groups. Results demonstrate that hydrolytic processing of whey protein is required for this diet to be effective in reducing DMBA-induced mammary tumors. The bioactive compounds produced during whey protein processing and mechanisms underlying the anticancer effects of WPH are yet to be identified.