Showing papers in "Journal of Nutrition in 1997"

Sarcopenia: Origins and Clinical Relevance

Abstract: This presentation reflects on the origins of the term sarcopenia. The Greek roots of the word are sarx for flesh and penia for loss. The term actually describes important changes in body composition and related functions. Clearly defining sarcopenia will allow investigators to appropriately classify patients and examine underlying pathogenic mechanisms and will allow funding agencies to appropriately target research funds to a taxonomically distinct syndrome.

Components of the AIN-93 Diets as Improvements in the AIN-76A Diet

Abstract: The AIN-93 rodent diets were formulated to substitute for the previous version (AIN-76A) and to improve the performance of animals that consume them. They are called AIN-93G, formulated for growth, and AIN-93M, for maintenance. Major changes included substituting cornstarch for sucrose and soybean oil for corn oil and increasing the amount in order to supply both essential fatty acids (linoleic and linolenic). L-Cystine was substituted for DL-methionine to supplement the casein component. The mineral mix was reformulated to lower the amounts of phosphorus, manganese and chromium, to increase the amount of selenium, and to add molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium. The amounts of vitamins E, K-1 and B-12 were increased over those in the AIN-76A vitamin mix. The AIN-93G diet contains 200 g of casein and 70 g of soybean oil/kg diet. The maintenance diet (AIN-93M) contains 140 g of casein and 40 g of soybean oil/kg diet. The 1993 diets have a better balance of essential nutrients than the 1976 diet and are better choices for studies with laboratory rodents.

Selected Indigestible Oligosaccharides Affect Large Bowel Mass, Cecal and Fecal Short-Chain Fatty Acids, pH and Microflora in Rats

Abstract: Certain indigestible oligosaccharides may benefit gastrointestinal tract health via fermentation and proliferation of desirable bacterial species. The purpose of this study was to elucidate effects of selected oligosaccharides on cecal and fecal short-chain fatty acid (SCFA) concentration, pH, total large bowel wet weight and wall weight, and gut microbiota levels in rats. Fifty male Sprague-Dawley rats were randomly assigned to one of five treatments: 1) control diet; 2) control diet + 5% microcrystalline cellulose (5% CC); 3) control diet + 5% CC + 6% fructooligosaccharides; 4) control diet + 5% CC + 6% oligofructose; or 5) control diet + 5% CC + 6% xylooligosaccharides. The control diet consisted of (dry matter basis) 20% protein, 65% carbohydrate, 10.5% fat, vitamin and mineral mixes. The duration of the study was 14 d. The oligofructose- and fructooligosaccharide-containing diets resulted in higher cecal butyrate concentrations compared with the control, cellulose and xylooligosaccharide diets. Generally, total cecal SCFA pools were higher while pH was lower from ingesting oligosaccharide-containing diets compared with control or cellulose diets. Cecal total weight and wall weight were higher from oligosaccharide consumption, whereas colonic total wet weight was higher for rats consuming xylooligosaccharides compared with other treatments; colon wall weight was unaffected by treatments. Cecal bifidobacteria and total anaerobes were higher whereas total aerobes were lower in rats fed oligosaccharide diets compared with those fed the control diet. Cecal lactobacilli levels were unaffected by treatment. Dietary incorporation of fermentable, indigestible oligosaccharides, by providing SCFA, lowering pH, and increasing bifidobacteria, may be beneficial in improving gastrointestinal health.

Cows' milk fat components as potential anticarcinogenic agents

Abstract: The optimum approach to conquering cancer is prevention. Although the human diet contains components which promote cancer, it also contains components with the potential to prevent it. Recent research shows that milk fat contains a number of potential anticarcinogenic components including conjugated linoleic acid, sphingomyelin, butyric acid and ether lipids. Conjugated linoleic acid inhibited proliferation of human malignant melanoma, colorectal, breast and lung cancer cell lines. In animals, it reduced the incidence of chemically induced mouse epidermal tumors, mouse forestomach neoplasia and aberrant crypt foci in the rat colon. In a number of studies, conjugated linoleic acid, at near-physiological concentrations, inhibited mammary tumorigenesis independently of the amount and type of fat in the diet. In vitro studies showed that the milk phospholipid, sphingomyelin, through its biologically active metabolites ceramide and sphingosine, participates in three major antiproliferative pathways influencing oncogenesis, namely, inhibition of cell growth, and induction of differentiation and apoptosis. Mice fed sphingomyelin had fewer colon tumors and aberrant crypt foci than control animals. About one third of all milk triacylglycerols contain one molecule of butyric acid, a potent inhibitor of proliferation and inducer of differentiation and apoptosis in a wide range of neoplastic cell lines. Although butyrate produced by colonic fermentation is considered important for colon cancer protection, an animal study suggests dietary butyrate may inhibit mammary tumorigenesis. The dairy cow also has the ability to extract other potential anticarcinogenic agents such as beta-carotene, beta-ionone and gossypol from its feed and transfer them to milk. Animal studies comparing the tumorigenic potential of milk fat or butter with linoleic acid-rich vegetable oils or margarines are reviewed. They clearly show less tumor development with dairy products.

Dietary Genistein Exerts Estrogenic Effects upon the Uterus, Mammary Gland and the Hypothalamic/Pituitary Axis in Rats

Abstract: These studies were undertaken to assess the estrogenic and antiestrogenic effects of dietary genistein. To determine estrogenic effects, genistein was mixed into a modified AIN-76 or AIN-93G semipurified diet at 0 (negative control), 150, 375 or 750 microg/g and 17, beta-estradiol at 1.0 microg/g and fed to ovariectomized 70-d-old Sprague-Dawley rats. Estrogenic potency was determined by analyzing uterine weight, mammary gland development, plasma prolactin and expression of uterine c-fos. Dietary genistein (375 and 750 microg/g) increased uterine wet and dry weights (P < 0.05). Mammary gland regression following ovariectomy was significantly inhibited by dietary genistein at 750 microg/g (P < 0.05). Plasma prolactin was significantly greater in ovariectomized rats fed genistein (750 microg/g) compared with comparable rats not receiving genistein. The relative binding affinity of genistein to the estrogen receptor (ER) was 0.01 that of estradiol. Genistein (750 microg/g) induced the uterine expression of c-fos. To evaluate potential antiestrogenic effects, genistein and estradiol were mixed into the modified AIN diets at the doses noted above and fed to ovariectomized rats. Dietary genistein (375 or 750 microg/g) did not inhibit the effects of estradiol on uterine weight, mammary gland development or plasma prolactin. Serum concentration of total genistein (conjugated plus free) in rats fed 750 microg/g was 2.2 micromol/L and free genistein was 0.4 micromol/L. Administration of dietary genistein at 750 microg/g can exert estrogenic effects in the uterus, mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 microg/g) did not antagonize the action of estradiol in estradiol-supplemented ovariectomized rats or in intact rats.

Periods of Risk in Childhood for the Development of Adult Obesity — What Do We Need to Learn?

Abstract: The prenatal period, the period of adiposity rebound and adolescence appear to represent critical periods for the development of obesity that persists into adulthood. Nonetheless, relatively little is known about the extent to which incident obesity at each of these intervals contributes to the prevalence of adult obesity. Similarly, little is known about the mechanisms that operate at each of these critical periods to entrain adult obesity.

Administration of Transgalacto-Oligosaccharides Increases Fecal Bifidobacteria and Modifies Colonic Fermentation Metabolism in Healthy Humans

Abstract: Transgalacto-oligosaccharides are a mixture of oligosaccharides consisting of glucose and galactose; they are not digested in the human small intestine. In vitro, they specifically stimulate the growth of bifidobacteria. The aim of the present work was to assess tolerance of transgalacto-oligosaccharides and the effects of their prolonged administration on bifidobacteria and fermentative activity of colonic flora. Eight healthy subjects were given 10 g of transgalacto-oligosaccharides per day for 21 d in two daily doses. A breath test and stool sample collection were carried out on d 1, 7, 14 and 21 of transgalacto-oligosaccharides ingestion. The stools of three subjects were collected and mixed before the study, and then inoculated in vitro into a fermentor to which 10 g transgalacto-oligosaccharides was added daily for 14 d. In the eight volunteers, administration of transgalacto-oligosaccharides led to a significant decrease in breath hydrogen excretion (P < 0.01) and a significant increase in fecal concentrations of bifidobacteria from (means +/- SEM) 8.6 +/- 0.6 to 9.7 +/- 0.5, 9.7 +/- 0.6 and 9.5 +/- 0.6 log colony-forming units (CFU)/g on d 1, 7, 14 and 21, respectively (P < 0.05). Fecal concentrations of enterobacteria, as well as stool weight, fecal water and pH did not change during the study. In vitro, transgalacto-oligosaccharides fermentation became more efficient and faster with time. In addition, metabolic alterations such as a rise in acetate proportion and lactate formation after 7 d of fermentation were observed, indicating the transformation of the inoculated fecal flora into an acid-resistant lactic flora. Prolonged administration of transgalacto-oligosaccharides, at a dose which does not induce digestive symptoms, increases the number of bifidobacteria and alters the fermentative activity of colonic flora in humans.

Intestinal Uptake and Biliary Excretion of the Isoflavone Genistein in Rats

Abstract: The intestinal absorption, biliary excretion and metabolism of genistein, a potent and specific protein tyrosine kinase inhibitor that occurs naturally in soy foods, was examined in anesthetized, adult female rats fitted with indwelling biliary cannulas. 4-14C-Genistein, when infused into the duodenum, was rapidly absorbed from the intestine, taken up by the liver and excreted into the bile as its 7-O-beta-glucuronide conjugate. Cumulative recovery of 14C-radioactivity in the bile over a 4-h period was 70-75% of the dose. When genistein was infused into the portal vein, it was also taken up efficiently by the liver, conjugated with glucuronic acid and transported into bile. However, portal blood collected after duodenal infusions of genistein contained mostly genistein 7-O-beta-glucuronide, suggesting that in vivo glucuronidation occurred in the intestinal wall rather than the liver. This was confirmed using everted intestinal sac preparations. Reinfusion of genistein 7-O-beta-glucuronide into the duodenum or into the mid small intestine resulted in its reappearance in the bile, albeit more slowly than when genistein was infused. Over a 4-h collection period, the cumulative recovery of 14C-radioactivity in bile was 27 and 70-75% of the administered dose for duodenal and ileal infusions, respectively. These data indicate that genistein is highly bioavailable in rats and because of its enterohepatic circulation may accumulate within the gastrointestinal tract.

Functional and Metabolic Consequences of Sarcopenia

Abstract: The capacity of older men and women to adapt to regularly performed exercise has been demonstrated by many laboratories. Aerobic exercise results in improvements in functional capacity and reduced risk of developing type II diabetes in the elderly. High intensity resistance training (above 60% of the 1 repetition maximum) causes large increases in strength in the elderly, and resistance training significant increases muscle size. Resistance training also significantly increases energy requirements and insulin action of the elderly. We recently demonstrated that resistance training has a positive effect on multiple risk factors for osteoporotic fractures in previously sedentary post-menopausal women. Because the sedentary lifestyle of individuals in a long-term care facility may exacerbate losses of muscle function, we applied this same training program to frail, institutionalized elderly men and women. In a population of 100 nursing home residents, a randomly assigned high intensity strength training program resulted in significant gains in strength and functional status. In addition, spontaneous activity, measured by activity monitors, increased significantly in those participating in the exercise program; there was no change in the sedentary control group. Before the strength training intervention, the relationship of whole-body potassium and leg strength was relatively weak (r2 = 0.29, P < 0.001), indicating that in very old persons muscle mass is an important but not the only determiner of functional status. Thus exercise may minimize or reverse the syndrome of physical frailty prevalent among very old individuals. Because of their low functional status and high incidence of chronic disease, there is no segment of the population that can benefit more from exercise training than the elderly.

Isoprenoids Suppress the Growth of Murine B16 Melanomas In Vitro and In Vivo

Abstract: Sundry mevalonate-derived constituents (isoprenoids) of fruits, vegetables and cereal grains suppress the growth of tumors. This study estimated the concentrations of structurally diverse isoprenoids required to inhibit the increase in a population of murine B16(F10) melanoma cells during a 48-h incubation by 50% (IC50 value). The IC50 values for d-limonene and perillyl alcohol, the monoterpenes in Phase I trials, were 450 and 250 micromol/L, respectively; related cyclic monoterpenes (perillaldehyde, carvacrol and thymol), an acyclic monoterpene (geraniol) and the end ring analog of beta-carotene (beta-ionone) had IC50 values in the range of 120-150 micromol/L. The IC50 value estimated for farnesol, the side-chain analog of the tocotrienols (50 micromol/L) fell midway between that of alpha-tocotrienol (110 micromol/L) and those estimated for gamma- (20 micromol/L) and delta- (10 micromol/L) tocotrienol. A novel tocotrienol lacking methyl groups on the tocol ring proved to be extremely potent (IC50, 0.9 micromol/L). In the first of two diet studies, experimental diets were fed to weanling C57BL female mice for 10 d prior to and 28 d following the implantation of the aggressively growing and highly metastatic B16(F10) melanoma. The isomolar (116 micromol/kg diet) and the Vitamin E-equivalent (928 micromol/kg diet) substitution of d-gamma-tocotrienol for dl-alpha-tocopherol in the AIN-76A diet produced 36 and 50% retardations, respectively, in tumor growth (P < 0.05). In the second study, melanomas were established before mice were fed experimental diets formulated with 2 mmol/kg d-gamma-tocotrienol, beta-ionone individually and in combination. Each treatment increased (P < 0.03) the duration of host survival. Our finding that the effects of individual isoprenoids were additive suggests the possibility that one component of the anticarcinogenic action of plant-based diets is the tumor growth-suppressive action of the diverse isoprenoid constituents of fruits, vegetables and cereal grains.

Lipoprotein Metabolism and Fattening in Poultry

Abstract: Because de novo fatty acid synthesis in birds takes place mainly in the liver, adipose tissue growth and subsequent fattening depend on the availability of plasma triglycerides, which are transported as components of lipoproteins. In growing birds, VLDL is the major transporter of triglycerides, and attempts to reduce excessive fatness in poultry have involved the control of VLDL metabolism. Lean and fat lines of chickens have been selected on the basis of either their abdominal fat content or plasma VLDL concentration. In both cases, hepatic lipogenesis or LPL activity in adipose tissue did not differ between lean and fat lines, and therefore they did not appear to be limiting factors of susceptibility to fattening. In contrast, hepatic secretion and plasma concentration of VLDL were always higher in fat chickens than in lean chickens. Thus, current methods of selection of broilers against excessive fatness are based on this direct relationship between plasma VLDL and adiposity. When hepatic lipogenesis exceeds the capacity of VLDL secretion, triglycerides accumulate in the liver, causing steatosis. Although fatty liver is associated with reduced egg production and increased mortality in laying hens, hepatic steatosis in overfed ducks and geese is of positive economic value, serving as the basis for "foie-gras" production. The balance between synthesis and secretion of VLDL is therefore the key point that regulates hepatic and extrahepatic fattening in poultry.

Socioeconomic and Demographic Factors Are Associated with Worldwide Patterns of Stunting and Wasting of Children

Abstract: We estimated the variability among nations in the prevalence of stunting and wasting, evaluated which national factors are associated with stunting and wasting and examined the relationship of stunting with wasting. The World Health Organization Global Database on Child Growth, a comprehensive conceptual model and a database of national factors were used with variance components and regression analyses. There was substantial variability among nations and among provinces within nations. Most national variability for stunting (76%) and wasting (66%) was explained by national factors and geographic region. Higher energy availability, female literacy and gross product were the most important factors associated with lower prevalence of stunting. The association of health expenditures and stunting differed by region. Higher immunization rate and, for Asia only, energy availability were the most important factors associated with lower prevalence of wasting. Regional differences in the relationship between stunting and wasting were accounted for by national factors. Some factors associated with stunting and wasting differ at the national level. Child malnutrition within a household is greatly influenced by issues at national and provincial levels, and intervention should be considered at all three levels.

The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells.

Abstract: We investigated the injurious effects of reactive oxygen metabolites on the intestinal epithelium and the possible protective role played by two olive oil phenolic compounds, (3,4-dihydroxyphenyl)ethanol and (p-hydroxyphenyl)ethanol, using the Caco-2 human cell line. We induced oxidative stress in the apical compartment, either by the addition of 10 mmol/L H2O2 or by the action of 10 U/L xanthine oxidase in the presence of xanthine (250 micromol/L); after the incubation, we evaluated the cellular and molecular alterations. Both treatments produced significant decreases in Caco-2 viability as assessed by the neutral red assay. Furthermore, we observed a significant increase in malondialdehyde intracellular concentration and paracellular inulin transport, indicating the occurrence of lipid peroxidation and monolayer permeability changes, respectively. The H2O2-induced alterations were completely prevented by preincubating Caco-2 cells with (3,4-dihydroxyphenyl)ethanol (250 micromol/L); when the oxidative stress was induced by xanthine oxidase, complete protection was obtained at a concentration of polyphenol as small as 100 micromol/L. In contrast, (p-hydroxyphenyl)ethanol was ineffective up to a concentration of 500 micromol/L. Our data demonstrate that (3,4-dihydroxyphenyl)ethanol can act as a biological antioxidant in a cell culture experimental model and that the ortho-dihydroxy moiety of the molecule is essential for antioxidant activity. This study suggests that dietary intake of olive oil polyphenols may lower the risk of reactive oxygen metabolite-mediated diseases such as some gastrointestinal diseases and atherosclerosis.

Prevention of Cardiac Arrhythmia by Dietary (n-3) Polyunsaturated Fatty Acids and Their Mechanism of Action

Abstract: The role of marine fish oil (n-3) polyunsaturated fatty acids in the prevention of fatal ventricular arrhythmia has been established in experimental animals. Prevention of arrhythmias arising at the onset of ischemia and reperfusion is important because if untreated, they result in sudden cardiac death. Animals supplemented with fish oils in their diet developed little or no ventricular fibrillation after ischemia was induced. Similar effects have also been observed in cultured neonatal cardiomyocytes. Several mechanisms have been proposed and studied to explain the antiarrhythmic effects of fish oil polyunsaturated fatty acids, but to date, no definite mechanism has been validated. The sequence of action of these mechanisms and whether more than one mechanism is involved is also not clear. Some of the mechanisms suggested to explain the antiarrhythmic action of fish oils include the incorporation and modification of cell membrane structure by (n-3) polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their role in eicosanoid metabolism. Other mechanisms that are currently being investigated include the role of (n-3) polyunsaturated fatty acids in cell signalling mediated through phosphoinositides and their effect on various enzymes and receptors. This article reviews these mechanisms and the antiarrhythmic studies using (n-3) polyunsaturated fatty acids.

Age-Specific Determinants of Stunting in Filipino Children

Abstract: This study identifies age-specific factors related to new cases of stunting that develop in Filipino children from birth to 24 mo of age. Data come from nearly 3000 participants in the Cebu Longitudinal Health and Nutrition Survey, a community-based study conducted from 1983 to 1995. Length, morbidity, feeding and health-related data were collected bimonthly during home visits. Stunting (length >2 SD below the WHO age- and sex-specific medians) occurred in 69% of rural and 60% of urban children by 24 mo of age. We used a multivariate discrete time hazard model to estimate the likelihood of becoming stunted in each 2-mo interval. The likelihood of stunting was significantly increased by diarrhea, febrile respiratory infections, early supplemental feeding and low birth weight. The effect of birth weight was strongest in the first year. Breast-feeding, preventive health care and taller maternal stature significantly decreased the likelihood of stunting. Males were more likely to become stunted in the first year, whereas females were more likely to become stunted in the second year of life. Because stunting is strongly related to poor functional outcomes such as impaired intellectual development during childhood, and to short stature in adulthood, these results emphasize the need for prevention of growth retardation through promotion of prenatal care and breast-feeding, as well as control of infectious diseases.

Dietary (n-3) Polyunsaturated Fatty Acids Suppress Murine Lymphoproliferation, Interleukin-2 Secretion, and the Formation of Diacylglycerol and Ceramide

Abstract: Elucidation of the mechanism(s) by which dietary fish oil, enriched in eicosapentaenoic acid (EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)], suppresses the inflammatory process is essential in maximizing this potentially therapeutic effect. Murine T-lymphocyte function and signal transduction were examined in response to a low fat, short term diet enriched in highly purified EPA or DHA ethyl esters. For 10 d, mice were fed comparable diets containing either 3% safflower oil ethyl esters (SAF), 2% SAF + 1% arachidonic acid triglyceride (AA), 2% SAF + 1% EPA, or 2% SAF + 1% DHA. Concanavalin A-induced T-lymphocyte proliferation in splenocyte cultures was significantly suppressed by dietary EPA and DHA while AA had no effect relative to the SAF control. The suppressed proliferative response in EPA- and DHA-fed mice was preceded temporally by a significant reduction in IL-2 secretion. Kinetics of mitogen-induced diacyl-sn-glycerol (DAG) and ceramide production did not differ significantly between SAF and AA diet groups. In contrast, DAG production was significantly suppressed in EP- and DHA-fed mice relative to the SAF and AA groups. The reduced DAG mass was paralleled by reduced ceramide mass following EPA and DHA feeding compared to the SAF and AA groups. Thus, low dose, short term dietary exposure to highly purified EPA or DHA appears to suppress mitogen-induced T-lymphocyte proliferation by inhibiting IL-2 secretion, and these events are accompanied by reductions in the production of essential lipid second messengers, DAG and ceramide.

Partial Substitution of Di- and Tripeptides for Native Proteins in Sea Bass Diet Improves Dicentrarchus labrax Larval Development

Abstract: To determine whether incorporation of peptides into diets can improve larval development, sea bass (Dicentrarchus labrax) larvae were fed for 21 d one of three isonitrogenous, isoenergetic semipurified diets in which enzymatic hydrolysate (75% di- and tripeptides) of fish meal proteins was substituted for 0, 20 or 40% of native fish meal proteins. Growth and survival were significantly greater (P < 0.05) in larvae fed peptide diets compared to those fed only native protein, with the best performance exhibited by those fed the 20% level of peptides. Chymotrypsin activity was much higher in groups fed peptide diets compared to that fed all native protein (P < 0.001), indicating a greater proteolytic capacity of the pancreas. At the intestinal level, activities of the brush border enzymes, aminopeptidase, maltase and gamma-glutamyl transpeptidase, increased with age while the cytosolic enzyme, leu-ala peptidase, decreased with age (P < 0.001). These changes in enzymatic activities correspond to the normal development of intestinal digestion. This development occurred earlier in the group fed 20% peptide-substituted diet than in the two other groups. The better larval performances observed in groups fed diets containing peptides can be related to the enhanced proteolytic capacity of the pancreas and the earlier development of intestinal digestion.

Plant Limitations to Fiber Digestion and Utilization

Abstract: Energy availability from forages is limited by fiber concentration because fiber is slowly and incompletely digested, whereas cell solubles are almost completely digested. Thus, the proportion of fiber to cell solubles is a major determinant of energy availability in forages. Grasses normally have more fiber than legumes, especially in leaves. Grass fiber is more digestible than that of legumes, but that of legumes digests at a faster rate. Ruminants digest 40-50% of legume fiber and 60-70% of grass fiber. Some fiber cannot be digested no matter how long it remains in the rumen. Lignin is thought to interfere with microbial degradation of fiber polysaccharides by acting as a physical barrier and by being cross-linked to polysaccharides by ferulate bridges. In addition to the effects of lignin, physical and structural barriers may limit fiber digestibility. Because the middle lamella and primary wall of thick-walled cells are so highly lignified, many cells can be digested only from the interior of the cell. For many cells, access to cell interiors is limited because of large particle sizes. Forage digestibility could be improved by reducing the amount of lignified cells or by developing improved cultivars so that lignified cells are more digestible.

Breast-Feeding Lowers the Frequency and Duration of Acute Respiratory Infection and Diarrhea in Infants under Six Months of Age

Abstract: It remains unclear whether breast-feeding protects infants against acute respiratory infection (ARI). To determine if breast-feeding protects against ARI as it does against diarrhea, 170 healthy newborns were followed for 6 mo. Feeding mode, incidence and duration of ARI and diarrhea were recorded biweekly. Infants were classified as fully or partially breast-fed, or formula-fed. Incidence and prevalence were computed monthly. The effects of duration of breast-feeding and potential confounders were analyzed by multiple and logistic regression analyses. Incidence and prevalence of ARI were significantly lower in fully breast-fed infants than in formula-fed infants from birth up to 4 mo, as was the mean duration of individual episodes (5.1 +/- 3.5 vs. 6.4 +/- 3.6 d, respectively). Incidence of ARI was negatively associated with duration of breast-feeding and positively associated with the presence of siblings (P < 0.05). The prevalence of ARI was associated only with the duration of breast-feeding (P < 0.05). Infants that were never breast-fed and that had one or more siblings were more likely to have an episode of ARI than those fully breast-fed for at least 1 mo. Incidence, prevalence, and duration of individual episodes of diarrhea were also lower in breast-fed infants. Incidence (r = -0.17, P < 0.02) and prevalence (r = -0.19, P < 0.008) were negatively associated with duration of full breast-feeding. Introduction of solid food was not associated with further episodes of diarrhea. The present results demonstrate protection against ARI as a result of breast-feeding similar to that for diarrhea, i.e., lower incidence and percentage of days ill, and episodes of shorter duration.

Regional Brain Iron, Ferritin and Transferrin Concentrations during Iron Deficiency and Iron Repletion in Developing Rats

Abstract: Iron deficiency in young rats leads to a decrease in brain iron and ferritin concentrations, an increase in transferrin (Tf) concentration, and an increased rate of uptake of iron from the plasma pool. We conducted two experiments to determine whether brain iron, Tf and ferritin respond quickly to iron repletion and to determine whether brain regions respond heterogeneously. Weanling male Sprague-Dawley rats were fed an iron-deficient diet (<5 mg/kg Fe) for 2 wk followed by an iron-adequate diet (REPL group, 35 mg/kg Fe in Experiment 1 and 15 mg/kg Fe in Experiment 2) for 2 or 4 wks, respectively. Age-matched iron-deficient (ID) and control rats composed the other two groups. Fourteen days of repletion with 35 mg/kg Fe dietary treatment were adequate to normalize hematology, brain microsomal and cytosolic Fe and brain ferritin (Experiment 1). Brain transferrin concentrations in REPL rats, however, were significantly above the levels of controls. Regional brain iron decreased heterogeneously due to dietary iron deficiency (Experiment 2), with some regions having a propensity to keep iron (e.g., substantia nigra, pons, and thalamus) and others losing significant amounts of iron (cortex and hippocampus). Ferritin and Tf concentrations also varied significantly across brain regions in ID and control rats. The hippocampus had the most dramatic Tf response to iron deficiency with elevations of approximately 100%, whereas other regions, except striatum, were unaffected. The brain of developing rats thus distributes iron and iron regulatory proteins differently from the brain of adult rats and is quite avid in its reacquisition of iron during iron therapy.

Development of an Approach for Estimating Usual Nutrient Intake Distributions at the Population Level

Abstract: Assessment of the dietary intake of a population must consider the large within-person variation in daily intakes. A 1986 report by the National Academy of Sciences (NAS), commissioned by the U.S. Department of Agriculture (USDA), marked an important milestone in the history of this issue. Since that time, USDA has been working cooperatively with statisticians at Iowa State University (ISU), who have further developed the measurement error model approach proposed by NAS. The method developed by the ISU statisticians can be used to estimate usual dietary intake distributions for a population but not for specific individuals. It is based on the assumption that an individual can more accurately recall and describe the foods eaten yesterday than foods eaten at an earlier time. The method requires as few as two independent days of nutrient intake information or three consecutive days for at least a subsample of the individuals. It removes biases of subsequent reporting days compared with the first day, and temporal effects such as day-of-the-week and seasonal effects can be easily removed. The method developed at ISU is described conceptually and applied to data collected in the 1989-91 USDA Continuing Survey of Food intakes by individuals to estimate the proportion of men and women age 20 y and older having "usual" (long-run average) intakes below 30% of energy from fat, below the 1989 Recommended Dietary Allowances for vitamin A and folate, and above 1000 micrograms for folate. These results were compared with the results from the distributions of 1-d intakes and of 3-d mean intakes to demonstrate the effect of within-person variation and asymmetry on usual nutrient intakes in a population.

Response of Rainbow Trout (Oncorhynchus mykiss) to Supplements of Individual Essential Amino Acids in a Semipurified Diet, Including an Estimate of the Maintenance Requirement for Essential Amino Acids

Abstract: We studied the effects of increasing dietary concentrations of each of the following amino acids on growth, feed intake, feed conversion ratio and composition of gain in rainbow trout in six dose-response experiments: L-lysine, L-tryptophan, L-histidine, L-valine, L-leucine and L-isoleucine. Semipurified diets containing 20.1 MJ digestible energy/kg dry matter, with wheat gluten and crystalline amino acids as sole sources of amino acids, were fed to rainbow trout [initial mean body weight (BW) 40-51 g, depending on the amino acid studied]. In one series of 24 diets, lysine concentration ranged from 4.5 to 58.0 g/kg dry matter; in five further series of 12 diets each, concentrations ranged from (in g/kg dry matter): tryptophan, 1.3 to 5.6; histidine, 2.6 to 13.5; valine, 6.2 to 34.2; leucine, 10.0 to 42.0 and isoleucine, 5.0 to 15.3. Each diet was fed to a group of 20 fish for 53-64 d, depending on the amino acid studied. Dry matter intake, weight gain, feed conversion ratio, protein concentration of gain and total protein deposition followed exponential response functions. To achieve 95% of the maximum protein deposition, dietary concentrations of 27.7 g lysine, 2.0 g tryptophan, 5.8 g histidine, 15.7 g valine, 13.6 g leucine and 13.7 g isoleucine/kg dry matter were required. Maintenance requirements, estimated from exponential functions for protein deposition, were [in mg/(100 g BW.d)]: lysine, 1.93; tryptophan, 1.05; histidine, 1.07; valine, 2.92; leucine, 8.26 and isoleucine, 0.91. This corresponds to 4% of the requirement for protein deposition for lysine and isoleucine but 32% for leucine, with the other amino acids being intermediate. Therefore, different dietary amino acid requirement patterns were derived from protein deposition data depending on the chosen level of performance.

Oxidants and Antioxidants in Viral Diseases: Disease Mechanisms and Metabolic Regulation

Abstract: Reactive oxygen and nitrogen metabolites play a complex role in many diseases and in metabolic regulation. Because viruses replicate in living cells, such metabolites influence the growth of viruses in addition to serving as a host defense mechanism. Low levels of reactive oxygen species (ROS) play a role in mitogenic activation, and the early phase of lytic and nonlytic virus infection indeed resembles that of mitogenic cell activation. In addition to these subtle cell-activating effects shared by many viruses, influenza and paramyxoviruses activate a respiratory burst in phagocytic cells. These viruses are toxic when injected in animals. Cells lavaged from the lungs of mice infected with influenza virus are primed for enhanced superoxide generation. Moreover, xanthine oxidase is enhanced and the buffering capacity of small molecular antioxidants is decreased in the lungs, suggesting that infection leads to oxidative stress. The wide array of cytokines produced in the lungs during influenza could contribute to the systemic effects of influenza. Oxidative stress has also been shown in human immunodeficiency virus (HIV) infection in humans. Via activation of NF kappa B, ROS may activate viral replication, but oxidants are believed to contribute also to the loss of CD4 T cells by apoptosis. Antioxidants, together with agents interfering with the harmful effects of cytokines and lipid mediators, may have a role in the treatment of viral diseases. Such agents could not only alleviate disease symptoms but also decrease the long-term effects of chronic oxidative stress, which have been linked to the development of cancer in some viral infections.

Inhibition of Proliferation of Estrogen Receptor–Negative MDA-MB-435 and –Positive MCF-7 Human Breast Cancer Cells by Palm Oil Tocotrienols and Tamoxifen, Alone and in Combination

Abstract: Tocotrienols are a form of vitamin E, having an unsaturated isoprenoid side-chain rather than the saturated side-chain of tocopherols. The tocotrienol-rich fraction (TRF) from palm oil contains alpha-tocopherol and a mixture of alpha-, gamma- and delta-tocotrienols. Earlier studies have shown that tocotrienols display anticancer activity. We previously reported that TRF, alpha-, gamma- and delta-tocotrienols inhibited proliferation of estrogen receptor-negative MDA-MB-435 human breast cancer cells with 50% inhibitory concentrations (IC50) of 180, 90, 30 and 90 microg/mL, respectively, whereas alpha-tocopherol had no effect at concentrations up to 500 microg/mL. Further experiments with estrogen receptor-positive MCF-7 cells showed that tocotrienols also inhibited their proliferation, as measured by [3H] thymidine incorporation. The IC50s for TRF, alpha-tocopherol, alpha-, gamma- and delta-tocotrienols were 4, 125, 6, 2 and 2 microg/mL, respectively. Tamoxifen, a widely used synthetic antiestrogen inhibits the growth of MCF-7 cells with an IC50 of 0.04 microg/mL. We tested 1:1 combinations of TRF, alpha-tocopherol and the individual tocotrienols with tamoxifen in both cell lines. In the MDA-MB-435 cells, all of the combinations were found to be synergistic. In the MCF-7 cells, only 1:1 combinations of gamma- or delta-tocotrienol with tamoxifen showed a synergistic inhibitory effect on the proliferative rate and growth of the cells. The inhibition by tocotrienols was not overcome by addition of excess estradiol to the medium. These results suggest that tocotrienols are effective inhibitors of both estrogen receptor-negative and -positive cells and that combinations with tamoxifen should be considered as a possible improvement in breast cancer therapy.

In Vivo Dopamine Metabolism Is Altered in Iron-Deficient Anemic Rats

Abstract: Previous studies of dopamine metabolism in iron-deficient rats demonstrated an elevation in extra-neuronal levels of dopamine and a depression in the number of dopamine D 2 receptors; however, the importance of anemia per se and the reversibility of these observations are not completely resolved. The purpose of this study was to determine if in vivo reuptake of caudate dopamine is altered by iron deficiency anemia, if it is reversible with iron therapy, and if anemia per se produced the same effects on dopamine metabolism. Male Sprague-Dawley rats (21-d old) were fed an iron-deficient diet (4 mg Fe/kg diet) and then iron repleted (5 mg iron dextran), or were fed an iron adequate diet (35 mg Fe/kg diet) and then given phenylhydrazine to induce hemolytic anemia. In vivo microdialysis was performed in steady-state conditions both before and after iron or no therapy and was followed by an intraperitoneal injection of a dopamine reuptake blocker (cocaine-HCI 30 mg/kg). Thirty percent higher extracellular dopamine levels in the caudate-putamen were observed in iron-deficient rats compared with control rats, but no differences were observed in tissue levels. Hemolytic anemic and iron-repleted rats had normal extracellular dopamine levels. The response to dopamine reuptake blockade was significantly attenuated in iron-deficient rats compared with control, iron-repleted, or hemolytic anemic rats. These experiments provide evidence that iron deficiency blunts the dopamine reuptake mechanism, that this is a reversible process in postweaning rats, and that anemia per se does not cause the increased extracellular dopamine levels.

Body Weight Set-Points: Determination and Adjustment

Abstract: It is proposed that body weight, like body water and body temperature, is physiologically regulated. In the case of body weight, coordinated adjustments in both the intake and expenditure of energy serve to stabilize the weights of individuals at a specified level and to resist their displacement from this level. Obese individuals also display these behavioral and metabolic adjustments to weight perturbations and thus appear to actively resist efforts to reduce their weight from the elevated levels they ordinarily display. Experimental studies of genetically transmitted and diet-induced forms of obesity in animals similarly suggest a view of obesity as a condition of body energy regulation at an elevated set-point. An individual's set-point for regulated body weight is apparently adjustable, shifting over a lifespan in conjunction with naturally occurring but still unspecified physiologic changes. Experimentally, the set-point for body weight can be adjusted by manipulation of specific hypothalamic sites. Lesions of the lateral hypothalamus, for example, cause a chronic reduction in the level at which laboratory animals regulate body weight. It thus appears that hypothalamic mechanisms play a primary role in setting the level at which individuals regulate body weight, and it is likely that the genetic, dietary and other lifespan influences on body weight are expressed through these mechanisms.

Decreasing traditional food use affects diet quality for adult Dene/Métis in 16 communities of the Canadian Northwest Territories

Abstract: We assessed diets in 16 Dene/Metis communities in the Canadian Arctic. We described nutrient intakes and identified nutrients at risk among adult Dene/Metis, evaluated the influence of traditional food on diet quality, and examined the direction of dietary change by comparing intergenerational and between-community differences in dietary intake. Diet varied according to sex, age and community. Nutrients of possibly inadequate intake (irrespective of subject sex, age or community) included calcium, vitamin A and folic acid. Dietary fiber intake was also of concern. Traditional food (animals and plants harvested from the local environment) was consumed on 65. 4% of interview days; on those days intakes of iron, zinc and potassium were higher (P < 0.05) and those of sodium, fat, saturated fat and sucrose were lower (P < 0.05) than on days when market food only was consumed. In this population, the shift away from traditional food towards a diet composed exclusively of market food was characterized by an increase (P < 0.05) in absolute energy intake and an increase (P < 0.01) in the relative contributions of carbohydrate (particularly sucrose), fat and saturated fat. This pattern of change calls for initiatives to document the current health status of this population and to prevent potential negative health consequences of dietary change.

Leptin Rapidly Lowers Food Intake and Elevates Metabolic Rates in Lean and ob/ob Mice

Abstract: Leptin, the ob gene product, is released from adipose tissue and likely acts in the central nervous system, particularly within the hypothalamus, to exert many of its effects. Obesity in C57BL/6J ob/ob mice is caused by a mutation in the ob gene resulting in a lack of functional leptin. In this study, we first compared effects of a single intracerebroventricular (ICV) injection of 3 pmol (50 ng) or 60 pmol (1 microg) leptin on food intake and oxygen consumption of lean and ob/ob mice deprived of food for 4 h during the 48-h period postinjection. Injection of 3 pmol leptin minimally lowered food intake in these mice without influencing oxygen consumption. Injection of 60 pmol of leptin rapidly lowered food intake within 30 min in both lean and ob/ob mice, with effects persisting for 24 h. Lean and ob/ob mice treated with leptin consumed 40 and 60% less food, respectively, in 24 h than vehicle-treated controls. Injection of leptin (60 pmol ICV) suppressed food intake of adrenalectomized mice as well (by 25 and 40% in lean mice and by 20 and 68% in ob/ob mice at 3 and 24 h, respectively), indicating that glucocorticoids are not essential for leptin to suppress food intake. Leptin increased oxygen consumption in conditions in which diet-induced thermogenesis was low, i.e., in fed ob/ob mice and in food-deprived lean mice, but not in fed adrenalectomized ob/ob mice or in fed lean mice. ICV injection of 60 pmol leptin along with 230 pmol (2 microg) of neuropeptide Y (NPY) attenuated NPY-induced feeding in ob/ob, but not in lean mice, suggesting an enhanced potential for crosstalk between the leptin and NPY signaling systems in ob/ob mice lacking endogenous leptin. Leptin exerts rapid-onset actions within the central nervous system to coordinate control of food intake and metabolic rate.

Endogenous Synthesis of Arginine Plays an Important Role in Maintaining Arginine Homeostasis in Postweaning Growing Pigs

Abstract: This study was conducted to determine whether endogenous synthesis of arginine plays a role in regulating arginine homeostasis in postweaning pigs. Pigs were fed a sorghum-based diet containing 0.98% arginine and were used for studies at 75 d of age (28.4 kg body weight). Mitochondria were prepared from the jejunum and other major tissues for measuring the activities of Δ 1 -pyrroline-5-carboxylate (P5C) synthase and proline oxidase (enzymes catalyzing P5C synthesis from glutamate and proline, respectively) and of ornithine aminotransferase (OAT) (the enzyme catalyzing the interconversion of P5C into ornithine). For metabolic studies, jejunal enterocytes were incubated at 37°C for 30 min in Krebs-Henseleit bicarbonate buffer containing 2 mmol/L L-glutamine, 2 mmol/L L-[U- 14 C]proline, and 0-200 μmol/L gabaculine (an inhibitor of OAT). The activities of P5C synthase, proline oxidase and OAT were greatest in enterocytes among all of the tissues studied. Incubation of enterocytes with gabaculine resulted in decreases (P < 0.05) in the synthesis of ornithine and citrulline from glutamine and proline. When gabaculine was orally administered to pigs (0.83 mg/kg body weight) to inhibit intestinal synthesis of citrulline from glutamine and proline, plasma concentrations of citrulline (-26%) and arginine (-22%) decreased (P < 0.05), whereas those of alanine (+21%), ornithine (+17%), proline (+107%), taurine (+56%) and branched-chain amino acids (+21-40%) increased (P < 0.05). On the basis of dietary arginine intake and estimated arginine utilization, the endogenous synthesis of arginine in the 28-kg pig provided ≥50.2% of total daily arginine requirement. Taken together, our results suggest an important role for endogenous synthesis of arginine in regulating arginine homeostasis in postweaning growing pigs, as previously shown in neonatal pigs.

Rice Bran Oil and Cholesterol Metabolism

Abstract: A range of human and animal studies have shown that rice bran oil (RBO) is an edible oil of preference for improving serum cholesterol levels and lipoprotein profiles with similarity to the more commonly used vegetable oils such as corn oil and safflower oil. Of particular interest is the observation that blending RBO with safflower oil at a definite proportion (7:3, wt/wt) magnifies the hypocholesterolemic efficacy, compared with the effect of each oil alone. Although the mechanism underlying this effect is not apparent at present, the blending may have a practical significance. The blending effect was reproduced in rats fed a cholesterol-enriched diet, and there was also a decrease in liver cholesterol. The occurrence of peculiar components such as gamma-oryzanol and tocotrienols could be responsible for the hypocholesterolemic effect of RBO.