Human selenite metabolism: a kinetic model.

A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element.

[The effect of food supplements on the bioavailability of breast milk for premature infants--fecal fat and carbohydrate excretion]. / Der Einfluss von Nahrungssupplementen auf die Bioverfügbarkeit der Frauenmilch für Frühgeborene. Die faecale Fett und Kohlenhydratexkretion.

Faecal excretion of fat and carbohydrates was studied in 14 preterm infants fed on raw mother's milk (group I) or banked fortified human milk (group II) at days 7, 14, 21 and 28 of postnatal life: group I: n = 5; 31.0 +/- 2.0 weeks; 1954 +/- 441 g; group II: n = 9; 32.0 +/- 1.0 weeks; 1806 +/- 176 g. Mixtures of amino acids, peptides, minerals, dextrine and maltose were designed for fortifying banked human milk. There were no significant differences between faecal excretion of fat and carbohydrates in both feeding groups. The investigated human milk fortifier helps to realize the protein-energy ratio needed in preterm infants with well tolerable volumes of feeding and without stressing their limited digestive capacity.

Relation of changes in amount and type of dietary fat to fecapentaenes in premenopausal women.

Correlation studies suggest that fecal mutagenicity is increased in groups eating high-fat diets, the same groups who are often found to have high colorectal cancer incidence and mortality. The fecapentaenes are the best characterized class of fecal mutagens, but the relationship of dietary fat intake to the excretion of these potent genotoxins is unknown. We studied the effect of changes in amount and type of dietary fat on fecapentaene levels in 31 premenopausal women 20-40 years of age who participated in a controlled feeding study. After a pre-diet free-living period lasting 1 menstrual cycle, women were placed on a high-fat (40% energy from fat) diet for 4 menstrual cycles and then switched to a low-fat (20% energy from fat) diet for an additional 4 menstrual cycles. One-half the subjects were maintained throughout the study at a ratio of polyunsaturated-to-saturated fatty acids (P/S ratio) of 1.0, the other half at 0.3; body weight was constant. All meals during the controlled diet periods were prepared at the Human Study Facility of the Beltsville Human Nutrition Research Center. Fecapentaene and fecapentaene precursor levels were measured in acetone extracts from 3-day pooled stool samples collected during the study. No differences in fecapentaene or precursor levels were observed between the high- and low-fat diets at either P/S ratio. Fecapentaene and precursor levels were higher while on controlled diets than during the pre-diet free-living period, and levels declined again in the post-diet free-living period. We conclude that dietary fat has no significant effect on fecapentaene or precursor levels in acetone extracts of stool in premenopausal women. The effect of other dietary or non-dietary factors on fecapentaenes remains unknown.

Effects of cottonseed dietary fiber on metabolic parameters in diabetic rats and non-insulin-dependent diabetic humans.

The objective of this study was to evaluate the effect of gland cottonseed dietary fiber (CSDF) containing 86% dietary fiber (mainly cellulose) on serum glucose levels in diabetic rats and in non-insulin-dependent diabetes mellitus (NIDDM) patients. A diet containing 15% CSDF given to streptozotocin-induced diabetic rats for 30 d tended to reduce the postprandial plasma glucose level curve. Alternatively, CSDF significantly increased fecal weight (15 +/- 3 vs. 5 +/- 2 g; P less than 0.01) and shortened transit time (20 +/- 2.24 vs. 11.2 +/- 0.8 h). CSDF had no effect on body weight and serum lipid levels. Twelve NIDDM subjects were given a meal tolerance test (MTT) with or without CSDF before and after daily supplementation of CSDF (16.5 g) in pita twice a day for a month. Incremental glucose levels were significantly (P less than 0.05) lower at 30, 60 and 180 min after the MTT containing CSDF than in subjects consuming a meal without CSDF. The insulin levels also tended to be lower. The NIDDM subjects tolerated the CSDF well. No flatulence or other side effects were exhibited. Plasma lipid levels remained unchanged. We therefore concluded that CSDF may have a potential benefit in the management of NIDDM.

Bioavailability of calcium and phosphorus in human milk fortifiers and formula for very low birth weight infants.

Growth, 96-hour balance of nutrients (nitrogen, fat, calcium (Ca), phosphorus (P), and magnesium), metabolizable energy, and serum biochemical markers of mineral status (Ca and P concentrations and alkaline phosphatase activity) were measured in 22 very low birth weight infants to investigate the bioavailability of minerals from specialized formula and from human milk fortifiers. The intakes of Ca and P were similar between group FORM ("Preemie" SMA) and group CMF (1:1 wt/wt, human milk and Similac Natural Care or Similac Special Care). The intakes of nitrogen, energy, fat, and magnesium differed between groups. Group CMF had significantly greater fecal losses and significantly lower absorption and retention of Ca and P in comparison with those of group FORM. Retention of Ca and P in both groups, however, was greater than 25% below intrauterine estimates of accretion. Retention rates of Ca, P, and magnesium were not correlated with their respective intakes. Weight gain during the balance study and during the entire study interval was significantly less in group CMF. The ratio of Ca retention to either weight gained or nitrogen retained was lower in group CMF, which suggested that the low retention of Ca was related less to the slower rate of growth in these infants than to their greater fecal losses of Ca. Although the cause of the greater fecal losses of Ca and P in this group is unclear, the data suggest an insolubility of the mineral sources. Our results indicate that sole reliance on the absolute mineral concentrations of the milk selected for very low birth weight infants may be unrealistic; the bioavailability of Ca and P from particular mineral sources should be evaluated.

Effect of lipophilic extract of Chlorella vulgaris on alimentary hyperlipidemia in cholesterol-fed rats.

The effect of glycolipid (GL) and phospholipid (PL) fractions obtained from Chlorella on serum lipid level and fecal excretion of steroids were examined in cholesterol-fed rats. The increase of the level of serum lipids were inhibited by the feeding of GL, PL and Chlorella powder almost the same degree. Fecal excretion of steroids (mostly of cholesterol, deoxycholic and lithocholic acid) were increased by feeding of GL and PL fractions. It is concluded that the feeding of each fraction inhibits the absorption of exogenous steroids and promotes turnover of bile acids in liver to suppress the increase of serum cholesterol level caused by administration of high cholesterol diet.

Effect of psyllium gum and wheat bran on spontaneous energy intake.

Energy intake, fecal energy output, and gastrointestinal symptoms were measured in 12 females who consumed either approximately 23 g/d supplementary fiber or a 4 g/d fiber control. Fiber supplements were crackers containing psyllium gum, wheat bran, or a combination of the two fiber sources. After 1 wk on the control cracker, subjects consumed the three high-fiber crackers and the control cracker for 2-wk periods in a balanced design. Gum and combination supplements gave increased bloating and flatulence. Increase in abdominal pain was reported with gum supplement. Mean daily fecal energy was 96 kcal/d with control crackers and was increased by 63 kcal with high-fiber crackers. Gum and combination supplements significantly decreased intake of digestible energy by 153 and 115 kcal/d, respectively. This suppression was not dependent upon fiber intolerance. Wheat bran supplement had no effect on energy intake.

Quantitation of phosphorus excretion in sheep by compartmental analysis.

The control of phosphorus excretion in sheep has been examined by constructing a kinetic model that contains a mechanistic set of connections between blood and gastrointestinal tract. The model was developed using experimental data from chaff-fed sheep and gives an accurate description of the absorption and excretion of phosphorus in feces and urine of the ruminating sheep. Simulation of the response to an intravenous phosphorus infusion by adding an inflow of 2 g/day of phosphorus into the compartment describing blood, predicted values for fecal output of phosphorus lower than found experimentally. However, by alteration of the parameters describing absorption or salivation, the predictions approached experimental values. Similarly simulation of the conditions existing when a liquid diet was infused directly into the abomasum, i.e., a decrease in salivation rate [L(4.1)] and dietary phosphorus entering compartment 5 (abomasum) instead of compartment 4 (rumen), gave incorrect predictions for plasma and urinary phosphorus, but when the parameter for urinary phosphorus was increased the predicted values approached experimental values. These results indicated the main control site for phosphorus excretion in the ruminating sheep was the gastrointestinal tract, whereas for the nonruminating sheep fed the liquid diet, control was exerted by the kidney. A critical factor in the induction of adaptation of phosphorus reabsorption by the kidney was the reduction in salivation, and since this response occurred independently of marked changes in the delivery of phosphorus to the kidney, a humoral factor may be involved in this communication between salivary gland and kidney.

Effects of whole cottonseed, cottonseed oil or animal fat on digestibility of wheat straw diets by steers.

Two completely random digestion trials were conducted, each with 12 beef steers (325 kg initial weight), to measure changes in digestibilities of fat and of forage components when fat was added to diets containing 62 to 76% wheat straw. Trial 1 diets contained either no added fat or 6.3% added fat from whole cottonseed (30% of the diet), cottonseed oil or animal fat; diets were formulated to contain equal levels of cottonseed hulls and cottonseed meal. Trial 2 diets contained 0, 2, 4 or 8% added animal fat. In all forms and at all levels, added fat increased apparent digestibility of dietary lipid (P less than .05). However, estimated true digestibility of lipid decreased (from 94 to 71%) as added fat was increased from 0 to 8% (P less than .05). Up to 6.3% added fat increased digestible energy (DE) content of the diet. Fat additions of 2 and 4% increased daily DE intake (P less than .05) and did not depress digestibility of diet components (P greater than .05). Fat additions of 6.3% or greater, either as free fats or as whole cottonseed, reduced (P less than .05) mean acid detergent fiber digestibility from 40 to 28%. In addition to depressing fiber digestibility, 8% added fat reduced (P less than .05) digestibilities of dry matter (from 54 to 47%), organic matter (60 to 52%) and gross energy (60 to 51%). Oil fed as whole cottonseed caused digestibility depressions similar to free fat addition at the same level.(ABSTRACT TRUNCATED AT 250 WORDS)

High dosage desferrioxamine therapy in a female patient with acquired aplastic anaemia and transfusion siderosis.

A 32 year old woman with severe aplastic anaemia required frequent transfusions and consequently developed hyperferrioxaemia (54 microMol/l) and hyperferritinaemia (1,700 ng/ml). For the treatment of transfusion siderosis she was given 18 high dose courses each comprising 35 g of desferrioxamine. Because of pre-existing thrombocytopenia (platelet count 5 X 10(9)/l) the iron chelating agent was given by continuous intravenous infusion over 3 1/2 days. High dose desferrioxamine had to be abandoned because of severe bone pain. The desferrioxamine infusions achieved a negative iron balance, iron loss after each infusion being 100 to 200 mg in the urine and 400 mg in the faeces. Serum iron and ferritin concentrations fell almost to normal. This report shows that faecal iron excretion must be taken into account in assessing the balance of iron input and output during desferrioxamine treatment.

Effects of dietary saturated and unsaturated fatty acids on fecal bile acids and colon carcinogenesis induced by azoxymethane in rats.

To determine whether the kind of dietary fat affects colon carcinogenesis, male Donryu rats were fed a 5% fat diet containing linoleate, an unsaturated fat, or stearate, a saturated fat, in semipurified fat-free chow. The rats were given azoxymethane (7.4 mg/kg body weight) s.c. once a week for 11 weeks and killed 15 weeks after the last injection of the carcinogen. The rats on the unsaturated fat diet had a significantly higher incidence of colon tumors. Fatty acid analysis of cholesterol esters in the liver and examination of the amount of fecal bile acids showed that the unsaturated fat diet increased the level of cholesterol linoleate and arachidonate in the liver and also increased the fecal excretion of bile acids, especially that of lithocholic acid. The colon tumors in rats on the unsaturated fat diet, compared with those in rats on the saturated fat diet, contained a higher level of lysophosphatidylcholine. These results suggest that increased fecal excretion of bile acids due to increased polyunsaturated cholesterol esters in the liver stimulates phospholipase A2 activity of colon initiated cells and enhances colon carcinogenesis in rats on the unsaturated fat diet.

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders.

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Plasma lipoprotein distribution, faecal cholesterol excretion, and activities of lipoprotein lipase, hepatic lipase and lecithin:cholesterol acyltransferase in rats fed diets rich in sucrose or sunflower oil.

Plasma HDL2 has been suggested to carry cholesterol to the liver for subsequent excretion in the bile and faeces. The enzymes lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin:cholesterol acyltransferase (LCAT) have been implicated in the centripetal cholesterol transport. Activities of these enzymes, the amount of faecal cholesterol excretion and the level of plasma lipoproteins were determined in male rats fed for 4 weeks on purified diets in which the sunflower oil:sucrose ratio was either 0.03 (group a) or 1.01 (group b). Whole plasma triacylglycerols (TG), unesterified cholesterol (UC) and phospholipids (PL) were highest in group (a). The concentration of cholesteryl esters (CE) was similar in the two groups. Protein, TG and UC of VLDL, and TG, UC, CE and PL of HDL2 were higher in group (a) than in group (b). The HDL3-protein and TG were lowest in group (a). Thus, total weight of VLDL and HDL2 were increased, and HDL3 reduced in group (a), which had also increased activities of HL and adipose tissue LPL. Activity of LCAT was lower, and faecal excretion of cholesterol was reduced by about 50% in group (a) compared to group (b). Accordingly, in the rat increased plasma levels of HDL2 are not necessarily indicative of increased faecal cholesterol excretion.

Effects of calcium source and level on site of digestion and calcium levels in the digestive tract of cattle fed high-concentrate diets.

The effect of calcium (Ca) source and level on site of digestion of an 88% concentrate diet was tested with four 431-kg, intestine-cannulated steers in a 4 X 4 Latin square experiment. Diets, limit-fed at 1.3% of body weight, contained .25% Ca with no supplemental Ca (B), .40 or .48% Ca from addition of either .95% CaCl2-2H2O (Cl) or .65% CaCO3 (LL), or 1.11% Ca from addition of 2.5% CaCO3 (HL). No effects of source of Ca (CaCl2-2H2O vs CaCO3) were observed, although ruminal pH and ruminal ammonia-nitrogen (N) concentrations tended to be lower with Cl. Ruminal fluid dilution rate increased linearly (P less than .05) with the addition of Ca to the diet. Ruminal fluid dilution rate and volume were negatively related (r = -.72; P less than .01). Organic matter (OM) and starch digestibilities in the rumen tended to decline with the addition of Ca to the diet, while postruminal OM and starch disappearance increased (P less than .05) to compensate. Flow of N to the duodenum decreased (P greater than .05) with addition of Ca to the diet. Concentrations of soluble Ca found in ruminal and duodenal fluid increased linearly (P less than .05) with dietary Ca intake. Intestinal Ca disappearance increased linearly and quadratically (P less than .05) with increasing dietary Ca and exceeded 80% of Ca entering the small intestine. In a second experiment, the rate of in situ dry matter (DM) disappearance of rolled corn was not greatly altered by addition of Ca to the diet.

Nutritional balance studies in very low-birth-weight infants: role of soy formula.

Although a soy-based lactose-free infant formula is sometimes used for feeding very low-birth-weight infants, the nutritional adequacy of this diet has not been thoroughly investigated. This study used the metabolic balance technique to compare nutrient retention rates in 19 very low-birth-weight (less than 1,530 gm) infants fed either a soy-based formula or a conventional milk-based formula. Serum chemistries and anthropometric measurements were assessed serially. The soy isolate supplemented with methionine as the sole dietary protein appeared to be adequately utilized, and nitrogen retention rates comparable to fetal accretion rates could be achieved in soy-fed infants in the limited period of study. The absence of lactose in the diet of soy-fed infants did not interfere with calcium metabolism. However, phosphorus absorption was diminished with the feeding of soy formula, which resulted in relative hypophosphatemia. Although the soy-fed infants showed increased renal conservation of phosphorus during the study period, the lesser absorption may, over time, stress phosphorus homeostatic control mechanisms. It is concluded that routine use of soy formula without specific therapeutic indications is undesirable in feeding very low-birth-weight infants. Extended use of such a formulation needs to be monitored for potential adverse effects on skeletal mineralization.

Chelation of cadmium with BAL and DTPA in rats.

Cadmium is unique among non-essential metals in several of its toxicological effects because of its long biological half life, slow excretion and delayed action on the kidneys. Although cadmium poisoning in humans is uncommon, there are reports of chronic cadmium poisoning in workmen and also in others in certain polluted areas. At present there are no suitable methods either to measure the body burden of cadmium or to treat cadmium poisoning. The therapeutic effects of various chelating agents including 2,3-dimercaptopropanol (BAL) and its soluble glycosides have been studied without much success in acute cadmium intoxication. However, those studies were done before anything was known of the specific binding of cadmium to metallothionein, an intracellular low molecular weight protein. The potential role of this protein in the detoxification and toxicity of metals has been reviewed recently. The induced synthesis of metallothionein has a marked effect on the pharmacokinetics of cadmium and other divalent metals. Thus it is important to consider the intracellular binding of cadmium with metallothionein in developing a suitable chelation therapy for chronic exposure to cadmium. The in vivo chelation of cadmium with BAL or BAL and diethylenetriamine pentaacetic acid (DTPA) from rats exposed to cadmium is reported here.