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Biomedical subjects

M Janghorbani

Publications and source records attributed to M Janghorbani.

At least 73 records · Page 4Linked to original sources

Labeling hen's egg with 74Se for use in human metabolic experiments.

Experiments were conducted with laying hens to explore quantitative aspects of incorporation of 75Se ( radioselenium ) at various dosing levels and for different chemical forms of an orally administered tracer. Quantitative distribution of the incorporated isotope in egg white and egg yolk was strongly influenced by both the chemical form of the label and the dosing level. The ratio of egg yolk:egg white selenium decreased with increased level of administered dose of selenite. In addition, the rate of incorporation and the amount of selenium in whole egg were higher when [75Se]selenomethionine was given as compared to [75Se]selenite. Characterization of the chemical form of selenium in egg white and egg yolk labeled biologically by giving hens radioactive selenite or selenomethionine was performed by classification as: selenite, selenoprotein and fat-bound selenium. Studies were then undertaken to achieve intrinsic labeling of egg white and egg yolk with stable isotope 74Se for purposes of exploring selenium bioavailability in humans. Enrichments of 74Se in egg white and egg yolk of hens given high dose selenite (54.4 micrograms 74Se ) were 20- and 28-fold, whereas in egg white and egg yolk of hens given low dose (10.9 micrograms 74Se ) they were 4- and 10-fold the level of natural abundance, respectively. The stable isotope-labeling studies indicated that a 7-day sequential dosing protocol with 20-100 micrograms Se per dose permitted sufficient enrichment of egg white (only high dose) and of yolk with the stable isotope 74Se for use in human metabolic studies.

Animals↗

Simultaneous determination of absorption of selenium from poultry meat and selenite in young men: application of a triple stable-isotope method.

A triple stable-isotope method was used to estimate simultaneously selenium absorption from poultry meat intrinsically labelled with 74Se and from an extrinsic tracer of 76SeO3(2-) in four young adult men. The subjects received an experimental diet based on chicken meat as the source of protein. Two diet periods, lasting from 5 to 10 d, depending on the frequency of stool output for each subject, were conducted to allow duplicate determinations within each subject of Se absorption from both sources. Absorption of Se was determined by the faecal isotope balance procedure through monitoring the stable isotopes 74Se, 76Se and 80Se by means of radiochemical neutron activation analysis. For the separate periods, mean (with SEM) absorption of 74Se from the intrinsically-labelled poultry meat was 70.9 (1.5)% and 72.0 (2.5)%. The absorption of Se from 76SeO3(2-) was 34.7 (5.5)% and 37.6 (3.2)% during the same periods. From these results it is concluded that, under the present experimental conditions, the intrinsic and extrinsic Se isotopes did not form a common pool before absorption. Possible reasons for this are discussed.

Adult↗

Absorption of stable70 Zn in healthy young men in relation to zinc intake.

Zinc absorption was measured in two groups of four healthy young men using the method of stable tracer isotope neutron activation analysis. All absorption measurements were made using a test dose of ZnCl2 in subjects who participated in an overnight fast and also in subjects from whom food was withheld for 5 h after ingestion of tracer. In one group of experimental subjects, dietary zinc intake was held constant (approximately 15 mg/day), and three different test doses of the tracer were administered at weekly intervals. Fractional absorption was 81% from a 4.52-mg dose, 67% from a 6.47 mg dose and 61% for a 24.52-mg dose. In the other group of subjects, dietary zinc was reduced from approximately 15 mg to less than 2 mg/day. This was accompanied by a significant increase in fractional zinc absorption of a fixed tracer zinc dose (1.19 mg), from 81 to 92%. This increase, which occurred within 6 days, was also measurable when the tracer zinc dose was increased to 4.76 mg. These data indicate that there is a significant effect of the dose level of stable zinc isotope on its fractional absorption. They also demonstrate that a restriction in dietary zinc intake results in a prompt increase in the absorption of a fixed pulse dose of zinc in healthy young men.

Adult↗

An evaluation of the nutritional value of a soy protein concentrate in young adult men using the short-term N-balance method.

Eight healthy young men participated in a metabolic balance study designed to assess the protein quality of soy protein concentrate (STAPRO-3200). Subjects received varying intakes of the test protein [0.35, 0.45, 0.55 and 0.65 g protein (N X 6.25) per kilogram body weight per day] during 10-day experimental periods. Each was preceded by a 1-day protein-free diet. A final diet period with a 0.65 g milk protein intake was included for comparative purposes. During this period and that with the 0.65 g test intake of soy concentrate the stable isotopes 70Zn and 58Fe were added to the diet for 2 days to obtain initial data on the absorption of zinc and iron when soy concentrate was the sole source of protein intake. Mean (+/- SEM) intake of soy concentrate determined to be sufficient for N balance (including allowance of 5 mg N/kg per day for integumental and miscellaneous losses) was 95 (+/- 7) mg N/kg per day. Absorption of the extrinsic doses of labeled iron and zinc did not differ between the soy protein- and milk-based diets. Comparison of these data was made with findings obtained previously with other protein sources evaluated in the same way. The conclusion is that the capacity of the soy concentration to support short-term nitrogen equilibrium in adult protein nutrition is the same as that for good quality animal protein sources. Thus, well-processed soy concentrates can make a nutritionally significant contribution to meeting adult human protein needs.

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The nutritional value of a soy protein concentrate (STAPRO-3200) for long-term protein nutritional maintenance in young men.

Six healthy young male M.I.T. students participated in a metabolic study to assess the capacity of a soy protein concentrate (STAPRO-3200) to serve as the sole source of dietary protein for long-term maintenance of protein nutritional status. Following an initial 9-day period, during which the subjects received an egg-protein, formula diet supplying 1.5 g protein per kilogram per day, the soy protein was given at a level of 0.8 g protein (N X 6.25) per kilogram per day for 82 days. Throughout, nitrogen balances were measured, and at intervals of 3 to 4 weeks, blood chemistries were determined, and evaluations of physical performance were undertaken. In addition measurements were made of zinc absorption and balance and of iron absorption, with the aid of 70Zn and 58Fe. Mean nitrogen balances were slightly positive for all subjects and the protein source was judged to support adequately maintenance of protein nutritional status, confirmed by the absence of changes in relevant blood parameters and maintenance of performance in the exercise tests. Mean zinc absorption was 23% of intake and did not change during the 82-day soy period and crude zinc balances remained slightly positive throughout. Iron intake was solely from the soy concentrate, and each meal was supplemented with ascorbic acid. Iron absorption was highly variable between and within subjects, as determined by the stable isotope balance procedure. Associated with the withdrawal of blood for purposes of monitoring the subjects, serum ferritin declined indicating a reduction in iron stores. These blood changes were used to approximate iron absorption and it was estimated to be 16%. It is concluded that well-processed soy concentrate can serve as the sole source of nitrogen and essential amino acids for long-term maintenance in adult humans.

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Urinary trimethylselenonium excretion by the rat: effect of level and source of selenium-75.

The purpose of this study was to explore in rats the urinary metabolites of selenium (Se), by using [75Se]selenomethionine, [75Se]selenocystine, and [75Se]selenite, and to assess the effects of low and high levels of Se intake on trimethylselenonium ion (TMSe) excretion in urine. Male adult rats were adapted for 6 weeks to a commercial rat laboratory stock diet (0.25 ppm Se). They were then starved for 24 hours and given an oral dose of either low (16 micrograms Se/kg body weight) or high (1500 micrograms Se/kg body weight) Se as the test Se compounds. Appearance of radioactivity in TMSe and non-TMSe Se metabolites in urine was monitored for 48 hours. About 40% of the 75Se dose was excreted in urine. TMSe was the major urinary Se metabolite (57-69% of urinary 75Se and 16-25% of oral 75Se dose) at high, and a minor urinary Se metabolite (10% of urinary 75Se and 3-4% of oral 75Se dose) at low dose levels of Se and for all three Se test compounds. At least 80% of urinary 75Se and 26-42% of the orally administered 75Se were excreted as non-TMSe Se metabolites in urine under the latter condition. It is hypothesized that at a requirement intake of Se either a trace or no TMSe is excreted in urine, and it becomes a major excretory metabolite of Se when the dietary trace mineral intake exceeds a requirement level, probably serving as a means of detoxification.

Animals↗

Labeling of soybeans with the stable isotope 70Zn for use in human metabolic studies.

Radiozinc (65Zn) was used to assess the efficiency of incorporation of the label into soybean seeds by means of a noncycling hydroponic system. It was found that 21.3 and 27.6% of the applied dose was incorporated into the mature seeds when the tracer was applied during vegetative or flowering stages of growth cycle, respectively. The latter method was adapted to labeling with the stable isotope 70Zn, and quantitative incorporation of this isotope was investigated within and among hydroponic culture pots each containing four plants. It was found that on the average 17.7% +/- 3.0% of the applied dose was recovered in the mature seeds harvested from each pot. The mass isotope enrichment ratio for 70Zn: 68Zn in these seeds was 2.93 +/- 0.38 (mean +/- SD) compared with the natural ratio of 0.0343, indicating a high degree of stable isotope enrichment. Results of soybean fractionation studies showed that the enrichment was somewhat higher in the defatted meal fraction as compared with the full-fat, the hull, and the whole seed, indicating somewhat preferential translocation of the applied stable isotope in the protein. Despite this small but observable difference, all fractions were highly enriched with 70Zn. The data from this study indicated that noncycling hydroponic culture may be effectively employed to intrinsically label soybeans with the stable isotopes of zinc for use in human feeding trials dealing with the issues of zinc availability. A 100-g portion of such labeled seeds provided 38-43 g protein and 490-620 micrograms 70Zn in various processed products for use in human feeding studies.

Humans↗

Selenium metabolism in healthy adults: quantitative aspects using the stable isotope 74SeO3(2-).

Using the novel method of stable isotopes, kinetics of appearance and disappearance of 74Se in feces, blood, and urine from four young adult males given single and multiple oral doses of 74SeO32- are described. It is shown that this method is suitable as an alternative to the use or radioselenium and permits detailed evaluation of both kinetics and quantitative aspects of absorption, excretion, and retention of selenium in human subjects. The data provided in this manuscript generally confirm the current understanding of the role of gastrointestinal tract and the kidneys in regard to the regulation of selenium nutriture of human subjects. From the peak appearance of the ingested label in urine it is apparent that there is an early preferential urinary excretion of he ingested label in comparison with the native plasma selenium. The present methodology is readily applicable in detailed studies of urinary forms of the excreted label and elucidation of the time course of metabolism of the ingested label as regards its conversion to the urinary metabolites.

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Selenium bioavailability with reference to human nutrition.

Various aspects of selenium metabolism and nutrition in relation to the question of selenium bioavailability in foods and the diet of man are reviewed. Few published studies exist on selenium metabolism in human subjects, particularly those representative of healthy individuals in the United States. Animal studies reveal that various factors, including the source and chemical form of selenium in foods and feeds, influence selenium bioavailability. However, the quantitative significance of animal assay data for human nutrition is not known. The limited number of published studies in man suggest that the metabolic fate and physiological function of dietary selenite may differ from that of selenomethionine or of food selenium. However, much additional research will be required to establish an adequate picture of the significance of dietary selenium bioavailability in human nutrition and health. Based on initial human experiments carried out at the Massachusetts Institute of Technology, use of stable isotopes of selenium offers promising opportunities for closing the gap of knowledge that now exists concerning the role and significance of factors that determine how the selenium present in foods is used to meet the physiological requirements of the consumer.

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Absorption of dietary zinc in man: comparison of intrinsic and extrinsic labels using a triple stable isotope method.

Determination of true absorption of dietary minerals in human subjects using "extrinsic-tag" approach with stable isotopes requires establishment of its validity. The present study was conducted to test with quantitative aspects absorption of an extrinsic-tag of zinc labeled with 70Zn as compared with an "intrinsic-tag" of the mineral as 68Zn-labeled chicken meat given simultaneously to health male subjects. Three diet periods were used in which diet modulation with respect to zinc dialy intake and nature of protein source (chicken/soy protein isolate) was also examined. Absorption was measured via quantitative fecal isotope balance of 64Zn, 68Zn, 70Zn. For the three diet period 1 (protein: chicken; Zn intake: ZN intake: 10 to 11 mg/day), 2 (protein: chicken/soy protein isolate, 50/50; Zn intake: 10 to 11 mg/day), and 3 (protein: chicken; Zn intake: 7 mg/day), fractional absorption of the extrinsic tag (mean +/- 1 SEM) was 0.46 +/- 0.06, 0.46 +/- 0.06, and 0.66 +/- 0.04 respectively. The comparable values for intrinsic 68Zn were 0.57 +/- 0.06, 0.57 +/- 0.06, and 0.72 +/- 0.04. There was a highly significant correlation (r=0.91), between zinc absorption from the two labels. However, absorption of intrinsic 68Zn was significantly higher (p less than 0.02) during all periods than that for the extrinsic 70Zn. A 50% replacement of protein from chicken meat with the soy protein isolate did not later fractional absorption of zinc from either tag. The ratio of fractional absorption of the extrinsic/intrinsic tag (mean +/- 1 SEM) was 0.79 +/- 0.06, 0.79 +/- 0.04, and 0.92 +/- 0.03 for periods 1, 2, 3, respectively.

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Bioavailability of zinc from a diet based on isolated soy protein: application in young men of the stable isotope tracer, 70Zn.

With the aid of the stable isotope, 70Zn, as a tracer and neutron activation analysis, a combination of extrinsic labeling of meals and fecal monitoring of isotope excretion was used as a safe and noninvasive approach for assessing the effects of the vegetable (soy) and animal (milk, beef) proteins on the absorption of zinc in healthy, adult human volunteers. A known amount of 70Zn was added as ZnCl2, to six consecutive meals over a 2-day period during which either one of three isonitrogenous liquid formulas (skim milk; soy isolate; or a 50:50 mixture) or one of two bologna sausages (soy isolate of beef) were given. The mean absorption of 70Zn from milk, soy and soy/milk was 41 +/- 4, 34 +/- 4, and 41 +/- 7% (mean +/- SEM), respectively, the presence of soy protein having no effect on absorption of the extrinsic label. For beef bologna and soy bologna, fractional absorption of the 70Zn tracer was 41 +/- 4 and 30 +/- 3%, respectively. Beef might favor absorption of extrinsic zinc. The kinetics of isotope excretion, pooling procedures, for stool samples and the utility of fecal markers were also evaluated.

Adult↗

Advances in the use of stable isotopes of minerals in human studies.

In this review, the current state of development of stable isotope methodology is discussed in relation to its application to human mineral nutrition. The minerals considered are magnesium, calcium, iron, copper, zinc, selenium, and lead. Such issues as analytical measurement methodology, the required degree of dietary enrichment, mode of isotope administration, and intrinsic labeling of human foods are reviewed and their current status is presented. It is shown that both mass spectrometry and neutron activation analysis have been applied to various aspects of this research, although the latter more widely. Research need, current problems, and the likely future direction of stable isotopes in human mineral research are summarized.

Animals↗

Comparative measurements of zinc-70 enrichment in human plasma samples with neutron activation and mass spectrometry.

Radiochemical neutron activation analysis (RNAA) is compared with isotope ratio mass spectrometry (IRMS) for the measurement of 70Zn isotopic enrichment in human plasma following oral administration of the isotope. It is shown that both techniques are suitable for this purpose, although IRMS yields more precise data. Each method, with its advantages and limitations, can be realistically employed to study kinetics of appearance of 70Zn in plasma obtained during human metabolic studies.

Humans↗

Accurate measurement of stable isotopes 46Ca and 48Ca in human feces, plasma, and urine in relation to human nutrition of calcium.

A method based on Radiochemical Neutron Activation Analysis (RNAA) is described which allows simultaneous measurement of two stable isotopes of calcium, 46Ca and 48Ca, in human feces, plasma, and urine for the purpose of studying human nutrition and metabolism of calcium. It is shown that these measurements can be made with relative analytical precision of 1--5% depending on the particulars of a given experiment. The method has been applied in humans and data are given showing that kinetics of plasma appearance of 46 Ca administered orally with food can be readily investigated. This method allows investigation of a number of important nutritional and metabolic issues in all human population groups without regard to radioisotope safety considerations, and should prove especially helpful in relation to studies of calcium bioavailability from different foods in a variety of population groups for whom use of radiocalcium is not warranted.

Calcium↗

Intrinsic labelling of chicken meat with stable isotopes of zinc, for intended use in human feeding studies: feasibility and design considerations.

1. The feasibility of intrinsically labelling poultry meat with the stable isotopes 68Zn and 70Zn was investigated. 2. Chickens (1-d-old) were gavaged with solutions of 68Zn and 70Zn several times over a 42 d period. 3. Isotopic analysis of edible tissues has shown that they were significantly enriched with respect to the gavaged isotope and that the extent of isotopic enrichment achieved was sufficient to permit their use in human feeding experiments designed to investigate availability of native Zn from such food models. 4. The absolute efficiency of retention of the stable isotopes from gavage solutions in the edible tissues has been calculated to be 2-3% of the administered dose; methods have been suggested to enhance this value, based on considerations of utilization of dietary Zn.

Animals↗

Use of stable isotopes of selenium in human metabolic studies: development of analytical methodology.

Use of stable isotopes of selenium in relation to enrichment of diets for studies of selenium absorption and metabolism in human subjects is discussed. A method based on radiochemical neutron activation analysis is described which allows accurate measurement of stable isotopes 74Se, 76Se, and 80Se in matrices (feces, plasma, red blood cells, and urine) of interest in metabolic studies. We show that these isotopes can routinely be measured with analytical precision and accuracy of 10% in samples of available size. This precision and accuracy is satisfactory for conduct of many nutritional experiments concerned with gastrointestinal absorption, plasma and red cell selenium turnover, and urinary excretion of the element, using an oral dose of 74Se. Original, experimental data are presented to illustrate the degree of enrichment of 74Se in feces, plasma, and urine after a single oral ingestion of 50 micrograms of the isotope with a breakfast meal in healthy young men.

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