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Biomedical subjects

M Janghorbani

Publications and source records attributed to M Janghorbani.

At least 37 records · Page 2Linked to original sources

Experimental selenium restriction in healthy adult humans: changes in selenium metabolism studied with stable-isotope methodology.

Mechanisms responsible for selenium homeostasis were investigated in healthy adult men receiving diets adequate or low in Se (eight subjects per group). The appearance of a stable isotope of Se, 74Se, in plasma, urine, and feces was measured after oral administration of 74Se-selenite. One group received a restricted level of Se (18 +/- 1 micrograms/d) for 30 d, which resulted in a decrease in urinary, fecal, and plasma Se content compared with the group that consumed 119 +/- 1 micrograms/d. Low Se intake also resulted in decreased urinary 74Se excretion (27.2 +/- 1.4% vs 32.5 +/- 2.3% of the absorbed dose for the adequate intake), increased body retention of 74Se (74.8 +/- 3.1% vs 67.6 +/- 3.8% of the absorbed dose for the adequate group), and a contracted selenite-exchangeable metabolic pool (Se-EMP) (9782 micrograms for adequate Se and 6314 micrograms for the low-Se group; p less than or equal to 0.05). Measurement of Se-EMP may provide an additional and sensitive approach for assessing Se nutriture in human subjects.

Absorption

Ascorbic acid-selenite interactions in humans studied with an oral dose of 74SeO3(2-).

The interaction between dietary ascorbic acid at extremes of ascorbic acid intake and selenium in young adult male humans was investigated with a stable-isotope approach using 74Se-selenite. Measurements were made of 74Se in plasma, urine, and feces with neutron-activation analysis after oral administration of 74SeO3(2-). Urine excretion and total body retention of isotope and the selenite-exchangeable metabolic pool (Se-EMP) were calculated. Limiting dietary ascorbic acid to about 20 mg/d appeared to reduce the time-related retention of absorbed selenite and the size of Se-EMP. Compared with a diet providing 1 g ascorbic acid/d the low ascorbic acid intake was associated with a lower fractional absorption of the isotope, a reduced retention of the label, and a smaller Se-EMP. These data and those previously obtained in subjects with more usual ascorbic acid intakes point to a possible important role for ascorbic acid in the maintenance of Se homeostasis.

Absorption

Determination of zinc and copper absorption at three dietary Zn-Cu ratios by using stable isotope methods in young adult and elderly subjects.

Nine young men and six elderly men and women ingested low-zinc, low-copper, and adequate diets for 2-wk periods. The Zn-Cu ratios averaged 2:1, 15:1, and 5:1. On day 8 of each period, subjects ingested doses of 70Zn and 65Cu so that net absorption could be determined. Zn absorption on the adequate diet was 39 +/- 3% (means +/- SEM) in young subjects and 21 +/- 1% (p less than 0.05) in the elderly subjects. During the low-Zn period, Zn absorption was higher as compared with that on the adequate diet in both young (64 +/- 5%, p less than 0.05) and elderly subjects (43 +/- 7%, p less than 0.05). Cu absorption on the adequate diet was 60 +/- 4% and 53 +/- 2% in young and elderly subjects, respectively. During the low-Cu period, Cu absorption was higher as compared with that on the adequate diet in the elderly subjects (67 +/- 4%, p less than 0.05). Cu absorption was higher in six of seven young subjects on the restricted Cu diet (p greater than 0.05). The effect upon absorption of the change in the Zn-Cu ratio was less than the effect of dietary restriction.

Absorption

Iron absorption from infant foods.

To determine the bioavailability of iron from iron-fortified infant foods, we have determined erythrocyte incorporation of the stable isotope, 58Fe, after feeding the following foods extrinsically labeled with 58Fe: 1) rice cereal with apples and bananas ("cereal-fruit product"), 2) Mead Johnson Enriched Baby Food (MJEBF), a vitamin, mineral, and protein-enriched rice cereal, 3) vegetables and beef ("vegetable-beef product"), 4) grape-juice, and 5) MJEBF. Foods 1-4 were fortified with ferrous sulfate, and food 5 was fortified with ferrous fumarate. Blood was obtained at ages 140, 168, and 196 d of age, and the test meal was fed under standardized conditions at 154 d of age. Erythrocyte incorporation of the 58Fe label was determined from the increase in the mass isotope ratio, 58Fe/57Fe, from the baseline value (at 140 d of age) to the follow-up values. The mass isotope ratio was determined by inductively coupled mass spectrometry. Geometric mean total iron incorporation into erythrocytes from the test meal of MJEBF fortified with ferrous sulfate (food 2) was 0.05 mg, and from the vegetable-beef product test meal (food 3) was 0.08 mg. The low value for MJEBF is presumably explained by the low level of iron fortification. The low value for the vegetable-beef product may reflect the presence of inhibitors of iron absorption. Geometric mean erythrocyte incorporations of iron from the test meals with foods 1, 4 and 5 were 0.15, 0.14, and 0.18 mg, respectively. These erythrocyte incorporation values are 20 to 26% of the estimated 0.7 mg requirement for absorbed iron, and therefore seem nutritionally important.

Biological Availability

Zinc and copper nutritional studies in very low birth weight infants: comparison of stable isotopic extrinsic tag and chemical balance methods.

Measurements of dietary zinc and copper absorption obtained after administration of a single dose of the extrinsic stable isotopic tags 70Zn and 65Cu were compared to measurements made with standard chemical balance methods in 41 appropriate for gestational age premature infants [body wt 1267 +/- 258 g, gestational age 29.8 +/- 1.9 wk (mean +/- SD), 4 to 83 postnatal d of age]. Fifty studies were performed; 33 with premature formula, five with term formula, seven with preterm human milk (PTHM), and five with fortified-PTHM. The percentages of net zinc and 70Zn absorption were found to be significantly greater from PTHM (66.4 +/- 15.2, 68.6 +/- 9.8) than from premature formula (14.0 +/- 29.9, 31.6 +/- 22.4), and term formula (23.6 +/- 18.5, 17.6 +/- 5.6). The percentages of net copper and 65Cu absorption were also found to be significantly greater from PTHM (61.5 +/- 14.0, 69.8 +/- 14.0) than from premature formula (16.6 +/- 20.6, 39.6 +/- 21.6) and term formula (20.6 +/- 24.1, 26.5 +/- 6.9). The percentages of net zinc and 70Zn absorption (35.9 +/- 29.1, 48.4 +/- 9.6) and net copper and 65Cu absorption (38.7 +/- 10.2 and 57.4 +/- 13.1) from fortified PTHM were similar to values from PTHM. Absorption of zinc and copper determined with extrinsic stable isotopic tag and standard nutrient balance methods were significantly correlated. Estimates of endogenous fecal losses of zinc and copper were substantial with each diet, but lower with PTHM. Stepwise, multiple linear regression analysis accounted for, at most, 58% of the variability in the measures of zinc and copper availability. We conclude that extrinsic 70Zn and 65Cu tags can be used to study absorption of dietary zinc and copper by very low birth wt infants.

Absorption

Use of the stable isotope, 58Fe, for determining availability of nonheme iron in meals.

Because of reluctance to use radioisotopes for studies of iron absorption in children, we have explored the feasibility of using the least abundant stable isotope of iron, 58Fe (natural abundance, 0.322 weight %) in a study of nonheme iron absorption. With a balanced cross-over design, each of 16 school-age children was fed a standardized lunch on 3 consecutive days and, 28 days later, an alternate standardized lunch on 3 consecutive days. The lunch included either a beef patty or a beef-soy patty. The mass isotope ratio, 58Fe/57Fe (MIR58/57), was measured in blood by inductively coupled plasma mass spectroscopy before and 14 days after (i.e. study day 15) consuming the three lunches. The MIR58/57 on study day 15 was used as a baseline value for lunches fed on study days 29, 30, and 31. Incorporation of 58Fe into erythrocytes was greater from the lunch with beef patty than from the lunch with beef-soy patty (geometric mean values 2.02 and 1.05% of the dose, p less than 0.03). Based on the similarity of our results with those obtained in adults with radioisotopes, we conclude that 58Fe is a satisfactory tag for studies of nonheme iron absorption from meals.

Child

Erythrocyte incorporation of ingested 58-iron by infants.

The least abundant stable isotope of iron, 58Fe (natural abundance 0.322 weight %), was administered orally to infants to explore the feasibility of using a stable rather than a radioisotope in studies of iron absorption. The dose of 58Fe was given between feedings at age 126 days. The mass isotope ratio, 58Fe/57Fe, was determined in blood by inductively coupled plasma mass spectroscopy and at ages 140, 168, and 196 days. The percentage of the 58Fe dose entering the circulation (3.2 to 16.0%) was inversely correlated with serum ferritin concentration (r = -0.867, p less than 0.01). For individual infants the SD of the percentage of administered dose of iron appearing in the circulation ranged from 0.22 to 1.28. We conclude that the method is likely to be suitable for within-subject comparisons of iron availability from foods. Because of the large between-subject variation, we are pessimistic for this age group about the usefulness of study designs based on group comparisons.

Absorption

Excretion of trimethylselenonium ion in human urine.

A method to permit isolation and measurement of trimethylselenonium ion [TMSe, (CH3)3Se+] from 1 liter of human urine was developed. The method was based on precipitation of TMSe with ammonium reineckate, preseparation with anion-exchange resin, and final thermal decomposition and collection of the product in HNO3. It was tested for recovery and separation from other selenium moieties present in urine using both in vivo-labeled rat urine and human urine spiked with unlabeled TMSe. Recoveries from the former were in the range 76.8-87.0% (mean +/- SD: 81.8 +/- 3.7%, n = 5), while for the latter they were in the range 72.0-93.0% (mean +/- SD for three occasions (%): 80.9 +/- 5.5, 81.4 +/- 7.8, and 78.9 +/- 1.0). The reliability of the method was tested against an HPLC procedure using in vivo-labeled rat's urine. The mean (+/- SD) percentage of urine radioactivity appearing as TMSe was 36.0 +/- 5.7% for the present and 36.2 +/- 6.6% for the HPLC method. The mean of deviations, as percentage of the HPLC method, was -0.03 +/- 8.8%. The linear regression equation for the two methods was y = -0.805 + 1.029x (r2 = 0.81). Excretion of TMSe was measured in urine samples from several persons (range: 0.18-0.37 micrograms Se/liter; mean +/- SD: 0.26 +/- 0.07, n = 9). One subject consumed three separate doses of unlabeled selenite on alternate days (Day 1, 197 micrograms Se; Day 3, 395; and Day 5, 592). For the first 24 h of each period, TMSe excretions (micrograms Se/24 h) were 0.24, 0.53, and 0.97, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Precipitation

Dose-response relations in urinary excretion of trimethylselenonium in the rat.

75Se-labeled selenite was administered to fasting rats by orogastric intubation (1.5-3000 micrograms/kg body wt). Urine was collected and characterized for total radioactivity as well as for radiolabeled trimethylselenonium (TMSe). At lower doses of selenite (up to 500 micrograms/kg body wt), 30% of the administered dose was excreted. At higher doses of selenite, fractional urine excretion decreased as a function of the dose. The observed decrease in fractional urine excretion was not caused by changes in the absorption of the administered radiolabel. There was a direct relationship between the amount of the administered dose of selenite (up to 1500 micrograms/kg body wt) and the proportion of urinary [75Se] excreted as TMSe. Pretreatment with seleno compounds (10 or 100 micrograms Se/kg body wt as selenite, or selenomethionine) for 35 d before a challenge dose of [75Se]selenite did not influence the excretion of total [75Se] or of [75Se]TMSe in urine. Ingestion of a choline-deficient diet, which should deplete the availability of methyl groups, did not have any effect on excretion of total [75Se] or of [75Se]TMSe in urine after a challenge dose of [75Se]selenite (500 micrograms/kg body wt). The data presented here permit the following conclusions: 1) Production of TMSe is dose dependent, 2) production of TMSe from a single acute dose does not depend on the history of selenium intake and 3) rats fed a methyl-deficient diet are able to eliminate Se via formation of TMSe.

Animals

Erythrocyte incorporation of ingested stable isotope of iron (58Fe).

Because of a possible hazard from the use of radioisotopes to determine iron absorption by infants, the use of stable isotopes for this purpose has much appeal. We have applied the method of inductively coupled plasma mass spectrometry (ICP/MS) to determine the mass ratio, 58Fe/57Fe, in blood before and after oral administration of 58Fe. From the increase in erythrocyte enrichment with 58Fe, we have calculated percentage absorption of iron. We have shown that the coefficient of variation of measured mass isotope ratio is 0.1-1.0%, depending on the conditions of the measurement. The method has been applied to a feasibility study involving four infants. Each infant was given 58Fe either as a single dose or as one dose on each of two consecutive days. Each dose provided 1.945 mg iron and 1.440 mg 58Fe. Samples of blood were obtained before isotope administration and at 14, 42, and 60 days thereafter. Isotopic analysis of the samples demonstrates that this approach results in a sufficiently large isotope enrichment to permit satisfactory measurement of iron availability. It is concluded that this new method is highly promising for studies of iron availability in infants and children.

Absorption

Absorption of selenium from milk protein and isolated soy protein formulas in preschool children: studies using stable isotope tracer 74Se.

Absorption of selenium as the stable isotopic tracer [74Se]selenite was measured in four preschool children who were receiving liquid formula diets based on casein, isolated soy protein, and a 50:50 combination of the two protein sources. The children were in continuous ambulatory balance studies within the Clinical Research Center during three consecutive 11-day collection periods. The enrichment of the 74Se/76Se ratio in feces was measured by radiochemical neutron activation analysis, with fractional absorption estimated therefrom. Mean fractional absorption of selenium (+/- SD) from the formulas based on milk, isolated soy protein, and milk-soy were 64.2 +/- 14.6, 73.4 +/- 19.0, and 45.0 +/- 10.9%, respectively, with the combined formula having a significantly lower intestinal uptake for added selenite than the casein formula. Stable isotopes of selenium are safe and potentially useful tools for examining its bioavailability in the diets of young children.

Biological Availability

Absorption and retention of selenium from intrinsically labeled egg and selenite as determined by stable isotope studies in humans.

A study was carried out with four healthy young adult men, consuming a self-selected diet, to investigate quantitative aspects of the gastrointestinal absorption, urinary excretion, and body retention of egg selenium in comparison with selenite. The approach involved simultaneous consumption of egg biologically labeled (intrinsic) with the stable isotope 74Se and a dose of selenite labeled with 76Se (extrinsic label). Four labeled test diets, given on days 6, 16, 26, and 36 of the study were employed, each differing in their protein source: test diet I, 74Se-labeled egg white; diet II, 74Se-labeled egg yolk (high labeling dose) plus balanced L-amino acid mixture; diet III, 74Se-labeled egg yolk (low labeling dose) plus balanced amino acid mixture; and diet IV, balanced amino acid mixture extrinsically labeled with both 74SeO32- and 76SeO32-. The latter diet was included to assess the magnitude of any cross-isotope methodological bias. Fractional absorption (means +/- SEM) for Diet IV was 0.771 +/- 0.010 for the 74SeO32- and 0.656 +/- 0.021 for the 76SeO32- (ratio: 0.851 +/- 0.020); reflecting a small overall cross-isotope bias. Accepting the measurements made with 74SeO32- as the more accurate, experimentally determined values of absorption for the extrinsic tag were adjusted accordingly. The corrected absorption for these diets (% of dose) was (mean +/- SEM; first value for intrinsic label, second value for extrinsic label): diet I, 54.1 +/- 0.7 and 55.4 +/- 2.2; diet II, 76.7 +/- 0.8 and 83.0 +/- 1.8; diet III, 79.0 +/- 1.5 and 85.2 +/- 4.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Absorption of calcium in premature infants as measured with a stable isotope 46Ca extrinsic tag.

Absorption of dietary calcium was evaluated with the extrinsic tag approach and stable isotope methodology in growing premature infants. Fractional absorption of a bolus dose of 46Ca was determined on 16 occasions in 13 premature infants (birth weight 1135 +/- 40 g, gestational age 29.5 +/- 0.4 wk, mean +/- SE) and was found to be 84.4 +/- 2.2%. Fractional absorption of 46Ca ranged between 65 and 97%, and did not appear to be influenced by postnatal age, postconceptual age, body weight, or intake of preterm human milk, fortified preterm human milk, or premature formula. Therefore, if absorption of the 46Ca dose reflects that of dietary calcium, about 80% of dietary calcium is absorbed.

Absorption

Measurement of trimethylselenonium ion in human urine.

A comparison is made between two methods (ion-exchange chromatography vs a difference method) for the quantitative measurement of trimethylselenonium ion (TMSe) in human urine. It is shown that the difference method yields reliable data only if TMSe constitutes a relatively large fraction of urine selenium. Under normal conditions of selenium intake in man, accurate measurement of this important metabolite can, at present, be carried out only with the ion-exchange chromatographic procedure. Preliminary data from a human subject employing stable isotope tracer methodology are given to show that the fraction of urine selenium present as TMSe varies with the level of intake as well as other factors.

Chemical Phenomena