Biomedical subjects
M B Reddy
Publications and source records attributed to M B Reddy.
Can propofol cause keratitis?
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Pneumocoele following psoas compartment block.
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Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet.
BACKGROUND: Ascorbic acid has a pronounced enhancing effect on the absorption of dietary nonheme iron when assessed by feeding single meals to fasting subjects. This contrasts with the negligible effect on iron balance of long-term supplementation with vitamin C. OBJECTIVE: Our goal was to examine the effect of vitamin C on nonheme-iron absorption from a complete diet rather than from single meals. DESIGN: Iron absorption from a complete diet was measured during 3 separate dietary periods in 12 subjects by having the subjects ingest a labeled wheat roll with every meal for 5 d. The diet was freely chosen for the first dietary period and was then altered to maximally decrease or increase the dietary intake of vitamin C during the second and third periods. RESULTS: There was no significant difference in mean iron absorption among the 3 dietary periods despite a range of mean daily intakes of dietary vitamin C of 51-247 mg/d. When absorption values were adjusted for differences in iron status and the 3 absorption periods were pooled, multiple regression analysis indicated that iron absorption correlated negatively with dietary phosphate (P = 0.0005) and positively with ascorbic acid (P = 0.0069) and animal tissue (P = 0.0285). CONCLUSIONS: The facilitating effect of vitamin C on iron absorption from a complete diet is far less pronounced than that from single meals. These findings may explain why several prior studies did not show a significant effect on iron status of prolonged supplementation with vitamin C.
Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors.
Soy protein favorably alters serum lipids and lipoproteins in hypercholesterolemic individuals, thereby reducing cardiovascular disease risk. The primary purpose was to determine the effect of soy protein (40 g/d) on circulating lipids and lipoproteins or coagulation and fibrinolytic factors in normocholesterolemic and mildly hypercholesterolemic perimenopausal women. We also determined the contribution of coagulation and fibrinolytic and other factors (e.g., body size and composition; serum estrogens, ferritin, iron; dietary intake) to lipid profiles. Subjects were randomly assigned to treatment: isoflavone-rich soy (n = 24), isoflavone-poor soy (n = 24), or whey control (n = 21) protein. We measured circulating lipids and lipoproteins at baseline, wk 12 and wk 24, and coagulation/fibrinolytic factors at baseline and wk 24. Coagulation and fibrinolytic factors were not adversely affected by treatment. Treatment did not alter lipid profiles in mildly hypercholesterolemic (n = 30) or in all subjects combined. Time significantly (P < 0.001) affected serum total cholesterol, triacylglycerol, LDL cholesterol and HDL cholesterol concentrations. We could not attribute changes over time to various factors, but at baseline accounted for 57% of the variability in HDL cholesterol (P < or = 0.0001) and for 50% in the total to HDL cholesterol ratio (P < or = 0.0001). Dietary vitamin E and % energy from fat had positive effects, whereas plasma plasminogen activator inhibitor-1, fibrinogen, body weight and serum ferritin had negative effects on HDL and total to HDL cholesterol. Isoflavone-rich or isoflavone-poor soy protein had no effect on lipid profiles or coagulation and fibrinolytic factors, whereas the effect of time suggested that the hormonal milieu during the menopausal transition may have overridden any detectable treatment effect on lipids. The relationship between coagulation factors and serum lipids should be examined further as indices of cardiovascular disease risk in midlife women.
Does epidermal turnover reduce percutaneous penetration?
PURPOSE: After its removal from the skin surface, chemical remaining within the skin can become systemically available. The fraction of chemical in the skin that eventually enters the body depends on the relative rates of percutaneous transport and epidermal turnover (i.e., stratum corneum desquamation). Indeed, some investigators have claimed that desquamation is an efficient mechanism for eliminating dermally absorbed chemical from the skin. METHODS: The fate of chemical within the skin following chemical contact was examined using a mathematical model representing turnover of and absorption into the stratum corneum and viable epidermis. The effects of turnover rate, exposure duration, penetrant lipophilicity, and lag time for chemical diffusion were explored. RESULTS: These calculations show that significant amounts of chemical can be removed from skin by desquamation if epidermal turnover is fast relative to chemical diffusion through the stratum corneum. However, except for highly lipophilic and/or high molecular weight (>350 Da) chemicals, the normal epidermal turnover rate is not fast enough and most of the chemical in the skin at the end of an exposure will enter the body. CONCLUSIONS: Epidermal turnover can significantly reduce subsequent chemical absorption into the systemic circulation only for highly lipophilic or high molecular weight chemicals.
Estimation of nonheme-iron bioavailability from meal composition.
BACKGROUND: Considerable data are available on the individual effects of dietary factors on nonheme-iron absorption, but their combined effect when they are present in the same meal is not known. OBJECTIVE: Our objective was to predict the bioavailability of iron from complex meals that are consumed commonly in the United States on the basis of the contents of factors that are known to promote or inhibit food iron absorption. DESIGN: Radioisotopic measurements of nonheme-iron absorption from 25 meals were made in 86 volunteer subjects by using extrinsic radioiron labeling. The meal contents of nonheme iron, calcium, ascorbic acid, polyphenols, and phytic acid were determined by biochemical analysis; energy and protein contents were estimated from food-composition tables. Animal tissue content was based on weight or was obtained from the manufacturer. RESULTS: After adjusting iron absorption for differences in iron status, the significant biochemical predictors of iron absorption as determined by multiple regression analysis were the contents of animal tissue (P = 0.0001), phytic acid (P = 0.0001), and ascorbic acid (P = 0. 0441). Collectively, these 3 variables accounted for 16.4% of the variation in absorption. On the basis of the multiple regression analysis, we developed the following equation to estimate iron absorption: Ln absorption, % (adjusted to serum ferritin concentration of 30 microg/L) = 1.9786 + (0.0123 x animal tissue in g) - (0.0034 x phytic acid in mg) + (0.0065 x ascorbic acid in mg). CONCLUSION: For the 25 meals evaluated, only the contents of animal tissue, phytic acid, and ascorbic acid were useful for estimating nonheme-iron absorption.
Caco-2 cells can be used to assess human iron bioavailability from a semipurified meal.
A Caco-2 cell model with extrinsic radioiron was used to evaluate the effect of dietary factors on nonheme iron bioavailability from a semipurified meal. Study 1 was conducted to evaluate the effect of enhancers (ascorbic acid) and inhibitors (bran, phytate and tea) on iron bioavailability when added to semipurified meal containing egg albumen as a protein source. The effect of various proteins [bovine serum albumin (BSA), casein, beef and soy] on iron bioavailability was evaluated in Study 2 by substituting the above protein sources for egg albumen. Protein solubilization following in vitro digestion for individual test meals was not significantly different from the control. On the other hand, nonheme iron solubilization (0.8+/-0.0 to 5.9+/-0.3 vs. 4.9+/-0.8 mg/L) varied significantly. The total iron uptake for each meal was calculated based on the percentage of radioiron taken up and transported by Caco-2 cells and the amount of nonheme iron present in uptake solutions. Iron uptake ratios represent test/control values. With the exception of BSA and ascorbic acid, the effect of dietary factors was similar to that found in humans reported in the literature. A significant correlation (r = 0.97; P<0.0001) was found between the published human absorption data and the iron uptake by the Caco-2 cells. The results of our study indicate the usefulness of Caco-2 cells in assessing human iron absorption and the feasibility of this cell model in studying iron bioavailability from various food combinations, otherwise not easily performed in humans.
An evaluation of EDTA compounds for iron fortification of cereal-based foods.
Fe absorption was measured in adult human subjects consuming different cereal foods fortified with radiolabelled FeSO4, ferrous fumarate or NaFeEDTA, or with radiolabelled FeSO4 or ferric pyrophosphate in combination with different concentrations of Na2EDTA. Mean Fe absorption from wheat, wheat-soyabean and quinoa (Chenopodium quinoa) infant cereals fortified with FeSO4 or ferrous fumarate ranged from 0.6 to 2.2%. For each infant cereal, mean Fe absorption from ferrous fumarate was similar to that from FeSO4 (absorption ratio 0.91-1.28). Mean Fe absorption from FeSO4-fortified bread rolls was 1.0% when made from high-extraction wheat flour and 5.7% when made from low-extraction wheat flour. Fe absorption from infant cereals and bread rolls fortified with NaFeEDTA was 1.9-3.9 times greater than when the same product was fortified with FeSO4. Both high phytate content and consumption of tea decreased Fe absorption from the NaFeEDTA-fortified rolls. When Na2EDTA up to a 1:1 molar ratio (EDTA:Fe) was added to FeSO4-fortified wheat cereal and wheat-soyabean cereal mean Fe absorption from the wheat cereal increased from 1.0% to a maximum of 5.7% at a molar ratio of 0.67:1, and from the wheat-soyabean cereal from 0.7% to a maximum of 2.9% at a molar ratio of 1:1. Adding Na2EDTA to ferric pyrophosphate-fortified wheat cereal did not significantly increase absorption (P > 0.05). We conclude that Fe absorption is higher from cereal foods fortified with NaFeEDTA than when fortified with FeSO4 or ferrous fumarate, and that Na2EDTA can be added to cereal foods to enhance absorption of soluble Fe-fortification compounds such as FeSO4.
The impact of food processing on the nutritional quality of vitamins and minerals.
Processing (including preparation) makes food healthier, safer, tastier and more shelf-stable. While the benefits are numerous, processing can also be detrimental, affecting the nutritional quality of foods. Blanching, for example, results in leaching losses of vitamins and minerals. Also, milling and extrusion can cause the physical removal of minerals during processing. The nutritional quality of minerals in food depends on their quantity as well as their bioavailability. The bioavailability of key minerals such as iron, zinc and calcium is known to be significantly affected by the fiber, phytic acid, and tannin content of foods. Concentrations of these constituents are altered by various processing methods including milling, fermentation, germination (sprouting), extrusion, and thermal processing. Vitamins, especially ascorbic acid, thiamin and folic acid, are highly sensitive to the same processing methods. The time and temperature of processing, product composition and storage are all factors that substantially impact the vitamin status of our foods.
Physiologically relevant one-compartment pharmacokinetic models for skin. 2. Comparison of models when combined with a systemic pharmacokinetic model.
Transport of chemicals through skin is best modeled as passive diffusion through a membrane, but mathematical solutions for realistic conditions are cumbersome. Compartment models, representing skin as a stirred tank, are mathematically simpler but less physiologically relevant. In a previous paper, several different compartment models were developed assuming constant blood and vehicle concentrations. Here, five skin models (four of the previously described compartment models and one membrane model) are combined with a one-compartment systemic pharmacokinetic (PK) model to examine the effects of changing vehicle and blood concentrations and to clarify how differences between skin models affect the predicted systemic response. The skin-PK models were solved with the same input parameters (i.e., permeability coefficients, partition coefficients, skin thickness, and cutaneous blood flow rates) and compared for five different exposure scenarios. Because the models have different underlying assumptions, they do predict different results. For many exposure situations compartment models give acceptable results, with the most pronounced differences from the membrane model during short exposure times. Generally, the compartment model that most closely represents the membrane model was developed by forcing it to match the membrane model for conditions similar to those of the given exposure scenario.
The influence of different cereal grains on iron absorption from infant cereal foods.
Iron absorption from various cereal grains was evaluated in the present study to identify possible preferences for the preparation of infant weaning foods. In six separate studies, four radioiron absorption tests were performed in each of 57 volunteer subjects by using a sequential double-isotopic method. Serum ferritin concentration was used to adjust for the effect of differences in the iron status of subjects participating in separate studies. Identical commercial processing and test meal composition were used to evaluate iron absorption from 50 g cooked cereal prepared from rice, wheat, maize, oats, millet, and sweet or bitter quinoa. In an initial evaluation of cereals fortified with 2.5 mg Fe as FeSO4, geometric mean absorption values were uniformly < 1% for all cereals and were not significantly different. In subsequent studies, percentage iron absorption was enhanced by either eliminating the fortifying iron or adding 50 mg ascorbic acid to the test meal. The effect was similar for most of the cereals tested with a composite mean increase in absorption of 37% when fortifying iron was removed and 270% when ascorbic acid was added. There was a strong inverse correlation between iron absorption and the phytate content of different cereals. Except for a modestly lower absorption of iron from quinoa and a remarkably higher absorption from one lot of maize, we conclude that the type of cereal grain has little influence on iron bioavailability of infant cereals. On the other hand, modification in the milling and processing methods for cereal grains that reduce their content of phytic acid is likely to improve iron availability significantly.
Effect of calcium intake on nonheme-iron absorption from a complete diet.
Recent studies based on radioiron measurements from single meals have suggested that calcium has a strongly inhibitory influence on nonheme-iron absorption. In view of evidence that the importance of various dietary enhancers and inhibitors of absorption is greatly diminished when assessed by labeling a complete diet, the present study evaluated the effect of variations in calcium intake on total dietary nonheme-iron absorption. Nonheme-iron absorption was measured in 14 healthy volunteers during three periods in which the diet was freely chosen or modified to decrease or increase dietary calcium intake maximally. The diet was labeled during each 5-d period by including with each of the two main meals of the day a small bread roll tagged extrinsically with radioiron. Carefully maintained dietary records indicated that 69-78% of the daily iron intake was labeled by this method. The basal calcium intake of 684 mg/d varied from 280 to 1281 mg/d when calcium intake was reduced or increased, respectively. Geometric mean iron-absorption values of 5.01%, 4.71%, and 5.83% for the three dietary periods were not significantly different from one another. No significant relation was observed between nonheme-iron absorption and dietary factors known to influence iron absorption. We conclude that calcium intake had no significant influence on nonheme-iron absorption from a varied diet.
The influence of different protein sources on phytate inhibition of nonheme-iron absorption in humans.
The inhibiting effect of phytate on nonheme-iron absorption from different protein sources was examined in human subjects using extrinsic radioiron labeling. A drink containing maltodextrose and corn oil was used as a control meal to which was added sufficient sodium phytate to provide 300 mg phytic acid and/or various protein sources. The proteins were selected to cover a broad range of effects on bioavailability and included egg white, meat, and phytate-free soy protein. When sodium phytate alone was added, there was a pronounced 83-90% reduction in mean absorption in separate studies with a composite average decline of 86%. Despite a wide range in absorption from meals containing the three protein sources, a remarkably similar relative inhibition was observed when sodium phytate was added. No significant difference in the inhibiting effect of phytate could be detected with additions ranging from the equivalent of 50-300 mg phytic acid to a meal containing egg white as the protein source. Our studies found no evidence that the inhibiting effect of phytate depends on the protein composition of the meal.
The effect of red and white wines on nonheme-iron absorption in humans.
The effect of the phenolic compounds in wine was examined in this study by performing radioiron-absorption measurements from extrinsically labeled test meals in 33 human subjects. In four separate studies we observed that absorption was 2- to 3-fold higher from white wine containing a low concentration of polyphenols than from two red wines containing a 10-fold higher concentration of polyphenols. The interaction between the polyphenols and alcohol in wine was evaluated by reducing the alcohol content of the wines by approximately 90%. When the alcohol concentration was reduced, there was a significant 28% decrease in nonheme-iron absorption with red wine but no effect with white wine. The inhibitory effect of red wines with reduced alcohol content was about twofold greater when they were consumed with a small bread roll than when taken without food. Our findings indicate that the inhibitory effect of phenolic compounds in red wine is unlikely to affect iron balance significantly.
Efficacy of weekly compared with daily iron supplementation.
A reduction in the frequency of iron supplement administration to once or twice weekly is being widely examined in developing countries on the assumption that the side effects of oral iron will decrease and that the reduction in administered iron will be offset by a lesser inhibition in absorption from iron taken on the previous day. We examined this premise by measuring iron absorption from 50 mg radiolabeled ferrous sulfate in 23 female volunteer subjects divided into two groups. In the first group, a labeled ferrous sulfate supplement was given with water, and in the second group it was given with a rice-based meal. In both groups, absorption was measured in a randomized fashion twice in each subject, once with daily and once with weekly supplementation. Those tested for daily supplementation were given an iron supplement daily for 6 d before testing whereas those tested for weekly supplementation were given no iron for 6 d before testing. When the labeled iron supplement was given with water only, absorption averaged 8.5% with daily and 9.8% with weekly administration compared with 2.3% and 2.6%, respectively, when given with food. The 13% lower absorption observed with daily administration in both groups was not statistically significant (P > 0.20). These results indicate that there is no significant absorptive advantage in giving iron less often than once daily.
Absorption of nonheme iron in ascorbic acid-deficient rats.
Prior studies have shown that the absorption of dietary nonheme iron in rats is much higher and less responsive to dietary variables than in human subjects. The aim of the present study was to determine whether this dissimilarity is explained by species differences in ascorbic acid status or metabolism. Iron absorption studies were performed with normal rats and with a genetic strain that lacks the ability to synthesize the vitamin. Ascorbic acid deficiency was produced in these animals by removing supplemental vitamin C from the diet for a brief period before the study. Iron absorption was measured from meals tagged extrinsically with 59Fe and measured by whole-body counting. We studied the effect on iron absorption of adding meat, ascorbic acid, soybean, tea, or bran to the test meal. A significant but modest effect of bran on iron absorption was observed in normal rats and of ascorbic acid and tea in ascorbate-depleted animals. However, the overall sensitivity of rats to dietary facilitators or inhibitors of nonheme iron absorption was not altered dramatically by ascorbic acid depletion. The relative insensitivity of rats to dietary factors affecting nonheme iron absorption in humans is not explained by differences in ascorbic acid metabolism between rats and humans.
Soy protein, phytate, and iron absorption in humans.
The effect of reducing the phytate in soy-protein isolates on nonheme-iron absorption was examined in 32 human subjects. Iron absorption was measured by using an extrinsic radioiron label in liquid-formula meals containing hydrolyzed corn starch, corn oil, and either egg white or one of a series of soy-protein isolates with different phytate contents. Iron absorption increased four- to fivefold when phytic acid was reduced from its native amount of 4.9-8.4 to less than 0.01 mg/g of isolate. Even relatively small quantities of residual phytate were strongly inhibitory and phytic acid had to be reduced to less than 0.3 mg/g of isolate (corresponding to less than 10 mg phytic acid/meal) before a meaningful increase in iron absorption was observed. However, even after removal of virtually all the phytic acid, iron absorption from the soy-protein meal was still only half that of the egg white control. It is concluded that phytic acid is a major inhibitory factor of iron absorption in soy-protein isolates but that other factors contribute to the poor bioavailability of iron from these products.