Influence of Dairy Products on Bioavailability of Zinc from Other Food Products: A Review of Complementarity at a Meal Level.

In this paper, we reviewed the role of dairy products in dietary zinc absorption. Dairy products can have a reasonable contribution for dietary zinc intake in Western diets, where dairy consumption is high. However, the co-ingestion of dairy products can also improve zinc absorption from other food products. Such improvements have been observed when dairy products (e.g., milk or yoghurt) were ingested together with food such as rice, tortillas or bread products, all of which are considered to be high-phytate foods with low inherent zinc absorption. For foods low in phytate, the co-ingestion of dairy products did not improve zinc absorption. Improved zinc absorption of zinc from high-phytate foods following co-ingestion with dairy products may be related to the beneficial effects of the citrate and phosphopeptides present in dairy products. Considering that the main dietary zinc sources in areas in the world where zinc deficiency is most prevalent are typically high in phytate, the inclusion of dairy products in meals may be a viable dietary strategy to improve zinc absorption.

Zinc status and its requirement by rural adults consuming wheat from control or zinc-treated fields.

Human zinc (Zn) deficiency is prevalent in areas where cereals dominate in the diet. Soil Zn application may enhance the concentration of Zn in wheat grains and dietary Zn intake by target populations. However, its value has never been practically quantified in Zn nutrition of any population group. We, therefore, studied farming families in rural Punjab (Pakistan). The selected adults (n = 156, grouped based on age and gender) were Zn undernourished (as assessed by estimated Zn bioavailability in their diet) and their plasma Zn levels also indicated Zn deficiency. On average, wheat consumption by the adults contributed about 68% in total Zn and 93% in total phytate intakes. Soil Zn application to wheat fields significantly increased Zn and decreased phytate concentration in chapati (flatbread made of whole-wheat flour). From dietary phytate intakes by the adults, we calculated desired chapati Zn concentration and dietary Zn intake that would meet their daily Zn requirement. The physiological Zn requirements of adult women and men were estimated to be achieved by intake of, respectively, 10.4-15.3 mg Zn d-1 (37-46 mg Zn kg-1 in chapati) and 14.4-23.3 mg Zn d-1 (41-52 mg Zn kg-1 in chapati). It was evident that soil Zn application aiming at optimum grain yield of wheat significantly improved Zn nutrition of the studied adults, but not up to desired levels. High Zn applications (via soil and/or foliage) to wheat and growing cultivars specifically selected for Zn biofortification may be needed to optimise Zn nutrition in rural Pakistan.

Potential thermodynamic and kinetic roles of phytate as an inhibitor of kidney stone formation: theoretical modelling and crystallization experiments.

Kidney stone formation is governed by thermodynamic (supersaturation) and kinetic (crystal nucleation, growth, aggregation) mechanisms. We adopted a dual theoretical and experimental approach to investigate the potential role of urinary phytate in this regard. Thermodynamic constants for eight protonated phytate species and seven calcium-phytate complexes were determined by potentiometry and incorporated into the speciation program JESS. Urine was collected from 16 heathy males and their urine compositions were used as input for JESS. Phytate concentration was varied during modelling. No statistically significant decreases in Ca2+ concentrations or in supersaturation values were predicted by JESS. Crystallization experiments were then performed in pooled urine. Endogenous phytate concentration was determined using a metal-dye assay. The pool was dosed with various concentrations of phytate to achieve final concentrations equivalent to those used for modelling. Experiments showed that phytate had no effects on Ca2+ concentrations (as predicted by our theoretical modelling), metastable limits or crystal nucleation and growth kinetics. However, crystal aggregation kinetics was inhibited. We speculate that HPhy-11, small amounts of which were revealed by modelling, may bind to crystal surfaces and inhibit aggregation. We conclude that phytate exerts a kinetic, but not a thermodynamic inhibitory effect on crystallization in urine.

A phase 1b randomized, placebo-controlled clinical trial with SNF472 in haemodialysis patients.

AIMS: SNF472 is a calcification inhibitor that is being studied as a novel treatment for calciphylaxis and cardiovascular calcification (CVC). A first study showed acceptable safety and tolerability in a single ascending dose administration in healthy volunteers and a single dose administration in haemodialysis (HD) patients. This study aimed to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics relationship of intravenous SNF472 in HD patients in a multiple ascending dose administration trial with 5 doses tested for 1 week (3 administrations) and 1 dose tested for 4 weeks (12 administrations). METHODS: This double blind, randomized, placebo-controlled Phase 1b study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of SNF472 after repeated administrations to HD patients for up to 28 days. A pharmacodynamic assessment was performed to evaluate the potential for SNF472 to inhibit hydroxyapatite (HAP) formation. Patients were grouped into 2 cohorts, receiving multiple ascending doses for 1 week (1 to 20 mg/kg, Cohort 1) and 1 dose of 10 mg/kg for 4 weeks (Cohort 2) of intravenous SNF472. RESULTS: Physical status, body weight, cardiorespiratory function, body temperature and laboratory parameters were in the normal range. No clinically relevant effects on heart rate or blood pressure were observed. No abnormal electrocardiogram or QTcB period were reported. The peak plasma concentration (7.6, 16.1, 46.0 and 66.9 µg/mL for 3, 5, 12.5 and 20 mg/kg, respectively) was observed at the end of the 4-hour infusion and thereafter concentrations declined rapidly with half-life between 32 and 65 min. SNF472 at 10 mg/kg inhibited dose dependently HAP crystallization in plasma samples after 28 days of treatment (78% inhibition, P < .001). CONCLUSIONS: SNF472 is safe and well tolerated in HD patients after 2 schemes: multiple ascending doses for 1 week and after repeated dosing of 10 mg/kg for 4 weeks. In both schemes, SNF472 inhibits the induction of HAP crystallization. These results provide support for the use of SNF472 as a novel treatment for CVC in end-stage renal disease.

First-time-in-human randomized clinical trial in healthy volunteers and haemodialysis patients with SNF472, a novel inhibitor of vascular calcification.

AIMS: SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS: This is a first-time-in-human, double-blind, randomized, placebo-controlled Phase I study to assess the safety, tolerability and PK of SNF472 after ascending single IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite formation. RESULTS: Twenty HV and eight HD patients were enrolled. The starting dose in HV was 0.5 mg kg-1 and the dose ascended to 12.5 mg kg-1 . The dose selected for HD patients was 9 mg kg-1 . Safety analyses support the safety and tolerability of IV SNF472 in HD patients and HV. Most treatment-emergent adverse events were mild in intensity. No clinically significant effects were observed on vital signs or laboratory tests. PK results were similar in HD patients and HV and indicate a lack of significant dialysability. Pharmacodynamic analyses demonstrated that SNF472 administration reduced hydroxyapatite crystallization potential in HD patients who received IV SNF472 9 mg kg-1 by 80.0 ± 2.4% (mean ± standard error of the mean, 95% CI, 75.3-84.8) compared to placebo (8.7 ± 21.0%, P < 0.001, 95% CI, -32.4 to 49.7). CONCLUSION: The results from this study showed acceptable safety and tolerability, and lack of significant dialysability of IV SNF472. It is a potential novel treatment for cardiovascular calcification in end-stage renal disease and calciphylaxis warranting further human studies.

Evaluation of inositol phosphates in urine after topical administration of myo-inositol hexaphosphate to female Wistar rats.

AIMS: Previous studies demonstrated a remarkable increase of urinary InsP6 by topical administration. However, the methodology used for InsP6 analysis was not specific. The aim of this paper is to measure urinary inositol phosphates InsPs using more advanced methodologies and to compare the results with those obtained by the non-specific method. MATERIALS AND METHODS: We fed 12 female rats with a diet without InsP6 for 16days. Then, we administered a topical InsP6 gel at high doses for 7days (50mgInsP6/day) or at low doses for 28days (20mgInsP6/day). We measured urine levels InsPs using a nonspecific method (based on the ability of InsPs to complex Al3+) and levels of InsP6 by a specific method (using polyacrylamide gel electrophoresis). Identification of different InsPs was performed by MS. KEY FINDINGS: At baseline, after dietary deprivation of InsP6, rats only excreted InsP2 in their urine, and there was no detectable InsP6 or other InsPs. Rats given the high dose treatment for 7days had abundant urinary InsP6, but also had other InsPs in their urine; cessation of InsP6 administration led to decreased levels of urinary InsPs. Rats given the low dose treatment for 28days had increasing levels of urinary InsPs over time. The maximum urinary InsP6 was at 21days, after which InsPs excretion decreased. SIGNIFICANCE: We conclude that the skin can absorb InsP6 from a topical gel, and that InsP6 is excreted in the urine, along with other InsPs (InsP5, InsP4, InsP3, and InsP2).

Zinc Bioavailability from Phytate-Rich Foods and Zinc Supplements. Modeling the Effects of Food Components with Oxygen, Nitrogen, and Sulfur Donor Ligands.

Aqueous solubility of zinc phytate (Ksp = (2.6 ± 0.2) × 10-47 mol7/L7), essential for zinc bioavailability from plant foods, was found to decrease with increasing temperature corresponding to ΔHdis of -301 ± 22 kJ/mol and ΔSdis of -1901 ± 72 J/(mol K). Binding of zinc to phytate was found to be exothermic for the stronger binding site and endothermic for the weaker binding site. The solubility of the slightly soluble zinc citrate and insoluble zinc phytate was found to be considerably enhanced by the food components with oxygen donor, nitrogen donor, and sulfur donor ligands. The driving force for the enhanced solubility is mainly due to the complex formation between zinc and the investigated food components rather than ligand exchange and ternary complex formation as revealed by quantum mechanical calculations and isothermal titration calorimetry. Histidine and citrate are promising ligands for improving zinc absorption from phytate-rich foods.

Preparation of 68 Ga-Mg-Ca-phytate colloid and its evaluation as a liver imaging agent.

The objective of this study was to investigate the radiosynthesis of 68 Ga-Mg-Ca-phytate colloid and then characterise the formulation for radiochemical purity (RCP), radioactive particle size distribution, and biodistribution in normal rats. This radiocolloid was prepared by mixing an aqueous solution of phytic acid, 68 Ga3+ ions, a dispersant, Mg2+ and Ca2+ ions, and then heating the contents at 100°C for 5 minutes. After cooling the vial to 5°C, the solution was basified to pH 5 and stored in the cold. The resulting product contained 92±3% RCP 68 Ga-colloidal particles and a low level (8±3%) of soluble 68 Ga-Mg-Ca-phytate. Particle size experiments defined the radioactive particle population was 6±4% <20 nm, 90±6% 20 to 200 nm, and 4% were >200 nm in diameter. Intravenous injection of the 68 Ga-colloid dispersion to rats resulted in 93% uptake by the liver plus spleen, 1% lungs, 1% total blood, and 6% in the carcass after 20 minutes. This optimal formulation remained stable at 5°C for 1½ hours in vitro, and it resulted in the same biodistribution as the formulation prepared at t = 0 hours. The preclinical data so far indicate that 68 Ga-Mg-Ca-colloid has excellent potential as a liver imaging agent.

Complexes of myo-Inositol-Hexakisphosphate (IP6) with Zinc or Lanthanum for the Decorporation of Radiocesium.

Radioactive nuclides leak into the surrounding environment after nuclear power plant disasters, such as the Chernobyl accident and the Fukushima Daiichi Nuclear Power Plant disaster. Cesium-137 (137Cs) (t1/2=30.1 year), a water-soluble radionuclide with a long physical half-life, contaminates aquatic ecosystems and food products. In humans, 137Cs concentrates in muscle tissue and has a long biological half-life, indicating it may be harmful. myo-Inositol-hexakisphosphate (IP6) is a compound found in grain, beans, and oil seeds. IP6 has the ability to form insoluble complexes with metals, including lanthanum (La) and zinc (Zn). We hypothesized that La-IP6 and Zn-IP6 may promote the elimination of 137Cs from the body through the adsorption of La-IP6 and Zn-IP6 to 137Cs in the gastrointestinal tract. Therefore, in this study, we evaluated the adsorptive capacity of La-IP6 and Zn-IP6 complexes with 137Cs in vitro and in vivo. La-IP6 and Zn-IP6 complexes were stable in acidic solution (pH 1.2) at 37°C. In vitro binding assays indicated that La-IP6 and Zn-IP6 complexes adsorbed 137Cs, with the adsorption capacity of Zn-IP6 to 137Cs greater than that of La-IP6. To evaluate the usefulness of La-IP6 and Zn-IP6 in vivo, La-IP6 or Zn-IP6 was administrated to mice after intravenous injection of 137Cs. However, the biodistribution of 137Cs in the La-IP6 treated group and the Zn-IP6 treated group was nearly identical to the non-treated control group, indicating that La-IP6 and Zn-IP6 were not effective at promoting the elimination of 137Cs in vivo.

The unresolved role of dietary fibers on mineral absorption.

Dietary fiber is a complex nutritional concept whose definition and method of analysis has evolved over time. However, literature on the role of dietary fiber on mineral bioavailability has not followed pace. Although in vitro studies revealed mineral binding properties, both animal and human studies failed to show negative effects on mineral absorption, and even in some cases reported absorption enhancing properties. The existing literature suggests that dietary fibers have negative effects on mineral absorption in the gastrointestinal tract largely due to mineral binding or physical entrapment. However, colonic fermentation of dietary fibers may offset this negative effect by liberating bound minerals and promoting colonic absorption. However, existing studies are limited since they did not control for more potent mineral absorption inhibitors such as phytates and polyphenols. Animal studies have mostly been on rats and hence difficult to extrapolate to humans. Human studies have been mostly on healthy young men, who likely to have an adequate store of iron. The use of different types and amounts of fibers (isolated/added) with varying physiological and physicochemical properties makes it difficult to compare results. Future studies can make use of the opportunities offered by enzyme technologies to decipher the role of dietary fibers in mineral bioavailability.

Increased iron bioavailability from lactic-fermented vegetables is likely an effect of promoting the formation of ferric iron (Fe(3+)).

BACKGROUND: Lactic fermentation of foods increases the availability of iron as shown in a number of studies throughout the years. Several explanations have been provided such as decreased content of inhibitory phytate, increased solubility of iron, and increased content of lactic acid in the fermented product. However, to our knowledge, there are no data to support that the bioavailability of iron is affected by lactic fermentation. OBJECTIVES: The objective of the present study was to investigate whether the bioavailability of iron from a vegetable mix was affected by lactic fermentation and to propose a mechanism for such an event, by conducting human and cell (Caco-2, HepG2) studies and iron speciation measurements (voltammetry). We also investigated whether the absorption of zinc was affected by the lactic fermentation. RESULTS: In human subjects, we observed that lactic-fermented vegetables served with both a high-phytate and low-phytate meal increased the absorption of iron, but not zinc. In vitro digested fermented vegetables were able to provoke a greater hepcidin response per ng Fe than fresh vegetables, indicating that Fe in the fermented mixes was more bioavailable, independent on the soluble Fe content. We measured that hydrated Fe(3+) species were increased after the lactic fermentation, while there was no significant change in hydrated Fe(2+). Furthermore, lactate addition to Caco-2 cells did not affect ferritin formation in response to Fe nor did lactate affect the hepcidin response in the Caco-2/HepG2 cell system. CONCLUSIONS: The mechanism for the increased bioavailability of iron from lactic-fermented vegetables is likely an effect of the increase in ferric iron (Fe(3+)) species caused by the lactic fermentation. No effect on zinc bioavailability was observed.

Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA.

Variable uptake feature of focal nodular hyperplasia in Tc-99m phytate hepatic scintigraphy/single-photon emission computed tomography-A parametric analysis.

Tc-99m phytate hepatic scintigraphy remains the standard method for evaluating the functional features of Kupffer cells. In this study, we demonstrate the variable uptake feature of focal nodular hyperplasia (FNH) in Tc-99m phytate scintigraphy. We reviewed all patients who underwent Tc-99m phytate hepatic scintigraphy between 2008 and 2012 in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Cases with FNH were diagnosed on the basis of pathology or at least one or more prior imaging with a periodic clinical follow-up. All patients received a standard protocol of dynamic flow study and planar and Tc-99m phytate single-photon emission computed tomography (E. CAM; Siemens). The correlation of variable nodular radioactivity with parameters such as tumor size and localization was analyzed. In total, 15 lesions of 14 patients in the clinic were diagnosed as FNH. The tumor size was approximately 2.9-7.4 cm (mean size 4.6 cm). Four lesions were larger than 5 cm. The major anatomic distribution was in the right hepatic lobe (10 lesions), particularly in the superior segments (7 lesions). Tc-99m phytate single-photon emission computed tomography imaging for determining the functional features of Kupffer cells included cool/cold (8 lesions), isoradioactive/warm (6 lesions), and hot (1 lesion) patterns of uptake. We did not observe any statistically significant correlation between variable nodular radioactivity and tumor size (p=0.68) or localization (p=0.04). Herein, we demonstrate the variable uptake feature of FNH in Tc-99m phytate scintigraphy. In small FNH tumors (< 5 cm), increased or equal uptake still provided specificity for the differential diagnosis of hepatic solid tumors.

99mTc-phytate as a diagnostic probe for assessing inflammatory reaction in malignant tumors.

OBJECTIVE: Once administered intravenously, technetium-99m (99mTc)-labeled phytate binds to calcium in the serum and behaves as a nanoparticle. On the basis of the high permeability of the tumor vasculature, 99mTc-phytate is expected to leak and accumulate specifically in inflammatory cells. The aim of this study was to evaluate the potential of 99mTc-phytate in assessing the degree of inflammation in Ehrlich solid tumors in mice. MATERIALS AND METHODS: 99mTc-phytate was prepared by adding pertechnetate to a solution containing phytic acid and stannous chloride. The blood half-life of this particle following intravenous injection was determined using blood samples from healthy animals, whereas its size was measured by photon correlation spectroscopy. Scintigraphic imaging and biodistribution studies were carried out in tumor-bearing mice at 30 min and 2 h after injection. RESULTS: The average size of the particles was in the range of 200 nm, suggesting that they are capable of passively passing through fenestrations in tumor vessels, which are 200-2000 nm in size. The blood half-life for 99mTc-phytate was found to be 2.1 min, a result that is in agreement with previous studies. Data from tumor-bearing mice showed high tumor uptake at 2 h after 99mTc-phytate administration. As a result, a high tumor-to-muscle ratio was achieved (T/M = 25.9 ± 7.54). CONCLUSION: These findings indicate that 99mTc-sodium phytate has promising properties for identifying the type of tumor. This approach will have significant implications for characterizing tumor biology and treatment of malignant lesions.

Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats.

PURPOSE: To evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with 99mtechnetium. METHODS: Twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received 99mTc-DMSA and the second sodium 99mTc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. RESULTS: The statistical analysis showed that there was a statistically significant decrease (p<0.05) in the uptake of %ATI/g in bladder (0.11±0.01and1.60±0.08), kidney (3.52±0.51and11.84±1.57) and blood (0.15±0.01and 0.54±0.05) between the treated group and control group, respectively. CONCLUSION: The A. muricata hydroalcoholic extract negatively influenced the uptake of 99mTc-DMSA in bladder, kidney and blood of rats.

Disappearance of infused phytate from the large intestine of dairy heifers.

The objective of this study was to investigate the disappearance of phytate from the large intestine of dairy heifers. Uncertainty about the availability of phosphorus (P) in different feeds may limit implementation of dietary strategies to reduce fecal P excretion by dairy cows. Increased understanding of the dynamics of phytate degradation and disappearance of P in the large intestine may improve prediction of intestinal P digestion and absorption. Eight ruminally- and ileally-cannulated crossbred dairy heifers were used in two 4×4 Latin square designs with 9-d periods, including 3d of washout. All heifers were fed a high-forage diet containing 0.14% P throughout the study. Ytterbium-labeled corn silage and Co-EDTA were dosed to the rumen 4 times daily as particulate and liquid phase markers, respectively, to measure ileal digesta flow. Ond 4 to 7 of each period, each heifer was infused ileally with 0, 5, 15, or 25 g/d of phytate (phytic acid) in solution and total fecal collection was conducted. When infusion ceased (d 8 and 9) ileal digesta was sampled to measure P flow to the ileum from the basal diet. Feed, digesta, and feces were dried, ground, and analyzed for phytate P, inorganic P, and total P using high performance ion chromatography, inductively coupled plasma atomic emission spectroscopy, and the molybdovanadate yellow method, respectively. Phytate degradation in the large intestine was observed but was not complete, and the amount of infused phytate did not influence the degradability of phytate. Fecal excretion of total P increased with increasing total P infused. The slope coefficient for ileal P flow (dietary only) to feces was 0.56 ± 0.26 (mean ± SE), whereas the slope coefficient for infused P was 0.75 ± 0.13. These indicate net absorption of P from the large intestine and greater disappearance of P from dietary P flowing to the ileum than from the infused pure phytate (44 vs. 25%). This data will support mechanistic modeling efforts to improve prediction of P digestion, allowing more accurate estimation of P bioavailability in feeds.

Zinc requirements: assessment and population needs.

Reliable estimates of zinc requirements have assumed greater priority as the global public health importance of preventing zinc deficiency has gained increasing recognition. On a global public health basis, our first most evident goal is reliable estimates of average population requirements. Despite expectations of rapid advances towards simpler and more sophisticated strategies, estimations of zinc requirements continue to depend on a factorial approach. Since the Dietary Reference Intakes (DRIs) were published, there have been important advances in techniques for the factorial approach but also confusion resulting from the subsequent publication of conflicting 'international' estimates. The reasons for these differences have now been fully elucidated, removing an obstruction to continuing progress and refinements of our knowledge base. A key advance has been the development and validation of a model that can be simply applied to determine the inhibitory effects of phytate on zinc absorption. Better understanding of maternal and young child zinc requirements continues to present a challenge of special importance.

Measurement of gastric emptying time of solids in healthy subjects using scintigraphic method: a revised technique.

The gastric emptying half time (GET) of solid food in 24 healthy volunteers (11M/13F) was evaluated using a revised technique and a gamma camera scan. Within 20 min and after 8 h of fasting, each volunteer ate two pieces of toast with a two-egg-omelette that was mixed with 18.5 MBq (99m)Tc-labelled phytate. The raw data were analysed in the MATLAB program to establish the gastric intestine tract (GI tract) biokinetic model. The GI tract model defines the metabolic mechanism with reference to five compartments, which are stomach, body fluid, small intestine (SI), upper large intestine and lower large intestine, according to the ICRP-30 report. The model was expressed using four simultaneous time-dependent differential equations. The gastric emptying half-time and T(1/2eff)(SI) of males were 62.6±15.4 and 149.8±204.1 min, respectively, and those of females were 98.8±16.3 and 131.6±38.4 min.

Bioavailability of iron and zinc from multiple micronutrient fortified beverage premixes in Caco-2 cell model.

Iron and zinc deficiencies are the most prevalent nutrient deficiencies worldwide. They often coexist as the dietary factors, especially phytate, which impairs iron absorption also affects zinc absorption. Therefore, suitable strategies are required to control multiple micronutrient deficiencies in populations that subsist on high-phytate foods such as the whole wheat flour based Indian bread (chapatti). The objective of the study, therefore, was to test the bioavailability of iron and zinc in 2 multiple micronutrient beverage premixes in the absence and presence of chapatti. The premix-1 contained iron, zinc, and vitamin A while premix-2 contained all micronutrients in premix-1, plus folic acid and ascorbic acid. Ferritin induction and (65)Zn uptake were assessed using coupled in vitro digestion/Caco-2 cell line model as the surrogate markers of iron and zinc bioavailability, respectively. The results show that iron bioavailability from premixes-1 and 2 was similar in the absence of chapatti. However, premix-2 showed significantly higher iron bioavailability compared to premix-1 in the presence of chapatti. In contrast, the zinc uptake was similar from both premixes-1 and 2 in the absence or presence of chapatti. These results suggest that both the premixes provide bioavailable minerals, but premix-2 appears to be promising in the presence of foods that have high phytate.

Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenografts.

Inositol hexaphosphate (IP(6)) is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, IP(6) has many other beneficial effects for human health, such as reduction in risk of developing cardiovascular disease and diabetes and inhibition of kidney stone formation. Studies presented here describe the pharmacokinetics, tissue distribution, and metabolism of IP(6) following intravenous (IV) or per os (PO) administration to mice. SCID mice bearing MDA-MB-231 xenografts were treated with 20 mg/kg IP(6) (3 µCi per mouse [(14)C]-uniformly ring-labeled IP(6)) and euthanized at various times after IP(6) treatment. Plasma and tissues were analyzed for [(14)C]-IP(6) and metabolites by high-performance liquid chromatography with radioactivity detection. Following IV administration of IP(6), plasma IP(6) concentrations peaked at 5 minutes and were detectable until 45 minutes. Liver IP(6) concentrations were more than 10-fold higher than plasma concentrations, whereas other normal tissue concentrations were similar to plasma. Only inositol was detected in xenografts. After PO administration, IP(6) was detected in liver; but only inositol was detectable in other tissues. After both IV and PO administration, exogenous IP(6) was rapidly dephosphorylated to inositol; however, alterations in endogenous IPs were not examined.