ascorbic-acid and calcium-phosphate--dibasic--anhydrous

Under physiological conditions, ferric ions are essentially insoluble because of the formation of polynuclear hydroxo-bridged complexes. Ferrous ions are more soluble but may produce hydroxyl radicals on reaction with hydrogen peroxide. Chelation of ferric and ferrous ions with organic ligands may prevent these undesirable reactions. Alternatively, iron(III)-hydroxide/oxide can be stabilized and solubilized by tight interactions with carbohydrates. The data presented in this work show that, because of its physicochemical properties, the iron(III)-hydroxide polymaltose complex (IPC, Maltofer) does not interact with the active ingredients of commonly used drugs such as acetylsalicylic acid (CAS 50-78-2), tetracycline hydrochloride (CAS 64-75-5), calcium hydrogen-phosphate (CAS 7757-93-9), methyl-L-dopa sesquihydrate (CAS 41372-08-1), and magnesium-L-aspartate hydrochloride (CAS 28184-71-6). In contrast, as confirmed by calculations using thermodynamic parameters, FeCl3 x 6H2O (CAS 10025-77-1) can form different types of complexes with these substances. Moreover, the data show that under aerobic conditions high concentrations of ascorbic acid (CAS 50-81-7) can lead to mobilization of iron from IPC and, thus, support the observation that orange juice slightly increases the uptake of iron from IPC.

Topics: Acetaminophen; Anaerobiosis; Ascorbic Acid; Aspartic Acid; Beverages; Calcium Phosphates; Citrus sinensis; Drug Interactions; Ferric Compounds; Food-Drug Interactions; Hydrogen-Ion Concentration; Indicators and Reagents; Methyldopa; Salicylic Acid; Spectrophotometry, Ultraviolet; Tetracycline

Sodium saccharin, ascorbate and other sodium salts fed at high doses to rats produce urinary bladder urothelial cytotoxicity with consequent regenerative hyperplasia. For sodium salts that have been tested, tumor activity is enhanced when administered either alone or after a brief exposure to a known genotoxic bladder carcinogen. These sodium salts alter urinary composition of rats resulting in formation of an amorphous precipitate. We examined the precipitate to ascertain its composition and further delineate the basis for its formation in rat urine. Using scanning electron microscopy with attached X-ray energy dispersive spectroscopy, the principal elements present were calcium, phosphorus, minor amounts of silicon and sulfur. Smaller elements are not detectable by this method. Infrared analyses demonstrated that calcium phosphate was in the tribasic form and silicon was most likely in the form of silica. Small amounts of saccharin were present in the precipitate from rats fed sodium saccharin (<5%), but ascorbate was not detectable in the precipitate from rats fed similar doses of sodium ascorbate. Large amounts of urea and mucopolysaccharide, apparently chondroitin sulfate, were detected in the precipitate by infrared analysis. Chemical analyses confirmed the presence of large amounts of calcium phosphate with variably small amounts of magnesium, possibly present as magnesium ammonium phosphate crystals, present in urine even in controls. Small amounts of protein, including albumin and alpha(2u)-globulin, were also detected (<5% of the precipitate). Calcium phosphate is an essential ingredient of the medium for tissue culture of epithelial cells, but when present at high concentrations (>5 mM) it precipitates and becomes cytotoxic. The nature of the precipitate reflects the unique composition of rat urine and helps to explain the basis for the species specificity of the cytotoxic and proliferative effects of high doses of these sodium salts.

Topics: Animals; Ascorbic Acid; Calcium Phosphates; Chemical Precipitation; Dose-Response Relationship, Drug; Female; Male; Osmolar Concentration; Rats; Rats, Inbred F344; Saccharin; Sex Factors; Sodium; Species Specificity; Urinary Bladder Neoplasms

Tumor necrosis factor-alpha (TNF-alpha) has a key role in skeletal disease in which it promotes reduced bone formation by mature osteoblasts and increased osteoclastic resorption. Here we show that TNF inhibits differentiation of osteoblasts from precursor cells. TNF-alpha treatment of fetal calvaria precursor cells, which spontaneously differentiate to the osteoblast phenotype over 21 days, inhibited differentiation as shown by reduced formation of multilayered, mineralizing nodules and decreased secretion of the skeletal-specific matrix protein osteocalcin. The effect of TNF was dose dependent with an IC50 of 0.6 ng/ml, indicating a high sensitivity of these precursor cells. Addition of TNF-alpha from days 2-21, 2-14, 7-14, and 7-10 inhibited nodule formation but addition of TNF after day 14 had no effect. Partial inhibition of differentiation was observed with addition of TNF on only days 7-8, suggesting that TNF could act during a critical period of phenotype selection. Growth of cells on collagen-coated plates did not prevent TNF inhibition of differentiation, suggesting that inhibition of collagen deposition into matrix by proliferating cells could not, alone, explain the effect of TNF. Northern analysis revealed that TNF inhibited the expression of insulin-like growth factor I (IGF-I). TNF had no effect on expression of the osteogenic bone morphogenic proteins (BMPs-2, -4, and -6), or skeletal LIM protein (LMP-1), as determined by semiquantitative RT-PCR. Addition of IGF-I or BMP-6 to fetal calvaria precursor cell cultures enhanced differentiation but could not overcome TNF inhibition, suggesting that TNF acted downstream of these proteins in the differentiation pathway. The clonal osteoblastic cell line, MC3T3-E1-14, which acquires the osteoblast phenotype spontaneously in postconfluent culture, was also studied. TNF inhibited differentiation of MC3T3-E1-14 cells as shown by failure of mineralized matrix formation in the presence of calcium and phosphate. TNF was not cytotoxic to either cell type as shown by continued attachment and metabolism in culture, trypan blue exclusion, and Alamar Blue cytotoxicity assay. These results demonstrate that TNF-alpha is a potent inhibitor of osteoblast differentiation and suggest that TNF acts distal to IGF-I, BMPs, and LMP-1 in the progression toward the osteoblast phenotype.

Topics: Adaptor Proteins, Signal Transducing; Animals; Ascorbic Acid; Blotting, Northern; Bone and Bones; Bone Morphogenetic Proteins; Calcium Phosphates; Carrier Proteins; Cell Differentiation; Cell Line; Cells, Cultured; Cytoskeletal Proteins; Gene Expression; Insulin-Like Growth Factor I; Intracellular Signaling Peptides and Proteins; LIM Domain Proteins; Osteoblasts; Phosphates; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GABP. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.

Topics: Animals; Ascorbic Acid; Aspirin; Biological Transport; Bioprosthesis; Calcinosis; Calcium; Calcium Phosphates; Cattle; Dipyridamole; Drug Combinations; Fixatives; Glutaral; Microscopy, Electron, Scanning; Pericardium; Platelet Aggregation Inhibitors; Pyridoxine; Vitamin E; Vitamins

The major goal of the study was to explore the possibility of developing an updated model that integrates the effect of various enhancers and inhibitors for predicting the potential availability of iron from typical Indian vegetarian meals. The interaction effects of four constituents namely ascorbic acid, citric acid, tannic acid and calcium phosphate was studied using a standard cereal meal (STD meal) providing 3 mg non-heme iron/250 ml homogenate. Based on the data, a regression equation was evolved which was tested for its predictive power as applied to a set of 10 typical Indian meals. Regression analysis of the data revealed that both ascorbate and citrate emerged as equally strong enhancers while tannate and calcium phosphate demonstrated strong inhibitory effect on iron availability in the STD meal. Further, when the prediction equation, generated on the basis of the interaction effect data was applied to the typical Indian meals, it showed a high correlation coefficient (r = 0.76) between the analysed values for iron availability vs the values computed using the enhancer and inhibitor contents of the meals. Comparison with the only other model available in the literature namely that of Monsen & Balintfy (1982) revealed that the present model was far better in predicting iron availability from cereal based Indian meals (r = 0.76) than Monsen's model (r = 0.19). The findings of the present study substantiated the hypothesis that a regression model, evolved from a cereal meal, by integrating the effect of enhancers as well as inhibitors, rather than only enhancers, provides a more precise estimate of iron availability from typical Indian meals. A limitation of the model however, was that phytate could not be incorporated into the equation.

Topics: Ascorbic Acid; Biological Availability; Calcium Phosphates; Citrates; Citric Acid; Diet, Vegetarian; Drug Interactions; Eating; Edible Grain; Humans; Hydrolyzable Tannins; India; Iron; Nutritional Status; Nutritive Value; Predictive Value of Tests; Regression Analysis

In former papers it was stated that the fetus can be exposed a considerable burden by traces of heavy metals and that a combined therapy with calcium phosphate and ascorbic acid has a good detoxifying effect. In fourty lead-burdened mothers who were treated in this way the excretion of 5-aminolevulinic acid in urine decreased by 65%, the lead content of placenta by 90% and the lead content of mother's milk by 15% compared with a control group without treatment. The cadmium content of the placenta was reduced to 4% of the content in untreated mothers.

Topics: Aminolevulinic Acid; Ascorbic Acid; Cadmium; Cadmium Poisoning; Calcium Phosphates; Female; Humans; Lead; Lead Poisoning; Maternal-Fetal Exchange; Milk, Human; Pregnancy; Pregnancy Complications; Zinc