PubMed Health⌕ Search

Biomedical subjects

N C Blumenthal

Publications and source records attributed to N C Blumenthal.

35 records · Page 2Linked to original sources
PubMed1989

The effect of aluminum and gallium ions on the mineralization process.

Metal ions have various and significant effects on the skeletal system. Aluminum accumulation in renal dialysis patients causes osteomalacia, while gallium is an effective therapeutic agent for treating the hypercalcemia accompanying certain malignancies. Using in-vitro systems that stimulate in-vivo mineralization, the authors have investigated the physical-chemical mechanisms of the actions of aluminum and gallium and report some of their findings.

Adsorption↗
PubMed1989

Mechanisms of inhibition of calcification.

Mineralization processes in the body are controlled by physicochemical and cellular regulation of hydroxyapatite (HA) nucleators and inhibitors. The chemical mechanism of action of HA inhibitors has been studied in vitro using solution pH-stat techniques or Types I and II collagen gel diffusion systems. Three biologically relevant systems are used with these methodologies: (1) transformation of amorphous calcium phosphate (ACP) to crystalline HA; (2) direct formation of HA; and (3) growth of HA crystals. Several different mechanisms have been identified for HA inhibition. Condensed phosphates (containing P-O-P linkages) and diphosphonates (containing P-C-P linkages) bind strongly to the surface of forming HA nuclei and crystals and poison growth sites at concentrations as low as 10(-6) M, blocking HA formation. From this in vitro work, diphosphonates have been developed for the treatment of Paget's disease. Proteoglycans, found in cartilage, delay HA formation by a steric effect whereby large volumes of solution become unavailable for HA formation and growth as these enormous macromolecules tumble about. Mg ions enter the structure of forming HA nuclei by replacing Ca, resulting in a distorted atomic structure that slows subsequent growth to HA. Al ions delay HA formation, not by entering the structure of forming HA nuclei, but by adsorbing on the surface of growing HA crystals. Serum proteins slow the transformation of ACP to HA by adsorbing on the ACP surface, which decreases its dissolution rate. Metal-citrate complexes can inhibit HA formation and growth at concentrations as low as 10(-5) to 10(-6) M. Phosphorylated molecules such as acidic proline-rich phosphoproteins and statherins found in saliva suppress HA crystal growth on tooth surfaces by adsorbing on active surface sites. Future research in this field lies in the study of interactions of HA inhibitors found together in calcifying tissues.

Aluminum↗
PubMed1988

The effect of glass-ceramic bone implant materials on the in vitro formation of hydroxyapatite.

The extracts of four glass-ceramic bone implant materials were investigated for dissolved material, for effects on in vitro formation of hydroxyapatite, and for surface morphology of glass-ceramic particles in scanning electron microscopy. In vitro leaching released substances that affected in vitro formation of hydroxyapatite, i.e., initiation time and growth of crystals. Leaching also changed the surface morphology of the materials. The ability of the materials to bond to bone did not correlate with the inhibition of hydroxyapatite formation by the released substances. Surface morphology and other factors at present not yet known are probably involved in controlling the bonding to bone of these ceramics.

Bone and Bones↗
PubMed1986

Gallium increases bone calcium and crystallite perfection of hydroxyapatite.

Gallium, a group IIIa metal, is known to interact with hydroxyapatite as well as the cellular components of bone. In recent studies we have found gallium to be a potent inhibitor of bone resorption that is clinically effective in controlling cancer-related hypercalcemia as well as the accelerated bone resorption associated with bone metastases. To begin to elucidate gallium's mechanism of action we have examined its effects on bone mineral properties. After short-term (14 days) administration to rats, gallium nitrate produced measurable changes in bone mineral properties. Using atomic absorption spectroscopy, low levels of gallium were noted to preferentially accumulate in regions of active bone formation, 0.54 +/- .07 microgram/mg bone in the metaphyses versus 0.21 +/- .03 microgram/mg bone in the diaphyses, P less than 0.001. The bones of treated animals had increased calcium content measured spectrophotometrically. Rats injected with radiolabeled calcium during gallium treatment had greater 45-calcium content compared to control animals. By wide-angle X-ray analyses, larger and/or more perfect hydroxyapatite was observed. The combined effects of gallium on bone cell function and bone mineral may explain its clinical efficacy in blocking accelerated bone resorption.

Animals↗
PubMed1983

Amorphous calcium phosphate in casein micelles of bovine milk.

The calcium phosphate remaining after hydrazine deproteination of casein micelles isolated from bulk skim milk exhibits under the electron microscope a very fine and uniform granularity being formed by small subunits with a true diameter of approximately 2.5 nm. This material, which is about 10 percent by weight citrate, termed calcium phosphate citrate (CPC) complex, also contains Mg and Zn at molar ratios of 0.03 and 0.003 respectively. Radial distribution function (RDF) and infrared analyses show that CPC is a Mg-containing amorphous calcium phosphate (ACP) similar to synthetic and cytoplasmic ACP. presence of CPC in casein micelles as an amorphous colloid bonded with phosphoproteins provides the means for storing in milk large amounts of Ca (16 mM) and Pi (10 mM) in a readily utilizable form but at a higher ion concentration than found in biological solutions.

Animals↗
PubMed1981

Formation and structure of Ca-deficient hydroxyapatite.

When amorphous calcium phosphate (ACP) was transformed to crystalline hydroxyapatite (HA) in a series of aqueous slurry concentrations ranging from low to high, the higher slurry concentrations produced more Ca-deficient HA as measured by Ca/P ratio and heat-produced pyrophosphate. We feel that the excess solution phosphate produced in the higher slurry transformations results in lower Ca/P ratio HA. It has been suggested that an ACP is the precursor to bone apatite. Regulation of the in vivo ACP slurry concentration could then control the stoichiometry and, therefore, the metabolic activity of bone apatite. X-ray radial distribution function (RDF) analyses showed that CO3(2-) substitution in HA creates far greater structural distortions than do Ca deficiencies. The latter, however, do produce small, but observable, structural distortions when compared to stoichiometric HA. It now seems clear that the RDF of bone apatite can be modeled by a synthetic, Ca-deficient, CO3(2-)-containing HA.

Calcium↗
PubMed1975

Effect of carbonate and biological macromolecules on formation and properties of hydroxyapatite.

Amorphous calcium phosphate (ACP) was transformed at 25 degrees to hydroxyapatite (HA) in horse and bovine serum; solutions of serum-protein fractions in tris-HC1 buffer (pH 7.4), and pH 7.4 buffers containing from 0.1 to 10 times physiological CO3(2-) concentration. The ACP-to-HA transformation was slower in whole serum and serum fractions than in control buffer solution. The observed adsorption of serum proteins on ACP and HA probably inhibits both the dissolution of the ACP particles and the growth of HA crystals. After 72 h all transformations were complete as determined by X-ray diffraction. The HA crystal dimensions decreased with increasing C03(2-) but the shape, as shown by X-ray linewidths, was relatively constant up to about 4% CO3(2-). At 15% CO3(2-) the crystals were more equiaxial and less needle-like in habit. The radial distribution function (RDF) of HA with 3.7% CO3(2-) is less well resolved than the RDF of HA with ambient CO3(2-) (1.1%). The peaks are less sharp and their amplitude falls more rapidly with increasing atomic separation than for low CO3(2-)-HA. These effects show that CO3(2-) decreases the regularity of the atomic arrangement when incorporated in HA. The rapid decrease, with increasing CO3(2-) content, of the IR splitting of the P-O bending mode of CO3(2-)-HA is attributed to reduced crystal size and possibly to a perturbation of the crystal field due to CO3(2-)-induced lattice distortion. Finally, for bone mineral, it is probable that the poor resolution of the X-ray and IR patterns is due, in large part, to small crystal size and internal disorder caused by CO3(2-).

Adsorption↗
PubMed1975

Atomic structure of intracellular amorphous calcium phosphate deposits.

The radial distribution function calculated from x-ray diffraction of mineralized cytoplasmic structures isolated from the hepatopancreas of the blue crab (Callinectes sapidus) is very similar to that previously found for synthetic amorphous calcium phosphate. Both types of mineral apparently have only short-range atomic order, represented as a neutral ion cluster of about 10 A in longest dimension, whose probable composition is expressed by the formula Ca9(PO4)6. The minor differences observed are attributed to the presence in the biological mineral of significant amounts of Mg-2+ and ATP. Synthetic amorphous calcium phosphate in contact with a solution containing an amount of ATP equivalent to that of the biological mineral failed to undergo conversion to the thermodynamically more stable hydroxyapatite. The amorphous calcium phosphate of the cytoplasmic mineral granules is similarly stable, and does not undergo conversion to hydroxyapatite, presumably owing to the presence of ATP and Mg-2+, known in inhibitors of the conversion process. The physiological implications of mineral deposits consisting of stabilized calcium phosphate ion clusters are discussed.

Animals↗