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Biomedical subjects

J Christoffersen

Publications and source records attributed to J Christoffersen.

At least 19 recordsLinked to original sources

Effects of strontium ions on growth and dissolution of hydroxyapatite and on bone mineral detection.

Preparation and analyses of a series of hydroxyapatites (HA) containing 1-10 mol % of Ca2+ replaced by Sr2+ is reported. The solubility of these apatites is found to increase with increasing content of Sr2+, 10% SrHA dissolves faster than CaHA at given values of Ca2+ and phosphate concentrations, but with a similar rate at the same degree of saturation. Sr2+ is found to inhibit the rates of both dissolution and growth of CaHA and 10% SrHA at pH 7.2, CaHA being more strongly inhibited by Sr2+ than 10% SrHA. The effect of partial substitution of Ca2+ in hydroxyapatite by Sr2+ on bone mineral content (BMC) and bone mineral density (BMD) measured by dual energy X-ray absorptiometry has been studied using three commercial densitometers. Extrapolating the absorption data for up to 10% replacement of Ca2+ by Sr2+ to 100% substitution of Ca2+ by Sr2+ in HA leads to an apparent increase in BMC or BMD of about a factor of 10. This factor is in agreement with theoretical calculations using attenuation coefficients of the atoms concerned. It is concluded that existing BMC scanners register artificially high values of BMC if the bone contains significant amounts of Sr2+ or other metal ions with atomic number larger than calcium.

Absorptiometry, Photon

Formation of phosphate-containing calcium fluoride at the expense of enamel, hydroxyapatite and fluorapatite.

During the caries process complex reactions involving calcium, phosphate, hydrogen and fluoride ions as main species take place. In this study the precipitation and dissolution reactions occurring in suspensions of enamel, hydroxyapatite (HAP) and fluorapatite (FAP) on addition of fluoride were investigated under well-defined conditions. pH and pF were monitored; calcium and phosphate concentrations were measured at selected times; the solid phases were examined by infra-red, X-ray diffraction and transmission electron microscopy. Precipitation of phosphate-containing calcium fluoride crystals, CaF2(P), can cause severe reduction in the calcium ion concentration and release of hydrogen ions from the precipitated phosphate. These reactions result in considerable dissolution of enamel, HAP and even of FAP. More of the added mineral dissolves with 50 mmol/l fluoride than with 10 mmol/l fluoride, mainly due to the greater reduction in calcium ion concentration. This work shows that phosphate-containing calcium fluoride is most likely an important compound to be considered in the caries process.

Animals

Retinoblastoma protein is rapidly dephosphorylated by elevated cyclic adenosine monophosphate levels in human B-lymphoid cells.

Elevated cyclic AMP levels induce a rapid block in the mid-G1 phase of the cell cycle in B-lymphoid Reh cells, accompanied by a transient block in G2. The retinoblastoma (Rb) gene product has been implicated as a key regulator of eukaryotic cell growth. The Rb protein enforces its growth-suppressive effect in early G1, where it is underphosphorylated and firmly bound in the nucleus. A possible link between the cyclic AMP-mediated growth arrest and regulation of Rb protein phosphorylation was explored by Western blot analysis. We found that both forskolin and 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate induced a rapid (within 3 h) dephosphorylation of Rb protein. These data were confirmed by flow-cytometric analysis of isolated nuclei costained with anti-Rb antibodies and propidium iodide. The percentage of cells containing underphosphorylated Rb protein (i.e., G1 nuclei with bound Rb protein) increased from 9 to 87% after 4 h of forskolin treatment. During the first 4 h of forskolin treatment, the cells were transiently blocked in the G2 phase of the cell cycle, and virtually no cells had passed through mitosis. The increased level of dephosphorylated Rb protein at 4 h was therefore not due to an accumulation in early G1 of cells containing underphosphorylated Rb protein. Instead, our data indicated that dephosphorylation of Rb protein occurred in cells that had already passed the point in G1 of Rb protein phosphorylation. Dephosphorylation of Rb protein was prevented by high concentrations of the protein phosphatase inhibitor okadaic acid, indicating that activation of a phosphatase is involved in the cyclic AMP-mediated dephosphorylation of Rb protein. We suggest that the dephosphorylation of Rb protein is required for the forskolin-mediated arrest of the Reh cells in mid-G1.

B-Lymphocytes

Effects of aluminum (III) and fluoride on the demineralization of bovine enamel: a longitudinal microradiographic study.

Longitudinal microradiography has been used to determine inhibiting effects of aluminum (III), Al, and fluoride on mineral loss from slices of bovine enamel exposed to a demineralizing solution 4 h daily for 35 days. Inhibitor treatment was 5 min four times daily. For the remaining time, the samples were immersed in a neutral calcium phosphate solution which allowed neither remineralization nor demineralization. This study indicates that a 1-mM (27 ppm) solution of Al in a 0.1-M lactate solution, pH 5, has an inhibitory effect on the in vitro demineralization of bovine enamel. Application of this solution alternating with 20 mM (380 ppm) fluoride gave the same total inhibition as treatment with 20 mM fluoride alone.

Alum Compounds

Rate and mechanism of enamel demineralization in situ.

In this paper, data are presented on the in situ demineralization of human enamel as a function of the demineralization period. To quantify the mineral loss parameters versus time, it is important to obtain information on the kinetics, and thus on the mechanism of dental caries. The results show that for in situ enamel demineralization, the lesion depth as well as the mineral loss parameter both vary linearly with the demineralization time. This is in contrast to in vitro lesion formation where the third power, or the square power of the lesion depth is linearly related to the demineralization time. In in situ demineralization, the rate-determining step of the demineralization process is the inhibitor-controlled dissolution process at the enamel crystallite surfaces, while the inhibitor content (F-, proteins etc.) in the lesion originating from the plaque, saliva and enamel is high. Furthermore, the study indicates that in in situ demineralization, interprismatic mineral loss is very important.

Dental Enamel

Effects of fluoride and methanehydroxydiphosphate on enamel and on dentine demineralization.

The aim of this article was to investigate the effects of methanehydroxydiphosphonate (MHDP) and fluoride (F) separately and combined, on the demineralization process in enamel and in dentine under constant composition conditions. The demineralization was carried out in solutions containing 3 mM calcium, 3 mM phosphate, pH = 5.0, and either 6 microM MHDP, 12 microM F or 6 microM MHDP and 12 microM F. After demineralization periods (t) between 24 and 140 h, the lesion depth l and the mineral loss delta Z were measured by transverse microradiography of the enamel and dentine specimens. The amount of mineral lost during demineralization averaged over the lesion depth, R = delta Z/l, was calculated. R approximately 17 vol% for both enamel and dentine, both delta Z and l being greater for dentine than for enamel by approximately the same factor. The results show that under the same conditions dentine is attacked much more strongly than enamel. The lesion progress with time is quite different for the two tissues: in enamel the lesion depth progresses als l3 = alpha t + beta, in dentine as l2 = alpha't + beta'. The slopes alpha and alpha' decrease in the order MHDP > F > MHDP+F. In enamel the combined inhibitor effect is only slightly larger than the effect of F alone; in dentine the inhibiting effects of F and MHDP are approximately additive. The inhibitor interactions can be described by the Langmuir adsorption theory.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

A contribution with review to the description of mineralization of bone and other calcified tissues in vivo.

This manuscript considers certain aspects of mineral deposition in bone and other vertebrate calcifying tissues in order to examine physical, chemical, and biological factors important in the mineralization process. The paper in a discussion format principally presents a new data and the formulation of concepts based on such data as well as a summary of background material as necessary review. Mineralization is found to occur at spatially independent sites throughout the organic extracellular tissue matrices. Matrix vesicles and collagen fibrils each may serve as independent nucleation centers for mineral with vesicle mineralization being local and collagen mineralization dominating the tissues as a whole. Collagen fibril organization is suggested to be such that hole zones are aligned in three dimensions, creating extensive channels for mineral accommodation. Nucleation occurs initially in hole zones and crystal growth leads to the development of plate-like mineral particles whose orientation, disposition, and sizes within fibrils are detailed. Effects of diffusion, crystallinity, and critical nucleation and growth events are described with respect to their influence on mineral deposition in bulk and local regions of tissue matrices.

Animals

Gonadal development and growth in 46,XX and 46,XY individuals with P450scc deficiency (congenital lipoid adrenal hyperplasia).

We have investigated gonadal development and growth in 4 individuals (3 with 46,XY and 1 with 46,XX karyotype) with P450scc deficiency. One patient died at 2 months of age from adrenal insufficiency, while the remaining 3 individuals were healthy and developed normally (age at follow-up: 18, 10 and 8 years). In the surviving individuals, the diagnosis was established during the first 2-4 months of life by extensive endocrine studies of blood and urine. In the remaining patient, the diagnosis was made on the basis of karyotype (46,XY), anatomy of internal and external genitalia and adrenal pathology. Gonadectomy was performed in the 2 surviving 46,XY individuals at the age of 7 years, and histological examination showed normal testicular morphology but very few germ cells. Postmortem examination of the testes of the 2-month-old subject showed normal testicular histology, and quantitative analysis revealed a normal number of germ cells. Ultrasound of the 46,XX individual showed normal internal female genitalia including ovaries with follicles. The 3 surviving patients grew along the 75th (46,XY), the 90th (46,XY) and the 50th percentile (46,XX), respectively. The oldest girl experienced normal breast and pubic hair development after oral estrogen replacement and topical testosterone administration. The glucocorticoid and mineralocorticoid replacement was adjusted in accordance with repeated measurements of serum sodium and serum potassium, plasma renin concentration and blood pressure. No attempts were made to normalize serum ACTH. We conclude that prenatal testicular maturation and development of female internal genitalia may take place in the absence of normal steroid hormone production. Normal growth and development may be obtained in P450scc-deficient individuals with adequate hormone replacement.

Adolescent

The effect of EHDP concentration on enamel demineralization in vitro.

The depth of caries lesions produced in bovine enamel situated in an unstirred 0.1 mol/L lactic acid buffer at pH 4.5 has been studied as a function of time and of concentration of the inhibitor ethane-1-hydroxy-1, 1-diphosphonate, EHDP. At concentrations of EHDP up to 5 mmol/L, the lesion progress decreased with increasing concentration of inhibitor. At higher concentrations, the opposite effect was observed. At low inhibitor concentration (0.1 mmol/L), the lesion depth to the third power varied linearly with time. At intermediate concentrations (0.25-5 mmol/L), the square of the lesion depth varied linearly with time. At high inhibitor concentrations (25-100 mmol/L), the lesion depth varied linearly with time. It was also shown that the rate of dissolution of calcium hydroxyapatite crystals was retarded by low concentrations of EHDP, but accelerated by high concentrations of EHDP. The results are related to a physico-chemical model describing lesion formation.

Animals

Remineralization of human dentine in vitro.

In this paper the in vitro remineralization of human dentine with 0, 0.5, 2 and 10 ppm F in the remineralization solution is presented and analyzed by microradiography. Furthermore, the remineralization data of human and bovine dentine are quantitatively compared. The main results of this paper are: (1) the efficacy of human (and bovine) remineralization is about proportional to the square root of the F level in the remineralizing solution, and (2) the amount of mineral effectively deposited in the dentine is most likely controlled by the diffusion of fluoride into the tissue. This study shows furthermore that although numerical differences exist in the remineralization of human and bovine dentine, the general remineralization behaviour is quite similar. The presence of F- in the parts per million range is essential for the remineralization efficacy in vitro and also for the 'overremineralization' of the outer dentine surface.

Adolescent

Nature and role of loosely bound fluoride in dental caries.

This paper discusses loosely bound fluoride and its role in dental caries and prevention. Loosely bound fluoride (abbr. by Fa) is fluoride adsorbed onto enamel mineral crystallites. Several recent studies indicate that a high total level of fluoride in enamel does not guarantee protection against caries. This leads to the conclusion that a major part of fluoride present in the solid enamel is not active in prevention. The adsorption of Fa to the mineral under acidic conditions is described. Most likely there is a dynamic equilibrium between fluoride in solution and adsorbed Fa at the crystal surface interface. When the crystallite is completely covered by adsorbed Fa, there is a maximum inhibition of dissolution. The rate of dissolution of mineral depends on pH, the actual concentrations of calcium and phosphate in the liquid in contact with the crystallites, and on the fraction of the surface covered by adsorbed fluoride. The fluoride, Fs, localized in the inner part of the crystallites is relatively unimportant. "CaF2-like" material can be formed on and in enamel depending on conditions. The in vivo-formed globular "CaF2-like" material is not pure CaF2 and releases F- ions when dissolving; these ions will also be partly adsorbed as Fa in and on enamel. Presently, the amount and importance of Fa originating from in vivo-formed "CaF2-like" material are not known. The level of fluoride, Fa, necessary for strong inhibition of enamel demineralization in vitro is estimated to correspond to a fluoride concentration, FL, in the liquid phase of 1 ppm or 50 mumol/L fluoride ions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption

Remineralization of bovine dentine in vitro. The influence of the F content in solution on mineral distribution.

In this paper remineralization of bovine dentine is reported. After demineralization of the dentine in an acidic gel system creating lesions of about 180 microns depth, the tissue was remineralized in a 1.5 mM Ca and 0.9 mM phosphate containing solution at pH 7 and 37 degrees C for 8 or 21 days. The F content in the remineralization solution was 0.02, 2, or 10 ppm as NaF. Samples were analyzed by means of microradiography and scanning electron microscopy. The results show that remineralization (without F added in solution) causes a decrease in mineral loss and in lesion depth. With 2 or 10 ppm in solution, however, a substantial mineral accumulation in the lesion, but particularly on the original dentine surface, was observed. During 3 weeks of remineralization, mineral accumulations of 67 and 70 vol% of mineral for 2 and 10 ppm F in solution, respectively, were found near the original outer surface, with the sound dentine mineral value being 48 vol%. The combined microradiography and scanning electron microscopy data show that the mineral accumulated is for a major part deposited on the dentine tissue and partly inside. The latter deposition occurred both inside the tubules as well as in the intertubular areas. Inside the tubules dense precipitates were observed. Because several differences exist between bovine and human dentine, an extrapolation to the human in vivo situation is speculative. The results indicate that the presence of fluoride in the parts per million range is important for dentine remineralization efficacy and that the outer surface area in dentine can be 'overremineralized'.

Animals

Interaction of cadmium ions with calcium hydroxyapatite crystals: a possible mechanism contributing to the pathogenesis of cadmium-induced bone diseases.

Cadmium ions adsorb onto calcium hydroxyapatite crystals (HA) and are as effective as inorganic pyrophosphate and aluminum ions in retarding the rate of in vitro dissolution of HA. In contrast, cadmium ions have no important retarding effect on the growth of HA, but are built into the crystals, thus making them very resistant to subsequent dissolution. These effects could interfere with bone remodeling, with cadmium protecting normal sites of resorption and thus causing resorption at pathological sites.

Bone Diseases, Metabolic

Kinetics of dissolution and growth of calcium fluoride and effects of phosphate.

The rate of growth of pure calcium fluoride crystals is controlled by a surface polynuclear mechanism when the supersaturation is less than 4.4. The surface free energy is found to be 120 mJ/m2. The dissolution process is also controlled by a surface process. Both of these processes are very strongly inhibited by phosphate ions. Calcium fluoride-like materials contaminated with phosphate are formed when calcium fluoride is precipitated in phosphate-containing solutions or suspensions. The physical and chemical properties of these materials have been investigated and compared with the corresponding properties of pure calcium fluoride. The former dissolve much faster than pure calcium fluoride in solutions containing phosphate, but an inhibitory effect is still shown. It is suggested that the calcium fluoride-like material formed on dental enamel during treatment of enamel with acidified solutions of high fluoride content is a phosphate-containing calcium fluoride.

Calcium Fluoride

Effects of aluminum(III), chromium(III), and iron(III) on the rate of dissolution of calcium hydroxyapatite crystals in the absence and presence of the chelating agent desferrioxamine.

Aluminum ions (Al) and chromium (III) ions (Cr), as they exist in aqueous solution at neutral pH, adsorb onto calcium hydroxyapatite crystals (HAP) and severely inhibit their dissolution process, when present in concentrations less than 1 microM. Iron (III) ions (Fe), at concentrations up to 10 microM, have no effect on the dissolution process of HAP. The Fe-chelating agent desferrioxamine also forms strong complexes with Al but not with Cr. Desferrioxamine prevents the adsorption of Al to HAP and removes pre-adsorbed Al from the HAP surface, although not instantaneously, but has no significant effect on the adsorption of Cr to HAP. Desferrioxamine is also found to be capable of removing Al preadsorbed to bone powder.

Adsorption