George Makris

Quantitative relationship between osteoclasts, osteoclast nuclei and the extent of the resorbing surface in hamster periodontal disease

Osteoclast activity in terms of number, nucleus content and position in relation to bone surface features was quantitated during experimental periodontal disease. The increase in total osteoclast population, particularly on periosteal rather than endosteal surfaces, was due mainly to the number of cells in direct contact with the bone surface (on-bone osteoclasts). On-bone cell nuclei per mm of bone surface was constantly significantly greater in experimental animals than in controls. There was a positive linear relationship between the extent of resorbing surface and the nucleus content of the on-bone osteoclasts. Thus, in experimental periodontal disease, increases in the number of on-bone osteoclasts are responsible for the changes in the total number of these cells and disease activity is expressed more accurately by the number of nuclei of on-bone osteoclasts per mm of bone surface.

Osteoporotic effect of a high-carbohydrate diet (Keyes 2000) in golden hamsters.

Animals fed the Keyes 2000 diet for 6 weeks exhibited severe bone disturbances. The volume of the bone was reduced as indicated by a decrease in diaphyseal width (p < 0.01): a reduction in the cortical thickness (p < 0.05) seemed to be the factor of alteration in the diaphyseal width, as medullary width was unmodified. The rate of bone formation was decreased along the endosteal surfaces of the cortices, but not significantly. Trabecular bone volume was significantly decreased (p < 0.05) by 30 per cent as was trabecular thickness (p < 0.01). These changes are characteristic of an osteoporotic state, the origin of which is unclear. Because of this important nutritional disturbance, use of Keyes 2000 diet is questionable for periodontal research in rodents.

Twelve-year follow-up of an autogenous mandibular canine transplant

Transplantation is the transfer of tissue or an organ from 1 site to another in the same person or between different persons. A transplantation in which donor and recipient are the same individual has been termed autogenous transplantation, autoplastic transplantation, or autotransplantation. The purpose of this report was to describe a patient undergoing autotransplantation of an impacted mandibular canine to its normal position in the mandible and the 12-year follow-up. Five years after the surgical procedure, the patient presented with pulp canal obliteration in the autotransplanted tooth. Twelve years after the autotransplantation, the tooth position was stable despite pulp canal obliteration, but with no sign of inflammatory resorption or a periapical lesion. In addition, there was no sign of replacement resorption (ankylosis). The endodontic literature has shown that the prognosis of patients undergoing autotransplantation may be good under specific considerations. Therefore, the technique may be a treatment plan option for the replacement of missing teeth.

Further data on the osteoporotic effect of the Keyes 2000 diet in the hamster.

Abstract Hamsters, 2 1 2 months old, were fed the diet for 2 months. The decrease found in trabecular bone volume and in trabecular thickness at the metaphysal area of the femur supported previous data but the previously reported decrease in cortical thickness was absent. The widening of the epiphysal plate suggests a relationship of the osteoporosis with disturbances in the growth process; the decrease in epiphysal trabecular thickness and trabecular bone volume could indicate that the diet affects bone remodeling.

Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity

Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

Development and Pharmacological Evaluation of New Bone-Targeted 99mTc-Radiolabeled Bisphosphonates

A novel bisphosphonate, 1-(3-aminopropylamino)ethane-1,1-diyldiphosphonic acid (3), was coupled to the tridentate chelators di-2-picolylamine, 2-picolylamine-N-acetic acid, iminodiacetic acid, 3-((2-aminoethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid, and 2-((2-carboxyethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid to form ligands 6, 9, 11, 15, and 19, respectively. Organometallic complexes of the general formula [Re/(99m)Tc(CO)3(κ(3)-L)] were synthesized, where L denotes ligand 6, 9, 11, 15, or 19. The rhenium complexes were prepared at the macroscopic level and characterized by spectroscopic methods. The technetium-99m organometallic complexes were synthesized in high yield and were identified by comparative reversed-phase HPLC with their Re analogues. The (99m)Tc tracers were stable in vitro and exhibited binding to hydroxyapatite. In biodistribution studies, all of the (99m)Tc complexes exhibited high bone uptake superior to that of 25, which is the directly (99m)Tc-labeled bisphosphonate 3, and comparable to that of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). The tracers [(99m)Tc(CO)3(6)] (26), [(99m)Tc(CO)3(9)] (27), [(99m)Tc(CO)3(11)] (28), and [(99m)Tc(CO)3(15)] (29) exhibited higher bone/blood ratios than (99m)Tc-MDP. 26 had the highest bone uptake at 1 h p.i. The new bisphosphonates showed no substantial growth inhibitory capacity in PC-3, Saos-2, and MCF-7 established cancer cell lines at low concentrations. Incubation of 26 with the same cancer cell lines indicated a rapid and saturated uptake. The promising properties of 26-29 indicate their potential for use as bone-imaging agents.

Crystallization and preliminary X-ray diffraction analysis of two N-terminal fragments of the DNA-cleavage domain of topoisomerase IV from Staphylococcus aureus

The crystallization and data collection of topoisomerase IV from S. aureus is described. Phasing by molecular replacement proved difficult owing to the presence of translational NCS and strategies used to overcome this are discussed.

Synthesis, characterization, and biological evaluation of new biotinylated (99m) Tc/Re-tricarbonyl complexes.

The synthesis and biological evaluation of three new biotinylated fac-[(99m)Tc/Re(CO)3](+) complexes with the tridentate ligands L1, L2, and L3 are reported. L1-L3 contain the chelators 2-((5-aminopentyl)(pyridin-2-ylmethyl)amino)acetic acid, 2-(2-aminoethylthio)-3-(1H-imidazol-4-yl)propanoic acid, and 2-amino-3-(1-carboxy-2-(1H-imidazol-4-yl)ethylthio)propanoic acid, respectively, which are conjugated to biotins carboxylate via their amine group. The fac-[Re(CO)3(L1-L3)] complexes were synthesized and characterized by NMR and IR, where the (N,N,O) coordination for ReL1 and the (N,S,O) coordination for ReL2 and ReL3 were confirmed. The tracer complexes fac-[(99m)Tc(CO)3(L1-L3)] were synthesized in high yield and were found highly stable in 10(-3) M L-histidine and L-cysteine over 24 h. Furthermore, they exhibited high binding affinity (>90%) for avidin. Rat plasma studies showed complete cleavage of biotin from (99m)TcL1 after 1 h and a low percentage of intact (99m)TcL2 and (99m)TcL3 with no biotin cleavage metabolites present, over 24 h. Similarly, rat urine analysis showed the presence of intact (99m)TcL2 and (99m)TcL3, while (99m)TcL1 was cleaved. Biodistribution studies of (99m)TcL2 and (99m)TcL3 revealed fast blood and tissue clearance.