Endodontic drug delivery for root surface disinfection: a laboratory feasibility evaluation

OBJECTIVES This study aims to assess the potential of a mixture of three antibiotics (TreVitaMix, TVM) as an intracanal dressing to disinfect the outer root surface by applying a new in vitro model. MATERIALS AND METHODS Fifty freshly extracted bovine roots were endodontically treated. Forty samples were then thoroughly scaled, mounted to petri dishes, gas sterilized, and randomly allocated to four groups (n = 10/group) according to their intracanal medication: sterile saline (NaCl; control, A); the TVM carrier material alone, i.e., propylene glycol (PG; B); TVM (C); and calcium hydroxide (D). In an additional group (E), the cementum was not removed and TVM was placed. Petri dishes were filled with Fastidious Anaerobe Agar, inoculated with Fusobacterium nucleatum suspension and then anaerobically incubated during 48-h intervals at 37 °C up to 192 h. Inhibition zones around the roots were then measured after each incubation period (mm(2)). RESULTS Only teeth inoculated with the TVM dressing showed inhibition at all time points, whereas the other treatments showed no peri-radicular growing inhibition. Presence of cementum had no negative effect on disinfection (p = 0.9320). CONCLUSION TVM was able to penetrate through the dentine and inhibit the bacterial growth of F. nucleatum up to 192 h. CLINICAL RELEVANCE TVM might have the potential to sustainably disinfect the outer root surface in perio-endo lesions and serve as an adjunctive antimicrobial agent

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method

Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm³ of clinically relevant CoCrMo, Ti-6Al-4V or Si₃N₄ particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si₃N₄ particles before and after the recovery process (KS tests, p > 0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues

The receptor activator of NF-κB ligand-osteoprotegerin system in pulpal and periapical disease

AIM: To summarize the collective in vitro, in vivo and clinical evidence of the involvement of the receptor activator of NF-κB ligand (RANKL)-osteoprotegerin (OPG) system, a system of two molecules controlling osteoclast differentiation and hard-tissue resorption, in pulpal and periapical pathophysiology. METHODOLOGY: A systematic search related to RANKL and/or OPG and pulp or periapical disease was conducted on Medline, Biosis, Cochrane, Embase and Web of Science databases using keywords and controlled vocabulary. No language restriction was applied. Two independent reviewers first screened titles and abstracts and then the full texts that were initially included. The reference lists of the identified publications were examined for additional titles. RESULTS: A total of 33 papers were identified. In vitro studies (N = 11) revealed that pulpal cells can be stimulated by various inflammatory agents to produce RANKL, whilst many studies did not consider the RANKL/OPG ratio. Animal studies (N = 9) mostly focused on the time course and development of periapical lesions in relation to the RANKL-OPG system. Levels of RANKL and OPG in the necrotizing pulp were not investigated. Human studies (N = 13) showed a steady-state expression of OPG in the odontoblast layer. Conflicting results have been reported regarding the role of RANKL in active apical periodontitis, again because the correlation of this molecule with its inhibitor (OPG) was often disregarded. CONCLUSIONS: There is relatively little information currently available that would highlight the specific role of RANKL and OPG in pulpal and periapical disease. OPG may play a protective role against internal resorption, whilst an increased periapical RANKL/OPG ratio might indicate bone resorption

The effect of cartilage and bone density of mushroom-shaped, photooxidized, osteochondral transplants: an experimental study on graft performance in sheep using transplants originating from different species

BACKGROUND: Differences in overall performance of osteochondral photooxidized grafts were studied in accordance of their species origin and a new, more rigorous cleansing procedure using alcohol during preparation. METHODS: Photooxidized mushroom-shaped grafts of bovine, ovine, human and equine origin were implanted in the femoral condyles of 32 sheep (condyles: n = 64). No viable chondrocytes were present at the time of implantation. Grafts were evaluated at 6 months using plastic embedded sections of non-decalcified bone and cartilage specimens. Graft incorporation, the formation of cyst-like lesions at the base of the cartilage junction as well as cartilage morphology was studied qualitatively, semi-quantitatively using a score system and quantitatively by performing histomorphometrical measurements of percentage of bone and fibrous tissue of the original defects. For statistical analysis a factorial analysis of variance (ANOVA- test) was applied. RESULTS: Differences of graft performance were found according to species origin and cleansing process during graft preparation. According to the score system cartilage surface integrity was best for equine grafts, as well as dislocation or mechanical stability. The equine grafts showed the highest percentage for bone and lowest for fibrous tissue, resp. cystic lesions. The new, more rigorous cleansing process decreased cartilage persistence and overall graft performance. CONCLUSION: Performance of grafts from equine origin was better compared to bovine, ovine and human grafts. The exact reason for this difference was not proven in the current study, but could be related to differences in density of cartilage and subchondral bone between species

Analysis of the Hydrogen-rich Magnetic White Dwarfs in the SDSS

We have calculated optical spectra of hydrogen-rich (DA) white dwarfs with magnetic field strengths between 1 MG and 1000 MG for temperatures between 7000 K and 50000 K. Through a least-squares minimization scheme with an evolutionary algorithm, we have analyzed the spectra of 114 magnetic DAs from the SDSS (95 previously published plus 14 newly discovered within SDSS, and five discovered by SEGUE). Since we were limited to a single spectrum for each object we used only centered magnetic dipoles or dipoles which were shifted along the magnetic dipole axis. We also statistically investigated the distribution of magnetic-field strengths and geometries of our sample.Comment: to appear in the proceedings of the 16th European Workshop on White Dwarfs, Barcelona, 200

Algorithms (X,sigma,eta) : quasi-random mutations for Evolution Strategies

International audienceRandomization is an efficient tool for global optimization. We here define a method which keeps : - the order 0 of evolutionary algorithms (no gradient) ; - the stochastic aspect of evolutionary algorithms ; - the efficiency of so-called "low-dispersion" points ; and which ensures under mild assumptions global convergence with linear convergence rate. We use i) sampling on a ball instead of Gaussian sampling (in a way inspired by trust regions), ii) an original rule for step-size adaptation ; iii) quasi-monte-carlo sampling (low dispersion points) instead of Monte-Carlo sampling. We prove in this framework linear convergence rates i) for global optimization and not only local optimization ; ii) under very mild assumptions on the regularity of the function (existence of derivatives is not required). Though the main scope of this paper is theoretical, numerical experiments are made to backup the mathematical results. Algorithm XSE: quasi-random mutations for evolution strategies. A. Auger, M. Jebalia, O. Teytaud. Proceedings of EA'2005

Osteoanabolic effect of alendronate and zoledronate on bone marrow stromal cells (BMSCs) isolated from aged female osteoporotic patients and its implications for their mode of action in the treatment of age-related bone loss

Summary: In the present study, we evaluated the potential for aminobisphosphonates to enhance the development of bone-forming osteoblasts from progenitor cells isolated from aged female osteoporotic patients. The aminobisphosphonates tested significantly enhanced osteoblast formation and thus lend further insights into their possible mode of action in the treatment of osteoporosis. Introduction: The primary aim of this study was to evaluate the influence of aminobisphosphonates on the osteogenesis of human bone marrow stromal cells (hBMSCs) and mineralization of differentiating bone-forming cells isolated from osteoporotic patients. Methods: The influence of aminobisphosphonate treatment on hBMSC osteogenesis was assessed by the quantitative measurement of alkaline phosphatase (ALP) activity, in addition to quantitative reverse transcription polymerase chain reaction and Western blot analysis of known osteogenic markers. Mineralized matrix formation by hBMSC-derived osteoblasts was visualized and quantified using Alizarin red staining. Results: hBMSC cultures treated with osteogenic medium supplemented with zoledronate demonstrated a significant increase in Alizarin red staining after 3weeks as compared to cells cultured in osteogenic medium alone. Similarly, cultures of differentiating hBMSCs isolated from patients receiving alendronate treatment also demonstrated an increased propensity for mineralization, even in the absence of further in vitro stimulation by zoledronate. The stimulatory effects of aminobisphosphonate treatment on hBMSC-derived osteoblast-mediated mineralization were independent of any alterations in ALP activity, although significant decreases in the expression levels of osteopontin (SPP1) were evident in hBMSCs following exposure to aminobisphosphonates. Further analysis including Western blotting and loss-of-function studies revealed osteopontin as having a negative influence on the mineralization of differentiating osteoporotic bone-forming cells. Conclusions: The results presented here demonstrate for the first time that aminobisphosphonate treatment of osteoporotic hBMSCs enhances their capacity for osteoblast formation and subsequent mineral deposition, thus supporting the concept of aminobisphosphonates as having an osteoanabolic effect in osteoporosis

Long term in-vivo studies of a photo-oxidized bovine osteochondral transplant in sheep

BACKGROUND: Articular cartilage has limited capacity to repair. Defects greater than 3 mm heal with formation of inferior fibrous cartilage. Therefore, many attempts have been made to find the ideal graft for larger cartilage lesions. Different grafts, such as untreated or cryopreserved osteochondral transplants, have been used with variable success. METHODS: Photo-oxidized osteochondral grafts were implanted in both femoral condyles of one ovine knee. Untreated xenogeneic and autogeneic grafts served as controls. Three groups of 8 sheep each were formed and they were sacrificed 6, 12 or 18 months after surgery. RESULTS: The macroscopic evaluation of the condyle and graft showed a well-maintained cartilage surface in most grafts at all time points. However, the host cartilage matrix deteriorated considerably in all xenogeneic, most autogeneic and fewer of the photo-oxidized grafts at 12 and 18 months, respectively. The blue colour of the photo-oxidized grafts resulting from the process of photo-oxidation was visible in all grafts at 6 months, had diminished at 12 months and had completely disappeared at 18 months after surgery. Histologically a loss of matrix staining was almost never noticed in untreated xenografts, transiently at 6 months in photo-oxidized grafts and increased at 12 and 18 months. Fusion between graft and host cartilage could be seen in photo-oxidized grafts at 12 and 18 months, but was never seen in autografts and xenografts. CONCLUSIONS: The photo-oxidation of osteochondral grafts and its use as transplant appears to have a beneficial effect on cartilage and bone remodelling. Osteochondral grafts pre-treated with photo-oxidation may be considered for articular cartilage replacement and therefore may delay artificial joint replacements in human patients