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Bibliographic data: ITNA20020060 (A1) ― 2004-04-12 MATERIALI PER LA PRODUZIONE DI CANALI DI DENTINA ARTIFICIALE PER LA VALUTAZIONE DELLA STRUMENTAZIONE ENDODONTICA E L'ESERCITAZIONE CLINICA ENDODONTICA. Page bookmark ITNA20020060 (A1) - MATERIALI PER LA PRODUZIONE DI CANALI DI DENTINA ARTIFICIALE PER LA VALUTAZIONE DELLA STRUMENTAZIONE ENDODONTICA E L'ESERCITAZIONE CLINICA ENDODONTICA. Inventor(s): APICELLA ANTONIO; DE ROSA ALFREDO; GAMBARINI GIANLUCA; SCHIRALDI CHIARA + (APICELLA ANTONIO, ; DE ROSA ALFREDO, ; GAMBARINI GIANLUCA, ; SCHIRALDI CHIARA) Applicant(s): APICELLA ANTONIO; DE ROSA ALFREDO; GAMBARINI GIANLUCA; SCHIRALDI CHIARA + (APICELLA ANTONIO, ; DE ROSA ALFREDO, ; GAMBARINI GIANLUCA, ; SCHIRALDI CHIARA) Classification: - international: A61K6/00; (IPC1-7): A61K6/00 - Euro: Application number: IT2002NA00060 20021011 Priority number(s): IT2002NA00060 20021011 Abstract not available for ITNA20020060 (A1)

An accelerator-based source of thermal neutrons for BNCT of skin melanoma is foreseen at the Legnaro National Laboratories (LNL, Italy) in the framework of the SPES program. The aim of the SPES project is to realize a high intensity linac, which will be dedicated to neutron production for generating exotic nuclei. Deuterons were formerly considered as projectiles for neutron generation, but the final design was addressed to a proton accelerator. A structure for neutron moderation, installed at the LNL Van De Graaff accelerator is utilized for characterizing the BNCT irradiation field for different combinations of projectiles and targets. 3.0-7.0 MeV protons and deuterons bombarding a thick beryllium target were considered for neutron production. Tissue equivalent proportional counters (TEPC) were designed and are currently under test for the microdosimetric characterization of the irradiation field, including fluctuations of absorbed energy in gas volumes of tissue-equivalent diameter of 1 µm or less. FriXy gels (based on the Fricke technique) are under development for the three-dimensional measurement of the absorbed dose in phantoms.

Last improvements are presented of the method for dose imaging and profiling in tissue-equivalent phantoms exposed to neutron fields suitable for BNCT. The method brings to separate knowledge of the various dose components of the secondary radiation induced by thermal or epithermal neutrons in tissue.

OBJECTIVE: Aim of the present study was to evaluate the cytotoxicity of Real Seal 1 compared to other commercially available endodontic filling materials: Real Seal (SybronEndo, Orange, CA, USA) and Thermafil (Tulsa Dental, Tulsa, OK, USA).,MATERIAL AND METHODS: Periodontal ligament cells from healthy patients were cultured. The eluate of Real Seal 1(TM) (RS1), Real Seal (RS) and Thermafil (TF) samples was used for the cells viability tests, both diluted (50%) or undiluted (100%). Incubation of the specimens was performed in culture medium for 24 h, 48 h and 72 h at 37 °C under sterile conditions. The cellular mortality was evaluated by MTT test. Results were statistically analysed and the statistical significance was set at p< 0.05.,RESULTS: None of the studied materials showed toxic effects during the period of observation (0 -72 h) when compared to the control group. Only RS induced a very modest increase in cell mortality (about 3% at both concentrations used, during the first 24 hours), when increasing the incubation time, however, only the lower concentration continued to show modest toxicity.,CONCLUSIONS: Results of the present study showed that all tested materials did not exhibit cytotoxic effects when compared to the control group.

In Boron Neutron Capture Therapy the discrimination of the different contributions to the absorbed dose in tissue is fundamental, owing to the different biological effectiveness of the emitted radiation. In a cylindrical phantom simulating a head, exposed to a thermal neutron flux from the fast-flux research reactor TAPIRO (located at the ENEA Casaccia Center near Rome), we have imaged the therapy dose from thermal neutron reactions with 10B and the dose in healthy tissue not containing boron.Our technique allows the measurement of the 3-D distribution of absorbed dose: it is based on a chemical dosimeter (ferrous sulphate solution) incorporated in a tissue-equivalent gel (Agarose). In a ferrous sulphate solution, which is the main component of the standard Fricke dosimeter, the chemical reactions occurring after exposure to ionising radiation give rise to oxidation of ferrous ions Fe2+ to ferric ions Fe3+ and the ferric ion yield is proportional to the absorbed dose. By incorporating in the dosimeter-gel a metal ion indicator (Xylenol Orange), it is possible to determine the absorbed dose through optical absorption measurements. We have set up a fast and practical method for dose imaging of such gel phantoms with a CCD camera. From differential measurements in phantoms having different gel compositions, exposed to the same neutron field, we have imaged the different contributions.The imaging results have been compared with the results obtained with other experimental techniques.

A thermal column has been designed and set up in the fast research reactor TAPIRO, in Casaccia ENEA Centre, near Rome, Italy. The TAPIRO reactor is a highly enriched (93.5%) Uranium-235 fast neutron facility. The power is 5 kW and the maximum neutron flux is 4(1012 cm-2(s-1. The reactor has a cylindrical core (12.58 diameter and 10.87 cm height) totally reflected by copper. A section of the copper reflector can be taken away and replaced by a convenient material. Weakly moderating materials can replace the graphite blocks of the thermal column; an epithermal column can be in such a way obtained. The epithermal column will be set on a trolley, which can be driven into the cave of the borate concrete shielding.In the present experiment, some preliminary measurements and simulations have been made in order to characterise the moderated neutron flux in the thermal column. The moderating structure, designed by means of MCNP simulations, is composed of 40 cm thick graphite blocks. The neutron flux in proximity of the copper reflector has been measured, with energy resolution, by means of Bonner spheres. The experimental results have been compared with simulation results obtained by means of MCNP-4B code using the Direct Statistical Approach for variance reduction.

Three-dimensional measurements of absorbed dose by thermal neutrons in a tissue-equivalent phantom were performed utilising a thermal column of the fast research reactor TAPIRO, in Casaccia ENEA Centre, near Roma, Italy.The TAPIRO reactor is a highly enriched (93.5%) Uranium-235 fast neutron facility.In this experiment, we have utilised the thermal column. Here a proper structure made with graphite blocks was set up to thermalize neutrons.We have set up a technique to measure the 3-D distribution of absorbed dose in a phantom exposed in the thermal neutron flux. The technique is based on a chemical dosimeter (ferrous sulphate solution) incorporated in a tissue-equivalent gel (Agarose).

The BNCT (Boron Neutron Capture Therapy) technique makes use of thermal or epithermal neutrons to irradiate tumors previously loaded with 10B.A thermal neutron beam can be very effective for the treatment of surface tumors such as skin melanoma, but it cannot be used for the treatment of deep pathologies, due to its limited penetration depth. Neutron sources providing an epithermal spectrum of energy ranging from 0.4 eV to 10 keV are being considered for clinical use for the treatment of deep-seated tumors.Reactors are currently seen as a suitable neutron source for BNCT implementation, due to the high intensity of the flux they can provide.The Tapiro reactor, that is located at the ENEA Casaccia Center near Rome, is a low-power fast-flux research reactor that can be useful employed for this application. It is a highly enriched uranium-235 fast neutron facility with a nominal power of 5 kW.In this work computer simulations and experimental arrangements were carried out for this reactor to obtain epithermal and thermal neutron beams for the application of BNCT in Italy in the framework of a specific research program.Using the MCNP-4B code, Monte Carlo calculations were carried out to determine the materials suitable for the design of the thermal and epithermal columns. Various arrangements of reflector and moderator materials have been investigated to achieve the desired experimental conditions.

The process of twisting has been used for decades to fabricate stainless steel instruments, but it was previously thought to be an impractical method for nickel-titanium (Ni-Ti) instrument manufacture A manufacturing method of twisting Nickel-Titanium wire to produce Ni-Ti files has been recently developed: the twisted files (TF). Theoretically, this new manufacturing process should overcome the problems associated with a grinding process, which previously limited instrument strength. Since TF manufacturing process is new and different from grinding, the aim of the present study was to evaluate the effects of a final deoxidation process (Deox) on torsional resistance of TF instruments.Testing was performed in accordance with the International Standard (ISO 3630-1) by comparing 20 TF instruments versus 20 TF prototype instruments produced without the final deoxidation process. Data were collected and statistically analyzed (t-test).Results show that TF instruments withstood 90% more torque (max. torque) than TF prototype instruments manufactured without the deoxidation process (88.7 vs. 53.3 g/cm). This difference was found to be statistically significant at the 0.05 level of significance.Since design and dimensions of tested instruments were the same, the deoxidation process could be the only explanation of the improvement in torsional resistance.

Methacrylic compounds, like bis-phenol A glycerolate dimethacrylate (Bis-GMA), triethyleneglycol-dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), urethane-dimethacrylate (UDMA) and 1,4-butanediol dimethacrylate (BDDMA) are used as polymerizable components of composite resins and some cements utilized in dentistry and in other medical fields. After performing dental restorations, amounts of uncured monomers are released either into the oral cavity or in pulpal tissues whence they can leach into the blood circulation causing, or contributing to, local or systemic adverse effects. Since the intracellular mechanisms of the aforesaid effects are still not completely clear, many in vitro studies with methacrylic monomers have been performed in the attempt to explain them. These studies have underlined that monomers display genotoxic, allergenic, cytotoxic, estrogenetic and mutagenic activity. Moreover, these monomers alter lipid metabolism, glutathione concentration, reactive oxygen species production, energy metabolism cell cycle and behave as differentiating agents on human promyelocytic HL-60 cell line. The last property was especially intriguing because HL-60 cells possess high telomerase activity, a phenotype related to their immortalized status. Telomerase, adding telomeric repeats to the 3'-end of telomeres, protects chromosomes from the telomeric attrition associated with the 'end-replication problem'. Telomerase activity is present in human stem cells, progenitor cells, and germ cells but is undetectable in the vast majority of adult somatic tissues. During cell differentiation telomerase looses its function of synthesis and maintenance of the telomeric units. In this work, we verified whether the differentiation of HL-60 cells, induced by Bis-GMA, HEMA, TEGDMA, UDMA or BDDMA, is also accompanied by a decrease of telomerase activity. The results show that all monomers and all-trans-retinoic acid (ATRA) - used as positive control - induce cell differentiation. Moreover, cells treated with TEGDMA, HEMA, UDMA, BDDMA or ATRA display a decrease of telomerase activity (about 50%) in respect to untreated cells. On the contrary, Bis-GMA does not provoke any alteration of enzymatic activity. These observations suggest that the ability of some methacrylic monomers to induce differentiation of promyelocytic leukemia cells may be mediated by their capacity to determine a down-regulation of telomerase activity.

The polymerization of methacrylic monomers present in dental composite resins never reaches completion and therefore the leakage of residual monomers into the oral cavity and into biological fluids can cause local and systemic adverse effects. This work was carried out to study the in vitro biochemical interactions of urethane dimethacrylate and 1,4-butanediol dimethacrylate monomers with HL-60 cells, a cell line assumed as an experimental model for simulating granulocyte behaviour. Our main finding was that both monomers induce cell differentiation at toxic concentrations and that cytotoxicity seems to be caused by alterations of glucose metabolism arising from mitochondrial dysfunction rather than from oxidative stress, which could not be altogether verified under our experimental conditions. Our study could be considered as a useful approach to investigate the biochemical mechanisms that contribute to the cytotoxicity of methacrylate compounds and it underlines the importance of assessing such parameters for testing biocompatibility in order to promote the development of better and safer dental materials.

Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are photo-polymerized, but this reaction is never complete, so release of uncured monomers in the periapical tissues and in biological fluids may happen and, potentially, alter the repair of pulpal and of periapical lesions by interfering with local phagocytes. The aim of this study was the evaluation of the functional activity of the monocyte-macrophage system after incubation with methacrylic monomers. The oxidative burst of two cellular systems was analysed using the chemiluminescence technique. Data were collected and statistically analysed. Monomers were found to reduce the in vitro oxidative burst of phagocytes independently from their cytotoxicity. These findings demand further evaluation of the effects of oxidative burst alteration in monocyte-macrophage function and may prompt the inclusion of the described chemiluminescence test in biocompatibility preliminary studies of dental materials.