Magnetic resonance was used to investigate the kinetic disposition of magnetite nanoparticles (9.4 nm core diameter) from the blood circulation after intravenous injection of magnetite-based dextran-coated magnetic fluid in female Swiss mice. In the first 60 min the time-decay of the nanoparticle concentration in the blood circulation follows the one-exponential (one-compartment) model with a half-life of (6.9 +/- 0.7) min. The X-band spectra show a broad single line at g approximately 2, typical of nanomagnetic particles suspended in a nonmagnetic matrix. The resonance field shifts toward higher values as the particle concentration reduces, following two distinct regimes. At the higher concentration regime (above 10(14) cm(-3)) the particle-particle interaction responds for the nonlinear behavior, while at the lower concentration regime (below 10(14) cm(-3)) the particle-particle interaction is ruled out and the system recovers the linearity due to the demagnetizing field effect alone.

Bone metastases, present in 70% of patients with metastatic breast cancer, lead to skeletal disease, fractures and intense pain, which are all believed to be mediated by tumor cells. Engraftment of tumor cells is supposed to be preceded by changes in the target tissue to create a permissive microenvironment, the pre-metastatic niche, for the establishment of the metastatic foci. In bone metastatic niche, metastatic cells stimulate bone consumption resulting in the release of growth factors that feed the tumor, establishing a vicious cycle between the bone remodeling system and the tumor itself. Yet, how the pre-metastatic niches arise in the bone tissue remains unclear. Here we show that tumor-specific T cells induce osteolytic bone disease before bone colonization. T cells pro-metastatic activity correlate with a pro-osteoclastogenic cytokine profile, including RANKL, a master regulator of osteoclastogenesis. In vivo inhibition of RANKL from tumor-specific T cells completely blocks bone loss and metastasis. Our results unveil an unexpected role for RANKL-derived from T cells in setting the pre-metastatic niche and promoting tumor spread. We believe this information can bring new possibilities for the development of prognostic and therapeutic tools based on modulation of T cell activity for prevention and treatment of bone metastasis.

Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications.

Human and animal immune functions present sex dimorphism that seems to be mainly regulated by sex hormones. In the present study, the activities of the antioxidant enzymes total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were measured in intraperitoneal resident macrophages from adult male and female rats. In addition to comparing males and females, we also examined the regulation of these enzyme activities in macrophages by sex steroids. GSH-Px activity did not differ between male and female macrophages. However, both total SOD and CAT activities were markedly higher in females than in males (83 and 180%). Removal of the gonads in both males and females (comparison between castrated groups) increased the difference in SOD activity from 83 to 138% and reduced the difference in CAT activity from 180 to 86%. Castration and testosterone administration did not significantly modify the activities of the antioxidant enzymes in male macrophages. Ovariectomy did not affect SOD or GSH-Px activity but markedly reduced (48%) CAT activity. This latter change was fully reversed by estrogen administration, whereas progesterone had a smaller effect. These results led us to conclude that differences in the SOD and CAT activities may partially explain some of the differences in immune function reported for males and females. Also, estrogen is a potent regulator of CAT in macrophages and therefore this enzyme activity in macrophages may vary considerably during the menstrual cycle.

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O using self-adhesive resin cements on the push-out bond strength and the presence of bubbles in the root thirds. The cements were either applied according to the manufacturer's instruction or using a commercial delivering system (Centrix), at which the cement pastes were collected and applied after manipulation. Material and Methods: Self-adhesive resin CSA) and a conventional cement (RelyX ARC/3M ESPE-ARC) were used to cement a post and applied either based on the manufacturer's instructions or using a Centrix syringe to deliver the cements directly onto the post of choice, or directly into canal. The roots were scanned with a micro-computed tomography (μCT) and then sectioned into nine 1-mm thick slices for a push-out bond strength test. The μCT images showed the percentage of bubbles in the root thirds (cervical, medium, and apical). Data were analyzed with threeway ANOVA/Tukey ( observed between "material" vs "application technique" (p<0.05). For ARC, U200, and delivered the cements. Equivalent percentages of voids were observed for CSA, irrespective when the self-adhesive resin cements were applied using the Centrix delivery system, in comparison with the manufacturer's instructions (p<0.05). Bond strength varied with the root third: cervical>medium>apical (p<0.05). No correlations were found between the

No abstract

The Caries Assessment Spectrum and Treatment (CAST) is a newly developed epidemiological instrument. The aim of this study was to investigate its construct validity. Four calibrated examiners, using CAST codes 0-6, visually examined 109 surfaces of extracted and exfoliated teeth. These teeth were then hemisectioned, photographed, and assessed histologically by two calibrated examiners using the Downer criteria. Twenty-eight of the 109 teeth were scanned using micro-computed tomography (micro-CT) and assessed by the same examiners using the same criteria. Validation was determined through calculation of the sensitivity, specificity, and Youden index for two categories of carious lesions examined visually, with histology and micro-CT as gold standards. Interexaminer consistency was κ = 0.76: SE ± 0.05 between visual and histological assessments of teeth and was κ = 0.89: SE ± 0.08 between visual and micro-CT assessments. For the category 'healthy' vs. 'diseased' (CAST codes 0-2 vs. CAST codes 3-6), sensitivity, specificity, and Youden index values of 100%, 92.9%, and 93%, respectively, for micro-CT, and 96.6%, 86%, and 83%, respectively, for histology, were obtained. For the category 'dentine' vs. 'non-dentine lesions' (CAST codes 0-3 vs. CAST codes 4-6) sensitivity, specificity, and Youden index values of 90%, 100%, and 90%, respectively, for micro-CT, and 81.4%, 100%, and 81%, respectively, for histology, were obtained. Construct validity of the CAST instrument was obtained.