INJECTABLE HYBRID SYSTEM FOR STRONTIUM LOCAL DELIVERY TO PROMOTE BONE REGENERATION

In bone tissue regeneration strategies, injectable bone substitutes are very attractive since they can be applied with minimally invasive surgical procedures and can perfectly fill irregular defects created in cases of trauma, infection or tumor resection. These materials must combine adequate mechanical properties with the ability to induce new bone formation. Incorporating strontium (Sr) in bone substitute biomaterials may be a strategy to achieve high Sr concentrations, not in a systemic but in a local environment, taking advantage of the osteoanabolic and anti-osteoclastic activity of Sr, for the enhancement of new bone formation. In this context, the aim of the present work was to evaluate the response of a Sr-hybrid injectable system for bone regeneration, designed by our group, consisting of hydroxyapatite microspheres doped with Sr and an alginate vehicle crosslinked in situ with Sr, in an in vivo scenario. Two different animal models were used, rat (Wistar) and sheep (Merino Branco) critical sized bone defect. Non Sr-doped similar materials (Ca-hybrid) or empty defects were used as control. Sr-hybrid system led to an increased bone formation in both center and periphery of a rat critical sized defect compared to a non Sr–doped similar system, where new bone formation was restricted to the periphery. Moreover newly formed bone was identified as early as one week after its implantation in a sheep model. After eight weeks, the bone surrounded the microspheres, both in the periphery and in the center of the defect. Most importantly, the hybrid system provided a scaffold for cell migration and tissue ingrowth and offered structural support, as observed in both models. The effective improvement of local bone formation suggests that this might be a promising approach for bone regeneration, especially in osteoporotic conditions

Co‐existing monophasic teratoma and uterine adenocarcinoma in a female dog

Ovarian teratomas are occasionally reported in dogs; the rarest type is the monophasic teratoma,composed of tissues originating from only one germ layer. Canine endometrial adenocarcinomas are also rare in dogs and mainly affect geriatric females. This report describes case of co-existing ovarian teratoma and uterine adenocarcinoma in a 10-year old nulliparous female Boxer presented with lethargy, anorexia and purulent vaginal discharge. Abdominal ultrasonography evidenced pyometra and a mass in the left ovary. This was composed of a uniform whitish tissue with multiple cystic structures. The histology revealed an atrophy of the ovarian parenchyma, compressed by a proliferation of well-differentiated nervous tissue staining positively to vimentin, S100 and neuronal specific enolase (NSE), and negatively to keratin and inhibin. The left uterine horn, whose diameter was markedly increased, showed foci of endometrial cellular atypia, evident nucleoli and mitoses, at light microscopy. To our best knowledge, this is the first report of a coexisting ovarian monophasic teratoma and endometrial adenocarcinoma, two rare reproductive neoplasia in dogs

Low-Temperature Long-Time Simulations of Ising Ferromagnets using the Monte Carlo with Absorbing Markov Chains method

The Monte Carlo with Absorbing Markov Chains (MCAMC) method is introduced. This method is a generalization of the rejection-free method known as the $n$-fold way. The MCAMC algorithm is applied to the study of the very low-temperature properties of the lifetime of the metastable state of Ising ferromagnets. This is done both for square-lattice and cubic-lattice nearest-neighbor models. Comparison is made with exact low-temperature predictions, in particular the low-temperature predictions that the metastable lifetime is discontinuous at particular values of the field. This discontinuity for the square lattice is not seen in finite-temperatures studies. For the cubic lattice, it is shown that these `exact predictions' are incorrect near the fields where there are discontinuities. The low-temperature formula must be modified and the corrected low-temperature predictions are not discontinuous in the energy of the nucleating droplet.Comment: Submitted to Computer Physics Communicatinos, for proceedings of the Conference CCP2001, 4 figure

Theories and analyses of functionally graded circular plates

This paper presents the governing equations and analytical solutions of the classical and shear deformation theories of functionally graded axisymmetric circular plates. The classical, first-order, and third-order shear deformation theories are presented, accounting for through-thickness variation of two-constituent functionally graded material, modified couple stress effect, and the von Kármán nonlinearity. Analytical solutions for bending of the linear theories, some of which are not readily available in the literature, are included to show the influence of the material variation, boundary conditions, and loads

Theories and analysis of functionally graded beams

This is a review paper containing the governing equations and analytical solutions of the classical and shear deformation theories of functionally graded straight beams. The classical, first-order, and third-order shear deformation theories account for through-thickness variation of two-constituent functionally graded material, modified couple stress (i.e., strain gradient), and the von Karman nonlinearity. Analytical solutions for bending of the linear theories, some of which are not readily available in the literature, are included to show the influence of the material variation, boundary conditions, and loads

IN VIVO STUDY OF THE EFFECT OF A STRONTIUM-­‐RICH INJECTABLE SYSTEM ON BONE REGENERATION, USING A SHEEP MODEL

Bone has the capacity to regenerate as part of the repair process,being newly formed boné indistinguishable from the adjacente uninjured bone. However,there are cases in which boné regeneration is required in large quantity, beyond the normal potential for self-­‐healing, such as for lesions caused by trauma, infection, tumour resection or cases in which the regenerative process is compromised such as avascular necrosis and osteoporosis. Biomaterials such as alginate are very promising due to its ability to form hydrogels in situ under mild conditions in the presence of divalente cations. The combination with ceramic microspheres results in a mechanically improved injectable system, adequate for minimally invasive procedures. Moreover, the combination with chemical elements such as strontium, described as promoter of boné formation, inhibiting boné resorption provides ion Exchange between the implanted biomaterial and surrounding tissue, enhancing boné regeneration. Our goal is to study in na invivo sheep model, the effect of na injectable system composed of strontium doped hydroxyapatite microspheres, delivered in na alginate vehicle, crosslinked with strontium

Simulations of metastable decay in two- and three-dimensional models with microscopic dynamics

We present a brief analysis of the crossover phase diagram for the decay of a metastable phase in a simple dynamic lattice-gas model of a two-phase system. We illustrate the nucleation-theoretical analysis with dynamic Monte Carlo simulations of a kinetic Ising lattice gas on square and cubic lattices. We predict several regimes in which the metastable lifetime has different functional forms, and provide estimates for the crossovers between the different regimes. In the multidroplet regime, the Kolmogorov-Johnson-Mehl-Avrami theory for the time dependence of the order-parameter decay and the two-point density correlation function allows extraction of both the order parameter in the metastable phase and the interfacial velocity from the simulation data.Comment: 14 pages, 4 figures, submitted to J. Non-Crystalline Solids, conference proceeding for IXth International Conference on the Physics of Non-Crystalline Solids, October, 199

CellFinder: a cell data repository

CellFinder (http://www.cellfinder.org) is a comprehensive one-stop resource for molecular data characterizing mammalian cells in different tissues and in different development stages. It is built from carefully selected data sets stemming from other curated databases and the biomedical literature. To date, CellFinder describes 3394 cell types and 50 951 cell lines. The database currently contains 3055 microscopic and anatomical images, 205 whole-genome expression profiles of 194 cell/tissue types from RNA-seq and microarrays and 553 905 protein expressions for 535 cells/tissues. Text mining of a corpus of >2000 publications followed by manual curation confirmed expression information on ∼900 proteins and genes. CellFinder's data model is capable to seamlessly represent entities from single cells to the organ level, to incorporate mappings between homologous entities in different species and to describe processes of cell development and differentiation. Its ontological backbone currently consists of 204 741 ontology terms incorporated from 10 different ontologies unified under the novel CELDA ontology. CellFinder's web portal allows searching, browsing and comparing the stored data, interactive construction of developmental trees and navigating the partonomic hierarchy of cells and tissues through a unique body browser designed for life scientists and clinicians

3-amino-1,2,4-triazole induces quick and strong fat loss in mice with high fat-induced metabolic syndrome

BACKGROUND: Obesity is a growing epidemic with limited effective treatments and an important risk factor for several diseases such as metabolic syndrome (MetS). In this study, we aimed to investigate the effect of 3-amino-1,2,4-triazole (ATZ), an inhibitor of catalase and heme synthesis, in a murine model for MetS. METHODS: Male C57BL/6 mice with high-fat diet-induced MetS received ATZ (500 mg·kg(-1)·24 h(-1)) for 12 weeks. RESULTS: The HFD group showed increased blood pressure and body weight, enhanced fat deposition accompanied by an increase in adipocyte diameter, and decreased lipolysis in white adipose tissue (WAT). The expression of genes related to inflammation was increased in WAT of the HFD group. Concurrently, these mice exhibited an increase in leptin, nonesterified fatty acid (NEFA), insulin, and glucose in plasma, coupled with glucose intolerance and insulin resistance. Strikingly, ATZ prevented the increase in blood pressure and the HFD-induced obesity as observed by lower body weight, WAT index, triglycerides, NEFA, and leptin in plasma. ATZ treatment also prevented the HFD-induced increase in adipocyte diameter and even induced marked atrophy and the accumulation of macrophages in this tissue. ATZ treatment also improved glucose metabolism by increasing glucose tolerance and insulin sensitivity, GLUT4 mRNA expression in WAT in parallel to decreased insulin levels. CONCLUSIONS: In the context of HFD-induced obesity and metabolic syndrome, the fat loss induced by ATZ is probably due to heme synthesis inhibition, which blocks adipogenesis by probably decreased RevErbα activity, leading to apoptosis of adipocytes and the recruitment of macrophages. As a consequence of fat loss, ATZ elicits a beneficial systemic antiobesity effect and improves the metabolic status