Francisco Collía

Injectable Acrylic Bone Cements for Vertebroplasty Based on a Radiopaque Hydroxyapatite. Bioactivity and Biocompatibility

Radiopaque bone cements have been formulated to provide injectable pastes with improved bioactivity to be applied in vertebroplasty and kyphoplasty techniques. The bioactive compound was strontium containing hydroxyapatite salt, which was introduced as obtained (SrHA) or after treatment with MMA monomer (SrHA-t). The in vitro bioactivity of the cements was tested in cement films or in cement pastes introduced directly in a simulated body fluid (SBF) solution at 37 degrees C to mimic the in vivo conditions. Precipitation of an apatite-like layer was observed for the 20 wt %-SrHA-t containing cement in the first experiments, and in all formulations in the second ones. The deposited particles were characterized by FTIR spectroscopy and by EDAX analysis. Radiopacity of cements after immersion in SBF was confirmed. The biocompatibility exhibited by the SrHA containing cements was, in some cases, superior to that shown by a formulation with 10 wt % of BaSO(4). The new formulations prepared with the treated filler exhibited the lowest cytotoxicity and enhanced cellular proliferation. The in vivo biocompatibility tested by an intramuscular model in rats indicated the formation of a membrane formed by collagen fibers containing fibroblasts with no inflammatory cells, such as macrophages, giant cells or lymphocytes in all formulations.

In vivo inhibition of inducible nitric oxide synthase decreases lung injury induced by Toxocara canis in experimentally infected rats.

The direct effect of nitric oxide (NO) on the viability of Toxocara canis larvae was studied. We observed that the nitric oxide donors, SIN‐1 and SNOG, exert no cytotoxic effect on the in vitro viability of T. canis larvae. In addition, we developed a model in rats to elucidate the role of NO during T. canis infection. We evaluated different indicators in four experimental groups: morphological parameters, the total number cells and cell types recovered, nitrite and protein concentration, lactate dehydrogenase and alkaline phosphatase enzymatic activity in the bronchoalveolar lavage fluid, lung index and detection of anti‐T. canis specific antibodies. We observed significant differences between non‐infected and infected groups. The infected animals treated with the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine were less damaged than infected, non‐treated animals. Our results suggest that the in vivo inhibition of the synthesis of NO triggered by iNOS diminishes the deleterious effects of the parasite upon the host, especially the vascular alterations in the lungs. We could show that in vivo production of NO induced by infection with T. canis results in direct host damage. Thus, this induction may constitute an evasion/adaptation mechanism of the parasite.

Gene Expression Profile in the Liver of BALB/c Mice Infected with Fasciola hepatica

Background Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with F. hepatica metacercariae using a microarray-based methodology. Methodology A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21). Results We found that F. hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death. Conclusion The present study provides us insights at the molecular level about the underlying mechanisms used by F. hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma. However, more studies should be performed to confirm this hypothesis.

In Vitro and In Vivo Behaviour of Bioactive Glass Composites Bearing a NSAID

Bioactive acrylic formulations based on PMMA, bioactive glasses in the system SiO2CaO-Na2O, and the drug fosfosal, have been effective in providing the formati on of an apatite layer on their surface in vitro. The in vivo behaviour studied in the femur of rabbits showed a clear integration between this material and the distal end of the femora l b ne shaft after 12 weeks, without a defined structural interface bone-cement. Osseous neoformati on was detected by the existence of areas of osteoid around the pellet of cement.

Time-course investigation of the gene expression profile during Fasciola hepatica infection: A microarray-based study

Fasciolosis is listed as one of the most important neglected tropical diseases according with the World Health Organization and is also considered as a reemerging disease in the human beings. Despite there are several studies describing the immune response induced by Fasciola hepatica in the mammalian host, investigations aimed at identifying the expression profile of genes involved in inducing hepatic injury are currently scarce. Data presented here belong to a time-course investigation of the gene expression profile in the liver of BALB/c mice infected with F. hepatica metacercariae at 7 and 21 days after experimental infection. The data published here have been deposited in NCBIs Gene Expression Omnibus and are accessible through GEO Series accession number GSE69588, previously published by Rojas-Caraballo et al. (2015) in PLoS One [1].

Application of calcium phosphates and fibronectin as complementary treatment for osteoporotic bone fractures

INTRODUCTION The gradual aging of the population results in increased incidence of osteoporotic bone fractures. In a good quality bone, the fixation with the usual methods is adequate, but not in osteoporotic bone, in which consolidation delays and other complications are common, with failure rates for screws up to 25%. OBJECTIVE To test fibronectin loaded hydroxyapatite as a complementary treatment for osteoporotic fractures. MATERIAL AND METHODS This study was performed in a vivo model; 42 female osteoporotic adult rabbits 4-5kg (White New Zealand) were used. Two groups (hydroxyapatite and fibronectin loaded hydroxyapatite) and a control group were tested. 3 time points 24h, 48h and 5days were studied. Defects were created in both femurs, in one of them, a cannulated screw (4mm) and a biocompatible material were placed; in the other femur a screw was inserted without supplemented material forming the control group. Osteoporosis was induced from models already known throughout administration of steroids. Samples were analyzed histologically and through imaging (micro Ct). RESULTS Basal levels of BMD are observed below to normal when compared to other studies (0.25/0.3 instead of 0.4). Global and dependent of time analysis of samples, show no significant differences for samples analyzed. However, an important trend was noted for variables that define the trabecular bone microarchitecture. Indices that define trabecular microarchitecture in the comparative analysis found to have statistical differences (p<0.01). DISCUSSION Osteosynthesis in an osteoporotic bone is a challenge for the surgeon, due to a reduced bone mineral density and different bone architecture. The main finding was the verification of the hypothesis that the trabecular bone parameters increases with our augmentation material in weak rabbit bone quality. Also, the histological analyses of samples show an increase of non inflammatory cells in protein samples (OHAp-Fn) from the first 24hours. CONCLUSION An early response of rabbit osteroporotic bone to a complementary treatment with fibronectin loaded hydroxyapatite has been observed. This response is reflected in greater values for indices that define the trabecular bone microarchitecture, thickness and separation, a greater non-inflammatory cellularity after only 24hours and an increased amount of connective tissue observed at 48hours.