P2‐052: Characterization of a mAb against human α‐synuclein
Background: Learning digital instruments is to democratize access to daily technology, include elder people in the information society and preserve independence, autonomy and citizenship. Methods: Forty workshops (130 hours) with 46 communities elder people above 60 years using digital instruments in Local Area Network Houses, between 2004 and 2006, in São Paulo city and Florianópolis city, Brazil. Sociodemographic, health, cognitive and functional variables were measured and compared to learning time of: mouse, electronic games, browser and e-mail. Kaplan-Meier curves were plotted to analyze learning time. Statistical differences between the covariates were evaluated by log-rank test. The impact of covariates on learning time was analyzed by Cox proportional risk model, in SPSS software. Results: The average age was 73 years with 4,2 pathologies per person, 9,1 years of scholarship, 26% presented falls in the last 6 months. The mean learning time (in hours) for ‘‘basic use of the mouse’’ was 8,5 (CI95%:6,610,5), for ‘‘game use’’ was 10,0 (CI95%:6,8-13,2), for ‘‘browser use’’ was 16,0 (CI95%:11,8-20,2) and for ‘‘e-mail use’’ was 27,0 (CI95%:24,629,4). Hypertension, diabetes and falls in the last 6 months were not significant variables even in the bivariate analysis. More than 3 pathologies, more than 3 continuous medications, dislipidemia, hypotiroidism, activities of the daily living losses and low scholarship had no independent significance for the outcomes studied. The cognitive status was an independent factor related to learning time of mouse, games and browser. Age above 75 years and cognitive status were independent factors related to e-mail use. Conclusions: Modifiable factors that influence learning time of elder people must be screened and treated to promote access to the information society by elder people. The ability to conquer new proficiencies is a characteristic of healthy elder people.
P4‐101: Urea cycle and Alzheimer's disease
P4‐107: Association study of the ADAM12 and SH3MD1 genes with the risk of developing Alzheimer's disease
(p<0.02). To study ESR1-APOE gene-gene interactions and sexual dimorphism of selected markers, we stratified our series according to APOE genotype and grouping AD cases and controls in accordance with gender or APOE genotypes. A weak evidence of genetic interaction was observed between APOE genotypes and ESR1 markers. In contrast sexual dimorphism was evident for ESR1 rs3844508 marker effect which appeared stronger in males (OR1⁄41.75 [C.I.1.27<OR<2.4], p1⁄40.0005, OR for MAF difference, Allele A) and for ESR1 NCD1/EU579440 deletion which was associated to AD in females (OR1⁄41.67 [C.I. 1.25<OR<2.22], p1⁄40.0003, OR for Dominant model and deletion present). Conclusions: Estrogen receptor alpha (ESR1) genetic markers are associated to AD in Spanish population. Sexual dimorphism is observed in the effect of rs3844508 and NCD1 markers.
Prediction of bone density around orthopedic implants delivering bisphosphonate
The fixation of an orthopedic implant depends strongly upon its initial stability. Peri-implant bone may resorb shortly after the surgery. This resorption is directly followed by new bone formation and implants fixation strengthening, the so-called secondary fixation. If the initial stability is not reached, the resorption continues and the implant fixation weakens, which leads to implant loosening. Studies with rats and dogs have shown that a solution to prevent peri-implant resorption is to deliver bisphosphonate from the implant surface. The aims of the study were, first, to develop a model of bone remodeling around an implant delivering bisphosphonate, second, to predict the bisphosphonate dose that would induce the maximal peri-implant bone density, and third to verify in vivo that peri-implant bone density is maximal with the calculated dose. The model consists of a bone remodeling equation and a drug diffusion equation. The change in bone density is driven by a mechanical stimulus and a drug stimulus. The drug stimulus function and the other numerical parameters were identified from experimental data. The model predicted that a dose of 0.3 microg of zoledronate on the implant would induce a maximal bone density. Implants with 0.3 microg of zoledronate were then implanted in rat femurs for 3, 6 and 9 weeks. We measured that peri-implant bone density was 4% greater with the calculated dose compared to the dose empirically described as best. The approach presented in this paper could be used in the design and analysis processes of experiments in local delivery of drug such as bisphosphonate.
Cells, growth factors and bioactive surface properties in a mechanobiological model of implant healing
Interface conditions are of prime importance for implant fixation in the early post-operative period and modelling of specific biochemical interactions at implant surface is still missing. We hypothesized that updating osteoblast adhesion properties and growth factor source in an active zone located at the implant surface was relevant to model biochemical interactions of implant with its environment. We proposed an innovative set of diffusive-convective-reactive equations which relevant parameters were the cell decay factor, the cell motility and the growth factor balance. Initial comparison with histomorphometic results from a stable PMMA canine implant model provided an encouraging base to implement a numerical sensitivity analysis to evaluate the role of three types of bioactive surfaces: acid-etched titanium, coarse grit-blasted acid-etched titanium and coarse grit-blasted acid-etched titanium with RGDS peptide. We found that cell diffusion decrease (acid-etched+RGDS peptide vs. PMMA), and increase of local growth factor fraction (PMMA vs. acid-etched+RGDS peptide), significantly improved the amount of mineralized tissue on the implant surface. When the variation of structural fraction to cell motility and growth factor synthesis was investigated, an envelope pattern with an optimum was obtained but this could be exceeded for strong surface modifications and/or for high growth factor concentrations. The model also confirmed that implant bioactive properties should play a limited role to reduce heterogeneity of new-formed tissue. In conclusion, we suggested that our innovative theoretical approach was relevant to investigate implant fixation and could potentially help in reduction of implant revision.
Mechanical interaction between cells and fluid for bone tissue engineering scaffold: Modulation of the interfacial shear stress
An analytical model of the fluid/cell mechanical interaction was developed. The interfacial shear stress, due to the coupling between the fluid and the cell deformation, was characterized by a new dimensionless number N(fs). For N(fs) above a critical value, the fluid/cell interaction had a damping effect on the interfacial shear stress. Conversely, for N(fs) below this critical value, interfacial shear stress was amplified. As illustration, the role of the dynamic fluid/cell mechanical coupling was studied in a specific biological situation involving cells seeded in a bone scaffold. For the particular bone scaffold chosen, the dimensionless number N(fs) was higher than the critical value. In this case, the dynamic shear stress at the fluid/cell interface is damped for increasing excitation frequency. Interestingly, this damping effect is correlated to the pore diameter of the scaffold, furnishing thus target values in the design of the scaffold. Correspondingly, an efficient cell stimulation might be achieved with a scaffold of pore size larger than 300 microm as no dynamic damping effect is likely to take place. The analytical model proposed in this study, while being a simplification of a fluid/cell mechanical interaction, brings complementary insights to numerical studies by analyzing the effect of different physical parameters.
In vitro model of a semicircular canal: Design and validation of the model and its use for the study of canalithiasis
We present an experimental model for a semicircular canal with canalithiasis. Canalithiasis is a pathological condition where free-floating particles disturb the flow field in the semicircular canals. It may lead to a specific form of vertigo known as BPPV or top-shelf vertigo. A careful scaling of the physical and geometrical parameters allows us to study the mechanics of this disease on an enlarged model of a single semicircular canal with laser vibrometry and video particle tracking. Early results confirm the proper operation of the model canal and support the current theories on the mechanisms of BPPV.
Azithromycin fails to reduce increased expression of neutrophil-related cytokines in primary-cultured epithelial cells from cystic fibrosis mice
Beneficial effects of azithromycin in cystic fibrosis (CF) have been reported, however, its mechanism of action remains unclear. The present study aimed at investigating the effect of azithromycin on CF airway epithelial cells.
Pharmacokinetics and safety of tobramycin administered by the PARI eFlow® rapid nebulizer in cystic fibrosis
Nebulization times have been identified as an issue in patient compliance with tobramycin solution for inhalation (TSI) therapy in cystic fibrosis (CF).