Novel ball head screw and screwdriver design for implant-supported prostheses with angled channels: a finite element analysis

The primary objective of this study was to design the optimal geometry of a novel screwdriver, create the grooves on a ball head screw, and demonstrate its resistance to a torque of up to 40 Ncm at angulations of 0°, 15°, and 30° by using nonlinear finite element analysis. A secondary objective was to create a foolproof, easily recognizable system. The grooved ball head screw and geometry of the screwdriver, functioning from an angulation of 0° to 30°, was generated using Pro-ENGINEER Wildfire 5.0 software. Static structural analyses among bodies in contact were performed at different angles of 0°, 15°, and 30° at a torque of 20 Ncm and 40 Ncm using nonlinear finite element simulation by means of ANSYS 12.0. The maximum stress supported by the ball head screw and screwdriver was similar at 20 Ncm and 40 Ncm. Although greater deformations were found at 40 Ncm, these were small and might not affect the performance of the system. Further, the rupture torque value for the M2 connection was 55 Ncm for 0° and 30°, and 47.5 Ncm for 15°. Numerical simulation showed that the ball head system design can achieve the mechanical strength requirements expected for screws used in implant-supported restorations at an angulation of up to 30°. Finite element analysis showed this novel ball head screw and screwdriver system to be a good solution for angled screw channels in implant-supported prostheses

Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>A critical component of disease progression in rheumatoid arthritis (RA) involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2) is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA) model.</p> <p>Methods</p> <p>Severe polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 μg of LPS (<it>E. coli </it>strain 0111:B4) via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily), or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining). In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d. <it>vs </it>q.w. <it>vs </it>q.w. × 2) were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis.</p> <p>Results</p> <p>Mice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21), blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of the study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2.</p> <p>Conclusion</p> <p>These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.</p

Real-Time Imaging of HIF-1α Stabilization and Degradation

HIF-1α is overexpressed in many human cancers compared to normal tissues due to the interaction of a multiplicity of factors and pathways that reflect specific genetic alterations and extracellular stimuli. We developed two HIF-1α chimeric reporter systems, HIF-1α/FLuc and HIF-1α(ΔODDD)/FLuc, to investigate the tightly controlled level of HIF-1α protein in normal (NIH3T3 and HEK293) and glioma (U87) cells. These reporter systems provided an opportunity to investigate the degradation of HIF-1α in different cell lines, both in culture and in xenografts. Using immunofluorescence microscopy, we observed different patterns of subcellular localization of HIF-1α/FLuc fusion protein between normal cells and cancer cells; similar differences were observed for HIF-1α in non-transduced, wild-type cells. A dynamic cytoplasmic-nuclear exchange of the fusion protein and HIF-1α was observed in NIH3T3 and HEK293 cells under different conditions (normoxia, CoCl2 treatment and hypoxia). In contrast, U87 cells showed a more persistent nuclear localization pattern that was less affected by different growing conditions. Employing a kinetic model for protein degradation, we were able to distinguish two components of HIF-1α/FLuc protein degradation and quantify the half-life of HIF-1α fusion proteins. The rapid clearance component (t1/2 ∼4–6 min) was abolished by the hypoxia-mimetic CoCl2, MG132 treatment and deletion of ODD domain, and reflects the oxygen/VHL-dependent degradation pathway. The slow clearance component (t1/2 ∼200 min) is consistent with other unidentified non-oxygen/VHL-dependent degradation pathways. Overall, the continuous bioluminescence readout of HIF-1α/FLuc stabilization in vitro and in vivo will facilitate the development and validation of therapeutics that affect the stability and accumulation of HIF-1α

Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas

Trastuzumab resistance hampers its well-known efficacy to control HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this mechanism is still not definitively confirmed. We selected 155 patients treated with trastuzumab after development of metastasis or as adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR, epidermal growth factor 1-receptor (EGFR), α -insulin-like growth factor 1-receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110 α, pAkt, pBad, pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN, and PTEN promoter hypermethylation. We found 46% ER/PR-positive tumours, overexpression of EGFR (15%), α -IGF1R (25%), p110 α (19%), pAkt (28%), pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17% and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with α -IGF1R or pBad overexpressing tumours presented shorter progression-free survival (PFS) (all P ⩽0.043). Also, p110 α and mTOR overexpression, liver and brain relapses implied poor overall survival (OS) (all P ⩽0.041). In patients with metastatic disease, decreased PFS correlated with p110 α expression (P =0.024), whereas for OS were the presence of vascular invasion and EGFR expression (P ⩽0.019; Cox analysis). Our results support that trastuzumab resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast carcinomas

La unión metal-resina en prostodoncia. Una revisión bibliográfica. Parte I: la retención mecánica

Podeu consultar la segona part de l'article a: http://hdl.handle.net/2445/134747La utilización de materiales estéticos en prótesis fija ha sido, y es, motivo de estudio con el fin de obtener mayor similitud en la restitución de dientes perdidos. Una de las posibilidades es la utilización de materiales plásticos con base acrílica, o resinas

La unión metal-resina en prostodoncia. Una revisión bibliogràfica. Parte II: la retención química

Podeu consultar la primera part de l'article a: http://hdl.handle.net/2445/134746La retención del material de resina a una estructura metálica puede obtenerse gracias a un diseño de la forma de la misma, el cual puede ser apreciable a simple vista y capaz el atrapar a aquél; es decir, con constituyendo un patrón retentivo mecánico o macromecánico. La resistencia al desalojo del elemento de resina de la estructura metálica dependerá de dicho patrón

La unión metal-resina en prostodoncia. Una revisión bibliográfica. Parte I: la retención mecánica

Podeu consultar la segona part de l'article a: http://hdl.handle.net/2445/134747La utilización de materiales estéticos en prótesis fija ha sido, y es, motivo de estudio con el fin de obtener mayor similitud en la restitución de dientes perdidos. Una de las posibilidades es la utilización de materiales plásticos con base acrílica, o resinas

2A peptides provide distinct solutions to driving stop-carry on translational recoding

Expression of viral proteins frequently includes non-canonical decoding events (‘recoding’) during translation. ‘2A’ oligopeptides drive one such event, termed ‘stop-carry on’ recoding. Nascent 2A peptides interact with the ribosomal exit tunnel to dictate an unusual stop codon-independent termination of translation at the final Pro codon of 2A. Subsequently, translation ‘reinitiates’ on the same codon, two individual proteins being generated from one open reading frame. Many 2A peptides have been identified, and they have a conserved C-terminal motif. Little similarity is present in the N-terminal portions of these peptides, which might suggest that these amino acids are not important in the 2A reaction. However, mutagenesis indicates that identity of the amino acid at nearly all positions of a single 2A peptide is important for activity. Each 2A may then represent a specific solution for positioning the conserved C-terminus within the peptidyl-transferase centre to promote recoding. Nascent 2A peptide:ribosome interactions are suggested to alter ribosomal fine structure to discriminate against prolyl-tRNAPro and promote termination in the absence of a stop codon. Such structural modifications may account for our observation that replacement of the final Pro codon of 2A with any stop codon both stalls ribosome processivity and inhibits nascent chain release