Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA

Influence of matrix composition on polymerization stress development of experimental composites

Objective. Stress development at the tooth/restoration interface is one of the most important reasons for failure of adhesive restorations. The aim of this study was to evaluate the influence of BisGMA/TEGDMA (B/T) and UDMA/TEGDMA (U/T) ratios on polymerization stress (PS) and on the variables related to its development: degree of conversion (DC), polymerization maximum rate (Rp(max)), volumetric shrinkage (VS), elastic modulus (E), stress relaxation (SR) and viscosity of experimental composites. Method. Composites were formulated containing B/T or U/T in mol% ratios of 2: 8, 3: 7, 4: 6, 5: 5, 6: 4, 7: 3 and 8: 2, and 15 wt% of fumed silica. PS was determined with a universal testing machine. VS was measured with a linometer. E and SR were obtained in three-point bending. DC and Rp(max) were determined by real time NIR spectroscopy and viscosity was measured in viscometer. Data were submitted to one-way ANOVA, Tukey test (alpha = 0.05%) and regression analyses. Results. PS, VS, E and DC decreased and viscosity and Rp(max) increased with base monomer content in both series. PS showed strong correlation with VS, DC and viscosity. PS, VS and DC were higher and viscosity was lower for UDMA-based materials. Significance. Reduced viscosity, kinetics parameters and molecular characteristics led UDMA-based composites to elevated conversion and relatively lower PS at lower TEGDMA contents, compared to B/T composites. (C) 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

BisGMA/TEGDMA ratio and filler content effects on shrinkage stress

Objective. To investigate the contributions of BisGMA:TEGDMA and filler content on polymerization stress, along with the influence of variables associated with stress development, namely, degree of conversion, reaction rate, shrinkage, elastic modulus and loss tangent for a series of experimental dental composites. Methods. Twenty formulations with BisGMA: TEGDMA ratios of 3: 7, 4: 6, 5: 5, 6: 4 and 7: 3 and barium glass filler levels of 40, 50, 60 or 70 wt% were studied. Polymerization stress was determined in a tensilometer, inserting the composite between acrylic rods fixed to clamps of a universal test machine and dividing the maximum load recorded by the rods cross-sectional area. Conversion and reaction rate were determined by infra-red spectroscopy. Shrinkage was measured by mercury dilatometer. Modulus was obtained by three-point bending. Loss tangent was determined by dynamic nanoindentation. Regression analyses were performed to estimate the effect of organic and inorganic contents on each studied variable, while a stepwise forward regression identified significant variables for polymerization stress. Results. All variables showed dependence on inorganic concentration and monomeric content. The resin matrix showed a stronger influence on polymerization stress, conversion and reaction rate, whereas filler fraction showed a stronger influence on shrinkage, modulus and loss tangent. Shrinkage and conversion were significantly related to polymerization stress. Significance. Both the inorganic filler concentration and monomeric content affect polymerization stress, but the stronger influence of the resin matrix suggests that it may be possible to reduce stress by modifying resin composition without sacrificing filler content. The main challenge is to develop formulations with low shrinkage without sacrificing degree of conversion. (C) 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Growth hormone is permissive for skeletal adaptation to mechanical loading

The Lewis dwarf (DW) rat was used as a model to test the hypothesis that growth hormone (GH) is permissive for new bone formation induced by mechanical loading in vivo. Adult female Lewis DW rats aged 6.2 +/- 0.1 months (187 +/- 18 g) were allocated to four vehicle groups (DW), four GH treatment groups at 32.5 mug/100 g body mass (DWGH1), and four GH treatment groups at 65 mug/100 g (DWGH2). Saline vehicle or GH was injected intraperitoneally (ip) at 6:30 p.m. and 6:30 a.m. before mechanical loading of tibias at 7:30 a.m. A single period of 300 cycles of four-point bending was applied to right tibias at 2.0 Hz, and magnitudes of 24, 29, 38, or 48N were applied. Separate strain gauge analyses in 5 DW rats validated the selection of loading magnitudes. After loading, double-label histomorphometry was used to assess bone formation at the periosteal surface (Ps.S) and endocortical surface (Ec.S) of tibias. Comparing left (unloaded) tibias among groups, GH treatment had no effect on bone formation. Bone formation in tibias in DW rats was insensitive to mechanical loading. At the Ec.S, mechanically induced lamellar bone formation increased in the DWGH2 group loaded at 48N (p < 0.05), and no significant increases in bone formation were observed among other groups. The percentage of tibias expressing woven bone formation (Wo.B) at the Ps.S was significantly greater in the DWGH groups compared with controls (p < 0.05). We concluded that GH influences loading-related bone formation in a permissive manner and modulates the responsiveness of bone tissue to mechanical stimuli by changing thresholds for bone formation.

Determination of displacement, stress- and strain-distribution in the human heart: a FE-model on the basis of MR imaging.

The determination of characteristic cardiac parameters, such as displacement, stress and strain distribution are essential for an understanding of the mechanics of the heart. The calculation of these parameters has been limited until recently by the use of idealised mathematical representations of biventricular geometries and by applying simple material laws. On the basis of 20 short axis heart slices and in consideration of linear and nonlinear material behaviour we have developed a FE model with about 100,000 degrees of freedom. Marching Cubes and Phong's incremental shading technique were used to visualise the three dimensional geometry. In a quasistatic FE analysis continuous distribution of regional stress and strain corresponding to the endsystolic state were calculated. Substantial regional variation of the Von Mises stress and the total strain energy were observed at all levels of the heart model. The results of both the linear elastic model and the model with a nonlinear material description (Mooney-Rivlin) were compared. While the stress distribution and peak stress values were found to be comparable, the displacement vectors obtained with the nonlinear model were generally higher in comparison with the linear elastic case indicating the need to include nonlinear effects.

Biomechanical characterization and in vitro mechanical injury of elderly human femoral head cartilage: comparison to adult bovine humeral head cartilage.

OBJECTIVES: In vitro mechanical injury of articular cartilage is useful to identify events associated with development of post-traumatic osteoarthritis (OA). To date, many in vitro injury models have used animal cartilage despite the greater clinical relevance of human cartilage. We aimed to characterize a new in vitro injury model using elderly human femoral head cartilage and compare its behavior to that of an existing model with adult bovine humeral head cartilage. DESIGN: Mechanical properties of human and bovine cartilage disks were characterized by elastic modulus and hydraulic permeability in radially confined axial compression, and by Young's modulus, Poisson's ratio, and direction-dependent radial strain in unconfined compression. Biochemical composition was assessed in terms of tissue water, solid, and glycosaminoglycan (GAG) contents. Responses to mechanical injury were assessed by observation of macroscopic superficial tissue cracks and histological measurements of cell viability following single injurious ramp loads at 7 or 70%/s strain rate to 3 or 14 MPa peak stress. RESULTS: Confined compression moduli and Young's moduli were greater in elderly human femoral cartilage vs adult bovine humeral cartilage whereas hydraulic permeability was less. Radial deformations of axially compressed explant disks were more anisotropic (direction-dependent) for the human cartilage. In both cartilage sources, tissue cracking and associated cell death during injurious loading was common for 14 MPa peak stress at both strain rates. CONCLUSION: Despite differences in mechanical properties, acute damage induced by injurious loading was similar in both elderly human femoral cartilage and adult bovine humeral cartilage, supporting the clinical relevance of animal-based cartilage injury models. However, inherent structural differences such as cell density may influence subsequent cell-mediated responses to injurious loading and affect the development of OA.

Adhesive cementation of zirconia posts to root dentin: Evaluation of the mechanical cycling effect

This study evaluated the effect of mechanical cycling on the bond strength of zirconia posts to root dentin. Thirty single-rooted human teeth were transversally sectioned to a length of 16 mm. The canal preparation was performed with zirconia post system drills (CosmoPost, Ivoclar) to a depth of 12 mm. For post cementation, the canals were treated with total-etch, 3-steps All-Bond 2 (Bisco), and the posts were cemented with Duolink dual resin cement (Bisco). Three groups were formed (n = 10): G1 - control, no mechanical cycling; G2 - 20,000 mechanical cycles; G3 - 2,000,000 mechanical cycles. A 1.6-mm-thick punch induced loads of 50 N, at a 45° angle to the long axis of the specimens and at a frequency of 8 Hz directly on the posts. To evaluate the bond strengths, the specimens were sectioned perpendicular to the long axis of the teeth, generating 2-mm-thick slices, approximately (5 sections per teeth), which were subjected to the push-out test in a universal testing machine at a 1 mm/min crosshead speed. The push-out bond strength was affected by the mechanical cycling (1-way ANOVA, p = .0001). The results of the control group (7.7 ± 1.3 MPa) were statistically higher than those of G2 (3.9 ± 2.2 MPa) and G3 (3.3 ± 2.3 MPa). It was concluded that the mechanical cycling damaged the bond strength of zirconia posts to root dentin.

Effect of unilateral misfit on preload of retention screws of implant-supported prostheses submitted to mechanical cycling

Purpose: The aim of this study was to evaluate the effect of different levels of unilateral angular misfit on preload maintenance of retention screws of single implant-supported prostheses submitted to mechanical cycling. Materials and methods: Premachined UCLA abutments were cast with cobalt-chromium alloy to obtain 48 crowns divided into four groups (n=12). The crowns presented no misfit in Group A (control group) and unilateral misfits of 50μm, 100μm and 200μm in the groups B, C and D, respectively. The crowns were attached to external hexagon implants with a titanium retention screw with torque of 30N/cm. Oblique loading of 130N at 2Hz was applied on each replica, totalizing 5×104 and 1×106cycles. Detorque values were measured initially and after each cycling period. Data were evaluated by analysis of variance and Tukey's HSD test (p<0.05). Results: All groups presented reduced initial detorque values (p< 0.05) in comparison to the insertion torque (30. ± 0.5. N/cm) and Group A (25.18. N/cm) exhibited the lowest reduction. After mechanical cycling, all groups presented detorque values from 19.5. N/cm to 22.38. N/cm and the mechanical cycling did not statistically influence the detorque values regardless the misfit level of the replicas. Conclusion: The unilateral misfit influenced the preload maintenance only before mechanical cycling. The mechanical cycling did not influence the torque reduction. © 2010 Japan Prosthodontic Society.

Regular and switching platform: Bone stress analysis with varying implant diameter

The aim of this study was to evaluate stress distribution of the peri-implant bone by simulating the biomechanical influence of implants with different diameters of regular or platform switched connections by means of 3-dimensional finite element analysis. Five mathematical models of an implant-supported central incisor were created by varying the diameter (5.5 and 4.5 mm, internal hexagon) and abutment platform (regular and platform switched). For the cortical bone, the highest stress values (rmax and rvm) were observed in situation R1, followed by situations S1, R2, S3, and S2. For the trabecular bone, the highest stress values (rmax) were observed in situation S3, followed by situations R1, S1, R2, and S2. The influence of platform switching was more evident for cortical bone than for trabecular bone and was mainly seen in large platform diameter reduction.

Stress analysis in oral obturator prostheses: Imaging photoelastic

Maxillary defects resulting from cancer, trauma, and congenital malformation affect the chewing efficiency and retention of dentures in these patients. The use of implant-retained palatal obturator dentures has improved the self-esteem and quality of life of several subjects. We evaluate the stress distribution of implant-retained palatal obturator dentures with different attachment systems by using the photoelastic analysis images. Two photoelastic models of the maxilla with oral-sinus-nasal communication were fabricated. One model received three implants on the left side of the alveolar ridge (incisive, canine, and first molar regions) and the other did not receive implants. Afterwards, a conventional palatal obturator denture (control) and two implant-retained palatal obturator dentures with different attachment systems (O-ring; bar-clip) were constructed. Models were placed in a circular polariscope and a 100-N axial load was applied in three different regions (incisive, canine, and first molar regions) by using a universal testing machine. The results were photographed and analyzed qualitatively using a software (Adobe Photoshop). The bar-clip system exhibited the highest stress concentration followed by the O-ring system and conventional denture (control). Images generated by the photoelastic method help in the oral rehabilitator planning. © 2013 SPIE.

Hydrostatic intestinal edema induced signaling pathways: potential role of mechanical forces.

BACKGROUND: Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema. METHODS: The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine. RESULTS: Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength. CONCLUSION: Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.

Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor beta

Understanding the impact of extracellular matrix sub-types and mechanical stretch on cardiac fibroblast activity is required to help unravel the pathophysiology of myocardial fibrotic diseases. Therefore, the purpose of this study was to investigate pro-fibrotic responses of primary human cardiac fibroblast cells exposed to different extracellular matrix components, including collagen sub-types I, III, IV, VI and laminin. The impact of mechanical cyclical stretch and treatment with transforming growth factor beta 1 (TGFβ1) on collagen 1, collagen 3 and alpha smooth muscle actin mRNA expression on different matrices was assessed using quantitative real-time PCR. Our results revealed that all of the matrices studied not only affected the expression of pro-fibrotic genes in primary human cardiac fibroblast cells at rest but also affected their response to TGFβ1. In addition, differential cellular responses to mechanical cyclical stretch were observed depending on the type of matrix the cells were adhered to. These findings may give insight into the impact of selective pathological deposition of extracellular matrix proteins within different disease states and how these could impact the fibrotic environment.

Photoelastic Analysis Of All-on-four Concept Using Different Implants Angulations For Maxilla.

Conventional tilted implants are used in oral rehabilitation for heavily absorbed maxilla to avoid bone grafts; however, few research studies evaluate the biomechanical behavior when different angulations of the implants are used. The aim of this study was evaluate, trough photoelastic method, two different angulations and length of the cantilever in fixed implant-supported maxillary complete dentures. Two groups were evaluated: G15 (distal tilted implants 15°) and G35 (distal tilted implants 35°) n = 6. For each model, 2 distal tilted implants (3.5 x 15 mm long cylindrical cone) and 2 parallel tilted implants in the anterior region (3.5 x 10 mm) were installed. Photoelastic models were submitted to three vertical load tests: in the end of cantilever, in the last pillar and in the all pillars at the same time. We obtained the shear stress by Fringes software and found values for total, cervical and apical stress. The quantitative analysis was performed using the Student tests and Mann-Whitney test; p ≥ 0.05. There is no difference between G15 and G35 for total stress regardless of load type. Analyzing the apical region, G35 reduced strain values considering the distal loads (in the cantilever p = 0.03 and in the last pillar p = 0.02), without increasing the stress level in the cervical region. Considering the load in all pillars, G35 showed higher stress concentration in the cervical region (p = 0.04). For distal loads, G15 showed increase of tension in the apical region, while for load in all pillars, G35 inclination increases stress values in the cervical region.

Comparison of the fracture torque of different Brazilian mini-implants

This study evaluated fracture torque by torsion, in relation to the length and diameter of orthodontic mini-implants, to demonstrate their viability for clinical and experimental use based on the torque recommended by the manufacturers. The fractures at the moment of insertion, whose incidence in the literature is around 4%, are principally due to excessive force and the inability of the implant to resist rotational forces. Thirty orthodontic mini-implants of three commercial brands available in Brazil (Neodent 1.6 x 9 mm, Dentoflex 1.6 x 9 mm and Kopp 1.6 x 9 mm) were attached to a device made specifically for this research, leaving the mini-implants with sufficient stability. The miniimplants were submitted to torsion torque, using a digital torque wrench, until their breaking point. The values obtained with the test were submitted to analysis of variance and the Tukey test. The mean values of mini-implant ruptures were 26 N.cm for group A (Dentoflex), 25.4 N. cm for group B (Kopp) and 32.8 N.cm for group C (Neodent). From the Tukey test we could observe that the relationships between the means of the Dentoflex and Neodent groups, and between the Kopp and Neodent groups, were significant. Between the Dentoflex and Kopp groups, significance was nonexistent. All the values found in our research for fracture torque were higher than the limits recommended by the manufacturers for clinical use in orthodontics. The highest values were found in the Neodent group.

Influence of Photoactivation Protocol and Light Guide Distance on Conversion and Microleakage of Composite Restorations

Purpose: To evaluate the effect of light guide distance and the different photoactivation methods on the degree of conversion (DC) and microleakage of a composite. Methods and Materials: Three photoactivation protocols (600mW/cm(2) x 40 seconds; 400 mW/cm(2) x 60 seconds or 200 mW/cm(2) x 20 seconds, followed by 500 mW/cm(2) X 40 seconds) and three distances from the light source (0, 3 or 7 mm) were tested. Cylindrical specimens (5 nun diameter; 2 mm tall; n=3) were prepared for the DC test (FT-Raman). Class V cavities were made in 90 bovine incisors to conduct the microleakage test. The specimens were conditioned for 15 seconds with phosphoric acid (37%), followed by application of the adhesive system Prime & Bond NT (Dentsply/Caulk). The preparations were restored in bulk. The specimens were stored for 24 hours in distilled water (37 degrees C) before being submitted to the silvernitrate microleakage protocol. The restorations were sectioned and analyzed under 25x magnification. Results: Statistical analyses (two-way ANOVAs and Tukey test, alpha=0.05) found significance only for the factor distance (p=0.015) at the top of the composite for the DC test. Conversion was statistically lower for the 7 mm groups compared to the 0 and 3 mm groups, which were equivalent to each other. At the bottom of the specimens, none of the factors or interactions was significant (p<0.05). The Kruskal-Wallis test showed that, in general, the soft-start method led to lower microleakage scores when compared to the continuous modes, mainly when associated with a distancing of 7 mm (p<0.01). With the exception of specimens irradiated with 400mW/cm(2) that did not demonstrate variations on scores for the distances tested, higher microleakage was observed for shorter distances from the light source. Conclusions: Soft-start methods may reduce microleakage when the light guide distancing provides a low level of irradiance, which also causes a discrete reduction in the DC.