Patterns in Protein Flexibility: A Comparison of NMR "Ensembles", MD Trajectories, and Crystallographic B-Factors.

Proteins are molecular machines requiring flexibility to function. Crystallographic B-factors and Molecular Dynamics (MD) simulations both provide insights into protein flexibility on an atomic scale. Nuclear Magnetic Resonance (NMR) lacks a universally accepted analog of the B-factor. However, a lack of convergence in atomic coordinates in an NMR-based structure calculation also suggests atomic mobility. This paper describes a pattern in the coordinate uncertainties of backbone heavy atoms in NMR-derived structural "ensembles" first noted in the development of FindCore2 (previously called Expanded FindCore: DA Snyder, J Grullon, YJ Huang, R Tejero, GT Montelione, Proteins: Structure, Function, and Bioinformatics 82 (S2), 219-230) and demonstrates that this pattern exists in coordinate variances across MD trajectories but not in crystallographic B-factors. This either suggests that MD trajectories and NMR "ensembles" capture motional behavior of peptide bond units not captured by B-factors or indicates a deficiency common to force fields used in both NMR and MD calculations.

Fracture strength analysis of titanium insert-reinforced zirconia abutments according to the axial height of the titanium insert with an internal connection.

This study aimed to analyze fracture strength in vitro by varying the axial height of the titanium insert and the labial height of the zirconia abutment in an internal connection implant to identify the titanium insert axial height with optimal mechanical stability. Sixty implants with an internal connection system were used. Two-piece zirconia abutments were used with the titanium inserts. Combinations of different titanium insert axial heights (mm) and zirconia abutment labial heights (mm) constituted five groups: Gr1 (1-3), Gr2 (3-3), Gr3 (3-5), Gr4 (5-3), and Gr5 (5-5). After thermocycling, a fracture load test was performed with a universal testing machine. The initial deformation load and the fracture load were measured and analyzed. The fractured surface and cross-section of the specimens were examined by scanning electron microscopy (SEM). The groups of titanium inserts with axial heights of 3 mm and 5 mm showed significantly greater initial deformation load and fracture load than the group with an axial height of 1 mm (p < 0.05), but there was no significant difference between the two groups with axial heights of 3 mm and 5 mm. The labial height of the zirconia abutment had no significant influence on the initial deformation load and fracture load. In some specimens in Gr4 and Gr5, cracking or bending of the titanium insert and abutment screw was observed on SEM. The axial height of the titanium insert should be designed to not be less than 3 mm to increase the fracture strength and promote the long-term stability of implants.

Relationship between upper limb injuries and hip range of motion and strength in high school baseball pitchers.

We aimed to examine the relationship between hip range of motion (ROM) and abduction strength and throwing-related shoulder/elbow injuries in high school baseball pitchers. The study included 135 baseball pitchers. We asked them to fill out a questionnaire at the checkups, that included the dominant arm and the years of baseball experience. To avoid a confirmation bias, the examiners were blinded to the participants' hand dominance. All players underwent physical function measurements, such as height, weight, shoulder and hip strength, and shoulder and hip ROM. Shoulder and elbow injury was defined as shoulder and elbow pain that the patient had been aware of in the past 3 years. The results of injured and non-injured pitchers were compared. Eighty-five pitchers had experienced a shoulder or elbow injury in the past 3 years. The shoulder ROM and strength in the injured and non-injured groups did not differ to a statistically significant extent. The hip external rotation ROM on the dominant side, the hip abduction strength on the non-dominant side, and the hip abduction strength on the dominant side were significantly lower in the injured group than in the non-injured group. The results may contribute to reducing the incidence of these injuries.

The effect of gluteus maximus tenotomy in primary total hip arthroplasty with posterior approach: Kinematic analysis of hip extensor strength.

BACKGROUND: The posterior approach (PA) is the most commonly used surgical approach for total hip arthroplasty (THA), but the proximity of the sciatic nerve may increase the likelihood of sciatic nerve injury (SNI). Gluteus maximus tenotomy can be performed to prevent SNI because tenotomy increases the distance between the femoral neck and sciatic nerve and prevents compression of the sciatic nerve by the gluteus maximus tendon (GMT) during hip movements. We aimed to kinematically compare the postoperative hip extensor forces of patients who have and have not undergone gluteus maximus tenotomy to determine whether there is a difference in hip extensor strength. METHODS: Seventy-two patients who underwent gluteus maximus tenotomy during THA were included in the group 1, and 86 patients who did not undergo tenotomy were included in group 2. The Harris hip score, body mass index and hip extensor forces were measured both preoperatively, and 6 months after surgery with an isokinetic dynamometer and compared. RESULTS: The mean age was 64.6 ± 2.3 years in group 1 and 63.8 ± 2.1 in group 2. Mean body mass index was 25.7 ± 1.1 in group 1, and 25.5 ± 1.3 in group 2. Baseline Harris hip score (HHS) was 42.36 ± 12 in group 1 and 44.07 ± 9.4 in group 2 (p = 0.31), whereas it was 89.1 ± 7.8 and 88.4 ± 8.1 at 6 months after surgery, respectively. Baseline hip extensor force (HEF) was 2 ± 0.4 Nm/kg in group 1, and 2.1 ± 0.7 Nm/kg in group 2 (p = 0.28), while it was 2.4 ± 0.6 Nm/kg, and 2.5 ± 0.5 Nm/kg, respectively at 6 month follow-up (p = 0.87). Both groups had significantly improved HHS and HEF when comparing baseline and postoperative measurements (p < 0.0001). No cases of sciatic nerve palsy were noted in group 1, whereas there were two (2.32%) cases in group 2, postoperatively. CONCLUSION: The release of the GMT during primary hip arthroplasty performed with the PA did not lead to significant decrease in hip extension forces. Hip extensor strength improves after THA regardless of tenotomy. Gluteus maximus tenotomy with repair does not reduce muscle strength and may offer better visualization.

In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength and Low Bone Turnover.

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown. METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) with and without T2D and between obese without and with T2D. RESULTS: Compared to MHO and MUHO without T2D, MUHO with T2D had significantly lower levels of osteocalcin ((7.49 ±â€…3.0 and 6.03 ±â€…2.47 vs 4.24 ±â€…2.72 ng/mL, respectively, P = 0.003) and C-terminal telopeptide of type I collagen (CTx) (0.28 ±â€…0.10 and 0.29 ±â€…0.13 vs 0.21 ±â€…0.15 ng/mL, respectively, P = 0.02). Dividing our subjects simply into those with and without T2D showed that obese men with T2D had significantly lower levels of osteocalcin (P = 0.003) and CTx (P = 0.005), greater trabecular separation at the tibia and radius (P = 0.03 and P = 0.04, respectively), and lower tibial failure load and stiffness (both P = 0.04), relative to obese men without T2D. CONCLUSION: In men, the combination of obesity and T2D is associated with reduced bone turnover and poorer trabecular bone microarchitecture and bone strength compared to those who are obese but without T2D, suggesting worse bone disease.

Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes.

CONTEXT: Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. OBJECTIVE: To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture. METHODS: Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years. RESULTS: No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. CONCLUSION: The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

Rotary-jet spun polycaprolactone/nano-hydroxyapatite scaffolds modified by simulated body fluid influenced the flexural mode of the neoformed bone.

Polycaprolactone (PCL) is a biocompatible, biodegradable synthetic polymer which in combination with nanohydroxyapatite (nHAp) can give rise to a low cost, nontoxic bioactive product with excellent mechanical properties and slow degradation. Here we produced, characterized and evaluated in vivo the bone formation of PCL/nHAp scaffolds produced by the rotary jet spinning technique. The scaffolds produced were firstly soaked into simulated body fluid for 21 days to also obtain nHAp onto PCL/nHAp scaffolds. Afterwards, the scaffolds were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy and Raman spectroscopy. For in vivo experiments, 20 male Wistar rats were used and randomly divided in 4 experimental groups (n = 5). A critical defect of 3 mm in diameter was made in the tibia of the animals, which were filled with G1 control (clot); G2-PCL scaffold; G3-PCL/nHAp (5%) scaffold; G4-PCL/nHAp (20%) scaffold. All animals were euthanized 60 days after surgery, and the bone repair in the right tibiae were evaluated by radiographic analysis, histological analysis and histomorphometric analysis. While in the left tibias, the areas of bone repair were submitted to the flexural strength test. Radiographic and histomorphometric analyses no showed statistical difference in new bone formation between the groups, but in the three-point flexural tests, the PCL/nHAp (20%) scaffold positively influenced the flexural mode of the neoformed bone. These findings indicate that PCL/nHAp (20%) scaffold improve biomechanical properties of neoformed bone and could be used for bone medicine regenerative.

Pretratamiento y mejoría de la fuerza de unión de los cementos autoadhesivos de resina a los postes / Pretreatment and improvement of bonding strength of self-adhesive resin cements to posts

ABSTRACT Introduction: Posts and core are frequently used in endodontically treated teeth with excessive loss of coronal tooth structure. Objective: To evaluate the effectiveness of self-adhesive cements under different pre-treatments of dentin in the resistance to extrusion of fiberglass posts. Methods: An experimental in vitro study was conducted. The randomly selected sample was 56 extracted bovine incisors with mature apices and without root curvature. Before the cementing procedure, pretreatment of dentin was performed with 11.5 percent polyacrylic acid, 17 percent EDTA or sodium hypochlorite. The type of failure between the post/cement/dentin was evaluated by stereomicroscope. Two hundred and sixteen bovine dentin discs were used. The disks were approximately 1 mm thick, and were obtained from 72 bovine roots restored with intraradicular retentions. Data were analyzed for better comprehension in an SPSS database for Windows version 15. Results: The highest values were found in groups G3, G4 and G5, and there was no bond strength significant difference in group G2. Conclusions: The pre-treatment had no effect on dentin bond strength, and the self-adhesive cement RelyX U100 appears to be a viable option in the cementation of fiber posts(AU)

RESUMEN Introducción: Los postes y el núcleo se utilizan con frecuencia en los dientes tratados endodónticamente con una pérdida excesiva de la estructura dental coronal. Objetivo: Evaluar la efectividad de los cementos autoadhesivos bajo diferentes pretratamientos de dentina en la resistencia a la extrusión de postes de fibra de vidrio. Métodos: Se realizó una investigación experimental in vitro en 56 dientes de ganado seleccionados al azar con cierre apical maduro y sin curvaturas radiculares. Antes del procedimiento de cementación, se llevó a cabo el pretratamiento de la dentina con 11,5 por ciento de ácido poliacrílico, 17 por ciento de EDTA o hipoclorito de sodio. El estereomicroscopio evaluó el tipo de falla entre el poste / cemento / dentina. Se usaron 216 discos de dentina bovina. Los discos tenían aproximadamente 1 mm de espesor y se obtuvieron de 72 raíces bovinas restauradas con retenciones intrarradiculares. Los datos se analizaron para una mejor comprensión en una base de datos de SPSS para Windows versión 15. Resultados: Los valores más elevados fueron encontrados en los grupos G3, G4 y G5 y no fue significativa la prueba de resistencia en el grupo G2. Conclusiones: El pretratamiento no tuvo efecto sobre la fuerza de unión dentinaria, y el cemento autoadhesivo RelyX U100 parece ser una opción viable en la cementación postes de fibra(AU)

Jump Exercise and Food Restriction on Bone Parameters in Young Female Rats.

We examined the effect of jump exercise on bone parameters in young female rats under food restriction. Seven-week-old female rats were divided into four groups: a sedentary and ad libitum feeding group (n = 10), a jump exercise and ad libitum feeding group (n = 9), a sedentary and 30% food restriction group (n = 9), and a jump exercise and 30% food restriction group (n = 10). The jump groups jumped 20 times/day, 5 times/week. The experiment lasted for 13 weeks. There were no interactions of jump exercise and food restriction on bone. Jump exercise under food restriction conditions induced higher bone strength, bone mineral content, bone area, bone mineral density (BMD), and cortical bone volume in young female rats, similar to rats under ad libitum feeding conditions. Bone strength parameters were not significantly different between ad libitum intake and food restriction with jump exercise training; however, BMD, bone size, and bone mass in the food restriction groups did not reach the levels of those in the ad libitum conditions group with jump exercise training. Neither jump exercise nor food restriction had a significant effect on serum estradiol or IGF-1. Our study reveals jump exercise attenuates loss of biomechanical properties and some bone sites with food restriction in young female rats.

An Investigation on the Correlation between the Mechanical Properties of Human Skull Bone, Its Geometry, Microarchitectural Properties, and Water Content.

With increasingly detailed imaging and mechanical analysis, modalities need arises to update methodology and assessment criteria for skull bone analysis to understand how bone microarchitecture and the presence of attached tissues may affect the response to mechanical load. The main aim was to analyze the effect of macroscopic and microstructural features, as well as periosteal attachment, on the mechanical properties of human skull bone. Fifty-six skull specimens from ethanol-phenoxyethanol-embalmed cadavers were prepared from two human cadavers. Assuming symmetry of the skull, all samples from one-half each were stripped of periosteum and dura mater, while the soft tissues were kept intact on the remaining samples on the contralateral side. The specimens were analyzed using microcomputed tomography to assess trabecular connectivity density, total surface area, and volume ratio. The specimens were loaded under three-point bend tests until fracture with optical co-registration. The bone fragments were then lyophilized to measure their water content. With increasingly detailed imaging and mechanical analysis modalities, there is a need to update methodology and assessment criteria for skull bone analysis to understand how the bone microarchitecture and the presence of attached tissues may affect the response to mechanical load. The mechanical properties were negatively correlated to bone thickness and water content. Conversely, most microarchitectural features did not influence either mechanical parameter. The correlation between mechanical response data and morphologic properties remains similar between the results of embalmed tissues presented here and fresh osseous tissue from literature data. The findings presented here add to the existing methodology to assess human skull for research purposes. The interaction between most microarchitectural features in ethanol-phenoxyethanol-embalmed embalmed skull samples and bending stress appear to be minute.

Fracture Strength and Stress Distribution in Premolars Restored with Cast Post-and-Cores or Glass-Fiber Posts Considering the Influence of Ferule.

OBJECTIVES: The aim of this study was to evaluate the influence of ferule and the post type on the fracture strength and stress distribution in premolars. MATERIALS AND METHODS: Forty human mandibular premolars were decoronated, allocated in four groups, and restored as follows: CPC-NF: cast post-and-core and absence of ferule; CPC-F: cast post-and-core and presence of ferule; FPC-NF: glass-fiber posts and absence of ferule; FPC-F: glass-fiber posts and presence of ferule. The fracture strength (FS) and failure patterns were evaluated. Finite element analysis (FEA) evaluated the stress distribution. RESULTS: FS did not differ between CPCs and FPC either in presence or in absence of ferule. The presence of ferule increased FS with both post types. Mean values of FS for ferule groups were higher than functional or parafunctional loads reported in literature, which was not the case for FPC-NF when compared to parafunctional loads. FEA with a functional load showed slightly higher compressive stresses in dentin in the group CPC-NF, which was much lower than the compressive strength of dentin. Lower percentage of catastrophic failures was observed in nonferule groups irrespective of post type, which was explained by the stress concentration in the cervical root region when FEA with the FS load was simulated. CONCLUSION: Ferule effect was shown to be more important than post type in the analysis. Both posts showed potential to withstand functional loads irrespective of presence of ferule. However, the mean FS was lower than parafunctional loads for FPC in the absence of ferule.

Isokinetic flexion strength recovery after ACL reconstruction: a comparison between all inside graft-link technique and full tibial tunnel technique.

INTRODUCTION: Recently, a new minimally invasive single bundle technique for anatomic ACL reconstruction has been described, called the 'All-Inside graft-link technique'. One of the advantages of this procedure is the reduced morbidity at the donor site as the graft choice is the quadrupled semitendinosus, thus sparing the gracilis tendon. The aim of this study was to evaluate isokinetic flexion strength recovery in patients who underwent a gracilis sparing technique compared to those with a full-tibial tunnel technique using a doubled gracilis and semitendinosus tendons (DGST) graft. METHODS: Patients were divided into two groups: Group A (22 patients) who underwent ACL reconstruction performed with an All-Inside graft-link technique; Group B (22 patients) who underwent ACL reconstruction with an Out-In technique and DGST graft. At a mean follow-up of 13 months, quadriceps and hamstring isokinetic peak torque deficits were recorded. RESULTS: In group A, the mean side to side peak torque flexion difference between the operated and non-operated limbs was -3% and the mean torque at 30° was -7.5% at high angular velocity (180°/sec); the mean peak flexion torque was 7.2% and the mean torque at 30° was 3.1% at low angular velocity (60°/sec). In group B, the mean side to side peak flexion torque was -3.5% and the mean torque at 30° was -7.6% at high angular velocity (180°/sec); the mean peak flexion torque was -7.2% and the mean torque at 30° was -11% at low angular velocity (60°/sec). A statistically significant difference was found between the two groups at lower angular velocity both for the mean peak flexion torque and the mean torque at 30° (p = 0.009), with better results in the study group. DISCUSSION/CONCLUSION: Gracilis sparing technique is a minimally invasive technique for ACL reconstruction and yielded a significantly better flexion strength recovery at lower angular velocity compared to a full tibial tunnel technique with DGST for ACL reconstruction.

Microstructure characteristics and mechanical properties of Meretrix lusoria shell.

The microstructure and mechanical properties of Meretrix lusoria shell were investigated. M. lusoria shell was comprised of three layers (outer layer, middle layer and inner layer). Outer layer with serried mastoid structure enhanced the connection strength with middle layer. The middle layer consisted of blocky pattern structure with porosity and crossed-lamellar structure. The inner layer exhibited the typical crossed-lamellar structure. Combined with structure characteristic, phase of aragonite confirmed the crossed-lamellar structure further, building material base for mechanical properties including flexure strength (296.26 MPa), compression strength (6.71 MPa) and crack arrest ability. Microstructure of the shell was the function base of crack deflection phenomenon, which dispersed and defused the applied load via the change of crack extension direction. The investigation of M. lusoria shell provided bionic models for the design and fabrication of bioinspired composites in engineering fields. RESEARCH HIGHLIGHTS: Microstructure and mechanical properties of Meretrix lusoria shell were investigated. Crossed-lamellar structure was the microstructure characterization. M. lusoria shell owned high flexure strength and crack arrest property.

Suspensory Tethers and Critical Point Membrane Displacement in Endolymphatic Hydrops

Abstract Introduction Grossly displaced membranes are characteristic of endolymphatic hydrops. The process whereby physiological membrane displacement becomes pathological may be mediated by stress, but the membrane biomechanics underlying this transition are unclear. Objective This study seeks to determine the role of suspensory tethers during pressure-induced membrane displacement in the generation of the membranous lesions seen in this disease entity using a biomechanical model approach. Methods The location of membrane suspensory tethers was identified histologically. The influence of tethers on model membrane configuration during displacement was assessed graphically. The relationship of membrane configuration during displacement to curvature radius was quantified trigonometrically. The relationship of curvature radius to stress susceptibility was determined mathematically. The net effect of suspensory tethers on membrane stress levels for various degrees of membrane distention and displacement was then calculated numerically. Results In the inferior labyrinth, suspensory tethers are found to occur on the membranes' boundaries. Such tethering is found to impose a biphasic effect on membrane curvature with increasing degrees of displacement. As a consequence, tensile stress susceptibility is found to decline with initial membrane displacement to a critical point nadir beyond which stress then increases monotonically. No such effect was found for the superior labyrinth. Conclusion Boundary tethers in the inferior labyrinth are associated with significant tensile stress reductions until a critical point of membrane displacement is reached. Displacements short of the critical pointmay be physiological and even reversible,whereas such displacements beyond the critical point are apt to be overtly hydropic and irreversible.

Evaluation of tensile strength of tissue adhesives made of fibrin and cyanoacrylate used as reinforcement of colon suture in "ex vivo" swine

ABSTRACT Aim: To evaluate rupture pressures of tissue adhesives of cyanoacrylate (Omnex®) and fibrin (Evicel®), used as reinforcement in colonic suture from "ex vivo" swine. Methods: Surgical procedures were performed in the Surgical Technique Laboratory. From a division in segments of 10 cm of descending colon and sigmoid colon from three "ex vivo" female swine, Landrace breed, which were resected in less than six hours after the slaughter time, 30 segments were selected, 10 of each animal. They were stored in saline solution 0.9% at 36 °C, being randomly allocated in three groups (Control, Evicel and Omnex), each one containing 10 segments. Results: The lower and higher pressure values found in the groups Control, Evicel and Omnex were 36 mmHg and 41 mmHg, 70 mmHg and 90 mmHg, 90 mmHg and 120 mmHg, respectively. Containing statistical significance (p-value <0.0001) concerning the 2 to 2 comparisons (Control, Evicel and Omnex) with 95% trusting rate based on the application of the Turkey Method. Conclusion: One concludes that the use of tissue adhesives in anastomoses colonic in an experimental animal model of "ex vivo" swine increased the anastomoses rupture pressures. Among the tested adhesives, cyanoacrylate presented higher rupture pressure in relation to fibrin adhesive.

RESUMO Objetivo: Avaliar as pressões de ruptura dos adesivos teciduais de Cianoacrilato (Omnex®) e de Fibrina (Evicel®), usados como reforço em suturas colônicas de suínos "ex-vivo". Métodos: Os procedimentos cirúrgicos realizados foram realizados no Laboratório de Técnica Cirúrgica. A partir da divisão em segmentos de 10 cm do colo descendente e colo sigmoide de três suínas fêmeas ex-vivo, da raça Landrace, ressecados em tempo inferior a seis horas em relação ao momento do abate, foram selecionados 30 segmentos, 10 de cada animal. Foram armazenados em soro fisiológico 0,9% a 36 °C, alocando-se aleatoriamente esses segmentos em três grupos (Controle, Evicel e Omnex) com 10 segmentos cada. Resultados: Os menores e maiores valores pressóricos encontrados nos grupos Controle, Evicel e Omnex foram 36 mmHg e 41 mmHg, 70 mmHg e 90 mmHg, 90 mmHg e 120 mmHg, respectivamente. Com significância estatística (Valor-p < 0,0001) para as comparações 2 a 2 (Sutura, Evicel e Omnex) com um intervalo de confiança de 95% construído a partir da aplicação do método de Turkey. Conclusão: A partir desse estudo conclui-se que o uso de adesivos teciduais em anastomoses colônicas, em modelo experimental animal de suíno ex-vivo, aumentou as pressões de ruptura das anastomoses. Dentre os adesivos testados, o adesivo de Cianoacrilato apresentou maiores pressões de ruptura em relação ao adesivo de Fibrina.

Galectin-3 is essential for proper bone cell differentiation and activity, bone remodeling and biomechanical competence in mice.

OBJECTIVE: Galectin-3 is constitutively expressed in bone cells and was recently shown to modulate osteogenic transdifferentiation of vascular smooth muscle cells and atherosclerotic calcification. However, the role of galectin-3 in bone physiology is largely undefined. To address this issue, we analyzed (1) the skeletal features of 1-, 3- and 6-month-old galectin-3 null (Lgals3-/-) and wild type (WT) mice and (2) the differentiation and function of osteoblasts and osteoclasts derived from these animals. METHODS: Long bone phenotype, gene expression profile, and remodeling were investigated by micro-computed tomography, real time-PCR, static and dynamic histomorphometry, and assessment of biochemical markers of bone resorption and formation. Bone competence was also evaluated by biomechanical testing at 3 months. In vitro, the effects of galectin-3 deficiency on bone cell differentiation and function were investigated by assessing (a) gene expression of osteoblast markers, alkaline phosphatase activity, mineralization assay, and WNT/ß-catenin signaling (of which galectin-3 is a known regulator) in osteoblasts; and (b) tartrate-resistant acid phosphatase activity and bone resorption activity in osteoclasts. RESULTS: Lgals3-/- mice revealed a wide range of age-dependent alterations including lower bone formation and higher bone resorption, accelerated age-dependent trabecular bone loss (p < 0.01 vs. WT at 3 months) and reduced bone strength (p < 0.01 vs. WT at 3 months). These abnormalities were accompanied by a steady inflammatory state, as revealed by higher bone expression of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6 (p < 0.001 vs. WT at 3 months), increased content of osteal macrophages (p < 0.01 vs. WT at 3 months), and reduced expression of markers of alternative (M2) macrophage activation. Lgals3-/- osteoblasts and osteoclasts showed impaired terminal differentiation, reduced mineralization capacity (p < 0.01 vs. WT cells) and resorption activity (p < 0.01 vs. WT cells). Mechanistically, impaired differentiation and function of Lgals3-/- osteoblasts was associated with altered WNT/ß-catenin signaling (p < 0.01 vs. WT cells). CONCLUSIONS: These data provide evidence for a contribution of galectin-3 to bone cell maturation and function, bone remodeling, and biomechanical competence, thus identifying galectin-3 as a promising therapeutic target for age-related disorders of bone remodeling.

Biomecánica de las fracturas por stress / Biomechanical features of stress fractures

Se define como estrés (stress) tanto la fuerza que una carga externa ejerce sobre un cuerpo sólido como la fuerza reactiva que acompaña a la primera (Ley de Newton), por unidad de área imaginaria transversal a su dirección. Las cargas internas reactivas inducen deformaciones proporcionales del cuerpo. La resistencia del cuerpo a deformarse se llama rigidez. La deformación puede resquebrajar el cuerpo y, eventualmente, producir una fractura por confluencia de trazos. La resistencia del cuerpo a separarse en fragmentos por esa causa se llama tenacidad. La resistencia del cuerpo a la fractura es proporcional al stress que puede soportar sin separarse en fragmentos por deformación (no hay fractura sin deformación y sin stress previo). El stress máximo que un cuerpo puede soportar sin fracturarse resulta de una combinación de ambas propiedades: rigidez y tenacidad, cada una con distintos determinantes biológicos. Una o varias deformaciones del cuerpo pueden provocarle resquebrajaduras sin fracturarlo. La acumulación de resquebrajaduras determina la "fatiga" del material constitutivo del cuerpo, que reduce su rigidez, tenacidad y resistencia a la fractura para la próxima ocasión ("fragilidad por fatiga"). En el caso de los huesos, en general, los términos stress y fatiga tienen las connotaciones amplias referidas, respecto de todas las fracturas posibles. La fatiga predispone a fracturas a cargas bajas, que se denominan (correctamente) "fracturas por fatiga" y también (incorrectamente) "fracturas por stress", para distinguirlas de las que ocurren corrientemente, sin resquebrajaduras previas al trauma, que se denominan (incorrectamente) "fracturas por fragilidad, o por insuficiencia". En realidad, todas las fracturas se producen por stress y por fragilidad o insuficiencia (en conjunto); pero la distinción grosera entre fracturas "por fatiga, o por stress", por un lado, y "por fragilidad" o "por insuficiencia", por otro, aceptando las amplias connotaciones referidas antes, tiene valor en la práctica clínica. Este artículo intenta explicar esas particularidades biomecánicas y describir las distintas condiciones que predisponen a las fracturas "por fatiga o por stress" en la clínica, distinguiéndolas de las fracturas "por fragilidad o por insuficiencia" (manteniendo estas denominaciones) y detallando las características de interés directo para su diagnóstico y tratamiento. (AU)

The term "stress" expresses the force exerted by an external load on a solid body and the accompanying, opposed force (Newton's Law), expressed per unit of an imaginary area perpendicular to the loading direction. The internal loads generated this way deform (strain) proportionally the body's structure. The resistance of the body to strain expresses its stiffness. Critical strain magnitudes may induce micro-fractures (microdamage), the confluence of which may fracture the body. The body's resistance to separation into fragments determines its toughness. Hence, the body's resistance to fracture is proportional to the stress the body can support (or give back) while it is not fractured by the loadinduced strain (no stress, no strain -> no fracture). Therefore, the maximal stress the body can stand prior to fracture is determined by a combination of both, its stiffness and its toughness; and each of those properties is differently determined biologically. One or more deformations of the body may induce some microdamage but not a fracture. Microdamage accumulation determines the fatigue of the material constitutive of the body and reduces body's toughness, leading to a "fatigue-induced fragility". In case of bones, in general, both stress and fatigue have the referred, wide connotations, regarding any kind of fractures. In particular, bone fatigue predisposes to low-stress fractures, which are named (correctly) "fatigue fractures" and also misnamed "stress fractures", to distinguish them from the current fractures that occur without any excess of microdamage, that are named (wrongly) "fragility" or "insufficiency" fractures. In fact, all fractures result from all stress and fragility or insufficiency as a whole; however, the gross distinction between "fatigue or stress fractures", on one side, and "fragility or insufficiency fractures", on the other, accepting the wide connotations of the corresponding terminology, is relevant to clinical practice. This article aims to explain the above biomechanical features and describe the different instances that predispose to "fatigue or stress fractures" in clinical practice, as a different entity from "insufficiency or fragility fractures" (maintaining this nomenclature), and describe their relevant features to their diagnosis and therapy. (AU)