Macroscopic anisotropic bone material properties in children with severe osteogenesis imperfecta

Children with severe osteogenesis imperfecta (OI) typically experience numerous fractures and progressive skeletal deformities over their lifetime. Recent studies proposed finite element models to assess fracture risk and guide clinicians in determining appropriate intervention in children with OI, but lack of appropriate material property inputs remains a challenge. This study aimed to characterize macroscopic anisotropic cortical bone material properties and investigate relationships with bone density measures in children with severe OI. Specimens were obtained from tibial or femoral shafts of nine children with severe OI and five controls. The specimens were cut into beams, characterized in bending, and imaged by synchrotron radiation X-ray micro-computed tomography. Longitudinal modulus of elasticity, yield strength, and bending strength were 32–65% lower in the OI group (p < 0.001). Yield strain did not differ between groups (p ≥ 0.197). In both groups, modulus and strength were lower in the transverse direction (p ≤ 0.009), but anisotropy was less pronounced in the OI group. Intracortical vascular porosity was almost six times higher in the OI group (p < 0.001), but no differences were observed in osteocyte lacunar porosity between the groups (p = 0.086). Volumetric bone mineral density was lower in the OI group (p < 0.001), but volumetric tissue mineral density was not (p = 0.770). Longitudinal OI bone modulus and strength were correlated with volumetric bone mineral density (p ≤ 0.024) but not volumetric tissue mineral density (p ≥ 0.099). Results indicate that cortical bone in children with severe OI yields at the same strain as normal bone, and that their decreased bone material strength is associated with reduced volumetric bone mineral density. These results will enable the advancement of fracture risk assessment capability in children with severe OI.     

Ilizarov method in combination with autologous mesenchymal stem cells from iliac crest shows improved outcome in tibial non-union

Autologous bone grafting and ilizarov technique are the preferred mode of treatment for bone nonunion, studies suggest that bone marrow derived mesenchymal stem cells can be effective in treatment of tibial non-union where there is length of bone defect. The current study investigates the beneficial clinical outcome of combining the ilizarov procedure with intraosseous injection of autologous mesenchymal stem cells. The open-label study enrolled 25 patients with infected tibial non-union at the Shanghai Fengxian District Central Hospital, Shanghai, China between April 2010 and July 2014. Patients were randomised to undergo the ilizarov procedure with (n = 11) or without (n = 13) intraosseous injection of bone marrow derived mesenchymal stem cells. All participants were followed prospectively until union was achieved (primary end point). The mean length of the bone defect in the Ilizarov group and Ilizarov group plus MSC group was 6.09 and 5.84 cm respectively. The mean time from the original injury to the time of the treatment for tibial non-union was 5–22 months (mean 13.5 months) for the Ilizarov group and 6–21 months (mean 13.5 months) for Ilizarov plus MSc group. All 24 patients were followed up for 12–34 months (mean 16 months). Both groups achieved the primary endpoint of stable union of the tibial fracture. No adverse events were observed in any of the group. Our study demonstrates that using autologous bone marrow derived mesenchymal stem cell as an add-on therapy to the ilizarov procedure shows significant clinical benefit in fixation of tibial non-union.     

Accounting for spatial variation of trabecular anisotropy with subject-specific finite element modeling moderately improves predictions of local subchondral bone stiffness at the proximal tibia

IntroductionPreviously, a finite element (FE) model of the proximal tibia was developed and validated against experimentally measured local subchondral stiffness. This model indicated modest predictions of stiffness (R² = 0.77, normalized root mean squared error (RMSE%) = 16.6%). Trabecular bone though was modeled with isotropic material properties despite its orthotropic anisotropy. The objective of this study was to identify the anisotropic FE modeling approach which best predicted (with largest explained variance and least amount of error) local subchondral bone stiffness at the proximal tibia.MethodsLocal stiffness was measured at the subchondral surface of 13 medial/lateral tibial compartments using in situ macro indentation testing. An FE model of each specimen was generated assuming uniform anisotropy with 14 different combinations of cortical- and tibial-specific density-modulus relationships taken from the literature. Two FE models of each specimen were also generated which accounted for the spatial variation of trabecular bone anisotropy directly from clinical CT images using grey-level structure tensor and Cowin’s fabric-elasticity equations. Stiffness was calculated using FE and compared to measured stiffness in terms of R² and RMSE%.ResultsThe uniform anisotropic FE model explained 53–74% of the measured stiffness variance, with RMSE% ranging from 12.4 to 245.3%. The models which accounted for spatial variation of trabecular bone anisotropy predicted 76–79% of the variance in stiffness with RMSE% being 11.2–11.5%.ConclusionsOf the 16 evaluated finite element models in this study, the combination of Synder and Schneider (for cortical bone) and Cowin’s fabric-elasticity equations (for trabecular bone) best predicted local subchondral bone stiffness.     

Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy

The growth plate (GP) is a dynamic tissue driving bone elongation through chondrocyte proliferation, hypertrophy and matrix production. The extracellular matrix (ECM) is the major determinant of GP biomechanical properties and assumed to play a pivotal role for chondrocyte geometry and arrangement, thereby guiding proper growth plate morphogenesis and bone elongation. To elucidate the relationship between morphology and biomechanics during cartilage morphogenesis, we have investigated age-dependent structural and elastic properties of the proliferative zone of the murine GP by atomic force microscopy (AFM) from the embryonic stage to adulthood. We observed a progressive cell flattening and arrangement into columns from embryonic day 13.5 until postnatal week 2, correlating with an increasing collagen density and ECM stiffness, followed by a nearly constant cell shape, collagen density and ECM stiffness from week 2 to 4 months. At all ages, we found marked differences in the density and organization of the collagen network between the intracolumnar matrix, and the intercolumnar matrix, associated with a roughly two-fold higher stiffness of the intracolumnar matrix compared to the intercolumnar matrix. This difference in local ECM stiffness may force the cells to arrange in a columnar structure upon cell division and drive bone elongation during embryonic and juvenile development.     

Primary stability of tibial plateaus under dynamic compression-shear loading in human tibiae – Influence of keel length,cementation area and tibial stem

The objective of our study was to evaluate the impact of the tibial keel & stem length in surface cementation, of a full cemented keel and of an additional tibial stem on the primary stability of a posterior stabilised tibial plateau (VEGA® System Aesculap Tuttlingen, Germany) under dynamic compression-shear loading conditions in human tibiae.We performed the cemented tibial plateau implantations on 24 fresh-frozen human tibiae of a mean donor age of 70.7 years (range 47–97). The tibiae were divided into four groups of matched pairs based on comparable trabecular bone mineral density. To assess the primary stability under dynamic compression shear conditions, a 3D migration analysis of the tibial component relative to the bone based on displacements and deformations and an evaluation of the cement layer including penetration was performed by CT-based 3D segmentation.Within the tested implant fixation principles the mean load to failure of a 28 mm keel and a 12 mm stem (40 mm) was 4700 ± 1149 N and of a 28 mm keel length was 4560 ± 1429 N (p = 0.996), whereas the mean load to failure was 4920 ± 691 N in full cementation (p = 0.986) and 5580 ± 502 N with additional stem (p = 0.537), with no significant differences regarding the dynamic primary stability under dynamic compression-shear test conditions.From our observations, we conclude that there is no significant difference between a 40 mm and a 28 mm tibial keel & stem length and also between a surface and a full cementation in the effect on the primary stability of a posterior stabilised tibial plateau, in terms of failure load, migration characteristics and cement layer thickness including the penetration into the trabecular bone.     

Intérêt de l’imagerie scintigraphique, à Madagascar,dans le diagnostic de l’adénome parathyroïdien ectopique – à propos d’un cas

This study reports the first case of ectopic parathyroid adenoma, diagnosed in the Department of Nuclear Medicine in Antananarivo. This clinical vignette illustrates the interest of the MIBI-Tc-99 m scan in locating this adenoma and its diagnostic confirmation after six years of erratic diagnosis. A whole body bone scintigraphy has also allowed to assess the state of bone metabolism and study outbreaks of fracture. The parathyroid scintigraphy was carried out after intra-venous administration of 666 MBq of MIBI-Tc99m. Dynamic images, static early and late static were acquired with a gamma camera E-Cam Siemens. The whole body bone scan was carried out after administration of 555 MBq of MDP-Tc-99 m. The results evidenced the presence of an para-aortic increased uptake area pointing to a left parathyroid adenoma. The persistence of a late left submaxillary increased uptake area raises, however, a reservation about the existence of a second adenoma. The bone scan displayed global skeletal remodeling, non suggestive of metastases, as it was mentioned with the CT-scan. In a diagnostic tools limited environment, skeletal pain refractory to painkillers, a chronic hypercalcemia associated with an increased parathyroid hormone level, should trigger the scintigarphic exploration in order to avoid bone and renal complications.     

Achilles tendon stress is more sensitive to subject-specific geometry than subject-specific material properties: A finite element analysis

This study used subject-specific measures of three-dimensional (3D) free Achilles tendon geometry in conjunction with a finite element method to investigate the effect of variation in subject-specific geometry and subject-specific material properties on tendon stress during submaximal isometric loading. Achilles tendons of eight participants (Aged 25–35 years) were scanned with freehand 3D ultrasound at rest and during a 70% maximum voluntary isometric contraction. Ultrasound images were segmented, volume rendered and transformed into subject-specific 3D finite element meshes. The mean (±SD) lengths, volumes and cross-sectional areas of the tendons at rest were 62 ± 13 mm, 3617 ± 984 mm³ and 58 ± 11 mm² respectively. The measured tendon strain at 70% MVIC was 5.9 ± 1.3%. Subject-specific material properties were obtained using an optimisation approach that minimised the difference between measured and modelled longitudinal free tendon strain. Generic geometry was represented by the average mesh and generic material properties were taken from the literature. Local stresses were subsequently computed for combinations of subject-specific and generic geometry and material properties. For a given geometry, changing from generic to subject-specific material properties had little effect on the stress distribution in the tendon. In contrast, changing from generic to subject-specific geometry had a 26-fold greater effect on tendon stress distribution. Overall, these findings indicate that the stress distribution experienced by the living free Achilles tendon of a young and healthy population during voluntary loading are more sensitive to variation in tendon geometry than variation in tendon material properties.     

A modelling approach demonstrating micromechanical changes in the tibial cemented interface due to in vivo service

Post-operative changes in trabecular bone morphology at the cement-bone interface can vary depending on time in service. This study aims to investigate how micromotion and bone strains change at the tibial bone-cement interface before and after cementation. This work discusses whether the morphology of the post-mortem interface can be explained by studying changes in these mechanical quantities. Three post-mortem cement-bone interface specimens showing varying levels of bone resorption (minimal, extensive and intermediate) were selected for this study Using image segmentation techniques, masks of the post-mortem bone were dilated to fill up the mould spaces in the cement to obtain the immediately post-operative situation. Finite element (FE) models of the post-mortem and post-operative situation were created from these segmentation masks. Subsequent removal of the cement layer resulted in the pre-operative situation. FE micromotion and bone strains were analyzed for the interdigitated trabecular bone. For all specimens micromotion increased from the post-operative to the post-mortem models (distally, in specimen 1: 0.1 to 0.5 µm; specimen 2: 0.2 to 0.8 µm; specimen 3: 0.27 to 1.62 µm). Similarly bone strains were shown to increase from post-operative to post-mortem (distally, in specimen 1: −185 to −389 µε; specimen 2: −170 to −824 µε; specimen 3: −216 to −1024 µε). Post-mortem interdigitated bone was found to be strain shielded in comparison with supporting bone indicating that failure of bone would occur distal to the interface. These results indicate that stress shielding of interdigitated trabeculae is a plausible explanation for resorption patterns observed in post-mortem specimens.     

Growth-dependent effects of dietary protein concentration and quality on the biomechanical properties of the diaphyseal rat femur

ObjectivesThis study compares the effects of feeding growing rats with increasing concentrations of casein (C) and wheat gluten (G), proteins that show different biological qualities, on the morphometrical and biomechanical properties of the femoral diaphysis.Materials and methodsFemale rats were fed with one of ten diets containing different concentrations (5–30%) of C and G between the 30th and 90th days of life (Control = C-20%). Biomechanical structural properties of the right femur middiaphysis were estimated using a 3-point bending mechanical test with calculation of some indicators of bone material properties.ResultsBody weight and length were affected by treatments, values being highest in rats fed the C-20% diet. G diets affected negatively both parameters. Changes in cross-sectional geometry (mid-diaphyseal cross-sectional and cortical areas, femoral volume, and rectangular moment of inertia) were positively related to the C content of the diet, while they were severely and negatively affected by G diets. Similar behaviors were observed in the bone structural properties (fracture load, yielding load, diaphyseal stiffness and elastic energy absorption). When values of strength and stiffness were normalized for body weight, the differences disappeared. The bone material quality indicators (elastic modulus, yielding stress, elastic energy absorption/volume) did not differ significantly among all studied groups. Femoral calcium concentration in ashes was not significantly different among groups.ConclusionThe clear differences in strength and stiffness of bone beams induced by dietary protein concentration and quality seemed to be the result of an induced subnormal gain in bone structural properties as a consequence of a correlative subnormal gain in bone growth and mass, yet not in bone material properties.     

Bone development: The effect of short-term alpha-ketoglutarate administration on long-term mechanical properties of ribs in ram lambs

The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram lambs were randomly assigned to two weight-matched groups at birth. During the first 14 days of life AKG was administered orally to the experimental group (n = 12) at the dosage of 0.1 g/kg body weight per day, while the control group (n = 11) received an equal dose of the vehicle. Lambs were slaughtered at 146 days of life and five left and right ribs (fourth to eighth) were removed for analysis. The influence of AKG on skeletal system development was evaluated in relation to both geometrical and mechanical properties, as well as quantitative computed tomography (QCT). No significant differences between the groups were recorded in terms of: (1) growth rate, (2) body weight at days 14, 28 and 130 of age or (3) final body weight. The weight and length of ribs were, however, significantly increased in the lambs given AKG for the first 14 days of neonatal life by 8.2% and 3.2%, respectively (P < 0.01). Furthermore, AKG administration induced significantly higher bone mineral density of the cortical bone by 7.1% (P < 0.01) and improved the mechanical endurance of ribs in terms of the moments of maximum elastic strength and ultimate strength by 10% and 8%, respectively (P < 0.05). It could be concluded that AKG has a long-term effect on skeletal development when given early in neonatal life, and that changes in rib properties serve to improve chest mechanics and functioning in young animals. Moreover, neonatal administration of AKG may be considered as an effective factor enhancing proper development and function of the skeleton during growth and later life.     

Declining tibial curvature parallels ∼6150 years of decreasing mobility in central european agriculturalists

Long bones respond to mechanical loading through functional adaptation in a suite of morphological characteristics that together ensure structural competence to in vivo loading. As such, adult bone structure is often used to make inferences about past behavior from archaeological remains. However, such biomechanical approaches often investigate change in just one aspect of morphology, typically cross‐sectional morphology or trabecular structure. The relationship between longitudinal bone curvature and mobility patterns is less well understood, particularly in the tibia, and it is unknown how tibial curvature and diaphyseal cross‐sectional geometry interact to meet the structural requirements of loading. This study examines tibial curvature and its relationship with diaphyseal cross‐sectional geometry (CSG) and body size in preindustrial Central Europeans spanning ～6150 years following the introduction of agriculture in the region. Anteroposterior centroid displacement from the proximo‐distal longitudinal axis was quantified at nine diaphyseal section locations (collectively representative of diaphyseal curvature) in 216 tibial three‐dimensional laser scans. Results documented significant and corresponding temporal declines in midshaft centroid displacement and CSG properties. Significant correlations were found between mid‐diaphyseal centroid displacement and all mobility‐related CSG properties, while the relationship weakened toward the diaphyseal ends. No significant relationship was found between centroid displacement and body size variables with the exception of the most distal section location. Results support a relationship between tibial curvature and cross‐sectional geometry among prehistoric Central European agricultural populations, and suggest that changes in mechanical loading may have influenced a suite of morphological features related to bone adaptation in the lower limb. Am J Phys Anthropol 157:260–275, 2015. © 2015 Wiley Periodicals, Inc.     

The effects of isometric and isotonic training on hamstring stiffness and anterior cruciate ligament loading mechanisms

Greater hamstring musculotendinous stiffness is associated with lesser ACL loading mechanisms. Stiffness is enhanced via training, but previous investigations evaluated tendon rather than musculotendinous stiffness, and none involved the hamstrings. We evaluated the effects of isometric and isotonic training on hamstring stiffness and ACL loading mechanisms. Thirty-six healthy volunteers were randomly assigned to isometric, isotonic, and control groups. Isometric and isotonic groups completed 6 weeks of training designed to enhance hamstring stiffness. Stiffness, anterior tibial translation, and landing biomechanics were measured prior to and following the interventions. Hamstring stiffness increased significantly with isometric training (15.7%; p = 0.006), but not in the isotonic (13.5%; p = 0.089) or control (0.4%; p = 0.942) groups. ACL loading mechanisms changed in manners consistent with lesser loading, but these changes were not statistically significant. These findings suggest that isometric training may be an important addition to ACL injury prevention programs. The lack of significant changes in ACL loading mechanisms and effects of isotonic training were likely due to the small sample sizes per group and limited intervention duration. Future research using larger sample sizes and longer interventions is necessary to determine the effects of enhancing hamstring stiffness on ACL loading and injury risk.     

A subject-specific anisotropic visco-hyperelastic finite element model of female pelvic floor stress and strain during the second stage of labor

ObjectivesTo develop an improved model representation of the biomechanics of the levator muscles during the second stage of labor and to use a sensitivity analysis to explore the pathomechanics of levator muscle injury.MethodsA subject-specific finite element model of human pelvic floor and fetal head was developed based on in vivo MRI data of a fetal head and maternal pelvis. An anisotropic visco-hyperelastic constitutive model employed material parameters estimated from biaxial tests on pelvic floor tissues. Boundary conditions reflected both anatomic constraints and the curve of Carus. A short second stage of labor, scaled to 10 min, was then simulated using a single expulsive push made in the absence of levator co-contraction.ResultsLarge levator stresses occurred near the levator hiatus reaching 9 MPa at the pubovisceral muscle enthesis. The dominant principal stresses were located at, and aligned with, the edge of the hiatus. Muscle stretch bordering the levator hiatus was inhomogeneous: the average levator stretch was 3.55 with a high of 4.64 at the pubovisceral muscle enthesis. Decreasing perineal body stiffness by 40%, 50%, and 60% led to reductions in the maximum principal stretch ratio at the pubovisceral muscle enthesis of 8%, 13%, and 18%, respectively.ConclusionsThe pubovisceral muscle enthesis and the muscle near the perineal body are the regions of greatest strain thereby placing them at highest risk for stretch-related injury. Decreasing perineal body tissue stiffness significantly reduced tissue stress and strain, and therefore injury risk, in those regions.     

Analyse et modélisation statistique linéaire de la structure osseuse crânienne à partir de données morphométriques et anthropométriques pour la prédiction de paramètres mécaniques

The aim of this study is to establish and quantify the relationship between quasi-static stiffness and anthropometric and morphometric parameters of cranial osseous bones. The purpose is to predict the fracture parameters of cranial bone in crashworthiness situation. Within an experimental protocol, 289 specimens are taken from 17 unembalmed human skulls; the subjects are aged between 53 and 82. The specimen are tested under quasi-static three-points bending tests, at 10 mm/min. Morphometric data are got by analysing specimens’ photography. Values are studied by statistical analysis based on linear methods. Data are resumed by Component Principal Analysis. Groups of specimen, in function of the area of extraction of the specimen, are detected. The relationship between the stiffness and the morphometric parameters of the specimen is studied by using multiple linear regression; the input data are the weight, the density and the curvature indices of each specimen. The regression equation for the frontal and parietal areas is confirmed by residuals study; the relative error between predicted values and observed values is 3 ± 25%. There is no linear regression for the specimen taken from the temporal area of the skull.     

Endothelial actin and cell stiffness is modulated by substrate stiffness in 2D and 3D

There is a growing appreciation of the profound effects that passive mechanical properties, especially the stiffness of the local environment, can have on cellular functions. Many experiments are conducted in a 2D geometry (i.e., cells grown on top of substrates of varying stiffness), which is a simplification of the 3D environment often experienced by cells in vivo. To determine how matrix dimensionality might modulate the effect of matrix stiffness on actin and cell stiffness, endothelial cells were cultured on top of and within substrates of various stiffnesses. Endothelial cells were cultured within compliant (1.0–1.5 mg/ml, 124±8 to 202±27 Pa) and stiff (3.0 mg/ml, 502±48 Pa) type-I collagen gels. Cells elongated and formed microvascular-like networks in both sets of gels as seen in previous studies. Cells in stiffer gels exhibited more pronounced stress fibers and ～1.5-fold greater staining for actin. As actin is a major determinant of a cell's mechanical properties, we hypothesized that cells in stiff gels will themselves be stiffer. To test this hypothesis, cells were isolated from the gels and their stiffness was assessed using micropipette aspiration. Cells isolated from relatively compliant gels were 1.9-fold more compliant than cells isolated from relatively stiff gels (p<0.05). Similarly, cells cultured on top of 1700 Pa polyacrylamide gels were 2.0-fold more compliant that those cultured on 9000 Pa (p<0.05). These data demonstrate that extracellular substrate stiffness regulates endothelial stiffness in both three- and two-dimensional environments, though the range of stiffnesses that cells respond to vary significantly in different environments.     

Préconditionnement laser en site osseux membraneux : mise au point d’un modèle d’étude

ObjectiveThe application of a supraphysiologic stress (preconditioning) prior to an injury induces cellular and tissular resistance on soft tissues. The aim of this study is to evaluate X-ray irradiated bone healing with and without laser preconditioning.Materials and methodsThe laser shot is defined to induce a controlled increase of the bone temperature. Then, bone healing is in vivo observed through the evolution of the vascularization process. Optical chambers implanted on the skull of 20 rabbits allow the weekly observation of bone vascular plexus during 12 weeks. An original image processing determines the vascular density (VD) on four groups: #1: control group (n = 5); #2: laser treatment (n = 5); #3: X-ray irradiation (n = 5); #4: laser preconditioning prior to X-ray irradiation (n = 5).ResultsPreconditioning is performed by a diode-laser (815 nm, 36 J/cm²). VD remains stable during the 12-week follow up for groups #1 and #2. X-ray radiation induces a significant decrease of the vascular network in groups #3 and #4 compared to the group #1 (p < 0.001). However, the decrease of the vascularization is limited in group #4 versus group #3 (p < 0.05).DiscussionThis in vivo original model reproducibly evaluates VD and the impact of different stresses on bone healing. Laser treatment is a controlled heating method, which preserves the vascular network of X-ray irradiated bone. This innovative approach promotes the bone healing in which the vascular supply has been damaged.     

The effect of zinc and phytoestrogen supplementation on the changes in mineral content of the femur of rats with chemically induced mammary carcinogenesis

The aim of this study was to assess skeletal effects of zinc or zinc with phytoestrogen (resveratrol or genistein) supplementation in an animal model of rats with DMBA-induced mammary carcinogenesis. The changes in bone parameters such as the length and mass were examined, as well as the changes in concentrations of selected minerals: calcium, magnesium, zinc, iron and phosphorus. Moreover, the investigations focused on finding the differences between the levels of iron and zinc in other tissues: the liver, spleen and serum of the examined rats.Fifty-six female Sprague–Dawley rats, 40 days old, were divided into four groups, regardless of the diets: standard (77 mg Zn kg/food), zinc (4.6 mg/mL via gavage), zinc (4.6 mg/mL) plus resveratrol (0.2 mg/kg bw), and zinc (4.6 mg/mL) plus genistein (0.2 mg/kg bw) for a period from 40 days until 20 weeks of age. The study rats were also treated with 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) to induce mammary carcinogenesis.The applied diet and the advanced mammary cancer did not affect macrometric parameters of the rats’ bones, but they strongly affected their mineral content. It was found that mammary cancer, irrespectively of the applied diet, significantly modified the iron level in the femur, liver, spleen and serum of the examined rats. In addition, zinc supplementation significantly lowered the levels of calcium, magnesium and phosphorus in the femur of rats with mammary cancer as compared with respective levels in the control group. So, it was found that additional supplementation with zinc, which is generally considered to be an antioxidant, with the co-existing mammary carcinoma, increased the unfavorable changes as concerns the stability of bone tissue. The appropriate combination of zinc and phytoestrogens (resveratrol or genistein) could help prevent or slow bone loss associated with a range of skeletal disorders in breast cancer.     

An in vivo microdialysis characterization of the transient changes in the interstitial dialysate concentration of metabolites and cytokines in human skeletal muscle in response to insertion of a microdialysis probe

Skeletal muscle has recently been described as an endocrine organ, capable of releasing cytokines and regulators of metabolism. Microdialysis of the interstitial space of skeletal muscle enables analysis of the release of such cytokines. The purpose of this study was to determine the transient changes in concentration of metabolites and cytokines in human skeletal muscle in a 7 h period following the insertion of a microdialysis probe. In total, sixteen microdialysis catheters were inserted into the vastus lateralis of male participants (age 26.2 ± 1.35 y, height 180.8 ± 3.89 cm, mass 83.9 ± 3.86 kg, BMI 25.7 ± 0.87 kg m⁻², body fat 26.1 ± 3.0%). Serial samples were analyzed by micro-enzymatic and multiplexed immunoassay. Muscle interstitial glucose and lactate levels remained stable throughout, amino acid concentrations stabilized after 2.5 h, however, insertion of a microdialysis catheter induced a 29-fold increase in peak IL-6 (p < 0.001) and 35-fold increase in peak IL-8 concentrations (p < 0.001) above basal levels 6 h post insertion. In contrast to stable amino acid, glucose and lactate concentrations after 2 h, commonly reported markers of tissue homeostasis in in vivo microdialysis, the multi-fold increase in IL-6 and IL-8 following insertion of a microdialysis catheter is indicative of a sustained disturbance of tissue homeostasis.     

Bone response of broiler chickens (Gallus gallus domesticus) induced by corticosterone

Experiments were conducted with chickens exposed to corticosterone (CORT), with the aim of determining its effects on bone characteristics. At 7 d of age, the experimental birds were injected daily with CORT (4 mg/kg of body mass) for 1 week. CORT administration significantly decreased the body weight while increasing relative liver weight of the chickens and the bone parameters were also decreased. Histology and immunohistochemistry of type X collagen revealed that CORT reduced the lengths of proliferative and prehypertrophic zone in growth plate and the number of positive chondrocytes in the prehypertrophic zone. In conclusion exposure to CORT depressed the growth performance and retarded the longitudinal growth of the long bones by inhibiting the proliferation and differentiation of chondrocytes in growth plate in broilers.