Is the sheep a suitable model to study the mechanical alterations of disc degeneration in humans? A probabilistic finite element model study

Intervertebral disc degeneration is one major source of low back pain, which because of its complex multifactorial nature renders the treatment challenging and thus necessitates extensive research. Experimental animal models have proven valuable in improving our understanding of degenerative processes and potentially promising therapies. Currently, the sheep is the most frequently used large animal in vivo model in intervertebral disc research. However, despite its undoubted value for investigations of the complex biological and cellular aspects, to date, it is unclear whether the sheep is also suited to study the mechanical aspects of disc degeneration in humans.A parametric finite element (FE) model of the L4–5 spinal motion segment was developed. Using this model, the geometry and the material properties of both the human and the ovine spinal segment as well as different appearances of disc degeneration can be depicted. Under pure and combined loads, it was investigated whether degenerative changes to both the human and the ovine model equivalent caused the same mechanical response.Different patterns of degeneration resulted in large variations in the ranges of motion, intradiscal pressure, ligament and facet loads. In the human, but not in the ovine model, all these results differed significantly between different degrees of degeneration.This FE model study highlighted possible differences in the mechanical response to disc degeneration between human and ovine intervertebral discs and indicates the necessity of further, more detailed, investigations.     

Response analysis of the lumbar spine during regular daily activities—A finite element analysis

A non-linear poroelastic finite element model of the lumbar spine was developed to investigate spinal response during daily dynamic physiological activities. Swelling was simulated by imposing a boundary pore pressure of 0.25 MPa at all external surfaces. Partial saturation of the disc was introduced to circumvent the negative pressures otherwise computed upon unloading. The loading conditions represented a pre-conditioning full day followed by another day of loading: 8 h rest under a constant compressive load of 350 N, followed by 16 h loading phase under constant or cyclic compressive load varying in between 1000 and 1600 N. In addition, the effect of one or two short resting periods in the latter loading phase was studied.The model yielded fairly good agreement with in-vivo and in-vitro measurements. Taking the partial saturation of the disc into account, no negative pore pressures were generated during unloading and recovery phase. Recovery phase was faster than the loading period with equilibrium reached in only ～3 h. With time and during the day, the axial displacement, fluid loss, axial stress and disc radial strain increased whereas the pore pressure and disc collagen fiber strains decreased. The fluid pressurization and collagen fiber stiffening were noticeable early in the morning, which gave way to greater compression stresses and radial strains in the annulus bulk as time went by. The rest periods dampened foregoing differences between the early morning and late in the afternoon periods. The forgoing diurnal variations have profound effects on lumbar spine biomechanics and risk of injury.     

How does the geometry affect the internal biomechanics of a lumbar spine bi-segment finite element model? Consequences on the validation process

Numerical modelling can provide a thorough understanding of the mechanical influence on the spinal tissues and may offer explanations to mechanically linked pathologies. Such objective might be achieved only if the models are carefully validated. Sensitivity study must be performed in order to evaluate the influence of the approximations inherent to modelling. In this study, a new geometrically accurate L3-L5 lumbar spine bi-segmental finite-element model was acquired by modifying a previously existing model. The effect of changes in bone geometry, ligament fibres distribution, nucleus position and disc height was investigated in flexion and extension by comparison of the results obtained from the model before and after the geometrical update. Additional calculations were performed in axial rotation and lateral bending in order to compare the computed ranges of motion (ROM) with experimental results. It was found that the geometrical parameters affected the stress distribution and strain energy in the zygapophysial joints, the ligaments, and the intervertebral disc, changing qualitatively and quantitatively their relative role in resisting the imposed loads. The predicted ROM were generally in good agreement with the experimental results, independently of the geometrical changes. Hence, although the model update affected its internal biomechanics, no conclusions could be drawn from the experimental data about the validation of a particular geometry. Hence the validation of the lumbar spine model should be based on the relative role of its structural components and not only on its global mobility.     

What have we learned from finite element model studies of lumbar intervertebral discs in the past four decades?

Finite element analysis is a powerful tool routinely used to study complex biological systems. For the last four decades, the lumbar intervertebral disc has been the focus of many such investigations. To understand the disc functional biomechanics, a precise knowledge of the disc mechanical, structural and biochemical environments at the microscopic and macroscopic levels is essential. In response to this need, finite element model studies have proven themselves as reliable and robust tools when combined with in vitro and in vivo measurements.     

Influence of morphology and material properties on the range of motion of the costovertebral joint – a probabilistic finite element analysis

Abstract

The motion of the costovertebral joint (CVJ) is governed by the material properties and its morphology. The goal of this numerical study was to identify the material and morphology parameters with the greatest influence on the motion of the CVJ. A fully parametric finite element model of the anatomy and material properties of the CVJ was developed. The impact of five morphology and thirteen material parameters was investigated and compared to in vitro data. The motion was influenced in particular by the rotational stiffness of the articulatio capitis costae and the lateral position of the fovea costalis transveralis.     

The effect of saccades on threshold perception — A model study

The effect of saccadic eye movements on threshold perception is investigated theoretically. The proposed model considers eye movements by taking into account the shifting of the stimulus pattern on the retina during the occurrence of an eye movement. Saccades are characterized by high velocity and short duration. These motions cause overshoots in the response of linear filters to certain stimulus patterns. Therefore, the model predicts facilitation effects of saccades in the perception of low spatial frequency patterns and patterns flickering with high temporal frequencies. These results agree with experimentally obtained data presented in a subsequent paper. A simple approach is formulated which approximates the complex shifting function of a saccade by a switching of the pattern.     

Investigation of different cage designs and mechano-regulation algorithms in the lumbar interbody fusion process – A finite element analysis

Lumbar interbody fusion cages are commonly used to treat painful spinal degeneration and instability by achieving bony fusion. Many different cage designs exist, however the effect of cage morphology and material properties on the fusion process remains largely unknown. This finite element model study aims to investigate the influence of different cage designs on bone fusion using two mechano-regulation algorithms of tissue formation. It could be observed that different cages play a distinct key role in the mechanical conditions within the fusion region and therefore regulate the time course of the fusion process.     

A poroelastic finite element model of the bone–cartilage unit to determine the effects of changes in permeability with osteoarthritis

The changes experienced in synovial joints with osteoarthritis involve coupled chemical, biological, and mechanical processes. The aim of this study was to investigate the consequences of increasing permeability in articular cartilage (AC), calcified cartilage (CC), subchondral cortical bone (SCB), and subchondral trabecular bone (STB) as observed with osteoarthritis. Two poroelastic finite element models were developed using a depth-dependent anisotropic model of AC with strain-dependent permeability and poroelastic models of calcified tissues (CC, SCB, and STB). The first model simulated a bone-cartilage unit (BCU) in uniaxial unconfined compression, while the second model simulated spherical indentation of the AC surface. Results indicate that the permeability of AC is the primary determinant of the BCU’s poromechanical response while the permeability of calcified tissues exerts no appreciable effect on the force-indentation response of the BCU. In spherical indentation simulations with osteoarthritic permeability properties, fluid velocities were larger in magnitude and distributed over a smaller area compared to normal tissues. In vivo, this phenomenon would likely lead to chondrocyte death, tissue remodeling, alterations in joint lubrication, and the progression of osteoarthritis. For osteoarthritic and normal tissue permeability values, fluid flow was predicted to occur across the osteochondral interface. These results help elucidate the consequences of increases in the permeability of the BCU that occur with osteoarthritis. Furthermore, this study may guide future treatments to counteract osteoarthritis.     

Search for critical loading condition of the spine–A meta analysis of a nonlinear viscoelastic finite element model

The relative vulnerability of spinal motion segments to different loading combinations remains unknown. The meta-analysis described here using the results of a validated L2–L3 nonlinear viscoelastic finite element model was designed to investigate the critical loading and its effect on the internal mechanics of the human lumbar spine. A Box-Behnken experimental design was used to design the magnitude of seven independent variables associated with loads, rotations and velocity of motion. Subsequently, an optimization method was used to find the primary and secondary variables that influence spine mechanical output related to facet forces, disc pressure, ligament forces, annulus matrix compressive/shear stresses and anulus fibers strain. The mechanical responses with respect to the two most-relevant variables were then regressed linearly using the response surface quadratic model. Axial force and sagittal rotation were identified as the most-relevant variables for mechanical responses. The procedure developed can be used to find the critical loading for finite element models with multi input variables. The derived meta-models can be used to predict the risk associated with various loading parameters and in setting safer load limits.     

Configuration of anchorage holes affects fixation of the acetabular component in cemented total hip replacement—a finite element study

Our survey of current practice among UK orthopaedic surgeons shows wide variations in fixation techniques. The aim of this study, is to investigate the effect of drilling different configurations of anchorage holes in the acetabulum on implant stability. To avoid variables that could incur during in vitro testing, we used commercially available COSMOS finite element analysis package to investigate the stress distributions, deformations, and strains on the cement mantle when drilling three large anchorage holes and six smaller ones, with straight and rounded cement pegs. The results, which are in line with our in vitro studies on simulated reconstructed acetabulae, indicate better stability of the acetabular component when three larger holes than six smaller holes are drilled and when the necks of the anchorage holes are rounded. The longevity of total hip replacements could be improved by drilling three large anchorage holes, rather than many smaller ones, as initially proposed by Charnley.     

Influence of lunar phases on suicide: the end of a myth? A population-based study

The hypothesis of lunar influence on suicide remains widespread, despite the fact that little scientific evidence to substantiate it. We conducted a population-based study to assess the influence of the lunar phases on suicides according to age, sex, and chosen method. The study included all suicides in Middle Franconia between 1998 and 2003. From a population-based sample of 3351 events, the files of 3054 suicides (1949 males and 1105 females) were complete for the study variables. Data were categorized by lunar phase, sex, age, and chosen method—“violent” vs. “non-violent” acts. No significant relationship was detected between the full, absent, and moon's interphases and suicide incidence. Nevertheless, there was a weak association between the absent moon and choice of a non-violent suicide method in men aged less than the median of 40.2 yrs. There was no evidence of a relationship between suicide and lunar phase. Some explanations for this phenomenon are discussed.     

Influence of aluminium on the immune system – an experimental study on volunteers

The purpose of this study was to examine whether oral exposure to aluminum (Al) can affect the human immune system. Eighteen healthy volunteers (mean age 42, 28–57 yr) were divided into a test group (9 females, 4 males) and a referent group (3 females, 2 males). Over 6 weeks, the test subjects ingested 10 ml of antacid (aluminum hydroxide, 59 mg Al/ml) three times daily. Aluminum was analyzed in urine before and during the exposure period (ICP-MS). Blood samples were used for analysis of lymphocyte subpopulations, mitogen-induced lymphocyte proliferation and in vitro production and circulating plasma concentrations of immunoglobulin (Ig) A, IgG, IgM, interleukin (IL) -2 and IL-4. Urinary Al concentration in the test subjects was approximately 10- to 20-fold higher than in the referent group during exposure. This indicates that ingestion of an Al-containing antacid is associated with an Al absorption far above that originating from food and drinking water. In both referents and test subjects the lymphocyte subpopulations, lymphocyte proliferation and the in vitro Ig and IL production showed similar, time-dependent changes before as well as during the exposure period. No major differences were seen between the referent and test groups regarding the immune parameters, except for a slightly smaller CD8+CD45R0+ population (primed cytotoxic T-cells), in the exposed individuals as compared to the referents. The results also show that subjects on antacid therapy may constitute a suitable population for studying biological effects of high-dose oral exposure to Al.     

Influence of β-cyclodextrin on the Properties of Norfloxacin Form A

Cyclodextrins are able to form host–guest complexes with hydrophobic molecules to result in the formation of inclusion complexes. The complex formation between norfloxacin form A and β-cyclodextrin was studied by exploring its structure affinity relationship in an aqueous solution and in the solid state. Kneading, freeze-drying, and physical mixture methods were employed to prepare solid complexes of norfloxacin and β-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with β-cyclodextrin as demonstrated by a solubility isotherm of the A_L type along with the results of an intrinsic dissolution study. The complexes were also characterized in the solid stated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffractometry, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (ssNMR) spectrometry. The thermal analysis showed that the thermal stability of the drug is enhanced in the presence of β-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug.KEY WORDS: bioassay, complexation, intrinsic dissolution, norfloxacin, β-cyclodextrin     

Effect of magnetic micropulsations on the biological systems — A bioenvironmental study

During the last decade considerable interest has been evinced by scientists on the possible influence of earth's electromagnetic environment on human and animal physiology. While some studies on this topic have been reported from high magnetic latitudes — USSR and central Europe — no work has been done in very low latitude and equatorial regions. The present study, undertaken to fill this gap, has been carried out at the low latitude of Madras (Magnetic Dip 10°). Pulsating magnetic fields in the frequency range of 0.01 Hz to 20 Hz and with amplitudes of ±5 and ±50 gamma were impressed on test animals, normal human subjects and Yoga practitioners lying supine inside a 4-member Fanselau-Braunbeck coil system with the heads oriented in the four cardinal directions with respect to earth's magnetic field. The entire set of exposures of the test animals and humans was given under two ambient magnetic fields namely, against full local geomagnetic field of about 40,000 gamma and half this value. In the animals ECG, EEG, Tail Blood Flow and Respiration were recorded continuously on a polygraph. The biochemical tests carried out were postprandial blood sugar, serum cholesterol and plasma cortisol. Neurochemical assays of Noradrenaline, Adrenaline, Dopamine, Serotonin and 5 Hydroxy Indole Acetic acid were done on the brain tissue, myocardium and adrenal glands, immediately after complete set of exposures of the animals in all four orientations. Motor activity and rectal temperature were also noted before and after the exposures. The Control animals were also subjected to exactly the same investigations as the test animals without, however, exposing them to the magnetic fields. These observations revealed some decisive changes in certain parameters for certain frequencies of the impressed field and also in specific orientations of the test animals. Similar studies carried out on normal human subjects and practitioners of Yoga and Meditation, also showed certain decisive changes in the electrophysiology, neurochemistry and biochemistry when oriented to North and East. The North orientation appeared to induce inhibition of brain electrical activity and associated neurochemical and biochemical changes, whereas the East orientation showed a response of calm, blissful alertness.     

A comparative study of the effect of 17β-estradiol and estriol on peripheral pain behavior in rats

Although estradiol has been reported to influence pain sensitivity, the role of estriol (an estradiol metabolite and another widely used female sex hormone) remains unclear. In this study, pain behavior tests, whole-cell patch clamp recording and Western blotting were used to determine whether estriol plays a role in pain signal transduction and transmission. Either systemic or local administration of 17β-estradiol produced a significant rise of mechanical pain threshold, while estriol lacked this effect in normal and ovariectomized (OVX) rats following estriol replacement. Local administration of 17β-estradiol or estriol significantly decreased ATP-induced spontaneous hind-paw withdrawal duration (PWD), which was blocked by an estrogen receptor antagonist, ICI 182, 780. However, systemic application of estriol in normal or OVX rats lacked this similar effect. In cultured dorsal root ganglion neurons, estriol attenuated α,β-methylene ATP-induced transient currents which were blocked by ICI 182, 780. In complete Freund's adjuvant treated (CFA) rats, systemic application of 17β-estradiol or estriol decreased the mechanical pain threshold significantly, but did not change the inflammatory process. Similar effects were observed after estriol replacement in OVX rats. The expression of c-fos in lumbosacral spinal cord dorsal horn (SCDH) was increased significantly by administration of 17β-estradiol but not estriol, and not by estriol replacement in OVX rats. These results suggest that 17β-estradiol but not estriol plays an anti-hyperalgesic role in physiological pain. However, both peripheral 17β-estradiol and estriol play anti-hyperalgesic roles in ATP-induced inflammatory pain. Systemic application of estriol as well as 17β-estradiol plays hyperalgesic roles in CFA-induced chronic pain.     

Sensitivity analysis of the Poisson Nernst–Planck equations: a finite element approximation for the sensitive analysis of an electrodiffusion model

Biological structures exhibiting electric potential fluctuations such as neuron and neural structures with complex geometries are modelled using an electrodiffusion or Poisson Nernst–Planck system of equations. These structures typically depend upon several parameters displaying a large degree of variation or that cannot be precisely inferred experimentally. It is crucial to understand how the mathematical model (and resulting simulations) depend on specific values of these parameters. Here we develop a rigorous approach based on the sensitivity equation for the electrodiffusion model. To illustrate the proposed methodology, we investigate the sensitivity of the electrical response of a node of Ranvier with respect to ionic diffusion coefficients and the membrane dielectric permittivity.

     

Trabecular bone strains around a dental implant and associated micromotions—A micro-CT-based three-dimensional finite element study

The first objective of this computational study was to assess the strain magnitude and distribution within the three-dimensional (3D) trabecular bone structure around an osseointegrated dental implant loaded axially. The second objective was to investigate the relative micromotions between the implant and the surrounding bone. The work hypothesis adopted was that these virtual measurements would be a useful indicator of bone adaptation (resorption, homeostasis, formation).In order to reach these objectives, a μCT-based finite element model of an oral implant implanted into a Berkshire pig mandible was developed along with a robust software methodology. The finite element mesh of the 3D trabecular bone architecture was generated from the segmentation of μCT scans. The implant was meshed independently from its CAD file obtained from the manufacturer. The meshes of the implant and the bone sample were registered together in an integrated software environment. A series of non-linear contact finite element (FE) analyses considering an axial load applied to the top of the implant in combination with three sets of mechanical properties for the trabecular bone tissue was devised. Complex strain distribution patterns are reported and discussed. It was found that considering the Young’s modulus of the trabecular bone tissue to be 5, 10 and 15 GPa resulted in maximum peri-implant bone microstrains of about 3000, 2100 and 1400. These results indicate that, for the three sets of mechanical properties considered, the magnitude of maximum strain lies within an homeostatic range known to be sufficient to maintain/form bone. The corresponding micro-motions of the implant with respect to the bone microstructure were shown to be sufficiently low to prevent fibrous tissue formation and to favour long-term osseointegration.     

Investigation of impact loading rate effects on the ligamentous cervical spinal load-partitioning using finite element model of functional spinal unit C2–C3

The cervical spine functions as a complex mechanism that responds to sudden loading in a unique manner, due to intricate structural features and kinematics. The spinal load-sharing under pure compression and sagittal flexion/extension at two different impact rates were compared using a bio-fidelic finite element (FE) model of the ligamentous cervical functional spinal unit (FSU) C2–C3. This model was developed using a comprehensive and realistic geometry of spinal components and material laws that include strain rate dependency, bone fracture, and ligament failure. The range of motion, contact pressure in facet joints, failure forces in ligaments were compared to experimental findings. The model demonstrated that resistance of spinal components to impact load is dependent on loading rate and direction. For the loads applied, stress increased with loading rate in all spinal components, and was concentrated in the outer intervertebral disc (IVD), regions of ligaments to bone attachment, and in the cancellous bone of the facet joints. The highest stress in ligaments was found in capsular ligament (CL) in all cases. Intradiscal pressure (IDP) in the nucleus was affected by loading rate change. It increased under compression/flexion but decreased under extension. Contact pressure in the facet joints showed less variation under compression, but increased significantly under flexion/extension particularly under extension. Cancellous bone of the facet joints region was the only component fractured and fracture occurred under extension at both rates. The cervical ligaments were the primary load-bearing component followed by the IVD, endplates and cancellous bone; however, the latter was the most vulnerable to extension as it fractured at low energy impact.     

A case–control study on the effects of the apolipoprotein E genotypes in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions being the most common cause of chronic liver disease in Western countries. The Apolipoprotein E (ApoE) gene has three major isoforms encoded by the ε2, ε3, and ε4 alleles, with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. The role of apoE genotypes on NAFLD has been previously investigated with conflicting results. Our hospital-based case-control study conducted in Italy aims to explore the effect of the apoE genotypes on NAFLD risk and their effect on the clinical features of NAFLD patients. 310 NAFLD cases and 422 controls were genotyped for apoE. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) from logistic regression were used to explore the relationship between NAFLD and apoE genotypes, as well as their interaction with selected demographic and lifestyle factors. ApoE ε4 allele carriers showed a statistically significant two-fold reduction of NAFLD risk (OR = 0.51, 95% CI: 0.28-0.93) compared with ε3 homozygotes. A statistically significant lower HDL cholesterol level was observed for ApoE ε4 carriers if compared with ε3/ε3 genotype or ApoE ε2 carriers with a nearly linear decreasing trend from ApoE ε2 to ApoE ε4 carriers. Our study reports for the first time a protective effect of the ε4 allele towards NAFLD that might be attributable to its role in the regulation of hepatic triglycerides rich very low-density lipoproteins secretion.