Influence of aspect ratios on the creep behaviour of articular cartilage in indentation

Indentation tests are commonly used to determine the mechanical behaviour of articular cartilage with varying properties, thickness, and geometry. This investigation evaluated the effect of changing geometric parameters on the properties determined from creep indentation tests. Finite element analyses simulated the indentation behaviour of two models, an excised cylindrical specimen of cartilage with either normal and repair qualities and an osteochondral defect represented as a cylindrical region of repair cartilage integrated with a surrounding layer of normal tissue. For each model, the ratios of indenter radius to cartilage height (a/h=0.5,1.5) and cartilage radius to indenter radius (r/a=2,5) were varied. The vertical displacement of the cartilage under the indenter obtained through finite element analysis was fitted to a numerical algorithm to determine the aggregate modulus, permeability, and Poisson's ratio. Indentation behaviours of cartilage specimens for either model with a/h=1.5 were not affected by r/a for values of 2 and 5. Aggregate modulus was not greatly affected by the geometric changes studied. Permeability was affected by changes in the ratio of specimen to indenter radii for a/h=0.5. These findings suggest that experimental configurations of excised cylindrical specimens, also representing osteochondral defects with no or unknown degree of integration, where the cartilage layer has a/h=0.5 should not have r/a values on the order of 2 for confidence in the mechanical properties determined. Indentation of osteochondral defects where the repair cartilage is fully integrated to the surrounding cartilage can be performed with confidence for all cases tested.     

Metatarsophalangeal fusion for hallux valgus: indications and effect on the first metatarsal ray.

Arthrodesis of metatarsophalangeal joint was performed in 31 cases of severe hallux valgus. With the surgical technique used, which is described in detail, internal fixation and plaster cast immobilization were not necessary. Analysis of the results suggested that the operation is indicated for severe deformities in elderly patients, preferably women. The basic metatarsal deformity was corrected by the procedure.     

Effect of varus/valgus malalignment on bone strains in the proximal tibia after TKR: an explicit finite element study

Malalignment is the main cause of tibial component loosening. Implants that migrate rapidly in the first two post-operative years are likely to present aseptic loosening. It has been suggested that cancellous bone stresses can be correlated with tibial component migration. A recent study has shown that patient-specific finite element (FE) models have the power to predict the short-term behavior of tibial trays. The stresses generated within the implanted tibia are dependent on the kinematics of the joint; however, previous studies have ignored the kinematics and only applied static loads. Using explicit FE, it is possible to simultaneously predict the kinematics and stresses during a gait cycle. The aim of this study was to examine the cancellous bone strains during the stance phase of the gait cycle, for varying degrees of varus/valgus eccentric loading using explicit FE. A patient-specific model of a proximal tibia was created from CT scan images, including heterogeneous bone properties. The proximal tibia was implanted with a commercial total knee replacement (TKR) model. The stance phase of gait was simulated and the applied loads and boundary conditions were based on those used for the Stanmore knee simulator. Eccentric loading was simulated. As well as examining the tibial bone strains (minimum and maximum principal strain), the kinematics of the bone-implant construct are also reported. The maximum anterior-posterior displacements and internal-external rotations were produced by the model with 20 mm offset. The peak minimum and maximum principal strain values increased as the load was shifted laterally, reaching a maximum magnitude for -20 mm offset. This suggests that when in varus, the load transferred to the bone is shifted medially, and as the bone supporting this load is stiffer, the resulting peak bone strains are lower than when the load is shifted laterally (valgus). For this particular patient, the TKR design analyzed produced the highest cancellous bone strains when in valgus. This study has provided an insight in the variations produced in bone strain distribution when the axial load is applied eccentrically. To the authors' knowledge, this is the first time that the bone strain distribution of a proximal implanted tibia has been examined, also accounting for the kinematics of the tibio-femoral joint as part of the simulation. This approach gives greater insight into the overall performance of TKR.     

Molecular set theory: II. An aspect of the biomathematical theory of sets

In an earlier paper (Molecular Set Theory: I.Bull. Math. Biophysics,22, 285–307, 1960) the author proposed a “Molecular Set Theory” as a formal mathematical meta-theoretic system for representing complex reactions not only of biological interest, but also of general chemical interest. The present paper is a refinement and extension of the earlier work along more formal algebraic lines. For example the beginnings of an algebra of molecular transformations is presented. It also emphasizes that this development, together with the genetical set theory of Woodger's and Rashevsky's set-theoretic contributions to Relational Biology, points to the existence of a biomathematical theory of sets which is not deducible from the general mathematical, abstract theory of sets.     

Mesenchymal stem cells in the treatment of articular cartilage degeneration: New biological insights for an old-timer cell

Osteoarthritis (OA) is a debilitating, degenerative joint disease characterized by progressive destruction of articular cartilage. Given the poor repair capacity of articular cartilage and the associated local destructive immune/inflammatory responses involving all joint structures, OA frequently ends up as a “whole joint failure” requiring prosthetic replacement. Current pharmacological efforts, belatedly started, mainly aim at symptomatic pain relief, underscoring the need for novel therapeutic schemes designed to modify the course of the disease. Mesenchymal stem cell (MSC)–based therapy has gained significant interest, sparking the design of multiple trials proving safety while providing promising preliminary efficacy results. MSCs possess ‘medicinal signaling cell’ properties related to their immunomodulatory and anti-inflammatory effects, which induce the establishment of a pro-regenerative microenvironment at the injured tissue. Those trophic effects are paralleled by the long-established chondroprogenitor capacity that can be harnessed to ex vivo fabricate engineered constructs to repair damaged articular cartilage. The present review focuses on these two aspects of the use of MSCs for articular cartilage damage, namely, cell therapy and tissue engineering, providing information on their use criteria, advancements, challenges and strategies to overcome them.     

Influence of slope aspect on Mediterranean woody formations: Comparison of a semiarid and an arid site in Israel

This study investigates the effects of slope aspect on plant community characteristics such as plant cover, species composition and above-ground biomass production in Mediterranean trees and shrubs in two climatological regions. Two experimental sites were selected in a climatic gradient that runs from the foothills of the Judean Hills to the northern Negev desert in Israel. In each site, 16 quadrats of 10 m × 10 m (eight south-facing and eight north-facing slopes) were established and the vegetation was recorded. Dominant tree and shrub species were measured using allometric parameters of area and volume, and representative branches were cut and weighed. Species studied were Quercus calliprinos, Phillyrea latifolia, Pistacia lentiscus, Cistus creticus, Coridothymus capitatus, and Sarcopoterium spinosum. The results showed that slope aspect had significant effects on the composition, structure and density of the plant communities developing in both sites. Vegetation structure within a site changed significantly in the short distance separating the north and south-facing slopes, and that pattern remained generally constant when comparing the two sites along the rainfall gradient. The data collected here provides new insight into the slope aspect effects on biomass allocation of different woody life forms of eastern Mediterranean plant communities.     

Hyperplasia of the intestinal smooth muscle tissue proximal to a partial surgical stenosis: an autoradiographic study]

Hypertrophy of the smooth muscle wall of the rat small intestine occurs in the loops upstream from a partial surgical stenosis. This phenomenon is due both to cell hypertrophy and cell proliferation (hyperplasia). The thickness of the muscular layers reached its maximum after ten days from the intervention and then was maintained over the following days. Hyperplasia of the smooth muscle tissue has been demonstrated by means of autoradiography after administration of tritiated-thymidine. This investigation revealed the presence of 37%-44.5% of heavily labeled smooth muscle nuclei, index of active DNA neo-synthesis. On the contrary, no labeled nuclei were observed in the downstream tract as well as in the small intestine of the controls. These results, together with those obtained by other researchers, confirms that the smooth muscle tissue can undergo cell proliferation under particular conditions and that this phenomenon is often associated with the hypertrophic process.     

Structural characterization of the nonameric assembly of an Archaeal alpha-L-fucosidase by synchrotron small angle X-ray scattering

alpha-l-Fucosidase is a lysosomal enzyme responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of carbohydrate moieties in glycoproteins. The first alpha-l-fucosidase from Archaea was recently identified in the genome of the hyperthermophile Sulfolobus solfataricus; the enzyme is encoded by two open reading frames separated by a -1 frameshift. A preliminary biochemical and biophysical characterization of this extremophile enzyme has been carried out both in solution, through small angle X-ray scattering experiments, and in the crystalline state, showing an unusual oligomeric assembly resulting from the association of nine subunits, endowed with 3-fold molecular symmetry.     

The effect of organic cryosolvents on actin structure: studies by small angle X-ray scattering

Small-angle X-ray scattering was used to probe the structure of actin in the presence of cryosolvents: 1,2-propanediol, glycerol, or a mixture of both solvents. In media devoid of polymerizing salts, a radius of gyration of 23 Å is measured, as expected from the literature. In the presence of 1,2-propanediol alone, the scattering pattern begins to exhibit the characteristic slope of elongated objects with a non-negligible thickness, such as actin filaments polymerized in 40 mM KCl and 1 mM MgCl₂. However, only short fragments (radius of gyration 40 Å) are generated. We infer that in a medium of low ionic strength containing 15% 1,2-propanediol, actin assumes a structure closer to that of filamentous actin. 1,2-propanediol apparently induces nucleation of oligomers, as with polymerizing salts, but no propagation occurs. Glycerol and/or propanediol induce no alteration in the structure of individual salt-polymerized actin filaments. Aggregation occurs with propanediol, even in the presence of glycerol. Glycerol alone has no such effect. No shortening is detected within the scale covered, with either solvent, although 1,2-propanediol is known to shorten actin filaments. We suggest that in the absence of salts, 1,2-propanediol induces a conformational change in monomeric actin that is necessary for nucleation. This could correlate with a conformational change of actin protomers within microfilaments observed in the presence of 1,2-propanediol by other authors using different techniques.Abbreviations SAXS small-angle X-ray scattering - G-actin globular monomeric actin - F-actin filamentous polymerized actinCorrespondence to: E. Pajot-Augy     

Ambulatory monitoring of the electrocardiogram: an important aspect of pacemaker surveillance

Of the 353 patients followed in the pacemaker surveillance clinic between July 1976 and July 1977, 25 patients complained of episodes of dizziness and faintness. 20 of these had normal pacing function and pacemaker parameters at routine clinic testing. 18 patients had 'demand' units and 2 had fixed-rate pacemakers. The indication for permanent pacing was complete heart block in 16 patients and sinoatrial disease in 5 patients. At clinic follow-up, there was unequivocal evidence of vertebrobasilar insufficiency in 5 patients and postural hypotension in 4 patients. In 11 patients, the cause of presyncope was not evident at the clinic. All patients were monitored by 24-hour tape recording until an episode of pre-syncope occurred. In 8 patients, there was evidence of intermittent failure to pace associated with the episodes of presyncope. In 2 patients, an additional cause for presyncope was found at clinic examination. Ambulatory 24-hour tape monitoring of the electrocardiogram is an important adjunct to pacemaker follow-up especially when other methods such as transtelephone monitoring are not available in the United Kingdom. Routine electronic testing of pacemaker function does not always reveal intermittent abnormalities related to changes in threshold or unstable electrode positions.     

Macromolecular crowding: an important but neglected aspect of the intracellular environment

Biological macromolecules have evolved over billions of years to function inside cells, so it is not surprising that researchers studying the properties of such molecules, either in extracts or in purified form, take care to control factors that reflect the intracellular environment, such as pH, ionic strength and composition, redox potential and the concentrations of relevant metabolites and effector molecules. There is one universal aspect of the cellular interior, however, that is largely neglected--the fact that it is highly crowded with macromolecules. It is proposed that the addition of crowding agents should become as routine as controlling pH and ionic strength if we are to meet the objective of studying biological molecules under more physiologically relevant conditions.     

Influence of patellofemoral articular geometry and material on mechanics of the unresurfaced patella

Patellar resurfacing during knee replacement is still under debate, with several studies reporting higher incidence of anterior knee pain in unresurfaced patellae. Congruency between patella and femur impacts the mechanics of the patellar cartilage and strain in the underlying bone, with higher stresses and strains potentially contributing to cartilage wear and anterior knee pain. The material properties of the articulating surfaces will also affect load transfer between femur and patella. The purpose of this study was to evaluate the mechanics of the unresurfaced patella and compare with natural and resurfaced conditions in a series of finite element models of the patellofemoral joint. In the unresurfaced analyses, three commercially available implants were compared, in addition to an 'ideal' femoral component which replicated the geometry, but not the material properties, of the natural femur. Hence, the contribution of femoral component material properties could be assessed independently from geometry changes. The ideal component tracked the kinematics and patellar bone strain of the natural knee, but had consistently inferior contact mechanics. In later flexion, compressive patellar bone strain in unresurfaced conditions was substantially higher than in resurfaced conditions. Understanding how femoral component geometry and material properties in unresurfaced knee replacement alters cartilage contact mechanics and bone strain may aid in explaining why the incidence of anterior knee pain is higher in the unresurfaced population, and ultimately contribute to identifying criteria to pre-operatively predict which patients are suited to an unresurfaced procedure and reducing the incidence of anterior knee pain in the unresurfaced patient population.     

Strategy for the development of a matched set of transport-competent, angiotensin receptor-deficient proximal tubule cell lines

In the proximal convoluted tubule (PCT) angiotensin II (Ang II) modulates fluid and electrolyte transport through at least two pharmacologically distinct receptor subtypes: AT(1) and AT(2). Development of cell lines that lack these receptors are potentially useful models to probe the complex cellular details of Ang II regulation. To this end, angiotensin receptor- deficient mice were bred with an Immortomouse(R), which harbors a thermolabile SV40 large-T antigen (Tag). S1 PCT segments from kidneys of F(2) mice were microdissected, placed in culture, and maintained under conditions that enhanced cell growth, i.e., promoted Tag expression and thermostability. Three different types of angiotensin receptor-deficient cell lines, (AT(1A) [-/-], Tag [+/-]), (AT(1B) [-/-], Tag [+/-]), and (AT(1A) [-/-], AT(1B) [-/-], Tag [+/+]), as well as wild type cell lines were generated. Screening and characterization, which were conducted under culture conditions that promoted cellular differentiation, included: measurements of transepithelial transport, such as basal monolayer short-circuit current (Isc; -3 to 3 microA/cm2), basal monolayer conductance (G, 2 to 10 mS/cm2), Na3(+)-phosphate cotransport (DeltaIsc of 2 to 3 microA/cm(2) at 1 mM), and Na(3)(+)-succinate cotransport (DeltaIsc of 1 to 9 microA/cm(2) at 2 mM). Morphology of cell monolayers showed an extensive brush border, well-defined tight junctions, and primary cilia. Receptor functionality was assessed by Ang II-stimulated beta-arrestin 2 translocation and showed an Ang II-mediated response in wild type but not (AT(1A) [-/ -], AT(1B) [-/-]) cells. Cell lines were amplified, yielding a virtually unlimited supply of highly differentiated, transport-competent, angiotensin receptor-deficient PCT cell lines.