Managing the variability of biomechanical characteristics before the preliminary design stage of a medical device

The very high level of requirements for certification procedures often limit research and development departments to innovate using increments and iterations during the design process for medical devices (MD). Instead of this semi-empirical approach, a structured procedure, a breakthrough innovation should be used when designing an articular MD (prosthesis, implant). The search for concepts can be based on functional analysis and producing behavioural models of the joint in its natural state and/or equipped with the prosthesis. This paper shows how anatomical variables can be managed and integrated using a modular design approach.This study has been realized under the two joint action projects PESSOA 14630YA and PTDC/EME-PME/112977

Making Sense out of Antisense Transcription in Human T-Cell Lymphotropic Viruses (HTLVs)

Retroviral gene expression generally depends on a full-length transcript that initiates in the 5′ long terminal repeat (LTR), which is either unspliced or alternatively spliced. We and others have demonstrated the existence of an antisense transcript initiating in the 3′ LTR of the Human T-cell Leukemia Virus type 1 (HTLV-1) that is involved in the production of HBZ (HTLV-1 basic leucine zipper (bZIP) factor). HBZ is a Fos-like factor capable of inhibiting Tax-mediated activation of the HTLV-1 LTR by interacting with the cellular transcription factor cAMP-response element-binding protein (CREB) and the pleiotropic cellular coactivators p300/CBP. HBZ can also activate cellular transcription through its interaction with p300/CBP. Interestingly, HBZ has also been found to promote T-lymphocyte proliferation. By down-regulating viral expression and by stimulating T-cell proliferation, HBZ could be essential in the establishment of a chronic infection. Antisense transcription also occurs in the closely related HTLV-2 retrovirus as well as in the recently discovered HTLV-3 and HTLV-4. These antisense transcripts are also involved in the production of retroviral proteins that we have termed Antisense Protein of HTLVs (APH). Like HBZ, the APH proteins are localized in the nucleus of transfected cells and repress Tax-mediated viral transcription

Elaboration et validation d'un protocole de caractérisation de l'articulation temporo-mandibulaire

La conception d'une prothèse articulaire, selon une démarche de conception de produit industriel, impose tout d'abord de modéliser l'articulation. Cette modélisation prend appui sur les résultats expérimentaux élaborés dans une phase de caractérisation de la liaison naturelle. Après une présentation de la place de l'implant dans la reconstruction de l'Articulation Temporo- Mandibulaire humaine (ATM), la méthode d'analyse de la valeur assemble des critères dans une perspective de conception. Cette approche innovante dégage les directions d'investigation et les techniques expérimentales associées en : - cinématique et analyse vidéo tridimensionnelle, - anatomie fonctionnelle et dissection de cadavres, - actions mécaniques et électromyographie. L'adaptation technique de l'analyse vidéo tridimensionnelle à la mesure des déplacements articulaires débouche sur une analyse partielle de la cinématique de l'ATM. La dissection de cadavres frais permet ensuite d'observer et de décrire la géométrie des surfaces de liaison et les insertions des muscles masticateurs. Les directions des actions des faisceaux ainsi relevées et l'exploitation de l'IRM et de l'électromyographie autorisent une évaluation des intensités des actions musculaires développées et un calcul des actions transmises, sous chargement, par les contacts articulaires. Si les résultats expérimentaux élaborés caractérisent déjà l'articulation, une étape suivante doit améliorer le protocole afin de fiabiliser les résultats numériques et de "durcir" ce premier modèle.The design of an articular prosthesis requires starting first with the modelling of the joint, like in industrial product design. The elaboration process of the model takes into account experimental results elaborated when characterizing the natural joint. The value analysis method first presents the place of the implant in the rebuilding process of the human Temporo-Mandibular Joint (TMJ) and then collects criteria from a design point of view. This innovating approach points out the directions for the investigation and the experimental techniques that are associated in : - kinematics and 3D video analysis, - functional anatomy and dissection of corpses, - mechanical actions and electromyography. The technical adaptation of the 3D video analysis to the measurement of articular displacements leads to a partial analysis of TMJ kinematics. The dissection of fresh corpses then makes it possible to observe and describe the geometry of the articular surfaces and of the muscle insertions. The directions of the muscular actions thus obtained, coupled with the exploitation of MRI and electromyography results permit to evaluate muscle action ranges and then to compute the actions transmitted by the articular contacts under loading. If the elaborated experimental results already provide a characterisation of the joint, a further stage must improve the protocol in order to reinforce the reliability of the numerical results and "to harden" this first model

Evaluation clinique, caractérisation mécanique et modélisation pour l'évolution de la conception d'un implant rachidien dynamique

L'objectif principal de tout dispositif médical implantable est d'améliorer l'état de santé du patient en lui assurant un risque minimum. Dans ce but, l'étude de l'implant rachidien B Dyn comporte plusieurs volets : - la réalisation d'un suivi clinique, - l analyse et la proposition de solutions techniques (actions correctives), - la création d'un outil numérique pour des évolutions ultérieures (actions préventives).L étude bibliographique initiale permet d'appréhender l'anatomie fonctionnelle du rachis lombaire, de comprendre les états pathologiques et leurs conséquences et enfin de faire un inventaire des techniques chirurgicales associées (résection osseuse, implantation de dispositifs...).Le suivi clinique d'une population de trente patients souligne ensuite les apports (somatiques et fonctionnels) du B Dyn dans sa conception première. Pour quelques cas, l'analyse des clichés radiographiques en position de flexion montre une détérioration naissante de l'anneau liée, probablement, à une surcharge accidentelle de l'implant. Ce constat impose une évolution de la conception de l'implant.Une analyse de la conception initiale et la caractérisation mécanique en traction, permettent de cibler les actions correctives à appliquer dans le cadre de cette évolution. La démarche mise en place s'appuie sur l'évaluation expérimentale pour sélectionner des solutions techniques satisfaisant aux critères fonctionnels ; elle conduit à une évolution du choix de matériau de l'anneau.Pour la réalisation d'évolutions ultérieures, un modèle éléments finis est créé. L approche numérique se substitue ainsi à l approche expérimentale contraignante et coûteuse. La caractérisation préalable des élastomères est nécessaire à l'obtention de données matériaux pour élaborer ce modèle. Les résultats des premières simulations d'un essai de traction sont comparés aux données expérimentales dans la perspective de la validation du modèle.A ce stade, l'étude du B Dyn propose une première solution d'évolution de l'implant et un outil numérique pour l'analyse future de solutions techniques.The main focus of any implantable medical device is to improve the health of the patient by providing minimum risk. For this purpose, the study of the B Dyn spinal implant comprises several constituents: - The carrying out of a clinical follow up, - The analysis and choice of technical solutions (corrective actions) - The creation of a digital tool for further development (preventive actions).The initial bibliographical study enables to comprehend the functional anatomy of the lumbar spine, to understand the pathological states and their consequences and finally to list the associated surgical techniques (osseous resection, implantation of devices ).The clinical follow-up of a population of thirty patients then underlines the contributions (somatic and functional) of the B Dyn in its first design. For a few cases, the analysis of radiographs in flexion shows an incipient deterioration in the ring probably related to an accidental overloading of the implant. This observation requires an evolution in the design of the implant.An analysis of the initial design and the mechanical characterization in traction, allow targeting the corrective actions to be applied in the context of this evolution. The developed approach is based on the experimental evaluation in order to select technical solutions that would satisfy the functional criteria; this leads to an evolution of the choice of the ring material.To conduct subsequent developments, a finite element model is created. Thus the digital approach replaces the restrictive and expensive experimental approach. The preliminary characterization of elastomers is necessary to obtain materials data to work out this model. The results of the first simulations of a tensile test are compared to experimental data in the perspective of the model validation.At this stage, the B Dyn study provides a first solution of implant evolution and a numerical tool for the future analysis of technical solutions.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Optimizing the Architecture of a Dynamic Spinal Implant for Customized Mechanical Behavior

Non-fusion technology in spine surgery reduces surgical morbidity and degeneration of the adjacent levels by the insertion of dynamic spinal implants. Despite these advantages, a dynamic spinal implant (DSI) generates complications which require clinical follow-up, the continuous development of constructive solutions and structured optimization of the implant architecture using current mechanical design methods. This study structures this optimization process of a DSI concept by incorporating the mechanical behavior of the device, design variables and functional requirements into a global design model. The geometric (descriptive anatomy) and mechanical (materials, components, etc.) characteristics are obtained from a literature review. By combining these parameters, variables and requirements, appropriate values can be determined. The resulting mathematical model is then used to design and implement a device that is suitably adapted in movements and stiffness. The model assumes linear or non-linear behavior. We describe the optimization of the design variables to ensure the correct functioning of the mechanism when adapted to the patient. The optimization purpose is to determine the architecture of the implant, the choice of materials and the geometric parameters of implantation. An optimized implant model corresponding to specific degrees of degeneration in the intervertebral joint can then be envisaged

A modified version of a Fos-associated cluster in HBZ affects Jun transcriptional potency

Like c-Fos, HBZ (HTLV-I bZIP factor) is able to interact with c-Jun but differs considerably from c-Fos in its ability to activate AP-1-responsive genes since HBZ rather inhibits transcriptional activity of c-Jun. To better understand the molecular mechanisms involved in this down-regulation of c-Jun activity, a large number of HBZ/c-Fos chimeras was constructed and analyzed for their ability to interact with c-Jun, to bind to the AP-1 motif and to stimulate expression of a reporter gene containing the collagenase promoter. By this approach, we demonstrate that the DNA-binding domain of HBZ is responsible for its inhibitory effect on the trans-activation potential of c-Jun. However, unexpectedly, we found that exchange of a cluster of six charged amino acids immediately adjacent to the DNA contact region altered significantly transcriptional activity of chimeras. This particular subdomain could be involved in efficient presentation of the AP-1 complex to the transcriptional machinery. To confirm this role, specific residues present in the cluster of HBZ were substituted for corresponding amino acids in c-Fos. Unlike the JunD-activating potential of wild-type HBZ, this mutant was no longer able to stimulate JunD activity, confirming the key role of this particular cluster in regulation of Jun transcriptional potency

Comparison of Packaging Strategy in Retroviruses and Pararetroviruses

AbstractReverse transcription is not solely a retroviral mechanism. Animal hepadnaviruses, plant caulimoviruses, and badnaviruses have a RNA intermediate which is reverse transcribed into double-stranded DNA genome. Based on this fact, these three groups of viruses have been regrouped under the name of pararetroviruses. Although each one has developed its own strategy to assure an efficient packaging of their genome, it is clear that they have adopted a strategy where encapsidation prepares for initiation of reverse transcription. This is discussed in this review

Detection, characterization and regulation of antisense transcripts in HIV-1

© 2007 Landry et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens