Measuring biological materials mechanics with atomic force microscopy - Determination of viscoelastic cell properties from stress relaxation experiments.

Cells are complex, viscoelastic bodies. Their mechanical properties are defined by the arrangement of semiflexible cytoskeletal fibers, their crosslinking, and the active remodeling of the cytoskeletal network. Atomic force microscopy (AFM) is an often-used technique for the study of cell mechanics, enabling time- and frequency-dependent measurements with nanometer resolution. Cells exhibit time-dependent deformation when stress is applied. In this work, we have investigated the stress relaxation of HeLa cells when subjected to a constant strain. We have varied the applied force (1, 2, 4, and 8 nN) and pause time (1, 10, and 60 s) to check for common assumptions for the use of models of linear viscoelasticity. Then, we have applied three models (standard linear solid, five element Maxwell, power law rheology) to study their suitability to fit the datasets. We show that the five element Maxwell model captures the stress relaxation response the best while still retaining a low number of free variables. This work serves as an introduction and guide when performing stress relaxation experiments on soft matter using AFM. RESEARCH HIGHLIGHTS: Cells exhibit linear viscoelastic properties when subjected to stress relaxation measurements at the studied different forces and times. The stress relaxation is best described by a five element Maxwell model. All three used models capture a softening and fluidization of cells when disrupting actin filaments.

Measuring (biological) materials mechanics with atomic force microscopy. 2. Influence of the loading rate and applied force (colloidal particles).

Atomic force microscopy (AFM) is the most often used tool to study the mechanical properties of eukaryotic cells. Due to their complex assembly, cells show viscoelastic properties. When performing experiments, one has to consider the influence of both loading rate and maximum load on the measured mechanical properties. Here, we employed colloidal particles of various sizes (from 2 to 20 µm diameter) to perform force spectroscopy measurements on endothelial cells at loading rates varying from 0.1 to 50 µm/s, and maximum loads ranging from 1 to 25 nN. We were able to determine the non-linear dependence of cell viscoelastic properties on the loading rate which followed a weak power law. In addition, we show that previous loading at high forces leads to a stiffening of cells. Based on these results we discuss a road map for determining cell mechanical properties using AFM. Finally, this work provides an experimental framework for cell mechanical measurements using force-cycle experiments.

Microtubule disruption changes endothelial cell mechanics and adhesion.

The interest in studying the mechanical and adhesive properties of cells has increased in recent years. The cytoskeleton is known to play a key role in cell mechanics. However, the role of the microtubules in shaping cell mechanics is not yet well understood. We have employed Atomic Force Microscopy (AFM) together with confocal fluorescence microscopy to determine the role of microtubules in cytomechanics of Human Umbilical Vein Endothelial Cells (HUVECs). Additionally, the time variation of the adhesion between tip and cell surface was studied. The disruption of microtubules by exposing the cells to two colchicine concentrations was monitored as a function of time. Already, after 30 min of incubation the cells stiffened, their relaxation times increased (lower fluidity) and the adhesion between tip and cell decreased. This was accompanied by cytoskeletal rearrangements, a reduction in cell area and changes in cell shape. Over the whole experimental time, different behavior for the two used concentrations was found while for the control the values remained stable. This study underlines the role of microtubules in shaping endothelial cell mechanics.

Resveratrol-Induced Temporal Variation in the Mechanical Properties of MCF-7 Breast Cancer Cells Investigated by Atomic Force Microscopy.

Atomic force microscopy (AFM) combined with fluorescence microscopy has been used to quantify cytomechanical modifications induced by resveratrol (at a fixed concentration of 50 µM) in a breast cancer cell line (MCF-7) upon temporal variation. Cell indentation methodology has been utilized to determine simultaneous variations of Young's modulus, the maximum adhesion force, and tether formation, thereby determining cell motility and adhesiveness. Effects of treatment were measured at several time-points (0-6 h, 24 h, and 48 h); longer exposures resulted in cell death. Our results demonstrated that AFM can be efficiently used as a diagnostic tool to monitor irreversible morpho/nano-mechanical changes in cancer cells during the early steps of drug treatment.

Measuring biomaterials mechanics with atomic force microscopy. 1. Influence of the loading rate and applied force (pyramidal tips).

Atomic force microscopy (AFM) is today an established tool in imaging and determination of mechanical properties of biomaterials. Due to their complex organization, those materials show intricate properties such as viscoelasticity. Therefore, one has to consider that the loading rate at which the sample is probed will lead to different mechanical response (properties). In this work, we studied the dependence of the mechanical properties of endothelial cells on the loading rate using AFM in force spectroscopy mode. We employed a sharp, four-sided pyramidal indenter and loading rates ranging from 0.5 to 20 µm/s. In addition, by variation of the load (applied forces from 100 to 10,000 pN), the dependence of the cell properties on indentation depth could be determined. We then showed that the mechanical response of endothelial cells depends nonlinearly on the loading rate and follows a weak power-law. In addition, regions of different viscous response at varying indentation depth could be determined. Based on the results we obtained, a general route map for AFM users for design of cell mechanics experiments was described.

A Probabilistic Model for Crystal Growth Applied toProtein Deposition at the Microscale.

A probabilistic discrete model for 2D protein crystal growth is presented. This model takesinto account the available space and can describe growing processes of a different nature due to theversatility of its parameters, which gives the model great flexibility. The accuracy of the simulation istested against a real recrystallization experiment, carried out with the bacterial protein SbpA fromLysinibacillus sphaericus CCM2177, showing high agreement between the proposed model and theactual images of the crystal growth. Finally, it is also discussed how the regularity of the interface(i.e., the curve that separates the crystal from the substrate) affects the evolution of the simulation.

Mechanical properties of gelatin nanoparticles in dependency of crosslinking time and storage.

Mechanical properties of nanoparticles are an important characteristic for drug delivery and therefore, they have gained interest in pharmaceutical research during the last years. Among others, cellular uptake, blood circulation time and accumulation in organs are influenced by the elastic modulus of nanoparticles. Thus, by varying the stiffness of nanoparticles a more specific drug targeting might be achieved. Gelatin nanoparticles (GNPs) show advantageous characteristics in respect to encapsulation and delivery of hydrophilic drugs such as antibodies or other biologicals. Furthermore, the GNPs as hydrogel-nanoparticles offer adjustable elastic behavior. In this study, a method for GNP sample preparation and the determination of the mechanical properties by nanoindentation experiments using atomic force microscopy (AFM) was developed. The obtained force-distance curves were evaluated and fitted with the Hertzian model in order to calculate the Young's modulus. GNPs were crosslinked with glutaraldehyde (GTA) for different incubation times to investigate a possible modification of the Young's modulus. In addition, this study addresses the influence of storage on the mechanical characteristics of GNPs. The results provide first insights about the elastic properties of GNPs and their development over time. In the tested range of crosslinking times no notable differences in the mechanical properties occurred. In turn, the influence of the storage on the mechanical particle properties was observed: particle stiffness raised over time. Furthermore, it could be observed that the cellular uptake in a model cell line (A549) was increased for harder particles.

Las acciones afectivas y el distrés del niño ante la venopunción / No disponible

OBJETIVO: determinar si una intervención enfermera sistematizada de acciones afectivas produce una disminución en el distrés experimentado por los niños ante la venopunción. MÉTODO: estudio de intervención antes y después, realizado en el centro de salud de Almuñécar (Granada) con niños de 1 a 5 años que requerían venopunción para determinación analítica. Para determinar el distrés se utilizó la Children's and Infants' Postoperative Pain Scale (CHIPPS). La intervención consistió en un conjunto de acciones afectivas: contacto continuo con padres/tutores; uso de lenguaje apropiado a la edad; muestra y explicación del material de venopunción y proyección de audiovisual preferido. RESULTADOS: muestra compuesta por 100 sujetos, distribuidos al 50% por sexo y dos categorías de edad (1-3 años y > 3-5 años). En el conjunto de la muestra se obtuvo un cambio significativo en todas las variables (p< 0,05), excepto en el llanto (p= 0,057). En los niños se observó cambio significativo en todos los parámetros, menos el llanto; en las niñas, el cambio se produjo en la expresión facial y postura del tronco, pero no para el llanto, inquietud motora y postura de las piernas. En el grupo de 1-2 años encontramos un cambio significativo en todas las variables, mientras que en el grupo de 3-5 años no se produjo el cambio en la postura de las piernas y llanto.CONCLUSIONES: se evidencia que la inclusión de unas sencillas técnicas afectivas produce una disminución del distrés del niño durante la venopunción

OBJECTIVE: to determine whether a structured nursing intervention of affective actions will cause a reduction in the distress suffered by children when faced with venipuncture. METHOD: before-and-after intervention study, conducted at the health centre in Almuñécar (Granada) with 1 to 5-year-old children who required venipuncture for blood tests. In order to determine distress, the Children's and Infants' Postoperative Pain Scale (CHIPPS) was used. The intervention consisted of a set of affective actions: continuous contact with parents / guardians; use of language adequate for their age; showing and explaining the venipuncture materials, and projection of their preferred audiovisual aids. RESULTS: the sample included 100 subjects, allocated on a 50% by gender and two age categories (1 to 3-year-old and > 3 to 5-year-old). There was a significant change in all variables (p< 0.05) in the overall sample, except for crying (p= 0.057). A significant change was observed in all parameters for boys, except in crying; while in girls, there was a change in facial expression and chest posture, but not in crying, motor restlessness, and leg posture. We found a significant change in all variables in the 1-2-year-old group, while no change in leg posture and crying occurred in the 3 to 5-year-old group.CONCLUSIONS: there is evidence showing that the inclusion of some simple affective techniques will cause a reduction in children's distress during venipuncture

Looking at cell mechanics with atomic force microscopy: experiment and theory.

This review reports on the use of the atomic force microscopy in the investigation of the mechanical properties of cells. It is shown that the technique is able to deliver information about the cell surface properties (e.g., topography), the Young modulus, the viscosity, and the cell the relaxation times. Another aspect that this short review points out is the utilization of the atomic force microscope to investigate basic questions related to materials physics, biology, and medicine. The review is written in a chronological way to offer an overview of phenomenological facts and quantitative results to the reader. The final section discusses in detail the advantages and disadvantages of the Hertz and JKR models. A new implementation of the JKR model derived by Dufresne is presented.

A new automatic contact point detection algorithm for AFM force curves.

A new method for estimating the contact point in AFM force curves, based on a local regression algorithm, is presented. The main advantage of this method is that can be easily implemented as a computer algorithm and used for a fully automatic detection of the contact points in the approach force curves on living cells. The estimated contact points have been compared to those obtained by other published methods, which were applied either for materials with an elastic response to indentation forces or for experiments at high loading rates. We have found that the differences in the values of the contact points estimated with three different methods were not statistically significant and thus the algorithm is reliable. Also, we test the convenience of the algorithm for batch-processing by computing the contact points of a force curve map of 625 (25×25) curves.

Protrusión acetabular en la artroplastia total de cadera / Acetabular protrusion in total hip arthroplasty

Introducción: la presencia de protrusión acetabular en un paciente que va a ser sometido a una artroplastia total de cadera indica un incremento de la dificultad de la intervención, toda vez que el tratamiento requiere la reconstrucción del defecto cavitario.Objetivo: evaluar los resultados del tratamiento de la protrusión acetabular con injerto óseo de la pared medial acetabular, en conjunción con una artroplastia total de cadera con componente acetabular no cementado.Métodos: estudio descriptivo, prospectivo y longitudinal en 38 pacientes que recibieron injerto óseo de la pared medial acetabular, en conjunción con una artroplastia total de cadera con componente acetabular no cementado, de enero de 2008 a diciembre de 2010. Se utilizó injerto autólogo en 23 pacientes y homólogo de banco en 15. Los pacientes se siguieron por examen físico y rayos X, realizados a las 4 semanas, a las 12 semanas, a los 6 meses y 1 año posterior a la cirugía.Resultados: todos los tipos de injerto aparentaron incorporase dentro del mismo período de aproximadamente 3 meses. Ningún paciente mostró progresión de la protrusión durante la etapa de consolidación del injerto o posterior. La puntuación en la escala de Harris mejoró de una media preoperatoria de 38 (22-55) a una media posoperatoria de 89 (80-95).Conclusión: la reconstrucción de la cavidad acetabular, con la utilización de injerto en la pared medial y componente acetabular no cementado, proporciona sustrato óseo suficiente para prolongar la vida útil de la artroplastia(AU)

Introduction: the presence of acetabular protrusion in a patient who will undergo total hip arthroplasty points to greater surgical difficulty, since treatment will require reconstruction of the cavitary defect.Objective: evaluate the results of treatment of acetabular protrusion with bone grafting of the medial acetabular wall combined with total hip arthroplasty with a cementless acetabular component.Methods: a prospective longitudinal descriptive study was conducted of 38 patients receiving bone grafts of the medial acetabular wall combined with total hip arthroplasty with a cementless acetabular component from January 2008 to December 2010. Autologous grafts were used in 23 patients and homologous bank bone grafts in 15. The patients were followed up through physical and radiographic examination conducted 4 weeks, 12 weeks, 6 months and 1 year after surgery.Results: all graft types seemed to incorporate within a period of approximately 3 months. No patient showed protrusion progression during the stage of graft consolidation or later. Harris hip score improved from a preoperative mean of 38 (22-55) to a postoperative mean of 89 (80-95).Conclusion: acetabular reconstruction with medial wall grafting and a cementless acetabular component provides sufficient bone substrate to extend the useful life of arthroplasty(AU)

Protrusión acetabular en la artroplastia total de cadera / Acetabular protrusion in total hip arthroplasty

Introducción: la presencia de protrusión acetabular en un paciente que va a ser sometido a una artroplastia total de cadera indica un incremento de la dificultad de la intervención, toda vez que el tratamiento requiere la reconstrucción del defecto cavitario. Objetivo: evaluar los resultados del tratamiento de la protrusión acetabular con injerto óseo de la pared medial acetabular, en conjunción con una artroplastia total de cadera con componente acetabular no cementado. Métodos: estudio descriptivo, prospectivo y longitudinal en 38 pacientes que recibieron injerto óseo de la pared medial acetabular, en conjunción con una artroplastia total de cadera con componente acetabular no cementado, de enero de 2008 a diciembre de 2010. Se utilizó injerto autólogo en 23 pacientes y homólogo de banco en 15. Los pacientes se siguieron por examen físico y rayos X, realizados a las 4 semanas, a las 12 semanas, a los 6 meses y 1 año posterior a la cirugía. Resultados: todos los tipos de injerto aparentaron incorporase dentro del mismo período de aproximadamente 3 meses. Ningún paciente mostró progresión de la protrusión durante la etapa de consolidación del injerto o posterior. La puntuación en la escala de Harris mejoró de una media preoperatoria de 38 (22-55) a una media posoperatoria de 89 (80-95). Conclusión: la reconstrucción de la cavidad acetabular, con la utilización de injerto en la pared medial y componente acetabular no cementado, proporciona sustrato óseo suficiente para prolongar la vida útil de la artroplastia(AU)

Introduction: the presence of acetabular protrusion in a patient who will undergo total hip arthroplasty points to greater surgical difficulty, since treatment will require reconstruction of the cavitary defect. Objective: evaluate the results of treatment of acetabular protrusion with bone grafting of the medial acetabular wall combined with total hip arthroplasty with a cementless acetabular component. Methods: a prospective longitudinal descriptive study was conducted of 38 patients receiving bone grafts of the medial acetabular wall combined with total hip arthroplasty with a cementless acetabular component from January 2008 to December 2010. Autologous grafts were used in 23 patients and homologous bank bone grafts in 15. The patients were followed up through physical and radiographic examination conducted 4 weeks, 12 weeks, 6 months and 1 year after surgery. Results: all graft types seemed to incorporate within a period of approximately 3 months. No patient showed protrusion progression during the stage of graft consolidation or later. Harris hip score improved from a preoperative mean of 38 (22-55) to a postoperative mean of 89 (80-95). Conclusion: acetabular reconstruction with medial wall grafting and a cementless acetabular component provides sufficient bone substrate to extend the useful life of arthroplasty(AU)

Protrusión acetabular en la artroplastia total de cadera / Protrusion acétabulaire dans une arthroplastie totale de hanche / Acetabular protrusion in total hip arthroplasty

Introducción: la presencia de protrusión acetabular en un paciente que va a ser sometido a una artroplastia total de cadera indica un incremento de la dificultad de la intervención, toda vez que el tratamiento requiere la reconstrucción del defecto cavitario. Objetivo: evaluar los resultados del tratamiento de la protrusión acetabular con injerto óseo de la pared medial acetabular, en conjunción con una artroplastia total de cadera con componente acetabular no cementado. Métodos: estudio descriptivo, prospectivo y longitudinal en 38 pacientes que recibieron injerto óseo de la pared medial acetabular, en conjunción con una artroplastia total de cadera con componente acetabular no cementado, de enero de 2008 a diciembre de 2010. Se utilizó injerto autólogo en 23 pacientes y homólogo de banco en 15. Los pacientes se siguieron por examen físico y rayos X, realizados a las 4 semanas, a las 12 semanas, a los 6 meses y 1 año posterior a la cirugía. Resultados: todos los tipos de injerto aparentaron incorporase dentro del mismo período de aproximadamente 3 meses. Ningún paciente mostró progresión de la protrusión durante la etapa de consolidación del injerto o posterior. La puntuación en la escala de Harris mejoró de una media preoperatoria de 38 (22-55) a una media posoperatoria de 89 (80-95). Conclusión: la reconstrucción de la cavidad acetabular, con la utilización de injerto en la pared medial y componente acetabular no cementado, proporciona sustrato óseo suficiente para prolongar la vida útil de la artroplastia(AU)

Introduction: the presence of acetabular protrusion in a patient who will undergo total hip arthroplasty points to greater surgical difficulty, since treatment will require reconstruction of the cavitary defect. Objective: evaluate the results of treatment of acetabular protrusion with bone grafting of the medial acetabular wall combined with total hip arthroplasty with a cementless acetabular component. Methods: a prospective longitudinal descriptive study was conducted of 38 patients receiving bone grafts of the medial acetabular wall combined with total hip arthroplasty with a cementless acetabular component from January 2008 to December 2010. Autologous grafts were used in 23 patients and homologous bank bone grafts in 15. The patients were followed up through physical and radiographic examination conducted 4 weeks, 12 weeks, 6 months and 1 year after surgery. Results: all graft types seemed to incorporate within a period of approximately 3 months. No patient showed protrusion progression during the stage of graft consolidation or later. Harris hip score improved from a preoperative mean of 38 (22-55) to a postoperative mean of 89 (80-95). Conclusion: acetabular reconstruction with medial wall grafting and a cementless acetabular component provides sufficient bone substrate to extend the useful life of arthroplasty(AU)

Introduction: la présence d'une protrusion acétabulaire chez un patient traité par arthroplastie totale de hanche indique une difficulté accrue du geste chirurgical, en tenant compte que ce traitement exige la reconstruction du défaut cavitaire. Objectif: évaluer les résultats du traitement de la protrusion acétabulaire par greffon osseux de la paroi médiale acétabulaire et par une arthroplastie totale de hanche avec un composant acétabulaire non cimenté. Méthodes: étude descriptive, prospective et longitudinale de 38 patients traités par greffon osseux de la paroi médiale acétabulaire et par arthroplastie totale de hanche avec un composant acétabulaire non cimenté, depuis janvier 2008 jusqu'à décembre 2010. Un greffon autologue a été utilisé chez 23 patients, et un greffon homologue chez 15. Un suivi physique et radiologique a été effectué à 4 - 12 semaines, à 6 mois, et un an après l'opération. Résultats: tous les types de greffon semblaient assimilés dans la même période de 3 mois environ. Aucun patient n'a montré de protrusion pendant ou après la consolidation du greffon. Dans l'échelle d'Harris, la moyenne préopératoire a été 38 (22-55), tandis que la moyenne postopératoire a été 89 (80- 95). Conclusion: la reconstruction de la cavité acétabulaire par greffon de la paroi médiale et par composant acétabulaire non cimenté fournit assez de substrat osseux pour prolonger la vie utile de l'arthroplastie(AU)

Consideraciones sobre el desgaste del polietileno en la artroplastia total de cadera / Considerations on polyethylene wear in jip total arthroplasty

INTRODUCCION: El desgaste del polietileno ha sido un problema desde la introducción de la artroplastia total de baja fricción y continua siéndolo en la actualidad en lo que influyen múltiples condiciones. OBJETIVO: Describir las consideraciones técnicas necesarias en la artroplastia total de cadera en aras de garantizar la mayor durabilidad de sus componentes. MÉTODOS: Se realiza una revisión de la literatura publicada al respecto tomándose en cuenta las variables que afectan el desgaste del polietileno así como las maniobras técnicas que pueden ser realizadas por el cirujano en aras de optimizar la durabilidad de los componentes protésicos. RESULTADOS: La inclinación de la cúpula mayor de 45º está directamente relacionada con el desgaste del polietileno. La restauración del centro de rotación de la cadera con el centro de rotación de la cúpula ha sido un importante objetivo en la técnica de cementación del acetábulo debido a reportes de su relación con el desgaste. La cobertura por el hueso es importante para evitar el pinzamiento del cuello de metal contra el polietileno o el anillo de metal de la cúpula. CONCLUSIÓN: El cirujano puede cambiar el centro de rotación del acetábulo para obtener una óptima inclinación y cobertura de forma segura sin que implique un incremento de la incidencia del efecto adverso de desgaste

INTRODUCTION: The polyethylene wear has been a problem from the introduction of low fraction total arthroplasty until nowadays where influencing many conditions. OBJECTIVE: To describe the technical conditions needed in the total hip arthroplasty to guarantee a greater durability of its components. METHODS: Literature published on this subject is reviewed taking into account the variables affecting the polyethylene wear as well as the possible technical manoeuvres carried out by surgeon to optimize the durability of prosthetic components. RESULTS: The 45º slope of major cupula is directly related to polyethylene wear. Restoration of the hip rotation center with the cupula rotation center has been a significant objective in acetabulum cementation due to reports of its relation to wear. The bone coverage is important to avoid the metal neck clamping against the polyethylene or the metal ring of cupula. CONCLUSION: The surgeon may to change the acetabulum rotation center to achieve an optimal and safe slope and coverage without an increase of incidence of wear adverse effect

Consideraciones sobre el desgaste del polietileno en la artroplastia total de cadera / Considerations on polyethylene wear in jip total arthroplasty

INTRODUCCION: El desgaste del polietileno ha sido un problema desde la introducción de la artroplastia total de baja fricción y continua siéndolo en la actualidad en lo que influyen múltiples condiciones. OBJETIVO: Describir las consideraciones técnicas necesarias en la artroplastia total de cadera en aras de garantizar la mayor durabilidad de sus componentes. MÉTODOS: Se realiza una revisión de la literatura publicada al respecto tomándose en cuenta las variables que afectan el desgaste del polietileno así como las maniobras técnicas que pueden ser realizadas por el cirujano en aras de optimizar la durabilidad de los componentes protésicos. RESULTADOS: La inclinación de la cúpula mayor de 45º está directamente relacionada con el desgaste del polietileno. La restauración del centro de rotación de la cadera con el centro de rotación de la cúpula ha sido un importante objetivo en la técnica de cementación del acetábulo debido a reportes de su relación con el desgaste. La cobertura por el hueso es importante para evitar el pinzamiento del cuello de metal contra el polietileno o el anillo de metal de la cúpula. CONCLUSIÓN: El cirujano puede cambiar el centro de rotación del acetábulo para obtener una óptima inclinación y cobertura de forma segura sin que implique un incremento de la incidencia del efecto adverso de desgaste(AU)

INTRODUCTION: The polyethylene wear has been a problem from the introduction of low fraction total arthroplasty until nowadays where influencing many conditions. OBJECTIVE: To describe the technical conditions needed in the total hip arthroplasty to guarantee a greater durability of its components. METHODS: Literature published on this subject is reviewed taking into account the variables affecting the polyethylene wear as well as the possible technical manoeuvres carried out by surgeon to optimize the durability of prosthetic components. RESULTS: The 45º slope of major cupula is directly related to polyethylene wear. Restoration of the hip rotation center with the cupula rotation center has been a significant objective in acetabulum cementation due to reports of its relation to wear. The bone coverage is important to avoid the metal neck clamping against the polyethylene or the metal ring of cupula. CONCLUSION: The surgeon may to change the acetabulum rotation center to achieve an optimal and safe slope and coverage without an increase of incidence of wear adverse effect(AU)

Stress relaxation and creep on living cells with the atomic force microscope: a means to calculate elastic moduli and viscosities of cell components.

In this work we present a unified method to study the mechanical properties of cells using the atomic force microscope. Stress relaxation and creep compliance measurements permitted us to determine, the relaxation times, the Young moduli and the viscosity of breast cancer cells (MCF-7). The results show that the mechanical behaviour of MCF-7 cells responds to a two-layered model of similar elasticity but differing viscosity. Treatment of MCF-7 cells with an actin-depolymerising agent results in an overall decrease in both cell elasticity and viscosity, however to a different extent for each layer. The layer that undergoes the smaller decrease (36-38%) is assigned to the cell membrane/cortex while the layer that experiences the larger decrease (70-80%) is attributed to the cell cytoplasm. The combination of the method presented in this work, together with the approach based on stress relaxation microscopy (Moreno-Flores et al 2010 J. Biomech. 43 349-54), constitutes a unique AFM-based experimental framework to study cell mechanics. This methodology can also be extended to study the mechanical properties of biomaterials in general.

Stress relaxation microscopy: imaging local stress in cells.

Biomechanics is gaining relevance as complementary discipline to structural and cellular biology. The response of cells to mechanical stimuli determines cell type and function, while the spatial distribution of mechanical forces within the cells is crucial to understand cell activity. The experimental methodologies to approach cell mechanics are diverse but either they are effective in few cases or they rule out the innate cell complexity. In this regard, we have developed a simple scanning probe-based methodology that overcomes the limitations of the available methods. Stress relaxation, the decay of the force exerted by the cell surface at constant deformation, has been used to extract relaxational responses at each cellular sublocalisation and generate maps. Surprisingly, decay curves exerted by test cells are fully described by a generalized viscoelastic model that accounts for more than one simultaneously occurring relaxations. Within the range of applied forces (0.5-4nN) a slow and a fast relaxation with characteristic times of 0.1 and 1s have been detected and assigned to rearrangements of cell membrane and cytoskeleton, respectively. Relaxation time mapping of entire cells is thus promising to simultaneously detect non-uniformities in membrane and cytoskeleton and as identifying tool for cell type and disease.

Glosario de medicaciones / Glossary of medications

Este glosario se confeccionó con el objetivo de proporcionar a los estudiantes de Ciencias Médicas y a los profesionales de la salud, información acerca de medicamentos recibidos de países extranjeros, que se encuentran en idioma Inglés.Compila 250 medicamentos en idioma Inglés, ordenados alfabéticamente, con una traducción al Español de sus correspondientes categorías y aplicaciones. El Glosario resulta útil para actualizar al estudiante y profesional de la salud sobre medicamentos que llegan a nuestro país por medio de donaciones, en su gran mayoría.Por la necesidad que constituye el conocimiento del significado en español de las categorías y de la aplicación de estos medicamentos para el tratamiento de las enfermedades, recomendamos su utilización en todas las carreras de Ciencias Médicas(AU)

HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease.

Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.

Enfermedad de zollinger-ellison: a propósito de un caso / Zollinger-ellison disease: a purpose of a case

Reportamos un caso de gastrinoma, en una paciente femenina, de 34 años de edad quien presentó cuadro clínico caracterizado por epigastralgia, urente, náuseas, vómitos. Además de síndrome diarréico, con 8 evacuaciones líquidas diarias. Los estudios realizados fueron: EDS: múltiples úlceras en estómago y duodeno. Gastrina sérica basal: 1200p/g, y post-estimulación: 1600p/g. US abdominal y TAC de abdomen: normal. Ultrasonido endoscópico: Tu de 3x3cm en la cola de páncreas. Se realiza laparotomía con hallazgo operatorio: tumor exofítico localizado en la cola del páncreas, de 4cm de diámetro (se realiza pancreatectomía esplenectomía). Dos meses después de la cirugía se realiza TAC de abdomen control, donde se observa lesiones a nivel del perénquima hepático que sugieren MT. Se inicia quimioterapia. Se revisa la literatura relativa al síndrome de zollinger ellison