Mechanical behavior of in-situ alloyed Ti6Al4V(ELI)-3 at.% Cu lattice structures manufactured by laser powder bed fusion and designed for implant applications.

In the present study, cellular lattice structures for implant applications are reported for the first-time incorporating copper directly by in-situ alloying in the laser powder bed fusion process. The aim to incorporate 3 at.% Cu into Ti6Al4V(ELI) is selected for improved antibacterial properties while maintaining appropriate mechanical properties. Previously, topologically optimized Ti6Al4V(ELI) lattice structures were successfully designed, manufactured and studied for implant applications. The development of a new alloy produced by in-situ alloying of elemental powder mixture of Ti6Al4V(ELI) and pure Cu powders was used here for the production of identical lattice structures with improved antibacterial properties. One of the same as-designed CAD models was used for the manufacturing of these lattices compared to previous work on pure Ti6Al4V(ELI) lattices, making direct comparison of mechanical properties possible. Similar manufacturability highlights the applicability of this alloying technique to other lattice designs. Microstructural characterization was performed by optical and electron microscopies, as well as microCT. Mechanical characterization was performed by means of compression tests and hardness measurements. Results showed that in-situ alloying with copper leads to the formation of localized Cu-rich regions, refinement of martensitic phase and the formation of CuTi2 intermetallic precipitates, which increased the hardness and strength of the material. Deviations in wall thickness between the as-designed and as-manufactured lattices led to anisotropy of the mechanical properties of the lattices. Higher compressive strength values were obtained when thicker walls were oriented along the loading direction. Nevertheless, alloying with Cu had a higher impact on the compressive strength of lattice structure than the wall thickness deviations. The direct in-situ alloying of copper in Ti6Al4V(ELI) is a promising route for direct manufacturing of antibacterial implants.

In-vitro comparison of hydroxyapatite coatings obtained by cold spray and conventional thermal spray technologies.

Hydroxyapatite (HA) coatings onto Ti6Al4V alloy substrates were obtained by several thermal spray technologies: atmospheric plasma spray (APS) and high velocity oxy fuel (HVOF), together with the cold spray (CS) technique. A characterization study has been performed by means of surface and microstructure analyses, as well as biological performance. In-vitro tests were performed with primary human osteoblasts at 1, 7 and 14 days of cell culture on substrates. Cell viability was tested by MTS and LIVE/DEAD assays, cell differentiation by alkaline phosphatase (ALP) quantification, and cell morphology was analyzed by scanning electron microscopy. The HA coatings showed an increase of HA crystallinity from 62,4% to 89%, but also an increase of hydrophilicity from ∼32° to 0°, with the decrease of the operating temperature of the thermal spray techniques (APS > HVOF > CS). Additionally, APS HA coatings showed more surface micro-features than HVOF and CS HA coatings; cells onto APS HA coatings showed faster attachment by acquiring osteoblastic morphology in comparison with the rounded cell morphology observed onto CS HA coatings at 1 day of cell culture. HVOF HA coatings also showed proper cell adherence but did not show extended filopodia as cells onto APS HA coatings. However, at 14 days of cell culture, higher cell proliferation and differentiation was detected on HA coatings with higher crystallinity (HVOF and CS techniques). Cell attachment is suggested to be favoured by surface micro-features but also moderate surface wettability whereas cell proliferation and differentiation is suggested to be highly influenced by HA crystallinity and crystal size.

X-ray microtomographic characterization of highly rough titanium cold gas sprayed coating for identification of effective surfaces for osseointegration.

A highly rough titanium coating obtained by Cold Gas Spray (CGS) has been characterized by means of high-resolution 3D microtomography (micro-CT) with the aim to evaluate its open and close porosity for possible use in orthopaedic implants to promote osseointegration. Micro-CT allowed a qualitative and quantitative description of the main features, morphology of the pores and surface roughness of the coating. Several numerical values were obtained to describe size, form and distribution of the closed/inner and open/outer pores. Additionally, surface roughness and open porosity were image-analyzed to find the effective surface for osseointegration.

In-vitro study of hierarchical structures: Anodic oxidation and alkaline treatments onto highly rough titanium cold gas spray coatings for biomedical applications.

Hierarchical structures were obtained applying two different nanotexturing surface treatments onto highly rough commercial pure titanium coatings by cold spray: (i) anodic oxidation and (ii) alkaline treatments. An extended surface characterization in terms of topography, composition, and wettability has been performed to understand how those parameters affect to cell response. Primary human osteoblasts extracted from knee were seeded onto the as-sprayed titanium surface before and after the nanotexturing treatments. Cell viability was tested by using MTS and LIVE/DEAD assays, as well as osteoblasts differentiation by alkaline phosphatase (ALP) quantification at 3 and 10 days of cell culture. The combination of micro-/nano-roughness results in a significantly increase of cell proliferation, as well as cell differentiation after 10 days of cell culture in comparison with the non-treated coatings.

Functionalized coatings by cold spray: An in vitro study of micro- and nanocrystalline hydroxyapatite compared to porous titanium.

Three different surface treatments on a Ti6Al4V alloy have been in vitro tested for possible application in cementless joint prosthesis. All of them involve the novelty of using the Cold Spray technology for their deposition: (i) an as-sprayed highly rough titanium and, followed by the deposition of a thin hydroxyapatite layer with (ii) microcrystalline or (iii) nanocrystalline structure. Primary human osteoblasts were extracted from knee and seeded onto the three different surfaces. Cell viability was tested by MTS and LIVE/DEAD assays, cell differentiation by alkaline phosphatase (ALP) quantification and cell morphology by Phalloidin staining. All tests were carried out at 1, 7 and 14 days of cell culture. Different cell morphologies between titanium and hydroxyapatite surfaces were exhibited. At 1 day of cell culture, cells on the titanium coating were spread and flattened, expanding the filopodia actin filaments in all directions, while cells on the hydroxyapatite coatings showed round like-shape morphology due to slower attachment. Higher cell viability was detected at all times of cell culture on titanium coating due to a better attachment at 1 day. However, from 7 days of cell culture, cells on hydroxyapatite showed good attachment onto surfaces and highly increased their proliferation, mostly on nanocrystalline, achieving similar cell viability levels than titanium coatings. ALP levels were significantly higher in titanium, in part, because of greatest cell number. Overall, the best cell functional results were obtained on titanium coatings whereas microcrystalline hydroxyapatite presented the worst cellular parameters. However, results indicate that nanocrystalline hydroxyapatite coatings may achieve promising results for the faster cell proliferation once cells are attached on the surface.

Osteoblastic cell response on high-rough titanium coatings by cold spray.

Highly rough and porous commercially pure titanium coatings have been directly produced for first time by the cold spray technology, which is a promising technology in front of the vacuum plasma spray for oxygen sensitive materials. The wettability properties as well as the biocompatibility evaluation have been compared to a simply sand blasted Ti6Al4V alloy substrate. Surface topographies were analysed using confocal microscopy. Next, osteoblast morphology (Phalloidin staining), proliferation (MTS assay), and differentiation (alkaline phosphatase activity) were examined along 1, 7 and 14 days of cell culture on the different surfaces. Finally, mineralization by alizarin red staining was quantified at 28 days of cell culture. The contact angle values showed an increased hydrophilic behaviour on the as-sprayed surface with a good correlation to the biological response. A higher cell viability, proliferation and differentiation were obtained for highly rough commercial pure titanium coatings in comparison with sand blasted substrates. Cell morphology was similar in all coatings tested; at 14 days both samples showed extended filopodia. A higher amount of calcium-rich deposits was detected on highly rough surfaces. In summary, in-vitro results showed an increase of biological properties when surface roughness increases.

Real-Time Protein and Cell Binding Measurements on Hydroxyapatite Coatings.

Although a lot of in vitro and in vivo assays have been performed during the last few decades years for hydroxyapatite bioactive coatings, there is a lack of exploitation of real-time in vitro interaction measurements. In the present work, real-time interactions for a plasma sprayed hydroxyapatite coating were measured by a Multi-Parametric Surface Plasmon Resonance (MP-SPR), and the results were compared with standard traditional cell viability in vitro assays. MP-SPR is proven to be suitable not only for measurement of molecule-molecule interactions but also molecule-material interaction measurements and cell interaction. Although SPR is extensively utilized in interaction studies, recent research of protein or cell adsorption on hydroxyapatite coatings for prostheses applications was not found. The as-sprayed hydroxyapatite coating resulted in 62.4% of crystalline phase and an average thickness of 24 ± 6 µm. The MP-SPR was used to measure lysozyme protein and human mesenchymal stem cells interaction to the hydroxyapatite coating. A comparison between the standard gold sensor and Hydroxyapatite (HA)-plasma coated sensor denoted a clearly favourable cell attachment on HA coated sensor as a significantly higher signal of cell binding was detected. Moreover, traditional cell viability and proliferation tests showed increased activity with culture time indicating that cells were proliferating on HA coating. Cells show homogeneous distribution and proliferation along the HA surface between one and seven days with no significant mortality. Cells were flattened and spread on rough surfaces from the first day, with increasing cytoplasmatic extensions during the culture time.

Evaluación mediante mapas estadísticos paramétricos de los cambios de la perfusión cerebral en pacientes con estenosis de la arteria carótida sometidos a endarterectomía / Evaluation by “statistical parametric mapping” of the cerebral perfusion changes in patients with carotid artery stenosis after endarterectomy

La eficacia de la endarterectomía carotídea (EC) en los accidentes cerebrovasculares producidos por estenosis carotídea puede ser evaluada mediante la tomografía computarizada de emisión de fotón único de perfusión cerebral, utilizando SPM (statistical parametric mapping ‘mapas estadísticos paramétricos’).Material y métodosSe incluyeron en el estudio 12 pacientes con estenosis significativa de la arteria carótida que fueron sometidos a endarterectomía. A todos se les realizó un estudio de perfusión cerebral con 99mTc-etilen cisteinato dietilester (ECD) basal tras la endarterectomía. Mediante los SPM se comparó de forma independiente el estudio basal/poscirugía con el grupo control formado por 20 pacientes y se obtuvieron los correspondientes SPM. Se valoraron los cambios tanto en extensión (o número de vóxeles) como en intensidad (cambio en el valor de T) de las zonas significativamente hipoperfundidas y el sentido de estos cambios.ResultadosEn el grupo de 12 pacientes se observó una mejoría de la perfusión cerebral posquirúrgica, en 5 pacientes con disminución en la extensión de las zonas hipoperfundidas del 50,56% y de intensidad del 30,9% de media. Cuatro pacientes mostraron un aumento en la extensión de la hipoperfusión cerebral del 85,53% y de la intensidad del 34,21% de media. En tres pacientes no se apreciaron cambios significativos entre ambos estudios.ConclusionesEl SPM ha demostrado ser una herramienta útil que permite objetivar los cambios de flujo sanguíneo cerebral que se producen tras la intervención quirúrgica, valorando los cambios en extensión e intensidad de las zonas significativamente hipoperfundidas(AU)

The efficacy of carotid endartectomy (CE) in cerebrovascular accidents produced by carotid stenosis can be evaluated with the cerebral perfusion with single photon emission tomography, using statistical parametric mapping (SPM).Material and methodsTwelve patients with significant carotid stenosis who underwent endartectomy were included in the study. All underwent a cerebral perfusion study with 99mTc-etilen cisteinato dietilester (ECD) at baseline and after the endartectomy. Using SPM, the baseline/post-surgery study was compared independently with the control group made up of 20 patients and the corresponding parametric statistical mappings were obtained. Changes in extension (kE or voxel number) and intensity (change in the T value) of the significantly hypoperfused zones and direction of these changes were evaluated.ResultsIn the group of 12 patients, improvement of the post-surgical cerebral perfusion was observed in 5 patients with an average 50.56% decrease in the extension of the hypoperfused zones and average 30.9% decrease of intensity. Four patients showed an average 85.53% increase in the extension of cerebral hypoperfusion and of 34.21% in intensity. No significant changes between both studies were found in three patients.ConclusionsSPM has been shown to be a useful tool that makes it possible to objectify the cerebral brain flow changes produced after the surgical intervention, evaluating the changes in extension and intensity of the significantly hypoperfused zones(AU)

[Evaluation by "statistical parametric mapping" of the cerebral perfusion changes in patients with carotid artery stenosis after endarterectomy]. / Evaluación mediante mapas estadísticos paramétricos de los cambios de la perfusión cerebral en pacientes con estenosis de la arteria carótida sometidos a endarterectomía.

UNLABELLED: The efficacy of carotid endartectomy (CE) in cerebrovascular accidents produced by carotid stenosis can be evaluated with the cerebral perfusion with single photon emission tomography, using statistical parametric mapping (SPM). MATERIAL AND METHODS: Twelve patients with significant carotid stenosis who underwent endartectomy were included in the study. All underwent a cerebral perfusion study with 99mTc-etilen cisteinato dietilester (ECD) at baseline and after the endartectomy. Using SPM, the baseline/post-surgery study was compared independently with the control group made up of 20 patients and the corresponding parametric statistical mappings were obtained. Changes in extension (k(E) or voxel number) and intensity (change in the T value) of the significantly hypoperfused zones and direction of these changes were evaluated. RESULTS: In the group of 12 patients, improvement of the post-surgical cerebral perfusion was observed in 5 patients with an average 50.56% decrease in the extension of the hypoperfused zones and average 30.9% decrease of intensity. Four patients showed an average 85.53% increase in the extension of cerebral hypoperfusion and of 34.21% in intensity. No significant changes between both studies were found in three patients. CONCLUSIONS: SPM has been shown to be a useful tool that makes it possible to objectify the cerebral brain flow changes produced after the surgical intervention, evaluating the changes in extension and intensity of the significantly hypoperfused zones.

Utilidad del propéptido amino-terminal del procolágeno tipo 1 (P1NP) como marcador de remodelado óseo en el paciente sometido a trasplante renal / Use of procollagen type 1 n-terminal propeptide (P1NP) as a marker of bone remodelling in renal transplant patients

Introducción y objetivo. El propéptido aminoterminal del procolágeno tipo I (P1NP) es un marcador de formación ósea que se altera en afecciones óseas tales como la osteoporosis. El objetivo de este estudio es ver la utilidad del marcador en el diagnóstico de la osteoporosis en una población de pacientes sometidos a un trasplante renal (TR). Material y métodos. Noventa pacientes sometidos a un TR (60 varones, 30 mujeres) con una edad media±desviación estándar (DE) de 55±15 años. Se determinó en suero P1NP, creatinina, paratirina (PTH) y vitamina D, en situación pretrasplante, a los 3 meses y al año. Se estimó el filtrado glomerular con la fórmula MDRD abreviado y se registró la terapia inmunosupresora. Se realizó una densitometría ósea a los 3 meses del trasplante. Según los criterios de la Organización Mundial de la Salud se clasificó la muestra en población con masa ósea baja (T-score<−1 DE) y población normal (T-score≥−1 DE). Resultados. No se observó correlación entre la concentración de P1NP y la función renal. Un 64% de los pacientes presentaron una masa ósea baja. El paciente con densidad mineral ósea disminuida presentaba unos valores de P1NP en situación pretrasplante mayores, respecto a los pacientes con masa ósea normal. El análisis de regresión logística puso de manifiesto que P1NP (p=0,028; odds ratio=10,755) podría ser un marcador de masa ósea baja independiente de la edad, el sexo, la dosis de glucocorticoides y la PTH (covariables en el estudio). Conclusiones. El P1NP es un buen marcador para estimar el estado óseo en el paciente renal. El valor de P1NP en situación pre-trasplante sería indicativo de un mayor riesgo de presentar una masa ósea disminuida (AU)

Introduction and objective. Type I procollagen N-terminal propeptide (P1NP) is a marker of bone formation which is altered in bone diseases such as osteoporosis. The objective of this study was to evaluate the use of this marker in the diagnosis of osteoporosis in patients who undergo a renal transplant. Material and methods. Ninety RT (renal transplant) patients (60 men, 30 women) with a mean age of 55±15 years were evaluated. Serum P1NP, creatinine, parathyroid hormone (PTH), and vitamin D were measured at baseline and at 3 months and 1 year after transplantation. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease (MDRD) formula and immunosuppression therapy was recorded. A bone densitometry scan was performed 3 months after transplant. The patients were classified,according to WHO guidelines, into two populations: a group with low bone mass (T-score<−1SD) and a normal group (T-score≥−1SD). Results. No correlation was observed between P1NP conentrations and kidney function. A low bone mass was seen in 64% of the RT patients. Patients in the group with low bone mass had higher pretransplant levels of P1NP compared to those in the normal group. The logistic regression analysis showed that P1NP (P=.028; OR=10.755) could be a marker of low bone mass, regardless of age, sex, glucosteroid dose and PTH (covariables in the study). Conclusions. P1NP is a good marker for estimating bone status in renal transplanted patients. Pretransplant P1NP values could be indicative of a higher risk of having a decreased bone mass (AU)

[Calculation of the left ventricular ejection fraction. Comparison between 4 different instruments]. / Determinación de la fracción de eyección del ventrículo izquierdo realizada con 4 programas de cálculo distintos.

AIM: The aim of this study was to analyse the relationship between left ventricular ejection fractions (EF) obtained using four different instruments. MATERIAL AND METHODS: Eighty-five EF values were analysed. Gated acquisition was performed with the same gammacamera (SOPHA) using 99mTc-labelled red cells. Each EF was obtained using four processing systems: NXT (SOPHA), Entegra (Gems), Odyssey (Philips) and Esoft (Siemens), always working in automated mode. The paired student's t-test, Spearman correlation and Bland-Altman analysis were used to compare methods, and Deming regression was applied. RESULTS: Mean values and standard deviations for each program were: NXT: 61 +/- 9; Entegra: 60 +/- 10; Odyssey: 60 +/- 9; Esoft: 60 +/- 10. Although no significant differences were found as a whole and the values were linearly related, the methods are not interchangeable. CONCLUSIONS: The same program should be used in the follow-up of each patient, which is now easily achievable by means of the DICOM standard.

Determinación de la fracción de eyección del ventrículo izquierdo realizada con 4 programas de cálculo distintos / Calculation of the left ventricular ejection fraction. Comparison between 4 different instruments

Objetivo. Analizar la relación existente entre los valores de la fracción de eyección (FE) del ventrículo izquierdo obtenidos mediante ventriculografía isotópica en equilibrio utilizando cuatro equipos de procesado distintos. Material y métodos. Se han estudiado 85 FE. Las adquisiciones se realizaron en una única gammacámara (Sopha®) mediante sincronización con el electrocardiograma (ECG) y utilizando hematíes marcados con Tc-99m. Se ha obtenido cada una de las FE por cuatro sistemas de procesado: NXT (Sopha®), Entegra (Gems®), Odissey (Philips®) y Esoft (Siemens®). El modo empleado por defecto era el de cálculo automático. Se aplicó la prueba de comparación de medias para datos apareados agrupando las 4 series de datos dos a dos. Asimismo, se buscó la correlación de Spearman y se aplicó la prueba de Bland-Altman para intercambiabilidad y se analizó su regresión por el método de Deming. Resultados. Los valores medios ± desviación estándar según cada programa fueron: NXT: 61 ± 9, Entegra: 60 ± 10, Odyssey: 60 ± 9, Esoft: 60 ± 10. No se han detectado globalmente diferencias, pero los 4 programas generan valores no intercambiables entre sí. Conclusiones. Aunque linealmente relacionados y sin diferencias significativas, se concluye que si se han de comparar estudios de un mismo paciente se emplee el mismo programa, cosa actualmente factible mediante el formato DICOM

Aim. The aim of this study was to analyse therelationship between left ventricular ejection fractions (EF) obtained using four different instruments.Material and methods. Eighty-five EF values were analysed. Gated acquisition was performed with the same gammacamera (SOPHA®) using 99mTc-labelled red cells. Each EF was obtained using four processing systems: NXT (SOPHA®), Entegra (Gems®), Odyssey (Philips®) and Esoft (Siemens®), always working in automated mode.The paired student’s t-test, Spearman correlation andBland-Altman analysis were used to compare methods,and Deming regression was applied. Results. Mean values and standard deviations for each program were: NXT: 61 ± 9; Entegra: 60 ± 10; Odyssey: 60 ± 9; Esoft: 60 ± 10.Although no significant differences were found as a wholeand the values were linearly related, the methods are not interchangeable. Conclusions. The same program should be used in the follow- up of each patient, which is now easily achievable by means of the DICOM standard (AU)

La amenaza bioterrorista. Aspectos básicos para el médico asistencial

Los médicos, en general, estamos poco informados sobre esta temática debido a que los antecedentes históricos son escasos y a que siempre se ha tratado con la máxima confidencialidad. Esto ha obligado a que los sistemas sanitarios de la mayoría de países occidentales hayan visto la necesidad de difundir información básica y precisa sobre este tema a aquellos médicos que potencialmente pueden detectar, en su actividad laboral, a una hipotética víctima del bioterrorismo (AU)

[Multicenter clinical, double blind, and randomized study to assess the effectiveness and safety of binifibrate versus gemfibrozil in type IIa, IIb, and IV hyperlipidemia]. / Estudio clínico multicéntrico, doble ciego y randomizado para valorar la eficacia y tolerancia de binifibrato versus gemfibrozil en hiperlipidemias tipo IIa, IIb y IV.

A multicentric, double-blind and randomized clinical study was conducted on a total of 54 patients with hyperlipidemias type IIa, IIb and IV in order to compare the effectivity and tolerance of two hyperlipemiant drugs: Binifibrate and Gemfibrozil. The treatment had a length of six months, performing clinical and analytical controls at: baseline, 1 month, 2 months, 4 months and 6 months. Both drugs showed a very good tolerance and the following results were obtained: Total cholesterol: Binifibrate -21.9%, Gemfibrozil -20.5%; Triglycerides: Binifibrate -48.6%, Gemfibrozil -43.27%; HDL: Binifibrate +18.2%, Gemfibrozil -12.8%; LDL: Binifibrate -24.3%, Gemfibrozil -22.8% VLDL: Binifibrate -48%, Gemfibrozil -43.2%; Apo A: Binifibrate +133.5%, Gemfibrozil +108.1%; Apo B: Binifibrate -59.7%, Gemfibrozil -46%. Both treatment were very effective, although the greater increase produced by Binifibrate on Chol-HDL, with a statistically significant difference versus the increase produced by Gemfibrozil, must be highlighted.

[Study of an inhibitor of lymphocyte proliferation present in spleen extracts]. / Estudio de un inhibidor de la proliferación linfocítica presente en extractos de bazo.

The spleen factor inhibiting the lymphoblastic transformation after mitogenic stimulation was concentrated thirty times by chromatography of spleen extracts. The inhibiting factor has a molecular weight of 3,000 D.

[Lipid composition of cutaneous lesions in different types of xanthomatosis]. / Estudio de la composición lipídica de las lesiones cutáneas en diferentes tipos de xantomatosis.

Twenty one specimens of cutaneous xanthomas from different types of hyperlipoproteinaemic and normolipidemic xanthomatosis were obtained and analyzed by thin layer chromatography. After separation and development, the areas were determinated by densitometry, and the results are given in percentages for each development. Acording to the results, the following data are of interest: -- Recents xanthomas have greater amount of lipids. -- Cholesterol esters (EC) are prevalent in xanthomas and in normal skin the triglycerides fraction. -- Monoenoic esters (EM) are prevalent on EC chromatography, like in normal skin. -- Finally, there are not significant variations between lipid composition of xanthomas in the different Xanthomatosis.