Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients

Murine muscle engineered from dermal precursors: an in vitro model for skeletal muscle generation, degeneration and fatty infiltration.

Skeletal muscle can be engineered by converting dermal precursors into muscle progenitors and differentiated myocytes. However, the efficiency of muscle development remains relatively low and it is currently unclear if this is due to poor characterization of the myogenic precursors, the protocols used for cell differentiation, or a combination of both. In this study, we characterized myogenic precursors present in murine dermospheres, and evaluated mature myotubes grown in a novel three-dimensional culture system. After 57 days of differentiation, we observed isolated, twitching myotubes followed by spontaneous contractions of the entire tissue-engineered muscle construct on an extracellular matrix (ECM). In vitro engineered myofibers expressed canonical muscle markers and exhibited a skeletal (not cardiac) muscle ultrastructure, with numerous striations and the presence of aligned, enlarged mitochondria, intertwined with sarcoplasmic reticula (SR). Engineered myofibers exhibited Na+- and Ca2+-dependent inward currents upon acetylcholine (ACh) stimulation and tetrodotoxin-sensitive spontaneous action potentials. Moreover, ACh, nicotine, and caffeine elicited cytosolic Ca2+ transients; fiber contractions coupled to these Ca2+ transients suggest that Ca2+ entry is activating calcium-induced calcium release from the SR. Blockade by d-tubocurarine of ACh-elicited inward currents and Ca2+ transients suggests nicotinic receptor involvement. Interestingly, after 1 month, engineered muscle constructs showed progressive degradation of the myofibers concomitant with fatty infiltration, paralleling the natural course of muscular degeneration. We conclude that mature myofibers may be differentiated on the ECM from myogenic precursor cells present in murine dermospheres, in an in vitro system that mimics some characteristics found in aging and muscular degeneration

Interaction of engineered surfaces with the living world: Ion implantation vs. osseointegration

The reaction of living tissues to foreign materials is a highly complex process that currently is insufficiently understood. Nevertheless, if specific reactions are to be promoted, this understanding is highly valuable and thus a significant research effort is being devoted to this issue. Typically, when a biomaterial is inserted in living tissue, proteins and other bio-molecules will adsorb to the surface. As this protein layer will mediate the interaction of the biomaterial with the living world, the consequent reactions will be highly dependant on this very first stage. Furthermore, different materials, i.e. surfaces, typically elicit a very different tissue response. It is commonly admitted that the primary adsorption depends heavily on the surface chemistry, surface topography and surface physical characteristics. Interactions between surface micro-topography and living cells have been widely studied, but protein specific reactions versus nano-topography have been barely explored. Ion beam modification of surfaces, which affect these key properties, can therefore be (i) a powerful tool to advance in the understanding of these nanoscale phenomena and (ii) useful as an industrial treatment of high value added medical devices. This work will explore the application of ion beam based surface treatments to cause specific reactions in hard tissue regeneration. A variety of in vitro and in vivo results are presented corresponding to ion implantation treatments promoting '' osseointegration '' or intimate binding between the biomaterial and the living tissue, without any soft tissue interlayer, and an overview of the mechanism behind is offered, i.e. among other behaviour of osteoblasts, signalling proteins as the integrins, nanotopographic parameters.Basque Government, Department of Industry, project ref. IC-2004/0027900

The effect of combined application of TGFbeta-1, BMP-2, and COLLOSS E on the development of bone marrow derived osteoblast-like cells in vitro.

Contains fulltext : 70796.pdf (publisher's version ) (Open Access)This study investigated the combined application of Transforming Growth Factor beta-1 (TGFbeta-1) and Bone Morphogenetic Protein-2 (BMP-2) to stimulate osteogenic expression in vitro. TGFbeta-1 and BMP-2 fulfill specific roles in the formation of new bone. COLLOSS E, a bone-derived collagen product containing a variety of naturally occurring growth factors, was also used. Growth factors were administered to osteoblast-like cells from rat bone marrow (RBM). Proliferation and differentiation were monitored up to 24 days, by measuring total DNA content, alkaline phosphatase activity, and calcium content. Genetic expression of a set of differentiation markers at day 7 was measured by Q-PCR. Adding BMP-2 alone induced high proliferation rates, compared to the growth factor supplemented groups, and it induced high differentiation rates, compared to the control group. Adding TGFbeta-1 combined with BMP-2, TGFbeta-1 alone, or COLLOSS E resulted in a significant decrease in proliferation rate, but an increase in differentiation rate, compared to the control group. Additive or synergistic effects of application of TGFbeta-1 and BMP-2 were not observed. The observed effects of COLLOSS E mainly resembled those of TGFbeta-1 application alone. It can be concluded that BMP-2 is the most suitable candidate for osteogenic stimulation of RBM cells in these settings

Bone cell adhesion on ion implanted titanium alloys

The authors have previously reported than ion implantation can have a significant effect on osseointegration of an implant, specially when the latter is introduced in areas of poorer bone density. These results indicate that this process is particularly suited for implant devices introduced in elderly patients or in those regions that have a poor quality of bone. The aim of this work is directed to study osteoblast adhesion on Ti alloy surfaces with different ion implantation treatments, so osseoconductive properties of several surfaces can be assessed. Polished discs of Ti–6Al–4V and Ti CP GR1 titanium alloy have been prepared and ion implanted with different species and parameters (dose and energy). Afterwards, the samples have been sterilized by UV light, inoculated with 1.5×105 human bone cells and incubated during 4 h at 37 C and 5% CO2 atmosphere. Then, once fixed and rinsed, image analysis has been used to quantify the number of cells attached to the Ti discs. On a second round of tests, cell proliferation tests have been conducted during 24, 48, 144 and 192 h, respectively. Furthermore, surface analysis techniques (e.g. AFM) have been applied to learn about the qualitative behavior, i.e. morphology, of the attached cells. Cell attachment has shown to be highly sensitive to ion implantation parameters. Although some quantitative differences have been observed, the more significant differences were qualitative. AFM analysis has shown that the star-shaped bone cells attached spread more and occupied larger surfaces like in osseointegration prone surfaces, most probably due to extracellular matrix synthesized around them, while other surfaces showed mainly large and narrow shaped or round shaped bone cells often with great cellular nucleus in the middle of the cells and little extracellular matrix around. So, ion implanted surfaces that facilitate osseointegration have been identified, in terms of initial bone cell attachment quality, where although the number of attached cells were not necessarily always larger, they tended to occupy wider areas with healthier cells.Basque Government (ETORTEK MAAB); Spanish Ministry of Science of Technology-CDTI (Neotec Ref. 20020327

La influencia de los procesos ambientales en la formación de costras en la piedra arenisca de monumentos y edificios del área de San Sebastián

En el presente artículo se han estudiado el origen de las costras   formadas en la piedra arenisca de edificios del área de San   Sebastián. Este tipo de costra, común en la mayor parte de las   piedras naturales de construcción suele deberse a la conversión   del carbonato de calcio presente en las mismas en sulfato de   calcio. Sin embargo, la ausencia de carbonato cálcico, y de otras   sales de calcio, en la piedra arenisca de San Sebastián pone en   evidencia la imposibilidad de este tipo de proceso, por lo que   debe ser otro mecanismo de formación de estas costras. La   analítica realizada para conocer las causas de dicho deteriodo   demuestra que el agente mediador en la formación y caída de la   costra es también el sulfato de calcio. Se hipotetiza aquí sobre   los mecanismos en los que se ha podido originar dicho sulfato de   calcio, siendo la lluvia ácida, la contaminación ambiental y la   actividad bacteriana los principales agentes causantes

Improved osseointegration in ion implantation-treated dental implants

Implants for knee, hip and dental part replacement are becoming increasingly used in surgery. Unfortunately, their use is sometimes accompanied by failure due to infection, inflammation, integration problems with the surrounding tissues or bone, and implant failure due to mishandling. Surface treatment, such as ion implantation, has been identified as a good candidate to modify the surface properties of the implant to significantly improve its osseointegration. This work reports on the ion implantation of light ions in commercial Ti6Al4V dental implants and subsequent osseointegration tests. Various light ions were implanted (C, N, CO, Ne) with energy ranging from 45 to 100 keV and doses up to 5×10e17 ions/cm2. Both ion-implanted and control dental implants were inserted in the tibial plateau of adult rabbits, the epiphysis and diaphysis of the tibia for the evaluation of their degree of osseointegration. After 3 months the implants were extracted and several histological sections were prepared from whole bones for evaluation of their osseointegration in the tibia. In addition, the surface of the implant, and the interface between the bone and the implant were examined by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) techniques. Some ion implantation treatments did not significantly change the performance of the dental implants relative to the untreated implants, while tests showed that the ion implantation of CO remarkably improved the osseointegration properties, i.e. the percentage of bone and implant in contact.Ministerio de Ciencia y Tecnología (España) - Proyecto MAT97-090

Wear reduction effect on ultra-high-molecular-weight polyethylene by application of hard coatings and ion implantation on cobalt chromium alloy, as measured in a knee wear simulation machine

The most important factor affecting performance and longevity of hip joint and knee implants is the wear rate of the ultra-high-molecular-weight polyethylene (UHMWPE) component. UHMWPE wear debris has been linked to complications including tissue inflammation, bone loss (osteolysis) and implant loosening. Reduction of debris has been addressed by investigating new polyethylene formulations, manufacturing and finishing processes, including surface treatments and coatings both on plastic and metallic components. There have been many studies on the effect of surface treatments and hard coatings on cobalt chromium and titanium alloys for prosthetic applications. However, most of them have used laboratory tribo-testers without much correlation to articulating movements in human joints. In this work, hard coatings (TiN and DLC) and surface treatments (nitrogen ion implantation) have been investigated as potential candidates to reduce wear of UHMWPE, when applied on the counter face cobalt chromium alloy. Also the effect of applying nitrogen ion implantation on the UHMWPE surface itself has been investigated. To evaluate wear performance a special knee wear simulator has been used with a combined rolling-sliding movement that corresponds to the most unfavourable situation in the knee. As testing materials, conventional coated and uncoated Co–Cr as well as Al2O3 femoral heads were used against UHMWPE plates to obtain comparative data. Testing was carried out at 50 MPa using distilled water at 37±2°C as a lubricant. Wear measurements on UHMWPE were made following ASTM F732 standard by weight loss measurements and also by laser profilometry. The results, up to 5 million wear cycles that represent approximately 3 years of implant life, clearly have demonstrated the beneficial effects of diamond-like carbon (DLC) and ion implantation (both on Co–Cr and UHMWPE) in reducing wear of UHMWPE. Similar values were also obtained for Al2O3 ceramic material. A wear reduction up to approximately five times was obtained by the former materials, in comparison with the uncoated control specimen. However, the ion plated TiN coating increased significantly wear on the UHMWPE. Transference of UHMWPE to the ball was very evident with the uncoated control and TiN coated Co–Cr, as observed by SEM, but with DLC and the ceramic material this occurred to a much lesser extent. Some micro-delamination at the worn surface of the UHMWPE was observed when wearing against uncoated Co–Cr, but was not clear in the rest options. Ion implantation and DLC can thus be two good candidate treatments to reduce wear of UHMWPE in cobalt chromium knee and hip joint implants in substitution of a more expensive ceramic material. This DLC has passed all biocompatible tests in accordance with FDA regulations and ISO 10993 standards for implantable devices. An example of a uniformly DLC coated femoral head and knee implant is shown.Comision Interministerial de Ciencia y Tecnología (SPAIN) -CICYT: project reference 95-0072-CT. Tratamientos Superficiales Iontech SA Industrias Quirúrgicas del Levante - IQL Dep. Education and Research of Basque Government (Project Ref. PI-1998-31

Genetic profiling of osteoblast-like cells cultured on a novel bone reconstructive material, consisting of poly-L-lactide, carbon nanotubes and microhydroxyapatite, in the presence of bone morphogenetic protein-2.

Contains fulltext : 88529.pdf (publisher's version ) (Closed access)In bone tissue engineering composite materials have been introduced, combining a degradable polymer matrix with, for instance, carbon nanotubes (CNTs) to improve mechanical properties or with microhydroxyapatite (muHA) to improve osteoconduction. The addition of bone morphogenetic protein-2 (BMP-2) can further improve the biological response to the material. However, the influence of such an elaborate composite formation on osteoprogenitor cells is unknown. To examine this, rat bone marrow (RBM) cells were cultured on porous poly-L-lactic acid and composite scaffolds, with or without added BMP-2. Cell proliferation and differentiation were studied using DNA, alkaline phosphatase and scanning electron microscopic analysis. Further, genetic profiles were examined by microarray investigation. Results showed that the composite scaffold had no significant effect on the proliferation of RBM cells, but indicated a negative effect on cell differentiation. The addition of BMP-2 also had no significant effect on the proliferation of RBM cells, but differentiation towards the osteogenic lineage was confirmed. In the arrays results, the addition of BMP-2 alone led to the expression of genes involved in (minor) inflammation. The composite scaffold, and even more distinctly the combination of the composite scaffold with BMP-2, led to the expression of genes, based on gene ontology, connected to tumorigenesis. Therefore, CNT- and muHA-containing composite materials are not recommended as a bone restorative material.1 november 201

In Vivo Magnetic Resonance Imaging of the Distribution Pattern of Gadonanotubes Released from a Degrading Poly(Lactic-Co-Glycolic Acid) Scaffold

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