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Biomedical subjects

B Vázquez

Publications and source records attributed to B Vázquez.

At least 19 recordsLinked to original sources

Biological response of new activated acrylic bone cements with antiseptic properties. Histomorphometric analysis.

The biological response to an acrylic bone cement cured with 4,4'-bis-dimethylamino benzydrol (BZN) as activator of reduced cytotoxicity and antiseptic properties, has been carried out and compared with that obtained for CMW 3 cement. Histomorphometrical data (undecalcified trichromic Goldner staining) were obtained by measuring the most significant variables at the bone-cement interface. Quantitative results of tissue response revealed that newly formed bone and connective tissue were maximum at 4 weeks whereas bone marrow increased with time of implantation for both cements. Statistical analysis (p < 0.05) showed no significant differences in newly formed bone and bone marrow with time and between both groups, however, connective tissue significantly decreased between 4 weeks and 12 weeks for BZN cement, and between 12 weeks and 24 weeks for CMW3. By comparing both cements at each time, lower significant percentage of connective tissue at the bone-cement interface of the BZN cement, was obtained at 12 and 24 weeks, however, a very low amount of connective tissue was found for both cements. All the results indicate that the new activated system could be applied clinically in a relatively short time, after the corresponding preclinical study.

Animals↗

Acrylic bone cements with bismuth salicylate: Behavior in simulated physiological conditions.

In a previous work, we reported the development of acrylic bone cement formulations for application in percutaneous vertebroplasty, by using bismuth salicylate (BS) as the radiopaque agent. Our objective was to obtain high radiopacity along with a therapeutical effect produced by the release of salicylic acid in situ. To follow that study, the setting kinetics and static and dynamical mechanical properties of the BS cements were studied in simulated physiological conditions. Moreover, radiopacity after various times of immersion in saline and the wettability of the cements surfaces were determined. The study finished with the analysis of the biological response. From the results, it can be concluded that physiological conditions did not affect negatively to the cements performance, since all BS-loaded cements fulfilled the ISO standard requirements. Radiopacity of the formulations was maintained over time and cements with BS were found to be biocompatible.

Acrylates↗

Injectable self-curing bioactive acrylic-glass composites charged with specific anti-inflammatory/analgesic agent.

Injectable bioactive acrylic formulations based on poly(methyl methacrylate) (PMMA) and different amounts of bioactive glasses in the system SiO2-CaO-Na2O-P2O5 have been prepared in the presence of the anti-inflammatory analgesic drug fosfosal, the sodium salt of 2-phosphonoxibenzoic acid, to be used in minimally invasive surgery. The injectability of the formulations evaluated according to the established protocol was around 80%. The experimental formulations provided maximum temperatures in the range 50-60 degrees C, which were lower than those of commercial acrylic bone cements currently used in percutaneous vertebroplasty (PVP). Residual monomer content of any formulation was inferior to 5%. Compressive yield strength of dry specimens was in the range 80-95 MPa, but it decreased after immersion in SBF to values in the range 30-50 MPa, due to the dissolution of the bioactive glasses and the drug in the medium. The release of fosfosal was evaluated in vitro (pH = 7.0). The release profile against time obtained from a PMMA cement was quasi-linear and the 80% of the initial amount of drug was released in 175 h. However, for bioactive cements, the 80-100% of the fosfosal charged was released in approximately 48 h, due to the dissolution of the glasses in the medium. Values of weight loss of the cements determined gravimetrically ranged between 16% and 26% depending on the initial amount of fosfosal, i.e. 20 or 30 wt%, respectively. The weight loss and the water uptake were simultaneous processes, and values of hydration degree were around 10-14%. The formation of an apatite-like layer was detected on the surface of the cements at different periods of time depending on the composition of the bioactive glasses. The cements containing the glasses with P2O5 produced the growth of the apatite layer in shorter periods of time. The presence of fosfosal accelerated the precipitation of this layer independently on the glasses. The in vivo biocompatibility studied by intramuscular implantation in rats showed the absence of an anti-inflammatory response and a fibrous layer around the implant for the cement prepared with PMMA/fosfosal which is attributed to the therapeutic action of fosfosal acting in situ. The response to cements prepared with bioactive glasses and fosfosal showed a mild inflammatory reaction with the formation of the typical fibrous capsule around the implanted material.

Analgesics↗

Anti-inflammatory cytokines induce lipopolysaccharide tolerance in human monocytes without modifying toll-like receptor 4 membrane expression.

Toll-like receptor 4 (TLR4) participates in innate immunity by detecting lipopolysaccharides (LPS) of Gram-negative bacterial cell walls. TLR4 macrophage expression in mice is modulated by LPS. This fact constitutes, at least partially, the molecular basis for LPS tolerance. Very recently, the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, has been described on TLR4 membrane expression of human monocytes. IFN-gamma up-regulates TLR4 expression and antagonizes the LPS-induced TLR4 down-regulation. These data prompted us to study the expression of membrane TLR4 in human mono- cytes in which LPS tolerance was induced by LPS and by anti-inflammatory cytokines [interleukin-10 (IL-10) and transforming growth factor beta1 (TGFbeta1)]. Data concerning this latter model, and more specifically, the effect of anti-inflammatory cytokines over TLR4 expression, are not available at present. We show here that membrane TLR4 expression in human monocytes falls after LPS exposure. The effect was prolonged for 12 h, but then expression returned to normal levels. The incubation of human monocytes with IL-10, TGFbeta1 or a mixture of both induces no alterations in membrane TLR4 expression. However, these cytokines are able to substitute the tolerizing LPS exposure in order to induce LPS tolerance. Our data help to achieve a better understanding of the way cytokines control the cellular expression of TLR.

Adult↗

Biocompatibility and other properties of acrylic bone cements prepared with antiseptic activators.

Acrylic bone cements prepared with activators of reduced toxicity have been formulated with the aim of improving the biocompatibility of the final material. The activators used were N,N-dimethylaminobenzyl alcohol (DMOH) and 4,4'-dimethylamino benzydrol (BZN). The toxicity, cytotoxicity, and antiseptic action of these activators were first studied. DMOH and BZN presented LD50 values 3-4 times higher than DMT, were less cytotoxic against polymorphonuclear leucocytes, and possessed an antimicrobial character, with a high activity against the most representative microorganisms involved in postoperative infections. The properties of the acrylic bone cements formulated with DMOH and BZN were evaluated to determine the influence of these activators on the curing process and the physicochemical characteristics of the cements. A decrease of the peak temperature was observed for the curing with DMOH or BZN with respect to that of one commercially available formulation (CMW 3). However, residual monomer content and mechanical properties in tension and compression were comparable to those of CMW 3. The biocompatibility of acrylic bone cements containing DMOH or BZN was studied and compared with CMW 3. To that end, intramuscular and intraosseous implantation procedures were carried out and the results were obtained from the histological analysis of the surrounding tissues at different periods of time. Implantation of rods of cement into the dorsal muscle of rats showed the presence of a membrane of connective tissue, which increased in collagen fibers with time of implantation, for all formulations. The intraosseous implantation of the cements in the dough state in the femur of rabbits, revealed a higher and early osseous neoformation, with the presence of osteoid material surrounding the rest of the cured material, for the cement prepared with the activator BZN in comparison with that obtained following the implantation of the cement cured with DMOH or DMT (CMW 3).

Alcohols↗

Elimination of barium sulphate from acrylic bone cements. Use of two iodine-containing monomers.

The aim of this work is to present a new approach to joint arthroplasty failure related to bone cement mantle. As barium sulphate is considered one of the main causes of mechanical weakness in the cement, we substituted this inorganic radiopacifier of the solid component for radiopaque monomers in the liquid component. We obtained two different cements, one containing 5 vol% 2-[2',3',5'-triiodobenzoyl] ethyl methacrylate (TIBMA) and the other containing 3,5-diiodine salicylic methacrylate (DISMA). In both cases, the mechanical properties of these new cements were better than those of the barium sulphate-containing cement. The radiopacity obtained was comparable to that of the aforementioned cement and all the samples showed good biocompatibility.

Barium Sulfate↗

New acrylic bone cements conjugated to vitamin E: curing parameters, properties, and biocompatibility.

Acrylic bone cement formulations with antioxidant character were prepared by incorporation of a methacrylic monomer derived from vitamin E (MVE). Increasing concentrations of this monomer provided decreasing peak temperature values, ranging from 62 to 36 degrees C, and increasing setting time with values between 17 and 25 min. Mechanical properties were evaluated by compression and tension tests. Compressive strength of the new formulations were superior to 70 MPa in all cases. The cement containing 25 wt % MVE, however, showed a significant decrease in tensile properties. Biocompatibility of the new formulations was studied in vitro. The analysis of the effect of leachables from cements into the media showed continued cell proliferation and cell viability with a significant increase for the cement containing 15 wt % MVE. This formulation also showed a significant increase in cellular proliferation over a period of 7 days as indicated by the Alamar Blue test. The cells were able to differentiate and express phenotypical markers in presence of all materials. A significant increase in alkaline phosphatase activity was observed on the cements prepared in presence of 15-25 wt % MVE compared with PMMA. Morphological assessment showed that the human osteoblast (HOB) cells were able to adhere, retain their morphology, and proliferate on all the cements.

Acrylates↗

Mechanical performance of acrylic bone cements containing different radiopacifying agents.

The effect that three different radiopacifying agents, two of them inorganic (BaSO4, ZrO2) and one organic (an iodine containing monomer, IHQM) have on the static and dynamic mechanical properties of acrylic bone cements was studied. Compressive and tensile strength, fracture toughness and fatigue crack propagation were evaluated. The effect of the inorganic fillers depends on their size and morphology. In relation to the radiolucent cement, the addition of zirconium dioxide improved significantly the tensile strength, the fracture toughness and the fatigue crack propagation resistance. In contrast, the addition of barium sulphate produced a decrease of the tensile strength, but did not affect the fracture toughness and improved the crack propagation resistance. When the iodine containing monomer was used, although the tensile strength and the fracture toughness increased, the fatigue crack propagation resistance remained as low as it was for the radiolucent cement.

Barium Sulfate↗

Acrylic-phosphate glasses composites as self-curing controlled delivery systems of antibiotics.

New antibiotic delivery systems based on self-hardening methyl methacrylate (MMA)/polymethyl methacrylate (PMMA) systems and phosphate glasses (PG) in the system P(2)O(5)-CaO-Na(2)O have been developed. Self-curing formulations were prepared by mixing the solid component containing PMMA beads, different proportions of PG (30-70 wt %) and vancomycin (5 wt %) as antibiotic, with the liquid component made of MMA monomer. Dough and setting times increased with the content of PG but peak temperature decreased to values well below to guarantee the chemical stability of the antibiotic drug, gentamicin or vancomycin. Mechanical properties of the PMMA/PG composites were evaluated in compression test giving rise to values of compressive strength in the range of 100 MPa. The release of vancomycin was analyzed in vitro by immersion of samples in phosphate buffer of pH=7.4. Release profiles were influenced by the content of PG present in the cement. An initial burst of drug release was observed in all cases. The composites with 70 wt % PG released nearly the total amount of drug loaded in a period of 45 days, and those containing 60 wt % PG released the 70% of the vancomycin in the same period of time. However, either the control of the composite with 30 wt % PG released only the 30% of the drug in 10-15 days. The surface of the drug-loaded composites before and after release experiments was analyzed by ESEM. The deposition of some aggregates at certain points of the surface was detected for the specimens immersed in buffer phosphate after 45 days. This material was characterized by FTIR and Raman spectroscopy as an amorphous phosphate formed by calcium ortho and pyrophosphates, and indicates an interaction between the hydrated layer at the place of the glass and the surrounding medium.

Journal Article↗

Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease.

We have recently developed a transmissible vaccine to immunize rabbits against myxomatosis and rabbit haemorrhagic disease based on a recombinant myxoma virus (MV) expressing the rabbit haemorrhagic disease virus (RHDV) capsid protein [Bárcena et al. Horizontal transmissible protection against myxomatosis and rabbit haemorragic disease using a recombinant myxoma virus. J. Virol. 2000;74:1114-23]. Administration of the recombinant virus protects rabbits against lethal RHDV and MV challenges. Furthermore, the recombinant virus is capable of horizontal spreading promoting protection of contact animals, thus providing the opportunity to immunize wild rabbit populations. However, potential risks must be extensively evaluated before considering its field use. In this study several safety issues concerning the proposed vaccine have been evaluated under laboratory conditions. Results indicated that vaccine administration is safe even at a 100-fold overdose. No undesirable effects were detected upon administration to immunosuppressed or pregnant rabbits. The recombinant virus maintained its attenuated phenotype after 10 passages in vivo.

Animals↗

The increase of IFN-gamma production through aging correlates with the expanded CD8(+high)CD28(-)CD57(+) subpopulation.

The use of flow cytometry to detect intracellular cytokines at the single cell level has the potential to quantify cytokine production together with the possibility of phenotypic identification of the cell population concerned. The unbalanced presence of intracellular cytokines produced by T cells has been recognized in some pathological conditions. To better address this issue, we studied the production of IFN-gamma and IL-4 in CD4(+) and CD8(+high) T cells in healthy donors of a broad range of age (17-62 years). Given that an increase of IFN-gamma and IL-4 with aging had been reported by some authors in healthy controls, we have performed a multivariate analysis to assess the intrinsic role of aging or of other external factors, such as chronic antigenic exposures (i.e., viruses), over the cytokine production of phenotypically characterized T cells. In this respect we show that, mainly in CD8(+high) T cells, the production of IFN-gamma is directly correlated with age. Besides, the cytokine production correlates with the CD8(+high)CD28(-)CD57(+) T-cell population, which we have recently reported elevated in aged individuals. Perhaps this T-cell subpopulation plays a regulatory role as a Tc1 response in aging individuals.

Adolescent↗

Chemiluminescence detection of nine corticosteroids in liver.

A method for the determination of nine corticosteroids in bovine liver was developed. The liquid-liquid extraction method consisted in the addition of sodium hydroxide to the tissue sample followed by extraction with ethyl acetate. After centrifugation, the extract was evaporated to dryness and the residue redissolved in acetonitrile. The removal of fats was performed with n-hexane and the acetonitrile layer was evaporated. Afterwards, analysis of the extracts was performed using high-performance liquid chromatography with chemiluminescence detection employing luminol as reagent. The recovery curves, performed at five spiking levels (different for each corticosteroid), showed that recoveries of at least 70.5% could be obtained from liver. The chemiluminescence detection gave satisfactory results with respect to sensitivity, and the LOQ ranged from 0.13 ppb for prednisolone to 8.40 ppb for betamethasone. The maximum mean RSD was 4.8% and 7.3% for intra- and inter-day assay, respectively.

Animals↗

Hydrophilic polymers derived from vitamin E.

Vitamin E containing copolymers for biomedical applications was obtained by copolymerization reaction of vitamin E methacrylate (VEMA) with 2-hydroxyethyl methacrylate (HEMA), N,N-dimethyl acrylamide (DMA) or vinyl pyrrolidone (VP), in different experiments. High molecular weight copolymers prepared by free radical reactions initiated by azobisisobutironitrilo, AIBN, present a random distribution of vitamin E derivatives along the macromolecular chains, and the average composition depends on the initial composition of the reaction medium. The relative flexibility of the polymeric systems was analyzed measuring the glass transition temperature of copolymeric sequences and that of the pure alternating diad (Tg12) obtained by the application of the treatments proposed by Johnston and Barton to all the systems. Tg12 was higher than the average T of both homopolymers (Tg) for the VEMA-HEMA system, Tg12 was lower than Tg for the VEMA-DMA system and Tg12 was similar to Tg for the VEMA-VP system. VEMA-HEMA copolymers gave rise to hydrogels in water, acidic and alkaline media. VEMA-DMA copolymers gave rise to hydrogels in acidic medium and dissolved in water and alkaline medium. VEMA-VP copolymers were soluble in all media. The swelling of all the hydrogels fit a second order kinetics. A VEMA-HEMA hydrogel was selected for in vivo experiments in order to study the influence of vitamin E on the regeneration process of Achilles tendon. The polymeric derivatives of vitamin E stimulated the regenerative process as a consequence of the antiaging effect in the local area of application.

Acrylamides↗

Horizontal transmissible protection against myxomatosis and rabbit hemorrhagic disease by using a recombinant myxoma virus.

We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field strain of myxoma virus (MV). The recombinant viruses expressed the RHDV major capsid protein (VP60) including a linear epitope tag from the transmissible gastroenteritis virus (TGEV) nucleoprotein. Following inoculation, the recombinant viruses induced specific antibody responses against MV, RHDV, and the TGEV tag. Immunization of wild rabbits by the subcutaneous and oral routes conferred protection against virulent RHDV and MV challenges. The recombinant viruses showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunization of contact uninoculated animals.

Animals↗

Hydrophilic polymers derived from vitamin E.

Vitamin E containing copolymers for biomedical applications were obtained by copolymerization reaction of vitamin E methacrylate (VEMA) with 2-hydroxyethyl methacrylate (HEMA), N,N-dimethyl acrylamide (DMA) or vinyl pyrrolidone (VP), in different experiments. High molecular weight copolymers prepared by free radical reactions initiated by azobisisobutironitrilo, AIBN, present a random distribution of vitamin E derivatives along the macromolecular chains, and the average composition depends on the initial composition of the reaction medium. The relative flexibility of the polymeric systems was analyzed measuring the glass transition temperature of copolymeric sequences and that of the pure alternating diad (Tg12) obtained by the application of the treatments proposed by Johnston and Barton to all the systems. Tg12 was higher than the average Tg of both homopolymers (Tg) for the VEMA-HEMA system, Tg12 was lower than Tg for the VEMA-DMA system and Tg12 was similar to Tg for the VEMA-VP system. VEMA-HEMA copolymers gave rise to hydrogels in water, acidic and alkaline media. VEMA-DMA copolymers gave rise to hydrogels in acidic medium and dissolved in water and alkaline medium. VEMA-VP copolymers were soluble in all media. The swelling of all the hydrogels fit a second-order kinetics. A VEMA-HEMA hydrogel was selected for in vivo experiments in order to study the influence of vitamin E on the regeneration process of Achilles tendon. The polymeric derivatives of vitamin E stimulated the regenerative process as a consequence of the antiaging effect in the local area of application.

Animals↗

Hydrophilic acrylic biomaterials derived from vitamin E with antioxidant properties.

Hydrogels based on polymeric derivatives of vitamin E for biomedical purposes have been prepared by copolymerization reaction of the alpha-tocopheryl methacrylate (V) with 2-hydroxyethyl methacrylate (H) in a range of composition between 5-20 wt % of V. The swelling behavior of the hydrogels in water, alkaline, and acidic media showed a slight decrease in the equilibrium water content with the content of V in the copolymer although in all cases it was superior to an EWC > 20%. The diffusion mechanism followed a Fickian behavior in all media. The values of the diffusion coefficients were in the range 2.5-1.6 10(-7) cm2/s. The states of water in the hydrogels were determined by DSC. A decrease in the content of freezing water was obtained with the V content for all media, and for all compositions lower values of freezing water were obtained in acidic or basic pHs than in distilled water. The copolymeric xerogels, analyzed by contact angle measurements, deviated from those expected taking into consideration those of the homopolymers and the average fraction of the monomers in the copolymer. The polar contribution dropped with the introduction of a small content (4 wt %) of the vitamin E-containing monomer, and it reached a value similar to that of poly-V for a composition of 49 wt % of V in the copolymer. This behavior is accounted for by the segregation of the macromolecular chains of both kinds of monomers, due mainly to differences in their polarity, molecular weights, and the reactivity of both monomers. Finally, thermogravimetric analysis showed a higher thermal (antioxidant) stability of the poly-V with respect to poly-H, giving rise to a residue of 18 wt %. The V-containing copolymers also showed an improved stability (antioxidant behavior), indicating the possibility of the V unit's interfering with the oxidative process, based on free-radical species, and, therefore, with the aging process at the cellular level.

Algorithms↗

Modified acrylic bone cement with high amounts of ethoxytriethyleneglycol methacrylate.

One cause of arthroplasty failure is the brittle mechanical behavior of bone cements. However, the improvement of cement formulations must also be accompanied by the maintenance of a wide variety of characteristics. New bone cements were obtained by the substitution of high percentages, up to 60% (v/v), of methyl methacrylate (MMA) by a higher molecular weight and more hydrophilic monomer, ethoxytriethyleneglycol methacrylate (TEG). The essential advantages of these materials were the decrease of maximum temperature together with a decrease in the residual monomer content with respect to conventional cement formulations. The water absorption process obeyed diffusion laws and the equilibrium water content increased by the introduction of higher percentages of the hydrophilic component. This characteristic had an appreciable effect on the viscoelastic behavior analyzed by DMTA. These modified bone cements had reduced polymerization shrinkage and similar levels of porosity. Tensile test revealed that the introduction of TEGMA gave rise to an important modification of the mechanical behavior, with a noticeable increase in the fracture strain. This fact was also confirmed by means of the analysis of the fracture surfaces by SEM.

Absorption↗

Radiopaque acrylic cements prepared with a new acrylic derivative of iodo-quinoline.

A novel iodine-containing methacrylate, 2,5-diiodo-8-quinolyl methacrylate, has been synthesized and used in the preparation of acrylic radiopaque cements. The effect of incorporation of this monomer to the self-curing resins, on the curing parameters, swelling behaviour and mechanical properties was studied. The incorporation of the radiopaque compound 2,5-diiodo-8-hydroxyquinoline to the solid phase was also carried out for comparative experiments. A decrease in the peak temperature and an increase in the setting time was observed with the addition of the radiopaque monomer, however, the curing parameters did not appreciably change with the addition of the radiopaque compound to the solid phase. Swelling of the modified cements was in the same range as that of the radiolucent cement; however, the diffusion coefficients calculated according to the Fick's law were higher for the iodine-containing materials. The addition of 5 wt% of the iodine-containing methacrylate provided a significant increase in the tensile properties with respect to either control radiolucent formulations or BaSO4-containing formulations. Biocompatibility of the modified cements was studied by implantation of rods of the cements into rats and histological analysis of the surrounding tissue.

Animals↗