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Biomedical subjects

J A Méndez

Publications and source records attributed to J A Méndez.

13 recordsLinked to original sources

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↗

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↗

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↗

Glutamate activates PP125(FAK) through AMPA/kainate receptors in Bergmann glia.

Glial glutamate receptors are likely to play a role in plasticity, learning, and memory and in a number of neuropathologies. An enhanced glutamate-dependent tyrosine phosphorylation has been detected in such processes. Using primary cultures of chick Bergmann glia cells and chick cerebellar slices, we addressed whether glial glutamate receptors can activate the nonreceptor tyrosine kinase pp125 focal adhesion kinase (pp125(FAK)). A dose- and time-dependent tyrosine phosphorylation of pp125(FAK) was found in both preparations upon glutamate treatment. This effect was mediated through alpha-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA)/kainate (KA) receptors, as shown by its inhibition by the specific antagonists 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7- sulfonamide (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the lack of effect of metabotropic agonists. FAK tyrosine phosphorylation was dependent on phosphatidylinositol 3-kinase activity. As expected, an increase in pp125(FAK) catalytic activity was found upon glutamate treatment. Immunprecipitation experiments demonstrated that FAK associates with ionotropic glutamate receptors. Taken together, these results suggest a role for glial glutamate receptors in cytoskeletal rearrengments and focal adhesion contact formation and provide new insight into the signaling transactions elicited by this neurotransmitter in glial cells.

Animals↗

Alloantibody from a patient with severe von Willebrand disease inhibits von Willebrand factor-FVIII interaction.

The aim of this study was to analyze the ability of an alloantibody from a patient with severe von Willebrand disease (vWD) to interfere with the vWF domain for FVIII, to inhibit factor VIII (FVIII), and to compare it with a rabbit polyclonal antibody. The vWF domain for binding to FVIII was assayed by a method previously described but using recombinant FVIII (r-FVIII, Kogenate), which contains no vWF, instead of Hemofil M (HM). Rabbit or human antibodies towards FVIII (FVIII-Ab) were analyzed using microtiter wells with immobilized r-FVIII through a monoclonal anti-FVIII antibody and an ELISA method. IgG from plasma of a patient with hemophilia A and FVIII inhibitor was used as a positive control. Normal human and rabbit IgGs were included as negative controls. Human vWD alloantibody IgG and the rabbit anti-vWF antibody IgG reacted with immobilized normal vWF, inhibiting its binding to r-FVIII in a dose-dependent manner, which suggests that it is specific. Normal human IgG fraction, as well as nonspecific rabbit IgG, did not interfere with this binding at all. The monoclonal antibody used in this assay to immobilize vWF did not alter this interaction at all. Human vWD alloantibody IgG and the rabbit antibody against vWF showed a partial inhibitory activity to plasma FVIII as well as r-FVIII. The inhibition reached a plateau with residual FVIII activity. FVIII-Ab were not detected in human alloantibody or in rabbit antibody preparations. In contrast, hemophiliac FVIII inhibitor showed FVIII-AB. This human vWD alloantibody behaves like polyclonal heterologous antibodies, and their inhibition of FVIII seems to be nonspecific due to a steric hindrance mechanism provided that both have no FVIII antibodies.

Animals↗

Twofold symmetry of human fibrinogen proved at the beta chain distal domains by monoclonal-immunoelectron microscopy and image analysis.

Using a murine antibody (F7) specific for the C-terminal domain of the beta chain of human fibrinogen combined with electron microscopy and image analysis, we show unequivocally that the epitopes for F7 are at the distal nodules of fibrinogen, equidistant from the center of the molecule and arranged not colinearly with the long axis of the molecule but at opposite sides of it, i.e., following twofold symmetry. Thus, given the monoclonality of the immunochemical probe used and the dimeric nature of the fibrinogen molecule, we can conclude that the distal domains of the two beta chains are arranged in the same manner as these epitopes and, therefore, that the fibrinogen molecule has twofold symmetry. This symmetry pattern found here for F7 is the same as that found recently for the platelet fibrinogen receptor binding sites [Weisel, J. W., Nagaswami, C., Vilaire, G., & Bennett, J. S. (1992) J. Biol. Chem. 23, 16637-16643], located almost certainly at the C-terminal end of the gamma chains, and gives further support to the most accurate model of fibrinogen available so far. We discuss the consequences of this symmetry pattern and of the molecular rigidity of fibrinogen in the actual models of fibrin polymerization and platelet aggregation and adhesion.

Amino Acid Sequence↗

Case report: ultrastructure of mature neurogenic implants from ovarian immature teratoma.

An ultrastructural study of mature (grade O) neurogenic peritoneal implants from an ovarian immature teratoma grade I is presented. The presence of different types of neuroectodermal cells challenges the current terminology of this lesion, which implies a single proliferating cell type. The ultrastructural features were indicative of maturity in all cell lines and even the neurons exhibited well formed synapses. Marked cytoplasmic fibrillary change, similar to that found in central nervous system gliosis, was observed in the astrocytes. The ependymal cells had abnormal cilia with an altered configuration and number of microtubules.

Astrocytes↗

[Urothelial tumor of the renal pelvis in horseshoe kidney].

The authors describe a case of tumour of transitional cells in patient with a horseshoe-shaped kidney, the suspected diagnosis of which was reached with the aid of a selective cinearteriography. They stress the low incidence of the same in the literature consulted which reveals the importance of studying the patients with this malformation in an attempt to prevent complications and in particular, to make an early diagnosis of a possible malignant transformation.

Carcinoma, Transitional Cell↗

[Evaluation of microtechnics in the study of coagulation].

Coagulation tests were performed in 20 children admitted to the Centro Médico Nacional, through the use of two different techniques: the classical microtechniques through which, blood samples are obtained by direct venous puncture and the microtechnique or capillary, where capillary puncture and micropipettes are used. We believed the latter would be of great usefulness, specially in very small babies. A statistical analysis showed trustworthiness in the microtechnical method, absence of lineal correlation between the two and it was seen that sensibility to detect changes in measurements is higher through the use of capillary puncture. A simple procedure is required for the microtechnique to obtain th sample which should not be stored in refrigeration and must be processed within two hours to avoid changes and mistakes in the interpretation. If such requirements are covered, the results obtained with this technique are of the highest quality and trustworthiness and show the advantage that they may be repeated as often as necessary to obtain the most adequate diagnosis of coagulation.

Blood Coagulation Factors↗