RESUMEN
Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3d transition metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of a Co-based exotic superconductor is the hydrated layered cobaltate, NaxCoO2·yH2O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still a subject of intense debate, and therefore, finding a new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here, we report the discovery of superconductivity at â¼6.3 K in our newly synthesized layered compound Na2CoSe2O, in which the edge-shared CoSe6 octahedra form [CoSe2] layers with a perfect triangular lattice of Co ions. It is the first 3d transition metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low TC, this material exhibits very high superconducting upper critical fields, µ0HC2(0), which far exceeds the Pauli paramagnetic limit by a factor of 3-4. First-principles calculations show that Na2CoSe2O is a rare example of a negative charge transfer superconductor. This cobalt oxychalcogenide with a geometrical frustration among Co spins shows great potential as a highly appealing candidate for the realization of unconventional and/or high-TC superconductivity beyond the well-established Cu- and Fe-based superconductor families and opens a new field in the physics and chemistry of low-dimensional superconductors.
RESUMEN
Zirconia containing bioceramics suffer from low temperature degradation in biological and hydrothermal environments, and the presence of transition metal contamination has been shown to greatly affect the zirconia stability in different materials. In this paper, X-ray photoelectron spectroscopy was used to investigate the compositional and structural variations of different zirconia containing hip-joint bioceramics with and without transition metal stains in hydrothermal environments. Non-stained and stainless-steel-stained femoral head samples of 3 mol% Y2O3 doped tetragonal zirconia polycrystals (3Y-TZP) and zirconia-toughened alumina (ZTA) subjected to isothermal treatments in water vapor were investigated with quantifying their respective compositional XP lines. The outputs of these spectroscopic experiments revealed a significant difference in the off-stoichiometric reactions taking place at the surface of zirconia-containing ceramics in the presence and absence of transition metal contamination. The complex off-stoichiometric chemistry that occurred in the presence of metal contaminants could be interpreted in terms of defect-related chemical reactions among metal, water vapor, and oxide lattice, with a crucial contribution of the alumina phase in the transformation kinetics of ZTA.
Asunto(s)
Óxido de Aluminio/química , Materiales Biocompatibles/química , Cerámica/química , Agua/química , Itrio/química , Circonio/química , Cinética , Ensayo de Materiales , Transición de Fase , Espectroscopía de Fotoelectrones , Propiedades de Superficie , TemperaturaRESUMEN
A chemically-treated titanium alloy (Ti6Al4V) surface, able to induce hydroxyapatite precipitation from body fluids (inorganic mineralization activity), was functionalized with a polyphenolic extract from green tea (tea polyphenols, TPH). Considering that green tea polyphenols have stimulating effects on bone forming cells (biological mineralization), the aim was to test their osteoinductive behavior due to co-operation of inorganic and biological mineralization on mesenchymal stem cells KUSA A1. The functionalized surfaces were characterized by using the Folinâ»Ciocalteu method and X-ray photoelectron spectroscopy to confirm the successful outcome of the functionalization process. Two cell cultures of mesenchymal stem cells, KUSA A1 were performed, with or without osteoinductive factors. The cells and surfaces were characterized for monitoring cell viability and hydroxyapatite production: Fourier Transform Infrared Spectroscopy and Raman spectroscopy analyses showed deposition of hydroxyapatite and collagen due to the cell activity, highlighting differentiation of KUSA A1 into osteoblasts. A higher production of extracellular matrix was highlighted on the functionalized samples by laser microscope and the fluorescence images showed higher viability of cells and greater presence of osteocalcin in these samples. These results highlight the ability of polyphenols to improve cell differentiation and to stimulate biological mineralization, showing that surface functionalization of metal implants could be a promising way to improve osteointegrability.
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Materiales Biocompatibles Revestidos/farmacología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Polifenoles/farmacología , Té/química , Titanio/farmacología , Aleaciones , Línea Celular , Materiales Biocompatibles Revestidos/química , Durapatita/metabolismo , Matriz Extracelular/metabolismo , Humanos , Células Madre Mesenquimatosas/citología , Osteocalcina/biosíntesis , Polifenoles/química , Titanio/químicaRESUMEN
In this paper, an updated analytical model for the kinetics of the tetragonal to monoclinic (tâm) polymorphic transformation in ZTA composites for hip joints is proposed and discussed. The model builds upon the so-called Mehl-Avrami-Johnson (MAJ) description of transformation kinetics, which combines two overlapping processes: nucleation of monoclinic sites, and their successive growth. Dependencies on two specific factors are introduced in the model, namely the initial fraction of monoclinic polymorph as received from the manufacturer, and the presence of different types of transition-metal stains (e.g., Ti, CoCr, and Fe) on the ZTA surface. These two factors were studied because clear indications of their potential roles on the environmental stability of implantable ZTA components were found in previous phenomenological analyses of retrievals. Nucleation and growth of monoclinic domains are two key processes whose interplay decides the actual kinetics of the overall transformation process according to two main parameters: an apparent activation energy value function of time and temperature, and a nuclei growth exponent. These parameters were clearly altered by the presence of transition metal contamination, whose effect was incorporated into the model to explain exacerbations of surface degradation. In accordance with a general analytical description of transformation kinetics for isothermal or isochronal evolutions in terms of time and temperature, the modified model of the MAJ description assesses the effect of the initial monoclinic fraction. The updated model has been validated using systematic in vitro experiments, and appears to partly reconcile in vitro and in vivo data of tâm transformation discrepancies in ZTA hip components.
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Óxido de Aluminio/química , Prótesis de Cadera , Modelos Biológicos , Modelos Químicos , Circonio/química , Humanos , CinéticaRESUMEN
Understanding the intrinsic reason(s) for the enhanced tetragonal to monoclinic (tâm) polymorphic phase transformation observed on metal-stained surfaces of zirconia-toughened alumina (ZTA) requires detailed knowledge of off-stoichiometry reactions at the molecular scale. In this context, knowledge of the mechanism(s) for oxygen vacancy creation or annihilation at the material surface is a necessary prerequisite. The crucial aspect of the surface destabilization phenomenon, namely the availability of electrons and holes that allow for vacancy creation/annihilation, is elucidated in this paper. Metal-enhanced alterations of the oxygen sublattice in both Al2O3 and ZrO2 of the ZTA composite play a decisive role in accelerating the polymorphic transformation. According to spectroscopic evidences obtained through nanometer-scale analyses, enhanced annihilation of oxygen vacancies triggers polymorphic transformation in ZrO2 near the metal stain, while the overall Al2O3 lattice tends to dehydroxylate by forming oxygen vacancies. A mechanism for chemically driven "reactive metastability" is suggested, which results in accelerating the polymorphic transformation. The Al2O3 matrix is found to play a key-role in the ZrO2 transformation process, with unambiguous confirmation of oxygen and hydrogen transport at the material surface. It is postulated that this transport is mediated by migration of dissociated O and H elements at the surface of the stained transition metal as they become readily available by the thermally activated surrounding.
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Óxido de Aluminio , Prótesis de Cadera , Modelos Biológicos , Modelos Químicos , Circonio , Óxido de Aluminio/química , Óxido de Aluminio/farmacocinética , Óxido de Aluminio/farmacología , Humanos , Cinética , Circonio/química , Circonio/farmacocinética , Circonio/farmacologíaRESUMEN
The effect of frictional sliding on the surface degradation of commercially available zirconia-toughened alumina (ZTA) femoral heads was studied using a pin-on-ball wear tester under three different lubricating conditions: dry, water, and squalene. Water and squalene were employed under boundary lubrication regimes. Despite the unique (non-standard) character of this apparatus, standard loading conditions could be applied, which effectively determined dynamic friction coefficients as basic material properties. Two types of surface degradation were observed: (i) the polymorphic tetragonal-to-monoclinic (tâm) transformation of the zirconia (ZrO2) dispersoids, and (ii) the off-stoichiometry drift caused by oxygen vacancy formation within the alumina matrix. Scanning laser microscopy (SLM), Raman spectroscopy (RS), scanning electron microscopy (SEM), cathodoluminescence (CL), and X-ray photoelectron spectroscopy (XPS) were utilized to evaluate the fractions of transformed zirconia phase and the stoichiometric evolution of the oxygen sub-lattice at the surface of wear-tested ZTA components. Wear tracks on the surface of the femoral heads were only detected under dry conditions. Dry wear also showed the highest frictional forces and the most pronounced formation of oxygen vacancies among the tested conditions. Conversely, equivalent or greater amounts of the tâm transformation were observed with water and squalene lubrication when compared to the dry wear condition.
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Óxido de Aluminio/análisis , Cabeza Femoral , Prótesis de Cadera , Lubrificación , Ensayo de Materiales , Circonio/análisis , Propiedades de SuperficieRESUMEN
Polarized Raman spectroscopy was applied to evaluate the full set of stress tensor components in the wear-induced residual stress fields on two long-term (>20 y) (monolithic) alumina (Al2O3) femoral head retrievals coupled to polyethylene liners. The tensor-resolved residual stress state stored onto the Al2O3 ceramic head surface was found to retain "memory" of the sliding conditions in vivo and of the wear-induced consumption of the polyethylene counterpart. The evolution of tensor-resolved residual stress motifs in the three-dimensional space was examined, and key features, including exceptionally high shear stresses in one case, were uncovered. The effect of such a body of concurrent complications and malfunctioning are neither easily reproducible by in vitro simulations nor obviously obtainable through merely computational approaches. It is demonstrated here that our latest developments of Raman spectroscopic algorithms could contribute to link the joint performance with the micromechanical features that occur in real in vivo situations.
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Óxido de Aluminio , Prótesis de Cadera , Ensayo de Materiales , Falla de Prótesis , Artroplastia de Reemplazo de Cadera , Cerámica , Articulación de la Cadera , Polietileno , Diseño de Prótesis , Espectrometría RamanRESUMEN
Exploitation of the toughening effect induced by polymorphic phase transformation of zirconia in zirconia-toughened alumina (ZTA) requires the composite being properly designed and carefully manufactured. A sound algorithm for predicting phase stability along with strict control over manufacturing steps are required in order to prevent possible in vivo surface degradation or implant fracture. This paper is the first in a series of three monographs, which aim at: (i) statistically comparing the in vitro/in vivo phenomenology of surface-metastability for currently marketed ZTA femoral heads; (ii) refining pre-existing theoretical models for predicting in vivo zirconia phase metastability via the use of accelerated in vitro ageing experiments; and, (iii) providing a rationale for the mechanism(s) involved with the observed in vivo surface metastability. This initial paper of a series of three, which specifically deals with item (i), shows discrepancies between the levels of polymorphic phase transformation detected in ZTA retrievals and in vitro predictions, and attempts a phenomenological analysis of the reasons behind such discrepancies. Moreover, marked inhomogeneities are also found among as-manufactured components through different years of production. The phenomenology of retrievals' data suggests key roles for both the presence of metallic stain and the initial value of monoclinic volume fraction.
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Óxido de Aluminio/química , Materiales Biocompatibles/química , Circonio/química , Artroplastia de Reemplazo de Cadera , Materiales Biocompatibles/uso terapéutico , Cabeza Femoral/química , Fracturas Óseas/terapia , Prótesis de Cadera , Humanos , Cinética , Microscopía Confocal , Diseño de Prótesis , Espectrometría RamanRESUMEN
Despite the recent introduction of mass detection techniques, ultraviolet detection is still widely applied in the field of the chromatographic analysis of natural medicines. Here, a neural network cascade model consisting of nine small artificial neural network units was innovatively developed to predict the chromatographic sequence of natural compounds by integrating five molecular descriptors as the input. A total of 117 compounds of known structure were collected for model building. The order of appearance of each compound was determined in gradient chromatography. Strong linear correlation was found between the predicted and actual chromatographic position orders (Spearman's rho = 0.883, p < 0.0001). Application of the model to the external validation set of nine natural compounds was shown to dramatically increase the prediction accuracy of the real chromatographic order of multiple compounds. A case study shows that chromatographic sequence prediction based on a neural network cascade facilitated compound identification in the chromatographic fingerprint of Radix Salvia miltiorrhiza. For natural medicines of known compound composition, our method provides a feasible means for identifying the constituents of interest when only ultraviolet detection is available.
Asunto(s)
Medicamentos Herbarios Chinos/química , Redes Neurales de la Computación , Salvia miltiorrhiza/química , Cromatografía Líquida de Alta PresiónRESUMEN
BACKGROUND: Accumulating evidence has shown that chronic cerebral ischemia (CCI) is one of the major causes of vascular dementia (VD) characterized by dysregulated cholesterol homeostasis and lipoprotein disturbances. Positive value of lipid-lowering agents has been widely evaluated for the treatment of VD. In the present study, we investigated whether Daming capsule (DMC) protected against CCI-induced VD and its possible mechanisms of action. DMC is a multi-herbal formula composed of Rheum palmatum L., Cassia obtusifolia L., Salvia miltiorrhiza, and Panax ginseng C.A., which has been used to treat hyperlipidemia for years in China. METHODS: A network pharmacology method was established to reveal whether DMC contained any chemical constituent targeting CCI-related proteins. Furthermore, the potential anti-CCI effects of DMC (100 mg/kg or 200 mg/kg) administered for 30 days were investigated in vivo on rats that were subjected to permanent bilateral occlusion of the carotid arteries (2-VO). Spatial learning and memory abilities were evaluated using a Morris water maze (MWM) and morphological changes of cerebral cortex and hippocampus were assessed using hematoxylin and eosin staining. Moreover, the lipid peroxidation levels and antioxidative capabilities were measured using biochemical analysis. RESULTS: Our network pharmacology analysis revealed the existence of multiple CCI-related chemical-target interactions in DMC, suggesting a potential protective effect. An in vivo experiment verified that 200 mg/kg DMC improved cognitive deficits of 2-VO rats in the MWM test and attenuated pathological alterations in both the cerebral cortex and the hippocampus. Biochemical assays indicated that DMC decreased malondialdehyde levels and CCI-elevated superoxide dismutase activities, but increased the activities of glutathione peroxidase and catalase. CONCLUSIONS: Our findings suggested that DMC protected against cognitive dysfunction and nerve injuries caused by CCI, which is most likely related to its antioxidant actions.
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Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Trastornos del Conocimiento/tratamiento farmacológico , Demencia Vascular/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Fitoterapia , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , Arterias Carótidas , Cassia , Catalasa/metabolismo , Enfermedad Crónica , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Demencia Vascular/etiología , Demencia Vascular/metabolismo , Medicamentos Herbarios Chinos/farmacología , Glutatión Peroxidasa/metabolismo , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Panax , Ratas Sprague-Dawley , Ratas Wistar , Rheum , Salvia miltiorrhizaRESUMEN
Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted pâ=â1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.
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Curcumina/farmacología , Hemina/farmacología , Sustancias Protectoras/farmacología , Protoporfirinas/farmacología , Autofagia , Células Cultivadas , Evaluación Preclínica de Medicamentos , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/metabolismo , Humanos , Peróxido de Hidrógeno , Enfermedades Renales/tratamiento farmacológico , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/farmacologíaRESUMEN
BACKGROUND: Although inadequate intake of essential nutrient choline has been known to significantly increase cardiovascular risk, whether additional supplement of choline offering a protection against cardiac hypertrophy remain unstudied. METHODS: The effects of choline supplements on pathological cardiac hypertrophic growth induced by transverse aorta constriction (TAC) for three weeks and cardiomyocyte hypertrophy in cultured cells induced by isoproterenol (ISO) 10 µM for 48 h stimulation were investigated. Western blot analysis and real-time PCR were used to determine the expression of ANP, BNP, ß-MHC, miR-133a and Calcineurin. RESULTS: Administration of 14 mg/kg choline to mice undergone TAC effectively attenuated the cardiac hypertrophic responses, as indicated by the reduced heart weight, left ventricular weight, ventricular thickness, and reduced expression of biomarker genes of cardiac hypertrophy. This anti-hypertrophic efficacy was reproduced in a cellular model of cardiomyocyte hypertrophy induced by isoproterenol in cultured neonatal cardiomyocytes. Our results further showed that choline rescued the aberrant downregulation of the muscle-specific microRNA miR-133a expression, a recently identified anti-hypertrophic factor, and restored the elevated calcineurin protein level, the key signaling molecule for the development of cardiac hypertrophy. These effects of choline were abolished by the M3 mAChR-specific antagonist 4-DAMP. CONCLUSION: Our study unraveled for the first time the cardioprotection of choline against cardiac hypertrophy, with correction of expression of miR-133a and calcineurin as a possible mechanism. Our findings suggest that choline supplement may be considered for adjunct anti-hypertrophy therapy.
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Cardiomegalia/prevención & control , Cardiotónicos/farmacología , Colina/farmacología , Animales , Calcineurina/metabolismo , Cardiomegalia/inducido químicamente , Cardiomegalia/patología , Células Cultivadas , Regulación hacia Abajo , Marcadores Genéticos , Isoproterenol , Masculino , Ratones , Ratones Endogámicos , MicroARNs/metabolismo , Miocardio/patología , Tamaño de los Órganos , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
Flavonoid extracts are widely used for preventing and treating ischemic heart disease. However, because many flavonoid extracts have been verified to inhibit CYP2D6 the main metabolic enzyme for the majority of antiarrhythmics and beta-blockers, co-administration of flavonoid extracts with these drugs may cause adverse herb-drug interaction in clinic. Here, we evaluated 43 common flavonoids on CYP2D6 inhibition in sillico and four commercial flavonoid extracts in vivo on the pharmacokinetics and pharmacodynamics of metoprolol in rats. Surprisingly, we found that the core skeletons of flavonoids instead of their substituents determine the extent of inhibiting CYP2D6 by a flavonoid extract. Isoflavones are less likely to inhibit CYP2D6, compared with other categories of flavonoids. Consistently, co-administration of soy extract that mainly contains isoflavones did not significantly increase plasma concentration of metoprolol and alter the systolic blood pressure of rats. Our results have implication in rationally selecting flavonoid extracts for therapeutic application.
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Simulación por Computador , Citocromo P-450 CYP2D6/metabolismo , Flavonoides/farmacología , Interacciones de Hierba-Droga , Metoprolol/farmacología , Extractos Vegetales/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Flavonoides/química , Frecuencia Cardíaca/efectos de los fármacos , Isoflavonas/química , Isoflavonas/farmacología , Masculino , Metoprolol/sangre , Modelos Moleculares , Extractos Vegetales/química , Ratas , Ratas Wistar , Estándares de Referencia , Sístole/efectos de los fármacosRESUMEN
The wear behavior of alumina femoral heads was examined at follow-up periods between 7.7 and 10.7 years. Four head retrievals of the same size (28 mm in diameter) were divided into two groups with different design characteristics. Systematically using scanning electron and atomic force microscopy procedures, wear characteristics could be classified on the entire heads according to five zones with increasing degrees of wear damage (Grade 1-5), in addition to one zone of stripe wear (Grade SW). The stripe wear zone showed quite different topographical features as compared to frictionally worn zones. Furthermore, hip implants designed with different clearances are shown to lead to different wear patterns on the femoral head surface, the smaller the clearance the wider the worn surface area. Cathodoluminescence piezo-spectroscopy provided information about the residual stress state in surfaces worn to different degrees and helped clarifying the wear mechanisms on the microscopic scale.
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Óxido de Aluminio/química , Articulación de la Cadera/patología , Prótesis de Cadera , Anciano , Artroplastia de Reemplazo de Cadera , Femenino , Fricción , Humanos , Luminiscencia , Masculino , Ensayo de Materiales , Microscopía de Fuerza Atómica/métodos , Microscopía Electrónica de Rastreo/métodos , Persona de Mediana Edad , Modelos Estadísticos , Diseño de Prótesis , Falla de Prótesis , Estrés Mecánico , Propiedades de SuperficieRESUMEN
We have visualized at the nanometer scale the topological, chemical and mechanical characteristics of long-term in vivo exposed bearing surfaces of femoral heads made of monolithic alumina. Four self-mated alumina retrievals were studied, which were exposed in the human body for relatively long periods of time ranging between 7.7 and 10.7 yrs. Besides conventional morphological features, monitored by atomic force microscopy, the topographic distributions of point defects and lattice strain on the surface of the heads were systematically probed by collecting high spatially and spectrally resolved cathodoluminescence spectra from zones of different wear severity. Three types of optically active point-defect site could be detected: (i) oxygen vacancies; (ii) substitutional (aliovalent) cations; and, (iii) interstitial aluminum cations. These luminescent sites represent the main defects progressively developed in the alumina lattice during exposure in human hip joints. A clear evolution toward (environmentally driven) off-stoichiometry was found with progressing wear. Moreover, the shallow electro-stimulated optical probe also detailed the presence of lattice strain fields (of both elastic and plastic nature) stored in the very neighborhood of the bearing surface. The present spectroscopic characterizations enable substantiating important tribochemical interactions between bearing surfaces and in vivo environment as pivotal parts of progressive events of wear degradation.
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Óxido de Aluminio/química , Materiales Biocompatibles/química , Articulación de la Cadera , Oxígeno/química , Prótesis e Implantes , Estrés Mecánico , Anciano , Fuerza Compresiva , Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nanotecnología , Propiedades de SuperficieRESUMEN
BACKGROUND: As playing important roles in gene regulation, microRNAs (miRNAs) are believed as indispensable involvers in the pathogenesis of myocardial infarction (MI) that causes significant morbidity and mortality. Working on a hypothesis that modulation of only some key members in the miRNA superfamily could benefit ischemic heart, we proposed a microarray based network biology approach to identify them with the recognized clinical effect of propranolol as a prompt. METHODS: A long-term MI model of rat was established in this study. The microarray technology was applied to determine the global miRNA expression change intervened by propranolol. Multiple network analyses were sequentially applied to evaluate the regulatory capacity, efficiency and emphasis of the miRNAs which dysexpression in MI were significantly reversed by propranolol. RESULTS: Microarray data analysis indicated that long-term propranolol administration caused 18 of the 31 dysregulated miRNAs in MI undergoing reversed expression, implying that intentional modulation of miRNA expression might show favorable effects for ischemic heart. Our network analysis identified that, among these miRNAs, the prime players in MI were miR-1, miR-29b and miR-98. Further finding revealed that miR-1 focused on regulation of myocyte growth, yet miR-29b and miR-98 stressed on fibrosis and inflammation, respectively. CONCLUSION: Our study illustrates how a combination of microarray technology and functional protein network analysis can be used to identify disease-related key miRNAs.
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Regulación de la Expresión Génica/efectos de los fármacos , MicroARNs/genética , Infarto del Miocardio/genética , Propranolol/farmacología , Animales , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Masculino , MicroARNs/metabolismo , Análisis por Micromatrices , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Propranolol/uso terapéutico , Ratas , Ratas Wistar , Estudios de Validación como AsuntoRESUMEN
A simple and specific high-performance liquid chromatographic (HPLC) method was developed for the pharmacokinetic study of vitexin-2''-O-rhamnoside (VOR) in rat after intravenous administration. The plasma samples were deproteinized with methanol after addition of internal standard (i.s.) hesperidin. HPLC analysis was performed on a Diamonsil ODS C18 analytical column, using acetonitrile-0.3% formic acid (20:80, v/v) as the mobile phase with UV detection at 270 nm. The standard curve was linear over the range of 0.1070-21.41 microg/mL in rat plasma. The average extraction recovery of VOR was 97.9+/-3.1%, and the relative standard deviations (R.S.D.s) of the intra- and inter-day precisions were no more than 7.4 and 8.5%, respectively. The lower limit of quantification (LLOQ) was 0.1070 microg/mL. The AUC of VOR was proportional to the dose after intravenous administration of 15, 30, 60 and 120 mg/kg body weight, and the elimination half-life (t1/2beta), systemic clearance (Cl) and apparent volume of distribution (Vc) were not significantly different among the four doses, and all the results indicated that the pharmacokinetics of VOR in rat obeyed first-order kinetics.
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Apigenina/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Animales , Apigenina/administración & dosificación , Apigenina/sangre , Apigenina/química , Área Bajo la Curva , Calibración , Cromatografía Líquida de Alta Presión/instrumentación , Crataegus/química , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Congelación , Semivida , Hesperidina/química , Inyecciones Intravenosas , Masculino , Tasa de Depuración Metabólica , Estructura Molecular , Extractos Vegetales/química , Hojas de la Planta/química , Ratas , Ratas Wistar , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Temperatura , Factores de TiempoRESUMEN
We aim to establish a confocal spectroscopic technique able to study the features of fluorescence spectra arising from native Cr3+ impurity in polycrystalline alumina (Al2O3) as a biomaterial and to use their emission lines as microscopic probes for the characterization of residual stress fields stored in artificial hip prostheses during their implantation in vivo. As an application of the technique, we report for the first time concerning the evolution of microscopic (residual) stress fields stored on the surface and in the subsurface of N=7 retrieved Al2O3 hip joints after exposure in the human body from a few months to 19 yr. The micrometric diameter of the laser beam waist impinging on the joint surface (typically about 1 microm in lateral resolution) enables us to estimate the patterns and magnitude of residual stress with high spatial resolution, at least comparable with the grain size of the material. In addition, a selected confocal configuration for the optical probe enables minimization of the probe size along the in-depth direction. According to a statistical collection of data on the microscopic level for retrieved femoral heads in toto, a residual stress field arising from loading history in vivo during the lifetime of the Al2O3 femoral head can be revealed. Finally, an interpretation is given of microscopic wear mechanisms in Al2O3 artificial hip joints consistent with the observed evolution of surface residual stress fields on elapsed time in vivo.