Carmen Quintana

Spanish National Research Council, Madrid, Madrid, Spain

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Publications (28)66.76 Total impact

  • Carmen Quintana, Lucía Gutiérrez
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    ABSTRACT: The concentration of iron in the brain increases with aging. Furthermore, it has also been observed that patients suffering from neurological diseases (e.g. Parkinson, Alzheimer...) accumulate iron in the brain regions affected by the disease. Nevertheless, it is still not clear whether this accumulation is the initial cause or a secondary consequence of the disease. Free iron excess may be an oxidative stress source causing cell damage if it is not correctly stored in ferritin cores as a ferric iron oxide redox-inert form. Both, the composition of ferritin cores and their location at subcellular level have been studied using analytical transmission electron microscopy in brain tissues from progressive supranuclear palsy (PSP) and Alzheimer disease (AD) patients. Ferritin has been mainly found in oligodendrocytes and in dystrophic myelinated axons from the neuropili in AD. In relation to the biomineralization of iron inside the ferritin shell, several different crystalline structures have been observed in the study of physiological and pathological ferritin. Two cubic mixed ferric-ferrous iron oxides are the major components of pathological ferritins whereas ferrihydrite, a hexagonal ferric iron oxide, is the major component of physiological ferritin. We hypothesize a dysfunction of ferritin in its ferroxidase activity. The different mineralization of iron inside ferritin may be related to oxidative stress in olygodendrocites, which could affect myelination processes with the consequent perturbation of information transference.
    Biochimica et Biophysica Acta 05/2010; 1800(8):770-82. DOI:10.1016/j.bbagen.2010.04.012 · 4.66 Impact Factor
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    ABSTRACT: Liver, spleen and heart tissues of DBA/2 Hfe knockout mice have been characterised by low temperature AC magnetic susceptibility measurements together with Transmission Electron Microscopy (TEM) and Selected Area Electron Diffraction in order to investigate the chemical iron speciation in a murine model of iron overload diseases. With emphasis on ferritin-like species, the temperature dependent in-phase and out-of-phase susceptibility profiles agree with the elemental analysis in that, in this model, iron accumulation takes place in the hepatic tissue while in the spleen and heart tissues no differences have been observed between knockout and wild type animals. The comparison of the magnetic properties between perfused and non-perfused liver tissues has made it possible to estimate the magnetic contribution of usually present blood remains. The TEM observations reveal that, besides the isolated ferritins and ferritin-containing lysosomes-siderosomes present in the hepatocytes, other iron deposits, of heterogeneous size, morphology and crystalline structure (haematite and/or goethite), are present in the cytoplasm, near the membrane, and in extracellular spaces.
    Biochimica et Biophysica Acta 05/2009; 1792(6):541-7. DOI:10.1016/j.bbadis.2009.03.007 · 4.66 Impact Factor
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    ABSTRACT: We show that Fe nanoislands capped with Al, Pd, and Pt protecting layers include an alloy at the interface with the capping layer, which explains the previously known capping layer dependence on the interparticle magnetic coupling. Vibrating sample magnetometry results, for instance, are evidencing a reduction in the magnetization measured under a magnetic field of 15 mT, which is larger in the case of the Al capping and which is due to the presence of a magnetically dead interface alloy. This reduction is also observed at the atomic level using x-ray magnetic circular dichroism measurements, showing a capping layer dependence of the Fe magnetic-moment reduction that is similar for the Pd and Pt capping, and stronger for the Al capping. The trend in the magnetic properties as a function of the capping layer is explained in the light of x-ray photoemission spectroscopy results that evidence the formation of alloys at the interface between the Fe nanoislands and the capping layers. The present results highlight the strong influence of interface alloying in systems of reduced dimensionality. In particular, it is shown that the magnetic properties are strongly affected at both the atomic and macroscopic level. Support from the SRS staff during the XMCD experiments is greatly acknowledged. Financial support from the Spanish Ministerio de Ciencia y Tecnología, under Contract No. MAT2005-05524-C02 is acknowledged. Y. H. also acknowledges financial support from the “Ramón y Cajal” program, Consejo Superior de Investigaciones Científicas (CSIC) and Comunidad Autónoma de Madrid (CAM) under Project No. S-505/MAT/0194 NANOMAGNET. Peer reviewed
    Physical Review B 04/2008; 78:104403. DOI:10.1103/PhysRevB.78.104403 · 3.66 Impact Factor
  • C Quintana
    Journal of Alzheimer's disease: JAD 10/2007; 12(2):157-60. · 3.61 Impact Factor
  • Carmen Quintana
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    ABSTRACT: Using analytical microscopies we have observed an increase of Fe(2+) iron-induced oxidative stress inside pathological ferritin (Ft). This finding, together with the presence of Ft in myelinated axons associated with oligodendrocyte processes and myelin sheet fraying, suggests that a dysfunction of ferritin (a ferritinopathy) may be the non-specific aging-dependent pathogenic event responsible for neurodegenerative disease.
    Mini Reviews in Medicinal Chemistry 10/2007; 7(9):961-75. DOI:10.2174/138955707781662654 · 3.19 Impact Factor
  • Carmen Quintana
    Journal of Alzheimer's disease: JAD 08/2007; 11(4):465-7; discussion 469-70. · 3.61 Impact Factor
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    ABSTRACT: Amyloid deposits are one of the hallmarks of Alzheimer's disease. Recent studies, in transgenic mice modeling Alzheimer's disease showed that, using in vivo, contrast agent-free, MRI, thalamic amyloid plaques are more easily detected than other plaques of the brain. Our study evaluated the characteristics of these thalamic plaques in a large population of APP/PS1, PS1 and C57BL/6 mice. Thalamic spots were detected in all mice but with different frequency and magnitude. Hence, the prevalence and size of the lesions were higher in APP/PS1 mice. However, even in APP/PS1 mice, thalamic spots did not occur in all the old animals. In APP/PS1 mice, spots detection was related to high iron and calcium load within amyloid plaques and thus reflects the ability of such plaque to capture large amounts of minerals. Interestingly, calcium and iron was also detected in extra-thalamic plaques but with a lower intensity. Hypointense lesions in the thalamus were not associated with the iron load in the tissue surrounding the plaques, nor with micro-hemorrhages, inflammation, or a neurodegenerative context.
    Neurobiology of aging 07/2007; 30(1):41-53. DOI:10.1016/j.neurobiolaging.2007.05.018 · 4.85 Impact Factor
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    ABSTRACT: Neurodegenerative diseases induce morphological and chemical alterations in well-characterized regions of the brain. Understanding their pathological processes requires the use of methods that assess both morphological and chemical alterations in the tissues. In the past, microprobe approaches such as scanning electron microscopy combined with an X-ray spectrometer, Proton induced X-ray emission, secondary ion mass spectrometry (SIMS), and laser microprobe mass analysis have been used for the study of pathological human brain with limited success. At the present, new SIMS instruments have been developed, such as the NanoSIMS-50 ion microprobe, that allow the simultaneous identification of five elements with high sensitivity, at subcellular spatial resolution (about 50-100 nm with the Cs(+) source and about 150-200 nm with O(-) source). Working in scanning mode, 2D distribution of five elements (elemental maps) can be obtained, thus providing their exact colocalization. The analysis can be performed on semithin or ultrathin embedded sections. The possibility of using transmission electron microscopy and SIMS on the same ultrathin sections allows the correlation between structural and analytical observations at subcellular and ultrastructural level to be established. Our observations on pathological brain areas allow us to establish that the NanoSIMS-50 ion microprobe is a highly useful instrument for the imaging of the morphological and chemical alterations that take place in these brain areas. In the human brain our results put forward the subcellular distribution of iron-ferritin-hemosiderin in the hippocampus of Alzheimer disease patients. In the thalamus of transgenic mice, our results have shown the presence of Ca-Fe mineralized amyloid deposits.
    Microscopy Research and Technique 04/2007; 70(4):281-95. DOI:10.1002/jemt.20403 · 1.17 Impact Factor
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    ABSTRACT: The magnetic properties and the ultrastructure, with special emphasis on the nanometric range, of liver tissues in an iron overload rat model have been investigated. The tissues of the animals, sacrificed at different times after a single iron dextran injection, have been characterised by magnetic AC susceptibility measurements together with transmission electron microscopy (TEM) and selected area electron diffraction (SAED) as helping techniques. It has been observed that few days after the iron administration the liver contains at least two iron species: (i) akaganéite nanoparticles, coming from iron dextran and (ii) ferrihydrite nanoparticles corresponding to ferritin. The magnetic susceptibility of the tissues depends not only on the elemental iron content but also on its distribution among chemical species, and varies in a remarkable regular manner as a function of the elapsed time since the iron administration. The results are of relevance with respect to non-invasive techniques for liver iron determination, directly or indirectly based on the magnetic susceptibility of the tissues, as biomagnetic liver susceptometry (BLS) and magnetic resonance (MRI) image treatment.
    Journal of Inorganic Biochemistry 12/2006; 100(11):1790-9. DOI:10.1016/j.jinorgbio.2006.06.010 · 3.27 Impact Factor
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    ABSTRACT: Previous studies of the structure of core nanocrystals of ferritin (Ft) in the brains of patients with Alzheimer's disease (AD) have shown differences in the mineral compound in comparison with physiological Ft. Both Ft cores have a polyphasic composition but whereas the major phase in physiological Ft is hexagonal ferric iron oxide (ferrihydrite), the major phases in brain AD Ft are two cubic mixed ferric-ferrous iron oxides (magnetite and wüstite). One of these (wüstite) is similar to what is detected in hemosiderin (Hm) cores in primary hemochromatosis (Quintana, C., Cowley, J.M, Marhic, C., 2004. Electron nanodiffraction and high resolution electron microscopy studies of the structure and composition of physiological and pathological ferritin. J. Struct. Biol. 147, 166-178). We have studied, herein, the distribution of iron, Ft, and Hm in sections of AD hippocampus using analytical microscopy. Iron present in Ft cores was directly mapped in a nanoSIMS microscope and the iron distribution has been correlated with the constituent elements N, P, and S. Ft and Hm cores were visualized at an ultrastructural level in an analytical transmission electron microscope. In senile plaques, Ft was observed in the coronal region associated with a non-beta-amyloid component and in the periphery of plaques, together with Hm, in sulfur-rich dense bodies of dystrophic neurites. Hm was also found in lysosomes and siderosomes of glial cells. Ft was observed in the cytoplasm and nucleus of oligodendrocytes. Ft was particularly abundant in myelinated axons in association with oligodendrocyte processes. These findings provide new arguments to support the hypothesis of a dysfunction of Ft (with eventual degradation to Hm) in AD resulting in an increase of toxic brain ferrous ions that may contribute to the production of free radicals that induce both cellular oxidative stress and aged-related myelin breakdown associated with cognitive decline and AD (Bartzokis, G., 2004. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging 25, 5-18).
    Journal of Structural Biology 02/2006; 153(1):42-54. DOI:10.1016/j.jsb.2005.11.001 · 3.37 Impact Factor
  • Article: P2-289
  • Article: P2-290
  • Article: ICP042
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    ABSTRACT: This paper reviews the most recent methodological advances in the field of biological imaging using dynamic secondary ion mass spectrometry (SIMS). After a short reminder of the basic principle of SIMS imaging, the latest high-resolution dynamic SIMS equipment is briefly described. This new ion nanoprobe (CAMECA NanoSIMS 50) has a lateral resolution of less than 50 nm with primary Cs+ ion, the ability to detect simultaneously 5 different ions from the same micro-volume and a very good transmission even at high mass resolution (60% at M/DeltaM=5000). Basic considerations related to sample preparation, mass resolution and primary ion implantation are given. The decisive capability of this new instrument, and more generally of high-resolution dynamic SIMS imaging in biology, are illustrated with the most recent examples of utilization.
    Biochimica et Biophysica Acta 09/2005; 1724(3):228-38. DOI:10.1016/j.bbagen.2005.05.013 · 4.66 Impact Factor
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    C Quintana, J M Cowley, C Marhic
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    ABSTRACT: Structures of core nanocrystals of physiological (horse spleen, human liver, and brain) and pathological human brain of patients with progressive supranuclear palsy (PSP) and Alzheimer's disease (AD) ferritin molecules were determined using electron nanodiffraction and high-resolution transmission electron microscopy. The poly-phasic structure of the ferritin cores is confirmed. There are significant differences in the mineral composition between the physiological and pathological ferritins. The physiological ferritin cores mainly consist of single nanocrystals containing hexagonal ferrihydrite (Fh) and hematite (Hm) and some cubic magnetite/maghemite phase. In the pathological cores, Fh is present but only as a minor phase and Hm is absent. The major phases are a face-centered-cubic (fcc) structure with a = 0.43 nm and a high degree of disorder, related to wustite, and a cubic magnetite-like structure. These two cubic phases are also present in human aged normal brain. Evidence for the presence of hemosiderin together with ferritin in the pathological brains is deduced from the similarities of the diffraction patterns with those from patients with primary hemochromatosis, and differences in the shapes and protein composition of the protein shell. These findings suggest a disfunction of the ferritin associated with PSP and AD, associated with an increase in the concentration of brain ferrous toxic iron.
    Journal of Structural Biology 09/2004; 147(2):166-78. DOI:10.1016/j.jsb.2004.03.001 · 3.37 Impact Factor
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    ABSTRACT: This work describes the application of the Lattice Fringe Spacing Measurement (LFSM) method to the study of complex multiquantum well heterostructures containing both low-misfit and strain compensated short period superlattices in barriers and wells, respectively. 90$^{\circ}$-wedge cross-sectional samples have been used. The adequate choice of both experimental conditions and digitized sampling allows the whole heterostructure to be visualized and studied in a single High Resolution Transmission Electron Microscopy (HRTEM) image. Sample preparation and image processing technique are simple and inexpensive, resulting a fast procedure particularly suited for the analysis of large areas. By this way, in a single HRTEM image we have measured, in the growth direction, the lattice spacings at either side of the multiple grown interfaces as well as the period variations of both types of superlattices; in addition, we have measure on the same image the lattice strain in a direction perpendicular to the growth direction by using the LFSM and the Cumulative Sum methods. We have observed local lateral variations within the wells, with regions tensile or compressively strained, while a vestige of the grown SL remains, indicating the occurrence of a strain induced lateral composition modulation process spontaneously produced during the growth of strain compensated short-period superlattices. This is further confirmed in cross-section prepared by the tripod mechanical polisher method.
    The European Physical Journal Applied Physics 03/2004; DOI:10.1051/epjap:2004012 · 0.79 Impact Factor
  • D. Golmayo, M. L. Dotor, C. Quintana
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    ABSTRACT: The lateral composition modulation of strain compensated (GaInP)m(GaInAs)m short-period superlattices (SPSL) has been investigated. Transmission electron microscopy results show that long-range lateral composition modulation is formed in m=2 SPSL grown at 400°C by atomic layer molecular beam epitaxy. The evolution of photoluminescence (PL) peak with temperature shows a blue shift with increasing temperature; in addition, low-temperature PL is strongly polarized. These properties are attributed to the lateral composition modulation. Quantum wires (QWRs) were formed using (GaInP)m(GaInAs)m SPSL as quantum wells in a multiquantum well heterostructure. The formation of QWR is confirmed by their PL properties.
    Journal of Crystal Growth 06/2003; 253(1):167-173. DOI:10.1016/S0022-0248(03)01094-7 · 1.69 Impact Factor
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    ABSTRACT: The morphology, size distribution, epitaxial relationships and lattice distortion in nanometer sized Fe(1 1 0) oriented islands grown on Al2O3(0 0 0 1) are studied and discussed as a function of the amount of deposited Fe. Combined scanning electron microscopy and transmission electron microscopy (TEM) as well as atomic force microscopy measurements show the dependence of these parameters with island size. For the smallest island sizes, an iron lattice distortion with respect to bulk values is found at their edges. Electron energy loss spectroscopy experiments demonstrate the absence of oxidation of the Fe islands either due to the high temperature deposition on Al2O3 or to the polishing procedure prior to TEM observations. From the analysis of the relative intensity for the L2 and L3 Fe peaks, a high spin ground state for the Fe atoms is deduced, probably correlated with the highly distorted regions at the edges of the islands.
    Thin Solid Films 04/2003; 434:228-238. DOI:10.1016/S0040-6090(03)00530-3 · 1.87 Impact Factor
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    ABSTRACT: The magneto-optical activity of Fe nanoparticulate systems is studied in this work as a function of the matrix that surrounds the particles and the Fe concentration in the effective layer. It is shown that the magneto-optical activity is not linear or proportional to the amount of Fe even at low coverages when the matrix surrounding the particles is an insulator. As a conclusion, it is also demonstrated that the magneto-optical response of a magnetic ultrathin film system strongly depends on its growth mode, with modifications of up to 100% in its magneto-optical activity. © 2002 American Institute of Physics.
    Applied Physics Letters 08/2002; 81(9):1603-1605. DOI:10.1063/1.1502913 · 3.52 Impact Factor
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    ABSTRACT: The magneto-optical response of nanometric Fe particles with varying size and shape has been studied, both in sputtered single layers and pulsed laser deposited nanocomposite films. The shape of Fe nanoparticles was controlled by varying growth conditions. An effective medium theory for arbitrary particle shapes has been derived and used to simulate the experimentally measured magneto-optical transverse Kerr spectra. The simulations show that the transverse Kerr magneto-optical spectra depend on the particles shape and correlate well with the experimentally determined spectra. From this result, it is deduced that Fe nanoparticles with dimensions down to 3-4 nm keep their bulk magneto-optical constants. On the other hand, large magneto-optical signals are reported in multilayered structures due to interferential effects
    IEEE Transactions on Magnetics 08/2001; DOI:10.1109/20.950858 · 1.21 Impact Factor

Publication Stats

602 Citations
66.76 Total Impact Points

Institutions

  • 2000–2008
    • Spanish National Research Council
      • Instituto de Ciencia de Materiales de Madrid
      Madrid, Madrid, Spain
  • 1998–2004
    • Barcelona Microelectronics Institute
      Barcino, Catalonia, Spain
    • Centro De Biología Molecular Severo Ochoa
      Madrid, Madrid, Spain