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1.
Phys Rev Lett ; 131(18): 186704, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37977632

RESUMO

EuCd_{2}As_{2} is now widely accepted as a topological semimetal in which a Weyl phase is induced by an external magnetic field. We challenge this view through firm experimental evidence using a combination of electronic transport, optical spectroscopy, and excited-state photoemission spectroscopy. We show that the EuCd_{2}As_{2} is in fact a semiconductor with a gap of 0.77 eV. We show that the externally applied magnetic field has a profound impact on the electronic band structure of this system. This is manifested by a huge decrease of the observed band gap, as large as 125 meV at 2 T, and, consequently, by a giant redshift of the interband absorption edge. However, the semiconductor nature of the material remains preserved. EuCd_{2}As_{2} is therefore a magnetic semiconductor rather than a Dirac or Weyl semimetal, as suggested by ab initio computations carried out within the local spin-density approximation.

2.
Life (Basel) ; 13(7)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37511912

RESUMO

(1) Background: We aimed to analyze the oxidative status of patients with unstable angina pectoris (UA), as well as to determine the correlation of these parameters between coronary arterial and peripheral venous blood samples. (2) Methods: The study included 47 human subjects with UA and 45 control subjects. We performed clinical examinations, hemodynamic and coronary angiography measures. Also, in the blood samples, we measured routine laboratory markers and the concentration of pro-oxidants: index of lipid peroxidation (TBARS), superoxide anion radical (O2-), hydrogen peroxide (H2O2) and nitrites (NO2-), while antioxidant parameters were determined from red blood cells: reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). All parameters were determined spectrophotometrically. (3) Results: Significantly higher values of TBARS and all measured antioxidants SOD, CAT and GSH were observed in the coronary arterial blood of the UA group relative to coronary arterial blood of the control subjects. On the other hand, in the peripheral venous blood samples, a significantly lower GSH value was found in the UA group compared to the control. (4) Conclusions: This study has shown that the majority of changes in all measured redox markers are found in coronary blood, especially related to the activity of antioxidant components. In patients with an unstable form of angina, prooxidants (superoxide anion radical and index of lipid peroxidation) and endogenous antioxidants (catalase, superoxide dismutase and reduced glutathione) are in direct correlation with the course of ischemic disease. Future studies, where participants would be randomized depending on symptom duration, are necessary to confirm these conclusions.

3.
Sci Data ; 6(1): 205, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619675

RESUMO

The Mediterranean Region has a long lasting legacy of mercury mining activities and a high density of sub-marine volcanoes that has strongly contributed to its mercury budget. In the last forty years, there have been recorded increases in mercury concentrations in biota that have spurred a growing number of research activities to assess the impact of mercury pollution on human health and environment. Field investigations that quantify mercury concentrations in marine biota have led to a large amount of experimental data scattered in many peer-reviewed publications making it difficult for modelling applications and regional environmental assessments. This paper reviews existing peer-reviewed literature and datasets on mercury concentration in marine flora and fauna (Animal, Plants and Chromista Kingdoms) in the Mediterranean basin. A total of 24,465 records have been retrieved from 539 sources and included in Mercury in Mediterranean Biota (M2B). Well-defined specimens account for 24,407 observations, while a few records include generic plankton and unidentified fish species. Among all considered species, we selected Diplodus sargus, Sardina pilchardus, Thunnus thynnus and Xiphias gladius to show trends of mercury concentration against WHO and EU limits. Few notes on how M2B is intended to support the implementation of the Minamata Convention on Mercury by a user-driven Knowledge Hub are finally reported.


Assuntos
Monitoramento Ambiental , Peixes , Mercúrio/análise , Poluentes Químicos da Água/análise , Animais , Biota , Mar Mediterrâneo
4.
Commun Phys ; 2(1)2019.
Artigo em Inglês | MEDLINE | ID: mdl-38915317

RESUMO

Topological defects are found ubiquitously in various kinds of matter, such as vortices in type-II superconductors, and magnetic skyrmions in chiral ferromagnets. While knowledge on the static behavior of magnetic skyrmions is accumulating steadily, their dynamics under forced flow is still a widely open issue. Here, we report the deformation of the moving magnetic skyrmion lattice in MnSi under electric current flow observed using small-angle neutron scattering. A spatially inhomogeneous rotation of the skyrmion lattice, with an inverse rotation sense for opposite sample edges, is observed for current densities greater than a threshold value j t ~ 1 MA m-2 (106 A m-2). Our result show that skyrmion lattices under current flow experience significant friction near the sample edges due to pinning, this being a critical effect that must be considered for anticipated skyrmion-based applications at the nanoscale.

5.
Sci Rep ; 8(1): 10466, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29992965

RESUMO

Magnetic skyrmions are topologically protected spin-whirls currently considered as promising for use in ultra-dense memory devices. Towards achieving this goal, exploration of the skyrmion phase response and under external stimuli is urgently required. Here we show experimentally, and explain theoretically, that in the magnetoelectric insulator Cu2OSeO3 the skyrmion phase can expand and shrink significantly depending on the polarity of a moderate applied electric field (few V/µm). The theory we develop incorporates fluctuations around the mean-field that clarifies precisely how the electric field provides direct control over the free energy difference between the skyrmion and the surrounding conical phase. The quantitative agreement between theory and experiment provides a solid foundation for the development of skyrmionic applications based on magnetoelectric coupling.

6.
Rev Sci Instrum ; 89(4): 046101, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29716319

RESUMO

We present a compact nuclear magnetic resonance (NMR) probe which is compatible with a magnet of a commercial superconducting quantum interference device magnetometer and demonstrate its application to the study of a quantum magnet. We employ trimmer chip capacitors to construct an NMR tank circuit for low temperature measurements. Using a magnetic insulator MoOPO4 with S = 1/2 (Mo5+) as an example, we show that the T-dependence of the circuit is weak enough to allow the ligand-ion NMR study of magnetic systems. Our 31P NMR results are compatible with previous bulk susceptibility and neutron scattering experiments and furthermore reveal unconventional spin dynamics.

7.
Phys Chem Chem Phys ; 20(4): 2431-2437, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29308795

RESUMO

The origin of the anomalous sharp phase transition from a ferromagnetic metal into a ferromagnetic insulator has been investigated in ruthenium (Ru)-doped RE0.55Sr0.45Mn1-xRuxO3 (0 ≤ x ≤ 0.25) manganites (RESRMO) with RE(A-site) = Sm, Eu and Gd. The transition is independent of RE and occurs at a Ru doping level x of around 0.16-0.18. The analysis of the temperature derivative of the resistivity and the magneto-resistance at high temperatures as a function of x suggests that the suppression of metallicity originates from the doping driven magnetic/spin disorder that coexist within the ferromagnetic metallic/insulating matrix in these compounds.

8.
Sci Rep ; 6: 21347, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26892190

RESUMO

The recent discovery of magnetic skyrmion lattices initiated a surge of interest in the scientific community. Several novel phenomena have been shown to emerge from the interaction of conducting electrons with the skyrmion lattice, such as a topological Hall-effect and a spin-transfer torque at ultra-low current densities. In the insulating compound Cu2OSeO3, magneto-electric coupling enables control of the skyrmion lattice via electric fields, promising a dissipation-less route towards novel spintronic devices. One of the outstanding fundamental issues is related to the thermodynamic stability of the skyrmion lattice. To date, the skyrmion lattice in bulk materials has been found only in a narrow temperature region just below the order-disorder transition. If this narrow stability is unavoidable, it would severely limit applications. Here we present the discovery that applying just moderate pressure on Cu2OSeO3 substantially increases the absolute size of the skyrmion pocket. This insight demonstrates directly that tuning the electronic structure can lead to a significant enhancement of the skyrmion lattice stability. We interpret the discovery by extending the previously employed Ginzburg-Landau approach and conclude that change in the anisotropy is the main driver for control of the size of the skyrmion pocket.

9.
Folia Biol (Praha) ; 62(6): 241-249, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28189147

RESUMO

Testing of every new vaccine involves investigation of its immunogenicity, which is based on monitoring its ability to induce specific antibodies in animals. The fastest and most sensitive method used for this purpose is enzyme-linked immunosorbent assay (ELISA). However, commercial ELISA kits with whole influenza virus antigens are not available on the market, and it is therefore essential to establish an adequate assay for testing influenza virusspecific antibodies. We developed ELISA with whole influenza virus strains for the season 2011/2012 as antigens and validated it by checking its specificity, accuracy, linearity, range, precision, and sensitivity. The results show that we developed high-quality ELISA that can be used to test immunogenicity of newly produced seasonal or pandemic vaccines in mice. The pre-existence of validated ELISA enables shortening the time from the process of vaccine production to its use in patients, which is particularly important in the case of a pandemic.


Assuntos
Ensaios Clínicos como Assunto , Ensaio de Imunoadsorção Enzimática/métodos , Vacinas contra Influenza/imunologia , Animais , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Limite de Detecção , Modelos Lineares , Camundongos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Vírion/imunologia
10.
Phys Rev Lett ; 113(10): 107203, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25238382

RESUMO

Uniquely in Cu2OSeO3, the Skyrmions, which are topologically protected magnetic spin vortexlike objects, display a magnetoelectric coupling and can be manipulated by externally applied electric (E) fields. Here, we explore the E-field coupling to the magnetoelectric Skyrmion lattice phase, and study the response using neutron scattering. Giant E-field induced rotations of the Skyrmion lattice are achieved that span a range of ∼25°. Supporting calculations show that an E-field-induced Skyrmion distortion lies behind the lattice rotation. Overall, we present a new approach to Skyrmion control that makes no use of spin-transfer torques due to currents of either electrons or magnons.

11.
Rev Sci Instrum ; 84(5): 054708, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23742576

RESUMO

Method in which lock-in detectors process signals from standard ac susceptometers, particularly in the detection of higher harmonics, is analyzed in details. The exact formulas have been derived and checked experimentally by measurements on soft ferromagnetic sample, using several available lock-in amplifiers. The reasons why the proper phase adjustment has to be implemented in the protocol of higher harmonics measurements have been elaborated. The procedure of the lock-in phase adjustment is described, enabling separation of Fourier or Taylor components of hysteretic ac susceptibility into real and imaginary sectors.

12.
J Phys Condens Matter ; 24(43): 432201, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-23032155

RESUMO

Small-angle neutron scattering has been employed to study the influence of applied electric (E-)fields on the skyrmion lattice in the chiral lattice magnetoelectric Cu(2)OSeO(3). Using an experimental geometry with the E-field parallel to the [111] axis, and the magnetic field parallel to the [11(-)0] axis, we demonstrate that the effect of applying an E-field is to controllably rotate the skyrmion lattice around the magnetic field axis. Our results are an important first demonstration for a microscopic coupling between applied E-fields and the skyrmions in an insulator, and show that the general emergent properties of skyrmions may be tailored according to the properties of the host system.

13.
Lupus ; 21(2): 195-202, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22235053

RESUMO

Successful induction of antiphospholipid syndrome (APS) in two different non-autoimmune prone mouse strains, BALB/c and C57BL/6, was achieved by tetanus toxoid (TTd) hyperimmunization using different adjuvants (glycerol or aluminium hydroxide), and different adjuvant pretreatments (glycerol or Complete Freund's Adjuvant (CFA)). APS had different manifestations of reproductive pathology in BALB/c and C57BL/6 mice: fetal resorption (as a consequence of extreme T-cell activation obtained in the course of pretreatment), and lowering of fecundity (as a consequence of polyclonal B-cell stimulation), respectively. In BALB/c mice fetal resorption coincided with glycerol and CFA pretreatments, while in C57BL/6 mice lowering of fecundity was most obvious in CFA-pretreated mice immunized with TTd in aluminium hydroxide. Both molecular mimicry and polyclonal B-cell activation occur in APS induction, with molecular mimicry effects being dominant in BALB/c mice, and polyclonal cell activation being dominant in C57BL/6 mice. Confirmation of molecular mimicry effects, which in the condition of T-cell stimulation generated fetal resorptions in the BALB/c strain, was achieved by passive infusion of monoclonal antibody (MoAb) T-26 specific for TTd and anti-ß(2)-glycoprotein I obtained after TTd hyperimunization. High polyclonal B-cell activation in C57BL/6 mice prevented fetal resorption but induced fecundity lowering, as was the case in passive administration of MoAb T-26 in this mouse strain. Passive infusion of anti-idiotypic MoAb Y7 into C57BL/6 mice induced fetal resorptions and confirmed the above suggestion on the protective role of polyclonal B-cell stimulation in fetal resorptions.


Assuntos
Síndrome Antifosfolipídica/etiologia , Síndrome Antifosfolipídica/imunologia , Reabsorção do Feto/imunologia , Toxoide Tetânico/efeitos adversos , Toxoide Tetânico/imunologia , Animais , Síndrome Antifosfolipídica/fisiopatologia , Autoanticorpos/imunologia , Linfócitos B/imunologia , Feminino , Adjuvante de Freund/imunologia , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Gravidez , Linfócitos T/imunologia , beta 2-Glicoproteína I/imunologia
14.
Phys Rev Lett ; 104(24): 247203, 2010 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-20867332

RESUMO

Here we present a detailed study of the spinel CdEr2Se4 and show it to be a new instance of spin ice, the first one in an erbium material and the first one in a spinel. Definitive experimental evidence comes from the temperature dependence of the magnetic entropy, which shows an excellent agreement with the predicted behavior for a spin ice state. Crystal field calculations demonstrate that the change in the local environment from that of the titanates completely alters the rare-earth anisotropy giving rise, in the case of Er3+, to the required Ising anisotropy, when Er2Ti2O7 behaves as an XY antiferromagnet. This finding opens up the possibility of new exotic ground states within the CdR2Se4 and CdR2Se4 families.

15.
J Biomech Eng ; 132(4): 041008, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20387971

RESUMO

This paper explores the effect of under-reaming on micromotion at the cup/bone interface of a press-fit acetabular cup. A cadaver experiment was performed on 11 acetabuli implanted with a cementless acetabular cup. The loading profile simulated hip impingement at the extremes of motion and subluxation relocation of the hip joint. Micromotion of each cup was measured in a custom made jig with linear variable differential transducers. A CAT scan and DEXA scan of the acetabulum and femoral head respectively were used to construct a three-dimensional patient specific finite element model of the hemi-pelvis. The model predicted cup micromotion under loading conditions and stresses in the acetabulum as a result of cup insertion. Micromotion was then calculated as a function of variable bone density and variable degree of underreaming. Simulated cup insertion with under-reaming of 2 mm or more approached or exceeded the yield strength of bone in acetabula with reduced bone mass density.


Assuntos
Acetábulo/fisiologia , Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Cabeça do Fêmur/fisiologia , Cabeça do Fêmur/cirurgia , Prótese de Quadril , Modelos Biológicos , Simulação por Computador , Humanos , Movimento (Física) , Estresse Mecânico
16.
J Phys Condens Matter ; 22(5): 056002, 2010 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-21386354

RESUMO

We report a comprehensive study of magnetic properties of Ni(3)TeO(6). The system crystallizes in a noncentrosymmetric rhombohedral lattice, space group R3. There are three differently coordinated Ni atoms in the unit cell. Two of them form an almost planar honeycomb lattice, while the third one is placed between the layers. Magnetization and specific heat measurements revealed a single magnetic ordering at T(N) = 52 K. Below T(N) the susceptibility with the magnetic field parallel to the c axis drops towards zero while the perpendicular susceptibility remains constant, a characteristic of antiferromagnetic materials. Neutron diffraction confirmed that the system is antiferromagnet below T(N) with ferromagnetic ab planes stacked antiferromagnetically along the c axis. All Ni moments are in the S = 1 spin state and point along the c axis.

17.
J Appl Microbiol ; 107(6): 2108-15, 2009 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19796123

RESUMO

AIMS: This study focuses on the isolation and characterization of a peptide with bacteriocin-like properties isolated from Lactobacillus rhamnosus strain 68, previously identified by 16S rRNA gene sequencing and originating from human gastrointestinal flora. METHODS AND RESULTS: The peptide was isolated from a supernatant of bacteria maintained under restrictive conditions by a combination of ethanol precipitation and reversed-phase chromatography. The molecular mass of the peptide as assessed by mass spectrometry was 6433.8 Da. An isoelectric point of 9.8 was determined by 2D-PAGE. The peptide designated rhamnosin A inhibited Micrococcus lysodeikticus ATCC 4698 but did not inhibit Lactobacillus plantarum 8014 or Lact. plantarum 39268. Inhibitory activity against M. lysodeikticus at concentrations used in this study was shown to be bacteriostatic rather than bacteriolytic or bactericidal. Rhamnosin A retained biological activity after heat treatment (95 degrees C, 30 min) but was sensitive to proteolytic activity of pepsin and trypsin. CONCLUSIONS: The N-terminal sequence of rhamnosin A, as determined by Edman degradation and in more detail by blast analysis, did not show identity with any currently available Lact. rhamnosus HN001-translated protein sequences, nor any significant similarity with other sequences in the nonredundant protein sequence database. Being a small, heat-stable, nonlanthionine-containing peptide, rhamnosin A should be categorized as a class II bacteriocin. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes a partial bacteriocin sequence isolated from Lact. rhamnosus 68 and broadens our understanding of bacteriocins.


Assuntos
Bacteriocinas/química , Bacteriocinas/isolamento & purificação , Lacticaseibacillus rhamnosus/metabolismo , Sequência de Aminoácidos , Bacteriocinas/farmacologia , Humanos , Ponto Isoelétrico , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Lacticaseibacillus rhamnosus/genética , Micrococcus/efeitos dos fármacos , Peso Molecular
18.
Histol Histopathol ; 20(3): 833-41, 2005 07.
Artigo em Inglês | MEDLINE | ID: mdl-15944933

RESUMO

In order to examine the influence of chronic alpha1-adrenergic receptor (alpha1-AR) blockade on the thymus structure and T-cell maturation, peripubertal and adult male rats were treated with urapidil (0.20 mg/kg BW/d; s.c.) over 15 consecutive days. Thymic structure and phenotypic characteristics of the thymocytes were assessed by stereological and flow cytometry analysis, respectively. In immature rats, treatment with urapidil reduced the body weight gain and, affecting the volume of cortical compartment and its cellularity decreased the organ size and the total number of thymocytes compared to age-matched saline-injected controls. The percentage of CD4+8- single positive (SP) thymocytes was decreased, while that of CD4-8+ was increased suggesting, most likely, a disregulation in final steps of the positively selected cells maturation. However, alpha1-AR blockade in adult rats increased the thymus weight as a consequence of increase in the cortical size and cellularity. The increased percentage of most immature CD4-8- double negative (DN) cells associated with decreased percentage of immature CD4+8+ double positive (DP) thymocytes suggests a decelerated transition from DN to DP stage of T-cell development. As in immature rats, the treatment in adult rats evoked changes in the relative numbers of SP cells, but contrary to immature animals, favoring the maturation of CD4+8- over CD4-8+ thymocytes. These results demonstrate that: i) chronic blockade of alpha1-ARs affects both the thymus structure and thymocyte differentiation, ii) these effects are age-dependent, pointing out to pharmacological manipulation of alpha1-AR-mediated signaling as potential means for modulation of the intrathymic T-cell maturation.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Antagonistas Adrenérgicos alfa/farmacologia , Diferenciação Celular/efeitos dos fármacos , Piperazinas/farmacologia , Timo/efeitos dos fármacos , Fatores Etários , Animais , Antígenos CD4/análise , Antígenos CD8/análise , Contagem de Células , Tamanho Celular/efeitos dos fármacos , Citometria de Fluxo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa 1/fisiologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Linfócitos T/química , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Timo/anatomia & histologia , Timo/citologia
19.
Neuropeptides ; 38(1): 25-34, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15003713

RESUMO

It is well known that somatostatin exerts a wide range of effects in the body, and acts as an autocrine or paracrine factor in the thymus. However, it has not been investigated yet whether somatostatin alters the thymus size and relation among the thymocyte subpopulations in the peripubertal rats. For this purpose, the peripubertal AO male rats were cannulated intracerebroventriculary and treated with repeated, low doses of somatostatin-14 (experimental group) or saline (control group). Twenty-four hours after the last treatment, we removed and prepared the thymuses for determination of thymocyte subpopulations by flow cytometry. After five days, animals were sacrificed and their thymuses taken for morphometrical analysis by stereological methods. We noticed that somatostatin-14 decreased volumes of thymus cortex and medulla, total number of thymocytes, number of thymocytes in the cortex and medulla and numerical density of thymocytes in deeper cortex. As a consequence of these changes, thymus size was also diminished. The phenotypic analysis of thymocyte subpopulations showed that somatostatin-14 decreased the percentage of CD4(+)CD8(+) cells with low level of TCR alphabeta expression, positively selected CD4(+)CD8(+)TCRalphabeta (high) cells and the most mature CD4(-)CD8(+)TCRalphabeta (high) cells, while the percentage of CD4(+)CD8(-)TCRalphabeta (high) thymocytes was slightly increased. Somatostatin-14 increased the relative proportion of the least mature CD4(-)CD8(-)TCRalphabeta (-/low), CD4(+)CD8(+)TCRalphabeta (-) cells and both of TCRalphabeta (-/low) single positive subpopulations. These results show that centrally applied somatostatin-14, induces hypotrophy of the thymus in peripubertal rats by changing the volumes and cellularities of the thymic compartments. Additionally, increased number of the least mature thymocytes and a deficiency of double positive cells indicate the involvement of somatostatin in the modulation of T cells maturation.


Assuntos
Somatostatina/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Timo/anatomia & histologia , Timo/efeitos dos fármacos , Animais , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/efeitos dos fármacos , Tamanho Celular , Citometria de Fluxo , Injeções Intraventriculares , Contagem de Linfócitos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Maturidade Sexual , Somatostatina/administração & dosagem , Timo/citologia
20.
J Pharmacol Exp Ther ; 272(1): 300-9, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7815345

RESUMO

7-Chloro-3-Methyl-3-4-Dihydro-2H-1,2,4 Benzothiadiazine S,S Dioxide (IDRA 21), which attenuates the rapid autodesensitization of DL-alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA)-selective glutamate receptors and increases excitatory synaptic strength, improves cognition (learning and memory), as revealed by its ability to improve performance in water maze and passive avoidance tests in rats. Normal rats trained to (15-20 sec) reach the exit platform rapidly in a water maze that included four incorrect choices were given oral IDRA 21 (4-120 mumol/kg) or vehicle and then exposed to a delayed retention trial in a maze that included seven incorrect choices. In this retention trial, the IDRA 21-treated rats performed considerably better than those that received the vehicle. Moreover, oral IDRA 21 (ED50 = 7.6 microM) attenuated the performance impairment induced by the AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F) quinoxaline in the water maze test. In this test and in a passive avoidance test, the performance impairment elicited by alprazolam, a full allosteric modulator at gamma-aminobutyric acid-A receptors, or by scopolamine, a competitive muscarinic receptor antagonist, was also reduced by oral administration of IDRA 21 (ED50 = 13 and 108 mumol/kg, against alprazolam and scopolamine, respectively); in all these tests, IDRA 21 was 20- to 30-fold more potent than aniracetam. Because IDRA 21 is a racemic molecule; the two stereoisomers were isolated and studied behaviorally. Only the (+) form was found to be behaviorally active. These results indicate that IDRA 21 given orally to rats presumably crosses the blood-brain barrier and acts stereoselectively on specific receptors that were operative during this behavioral procedure. Because the activity of IDRA 21 on rat cognition tests appears to be related to its ability to potentiate AMPA-activated currents, one can suggest that IDRA 21 improves cognition by acting on a stereoselective site of AMPA receptor that is operative in attenuating the rapid autodesensitization of these receptors.


Assuntos
Benzotiadiazinas/farmacologia , Encéfalo/fisiologia , Cognição/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Receptores de AMPA/efeitos dos fármacos , Alprazolam/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Clorotiazida/farmacologia , Diazóxido/farmacologia , Eletrofisiologia , Glutamatos/farmacologia , Ligantes , Masculino , Fosfatidilinositóis/metabolismo , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo , Escopolamina/farmacologia , Estereoisomerismo , Sinaptossomos/metabolismo
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