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2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 44(5): 828-836, 2023 May 10.
Artículo en Chino | MEDLINE | ID: mdl-37221075

RESUMEN

The common data model (CDM) is an important tool to facilitate the standardized integration of multi-source heterogeneous healthcare big data, enhance the consistency of data semantic understanding, and promote multi-party collaborative analysis. The data collections standardized by CDM can provide powerful support for observational studies, such as large-scale population cohort study. This paper provides an in-depth comparative analysis of the data storage structure, term mapping pattern, and auxiliary tools development of the three international typical CDMs, then analyzes the advantages and limitations of each CDM and summarizes the challenges and opportunities faced in the CDM application in China. It is expected that exploring the advanced technical concepts and practical patterns of foreign countries in data management and sharing will provide references for promoting FAIR (findable, accessible, interoperable, reusable) construction of healthcare big data in China and solving the current practical problems, such as the poor quality of data resources, the low degree of semantization, and the inabilities of data sharing and reuse.


Asunto(s)
Macrodatos , Difusión de la Información , Humanos , China , Estudios de Cohortes , Recolección de Datos
3.
Phys Rev Lett ; 130(18): 185001, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37204906

RESUMEN

Propagation of high-current relativistic electron beam (REB) in plasma is relevant to many high-energy astrophysical phenomena as well as applications based on high-intensity lasers and charged-particle beams. Here, we report a new regime of beam-plasma interaction arising from REB propagation in medium with fine structures. In this regime, the REB cascades into thin branches with local density a hundred times the initial value and deposits its energy 2 orders of magnitude more efficiently than that in homogeneous plasma, where REB branching does not occur, of similar average density. Such beam branching can be attributed to successive weak scatterings of the beam electrons by the unevenly distributed magnetic fields induced by the local return currents in the skeletons of the porous medium. Results from a model for the excitation conditions and location of the first branching point with respect to the medium and beam parameters agree well with that from pore-resolved particle-in-cell simulations.

4.
Phys Rev Lett ; 127(24): 245002, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34951809

RESUMEN

Transport of high-current relativistic electron beams in dense plasmas is of interest in many areas of research. However, so far the mechanism of such beam-plasma interaction is still not well understood due to the appearance of small time- and space-scale effects. Here we identify a new regime of electron beam transport in solid-density plasma, where kinetic effects that develop on small time and space scales play a dominant role. Our three-dimensional particle-in-cell simulations show that in this regime the electron beam can evolve into layered short microelectron bunches when collisions are relatively weak. The phenomenon is attributed to a secondary instability, on the space- and timescales of the electron skin depth (tens of nanometers) and few femtoseconds of strong electrostatic modulation of the microelectron current filaments formed by Weibel-like instability of the original electron beam. Analytical analysis on the amplitude, scale length, and excitation condition of the self-generated electrostatic fields is clearly validated by the simulations.

6.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(8): 537-539, 2019 Aug 09.
Artículo en Chino | MEDLINE | ID: mdl-31378032

RESUMEN

This pilot study aimed to investigate the feasibility of trans-oral ultrasonography of the temporomandibular joint (TMJ) in oblique sagittal plane. Six volunteers who were receiving residency training at Hainan Hospital of General Hospital of Chinese PLA were recruited into this study, five of them had normal TMJ and one had anterior displaced disc all of which had been confirmed by MRI. A hockey-stick-shaped ultrasound probe was placed between the cheek and maxilla to push against the mucosa lateral to posterior maxillary tuberosity, and every volunteer underwent bilateral scans. The sonographic imaging were completed successfully on the six volunteers; the condyle, the superior and the inferior head of the lateral pterygoid muscle, the disc and the maxillary vein were clearly identified in all the twelve ultrasonographic scans. The feasibility of trans-oral ultrasonography of TMJ in oblique sagittal plane was confirmed.


Asunto(s)
Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Luxaciones Articulares/diagnóstico por imagen , Imagen por Resonancia Magnética , Cóndilo Mandibular , Proyectos Piloto , Articulación Temporomandibular , Disco de la Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Ultrasonografía
7.
Zhonghua Yi Xue Za Zhi ; 99(21): 1631-1635, 2019 Jun 04.
Artículo en Chino | MEDLINE | ID: mdl-31189261

RESUMEN

Objective: To evaluate the effects of modified posteromedial approach combined raft technique in the treatment of posterior Pilon fractures with collapsed articular surface. Methods: A retrospective analysis was conducted on the clinical data of 51 patients with posterior Pilon fractures combined with collapsed articular surface treated in West China Hospital between January 2014 and June 2017. There were 30 males and 21 females with an average age of 49 years (range, 19-66 years).Subjective assessment of the results was performed according to the pain visual analog scale (VAS).The general function recovery was assessed with American Orthopaedic Foot & Ankle Society (AOFAS) ankle hindfoot scale at the latest follow-up. The fracture reduction quality was determined according to Burwell-Charnley imaging standard by the anteroposterior(AP)/mortise X-ray view and three-dimensional CT of the ankle on the 3rd day after operation. The t-test was used to compare the normal distribution parameters. Results: Primary healing of incision and bone were obtained in all patients without loosening, breakage or infection of internal fixation in (3.7±0.7) months (range, 3-6 months). According to the Burwell-Charnley's standards, 50 cases achieved anatomical reduction, 1 case achieved fair reduction. According to AOFAS scales, the results were excellent in 41 cases, good in 9, and fair in 1; the excellent rate was 98.0%. According to the AOFAS scores, the average score was 93.6±2.2. The preoperative VAS score was 7.5±1.1, and the postoperative score was 0.3±0.7, in which the difference was statistically significant (t=31.231, P=0.000). At the last follow-up, the angle of injured side were 13.3°±3.4° in dorsal extension, 33.5°±4.7° in plantar flexion, and 46.9°±6.1° in the range, while angel of uninjured side were 19.8°±2.3°, 36.0°±5.7° and 55.6°±2.7°, respectively; there were significant differences in the up-mentioned indexes between the both sides (t=78.932, 121.231, 113.432, all P<0.05). Conclusion: Excellent short-term effectiveness can be achieved through the modified medial approach in patients with posterior Pilon fractures, which can be used to restore the ankle joint surface under direct vision; and with the raft technique, a small plate is used to fix small fragments firmly with less soft tissue complications.


Asunto(s)
Fracturas de Tobillo , Fracturas de la Tibia , Adulto , Anciano , China , Femenino , Fijación Interna de Fracturas , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
8.
J Dent Res ; 97(13): 1477-1484, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29969955

RESUMEN

The VicRK 2-component system of Streptococcus mutans regulates genes associated with cell wall biogenesis and biofilm formation. A putative RNase III-encoding gene ( rnc) is located downstream from the vicRKX operon. The goals of this study were to investigate the potential role of VicR in the regulation of adjacent downstream genes and evaluate transcription levels of vicR during planktonic and biofilm growth. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate whether vicRKX and adjacent downstream genes were cotranscribed. Binding of purified recombinant VicR protein to promoter regions of vicR, rnc, and syfA genes was confirmed by electrophoretic mobility shift assay and by chromatin immunoprecipitation analyses. VicR antisense (AS vicR) RNA was detected by Northern blotting and qRT-PCR assays. AS vicR overexpression mutants were constructed, and the biofilm biomass was determined by crystal violet microtiter assay. Adjacent downstream genes rnc, smc, syfA, smu.1511, and syfB were cotranscribed with vicRKX. The predicted promoter regions of vicR, rnc, and syfA genes were directly regulated by VicR. An AS vicR RNA transcript was detected upstream of the rnc gene. Expression of the AS vicR RNA transcript was elevated in planktonic cultures and repressed during biofilm growth. In addition, Western blot data showed that expression of the VicR protein decreased by 35% in planktonic as compared with biofilm cultures. Furthermore, we show that overexpression of AS vicR led to a reduction in biofilm formation. The downstream genes rnc, smc, syfA, smu.1511, and syfB are cotranscribed with vicRKX. VicR is autophosphorylated, and rnc and syfA are directly regulated by VicR. Expression of VicR protein correlated inversely with different levels of AS vicR RNA transcript and growth conditions. The biofilm biomass decreased in the AS vicR overexpression mutant. These data suggest a role for the AS vicR RNA transcript in posttranscriptional regulation of VicR protein production in S. mutans.


Asunto(s)
Proteínas Bacterianas/fisiología , Biopelículas/crecimiento & desarrollo , Regulación Bacteriana de la Expresión Génica/fisiología , Genes Bacterianos/fisiología , Interferencia de ARN/fisiología , ARN sin Sentido/fisiología , Streptococcus mutans/fisiología , Proteínas Bacterianas/genética , Biomasa , Northern Blotting , Western Blotting , Ensayo de Cambio de Movilidad Electroforética , Genes Bacterianos/genética , Inmunoprecipitación , Regiones Promotoras Genéticas , ARN sin Sentido/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Streptococcus mutans/genética
9.
Eur Rev Med Pharmacol Sci ; 22(5): 1437-1450, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29565505

RESUMEN

OBJECTIVE: To study changes in the cerebrovascular reactivity (CVR) at different altitude area in healthy adults. SUBJECTS AND METHODS: CVR was tested using transcranial Doppler combined with CO2 inhalation, near-infrared spectroscopy (NIRS) was used to detect the regional cerebral oxygen saturation (rScO2). Blood samples were collected, and the vasoactive substances in serum were detected using the enzyme-linked immunosorbent assay. In this study, 59 healthy adults were divided into 3 groups: low altitude group, medium altitude group and high altitude group. All the indicators in low altitude group were tested at 24h before departure and after arrival from Beijing (at an altitude of 44.4 m) to Xining (at a medium altitude of 2200 m). Then, after resting for 48h, all the indicators were tested at 24h and 48h after arrival from Xining (at a medium altitude of 2200 m) to Yushu Jiegu town (at a high altitude of 3700 m) together with those at the medium altitude. Intergroup comparisons were made for the subjects in the three altitudes. RESULTS: There was an increase in the CVR in low altitude group after acute exposure to high altitude, and the difference was significant (CVR: 1.94re was vs. 0.91±0.53, p<0.001); the CVR index was increased, and the difference was significant [cerebrovascular reserve index (CVRI): 3.65he CVR vs. 1.37e CVR, p<0.001]; the rScO2 level was decreased with the increase of altitude, and the difference was significant [(66.78±4.61)% vs. (70.29±4.52)%, p<0.001]. The levels of vasoactive substances in low altitude group were decreased after acute exposure to high altitude compared with those before exposure: NO: [(79.14±9.54) µmol/L vs. (58.01±9.93) µmol/L, p<0.001]; serum eNOS level was increased, and the difference was significant [(77.23±6.20) pg/ml vs. (65.07±9.82) pg/ml, p<0.001]; EPO: [(84.68±13.16) pg/ml vs. (65.01±5.92) pg/ml, p<0.001]; VEGF: [(71.91±11.62) pg/ml vs. (54.92±11.86) pg/ml, p<0.001]; sFlt: [(384.18±42.73) pg/ml vs. (320.62±78.96) pg/ml, p<0.001]. There was also an increase in CVR in medium altitude group after acute exposure to high altitude, and the difference was significant [CVR: 2.00±0.79 vs. 0.91±0.66, p<0.001]; the difference of CVRI was significant [3.83±0.67 vs. 1.67±0.87, p<0.001]; rScO2 was slightly decreased with the increase of altitude, and the difference was not statistically significant [(67.53±4.61) % vs. (69.63±5.59) %, p<0.001]. Before exposure to high altitude area, the levels of NO, NOS, EPO, VEGF, and sFlt in low and medium altitude groups were higher than those in high altitude group. CVR level of subjects at different altitudes was negatively related to the ScO2 (r=-0.91) but positively related to NO and NOS levels (rs=0.89, r=0.75); CVR was moderately related to VEGF and EPO (rs=0.45, r=0.42). rScO2 was positively related to RBC, HB and VEGF levels (r=0.89, r=0.75, rs=0.86), but had a moderately negative correlation with NO and NOS levels (rs=-0.52, r=-0.57). CONCLUSIONS: After subjects at a low altitude are exposed to high altitude rapidly, CVR is increased, RBC and vasoactive substances in serum, such as NO, eNOS, and EPO, are dramatically increased, VEGF is increased first and then decreased, sFlt-1 level is increased gradually, and rScO2 level is gradually decreased with the increase of altitude, indicating the local brain anoxia of subjects at a high altitude.


Asunto(s)
Altitud , Circulación Cerebrovascular , Adulto , Humanos , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/sangre , Oxígeno/sangre , Factor A de Crecimiento Endotelial Vascular/sangre
10.
Phys Rev E ; 95(5-1): 053205, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28618622

RESUMEN

It was shown that in the interactions of ultra-intense circularly polarized laser pulse with the near-critical plasmas, the angular momentum can be transferred efficiently from the laser beam to electrons through the resonance acceleration process. The transferred angular momentum increases almost linearly with the acceleration time t_{a} when the electrons are resonantly accelerated by the laser field. In addition, it is shown analytically that the averaged angular momentum of electrons is proportional to the laser amplitude a_{L}, and the total angular momentum of the accelerated electron beam is proportional to the square of the laser amplitude a_{L}^{2} for a fixed parameter of n_{e}/n_{c}a_{L}. These results are verified by three-dimensional particle-in-cell simulations. This regime provides an efficient and compact alternative for the production of high angular momentum electron beams, which may have many potential applications in condensed-matter spectroscopy, new electron microscopes, and bright x-ray vortex generation.

11.
Phys Rev E ; 95(4-1): 043207, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28505773

RESUMEN

The hosing processes of a relativistic laser pulse, electron acceleration, and betatron radiation in a parabolic plasma channel are investigated in the direct laser acceleration regime. It is shown that the laser hosing instability would result in the generation of a randomly directed off-axis electron beam and radiation source with a large divergence angle. While employing a preformed parabolic plasma channel, the restoring force provided by the plasma channel would correct the perturbed laser wave front and thus suppress the hosing instability. As a result, the accelerated electron beam and the emitted photons are well guided and concentrated along the channel axis. The employment of a proper plasma density channel can stably guide the relativistically intense laser pulse and greatly improve the properties of the electron beam and radiation source. This scheme is of great interest for the generation of high quality electron beams and radiation sources.

12.
Phys Rev E ; 94(3-1): 033202, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27739750

RESUMEN

Filamentation dynamics of relativistic optical vortex beams (OVBs) propagating in underdense plasma is investigated. It is shown that OVBs with finite orbital angular momentum (OAM) exhibit much more robust propagation behavior than the standard Gaussian beam. In fact, the growth rate of the azimuthal modulational instability decreases rapidly with increase of the OVB topological charge. Thus, relativistic OVBs can maintain their profiles for significantly longer distances in an underdense plasma before filamentation occurs. It is also found that an OVB would then break up into regular filament patterns due to conservation of the OAM, in contrast to a Gaussian laser beam, which in general experiences random filamentation.

13.
Zhonghua Er Ke Za Zhi ; 54(10): 761-766, 2016 Oct 02.
Artículo en Chino | MEDLINE | ID: mdl-27784479

RESUMEN

Objective: To report a case of the pulmonary surfactant protein(SP) adenosine triphosphate-binding-cassette-A3 (ABCA3) gene mutations in infant congenital interstitial lung disease(ILD), and review the related literature, to investigate the relationships of ABCA3 gene mutation associated with ILD in infants. Method: A 6-months-old boy was hospitalized in the department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University. The clinical, radiological, histological information from transbronchial lung biopsy (TBLB) and genetic testing in this case was analyzed; 12 reports retrieved on literature search at Pubmed, OVID databases from 2004 to 2015 by using the ABCA3 as keyword were reviewed and analyzed. Result: (1)The patient, a 6-months-old boy, had progressive tachypnea and dyspnea since 4 months old. Physical examination on admission revealed respiratory rate of 78 times/min , heart rate of 187 times/min, SpO2 0.93(mask oxygen-inspiration with 6 L/min), scattered fine moist crackles could be heard over the both lungs, clubbing fingers were found. High-resolution computed tomography(HRCT) revealed diffuse ground-glass opacity, interlobular and intralobular septal thickening. Lung biopsies showed evidences of the alveolar cavity atelectatic changes and interstitial fibrosis. SP-A and SP-B were negative in immunohistochemical stainting. SP-related gene sequence analysis found that there was compound heterozygous missense mutation of ABCA3 gene in c. 1942A>G, c.2701-33G>C and c. 991-105C>A. (2)The review of related literature found that totally 12 cases were reported. The main manifestations were progressive tachypnea and dyspnea, age of onset was between birth and 4 years of age. The imaging characteristics of chest HRCT revealed diffuse infiltration or diffuse ground-glass pattern in the lung. PROGNOSIS: 6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Enfermedades Pulmonares Intersticiales/genética , Mutación , Adenosina Trifosfato , Biopsia , Disnea , Exones , Heterocigoto , Homocigoto , Humanos , Lactante , Recién Nacido , Pulmón , Masculino , Fenotipo , Surfactantes Pulmonares , Radiografía , Síndrome de Dificultad Respiratoria del Recién Nacido , Tomografía Computarizada por Rayos X
14.
Phys Rev E ; 93: 043207, 2016 04.
Artículo en Inglés | MEDLINE | ID: mdl-27176418

RESUMEN

Energetic electron acceleration processes in a plasma hollow tube irradiated by an ultraintense laser pulse are investigated. It is found that the longitudinal component of the laser field is much enhanced when a linear polarized Gaussian laser pulse propagates through the plasma tube. This longitudinal field is of π/2 phase shift relative to the transverse electric field and has a π phase interval between its upper and lower parts. The electrons in the plasma tube are first pulled out by the transverse electric field and then trapped by the longitudinal electric field. The trapped electrons can further be accelerated to higher energy in the presence of the longitudinal electric field. This acceleration mechanism is clearly illustrated by both particle-in-cell simulations and single particle modelings.

15.
Phys Rev E ; 93(3): 033206, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27078474

RESUMEN

The dynamics of magnetic reconnection (MR) in the high-energy-density (HED) regime, where the plasma inflow is strongly driven and the thermal pressure is larger than the magnetic pressure (ß>1), is reexamined theoretically and by particle-in-cell simulations. Interactions of two colliding laser-produced plasma bubbles with self-generated poloidal magnetic fields of, respectively, antiparallel and parallel field lines are considered. Through comparison, it is found that the quadrupole magnetic field, bipolar poloidal electric field, plasma heating, and even the out-of-plane electric field can appear in both cases due to the mere plasma bubble collision, which may not be individually recognized as evidences of MR in the HED regime separately. The Lorentz-invariant scalar quantity D(e) ≃ γ(e)j · (E + v(e) × B) (γ(e) = [1-(v(e)/c)(2)](-1/2)) in the electron dissipation region is proposed as the key sign of MR occurrence in this regime.

16.
Artículo en Inglés | MEDLINE | ID: mdl-26651801

RESUMEN

It is shown that the filamentation instability of relativistically intense laser pulses in plasmas can be mitigated in the case where the laser beam has an elliptically distributed beam profile. A high-power elliptical Gaussian laser beam would break up into a regular filamentation pattern-in contrast to the randomly distributed filaments of a circularly distributed laser beam-and much more laser power would be concentrated in the central region. A highly elliptically distributed laser beam experiences anisotropic self-focusing and diffraction processes in the plasma channel ensuring that the unstable diffractive rings of the circular case cannot be produced. The azimuthal modulational instability is thereby suppressed. These findings are verified by three-dimensional particle-in-cell simulations.

17.
Artículo en Inglés | MEDLINE | ID: mdl-26651802

RESUMEN

A scheme for enhanced quantum electrodynamics (QED) production of electron-positron-pair plasmas is proposed that uses two ultraintense lasers irradiating a thin solid foil from opposite sides. In the scheme, under a proper matching condition, in addition to the skin-depth emission of γ-ray photons and Breit-Wheeler creation of pairs on each side of the foil, a large number of high-energy electrons and photons from one side can propagate through it and interact with the laser on the other side, leading to much enhanced γ-ray emission and pair production. More importantly, the created pairs can be collected later and confined to the center by opposite laser radiation pressures when the foil becomes transparent, resulting in the formation of unprecedentedly overdense and high-energy pair plasmas. Two-dimensional QED particle-in-cell simulations show that electron-positron-pair plasmas with overcritical density 10(22) cm(-3) and a high energy of 100s of MeV are obtained with 10 PW lasers at intensities 10(23) W/cm(2), which are of key significance for laboratory astrophysics studies.

18.
Sci Rep ; 5: 8905, 2015 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-25752272

RESUMEN

The electric-field (E-field) controlled exchange bias (EB) in a Co90Fe10/BiFeO3 (BFO)/SrRuO3/PMN-PT heterostructure has been investigated under different tensile strain states. The in-plane tensile strain of the BFO film is changed from +0.52% to +0.43% as a result of external E-field applied to the PMN-PT substrate. An obvious change of EB by the control of non-volatile strain has been observed. A magnetization reversal driven by E-field has been observed in the absence of magnetic field. Our results indicate that a reversible non-volatile E-field control of a ferromagnetic layer through strain modulated multiferroic BFO could be achieved at room temperature.

19.
Braz. j. med. biol. res ; 44(11): 1118-1124, Nov. 2011. ilus
Artículo en Inglés | LILACS | ID: lil-604270

RESUMEN

The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.


Asunto(s)
Animales , Masculino , Ratones , Envejecimiento/metabolismo , Senescencia Celular/fisiología , Estradiol/metabolismo , Miocitos Cardíacos/fisiología , Receptores Androgénicos/metabolismo , Testosterona/farmacología , Envejecimiento/patología , Biomarcadores/análisis , /efectos de los fármacos , Modelos Animales , Orquiectomía , Distribución Aleatoria , Proteína de Retinoblastoma/metabolismo , Acortamiento del Telómero/efectos de los fármacos , Testosterona/deficiencia , /metabolismo
20.
Braz J Med Biol Res ; 44(11): 1118-24, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21971687

RESUMEN

The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.


Asunto(s)
Envejecimiento/metabolismo , Senescencia Celular/fisiología , Estradiol/metabolismo , Miocitos Cardíacos/fisiología , Receptores Androgénicos/metabolismo , Testosterona/farmacología , Envejecimiento/patología , Animales , Biomarcadores/análisis , Genes p16/efectos de los fármacos , Masculino , Ratones , Modelos Animales , Orquiectomía , Distribución Aleatoria , Proteína de Retinoblastoma/metabolismo , Acortamiento del Telómero/efectos de los fármacos , Testosterona/deficiencia , Proteína p53 Supresora de Tumor/metabolismo
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