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1.
Phys Rev Lett ; 126(23): 230506, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34170169

RESUMO

Long-distance quantum communication requires quantum repeaters to overcome photon loss in optical fibers. Here we demonstrate a repeater node with two memory atoms in an optical cavity. Both atoms are individually and repeatedly entangled with photons that are distributed until each communication partner has independently received one of them. An atomic Bell-state measurement followed by classical communication serves to establish a key. We demonstrate scaling advantage of the key rate, increase the effective attenuation length by a factor of 2, and beat the error-rate threshold of 11% for unconditionally secure communication, the corner stones for repeater-based quantum networks.

2.
Phys Rev Lett ; 123(13): 133602, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31697544

RESUMO

Thorough control of the optical mode of a single photon is essential for quantum information applications. We present a comprehensive experimental and theoretical study of a light-matter interface based on cavity quantum electrodynamics. We identify key parameters like the phases of the involved light fields and demonstrate absolute, flexible, and accurate control of the time-dependent complex-valued wave function of a single photon over several orders of magnitude. This capability will be an important tool for the development of distributed quantum systems with multiple components that interact via photons.

3.
Phys Rev Lett ; 114(18): 180503, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-26000992

RESUMO

We report the experimental observation of slow-light and coherent storage in a setting where light is tightly confined in the transverse directions. By interfacing a tapered optical nanofiber with a cold atomic ensemble, electromagnetically induced transparency is observed and light pulses at the single-photon level are stored in and retrieved from the atomic medium. The decay of efficiency with storage time is also measured and related to concurrent decoherence mechanisms. Collapses and revivals can be additionally controlled by an applied magnetic field. Our results based on subdiffraction-limited optical mode interacting with atoms via the strong evanescent field demonstrate an alternative to free-space focusing and a novel capability for information storage in an all-fibered quantum network.

4.
Phys Rev Lett ; 115(2): 023602, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26207468

RESUMO

We propose and experimentally realize a novel versatile protocol that allows the quantum state engineering of heralded optical coherent-state superpositions. This scheme relies on a two-mode squeezed state, linear mixing, and a n-photon detection. It is optimally using expensive non-Gaussian resources to build up only the key non-Gaussian part of the targeted state. In the experimental case of a two-photon detection based on high-efficiency superconducting nanowire single-photon detectors, the freely propagating state exhibits a 67% fidelity with a squeezed even coherent-state superposition with a size |α|(2)=3. The demonstrated procedure and the achieved rate will facilitate the use of such superpositions in subsequent protocols, including fundamental tests and optical hybrid quantum information implementations.

5.
J Evol Biol ; 27(2): 231-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24329934

RESUMO

Transmitted culture can be viewed as an inheritance system somewhat independent of genes that is subject to processes of descent with modification in its own right. Although many authors have conceptualized cultural change as a Darwinian process, there is no generally agreed formal framework for defining key concepts such as natural selection, fitness, relatedness and altruism for the cultural case. Here, we present and explore such a framework using the Price equation. Assuming an isolated, independently measurable culturally transmitted trait, we show that cultural natural selection maximizes cultural fitness, a distinct quantity from genetic fitness, and also that cultural relatedness and cultural altruism are not reducible to or necessarily related to their genetic counterparts. We show that antagonistic coevolution will occur between genes and culture whenever cultural fitness is not perfectly aligned with genetic fitness, as genetic selection will shape psychological mechanisms to avoid susceptibility to cultural traits that bear a genetic fitness cost. We discuss the difficulties with conceptualizing cultural change using the framework of evolutionary theory, the degree to which cultural evolution is autonomous from genetic evolution, and the extent to which cultural change should be seen as a Darwinian process. We argue that the nonselection components of evolutionary change are much more important for culture than for genes, and that this and other important differences from the genetic case mean that different approaches and emphases are needed for cultural than genetic processes.


Assuntos
Comportamento , Evolução Biológica , Evolução Cultural , Modelos Teóricos , Altruísmo , Humanos , Seleção Genética
6.
J Evol Biol ; 24(12): 2531-42, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21995943

RESUMO

The evolutionary foundations of helping among nonkin in humans have been the object of intense debates in the past decades. One thesis has had a prominent influence in this debate: the suggestion that genuine altruism, strictly defined as a form of help that comes at a net fitness cost for the benefactor, might have evolved owing to cultural transmission. The gene-culture coevolution literature is wont to claim that cultural evolution changes the selective pressures that normally act to limit the emergence of altruistic behaviours. This paper aims to recall, however, that cultural transmission yields altruism only to the extent that it relies on maladaptive mechanisms, such as conformist imitation and (in some cases) payoff-biased transmission. This point is sometimes obscured in the literature by a confusion between genuine altruism, maladaptive by definition, and mutualistic forms of cooperation, that benefit all parties in the long run. Theories of cultural altruism do not lift the selective pressures weighing on strictly altruistic actions; they merely shift the burden of maladaptation from social cognition to cultural transmission.


Assuntos
Altruísmo , Evolução Cultural , Relações Interpessoais , Cognição , Genética Comportamental , Humanos , Comportamento Imitativo , Seleção Genética
7.
Int J Radiat Oncol Biol Phys ; 109(4): 1086-1095, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33197530

RESUMO

PURPOSE: Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019. METHODS AND MATERIALS: In this study, 1464 inversely planned treatments using Pinnacle or Raystation treatment planning software (TPS) were delivered using Elekta Versa HD and Varian Truebeam and Truebeam STx linear accelerators between June 2018 and November 2019. For each plan, an independent dose calculation was performed using M3D, and an absolute dose measurement was taken using a Pinpoint IC inside the Mobius phantom. The point dose differences between the TPS and M3D calculation and between TPS and IC measurements were calculated. Agreement between the TPS and IC was used to define the ground truth plan failure. To reduce the on-site personnel during the pandemic, 2 methods of receiver operating characteristic analysis (n = 1464) and machine learning (n = 603) were used to identify patient plans that would require physical dose measurements. RESULTS: In the receiver operating characteristic analysis, a predelivery M3D difference threshold of 3% identified plans that failed an IC measurement at a 4% threshold with 100% sensitivity and 76.3% specificity. This indicates that fewer than 25% of plans required a physical dose measurement. A threshold of 1% on a machine learning model was able to identify plans that failed an IC measurement at a 3% threshold with 100% sensitivity and 54.3% specificity, leading to fewer than 50% of plans that required a physical dose measurement. CONCLUSIONS: It is possible to identify plans that are more likely to fail IC patient-specific quality assurance measurements before delivery. This possibly allows for a reduction of physical measurements taken, freeing up significant clinical resources and reducing the required amount of on-site personnel while maintaining patient safety.


Assuntos
Aprendizado de Máquina , Curva ROC , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Garantia da Qualidade dos Cuidados de Saúde
8.
Med Phys ; 37(3): 1246-53, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20384262

RESUMO

PURPOSE: To determine the properties of a megavoltage cone-beam CT system using the unflattened beam from a sintered diamond target at 4 and 6 MV. METHODS: A sintered diamond target was used in place of a graphite target as part of an imaging beam line (an unflattened beam from a graphite target) installed on a linear accelerator. The diamond target, with a greater density than the graphite target, permitted imaging at the lower beam energy (4 MV) required with the graphite target and the higher beam energy (6 MV) conventionally used with the tungsten/stainless steel target and stainless steel flattening filter. Images of phantoms and patients were acquired using the different beam lines and compared. The beam spectra and dose distributions were determined using Monte Carlo simulation. RESULTS: The diamond target allowed use of the same beam energy as for treatment, simplifying commissioning and quality assurance. Images acquired with the diamond target at 4 MV were similar to those obtained with the graphite target at 4 MV. The slight reduction in low energy photons due to the higher-Z sintering material in the diamond target had minimal effect on image quality. Images acquired at 6 MV with the diamond target showed a small decrease in contrast-to-noise ratio, resulting from a decrease in the fraction of photons in the beam in the energy range to which the detector is most sensitive. CONCLUSIONS: The diamond target provides images of a similar quality to the graphite target. Diamond allows use of the higher beam energy conventionally used for treatment, provides a higher dose rate for the same beam current, and potentially simplifies installation and maintenance of the beam line.


Assuntos
Tomografia Computadorizada de Feixe Cônico/instrumentação , Diamante/efeitos da radiação , Aumento da Imagem/instrumentação , Tomografia Computadorizada de Feixe Cônico/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Med Phys ; 35(4): 1310-6, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18491525

RESUMO

This article reports on the image characteristics of megavoltage cone-beam digital tomosynthesis (MVCB DT). MVCB DT is an in-room imaging technique, which enables the reconstruction of several two-dimensional slices from a set of projection images acquired over an arc of 20 degrees-40 degrees. The limited angular range reduces the acquisition time and the dose delivered to the patient, but affects the image quality of the reconstructed tomograms. Image characteristics (slice thickness, shape distortion, and contrast-to-noise ratio) are studied as a function of the angular range. Potential clinical applications include patient setup and the development of breath holding techniques for gated imaging.


Assuntos
Algoritmos , Tomografia Computadorizada de Feixe Cônico/métodos , Imageamento Tridimensional/métodos , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada de Feixe Cônico/instrumentação , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Neurophysiol Clin ; 38(3): 189-95, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18539253

RESUMO

We review the findings of 24 fMRI studies examining activations in the premotor cortex (Brodmann's areas 6 and 44) during passive observation of actions. We found that such activations regularly occurred. Looking for functional differentiation in the premotor cortex, we found that one parameter was associated with systematic differences in location: this was the presence or absence of targets. Observing biological actions with a physical target, compared to a visual control showing no action at all, consistently activated the ventral premotor cortex (BA 6), and did so significantly more than observing target-less actions (with the same control). In contrast, the activity in BA 44 ("Broca's area") was not modulated by the presence or absence of targets. We propose that the ventral precentral gyrus, and not BA 44, shares the visual properties of "mirror" neurons found in area F5 of the macaque brain.


Assuntos
Córtex Motor/fisiologia , Animais , Lobo Frontal/anatomia & histologia , Lobo Frontal/fisiologia , Humanos , Imageamento por Ressonância Magnética , Córtex Motor/anatomia & histologia , Movimento/fisiologia , Córtex Somatossensorial/fisiologia , Percepção Visual/fisiologia
11.
Rev Mal Respir ; 24(5): 617-21, 2007 May.
Artigo em Francês | MEDLINE | ID: mdl-17519813

RESUMO

INTRODUCTION: Mucormycosis is a rare opportunistic fungal infection due to filamentous fungi of the order Mucorales in the class Zygomycetes. Rhino-cerebral and pulmonary manifestations predominate on account of the airborn spread of the spores. Gastro-intestinal, cutaneous and disseminated disease is less common. The principal risk factors are immuno-suppression and diabetic keto-acidosis. CASE REPORTS: One case of fatal pulmonary mucormycosis and two cases of colonisation illustrate both the extreme severity of this disease and the diagnostic difficulties facing the physician. The ubiquitous nature of the organism leads to frequent colonisation and, moreover, the symptomatology readily mimics that of invasive pulmonary aspergillosis. The diagnosis of mucormycosis can only be confirmed by pathological and mycological examination of biopsy specimens. These requirements conflict with the need for urgent treatment with surgical debridement, amphotericin B and control of the underlying pathology. Sadly the mortality remains very high, between 50 and 80% in published series. CONCLUSION: Currently there is hope of new therapeutic approaches with posaconozole but the ineffectiveness of voriconozole and the echinocandines, used more and more against aspergillus, raises the possibility of an increase in mucormycosis by selection.


Assuntos
Pneumopatias Fúngicas/diagnóstico , Mucormicose/diagnóstico , Adulto , Idoso , Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Biópsia , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Fibrose Cística/cirurgia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Transplante de Coração-Pulmão , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mucormicose/tratamento farmacológico , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Fibrose Pulmonar/complicações , Rhizopus/isolamento & purificação
12.
Cancer Radiother ; 10(5): 258-68, 2006 Sep.
Artigo em Francês | MEDLINE | ID: mdl-16861025

RESUMO

The Megavoltage cone-beam (MV CBCT) system consists of a new a-Si flat panel adapted for MV imaging and an integrated workflow application allowing the automatic acquisition of projection images, cone-beam CT image reconstruction, CT to CBCT image registration and couch position adjustment. This provides a 3D patient anatomy volume in the actual treatment position, relative to the treatment isocenter, moments before the dose delivery, that can be tightly aligned to the planning CT, allowing verification and correction of the patient position, detection of anatomical changes and dose calculation. In this paper, we present the main advantages and performance of this MV CBCT system and summarize the different clinical applications. Examples of the image-guided treatment process from the acquisition of the MV CBCT scan to the correction of the couch position and dose delivery will be presented for spinal and lung lesions and for head and neck, and prostate cancers.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Prótese de Quadril , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neoplasias Pulmonares/radioterapia , Masculino , Postura , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Assistida por Computador , Neoplasias da Coluna Vertebral/radioterapia
13.
Med Phys ; 43(5): 2283, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27147340

RESUMO

PURPOSE: To characterize a new air vented ionization chamber technology, suitable to build detector arrays with small pixel pitch and independence of sensitivity on dose per pulse. METHODS: The prototype under test is a linear array of air vented ionization chambers, consisting of 80 pixels with 3.5 mm pixel pitch distance and a sensitive volume of about 4 mm(3). The detector has been characterized with (60)Co radiation and MV x rays from different linear accelerators (with flattened and unflattened beam qualities). Sensitivity dependence on dose per pulse has been evaluated under MV x rays by changing both the source to detector distance and the beam quality. Bias voltage has been varied in order to evaluate the charge collection efficiency in the most critical conditions. Relative dose profiles have been measured for both flattened and unflattened distributions with different field sizes. The reference detectors were a commercial array of ionization chambers and an amorphous silicon flat panel in direct conversion configuration. Profiles of dose distribution have been measured also with intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and volumetric modulated arc therapy (VMAT) patient plans. Comparison has been done with a commercial diode array and with Gafchromic EBT3 films. RESULTS: Repeatability and stability under continuous gamma irradiation are within 0.3%, in spite of low active volume and sensitivity (∼200 pC/Gy). Deviation from linearity is in the range [0.3%, -0.9%] for a dose of at least 20 cGy, while a worsening of linearity is observed below 10 cGy. Charge collection efficiency with 2.67 mGy/pulse is higher than 99%, leading to a ±0.9% sensitivity change in the range 0.09-2.67 mGy/pulse (covering all flattened and unflattened beam qualities). Tissue to phantom ratios show an agreement within 0.6% with the reference detector up to 34 cm depth. For field sizes in the range 2 × 2 to 15 × 15 cm(2), the output factors are in agreement with a thimble chamber within 2%, while with 25 × 25 cm(2) field size, an underestimation of 4.0% was found. Agreement of field and penumbra width measurements with the flat panel is of the order of 1 mm down to 1 × 1 cm(2) field size. Flatness and symmetry values measured with the 1D array and the reference detectors are comparable, and differences are always smaller than 1%. Angular dependence of the detector, when compared to measurements taken with a cylindrical chamber in the same phantom, is as large as 16%. This includes inhomogeneity and asymmetry of the design, which during plan verification are accounted for by the treatment planning system (TPS). The detector is capable to reproduce the dose distributions of IMRT and VMAT plans with a maximum deviation from TPS of 3.0% in the target region. In the case of VMAT and SRS plans, an average (maximum) deviation of the order of 1% (4%) from films has been measured. CONCLUSIONS: The investigated technology appears to be useful both for Linac QA and patient plan verification, especially in treatments with steep dose gradients and nonuniform dose rates such as VMAT and SRS. Major limitations of the present prototype are the linearity at low dose, which can be solved by optimizing the readout electronics, and the underestimation of output factors with large field sizes. The latter problem is presently not completely understood and will require further investigations.


Assuntos
Garantia da Qualidade dos Cuidados de Saúde , Radiometria/instrumentação , Radiocirurgia/instrumentação , Radioterapia de Intensidade Modulada/instrumentação , Radioisótopos de Cobalto , Desenho de Equipamento , Aceleradores de Partículas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Radiometria/métodos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Reprodutibilidade dos Testes , Raios X
14.
Int J Antimicrob Agents ; 25(4): 321-8, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15784312

RESUMO

Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest and compared with those of amphotericin B, itraconazole and fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.


Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida/efeitos dos fármacos , Pirimidinas/farmacologia , Triazóis/farmacologia , Anfotericina B/farmacologia , Aspergillus/classificação , Candida/classificação , Farmacorresistência Fúngica , Humanos , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Voriconazol
15.
J Clin Endocrinol Metab ; 77(1): 221-8, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8325946

RESUMO

To test the hypothesis that 3,5,3'-triiodothyroacetic acid (Triac) is more active as a TSH suppressor than on peripheral parameters of thyroid hormone action, the following parameters were studied: basal metabolic rate, sleeping energy expenditure (SEE), sex hormone-binding globulin, and cholesterol. In a double blind trial, 14 subjects received during 3 weeks (phase 1) 180 micrograms T4 or 1700 micrograms Triac daily, divided into 3 doses, to suppress thyroidal secretion. The dosage was doubled for the next 3 weeks (phase 2). Under T4 treatment, TSH reached 0.11 mU/L during phase 1 and less than 0.03 mU/L during phase 2. With Triac, a marked TSH inhibition occurred after 1 week (0.17 mU/L), followed by an escape during the following 2 weeks (0.63 mU/L). During phase 2, an almost complete TSH suppression was obtained (0.03 mU/L). Both Triac doses suppressed endogenous thyroid hormone secretion, as evidenced by T4 and rT3 levels. Both substances induced a 2-fold stimulation of sex hormone-binding globulin during phase 2. Serum cholesterol decreased similarly, without affecting the high/low density lipoprotein ratio. T4 increased SEE by 4.1% and 8.5% during phases 1 and 2. Triac failed to induce the expected peripheral metabolic responses of the thyroid hormones, as demonstrated by an unchanged SEE and basal metabolic rate. These results clearly show a preferential action of Triac on TSH suppression.


Assuntos
Tireotropina/metabolismo , Tiroxina/farmacologia , Tri-Iodotironina/análogos & derivados , Metabolismo Basal/efeitos dos fármacos , Colesterol/sangue , Metabolismo Energético/efeitos dos fármacos , Meia-Vida , Humanos , Cinética , Masculino , Respiração/efeitos dos fármacos , Globulina de Ligação a Hormônio Sexual/metabolismo , Sono/fisiologia , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/administração & dosagem , Tri-Iodotironina/farmacocinética , Tri-Iodotironina/farmacologia , Tri-Iodotironina Reversa/sangue
16.
J Endocrinol ; 151(1): 147-57, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8943779

RESUMO

Interleukin-1 beta has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1 beta dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1 beta. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1 beta-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1 beta-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor NG-monomethylarginine did not ameliorate the effect of interleukin-1 beta on FRTL-5 cell iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1 beta for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1 beta-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1 beta in diabetes-prone BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells.


Assuntos
Hipotireoidismo/induzido quimicamente , Interleucina-1/farmacologia , Óxido Nítrico , Glândula Tireoide/efeitos dos fármacos , Tireoidite/induzido quimicamente , Animais , Linhagem Celular , Células Cultivadas , Diabetes Mellitus , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Nitroarginina/farmacologia , RNA Mensageiro/análise , Ratos , Ratos Brattleboro , Ratos Endogâmicos WKY , Proteínas Recombinantes/farmacologia
17.
Mol Cell Endocrinol ; 25(3): 339-52, 1982 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7040139

RESUMO

Insulin and glucagon binding, and the subsequent stimulation of amino-acid transport, were investigated in adult-rat hepatocytes. Cells were used either in suspension shortly after isolation, or as monolayers after 20 h of culture in a serum-free medium. At 37 degrees C, hepatocytes in monolayer cultures bound 2.5 times as much insulin and glucagon as did freshly isolated cells, owing to an increase in the total number of binding sites per cell. For both hormones, these differences could be accounted for mainly by a greater number of low-affinity binding sites in primary cultured hepatocytes compared with freshly isolated cells. Exposure of hepatocytes to insulin or glucagon for 2-3 h at 37 degrees C in a medium free from amino acids increased the capacity (primary cultures) or induced the emergence (fresh suspensions) of a similar high-affinity component (Km approximately mM) of alpha-aminoisobutyric-acid (AIB) transport. Primary cultured hepatocytes were more sensitive to insulin (half-maximal effect occurred with insulin at approximately 0.3 nM) than freshly isolated cells (half-maximal effect approximately 0.7 nM) for the stimulation of AIB transport, whereas the dose-response curves were virtually indistinguishable for the glucagon stimulation of AIB transport in both preparations of cells (half-maximal effect occurred with glucagon at approximately 1.5 nM). These results indicate that, despite differences in the apparent insulin- and glucagon-binding capacities (which involved mainly a low affinity site), both freshly isolated and primary cultured (20-h monolayers) hepatocytes behave similarly in response to insulin and glucagon with regard to the stimulation of amino acid transport.


Assuntos
Aminoácidos/metabolismo , Glucagon/farmacologia , Insulina/farmacologia , Fígado/metabolismo , Ácidos Aminoisobutíricos/metabolismo , Animais , Sítios de Ligação , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Glucagon/metabolismo , Insulina/metabolismo , Cinética , Masculino , Ratos , Ratos Endogâmicos
18.
Eur J Endocrinol ; 132(6): 751-8, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7788017

RESUMO

The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For this purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T4) and a short-acting one, triiodothyroacetic acid (Triac). Based on preliminary experiments with different doses of T4 and Triac, hypothyroid rats (N = 84) received over 6 days' injections of 10 nmol Triac or 2 nmol T4/100 g body wt per day. Biological effects of Triac and T4 were measured in the pituitary, liver and kidney up to 8 days after stopping treatment. With Triac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9 +/- 1.8 micrograms/l (hypothyroid 14.5 +/- 0.8 micrograms/l). The rapid changes in serum TSH levels were followed by a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to that after T4 injection. Even 8 days after Triac treatment, serum TSH levels did not reach the hypothyroid control levels. Changes in beta-TSH mRNA levels also showed a prolonged inhibition after both treatments and a slow return to hypothyroid values, which was not complete 8 days after stopping treatment. A second parameter was hepatic 5'-deiodinase type I (5'D-I). The 6-day treatment with Triac had a markedly stronger effect on 5'D-I enzyme activity and mRNA levels than treatment with T4.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Iodeto Peroxidase/metabolismo , Tireotropina/sangue , Tiroxina/farmacologia , Tri-Iodotironina/análogos & derivados , Animais , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/genética , Hipotireoidismo/metabolismo , Iodeto Peroxidase/genética , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Especificidade de Órgãos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Tireotropina/genética , Tiroxina/administração & dosagem , Tri-Iodotironina/administração & dosagem , Tri-Iodotironina/farmacologia
19.
Metabolism ; 31(8): 766-72, 1982 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7047983

RESUMO

The binding of insulin and glucagon and the effects of these hormones on amino acid transport were examined in isolated rat hepatocytes from streptozotocin diabetic rats. Hepatocytes from diabetic rats bound more insulin than cells from control animals. These changes were accounted for by a 50%-60% increase in the number of insulin receptors per cell. Glucagon binding did not significantly differ in hepatocytes from both groups. Following a 2 hr incubation of the cells in vitro, the basal rate of alpha-aminoisobutyric acid (AIB) influx was enhanced in diabetic rat hepatocytes compared to controls. This alteration was accounted for by an increase in the Vmax of both a low affinity and a high affinity component of transport. The ability of diabetic rat hepatocytes to respond to maximally stimulating concentrations of insulin or glucagon by enhancing further the rate of AIB influx was markedly diminished. Hormone responsiveness was restored to normal in hepatocytes from insulin-treated diabetic animals. The data suggest that in diabetic rat hepatocytes the diminished insulin and glucagon responsiveness with regard to the stimulation of amino acid transport stems from postreceptor alteration(s).


Assuntos
Ácidos Aminoisobutíricos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glucagon/metabolismo , Insulina/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucagon/farmacologia , Insulina/farmacologia , Cinética , Masculino , Ratos
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