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1.
Phys Rev Lett ; 129(22): 227701, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36493424

RESUMO

Electrostatic charging affects the many-body spectrum of Andreev states, yet its influence on their microwave properties has not been elucidated. We developed a circuit quantum electrodynamics probe that, in addition to transition spectroscopy, measures the microwave susceptibility of different states of a semiconductor nanowire weak link with a single dominant (spin-degenerate) Andreev level. We found that the microwave susceptibility does not exhibit a particle-hole symmetry, which we qualitatively explain as an influence of Coulomb interaction. Moreover, our state-selective measurement reveals a large, π-phase shifted contribution to the response common to all many-body states which can be interpreted as arising from a phase-dependent continuum in the superconducting density of states.


Assuntos
Eletricidade Estática
2.
Osteoarthritis Cartilage ; 29(1): 113-123, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33161100

RESUMO

OBJECTIVE: miR-122 stimulates proliferation of growth plate chondrocytes whereas miR-451 stimulates terminal differentiation and matrix turnover. Here, we examined the potential of these microRNA as regulators of articular chondrocytes using an in vitro model of osteoarthritis. METHODS: miR-122 and miR-451 presence in rat articular cartilage was assessed using the anterior cruciate ligament transection model of OA. In vitro testing used first passage rat articular chondrocytes (rArCs) that were transfected with lipofectamine (Lipo) and miR-122 or miR-451 for 24-h, then treated with 10 ng/mL IL-1ß in order to mimic an osteoarthritic environment. Conditioned media were collected and MMP13, PGE2 and OA-related cytokines were measured. Matrix vesicles were collected from cell layer lysates using ultra-centrifugation. Cells were treated with miR-122 or miR-451 inhibitors to verify miR-specific effects. RESULTS: Both miR-122 and miR-451 were increased in the OA articular cartilage compared to healthy tissue; rArCs expressed both microRNAs in MVs. miR-122 prevented IL-1ß-dependent increases in MMP-13 and PGE2, whereas miR-451 significantly increased the IL-1ß effect. Multiplex data indicated that miR-122 reduced the stimulatory effect of IL-1ß on IL-1α, IL-2, Il-4, IL-6, GM-CSF, MIP-1A, RANTES and VEGF. In contrast, IL-2, IL-4, IL-6, GM-CSF, and MIP-1A were increased by miR-451 while VEGF was decreased. Inhibiting miR-122 exacerbated the response to IL-1ß indicating endogenous levels of miR-122 were present. There were no differences in MMP-13 or PGE2 with miR-451 Locked Nucleic Acid (LNA) inhibitor treatment. CONCLUSIONS: Both miRs were elevated in OA in a rat bilateral anterior cruciate ligament transection (ACLT) model. miR-122 prevented, while miR-451 exacerbated the effects of IL-1ß on rArCs.


Assuntos
Artrite Experimental/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , MicroRNAs/genética , Osteoartrite do Joelho/metabolismo , Animais , Lesões do Ligamento Cruzado Anterior/complicações , Artrite Experimental/etiologia , Cartilagem Articular/citologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Técnicas In Vitro , Metaloproteinase 13 da Matriz/metabolismo , Oligonucleotídeos , Osteoartrite do Joelho/etiologia , Ratos
3.
J Toxicol Environ Health A ; 84(16): 674-688, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006202

RESUMO

Human exposure to wildfire-derived particulate matter (PM) is linked to adverse health outcomes; however, little is known regarding the influence of biomass fuel type and burn conditions on toxicity. The aim of this study was to assess the irritant potential of extractable organic material (EOM) of biomass smoke condensates from five fuels (eucalyptus, pine, pine needle, peat, or red oak), representing various fire-prone regions of the USA, burned at two temperatures each [flaming (approximately 640°C) or (smoldering approximately 500°C)] using a locomotor assay in zebrafish (Danio rerio) larvae. It was postulated that locomotor responses, as measures of irritant effects, might be dependent upon fuel type and burn conditions and that these differences relate to combustion byproduct chemistry. To test this, locomotor activity was tracked for 60 min in 6-day-old zebrafish larvae (25-32/group) immediately after exposure to 0.4% dimethyl sulfoxide (DMSO) vehicle or EOM from the biomass smoke condensates (0.3-30 µg EOM/ml; half-log intervals). All EOM samples produced concentration-dependent irritant responses. Linear regression analysis to derive rank-order potency indicated that on a µg PM basis, flaming pine and eucalyptus were the most irritating. In contrast, on an emission-factor basis, which normalizes responses to the amount of PM produced/kg of fuel burned, smoldering smoke condensates induced greater irritant responses (>100-fold) than flaming smoke condensates, with smoldering pine being the most potent. Importantly, irritant responses significantly correlated with polycyclic aromatic hydrocarbon (PAH) content, but not with organic carbon or methoxyphenols. Data indicate that fuel type and burn condition influence the quantity and chemical composition of PM as well as toxicity.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Irritantes/efeitos adversos , Fumaça/efeitos adversos , Incêndios Florestais/classificação , Peixe-Zebra , Poluentes Atmosféricos/química , Animais , Biomassa , Irritantes/química
4.
Phys Rev Lett ; 121(4): 047001, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30095962

RESUMO

The modern understanding of the Josephson effect in mesosopic devices derives from the physics of Andreev bound states, fermionic modes that are localized in a superconducting weak link. Recently, Josephson junctions constructed using semiconducting nanowires have led to the realization of superconducting qubits with gate-tunable Josephson energies. We have used a microwave circuit QED architecture to detect Andreev bound states in such a gate-tunable junction based on an aluminum-proximitized indium arsenide nanowire. We demonstrate coherent manipulation of these bound states, and track the bound-state fermion parity in real time. Individual parity-switching events due to nonequilibrium quasiparticles are observed with a characteristic timescale T_{parity}=160±10 µs. The T_{parity} of a topological nanowire junction sets a lower bound on the bandwidth required for control of Majorana bound states.

5.
Phys Rev Lett ; 121(15): 157701, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30362798

RESUMO

Nonequilibrium quasiparticle excitations degrade the performance of a variety of superconducting circuits. Understanding the energy distribution of these quasiparticles will yield insight into their generation mechanisms, the limitations they impose on superconducting devices, and how to efficiently mitigate quasiparticle-induced qubit decoherence. To probe this energy distribution, we systematically correlate qubit relaxation and excitation with charge-parity switches in an offset-charge-sensitive transmon qubit, and find that quasiparticle-induced excitation events are the dominant mechanism behind the residual excited-state population in our samples. By itself, the observed quasiparticle distribution would limit T_{1} to ≈200 µs, which indicates that quasiparticle loss in our devices is on equal footing with all other loss mechanisms. Furthermore, the measured rate of quasiparticle-induced excitation events is greater than that of relaxation events, which signifies that the quasiparticles are more energetic than would be predicted from a thermal distribution describing their apparent density.

6.
Environ Sci Technol ; 46(12): 6637-44, 2012 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-22621615

RESUMO

The chemical factors influencing iron solubility (soluble iron/total iron) were investigated in source emission (e.g., biomass burning, coal fly ash, mineral dust, and mobile exhaust) and ambient (Atlanta, GA) fine particles (PM2.5). Chemical properties (speciation and mixing state) of iron-containing particles were characterized using X-ray absorption near edge structure (XANES) spectroscopy and micro-X-ray fluorescence measurements. Bulk iron solubility (soluble iron/total iron) of the samples was quantified by leaching experiments. Major differences were observed in iron solubility in source emission samples, ranging from low solubility (<1%, mineral dust and coal fly ash) up to 75% (mobile exhaust and biomass burning emissions). Differences in iron solubility did not correspond to silicon content or Fe(II) content. However, source emission and ambient samples with high iron solubility corresponded to the sulfur content observed in single particles. A similar correspondence between bulk iron solubility and bulk sulfate content in a series of Atlanta PM2.5 fine particle samples (N = 358) further supported this trend. In addition, results of linear combination fitting experiments show the presence of iron sulfates in several high iron solubility source emission and ambient PM2.5 samples. These results suggest that the sulfate content (related to the presence of iron sulfates and/or acid-processing mechanisms by H(2)SO(4)) of iron-containing particles is an important proxy for iron solubility.


Assuntos
Poluentes Atmosféricos , Ferro/química , Enxofre/análise , Biomassa , Tamanho da Partícula , Solubilidade , Espectroscopia por Absorção de Raios X
7.
Environ Sci Technol ; 45(8): 3415-21, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21428391

RESUMO

This paper addresses the need for detailed chemical information on the fine particulate matter (PM) generated by commercial aviation engines. The exhaust plumes of seven turbofan engine models were sampled as part of the three test campaigns of the Aircraft Particle Emissions eXperiment (APEX). In these experiments, continuous measurements of black carbon (BC) and particle surface-bound polycyclic aromatic compounds (PAHs) were conducted. In addition, time-integrated sampling was performed for bulk elemental composition, water-soluble ions, organic and elemental carbon (OC and EC), and trace semivolatile organic compounds (SVOCs). The continuous BC and PAH monitoring showed a characteristic U-shaped curve of the emission index (EI or mass of pollutant/mass of fuel burned) vs fuel flow for the turbofan engines tested. The time-integrated EIs for both elemental composition and water-soluble ions were heavily dominated by sulfur and SO(4)(2-), respectively, with a ∼2.4% median conversion of fuel S(IV) to particle S(VI). The corrected OC and EC emission indices obtained in this study ranged from 37 to 83 mg/kg and 21 to 275 mg/kg, respectively, with the EC/OC ratio ranging from ∼0.3 to 7 depending on engine type and test conditions. Finally, the particle SVOC EIs varied by as much as 2 orders of magnitude with distinct variations in chemical composition observed for different engine types and operating conditions.


Assuntos
Poluentes Atmosféricos/análise , Aeronaves , Material Particulado/análise , Emissões de Veículos/análise , Poluentes Atmosféricos/química , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/química , Fuligem/análise , Fuligem/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química
8.
Science ; 373(6553): 430-433, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437115

RESUMO

Two promising architectures for solid-state quantum information processing are based on electron spins electrostatically confined in semiconductor quantum dots and the collective electrodynamic modes of superconducting circuits. Superconducting electrodynamic qubits involve macroscopic numbers of electrons and offer the advantage of larger coupling, whereas semiconductor spin qubits involve individual electrons trapped in microscopic volumes but are more difficult to link. We combined beneficial aspects of both platforms in the Andreev spin qubit: the spin degree of freedom of an electronic quasiparticle trapped in the supercurrent-carrying Andreev levels of a Josephson semiconductor nanowire. We performed coherent spin manipulation by combining single-shot circuit-quantum-electrodynamics readout and spin-flipping Raman transitions and found a spin-flip time T S = 17 microseconds and a spin coherence time T 2E = 52 nanoseconds. These results herald a regime of supercurrent-mediated coherent spin-photon coupling at the single-quantum level.

9.
East Afr Med J ; 87(7): 284-93, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23451547

RESUMO

OBJECTIVE: To test whether a single take home dose of infant nevirapine increased infant uptake without decreasing institutional deliveries. DESIGN: Cluster randomised post-test only study with control group. SETTING: Ten hospitals in urban areas of Coast, Rift Valley, and Western provinces, Kenya. PARTICIPANTS: Pregnant women with HIV, 18 years and older, and at least 32 weeks gestation recruited during antenatal care and followed up at home approximately one week after delivery. INTERVENTION: In the intervention group, women were given a single infant's dose of nevirapine to take home prior to delivery. In the control group, no changes were made to the standard of care. MAIN OUTCOME MEASURES: Mothers' reports of infant uptake of nevirapine and place of delivery. RESULTS: Uptake of the infant's nevirapine dose was high, 94% in the intervention group and 88% in the control group (p=0.096). Among women who delivered at home, uptake was higher significantly among infants whose mothers got the take home dose compared to women who did not get the dose (93% vs. 53%, p<0.01). The intervention did not influence place of delivery. Providers were positive about the take home dose concept; difficulties were attributed to HIV-related stigma. CONCLUSIONS: Making take home infant nevirapine available, either as a single dose administered within 72 hours of birth or as part of a more complex six week postnatal regimen, will increase infant uptake especially among women who deliver at home without affecting place of delivery.


Assuntos
Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/administração & dosagem , Cooperação do Paciente , Inibidores da Transcriptase Reversa/administração & dosagem , Adolescente , Adulto , Feminino , Infecções por HIV/prevenção & controle , Humanos , Recém-Nascido , Quênia , Gravidez , Cuidado Pré-Natal , Adulto Jovem
10.
J Clin Invest ; 48(6): 1114-23, 1969 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-4977031

RESUMO

10 normal young men received repository epinephrine repeatedly for 4 days during the course of a radiothyroxine (radio-T4) disappearance curve. During epinephrine administration, serum radio-T4 disappearance rate (k) slowed abruptly, fecal clearance decreased, urinary clearance was initially unchanged but later decreased slightly, volume of thyroxine distribution decreased, and external radioactivity over the liver remained unchanged. Beginning on day 2 of epinephrine and persisting at least 1 day after epinephrine was discontinued, serum thyroxine-binding globulin (TBG) maximal binding capacity increased, thyroxine-binding prealbumin (TBPA) maximal binding capacity decreased, and free T4 iodine decreased. Stable serum T4 iodine decreased during the experiment. Three indexes, namely the free T4 iodine, the reciprocal of TBG capacity, and the urinary radio-T4 "clearance" changed in parallel, suggesting that the increase in TBG capacity was responsible for a delayed decrease in radio-T4 metabolism. However, these changes were temporally dissociated from the decrease in k, which began and ended abruptly with initiation or discontinuing of epinephrine administration. This dissociation is unexplained, but may be caused by alterations in T4 binding in tissue sites.


Assuntos
Epinefrina/farmacologia , Tiroxina/sangue , Fezes/análise , Humanos , Iodo/metabolismo , Isótopos de Iodo , Fígado/metabolismo , Masculino , Albumina Sérica/metabolismo , Soroglobulinas/metabolismo , Glândula Tireoide/metabolismo , Tiroxina/análise , Tiroxina/metabolismo , Tiroxina/urina , Proteínas de Ligação a Tiroxina/metabolismo , Tri-Iodotironina/metabolismo
11.
Biochim Biophys Acta ; 1279(1): 43-8, 1996 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-8624359

RESUMO

A number of fatty acids and derivatives have been shown to activate Na+/K(+)-ATPase when ATP is suboptimal. To explore the relation of the structures of these amphiphiles to enzyme activation, the effects of varying amphiphile concentrations on the activity of the highly purified kidney Na+/K(+)-ATPase at 50 microM ATP were determined. Among fatty acids, efficacy (maximal level of activation) and potency were found to be dependent, in different ways, on chain length and unsaturation. Compared to fatty acids, the corresponding alcohols had lower efficacies. Methyl esters of fatty acids inhibited, but CoA esters and monoacyl esters of glycerol activated the enzyme. Relation between chain length and potency among CoA esters and monoacylglycerols was the same as that observed with acids. Diacylglycerols did not activate, but they antagonized the effects of the activator amphiphiles. The substantial specificities of the amphiphile effects support the hypothesis that these ligands bind to a distinct amphipathic peptide segment of the intracellular central loop of the alpha-subunit to regulate ATP binding to the enzyme. The findings also suggest that direct effects of the changing intracellular levels of fatty acids and derivatives on Na+/K(+)-ATPase should be considered as a possible mechanism for the regulation of its function in the intact cell.


Assuntos
Ácidos Graxos/farmacologia , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Animais , Diglicerídeos/farmacologia , Cães , Ativação Enzimática/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Relação Estrutura-Atividade
12.
Endocrinology ; 122(6): 2444-61, 1988 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3371254

RESUMO

A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in the euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4. Analysis of the data indicates that the increased overall T4* turnover (decreased MRT) in hyperthyroidism is due to increased losses through pathways other than T3 formation. Conjugation, with subsequent deiodination, is proposed as one possibly important pathway. Results of this multicompartmental analysis are compared with those of noncompartmental analysis of the same data and with results of similar model analyses in other species.


Assuntos
Hipertireoidismo/metabolismo , Iodetos/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Animais , Gatos , Fezes/análise , Iodetos/sangue , Iodetos/urina , Radioisótopos do Iodo , Cinética , Matemática , Taxa de Depuração Metabólica , Modelos Biológicos , Estatística como Assunto , Glândula Tireoide/metabolismo , Tiroxina/sangue , Tiroxina/urina , Tri-Iodotironina/sangue , Tri-Iodotironina/urina
13.
J Clin Endocrinol Metab ; 51(5): 1112-7, 1980 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7419686

RESUMO

Distributional kinetics of radioiodinated T4 (T4), T3 (T3), and albumin (RISA), after simultaneous administration by the sc and iv routes of 125I- and 131I-labeled compounds, were measured in normal subjects. Data were analyzed by fitting them, using the SAAM technique, to models with three compartments for the iv administered compounds and a fourth compartment for the site of the sc injection. The radiopharmaceuticals administered sc transfered by first order kinetics from the injection site to plasma with half-lives of 20.4, 5.6, and 63.0 h for T4, T3, and RISA, respectively. Percentages of 3.3, 1.2, and 2.1 of the sc dose appeared directly in the vascular compartment. In some, but not all, studies with sc T4 and RISA, a portion of the disappearance from the sc site appeared to be due to in situ deiodination, rather than to transfer of the parent compound into the circulation. After T3 administration, both iv and sc, a product with kinetics similar to RISA appeared, accounting for 3% of the T3 decay for the averaged data and ranging from 0.9--19.4% in individual cases. Comparing T3 kinetic analysis by this technique (in which the iodoprotein byproduct is accounted for by modeling instead of chemical separation), the resulting parameters are similar to those reported by others after chemical separation of T3. Judging by compartment size and distributional kinetics, the model compartments derived for iv administration of these compounds appear to represent the vascular pool (central compartment), the hepatic and renal distribution sites (fast peripheral compartment), and other peripheral tissues (slow peripheral compartment). The latter, which presumably includes the site of sc injection, transfers into the central compartment at approximately the same rate as does the compartment representing the sc injection site itself.


Assuntos
Albumina Sérica/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Adulto , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Cinética , Valores de Referência , Albumina Sérica/administração & dosagem , Tiroxina/administração & dosagem , Tri-Iodotironina/administração & dosagem
14.
J Clin Endocrinol Metab ; 53(4): 852-62, 1981 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7287869

RESUMO

We have examined the in vivo distribution and metabolism of radiolabeled T4 and T3 in 14 normal subjects using a kinetic model. Tracer amounts of [131I]T4 and [125I]T3 were injected simultaneously, and plasma samples were obtained for up to 7 days thereafter. Separation of these samples by thin layer chromatography yielded kinetic curves for 131I- and 125I-labeled T4, T3, iodide, and iodoprotein, which were then used to develop a kinetic model. The model includes several features. 1) Submodels were developed for T4, T3, iodide, and iodoprotein which simultaneously fit the observed data. 2) Two other submodels were needed for data fit, the first representing rT3, the other representing other intermediates, including the various diiodothyronines. The latter submodel was patterned initially after 3,3'-diiodothyronine kinetics. It was required to account for the delay in appearance of labeled iodide produced from the degradation of T4, and rT3 and proved to be essential for the successful fit of the data. 3) The model accounts for the conversion of T4 to T3 and rT3. Even though rT3 is quantitatively significant as a degradation pathway for T4, its presence does not contribute significantly to total plasma radioactivity after T4 administration because of its rapid turnover in comparison with T4. 4) The small amount of iodoprotein formed is a major contributor to total plasma radioactivity within 3 days after T3 administration. 5) The model permits the elimination of two methodological errors: that due to the presence of labeled iodide, T3, or T4 contaminants in the administered labeled hormones, and that due to the small amount of cross-over between thin layer chromatography peaks. The model provides a concise description of our current understanding of thyroid hormone metabolism and suggests areas where further information is required.


Assuntos
Modelos Biológicos , Hormônios Tireóideos/metabolismo , Adulto , Humanos , Iodetos/metabolismo , Radioisótopos do Iodo , Iodoproteínas/metabolismo , Cinética , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Tri-Iodotironina Reversa/metabolismo
15.
Int J Radiat Oncol Biol Phys ; 11(2): 335-48, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3882643

RESUMO

Cancer-seeking antibodies carrying radionuclides can, in theory, be very powerful agents for the radiotherapy of cancer. However, as with all radiotherapy, the undesired dose to critical normal organs is the limiting factor that determines success or failure. The distribution of radiation dose in cancer and noncancer tissue is highly dependent on choices the therapist can make: choices of the antigens to be targeted, choices of the antibodies or antibody fragments to be used, choices of radionuclides, of amounts, of timing, and other electives. New technologies, especially of monoclonal antibody production, make the options myriad. Optimization of this therapy depends on a foreknowledge of the radiation dose distributions to be expected. The necessary data can be acquired by established tracer techniques, in individual patients, for particular treatment selections. These tracer techniques can now be implemented by advanced equipment for quantitative, tomographic radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution.


Assuntos
Anticorpos Antineoplásicos/administração & dosagem , Neoplasias/radioterapia , Planejamento de Assistência ao Paciente/métodos , Radioisótopos/administração & dosagem , Animais , Anticorpos Monoclonais/administração & dosagem , Cobre/administração & dosagem , Humanos , Radioisótopos do Iodo/administração & dosagem , Camundongos , Modelos Biológicos , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada de Emissão
16.
J Nucl Med ; 26(9): 1068-74, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-4032047

RESUMO

A physiologically based compartmental model for T4 and T3 metabolism in man was used to generate time-activity curves for residence of radioiodine in key organs. T4 and T3 labeled with 123I, 124I, 125I, and 131I were studied. Conditions modeled included radioactive iodine uptake (RAIU) values of 0%, 1%, 5%, 15% and 25%, and RAIU of 15% combined with various degrees of pharmacologic block of thyroidal RAIU. Using the MIRD "S" tables, rad doses were generated for each condition. While the shapes of the time-activity curves varied widely with alterations in physical and biological turnover and with changes in steady-state due to iodine administration, it was possible to calculate overall effective half-lives for each organ of interest from the integral of the time-activity curve projected by solution of the model. This overall effective half-life of the hormone for the body's exchangeable hormone compartments correlated well with calculated radiation dose to the thyroid in the unblocked state. With progressive degrees of iodine block, this correlation persisted, though with proportionately reduced thyroid radiation doses. Use and manipulation of a compartmental model, rather than the usual multiexponential model, for radiation dosimetry facilitates conceptualization and the projection of the effects of interventions such as iodide block.


Assuntos
Radioisótopos do Iodo , Doses de Radiação , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Humanos , Radioisótopos do Iodo/metabolismo , Marcação por Isótopo , Modelos Biológicos , Distribuição Tecidual
17.
J Nucl Med ; 19(7): 789-95, 1978 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-660281

RESUMO

Thyroidal pertechnetate was measured continuously in normal subjects for 40 min after i.v. injection, using a multicrystal camera. Digital counts (1-min increments) were read directly from the magnetic tape and summed for the thyroid area and for adjacent neck background. The net thyroidal data were used as the basis for development of a compartmental model of the thyroidal trap, using the SAAM program. Input to the trap in the model is plasma pertechnetate radioactivity, measured frequently during the study and fitted to a multiexponential equation. Best fit of the thyroid data was achieved with a model in which the trap is described by two compartments, a fast ("follicular cell") compartment and a slower ("colloid") compartment. Iodide blockade, administered either during the study or 1 hr before its initiation, rapidly blocked the trap at the point of input from plasma into the follicular cells. Iodide did not affect the other parameters of the model.


Assuntos
Tecnécio , Glândula Tireoide/fisiologia , Adulto , Feminino , Humanos , Iodo/metabolismo , Cinética , Masculino , Modelos Biológicos , Glândula Tireoide/metabolismo
18.
J Nucl Med ; 20(3): 219-23, 1979 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24180041

RESUMO

Kinetics of the thyroid pertechnetate trap were assessed in 85 studies of 39 normal subjects, in five untreated patients with Graves' disease (two of them both before and after treatment), in two hypothyroid patients, and in one patient each with Hashimoto's thyroiditis of recent onset, subacute thyroiditis, and massive anaplastic carcinoma. In normal subjects, the effects of sex, time of day, and the order of experimental sessions were studied. For the analysis, a three-compartment model was assumed for all studies. Data on thyroidal and neck-background pertechnetate were collected with a multi-crystal camera during 40 min after i.v. injection. Input to the two thyroidal compartments in the model--the follicular cell, V2, and the colloidal plasma-equivalent space, V3--is a multi-exponential function of plasma radioactivity, V1, which was measured frequently. None of the model parameters was systematically affected by the sex of the subject, and order of session did not consistently alter any parameter, except for V3, which was greater in session 2 than in session 1. That increase was not consistent among data subsets, however, and is believed to be spurious. Time of day affected only the exit rate constant from the colloid, lambda23, which is increased later in the day (P < 0.02). Distribution of the normal parameters was more nearly log-normal than normal. After 5% were excluded at the high end and 5% at the low end, the range for a parameter, p, was found empirically to be: antiln (mean ln p - 1.7 s.d. ln p), and antiln (mean ln p + 1.5 s.d. ln p). In Graves' disease, V2 is increased (P < 0.02), but the increases in V3 and in lambda21 (the clearance into the thyroid from serum) are much more dramatic (P < 10(-8)). After treatment, V3 and lambda21 fell toward normal. The hypothyroid patients showed no trap activity, and the trap was normal in the patient with early Hashimoto's thyroiditis. The patients with subacute thyroiditis and with anaplastic carcinoma had increases in V2, V3, and lambda21, but the pattern differed from that seen in Graves' disease.


Assuntos
Pertecnetato Tc 99m de Sódio/metabolismo , Doenças da Glândula Tireoide/metabolismo , Glândula Tireoide/metabolismo , Adulto , Transporte Biológico , Estudos de Casos e Controles , Feminino , Humanos , Cinética , Masculino , Cintilografia , Doenças da Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem , Adulto Jovem
19.
J Nucl Med ; 20(9): 944-9, 1979 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-536840

RESUMO

Effects on the thyroidal pertechnetate trap of iodide, thyrotropin (TSH), and propylthiouracil (PTU), compared with duplicated control studies, were assessed in normal subjects using i.v. [Tc99m] pertechnetate, a multicrystal scintillation camera, and a compartmental model. Sodium iodide (1 g), administered orally on two occasions, 2 wk apart, caused an early drop in plasma clearance into the follicular cell (p less than 0.05), with later return to normal clearance 1 wk after the second NaI dose. In this later study, exit from the colloid was elevated (p less than 0.01). Plasma equivalent volume of the "colloid" compartment was reduced in both postiodine studies (p less than 0.05). Thyrotropin, 10 units intramuscularly, was followed by no significant changes in trap parameters at 2 hr. At 24 hr, plasma clearance had doubled (p less than 0.05), and the plasma equivalent "colloid" volume had tripled (p less than 0.01). Propylthiouracil was given as a single 1 g dose 1 hr before a trapping study followed by 200 mg PTU every 8 hr for 1 wk. The first dose resulted in apparent reduction in all of the rate constants for transport across the basal and apical thyroid follicular cell membranes; these rates returned toward control levels after 1 wk. The plasma equivalent "follicular cell" volume was reduced to 66% of controls levels (p less than 0.025) after 1 wk PTU. These effects must be taken into account in the interpretation of studies of the trap based on PTU pretreatment to inhibit organification.


Assuntos
Iodetos , Propiltiouracila , Glândula Tireoide/fisiologia , Tireotropina , Adulto , Feminino , Humanos , Cinética , Masculino , Modelos Biológicos , Tecnécio , Glândula Tireoide/metabolismo
20.
J Nucl Med ; 17(7): 657-9, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1271113

RESUMO

Plasma radioactivity was measured over 21 days after an intravenous injection of 50 muCi of 125I-T4 in eight normal men. No thyroid-blocking medication was given. Four subjects (castor oil group) received 30 ml of castor oil on each of Days 13, 14, and 15, while the other four subjects (control group) were studied without medication. After A 5-day equilibration period, plasma 125I-T4 was measured on Days 5-13 in order to calculate the disappearance curve for each subject and to derive the mean for each experimental group. The curves were then extrapolated to Day 21. Measured radioactivity did not depart significantly from the extrapolated line, either during the castor oil period (Days 14, 15, and 16) or during the recovery period (Days 17, 19, and 21). The castor oil, therefore, had no observable effect on the clearance of plasma radioactivity. None of the subjects had a late increase in plasma radioactivity to suggest recirculation of radioiodide or buildup of iodoproteins. In normal subjects, radiothyroxine plasma levels up to 21 days are not significantly affected by short-term catharsis or by failure to block thyroidal radioiodide uptake.


Assuntos
Catárticos , Radioisótopos do Iodo , Tiroxina/sangue , Adulto , Humanos , Iodo/farmacologia , Masculino , Glândula Tireoide/efeitos dos fármacos
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