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1.
Int J Mol Sci ; 23(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563272

RESUMO

Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of 18FDG-PET/CT and 125I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of 18FDG and 125I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUVmean) for 18FDG and 125I-BMIPP significantly correlated in these depots, although uptake of 125I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than 18FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans.


Assuntos
Tecido Adiposo Marrom , Fluordesoxiglucose F18 , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Animais , Ácidos Graxos/metabolismo , Fluordesoxiglucose F18/metabolismo , Iodobenzenos , Camundongos , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos
2.
Diabetes Metab Res Rev ; 32(3): 297-307, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26408818

RESUMO

BACKGROUND: Recent work in Pima Indians, a population with high rates of obesity and type 2 diabetes mellitus (T2DM), demonstrated that human leukocyte antigen haplotype DRB1*02 carriers have an increased acute insulin response and decreased risk for the development of T2DM, implicating loss of self-tolerance in the pathogenesis of T2DM. Advances in genomic sequencing have made T-cell receptor repertoire analysis a practical mode of investigation. METHODS: High-throughput sequencing of T-cell receptor complementarity-determining region 3 was carried out in male Pima Indians with normal glucose regulation (n = 11; age = 31 ± 8 years; %fat = 30.2 ± 8.7%) and the protective DRB1*02 haplotype versus those with T2DM without DRB1*02 (n = 7; age = 34 ± 8 years; %fat = 31.2 ± 4.7%). Findings were partially replicated in another cohort by assessing the predictive ability of T-cell receptor variation on risk of T2DM in Pima Indian men (n = 27; age = 28.9 ± 7.1 years; %fat = 28.8 ± 7.1%) and women (n = 20; age = 29 ± 7.0 years; %fat = 37.1 ± 6.8%) with baseline normal glucose regulation but without the protective haplotype who were invited to follow-up examinations as frequently as every 2 years where diabetes status was assessed by a 75-g oral glucose tolerance test. Of these subjects, 13 developed diabetes. RESULTS: T-cell receptor complementarity-determining region 3 length was shorter in those with T2DM, and a one-nucleotide decrease in complementarity-determining region 3 length was associated with a nearly threefold increase in risk for future diabetes. The frequency of one variable gene, TRBV7-8, was higher in those with T2DM. A 1% increase in TRBV7-8 frequency was associated with a greater than threefold increase in diabetes risk. CONCLUSIONS: These results indicate that T-cell autoimmunity may be an important component in progression to T2DM in Pima Indians.


Assuntos
Regiões Determinantes de Complementaridade/genética , Diabetes Mellitus Tipo 2/genética , Cadeias HLA-DRB1/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Antígenos de Linfócitos T/genética , Adulto , Feminino , Teste de Tolerância a Glucose , Haplótipos/genética , Humanos , Indígenas Norte-Americanos , Estudos Longitudinais , Masculino
3.
J Nucl Med Technol ; 46(2): 149-150, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29273699

RESUMO

Dopamine transporter SPECT is an accurate adjunct to clinical evaluation for Parkinson disease when the diagnosis is difficult. Dopaminergic medications may significantly affect dopamine transporter availability and, thus, uptake of dopamine transporter tracers. A patient had a false-positive dopamine transporter SPECT result while she was taking dextroamphetamine and amphetamine for attention-deficit hyperactivity disorder. The SPECT findings normalized after amphetamine therapy was withheld. An accurate medication history combined with knowledge of drugs that interfere with dopamine transporter imaging is critical to ensure accuracy.


Assuntos
Anfetamina/uso terapêutico , Dextroanfetamina/uso terapêutico , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Reações Falso-Positivas , Feminino , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
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