排序方式: 共有35条查询结果,搜索用时 31 毫秒
1.
Maria Angela Guzzardi Leanne Hodson Letizia Guiducci Elena Sanguinetti Pietro Di Cecco Tiziana Liistro Cristina Vassalle Silvia Pardini Lucia Giorgetti Piero A. Salvadori Silvia Burchielli Patricia Iozzo 《Diabetologia》2014,57(9):1937-1946
Aims/hypothesis
Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake.Methods
Twenty-two pigs were stratified according to four protocols: low NEFA?+?low insulin (nicotinic acid), high NEFA?+?low insulin (fasting) and high insulin?+?low NEFA?±?high glucose (hyperinsulinaemia–hyperglycaemia or hyperinsulinaemia–euglycaemia). Positron emission tomography, [U-13C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate–pressure product (RPP) were monitored.Results
Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemia–hypergylcaemia, hyperinsulinaemia–euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia–euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content.Conclusions/interpretation
Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to ‘normalise’ adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucose-lowering and NEFA-lowering clinical trials. 相似文献2.
3.
L. Menichetti D. Petroni D. Panetta S. Burchielli Silva Bortolussi M. Matteucci G. Pascali S. Del Turco A. Del Guerra S. Altieri P.A. Salvadori 《Applied radiation and isotopes》2011,69(12):1717-1720
The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that 18F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose–boronophenylalanine (BPA). Therefore, FET–PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT. 相似文献
4.
5.
Tiziana Liistro Letizia Guiducci Silvia Burchielli Daniele Panetta Nicola Belcari Silvia Pardini Alberto Del Guerra Piero A Salvadori Patricia Iozzo 《Journal of cerebral blood flow and metabolism》2010,30(5):895-899
Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with 18F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and is stimulated by acute glucose intake in healthy rats. In diseased animals, the organ was chronically overexposed to glucose, due to high fasting glucose uptake, almost abolishing the physiologic response to glucose loading. 相似文献
6.
Alloreactive natural killer cells in mismatched hematopoietic stem cell transplantation 总被引:10,自引:0,他引:10
Ruggeri L Capanni M Mancusi A Urbani E Perruccio K Burchielli E Tosti A Topini F Aversa F Martelli MF Velardi A 《Blood cells, molecules & diseases》2004,33(3):216-221
Natural killer (NK) cell-mediated, donor-vs.-recipient alloresponses occur following transplantation of human leukocyte antigen (HLA) haplotype-mismatched hematopoietic stem cells (HSCs). NK cell alloreactivity reduced the risk of relapse in acute myeloid leukemia patients while improving engraftment and protecting against graft-vs.-host disease (GvHD). NK cells are primed to kill by several activating receptors. NK killing of autologous cells is prevented because NK cells co-express inhibitory receptors (killer cell Ig-like receptors, KIR) that recognize groups of (self) MHC class I alleles. As KIRs are clonally distributed, the NK population in any individual is constituted of a repertoire with different allospecificities. NK cells in the repertoire mediate alloreactions when the allogeneic targets do not express class I alleles that block them. High resolution molecular HLA typing of recipient and donor, positive identification of donor KIR genes, and in some cases, functional assessment of donor NK clones will identify haploidentical donors who are able to mount donor-vs.-recipient NK alloreactions. 相似文献
7.
8.
9.
Maria Angela Guzzardi Tiziana Liistro Luna Gargani Lamia Ait Ali Gennaro D’Angelo Silvia Rocchiccioli Federica La Rosa Alessandra Kemeny Elena Sanguinetti Nadia Ucciferri Mariarosaria De Simone Antonietta Bartoli Pierluigi Festa Piero A. Salvadori Silvia Burchielli Rosa Sicari Patricia Iozzo 《JACC: Cardiovascular Imaging》2018,11(12):1750-1755
Objectives
The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term).Background
The epidemic of overweight involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality.Methods
Echocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood.Results
In neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p < 0.05) and larger end-diastolic and stroke volumes at 1 year. Minipigs born to mothers fed a high-fat diet showed greater left ventricular mass (p = 0.0001), chambers (+100%; p < 0.001), stroke volume (+75%; p = 0.001), cardiomyocyte nuclei (+28%; p = 0.02), glucose uptake, and glycogen accumulation at birth (+100%; p < 0.005), with lower levels of oxidative enzymes, compared with those born to mothers fed a normal diet. Subsequently, they developed myocardial insulin resistance and glycogen depletion. Late adulthood showed elevated heart rate (111 ± 5 vs. 84 ± 8 beats/min; p < 0.05) and ejection fraction and deficient fatty acid oxidative enzymes.Conclusions
Neonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs can justify early human findings. Longer term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function. 相似文献10.
Perruccio K Topini F Tosti A Carotti A Burchielli E Ruggeri L Mancusi A Urbani E Aversa F Martelli MF Velardi A 《Bone marrow transplantation》2012,47(9):1196-1200
In adults, one-haplotype-mismatched haematopoietic SCT (haploidentical HSCT) is associated with slow immune recovery due to decaying thymic function and extensive T-cell depletion of the graft. Although essential for preventing GVHD, T-cell depletion underlies the major reasons for transplant failure: leukemia relapse and infections, with infection-related mortality accounting for about 40% of non-leukemic deaths. Adoptive T-cell therapy would be helpful for these patients but to administer it without causing GVHD, alloreactive T cells need to be eliminated from donor T lymphocytes before infusion. In a preclinical study, to address this problem, we determined the efficacy of photodynamic purging of alloreactive T cells, by investigating combinations of parameters in order to achieve maximum allodepletion, preservation of T-regulatory cells and of pathogen and leukemia-specific T-cell responses in donor-vs-recipient MLR. We also needed to identify an optimal method to quantify the Ag-specific T-cell repertoires. Optimal procedures were identified. In particular, we compared limiting-dilution analyses (LDA) of proliferating T cells with H(3)-thymidine incorporation by bulk T cells and with flow cytometry CD25 expression, which is accepted as a T-cell activation marker. This study demonstrated that LDA is a reliable, predictable and sensitive method for measuring alloreactive, pathogen- and leukemia-specific T-cell frequencies. 相似文献