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OBJECTIVE: This study examines the extent of variation in anesthesia practices among Finnish neuromodulation units providing electroconvulsive therapy (ECT) and investigates recent changes within individual units. METHODS: An electronic survey was carried out among Finnish neuromodulation units exploring staff demographics, anesthesia practices (including agents and adjuvants), patient physiology monitoring, observed adverse effects, patient follow-up times, and recent anesthesia protocol changes. RESULTS: Finland has 26 neuromodulation units providing ECT, of which 18 (69%) responded to our study. The research uncovered significant differences in anesthesia practices, including induction agent choice, convulsion motor component monitoring, staff educational backgrounds, and reported adverse effects. Propofol was the most commonly used anesthetic in 14 units (78%). Three units (17%) reported using methohexital in 80%-100% of their patients, whereas in contrast, methohexital was not used at all in 10 units (56%). Electromyography seizure activity was quantitatively measured in 6 units (33%), whereas 10 units (56%) did not measure electromyography seizure activity at all. The remaining 2 units assessed seizure activity through visual observation. Headache requiring medication was the most commonly reported adverse effect, and it was reported as a frequent problem in 3 units (18%). CONCLUSIONS: Based on the variation in anesthesia practices identified in the study, we suggest there may be benefits to developing a national guideline for standardizing treatment.
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PURPOSE: To determine predictors for postoperative urinary retention in adolescents undergoing posterior spinal fusion for idiopathic scoliosis. Postoperative urinary retention affects almost every third adolescent after spinal fusion for idiopathic scoliosis. There are limited data regarding the risk factors of postoperative urinary retention in this patient group. METHODS: A retrospective study with prospectively collected urinary retention data from paediatric spine register with 159 consecutive patients (114 females, mean age 15.6 years, range 10-21 years) undergoing pedicle screw instrumentation for adolescent idiopathic scoliosis at a university hospital between May 2010 and April 2020. Postoperative urinary retention was defined as an inability to void after catheter removal and documented residual over 300 mL as confirmed using an ultrasound or by catheterization. RESULTS: Postoperative urinary retention was diagnosed in 33% (53 of 159) of the patients during hospital stay. Opioid amount on the day of catheter removal (OR 6.74 [95% CI: 2.47, 18.36], p < 0.001), male gender (OR 2.26 [95% CI: 1.01, 5.05], p = 0.048), and increasing weight (OR 1.04 [95% CI: 1.01, 1.07], p = 0.014) were associated with postoperative urinary retention. Mean opioid consumption on the day of catheter removal was 0.81 mg/kg (95% CI: 0.66, 0.96) in the retention group vs 0.57 mg/kg (95% CI: 0.51, 0.64) in the non-retention group, p < 0.001. CONCLUSIONS: Higher total opioid consumption, opioid amount on the day of catheter removal, higher weight, and male gender increases the risk of postoperative urinary retention in adolescents with idiopathic scoliosis undergoing posterior spinal fusion.
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Parafusos Pediculares , Escoliose , Fusão Vertebral , Retenção Urinária , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Resultado do Tratamento , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Adulto JovemRESUMO
Mitochondrial mutations impair glucose oxidation and increase glucose uptake in cell cultures and lead to cardiomyopathy in patients. Here we characterize cardiac glucose uptake in 14 patients with the m.3243A > G mutation in mitochondrial DNA. The 14 patients with m.3243A > G and 13 controls were similar in age, physical activity and body mass index. Ten patients had diabetes. Left ventricular glucose uptake per tissue mass (LVGU) was measured with 2-[(18) F]fluoro-2-deoxyglucose positron emission tomography during euglycemic hyperinsulinemia. Cardiac morphology and function were assessed with magnetic resonance imaging. We found that the LVGU was 25% lower in the patients than that in the controls (P = 0.029). LVGU was inversely correlated with mutation heteroplasmy, glycated haemoglobin and fasting lactate in patients. The seven patients with mutation heteroplasmy ≥ 49% had 44% lower LVGU than the seven patients with heteroplasmy < 49%. This difference remained significant after adjustment for concurrent free fatty acid concentration or glycated haemoglobin or glucose uptake in skeletal muscle or all (p < 0.048 [All]). Patients with m.3243A > G had a lower stroke volume and a higher heart rate than the controls, whereas cardiac output and work were similar. Myocardial glucose uptake is not increased but decreased with a threshold effect pattern in patients with the m.3243A > G mutation. The glucose hypometabolism adds to the impaired cardiac energetics and likely contributes to the progression of the mitochondrial cardiomyopathy.
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DNA Mitocondrial/genética , Glucose/metabolismo , Mitocôndrias/genética , Mutação/genética , Miocárdio/metabolismo , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Epitélio/metabolismo , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismoRESUMO
Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1, which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent 18F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat-the fat proximal to the carotid arteries supplying the brain with warm blood-was performed to determine the mRNA expression of the thermogenic protein UCP-1. Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation (rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2. These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress.
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Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.
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Tecido Adiposo Marrom/metabolismo , Metabolismo Energético , Fluordesoxiglucose F18/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/citologia , Adiposidade , Adulto , Biópsia , Temperatura Baixa , Expressão Gênica , Marcadores Genéticos/fisiologia , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Tomografia por Emissão de Pósitrons , RNA Mensageiro/metabolismo , Proteína Desacopladora 1 , Regulação para CimaRESUMO
Persistent pain after posterior spinal fusion affects 12 to 42% of patients with adolescent idiopathic scoliosis. The incidence of persistent pain among surgically treated children with Scheuermann kyphosis and spondylolisthesis is not known. The aim of our study was to determine the predictors and incidence of acute and chronic postoperative pain in adolescents undergoing posterior spinal fusion surgery. The study was a retrospective analysis of a prospectively collected pediatric spine register data. The study included 213 consecutive patients (158 AIS, 19 Scheuermann kyphosis, and 36 spondylolisthesis), aged 10-21 years undergoing posterior spinal fusion at a university hospital between March 2010 and March 2020. The mean (SD) daily postoperative opioid consumption per kilogram was significantly lower in the spondylolisthesis patients 0.36 mg/kg/day (0.17) compared to adolescent idiopathic scoliosis 0.51 mg/kg/day (0.25), and Scheuermann kyphosis 0.52 mg/kg/day (0.25) patients after surgery (p = 0.0004). Number of levels fused correlated with the daily opioid consumption (rs = 0.20, p = 0.0082). The SRS-24 pain domain scores showed a statistically significant improvement from preoperative levels to two-year follow-up in all three groups (p ≤ 0.03 for all comparisons). The spondylolisthesis patients had the lowest SRS pain domain scores (mean 4.04, SD 0.94), reporting more pain two years after surgery, in comparison to AIS (mean 4.31, SD 0.60) (p = 0.043) and SK (mean 4.43, SD 0.48) patients (p = 0.049). Persistent postoperative pain in adolescents undergoing posterior spinal fusion is related to disease pathology while higher acute postoperative pain is associated with a more extensive surgery. Spondylolisthesis patients report more chronic pain after surgery compared to AIS and SK patients.
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An impaired ability to store fatty acids (FA) in subcutaneous adipose tissue (SAT) may be implicated in the pathogenesis of obesity-related diseases via overexposure of lean tissues and production of free radicals from FA oxidation (FAO). We studied regional FA metabolism in skeletal muscle and adipose tissue in humans and investigated the long-term effects of the FAO inhibitor trimetazidine on glucose and FA metabolism. Positron emission tomography (PET) and [(11)C]palmitate were used to compare FA metabolism in SAT and skeletal muscle between eight obese and eight nonobese subjects (BMI ≥/< 30 kg/m(2)). A subgroup of nine subjects underwent a 1-mo trimetazidine administration. PET with [(11)C]palmitate and [(18)F]fluorodeoxyglucose, indirect calorimetry, and MRI before and after this period were performed to characterize glucose and FA metabolism, fat masses, skeletal muscle triglyceride, and creatine contents. Obesity was characterized by a 100% elevation in FAO and a defect in the FA esterification rate constant (P < 0.05) in skeletal muscle. FA esterification was reduced by ~70% in SAT (P < 0.001) in obese vs. control subjects. The degrees of obesity and insulin resistance were both negatively associated with esterification-related parameters and positively with FAO (P < 0.05). Trimetazidine increased skeletal muscle FA esterification (P < 0.01) and mildly upregulated glucose phosphorylation (P = 0.066). Our data suggest that human obesity is characterized by a defect in tissue FA storage capability, which is accompanied by a (potentially compensatory) elevation in skeletal muscle FAO; trimetazidine diverted FA from oxidative to nonoxidative pathways and provoked an initial activation of glucose metabolism in skeletal muscle.
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Gorduras/metabolismo , Ácidos Graxos/metabolismo , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Trimetazidina/uso terapêutico , Adulto , Idoso , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Estudos Transversais , Fluordesoxiglucose F18/farmacocinética , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Obesidade/diagnóstico por imagem , Oxirredução/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Trimetazidina/farmacologia , Regulação para Cima/efeitos dos fármacos , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Surgical correction of spinal deformity requires major surgical intervention with extensive manipulation of the spine and neural elements. Persistent postoperative pain affects patient quality of life and can also cause financial burden for patient families and for society. We aimed to investigate the effect of perioperative pregabalin on the incidence of persistent pain following instrumented spinal fusion. METHODS: We conducted a randomized, double-blinded, and placebo-controlled single-center clinical trial. Adolescents and children 10 to 21 years old with a spinal deformity who were scheduled for pedicle screw instrumentation and fusion were randomized into either the pregabalin or placebo group. Patients received 2 mg/kg of pregabalin or a placebo twice daily preoperatively and for 5 days postoperatively. The duration of follow-up was 2 years. The primary outcomes were cumulative opioid consumption during the first 48 hours postoperatively and the incidence of persistent postoperative pain over the course of the 2-year follow-up. RESULTS: Sixty-four of 77 eligible patients were enrolled in the study, with all patients completing the 2-year follow-up. Thirty-three patients were randomized into the pregabalin group and 31 into the placebo group. There was no significant difference in cumulative 48-hour opioid consumption between the study groups. The Scoliosis Research Society 24-Item Questionnaire pain domain score improved significantly, from a mean value of 3.8 in both groups to 4.3 in the pregabalin and 4.0 in the placebo group at 2 years postoperatively, with no differences between the study groups at any time point (p = 0.317). The Scoliosis Research Society total scores of the study groups were similar (p = 0.678). Back pain, as measured with use of a visual analogue scale, improved significantly (p = 0.001) with no significant differences at any time point (preoperatively and 6 months, 1 year, and 2 years postoperatively). CONCLUSIONS: Perioperative pregabalin does not reduce postoperative opioid consumption or the incidence of persistent postoperative pain following instrumented posterior spinal fusion for spinal deformities in an adolescent population. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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Brown adipose tissue (BAT) thermogenesis is activated by feeding. Recently, we revealed a secretin-mediated gut-BAT-brain axis, which stimulates satiation in mice, but the purpose of meal-induced BAT activation in humans has been unclear. In this placebo-controlled, randomized crossover study, we investigated the effects of intravenous secretin on BAT metabolism (measured with [18F]FDG and [15O]H2O positron emission tomography) and appetite (measured with functional magnetic resonance imaging) in healthy, normal weight men (GUTBAT trial no. NCT03290846). Participants were blinded to the intervention. Secretin increased BAT glucose uptake (primary endpoint) compared to placebo by 57% (median (interquartile range, IQR), 0.82 (0.77) versus 0.59 (0.53) µmol per 100 g per min, 95% confidence interval (CI) (0.09, 0.89), P = 0.002, effect size r = 0.570), while BAT perfusion remained unchanged (mean (s.d.) 4.73 (1.82) versus 6.14 (3.05) ml per 100 g per min, 95%CI (-2.91, 0.07), P = 0.063, effect size d = -0.549) (n = 15). Whole body energy expenditure increased by 2% (P = 0.011) (n = 15). Secretin attenuated blood-oxygen level-dependent activity (primary endpoint) in brain reward circuits during food cue tasks (significance level false discovery rate corrected at P = 0.05) (n = 14). Caloric intake did not significantly change, but motivation to refeed after a meal was delayed by 39 min (P = 0.039) (n = 14). No adverse effects were detected. Here we show in humans that secretin activates BAT, reduces central responses to appetizing food and delays the motivation to refeed after a meal. This suggests that meal-induced, secretin-mediated BAT activation is relevant in the control of food intake in humans. As obesity is increasing worldwide, this appetite regulating axis offers new possibilities for clinical research in treating obesity.
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Tecido Adiposo Marrom/metabolismo , Saciação , Secretina/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Encéfalo/fisiologia , Ingestão de Energia , Metabolismo Energético , Comportamento Alimentar , Trato Gastrointestinal/fisiologia , Glucose/metabolismo , Humanos , Camundongos , TermogêneseRESUMO
The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti-obesity potential.
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Envelhecimento/metabolismo , Obesidade/metabolismo , Receptor A2B de Adenosina/metabolismo , Adolescente , Adulto , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Pessoa de Meia-Idade , Receptor A2B de Adenosina/deficiência , Transdução de Sinais , Adulto JovemRESUMO
Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography radioligand [18F]FMPEP-d2 and measured BAT activation in parallel with the glucose analog [18F]fluorodeoxyglucose. Activation by cold exposure markedly increased CB1R density and glucose uptake in the BAT of lean men. Similarly, ß3-receptor agonism increased CB1R density in the BAT of rats. In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are significant for human BAT activity, and the CB1Rs provide a novel therapeutic target for BAT activation in humans.
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Tecido Adiposo Marrom/metabolismo , Resposta ao Choque Frio/genética , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/patologia , Adulto , Animais , Células Cultivadas , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/diagnóstico por imagem , Sobrepeso/genética , Sobrepeso/metabolismo , Tomografia por Emissão de Pósitrons , Pirrolidinonas , Ratos , Ratos Sprague-Dawley , Termogênese/genética , Regulação para Cima/genética , Adulto JovemRESUMO
Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans.
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Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Biomarcadores/análise , Biologia Computacional/métodos , Obesidade/fisiopatologia , Software , Adipogenia , Tecido Adiposo Marrom/citologia , Tecido Adiposo Branco/citologia , Adulto , Idoso , Animais , Estudos de Coortes , Metabolismo Energético , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Termogênese , Adulto JovemRESUMO
In response to cold or ß3-adrenoreceptor stimulation brown adipose tissue (BAT) promotes non-shivering thermogenesis, leading to energy dissipation. BAT has long been thought to be absent or scarce in adult humans. The recent discovery of thermogenic brite/beige adipocytes has opened the way to development of novel innovative strategies to combat overweight/obesity and associated diseases. Thus it is of great interest to identify regulatory factors that govern the brite adipogenic program. Here, we carried out global microRNA (miRNA) expression profiling on human adipocytes to identify miRNAs that are regulated upon the conversion from white to brite adipocytes. Among the miRNAs that were differentially expressed, we found that Let-7i-5p was down regulated in brite adipocytes. A detailed analysis of the Let-7i-5p levels showed an inverse expression of UCP1 in murine and human brite adipocytes both in vivo and in vitro. Functional studies with Let-7i-5p mimic in human brite adipocytes in vitro revealed a decrease in the expression of UCP1 and in the oxygen consumption rate. Moreover, the Let-7i-5p mimic when injected into murine sub-cutaneous white adipose tissue inhibited partially ß3-adrenergic activation of the browning process. These results suggest that the miRNAs Let-7i-5p participates in the recruitment and the function of brite adipocytes.
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Adipócitos Bege/metabolismo , MicroRNAs/metabolismo , Adipócitos Bege/fisiologia , Adipócitos Marrons/metabolismo , Adipócitos Marrons/fisiologia , Adipogenia/fisiologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiologia , Animais , Regulação para Baixo/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Consumo de Oxigênio/fisiologia , Receptores Adrenérgicos beta 3/metabolismo , Termogênese/fisiologia , Proteína Desacopladora 1/metabolismoRESUMO
Human brown adipocytes are able to burn fat and glucose and are now considered as a potential strategy to treat obesity, type 2 diabetes and metabolic disorders. Besides their thermogenic function, brown adipocytes are able to secrete adipokines. One of these is visfatin, a nicotinamide phosphoribosyltransferase involved in nicotinamide dinucleotide synthesis, which is known to participate in the synthesis of insulin by pancreatic ß cells. In a therapeutic context, it is of interest to establish whether a potential correlation exists between brown adipocyte activation and/or brite adipocyte recruitment, and adipokine expression. We analyzed visfatin expression, as a pre-requisite to its secretion, in rodent and human biopsies and cell models of brown/brite adipocytes. We found that visfatin was preferentially expressed in mature adipocytes and that this expression was higher in brown adipose tissue of rodents compared to other fat depots. However, using various rodent models we were unable to find any correlation between visfatin expression and brown or brite adipocyte activation or recruitment. Interestingly, the situation is different in humans where visfatin expression was found to be equivalent between white and brown or brite adipocytes in vivo and in vitro. In conclusion, visfatin can be considered only as a rodent brown adipocyte biomarker, independently of tissue activation.
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OBJECTIVE: In rodents and humans, besides brown adipose tissue (BAT), islands of thermogenic adipocytes, termed "brite" (brown-in-white) or beige adipocytes, emerge within white adipose tissue (WAT) after cold exposure or ß3-adrenoceptor stimulation, which may protect from obesity and associated diseases. microRNAs are novel modulators of adipose tissue development and function. The purpose of this work was to characterize the role of microRNAs in the control of brite adipocyte formation. METHODS/RESULTS: Using human multipotent adipose derived stem cells, we identified miR-125b-5p as downregulated upon brite adipocyte formation. In humans and rodents, miR-125b-5p expression was lower in BAT than in WAT. In vitro, overexpression and knockdown of miR-125b-5p decreased and increased mitochondrial biogenesis, respectively. In vivo, miR-125b-5p levels were downregulated in subcutaneous WAT and interscapular BAT upon ß3-adrenergic receptor stimulation. Injections of an miR-125b-5p mimic and LNA inhibitor directly into WAT inhibited and increased ß3-adrenoceptor-mediated induction of UCP1, respectively, and mitochondrial brite adipocyte marker expression and mitochondriogenesis. CONCLUSION: Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.
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AIMS: Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. METHODS AND RESULTS: We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). CONCLUSION: Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD.
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Angina Estável/diagnóstico , Angina Estável/terapia , Ecocardiografia sob Estresse/métodos , Reserva Fracionada de Fluxo Miocárdico , Hemodinâmica , Tomografia por Emissão de Pósitrons/métodos , Estimulação da Medula Espinal , Idoso , Angina Estável/fisiopatologia , Índice de Massa Corporal , Ponte de Artéria Coronária/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Qualidade de Vida , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
INTRODUCTION: The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized. AIMS: To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover. RESULTS: Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P ≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 µmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 µmol/min, respectively; P ≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 10(2), NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 10(2), P = 0.036). CONCLUSIONS: In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency.
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Ácidos Graxos não Esterificados/metabolismo , Obesidade/tratamento farmacológico , Trimetazidina/farmacologia , Vasodilatadores/farmacologia , Adulto , Idoso , Índice de Massa Corporal , Feminino , Glucose/metabolismo , Testes de Função Cardíaca , Hemodinâmica , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Palmitatos/metabolismo , Tomografia por Emissão de PósitronsRESUMO
CONCLUSION: This study suggests that although oxygen partial pressure in tissue (p(ti)O(2)) measurement is a feasible method for continuous postoperative monitoring of free flaps, low correlation between blood pressure (BP) and p(ti)O(2) might predict compromised overall outcome. Thus, it is of utmost importance to keep the BP optimal for adequate perfusion of re-anastomosed tissue transfers. OBJECTIVE: Optimal BP is an important factor in assuring adequate blood flow in a free flap. Tissue oxygenation in free flaps as a postoperative monitoring target is in routine clinical use in some clinics. Correlation between p(ti)O(2) and systemic BP was investigated. METHODS: Ten consecutive patients underwent resection of head and neck squamous cell carcinoma followed by microvascular reconstruction with a free microvascular flap. P(ti)O(2) of each flap was continuously monitored for 3 postoperative days with a polarographic measurement system. BP was measured invasively and continuously during the operation and during the first postoperative day at the intensive care unit. The correlation coefficient between p(ti)O(2) and BP was analysed. RESULTS: The correlation coefficient between p(ti)O(2) and BP was relatively high in all patients with uneventful flap survival (r (mean) = 0.63, n = 5). In flaps with haemodynamic problems or compromised flap vitality the correlation appeared low (r(mean) = -0.02, n = 5).
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Pressão Sanguínea/fisiologia , Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico/fisiologia , Microcirurgia/métodos , Monitorização Fisiológica/métodos , Neoplasias Bucais/cirurgia , Consumo de Oxigênio/fisiologia , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/fisiopatologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/fisiopatologia , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Prospectivos , Fluxo Sanguíneo Regional , Resultado do TratamentoRESUMO
We investigated the metabolism of human brown adipose tissue (BAT) in healthy subjects by determining its cold-induced and insulin-stimulated glucose uptake and blood flow (perfusion) using positron emission tomography (PET) combined with computed tomography (CT). Second, we assessed gene expression in human BAT and white adipose tissue (WAT). Glucose uptake was induced 12-fold in BAT by cold, accompanied by doubling of perfusion. We found a positive association between whole-body energy expenditure and BAT perfusion. Insulin enhanced glucose uptake 5-fold in BAT independently of its perfusion, while the effect on WAT was weaker. The gene expression level of insulin-sensitive glucose transporter GLUT4 was also higher in BAT as compared to WAT. In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner.