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2.
Am J Clin Exp Urol ; 11(5): 429-434, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941648

RESUMO

Clear cell renal cell carcinoma is the most common subtype of renal cell carcinomas (RCCs) and accounts for 60%-70% of all RCCs cases in adults. Aberrations in the von Hippel-Lindau (VHL) gene on chromosome 3p occurred in > 90% of clear cell RCCs. Other tumor suppressor genes located on chromosome 3p, such as BAP1, PBRM1, and SETD2, also contribute to tumorigenesis. Clear cell RCCs with both BAP1 and VHL mutations may display distinctive histopathological features. Here, we report two cases of clear cell RCCs with BAP1 mutation. One tumor had VHL, BAP-1, and RAF1 mutations and the tumor nests and alveoli of tumor cells were surrounded by proliferative vessels and the optically clear cytoplasm contained numerous eosinophilic granules and hyaline globules of varying sizes. The other tumor had BAP1 and ATM mutations, and demonstrated clear cells with numerous eosinophilic granules and other typical histopathological features of conventional clear cell RCC. Furthermore, many tumor nodules with dense peripheral lymphocytic infiltrates contained rhabdoid cells. Sarcomatoid cells were also observed. Both tumor cells showed high-grade nuclei. Clear cell RCCs with BAP1 mutation exhibit aggressive clinical behaviors.

3.
Open Forum Infect Dis ; 10(10): ofad492, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37829442

RESUMO

We report an Epstein-Barr virus-associated smooth muscle tumor in an adult male with AIDS. The patient had multiple lung nodules seen on computed tomography of the chest and an endobronchial lung tumor identified on bronchoscopy. Initiation of antiretroviral therapy slowed the progression of the tumors.

4.
Front Cardiovasc Med ; 10: 1190460, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37539090

RESUMO

Introduction: Atherosclerosis is a progressive disease that develops in areas of disturbed flow (d-flow). Progressive atherosclerosis is characterized by bulky plaques rich in mesenchymal cells and high-grade inflammation that can rupture leading to sudden cardiac death or acute myocardial infarction. In response to d-flow, endothelial cells acquire a mesenchymal phenotype through endothelial-to-mesenchymal transition (EndMT). However, the signaling intermediaries that link d-flow to EndMT are incompletely understood. Methods and Results: In this study we found that in human atherosclerosis, cells expressing SNAI1 (Snail 1, EndMT transcription factor) were highly expressed within the endothelial cell (EC) layer and in the pre-necrotic areas in unstable lesions, whereas stable lesions did not show any SNAI1 positive cells, suggesting a role for EndMT in lesion instability. The interleukin-1 (IL-1), which signals through the type-I IL-1 receptor (IL-1R1), has been implicated in plaque instability and linked to EndMT formation in vitro. Interestingly, we observed an association between SNAI1 and IL-1R1 within ECs in the unstable lesions. To establish the causal relationship between EndMT and IL-1R1 expression, we next examined IL-1R1 levels in our Cre-lox endothelial-specific lineage tracing mice. IL-1R1 and Snail1 were highly expressed in ECs under atheroprone compared to athero-protective areas, and oscillatory shear stress (OSS) increased IL-1R1 protein and mRNA levels in vitro. Exposure of ECs to OSS resulted in loss of their EC markers and higher induction of EndMT markers. By contrast, genetic silencing of IL-1R1 significantly reduced the expression of EndMT markers and Snail1 nuclear translocation, suggesting a direct role for IL-1R1 in d-flow-induced EndMT. In vivo, re-analysis of scRNA-seq datasets in carotid artery exposed to d-flow confirmed the IL-1R1 upregulation among EndMT population, and in our partial carotid ligation model of d-flow, endothelial cell specific IL-1R1 KO significantly reduced SNAI1 expression. Discussion: Global inhibition of IL-1 signaling in atherosclerosis as a therapeutic target has recently been tested in the completed CANTOS trial, with promising results. However, the data on IL-1R1 signaling in different vascular cell-types are inconsistent. Herein, we show endothelial IL-1R1 as a novel mechanosensitive receptor that couples d-flow to IL-1 signaling in EndMT.

5.
Cureus ; 15(6): e40415, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37456451

RESUMO

Acute graft vs. host disease (aGVHD) results from newly transplanted donor immune cells recognizing recipient tissues as foreign, leading to end-organ damage. Diagnosing aGVHD typically involves a combination of clinical evaluation, histological examination, laboratory tests, and imaging studies. Although typically associated with allogeneic stem cells transplant and less frequently with liver or small bowel transplants, solid organ transplant GVHD (SOT-GVHD) associated with kidney-pancreas transplants is exceedingly rare. Our patient presented with pancytopenia unexplained by typical causes. He developed classical aGVHD findings of fever, diarrhea, rash, and abnormal liver tests. Our case underscores the importance of keeping a broad differential when evaluating solid organ transplant patients.

6.
Dig Dis Sci ; 68(5): 2123-2139, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36538276

RESUMO

BACKGROUND: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). AIMS: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. METHODS: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O2peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate. RESULTS: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min). CONCLUSIONS: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016).


Assuntos
Treinamento Intervalado de Alta Intensidade , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/terapia , Austrália , Exercício Físico/fisiologia
8.
Eur J Endocrinol ; 187(3): 361-372, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35895721

RESUMO

Background: Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics. Methods: We conducted a retrospective multicenter study including 3566 patients with APA or IHA of Caucasian and Asian origin. We compared the prevalence of metabolic disorders between APA and IHA patients at the time of diagnosis and 1-year post-intervention, with special references to sex differences. Furthermore, correlations between metabolic parameters and plasma aldosterone, renin, or plasma cortisol levels after 1 mg dexamethasone (DST) were performed. Results: As expected, APA patients were characterized by higher plasma aldosterone and lower serum potassium levels. Only female IHA patients demonstrated significantly worse metabolic parameters than age-matched female APA patients, which were associated with lower cortisol levels upon DST. One-year post-intervention, female adrenalectomized patients showed deterioration of their lipid profile, when compared to patients treated with mineralocorticoid receptor antagonists. Plasma aldosterone levels negatively correlated with the BMI only in APA patients. Conclusions: Metabolic alterations appear more prominent in women with IHA. Although IHA patients have worse metabolic profiles, a correlation with cortisol autonomy is documented only in APAs, suggesting an uncoupling of cortisol action from metabolic traits in IHA patients.


Assuntos
Adenoma , Diabetes Mellitus Tipo 2 , Hiperaldosteronismo , Hipertensão , Adenoma/complicações , Aldosterona , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hidrocortisona , Hipertensão/complicações , Masculino , Fenótipo
9.
Australas Psychiatry ; 30(4): 518-522, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35331017

RESUMO

OBJECTIVE: Metabolic syndrome is highly prevalent among people with schizophrenia. This study aims to assess the impact on metabolic and attendance outcomes of a co-located, dedicated, endocrinologist-led metabolic clinic in a stand-alone public community mental health service. METHODS: Demographic and metabolic data on the first 48 consecutive referrals over a 12-month period were retrospectively collected and analysed. Attendance rates at the co-located clinic were compared to the general hospital obesity and diabetes clinics. RESULTS: Clinic attendees had significant reductions in triglycerides and total cholesterol, but not mean weight, BMI, waist circumference, blood pressure or HbA1c. Attendance rates were significantly higher in the co-located clinic compared to the general hospital obesity and diabetes clinics for both initial consult (80.0% vs 51.2%, p < 0.001) and review appointment (64.3% vs 47.6%, p < 0.001). CONCLUSION: The co-location of a specialist metabolic clinic within a mental health service resulted in enhanced engagement and improvement of metabolic health in people with schizophrenia.


Assuntos
Diabetes Mellitus , Síndrome Metabólica , Esquizofrenia , Atenção à Saúde , Humanos , Síndrome Metabólica/terapia , Obesidade , Estudos Retrospectivos , Esquizofrenia/terapia
10.
Anaesth Crit Care Pain Med ; 40(6): 100947, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34534700

RESUMO

Our understanding of chronic inflammation in obesity is evolving. Suggested mechanisms include hypoxia of adipose tissue and a subsequent increase in circulating cytokines. It is now known that adipose tissue, far from being an inert tissue, produces and secretes multiple peptides that influence inflammation and metabolism, including substrates of the renin-angiotensin-aldosterone system (RAAS). RAAS blocking antihypertensive medication and cholesterol-lowering agents are now being evaluated for their metabolic and inflammation-modulating effects. Surgery also has pro-inflammatory effects, which may be exacerbated in patients with obesity. This narrative review will summarise the recent literature surrounding obesity, metabolic syndrome, inflammation, and interplay with the RAAS, with evidence-based recommendations for the optimisation of patients with obesity, prior to surgery and anaesthesia.


Assuntos
Síndrome Metabólica , Anestesistas , Humanos , Inflamação , Síndrome Metabólica/terapia , Obesidade/complicações , Obesidade/terapia , Assistência ao Paciente
11.
J Hum Hypertens ; 35(2): 117-123, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33526798

RESUMO

Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular diseases, and comprises obesity, hypertension, impaired glucose metabolism and dyslipidaemia. It is well recognised that the mineralocorticoid receptor (MR) plays an important role in blood pressure regulation via its effect on salt and water retention in renal tubules, with hypertension being a key feature in primary aldosteronism patients with excess adrenal production of aldosterone, the primary ligand for MRs in the epithelial tissues. MRs are also expressed in a number of non-epithelial tissues including adipose tissue; in these tissues, glucocorticoids or cortisol can also activate MRs due to low levels of 11-beta-hydroxysteroid-dehydrogenase type 2 (11-ßHSD2), the enzyme which inactivates cortisol. There is increasing evidence suggesting that over-activation of MRs plays a role in the pathophysiology of the other components of metabolic syndrome, promoting adiposity, inflammation and glucose intolerance, and that MR antagonists may confer beneficial effects on energy and substrate homeostasis and cardiometabolic diseases. This review discusses the advances in the literature shedding light on the MR as an emerging player in metabolic syndrome.


Assuntos
Hiperaldosteronismo , Hipertensão , Síndrome Metabólica , Aldosterona , Humanos , Antagonistas de Receptores de Mineralocorticoides , Receptores de Mineralocorticoides
12.
J Clin Endocrinol Metab ; 105(9)2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32516371

RESUMO

CONTEXT AND OBJECTIVE: Posture-responsive and posture-unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of these 2 types of APA. METHODS: Plasma levels of aldosterone and hybrid steroids (18-oxocortisol and 18-hydroxycortisol) were measured by liquid chromatography-tandem mass spectrometry. Immunohistochemistry for CYP11B2 (aldosterone synthase) and CYP17A1 (17α-hydroxylase) and deoxyribonucleic acid sequencing (Sanger and next-generation sequencing) were performed on APA tissue collected from 23 posture-unresponsive and 17 posture-responsive APA patients. RESULTS: Patients with posture-unresponsive APA displayed higher (P < 0.01) levels of hybrid steroids, recumbent aldosterone and cortisol, larger (P < 0.01) zona fasciculata (ZF)-like tumors with higher (P < 0.01) expression of CYP17A1 (but not of CYP11B2) than patients with posture-responsive APA (most of which were not ZF-like). Of 40 studied APAs, 37 (92.5%) were found to harbor aldosterone-driving somatic mutations (KCNJ5 = 14 [35.0%], CACNA1D = 13 [32.5%], ATP1A1 = 8 [20.0%], and ATP2B3 = 2 [5.0%]), including 5 previously unreported mutations (3 in CACNA1D and 2 in ATP1A1). Notably, 64.7% (11/17) of posture-responsive APAs carried CACNA1D mutations, whereas 56.5% (13/23) of posture-unresponsive APAs harbored KCNJ5 mutations. CONCLUSIONS: The elevated production of hybrid steroids by posture-unresponsive APAs may relate to their ZF-like tumor cell composition, resulting in expression of CYP17A1 (in addition to somatic gene mutation-driven CYP11B2 expression), thereby allowing production of cortisol, which acts as the substrate for CYP11B2-generated hybrid steroids.


Assuntos
Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Aldosterona/metabolismo , Hiperaldosteronismo , Postura/fisiologia , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Hiperaldosteronismo/genética , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Best Pract Res Clin Endocrinol Metab ; 34(3): 101400, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32115358

RESUMO

Adrenal venous sampling (AVS) is a key part of the diagnostic workup of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. Although AVS is a well-established procedure, many aspects remain controversial, including optimal patient selection for the procedure and exactly how AVS is performed and interpreted. Despite the controversies, a growing body of evidence supports the use of AVS in most patients with primary aldosteronism, though some specific patient groups may be able to forego AVS and proceed directly to treatment. Although AVS remains a difficult procedure, success rates may be improved with the use of advanced CT imaging techniques and/or rapid cortisol assays. New advances in nuclear imaging and steroid profiling may also offer alternatives or adjuncts to AVS in the future.


Assuntos
Glândulas Suprarrenais/irrigação sanguínea , Coleta de Amostras Sanguíneas/métodos , Técnicas de Diagnóstico Endócrino , Hiperaldosteronismo/diagnóstico , Glândulas Suprarrenais/patologia , Aldosterona/análise , Aldosterona/sangue , Técnicas de Diagnóstico Endócrino/normas , Técnicas de Diagnóstico Endócrino/tendências , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Hiperaldosteronismo/sangue , Veias
14.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676899

RESUMO

BACKGROUND: In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cutoff 4-hour plasma aldosterone concentration (PAC) measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS is 162 pmol/L. Most diagnostic laboratories, however, use immunoassays to measure PAC. The cutoff for SSST using immunoassay is not known. We hypothesized that the cutoff is different between the assays. METHODS: We analyzed 80 of the 87 SSST tests that were performed during our recent study defining the HPLC-MS/MS cutoff. PA was confirmed in 65 by positive fludrocortisone suppression testing (FST) and/or lateralization on adrenal venous sampling and excluded in 15 by negative FST. PAC was measured by a chemiluminescence immunoassay (PACIA) in the SSST samples using the DiaSorin Liaison XL analyzer, and receiver operating characteristics (ROC) analysis was performed to identify the PACIA cutoff. RESULTS: ROC revealed good performance (area under the curve = 0.893; P < .001) of 4-hour postsaline PACIA for diagnosis of PA and an optimal diagnostic cutoff of 171 pmol/L, with sensitivity and specificity of 95.4% and 80.0%, respectively. A higher cutoff of 217 pmol/L improved specificity (86.7%) with lower sensitivity (86.2%). PACIA measurements strongly correlated with PAC measured by HPLC-MS (r = 0.94, P < .001). CONCLUSIONS: A higher diagnostic cutoff for SSST should be employed when PAC is measured by immunoassay rather than HPLC-MS/MS. The results suggest that (i) PA can be excluded if 4-hour PACIA is less than 171 pmol/L, and (ii) PA is highly likely if the PACIA is greater than 217 pmol/L by chemiluminescence immunoassay. A gray zone exists between the cutoffs of 171 and 217 pmol/L, likely reflecting a lower specificity of immunoassay.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/diagnóstico , Imunoensaio/normas , Espectrometria de Massas em Tandem/normas , Aldosterona/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Estudos de Coortes , Feminino , Humanos , Hiperaldosteronismo/sangue , Imunoensaio/métodos , Medições Luminescentes/métodos , Medições Luminescentes/normas , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Reprodutibilidade dos Testes , Solução Salina/administração & dosagem , Postura Sentada , Espectrometria de Massas em Tandem/métodos
15.
Diabetes Obes Metab ; 21(3): 509-516, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225967

RESUMO

AIM: To investigate whether mineralocorticoid (MC) antagonism enhances brown adipose tissue (BAT) function in humans. MATERIALS AND METHODS: In a randomized double-blind, cross-over designed trial, 10 healthy adults (two men, eight women) underwent 2 weeks of spironolactone (100 mg/d) treatment and placebo, with an intervening 2-week wash-out period. BAT function was assessed in response to cooling and to a mixed meal. Metabolic activity was measured by fluoro-deoxyglucose (FDG) uptake (maximal standardized uptake value, SUVmax ) using PET-CT. Thermogenic activity was measured by skin temperatures overlying supraclavicular (SCL) BAT depots using infrared thermography. Postprandial metabolism was measured by energy production rate (EPR) and lipid synthesis using indirect calorimetry. RESULTS: During cooling, BAT metabolic activity (SUV 6.30 ± 2.16 vs 3.98 ± 1.34; P < 0.05) and volume (54.9 ± 22.8 vs 21.6 ± 11.8 cm3 ; P < 0.05) were significantly higher, and mean SCL temperature decreased by a smaller degree (-0.3°C°± 0.2°C vs -0.9°C ± 0.2°C; P = 0.05) with spironolactone treatment. A mixed meal increased SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4°C ± 0.1°C vs +0.1°C ± 0.1°C; P < 0.05) but not in EPR was greater during spironolactone treatment. Postprandial lipid synthesis occurred in three participants with placebo but in none with spironolactone treatment (P = 0.06). CONCLUSION: MC antagonism enhanced human BAT function in response to cooling and to a meal during which lipid synthesis was suppressed. As postprandial EPR comprises energy dissipated as heat and energy required to store nutrients, the reduction in lipid synthesis during MC antagonism is a probable consequence of concurrent stimulation of BAT thermogenesis. The shift in energy usage from storage to heat dissipation indicates that MC antagonists may have therapeutic benefit for obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiologia , Adolescente , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Fluordesoxiglucose F18 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Mineralocorticoides/farmacologia , Placebos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Período Pós-Prandial/efeitos dos fármacos , Temperatura Cutânea/efeitos dos fármacos , Adulto Jovem
16.
Diabetes Obes Metab ; 20(4): 840-848, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29119718

RESUMO

AIM: To investigate the effect of glucocorticoids on brown adipose tissue (BAT) function in humans. MATERIALS AND METHODS: In a randomized double-blind cross-over design, 13 healthy adults underwent 1 week of oral prednisolone treatment (15 mg/d) and placebo with an intervening 2-week wash-out period. BAT function was assessed in response to cooling (19°C) and to a standardized meal, by measuring fluoro-deoxyglucose (FDG) uptake using positron emission tomography-computed tomography and skin temperatures overlying the supraclavicular (SCL) BAT depots using infrared thermography. Postprandial energy and substrate metabolism was assessed by indirect calorimetry. RESULTS: During cooling, prednisolone significantly reduced BAT FDG uptake (standardized uptake value, SUVmax, 6.1 ± 2.2 vs 3.7 ± 1.2; P < .05) and SCL temperature (-0.45 ± 0.1 vs -1.0 ± 0.1°C; P < .01) compared to placebo. Postprandially, prednisolone significantly blunted the rise in SCL temperature (+0.2 ± 0.1 vs -0.3 ± 0.1°C; P < .05), enhanced energy production (+221 ± 17 vs +283 ± 27 kcal/d; P < .01) and lipid synthesis (+16.3 ± 3.2 vs +23.6 ± 4.9 mg/min; P < .05). The prednisolone-induced reduction in SCL temperature significantly correlated with the reduction in FDG uptake (r = 0.65, P < .05), while the increase in energy production significantly correlated with the increase in lipogenesis (r = 0.6, P < .05). CONCLUSION: Prolonged exposure to glucocorticoid suppresses the function of human BAT. The enhancement of energy production and lipogenesis in the face of reduced dissipation of energy as heat suggests that glucocorticoids channel energy towards fat storage after nutrient intake. This is a novel mechanism of glucocorticoid-induced obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Glucocorticoides/farmacologia , Prednisolona/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/fisiologia , Adolescente , Adulto , Temperatura Baixa , Estudos Cross-Over , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Placebos , Prednisolona/administração & dosagem , Temperatura Cutânea/efeitos dos fármacos , Adulto Jovem
17.
Eur J Endocrinol ; 175(1): R11-25, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27220620

RESUMO

The recent discovery that functional brown adipose tissue (BAT) persists in adult humans has enkindled a renaissance in metabolic research, with a view of harnessing its thermogenic capacity to combat obesity. This review focuses on the advances in the regulation and the metabolic significance of BAT in humans. BAT activity in humans is stimulated by cold exposure and by several factors such as diet and metabolic hormones. BAT function is regulated at two levels: an acute process involving the stimulation of the intrinsic thermogenic activity of brown adipocytes and a chronic process of growth involving the proliferation of pre-existing brown adipocytes or differentiation to brown adipocytes of adipocytes from specific white adipose tissue depots. BAT activity is reduced in the obese, and its stimulation by cold exposure increases insulin sensitivity and reduces body fat. These observations provide strong evidence that BAT plays a significant role in energy balance in humans and has the potential to be harnessed as a therapeutic target for the management of obesity.


Assuntos
Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Metabolismo Energético/fisiologia , Termogênese/fisiologia , Dieta , Humanos , Insulina/metabolismo , Obesidade/metabolismo , Temperatura
18.
J Reconstr Microsurg ; 32(5): 336-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26636888

RESUMO

Background In this article, we reviewed the training results of medical students using the Microvascular Research Center Training Program (MRCP), and proposed an ideal microsurgical training program for all individuals by analyzing the training results of medical students who did not have any surgical experience. Methods As of 2015, a total of 29 medical students completed the MRCP. In the most recent 12 medical students, the number of trials performed for each training stage and the number of rats needed to complete the training were recorded. Additionally, we measured the operating time upon finishing stage 5 for the recent six medical students after it became a current program. Results The average operating time upon finishing stage 5 for the recent six medical students was 120 minutes ± 11 minutes (standard deviation [SD]). The average vascular anastomosis time (for the artery and vein) was 52 minutes ± 2 minutes (SD). For the most recent 12 medical students, there was a negative correlation between the number of trials performed in the non-rat stages (stages 1-3) and the number of rats used in the rat stages (stages 4-5). Conclusion Analysis of the training results of medical students suggests that performing microsurgery first on silicon tubes and chicken wings saves animals' lives later during the training program. We believe that any person can learn the technique of microsurgery by performing 7 to 8 hours of training per day over a period of 15 days within this program setting.


Assuntos
Competência Clínica/normas , Educação de Graduação em Medicina , Microcirurgia , Microvasos/cirurgia , Estudantes de Medicina , Procedimentos Cirúrgicos Vasculares , Anastomose Cirúrgica , Animais , Modelos Animais de Doenças , Humanos , Japão , Microcirurgia/educação , Duração da Cirurgia , Avaliação de Programas e Projetos de Saúde , Procedimentos Cirúrgicos Vasculares/educação , Procedimentos Cirúrgicos Vasculares/instrumentação
19.
J Clin Lipidol ; 8(6): 630-634, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25499946

RESUMO

Extreme hypertriglyceridemia can lead to acute pancreatitis and rapid lowering of serum triglycerides (TG) is necessary for preventing such life-threatening complications. However, there is no established consensus on the acute management of extreme hypertriglyceridemia. We retrospectively reviewed 10 cases of extreme hypertriglyceridemia with mean serum TG on presentation of 101.5 ± 23.4 mmol/L (8982 ± 2070 mg/dL) managed with insulin. Serum TG decreased by 87 ± 4% in 24 hours in those patients managed with intravenous insulin and fasting and 40 ± 8.4% in those managed with intravenous insulin alone (P = .0003). The clinical course was uncomplicated in all except 1 patient who subsequently developed a pancreatic pseudocyst. Thus, combination of intravenous insulin with fasting appears to be an effective, simple, and safe treatment strategy in immediate management of extreme hypertriglyceridemia.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Insulina/administração & dosagem , Administração Intravenosa , Adulto , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Jejum/efeitos adversos , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipertrigliceridemia/complicações , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Triglicerídeos/sangue
20.
Physiol Rep ; 2(11)2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25413316

RESUMO

PET-CT using (18)F-FDG is employed for detecting brown adipose tissue (BAT) in humans. Alternative methods are needed because of the radiation and cost of PET-CT imaging. The aim was to evaluate the accuracy of infrared thermography (IRT) in detecting human BAT benchmarked to PET-CT imaging. Seventeen individuals underwent a total of 29 PET-CT scans, 12 of whom were studied twice, after 2 h of cold stimulation at 19°C, in parallel with measurement of skin temperatures overlying the supraclavicular (SCV) fossa and the lateral upper chest (control), before and after cold stimulation. Of the 29 scans, 20 were BAT positive after cold stimulation. The mean left SCV temperature tended to be higher in the BAT-positive group before and during cooling. It was significantly higher (P = 0.04) than the temperature of the control area, which fell significantly during cooling in the BAT-positive (-1.2 ± 0.3°C, P = 0.002) but not in the negative (-0.2 ± 0.4°C) group. The temperature difference (Δtemp) between left SCV and chest increased during cooling in the BAT-positive (1.2 ± 0.2 to 2.0 ± 0.3°C, P < 0.002) but not in the negative group (0.6 ± 0.1 to 0.7 ± 0.1°C). A Δtemp of 0.9°C conferred a positive predictive value of 85% for SCV BAT, superior to that of SCV temperature. The findings were similar on the right. In conclusion, the Δtemp is significantly and consistently greater in BAT-positive subjects. The Δtemp quantified by IRT after 2-h cooling shows promise as a noninvasive convenient technique for studying SCV BAT function.

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