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1.
FASEB J ; 34(6): 7520-7539, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32293066

RESUMO

Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity-associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Thus, abnormal accumulation of the small leucine-rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes [endoplasmic reticulum and oxidative stress] in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin-stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot-dependent, pathogenic roles in obesity-associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR.


Assuntos
Tecido Adiposo/patologia , Matriz Extracelular/patologia , Resistência à Insulina/fisiologia , Obesidade/patologia , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/fisiologia , Tecido Adiposo/metabolismo , Adulto , Sinais (Psicologia) , Matriz Extracelular/metabolismo , Feminino , Inibidores de Dissociação do Nucleotídeo Guanina/metabolismo , Humanos , Lumicana/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Proteômica/métodos , Gordura Subcutânea/metabolismo
2.
J Pineal Res ; 49(3): 264-70, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20626589

RESUMO

Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin (MEL) has antioxidant activity and prevents experimental genotoxicity. The specific inhibitor of cyclooxygenase-2 (COX-2), celecoxib (CEL), increases the efficacy of chemoradiotherapy in advanced pancreatic cancer. The objective of the study was the comparison and synergic effect of MEL and CEL during either the induction or progression phases of the tumor process, measuring parameters of oxidative stress, number of tumor nodules and survival of animals with pancreatic cancer. Pancreatic cancer was induced by N-nitrosobis (2-oxopropyl)amine) (BOP) in Syrian hamsters. Melatonin and/or CEL were administered during the induction, postinduction as well as during both phases. The presence of tumor nodules were observed macroscopically in pancreatic and splenic areas, and the levels of lipoperoxides (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in pancreatic tissue were measured. The increases in tumor nodules and LPO as well as the reductions in GSH and enzymatic antioxidants in the pancreas induced by BOP were related to a lower survival rate of animals. The administration of MEL exerted a more potent beneficial effect than CEL treatment on the reduction in tumor nodules, oxidative stress and death of experimental BOP-treated animals. The combined treatment only exerted a synergistic beneficial effect when administered during the induction phase. Melatonin by itself had significant beneficial actions in improving the survival of hamsters.


Assuntos
Antioxidantes/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Melatonina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Celecoxib , Cricetinae , Inibidores de Ciclo-Oxigenase 2/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peróxidos Lipídicos/metabolismo , Melatonina/farmacologia , Mesocricetus , Estresse Oxidativo/efeitos dos fármacos , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Superóxido Dismutase/metabolismo
3.
J Surg Educ ; 76(4): 1107-1115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30691989

RESUMO

OBJECTIVE: To assess the sensitivity of an electroencephalographic (EEG)-based index, the prefrontal beta power, to quantify the mental workload in surgeons in real scenarios. Such EEG-based index might offer unique and unbiased measures of overload, a crucial factor when designing learning and training surgical programs. DESIGN: The experiment followed a 2 × 2 × 2 within subjects design with 3 factors: (1) Surgical Role during the surgery (primary surgeon vs. assistant surgeon), (2) the Surgical Procedure (laparo-endoscopic single-site [LESS] surgery vs. multiport laparoscopic surgery [MPS]), and (3) the Suturing Techniques (interrupted vs. continuous suture). SETTING: The study was carried out at the Advanced Multi-Purpose Simulation and Technological Innovation Complex situated at IAVANTE (Granada, Spain). METHODS: Four surgical teams (primary surgeon and assistant surgeon, experts in MPS) performed 8 surgical exercises on porcine models, under different task complexities. They performed 2 suturing techniques (continuous and interrupted), employing a low complex procedure (MPS) and a high complex procedure (LESS). Surgeons acted as the primary surgeon during half of the exercises, and, as the assistant surgeon, during the rest of them. Simultaneously, we monitored EEG prefrontal EEG beta power spectra of both surgeons, using 2 synchronized wearable EEG devices. We also collected performance and subjective data. RESULTS: Surgical complexity modulated prefrontal beta power. LESS surgery caused significant higher prefrontal beta power for both suturing techniques for both surgical roles which indicates higher demands than MPS. Perceived task complexity, overall surgical evaluation, and laparoscopic execution time confirmed EEG-based results. Finally, subjective ratings of surgical complexity differentiated between surgical roles within the same exercise, even when prefrontal beta power did not. CONCLUSIONS: To detect mental overload when surgeons are engaged with complex surgeries, real or simulated, is still guesswork. EEG-based indices have great potential as objective and nonintrusive measures to assess mental overload in surgeons. Furthermore, EEG-based indices might play a relevant role in monitoring surgeons and residents' cognitive state during their training.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Simulação por Computador , Eletroencefalografia/métodos , Laparoscopia/métodos , Adulto , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Espanha , Procedimentos Cirúrgicos Operatórios/métodos , Técnicas de Sutura , Suínos , Análise e Desempenho de Tarefas , Dispositivos Eletrônicos Vestíveis
4.
J Gastrointest Surg ; 14(4): 756-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19475460

RESUMO

INTRODUCTION: Bronchogenic cyst is pathology of the respiratory track. It consists of a defect during the embryological development of the tracheobronchial tree. Most common presentation is as a solid or cystic mass located in mediastinum, and it is usually diagnosed in relation to respiratory problems or recurrent infections in children. In adulthood, it is a rare pathology, and its diagnosis is usually incidental. CASE REPORT: We present a case of a patient with a paraesophageal cystic mass suggestive of intraabdominal esophageal duplication cyst but, after the histopathological examination, was discovered to be a bronchogenic cyst, something extremely rare as in most cases of subdiaphragmatic location; bronchogenic cysts appear as retroperitoneal lesions. DISCUSSION: After we review the current literature, surgical extirpation appears to be the treatment of choice due to potential complications, and laparoscopic approach is a feasibily and safe procedure for this pathology up to date.


Assuntos
Abdome/cirurgia , Cisto Broncogênico/cirurgia , Laparoscopia/métodos , Idoso , Cisto Broncogênico/diagnóstico , Diagnóstico Diferencial , Cisto Esofágico/diagnóstico , Humanos , Masculino
5.
J Pineal Res ; 43(3): 270-5, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17803524

RESUMO

Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin has antioxidant activity and prevents experimental genotoxicity. However, the effect of melatonin in pancreatic cancer has not been tested. Pancreatic carcinogenesis was induced by N-nitrosobis (2-oxopropyl)amine (BOP) in Syrian hamsters. Melatonin was administered during the BOP-induction phase (12 wk) and/or following the postinduction phase (12 wk). Different parameters of oxidative stress including lipid peroxides (LPO) and antioxidants (superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase) were determined in pancreatic tissue. Also, the presence of atypical hyperplasia (AH), well and moderately differentiated adenomacarcinoma (ADC-WD and ADC-MD, respectively) were studied. The administration of BOP induced an intense oxidative stress and ADC induction in the pancreas. The administration of melatonin during the induction or postinduction phase reduced LPO and improved the antioxidant status, as well as drastically reducing the presence of ADC but some AH remained. In conclusion, treatment with melatonin reduced oxidative damage and cancer nodules induced by BOP in the pancreas.


Assuntos
Melatonina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Cricetinae , Modelos Animais de Doenças , Peróxidos Lipídicos/metabolismo , Masculino , Nitrosaminas/farmacologia , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/metabolismo
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