RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin.

We addressed the involvement of the receptor for advanced glycation end products (RAGE) in the impairment of the cellular cholesterol efflux elicited by glycated albumin. Albumin was isolated from type 1 (DM1) and type 2 (DM2) diabetes mellitus (HbA1c > 9%) and non-DM subjects (C). Moreover, albumin was glycated in vitro (AGE-albumin). Macrophages from Ager null and wild-type (WT) mice, or THP-1 transfected with siRNA-AGER, were treated with C, DM1, DM2, non-glycated or AGE-albumin. The cholesterol efflux was reduced in WT cells exposed to DM1 or DM2 albumin as compared to C, and the intracellular lipid content was increased. These events were not observed in Ager null cells, in which the cholesterol efflux and lipid staining were, respectively, higher and lower when compared to WT cells. In WT, Ager, Nox4 and Nfkb1, mRNA increased and Scd1 and Abcg1 diminished after treatment with DM1 and DM2 albumin. In Ager null cells treated with DM-albumin, Nox4, Scd1 and Nfkb1 were reduced and Jak2 and Abcg1 increased. In AGER-silenced THP-1, NOX4 and SCD1 mRNA were reduced and JAK2 and ABCG1 were increased even after treatment with AGE or DM-albumin. RAGE mediates the deleterious effects of AGE-albumin in macrophage cholesterol efflux.

New PPARγ partial agonist improves obesity-induced metabolic alterations and atherosclerosis in LDLr(-/-) mice.

Peroxisome proliferator-activated receptor gamma (PPARγ) regulates multiple pathways involved in the pathogenesis of obesity and atherosclerosis. Here, we evaluated the therapeutic potential of GQ-177, a new thiazolidinedione, on diet-induced obesity and atherosclerosis. The intermolecular interaction between PPARγ and GQ-177 was examined by virtual docking and PPAR activation was determined by reporter gene assay identifying GQ-177 as a partial and selective PPARγ agonist. For the evaluation of biological activity of GQ-177, low-density lipoprotein receptor-deficient (LDLr(-/-)) C57/BL6 mice were fed either a high fat diabetogenic diet (diet-induced obesity), or a high fat atherogenic diet, and treated with vehicle, GQ-177 (20mg/kg/day), pioglitazone (20mg/kg/day, diet-induced obesity model) or rosiglitazone (15mg/kg/day, atherosclerosis model) for 28 days. In diet-induced obesity mice, GQ-177 improved insulin sensitivity and lipid profile, increased plasma adiponectin and GLUT4 mRNA in adipose tissue, without affecting body weight, food consumption, fat accumulation and bone density. Moreover, GQ-177 enhanced hepatic mRNA levels of proteins involved in lipid metabolism. In the atherosclerosis mice, GQ-177 inhibited atherosclerotic lesion progression, increased plasma HDL and mRNA levels of PPARγ and ATP-binding cassette A1 in atherosclerotic lesions. GQ-177 acts as a partial PPARγ agonist that improves obesity-associated insulin resistance and dyslipidemia with atheroprotective effects in LDLr(-/-) mice.

In type 2 diabetes mellitus glycated albumin alters macrophage gene expression impairing ABCA1-mediated cholesterol efflux.

Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis. AGE-albumin induces oxidative stress, which is linked to a reduction in ABCA-1 and cholesterol efflux. We characterized the glycation level of human serum albumin (HSA) isolated from poorly controlled DM2 (n = 11) patients compared with that of control (C, n = 12) individuals and determined the mechanism by which DM2-HSA can interfere in macrophage lipid accumulation. The HSA glycation level was analyzed by MALDI/MS. Macrophages were treated for 18 h with C- or DM2-HSA to measure the (14) C-cholesterol efflux, the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyze gene expression, and the differentially expressed genes were validated by real-time RT-PCR. An increased mean mass was observed in DM2-HSA compared with C-HSA, reflecting the condensation of at least 5 units of glucose. The cholesterol efflux mediated by apo AI, HDL3 , and HDL2 was impaired in DM2-HSA-treated cells, which was related to greater intracellular lipid accumulation. DM2-HSA decreased Abcg1 mRNA expression by 26%. Abca1 mRNA was unchanged, although the final ABCA-1 protein content decreased. Compared with C-HAS-treated cells, NADPH oxidase 4 mRNA expression increased in cells after DM2-HSA treatment. Stearoyl-Coenzyme A desaturase 1, janus kinase 2, and low density lipoprotein receptor mRNAs were reduced by DM2-HSA. The level of glycation that occurs in vivo in DM2-HSA-treated cells selectively alters macrophage gene expression, impairing cholesterol efflux and eliciting intracellular lipid accumulation, which contribute to atherogenesis, in individuals with DM2.

Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta.

BACKGROUND: Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice. METHODS: Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of (3)H-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. (14)C-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of (3)H-cholesteryl oleoyl ether ((3)H-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session. RESULTS: Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of (3)H-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in (3)H-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, (14)C-cholesterol efflux and uptake of (3)H-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals. CONCLUSION: Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.

Advanced glycation end products consumption and the decline of functional capacity in patients with Parkinson's disease: Cross-sectional study.

INTRODUCTION: Advanced Glycation End-Products (AGEs) are a diverse group of highly reactive molecules that play a vital role in the development of neurodegenerative disorders, such as Parkinson's Disease (PD), leading to a decline in functional and cognitive capacity. The objective of this study was to assess the intake and quantification of AGEs in individuals with PD and to correlate them with their functional and cognitive abilities. METHODS: This was a cross-sectional study involving 20 PD patients and 20 non-PD individuals as the Control group (C). The autofluorescence reader was used to evaluate skin AGEs, while food recall was used to quantify AGEs consumed for three different days. The Montreal Cognitive Assessment, Short Physical Performance Battery, and handgrip tests were used. PD patients demonstrated greater impairment in functional capacity compared to the control group. RESULTS: Dominant Handgrip (p = 0.02) and motor performance, in the sit and stand test (p = 0.01) and Short Physical Performance Battery (SPPB) (p = 0.01) were inferior in PD patients than the control group. Although PD patients tended to consume less AGEs than the control group, AGE intake was negatively correlated with handgrip strength in individuals with PD (r = -0.59; p < 0.05). CONCLUSION: PD patients had lower strength and functional capacity, suggesting that the effects of AGEs might be exacerbated during chronic diseases like Parkinson's.

Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1-mediated reverse cholesterol transport.

BACKGROUND: We evaluated the effects of albumin isolated from control individuals and from patients with poorly controlled type 1 diabetes mellitus on macrophage gene expression and on reverse cholesterol transport. METHODS: Serum albumin was purified from control subjects (n = 12) and from patients with poorly controlled type 1 diabetes mellitus (n = 13). (14)C-cholesterol-labelled J774 macrophages treated with albumin were employed to measure cholesterol efflux mediated by apo A-I, HDL(3) or HDL(2), the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyse gene expression. Several differentially expressed genes were validated by real-time reverse transcription-PCR using TaqMan Two Step RT-PCR. RESULTS: Levels of glycation-modified and (carboxymethyl)lysine-modified albumin were higher in diabetic patients than in control subjects. Apo A-I-mediated and HDL(2)-mediated cellular cholesterol efflux were impaired in macrophages treated with albumin from diabetic patients in comparison with control albumin-treated cells, which was attributed to the reduction in ABCA-1 protein content. Even in the presence of cholesterol acceptors, a higher level of intracellular lipid was observed in macrophages exposed to albumin from diabetic individuals in comparison with the control. The reduction in ABCA-1 content was associated with enhanced expression of stearoyl CoA desaturase 1 and decreased expression of janus kinase 2, which were induced by albumin from patients with type 1 diabetes mellitus. CONCLUSIONS: (Carboxymethyl)lysine-modified albumin isolated from poorly controlled type 1 diabetic patients impairs ABCA-1-mediated reverse cholesterol transport and elicits intracellular lipid accumulation, possibly contributing to atherosclerosis.

Dual effect of advanced glycation end products in pancreatic islet apoptosis.

BACKGROUND: Loss of ß-cell function hastens deterioration of metabolic control in type 2 diabetes patients. Besides amyloid deposit and glucolipotoxicity, advanced glycation end products (AGEs) acting through their receptors (RAGE) seem to contribute to this process by promoting islet apoptosis. In order to investigate the role of AGEs in ß-cell deterioration, we evaluated the temporal and dose effects of AGE compounds on apoptosis rate, reactive oxygen species generation and expression of pro-apoptotic and anti-apoptotic genes in cultured islets. METHODS: Rat pancreatic islets were exposed or not for 24, 48, 72 and 96 h to albumin modified by glycoaldehyde. Apoptosis, reactive oxygen species and superoxide content and NADPH oxidase activity were evaluated as well as RNA expression of the genes Ager (codes for RAGE), Bax, Bcl2 and Nfkb1. RESULTS: In 24 and 48 h, glycoaldehyde elicited a decrease in apoptosis rate in comparison with the control condition concomitantly with a reduction in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In contrast, after 72 and 96 h, glycoaldehyde promoted an increase in apoptosis rate concomitantly with an increase in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In 24 h, glycoaldehyde elicited a decrease in the islet content of reactive oxygen species, whereas after 48 and 72 h, it promoted an opposite effect, increasing superoxide generation. The NADPH oxidase inhibitor VAS2870 attenuated superoxide production, implicating NADPH oxidase as an important source of reactive oxygen species in islets exposed to AGEs. CONCLUSIONS: Albumin modified by glycoaldehyde exerted a dual effect in cultured pancreatic islets, being protective against apoptosis after short exposure but pro-apoptotic after prolonged exposure.

Quality of life and socio-demographic factors associated with nutritional risk in Brazilian community-dwelling individuals aged 80 and over: cluster analysis and ensemble methods.

Introduction: The aim of the present study was to use cluster analysis and ensemble methods to evaluate the association between quality of life, socio-demographic factors to predict nutritional risk in community-dwelling Brazilians aged 80 and over. Methods: This cross-sectional study included 104 individuals, both sexes, from different community locations. Firstly, the participants answered the sociodemographic questionnaire, and were sampled for anthropometric data. Subsequently, the Mini-Mental State Examination (MMSE) was applied, and Mini Nutritional Assessment Questionnaire (MAN) was used to evaluate their nutritional status. Finally, quality of life (QoL) was assessed by a brief version of World Health Organizations' Quality of Life (WHOQOL-BREF) questionnaire and its older adults' version (WHOQOL-OLD). Results: The K-means algorithm was used to identify clusters of individuals regarding quality-of-life characteristics. In addition, Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms were used to predict nutritional risk. Four major clusters were derived. Although there was a higher proportion of individuals aged 80 and over with nutritional risk in cluster 2 and a lower proportion in cluster 3, there was no statistically significant association. Cluster 1 showed the highest scores for psychological, social, and environmental domains, while cluster 4 exhibited the worst scores for the social and environmental domains of WHOQOL-BREF and for autonomy, past, present, and future activities, and intimacy of WHOQOL-OLD. Conclusion: Handgrip, household income, and MMSE were the most important predictors of nutritional. On the other hand, sex, self-reported health, and number of teeth showed the lowest levels of influence in the construction of models to evaluate nutritional risk. Taken together, there was no association between clusters based on quality-of-life domains and nutritional risk, however, predictive models can be used as a complementary tool to evaluate nutritional risk in individuals aged 80 and over.

The Influence of Whey Protein on Muscle Strength, Glycemic Control and Functional Tasks in Older Adults with Type 2 Diabetes Mellitus in a Resistance Exercise Program: Randomized and Triple Blind Clinical Trial.

OBJECTIVES: To evaluate the effect of whey protein (WP) supplementation associated with resistance training (RT) on glycemic control, functional tasks, muscle strength, and body composition in older adults living with type 2 diabetes mellitus (T2DM). Secondly, to evaluate the safety of the protocol for renal function. METHODS: The population comprised twenty-six older men living with T2DM (68.5 ± 11.5 years old). The participants were randomly assigned to the Protein Group (PG) and the Control Group (CG). The handgrip test and evolution of exercise loads, according to the Omni Resistance Exercise Scale, evaluated muscle strength. Functional tasks were assessed by force platform in three different protocols: Sit-to-Stand, Step/Quick Turn, and Step Up/Over. Body composition was evaluated by bioimpedance and glycemic control and renal function were assessed by biochemical analyses. Both groups performed RT for 12 weeks, twice a week, prioritizing large muscle groups. Protein supplementation was 20 g of whey protein isolate and the CG was supplemented with an isocaloric drink, containing 20 g of maltodextrin. RESULTS: There was a significant difference in muscle strength, according to the evolution of the exercise loads, but it was not confirmed in the handgrip test. However, there was no significant difference between the groups, regarding performance in functional tasks, glycemic control, or body composition. Renal function showed no alteration. CONCLUSION: The intake of 20 g of WP in older male adults living with T2DM did not increase the effect of RT on muscle strength, functional tasks, and glycemic control. The intervention was proven safe regarding renal function.

Advanced glycation in macrophages induces intracellular accumulation of 7-ketocholesterol and total sterols by decreasing the expression of ABCA-1 and ABCG-1.

BACKGROUND: Advanced glycation end products (AGE) alter lipid metabolism and reduce the macrophage expression of ABCA-1 and ABCG-1 which impairs the reverse cholesterol transport, a system that drives cholesterol from arterial wall macrophages to the liver, allowing its excretion into the bile and feces. Oxysterols favors lipid homeostasis in macrophages and drive the reverse cholesterol transport, although the accumulation of 7-ketocholesterol, 7alpha- hydroxycholesterol and 7beta- hydroxycholesterol is related to atherogenesis and cell death. We evaluated the effect of glycolaldehyde treatment (GAD; oxoaldehyde that induces a fast formation of intracellular AGE) in macrophages overloaded with oxidized LDL and incubated with HDL alone or HDL plus LXR agonist (T0901317) in: 1) the intracellular content of oxysterols and total sterols and 2) the contents of ABCA-1 and ABCG-1. METHODS: Total cholesterol and oxysterol subspecies were determined by gas chromatography/mass spectrometry and HDL receptors content by immunoblot. RESULTS: In control macrophages (C), incubation with HDL or HDL + T0901317 reduced the intracellular content of total sterols (total cholesterol + oxysterols), cholesterol and 7-ketocholesterol, which was not observed in GAD macrophages. In all experimental conditions no changes were found in the intracellular content of other oxysterol subspecies comparing C and GAD macrophages. GAD macrophages presented a 45% reduction in ABCA-1 protein level as compared to C cells, even after the addition of HDL or HDL + T0901317. The content of ABCG-1 was 36.6% reduced in GAD macrophages in the presence of HDL as compared to C macrophages. CONCLUSION: In macrophages overloaded with oxidized LDL, glycolaldehyde treatment reduces the HDL-mediated cholesterol and 7-ketocholesterol efflux which is ascribed to the reduction in ABCA-1 and ABCG-1 protein level. This may contribute to atherosclerosis in diabetes mellitus.

DYNAMIC POSTURAL BALANCE IS MEDIATED BY ANTHROPOMETRY AND BODY COMPOSITION IN OLDER WOMEN.

OBJECTIVE: To investigate the relationship between anthropometry and body composition with dynamic postural balance in elderly women with low bone mineral density (BMD). METHODS: 45 older women (≥ 60 years), low BMD and nutritional diagnosis of low weight to overweight. For the assessment of body composition, Dual energy X-ray emission densitometry and anthropometric examination were used to measure: body mass (kg), height (cm) and BMI (k/m2). The assessment of dynamic postural balance was performed by the mini Balance Master Evaluation System clinical test and the computerized Balance Master® System test by the Sit to Stand and Step Up/Over tests. RESULTS: There was a negative correlation between miniBESTest (r = - 0.566; p ≤ 0.001) and time to ascend and descend step (r = - 0.393; p ≤ 0.007) with fat mass, and positive correlation with miniBESTest (r = 0.526; p ≤0.001) and time to go up and down a step with muscle mass (r = 0.297; p ≤ 0.04). As for anthropometric variables, only height showed a positive correlation (r = 0.296; p ≤ 0.04) with the speed in the sit and stand test. CONCLUSION: Lean mass reduces postural oscillations; in contrast, fat mass negatively interfered with dynamic postural balance in women with low BMD. Height was related to dynamic postural balance, the taller the elderly, the worse their balance. Level of Evidence II, Prognostic Studies - Investigating the Effect of a Patient Characteristic on the Outcome of Disease.

OBJETIVO: Investigar a relação da antropometria e composição corporal com o equilíbrio postural dinâmico em idosas com baixa Densidade Mineral Óssea (DMO). MÉTODOS: 45 idosas (≥ 60 anos), baixa DMO e diagnóstico nutricional entre baixo peso e sobrepeso. Para a avaliação da composição corporal utilizou-se a densitometria por emissão de raios x de dupla energia e exame antropométrico para aferir: massa corporal (kg), estatura (cm) e índice de massa corporal (IMC) (k/m2). A avaliação do equilíbrio postural dinâmico foi realizada pelo teste clínico mini Balance Master Evaluation System, pelo teste computadorizado Balance Master ® System e pelos testes Sit-to-Stand e Step Up/Over. Resultados: Houve correlação negativa do miniBESTest (r = − 0,566; p ≤ 0,001) e tempo de subir e descer um degrau (r = − 0,393; p ≤ 0,007) com a massa gorda, e correlação positiva do miniBESTest (r = 0,526; p ≤ 0,001) e tempo de subir e descer um degrau com a massa muscular (r = 0,297; p ≤ 0,04). Quanto às variáveis antropométricas, apenas a estatura apresentou correlação positiva (r = 0,296; p ≤ 0,04) com a velocidade no teste de sentar-se e levantar-se. CONCLUSÃO: A massa magra reduz as oscilações posturais. Em contrapartida, a massa gorda interfere de forma negativa no equilíbrio postural dinâmico de mulheres com baixa DMO. A estatura esteve relacionada ao equilíbrio postural dinâmico: quanto mais altas as idosas pior era seu equilíbrio. Nível de Evidência II, Estudos prognósticos - Investigação do efeito de característica de um paciente sobre o desfecho da doença.

Corrigendum: Self-Perception of Changes in Routines in Adults and Older Adults Associated to Social Distancing Due to COVID-19-A Study in São Paulo, Brazil.

[This corrects the article DOI: 10.3389/fpsyg.2021.607559.].

Vitamin D supplementation associated with 12-weeks multimodal training in older women with low bone mineral density: A randomized double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the influence of vitamin D supplementation with a multimodal exercise program on postural balance and muscle strength in older women with low bone mineral density (BMD) and vitamin D insufficiency. METHODS: 12-week, randomized, double-blind, placebo-controlled clinical trial. Total of 422 subjects were screened for participation, and 46 met the inclusion criteria. Those were randomized into an experimental group (EG; n = 23) and control group (CG; n = 23). At the time of enrollment, all subjects had low BMD, vitamin D insufficiency, and were not practicing resistance exercise. Muscle strength assessments were performed by the 30-s sit to stand test; 15-steps climbing test; handgrip dynamometer and knee muscle strength using an isokinetic dynamometer at 60°/sec. Postural balance was clinically evaluated by the MiniBESTest and by a force platform. Dynamic balance was assessed by standing up from a chair and walk over a step, using also a force platform. RESULTS: In the EG, vitamin D levels increased in the post-treatment period (P < 0.001) whereas in CG levels remained unchanged (P = 0.86). Both groups improved muscular strength in the dynamometry isokinetic test: flexors PT/BW - right (P < 0.02) and left side (P < 0.04). In the dynamic postural balance during the task to step up over: the Lift Up Left was better in the CG (P = 0.01); the Moment Time left was better in the CG (P = 0.01); the Impact index left was better in the EG (P = 0.01). The Mini-BESTest - both groups improved the postural balance test (P < 0.001). CONCLUSION: Vitamin D supplementation associated with multimodal exercise program did not augment muscle strength adaptation or postural balance in older women with low bone mineral density and vitamin D insufficiency.

Self-Perception of Changes in Routines in Adults and Older Adults Associated to Social Distancing Due to COVID-19-A Study in São Paulo, Brazil.

COVID-19 is an acute respiratory illness with higher mortality in older adults. This condition is spread person-to-person through close contact, and among policies employed to decrease transmission are the improvement of hygiene habits and physical distancing. Although social distancing has been recognized as the best way to prevent the transmission, there are concerns that it may promote increased depression symptoms risk and anxiety, mainly in older adults. This cross-sectional study aimed to verify self-concept of social distancing in adults compared to older adults. All participants, over 18 years and residents of São Paulo state (Brazil), were invited to join this research study by a message application and answered an interdisciplinary questionnaire during the period from May 23 to June 23, 2020. The questions were divided into the following aspects: sociodemographic data, financial conditions, routine-related perception, perception of health, physical and emotional state, and eating habits. The younger adult group was composed of 139 participants, with a mean age of 43.15 years (±10.92), and the older adult group was composed of 437 participants with a mean age of 67.59 years (±6.13) of both sex. Changes in routine during the period of social distance were reported by 95% of adults and 96.8% of older adults, but adults indicated more significant alterations in routine. Although there was no difference between groups for several aspects, adults revealed greater alterations in sleep quality, evacuation frequency, and more difficulty to perform daily activities at home. Further studies are necessary to follow up the impacts of social distancing among adults and older adults in different socioeconomic contexts to better understand the long-term alterations and the necessity of interventions.

Persistent Effect of Advanced Glycated Albumin Driving Inflammation and Disturbances in Cholesterol Efflux in Macrophages.

Advanced glycated albumin (AGE-albumin) impairs cholesterol efflux and contributes to inflammation in macrophages. The current study evaluated: (1) the persistence of the deleterious effect of AGE-albumin in cholesterol efflux and in inflammation, and (2) how metabolic control in diabetes mellitus (DM) contributes to attenuate the deleterious role of AGE-albumin in macrophage cholesterol homeostasis. Methods: AGE-albumin was produced in vitro or isolated from uncontrolled DM subjects' serum before (bGC) and after improved glycemic control (aGC). Albumin samples were incubated with bone marrow-derived macrophages and 14C-cholesterol efflux or LPS- induced cytokine secretion were determined immediately, or after cell resting in culture media alone. The ABCA-1 degradation rate was determined after cell incubation with cycloheximide, and ABCA1 protein level by immunoblot. Oil Red O staining was used to assess intracellular lipid accumulation. Results: A persistent effect of AGE-albumin was observed in macrophages in terms of the secretion of inflammatory cytokines and reduced cholesterol efflux. HDL-mediated 14C-cholesterol efflux was at least two times higher in macrophages treated with aCG-albumin as compared to bGC-albumin, and intracellular lipid content was significantly reduced in aGC-albumin-treated cells. As compared to bGC-albumin, the ABCA-1 protein content in whole cell bulk was 94% higher in aCG-albumin. A 20% increased ABCA-1 decay rate was observed in macrophages treated with albumin from poorly controlled DM. AGE-albumin has a persistent deleterious effect on macrophage lipid homeostasis and inflammation. The reduction of AGEs in albumin ameliorates cholesterol efflux.

BONE MINERAL DENSITY AND BODY COMPOSITION IN ELDERLY RUNNERS: SIX-YEAR FOLLOW-UP.

OBJECTIVE: To evaluate bone mineral density (BMD) and body composition over a six-year period in elderly long-distance runners. METHODS: We analyzed the medical records of elderly athletes who were long-distance runners, were participants of the IOT-HCFMUSP Orthogeriatric Group, and had their BMD evaluated between 2001 and 2007; of these athletes, 11 were included in the study. Inclusion criteria: athletes should be long-distance runners, should not stop long-distance running during the six-year period, and should have undergone BMD and body composition evaluations. Body composition was evaluated using bone densitometry with dual-energy X-ray absorptiometry with a Lunar-DPX device. RESULTS: Over the six-year period, body composition remained stable, but there was a significant increase only in the fat percentage (p = 0.003). CONCLUSION: Long-distance running may maintain BMD but may lead to an increase in the fat percentage in elderly runners. Level of Evidence II; Prognostic Study - Investigating the Effect of Patient Characteristics on Disease Outcome.

OBJETIVO: Acompanhar a densidade mineral óssea (DMO) e a composição corporal, ao longo de seis anos, em idosos corredores de longa distância. MÉTODOS: analisamos os prontuários médicos de um grupo de atletas idosos, corredores de longa distância, participantes do Grupo de Ortogeriatria do IOT-HC-FMUSP, e reunimos todos os atletas que tiveram a DMO avaliada no ano de 2001 e de 2007, sendo destes, 11 prontuários selecionados. Critérios de inclusão: ser corredor de longa distância; não parar de correr ao longo dos seis anos e ter os dois exames de DMO e composição corporal avaliados. A composição corporal foi avaliada por meio de densitometria óssea, com uma dupla energia de absorção de raios-X (DEXA), em um aparelho LUNAR-DPX. RESULTADOS: Ao longo dos seis anos, a composição corpórea se manteve estável, havendo apenas um aumento significante na gordura expressa em (%) (p=0,003). CONCLUSÃO: A corrida de longa distância parece conservar a DMO de idosos corredores, porém com aumento de gordura. Nível do Evidência II; Estudos prognósticos - Investigação do efeito de características de um paciente sobre o desfecho da doença.

Advanced glycation end products consumption and the decline of functional capacity in patients with Parkinson's disease: Cross-sectional study

Abstract Introduction Advanced Glycation End-Products (AGEs) are a diverse group of highly reactive molecules that play a vital role in the development of neurodegenerative disorders, such as Parkinson's Disease (PD), leading to a decline in functional and cognitive capacity. The objective of this study was to assess the intake and quantification of AGEs in individuals with PD and to correlate them with their functional and cognitive abilities. Methods This was a cross-sectional study involving 20 PD patients and 20 non-PD individuals as the Control group (C). The autofluorescence reader was used to evaluate skin AGEs, while food recall was used to quantify AGEs consumed for three different days. The Montreal Cognitive Assessment, Short Physical Performance Battery, and handgrip tests were used. PD patients demonstrated greater impairment in functional capacity compared to the control group. Results Dominant Handgrip (p = 0.02) and motor performance, in the sit and stand test (p = 0.01) and Short Physical Performance Battery (SPPB) (p = 0.01) were inferior in PD patients than the control group. Although PD patients tended to consume less AGEs than the control group, AGE intake was negatively correlated with handgrip strength in individuals with PD (r = -0.59; p < 0.05). Conclusion PD patients had lower strength and functional capacity, suggesting that the effects of AGEs might be exacerbated during chronic diseases like Parkinson's.

RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND BODY COMPOSITION IN ELDERLY.

OBJECTIVE: To evaluate the association between bone mineral density (BMD) and body composition in healthy older adults at different skeletal sites. METHODS: We analyzed 87 medical records and BMD along with the body composition of men ranging from 60 to 87 years of age (mean: 68.5, standard deviation: 6.5). Inclusion criteria were normal BMD values (T-score greater than or equal to -1.0) and body mass index within normal or overweight range (18.5 to 29.5 kg/m2). Body composition was evaluated using bone densitometry with dual-energy X-ray absorptiometry (DEXA) in a LUNAR-DPX apparatus. RESULTS: Greater lean mass, fat mass, and soft tissue was associated with better BMD values in older adults, and higher age was associated with poorer BMD. CONCLUSION: Body composition (lean and fat masses and soft tissue) in older men is positively associated with BMD at all body sites (arms, legs, and trunk). Level of Evidence II; Prognostic studies - Investigating the effect of a patient characteristic on the outcome of disease.

OBJETIVO: Avaliar a associação entre a DMO e a composição corporal em idosos hígidos em diferentes sítios esqueléticos. MÉTODOS: Foram analisados 87 prontuários e exames de DMO com composição corporal de idosos do sexo masculino com média de idade de 68,5 (6,5) variando de 60 a 87 anos. Os critérios de inclusão foram valores de DMO dentro do normal (T-score maior ou igual a -1,0); IMC dentro dos valores normais ou sobrepeso (18,5 a 29,5 kg/m2). A composição corporal foi avaliada por meio de densitometria óssea por dupla emissão de raios-X (DEXA) em aparelho LUNAR-DPX. RESULTADOS: Quanto maior as massas magra e gorda e os tecidos moles, melhor os valores da DMO dos idosos e quanto maior a idade, pior a qualidade da DMO. CONCLUSÃO: A composição corporal (massas magra e gorda e tecidos moles) de homens idosos associa-se positivamente na DMO em todos os locais do corpo (membros superiores, inferiores e tronco). Nível do Evidênci II; Estudos prognósticos - Investigação do efeito de caractetísticas de um paciente sobre o desfecho da doença.

Análise da satisfação corporal em mulheres após cirurgia bariátrica e suas alterações psicológicas, comportamentais e alimentares / Analysis of body satisfaction in women after bariatric surgery and its psychological, bahavioral and eating changes / Análisis de la satisfacción corporal en mujeres tras la cirugía bariátrica y sus cambios psicológicos, conductuales y alimentarios

INTRODUÇÃO: A obesidade é uma doença crônica e de causa multifatorial caracterizada pelo acúmulo excessivo de gordura no corpo. A cirurgia bariátrica é um dos procedimentos indicados para o tratamento da obesidade. OBJETIVO: Este estudo teve como objetivo analisar a satisfação física de mulheres submetidas à cirurgia bariátrica, avaliando a incidência de alterações psicológicas pós-operatórias, comportamentos alimentares, escores de autoestima e compulsão alimentar. MÉTODOS: Este projeto foi aprovado pelo Comitê de Ética da Universidade São Judas Tadeu (CAAE 46628521.5.0000.0089). Trata-se de um estudo de caráter quantitativo com delineamento transversal que foi realizado em um grupo de 39 indivíduos do sexo feminino, com idade entre 27 e 56 anos, que se submeteram à cirurgia bariátrica do tipo Bypass Gástrico em Y de Roux há pelo menos 2 anos. Foi utilizado um formulário (Google Forms - http://gg.gg/pesquisacirurgiabariatrica) para a coleta dos dados. RESULTADOS: A análise dos dados evidenciou que as participantes apresentam sobrepeso e insatisfação corporal, mas manifestam autoestima satisfatória. A maioria das participantes afirma experimentar sentimentos positivos ou negativos quando comem, além de não fazer acompanhamento psicológico. CONCLUSÃO: Nota-se a importância do acompanhamento multidisciplinar antes, durante e depois da cirurgia bariátrica para que os resultados sejam duradouros. A terapia cognitivo-comportamental pode ser extremamente eficaz nesse processo, pois atua na modificação de pensamentos e comportamentos disfuncionais diante das necessidades individuais.

INTRODUCTION: Obesity is a chronic, multifactorial disease characterized by the excessive accumulation of fat in the body. Bariatric surgery is one of the procedures indicated for the treatment of obesity. OBJECTIVE: This study aimed to analyze the physical satisfaction of women undergoing bariatric surgery, assessing the incidence of postoperative psychological changes, eating behaviors, self-esteem scores, and binge eating. METHODS: This project was approved by the Ethics Committee of São Judas Tadeu University (CAAE 46628521.5.0000.0089). This is a quantitative cross-sectional study that was carried out on a group of 39 females aged between 27 and 56 who had undergone Roux-en-Y gastric bypass surgery at least two years previously. A form (Google Forms - http://gg.gg/pesquisacirurgiabariatrica) was used to collect the data. RESULTS: Analysis of the data showed that the participants were overweight and had body dissatisfaction but expressed satisfactory self-esteem. Most of the participants said that they experience positive or negative feelings when they eat, and that they do not receive psychological counseling. CONCLUSION: It is important to have multidisciplinary support before, during, and after bariatric surgery so that the results are long-lasting. Cognitive-behavioral therapy can be extremely effective in this process, as it works to modify dysfunctional thoughts and behaviors in the face of individual needs.

INTRODUCCIÓN: La obesidad es una enfermedad crónica y multifactorial caracterizada por la acumulación excesiva de grasa en el organismo. La cirugía bariátrica es uno de los procedimientos indicados para el tratamiento de la obesidad. OBJETIVO: Este estudio tuvo como objetivo analizar la satisfacción física de mujeres sometidas a cirugía bariátrica, evaluando la incidencia de cambios psicológicos postoperatorios, comportamientos alimentarios, puntuaciones de autoestima y atracones. MÉTODOS: Este proyecto fue aprobado por el Comité de Ética de la Universidad São Judas Tadeu (CAAE 46628521.5.0000.0089). Se trata de un estudio cuantitativo, transversal, realizado en un grupo de 39 mujeres con edades comprendidas entre 27 y 56 años que habían sido sometidas a cirugía de bypass gástrico en Y de Roux al menos dos años antes. Para la recogida de datos se utilizó un formulario (Google Forms - http://gg.gg/pesquisacirurgiabariatrica). RESULTADOS: El análisis de los datos mostró que los participantes tenían sobrepeso e insatisfacción corporal, pero expresaron una autoestima satisfactoria. La mayoría de los participantes dijeron que experimentan sentimientos positivos o negativos cuando comen, y que no reciben asesoramiento psicológico. CONCLUSIÓN: Es importante recibir asesoramiento multidisciplinar antes, durante y después de la cirugía bariátrica para que los resultados sean duraderos. La terapia cognitivo-conductual puede ser extremadamente eficaz en este proceso, ya que trabaja para modificar los pensamientos y comportamientos disfuncionales frente a las necesidades individuales.

AGE-albumin enhances ABCA1 degradation by ubiquitin-proteasome and lysosomal pathways in macrophages.

BACKGROUND AND AIMS: Advanced glycation end products (AGEs) induce cellular oxidative/endoplasmic reticulum stress and inflammation. We investigated its underlying mechanisms for atherogenesis focusing on regulation of ABCA1 protein decay in macrophages. METHODS: The ABCA1 decay rate was evaluated in macrophages after treatment with LXR agonist and by incubation with control (C) or AGE-albumin concomitant or not with cycloheximide, MG-132, ammonium chloride and calpain inhibitors were utilized to inhibit, respectively, proteasome, lysosome and ABCA1 proteolysis at cell surface. ABCA1 was determined by immunoblot and the protein decay rate calculated along time by the slope of the linear regression. Ubiquitination level was determined in ABCA1 immunoprecipitated from whole cell lysate or bulk cell membrane. AGE effect was also analyzed in THP-1 cells transfected with siRNA-RAGE. Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/MS. One-way ANOVA and Student t test were utilized to compare results. RESULTS: CML and PYR-albumin were higher in AGE-albumin as compared to C. AGE-albumin reduced ABCA1 in J774 and THP-1 macrophages (20-30%) and induced a higher ABCA1 ubiquitination and a faster protein decay rate that was dependent on the presence of AGE during the kinetics of measurement in the presence of cycloheximide. Proteasomal inhibition restored and lysosomal inhibition partially recovered ABCA1 in cells treated with AGE-albumin. Calpain inhibition was not able to rescue ABCA1. RAGE knockdown prevented the reduction in ABCA1 elicited by AGE. CONCLUSIONS: AGE-albumin diminishes ABCA1 by accelerating its degradation through the proteasomal and lysosomal systems. This may increase lipid accumulation in macrophages by diminishing cholesterol efflux via RAGE signaling contributing to atherosclerosis in diabetes mellitus.