ADRIANA MACHADO SALDIBA DE LIMA
Projetos de Pesquisa
Unidades Organizacionais
LIM/10 - Laboratório de Lípides, Hospital das Clínicas, Faculdade de Medicina
19 resultados
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- Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids(2012) MACHADO, Roberta M.; NAKANDAKARE, Edna R.; QUINTAO, Eder C. R.; CAZITA, Patricia M.; KOIKE, Marcia K.; NUNES, Valeria S.; FERREIRA, Fabiana D.; AFONSO, Milessa S.; BOMBO, Renata P. A.; MACHADO-LIMA, Adriana; SORIANO, Francisco G.; CATANOZI, Sergio; LOTTENBERG, Ana MariaThe development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or omega-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-alpha) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-alpha concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-alpha as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.
article CONTEMPORARY INVOLVEMENTS IN HIGHER EDUCATION: ARRANGEMENTS PERTINENT TO AN AGING POPULATION(2024) FERREIRA-COSTA, Jeniffer; SILVA-FERREIRA, Thais da; OGASSAVARA, Dante; LIMA, Adriana Machado Saldiba de; MONTIEL, Jose MarialThe structuring of education in formal settings follows hierarchical guidelines monitored by state institutions to assess the learning process. There is a need to analyze the emerging phenomena within Brazilian education due to the benefits it provides to individuals throughout their lives and society. This essay aims to address the position of higher education in relation to the aging population, with a focus on opportunities for Stricto Sensu postgraduate programs. Changes in the educational landscape are observed, including an increase in enrollments and graduates, with the latter having the possibility to enter postgraduate programs, and a growing interest in distance education. Therefore, the importance of educational guidelines to guide actions in these sectors is emphasized. Furthermore, from the perspective of human aging, scientific research is crucial in providing essential information to address the emerging demands resulting from this phenomenon. It is concluded that Brazilian higher education is experiencing growth and, as it relates to the aging process, activities carried out in different educational institutions can provide support to address the challenges related to the elderly and public systems.- Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease(2021) LIRA, Aecio Lopes de Araujo; SANTANA, Monique de Fatima Mello; PINTO, Raphael de Souza; MINANNI, Carlos Andre; IBORRA, Rodrigo Tallada; LIMA, Adriana Machado Saldiba de; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, Marisa; QUEIROZ, Marcia SilvaBackground and aims: Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. Material and methods: 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry. In the isolated albumins, we quantified CBL (ELISA) and total AGE and pentosidine by fluorescence. Macrophages were treated with albumin isolated, and 14C-Cholesterol efflux mediated by HDL2 or HDL3 was measured. Kruskal-Wallis test, Jonckheere-Terpstra test and Brunner's posttest were used for comparisons among groups. Results: Determination of CML, HCit, CBL in plasma, as total AGE and pentosidine in albumins, did not differ between groups; however, CBL in the isolated albumins was higher in the more advanced stages of CKD (p = 0.0414). There was reduction in the 14C-cholesterol efflux after treatment for 18 h with albumin isolated from patients with eGFR<60 mL/min/1.73m2 compared with control group mediated by HDL2 (p = 0.0288) and HDL3 (p < 0.0001), as well as when compared with eGFR >= 60 mL/min/1.73m2 per HDL2 (p = 0.0001) and HDL3 (p < 0.0001). Treatment for 48 h showed that eGFR<15 mL/min/1.73m2 had a lower percentage of 14Ccholesterol efflux mediated by HDL2 compared to control and other CKD groups (p = 0.0274). Conclusions: Albumins isolated from individuals with T2DM and eGFR<60 mL/min/1.73m2 suffer greater carbamoylation, and they impair the cholesterol efflux mediated by HDL2 and HDL3. In turn, this could promote lipids accumulation in macrophages and disorders in reverse cholesterol transport.
- 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(2023) SOARES, A. L. D. S.; MACHADO-LIMA, A.; BRECH, G. C.; GREVE, J. M. D.; SANTOS, J. R. dos; INOJOSSA, T. R.; ROGERO, M. M.; SALLES, J. E. N.; SANTAREM-SOBRINHO, J. M.; DAVIS, C. L.; ALONSO, A. C.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.
- New PPAR gamma partial agonist improves obesity-induced metabolic alterations and atherosclerosis in LDLr-/- mice(2016) SILVA, Jacqueline C.; CESAR, Fernanda A.; OLIVEIRA, Edson M. de; TURATO, Walter M.; TRIPODI, Gustavo L.; CASTILHO, Gabriela; MACHADO-LIMA, Adriana; HERAS, Beatriz de las; BOSCA, Lisardo; RABELLO, Marcelo M.; HERNANDES, Marcelo Z.; PITTA, Marina G. R.; PITTA, Ivan R.; PASSARELLI, Marisa; RUDNICKI, Martina; ABDALLA, Dulcineia S. P.Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma 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 PPAR gamma 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 (20 mg/kg/day), pioglitazone (20 mg/kg/day, diet-induced obesity model) or rosiglitazone (15 mg/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 PPAR), and ATP-binding cassette A1 in atherosclerotic lesions. GQ-177 acts as a partial PPAR gamma agonist that improves obesity-associated insulin resistance and dyslipidemia with atheroprotective effects in LDLr-/- mice.
- Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients(2018) SANTOS-BEZERRA, Daniele P.; MACHADO-LIMA, Adriana; MONTEIRO, Maria Beatriz; ADMONI, Sharon N.; PEREZ, Ricardo V.; MACHADO, Cleide G.; SHIMIZU, Maria Heloiza; CAVALEIRO, Ana M.; THIEME, Karina; QUEIROZ, Marcia S.; MACHADO, Ubiratan F.; GIANNELLA-NETO, Daniel; PASSARELLI, Marisa; CORREA-GIANNELLA, Maria LuciaQuantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE (AGER) and AGER1 (DDOST)] and of the gene coding the deacetylase SIRT1 (SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming >= 12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.
- Glycated human serum albumin isolated from poorly controlled diabetic patients impairs cholesterol efflux from macrophages: an investigation by mass spectrometry(2015) CASTILHO, Gabriela; SARTORI, Camila H.; MACHADO-LIMA, Adriana; NAKANDAKARE, Edna R.; CORREA-GIANNELLA, Maria Lucia C.; ROVERSO, Marco; PORCU, Simona; LAPOLLA, Annunziata; TRALDI, Pietro; PASSARELLI, MarisaAdvanced glycation end-products impair ABCA-1-mediated cholesterol efflux by eliciting inflammation, the generation of reactive oxygen species and endoplasmatic reticulum (ER) stress. The glycation level of human serum albumin (HSA) from type 1 and type 2 diabetic patients was determined by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and related to possible impairment of ER function and cellular cholesterol efflux. Comparison of the MALDI spectra from healthy and diabetic subjects allowed us to determine an increased HSA mean mass of 1297 Da for type 1 and 890 Da for type 2. These values reflect a mean condensation of at least 8 glucose units and 5 glucose units, respectively. Mouse peritoneal macrophages were treated with HSA from control, type 1 and type 2 diabetic subjects in order to measure the expression of Grp78, Grp94, protein disulfide isomerase (PDI), calreticulin (CRT), and ABCA-1. C-14-cholesterol overloaded-J774 macrophages were treated with HSA from control and diabetic subjects and further incubated with apo A-1 to determine the cholesterol efflux. Combined analyses comprising HSA from type 1 and type 2 diabetic patients were performed in cellular functional assays. In macrophages, PDI expression increased 89% and CRT 3.4 times in comparison to HSA from the control subjects. ABCA-1 protein level and apo A-I-mediated cholesterol efflux were, respectively, 50% and 60% reduced in macrophages exposed to HSA from type 1 and type 2 diabetic patients when compared to that exposed to HSA from control subjects. We provide evidence that the level of glycation that occurs in albumin in vivo damages the ER function related to the impairment in macrophage reverse cholesterol transport, and so contributes to atherosclerosis in diabetes.
- RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND BODY COMPOSITION IN ELDERLY(2018) ALONSO, Angelica Castilho; GONCALVES, Tuane Andreatta; ALMEIDA, Jenifer Kristina Alves de; MACHADO-LIMA, Adriana; ERNANDES, Rita de Cassia; GREVE, Julia Maria D'Andrea; GARCEZ-LEME, Luiz EugenioObjective: 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/m(2)). 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).
- Brazilian psychiatric brain bank: a new contribution tool to network studies(2012) OLIVEIRA, K. C. de; NERY, F. G.; FERRETI, R. E. L.; LIMA, M. C.; CAPPI, C.; MACHADO-LIMA, A.; POLICHISO, L.; CARREIRA, L. L.; AVILA, C.; ALHO, A. T. D. L.; BRENTANI, H. P.; MIGUEL, E. C.; HEINSEN, H.; JACOB-FILHO, W.; PASQUALUCCI, C. A.; LAFER, B.; GRINBERG, L. T.There is an urgent need for expanding the number of brain banks serving psychiatric research. We describe here the Psychiatric Disorders arm of the Brain Bank of the Brazilian Aging Brain Study Group (Psy-BBBABSG), which is focused in bipolar disorder (BD) and obsessive compulsive disorder (OCD). Our protocol was designed to minimize limitations faced by previous initiatives, and to enable design-based neurostereological analyses. The Psy-BBBABSG first milestone is the collection of 10 brains each of BD and OCD patients, and matched controls. The brains are sourced from a population-based autopsy service. The clinical and psychiatric assessments were done by an expert team including psychiatrists, through an informant. One hemisphere was perfused-fixed to render an optimal fixation for conducting neurostereological studies. The other hemisphere was comprehensively dissected and frozen for molecular studies. In 20 months, we collected 36 brains. A final report was completed for 14 cases: 3 BDs, 4 major depressive disorders, 1 substance use disorder, 1 mood disorder NOS, 3 obsessive compulsive spectrum symptoms, 1 OCD and 1 schizophrenia. The majority were male (64%), and the average age at death was 67.2 +/- 9.0 years. The average postmortem interval was 16 h. Three matched controls were collected. The pilot stage confirmed that the protocols are well fitted to reach our goals. Our unique autopsy source makes possible to collect a fairly number of high quality cases in a short time. Such a collection offers an additional to the international research community to advance the understanding on neuropsychiatric diseases.
- N-acetylcysteine prevents endoplasmic reticulum stress elicited in macrophages by serum albumin drawn from chronic kidney disease rats and selectively affects lipid transporters, ABCA-1 and ABCG-1(2014) MACHADO, Juliana T.; IBORRA, Rodrigo T.; FUSCO, Fernanda B.; CASTILHO, Gabriela; PINTO, Raphael S.; MACHADO-LIMA, Adriana; NAKANDAKARE, Edna R.; SEGURO, Antonio C.; SHIMIZU, Maria H.; CATANOZI, Sergio; PASSARELLI, MarisaIn chronic kidney disease (CKD) nontraditional risk factors, such as oxidative stress and advanced glycation end products (AGE) contribute to cardiovascular disease. Particularly, disturbances in reverse cholesterol transport favor the development of atherosclerosis. We analyzed the influence of N-acetylcysteine (NAC) in CKD rats on plasma concentration of lipid peroxides (TBARS) and AGE and on the impact of serum albumin in the development of macrophage endoplasmic reticulum stress (ERS) and cholesterol efflux, namely apo A-I and HDL2-mediated cholesterol removal and ABCA-1 and ABCG-1 protein level. CKD was induced by 5/6 nephrectomy in 2-month old male Wistar rats. Controls (Sham) were false operated. Animals were treated or not with NAC (600 mg/L of water). After 60 days serum albumin was isolated by FPLC and purified by alcoholic extraction. J774 macrophages were incubated with serum albumin (1 mg/mL; 18 h) from all groups, and the expression of ERS markers (protein disulfide isomerase - PDI, Grp78 and Grp94), ABCA-1 and ABCG-1 determined by immunoblot. HDL2 or apo A-I were used for cholesterol efflux assays. Protein and lipid composition of total HDL from Sham and CKD was determined and these particles tested on their abilities to accept cell cholesterol. Comparisons were done by one-way ANOVA and Newman Keuls post test. After 60 days of CKD, body weight was 10% lower in CKD compared to Sham (p < 0.01). This was prevented by NAC. Urea, creatinine, total cholesterol (TC), triglycerides (TG) (mg/dL), proteinuria (mg/24 h) (Sham, n = 31; Sham + NAC, n = 20; CKD, n = 74; CKD + NAC, n = 32), total AGE and pentosidine (n = 8; fluorescence arbitrary unit) and TBARS (n = 7; nmoL/mL) were higher in CKD (122 +/- 8; 0.9 +/- 0.07; 151 +/- 6; 83 +/- 4; 46 +/- 2.5; 32,620 +/- 673; 16,700 +/- 1,370; 6.6 +/- 0.5, respectively) and in CKD + NAC (91.4 +/- 5; 0.6 +/- 0.02; 126 +/- 7.5; 73 +/- 6; 51 +/- 3.5; 24,720 +/- 1,114; 10,080 +/- 748; 4.5 +/- 0.5, respectively) in comparison to Sham (41 +/- 0.9; 0.4 +/- 0.03; 76 +/- 2.7; 51.5 +/- 3; 14 +/- 0.9; 21,750 +/- 960; 5,314 +/- 129; 2.0 +/- 0.2, respectively; p < 0.001) and Sham + NAC (40 +/- 0.9; 0.3 +/- 0.02; 76 +/- 2.6; 68 +/- 4; 18.4 +/- 1.5; 20,040 +/- 700; 5,050 +/- 267; 1.8 +/- 0.2, respectively; p < 0.001). TC, urea, creatinine, total AGE, pentosidine and TBARS were respectively, 17%, 25%, 33%, 24%, 40% and 28% (p < 0.01) lower in CKD + NAC, than in CKD. Glycemia was higher in Sham + NAC (107 +/- 4.6) and CKD + NAC (107 +/- 2.6) than in Sham (96 +/- 1.8; p < 0.05) and CKD (98 +/- 1.6; p < 0.01), respectively. In macrophages (n = 6), CKD albumin increased PDI (3 and 6 times, p < 0.01) and Grp94 (66% and 80%, p < 0.01) in comparison to Sham and CKD + NAC-albumin treated cells, respectively. ABCA-1 expression was lower (87% and 70%, p < 0.001) in macrophage treated with Sham + NAC and CKD albumin respectively in comparison to Sham albumin; ABCG-1 was higher (4 and 7 times, p < 0.001) in macrophages treated with Sham + NAC and CKD + NAC albumin, respectively in comparison to Sham and CKD albumin. Apo A-I mediated cholesterol efflux was lower (59% and 70%, p < 0.0001) in macrophage treated with Sham + NAC and CKD albumin respectively in comparison to Sham albumin, however, the HDL2 mediated cholesterol efflux was higher (54% and 25%, p < 0. 0001) in macrophage treated with Sham + NAC albumin, in comparison to Sham and CKD + NAC albumin, respectively. CKD-HDL was enriched in total protein and lipids compared to Sham-HDL but preserved its capacity to remove cholesterol from macrophages. NAC reduces plasma lipid peroxidation and AGE and abrogates ERS induced by CKD-albumin. Despite diminishing ABCA-1, NAC increases ABCG-1 that counteracts the reduction in apo A-I-mediated cholesterol efflux. NAC may contribute to attenuate the deleterious effects of CKD-albumin on lipid accumulation in macrophages helping to prevent atherogenesis in CKD.