FERNANDA MARCIANO CONSOLIM COLOMBO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
17 resultados
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conferenceObject Improvement of the Adipokines Profile and Insulin Resistance in Metabolic Syndrome Patients Induced by Galantamine Activation of Cholinergic Pathway(2016) SANGALETI, Carine Teles; COSTA, Fernando Oliveira; MORAES, Tercio Lemos; IRIGOYEN, Maria Claudia; BORTOLOTTO, Luiz Aparecido Teles; LOPES, Heno Ferreira; PAVLOV, Valentin; TRACEY, Kevin; CONSOLIM-COLOMBO, Fernanda Marciano- Acute physical and mental stress resulted in an increase in fatty acids, norepinephrine, and hemodynamic changes in normal individuals: A possible pathophysiological mechanism for hypertension-Pilot study(2021) MOTTA, Jasiane Motta e; SOUZA, Ludmila Neves; VIEIRA, Bianca Bassetto; DELLE, Humberto; CONSOLIM-COLOMBO, Fernanda Marciano; EGAN, Brent M.; LOPES, Heno FerreiraHypertension is often associated with metabolic changes. The sustained increase in sympathetic activity is related to increased blood pressure and metabolic changes. Environmental stimuli may be related to increased sympathetic activity, blood pressure, and metabolic changes, especially in genetically predisposed individuals. The aim of this study was to evaluate the response of fatty acids to physical and mental stress in healthy volunteers and the hemodynamic, hormonal, and metabolic implications of these stimuli. Fifteen healthy individuals with a mean age of 31 +/- 7 years, of both sexes, were evaluated. They were assessed at baseline and after combined physical and mental stress (isometric exercise test, Stroop color test). Blood samples were collected at baseline and after stimulation for glucose, insulin, fatty acid, and catecholamine levels. Blood pressure, heart rate, cardiac output, systemic vascular resistance, and distensibility of the large and small arteries were analyzed. The data obtained at baseline and after stimuli were from the same individual, being the control itself. Compared to baseline, after physical and mental stress there was a statistically significant increase (p < .05) in free fatty acids, norepinephrine, diastolic blood pressure, peripheral vascular resistance, and distensibility of the large and small arteries. In conclusion, the combination of physical and mental stress raised fatty acids, norepinephrine, diastolic blood pressure, and peripheral vascular resistance in healthy individuals.
- The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial(2021) SANGALETI, Carine Teles; KATAYAMA, Keyla Yukari; ANGELIS, Katia De; MORAES, Tercio Lemos de; ARAUJO, Amanda Aparecida; LOPES, Heno F.; CAMACHO, Cleber; BORTOLOTTO, Luiz Aparecido; MICHELINI, Lisete Compagno; IRIGOYEN, Maria Claudia; OLOFSSON, Peder S.; BARNABY, Douglas P.; TRACEY, Kevin J.; PAVLOV, Valentin A.; COLOMBO, Fernanda Marciano ConsolimBackground: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 mu mol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.
- Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial(2016) FUCHS, Sandra Costa; POLI-DE-FIGUEIREDO, Carlos E.; FIGUEIREDO NETO, Jose A.; SCALA, Luiz Cesar N.; WHELTON, Paul K.; MOSELE, Francisca; MELLO, Renato Bandeira de; VILELA-MARTIN, Jose F.; MOREIRA, Leila B.; CHAVES, Hilton; GOMES, Marco Mota; SOUSA, Marcos R. de; SILVA, Ricardo Pereira e; CASTRO, Iran; CESARINO, Evandro Jose; JARDIM, Paulo Cesar; ALVES, Joao Guilherme; STEFFENS, Andre Avelino; BRANDAO, Andrea Araujo; CONSOLIM-COLOMBO, Fernanda M.; ALENCASTRO, Paulo Ricardo de; NETO, Abrahao Afiune; NOBREGA, Antonio C.; FRANCO, Roberto Silva; SOBRAL FILHO, Dario C.; BORDIGNON, Alexandro; NOBRE, Fernando; SCHLATTER, Rosane; GUS, Miguel; FUCHS, Felipe C.; BERWANGER, Otavio; FUCHS, Flavio D.Background-Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. Methods and Results-This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm(P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). Conclusions-A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension.
- Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial(2017) CONSOLIM-COLOMBO, Fernanda M.; SANGALETI, Carine T.; COSTA, Fernando O.; MORAIS, Tercio L.; LOPES, Heno F.; MOTTA, Josiane M.; IRIGOYEN, Maria C.; BORTOLOTO, Luiz A.; ROCHITTE, Carlos Eduardo; HARRIS, Yael Tobi; SATAPATHY, Sanjaya K.; OLOFSSON, Peder S.; AKERMAN, Meredith; CHAVAN, Sangeeta S.; MACKAY, Meggan; BARNABY, Douglas P.; LESSER, Martin L.; ROTH, Jesse; TRACEY, Kevin J.; PAVLOV, Valentin A.BACKGROUND. Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. METHODS. In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). RESULTS. Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 mu g/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. CONCLUSION. Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy.
- The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome(2021) CHOQUE, Pamela Nithzi Bricher; VIEIRA, Rodolfo P.; ULLOA, Luis; GRABULOSA, Caren; IRIGOYEN, Maria Claudia; ANGELIS, Katia De; OLIVEIRA, Ana Paula Ligeiro De; TRACEY, Kevin J.; PAVLOV, Valentin A.; CONSOLIM-COLOMBO, Fernanda MarcianoAcute respiratory distress syndrome (ARDS) is a critical illness complication that is associated with high mortality. ARDS is documented in severe cases of COVID-19. No effective pharmacological treatments for ARDS are currently available. Dysfunctional immune responses and pulmonary and systemic inflammation are characteristic features of ARDS pathogenesis. Recent advances in our understanding of the regulation of inflammation point to an important role of the vagus-nerve-mediated inflammatory reflex and neural cholinergic signaling. We examined whether pharmacological cholinergic activation using a clinically approved (for myasthenia gravis) cholinergic drug, the acetylcholinesterase inhibitor pyridostigmine alters pulmonary and systemic inflammation in mice with lipopolysaccharide (LPS)-induced ARDS. Male C57Bl/6 mice received one intratracheal instillation of LPS or were sham manipulated (control). Both groups were treated with either vehicle or pyridostigmine (1.5 mg/kg twice daily, 3 mg/day) administered by oral gavage starting at 1 h post-LPS and euthanized 24 h after LPS administration. Other groups were either sham manipulated or received LPS for 3 days and were treated with vehicle or pyridostigmine and euthanized at 72 h. Pyridostigmine treatment reduced the increased total number of cells and neutrophils in the bronchoalveolar lavage fluid (BALF) in mice with ARDS at 24 and 72 h. Pyridostigmine also reduced the number of macrophages and lymphocytes at 72 h. In addition, pyridostigmine suppressed the levels of TNF, IL-1 beta, IL-6, and IFN-gamma in BALF and plasma at 24 and 72 h. However, this cholinergic agent did not significantly altered BALF and plasma levels of the anti-inflammatory cytokine IL-10. Neither LPS nor pyridostigmine affected BALF IFN-gamma and IL-10 levels at 24 h post-LPS. In conclusion, treatments with the cholinergic agent pyridostigmine ameliorate pulmonary and systemic inflammatory responses in mice with endotoxin-induced ARDS. Considering that pyridostigmine is a clinically approved drug, these findings are of substantial interest for implementing pyridostigmine in therapeutic strategies for ARDS.
- Sympathetic Neural Overdrive, Aortic Stiffening, Endothelial Dysfunction, and Impaired Exercise Capacity in Severe COVID-19 Survivors: A Mid-Term Study of Cardiovascular Sequelae(2023) FARIA, Diego; MOLL-BERNARDES, Renata J.; TESTA, Laura; MONIZ, Camila M. V.; RODRIGUES, Erika C.; RODRIGUES, Amanda G.; ARAUJO, Amanda; ALVES, Maria J. N. N.; ONO, Bruna E.; IZAIAS, Joao E.; SALEMI, Vera M. C.; JORDAO, Camila P.; AMARO-VICENTE, Graziela; RONDON, Maria U. P. B.; LUDWIG, Katelyn R.; CRAIGHEAD, Daniel H.; ROSSMAN, Matthew J.; CONSOLIM-COLOMBO, Fernanda M.; ANGELIS, Katia De; IRIGOYEN, Maria C. C.; SEALS, Douglas R.; NEGRAO, Carlos E.; SALES, Allan R. K.Background:COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress. Methods:Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured similar to 3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. Results:Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e ' ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors. Conclusions:Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.
- Abnormalities of Anthropometric, Hemodynamic, and Autonomic Variables in Offspring of Hypertensive Parents(2016) MOTTA, Josiane M.; LEMOS, Tercio M.; CONSOLIM-COLOMBO, Fernanda M.; MOYSES, Rosa M. A.; GUSMAO, Marcelo A. N.; EGAN, Brent M.; LOPES, Heno F.Young adult offspring of hypertensive parents (pHTN circle plus) are a good model for assessing abnormalities of anthropometric, cardiometabolic, and autonomic variables prior to clinical hypertension. The objectives of this study were to determine whether these variables and autonomic responses to oral carbohydrates were altered in offspring of pHTN circle plus. Two hundred consecutive patients, including 100 pHTN circle plus, were evaluated, with 29 patients, including 14 pHTN circle plus, given a 70-gram carbohydrate load. The pHTN circle plus group had higher blood pressure, pulse pressure, abdominal circumference (AC), weight, body mass index, and basal metabolic rate than offspring of normotensive parents (pHTN empty set). At baseline, the low-frequency (LF, sympathetic) to high-frequency (HF, parasympathetic) ratio, assessed by spectral analysis of heart rate variability, was similar in both groups. After the carbohydrate load, the LF/HF ratio was greater in offspring of pHTN circle plus. pHTN circle plus individuals have abnormalities of anthropometric and hemodynamic variables at baseline and autonomic responses to oral carbohydrates before developing hypertension.
- Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial (vol 58, pg 215, 2021)(2021) FUCHS, Flavio D.; SCALA, Luiz C. N.; VILELA-MARTIN, Jose F.; WHELTON, Paul K.; POLI-DE-FIGUEIREDO, Carlos E.; SILVA, Ricardo; GUS, Miguel; BORTOLOTTO, Luiz A.; CONSOLIM-COLOMBO, Fernanda M.; SCHLATTER, Rosane P.; CESARINO, Jose E.; CASTRO, Iran; FIGUEIREDO NETO, Jose A.; CHAVES, Hilton; STEFFENS, Andre A.; ALVES, Joao G.; BRANDAO, Andrea A.; SOUSA, Marcos R. de; JARDIM, Paulo C.; MOREIRA, Leila B.; FRANCO, Roberto S.; GOMES, Marco M.; AFIUNE NETO, Abrahao; FUCHS, Felipe C.; SOBRAL FILHO, Dario C.; NOBREGA, Antonio C.; NOBRE, Fernando; BERWANGER, Otavio; FUCHS, Sandra C.
- Hypertensive heart disease: Benefit of carvedilol in hemodynamic, left ventricular remodeling, and survival(2019) DOMINGUEZ, Renata F.; COSTA-HONG, Valeria A. da; FERRETTI, Luan; FERNANDES, Fabio; BORTOLOTTO, Luiz A.; CONSOLIM-COLOMBO, Fernanda M.; EGAN, Brent M.; LOPES, Heno F.Objectives: The aim of this study was to determine if carvedilol improved structural and functional changes in the left ventricle and reduced mortality in patients with hypertensive heart disease. Methods: Blood pressure, heart rate, echocardiographic parameters, and laboratory variables, were assessed pre and post treatment with carvedilol in 98 eligible patients. Results: Carvedilol at a median dose of 50 mg/day during the treatment period in hypertensive heart disease lowered blood pressure 10/10 mmHg, heart rate 10 beats/min, improved left ventricular ejection fraction from baseline to follow-up (median: 6 years) (36%-47%)) and reduced left ventricular end-diastolic and end-systolic dimensions (62 vs 56 mm; 53 vs 42 mm, respectively, all p-values <0.01). Left ventricular ejection fraction increased in 69% of patients. Patients who did not have improved left ventricular ejection fraction had nearly six-fold higher mortality than those that improved (relative risk; 5.7, 95% confidence interval: 1.3-25, p = 0.022). Conclusion: Carvedilol reduced cardiac dimensions and improved left ventricular ejection fraction and cardiac remodeling in patients with hypertensive heart disease. These treatment-related changes had a favorable effect on survival.