GILBERT ALEXANDRE SIGAL

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico

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  • article 1 Citação(ões) na Scopus
  • bookPart
    HDL e endotélio
    (2016) MARANHãO, Raul Cavalcante; CASELA FILHO, Antonio; SIGAL, Gilbert Alexandre; CHAGAS, Antonio Carlos Palandri; LUZ, Protásio Lemos da
  • article 22 Citação(ões) na Scopus
    Effects of Short-Term Hypothyroidism on the Lipid Transfer to High-Density Lipoprotein and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer
    (2019) SIGAL, Gilbert A.; TAVONI, Thauany M.; SILVA, Bruna M. O.; KALIL FILHO, Roberto; BRANDAO, Lenine G.; MARANHAO, Raul C.
    Background: Elevation of low-density lipoprotein (LDL) cholesterol is the hallmark of the dyslipidemia observed in hypothyroidism, but alterations on high-density lipoprotein (HDL) plasma levels and metabolism are less understood. The aim of this study was to explore aspects of HDL metabolism and enzymes that act on HDL after a short period of overt hypothyroidism. Methods: Eighteen women (age 44 +/- 11 years; body mass index 27.9 +/- 5.2 kg/m(2)) were studied before total thyroidectomy for thyroid cancer, when they were euthyroid, and after thyroidectomy, in overt hypothyroidism for three weeks, following levothyroxine withdrawal for performance of a whole-body scan. Results: Thyrotropin and free thyroxine confirmed hypothyroidism; low thyroglobulin and radioiodine uptake indicated near absence of thyroid tissue. LDL cholesterol (125 +/- 35 vs. 167 +/- 40 mg/dL; p = 0.0002), HDL cholesterol (HDL-C; 39 +/- 8 vs. 46 +/- 10 mg/dL; p = 0.0025), non-HDL-C (149 +/- 38 vs. 201 +/- 46 mg/dL; p < 0.0001), unesterified cholesterol (53 +/- 10 vs. 70 +/- 16 mg/dL; p = 0.0003), apolipoprotein (apo) A-I (1.32 +/- 0.19 vs. 1.44 +/- 0.22 g/L; p < 0.04), and apo B (0.97 +/- 0.25 vs. 1.31 +/- 0.28 g/L; p < 0.0001) plasma concentrations were all higher in hypothyroidism compared to values in the euthyroid state, but triglycerides and Lp(a) were unchanged. There were no changes in HDL particle size and lipid composition, cholesteryl ester transfer protein and lecithin cholesterol acyltransferase concentrations and in paraoxonase-1 activity. Regarding the in vitro assay to estimate lipid transfer to HDL, there were no changes when comparing the euthyroid to the hypothyroid state, but when adjusted for HDL-C, the unesterified cholesterol (0.14 +/- 0.03 vs. 0.11 +/- 0.02; p < 0.0001), triglycerides (0.11 +/- 0.02 vs. 0.09 +/- 0.02; p < 0.0001), phospholipids (0.44 +/- 0.09 vs. 0.40 +/- 0.07; p = 0.0205), and esterified cholesterol (0.14 +/- 0.03 vs. 0.13 +/- 0.03; p = 0.0043) transfer to HDL were all diminished in hypothyroidism. Conclusions: In short-term hypothyroidism, HDL-C increased, but this did not increase the capacity of the HDL fraction to receive lipids or the activity of paraoxonase-1, the anti-oxidation enzyme associated to HDL.
  • article 30 Citação(ões) na Scopus
    Lipid Metabolism in Subclinical Hypothyroidism: Plasma Kinetics of Triglyceride-Rich Lipoproteins and Lipid Transfers to High-Density Lipoprotein Before and After Levothyroxine Treatment
    (2011) SIGAL, Gilbert A.; MEDEIROS-NETO, Geraldo; VINAGRE, Juliana C.; DIAMENT, Jayme; MARANHAO, Raul C.
    Background: Subclinical hypothyroidism (SCH) has been associated with atherosclerosis, but the abnormalities in plasma lipids that can contribute to atherogenesis are not prominent. The aim of this study was to test the hypothesis that patients with normocholesterolemic, normotriglyceridemic SCH display abnormalities in plasma lipid metabolism not detected in routine laboratory tests including abnormalities in the intravascular metabolism of triglyceride-rich lipoproteins, lipid transfers to high-density lipoprotein (HDL), and paraoxonase 1 activity. The impact of levothyroxine (LT4) treatment and euthyroidism in these parameters was also tested. Methods: The study included 12 SCH women and 10 matched controls. Plasma kinetics of an artificial triglyceride-rich emulsion labeled with radioactive triglycerides and cholesteryl esters as well as in vitro transfer of four lipids from an artificial donor nanoemulsion to HDL were determined at baseline in both groups and after 4 months of euthyroidism in the SCH group. Results: Fractional clearance rates of triglycerides (SCH 0.035 +/- 0.016 min(-1), controls 0.029 +/- 0.013 min(-1), p=0.336) and cholesteryl esters (SCH 0.009 +/- 0.007 min(-1), controls 0.009 +/- 0.009 min(-1), p=0.906) were equal in SCH and controls and were unchanged by LT4 treatment and euthyroidism in patients with SCH, suggesting that lipolysis and remnant removal of triglyceride-rich lipoproteins were normal. Transfer of triglycerides to HDL (SCH 3.6 +/- 0.48%, controls 4.7 +/- 0.63%, p=0.001) and phospholipids (SCH 16.2 +/- 3.58%, controls 21.2 +/- 3.32%, p=0.004) was reduced when compared with controls. After LT4 treatment, transfers increased and achieved normal values. Transfer of free and esterified cholesterol to HDL, HDL particle size, and paraoxonase 1 activity were similar to controls and were unchanged by treatment. Conclusions: Although intravascular metabolism of triglyceride-rich lipoproteins was normal, patients with SCH showed abnormalities in HDL metabolism that were reversed by LT4 treatment and achievement of euthyroidism.
  • article 7 Citação(ões) na Scopus
    Subclinical Hyperthyroidism: Status of the Cholesterol Transfers to HDL and Other Parameters Related to Lipoprotein Metabolism in Patients Submitted to Thyroidectomy for Thyroid Cancer
    (2020) SIGAL, Gilbert A.; TAVONI, Thauany M.; SILVA, Bruna M. O.; KHALIL-FILHO, Roberto; BRANDAO, Lenine G.; BARACAT, Edmund C.; MARANHAO, Raul C.
    Purpose: Lipid metabolism has been poorly explored in subclinical hyperthyroidism. The aim was to examine the effects of exogenous subclinical hyperthyroidism in women under levothyroxine treatment upon plasma lipids and aspects of HDL metabolism. Methodology: Ten women were studied in euthyroidism and again in exogenous subclinical hyperthyroidism. Thyroid function tests and plasma lipids were studied. Results: HDL-cholesterol (increased 21.6%, p = 0.0004), unesterified cholesterol (increased 12.3%, p = 0.04) and Lp(a) (increased 33,3%, P = 0.02) plasma concentrations were higher in subclinical hyperthyroidism compared to euthyroidism, but total cholesterol, LDL, non-HDL cholesterol, triglycerides, apo A-I, apo B were unchanged. PON1 activity (decreased 75%, p = 0.0006) was lower in subclinical hyperthyroidism. There were no changes in HDL particle size, CETP and LCAT concentrations. The in vitro assay that estimates the lipid transfers to HDL showed that esterified cholesterol (increased 7.1%, p = 0.03), unesterified cholesterol (increased 7.8%, p = 0.02) and triglycerides (increased 6.8%, p = 0.006) transfers were higher in subclinical hyperthyroidism. There were no changes in phospholipid transfers to HDL in subclinical hyperthyroidism. Conclusions: Several alterations in the plasma lipid metabolism were observed in the subclinical hyperthyroidism state that highlight the importance of this aspect in the follow-up of those patients. The increase in HDL-C and in the transfer of unesterified and esterified cholesterol to HDL, an important anti-atherogenic HDL function are consistently protective for cardiovascular health. The increase in Lp(a) and the decrease in PON-1 activity that are important risk factors were documented here in subclinical hyperthyroidism and these results should be confirmed in larger studies due to great data variation but should not be neglected in the follow-up of those patients.