Hyperlipidemias: Faludi AA

Sposito AC, Caramelli B, Fonseca FA, Bertolami MC, Afiune Neto A, Souza AD, Lottenberg AM, Chacra AP, Faludi AA, Loures-Vale AA, Carvalho AC, Duncan B, Gelonese B, Polanczyk C, Rodrigues Sobrinho CR, Scherr C, Karla C, Armaganijan D, Moriguchi E, Saraiva F, Pichetti G, Xavier HT, Chaves H, Borges JL, Diament J, Guimarães JI, Nicolau JC, dos Santos JE, de Lima JJ, Vieira JL, Novazzi JP, Faria Neto JR, Torres KP, Pinto Lde A, Bricarello L, Bodanese LC, Introcaso L, Malachias MV, Izar MC, Magalhães ME, Schmidt MI, Scartezini M, Nobre M, Foppa M, Forti NA, Berwanger O, Gebara OC, Coelho OR, Maranhão RC, dos Santos RD, Costa RP, Barreto S, Kaiser S, Ihara S, Carvalho T, Martinez TL, Relvas WG, Salgado W, Anonymous00455. · No affiliation provided · Arq Bras Cardiol. · Pubmed #17515982 links to  free full text

This publication has no abstract.

Faludi AA, Aldrighi JM, Bertolami MC, Saleh MH, Silva RA, Nakamura Y, Pereira IR, Abdalla DS, Ramires JA, Sousa JE. · Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. · Atherosclerosis. · Pubmed #15488870 No free full text.

Abstract: This double blind randomized placebo controlled study assessed the effects of atorvastatin, estradiol and norethisterone, isolated and in combination, on the lipid profile and on vascular reactivity, in post-menopausal women with hypercholesterolemia and arterial hypertension. Ninety-four women aged 50-65 were selected. All have received dietary counseling (4 weeks), placebo (4 weeks), and drug therapy (12 weeks): 17-beta estradiol 2mg/day (E) (n=17); E + norethisterone acetate 1mg/day (P) (n=18); Atorvastatin 10mg/day (A) (n=20); E + A (n=21) and E + P + A (n=18). All treatment modalities have significantly reduced total cholesterol (TC) (E=8.8%, E + P=10.1%, A=27.9%, A + E=29.4% and E + P + A=35.7%) and LDL-cholesterol (LDL-c) levels (E + P + A=46.6%, E + A=45.9%, A=40.2%, E=20.3%, and E + P=12.1%). As concerns HDL-cholesterol (HDL-c), Groups E and E + A had increases of 15.5% and 13.1%, respectively. The addition of a progesterone compound reduced its concentration (Group E + P=-9.1%, and Group E + P + A=-9.5%). By random, approximately half of the patients in each group were designated to the endothelial function evaluation (brachial artery ultrasound). We observed that in Group A (n=10), in Group E (n=10) and with the association (Group E + A) (n=7), there was a significant increase in the flow-mediated vasodilatation as compared to basal measurements. The addition of a progestin has annulled these benefits. CONCLUSIONS: Atorvastatin has promoted more beneficial effects on TC and LDL-c, whereas estradiol was responsible for an increase in HDL-c. The addition of a progesterone derivative abolished these benefits. Atorvastatin, estradiol or both together improved endothelial function, an effect suppressed by the addition of norethisterone.

Pereira EC, Bertolami MC, Faludi AA, Salem M, Bersch D, Abdalla DS. · Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prates, 580, Cidade Universitária-Butantã, 05508-900 São Paulo, Brazil. · Free Radic Res. · Pubmed #12797474 No free full text.

Abstract: Hypercholesterolemia is linked to endothelial dysfunction and enhancement of the endogenous inhibitor of NO synthase. The statins have lipid-lowering and pleiotropic properties, which could exert protective effects on the endothelium in hypercholesterolemia. The association of L-arginine with simvastatin could promote a further improvement on endothelial function in this condition. Thus, we investigated whether simvastatin, with or without supplementation with L-arginine, could improve endothelium-dependent vasodilation. In this study, 25 hypercholesterolemic subjects were treated according to the following protocol: washout period of 1 month; simvastatin (20 mg/day) for 2 months; simvastatin (20 mg/day) + L-arginine (7 g/day) for 2 months. From these patients, 10 were chosen at random for evaluation of vascular function by high resolution ultrasonography of the brachial artery. In subjects treated with simvastatin plus L-arginine, an increase of L-arginine levels (68%) and L-arginine/asymmetric dimethylarginine (ADMA) ratio (67%) were observed. Simvastatin reduced the plasma concentrations of NO metabolites nitrite + nitrate (NOx: 34%), S-nitrosothiols (RSNO: 42%), total cholesterol (25%), low density lipoprotein (LDL)-cholesterol (36%) and the LDL-cholesterol/high density lipoprotein (HDL-cholesterol ratio (34%). Simvastatin, associated or not to L-arginine, did not affect ADMA levels and endothelium-dependent vasodilation. Our data showed that simvastatin reduced the plasma concentrations of NOx and RSNO without affecting either the levels of ADMA or endothelium-dependent vasodilation in hypercholesterolemia.

Bertolami MC, Faludi AA, Batlouni M. · Instituto Dante Pazzanese de Cardiologia de São Paulo, Brazil. · Eur J Clin Nutr. · Pubmed #10099941 No free full text.

Abstract: OBJECTIVE: To verify the effects on the lipid profile of a product of fermented milk (Gaio) in patients with mild to moderate primary hypercholesterolemia. DESIGN: The study was prospective, randomized, double-blinded and placebo controlled, with a crossover design. SUBJECTS: Thirty-two patients (21 women and 11 men) with ages ranging between 36 and 65 years old were included in the study. All of them were on a controlled diet for at least 8 weeks. INTERVENTION: Patients began, after clinical and laboratory analysis, in a randomized and double-blind manner to take 200 g daily of Gaio or its placebo. After 8 weeks blood was collected again for lipid profile evaluation and the crossover was made. After an additional 8 weeks blood was collected for another lipid profile determination. RESULTS: All patients included completed the study. Comparisons were made between means of lipid profile constituents after the placebo and active product periods. These showed significant mean reduction of 5.3% (P = 0.004) for total cholesterol, 6.15% (P = 0.012) for LDL-cholesterol and no significant variation for HDL-cholesterol and triglycerides. The majority of patients presented no variation or had a decrease in their total cholesterol level. However, during the active product period, three patients showed an increase in cholesterol level by more than 5%. CONCLUSION: The fermented milk (Gaio) produced a small but statistically significant decrease in total and LDL-cholesterol mean. However, not all subjects seem to respond to the product, and a few subjects showed a cholesterol increment. Further investigations are necessary to clarify this aspect.

Willrich MA, Hirata MH, Genvigir FD, Arazi SS, Rebecchi IM, Rodrigues AC, Bernik MM, Dorea EL, Bertolami MC, Faludi AA, Hirata RD. · Department Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil. · Clin Chim Acta. · Pubmed #18727922 No free full text.

Abstract: BACKGROUND: The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on biotransformation of xenobiotics. CYP3A5 SNPs have been associated with variations on enzyme activity that can modify the metabolism of several drugs. METHODS: In order to evaluate the influence of CYP3A5 variants on response to lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were selected. After a wash-out period of 4 weeks, individuals were treated with atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA sequencing. RESULTS: >Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non-Africans (*3C: 84.9% and *1D 84.8%, p<0.01). Non-Africans carrying *3A allele (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to atorvastatin than non-*3A allele carriers (p<0.05). CONCLUSION: CYP3A5*3A allele is associated with reduced cholesterol-lowering response to atorvastatin in non-African individuals.

Pereira IR, Faludi AA, Aldrighi JM, Bertolami MC, Saleh MH, Silva RA, Nakamura Y, Campos MF, Novaes N, Abdalla DS. · School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. · Menopause. · Pubmed #17019381 No free full text.

Abstract: OBJECTIVE: To evaluate the effects of soy germ isoflavones and hormone therapy on vascular reactivity, the formation of nitric oxide derivatives, and lipid peroxidation in hypercholesterolemic postmenopausal women. DESIGN: Women were treated with soy germ, 17beta-estradiol or 17beta-estradiol + noretisterone acetate for 3 months after taking placebo for 1 month. The plasma concentrations of nitrite + nitrate and S-nitrosothiols were evaluated by gaseous phase chemiluminescence; nitrotyrosine, electronegative low-density lipoprotein, and estradiol levels were determined by enzyme-linked immunosorbent assay; cholesterol oxides and isoflavones were determined by gas chromatography and high-performance liquid chromatography, respectively. Vascular reactivity was analyzed by high-resolution ultrasonography. RESULTS: Soy germ isoflavones and hormone therapy induced a decrease in nitrite + nitrate, electronegative low-density lipoprotein, and cholesterol oxides, as well as an increase in S-nitrosothiols. Soy germ isoflavones lowered electronegative low-density lipoprotein, and cholesterol oxides more efficiently than did hormone therapy. Only soy isoflavones inhibited nitrotyrosine formation. A significant improvement of vascular reactivity was only seen in women treated with 17beta-estradiol. CONCLUSIONS: The soy germ isoflavones and 17beta-estradiol, alone or associated with noretisterone acetate, in the doses and forms used here, have similar effects on the bioavailability of nitric oxide. Soy germ treatment inhibited lipid peroxidation more effectively than hormone therapy.

Rodrigues AC, Rebecchi IM, Bertolami MC, Faludi AA, Hirata MH, Hirata RD. · Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil. · Braz J Med Biol Res. · Pubmed #16138223 links to  free full text

Abstract: The MDR1 gene encodes the P-glycoprotein, an efflux transporter with broad substrate specificity. P-glycoprotein has raised great interest in pharmacogenetics because it transports a variety of structurally divergent drugs, including lipid-lowering drugs. The synonymous single-nucleotide polymorphism C3435T and the nonsynonymous single-nucleotide polymorphism G2677T/A in MDR1 have been indicated as potential determinants of variability in drug disposition and efficacy. In order to evaluate the effect of G2677T/A and C3435T MDR1 polymorphisms on serum levels of lipids before and after atorvastatin administration, 69 unrelated hypercholesterolemic individuals from São Paulo city, Brazil, were selected and treated with 10 mg atorvastatin orally once daily for four weeks. MDR1 polymorphisms were analyzed by PCR-RFLP. C3435T and G2677T polymorphisms were found to be linked. The allelic frequencies for C3435T polymorphism were 0.536 and 0.464 for the 3435C and 3435T alleles, respectively, while for G2677T/A polymorphism allele frequencies were 0.580 for the 2677G allele, 0.384 for the 2677T allele and 0.036 for the 2677A allele. There was no significant relation between atorvastatin response and MDR1 polymorphisms (repeated measures ANOVA; P > 0.05). However, haplotype analysis revealed an association between T/T carriers and higher basal serum total (TC) and LDL cholesterol levels (TC: 303 +/- 56, LDL-C: 216 +/- 57 mg/dl, respectively) compared with non-T/T carriers (TC: 278 +/- 28, LDL-C: 189 +/- 24 mg/dl; repeated measures ANOVA/Tukey test; P < 0.05). These data indicate that MDR1 polymorphism may have an important contribution to the control of basal serum cholesterol levels in Brazilian hypercholesterolemic individuals of European descent.

Pereira EC, Bertolami MC, Faludi AA, Sevanian A, Abdalla DS. · Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil. · Free Radic Biol Med. · Pubmed #15454283 No free full text.

Abstract: Among the pleiotropic effects of statins, their antioxidant action may be involved in their protective effects. Thus, we investigated the antioxidant effect of simvastatin, associated or not with alpha-tocopherol, on levels of electronegative low-density lipoprotein (LDL-), nitrotyrosine, thiols (homocysteine, glutathione, cysteine, methionine), and lipid-soluble antioxidants in blood plasma of hypercholesterolemic subjects. In this study, 25 hypercholesterolemic subjects were treated for 2 months with simvastatin (20 mg/day) and with simvastatin (20 mg/day) + alpha-tocopherol (400 IU/day). Concentrations of thiols were determined by high-performance capillary electrophoresis-laser-induced fluorescene. Lipid-soluble antioxidants were determined by HPLC, and LDL-, and nitrotyrosine by ELISA. Simvastatin, independent of its association with alpha-tocopherol, reduced plasma concentrations of LDL-, nitrotyrosine, total cholesterol, and LDL cholesterol and the LDL cholesterol/HDL cholesterol ratio. Neither simvastatin nor simvastatin plus alpha-tocopherol altered plasma levels of the thiols analyzed. alpha-Tocopherol did not change the antioxidant effect of simvastatin on the levels of LDL- and nitrotyrosine in hypercholesterolemic subjects. The reduction of LDL- and nitrotyrosine by simvastatin seems to be related to the pleiotropic effects of this statin, and it may have an important protective effect against endothelial dysfunction and atherosclerosis.