Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study.

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Peripheral Blood miRome Identified miR-155 as Potential Biomarker of MetS and Cardiometabolic Risk in Obese Patients.

This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients (p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta-CEBPB, KRAS proto-oncogene, GTPase-KRAS and suppressor of cytokine signaling 1-SOCS1) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients (p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.

Effects of short-term add-on ezetimibe to statin treatment on expression of adipokines and inflammatory markers in diabetic and dyslipidemic patients.

AIM: The influence of short-term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and nondiabetic patients with hypercholesterolemia. METHOD: Hypercholesterolemic nondiabetic (HC, n = 37) and diabetic (DM, n = 47) patients were treated with simvastatin (SV, 10 or 20 mg/d/8-wk) and then SV plus ezetimibe (SV + EZ, 10 mg each/d/4 wk). Serum lipids, glycemic profile, and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1, and ICAM-1) were evaluated before and after the add-on ezetimibe therapy. mRNA expression of ADIPOR1, ADIPOR2, RETN, VCAM1, and ICAM1 was measured by real-time PCR in peripheral blood mononuclear cells (PBMC). RESULTS: Serum concentrations of LDL and HDL cholesterol, and adiponectin were higher in HC than DM patients (P < .05). The add-on ezetimibe therapy reduced total and LDL cholesterol, apoB and adiponectin serum levels in HC and DM groups, and resistin in HC subjects (P < .05). DM patients showed higher expression of ADIPOR1, ADIPOR2, RETN, and VCAM1 in PBMC than subjects in HC group, before and after add-on ezetimibe therapy (P < .05). PBMC RETN mRNA expression was reduced by add-on ezetimibe therapy in HC individuals (P < .05), but not in DM subjects. CONCLUSION: Short-term add-on ezetimibe to simvastatin treatment suppressing effects on hypercholesterolemia and adiponectinemia is independent of the diabetes status. Resistin serum levels and leukocyte mRNA expression are influenced by add-on ezetimibe to statin treatment.

Effects of short-term add-on ezetimibe to statin treatment on expression of adipokines and inflammatory markers in diabetic and dyslipidemic patients

AIM: The influence of short-term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and nondiabetic patients with hypercholesterolemia. METHOD: Hypercholesterolemic nondiabetic (HC, n = 37) and diabetic (DM, n = 47) patients were treated with simvastatin (SV, 10 or 20 mg/d/8-wk) and then SV plus ezetimibe (SV + EZ, 10 mg each/d/4 wk). Serum lipids, glycemic profile, and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1, and ICAM-1) were evaluated before and after the add-on ezetimibe therapy. mRNA expression of ADIPOR1, ADIPOR2, RETN, VCAM1, and ICAM1 was measured by real-time PCR in peripheral blood mononuclear cells (PBMC). RESULTS: Serum concentrations of LDL and HDL cholesterol, and adiponectin were higher in HC than DM patients (P < .05). The add-on ezetimibe therapy reduced total and LDL cholesterol, apoB and adiponectin serum levels in HC and DM groups, and resistin in HC subjects (P < .05). DM patients showed higher expression of ADIPOR1, ADIPOR2, RETN, and VCAM1 in PBMC than subjects in HC group, before and after add-on ezetimibe therapy (P < .05). PBMC RETN mRNA expression was reduced by add-on ezetimibe therapy in HC individuals (P < .05), but not in DM subjects...

ADIPOQ and IL6 variants are associated with a pro-inflammatory status in obeses with cardiometabolic dysfunction.

BACKGROUND: Polymorphisms in genes encoding adiponectin (ADIPOQ) and interleukin-6 (IL6) have been associated with adiposity and obese-related phenotypes. This study investigated the relationship of ADIPOQ and IL6 gene polymorphisms with pro-inflammatory and cardiometabolic markers in obese patients. METHODS: Anthropometric and body composition parameters were measured in 249 Brazilian subjects (30 to 68 yr). Metabolic and inflammatory markers and adipokines were analyzed in blood samples. ADIPOQ rs2241766 (45 T > G) and IL6 rs1800795 (-174G > C) polymorphisms were analyzed by real-time PCR and PCR-RFLP, respectively. RESULTS: Type 2 diabetes, hypertension, dyslipidemia and increased values of waist circumference, body fat, leptin, fibrinogen, IL-1ß, hsCRP and TNFα were related to obesity (p < 0.05). Multiple linear regression analysis showed a positive correlation between BMI and waist circumference, body fat, leptin, fibrinogen, PAI-1, IL-1ß, hsCRP and TNFα values (p < 0.001) but not with adiponectin. Obese group had altered metabolic status, resistance to leptin and insulin, and atherogenic and pro-inflammatory profiles. ADIPOQ and IL6 variants were not directely related to obesity, leptin resistance or alterations in cardiometabolic markers. Individuals carrying ADIPOQ 45G allele (TG + GG genotype) had higher IL-6, IL-1ß and TNFα levels than TT genotype carriers (p < 0.05). IL6 -174GG genotype was associated with increased IL-1ß levels (p = 0.033). CONCLUSION: Obesity is associated with leptin resistance, cardiometabolic alterations and a pro-inflammatory status. Our results are suggestive that ADIPOQ and IL6 polymorphisms contribute to cardiometabolic risk in obese individuals.

ADIPOQ and IL6 variants are associated with a pro-inflammatory status in obeses with cardiometabolic dysfunction

Background: Polymorphisms in genes encoding adiponectin (ADIPOQ) and interleukin-6 (IL6) have been associated with adiposity and obese-related phenotypes. This study investigated the relationship of ADIPOQ and IL6 gene polymorphisms with pro-inflammatory and cardiometabolic markers in obese patients. Methods: Anthropometric and body composition parameters were measured in 249 Brazilian subjects (30 to 68 yr). Metabolic and inflammatory markers and adipokines were analyzed in blood samples. ADIPOQ rs2241766 (45 T > G)and IL6 rs1800795 (−174G > C) polymorphisms were analyzed by real-time PCR and PCR-RFLP, respectively. Results: Type 2 diabetes, hypertension, dyslipidemia and increased values of waist circumference, body fat, leptin, fibrinogen, IL-1β, hsCRP and TNFα were related to obesity (p < 0.05). Multiple linear regression analysis showed apositive correlation between BMI and waist circumference, body fat, leptin, fibrinogen, PAI-1, IL-1β, hsCRP and TNFαvalues (p < 0.001) but not with adiponectin. Obese group had altered metabolic status, resistance to leptin andinsulin, and atherogenic and pro-inflammatory profiles. ADIPOQ and IL6 variants were not directely related toobesity, leptin resistance or alterations in cardiometabolic markers. Individuals carrying ADIPOQ 45G allele (TG + GGgenotype) had higher IL-6, IL-1β and TNFα levels than TT genotype carriers (p < 0.05). IL6 -174GG genotype wasassociated with increased IL-1β levels (p = 0.033).Conclusion: Obesity is associated with leptin resistance, cardiometabolic alterations and a pro-inflammatory status.Our results are suggestive that ADIPOQ and IL6 polymorphisms contribute to cardiometabolic risk in obese individuals.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals / Polimorfismos no gene do receptor de leptina são associados com adiposidade e alterações metabólicas em indivíduos brasileiros

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

OBJETIVO: O estudo teve por objetivo investigar a influência de polimorfismos nos genes da leptina (LEP) e do receptor de leptina (LEPR) na adiposidade e em marcadores metabólicos, como leptina, glicose e lipí­deos, em uma amostra de nossa população. SUJEITOS E MÉTODOS: Um grupo de 326 indivíduos com idade de 30 a 80 anos, 87 homens e 239 mulheres, 148 obesos e 178 não obesos, e de etnia branca foi selecionado aleatoriamente em dois hospitais clínicos da cidade de São Paulo, Brasil. Medidas antropométricas, índice de massa corporal (IMC) e gordura corporal foram avaliados. Amostras de sangue foram obtidas para extração de DNA e determinações de leptina, receptor de leptina solúvel, glicose e lipídeos. Os polimorfismos LEP -2548G>A e LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) e Lys656Asn (c.1968G>C) foram detectados por PCR-RFLP. RESULTADOS: Leptina e lipídeos séricos aumentados e LEPR Arg223Arg (genótipo GG) foram associados com maior risco de obesidade (p < 0,05), enquanto foi encontrado risco reduzido de obesidade, em portadores de LEPR Arg109Arg (genótipo GG) (OR: 0,38, 95%CI: 0,19-0,77, p = 0,007). A análise de regressão linear múltipla mostrou relação entre o alelo LEPR 223Arg e circunferência abdominal e leptinemia aumentadas (p < 0,05), enquanto o alelo LEPR 109Arg foi associado com aumento de colesterol total e triglicerídeos (p < 0,05). Os portadores do haplotipo 3 do LEPR (AGG: 109Lys/233Arg/656Lys) tiveram maior risco aumentado para obesidade (OR: 2.56, 95% CI: 1.19-5.49, p = 0,017). Além disso, esse haplótipo foi associado com IMC, circunferência abdominal e leptinemia aumentados (p < 0,05). CONCLUSÕES: Polimorfismos de LEPR são associados com obesidade, hiperleptinemia e perfil lipídico aterogênico sugerindo seu papel potencial para a resistência à leptina e risco cardiovascular.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals.

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

Influence of polymorphisms and cholesterol-lowering treatment on SCARB1 mRNA expression.

AIM: This study evaluated the influence of polymorphisms and cholesterol-lowering treatments on SCARB1 mRNA expression in peripheral blood mononuclear cells and in HepG2 and Caco-2 cells. METHODS: Blood samples were drawn from normolipidemic (NL, n = 166) and hypercholesterolemic (HC, n = 123) individuals to extract DNA and total RNA and to analyze the lipid profile. After a 4-week washout period, 98 HC individuals were treated with atorvastatin (10 mg/day/4 weeks) whereas 25 were treated with ezetimibe (10 mg/day/4 weeks), followed by simvastatin (10 mg/day/8 weeks) and simvastatin plus ezetimibe (10 mg each/day/4 weeks). HepG2 and Caco-2 cells were treated with atorvastatin, simvastatin and ezetimibe at various concentrations for 12 and 24 h and collected for RNA extraction. SCARB1 mRNA expression was measured by TaqMan® assay and SCARB1 c.4G> A, c.726 + 54C> T and c.1080C> T polymorphisms were detected by PCR-RFLP. RESULTS: High LDL cholesterol (> 160 mg/dL) values were associated with low baseline SCARB1 mRNA expression in PBMC. Allele T carriers for SCARB1 c.726+54C> T had lower basal SCARB1 transcription in PBMC (p < 0.05). Simvastatin, atorvastatin and ezetimibe treatments did not modify the SCARB1 mRNA level in PBMC from HC patients. Similarly, these cholesterol-lowering drugs did not modulate the SCARB1 expression in HepG2 and Caco-2 cells in spite of the concentration and time of exposure (p > 0.05). CONCLUSION: LDL cholesterol levels and SCARB1 c.726 + 54C> T are associated with low mRNA expression in mononuclear cells. Cholesterol-lowering drugs do not modulate SCARB1 expression in PBMC from HC subjects or in HepG2 and Caco-2 cells.

Pharmaceutic guidance to hypertensive patients at USP University Hospital: effect on adherence to treatment

This study was carried out in the outpatient unit of the Teaching Hospital of the University of São Paulo (USP), and studied the impact of an educational program aimed at improving hypertensive patients' compliance to treatment. Seventy five (75) hypertensive patients of both sexes took part in the study which had no age or race discrimination. Participants presented no other concomitant pathology, except obesity, diabetes and dyslipidemia. Forty one patients were allocated to an experimental group (EG). Experimental patients attended lectures on the use of medication and artery hypertension (AH) and received personal pharmaceutical guidance for nine months. The control group (CG) comprised 34 patients who did not attend lectures or receive pharmaceutical advice in this period. The results were assessed by means of serum levels of cholesterol and fractions of tryacylglicerol (TG), urine sodium and potassium, arterial pressure (AP), body mass index (BMI), waist-hip ratio (WHR), and also based on responses to a questionnaire focusing on AH and treatment. Patients who received the guidance showed a greater decrease in AP, TG and WHR, besides an increase of potassium excretion through urine. The experimental group also scored higher on the questionnaires compared to the CG. It was concluded that the educational process, applied under the conditions of the present study, improves clients' clinical response to antihypertensive treatment and should be included in therapeutic strategies of health care services dealing with hypertensive patients.

Este trabalho, realizado no ambulatório do Hospital Universitário da USP, estudou a repercussão de um programa educacional visando melhorar a adesão do paciente hipertenso ao tratamento. Participaram do trabalho 75 pacientes de ambos os sexos, sem discriminação de idade ou raça, sem outras patologias concomitantes, exceto obesidade, diabetes e dislipidemia. Quarenta e um pacientes assistiram palestras sobre uso de medicamentos e hipertensão arterial (HA), receberam orientação farmacêutica individualizada durante nove meses e foram denominados grupo experimental (GE); o grupo controle (GC), composto por 34 pacientes não assistiu palestras nem recebeu orientação farmacêutica, neste período. Os resultados foram avaliados por meio de níveis séricos de colesterol e frações, triacil-gliceróis (TG), sódio e potássio urinários, pressão arterial (PA), índice de massa corpórea (IMC), relação cintura/quadril (RCQ), além de respostas a questionário enfocando HA e tratamento. Verificou-se que os pacientes orientados apresentaram maior decréscimo da PA, TG e da RCQ, além de aumento da excreção urinária de potássio e do percentual de acertos em questionários, em relação ao GC. Concluiu-se que o processo educativo, utilizado nas condições deste estudo, melhora a resposta clínica do paciente ao tratamento anti-hipertensivo e deve fazer parte das estratégias terapêuticas de serviços de atendimento a pacientes hipertensos.

ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment.

This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphisms and lowering-cholesterol response. One hundred and thirty-six individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) (p<0.05). After atorvastatin treatment, both ABCB1 and ABCC1 genes showed 50% reduction of the mRNA expression (p<0.05). Reduction of ABCB1 expression was associated with ABCB1 G2677T/A polymorphism (p=0.039). Basal ABCB1 mRNA in the lower quartile (<0.024) was associated with lower reduction rate of serum low-density lipoprotein (LDL) cholesterol (33.4+/-12.4%) and apolipoprotein B (apoB) (17.0+/-31.3%) when compared with the higher quartile (>0.085: LDL-c=40.3+/-14.3%; apoB=32.5+/-10.7%; p<0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversed the effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin.

ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment

This study investigated the effects of atorvastatin on ABCB1 and ABCC1 mRNA expression on peripheral blood mononuclear cells (PBMC) and their relationship with gene polymorphismsand lowering-cholesterol response. One hundred and thirty-six individuals withhypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). Blood samples were collected for serum lipids and apolipoproteins measurements and DNA and RNA extraction. ABCB1 (C3435T and G2677T/A) and ABCC1 (G2012T) gene polymorphisms were identified by polymerase chain reaction-restriction (PCR)-RFLP and mRNA expression was measured in peripheral blood mononuclear cells by singleplex real-time PCR. ABCB1 polymorphisms were associated with risk for coronary artery disease (CAD) ( p 0.085: LDL-c = 40.3 14.3%; apoB = 32.5 10.7%; p < 0.05). ABCB1 substrates or inhibitors did not affect the baseline expression, while ABCB1 inhibitors reversedthe effects of atorvastatin on both ABCB1 and ABCC1 transporters. In conclusion, ABCB1 and ABCC1 mRNA levels in PBMC are modulated by atorvastatin and ABCB1 G2677T/A polymorphism and ABCB1 baseline expression is related to differences in serum LDL cholesterol and apoB in response to atorvastatin.

Changes in plasma free fatty acid levels in septic patients are associated with cardiac damage and reduction in heart rate variability.

Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. Thirty-one patients with sepsis were included. The patients were divided into two groups: survivors(n = 12) and nonsurvivors (n = 19). The following associations were investigated: (a) troponin I elevation and HRV reduction and (b) clinical evolution and HRV index, plasma troponin, and plasma FFA levels. Initial measurements of C-reactive protein and gravity Acute Physiology and Chronic Health Evaluation scores were similar in both groups. Overall, an increase in plasma troponin level was related to increased mortality risk. From the first day of study, the nonsurvivor group presented a reduced left ventricular stroke work systolic index and a reduced low frequency (LF) that is one of HRV indexes. The correlation coefficient for LF values and troponin was r(2) = 0.75 (P < 0.05). All patients presented elevated plasma FFA levels on the first day of the study (5.11 +/- 0.53 mg/mL), and this elevation was even greater in the nonsurvivor group compared with the survivors (6.88 +/- 0.13 vs. 3.85 +/- 0.48 mg/mL, respectively; P < 0.05). Cardiac damage was confirmed by measurement of plasma troponin I and histological analysis. Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.

Efeitos da intervenção fisioterapêutica nas respostas sensoriais e funcionais de diabéticos neuropatas / Effects of a physical treatment in sensory and functional responses of neuropathic diabetic patients

O objetivo foi elaborar e aplicar um tratamento fisioterapêutico para diabéticos neuropatas e comparar suas respostas sensoriais, motoras e funcionais pré e pós-intervenção, com um grupo de sujeitos não diabéticos assintomáticos...

The purpose of this study was to elaborate an apply a physical therapy treatment for diabetic neuropathic patients, comparing the sensorial, motor an functional responses before and after treatment to those of a healthy control group. Ten healthy subjetcs (CG) and 10 neuropathic diabetes patients...