High serum miR-421 is associated with metabolic dysregulation and inflammation in patients with metabolic syndrome.

To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study.

Association of the c.249G>A variant with clinical outcomes of tacrolimus-based therapy in kidney transplant recipients.

Background: The effects of genetic variants related to the pharmacodynamic mechanisms of immunosuppressive drugs on their therapeutic efficacy and safety have been poorly explored. This study was performed to investigate the influence of the c.249G>A variant on the clinical outcomes of kidney transplant recipients.

ABCC3 Polymorphisms and mRNA Expression Influence the Concentration of a Carboxylic Acid Metabolite in Patients on Clopidogrel and Aspirin Therapy.

Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated.

The relationship of the oleic acid level and ECHDC3 mRNA expression with the extent of coronary lesion.

Background: The fatty acid profile is associated with the risk and progression of several diseases, probably via mechanisms including its influence on gene expression. We previously reported a correlation between ECHDC3 upregulation and the severity of acute coronary syndrome. Here, we assessed the relationship of serum fatty acid profile and ECHDC3 expression with the extent of coronary lesion.

Atorvastatin attenuation of ABCB1 expression is mediated by microRNA miR-491-3p in Caco-2 cells.

Aim: Atorvastatin, a HMG-CoA reductase inhibitor, used in the treatment of hypercholesterolemia, has been previously shown to regulate ABCB1 expression in vivo and in vitro. We hypothesized that the statin could regulate gene expression of ABCB1 transporter via microRNAs.

Methods: Expression of microRNAs and ABCB1 mRNA was examined in atorvastatin-treated and control cells using real-time PCR.

Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients.

Background: Polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment.

Objective: The aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes.

Material And Methods: Brazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g.

Impact of 3'UTR genetic variants in PCSK9 and LDLR genes on plasma lipid traits and response to atorvastatin in Brazilian subjects: a pilot study.

Background: Hypercholesterolemia is a complex trait, resulting from a genetic interaction with lifestyle habits. Polymorphisms are a major source of genetic heterogeneity, and variations in 2 key cholesterol homeostasis genes; low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type-9 (PCSK9), lead to dyslipidemia. So, we investigated the relation of 2 variants located in the 3'-UTR (3'-untranslated region) of LDLR (rs14158, G>A) and PCSK9 (rs17111557, C>T) with lipid profile and atorvastatin response.

Modulation of adhesion molecules by cholesterol-lowering therapy in mononuclear cells from hypercholesterolemic patients.

Introduction: Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described.

Aims: To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells.

Methods: The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics.

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).

Influence of cardiorespiratory fitness on PPARG mRNA expression using monozygotic twin case control.

The influence of cardiorespiratory fitness (VO2max) on anthropometric variables and PPARG mRNA expression was investigated. Monozygotic twin pairs aged 11-18 years were grouped into discordant (D) and concordant (C) high and low VO2max groups. VO2max was determined by progressive maximal exercise test on treadmill with gas exchange analysis.

Antimicrobial photodynamic effect to treat residual pockets in periodontal patients: a randomized controlled clinical trial.

Aim: A randomized controlled clinical trial was designed to evaluate the efficacy of the photodynamic therapy (PDT) in the treatment of residual pockets of chronic periodontitis patients.

Material And Methods: Thirty-four patients with at least four residual periodontal pockets undergoing maintenance care were included and randomly assigned to test group (PDT, n = 18) or control group (sham procedure, n = 16). The intervention was performed at baseline, 3, 6 and 12 months.

Role of microRNAs 221/222 on statin induced nitric oxide release in human endothelial cells.

Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function.

Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability.

Association of polymorphisms in IL6 gene promoter region with type 1 diabetes and increased albumin-to-creatinine ratio.

Background: Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been considered as key factors in type 1 diabetes mellitus (T1DM) and diabetic nephropathy, thus, our aim was to investigate the association of IL6-174G>C (rs1800795) and -634C>G (rs1800796) polymorphisms with T1DM susceptibility and diabetic nephropathy.

Methods: These polymorphisms were analyzed in 144 children and adolescents with T1DM and 173 normoglycemic control subjects. Glycemic control, laboratory parameters of kidney function and serum lipids were evaluated.

Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ single-nucleotide polymorphisms with lipid and glycemic profiles of patients with Berardinelli-Seip syndrome.

Background/aims: Berardinelli-Seip syndrome (BSS) is a recessive autosomal genetic disorder characterized by the near loss of adipose tissue with disturbance in lipid metabolism.

Methods: Biochemical and hormonal parameters and Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS were analyzed and examined for a possible association with lipid profiles.

Results: Parental consanguinity, insulin resistance and diabetes mellitus were observed in 63.

Occurrence of Mycobacterium bovis and non-tuberculous mycobacteria (NTM) in raw and pasteurized milk in the northwestern region of Paraná, Brazil.

Milk is widely consumed in Brazil and can be the vehicle of agent transmission. In this study, was evaluated the occurrence of Mycobacterium bovis and non-tuberculous mycobacteria (NTM) in raw and pasteurized milk consumed in the northwestern region of Paraná, Brazil. Fifty-two milk samples (20 pasteurized and 32 raw) from dairy farms near the municipality of Maringa, Parana State, Brazil were collected.

Relationship between SLCO1B3 and ABCA3 polymorphisms and imatinib response in chronic myeloid leukemia patients.

Background: Genetic variations in membrane transporters may contribute to imatinib mesylate (IM) resistance in chronic myeloid leukemia (CML). Objective To investigate the relationship between SLCO1B3, SLCO1A2, and ABCA3 polymorphisms and IM response in CML patients.

Methods: Patients in chronic phase CML (N = 118) were studied.

Detection and quantification of periodontal pathogens in smokers and never-smokers with chronic periodontitis by real-time polymerase chain reaction.

Background: The purpose of the present investigation is to compare the presence and number of periodontal pathogens in the subgingival microbiota of smokers versus never-smokers with chronic periodontitis and matched probing depths (PDs) using real-time polymerase chain reaction (RT-PCR).

Methods: Forty current smokers and 40 never-smokers, matched for age, sex, and mean PD of sampling site, were included in this investigation. A full-mouth periodontal examination was performed, and a pooled subgingival plaque sample was collected from the deepest site in each quadrant of each participant.

Influence of PCSK9 polymorphisms on plasma lipids and response to atorvastatin treatment in Brazilian subjects.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has a key role in the regulation of plasma low-density lipoprotein (LDL) cholesterol by enhancing the degradation of LDL receptor. Functional variants in PCSK9 have been associated with differences in plasma lipids and may contribute to the variability of the response to cholesterol-lowering drugs.

Objective: To investigate the influence of PCSK9 variants on plasma lipid profile and response to atorvastatin in Brazilian subjects.

Pharmacogenetics of drug metabolizing enzymes in Brazilian populations.

Phase I and II drug metabolizing enzymes (DMEs) play an important role in biotransformation of endogenous and exogenous compounds including drugs currently used in pharmacoterapy. Moreover, the genetic variability of DMEs causes important interindividual differences in drug and metabolite exposure, drug response, and risk of adverse drug reactions. We reviewed pharmacogenetics/pharmacogenomics (PGx) studies that evaluated the influence of polymorphisms in the CYPs genes - mainly CYP1, CYP2 and CYP3 gene families - and in the phase II genes - TPMT, NAT2, GSTs and UGTs - on therapeutic response in Brazilian cohorts.

Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes.

Aims: To investigate early alterations on bone mineral density (BMD) and RANK, RANKL and OPG mRNA expression in peripheral blood leukocytes (PBL) in children and adolescents with type 1 diabetes (T1D) and the relationship with glycemic control and bone biomarkers.

Methods: This cross-sectional study included 75 children and adolescents with T1D and 100 individuals without diabetes (normoglycemic-NG) aged 6-20 years old. T1D individuals were considered to have good (T1DG) or poor (T1DP) glycemic control according to the values of HbA1c.

Reduced ABCG2 and increased SLC22A1 mRNA expression are associated with imatinib response in chronic myeloid leukemia.

Imatinib mesylate (IM) has become a standard of care in chronic myeloid leukemia (CML) therapy. Single nucleotide polymorphisms (SNPs) and altered expression in drug transporter genes may influence IM response. In order to investigate whether mRNA expression and SNPs in drug transporters are associated with IM resistance, we studied 118 chronic-phase CML patients receiving the standard dose of IM (400 mg/day).

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.