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1.
Arch. endocrinol. metab. (Online) ; 63(4): 402-410, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1019361

RESUMO

ABSTRACT Objective The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

2.
Eur J Clin Pharmacol ; 75(11): 1541-1545, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402421

RESUMO

BACKGROUND: The identification of variants in genes involved in nicotine metabolism may have implications for the pharmacological therapy of smoking. In the scenario of precision medicine, the aim of this study was to evaluate a possible association of cytochrome P450 2A6 and 2B6 polymorphisms with varenicline pharmacotherapy. METHODS: The present study included 167 patients treated with varenicline in monotherapy who were from a cohort study of 1049 patients (treated with smoking cessation drugs: nicotine replacement therapy, bupropion, varenicline, or combinations of same). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. The CYP2A6 rs1801272 and rs28399433 and CYP2B6 rs8109525 polymorphisms were genotyped by real-time PCR using the TaqMan® platform. RESULTS: Patients with AG or GG genotypes for CYP2B6 rs8109525 had a higher success rate of smoking cessation with varenicline (51.2%) compared with carriers of the AA genotypes (33.3%, P = 0.03, n = 167). The AG or GG genotypes were also associated with a higher odds ratio of success, even in a multivariate analysis adjusting for potential confounders (OR = 2.01; 95%CI = 1.01 to 4.00; P = 0.047). CONCLUSION: CYP2B6 rs8109525 was associated with a higher success rate of smoking cessation with varenicline treatment. This finding may be useful in pharmacogenomic strategies for smoking cessation therapy.

3.
Arch Endocrinol Metab ; 63(4): 402-410, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365628

RESUMO

OBJECTIVE: The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. SUBJECTS AND METHODS: The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. RESULTS: The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). CONCLUSIONS: We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.


Assuntos
Obesidade/genética , Sobrepeso/genética , Polimorfismo Genético/genética , Sistema Renina-Angiotensina/genética , Adulto , Distribuição por Idade , Angiotensinogênio/genética , Pressão Sanguínea , Índice de Massa Corporal , Brasil , Estudos Transversais , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Distribuição por Sexo , Circunferência da Cintura
4.
Vox Sang ; 114(6): 616-621, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183870

RESUMO

BACKGROUND AND OBJECTIVES: Antibodies of unknown specificity (AUS) are frequently identified in the pre-transfusion testing. These antibodies can be insignificant or potentially cause post-transfusion haemolysis. Information about the prevalence of clinically relevant AUS is still lacking. Our aim was to predict the potential clinical relevance of AUS using the monocyte monolayer assay (MMA) and to identify the clinical and laboratorial determinants of AUS' significance. MATERIALS AND METHODS: Antibodies of unknown specificity identified at a single institution from 2015-2017 were evaluated through MMA. A monocyte index (MI) of more than 5% was predictive of potential post-transfusion haemolysis. RESULTS: Thirty-two patients with AUS were included in the study. Of the studied AUS, 37·5% (12/32) presented with a monocyte index (MI) more than 5%. In the group of significant AUS, 41·7% of the patients presented with sickle cell disease (SCD) and the AUS were associated with Rh antibodies in 75% of the cases. In the group of insignificant AUS, only 10% of the patients had SCD and the association with Rh antibodies was detected in 20% of the cases. The presence of Rh antibodies was independently associated with the AUS clinical relevance (P = 0·012). CONCLUSION: More than one-third of the AUS are potentially clinically relevant, and the association with Rh antibodies is predictive of AUS relevance. Services must honour AUS in the pre-transfusion process in order to ensure transfusion safety.


Assuntos
Anemia Falciforme , Isoanticorpos/sangue , Reação Transfusional/prevenção & controle , Especificidade de Anticorpos , Transfusão de Sangue , Humanos , Masculino , Monócitos , Reação Transfusional/diagnóstico , Reação Transfusional/etiologia
5.
Blood Cells Mol Dis ; 77: 23-28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30939337

RESUMO

BACKGROUND: There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. METHODS: Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. RESULTS: SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. CONCLUSION: The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.

6.
Sleep Med ; 57: 30-35, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897453

RESUMO

AIM: To test the association between cardiometabolic risk factors and subjective sleep quality assessed by the Pittsburgh sleep quality index (PSQI), independent of obstructive sleep apnea (OSA) and sleep duration. METHODS: A total of 573 participants from the Baependi Heart Study, a rural cohort from Brazil, completed sleep questionnaires and underwent polygraphy for OSA evaluation. Multivariable linear regression analysis tested the association between cardiovascular risk factors (outcome variables) and sleep quality measured by PSQI, adjusting for OSA and other potential confounders (age, sex, race, salary/wage, education, marital status, alcohol intake, obesity, smoking, hypertension, and sleep duration). RESULTS: The sample mean age was 43 ± 16 years, 66% were female, and mean body mass index (BMI) was 26 ± 5 kg/m2. Only 20% were classified as obese (BMI ≥30). Overall, 50% of participants reported poor sleep quality as defined by a PSQI score ≥5. A high PSQI score was significantly associated with higher very-low-density lipoprotein (VLDL) cholesterol levels (beta = 0.392, p = 0.012) and higher triglyceride levels (beta = 0.017, p = 0.006), even after adjustments, including the apnea-hypopnea index. Further adjustments accounting for marital status, alcohol intake, and medication use did not change these findings. No significant association was observed between PSQI scores and glucose or blood pressure. According to PSQI components, sleep disturbances (beta = 1.976, p = 0.027), sleep medication use (beta = 1.121, p = 0.019), and daytime dysfunction (beta = 1.290, p = 0.024) were significantly associated with higher VLDL serum levels. Only the daytime dysfunction domain of the PSQI components was significantly associated with higher triglyceride levels (beta = 0.066, p = 0.004). CONCLUSION: Poorer lipid profile was independently associated with poor sleep quality, assessed by the PSQI questionnaire, regardless of a normal sleep duration and accounting for OSA and socio-economic status.

7.
Cell Stress Chaperones ; 24(1): 273-282, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30645756

RESUMO

Heat shock protein-70 (HSP70) is crucial for proteostasis and displays cell-protective effects. Meanwhile, enhanced levels of cell-surface (cs) and secreted HSP70 paradoxically associate with pathologic cardiovascular conditions. However, mechanisms regulating csHSP70 pool are unknown. We hypothesized that total and csHSP70 expressions are modulated by hemodynamic forces, major contributors to endothelial pathophysiology. We also investigated whether thrombomodulin, a crucial thromboresistance cell-surface protein, is a csHSP70 target. We used proteomic/western analysis, confocal microscopy, and cs-biotinylation to analyze the pattern and specific characteristics of intracellular and csHSP70. HSP70 interaction with thrombomodulin was investigated by confocal colocalization, en face immunofluorescence, proximity assay, and immunoprecipitation. Thrombomodulin activity was assessed by measured protein C activation two-step assay. Our results show that csHSP70 pool in endothelial cells (EC) exhibits a peculiar cluster-like pattern and undergoes enhanced expression by physiological arterial-level laminar shear stress. Conversely, total and csHSP70 expressions were diminished under low shear stress, a known proatherogenic hemodynamic pattern. Furthermore, total HSP70 levels were decreased in aortic arch (associated with proatherogenic turbulent flow) compared with thoracic aorta (associated with atheroprotective laminar flow). Importantly, csHSP70 co-localized with thrombomodulin in cultured EC and aorta endothelium; proximity ligation assays and immunoprecipitation confirmed their physical interaction in EC. Remarkably, immunoneutralization of csHSP70 enhanced thrombomodulin activity in EC and aorta ex vivo. Overall, proatherogenic hemodynamic forces promote reduced total HSP70 expression, which might implicate in disturbed proteostasis; meanwhile, the associated decrease in cs-HSP70 pool associates with thromboresistance signaling. Cell-surface HSP70 (csHSP70) expression regulation and csHSP70 targets in vascular cells are unknown. We showed that HSP70 levels are shear stress-modulated and decreased under proatherogenic conditions. Remarkably, csHSP70 binds thrombomodulin and inhibits its activity in endothelial cells. This mechanism can potentially explain some deleterious effects previously associated with high extracellular HSP70 levels, as csHSP70 potentially could restrict thromboresistance and support thrombosis/inflammation in stress situations.


Assuntos
Membrana Celular/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Trombomodulina/metabolismo , Aorta/metabolismo , Humanos , Ligação Proteica , Estresse Fisiológico
8.
Front Pharmacol ; 9: 1052, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298004

RESUMO

Thromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist's warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range- TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient's INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2-3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 ± 0.010 vs. 0.382 ± 0.016; and 0.144 ± 0.010 vs. 0.543 ± 0.014, p < 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 ± 0.015; 0.540 ± 0.015, p < 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.

9.
Arq. bras. cardiol ; 111(4): 578-584, Oct. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-973776

RESUMO

Abstract Background: Genetic cascade screening is the most cost-effective method for the identification of individuals with familial hypercholesterolemia (FH), but the best strategies for the enrollment of at-risk individuals in a FH screening program are not fully known. Objective: The aim of this study is to identify the best predictors of familial enrollment into genetic screening, using features derived from tested probands. Methods: One hundred and eighty-three index-cases (ICs) with a positive genetic result that had relatives screened from 01/2011 to 07/2015 were included. The response variable was the number of relatives for each enrolled IC. All variables in the study were based on ICs' derived clinical and socioeconomical features. The effect size of predictor variables were obtained through a general linear model using a negative binomial regression link function. Significance was considered with a p < 0.05. Results: Mean IC age when enrolling into the program was 50 years old; 78.1% of individuals reported knowledge of relatives with dyslipidemia. Mean baseline LDL-cholesterol level was 316 ± 90 mg/dL. Referral origin through the cascade program website vs. tertiary care, IC LDL-cholesterol and familial history of high LDL-cholesterol levels were independent predictors associated with a higher number of enrolled relatives. Conclusions: Our data suggest that FH cascade screening programs can predict family enrollment based on IC features. This information may be useful for devising better and more effective screening approaches for at-risk individuals.


Resumo Fundamento: O rastreamento genético em cascata é o método mais economicamente viável para a identificação de indivíduos com hipercolesterolemia familiar, mas as melhores estratégias para o recrutamento de indivíduos em risco em um programa de rastreamento deste tipo não são inteiramente conhecidas. Objetivo: Identificar os melhores preditores de recrutamento familiar em rastreamento genético, usando características derivadas de probandos testados. Métodos: Foram inscritos 183 casos índices com resultado genético positivo, que tiveram familiares rastreados de janeiro de 2011 a julho de 2015. A variável de resposta foi o número de familiares para cada caso índice inscrito. Todas as variáveis do estudo foram baseadas em características clínicas e socioeconômicas derivadas dos casos índices. O tamanho do efeito das variáveis preditoras foi obtido de modelo linear geral utilizando função de associação de regressão binomial negativa. A significância foi considerada com p < 0,05. Resultados: A média de idade dos casos índices ao ingressar no programa foi de 50 anos; 78,1% dos indivíduos relataram conhecimento de familiares com dislipidemia. O nível médio de LDL-colesterol inicial foi de 316 ± 90 mg/dL. Origem de referência por meio do site do programa em cascata vs. cuidados terciários, LDL-colesterol do caso índice e história familiar de níveis elevados de LDL-colesterol foram preditores independentes associados a um maior número de familiares inscritos. Conclusões: Programas de rastreamento genético em cascata da hipercolesterolemia familiar podem prever o recrutamento da família com base nas características do caso índice. Esta informação pode ser útil para criar abordagens de rastreamento melhores e mais eficazes para indivíduos em risco.

10.
Arq Bras Cardiol ; 111(4): 578-584, 2018 Oct.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30156605

RESUMO

BACKGROUND: Genetic cascade screening is the most cost-effective method for the identification of individuals with familial hypercholesterolemia (FH), but the best strategies for the enrollment of at-risk individuals in a FH screening program are not fully known. OBJECTIVE: The aim of this study is to identify the best predictors of familial enrollment into genetic screening, using features derived from tested probands. METHODS: One hundred and eighty-three index-cases (ICs) with a positive genetic result that had relatives screened from 01/2011 to 07/2015 were included. The response variable was the number of relatives for each enrolled IC. All variables in the study were based on ICs' derived clinical and socioeconomical features. The effect size of predictor variables were obtained through a general linear model using a negative binomial regression link function. Significance was considered with a p < 0.05. RESULTS: Mean IC age when enrolling into the program was 50 years old; 78.1% of individuals reported knowledge of relatives with dyslipidemia. Mean baseline LDL-cholesterol level was 316 ± 90 mg/dL. Referral origin through the cascade program website vs. tertiary care, IC LDL-cholesterol and familial history of high LDL-cholesterol levels were independent predictors associated with a higher number of enrolled relatives. CONCLUSIONS: Our data suggest that FH cascade screening programs can predict family enrollment based on IC features. This information may be useful for devising better and more effective screening approaches for at-risk individuals.

11.
J Renin Angiotensin Aldosterone Syst ; 19(2): 1470320318761725, 2018 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29629833

RESUMO

INTRODUCTION: Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. MATERIALS AND METHODS: A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O2 consumption (VO2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. RESULTS: In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD genotype. CONCLUSIONS: AET differentially affects the ACE C- and N-domain activities, and the N-domain activity is dependent on ACE polymorphism.


Assuntos
Vasos Sanguíneos/patologia , Exercício/fisiologia , Estudos de Associação Genética , Mutação INDEL/genética , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Pressão Sanguínea/genética , Genótipo , Hemodinâmica , Humanos , Masculino , Consumo de Oxigênio , Peptidil Dipeptidase A/sangue , Domínios Proteicos , Adulto Jovem
12.
BMC Med Genet ; 19(1): 55, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29621993

RESUMO

BACKGROUND: The identification of variants in the nicotinic acetylcholine receptor (nAChR) subunit genes associated with smoking phenotypes are increasingly important for prevention and treatment of nicotine dependence. In the context of personalized medicine, the aims of this study were to evaluate whether cholinergic receptor nicotinic alpha 2 (CHRNA2), cholinergic receptor nicotinic alpha 3 (CHRNA3), cholinergic receptor nicotinic alpha 5 (CHRNA5) and cholinergic receptor nicotinic beta 3 (CHRNB3) polymorphisms were associated with nicotine dependence severity, and to investigate possible pharmacogenetics markers of smoking cessation treatment. METHODS: This study cohort enrolled 1049 smoking patients who received pharmacological treatment (varenicline, varenicline plus bupropion, bupropion plus/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores (Issa score) were analyzed for nicotine dependence. CHRNA2 (rs2472553), CHRNA3 (rs1051730), CHRNA5 (rs16969968 and rs2036527) and CHRNB3 (rs6474413) polymorphisms were genotyped by high resolution melting analysis. RESULTS: Females with GA and AA genotypes for CHRNA5 rs16969968 and rs2036527 polymorphisms had higher success rate in smoking cessation treatment: 44.0% and 56.3% (rs16969968), 41.5% and 56.5% (rs2036527), respectively, compared with carriers of the GG genotypes: 35.7% (rs16969968), 34.8% (rs2036527), (P = 0.03, n = 389; P = 0.01, n = 391). The GA or AA genotypes for the rs16969968 and rs2036527 were associated with higher odds ratio for success in women (OR = 1.63; 95% CI = 1.04 to 2.54; P = 0.03 and OR = 1.59, 95% CI = 1.02 to 2.48; P = 0.04; respectively). We did not find association of these polymorphisms with nicotine dependence related scores. Polymorphisms in the CHRNA2, CHRNA3 and CHRNB3 genes were not associated with the phenotypes studied. CONCLUSION: CHRNA5 rs16969968 and rs2036527 were associated with higher success rate in the smoking cessation treatment in women. These findings might contribute to advances in personalized medicine.

13.
BMC Med Genet ; 19(1): 3, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29301508

RESUMO

BACKGROUND: Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical and magnetic resonance imaging (MRI) assessment, and genetic testing. Questionnaires, such as SF-36 (short form health survey), have been increasingly used to assess the impact of diseases on the patient's quality of life (QL). In addition, different genotypes are identified as results of genetic tests in patients with suspected primary iron overload. In the present study, our aim was to evaluate whether domains of QL are different according to genotypic groups in patients suspected of HH. METHODS: Seventy-nine patients with primary iron overload were included and two genotypic groups were formed (group 1: homozygous genotype for the HFE p.Cys282Tyr mutation; group 2: other genotypes). RESULTS: Group 1 had higher means of plasma transferrin saturation (86 ± 19%) and serum ferritin (1669 ± 1209 ng/mL) compared to group 2 (71 ± 12%, 1252 ± 750 ng/mL, respectively; p = 0.001). Four domains were significantly different among groups 1 and 2: physical functioning (p = 0.03), bodily pain (p = 0.03), vitality (p = 0.02) and social functioning (p = 0.01). CONCLUSIONS: Our main finding was that patients with p.Cys282Tyr homozygosity had a worse QL scenario assessed by SF-36, compared with patients with iron overload without the same genotype. Being aware of this relationship between genotypes and QL might be helpful in the overall management of patients suspected of hereditary hemochromatosis.

14.
Thorac Cardiovasc Surg ; 66(6): 477-482, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28355655

RESUMO

BACKGROUND: Proper treatment of patients with diffuse, severe coronary artery disease (CAD) is a challenge due to its complexity. Thus, data on the outcomes after coronary artery bypass graft (CABG) in this population is scarce. In this study, we aimed to determine the impact of CABG on the clinical and functional status, as well as graft patency in those individuals. METHODS: Patients with severe and diffuse CAD who underwent incomplete CABG due to complex anatomy or extensive distal coronary involvement were evaluated preoperatively and 1 year after surgery. Postoperative coronary angiography was performed to evaluate graft patency. Graft occlusion was defined as the complete absence of opacification of the target vessel. Stratified analysis of graft occlusion was performed by graft type and territories, defined as left anterior descending artery (LAD), the left circumflex branch, and the right coronary artery territories; the latter two, grouped, were further classified as non-LAD territory. RESULTS: A total of 57 patients were included, in whom 131 grafts were placed. There was a significant improvement in Canadian Cardiovascular Society angina symptom severity (Z = -6.1; p < 0.001) and maximum oxygen uptake (p < 0.001), with a corresponding decrease in the use of long-acting nitrates (p < 0.001). The overall graft occlusion rate was 19.1%, with no significant difference between LAD and non-LAD territories (p = 0.08). However, a significantly lower occlusion rate was noted for the internal mammary artery (IMA) grafts when compared with saphenous vein grafts (p = 0.01), though this difference was only significant in the LAD territory (p = 0.04). Overall, the use of venous graft was the only predictor occlusion at 1 year (odds ratio: 4.03; p = 0.016). CONCLUSION: In patients with diffuse CAD, incomplete CABG surgery resulted in a significant clinical improvement, with acceptable graft occlusion rates at 1 year, particularly for IMA grafts to the LAD territory.


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Idoso , Brasil , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
15.
J Chromatogr A ; 1528: 41-52, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29102378

RESUMO

A novel analytical method was developed to determine 5 antihypertensive drugs of different pharmacological classes (angiotensin-converting enzyme inhibitors, calcium channel blockers, α-2 adrenergic receptor agonists, angiotensin II receptor blockers, and aldosterone receptor antagonists) and some of their metabolites in human serum. The untreated samples were directly analyzed in a column switching system using an extraction column packed with restricted access carbon nanotubes (RACNTs) in an ultra-high performance liquid chromatography coupled to a mass spectrometer (UHPLC-MS/MS). The RACNTs column was able to exclude approximately 100% of proteins from the samples in 2.0min, maintaining the same performance for about 300 analytical cycles. The method was validated in accordance with Food and Drug Administration (FDA) guidelines, being linear for all the determined analytes in their respective analytical ranges (coefficients of determination higher than 0.99) with limits of detection (LODs) and quantification (LOQs) ranging from 0.09 to 10.85µgL-1 and from 0.30 to 36.17µgL-1, respectively. High recovery values (88-112%) were obtained as well as suitable results for inter and intra-assay accuracy and precision. The method provided an analytical frequency of 5 samples per hour, including the sample preparation and separation/detection steps. The validated method was successfully used to analyze human serum samples of patients undergoing treatment with antihypertensive drugs, being useful for pharmacometabolomic, pharmacogenomic, and pharmacokinetic studies.


Assuntos
Anti-Hipertensivos/sangue , Anti-Hipertensivos/isolamento & purificação , Análise Química do Sangue/métodos , Cromatografia Líquida de Alta Pressão/instrumentação , Nanotubos de Carbono/química , Análise Química do Sangue/instrumentação , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
16.
Front Immunol ; 8: 1213, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29033934

RESUMO

The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3 dampens cardiac inflammation by modulating the overproduction of IFN-γ, the bona fide culprit of Chagas disease cardiomyopathy.

17.
Blood Cells Mol Dis ; 65: 8-15, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28388467

RESUMO

BACKGROUND: The complexity of Rh genetic variation among sickle cell disease (SCD) patients is high. Conventional molecular assays cannot identify all genetic variants already described for the RH locus as well as foresee novel alleles. Sequencing RHD and RHCE is indicated to broaden the search for Rh genetic variants. AIMS: To standardize the Next Generation Sequencing (NGS) strategy to assertively identify Rh genetic variants among SCD patients with serologic suspicion of Rh variants and evaluate if it can improve the transfusion support. METHODS: Thirty-five SCD patients with unexplained Rh antibodies were enrolled. A NGS-based strategy was developed to genotype RHD and RHCE using gene-specific primers. Genotype and serological data were compared. RESULTS: Data obtained from the NGS-based assay were gene-specific. Ten and 25 variant RHD and RHCE alleles were identified, respectively. Among all cases of unexplained Rh antibodies, 62% had been inaccurately classified by serological analysis and, of these, 73.1% were considered as relevant, as were associated with increased risk of hemolytic reactions and shortage of units suitable for transfusion. CONCLUSION: The NGS assay designed to genotype RH coding regions was effective and accurate in identifying variants. The proposed strategy clarified the Rh phenotype of most patients, improving transfusion support.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Variação Genética , Genótipo , Sistema do Grupo Sanguíneo Rh-Hr/genética , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/terapia , Transfusão de Sangue/métodos , Gerenciamento Clínico , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Fenótipo , Reprodutibilidade dos Testes
18.
Clinics (Sao Paulo) ; 72(2): 106-110, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28273234

RESUMO

OBJECTIVES:: Increased arterial stiffness is an important determinant of the risk of cardiovascular disease. Lipid profile impairment, especially hypercholesterolemia, is associated with stiffer blood vessels. Thus, the aim of this study was to determine which of the five circulating lipid components (high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL), total cholesterol (TC) and triglycerides) is the best predictor of increased arterial stiffness in an urban Brazilian population. METHODS:: A random sample of 1,662 individuals from the general population of Vitoria, Brazil (25-64 years), was selected, and lipid components were measured using standard methods. Pulse wave velocity was measured using a non-invasive automatic device, and increased arterial stiffness was defined as a pulse wave velocity ≥10 m/s. RESULTS:: In men, only total cholesterol (OR=1.59; CI=1.02 to 2.48, p=0.04) was associated with the risk of increased arterial stiffness. In women, HDL-C (OR=1.99; CI=1.18 to 3.35, p=0.01) and non-HDL-C (OR=1.61; CI=1.01 to 2.56, p=0.04) were good predictors of the risk of increased arterial stiffness. However, these associations were only found in postmenopausal women (OR=2.06; CI=1.00 to 4.26, p=0.05 for HDL-C and OR=1.83; CI=1.01 to 3.33, p=0.04 for non-HDL-C). CONCLUSION:: Our findings indicate that both HDL-C and non-HDL-C are good predictors of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population and may be useful tools for assessing the risk of arterial stiffness.


Assuntos
Colesterol/sangue , Doença da Artéria Coronariana/sangue , Dislipidemias/sangue , Pós-Menopausa/sangue , Triglicerídeos/sangue , Rigidez Vascular/fisiologia , Adulto , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Dislipidemias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , População Urbana
19.
Clinics ; 72(2): 106-110, Feb. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-840043

RESUMO

OBJECTIVES: Increased arterial stiffness is an important determinant of the risk of cardiovascular disease. Lipid profile impairment, especially hypercholesterolemia, is associated with stiffer blood vessels. Thus, the aim of this study was to determine which of the five circulating lipid components (high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL), total cholesterol (TC) and triglycerides) is the best predictor of increased arterial stiffness in an urban Brazilian population. METHODS: A random sample of 1,662 individuals from the general population of Vitoria, Brazil (25-64 years), was selected, and lipid components were measured using standard methods. Pulse wave velocity was measured using a non-invasive automatic device, and increased arterial stiffness was defined as a pulse wave velocity ≥10 m/s. RESULTS: In men, only total cholesterol (OR=1.59; CI=1.02 to 2.48, p=0.04) was associated with the risk of increased arterial stiffness. In women, HDL-C (OR=1.99; CI=1.18 to 3.35, p=0.01) and non-HDL-C (OR=1.61; CI=1.01 to 2.56, p=0.04) were good predictors of the risk of increased arterial stiffness. However, these associations were only found in postmenopausal women (OR=2.06; CI=1.00 to 4.26, p=0.05 for HDL-C and OR=1.83; CI=1.01 to 3.33, p=0.04 for non-HDL-C). CONCLUSION: Our findings indicate that both HDL-C and non-HDL-C are good predictors of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population and may be useful tools for assessing the risk of arterial stiffness.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Colesterol/sangue , Doença da Artéria Coronariana/sangue , Dislipidemias/sangue , Pós-Menopausa/sangue , Triglicerídeos/sangue , Rigidez Vascular/fisiologia , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Dislipidemias/diagnóstico , Valor Preditivo dos Testes , Fatores de Risco , População Urbana
20.
Comun. ciênc. saúde ; 28(1): 96-101, jan. 2017. ilus
Artigo em Português | LILACS | ID: biblio-972639

RESUMO

OBJETIVOS: 1- Padronizar a genotipagem em larga escala para determinação de antígenos eritrocitários e plaquetários pela plataforma de OpenArray®em doadores de sangue. 2- Elaboração de software para registro destes doadores, com interface com o equipamento de genotipagem. METODOLOGIA: Extração automatizada de DNA e genotipagem através demicroarranjos líquidos (OpenArray®) para 32 alelos codificantes de antígenos eritrocitários e plaquetários. RESULTADOS: Foi realizada a genotipagem de 5487 doadores para os antígenos propostos, de forma completamente interfaceada e automatizada. O ensaio customizado de Open Array® mostrou-se acurado e de rápida execução. Elaborou-se software próprio para interfaceamento dos resultados da genotipagem e busca dos genótipos. CONCLUSÃO: Padronizou-se estratégia efetiva para rastreamento de doadores de sangue com fenótipos raros. A automação de todas as etapas experimentais e o interfaceamento completo dos dados minimizaram os erros humanos e aumentaram a rapidez do processo descrito, que pode ser aplicado como estratégia de genotipagem de doadores de todo o Estado de São Paulo.


Assuntos
Humanos , Software , Genótipo , Antígenos , Variação Genética
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