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1.
PLoS Med ; 17(9): e1003302, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32915777

RESUMO

BACKGROUND: A number of epidemiological and genetic studies have attempted to determine whether levels of circulating lipids are associated with risks of various cancers, including breast cancer (BC). However, it remains unclear whether a causal relationship exists between lipids and BC. If alteration of lipid levels also reduced risk of BC, this could present a target for disease prevention. This study aimed to assess a potential causal relationship between genetic variants associated with plasma lipid traits (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with risk for BC using Mendelian randomization (MR). METHODS AND FINDINGS: Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard-deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04-1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03-1.10, P = 4.9 × 10-4) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01-1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06-1.16, P = 1.5 × 10-6), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study. CONCLUSIONS: We observed that genetically elevated plasma HDL and LDL levels appear to be associated with increased BC risk. Future studies are required to understand the mechanism underlying this putative causal relationship, with the goal of developing potential therapeutic strategies aimed at altering the cholesterol-mediated effect on BC risk.


Assuntos
Neoplasias da Mama/genética , Lipídeos/análise , Lipídeos/sangue , Adulto , Neoplasias da Mama/metabolismo , Colesterol/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos/sangue
2.
PLoS One ; 15(8): e0238079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845916

RESUMO

BACKGROUND: Sitosterolemia is an inherited lipid disorder which presents with elevated serum sitosterol and can result in an increased risk of premature cardiovascular disease. However, sitosterol cannot be accurately measured by routine diagnostic assays, meaning that sitosterolemia diagnosis can often be difficult, especially with many clinical features overlapping with familial hypercholesterolemia. With such complications resulting in increasing reports of misdiagnosis, the prevalence of sitosterolemia is predicted to be much higher than previously reported. METHODS: Gas chromatography-mass spectrometry was utilized to measure sitosterol levels of normocholesterolemic and hypercholesterolemic children. Subsequently, an epidemiologically determined cutoff level of sitosterol was calculated and applied to estimate the prevalence of children with increased sitosterol and identify potential sitosterolemia patients. Massively parallel sequencing was used to confirm the diagnosis in suspected patients. RESULTS: Samples from 109 normocholesterolemic and 220 hypercholesterolemic were tested for phytosterols. Sitosterol and campesterol levels were significantly increased in hypercholesterolemic children (mean 22.0±45.9 µmol/L for sitosterol and 26.0±32.8 µmol/L for campesterol) compared to normocholesterolemic children (mean 12.1±4.9 µmol/L for sistosterol and 14.8±6.7 µmol/L for campesterol). Via application of a cutoff of 35.9 µmol/L, the prevalence rates for increased and overtly increased sitosterol in hypercholesterolemic children were 6.4% and 1.4% respectively. Furthermore, 3 suspected sitosterolemia patients were identified, with 2 patients receiving molecular confirmation for sitosterolemia diagnosis. CONCLUSIONS: Our findings reaffirm that the prevalence of sitosterolemia is probably much higher than previously reported, which also indicates the significant risk of misdiagnosis of sitosterolemia with familial hypercholesterolemia. Special lipid testing including sitosterol, especially in children with uncontrolled hypercholesterolemia, is recommended in children in order to identify potential sitosterolemia patients that would otherwise be neglected.


Assuntos
Hipercolesterolemia/diagnóstico , Sitosteroides/análise , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Criança , Pré-Escolar , Colesterol/análogos & derivados , Colesterol/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/genética , Lactente , Enteropatias/diagnóstico , Enteropatias/epidemiologia , Enteropatias/genética , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/epidemiologia , Erros Inatos do Metabolismo Lipídico/genética , Lipoproteínas/genética , Masculino , Linhagem , Fitosteróis/efeitos adversos , Fitosteróis/análise , Fitosteróis/genética , Prevalência
3.
Sanid. mil ; 76(1): 13-18, ene.-mar. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193135

RESUMO

ANTECEDENTES: Los índices aterogénicos son indicadores bioquímicos que suelen relacionarse con la adiposidad corporal y con el desarrollo de enfermedades cardiometabólicas, las cuales representan un serio problema en salud pública, no sólo por la morbimortalidad asociada, sino por el gasto sanitario que conlleva, situación que no resulta ajena en la población militar. OBJETIVO: Determinar si el índice de masa corporal en cadetes colombianos con sobrepeso se debe a masa magra o grasa y si se relaciona con los índices aterogénicos. MATERIALES Y MÉTODOS: Estudio descriptivo - observacional, en cadetes con sobrepeso, valorados en el centro de investigaciones de la cultura física (CICFI) de la Escuela militar de cadetes "General José María Córdova". Para el análisis de la información se empleó el paquete estadístico SPSS 24, aplicando pruebas de normalidad, estadísticos descriptivos para datos de comportamiento normal y correlación de Pearson. RESULTADOS: 90 cadetes con edad promedio de 22,0 ± 3,0 años e índice de masa corporal en 27,3 ± 1,8 kg/ m2, fueron incluidos, 58,0% hombres y 32,0% mujeres. El índice preaterogénico se relacionó con el IMC (r = 0,305 p = 0,02), el índice de Castelli se relacionó, débilmente con el índice de masa corporal (r = 0,254 p = 0,05). En ningún grupo, el cociente de Triglicéridos se relacionó con el IMC. CONCLUSIONES: Los índices aterogénicos en cadetes con sobrepeso, se encuentran en rangos de normalidad y presentan relaciones débiles con el índice de masa corporal. El sobrepeso se debe a mayor masa magra


ANTECEDENTS: The atherogenic indices are biochemical indicators that are usually related to body fat and the development of cardiometabolic diseases, which represent a serious problem in public health, not only because of the associated morbidity and mortality, but also due to the health costs involved, a situation that it is'nt alien in the military population. AIM: To determine if the body mass index in overweight colombian cadets is due to lean or fat mass and if it is related to atherogenic indices. MATERIALS AND METHODS: Descriptive - observational study, in overweight cadets, assessed in the center of physical culture research (CICFI) of the Military School of cadets "General Jose Maria Cordova". For the analysis of the information the statistical package SPSS 24 was used, applying normality tests, descriptive statistics for normal behavior data and Pearson's correlation. RESULTS: 90 cadets with an average age of 22.0 ± 3.0 years and a body mass index of 27.3 ± 1.8 kg / m2, 58.0% men and 32.0% women were included. The pre-erogenous index was related to the BMI (r = 0,305 p = 0,02), the Castelli index was weakly related to the body mass index (r = 0,254 p = 0,05). In no group, the ratio of triglycerides was related to BMI. CONCLUSIONS: The atherogenic indices in overweight cadets are in normal ranges and have weak relations with the body mass index. Overweight is due to greater lean mass


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Índice de Massa Corporal , Militares , Sobrepeso/diagnóstico , Valor Nutritivo , Colômbia , Adiposidade , Colesterol/análise , Composição Corporal
4.
Proc Natl Acad Sci U S A ; 117(11): 5749-5760, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32132201

RESUMO

Dysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatization in combination with microliquid extraction for surface analysis and liquid chromatography-mass spectrometry to locate sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400-µm spot diameter with a limit of quantification of 0.01 ng/mm2 It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low-abundance and difficult-to-ionize sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild-type and cholesterol 24S-hydroxylase knockout mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.


Assuntos
Encéfalo/metabolismo , Colesterol/análogos & derivados , Hidroxicolesteróis/metabolismo , Espectrometria de Massas/métodos , Animais , Química Encefálica , Colesterol/análise , Colesterol/metabolismo , Hidroxicolesteróis/análise , Limite de Detecção , Masculino , Espectrometria de Massas/normas , Camundongos , Camundongos Endogâmicos C57BL
5.
Anim Sci J ; 91(1): e13346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219928

RESUMO

The aim of this research was to perform comparison studies of the chemical, physical, technological, and microbiological characteristics, including biogenic amines (BAs) and volatile compounds (VC), of the European roe deer (RDM), boar (BoM), red deer (ReDM), and beaver (BM) hunted wild game meat (HWGM). The outcome of this study showed a significant effect (p < .05) of animal species on protein content, pH, drip loss, shear force, cooking loss, color coordinates, total count of enterobacteria, and most of the VC. ReDM had the highest protein content (23.15%), cooking loss, L* and b* values. The lowest protein and cholesterol content and L* value and the highest pH, shear force, drip loss, and fat content were established in BM having the highest content of unsaturated fatty acids (UFA) (64.12% from total FA). The total UFA content in ReDM and BM was almost twofold higher, compared with saturated FA. Small amounts of main BAs (<7.8 mg/kg) were found in ReDM and BM, while a higher content of putrescine in RDM and BoM was established. The main VCs in HWGM were acetoin, pelargonic, and acetic acid. These findings provide a valuable data about the HWGM quality characteristics and might aid food manufacturers to improve and enhance the processing of the HWGM.


Assuntos
Cervos , Qualidade dos Alimentos , Carne , Roedores , Sus scrofa , Aminas/análise , Animais , Fenômenos Químicos , Colesterol/análise , Combinação de Medicamentos , Enterobacteriaceae/isolamento & purificação , Ácidos Graxos Insaturados/análise , Carne/análise , Carne/microbiologia , Óleos , Fenóis , Proteínas/análise , Compostos Orgânicos Voláteis/análise
6.
PLoS One ; 15(1): e0228170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978159

RESUMO

We describe a sensitive high performance liquid chromatography (HPLC)-based method for the determination of cholesterol in brain tissue. The method does not require the derivatization of the analyte and uses separation and quantification by reversed-phase HPLC coupled to UV detection. Lipids were methanol/chloroform extracted following the method of Bligh and Dyer, and separated using isopropanol/acetonitrile/water (60/30/10, v/v/v) as mobile phase. We observed lineal detection in a wide range of concentrations, from 62.5 to 2000 ng/µL, and were able to detect a significant increase in the brain cholesterol levels between postnatal days 2 and 10 in C57BL6 mice. Based on our validation parameters, we consider this analytical method a useful tool to assess free cholesterol in rodent brain samples and cell cultures.


Assuntos
Encéfalo/metabolismo , Colesterol/análise , Cromatografia Líquida de Alta Pressão/métodos , Animais , Colesterol/isolamento & purificação , Cromatografia de Fase Reversa , Limite de Detecção , Extração Líquido-Líquido , Camundongos , Camundongos Endogâmicos C57BL , Espectrofotometria Ultravioleta
7.
Cell Physiol Biochem ; 54(1): 110-125, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31999897

RESUMO

BACKGROUND/AIMS: Cystic Fibrosis (CF) is an inherited disease associated with a variety of mutations affecting the CFTR gene. A deletion of phenylalanine 508 (F508) affects more than 70% of patients and results in unfolded proteins accumulation, originating a proteinopathy responsible for inflammation, impaired trafficking, altered metabolism, cholesterol and lipids accumulation, impaired autophagy at the cellular level. Lung inflammation has been extensively related to the accumulation of the lipotoxin ceramide. We recently proved that inhibition of ceramide synthesis by Myriocin reduces inflammation and ameliorates the defence response against pathogens infection, which is downregulated in CF. Here, we aim at demonstrating the mechanisms of Myriocin therapeutic effects in Cystic Fibrosis broncho-epithelial cells. METHODS: The effect of Myriocin treatment, on F508-CFTR bronchial epithelial cell line IB3-1 cells, was studied by evaluating the expression of key proteins and genes involved in autophagy and lipid metabolism, by western blotting and real time PCR. Moreover, the amount of glycerol-phospholipids, triglycerides, and cholesterols, sphingomyelins and ceramides were measured in treated and untreated cells by LC-MS. Finally, Sptlc1 was transiently silenced and the effect on ceramide content, autophagy and transcriptional activities was evaluated as above mentioned. RESULTS: We demonstrate that Myriocin tightly regulates metabolic function and cell resilience to stress. Myriocin moves a transcriptional program that activates TFEB, major lipid metabolism and autophagy regulator, and FOXOs, central lipid metabolism and anti-inflammatory/anti-oxidant regulators. The activity of these transcriptional factors is associated with the induction of PPARs nuclear receptors activity, whose targets are genes involved in lipid transport compartmentalization and oxidation. Transient silencing of SPTCL1 recapitulates the effects induced by Myriocin. CONCLUSION: Cystic Fibrosis bronchial epithelia accumulate lipids, exacerbating inflammation. Myriocin administration: i) activates the transcriptions of genes involved in enhancing autophagy-mediated stress clearance; ii) reduces the content of several lipid species and, at the same time, iii) enhances mitochondrial lipid oxidation. Silencing the expression of Sptlc1 reproduces Myriocin induced autophagy and transcriptional activities, demonstrating that the inhibition of sphingolipid synthesis drives a transcriptional program aimed at addressing cell metabolism towards lipid oxidation and at exploiting autophagy mediated clearance of stress. We speculate that regulating sphingolipid de novo synthesis can relieve from chronic inflammation, improving energy supply and anti-oxidant responses, indicating an innovative therapeutic strategy for CF.


Assuntos
Ácidos Graxos Monoinsaturados/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Esfingolipídeos/metabolismo , Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular , Colesterol/análise , Cromatografia Líquida de Alta Pressão , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Humanos , Espectrometria de Massas , PPAR gama/genética , PPAR gama/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Serina C-Palmitoiltransferase/antagonistas & inibidores , Serina C-Palmitoiltransferase/genética , Serina C-Palmitoiltransferase/metabolismo , Esfingolipídeos/análise , Esfingomielinas/análise
8.
J Stroke Cerebrovasc Dis ; 29(2): 104579, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31852598

RESUMO

OBJECTIVE: Vulnerable carotid plaque is associated with cerebrovascular events. Cholesterol crystals are often seen in the atherosclerotic plaques. However, the potential role of cholesterol crystals in carotid plaques destabilization is unknown. We aimed to identify the association between cholesterol crystals and carotid plaque vulnerability. METHODS: Optical coherence tomography assessment of carotid plaque was performed in 95 patients. Clinical characteristics and plaque morphology were examined. The differences in plaque characteristics (thrombus, calcification, neovascularization, and macrophage accumulations) and clinical parameters (age, symptom, coronary heart disease, total cholesterol, triglycerides, and C-reactive protein) between patients with or without cholesterol crystals were analyzed with multivariate logistic regression. RESULTS: Among 66 patients with acceptable carotid atherosclerotic optical coherence tomography images, 16 were with and 50 were without cholesterol crystals. 56.3% patients (9 of 16) with cholesterol crystals had cerebrovascular ischemic symptom related to ipsilateral internal carotid artery, whereas only 26.0% patients (13 of 50) without cholesterol crystals had symptom (OR, 3.66; 95% CI, 1.13-11.82; P = .025). 75.0% of the plaques with cholesterol crystals had concomitant macrophage accumulation (OR, 4.14; 95% CI, 1.17-14.65; P = .04). In segments with cholesterol crystals, a higher presence of calcification could be demonstrated compared to those without cholesterol crystals (62.5% versus 32.0%, P = .03). 70.0% plaques with cholesterol crystals and calcification were classified as symptomatic plaques (OR, 6.38; 95% CI, 1.46-27.91; P = .01). No association between plaque rupture and cholesterol crystals was identified. Multivariate logistic regression showed that age and macrophage accumulation were independently associated with cholesterol crystals. CONCLUSIONS: Carotid atherosclerotic plaques with cholesterol crystals were more likely to have concomitant macrophage and calcification accumulations. Patients with cholesterol crystals plaque experienced more cerebrovascular symptoms. Thus, cholesterol crystals, especially together with macrophage and calcification, may serve as an important component of venerable carotid plaques.


Assuntos
Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Colesterol/análise , Placa Aterosclerótica , Tomografia de Coerência Óptica , Idoso , Isquemia Encefálica/etiologia , Artéria Carótida Interna/química , Estenose das Carótidas/complicações , Estenose das Carótidas/metabolismo , Cristalização , Feminino , Humanos , Macrófagos/química , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ruptura Espontânea , Índice de Gravidade de Doença , Calcificação Vascular/diagnóstico por imagem
9.
Respir Physiol Neurobiol ; 271: 103309, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561012

RESUMO

Pulmonary surfactant main function is to reduce surface tension at alveolar interface. Two lipids phases coexist in surfactant membranes: a liquid-ordered (Lo) and a liquid-disordered (Ld) phases. This coexistence of phases would be crucial for the surfactant activity. Until now, the proportion of phases was determined qualitatively. We design an electronic spin resonance technique to quantify the lipid fraction in Ld phase. An exogenous pulmonary surfactant (EPS) with or without extra Cho was labeled with 5-doxil stearic acid to estimate the membrane fluidity and with TEMPO to determine the PL in Ld phase. A unique equation was established for the calculation of PL in Ld phase with an error of less than 3%. TEMPO partition coefficient was (0.78 ±â€¯0.03). Cholesterol added to EPS did not modify this coefficient. The equation is valid for different batches of surfactant regardless of the cholesterol content. The proposed method is simple, precise and allows evaluating changes in lateral structure that could affect surfactant biophysical properties.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Surfactantes Pulmonares/análise , Surfactantes Pulmonares/química , Animais , Bovinos , Colesterol/análise , Colesterol/química , Tensão Superficial
10.
Einstein (Sao Paulo) ; 18: eAO4876, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576909

RESUMO

OBJECTIVE: To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. METHODS: Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. RESULTS: Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. CONCLUSION: Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Sericinas/uso terapêutico , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/análise , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Fígado Gorduroso/patologia , Trânsito Gastrointestinal/efeitos dos fármacos , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/fisiopatologia , Reprodutibilidade dos Testes , Sericinas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/análise , Ganho de Peso/efeitos dos fármacos
11.
Mol Biol Rep ; 47(2): 867-875, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31873873

RESUMO

Metabolic syndrome (MetS) is associated with a pro-inflammatory state and endothelial dysfunction that places subjects with MetS at a higher risk of atherosclerosis. Inflammatory biomarkers are raised in patients at risk of developing cardiovascular diseases. In the current study, we aimed to examine the possible association between MetS and serum soluble adhesion molecules, hs-CRP, uric acid, and the genetic variations related to vascular endothelial growth factor (VEGF) gene. In this cross-sectional study, participants were enrolled from the Mashhad stroke and heart atherosclerotic disorders (MASHAD) study. The International Diabetes Federation criteria were used to define the MetS. Cell adhesion molecules (CAM) and serum hs-CRP were measured by ELISA and PEG-enhanced immunoturbidimetry method, respectively. We used a logistic regression analysis to determine independent associations of CAMs with the VEGF polymorphisms and MetS. Two hundred and 59 participants with and without MetS were enrolled. Participants with MetS and DM had a significantly higher serum E-selectin level (p < 0.05). Participants with a high serum E-selectin level had higher levels of hs-CRP, FBG, TG, uric acid, BMI and lower levels of serum HDL-C (p < 0.05). Interestingly, individuals with MetS with a genetic variant of the VEGF gene (rs6921438) had higher level of serum ICAM-1 (p = 0.04). There were significant associations between serum E-selectin concentrations and the presence of MetS, and its risk factors. Moreover, we demonstrated that MetS subjects with the rs6921438 genetic variant had a higher serum level of ICAM-1 (p < 0.05).


Assuntos
Moléculas de Adesão Celular/genética , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Moléculas de Adesão Celular/análise , Moléculas de Adesão Celular/sangue , Colesterol/análise , Colesterol/sangue , Estudos Transversais , Diabetes Mellitus/sangue , Selectina E/sangue , Selectina E/genética , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue , Ácido Úrico/análise , Ácido Úrico/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
J Colloid Interface Sci ; 560: 208-212, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31670018

RESUMO

In this article, we report the simultaneous determination cholesterol (CL), ascorbic (AA) acid and uric acid (UA) at a carbon paste electrode (CPE) modified with copper oxide decorated reduced graphene (CuO-rGR), with 1-methyl-3-octylimidazolium tetrafluoroborate (1M3OIDTFB) as a binder. The electrode, CuO-rGR/1M3OIDTFB/CPE, showed remarkable sensitivities towards the determination of the analytes, and well defined and clearly separated oxidation peaks were obtained during their simultaneous analysis in a buffer solution at pH 7.4. The differences observed between their peaks potentials are as follows: 430 mV (between CL and AA), 270 mV (between AA and UA) and 700 mV (between CL and UA). The morphologies and structure properties of the CuO-rGR were investigated by FESEMD and EDAX methods. The CuO-rGR/1M3OIDTFB/CPE displayed linear response in the concentration ranges 0.04-300.0 µM, 0.04-240.0 µM and 0.4-400.0 µM for CL, AA and UA with the detection limits 9.0 nM, 9.0 nM and 0.08 µM, respectively. The CuO-rGR/1M3OIDTFB/CPE displayed high performance for the determination of CL, AA and UA in real samples.


Assuntos
Ácido Ascórbico/análise , Colesterol/análise , Eletroquímica , Eletrodos , Líquidos Iônicos/química , Nanocompostos/química , Ácido Úrico/análise , Técnicas Biossensoriais , Carbono/química , Cobre/química , Grafite/química , Limite de Detecção , Oxirredução
13.
PLoS One ; 14(12): e0223189, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31809516

RESUMO

BACKGROUND: Dyslipidemia is a leading risk factor for atherosclerotic cardiovascular disease. There are few published epidemiological data regarding dyslipidemia in Africa. We determined full lipid and apolipoprotein profiles and investigated factors associated with lipid levels in urban and rural populations of north-western Tanzania and southern Uganda. METHODS: We conducted a cross-sectional survey of randomly-selected, community-dwelling adults (≥18yrs) including five strata per country: one municipality, two district towns and two rural areas. Participants were interviewed and examined using the World Health Organization STEPwise survey questionnaire. Serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoproteins were measured. Factors associated with mean lipid levels were assessed by multivariable linear regression. Framingham 10-year cardiovascular risk scores were calculated with and without lipids. RESULTS: One-third of adults in the study population had dyslipidemia. Low high-density lipoprotein cholesterol affected 32-45% of rural adults. High total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were found in <15% of adult population in all strata, but were more common in urban adults. Factors independently associated with higher mean low-density lipoprotein cholesterol and apolipoprotein B were female gender, older age, higher education, higher income, obesity, and hypertension. Framingham cardiovascular risk scores with and without lipids yielded similar results and 90% of study subjects in all strata were classified as "low risk". Among older adults (>55 years), 30% were classified as "high" or "very high" risk. CONCLUSIONS: Dyslipidemias are common among adults in north-western Tanzania and southern Uganda affecting one third of adult population. Overall, cardiovascular risk scores are low but high risk scores are common with older adults. Health services designed and equipped to diagnose and treat dyslipidemia are urgently needed.


Assuntos
Doenças Cardiovasculares/epidemiologia , Dislipidemias/epidemiologia , Adulto , Apolipoproteínas/análise , Apolipoproteínas/sangue , Doenças Cardiovasculares/sangue , Sistema Cardiovascular/fisiopatologia , Colesterol/análise , Colesterol/sangue , HDL-Colesterol/análise , HDL-Colesterol/sangue , LDL-Colesterol/análise , LDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/sangue , Feminino , Humanos , Hipertensão/fisiopatologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade , Prevalência , Fatores de Risco , População Rural , Inquéritos e Questionários , Tanzânia/epidemiologia , Triglicerídeos/análise , Triglicerídeos/sangue , Uganda/epidemiologia , População Urbana
14.
J Chromatogr Sci ; 58(1): 53-59, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31867607

RESUMO

A high-performance liquid chromatography method with evaporative light-scattering detection (ELSD) was performed for simultaneous determination of dipalmitoyl phosphatidylglycerol (DPPG), dierucoyl phosphatidylcholine (DEPC) and cholesterol in propofol liposome by the pretreatment of alkaline hydrolysis (temperature, concentration of KOH anhydrous ethanol solution and reaction time were 90°C, 1 mol · L-1 and 10 min, respectively). The analysis was carried out on an Agilent TC-C18 column (4.6 mm × 250 mm, 5 µm) with isocratic elution of methanol and 0.1% acetic acid aqueous solution (95:5, v/v) at a flow rate of 1.0 mL · min-1. The column temperature was 30°C. The drift tube temperature of the ELSD system was set at 30°C, and the pressure of carrier gas was 350 KPa. The regression equation revealed a good linear relationship (r = 0.9990-0.9993) during the test ranges. The RSD of stability and repeatability (n = 6) was found to be less than 1.96 and 1.46%, respectively. The average recoveries ranged from 97.90 to 101.00%. The proposed method was validated and showed good precision, stability, repeatability and recovery, which indicated that the method could be readily utilized as a quality evaluation method for the determination of DPPG, DEPC and cholesterol in propofol liposome.


Assuntos
Colesterol/análise , Cromatografia Líquida de Alta Pressão/métodos , Lipossomos/química , Fosfatidilcolinas/análise , Fosfatidilgliceróis/análise , Propofol/química , Hidrólise , Reprodutibilidade dos Testes , Temperatura
15.
Actual. osteol ; 15(3): 214-224, Sept-Dic. 2019. graf, tab
Artigo em Espanhol | LILACS | ID: biblio-1116039

RESUMO

En la Argentina, las embarazadas presentan alta prevalencia (80%) de hipovitaminosis D y de sobrepeso u obesidad (27,4%). Ambas condiciones pueden aumentar la morbimortalidad materno-fetal. Bajos niveles de vitamina D se han relacionado con aumento del colesterol total, LDL, triglicéridos (Tg) y descenso de HDL. Objetivo: evaluar los niveles de 25-hidroxivitamina D (25OHD) y su relación con el perfil lipídico en pacientes embarazadas de alto riesgo. Materiales y métodos: estudio de corte transversal entre septiembre de 2016 y abril de 2017. Se excluyeron pacientes que recibieron suplementos de vitamina D, con disfunción tiroidea no compensada, malabsorción, insuficiencia cardíaca, renal o hepática y dislipidemia familiar. Niveles circulantes de 25OHD < 30 ng/ml se consideraron hipovitaminosis. Resultados: se evaluaron 86 embarazadas de 29,3 ± 7,1 años durante la semana 28 ± 6,5. El IMC pregestacional fue 28,3 ± 6,5 kg/m2 y la ganancia de peso 7 ± 4,3 kg. Perfil lipídico: colesterol total 240 ± 54 mg/dl; LDL 156 ± 54 mg/dl; HDL 66 ± 15 mg/dl; Tg 204 ± 80 mg/dl. La media de 25OHD fue de 23,8 ± 9 ng/ml, con una prevalencia de hipovitaminosis D de 77,9 %. Las pacientes con hipovitaminosis D presentaron mayores valores de colesterol total y LDL (p < 0,05), con tendencia no significativa a presentar mayores valores de Tg. Conclusión: en embarazadas de alto riesgo se observó una alta prevalencia de hipovitaminosis D, asociada con mayores concentraciones de colesterol total y LDL. (AU)


In Argentina, pregnant women have a high prevalence (80 %) of hypovitaminosis D and verweight/obesity (27.4%), conditions that can increase maternal-fetal morbidity and mortality. Low levels of 25-hydroxyvitamin D (25OHD) have been linked to an increase in total cholesterol, LDL cholesterol, triglycerides (TG) and a decrease in HDL cholesterol. Objective: to evaluate the levels of vitamin D and its relationship with the lipid profile in high risk pregnant patients. Materials and methods: cross-sectional study between September 2016 and April 2017. Patients who received vitamin D supplements or had non-compensated thyroid dysfunction, malabsorption, heart failure, renal or hepatic failure, or familial dyslipidemia were excluded. Hypovitaminosis D was defined as a circulating level of 25OHD < 30 ng/ml. Results: We assessed 86 women of 29.3 ± 7.1 years during pregnancy week 28 ± 6.5. Pre-gestational BMI was 28.3 ± 6.5 kg/m2. Their weight gain was 7 ± 4.3 kg. Lipid profile: total cholesterol 240 ± 54 mg/dl; LDL cholesterol 156 ± 54 mg/dl; HDL cholesterol 66 ± 15 mg/dL; TG 204 ± 80 mg/dl. The mean 25OHD level was 23.8 ± 9 ng/ml, with a 77.9 % prevalence of hypovitaminosis D. Patients with hypovitaminosis D had higher values of total cholesterol and LDL cholesterol (p<0.05), and a non-significant trend toward higher triglyceridemia. Conclusion: A high prevalence of hypovitaminosis D, associated with high total and LDL cholesterol was found in high risk pregnant women. (AU)


Assuntos
Humanos , Feminino , Gravidez , Adulto , Adulto Jovem , Deficiência de Vitaminas/metabolismo , Vitamina D/metabolismo , Gravidez de Alto Risco/metabolismo , Argentina/epidemiologia , Deficiência de Vitaminas/sangue , Deficiência de Vitaminas/epidemiologia , Vitamina D/análise , Vitamina D/sangue , Estudos Epidemiológicos , Índice de Massa Corporal , Colesterol/análise , Colesterol/sangue , Indicadores de Morbimortalidade , Saúde Pública/estatística & dados numéricos , Estudos Transversais/estatística & dados numéricos , Diabetes Gestacional/metabolismo , Gravidez de Alto Risco/sangue , Dislipidemias/metabolismo , Sobrepeso/metabolismo , Trabalho de Parto Prematuro/metabolismo , LDL-Colesterol/análise , LDL-Colesterol/sangue , Obesidade/metabolismo
16.
Clín. investig. arterioscler. (Ed. impr.) ; 31(6): 251-260, nov.-dic. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-185150

RESUMO

Introduction: High Density Lipoproteins (HDL) are dysfunctional in hypercholesterolemia patients. The hypothesis was tested that nicotinamide (NAM) administration will influence HDL metabolism and reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT) in a murine model of hypercholesterolemia. Methods: Apolipoprotein E-deficient (KOE) mice were challenged with a high-fat diet for 4 weeks. The effect of different doses of NAM on cholesterol metabolism, and the ability of HDL to promote m-RCT was assessed. Results: The administration of NAM to KOE mice produced an increase (∼1.5-fold; P < 0.05) in the plasma levels of cholesterol, which was mainly accounted for by the non-HDL fraction. NAM produced a [3H]-cholesterol plasma accumulation (∼1.5-fold) in the m-RCT setting. As revealed by kinetic analysis, the latter was mainly explained by an impaired clearance of circulating non-HDL (∼0.8-fold). The relative content of [3H]-tracer was lowered in the livers (∼0.6-fold) and feces (> 0.5-fold) of NAM-treated mice. This finding was accompanied by a significant (or trend close to significance) up-regulation of the relative gene expression of Abcg5 and Abcg8 in the liver (Abcg5: 2.9-fold; P < 0.05; Abcg8: 2.4-fold; P = 0.06) and small intestine (Abcg5: 2.1-fold; P = 0.15; Abcg8: 1.9-fold; P < 0.05) of high-dose, NAM-treated mice. Conclusion: The data from this study show that the administration of NAM to KOE mice impaired m-RCT in vivo. This finding was partly due to a defective hepatic clearance of plasma non-HDL


No dispnible


Assuntos
Animais , Camundongos , Apolipoproteínas E/deficiência , Niacinamida/administração & dosagem , Colesterol/análise , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamento farmacológico , Apolipoproteínas E/administração & dosagem , Niacinamida/metabolismo , Colesterol/metabolismo , Gorduras na Dieta , Expressão Gênica , HDL-Colesterol
17.
J Med Food ; 22(12): 1199-1207, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31747330

RESUMO

This study researched the effects of Lactobacillus plantarum PMO 08 alone and combined with chia seeds on metabolic syndrome and parameters related to microbiota modulation and intestinal barrier integrity in obese mice fed high-fat diets (HFDs; 45% kcal fat). Male C57BL/6J mice were acclimated for a period of 2 weeks and then randomly separated into five groups depending on whether they received a normal diet (ND group), an HFD (HFD group), an HFD with L. plantarum (PMO group), an HFD with L. plantarum combined with chia seeds (PMOChia group), or an HFD with chia seeds (Chia group). Serum lipid profiles and related markers (cholesterol metabolism-related gene expression) were measured. Intestinal barrier integrity was assessed by measuring occludin mRNA expression of tight junction proteins. Mucosal bacteria were checked with quantitative reverse transcript polymerase chain reaction (qRT-PCR). After 16 weeks of feeding, the PMO group showed significantly lower serum total cholesterol, low-density lipoprotein cholesterol levels, atherogenic index, and cardiac risk factors compared to the HFD group. Moreover, the hepatic mRNA expression of SREBP2 (sterol regulatory element binding protein 2), a protein related to cholesterol metabolism, was significantly downregulated in the PMO group. We also found a positive synergistic effect in the PMOChia group, as manifested by the hepatic mRNA expression of hepatic CYP7A1 (cholesterol 7α-hydroxylase), strengthening of the gut barrier function, and the promotion of more L. plantarum in the colonic mucosa than in either the HFD or PMO group. In conclusion, our results indicate that PMO 08 may protect against metabolic syndrome by exerting effects on the regulation of lipid metabolism. Although the effects of chia seeds alone remain uncertain based on this experiment, its combination with PMO 08 was demonstrated to improve multiple beneficial effects of PMO 08 in obese mice fed HFD, which is a promising possibility for future research.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Lactobacillus plantarum/fisiologia , Síndrome Metabólica/terapia , Salvia/química , Sementes/química , Animais , Peso Corporal , Colesterol/análise , Colesterol 7-alfa-Hidroxilase/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Intestinos/microbiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Probióticos/uso terapêutico , RNA Mensageiro/metabolismo , Fatores de Risco , Proteínas de Junções Íntimas/metabolismo , Triglicerídeos/análise
18.
J Nutr Sci Vitaminol (Tokyo) ; 65(5): 421-429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666479

RESUMO

Diosgenin (Dio) is a steroid sapogenin found in plants such as Dioscorea species, and is recognized as a phytochemical against various disorders as well as a natural precursor of steroidal drugs. The present study used rats fed high-cholesterol (Chol) diets supplemented with or without 0.5% Dio for 6 wk to investigate the effects of dietary Dio on lipid metabolism. Dio supplementation significantly increased serum high-density lipoprotein Chol concentrations and fecal Chol content, and significantly decreased fecal bile acid content compared rats fed a high-Chol diet alone, showing that dietary Dio may facilitate excretion of Chol rather than bile acids. A reduction in the liver triglyceride content and intra-abdominal visceral fat was observed in Dio-supplemented rats. Interestingly, dietary Dio also significantly increased the skeletal muscle-fiber diameter and area in the thigh muscles of the rats. Mouse myoblast-derived C2C12 cells were used to examine whether Dio directly affected skeletal muscle. Dio promoted fusion of myoblasts into multinucleated cells or myotubes. Furthermore, in myotube C2C12 cells, protein levels of phosphorylated AMP-activated protein kinase (AMPK) increased with Dio treatment in a dose-dependent manner. These results indicate that Dio may not only induce myoblast fusion and enhance skeletal muscle as an energy expenditure organ, but may also activate the catabolic pathway via AMPK in skeletal muscle cells. Thus, these effects of Dio on skeletal muscles may contribute to inhibition of visceral fat accumulation.


Assuntos
Suplementos Nutricionais , Diosgenina/administração & dosagem , Hipercolesterolemia/terapia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Ácidos e Sais Biliares/análise , Colesterol/análise , HDL-Colesterol/sangue , Dieta Hiperlipídica , Fezes/química , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipertrofia , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Ratos , Coxa da Perna/patologia , Triglicerídeos/análise
19.
Anal Chim Acta ; 1089: 115-122, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31627808

RESUMO

Cholesterol is related to many health diseases and is considered as a metabolic disorder biomarker. This compound, present in all food products of animal origin, can also be used as food authentication biomarker. In this work and for the first time, positional 13C isotope contents were determined for such a high molecular weight compound. This was possible by means of NMR using adiabatic refocused INEPT. In order to test the potential of this approach for discrimination, hen eggs from different origins were collected. Quantitative extraction of egg yolk cholesterol was optimized, and partial reduced molar fractions of its different 13C isotopomers were used as predictors in discriminant analysis. Compared with the global 13C isotopic composition determined using isotope ratio monitoring by Mass Spectrometry, the relative content of cholesterol 13C isotopomers added valuable power to sample classifications according to their origins. This study paves the way to isotopomics of other steroids and similar molecular weight compounds.


Assuntos
Colesterol/análise , Criação de Animais Domésticos/classificação , Animais , Biomarcadores/análise , Biomarcadores/química , Isótopos de Carbono/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/métodos , Galinhas/classificação , Colesterol/química , Colesterol/isolamento & purificação , Gema de Ovo/química , Extração Líquido-Líquido , Reprodutibilidade dos Testes
20.
J Food Sci ; 84(11): 3075-3082, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599971

RESUMO

The hypocholesterolemic effect of amaranth was studied in male Wistar rats fed a high-fat diet that was supplemented with amaranth flour, AF, or isolated protein, AI. Likewise, an in vitro test was carried out, in which the capacity of the AI, AF, the digested isolate, DAI, and the digested amaranth flour, DAF, to displace the cholesterol of the model micelles was evaluated. The in vivo results showed an increase in the excretion of cholesterol through feces (77% for AF7; 23% and 108% for AI30 and AF30, respect control) and a decrease in the content of hepatic cholesterol (98% for AF7; 96% and 53% for AI30 and AF30 respect control); whereas in vitro it was shown that both AF and DAF have greater power to displace cholesterol than the AI and DAI (IC50 0.1, 0.71, 0.2, and 2.1 for AF, DAF, AI, and DAI, respectively). These evidences show that the proteins and fibers of amaranth have an effect on cholesterol metabolism. PRACTICAL APPLICATION: Nowadays, consumers give great importance to the effect that food has on health. The results shown in this work evidence the potential hypocholesterolemic activity presented by amaranth, this is of great importance due to the increase in the incidence of dyslipidemia in the world population and the importance of amaranth as a nonextensive crop of excellent agronomic, nutritional, and bioactive properties suitable for preparation of functional foods.


Assuntos
Amaranthus/química , Anticolesterolemiantes/administração & dosagem , Dieta Hiperlipídica , Animais , Anticolesterolemiantes/análise , Colesterol/análise , Colesterol/metabolismo , Colesterol na Dieta , Fezes/química , Fígado/química , Masculino , Ratos , Ratos Wistar
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