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1.
Anal Bioanal Chem ; 412(4): 805-810, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31858169

RESUMO

Recently, pre-analytical, analytical, and post-analytical issues have been addressed to implement biofluid FTIR spectroscopy as a novel diagnostic tool in the clinical setting. Although hemolysis, icterus, and hyperlipidemia are known to interfere with colorimetric and turbidimetric biochemical methods, there are no data on their impact on serum/plasma FTIR spectra. This study aimed at investigating the impact of hemoglobin, bilirubin, and triglycerides concentrations on plasma spectral analysis. Plasma samples with high concentrations of hemoglobin, conjugated bilirubin, or triglycerides were studied. To mimic the various concentrations observed in clinical setting, samples were diluted using normal plasma and analyzed using high-throughput FTIR spectroscopy. Hemolytic, icteric, and hyperlipidemic plasma spectra were compared with control plasma spectra. Unsupervised analysis of all spectra was performed using principal component analysis. The comparison between control and hemolytic plasmas did not show spectral differences in the range of hemoglobin concentrations observed in spurious or pathological hemolysis. By contrast, spectra from lipidemic plasmas had different spectral profiles compared with control plasma, exhibiting increased absorbance in lipid bands. Differences in the same spectral regions were observed in spectra from icteric plasma, which may be explained by the hyperlipidemia associated with cholestasis. PCA did not discriminate between control and hemolytic plasmas up to 1 g/L hemoglobin but confirmed the interference of bilirubin and triglycerides concentrations on spectral classification. Our results show that hemolysis does not have an impact on the plasma spectral profile except for high concentrations of hemoglobin rarely observed in clinical practice, whereas icterus and hyperlipidemia constitute significant confounding factors. Graphical abstract.


Assuntos
Plasma/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Bilirrubina/sangue , Hemoglobinas/análise , Hemólise , Humanos , Hiperlipidemias/sangue , Icterícia/sangue , Triglicerídeos/sangue
2.
Eur J Endocrinol ; 182(3): 255-264, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31863690

RESUMO

Background/objective: Data on metabolic impairments in Cushing's syndrome and GH deficiency all suggest that the relationship between cortisol and GH/IGF-I axis in obesity may have a role in the related diseases. However, studies focusing only on one of these hormones are often controversial in paediatrics. We aimed to explore the simultaneous relationship between cortisol and IGF-I with the metabolic alterations in paediatric obesity. Subjects/methods: Retrospective cross-sectional study in a tertiary care center. We recruited 876 (441 males and 435 females) overweight and obese children and adolescents. A complete clinical and biochemical evaluation including OGTT was performed. Cortisol and IGF-I SDS were divided in quartiles and then crossed to explore the reciprocal influence of high/high, low/low, and high/low levels of each one on the metabolic alterations of obesity. Results: Subjects in the higher quartiles of IGF-I-SDS and cortisol had an increased risk of hypertension, hypercholesterolemia, high levels of triglycerides, and reduced HDL cholesterol. Diversely, lower IGF-I-SDS quartiles were associated with higher blood glucose, insulin, insulin resistance, and reduced insulin sensitivity levels with the rise of cortisol quartiles. Conclusions: We observed that apart from glucose metabolism that is associated with low IGF-I and high cortisol levels, the other parameters known to be associated with increased cardiovascular risk were related to high levels of both IGF-I and cortisol, even if within normal range. Cortisol and IGF-I play a complex role in the comorbidities of obesity, and the evaluation of both variables could clarify some of the discordant results.


Assuntos
Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/análise , Obesidade/metabolismo , Sobrepeso/metabolismo , Adolescente , Glicemia/metabolismo , Criança , Colesterol/sangue , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/epidemiologia , Hipertensão/sangue , Hipertensão/epidemiologia , Resistência à Insulina , Masculino , Estudos Retrospectivos , Risco , Triglicerídeos/sangue
3.
PLoS One ; 14(12): e0226763, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877157

RESUMO

BACKGROUND: To investigate the association of systemic, serum lipids and genetic variants in the high-density lipoprotein (HDL) metabolic pathway with polypoidal choroidal vasculopathy (PCV) in China. METHODS: The case-control study was included 150 controls and 66 cases with PCV. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), apolipoprotein A1 (APOA1), apolipoprotein B (APOB) together with systemic risk factors including gender, hyperlipidemia, diabetes mellitus (DM), hypertension, coronary artery disease (CAD) and asthma were identified. All subjects were genotyped for four single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway: rs10468017 of hepatic lipase (LIPC), rs12678919 of lipoprotein lipase (LPL), rs3764261 and rs173539 of cholesterol ester transfer protein (CETP) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Student's t-tests, chi-square tests, anova and logistic regression were used to evaluate associations. RESULTS: Hyperlipidemia was a risk factor (odds ratio (OR) = 1.19, P = 0.001) for PCV. HDL, LDL and APOB levels were associated with PCV (OR = 0.001, P = 0.004; OR = 0.099, P = 0.010; OR = 0.839, P = 0.018). Higher level of TC was potently associated with increased risk of PCV (OR = 109.8, P = 0.000). LIPC rs10468017 was a risk factor for PCV (OR = 11.68, P = 0.000). CETP rs3764261 conferred a decreased risk for PCV (OR = 0.08, P = 0.000). No associations of LPL rs12678919 or CETP rs173539 with PCV were found. Mean level of HDL increased with T allele of the CETP gene (p = 0.026): 1.24 mmol/L (±0.31) for the GG genotype and 1.66 mmol/L (±0.54) for the TT genotype. Additionally, T allele was associated with the following increase in APOA1: 136.78 mg/dl (±20.53) for the CC genotype and 149.57 mg/dl (±22.67) for the TT genotype of LIPC and 137.91 mg/dl (±20.36) for the GG genotype and 162.67 mg/dl (±22.50) for the TT genotype of CETP gene. CONCLUSION: Our study suggested that the significant association was found between hyperlipidemia, the serum levels of TC, HDL, LDL and APOB and PCV. The result of present study also showed that the association of LIPC rs10468017 and CETP rs3764261 with PCV.


Assuntos
Hiperlipidemias/sangue , Lipídeos/sangue , Lipoproteínas/sangue , Doenças Vasculares/sangue , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/genética , Lipoproteínas/genética , Lipoproteínas/metabolismo , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Doenças Vasculares/epidemiologia , Doenças Vasculares/genética , Doenças Vasculares/metabolismo
4.
J Diabetes Res ; 2019: 8507453, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583253

RESUMO

Background: Many drugs are commercially available for use in the management of diabetes. However, their side effects and high costs underscore the need for herbal alternative drugs. Trigonella foenum-graecum is one of the medicinal plants which are important in the management of diabetes mellitus. This study investigated the effect of Trigonella foenum-graecum seed powder solution on the lipid profile of newly diagnosed type II diabetic patients. Methods: A total of N = 114 newly diagnosed type II diabetic patients without any significant diabetes complication were selected. They were grouped into two groups: the treatment group (n = 57) consumed 25 g Trigonella foenum-graecum seed powder solution orally twice a day for one month and the second group is the control (n = 57) which receives metformin. Blood sample was collected from each participant by a medical technologist/technician before and after the study. Lipid profile was analyzed by using Mindray BS 200E fully automated clinical chemistry analyzer. Result: By the end of the intervention period, the treatment group showed significantly lower total cholesterol level by 13.6% as compared with the baseline level (219.1 ± 35.51 vs. 189.29 ± 29.06, P < 0.001) and the control group (189.29 ± 29.06 vs. 208.2 ± 40.2, P < 0.001); triglyceride level also reduced by 23.53% compared with the baseline level (256.1 ± 15.4 vs. 195.8 ± 82.95, P < 0.001) and compared with the control group (195.8 ± 82.95 vs. 244.1 ± 96.9, P < 0.05); and low-density lipoprotein cholesterol level also reduced by 23.4% as compared to the baseline level (137.9 ± 26.9 vs. 105.6 ± 24.2, P < 0.001) and the control group (between groups) (105.6 ± 24.2 vs. 144.1 ± 23.3, P < 0.001), but the treatment group showed significantly increased high-density lipoprotein cholesterol level by 21.7% as compared to the baseline level, within group (37.8 ± 1.51 vs. 48.3 ± 11.9, P < 0.001), and the control group, between groups (48.3 ± 11.9 vs. 36.01 ± 9.5, P < 0.001). However, lipid profile levels in the control group were not significantly changed. Conclusion: The present study showed that the administration of Trigonella foenum-graecum seed powder solution had pronounced effects in improving lipid metabolism in type II diabetic patients with no adverse effects. Therefore, Trigonella foenum-graecum seed may provide new alternatives for the clinical management of type II diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Extratos Vegetais/uso terapêutico , Trigonella , Adulto , Idoso , Glicemia , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hiperlipidemias/sangue , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Sementes , Resultado do Tratamento
5.
Biomed Pharmacother ; 119: 109410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518877

RESUMO

AIMS: The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin. MATERIALS AND METHODS: ApoE-/- male mice were divided randomly into control, streptozocin-induced diabetes mellitus and metformin groups. Metabolic parameters, atherosclerotic lesion, activation of NLRP3 inflammasomes and related signaling pathways were detected. THP-1-differentiated macrophages were used in in vitro experiments. RESULTS: Compared with control mice, increased plasma lipids and proinflammatory interleukin-1ß, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein. Treatment with metformin alleviated diabetes-induced metabolic disorders and atherosclerosis, as well as NLRP3 inflammasomes activation and dysregulation of thioredoxin-1/thioredoxin-interacting protein. In vitro experiments showed that high glucose induced the accumulation of reactive oxygen species and activated NLRP3 inflammasomes, which was significantly suppressed by treatment with metformin or antioxidant N-acetyl-L-cysteine. Moreover, Compound C, an inhibitor of adenosine 5'-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation. Moreover, high glucose decreased thioredoxin-1 expression and increased thioredoxin-interacting protein expression, which was also reversed by metformin. CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Diabetes Mellitus/tratamento farmacológico , Inflamassomos/metabolismo , Metformina/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Adenilato Quinase/metabolismo , Animais , Aorta/patologia , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/patologia , Glicemia/metabolismo , Proteínas de Transporte/metabolismo , Ativação Enzimática/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Lipídeos/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metformina/farmacologia , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo
6.
J Ayub Med Coll Abbottabad ; 31(3): 326-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535499

RESUMO

BACKGROUND: Hyperlipidemia is one of the major risk factors of cardiovascular diseases. In addition to current therapeutic strategies, a lot of work is being done on nutraceutical management of this condition. This study was designed to assess the effect of date seed powder on lipid profile of diet induced hyperlipidemic rabbits. METHODS: Thirty male rabbits were divided into five groups, having six animals in each. One group was given normal rabbit chow throughout the study period of eight weeks. The remaining four groups were fed high fat diet (4% coconut oil and 1% cholesterol powder) for first four weeks in order to induce hyperlipidemia. After first four weeks, 2% date seed powder of three Pakistani varieties namely Dhakki, Khudrawi and Desi was added to the diet of three experimental hyperlipidemic groups for the next four weeks. Body weight and blood samples were taken at zero, 4th and 8th week of study. Serum was analyzed for total cholesterol, LDL-cholesterol, HDL-cholesterol and serum triglycerides. LDL/HDL ratio and AIP were calculated. RESULTS: It was observed that date seed powder of the three varieties significantly decreased total cholesterol, serum triglycerides and AIP. There was no significant change in body weight, HDL-cholesterol, and LDL/HDL ratio. LDL cholesterol was decreased significantly only by Khudrawi date seed powder. CONCLUSIONS: It was concluded that date seed powder has marked antihyperlipidemic properties. However, the difference in appearance, taste and price of different dates does not affect their lipid lowering capacity.


Assuntos
Hiperlipidemias , Hipolipemiantes/farmacologia , Lipídeos/sangue , Phoeniceae/química , Preparações de Plantas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/sangue , Hiperlipidemias/dietoterapia , Hiperlipidemias/etiologia , Masculino , Paquistão , Coelhos , Sementes
7.
Int J Mol Sci ; 20(14)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373312

RESUMO

Diabetic nephropathy is increasingly recognized as a major contributor to kidney failure in patients with obesity and type 2 diabetes. This study was designed to identify the molecular mediators of kidney injury associated with metabolic syndrome with or without hyperglycemia. We compared renal gene expression profiles in Zucker lean (ZL), Zucker obese (ZO), and Zucker diabetic (ZD) rats using cDNA microarray with quantitative verification of selected transcripts by real-time PCR. Compared to the 20-week-old ZL control (glucose: 110 ± 8 mg/dL), both prediabetic ZO (glucose: 157 ± 11 mg/dL) and diabetic ZD (glucose: 481 ± 37 mg/dL) rats displayed hyperlipidemia and kidney injury with a high degree of proteinuria. cDNA microarray identified 25 inflammation and injury-related transcriptomes whose expression levels were similarly increased in ZO and ZD kidneys. Among them, kidney injury molecule-1 (KIM-1) was found to be the most highly upregulated in both ZO and ZD kidneys. Immunofluorescence staining of kidney sections revealed a strong correlation between lipid overload and KIM-1 upregulation in proximal tubules of ZO and ZD rats. In cultured primary renal tubular epithelial cells (TECs), administration of saturated fatty acid palmitate resulted in an upregulation of KIM-1, osteopontin, and CD44, which was greatly attenuated by U0126, an inhibitor of extracellular signal-regulated kinase (ERK)1/2. Moreover, knockdown of KIM-1 by siRNA interference inhibited palmitate-induced cleaved caspase-3, osteopontin, and CD44 proteins in primary TECs. Our results indicate that KIM-1 expression is upregulated in renal lipotoxicity and may play an important role in fatty acid-induced inflammation and tubular cell damage in obesity and diabetic kidney disease.


Assuntos
Moléculas de Adesão Celular/metabolismo , Nefropatias Diabéticas/patologia , Hiperlipidemias/patologia , Túbulos Renais/patologia , Obesidade/patologia , Animais , Caspase 3/biossíntese , Moléculas de Adesão Celular/genética , Perfilação da Expressão Gênica , Receptores de Hialuronatos/biossíntese , Hiperglicemia/patologia , Hiperlipidemias/sangue , Túbulos Renais/lesões , Síndrome Metabólica/patologia , Osteopontina/biossíntese , Palmitatos/toxicidade , Proteinúria/urina , Interferência de RNA , RNA Interferente Pequeno/genética , Ratos , Ratos Zucker , Transcriptoma/genética
8.
Med Sci Monit ; 25: 6097-6103, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31413252

RESUMO

BACKGROUND To investigate the clinical characteristics of hypertriglyceridemia pancreatitis (HTGP) and evaluate the correlative risk factors for severe acute pancreatitis (SAP) in HTGP patients. MATERIAL AND METHODS A total of 1005 patients with acute pancreatitis (AP) admitted to Peking Union Medical College Hospital (PUMCH) from 1 Jan 2013 to 1 Aug 2018 were retrospectively reviewed. After screening, we enrolled 159 patients with HTGP and 172 with non-hypertriglyceridemia pancreatitis (NHTGP). We gathered and assessed demographic and blood biochemical information and analyzed the risk factors for SAP. RESULTS Age, serum amylase (AMY), lipase (LIP), and serum ionized calcium (Ca²âº) in the HTGP group were lower than in the NHTGP group (P<0.05), while high-sensitivity C-reactive protein (hsCRP), neutrophil-lymphocyte ratio (NLR), and body mass index (BMI) in the HTGP group were higher than in the NHTGP group (P<0.05). Among the HTGP patients, the results indicated that Ca²âº (OR=0.018, P<0.001, 95%CI: 0.002-0.129) was an independent protective factor for SAP, while higher CRP (OR=1.008, P=0.004, 95%CI: 1.003-1.013), NLR (OR=1.314, P<0.001, 95%CI: 1.161-1.488), and BMI (OR=1.597, P=0.002, 95%CI: 1.195-2.314) were independent risk factors for SAP. CONCLUSIONS Patients with HTGP had lower serum Ca²âº and higher hsCRP, NLR, and BMI, and these were associated with higher risk of developing SAP.


Assuntos
Proteína C-Reativa/metabolismo , Cálcio/sangue , Hiperlipidemias/sangue , Linfócitos/patologia , Neutrófilos/patologia , Pancreatite/sangue , Adulto , Amilases/sangue , Índice de Massa Corporal , Cálcio/metabolismo , Feminino , Humanos , Hiperlipidemias/complicações , Hipertrigliceridemia/complicações , Lipase/sangue , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Pancreatite/patologia , Estudos Retrospectivos , Fatores de Risco
9.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414755

RESUMO

BACKGROUND: The instructions of manufacturers of methodologies for anti-HIV-1/2 antibodies screening tests re-commend avoiding analyzing blood samples with hemolysis or lipemia, but they do not mention references about scientific studies evaluating their interference. The increased need for an opportune detection of HIV infection to avoid its spread has led to public health institutions including routine HIV screening even in internal medicine and emergency rooms. Nevertheless, these blood samples are usually associated with the presence of lipemia and/ or hemolysis, leaving doubt for probable misinterpretations. This fact highlights the need for applying verification techniques, established under the internal methodological conditions of each laboratory, in order to increase the coverage of HIV screening and to ensure the reliability of their results. METHODS: Following the ethics committee approval and patient's informed consent, a confirmed anti-HIV-1 positive human serum (undetectable viral load and p24 antigen, and stable total lymphocytes > 30%) was obtained. This work describes techniques for the semiquantitative analysis of anti-HIV antibodies of three commercial HIV-screening methodologies (immunochromatography, enzyme-immunoassay and chemiluminescence) and to deter-mine the detection limit of these screening tests, as well as evaluating the maximum concentration of total lipids and of free hemoglobin that do not interfere in the detection limits. RESULTS: The highest analyzed concentration of total lipid (870 mg/dL) did not interfere with the detection limits of anti-HIV-1 antibodies in any of the evaluated methodologies. Free hemoglobin presented interference at different concentrations depending on the methodology: immunochromatography (0.57 g/dL)), enzyme-immunoassay (8.6 g/dL), and chemiluminescence (11.5 g/dL)). CONCLUSIONS: Concentrations of lipemia above postprandial levels or hemolysis induced by experimental manipulation might not interfere with HIV-serological screening. Determining the maximum permissible limits of lipemia and hemolysis by each manufacturer or laboratory based on an internal evaluation of their serological methodology would increase the reliability of HIV-diagnosis in internal medicine and emergency rooms and in patients with dyslipidemia or physiological hemolysis.


Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , HIV-1/imunologia , Sorodiagnóstico da AIDS/métodos , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Infecções por HIV/virologia , Soropositividade para HIV/sangue , Soropositividade para HIV/virologia , HIV-1/fisiologia , Hemoglobinas/imunologia , Hemoglobinas/metabolismo , Hemólise/imunologia , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/imunologia , Limite de Detecção , Lipídeos/sangue , Lipídeos/imunologia , Sensibilidade e Especificidade
10.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121762, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31430685

RESUMO

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs), including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), play critical roles in numerous biochemical reactions. Our aim is to develop a rapid and sensitive method for simultaneous determination of ALA, EPA, DHA and DPA in the plasma of hyperlipidemic and normolipidemic subjects. METHODS: An ultra-high-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method of ALA, EPA, DHA, and DPA was developed with chlorzoxazone as the internal standard (IS). The analytes were separated on an Acquity BEH C18 column (2.1 mm × 100 mm, 1.7 µm) with gradient elution by acetonitrile and 0.1% ammonia water. ALA, EPA, DHA, DPA, and IS were determined by negative electrospray ionization (ESI-) with multiple reaction monitoring (MRM) at m/z 277.42/259.05, 301.20/257.00, 327.30/283.40, 329.24/285.32, and 168.03/132.02. A total of 80 normolipidemic subjects and 83 hyperlipidemic subjects, who underwent testing for plasma lipids, liver and kidney functions, and blood routine blood test (BRT), were enrolled. RESULTS: There was good linearity for ALA within 1-10 µg/mL, and EPA, DHA and DPA were within 0.125-10 µg/mL. The relative standard deviation (RSD) of precision was below 15%. The concentrations of ALA, EPA, DHA and DPA were 3.47 ±â€¯2.58, 0.41 ±â€¯0.26, 2.93 ±â€¯1.39 and 0.25 ±â€¯0.21 µg/mL, respectively, in normolipidemic subjects, increasing to 4.14 ±â€¯3.71, 0.57 ±â€¯0.46, 3.43 ±â€¯2.13, 0.27 ±â€¯0.25 µg/mL, respectively in hyperlipidemic subjects. Among them, only the EPA concentration was significantly different between two groups. There was a high correlation between ALA, EPA, DHA and DPA. CONCLUSION: We developed a rapid and sensitive method for simultaneously determination of ALA, EPA, DHA and DPA in hyperlipidemic and normolipidemic subjects. In hyperlipidemic and normolipidemic subjects, concentrations of ALA were highest, followed by DHA, EPA and DPA; there were high degrees of correlation between each value.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos Ômega-3/sangue , Hiperlipidemias/sangue , Espectrometria de Massas em Tandem/métodos , Adulto , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
11.
Drug Dev Ind Pharm ; 45(11): 1725-1739, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31432703

RESUMO

Objective and methods: This study predicted the nature of chitosan interactions and effects of this interaction on drug release mechanism in simvastatin-loaded chitosan nanoformulation using molecular docking, spectroscopic and thermal analysis. Significance: This work explains in depth the molecular mechanism of simvastatin and chitosan bond formation in nanoformulation. Results: The effective encapsulation and sustain release properties of chitosan were indicated by increase in melting endotherm of simvastatin. Intermolecular hydrogen bond between third hydroxyl group pyranone ring of simvastatin and amino group of chitosan represented the stability of active lactone moiety that was not cleaved during formulation which is prerequisite for biological activity. UV-vis spectroscopic characterization, shift in infrared vibration wavenumber of simvastatin and chitosan, ligand titration, 1HNMR and 13C-NMR analyses confirmed this interaction pattern. The pharmacokinetic evaluation in mouse model revealed the sustain release property of nanoformulation. Conclusion: Thus formation of intermolecular hydrogen bond in nanoformulation contributed to modified physicochemical properties and improved in vivo performance of simvastatin.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Hiperlipidemias/tratamento farmacológico , Sinvastatina/farmacocinética , Administração Oral , Animais , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Modelos Animais de Doenças , Esquema de Medicação , Composição de Medicamentos , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Camundongos , Simulação de Acoplamento Molecular , Nanopartículas/química , Tamanho da Partícula , Espectroscopia de Prótons por Ressonância Magnética , Sinvastatina/administração & dosagem , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443409

RESUMO

Oxidative stress is a common condition described in risk factors for cardiovascular disease. Betanin, a bioactive pigment from red beetroot demonstrates anti-inflammatory and antioxidant properties. The main aim of this study was to evaluate the short-term intake of betanin against oxidative stress in a rodent model, a common condition described in several risk factors for cardiovascular disease. Oxidative stress was induced in Wistar rats by a hyperlipidemic diet for 60 days, followed by betanin administration (20 mg·kg-1) through oral gavage for 20 days. Plasma biochemical parameters and antioxidant enzyme activities were evaluated. Lipid peroxidation and histopathological changes were determined in the liver. The hyperlipidemic diet caused hyperglycemia, hyperinsulinemia, insulin resistance, and increases in alanine transaminase and aspartate transaminase levels. Oxidative stress status was confirmed by reduction of antioxidant enzyme activities, increased lipid peroxidation, and liver damage. Purified betanin regulated glucose levels, insulin, and insulin resistance. Hepatic damage was reversed as evidenced by the reduction in alanine transaminase and aspartate transaminase levels and confirmed by histological analyses. Betanin reduced hepatic malondialdehyde and increased superoxide dismutase, catalase, and glutathione peroxidase activities. Short-term betanin intake modulated biochemical parameters, reversed hepatic tissue damage, and attenuated oxidative stress in Wistar rats.


Assuntos
Antioxidantes/administração & dosagem , Betacianinas/administração & dosagem , Hiperlipidemias/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Esquema de Medicação , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Insulina/sangue , Resistência à Insulina , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos Wistar , Fatores de Tempo
13.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443489

RESUMO

Blood lipids are an important biomarker of cardiovascular health and disease. Among the lipid biomarkers that have been widely used to monitor and predict cardiovascular diseases (CVD), elevated LDL and low HDL cholesterol (C), as well as elevated triglyceride-rich lipoproteins, deserve special attention in their predictive abilities, and thus have been the targets of several therapeutic and dietary approaches to improving lipid profiles. Among natural foods and nutraceuticals, dietary berries are a rich source of nutrients, fiber, and various types of phytochemicals. Berries as whole fruits, juices, and purified extracts have been shown to lower total and LDL-C, and increase HDL-C in clinical studies in participants with elevated blood lipids, type 2 diabetes or metabolic syndrome. This short review aimed to further discuss the mechanisms and magnitude of the lipid-lowering effects of dietary berries, with emphasis on reported clinical studies. Based on the emerging evidence, colorful berry fruits may thus be included in a healthy diet for the prevention and management of CVD.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/dietoterapia , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Frutas/química , Hiperlipidemias/dietoterapia , Hipolipemiantes/administração & dosagem , Lipídeos/sangue , Lipoproteínas/sangue , Síndrome Metabólica/dietoterapia , Compostos Fitoquímicos/administração & dosagem , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Hipolipemiantes/isolamento & purificação , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Compostos Fitoquímicos/isolamento & purificação
15.
Curr Pharm Biotechnol ; 20(10): 825-844, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264546

RESUMO

BACKGROUND: Cardiovascular Diseases (CVD) are, currently, the major contributor to global mortality and will continue to dominate mortality rates in the future. Hyperlipidemia refers to the elevated levels of lipids and cholesterol in the blood, and is also identified as dyslipidemia, manifesting in the form of different disorders of lipoprotein metabolism. These abnormalities may lead to the development of atherosclerosis, which can lead to coronary artery disease and stroke. In recent years, there is a growing interest in the quest for alternative therapeutic treatments based on natural products, offering better recovery and the avoidance of side effects. Recent technological advances have further improved our understanding of the role of epigenetic mechanisms in hyperlipidemic disorders and dietary prevention strategies. OBJECTIVE: This is a comprehensive overview of the anti-hyperlipidemic effects of plant extracts, vegetables, fruits and isolated compounds thereof, with a focus on natural products from the Mediterranean region as well as the possible epigenetic changes in gene expression or cardiometabolic signaling pathways. METHODS: For the purpose of this study, we searched the PubMed, Scopus and Google Scholar databases for eligible articles and publications over the last five years. The keywords included: "hyperlipidemia", "plant extract", "herbs", "natural products", "vegetables", "cholesterol" and others. We initially included all relevant articles referring to in vitro studies, animal studies, Randomized Controlled Trials (RCTs) and previous reviews. CONCLUSION: Many natural products found in the Mediterranean diet have been studied for the treatment of hyperlipidemia. The antihyperlipidemic effect seems to be dose and/or consumption frequency related, which highlights the fact that a healthy diet can only be effective in reversing disease markers if it is consistent and within the framework of a healthy lifestyle. Finally, epigenetic biomarkers are increasingly recognized as new lifestyle management tools to monitor a healthy dietary lifestyle for the prevention of hyperlipidaemic disorders and comorbidities to promote a healthy life.


Assuntos
Produtos Biológicos/farmacologia , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Epigênese Genética , Hiperlipidemias/prevenção & controle , Produtos Biológicos/isolamento & purificação , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Colesterol/sangue , Frutas/química , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/genética , Estilo de Vida , Verduras/química
16.
Int J Mol Sci ; 20(14)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31323736

RESUMO

OBJECTIVE: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/- hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/- hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/- hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/- hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. CONCLUSIONS: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/- hamsters, suggesting that the LDLR+/- hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.


Assuntos
Aterosclerose/sangue , Aterosclerose/patologia , Colesterol na Dieta , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/patologia , Animais , Aterosclerose/metabolismo , Colesterol/sangue , Cricetinae , Feminino , Hiperlipidemias/metabolismo , Hiperlipoproteinemia Tipo II/metabolismo , Masculino , Receptores de LDL/deficiência , Receptores de LDL/metabolismo
17.
Clin Lab ; 65(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307169

RESUMO

BACKGROUND: The current study aims to explore the changes of serum miR-587 level in patients with metabolic syndrome (MS) and analyze its clinical diagnostic value. METHODS: The serum levels of miR-587 in 50 patients with hyperglycemia, 50 patients with hyperlipidemia, and 50 healthy controls were detected by RT-qPCR. The diagnostic value of serum miR-587 was detected by ROC analy-sis and correlation analysis in MS. Dual luciferase reporter assay was carried out to determine the possible target gene of miR-587. RESULTS: The results of RT-qPCR showed that the relative content of serum miR-587 in patients with hyperglyce-mia and hyperlipidemia was 0.45 ± 0.30, 0.41 ± 0.30, compared with 1 ± 0.87 in healthy people. The area under ROC curve (AUC) of serum miR-587 in hyperglycemic patients was 0.830 (95% CI = 0.716 - 0.863, p < 0.001), with the sensitivity of 68.6% and specificity of 89.3%. The AUC of serum miR-587 in hyperlipidemia patients was 0.790 (95% CI = 0.759 - 0.851, p < 0.001), with the sensitivity of 78% and specificity of 89.7%. Correlation analysis showed that serum miR-587 level was negatively correlated with fasting blood glucose (FBG) (r = -0.291, p < 0.05), and negatively correlated with total cholesterol (TC) (r = -0.243, p < 0.01). Furthermore, dual luciferase reporter assay showed that PTEN was the target gene of miR-587. CONCLUSIONS: In summary the decreased expression of miR-587 in serum is a potential diagnostic marker and in-dependent risk factor in patients with MS.


Assuntos
Biomarcadores/sangue , Regulação da Expressão Gênica , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , MicroRNAs/sangue , Glicemia/metabolismo , Colesterol/sangue , Jejum/sangue , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Hiperglicemia/genética , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Hiperlipidemias/genética , Masculino , Síndrome Metabólica/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC
18.
Food Chem Toxicol ; 132: 110663, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279046

RESUMO

The objective was to investigate the hypolipidemic effect of polysaccharides from Fortunellamargarita (Lour.) Swingle (FMPS) in hyperlipidemic rats and the comparative relationship between in vitro and in vivo. After FMPS feeding, the body weight, liver and spleen index of the hyperlipidemic rats decreased significantly, in a dose-dependent manner. The content of triglyceride, total cholesterol, low density lipoprotein and serum non-esterified fatty acid decreased, and high density lipoprotein, and serum lipase significantly increased after FMPS feeding in hyperlipidemic rats. Notably, high-dose FMPS, exhibited effective hypolipidemic activity, as compared with that of simvastatin. Moreover, histopathological micrographs of hepatic tissue and blood vessel morphology indicated that the fat deposition in liver cells decreased, and the vascular endothelial cells were protected by FMPS. Furthermore, the activities of superoxide dismutase, total antioxidant capacity, glutathione peroxidase, and glutathione-S-transferase were enhanced, and the content of malondialdehyde was decreased by FMPS feeding in the hyperlipidemic rats. A concentration-dependent response was observed. Similarly to the hypolipidemic effect observed in vitro, the hypolipidemic effect of FMPS in hyperlipidemic rats was achieved by decreasing the lipid content and enhancing the activity of antioxidant enzymes. Thus, FMPS had a major role in regulating the lipid metabolism disorder in hyperlipidemic rats.


Assuntos
Hipolipemiantes/farmacologia , Polissacarídeos/farmacologia , Rutaceae/química , Animais , Antioxidantes/metabolismo , Peso Corporal , Dieta Hiperlipídica , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
19.
Lipids Health Dis ; 18(1): 157, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351498

RESUMO

BACKGROUND: The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, ß-sitosterol ester with linoleic acids and ß-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied. METHODS: Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with ß-sitosterol ester with linoleic acid, ß-sitosterol self-microemulsion, commercial ß-sitosterol health tablets and ß-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* < 0.05 and p** < 0.01 levels . RESULTS: The order of lowering blood lipid effect is listed as: SSSM> SELA-TSO > SSHT-TSO > SS-TSO, which shows that ß-sitosterolself-microemulsion have the highest treatment effect among the experimental groups. CONCLUSIONS: In this study, a new formulation of ß-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that ß-sitosterol self-microemulsion has a good blood lipid lowering effect.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Ácido Linoleico/farmacologia , Sitosteroides/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacologia , Fezes/química , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Lipídeos/sangue , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho do Órgão/efeitos dos fármacos , Sitosteroides/administração & dosagem , Sitosteroides/química , Comprimidos/administração & dosagem , Comprimidos/farmacologia
20.
Vopr Pitan ; 88(3): 44-52, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31265774

RESUMO

Changes in plasma levels of the main groups of cytokines and adipokines may correlate with the severity of metabolic disorders in hyperlipidemia and obesity. The aim of the study was to assess the significance of ghrelin, leptin, their ratio (L/Gh), and the cytokine profile as biomarkers at dietary-induced hyperlipidemia. Material and methods. We used 48 female Wistar rats with an initial body weight of 123±1 g, which were divided into 6 groups. Group 1 (control) received a balanced semi-synthetic diet according to AIN93; group 2 - diet with excess fat (30% by weight); group 3 - a diet with the addition of 20% fructose solution instead of drinking water, group 4 - a diet with excess fat and fructose, group 5 - a diet with added cholesterol (0.5%), group 6 - a diet with cholesterol and fructose. On the 64th day of the experiment, the mass of internal organs was determined; the levels of cytokines and adipokines in blood plasma were measured by multiplex immunoassay. Results and discussion. A decrease in the level of leptin was found in group 5 compared with the control and with groups 2, 4 and 6 groups (p<0.05). The lowest level of ghrelin was found in group 2 (p<0.05) against the background of high concentrations of leptin. Significant correlations were found between L/Gh and the total mass of animals (r=0.321; р=0.034), the relative mass of adipose tissue (r=0.439; р=0.003) and with the relative mass of the spleen (r=-0.460; р=0.003). In group 2, at the maximum L/Gh ratio, a significantly higher weight of adipose tissue was found, whereas in groups 3 and 5, at the lowest L/Gh ratio, the relative amount of total fat was the lowest. L/Gh ratio correlated with the level of monocyte chemotactic protein-1 (MCP-1), RANTES, IL-18 and macrophage colony-stimulating factor (M-CSF). The concentrations of IL-17, IL-18, IL-4, IL-5, MIP-3a, IFN-γ, M-CSF and RANTES in the experimental groups were reduced compared with the control, with the most pronounced effect in group 5 together with the lowest L/Gh ratio. Conclusion. The presence of a significant correlation between L/Gh ratio and changes in the weight of rats' body, spleen, adipose tissue, as well as levels of cytokines involved in inflammation regulation, confirms the importance of L/Gh ratio as a biomarker in an in vivo model of dyslipidemia.


Assuntos
Adipocinas/sangue , Tecido Adiposo/metabolismo , Citocinas/sangue , Alimentos Formulados/efeitos adversos , Hiperlipidemias , Obesidade , Animais , Biomarcadores/sangue , Feminino , Hiperlipidemias/sangue , Hiperlipidemias/induzido quimicamente , Obesidade/sangue , Obesidade/induzido quimicamente , Ratos , Ratos Wistar
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