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1.
Int J Obes (Lond) ; 47(11): 1081-1087, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37592059

RESUMO

INTRODUCTION: Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth. METHODS: The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings' first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm). RESULTS: From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002). CONCLUSION: Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, http://www. CLINICALTRIALS: com , NCT01698385.


Assuntos
Diabetes Gestacional , Obesidade Infantil , Criança , Feminino , Humanos , Gravidez , Colesterol , Sangue Fetal/química , Lipoproteínas/análise
2.
Proteomics ; 23(9): e2200364, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36624553

RESUMO

Extracellular vesicles (EVs) are lipid membrane vesicles released by live cells that carry a variety of biomolecules, including nucleic acids, lipids, and proteins. Recently, proteins in plasma-derived EVs have emerged as novel biomarkers with essential functions in the diagnosis and prognosis of human diseases. However, the current methods of isolating EVs from plasma often lead to coisolated impurities in biological fluids. Therefore, before performing any research protocol, the process of extracting EVs from plasma for proteomic analysis must be optimized. In this study, two EV isolation strategies, size exclusion chromatography (SEC) and SEC combined with ion exchange adsorption (SEC + IEA), were compared in terms of the purity and quantity of protein in EVs. Our results demonstrated that, compared to single-step SEC, SEC combined with IEA could produce plasma-derived EVs with a higher purity by decreasing the abundance of lipoprotein. Additionally, with MS analysis, we demonstrated that the combination approach maintained the stability and improved the purity of EVs in many plasma samples. Furthermore, by combining SEC with IEA, more cancer-associated proteins were detected in the plasma of various cancer samples.


Assuntos
Vesículas Extracelulares , Proteômica , Humanos , Proteômica/métodos , Adsorção , Troca Iônica , Vesículas Extracelulares/metabolismo , Cromatografia em Gel , Lipoproteínas/análise
3.
Int. j. cardiovasc. sci. (Impr.) ; 34(5,supl.1): 121-127, Nov. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1346340

RESUMO

Abstract The association between periodontitis and myocardial infarction remains unclear in the literature. Few studies have addressed periodontitis exposure as a predisposing factor for the development of myocardial infarction. Therefore, the present systematic review aims to analyze the association between periodontitis and myocardial infarction. This meta-analysis systematically searched MEDLINE, EMBASE, The Cochrane Controlled Trials Register, SCIELO, LILACS, CINAHL, Scopus, Web of Science and grey literature for studies estimating the association between periodontitis and myocardial infarction. Quality of evidence was assessed for all studies. The meta-analysis was conducted using random-effects models. Four of the six studies selected were included in the meta-analysis, including 1,035,703 subjects. The association between periodontitis and myocardial infarction was: RR: 5.99 (95% CI: 1.17-30.68), but with high heterogeneity (I2 = 100%; p <0.01). The results including only the highest quality articles, was lower: RR: 2.62 (95% CI: 1.47-4.70 3.83), but with lower heterogeneity (I2 = 85.5%; p < 0.01).The present systematic review with meta-analysis showed an association between periodontitis and acute myocardial infarction, but with a high level of heterogeneity.


Assuntos
Humanos , Periodontite/complicações , Infarto do Miocárdio/complicações , Pulpite/complicações , Aterosclerose/complicações , Lipoproteínas/análise , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade
4.
J Extracell Vesicles ; 10(10): e12122, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34429857

RESUMO

Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size-exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context-dependent and time-dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation. Using serial blood plasma samples from HIV and ovarian cancer patients (n = 10) we next show that EV carry a clinical context-dependent and/or time-dependent protein and small RNA composition, including miRNA and tRNA. In addition, differential analysis of blood plasma fractions provides a catalogue of putative proteins not associated with systemically circulating EV. In conclusion, the implementation of blood plasma fractionation allows to advance the biological understanding and biomarker development of systemically circulating EV.


Assuntos
Centrifugação com Gradiente de Concentração/métodos , Fracionamento Químico/métodos , Vesículas Extracelulares/química , Lipoproteínas/análise , Plasma/química , Proteoma , Biomarcadores/análise , Neoplasias da Mama/sangue , Neoplasias da Mama/química , Cromatografia em Gel , Feminino , Infecções por HIV/sangue , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/química
5.
Int J Lab Hematol ; 43(1): 123-130, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32892505

RESUMO

INTRODUCTION: Patients with COVID-19 are known to have a coagulopathy with a thrombosis risk. It is unknown whether this is due to a generalized humoral prothrombotic state or endothelial factors such as inflammation and dysfunction. The aim was to further characterize thrombin generation using a novel analyser (ST Genesia, Diagnostica Stago, Asnières, France) and a panel of haematological analytes in patients with COVID-19. METHODS: Platelet poor plasma of 34 patients with noncritical COVID-19 was compared with 75 patients with critical COVID-19 (as defined by WHO criteria) in a retrospective study by calibrated automated thrombography and ELISA. Patients were matched for baseline characteristics of age and gender. RESULTS: Critical patients had significantly increased fibrinogen, CRP, interleukin-6 and D-dimer compared to noncritical patients. Thrombin generation, in critical patients, was right shifted without significant differences in peak, velocity index or endogenous thrombin potential. Tissue plasminogen activator (tPA), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor (VEGF) were significantly increased in the critical versus noncritical patients. Critically ill patients were on haemodiafiltration (31%; heparin used in the circuit) or often received escalated prophylactic low-molecular weight heparin. CONCLUSION: These results confirm increased fibrinogen and D-dimer in critical COVID-19-infected patients. Importantly, disease severity did not increase thrombin generation (including thrombin-antithrombin complexes and prothrombin fragment 1 + 2) when comparing both cohorts; counter-intuitively critical patients were hypocoaguable. tPA, TFPI and VEGF were increased in critical patients, which are hypothesized to reflect endothelial dysfunction and/or contribution of heparin (which may cause endothelial TFPI/tPA release).


Assuntos
Testes de Coagulação Sanguínea/métodos , COVID-19/sangue , Pandemias , SARS-CoV-2 , Trombina/biossíntese , Trombofilia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Testes de Coagulação Sanguínea/instrumentação , COVID-19/complicações , Estado Terminal , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Lipoproteínas/análise , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Trombofilia/sangue , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Ativador de Plasminogênio Tecidual/análise , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
6.
Eur Rev Med Pharmacol Sci ; 24(17): 9147-9150, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32965006

RESUMO

OBJECTIVE: Familial hypercholesterolemia (FH) is an autosomal codominant genetic disorder associated with defective hepatic uptake of circulating low-density lipoproteins (LDL), which can lead to premature atherosclerotic cardiovascular disease (ASCVD). Evidence suggests elevated lipoprotein(a) (Lp(a)) levels in FH patients may also increase their ASCVD risk. We present a case series of 2 FH patients where a daughter has a higher ASCVD burden than her mother due to the daughter having elevated Lp(a). This underscores the importance of including Lp(a) in cascade lipid screening in FH patients and their first-degree relatives.


Assuntos
Aterosclerose/diagnóstico , Colesterol/análise , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteínas/análise , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
7.
Crit Rev Clin Lab Sci ; 57(7): 458-469, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32255405

RESUMO

Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is a potentially underdiagnosed inherited dyslipidemia associated with greatly increased risk of coronary and peripheral vascular disease. The mixed hyperlipidemia observed in this disorder usually responds well to appropriate medical therapy and lifestyle modification. Although there are characteristic clinical features such as palmar and tuberous xanthomata, associated with dysbetalipoproteinemia, they are not always present, and their absence cannot be used to exclude the disorder. The routine lipid profile cannot distinguish dysbetalipoproteinemia from other causes of mixed hyperlipidemia and so additional investigations are required for confident diagnosis or exclusion. A range of investigations that have been proposed as potential diagnostic tests are discussed in this review, but the definitive biochemical test for dysbetalipoproteinemia is widely considered to be beta quantification. Beta quantification can determine the presence of "ß-VLDL" in the supernatant following ultracentrifugation and whether the VLDL cholesterol to triglyceride ratio is elevated. Both features are considered hallmarks of the disease. However, beta quantification and other specialist tests are not widely available and are not high-throughput tests that can practically be applied to all patients with mixed hyperlipidemia. Using apolipoprotein B (as a ratio either to total or non-HDL cholesterol or as part of a multi-step algorithm) as an initial test to select patients for further investigation is a promising approach. Several studies have demonstrated a high degree of diagnostic sensitivity and specificity using these approaches and apolipoprotein B is a relatively low-cost test that is widely available on high-throughput platforms. Genetic testing is also important in the diagnosis, but it should be noted that most individuals with an E2/2 genotype do not suffer from remnant hyperlipidemia and around 10% of familial dysbetalipoproteinemia cases are caused by rarer, autosomal dominant mutations in APOE that will only be detected if the gene is fully sequenced. Wider implementation of diagnostic pathways utilizing apo B could lead to more rational use of specialist investigations and more consistent detection of patients with dysbetalipoproteinemia. Without the application of a consistent evidence-based approach to identifying dysbetalipoproteinemia, many cases are likely to remain undiagnosed.


Assuntos
Hiperlipoproteinemia Tipo III/diagnóstico , Hiperlipoproteinemia Tipo III/metabolismo , Hiperlipoproteinemia Tipo III/fisiopatologia , Colesterol/análise , Humanos , Laboratórios , Lipoproteínas/análise , Lipoproteínas VLDL/análise , Triglicerídeos/análise
8.
Methods Mol Biol ; 2009: 45-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31152394

RESUMO

Protein S-fatty-acylation, the covalent addition of a long-chain fatty acid, predominantly palmitate (S-palmitoylation), to cysteine, is a highly dynamic and regulated process that controls protein function and localization of membrane-associated proteins in eukaryotes. The analysis of S-fatty acylated peptides by mass spectrometry remains challenging due to the hydrophobic and potentially labile thioester linkage of the S-fatty acylated peptides.Here we describe an optimized protocol for the global analysis of S-palmitoylated proteins based on the combination of an alkyne-tagged chemical reporter of palmitoylation, alk-16 with hydroxylamine-selective hydrolysis of thioester bonds. This protocol decreased the number of false positive proteins and was applied to identify S-fatty acylation sites, providing modification sites for 44 proteins out of the 106 S-fatty acylated proteins identified.


Assuntos
Lipoproteínas , Lipoilação , Processamento de Proteína Pós-Traducional , Proteômica/métodos , Acilação , Células HeLa , Humanos , Lipoproteínas/análise , Lipoproteínas/metabolismo
9.
J Vet Diagn Invest ; 30(6): 878-886, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30175670

RESUMO

Changes in proportions of lipoprotein classes have been described in disease states in humans. In veterinary medicine, hyperlipidemia can cause complications, such as cutaneous xanthomas, liver disease, cholelithiasis, pancreatitis, glomerular disease, lipemia retinalis, or peripheral neuropathy, but there are few reports regarding lipoproteins in diseased animals. For canine serum, we partially validated continuous lipoprotein density profiling (CLPDP), a novel density gradient ultracentrifugation technique. We examined canine lipoproteins separated by CLPDP by transmission electron microscopy (TEM). We compared lipoprotein profiles between healthy control dogs ( n = 29) and dogs with exocrine pancreatic insufficiency (EPI; n = 28) using CLPDP. Dogs with EPI included those untreated (EPI-NT; n = 6) and those treated with enzyme supplementation (EPI-T; n = 22). Our preliminary assay validation showed that CLPDP was repeatable (CV = 11.2%) and reproducible (CV = 10.6%) in canine serum. The diameters of lipoproteins analyzed by TEM were similar to those reported previously. Dogs in the EPI-NT group had more severe dyslipidemia than dogs in the EPI-T group. Dogs in the EPI-T group had lipoprotein profiles similar to healthy control dogs. CLPDP might be a useful tool for evaluating dyslipidemia in dogs.


Assuntos
Centrifugação com Gradiente de Concentração/veterinária , Doenças do Cão/diagnóstico , Dislipidemias/veterinária , Insuficiência Pancreática Exócrina/veterinária , Lipoproteínas/análise , Animais , Centrifugação com Gradiente de Concentração/métodos , Cães , Dislipidemias/etiologia , Dislipidemias/terapia , Insuficiência Pancreática Exócrina/complicações , Insuficiência Pancreática Exócrina/diagnóstico , Feminino , Lipoproteínas/química , Lipoproteínas/ultraestrutura , Masculino
10.
Med Sci Monit ; 24: 6774-6780, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30252834

RESUMO

BACKGROUND The aim of this study was to compare androgen levels, endocrine and metabolic indices, and clinical findings in women with polycystic ovary syndrome (PCOS) in Uygur and Han ethnic groups from Xinjiang Province, China. MATERIAL AND METHODS Between January 2016 to May 2017 clinical data were collected from Uygur (N=82) and Han (N=100) women diagnosed with PCOS, including age, body mass index (BMI), the Ferriman-Gallwey (mFG) hirsutism score, and waist-to-hip ratio (WHR). Blood samples obtained from all study participants were used to measure androgenic steroid levels, including androgen, androstenedione, dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and the free androgen index (FAI). Endocrine indices measured included sex-hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and prolactin (PL). Metabolic indices measured included insulin, glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), triglyceride (TG), and low-density lipoprotein (LDL). RESULTS The FAI in Uygur women with PCOS (4.89) was significantly increased compared with Han women with PCOS (2.78) (p<0.05); androgen levels were significantly correlated with the FAI, glucose, insulin, TC, HDL, and LDL (p<0.05); androstenedione levels were positively correlated with glucose and insulin levels (p<0.05). In Han women with PCOS, androgen levels were negatively correlated with TG levels and positively correlated with TC levels (p<0.05); the FAI was positively correlated with glucose and insulin levels (p<0.05). CONCLUSIONS There were significant differences in androgen levels, endocrine, and metabolic indices in women with PCOS between the Uygur and Han ethnic groups from Xinjiang Province in China.


Assuntos
Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Adulto , Androgênios/análise , Androgênios/sangue , Androstanóis/análise , Androstanóis/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Pesos e Medidas Corporais , China , Etnicidade/genética , Feminino , Gonadotropinas Hipofisárias/análise , Gonadotropinas Hipofisárias/sangue , Humanos , Insulina/sangue , Resistência à Insulina , Lipoproteínas/análise , Lipoproteínas/sangue , Obesidade/sangue , Testosterona/sangue , Triglicerídeos/sangue
11.
Am J Cardiovasc Drugs ; 18(6): 503-511, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30144017

RESUMO

BACKGROUND: The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471). METHODS AND RESULTS: A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes. Target anticoagulation levels at T2 were more readily achieved in patients receiving enoxaparin compared to those receiving UFH (80.3 vs 18.2%, p < 0.0001). Increased levels of F1 + 2 and TAT measured at T2 were associated with the incidence of the composite ischemic endpoint (p = 0.04 and p = 0.03) and all-cause mortality (p < 0.0001 and p = 0.002). Release of F1 + 2 between T1 and T2 also predicted the composite ischemic endpoint (312 ± 513 vs 37 ± 292, p = 0.04) and net clinical outcome (185 ± 405 vs 3.2 ± 278, p = 0.03). CONCLUSIONS: During primary PCI, enoxaparin achieved therapeutic levels more frequently than UFH. Higher level of thrombin generation measured at the end of the PCI procedure was associated with more frequent ischemic events.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Antitrombina III , Biomarcadores , Ligante de CD40/sangue , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Fator Xa/análise , Feminino , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Lipoproteínas/análise , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Peptídeo Hidrolases/sangue , Protrombina/análise , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fator de von Willebrand/análise
12.
Adv Clin Exp Med ; 26(8): 1219-1224, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29264878

RESUMO

BACKGROUND: In patients with intracranial tumors, hypercoagulability is observed due to brain tissue and tumor cells being the source of tissue factor. OBJECTIVES: The aim of the study was to assess tissue factor (TF), tissue factor pathway inhibitor (TFPI) and protein C in the plasma and tumor tissue homogenate in patients with intracranial tumors. MATERIAL AND METHODS: The study included 77 patients; 24 patients were diagnosed with glioma, 20 patients with meningioma and 33 patients with metastatic tumors; mean age - 54 years. The material for the study was the plasma and tumor tissue homogenate sampled during surgery. The control group consisted of 30 controls; mean age - 51 years. In the plasma of all the participants and in tumor tissue homogenate, the concentrations of TF-Ag, TFPI-Ag and protein C activity, and the concentration of total protein were measured. The results were converted per mg of protein. RESULTS: In patients with intracranial tumors, elevated concentrations of TF-Ag, TFPI-Ag and protein C activity were noted, also after the conversion per mg of protein. A 100-fold higher concentration of TF per 1 mg of protein was found in tumor tissue compared to the patients' plasma. In tumor tissue homogenate, a lower TFPI concentration and a lower protein C activity were recorded. CONCLUSIONS: The study confirmed the essential prothrombotic properties in patients with intracranial tumors, expressed with an elevated TF level, as well as a tremendous amount of TF in tumor tissue homogenate derived from tumors. The elevated concentration of TFPI and protein C activity converted per mg of total protein should be analyzed in terms of their pleiotropic function, along with the participation in hemostasis control. It seems that the reduced protein C activity and low TFPI level are associated with the enormous TF value in tumor tissue homogenates.


Assuntos
Neoplasias Encefálicas/sangue , Lipoproteínas/análise , Proteína C/análise , Adulto , Idoso , Neoplasias Encefálicas/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboplastina/análise
13.
Minerva Stomatol ; 66(5): 212-225, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28707864

RESUMO

BACKGROUND: Oxidative stresses and dyslipidemia are an important risk factor in the development of coronary atherosclerotic complications like angina pectoris and myocardial infarction. The aim of this study was to find the relationship between the salivary lipid profile, lipid peroxidation and antioxidants and the periodontal health status of patients with acute coronary heart disease (CHD). METHODS: Forty patients who had experienced a recent attack of angina pectoris or myocardial infarction and another 40 noncardiac patients matched for age, sex and residence (control) were recruited. The lipid profile level, lipid peroxidation and antioxidant status were measured in the serum and saliva of all participants together with lactate dehydrogenase (LDH) and C-reactive protein. The studied parameters were then correlated with the periodontal status of the participant using the Clinical Periodontal Sum Score (CPSS). A multiple linear regression was used to assess the net effect of each set of independent variables on the outcome variable using SPSS-21. A P value ≤0.05 was considered statistically significant. RESULTS: Salivary total cholesterol, triglycerides, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, malondialdehyde, uric acid, superoxide dismutase and LDH levels increased with the upper tertile of the CPSS, while salivary high-density lipoprotein-cholesterol decreased with the upper tertile of the CPSS. CONCLUSIONS: Periodontal health status could be considered as an independent risk factor for acute CHD.


Assuntos
Antioxidantes/metabolismo , Doença das Coronárias/metabolismo , Lipídeos/análise , Estresse Oxidativo , Periodontite/metabolismo , Saliva/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Instável/epidemiologia , Angina Instável/metabolismo , Proteína C-Reativa/análise , Estudos de Casos e Controles , Comorbidade , Doença das Coronárias/epidemiologia , Feminino , Hemorragia Gengival/epidemiologia , Humanos , L-Lactato Desidrogenase/análise , Peroxidação de Lipídeos , Lipoproteínas/análise , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/metabolismo , Obesidade/epidemiologia , Periodontite/epidemiologia , Soro , Fatores Sexuais , Fumar/epidemiologia , Superóxido Dismutase/análise
14.
Methods Mol Biol ; 1600: 143-150, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28478565

RESUMO

The availability of convenient assays for the detection and quantification of pathogen-associated molecular patterns (PAMPs) is limited. In the case of lipopolysaccharide (LPS) the so-called LAL (limulus amebocyte lysate) test is available, an assay that is performed with the lysate of the blood of the horse shoe crab. Although a sensitive and convenient assay, it lacks specificity, since it is affected by other endotoxins like, for instance, fungal cell walls as well. Here, we describe a bioassay that can be used to detect and quantitate PAMPs in environmental samples. More specific we demonstrate the usage of TLR2 and TLR4/CD14/MD2 transfected Hek293 cells to quantitatively determine bacterial lipoproteins and LPS, respectively. We show the usefulness of these assays to measure LPS in tobacco before and after combustion.


Assuntos
Bioensaio/métodos , Lipopolissacarídeos/análise , Lipoproteínas/análise , Animais , Células HEK293 , Humanos
15.
AIDS ; 30(17): 2625-2633, 2016 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-27603288

RESUMO

OBJECTIVE: The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized HDL and LDL (HDLox and LDLox) contribute to HIV-1-related immune dysfunction. STUDY: In the AIDS Clinical Trials Group A5260, 234 HIV-infected antiretroviral therapy (ART)-naive participants were randomized to receive tenofovir-emtricitabine and protease inhibitors or raltegravir and had HIV-1 RNA less than 50 copies/ml by week 24 and thereafter. METHODS: Associations between biomarkers of inflammation (IL-6, high-sensitivity C-reactive protein and D-dimer), immune activation (sCD163, sCD14, soluble IL-2 receptor, CD38 and HLA-DR), inflammatory monocytes (CD14CD16), T-cell senescence (CD28 and CD57) and exhaustion (PD1), and HDLox, LDLox were assessed at entry and after ART (week 96) with Spearman (partial) correlations. RESULTS: HDLox declined and LDLox increased over 96 weeks of ART. Positive associations were observed at baseline and over time between HDLox (but not consistently for LDLox) and most markers of inflammation and immune activation (but not senescence/exhaustion), even after adjustment for multiple comparisons, demographics, entry CD4 cell count and HIV-1 RNA. HDLox was positively associated with IL-6 (r = 0.19 - 0.29, P < 0.01) and sCD163 (r = 0.14 - 0.41, P ≤ 0.04) at all time points. CONCLUSION: These prospective longitudinal data suggest that oxidized lipoproteins may contribute to persistent immune activation on ART.


Assuntos
Infecções por HIV/patologia , Inflamação/patologia , Lipoproteínas/análise , Adulto , Fármacos Anti-HIV/uso terapêutico , Antígenos CD/análise , Terapia Antirretroviral de Alta Atividade/métodos , Proteína C-Reativa/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Infecções por HIV/tratamento farmacológico , Humanos , Interleucina-6/sangue , Lipoproteínas/química , Estudos Longitudinais , Masculino , Monócitos/química , Monócitos/imunologia , Oxirredução , Estudos Prospectivos , Resposta Viral Sustentada , Linfócitos T/química , Linfócitos T/imunologia
16.
Prog Nucl Magn Reson Spectrosc ; 96: 58-72, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27573181

RESUMO

In human nutritional science progress has always depended strongly on analytical measurements for establishing relationships between diet and health. This field has undergone significant changes as a result of the development of NMR and mass spectrometry methods for large scale detection, identification and quantification of metabolites in body fluids. This has allowed systematic studies of the metabolic fingerprints that biological processes leave behind, and has become the research field of metabolomics. As a metabolic profiling technique, NMR is at its best when its unbiased nature, linearity and reproducibility are exploited in well-controlled nutritional intervention and cross-sectional population screening studies. Although its sensitivity is less good than that of mass spectrometry, NMR has maintained a strong position in metabolomics through implementation of standardisation protocols, hyphenation with mass spectrometry and chromatographic techniques, accurate quantification and spectral deconvolution approaches, and high-throughput automation. Thus, NMR-based metabolomics has contributed uniquely to new insights into dietary exposure, in particular by unravelling the metabolic fates of phytochemicals and the discovery of dietary intake markers. NMR profiling has also contributed to the understanding of the subtle effects of diet on central metabolism and lipoprotein metabolism. In order to hold its ground in nutritional metabolomics, NMR will need to step up its performance in sensitivity and resolution; the most promising routes forward are the analytical use of dynamic nuclear polarisation and developments in microcoil construction and automated fractionation.


Assuntos
Líquidos Corporais/química , Dieta , Metabolômica , Ressonância Magnética Nuclear Biomolecular/métodos , Avaliação Nutricional , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Cromoterapia/métodos , Comportamento Alimentar , Humanos , Lipoproteínas/análise , Lipoproteínas/sangue , Lipoproteínas/metabolismo , Lipoproteínas/urina , Espectrometria de Massas/métodos , Polifenóis/análise , Polifenóis/sangue , Polifenóis/metabolismo , Polifenóis/urina
17.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 26(3): 195-204, jul.-set. 2016. tab, ilus
Artigo em Português | LILACS | ID: biblio-832613

RESUMO

O Diabetes mellitus é uma doença com elevada prevalência global, associada à mortalidade cardiovascular e complicações microvasculares, que conferem o caráter crônico a essa patologia. No diabetes tipo II, o processo aterosclerótico tem início antes mesmo do diagnóstico, daí a importância do reconhecimento dos fatores de risco implicados na fisiopatologia da doença vascular nessa população. A dislipidemia no diabético é caracterizada por lipoproteínas ricas em triglicérides, LDL pequenas, densas e muito aterogênicas e HDL-c baixo. As estatinas são os medicamentos de escolha para tratar a dislipidemia e reduzir de forma significativa o risco cardiovascular nesses pacientes. Apesar do controle glicêmico intensivo não reduzir eventos cardiovasculares nos estudos randomizados, alguns hipoglicemiantes apresentam efeito favorável sobre o perfil lipídico, com redução de futuros eventos


Diabetes mellitus is a disease with high global prevalence, associated with cardiovascular mortality and microvascular complications, which give this disease its chronic nature. In type II diabetes, the atherosclerotic process begins even before diagnosis, hence the importance of recognizing the risk factors involved in pathophysiology of vascular disease in this population. Dyslipidemia in the diabetic patient is characterized by triglyceride-rich lipoproteins; small-dense and very atherogenic LDLs and low HDL-c. Statins are the drugs of choice for treating dyslipidemia and significantly reducing the cardiovascular risk in these patients. Although intensive glycemic control did not reduce cardiovascular events in randomized trials, some hypoglycemic drugs have demonstrated a favorable effect on the lipid profile, and may reduce future events


Assuntos
Humanos , Resistência à Insulina , Diabetes Mellitus/diagnóstico , Dislipidemias/complicações , Dislipidemias/diagnóstico , Hipertensão/complicações , Hipertensão/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Doença Crônica , Fatores de Risco , Lipoproteínas/análise , Lipoproteínas/sangue , HDL-Colesterol/análise , HDL-Colesterol/sangue , LDL-Colesterol/análise , LDL-Colesterol/sangue , Fígado/fisiopatologia
18.
Cir Cir ; 84(1): 45-9, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-26242826

RESUMO

BACKGROUND: Chylopericardium is a rare occurrence in children. The most common causes are associated with cardiac surgery, malformations of the lymphatic system, idiopathic reasons, among others. OBJECTIVE: The case is presented of a patient with traumatic chylopericardium, the diagnostic methodology, and in particular, its successful resolution by surgical means. CLINICAL CASE: Male patient of 6 years old, previous accident of fall from patient's height. Chest x-ray showed evidence of cardiomegaly. An echocardiogram with pericardial effusion was performed. Pericardial puncture was performed with drainage of milky material, confirming chylous liquid. Treatment included pericardial catheterisation, total parenteral nutrition, octreotide, and diet with medium chain triglycerides, with persistent increased pericardial fluid. Lymphatic abnormalities were ruled out by MRI. He underwent surgical treatment due to failure of prior treatment. A thoracoscopic approach was adopted with a favourable outcome. CONCLUSIONS: Chylopericardium occurs in children in most cases after cardiovascular surgery. The case presented here was classified as idiopathic. Patients with this condition may present with severe symptoms, such as tamponade, or can be asymptomatic as in the case presented. If medical treatment fails, it should be resolved by surgery; the best choice is minimally invasive treatment with its well-known advantages.


Assuntos
Derrame Pericárdico/cirurgia , Toracoscopia , Acidentes por Quedas , Criança , Terapia Combinada , Drenagem , Humanos , Lipídeos/análise , Lipoproteínas/análise , Masculino , Mediastino/lesões , Octreotida/uso terapêutico , Nutrição Parenteral Total , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/etiologia , Derrame Pericárdico/terapia , Líquido Pericárdico/química , Técnicas de Janela Pericárdica , Pericardiocentese , Ducto Torácico/cirurgia , Triglicerídeos/uso terapêutico
19.
Nutrire Rev. Soc. Bras. Aliment. Nutr ; 40(1): 54-62, abr. 2015. graf, tab
Artigo em Português | LILACS | ID: lil-749173

RESUMO

Objective: To evaluate the correlation between ultrasensitive C-reactive protein (us-CRP) and markers of cardiovascular risk in hypercholesterolemic adults of differing nutritional status. Methods: Forty-six hypercholesterolemic subjects (7 men: 30 to 70 years; 39 women: 45 to 70 years) with total cholesterol >240 mg/dL were studied. Anthropometric variables (weight, height, and waist and hip circumference) were measured, as well as us-CRP, total cholesterol (TC), HDL-C, LDL-C, VLDL-C, triglycerides, apolipoprotein AI, apolipoprotein B, glucose and fasting insulin, and homeostasis model assessment (HOMA-IR) of insulin resistance. Spearman correlations and multiple linear regression analysis were performed at a level of significance of 5%. Results: Plasma levels of triglycerides, VLDL-C, glucose, HDL-C and us-CRP were higher in overweight subjects (p<0.05). Ultrasensitive CRP was positively correlated with body mass index (r=0.32) and hip circumference (r=0.30), as well as with TC (r=0.33), apolipoprotein B (r=0.36) and glucose (r=0.42). Regression analysis showed that us-CRP concentration was positively associated with TC, glucose, and waist-hip ratio. These parameters explained 41% of the variability in us-CRP. Conclusion: Obese individuals present a higher concentration of us-CRP, fasting glucose, triglycerides, and VLDL-C. Excess weight is associated with us-CRP, a finding highlighting the importance of this biomarker for the detection of individuals at cardiovascular risk.


Objetivo: Avaliar a correlação entre a proteína C reativa ultrasensível (PCR-us) e os marcadores clássicos de risco cardiovascular em adultos hipercolesterolêmicos em diferentes estados nutricionais. Métodos: Amostra de 46 indivíduos hipercolesterolêmicos (7 homens: 30 a 70 anos e 39 mulheres: 45 a 70 anos) com colesterol total (CT) >240 mg/dL. Realizou-se determinações antropométricas como peso, altura, circunferência da cintura (CC) e do quadril (CQ), além de medidas plasmáticas de PCR-us, CT, HDL-C, LDL-C, VLDL-C, triglicerídeos (TG), apolipoproteína AI (Apo AI), apolipoproteína B (Apo B), glicose e insulina de jejum e HOMA-IR. Realizou-se correlações de Spearman e análise de regressão linear múltipla ao nível de significância de 5%. Resultados: Os níveis plasmáticos de TG, VLDL-C, glicose, HDL-C e PCR-us foram maiores em indivíduos com sobrepeso (p<0,05). A PCR-us foi positivamente correlacionada com o índice de massa corporal (r=0,32) e com a CQ (r=0,30), bem como com o CT (r=0,33), Apo B (r=0,36) e glicose (r=0,42). A análise de regressão mostrou que a concentração de PCR-us foi positivamente associada ao CT, glicose e razão cintura-quadril. Esses parâmetros explicam a variabilidade da PCR-us em 41%. Conclusão: Os indivíduos obesos têm maior concentração plasmática de PCR-us, glicose, TG e VLDL-C. O excesso de peso está correlacionado com a PCR-us, mostrando a importância deste biomarcador para triagem de indivíduos de risco cardiovascular.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Hipercolesterolemia/classificação , Antropometria/instrumentação , Biomarcadores , Inflamação/classificação , Lipoproteínas/análise , Estado Nutricional
20.
J Proteome Res ; 13(9): 4104-12, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25072840

RESUMO

High-resolution proton nuclear magnetic resonance (NMR) spectrometry of biofluids has been increasingly used in laboratory diagnosis of various diseases. In this study, we extended the use of (1)H NMR spectroscopy for laboratory diagnosis of exudative pleural effusions using pleural fluids. We compared this new NMR-based test with Light's criteria, the current gold standard for laboratory diagnosis of exudative pleural effusions. We analyzed 67 samples of pleural effusions from patients with pulmonary malignancy (N = 32), pulmonary tuberculosis (N = 18), and congestive heart failure (N = 17). The metabolomes of pleural effusions were analyzed using (1)H NMR spectroscopy on a Bruker 600 MHz spectrometer. Through a metabolome-wide association approach with filtering of insignificant markers (p value <4 × 10(-6)) and multivariate analysis (principal component analysis and orthogonal partial least squares-discriminant analysis), lipoprotein was found to be the best biomarker that distinguished exudates from transudates. Using NMR-based lipoprotein profiling to classify exudative pleural effusions from transudates, the area-under-receiver operating characteristic (ROC) curve was 0.96 with sensitivity of 98%, specificity of 88%, and accuracy of 98%. In contrast, the current gold standard, Light's criteria, give a specificity of only 65% at the same sensitivity level of 98%. Using the principle of size exclusion, NMR-based lipoprotein profiling of pleural fluids has an unprecedented diagnostic performance superiority over the Light's criteria. The capillary leaks secondary to inflammation result in a larger pleural pore-size, which allows the large-sized lipoproteins to accumulate in exudative pleural effusions. In contrast, the pleural permeability is intact in transudates, which allow only small-sized lipoproteins to pass into the pleural effusions. The average capillary pore-size of the pleura can therefore be determined by using NMR-based lipoprotein profiling of pleural fluids. We believe this new test will change the current clinical practice for management of pleural effusions and will become a new standard for clinical practice.


Assuntos
Lipoproteínas/análise , Lipoproteínas/química , Espectroscopia de Ressonância Magnética/métodos , Derrame Pleural/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/química , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Derrame Pleural Maligno/metabolismo , Porosidade , Análise de Componente Principal
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