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1.
Medicine (Baltimore) ; 99(26): e20817, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590767

RESUMO

RATIONALE: Although there are several reports on the effect of herbal medicine on weight loss in adults, evidence supporting its efficacy and safety in obese pediatrics is insufficient. Herein, we clinically investigated the preliminary experience of community-based healthcare program in cases of childhood obesity treated with an herbal complex, Slim-diet (SD), along with lifestyle modification. PATIENT CONCERNS: Seventeen subjects with childhood obesity participated in a community-based healthcare program, which consisted of twice-a-week play type physical activity and dietary counseling program with simultaneous twice-a-day administration of SD for 4 weeks. DIAGNOSES: The data of 13 obese pediatrics (body mass index [BMI] ≥ the 95th percentile for children of the same age and sex) in their 3rd to 6th grade who finally completed at least 6 visits out of a total of 8 visits of the program including baseline and endpoint assessments were analyzed. INTERVENTIONS: Participants received 20 g of SD daily. Simultaneously, play-type physical activity program with an exercise therapist and dietary counseling with a dietitian for lifestyle modification were conducted at every visit. Body composition, blood chemistry, the Korean Youth Physical Activity Questionnaire (KYPAQ) score, and the preference for salt density and sugar content were assessed at baseline and endpoint. OUTCOMES: After SD administration, body mass index decreased from 26.74 ±â€Š2.11 kg/m to 26.50 ±â€Š2.20 kg/m (P < .05) with statistically significant increases in height, weight, and skeletal muscle mass. The results of blood chemistry and the KYPAQ score showed no significant change. The preferences for salt density were improved in 8, maintained in 2, and worsened in 3 participants and those for sugar content were improved in 6 and maintained in 7 participants with no worsening. LESSONS: In the present study, we showed the clinical effects of SD with lifestyle modification in patients with childhood obesity who participated in community-based healthcare program. Further clinical studies investigating the effects of SD are required.


Assuntos
Dieta Redutora/normas , Obesidade Pediátrica/dietoterapia , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Dieta Redutora/métodos , Feminino , Humanos , Lipoproteínas LDL/análise , Lipoproteínas LDL/sangue , Masculino , República da Coreia , Comportamento de Redução do Risco , Inquéritos e Questionários , Triglicerídeos/análise , Triglicerídeos/sangue
2.
Ultrason Sonochem ; 60: 104767, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31539731

RESUMO

The effects of high-intensity ultrasonic (HIU) treatment on the functional properties of egg yolk were studied in the present work. After HIU treatment, the emulsifying, foaming and gel properties of the egg yolk solution significantly increased, but the foam stability decreased. SDS-PAGE results showed that there was no obvious change in the protein bands of egg yolk, indicating that the yolk proteins did not undergo covalent crosslinking or degradation. HIU treatment enhanced the zeta potential of egg yolk components in solution and increased the free sulfhydryl content of egg yolk proteins. Moreover, the particle size distribution of egg yolk components in solution changed markedly, and these changes demonstrated that HIU treatment caused the aggregation of yolk low-density lipoprotein and the partial dissociation of yolk granules. These results revealed that HIU treatment could change the aggregation of yolk components, which in turn could influence the solution characteristics of egg yolk, finally resulting in changes to the functional properties of egg yolk.


Assuntos
Gema de Ovo/fisiologia , Ondas Ultrassônicas , Animais , Galinhas , Gema de Ovo/química , Gema de Ovo/ultraestrutura , Interações Hidrofóbicas e Hidrofílicas , Lipoproteínas LDL/análise , Microscopia Eletrônica de Varredura , Tamanho da Partícula
4.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(12): 158518, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31479734

RESUMO

Unhealthy Western-type diet and physical inactivity are highly associated with the current obesity epidemic and its related metabolic diseases such as atherosclerosis and non-alcoholic steatohepatitis. In addition, increasing evidence indicates that obesity is also a major risk factor for several types of common cancers. Recent studies have provided correlative support that disturbed lipid metabolism plays a role in cancer risk and development, pointing towards parallels in metabolic derangements between metabolic diseases and cancer. An important feature of disturbed lipid metabolism is the increase in circulating low-density lipoproteins, which can be oxidized (oxLDL). Elevated oxLDL and the level of its receptors have been positively associated with increased risk of various types of cancer. This review discusses the pro-oncogenic role of oxLDL in tumor development, progression and potential therapies, and provides insights into the underlying mechanisms.


Assuntos
Carcinogênese/metabolismo , Lipoproteínas LDL/metabolismo , Neoplasias/metabolismo , Animais , Carcinogênese/patologia , Progressão da Doença , Humanos , Lipoproteínas LDL/análise , Neoplasias/patologia , Neoplasias/terapia
5.
Nat Commun ; 10(1): 3426, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366908

RESUMO

Apolipoprotein-B (ApoB) is the structural component of atherogenic lipoproteins, lipid-rich particles that drive atherosclerosis by accumulating in the vascular wall. As atherosclerotic cardiovascular disease is the leading cause of death worldwide, there is an urgent need to develop new strategies to prevent lipoproteins from causing vascular damage. Here we report the LipoGlo system, which uses a luciferase enzyme (NanoLuc) fused to ApoB to monitor several key determinants of lipoprotein atherogenicity including particle abundance, size, and localization. Using LipoGlo, we comprehensively characterize the lipoprotein profile of individual larval zebrafish and collect images of atherogenic lipoprotein localization in an intact organism. We report multiple extravascular lipoprotein localization patterns, as well as identify Pla2g12b as a potent regulator of lipoprotein size. ApoB-fusion proteins thus represent a sensitive and specific approach to study atherogenic lipoproteins and their genetic and small molecule modifiers.


Assuntos
Apolipoproteínas B/química , Aterosclerose/patologia , Lipoproteínas LDL/análise , Luciferases/química , Coloração e Rotulagem/métodos , Animais , Apolipoproteínas B/metabolismo , Humanos , Larva/metabolismo , Luciferases/metabolismo , Fosfolipases A2/genética , Fosfolipases A2/metabolismo , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
6.
Med Sci Monit ; 25: 2361-2367, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30931920

RESUMO

BACKGROUND The disordered metabolism of liver function in liver cancer patients can affect postoperative survival after liver transplantation. We assessed whether the levels of various chemicals in liver metabolism prior to receiving a liver transplant were prognostic factors and metabolism markers in predicting survival rate. MATERIAL AND METHODS Seventy-seven patients received a donor liver transplant between June 2012 and April 2016. The basic level of fasting serum GLU, Crea, TBil, TC, TG, HDL, LDL, ApoA1, ApoB100, INR, and MELD scores of 77 patients were retrospectively analyzed. Each patient's survival was monitored to evaluate prognosis and long-term survival. RESULTS The overall survival rates of all patients post-transplant at 6-, 12-, 24-, and 36-month follow-up were 90.9%, 79.2%, 68.8%, and 64.9% respectively. Fasting serum levels of GLU (P=0.004), HDL (P=0.010), LDL (P=0.008), ApoA1 (P=0.028), and MELD scores (P=0.013) prior to liver transplantation were closely associated with the cumulative survival post-transplant in univariate analyses. Controlled fasting GLU of ≤5.12 mmol/L (P=0.019), LDL of ≤2.62 mmol/L (P=0.031), and MELD scores of ≤9 (P=0.013) before LT were significantly and independently associated with increased cumulative survival in the multivariate analyses. CONCLUSIONS Decreased fasting serum GLU, LDL, and MELD scores as independent risk factors prior to liver transplantation markedly increase cumulative survival.


Assuntos
Lipoproteínas LDL/análise , Transplante de Fígado/mortalidade , Adulto , Idoso , Biomarcadores/sangue , China , Jejum/sangue , Feminino , Sobrevivência de Enxerto , Humanos , Lipoproteínas LDL/sangue , Fígado/metabolismo , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida
7.
Cell Physiol Biochem ; 52(4): 681-695, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30921507

RESUMO

BACKGROUND/AIMS: Oxidative modifications of low-density lipoprotein (ox-LDL) play a key role in initial steps of atheroprogression possibly via specific scavenger receptors on inflammatory and endothelial cells. Amongst others, CD68 might play a crucial role in this leading to fatty streak formation. METHODS: Different CD68-Fc fusion proteins were cloned, expressed and tested in vitro for their oxLDL binding properties as a decoy for endogenous oxLDL. Physiological functions were tested in foam cell assays with human monocytes in culture and by binding oxLDL from human blood. The best suited candidate FcIgG2-FL-CD68 was injected twice weekly in LDL receptor and ApoBec deficient mice (LDLR-/-/Apobec-/-), and the oxLDL content was measured in peripheral blood, in different cell types of the spleen and aortic wall by specific oxLDL antibodies using flow cytometry. RESULTS: Different variants of the CD68-Fc bound to copper-oxided LDL (oxLDL), LDL and to a lesser extent HDL with different efficacy in an ELISA based binding assay in vitro. Native oxLDL content in human blood derived from patients with extended atherosclerosis was reduced after passage through a specific protein G column conjugated with the different CD68-Fc fusion proteins. Foam cell formation from human peripheral blood monocyte-platelet co-culture was reduced by the most effective CD68-Fc fusion proteins. oxLDL was not increased in the blood but markedly increased in the vessel wall from LDLR-/-/Apobec-/- mice at an early stage of atherosclerosis. Platelet-like cells in the vessel well contributed most to the increase in tissue oxLDL. FcIgG2-FL-CD68, reduced oxLDL content of aortic vessel wall cells from LDLR-/-/Apobec-/- mice. However a tissue specific reduction on the oxLDL content in peripheral blood, the spleen or cells from the aortic vessel by FcIgG2-FL-CD68 could not be shown. CONCLUSION: Platelets contribute to increased tissue oxLDL in the aortic wall but not in peripheral blood. CD68 seems to play a role in the oxLDL metabolism in the vessel wall at early stages of atherosclerosis. FcIgG2-FL-CD68 could serve as a novel therapeutic option to modify the oxLDL content in the vessel wall.


Assuntos
Desaminase APOBEC-1/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Plaquetas/metabolismo , Lipoproteínas LDL/genética , Desaminase APOBEC-1/deficiência , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Plaquetas/citologia , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Modelos Animais de Doenças , Células Espumosas/citologia , Células Espumosas/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/análise , Lipoproteínas LDL/deficiência , Lipoproteínas LDL/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Ligação Proteica , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação
8.
Curr Med Chem ; 26(9): 1576-1593, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29521196

RESUMO

Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of ox-LDL and LDL rather than oxLDL concentration alone has also been focused. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in the circulatory system.


Assuntos
Líquidos Corporais/metabolismo , Diabetes Mellitus/diagnóstico , Lipoproteínas LDL/metabolismo , Infarto do Miocárdio/diagnóstico , Doença Aguda , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Líquidos Corporais/química , Diabetes Mellitus/metabolismo , Humanos , Lipoproteínas LDL/análise , Infarto do Miocárdio/metabolismo
9.
Neuro Endocrinol Lett ; 40(4): 195-198, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32087095

RESUMO

OBJECTIVES: To compare two different analytical methods for determination of small dense LDL and to determine a share of corresponding and non-corresponding (inconsistent) results METHODS: In the group of 104 hyperlipidemic patients and 20 healthy individuals of the control group we analysed the total cholesterol and triglycerides by enzymatic CHOD PAP method (Roche Diagnostics, Germany) in EDTA-K2 plasma. Small dense LDL (sdLDL) were quantified by the electrophoretic method for lipoprotein analysis on polyacrylamide gel (PAG) (Lipoprint LDL System, Quantimetrix, CA, USA) and simultaneously, the small dense LDL concentrations in the indentical samples were analysed by an enzymatic method LDL-EX ´Seiken´(Randox, England). RESULTS: In 31 patients we found the discrepancy in the sdLDL levels using the two different procedures. Out of them, 24 patients tested by enzymatic method ´SEIKEN´ had higher sdLDL values (more than 0.9 mmol/l) compared to the Lipoprint LDL results, which identified normal sdLDL values in the same samples (in 23% of tested patients). In 7 patients out of the 31 tested patients with discrepant sdLDL values, the Lipoprint LDL identified increased values of plasma sdLDL (more than 0.155 mmol/l), while the enzymatic LDL-EX Seiken did not find an increased concentration of sdLDL (in 7% of tested patients). In the control group a discrepancy in the sdLDL results between the two tested analytical methods was not found. CONCLUSION: The concentration of sdLDL in plasma lipoprotein spectrum obtained by two different laboratory procedures was analysed, compared, evaluated and 70% identical corresponding results have been confirmed.


Assuntos
Hiperlipoproteinemias/metabolismo , Lipoproteínas LDL/análise , Adulto , Idoso , Aterosclerose/metabolismo , Eletroforese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
São Paulo; s.n; s.n; 2019. 72 p. ilus, graf, tab.
Tese em Português | LILACS | ID: biblio-999825

RESUMO

A hipercolesterolemia familial (HF) é uma doença autossômica dominante considerada como uma das formas mais graves de hiperlipidemia, assim como, a principal causa de morbi-mortalidade por ser o principal fator desencadeante da aterosclerose. A alteração primária e mais freqüente da HF incide no gene do receptor da LDL (LDLr), sabe-se que mais de 1600 mutações são descritas na literatura e a principal consequência dessas alterações resultam no comprometimento da remoção da LDL, aumentando a concentração plasmática. Atualmente, o ultrasequenciamento genômico permite gerar muitos dados, que podem identificar novas mutações gênicas de forma eficiente, reprodutiva e rápida. No entanto, somente a validação da nova mutação por atividade funcional pode realmente estabelecer a associação com a doença. O presente estudo tem como objetivo realizar a análise da atividade do receptor da LDL, identificadas através do sequenciamento de alto rendimento, no gene LDLr realizado pelo nosso grupo de pesquisa e correlacionar com dados clínicos, in vitro, in silico e estrutural. Para cumprir esta meta, os linfócitos T dos portadores de HF foram isolados do sangue periférico, cultivados e submetidos a estímulo para a expressão de receptores da LDL, incubados com LDL marcada para avaliação de ligação e interiorização pelas células de cada paciente. Dos 30 pacientes selecionados para esse estudo, 63% apresentaram mutação no LDLR, sendo que quase todas as variantes (p.Gly373Asp, p.Asp601His, p.Ile488Thr, p.Gly549Asp, p.Gly592Glu e Gly681Asp) são localizadas no segundo domínio entre os éxons 7 ao 14. De acordo com o docking molecular a variante p.Gly592Glu (rs137929307), que já foi identificada na população polonesa, espanhola e brasileira, já relacionada com a HF, pode aumentar a interação do LDLr com a ApoB e consequentemente o modo de interação entre as proteínas, no estudo in vitro foi possível notar um aumento tanto na média de fluorescência da ligação e da ligação e interiorização em relação a quantidade de LDLr na superfície celular


Familial hypercholesterolemia (HF) is an autosomal dominant disease considered as one of the most severe forms of hyperlipidemia, as well as the main cause of morbidity and mortality because it is the main triggering factor for atherosclerosis. The primary and more frequent alteration of the HF affects the LDL receptor gene (LDLr), it is known that more than 1600 mutations are described in the literature and the main consequence of these alterations results in the compromise of the LDL removal, increasing the plasma concentration. Nowadays, genomic ultrasequencing allows the generation of many data, which can identify new gene mutations efficiently, reproductively and rapidly. However, only the validation of the new functional activity mutation can actually establish association with the disease. The aim of the present study was to analyze LDL receptor activity, identified by high-throughput sequencing, in the LDLr gene performed by our research group and to correlate with clinical, in vitro, in silico and structural data. To meet this goal, the T lymphocytes from the HF carriers were isolated from the peripheral blood, cultured and challenged for the expression of LDL receptors, incubated with labeled LDL for binding assessment and internalization by the cells of each patient. Of the 30 patients selected for this study, 63% had a mutation in LDLR, and almost all variants (p.Gly373Asp, p.Asp601His, p.Ile488Thr, p.Gly549Asp, p.Gly592Glu and Gly681Asp) are located in the second domain between exons 7 to 14. According to the molecular docking the variant p.Gly592Glu (rs137929307), which has already been identified in the Polish, Spanish and Brazilian population, already related to HF, can increase the interaction of LDLr with ApoB and consequently the mode of interaction between proteins, in the in vitro study it was possible to note an increase in both the mean fluorescence of binding and binding and internalization in relation to the amount of LDLr on the cell surface


Assuntos
Humanos , Masculino , Feminino , Adulto , Receptores de LDL/análise , Estudo de Validação , Lipoproteínas LDL/análise , Linfócitos , Simulação de Acoplamento Molecular/estatística & dados numéricos , Hiperlipoproteinemia Tipo II/classificação
11.
Acta Biomed ; 89(9-S): 87-96, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30561400

RESUMO

BACKGROUND: Adherence to a healthy diet has been reported to be essential for the primary prevention of colorectal cancer, through a reduction of tissue inflammation, a low concentration of circulating lipoproteins and lower levels of serum cholesterol. Since an altered expression of the fatty acids pattern has been demonstrated to be a crucial event in colorectal carcinogenesis, lipidomic analysis is considered able to identify early diagnostic and prognostic biomarkers of complex diseases such as colorectal cancer. METHODS: cell membrane fatty acid profile and serum lipoproteins pattern were evaluated by gas chromatography and electrophoresis method respectively. RESULTS: There is a close association between diet and lipidomic profile in colorectal cancer, both in pre-clinical and clinical studies. A modified serum lipoproteins pattern has been demonstrated to be predominant in intestinal tumors. CONCLUSIONS: The study of fatty acids profile in cell membrane and the evaluation of serum lipoproteins subfractions could be useful to have an integrate vision on the interactions between lipids and the pathogenesis of colorectal cancer and to understand the mechanisms of action and the consequences of these interactions on human health status.


Assuntos
Neoplasias Colorretais/etiologia , Lipídeos/análise , Estado Nutricional , Animais , Cocarcinogênese , Neoplasias Colorretais/química , Neoplasias Colorretais/prevenção & controle , Dieta/efeitos adversos , Dieta Mediterrânea , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/toxicidade , Dislipidemias/complicações , Ácidos Graxos/análise , Humanos , Inflamação , Lipoproteínas LDL/análise , Camundongos , Micronutrientes/fisiologia , Metástase Neoplásica
12.
PLoS One ; 13(10): e0204841, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30286142

RESUMO

The antinociceptive effects of the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well documented, but most of its possible side-effects remain poorly understood. In this work, we examine the impact of CORM-2 treatment on the lipoprotein profile and two main atheroprotective functions attributed to high-density lipoprotein (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of this drug on the modulation of painful diabetic neuropathy using nociceptive behavioral tests. Plasma and tissue samples were used for chemical and functional analyses, as appropriate. Two main antiatherogenic properties of HDL, i.e., the ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to promote reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10 mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia and significantly ameliorated spinal cord markers (Cybb and Bdkrb1expression) of neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia shown in Stz-treated mice. Its administration to Stz-treated mice led to a significant increase in the plasma levels of cholesterol (∼ 1.4-fold vs. Ctrl, ∼ 1.3- fold vs. Stz-vehicle; p < 0.05) and was attributed to significant elevations in both non-HDL (∼ 1.8-fold vs. Ctrl; ∼ 1.6-fold vs. Stz-vehicle; p < 0.05) and HDL cholesterol (∼ 1.3-fold vs. Ctrl, ∼ 1.2-fold vs. Stz-vehicle; p < 0.05). The increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed by decreased [3H]-tracer trafficking into the feces in vivo. Furthermore, the HDL-mediated protection against LDL oxidation ex vivo shown by the HDL isolated from Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In conclusion, the antinociceptive effects produced by a high dose of CORM-2 were accompanied by antioxidative effects but were without favorable effects on the dyslipidemia manifested in diabetic mice.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Dislipidemias/metabolismo , Compostos Organometálicos/administração & dosagem , Animais , Colesterol/sangue , Colesterol/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Neuropatias Diabéticas/metabolismo , Esquema de Medicação , Hiperalgesia/metabolismo , Hiperalgesia/prevenção & controle , Lipoproteínas LDL/análise , Camundongos , Compostos Organometálicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estreptozocina
13.
Chem Phys Lipids ; 217: 51-57, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30287220

RESUMO

Oxidation of low density lipoprotein (LDL) has been proposed to be involved in the pathogenesis of atherosclerosis. We have previously shown that LDL can be oxidised by iron in lysosomes. As the iron-storage protein ferritin might enter lysosomes by autophagy, we have investigated the ability of ferritin to catalyse LDL oxidation at lysosomal pH. LDL was incubated with ferritin at 37 °C and pH 4.5 and its oxidation monitored spectrophotometrically at 234 nm by the formation of conjugated dienes and by measuring oxidised lipids by HPLC or a tri-iodide assay. Iron released from ferritin was measured using the ferrous iron chelator bathophenanthroline and by ultrafiltration followed by atomic absorption spectroscopy. LDL was oxidised effectively by ferritin (0.05-0.2 µM). The oxidation at lysosomal pH (pH 4.5) was much faster than at pH 7.4. Ferritin increased cholesteryl linoleate hydroperoxide, total lipid hydroperoxides and 7-ketocholesterol. Iron was released from ferritin at acidic pH. The iron chelators, diethylenetriaminepentaacetate and EDTA, and antioxidant N,N׳-diphenyl-p-phenylenediamine inhibited the oxidation considerably, but not entirely. The antioxidant tempol did not inhibit the initial oxidation of LDL, but inhibited its later oxidation. Cysteamine, a lysosomotropic antioxidant, inhibited the initial oxidation of LDL in a concentration-dependent manner, however, the lower concentrations exhibited a pro-oxidant effect at later times, which was diminished and then abolished as the concentration increased. These results suggest that ferritin might play a role in lysosomal LDL oxidation and that antioxidants that accumulate in lysosomes might be a novel therapy for atherosclerosis.


Assuntos
Ferritinas/química , Lipoproteínas LDL/química , Lisossomos/química , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Ferro/análise , Ferro/metabolismo , Lipoproteínas LDL/análise , Oxirredução , Espectrofotometria , Espectrofotometria Atômica
14.
PLoS One ; 13(10): e0205460, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30307996

RESUMO

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is commonly used for CVD risk assessment; however, recent research has shown LDL particle (LDL-P) number to be a more sensitive indicator of CVD risk than both LDL-C and non-high-density lipoprotein cholesterol (HDL-C). Described herein are five single stranded DNA aptamers with dissociation constants in the low picomolar range specific to LDL-P and its subfractions. Furthermore, a set of antisense sequences have been developed and characterized that are capable of binding to the best aptamers and undergoing displacement by LDL-P for use in a simple, affordable diagnostic assay.


Assuntos
Aptâmeros de Nucleotídeos/farmacologia , Doenças Cardiovasculares/diagnóstico , Lipoproteínas LDL/análise , Aptâmeros de Nucleotídeos/genética , Doenças Cardiovasculares/sangue , Humanos , Lipoproteínas LDL/sangue , Fatores de Risco
15.
Arch. Soc. Esp. Oftalmol ; 93(10): 476-480, oct. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-175121

RESUMO

OBJETIVO: Determinar la relación entre los componentes del síndrome metabólico con la presencia de blefaritis. MÉTODOS: Se incluyeron 60 pacientes con diagnóstico de blefaritis y 30 sujetos control. Se realizaron medidas antropométricas, presión sanguínea y se obtuvieron muestras de sangre venosa periférica en condiciones de ayuno para la determinación de concentración de glucosa, colesterol y triglicéridos. El colesterol de las lipoproteínas de alta densidad (c-HDL) se determinó después de precipitar las lipoproteínas que contienen apoB-100 con ácido fosfotúngstico/Mg2+. La concentración de las lipoproteínas de baja densidad (c-LDL) se calculó utilizando la fórmula de Friedewald modificada por DeLong. RESULTADOS: En el análisis comparativo se encontraron diferencias estadísticamente significativas en la circunferencia de cintura (p = 0,0491), presión arterial sistólica (p = 0,0149), glucosa (p = 0,0045), colesterol total (p = 0,0001), c-HDL (p = 0,0049), c-LDL (p = 0,0266) y triglicéridos (p = 0,0059); mientras que en el IMC y en la presión diastólica no hubo diferencia significativa. CONCLUSIONES: Los resultados encontrados apoyan la hipótesis de que el síndrome metabólico podría ser considerado un factor de riesgo para el desarrollo de blefaritis y su detección oportuna es fundamental para evitar las complicaciones futuras


OBJECTIVE: To determine the relationship between the components of the metabolic syndrome with the presence of blepharitis. METHODS: The study included 60 patients with a diagnosis of blepharitis and 30 control subjects. Anthropometric measurements and blood pressure were recorded, and peripheral venous blood samples were obtained under fasting conditions to determine the concentration of Glucose, Cholesterol, and Triglycerides. High-density lipoprotein cholesterol (HDL-C) was determined after precipitating lipoproteins containing apoB-100 with phosphotungstic acid/Mg2+. The concentration of low density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula modified by DeLong. RESULTS: In the comparative analysis, statistically significant differences were found in the waist circumference (P = .0491), systolic blood pressure (P = .0149), glucose (P = .0045), total cholesterol (P = .0001), HDL-C (P = .0049), LDL-C (P = .0266), and triglycerides (P = .0059); while there was no significant differences in the BMI or the diastolic pressure. CONCLUSIONS: The results support the hypothesis that the metabolic syndrome could be considered a risk factor for the development of blepharitis, and its timely detection is essential to avoid future complications


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Blefarite/diagnóstico , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Dislipidemias/diagnóstico , Estudos de Casos e Controles , Blefarite/complicações , Antropometria , Pressão Sanguínea , Jejum , Lipoproteínas LDL/análise , Dislipidemias/sangue , Glândulas Tarsais , Estudos Prospectivos , Estudos Transversais
16.
Clín. investig. arterioscler. (Ed. impr.) ; 30(4): 170-178, jul.-ago. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-175432

RESUMO

Introducción: La hipercolesterolemia familiar (HF) infantil está infradiagnosticada y su diagnóstico no es fácil en la práctica clínica. El objetivo fue evaluar qué características clínicas, bioquímicas y de imagen vascular pueden ayudarnos a detectar a niños/as y adolescentes con hipercolesterolemia afectados de HF. Métodos: Doscientos veintidós niños y adolescentes de entre 4 y 18 años fueron reclutados para participar en un proyecto de detección precoz de HF (proyecto DECOPIN). La HF se diagnosticó por criterios genéticos o clínicos. Se definió hipercolesterolemia poligénica (HP) cuando el c-LDL >135mg/dl pero sin criterios clínicos ni genéticos de HF. Participantes con c-LDL < 135mg/dl se incluyeron en el grupo control (GC). Se recogieron la historia familiar, los datos antropométricos y las variables clínicas. Se analizaron parámetros bioquímicos y lipídicos. Se determinó el grosor íntima-media carotídeo (GIMc) y los tendones de Aquiles por ecografía. Resultados: Noventa y un niños fueron diagnosticados de HF y 23 de HP, y 108 como GC. El grupo HF presentó mayores concentraciones de CT, c-LDL, índice ApoB/ApoA1 e índice colesterol año. El c-HDL fue menor en grupo HF que en el GC. Si bien el c-LDL fue el parámetro más definitorio de HF, el índice ApoB/ApoA1 > 0,82 fue el que de forma aislada mostró mayor sensibilidad y especificad para predecir la presencia de mutación en el grupo de niños HF. El grosor de los tendones de Aquiles no mostró diferencias entre grupos. El GIMc fue mayor en los niños HF sin diferencias significativas. Conclusiones: Los niveles de c-LDL son el marcador de HF. Un índice ApoB/ApoA1 > 0,82 puede ser una herramienta útil para decidir el estudio genético en niños con sospecha de HF


Background: Familial hypercholesterolaemia (FH) in children is under-detected and is difficult to diagnose in clinical practice. The aim of this study was to evaluate clinical, biochemical and vascular imaging variables in order to detect children and adolescents with FH. Methods: A total of 222 children aged 4-18 years old were recruited to participate in a project for the early detection of FH (The DECOPIN Project). They were distributed into 3groups: FH, if genetic study or clinical criteria were positive (n=91); Polygenic hypercholesterolaemia (PH) if LDL-Cholesterol >135mg/dL without FH criteria (n=23), and Control group (CG) if LDL-C <135mg/dL (n=108). Data were collected from family history, anthropometric data, and clinical variables. The usual biochemical parameters, including a complete lipid profile were analysed. The carotid intima-media thickness (cIMT) and thickness of Achilles tendons were determined using ultrasound in all participants. Results: A total of 91 children had a diagnosis of FH, 23 with PH, and 108 with CG. Children with FH had higher concentrations of total cholesterol, LDL-C, ApoB/ApoA1 ratio, and cholesterol-year score, than the other groups. HDL-C was lower in the FH group than in the CG. Thickness of the Achilles tendon and cIMT did not show any differences between groups, although a greater cIMT trend was observed in the FH group. ApoB/ApoA1 ratio >0.82 was the parameter with the highest sensitivity and specificity to predict the presence of mutation in children with FH. Conclusions: Although LDL-C is the main biochemical parameter used to define FH, the ApoB/ApoA1 ratio (>0.82) may be a useful tool to identify children with FH and a positive mutation


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteínas LDL/análise , LDL-Colesterol/uso terapêutico , Apolipoproteínas B/genética , Hiperlipoproteinemia Tipo II/metabolismo , Hiperlipoproteinemia Tipo II/fisiopatologia , Erros Inatos do Metabolismo Lipídico/diagnóstico , Criança , Biomarcadores/análise
17.
Anticancer Res ; 38(7): 4289-4294, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970563

RESUMO

BACKGROUND/AIM: A system is being developed that can be used to easily evaluate the health condition of an individual with the help of trace amounts of a blood sample by focusing on xenobiotics. The system is called "Multimodal homeostasis evaluation system" (measurement of neutrophil activity, phagocytic activity of phagocytes and quantification of oxidized LDL (OxLDL)). To elucidate the possibility of using this system as an evaluation system for the health condition of an individual, clearly explaining the changes in various diseases is essential. In this study, evaluations were carried out using hypertensive model animals. MATERIALS AND METHODS: Spontaneously hypertensive model rats SHR/NCrlCrlj and control rats WKY/NCrlCrlj were raised for 10 weeks from 6 to 16 weeks of age and their blood pressure was measured over time. Blood neutrophil activity (superoxide anion (O2•-) generation and myeloperoxidase (MPO) activity) and phagocytic activity of phagocytes was measured by our developed apparatus (a simple prototype device under development). OxLDL was measured by an ELISA kit, and biochemical markers were measured using the blood sample. RESULTS: Compared to WKY rats of the control group, systolic blood pressure, diastolic blood pressure, and mean blood pressure of SHR rats increased significantly with age. In SHR rats, there was a significant elevation in O2•- generation and MPO activity of neutrophils, alanine aminotransferase and triglycerides of blood, while phagocytic activity, OxLDL, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol and total-bilirubin decreased. CONCLUSION: In the hypertensive model, biochemical markers were found to have a relationship with O2•- generation, MPO activity, phagocytic activity of phagocytes, and OxLDL. This system is expected to be useful for clinical monitoring of hypertension diseases.


Assuntos
Biomarcadores/sangue , Hipertensão/sangue , Lipoproteínas LDL/análise , Neutrófilos , Animais , Modelos Animais de Doenças , Masculino , Fagocitose , Ratos , Ratos Endogâmicos SHR
18.
Anal Chem ; 90(11): 6353-6356, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29756771

RESUMO

Lipoproteins are micelle-like assemblies that are key players in the pathogenesis of atherosclerosis. High-density lipoprotein (HDL), low-density lipoproteins (LDL), and very low density lipoprotein (VLDL) are the three major classes present in fasting plasma. Within each class, there is a broad size distribution with wide variations in protein and lipid content. The development of better metrics for cardiovascular risk is thought to depend on better characterization of lipoprotein subclasses. Using charge detection mass spectrometry (CDMS), the mass distributions of HDL, LDL, and VLDL have been directly measured for the first time. In the case of HDL, seven distinct subpopulations were resolved using a two-dimensional correlation of charge and mass. The resolved components are assigned to HDL particles containing different numbers of the key structural proteins apolipoprotein A-I and apolipoprotein A-II.


Assuntos
Lipoproteínas HDL/análise , Lipoproteínas LDL/análise , Lipoproteínas VLDL/análise , Espectrometria de Massas/métodos , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Eletricidade Estática
19.
Medicine (Baltimore) ; 97(17): e0612, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29703063

RESUMO

Although the Friedewald method has been used as the clinical standard to estimate low-density lipoprotein cholesterol (LDL-C) levels, a novel method with better accuracy was suggested and is now being adopted in real practice. We investigated the effect of this novel method on determining the eligibility for statin treatment for primary prevention in the United States.In this cross-sectional study, we determined the discordance in the statin-eligible population for primary prevention according to the 2 different LDL-C estimating methods based on the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Using data from the National Health and Nutrition Examination Survey 2005-2014, we included 5302 nationally representative US adults aged between 40 and 75 years without history of atherosclerotic cardiovascular disease (ASCVD). Sampling weights were used in all statistical analyses to account for complex sampling design and nonresponse.If the Friedewald method is replaced by the novel method for analysis of the fasting samples, 0.2% (95% confidence interval [CI], 0.0-0.8) and 0.4% (95% CI, 0.3-0.6) of the population would no longer be eligible or would become newly eligible for statin treatment, respectively. Among the individuals with a TG level ≥150 mg/dL and LDL-C level estimated using the Friedewald method <70 mg/dL, 11.6% (95% CI, 4.0-29.3) would become newly eligible for the statin treatment when using the novel method.The use of the novel method for estimating LDL-C instead of the Friedewald method would be associated with a small net increase in statin eligible/needed US adults for primary prevention based on the 2013 ACC/AHA guidelines. Reassessment of individuals' statin eligibility using the novel method may be beneficial, particularly when their TG level is 150 mg/dL or higher and LDL-CF level is lower than 70 mg/dL.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Definição da Elegibilidade/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteínas LDL/análise , Prevenção Primária/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevenção Primária/métodos , Estados Unidos
20.
J Pept Sci ; 24(4-5): e3072, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29602217

RESUMO

The probes for detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to facilitate the diagnosis, prevention, and treatment of atherosclerosis. Recently, we have reported that a heptapeptide (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6) coupled through the ε-amino group of N-terminal Lys to fluorescein isothiocyanate (FITC), (FITC)KP6, can be useful as a fluorescent probe for specific detection of ox-LDL. In the present study, to develop a novel fluorescent peptide for specific detection of ox-LDL, we investigated the interaction (with ox-LDL) of an undecapeptide corresponding to positions 41 to 51 of a potent antimicrobial protein (royalisin, which consists of 51 residues; from royal jelly of honeybees), conjugated at the N-terminus to FITC in the presence of 6-amino-n-caproic acid (AC) linker, (FITC-AC)-royalisin P11, which contains both sequences, Phe-Lys-Asp and Asp-Lys-Tyr, similar to Tyr-Lys-Asp in (FITC)KP6. The (FITC-AC)-royalisin P11 bound with high specificity to ox-LDL in a dose-dependent manner, through the binding to major lipid components in ox-LDL (lysophosphatidylcholine and oxidized phosphatidylcholine). In contrast, a (FITC-AC)-shuffled royalisin P11 peptide, in which sequences Phe-Lys-Asp and Asp-Lys-Tyr were modified to Lys-Phe-Asp and Asp-Tyr-Lys, respectively, hardly bound to LDL and ox-LDL. These findings strongly suggest that (FITC-AC)-royalisin P11 may be an effective fluorescent probe for specific detection of ox-LDL and that royalisin from the royal jelly of honeybees may play a role in the treatment of atherosclerosis through the specific binding of the region at positions 41 to 51 to ox-LDL.


Assuntos
Abelhas/metabolismo , Lipoproteínas LDL/análise , Fragmentos de Peptídeos/síntese química , Proteínas/química , Sequência de Aminoácidos , Animais , Ácidos Graxos/química , Fluoresceína-5-Isotiocianato/química , Humanos , Proteínas de Insetos/química , Peptídeos e Proteínas de Sinalização Intercelular , Lipoproteínas LDL/sangue , Estrutura Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo
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