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Purpose: Fasting has been promoted as a method of preventing disease and aging for thousands of years. With heart disease being a leading cause of death in the U.S., researchers have explored the effects of fasting on variables that influence cardiovascular disease (CVD), like LDL cholesterol. Therefore, the purpose of this study was to assess the effects of weekly water-only fasting on LDL cholesterol (LDL-C) in men and women with metabolic risk factors for CVD. Methods: This study was a randomized control trial in adult men and women. Participants were randomized to fasting (treatment) or normal diet (control). The fasting protocol consisted of four weeks of two 24-hour water-only fasts, followed by 22 weeks of once-weekly water-only 24-hour fasts. Measurements such as height, weight, waist circumference and LDL-C were assessed at baseline, 4 weeks, 13 weeks, and 26 weeks. Results: Intermittent fasting (n = 50) and control (n = 53) participants were 49.3 ± 12.0 and 47.0 ± 9.8 years, respectively, predominantly females (66.0% and 67.9%), overweight (103 ± 24 and 100 ± 21 kg), and with mild LDL-C elevation (124 ± 19 and 128 ± 20 mg/dL). Change in weight was −1.70 ± 4.69 (kg) in the fasting group and 0.20 ± 3.45 (kg) in the control group and not different between conditions (p = 0.06). There was no condition-by-period interaction for LDL-C (p = 0.06). Similarly, the change in LDL-C from baseline to follow-up was not different between conditions (t = −0.538, p = 0.59; Cohens D = 0.12) Conclusions: A once-per-week intermittent fasting regimen did not reduce weight or LDL-C. Further research of such fasting regimens is needed to evaluate their potential impact on cardiometabolic health.

Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plasmon resonance to examine the binding of glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25°C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the interaction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phosphate interacts with all sites, and the CM-glucans and laminarin interact with a subset of sites. Polymer charge has a dramatic effect on the affinity of glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic glucan structure independent of charge.

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OBJECTIVE: The 10th leading cause of death in the United States is heart disease. Most of the deaths by heart disease has a correlation with an occlusion of the coronary arteries. While diabetes mellitus is currently the 7th leading cause of death, which is a chronic condition that affects more than 37 million people in America. The global epidemic of obesity largely explains the dramatic increase in the incidence and prevalence of type 2 diabetes (T2D) over the past 25 years. Statins are well known drugs to decrease LDL for individuals who suffer from hypercholesterinemia; however, there is also an increased risk of developing diabetes mellitus. An estimation of 10-20 per 10,000 patients per year demonstrated an excess risk of T2D with the long-term use of statin. Here we examine the effects of simvastatin and pitavastatin on pancreatic ß-cell function to determine whether altered insulin secretion may contribute to an increased risk of T2D. METHODS: The experiments were performed using clonal pancreatic ß-cells (INS-1). The cells were grown in 4 mM glucose in RPMI media. Cells were grown for three days before adding the different types of statins: simvastatin and pitavastatin for one day. Then the cells were used to perform the glucose-induced insulin secretion (GSIS) experiment. Insulin secretion and insulin content were assay using a fluorescence-based immunoassay. The study was calculated using Microsoft Excel. Standard variance and standard error were used to assess the difference sets of data. RESULTS: INS-1 cells responded to acute glucose stimulation after chronic culture in both low (4 mM) and high (11 mM) glucose. Secretion from cells cultured at 4 mM glucose was higher than cells cultured at 11 mM glucose at all glucose concentrations tested, characteristic of the effects of glucolipotoxicity (GLT). Insulin content in cells cultured at high glucose was decreased 8.6-fold compared to cells cultured at the more physiological low glucose condition. When normalized to basal secretion cells cultured at high glucose exhibited basal hypersecretion and increased GSIS compared to those in low glucose. Simvastatin (100 nM, 24 hrs) increased basal insulin secretion to a greater extent than Pitavastatin. The effects of pitavastatin on basal insulin secretion were less consistent than seen with simvastatin. Simvastatin was also shown to inhibit GSIS from cells cultured at 4 mM glucose, while pitavastatin increased GSIS. CONCLUSION: Both pitavastatin and simvastatin alter insulin secretion from pancreatic ß-cells. The effect of simvastatin to both increase basal and decrease GSIS, characteristic of GLT suggests pitavastatin may be the statin of choice to reduce the risk of statin-induced T2D.

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No description available.

Kolesterol transporteras i blodet med hjälp av lipoproteinpartiklar. Höga nivåer av low-density lipoprotein (LDL)-kolesterol i blodet är en riskfaktor för kardiovaskulär sjukdom. Koncentrationen av LDL-kolesterol kan beräknas med hjälp av Friedewalds formel men det finns även metoder där LDL-kolesterol kan analyseras direkt. Syftet med arbetet var att verifiera metoden direkt LDL-kolesterol på analysinstrumentet Beckman Coulter AU680. Metodens inomserie- och totalimprecision analyserades. Två korrelationsstudier utfördes mellan direkt LDL-kolesterol och beräknat LDL-kolesterol, en med 43 patientprover med triglycerider < 4,5 mmol/L och en med 11 patientprover med triglycerider > 4,5 mmol/L. Friedewalds formel ska egentligen inte användas vid triglycerider > 4,5 mmol/L, men i detta fall användes formeln ändå för att utvärdera eventuella skillnader mellan metodernas resultat vid höga triglyceridkoncentrationer. Vid analys av metodens inomserieimprecision blev variationskoefficienten (CV) omkring 0,5 % vid analys av både den låga kontrollen (A1) och den höga kontrollen (A2). CV för totalimprecisionen blev 1,21 % vid analys av A1 och 1,11 % vid analys av A2. Korrelationsstudierna visade ett linjärt samband mellan metoderna men den direkta metoden gav något högre resultat vid lägre koncentrationer och något lägre resultat vid högre koncentrationer jämfört med beräknat LDL-kolesterol. Vid triglycerider > 4,5 mmol/L gav den direkta metoden betydligt högre resultat än beräknat LDL-kolesterol. Slutsatsen blev att metoden hade god precision. Överensstämmelsen mellan metodernas resultat var relativt bra för proverna med triglycerider < 4,5 mmol/L. Vid triglycerider > 4,5 mmol/L var differensen mellan metoderna stor, troligtvis på grund av falskt för låga resultat från beräknat LDL-kolesterol. / Cholesterol is transported in the blood by lipoproteins. High levels of low-density lipoprotein (LDL)-cholesterol in the blood is a risk factor for cardiovascular disease. The concentration of LDL-cholesterol can be calculated using the Friedewald formula but there are also methods that measure LDL-cholesterol directly. The aim of this study was to verify the method P-LDL-cholesterol on a Beckman Coulter AU680 analyzer. Within-run imprecision and total imprecision were analyzed. The correlation between direct LDL-cholesterol and calculated LDL-cholesterol was examined using 43 patient samples with triglyceride levels < 4,5 mmol/L and 11 patient samples with triglyceride levels > 4,5 mmol/L. The Friedewald formula is not supposed to be used on triglyceride levels > 4,5 mmol/L, but in this case the formula was used anyway to evaluate differences between the methods at high triglyceride concentrations. The coefficient of variation (CV) for the within-run imprecision was about 0,5 %, both for the low control (A1) and the high control (A2). Total imprecision had a CV of 1,21 % for A1 and 1,11 % for A2. There was a linear relationship between the methods, but the direct method gave slightly higher results at low concentrations and slightly lower results at high concentrations compared to calculated LDL-cholesterol. At triglyceride levels > 4,5 mmol/L the results from the direct method was considerably higher than calculated LDL-cholesterol. The conclusion is that the precision of the method was good. The correlation between the results from direct LDL-cholesterol and calculated LDL-cholesterol was relatively high for samples with triglyceride levels < 4,5 mmol/L. At triglyceride levels > 4,5 mmol/L there was a big difference between the methods, probably because of falsely low results from calculated LDL-cholesterol.

INTRODUÇÃO: A erva-mate (Ilex paraguarienis), uma planta nativa e consumida em grande parte da América do Sul, apresenta diversos compostos bioativos que já demonstraram importante atividade antioxidante in vitro e in vivo. O chá mate é um produto desta planta cujas propriedades antioxidantes ainda não foram avaliadas em ensaios com humanos. OBJETIVO: Este projeto visa avaliar o potencial antioxidante do chá mate in vivo e ex vivo sobre o plasma e LDL de humanos após a ingestão de chá-mate. MÉTODOS: Indivíduos em jejum (n=20) tiveram seu sangue coletado em três momentos: antes, após uma hora e depois de 1 semana (7 dias) da ingestão diária de chá-mate. O plasma e a LDL obtidos nos três momentos foram submetidos à oxidação por três mecanismos diferentes [Cobre (Cu+2), lipoxigenase e peroxinitrito (SIN-1)] e em seguida foram medidos os produtos de peroxidação lipídica formados: a concentração de TBARs (substâncias reativas ao ácido tiobarbitúrico) e a formação de dienos conjugados empregando-se métodos espectrofotométricos. Também foram determinados o perfil antioxidante total do plasma (TAS), avaliação da lipoperoxidação plasmática basal (TBARs), avaliação da fragmentação da Apolipoproteína B após oxidação da LDL, por eletroforese em gel com SDS-PAGE e os níveis de expressão, por meio de análise de PCR real time, de alguns genes relacionados à produção de enzimas antioxidantes. Teste t de Student pareado foi utilizado para verificar se houve diferença estatisticamente significante entre os resultados das diversas análises antes e após o consumo do chá. RESULTADOS: Os resultados obtidos pela maioria dos ensaios realizados demonstraram que o consumo de chá mate aumentou a resistência à oxidação, a capacidade antioxidante plasmática e a expressão de genes relacionados à produção de enzimas antioxidantes. CONCLUSÃO: Esses resultados sugerem que o consumo de chá mate por período curto pode atuar como antioxidante por múltiplos mecanismos e portanto pode contribuir para diminuição do risco de desenvolvimento de doenças crônicas relacionadas a processos oxidativo. / Yerba Mate (Ilex paraguariensis) is a native and widely consumed South American plant. It contains high concentrations of bioactive compounds that respond for its high antioxidant activity in vitro and in vivo. This activity has not been demonstrated yet in humans for the mate tea, a product derived from Yerba Mate. OBJECTIVE: The aim of this study was to evaluate the antioxidant activity of maté tea in vivo and ex vivo on plasma and LDL human after ingestion of mate tea infusion. METHODS: Fasting peripheral venous blood samples of twenty healthy women (n=20) were taken in three different times: before drinking the tea, one hour later and after one week of daily consumption (7 days) of mate tea. The plasma and isolated LDL were oxidated with 3 different systems [copper (CuSO4), lipoxygenase and peroxynitrite (SIN-1)]. Next, the peroxidation products evaluated were: concentration of malonaldeyde (TBA) and conjugated dienes (lag time), using spectrophotometric methods. We also measured the plasma total antioxidant status (TAS), serum levels of malondialdehyde (MDA) as thiobarbituric substances (TBARS), fragmentation of apo B using SDS-PAGE and the level of antioxidant enzyme gene expression by PCR real time. Paired t student test was used to analyze the results before and after ingestion of mate tea. RESULTS: The results obtained by most of the tests showed that mate tea ingestion increased the plasma and LDL resistance by ex vivo oxidation, the plasma antioxidant capacity and the level of antioxidant enzyme gene expression. CONCLUSION: This study suggests that regular consumption of mate tea can act as an antioxidant by multiple mechanisms and thus may contribute decrease the risk of developing chronic diseases related to oxidative processes.

Nesta dissertação, estudamos o efeito da Rosuvastatina (Ros) sob pacientes hipercolesterolêmicos. Dentro de 180 dias de estudo prospectivo, avaliamos a eficácia da utilização de anticorpos contra a LDL oxidada ou contra sequência peptídica da apolipoproteína B (apoBD) como marcadores no acompanhamento de resposta à droga. Acompanhamos 76 pacientes (Ros.,n=40/cont.,n=36) através das seguintes variáveis: perfil lipídico, TBARS, anticorpos IgG e IgM anti-oxLDL e IgG anti-apoBD. A partir dos resultados obtidos, concluímos que: não houve alterações consideradas significativas dentro do perfil lipídico; o tratamento controle reduziu significativamente TBARS; os anticorpos IgM anti-oxLDL e IgG anti-apoBD foram sensíveis como marcadores e houve redução significativa destes apenas no tratamento com Rosuvastatina; os níveis de anticorpos IgM e IgG anti-oxLDL não são correlacionados; existe correlação direta entre anticorpos IgG anti-oxLDL e anti-apoBD; os níveis de LDL se correlacionam inversamente aos níveis de IgG anti-oxLDL e IgG anti-apoBD. / In this dissertation, we studied the effect of rosuvastatin (Ros) in hypercholesterolemic patients. During 180 days, we evaluated t if antibodies against oxidized LDL or against a peptide from apolipoprotein B (apoBD) would work as markers to monitor a response to the drug. We enrolled 76 patients (Ros.,n = 40/cont.,n = 36 and used the following variables: lipid profile, TBARS, IgG and IgM anti-oxLDL and IgG anti-apoBD., We conclude that there were no significant changes seen in the lipid profile, the control treatment significantly reduced TBARS ,IgM anti-oxLDL and IgG anti-apoBD were sensitive markers and decreased significantly only in the treatment in Ros group; levels of IgM and IgG anti-oxLDL are not correlated; there is a direct correlation between IgG anti-oxLDL and anti-apoBD; LDL levels correlate inversely with levels of IgG anti-oxLDL and IgG anti-apoBD.