High-density Lipoprotein In Patients Research Articles

Lipid radicals and oxidized cholesteryl esters in low- and high-density lipoproteins in patients with β-thalassemia: Effects of iron overload and iron chelation therapy

Iron overload results in lipid peroxidation (LPO) and the oxidative modification of circulating lipoproteins, which contributes to cardiovascular complications in patients with β-thalassemia. Investigating LPO may provide opportunities for the development of novel therapeutic strategies; however, the chemical pathways underlying iron overload-induced LPO in β-thalassemia lipoproteins remain unclear. In this study, we identified various species of lipid radicals (L•), the key mediators of LPO, and oxidized cholesteryl esters (oxCE) derived from the in vitro oxidation of major core lipids, cholesteryl linoleate (CE18:2) and cholesteryl arachidonate (CE20:4); the levels of these radical products in low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were measured and compared between β-thalassemia patients and healthy subjects by using a specific fluorescent probe for L• with a liquid chromatography-tandem mass spectrometric method. Our results demonstrated that iron overload substantially decreased the levels of CE18:2 and CE20:4 substrates and α-tocopherol, resulting in higher levels of full-length and short-chain truncated L• and oxCE products. In particular, CE epoxyallyl radicals (•CE-O) were observed in the lipoproteins of β-thalassemia, revealing the pathological roles of iron overload in the progression of LPO. In addition, we found that intermission for two weeks of iron chelators can increase the production of these oxidized products; therefore, suggesting the beneficial effects of iron chelators in preventing LPO progression. In conclusion, our findings partly revealed the primary chemical pathway by which the LPO of circulating lipoproteins is influenced by iron overload and affected by iron chelation therapy. Moreover, we found that •CE + O shows potential as a sensitive biomarker for monitoring LPO in individuals with β-thalassemia.

RETRACTION: High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells.

Retraction: B. Pan , H. Ren , Y. Ma , D. Liu , B. Yu , L. Ji , L. Pan , J. Li , L. Yang , X. Lv , X. Shen , B. Chen , Y. Zhang , B. Willard , Y. He , and L. Zheng , "High-Density Lipoprotein of Patients with Type 2 Diabetes Mellitus Elevates the Capability of Promoting Migration and Invasion of Breast Cancer Cells," International Journal of Cancer 131, no. 1 (2012): 70-82. https://doi.org/10.1002/ijc.26341. The above article, published online on 29 April 2011, in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Prof. Christoph Plass; the Union for International Cancer Control; and John Wiley and Sons Ltd. A third party reported that they had detected image similarities between figures 3B and 3F. The publisher requested original raw data and images for all Western Blot figures included in the published article, and in response the authors shared what they reported as raw images. A detailed investigation by the editors revealed additional irregularities in the raw data, including the discovery that the data for the Akt and p-Akt bands in Figure 5A had been manipulated between the original images and those presented in the published article. The retraction has been agreed to as the results presented in the article can no longer be considered reliable. The authors disagree with the retraction.

Impact of Vitamin E Supplementation on High-Density Lipoprotein in Patients With Haptoglobin Genotype-Stratified Diabetes: A Systematic Review of Randomized Controlled Trials.

Background: Vitamin E, an essential micronutrient with antioxidant potential, can dramatically reduce the cardiovascular risk in individuals with haptoglobin (Hp) 2-2 genotype diabetes; however, the underlying mechanism remains unclear. Objective: The objective of this study is to evaluate the effect of vitamin E supplementation on high-density lipoprotein (HDL) levels and function in individuals with diabetes stratified by Hp genotype. Methods: All relevant studies published up to May 2023 were systematically reviewed using PubMed, Cochrane Library, Web of Science, Chinese Wanfang, China Science and Technology Journal, and Chinese National Knowledge Infrastructure databases. Randomized controlled trials that evaluated the effects of vitamin E supplementation on HDL levels were included. The outcomes assessed were changes in HDL concentrations, cholesterol efflux, and HDL-associated lipid peroxides. Results: In total, 163 publications were selected. Based on inclusion and exclusion selection and quality assessment, five studies with 463 participants were included. Vitamin E supplementation did not exert any effect on HDL levels in individuals with diabetes with any Hp genotype. Three of the five studies revealed that vitamin E improved cholesterol efflux and HDL lipid peroxides in individuals with Hp2-2 diabetes but did not positively impact HDL function in Hp1 carriers. Conclusions: Although vitamin E supplementation did not significantly impact HDL levels in individuals with diabetes of any Hp genotype, it may improve HDL function in individuals with Hp2-2 diabetes. These findings indicate a pharmacogenetic interaction between vitamin E and the Hp genotype on HDL function. Moreover, vitamin E supplementation may be an effective strategy for specific individuals with diabetes.

A novel method to derive personalized minimum viable recommendations for type 2 diabetes prevention based on counterfactual explanations.

Despite the growing availability of artificial intelligence models for predicting type 2 diabetes, there is still a lack of personalized approaches to quantify minimum viable changes in biomarkers that may help reduce the individual risk of developing disease. The aim of this article is to develop a new method, based on counterfactual explanations, to generate personalized recommendations to reduce the one-year risk of type 2 diabetes. Ten routinely collected biomarkers extracted from Electronic Medical Records of 2791 patients at low risk and 2791 patients at high risk of type 2 diabetes were analyzed. Two regions characterizing the two classes of patients were estimated using a Support Vector Data Description classifier. Counterfactual explanations (i.e., minimal changes in input features able to change the risk class) were generated for patients at high risk and evaluated using performance metrics (availability, validity, actionability, similarity, and discriminative power) and a qualitative survey administered to seven expert clinicians. Results showed that, on average, the requested minimum viable changes implied a significant reduction of fasting blood sugar, systolic blood pressure, and triglycerides and a significant increase of high-density lipoprotein in patients at risk of diabetes. A significant reduction in body mass index was also recommended in most of the patients at risk, except in females without hypertension. In general, greater changes were recommended in hypertensive patients compared to non-hypertensive ones. The experts were overall satisfied with the proposed approach although in some cases the proposed recommendations were deemed insufficient to reduce the risk in a clinically meaningful way. Future research will focus on a larger set of biomarkers and different comorbidities, also incorporating clinical guidelines whenever possible. Development of additional mathematical and clinical validation approaches will also be of paramount importance.

Elevated Neutrophil Counts, Triglycerides, Monocyte/High-Density Lipoprotein Ratios, and Lower High-Density Lipoprotein in Patients with Retinal Vein Occlusion

Introduction: The aim of the study was to evaluate associations of peripheral blood immune cells and blood lipid profile levels with retinal vein occlusion (RVO). Methods: This retrospective study included 127 patients with RVO and 108 controls. Patients with RVO were divided into branch RVO (BRVO), central RVO (CRVO), ischemic RVO, or nonischemic RVO groups. Medical records were collected and analyzed. Results: The RVO group had higher mean neutrophil, triglyceride (TG), and monocyte/high-density lipoprotein (HDL) ratio (MHR) levels and lower HDL levels (p = 0.037, p < 0.001, p = 0.004, and p = 0.002, respectively). TG and MHR levels were significantly higher in the BRVO and CRVO groups compared with the control group (p < 0.001 and p = 0.016, respectively), but there was no difference in BRVO and CRVO group (p = 0.972 and p = 0.916, respectively). Mean HDL levels were significantly lower in the BRVO and CRVO groups than in the control group (p = 0.005), but the difference between the BRVO group and CRVO group was not significant (p = 0.290). Neutrophils, TG, and MHR were independent risk factors for RVO. HDL was an independent protective factor for RVO. Age was an independent risk factor for ischemic RVO. Conclusions: Lower HDL, and higher neutrophil, TG, and MHR levels are associated with RVO. Age is an independent risk factor for ischemic RVO.

Effectiveness of Daily Living Activities Program on Total Cholesterol, Low-Density Lipoprotein, and High-Density Lipoprotein of Patients with coronary artery disease

Background: High levels of total cholesterol, low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL) are risk factors for patients with coronary artery disease (CAD). Daily activities are very important for CAD patients due to their effect on improving heart functions, lipid profile, reduced risk factors, decreased incidence and the recurrence rate of CAD. &#x0D; Aims of the study: To find out the effectiveness of daily living activities program on Total Cholesterol, LDL, and HDL of Patients with coronary artery disease. &#x0D; Methodology: A pre-experimental study design was implemented of the period 20th of December 2020 to the 4th of April 2021.The study was carried out in AL-Nasiriya Heart Center in AL-Nasiriya city on 40 coronary artery disease patients selected by using A non-probability (purposive) sampling method was used for selecting the study sample. The study instrument is composed of 4 parts. The first is demographic characteristics, the second part is the clinical history of patient and unhealthy behaviors, the third part is about investigation of total cholesterol, low-density lipoprotein, and levels of high-density lipoprotein, and the fourth part consists of two items related to patients’ responses regarding risk factors, importance of activity, healthy diet, and stress management. &#x0D; Results: The study reveals that (50.0%) of the participants in the study sample at age group (56–66) years old, and (57.5%) of the participants in the study sample are females, (82.5%) of study sample is married and (85.0%) was urban resident, (35.0%) of the study sample was Graduated of middle school education, (52.5%) of study sample was housewives, and (52.0%) of them are in sufficient income, also (55.0%) of them have (7-9) persons in their family. The results indicate that there is significant statistically differences between pre and post-test for total cholesterol p value (0.044), high density lipoprotein p value (0.00), and low density lipoprotein p value (0.006). Also showed that the cholesterol normal category was (2.5%) changed to (12.5%); Borderline high category was (97.5%) decreased to (87.5%) at post-test, high density lipoprotein normal category was (00.0%) changed to (17.5%); borderline high category was (12.5%) changed to (37.5%); high category was (87.5%) changed to (45%) at post-test, low density lipoprotein normal category was (00.0%) increased to (17.5%); borderline high category was (100%) changed to (82.5). &#x0D; Conclusion: The study concluded that the instructional program of daily living activities was effective in improving the levels of total cholesterol, low-density lipoprotein (LDL), and levels of high-density lipoprotein (HDL) of the study sample after the program implementation. &#x0D; Recommendations: Educating coronary patients on the effects of hyperlipidemia on the health of their coronary arteries, as well as encouraging them to participate in daily activities. Increase patient awareness by using Mass Media about the importance of exercise and a healthy lifestyle and its impact on the lipid profile to reduce the incidence and the recurrence rate of CHD.&#x0D;

Prognostic Value of Platelet-Lymphocyte Ratio and High-Density Lipoprotein in Patients with Acute Myocardial Infarct

Acute Myocardial Infarct (AMI) is the main reason for mortality. Platelet to Lymphocyte Ratio (PLR) describesthrombocyte aggregation and inflammation that is linked to cardiovascular disease. High-Density Lipoprotein (HDL) is antiatherogenic.This study aims to analyze the prognostic value of PLR and HDL in patients with AMI. This study was aretrospective observational study by obtaining laboratory results from complete blood count and lipid profiles frominpatients with AMI (STEMI and NSTEMI) medical records during Mei 2019–August 2020. Receiver Operating Characteristics(ROC) analysis was done to get the PLR and HDL cut-off. Prognostic value evaluation was based on sensitivity, specificity,positive and negative predictive value, and accuracy. Results obtained were from 302 subjects with a mean age of 58.4+9.6years old, with most male patients (74.5%). Receiver operating characteristics curve analysis showed an 0.514 Area UnderCurve (AUC) for PLR with p=0.685. High-density lipoprotein ROC was 0.573 with a p=0.033 (p&lt; 0.05), with HDL cut-off = 50.0;sensitivity 72.7%, specificity 32.3%, positive predictive value 63.3%, negative predictive value 42.0% and 57.3% accuracy.Platelet to lymphocyte ratio mean was lower in the HDL &lt;50 group (187.9) compared to the HDL &gt; 50 (210.8), (p=0.009).High-density lipoprotein can be concluded as a potential prognostic factor of acute myocardial infarct. The lower the HDL,the greater the risk for a poor prognosis. A big-scale prospective study should be held to clarify and confirm these findings.

Low Levels of High-density Lipoprotein in Patients with Pediatric Cancer at Diagnosis

Introduction: Cancer patients have metabolic imbalances due to the disease, treatment and their complications. Increases in triglycerides and glucose profile and catabolism of protein have been described and are associated with inflammatory response as result of the tumor activity or necrosis. Objective: To evaluate the blood lipid, lipoproteins, glucose and albumin levels in pediatric cancer patients at diagnosis. Method: Observational cross-sectional study. The inclusion criteria were children and adolescents with newly diagnosed malignancies and blood analysis results. The exclusion criteria were: previous anticancer therapy or surgical treatment, blood sample not collected and patients who refused to participate in the study. Results: It were evaluated 81 children and adolescents with newly diagnosed malignancies. There was decrease of 56% and 41% of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), 14% and 10% of albumin and glucose, and 10% and 7.6% of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), respectively, for the patients. HDL-C showed statistical differences between solid and hematological cancer patients (p &lt; 0.05). The means and medians of albumin, glucose, HDL-C and TG demonstrated that hematological patients are more prone to metabolic disturbances. HDL-C in this group was 24 ± 12 versus 40 ± 15mg/dl in other cancers. Conclusion: The primary result found in the present study was in HDL-C, mainly in patients with hematological and metastatic cancer. These disturbances could be associated with cancer-related acute inflammatory response.

Gamma-background environment during magnetic storms and the content of high density lipoprotein in patients with arterial hypertension depending on the temperament and variant of antihypertensive therapy

Gamma-background environment during magnetic storms and the content of high density lipoprotein in patients with arterial hypertension depending on the temperament and variant of antihypertensive therapy

Dysfunctional High-density Lipoproteins in Patients with Thyroid Disorders

Dysfunctional High-density Lipoproteins in Patients with Thyroid Disorders

PHARMACOLOGICAL EFFECTS OF GEMFIBROZIL ON SOME CARDIOVASCULAR PREPARATIONS OF EXPERIMENTAL ANIMALS

Gemfibrozil (member of fibrates) is Peroxisome proliferator activated receptors (PPAR-α) agonist which improves lipid profiles particulary very low density lipoprotein and high density lipoprotein in patients with dyslipidemia.Objective: Studying the pharmacological effects of Gemfibrozil on some cardiovascular preparations of experimental animals. Materials and Methods: The experiments were conducted to study the effect of different doses of gemfibrozil on isolated perfused rabbit heart & coronary flow, isolated rabbit aortic spiral strip and mean arterial blood pressure of anaesthetized cats. Each experiment was done on six preparations. Results: In-vitro study: onisolated perfused rabbit heart, gemfibrozil (25-800µg/ml) produced a dose-dependent reduction on the amplitude of myocardial contractions. The inhibitory effect of gemfibrozil (100µg/ml) was not abolished after complete blockade of nicotinic and muscarinic receptors while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of calcium gluconate, isoprenaline, histamine and serotonin were not abolished after administration of gemfibrozil (100µg/ml). On coronary flow of isolated perfused rabbit heart, gemfibrozil (25-800μg/ml) produced also a dose-dependent reduction of coronary flow. On isolated spiral aortic strips of rabbit , gemfibrozil produced dose-dependent significant reduction on nor-epinpherine (NE) induced contraction. In-vivo study gemfibrozil produced a dose-dependent significant reduction in mean arterial blood pressure (MABP) of anaesthetized cats. Conclusion: Gemfibrozil produced a negative inotropic effect through nitric oxide release with a decrease in coronary flow. It also reduced NE- induced contractions of aortic spiral strips with reduction in mean arterial blood pressure. So it must me used cauciously in cases of heart failure, but it could be beneficial in hypertensive patient with atherosclerosis.

High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation.

Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis. This work indicates a prospective utilization of HDL-based strategies in the treatment of breast cancer patients with type 2 diabetes.

Lipid metabolism in patients with hematologic cancers

It is considered that hypercholesterolemia is life-threatening and low cholesterol levels are a positive factor. However, taking into consideration the fact that cholesterol plays a key role in cell proliferation, it should be remembered that its low blood level may be linked to high cholesterol demands from neoplastic cells. The literature review analyzes the results of recent investigations of lipid metabolism in patients with hematologic cancers and their other types. All given investigations show a significant reduction in the serum levels of total cholesterol and high-density lipoproteins in patients with hematological disease at its onset. The data for other indicators of the lipid transport system are ambiguous. Such changes have been elucidated to be associated with the accumulation of cholesterol in the leukemia cells due to enhanced synthesis de novo, a more active absorption from circulation and blocked release of its surplus. If the disease runs a favorable course, lipid metabolic parameters become normalized and, in case of remission, correspond to those seen in healthy individuals. They continue to decline in patients with disease progression. This allows the consideration of cholesterol, its fractions, and apolipoproteins as biochemical prognostic markers in hematological cancer patients and as indicators for assessment of treatment results. In addition, there is evidence for the effect of chemotherapeutic agents on lipid metabolism. Recent attempts to elaborate new treatment strategies, by using the current knowledge on the role of lipid metabolism in cancers, are considered.

Impaired Antiatherogenic Functions of High-density Lipoprotein in Patients with Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with increased risk of cardiovascular disease (CVD). High-density lipoprotein (HDL) exerts a series of antiatherogenic properties and protects from CVD. We evaluated whether HDL antiatherogenic properties are impaired in patients with AS. HDL (apoB-depleted serum) was isolated from 35 patients with AS and 35 age- and sex-matched controls. We measured the antioxidant capacity of HDL, the ability of HDL to induce cholesterol efflux, the activity of HDL-associated enzymes paraoxonase-1 (PON1) and myeloperoxidase (MPO), as well as the ability of HDL to induce Akt kinase activation. HDL from patients with AS had decreased antioxidant capacity and decreased ability to promote cholesterol efflux from macrophages compared to controls. HDL-associated PON1 activity was lower and HDL-associated MPO activity higher in patients with AS compared to controls. Higher MPO activity correlated positively with lower antioxidant capacity of HDL in patients with AS. In addition, HDL from patients with AS had impaired endothelial Akt kinase activating properties that were inversely correlated with the MPO/PON1 ratio and positively correlated with the cholesterol efflux capacity of HDL. HDL from patients with AS displays impaired antiatherogenic properties. Attenuation of HDL properties may constitute a link between AS and CVD.

Investigating the Effect of a Single Infusion of Reconstituted High-Density Lipoprotein in Patients with Symptomatic Carotid Plaques

BackgroundElevation of plasma high-density lipoprotein (HDL) cholesterol concentration reduces cardiovascular mortality and morbidity. HDLs have been shown to possess acute anti-inflammatory, antioxidant, and antithrombotic properties. We hypothesize that HDL therapy can acutely alter local and systemic manifestations of plaque instability.MethodsForty patients with early symptomatic carotid disease were randomized to either receive reconstituted HDL (rHDL) 40 mg/kg (n = 20) or placebo (n = 20). Carotid endarterectomies were performed 24 hr later. Plaques were obtained intraoperatively and used for measurement of thrombomodulatory genes expression. Plasma samples were collected before the infusion, 24 and 48 hr later to measure changes in systemic markers of plaque instability.ResultsNo significant differences were noted in thrombomodulatory genes expression between the 2 groups. Systemic levels of tissue factor, matrix metalloproteinase 9 (MMP-9), and monocyte chemotactic factor-1 (MCP-1) were significantly reduced in the rHDL group. However, the effects on MMP-9 and MCP-1 were abolished in the immediate postoperative period. Although rHDL did not affect plasma interleukin-6 levels 24 hr following the infusion, it prevented the significant postoperative elevation seen in the placebo group.ConclusionsA single infusion of rHDL can acutely alter plasma biomarkers associated with plaque instability and cardiovascular morbidity.

SP0159 Exercise therapy in systemic lupus erythematosus

Low physical activity has been reported in systemic lupus erythematosus (SLE). It has been noted that patients with SLE exercise less than population controls and patients with more organ damage...

High-density lipoprotein of patients with Type 2 Diabetes Mellitus upregulates cyclooxgenase-2 expression and prostacyclin I-2 release in endothelial cells: relationship with HDL-associated sphingosine-1-phosphate

BackgroundDysfunctional high-density lipoprotein (HDL) may have pro-inflammatory effects on the endothelial cells,which causes atherosclerosis in type 2 diabetes mellitus (T2DM). HDL is a major carrier of sphingosine-1-phosphate (S1P) in plasma while S1P exhibits multiple biological activities. However, potential role of HDL and S1P in T2DM remains unexplored. We hypothesized that diabetic HDL with higher contents of S1P exerts beneficial effects on the vascular system.MethodsSubjects with T2DM with or without proved large arteries atherosclerosis and normal controls (n=15 for each group) were recruited in the present study. HDL was isolated from the subjects by ultracentrifugation. The levels of HDL-associated S1P were determined by UPLC-MS/MS. The protective function of diabetic HDL and S1P was evaluated by measuring cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release by human umbilical vein endothelial cells (HUVECs) using western blot and enzyme-linked immunosorbent assay (ELISA), respectively.ResultsThe S1P levels in isolated HDL were significantly increased in T2DM subjects compared with controls (235.6 ± 13.4 vs 195.0 ± 6.4 ng/mg, P< 0.05). The diabetic HDL exerted greater protective effects on inducing COX-2 expression and PGI-2 release by HUVECs than those of control HDL (p < 0.05, p < 0.01, respectively). Pertussis toxin, a common inhibitor of G-couple protein receptors, and VPC 23019, an antagonist of S1P receptor 1 and 3 significantly attenuated HDL-induced COX-2 expression and PGI-2 release.ConclusionsDiabetic HDL carries higher level of S1P compared with normal HDL, which has the potential to contribute to protective effects on endothelial cells by inducing COX-2 expression and PGI-2 release. These findings provide a new insight of S1P function in T2DM patients, possibly leading to a new therapeutic target.

Impact of improving quality of dialysis fluid on oxidative stress and lipid profile in hemodialysis patients.

The aim of this study was to evaluate the levels of malondialdehyde as an oxidative stress marker in the same hemodialysis patients after changing the quality of dialysate with ultrapure dialysis fluid. Methods. This prospective study concerns hemodialysis patients; all patients were in the first step treated with conventional dialysate, and in the second step (three months later) the same patients were treated with online produced ultrapure dialysis fluid. The malondialdehyde, C-reactive protein, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, fibrinogen, and albumin were quantified before the two steps. Results. Thirty-seven patients completed the study. Ultrapure dialysis fluid reduced but not significantly the malondialdehyde concentrations. Both dialysis fluids were associated with improvement in the malondialdehyde level before and after the hemodialysis session. In lipid parameters, there was a significant decrease with conventional dialysis fluid versus ultrapure dialysis fluid of triglycerides, total cholesterol, and high-density lipoprotein in patients' blood. Instead, the level of low-density lipoprotein, fibrinogen, albumin, and C-reactive protein does not change significantly. Conclusion. The lipid parameters were improved for triglycerides and total cholesterol. Malondialdehyde increases following the hemodialysis session, and the conventional dialysate increased malondialdehyde levels more than the ultrapure dialysis but the differences were not statistically significant.

Dysfunctional High-Density Lipoprotein in Patients on Chronic Hemodialysis

This study examined the functionality of high-density lipoprotein (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD). The high rate of cardiovascular disease (CVD) in chronic kidney disease is not explained by standard risk factors, especially in patients with ESRD-HD who appear resistant to benefits of statin therapy. HDL is antiatherogenic because it extracts tissue cholesterol and reduces inflammation. Cellular cholesterol efflux and inflammatory response were assessed in macrophages exposed to HDL of patients with ESRD-HD or controls. HDL from patients with ESRD-HD was dramatically less effective than normal HDL in accepting cholesterol from macrophages (median 6.9%; interquartile range [IQR]: 1.4% to 10.2%) versus control (median 14.9%; IQR: 9.8% to 17.8%; p < 0.001). The profound efflux impairment was also seen in patients with ESRD-HD and diabetes compared with patients with diabetes without renal disease (median 8.1%; IQR: 3.3% to 12.9%) versus control (median 13.6%; IQR: 11.0% to 15.9%; p = 0.009). In vitro activation of cellular cholesterol transporters increased cholesterol efflux to both normal and uremic HDL. HDL of patients with ESRD-HD had reduced antichemotactic ability and increased macrophage cytokine response (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). HDL of patients with ESRD-HD on statin therapy had reduced inflammatory response while maintaining impaired cholesterol acceptor function. Interestingly, impaired HDL-mediated efflux did not correlate with circulating C-reactive protein levels or cellular inflammatory response. These findings suggest that abnormal HDL capacity to mediate cholesterol efflux is a key driver of excess CVD in patients on chronic hemodialysis and may explain why statins have limited effect to decrease CV events. The findings also suggest cellular cholesterol transporters as potential therapeutic targets to decrease CV risk in this population.

High density lipoprotein in patients with liver failure; relation to sepsis, adrenal function and outcome of illness

High density lipoprotein (HDL) plays an important role in the transport of cholesterol to the adrenal gland for steroidogenesis and may have actions that modulate response to infection and critical illness. The clinical relevance of HDL level in patients with liver failure remains poorly characterised. In 164 critically-ill patients with acute (ALF) and acute on chronic liver failure (AOCLF) we evaluated the relationship between HDL levels measured on admission to intensive care unit (ICU) and survival, predisposition to sepsis and adrenocortical function assessed through the cortisol response to short synacthen testing (SST). In acute liver failure and acute on chronic liver failure, high density lipoprotein levels were significantly lower in non-survivors (P<0.01). Levels correlated closely with biochemical markers of liver function and the duration of liver failure. However, predictive accuracy was not superior to conventional markers and on multi-variate analysis did not show independent association with survival. Low HDL concentration was not associated with an increased incidence of sepsis either precipitating or complicating ICU admission. Evidence of adrenocortical insufficiency was present in more than half of patients undergoing SST and HDL level but not other lipid parameters correlated closely with cortisol increment after SST (r=0.364, P<0.0001). High density lipoprotein levels are low in patients with liver failure and reflect its severity. Levels are lower in non-survivors but do not offer an advantage as early indicators of prognosis over conventional markers. No evidence of a major predisposing role for infection was found, but findings suggest a close link to adrenal function.