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Hassan K.,Bar - Ilan University | Hassan K.,Peritoneal Dialysis Unit Galilee Medical Center | Hassan D.,Galilee Medical Center | Fadi H.,Tel Aviv University | Michelis R.,Eliachar Research Laboratory
International Journal of Clinical and Experimental Medicine | Year: 2016

Introduction: Oxidative stress in peritoneal dialysis (PD) patients produces molecular modifications of serum albumin that disturb its biological functions and interfere with its detection by the commonly used bromocresol green (BCG) assay. This study aimed to evaluate the role of oxidized serum albumin (OSA) in hypoalbuminemic PD patients. Methods: Twenty four PD stable patients with serum albumin levels measured by BCG assay (SACBCG) ≤ 3.0 g/dl enrolled in the study. Serum albumin, OSA, oncotic pressure, hydration status, lean tissue index (LTI), normalized protein equivalent of total nitrogen appearance (nPNA) and high sensitivity C-reactive protein (hsCRP) were determined. OSA was assessed by a specific albumin detection index (ADI). ADI was defined as the ratio between the readout of the non-oxidized serum albumin measured by the BCG assay (SACBCG) to the total (non-oxidized and oxidized) serum albumin concentration in the fraction that determined by absorbance at 280 nm (OD280) (TSACOD280): ADI = SACBCG/TSACOD280. When the SACBCG decreased, as a result of the oxidation of serum albumin, the ADI will be < 1. When low serum albumin levels was determined by the BCG assay (SACBCG) in hypoalbuminemic PD patients with ADI < 1, it was usually refers to “pseudo” hypoalbuminemia because it is not includes the OSA fraction. To establish a diagnosis of true hypoalbuminemia, the total serum albumin including the non-oxidized and oxidized fractions (TSACOD280) should be determined. Participants were assigned to two groups according to their ADI (< 0.5 or ≥ 0.5). Results: Both study groups were comparable in age, BMI, gender, presence of diabetes, PD modality, peritoneal membrane characteristics, Kt/v, residual renal function (RRF), PD vintage and serum albumin levels. All participants had ADI < 1.0 and, therefore, had “pseudo” hypoalbuminemia. Mean ADI was 0.53±0.12 in all patients, 0.43±0.01 in patients with ADI < 0.50 and 0.62±0.03 in patients with ADI ≥ 0.50 (P < 0.001). Extracellular/Intracellular water ratio (E/I ratio) was lower in patients with ADI < 0.5 than in patients with ADI ≥ 0.5 (P = 0.002). Oncotic pressure and hsCRP were higher in patients with ADI < 0.5 than in patients with ADI ≥ 0.5 (P = 0.024, P = 0.032, respectively). nPNA, RRF and LTI were similar in both groups. Conclusions: “Pseudo” hypoalbuminemia, results from the presence of undetectable OSA fraction by the BCG assay, seems to be a very common finding and may mislead medical staff decisions in PD patients. Although OSA may contribute to better oncotic pressure and hydration status of these patients, its pathogenic ability to accelerate atherosclerosis should be kept in mind. © 2016, E-Century Publishing Corporation. All rights reserved. Source

Shema-Didi L.,Western Galilee Hospital | Kristal B.,Western Galilee Hospital Nahariya | Kristal B.,Bar - Ilan University | Sela S.,Bar - Ilan University | And 4 more authors.
Nutrition Journal | Year: 2014

Background: Atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality among hemodialysis (HD) patients. It has been attributed, among other causes, to hypertension and dyslipidemia. The aim of the present study was to investigate the effect of a year-long consumption of Pomegranate juice (PJ), on two traditional cardiovascular (CV) risk factors: hypertension and lipid profile, as well as on cardiovascular events. Methods. 101 HD patients were randomized to receive 100 cc of PJ (0.7 mM polyphenols) or matching placebo juice, three times a week for one year. The primary endpoints were traditional CV risk factors; blood pressure and lipid profile. Systolic, diastolic and pulse pressure, plasma levels of triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol were monitored quarterly during the study year. Secondary endpoint was incidence of cardiovascular events. Results: PJ consumption yielded a significant time response improvement in systolic blood pressure, pulse pressure, triglycerides and HDL level; an improvement that was not observed in the placebo intake group. These beneficial outcomes were more pronounced among patients with hypertension, high level of triglycerides and low levels of HDL. Conclusion: Regular PJ consumption by HD patients reduced systolic blood pressure and improved lipid profile. These favorable changes may reduce the accelerated atherosclerosis and high incidence of CVD among HD patients. Trial registration. ClinicalTrials.gov registry, Identifier number: NCT00727519. © 2014Shema-Didi et al.; licensee BioMed Central Ltd. Source

Ertracht O.,Eliachar Research Laboratory | Malka A.,Technion - Israel Institute of Technology | Atar S.,Western Galilee Medical Center | Atar S.,Bar - Ilan University | Binah O.,Technion - Israel Institute of Technology
Pharmacology and Therapeutics | Year: 2014

The ischemic heart suffers from nutrient deprivation, lack of oxygen, metabolic acidosis, hyperkalemia and Ca2+ overload as well as high level of reactive oxygen species (ROS) generation; these risk factors endanger the cardiomyoctes and may cause their demise. Nevertheless, the treatment of acute myocardial infarction includes reperfusion, although it can exacerbate the effects of ischemia since resumption of blood supply to the ischemic myocardium is associated with increased ROS production. In the past 20 years, preconditioning and postconditioning were revealed, directing research efforts at finding pharmacological agents that can mimic these techniques. Soon thereafter, the involvement of several molecular pathways such as the reperfusion injury salvage kinase, the ATP-sensitive K+ channel, the survivor-activating factor enhancement and the adenosine mono phosphate activated protein kinase pathways were discovered. Further, studies have shown that these pathways convey the adverse effects of ischemia, reperfusion and the combination thereof to the mitochondria, suggesting that the death signals during ischemia and reperfusion are controllable, and can therefore be partially inhibited or even reversed. Hence, the aim of this review is to describe these signaling pathways, the established pre-clinical means to manipulate them, and their current application status in the clinic. © 2013 Published by Elsevier Inc. Source

Shema-Didi L.,Western Galilee Hospital | Kristal B.,Western Galilee Hospital | Kristal B.,Bar - Ilan University | Ore L.,Haifa University | And 4 more authors.
Nutrition Research | Year: 2013

The hemodialysis (HD) procedure induces oxidative stress (OS), which is further aggravated by intravenous (IV) iron administration, aimed at correcting anemia of patients with HD. We have recently shown that 1 year of pomegranate juice (PJ) intake attenuated OS and inflammation in patients with HD. In the current study, we hypothesized that a single dose of PJ can attenuate the enhanced OS and inflammation induced by both the dialysis procedure and IV iron administration during HD session. Twenty-seven patients with HD were randomized to receive PJ or placebo during 1 dialysis session with IV iron. Blood samples were drawn before and after the session to asses OS biomarkers such as advanced oxidation protein products and myeloperoxidase (MPO), whereas polymorphonuclear leukocyte (PMNL) counts served as an indirect measure of inflammation. At the end of the dialysis session, an increase in advanced oxidation protein products and MPO levels as well as a decrease in PMNLs counts were observed in the placebo group, whereas no significant changes occurred in the PJ group. The postdialysis increase in MPO levels in the placebo group is a direct result of PMNL degranulation, associated with postdialysis decrease in PMNL counts. Degranulation of PMNLs leads to the release of other cell moieties, such as inflammatory mediators and proteases that enhance inflammation. We conclude that PJ intake attenuated the increase in systemic OS and inflammation induced by IV iron administration during the dialysis session. These beneficial effects illuminate the previously observed attenuation in OS and inflammation in patients with HD on prolonged PJ intake. © 2013 Elsevier Inc. Source

Farah R.,Western Galilee Hospital | Shurtz-Swirski R.,Eliachar Research Laboratory | Dorlechter F.,Eliachar Research Laboratory
Minerva Cardioangiologica | Year: 2010

Aim. Oxidative stress (OS) and inflammation and are among the mechanisms that have been recently implicated in pathogenesis of hyperlipidemia. Peripheral polymorphonuclear leukocytes (PMNLs) are primed in metabolic syndrome patients, which include hyperlipidemic patients, releasing uncontrolled superoxide contributing to OS and inflammation. Recent studies have attributed additional anti-ischemic and antioxidative characteristics to the antihyperlipidemic antiatherogenic drug, simvastatin. The aim of this paper was to evaluate the possible non-traditional effect of five months' simvastatin treatment on PMNL priming and inflammation in hyperlipidemia. Methods. Thirty non-smoking hyperlipidemic patients were treated for 5 months with Simvastatin and compared with age and gender-matched healthy controls (HC). PMNL priming was assessed by the rate of superoxide release from separated, phorbol ester-stimulated PMNLs and by PMNL-CD11b levels. Inflammation was reflected by blood albumin, transferrin, C-reactive protein (CRP) and fibrinogen levels, white blood cells (WBC), PMNL counts and by PMNL apoptosis. Results. Five months of simvastatin treatment showed a decrease in lipid levels, concomitantly with reduction in PMNL priming, PMNL apoptosis, fibrinogen and CRP levels. Conclusion. PMNLs are primed in hyperlipidemic patients contributing to OS and inflammation in these patients. Treating these patients with Simvastatin may be beneficial due to its combined anti-PMNL priming and anti-inflammatory effects, in addition to its traditional antiatherogenic characteristics. Source

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