Ozge Tugce Pasaoglu

Neutrophil to Lymphocyte Ratio in Evaluation of Inflammation in Patients with Chronic Kidney Disease

Aim: The current data have proven the pivotal role of inflammation in the development of atherosclerosis and cardiovascular diseases in patients with chronic kidney disease (CKD). Neutrophil to lymphocyte (N/L) ratio has increasingly been reported as a measure of systemic inflammation. This study assessed N/L ratio and investigated its associations with standard inflammatory biomarkers in different stages of CKD patients. Material and methods: This cross-sectional study included 30 predialysis, 40 hemodialysis, 35 peritoneal dialysis patients, and 30 healthy subjects. N/L ratio and important clinical and laboratory parameters were registered. Multivariate regression analyses were carried out to investigate the relations of N/L ratio. Results: N/L ratio was significantly higher in each patient group compared to the healthy subjects (for all, p < 0.001). It was positively correlated with interleukin-6 (IL-6) (r = 0.393, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.264, p = 0.002) levels and negatively correlated with hemoglobin (r = −0.271, p = 0.001), serum albumin (r = −0.400, p < 0.001), and high-density lipoprotein (HDL) cholesterol levels (r = −0.302, p < 0.001). In CKD patients with hypertension (HT), higher N/L ratio was detected when compared to those without HT (p = 0.006). Having CKD, the presence of HT, serum albumin, HDL-cholesterol, IL-6, and hs-CRP levels were found to be independent predictors of the ratio after adjusting for significant covariates (p < 0.001). Conclusion: An easy and inexpensive laboratory measure of N/L ratio might provide significant information regarding inflammation in CKD including predialysis and dialysis patients.

Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats.

Abstract Context: Melatonin, a pineal hormone and a potent antioxidant, has important roles in metabolic regulation. Objective: This study investigated serum asymmetric dimethylarginine (ADMA), homocysteine (Hcy), nitric oxide (NO) levels, known to be reliable markers of cardiovascular diseases, and determined possible protective effects of melatonin in fructose-fed rats. Materials and methods: Sprague–Dawley rats were divided into four groups: control, fructose, melatonin, and fructose plus melatonin. Metabolic syndrome was induced in rats by 20% (w/v) fructose solution in tap water, and melatonin was administered at the dose of 20 mg/kg bw per day by oral gavage. After 8 weeks, serum lipids, glucose, insulin, ADMA, Hcy, and NOx (the stable end products of NO) levels were quantified. Results: Fructose administration caused a statistically significant increase in systolic blood pressure (SBP), serum insulin, triglycerides, and very low-density lipoprotein (VLDL)–cholesterol levels compared with the control group and the metabolic syndrome model was successfully demonstrated. In comparison with the control group, fructose caused a significant increase in serum ADMA, Hcy, and NOx levels. Melatonin counteracted the changes in SBP, serum ADMA, and Hcy levels found in rats both alone and administered with fructose. Discussion and conclusion: These results show that high fructose consumption leads to elevated SBP, atherogenic lipid profile, increased serum ADMA, and Hcy levels and melatonin treatment has beneficial effects on these biochemical parameters in rats. Melatonin might be beneficial for the prevention and/or treatment of the cardiovascular complications of metabolic syndrome not only by reducing the well-known risk factors of the disease but also by diminishing blood ADMA and Hcy levels.

Novel Inflammatory Marker in Dialysis Patients: YKL-40

YKL‐40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL‐40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL‐40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine‐6 (IL‐6) and an acute phase mediator, high sensitivity C‐reactive protein (hs‐CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL‐40, IL‐6, hs‐CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL‐40, IL‐6, hs‐CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein‐cholesterol (P < 0.001). YKL‐40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL‐6 (P < 0.001, r = 0.306), hs‐CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = −0.285), serum albumin (P < 0.001, r = −0.355) and high density lipoprotein‐cholesterol (P = 0.001, r = −0.306). In multivariate regression analysis YKL‐40 was associated with creatinine, serum albumin and hs‐CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL‐40 concentrations. Associations with standard inflammatory parameters suggest that YKL‐40 might be a novel inflammatory marker in this population.

Protective effect of adrenomedullin on contrast induced nephropathy in rats

BACKGROUND AND AIMS Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. METHODS Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. RESULTS Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. CONCLUSION This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue.

Echocardiographic epicardial adipose tissue measurements provide information about cardiovascular risk in hemodialysis patients

Epicardial adipose tissue (EAT) is a cardiovascular risk predictor in general population. However, its value has not been well validated in maintainance hemodialysis (MHD) patients. We aimed to assess associations of EAT with cardiovascular risk predictors in nondiabetic MHD patients. In this cross‐sectional study, we measured EAT thickness by transthoracic echocardiography in 50 MHD patients (45.8 ± 14.6 years of age, 37 male). Antropometric measurements, bioimpedance analysis, left ventricular (LV) mass, carotis intima media thickness, blood tests, homeostasis model assessment for insulin resistance (HOMA‐IR) and hemodialysis dose by single‐pool urea clearence index (spKt/V) were determined. The mean EAT thickness was 3.28 ± 1.04 mm. There were significant associations of EAT with body mass index (β = 0.590, P < 0.001), waist circumference (β = 0.572, P < 0.001), body fat mass (β = 0.562, P < 0.001), percentage of body fat mass (β = 0.408, P = 0.003), percentage of lean tissue mass (β = −0.421, P = 0.002), LV mass (β = 0.426, P = 0.002), carotis intima media thickness (β = 0.289, P = 0.042), triglyceride/high‐density lipoprotein cholesterol ratio (β = 0.529, P < 0.001), 1/HOMA‐IR (β = −0.386, P = 0.006), and spKt/V (β = −0.311, P = 0.028). No association was exhibited with visfatin C, high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor‐alpha (for all, P > 0.05). Body mass index, waist circumference, body fat mass, percentage of lean tissue mass, LV mass, triglyceride/high‐density lipoprotein cholesterol ratio, HOMA‐IR, and spKt/V appeared as independent predictors of EAT. EAT was significantly associated with body fat measures, cardiovascular risk predictors, and dialysis dose in MHD patients.

The effects of ventilation with high density oxygen on the strength of gastrointestinal anastomosis

Purpose The aim of our study is to evaluate the effects of administration of perioperative supplemental oxygen on anastomoses. Methods Forty male Wistar albino rats were used in the study and randomized into 4 groups. Ischemia-reperfusion models were built in groups 3 and 4. Jejunojejunostomy was performed in all rats and assigned to an oxygen/nitrous oxide mixture with a fraction of inspired oxygen of 30% in groups 1 and 3 and 80% in groups 2 and 4. The measurements of perianastomotic tissue oxygen pressure, bursting pressure, level of hydroxyproline were evaluated and compared in all groups. Results The perianastomotic tissue oxygen pressures, bursting pressures and levels of hydroxyproline were identified as significantly high in groups 2 and 4, administered a fraction of inspired oxygen of 80%, compared to groups 1 and 3, administered a fraction of inspired oxygen of 30%. Conclusion Perioperative supplemental oxygen contributes positively to the anastomotic healing.

Inflammatory markers, oxidative stress, and antioxidant capacity in healthy allo-HSCT donors during hematopoietic stem cell mobilization

The aim of this study is to investigate the impact of mobilization with granulocyte colony stimulating factor (G‐CSF) and apheresis procedure on inflammatory and oxidative stress markers, and antioxidant capacity in healthy allo‐HSCT donors. The study was conducted in the Stem Cell Transplantation Unit of Gazi University Hospital between October 2010 and March 2011, and 25 consecutive allo‐HSCT donors were included. The alteration in the serum levels of iron, iron binding capacity, albumin, ferritin, IL‐6, hs‐CRP, TAC, MDA, and AOPP were determined at five different time points. (1) Prior to the first dose of G‐CSF (T0), (2) preapheresis (on the fourth day of G‐CSF before the apeheresis procedure) (T1), (3) immediately postapheresis (T2), (4) 24 h postapheresis (T3), and (5) a week after apheresis (T4). Serum ferritin levels increased steadily after administration of G‐CSF and remained high up toT4. Both serum IL‐6 and hs‐CRP levels began to increase in the T1 sampling and reached to a maximum level at T3 and decreased even below the basal levels at T4. Serum AOPP levels decreased at preapheresis and postapheresis time points, while they increased at T3 and T4 samples. Serum MDA levels decreased at T1, T2, T3, and T4 samples. Serum TAC increased significantly and steadily at all time points post G‐CSF. In conclusion; mobilization with G‐CSF and apheresis caused a transient inflammatory reaction and a protein limited oxidative stress in healthy allo‐HCT donors. J. Clin. Apheresis 30:197–203, 2015.

Serum antimicrobial peptides in patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is characterized by recurrent inflammation of serosal and synovial membranes. Despite the fact that it is a genetic disease, environmental factors, including infections, are shown to be triggering factors associated with the precipitation of attacks in FMF. Antimicrobial peptides (AMPs) are components of innate immunity which exert antimicrobial activity against many microorganisms. Human AMPs; cathelicidin (LL37) and defensins have immunomodulatory properties and are involved in the pathogenesis of many inflammatory disorders. Hence, we investigated serum AMPs in 23 newly diagnosed FMF patients. Blood samples were obtained at baseline, 6 months after initiation of colchicine and during an attack. Twenty-four healthy individuals constituted the control group. The concentrations of LL37, alpha-1, beta-1 and beta-2 defensins were determined by ELISA. Serum AMPs did not change during attacks and did not correlate with acute phase reactants. However, serum LL37 and defensins were found to be remarkably higher in FMF patients compared to healthy individuals both at baseline and 6 months after initiation of colchicine therapy which suggest that AMPs might have a role in the pathogenesis of FMF.

Exogenous Recombinant Adiponectin Improves Survival in Experimental Abdominal Sepsis

BACKGROUND Adiponectin, which has anti-inflammatory features, is an important substance in several metabolic mechanisms. AIMS The aim of this study is to evauate the effects of exogenous intraperitoneal administration of adiponectin on the survival, intrabdominal adhesion and inflammatory cytokine levels in an experimental sepsis model. STUDY DESIGN Animal experimentation. METHODS Ninety rats were divided into a control group, adiponectin group and sham group. A cecal puncture abdominal sepsis model was performed in the adiponectin and control groups. Every three hours, exogenous adiponectin was administrated to the adiponectin group. At the 3(rd) and 24(th) hours, 10 rats were sacrified in each group in order to measure plasma tumor necrosis factor-α (TNF-α), interleukin (IL) 10, soluble intracellular adhesion molecule (ICAM)-1, IL-6 and macrophage inhibitory factor levels, and the activity of nuclear factor (NF)-kB. The remaining rats were followed for survival. RESULTS The plasma levels of TNF-α, soluable ICAM-1, IL-6, and macrophage inhibitory factor were significantly higher in the control group than in the adiponectin and sham group (p<0.05). The increase in inflammatory cytokines with time was more prominent in the control group. The activity of NF-kB in the control group was higher than in the adiponectin group (p<0.05). The survival rate of the adiponectin group was higher than in the control group. CONCLUSION Administration of exogenous adiponectin to the peritoneum in abdominal sepsis increased survival and decreased intrabdominal adhesions by decreasing the inflammatory response.

Relationship between obesity and iron deficiency anemia: is there a role of hepcidin?

ABSTRACT Objectives: Iron deficiency is common in obese children although the underlying mechanism is unclear. The aim of this study was to investigate the associations between iron parameters, leptin, hepcidin and adiponectin levels in obese children. Methods: A total of 237 children, ranging in age from 5 to 18 years, 180 with primary obesity and 57 healthy children and adolescents, were enrolled. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, leptin, hepcidin and adiponectin levels were studied. Results: White blood cell and platelet count, iron-binding capacity, high-sensitive C-reactive protein, leptin and hepcidin values in the obese group were higher than those of the control group (p < 0.001, p = 0.002, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). However, mean corpuscular volume, adiponectin and transferrin saturation values in the obese group were lower than in the control group (p = 0.026, p = 0.003, and p < 0.001, respectively). No significant differences were found in terms of hemoglobin, serum ferritin, iron and IL-6 levels. Conclusions: Our study suggests that hepcidin levels do not contribute to the development of iron deficiency anemia in pediatric obese individuals.