Hatice 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.

Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome

Aim. This study was designed to examine the relationship between homocysteine (Hcy), lipoprotein levels and insulin resistance in obese and non-obese patients with polycystic ovary syndrome (PCOS). Materials and methods. Eighty-five patients (38 obese, 47 non-obese) with PCOS and 50 healthy subjects (25 obese, 25 non-obese) were included in the study. PCOS was defined according to the Homburg criterion. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), insulin, 17-hydroxyprogesterone, free testosterone, androstenedione, vitamin B12 and folate were measured. Also, serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), apoprotein B (Apo B) and apoprotein A (Apo A) were determined. Plasma Hcy levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). Results. Plasma Hcy levels were significantly higher in women with PCOS than in healthy women. HOMA-R (insulin resistance) was significantly higher in women with PCOS compared with healthy women. Serum fasting TC, LDL-C, TG, Apo B, vitamin B12 and folate levels were similar between PCOS and control groups. Lp(a) levels were higher in PCOS patients than in control subjects, whereas HDL-C and Apo A levels were lower. Compared with obese PCOS subjects, non-obese PCOS subjects had low HOMA-R, TC, LDL-C, TG, Apo B, Lp(a) and androgen levels. Plasma Hcy levels, serum HDL-C and Apo A levels were similar between obese and non-obese women with PCOS. Levels of HDL-C and Apo A were lower in both obese and non-obese PCOS patients than in obese and non-obese control subjects, whereas Lp(a) levels were higher. No correlation was observed between plasma Hcy, body mass index, HOMA-R, serum androgen levels, TC, LDL-C, HDL-C, Apo A, Apo B and Lp(a) levels. Conclusion. These results showed that elevated insulin resistance and plasma Hcy levels, and changes in serum lipid profile, which are possible risk factors for cardiovascular disorders, play important roles in the development of cardiovascular disease in both obese and non-obese patients with PCOS.

Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis.

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). &bgr;-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of &bgr;-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received &bgr;-glucan or &bgr;-glucan + &bgr;-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) &agr;, interleukin (IL) 1&bgr;, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. &bgr;-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the &bgr;-glucan inhibitor abrogated &bgr;-glucans survival benefit (50%). After CLP, plasma TNF-&agr;, IL-1&bgr;, and IL-6 concentrations were increased in control animals. When &bgr;-glucan was administered, it completely blocked the elevation of TNF-&agr;, IL-1&bgr;, and IL-6. Administration of &bgr;-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with &bgr;-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, &bgr;-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that &bgr;-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of &bgr;-glucanase inhibited the &bgr;-glucan activity and resulted in enhanced lung injury.

Hepatic Energy Metabolism and the Differential Protective Effects of Sevoflurane and Isoflurane Anesthesia in a Rat Hepatic Ischemia-Reperfusion Injury Model

BACKGROUND: We investigated the effects of isoflurane and sevoflurane in a warm liver ischemia-reperfusion (IR) model on cytokines, hepatic tissue blood flow (HTBF), energy content, and liver structure. METHODS: Seventy-two Wistar rats were randomly assigned into 1 of 3 groups: Control group, no volatile anesthetics; sevoflurane group, 2% sevoflurane; isoflurane group, 1.5% isoflurane. Thirty minutes after the start of volatile anesthetics, rats were subjected to 45 min hepatic ischemia and 2 and 4 h of reperfusion. Rats were killed at the end of ischemia, 2 and 4 h of reperfusion. Aspartate aminotransferase and alanine aminotransferase, HTBF, malondialdehyde, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, energy charge, and histologic examination were used to evaluate the extent of liver injury. RESULTS: Serum alanine aminotransferase and aspartate aminotransferase levels were similar in control and isoflurane groups while there was a significant decrease in the sevoflurane group in the postischemic period (P < 0.01). HTBF was remarkably better in the sevoflurane group than in the isoflurane group and worse in the control group. Tissue malondialdehyde levels were significantly low in the sevoflurane group compared with the isoflurane group at 2 h of reperfusion (P < 0.05) and reached its maximum value in the postischemic period in the control group. After ischemia, 2 and 4 h of reperfusion, tumor necrosis factor-α and interleukin-1β values were lowest in the sevoflurane group and highest in the control group but it was not statistically significant (P > 0.05). In the sevoflurane group, hepatic adenosine triphosphate and energy charge were significantly high at all measurement times. At the postischemic period, energy charge was lower compared with the sevoflurane and isoflurane groups. The degree of hepatocyte injury was small in the sevoflurane group. CONCLUSIONS: Clinically relevant concentrations of sevoflurane given before, during, and after hepatic ischemia protected the liver against IR injury, whereas the effects of isoflurane on hepatic IR injury were not notable.

Volatile anesthetic preconditioning attenuated sepsis induced lung inflammation

BACKGROUND This study aimed to evaluate the differential protective effects of isoflurane or sevoflurane on lung inflammation in a rat model of cecal ligation and puncture (CLP) induced sepsis. METHODS Seventy-two rats were assigned to control, sevoflurane, or isoflurane groups. At 2 and 4 h, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), nitrate/nitrate levels (NO), total antioxidant capacity (TAC), and intercellular cell adhesion molecule-1 (ICAM-1) were determined. At 12 and 24 h, malondialdehyde (MDA), myeloperoxidase (MPO), and histologic changes were evaluated. Survival was monitored for 7 d after CLP. RESULTS Sevoflurane (75%) and isoflurane (63%) significantly improved survival rate compared with control rats (38%). When sevoflurane and isoflurane groups were compared, sevoflurane pretreatment showed significant decrease in NO at 2 h [1045 (803-1274)/1570 (1174-2239) and 4 h [817 (499-1171)/1493 (794-2080)]; increase in TAC at 4 h [580.0 (387-751)/320 (239-512)]; decrease in MDA at 12 h [2.5 (1.1-4.2)/5.4 (4-73)] and 24 h [10.8 (6.0-14.0)/15.9 (9-28)]; and decrease in MPO at 24 h [145.8 (81-260)/232 (148-346)]. The difference in the ICAM-1 expression of the isoflurane and sevoflurane groups was not significant at both measurement times. The architectural integrity of the alveoli was preserved in all the groups. The injury scores of the three groups at 12 and 24 h did not show any significant difference. CONCLUSIONS Both sevoflurane and isoflurane attenuated inflammatory response, lipid peroxidation, and oxidative stress. Furthermore, sevoflurane was more effective in modulating sepsis induced inflammatory response at the chosen concentration in sepsis model.

Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients

Background:  Sleep complaints are common in end‐stage renal disease. We aimed to investigate the relationship between sleep‐related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels.

The effect of allopurinol on focal cerebral ischaemia: an experimental study in rabbits

Abstract In this experimental study, the neuroprotective effect of the xanthine oxidase inhibitor allopurinol on focal cerebral ischaemia created by permanent middle cerebral artery occlusion (MCAO) was investigated. Using high performance liquid chromatography (HPLC), we measured hypoxanthine, xanthine, and uric acid (UA) levels in rabbit brains following focal cerebral ischaemia. Rabbits were randomly and blindly assigned into four groups of eight animals each. The control groups received 2% carboxymethylcellulose solution, while 10% allopurinol 150 mg/kg was given to the treatment group 1 h before ischaemia. Each group was subdivided into two groups which were sacrificed 4 h or 24 h after ischaemia, respectively. UA and xanthine values of the rabbits in the control groups were quite high at both times and highest after 24 h, particularly in the centre of the ischaemia. A significant decrease in UA and xanthine values was observed in rabbits that were given allopurinol (P<0.05). According to our results, it was concluded that allopurinol pretreatment protects neural tissue in the early period after arterial occlusion and prevents cerebral injury in the late period, especially in the perifocal area, possibly by preventing the formation of free radicals with xanthine oxidase inhibition.

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.

The Effects of Caffeine on l-Arginine Metabolism in the Brain of Rats

In our study, the short-term effects of caffeine on L- arginine metabolism in the brains of rats were investigated. Caffeine was given orally at two different doses: 30 mg/kg and 100 mg/kg (a high non-toxic dose). Brain tissue arginase activity in rats from the caffeine-treated groups decreased significantly compared with the control group. Malondialdehyde (MDA) levels in the brain tissue and serum of animals in the caffeine groups also decreased significantly. Brain tissue and serum nitric oxide (NO) levels increased significantly after caffeine administration. Tumor necrosis factor-α (TNF-α) levels were also investigated in rat serum, but there was no statistically significant difference between the TNF-α levels of the caffeine-treated rats groups and the control rats. Our study indicates that brain arginase activity decreases after caffeine administration at doses of 30 mg/kg and 100 mg/kg. As a result, we can say that arginine induces production of NO in the organism.

Adiponectin levels and arteriosclerotic risk factors in pediatric renal transplant recipients

Abstract:  ADPN, a recently discovered adipocytokine, has attracted great attention because of its anti‐atherogenic properties. It was suggested as a protective factor for the cardiovascular system because of its close correlation with several risk factors. Our aim was to investigate serum ADPN levels in pediatric RTR and to document possible relationships between ADPN and arteriosclerotic risk factors. Twenty‐one RTR, aged 16.3 ± 4.0 yr, and 23 healthy age and sex‐matched control subjects were enrolled in this study. Serum lipid/lipoprotein fractions, homocysteine and ADPN levels as well as intima‐media thickness of the cIMT were determined in both groups. Significantly higher serum ADPN (p < 0.001) and homocysteine (p < 0.05) levels as well as higher cIMT (p < 0.001) were found in RTR compared with the control subjects, whereas apolipoprotein B and lipoprotein (a) levels were not significantly different. HDL cholesterol was positively correlated with log ADPN (r = 0.585, p < 0.01). There were inverse correlations between log time post‐transplantation and log ADPN as well as HDL cholesterol (r = −0.438, p < 0.05 and r = −0.578, p < 0.05, respectively). There were no correlation between log ADPN, log homocysteine, log apolipoprotein B, lipoprotein (a), creatinine clearance and cumulative steroid dose. Despite reasonable lipid profiles and remarkably elevated ADPN levels, our pediatric RTR with stable graft function displayed a risk for arteriosclerosis because of increased cIMT and mild hyperhomocysteinemia. Regarding the close positive correlation between ADPN and HDL cholesterol, it could be speculated that ADPN is a novel negative surrogate marker of arteriosclerosis. To our knowledge, this is the only report investigating levels and diverse correlates of ADPN in a pediatric RTR group. Further studies in larger groups of recipients are needed to clarify the interaction between arteriosclerotic risk factors and ADPN.