Role of silymarin (Silybum marianum) in the prevention of colistin-induced acute nephrotoxicity in rats.

Silymarin (Silybum marianum) has some protective effects against drug toxicity (cisplatin, acetaminophen, adriamycin, gentamicin etc.). Colistin is a strong antimicrobial, which is frequently used in the treatment of resistant gram-negative bacterial infections in recent years although it has nephrotoxic potential. This study was aimed to determine the role of silymarin against colistin-induced acute nephrotoxicity (CIN). Rats were randomly divided into four groups. The control group was treated with tap water whereas groups 2 and 3 received silymarin (orally, 100 mg/kg/day) and colistin (intraperitoneally, 750.000 IU/kg/day) for seven days, respectively. Group 4 received both 750,000 IU/kg/day colistin and 100 mg/kg/day silymarin for seven days. After euthanasia, histopathological and biochemical examinations were completed for the kidney tissue specimens and blood samples. All parameters of the control and silymarin groups were similar. Severe weight loss was seen in the groups receiving colistin (groups 3 and 4). Silymarin significantly increased glutathione peroxidase and superoxide dismutase levels when administered with colistin in group 4 only. Acute tubular injury, tubular necrosis, meduller congestion, interstitial inflammation and apoptotic indices of colistin group were significantly higher than the control group. The administration of colistin with silymarin (group 4) was able to make some improvements in tubular necrosis and significant increase in antioxidant capacity. Silymarin increased antioxidant enzyme activity only when used in combination with colistin. The effects of silymarin may become more pronounced when used at higher doses or with a longer duration of treatment and may prevent nephrotoxicity.

Serum defensin levels in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. METHODS: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. RESULTS: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). CONCLUSIONS: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. TRIAL REGISTRATION: This study is not a clinical trial study.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy.

PURPOSE: To evaluate the effects of cigarette smoking on oxidative stress (OS) and mitochondrial biogenesis related parameters in patients Graves Ophthalmopathy (GO). METHODS: Patients with moderate-to-severe GO according to the European Group on Graves Orbitopathy (EUGOGO) criteria were prospectively enrolled in this study. Age- and sex-matched healthy volunteers who applied to outpatient clinic due to refractive problems consisted the control group. Participants were divided into 4 groups based on their diagnosis and smoking status: group 1 (n = 30) smoker GO patients, group 2 (n = 30) nonsmoker GO patients, group 3 (n = 30) smoker healthy controls, and group 4 (n = 30) nonsmoker healthy controls. In the sera, total antioxidant status, total oxidant status and OS index values, peroxisome proliferator-activated receptor-γ coactivator 1-α, mitochondrial transcriptional factor A levels, and paraoxonase-1 enzyme activity were evaluated. RESULTS: Total oxidant status and OS index values were the highest in group 1 compared to other groups (p = 0.031, p = 0.042; respectively). There was no statistically significant difference in total antioxidant status and peroxisome proliferator-activated receptor-γ coactivator 1α levels among the groups (p = 0.521, p = 0.388; respectively). Paraoxonase-1 enzyme activity was the lowest in group 1 and highest in group 4 (p = 0.024). The levels of mitochondrial transcriptional factor A was the lowest in group 1 compared to other groups (p = 0.012). CONCLUSIONS: Cigarette smoking in GO patients seems to be a risk factor that increases OS, and therefore, it may have an unfavorable impact on the mitochondrial biogenesis.

Serum defensin levels in patients with systemic sclerosis

Abstract Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. Methods: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. Results: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). Conclusions: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. Trial registration: This study is not a clinical trial study.(AU)

Acute effects of different doses of malathion on the rat liver.

AIM OF THE STUDY: Our study was designed to evaluate the acute effects of malathion on rat liver tissues. MATERIAL AND METHODS: The animals were divided into 4 groups of 6 animals/each. Group 1 (control group) received corn oil, while groups 2, 3, and 4 were given malathion dissolved in corn oil at a dose of 100, 200 and 400 mg/kg, respectively. 24 hours after malathion administration, animals were sacrificed and liver tissues were collected. The liver tissues were then analysed biochemically and histopathologically. RESULTS: Butyrylcholinesterase levels in groups 2, 3 and 4 were significantly lower than that of group 1. Total oxidant status and tumour necrosis factor alpha level were significantly increased in group 4 compared to group 1. Catalase activities of groups 3 and 4 were significantly higher than that of group 1. Arylesterase activity was significantly decreased in groups 3 and 4 compared to group 1. In groups 3 and 4, some vacuoles in hepatocytes were revealed and hydropic degeneration was observed in group 4. CONCLUSIONS: Acute administrations of malathion results in hepatotoxicity in a dose-dependent manner.

Is it possible to prevent contrast-induced nephropathy with dexpanthenol?

PURPOSE: Contrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN. METHODS: Twenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp + CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500 mg/kg for 5 days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp + CIN groups, L-NAME (10 mg/kg), tenoxicam (0.5 mg/kg) and sodium amidotrizoate (10 ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected. RESULTS: When the Dexp + CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels. CONCLUSIONS: Dexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.

Hypothalamic Energy Regulatory Peptides in Chronic Kidney Disease.

Loss of appetite affects one-third of patients with CKD and is the leading cause of malnutrition in this population. Orexigenic Agouti-related peptide (AgRP) with neuropeptide-Y (NPY) and anorexigenic melanocyte-stimulating hormone-α (MSH-α) with cocaine- and amphetamine-regulated transcript (CART) are known to regulate appetite. In this study, we aimed to evaluate the levels of these peptides in CKD patients compared to healthy subjects and demonstrate the effects of dialysis treatment and erythropoiesis-stimulating agent (ESA) therapy. The cross-sectional study is composed of consecutive inclusion of 20 healthy individuals, 20 predialysis CKD patients, 20 HD, and 20 peritoneal dialysis (PD) patients. Exclusion criteria were an active infection, history of malignancy, hypo- or hyperthyroidism, and diabetes. Patients on dialysis had targeted Kt/Vs. Demographic features and BMIs of the four groups were similar. Levels of AgRP, NPY, AMSH, and CART were significantly different between groups. Nondialysis CKD patients had significantly lower hypothalamic hormones compared to healthy individuals, HD and PD patients (P = 0.02, P = 0.03, and P = 0.07 for AgRP; P = 0.02, P = 0.01, and P = 0.09 for NPY; P = 0.02, P = 0.02, and P = 0.03 for AMSH; P = 0.02, P = 0.005, and P = 0.030 for CART). Dialysis patients with or without ESA treatment had similar hormone levels (P = 0.13 for AgRP; P = 0.11 for NPY; P = 0.23 for AMSH, and P = 019 for CART). Predialysis CKD patients have lower orexigenic and presumably indirectly lower anorexigenic peptides compared to healthy subjects and dialysis patients. ESA treatment does not affect these hypothalamic peptides in dialysis patients.

Circulating gelatinases are not prognostic of treatment response and survival in locally advanced rectal cancer patients undergoing preoperative chemoradiotherapy.

PURPOSE: To investigate whether the serum levels of matrix metalloproteinases (MMPs) are predictive on treatment response and survival in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy. PATIENTS AND METHODS: Serum MMP-2 and MMP-9 was analyzed by enzyme-linked immunosorbent assay and obtained before, midway, and 1-month after the end of preoperative radiotherapy treatment. The prognostic significance of serum MMP-2 and MMP-9 levels and their association with other pathological findings for LARC patients were evaluated. RESULTS: Serum levels of MMP-2 or MMP-9 were found to decrease with increasing clinical stage and negative correlation was statistically significant (P < 0.05). There was no statistically significant difference in tumor response and survival between the low and high MMP-2 and MMP-9 groups. MMP-2 and MMP-9 were not correlated with local-regional recurrence. CONCLUSIONS: We propose that serum levels of MMP-2 and MMP-9 are not predictive on treatment response and survival in LARC patients.

The Effects of Bougie Diameters on Tissue Oxygen Levels After Sleeve Gastrectomy: A Randomized Experimental Trial

Background: Staple-line leak is the most frightening complication of laparoscopic sleeve gastrectomy and several predisposing factors such as using improper staple sizes regardless of gastric wall thickness, narrower bougie diameter and ischemia of the staple line are asserted. Aims: To evaluate the effects of different bougie diameters on tissue oxygen partial pressure at the esophagogastric junction after sleeve gastrectomy. Study Design: A randomized and controlled animal experiment with 1:1:1:1 allocation ratio. Methods: Thirty-two male Wistar Albino rats were randomly divided into 4 groups of 8 each. While 12-Fr bougies were used in groups 1 and 3, 8-Fr bougies were used in groups 2 and 4. Fibrin sealant application was also carried out around the gastrectomy line after sleeve gastrectomy in groups 3 and 4. Burst pressure of gastrectomy line, tissue oxygen partial pressure and hydroxyproline levels at the esophagogastric junction were measured and compared among groups. Results: Mortality was detected in 2 out of 32 rats (6.25%) and one of them was in group 2 and the cause of this mortality was gastric leak. Gastric leak was detected in 2 out of 32 rats (6.25%). There was no significant difference in terms of burst pressures, tissue oxygen partial pressure and tissue hydroxyproline levels among the 4 groups. Conclusion: The use of narrower bougie along with fibrin sealant has not had a negative effect on tissue perfusion and wound healing.

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

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.

The role of inflammatory biomarkers in CHD-associated pulmonary hypertension in children.

OBJECTIVE: The present study aims to identify the role of inflammatory markers such as C-reactive protein, interleukin-6, and fractalkine in CHD-associated pulmonary hypertension in children. METHODS: This is a prospective review of 37 children with CHD-related pulmonary hypertension, 21 children with congenital heart defects, and 22 healthy children. RESULTS: Serum C-reactive protein and interleukin-6 levels were significantly higher in the children with CHD-related pulmonary hypertension (respectively, p=0.049 and 0.026). Serum C-reactive protein concentrations correlated negatively with ejection fraction (r=-0.609, p=0.001) and fractional shortening (r=-0.452, p=0.007) in the pulmonary hypertension group. Serum fractalkine concentrations correlated negatively with ejection fraction (r=-0.522, p=0.002) and fractional shortening (r=-0.395, p=0.021) in the children with pulmonary hypertension. Serum interleukin-6 concentrations also correlated negatively with Qs (r=-0.572, p=0.021), positively with Rs (r=0.774, p=0.001), and positively with pulmonary wedge pressure (r=0.796, p=0.006) in the pulmonary hypertension group. A cut-off value of 2.2 IU/L for C-reactive protein was able to predict pulmonary hypertension with 77.5% sensitivity and 77.5% specificity. When the cut-off point for interleukin-6 concentration was 57.5 pg/ml, pulmonary hypertension could be predicted with 80% sensitivity and 75% specificity. CONCLUSION: Inflammation is associated with the pathophysiology of pulmonary hypertension. The inflammatory markers C-reactive protein and interleukin-6 may have a role in the clinical evaluation of paediatric pulmonary hypertension related to CHDs.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

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 (ß = 0.590, P < 0.001), waist circumference (ß = 0.572, P < 0.001), body fat mass (ß = 0.562, P < 0.001), percentage of body fat mass (ß = 0.408, P = 0.003), percentage of lean tissue mass (ß = -0.421, P = 0.002), LV mass (ß = 0.426, P = 0.002), carotis intima media thickness (ß = 0.289, P = 0.042), triglyceride/high-density lipoprotein cholesterol ratio (ß = 0.529, P < 0.001), 1/HOMA-IR (ß = -0.386, P = 0.006), and spKt/V (ß = -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.

An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis.

UNLABELLED: The link between Helicobacter pylori and iron deficiency (ID) or iron deficiency anemia (IDA) has been investigated recently. We suggested that IDA/ID associated with H. pylori infection might be mediated by inflammation-driven hepcidin production. Patients with complaints of recurrent abdominal pain and dyspepsia aged between 7-16 years were included in this study. Patients were divided into two groups according to H. pylori status in upper gastrointestinal endoscopy. Group I who had H. pylori gastritis (n=50) received triple antibiotic therapy. Group II (n=50) who had H. pylori-negative gastritis only received proton pump inhibitor. Thirty healthy children with the similar age and gender were included in the study as a control group. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, prohepcidin and interleukin-6 (IL-6) values were evaluated in all children at the first visit. Initial tests were repeated after H. pylori eradication. Initial levels of ferritin (p=0.002), prohepcidin (p=0.003), and IL-6 (p=0.004) were found significantly lower in group I compared to group II and the control group. The mean prohepcidin level was lower in the anemic H. pylori-positive group than in non-anemic H. pylori-positive group; however, the difference was not statistically significant. While significant increases in hematocrit and mean corpuscular volume were observed, no significant difference was found in serum ferritin, prohepcidin, or IL-6 level after eradication treatment in H. pylori-positive group. CONCLUSION: H. pylori-induced gastritis appears to cause an increase in prohepcidin levels and a decrease in ferritin levels, supporting our hypothesis; but this relationship has not been proven.

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.

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.

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.

Plasma orexin-A and ghrelin levels in patients with chronic obstructive pulmonary disease: Interaction with nutritional status and body composition.

Orexin-A and ghrelin are two important polypeptides that stimulate food intake, however, there is a lack of sufficient information concerning their plasma levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the association between plasma orexin-A and ghrelin levels with food consumption and body composition in patients with stable phase COPD. In total, 40 patients (age, 44-80 years; male, 31; female 9) who were in the stable phase of COPD were included in the study. Blood samples for plasma orexin-A and ghrelin analysis were collected after 8-12 h of fasting; certain anthropometric measurements were obtained and a 24-h dietary recall was recorded. The mean plasma orexin-A levels in the male and female patients were 1.3±0.37 and 1.4±0.13 ng/ml, respectively, while the mean plasma ghrelin levels were 25.9±7.31 and 27.3±8.54 ng/ml, respectively. No significant correlation was observed between the body mass index and plasma orexin-A and ghrelin levels or between the plasma ghrelin levels and dietary nutrient intake (P>0.05). The plasma orexin-A levels were demonstrated to be higher in patients with a higher dietary total fibre intake (r=0.303, P=0.022). A similar correlation was observed between plasma orexin-A levels and dietary intake of soluble (r=0.033, P=0.029) and insoluble (r=0.335, P=0.024) fibre, as well as between the daily consumption of calcium and the levels of plasma orexin-A (r=0.065, P=0.046). Therefore, the results of the present study indicated that a positive correlation existed between dietary nutrient intake and plasma orexin-A levels in patients with COPD.

Apheresis-inducible cytokine pattern change in children with homozygous familial hypercholesterolemia.

Familial hypercholesterolemia is a genetic disorder that leads to severe atherosclerosis related cardiovascular complications in young adults. Extracorporeal elimination is a method of LDL-lowering procedures effective in patients with homozygous or severe heterozygous FH utilized in cases. The recruitment of leucocytes into the arterial intima is dependent on a cascade of events mediated through a diverse family of adhesion molecules. Several pro-inflammatory adhesion molecules are cleared by various lipid apheresis methods. This study showed that, LDL-apheresis led to several changes in circulating inflammatory factors which induced antiinflammatory and antiatherogenic changes in the plasma profile in homozygous familial hypercholesterolemic patients.