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Background/aim Methotrexate (MTX), widely used as a drug in cancer, has many adverse effects on tissues. Apocynin (APO) is a NADPH oxidase inhibitor and is known with many antioxidant properties. In this study, we aimed to evaluate the adverse effects of MTX on testicular tissue and the protective effects of APO at two different doses (20 mg/kg and 50 mg/kg) on MTX-induced testicular damage. Materials and methods Fifty adult male Wistar albino rats (8 weeks old and weighing 200–250 g) were divided into five groups of 10 rats each: 1. saline control, 2. dimethyl sulfoxide (DMSO) control, 3. MTX, 4. APO-20 + MTX, and 5. APO-50 + MTX. All injections were performed intraperitoneally. At the end of day 28, all rats were sacrificed under anesthesia. The testes were evaluated histologically and the blood samples were analyzed biochemically. Results According to histological and biochemical analyses, there was no significant difference between the DMSO and control groups. In terms of the histological findings, MTX group was significantly the worst affected group compared to the others, and in this group, apoptotic cell number (P = 0.011) was significantly increased in comparison with the control group. Except MTX, there was no significant difference in apoptotic cell number of the other groups compared to the control group. In the MTX group, malondialdehyde (MDA, P = 0.017) and myeloperoxidase (MPO, P < 0.001) levels were significantly increased in tissue and in blood (MDA P < 0.001, MPO P < 0.001), while tissue glutathione (GSH, P < 0.05) and serum testosterone levels (P < 0.01) were decreased compared with the control group. APO + MTX treatment groups exhibited better testis morphology, and apoptotic cells were also significantly decreased compared to MTX group (P < 0.001). Conclusion Our results suggest that MTX induced defects on testis via oxidative stress and APO reversed the effects of MTX with its antioxidant properties.

OBJECTIVES Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) belongs to the tumor necrosis factor (TNF) superfamily and is reported to play a role in autoimmune diseases. In this study, we aimed to measure serum TRAIL receptor 1 (TRAIL-R1) concentration and assess any phenotypic relationship in patients with ankylosing spondylitis (AS). METHODS Fifty-three patients with AS were recruited from August 2014 to December 2014 cross-sectionally. Fifty-three sex- and age-matched healthy controls were also recruited. Serum TRAIL-R1 concentrations were measured using an enzyme-linked immunosorbent assay. The association between serum TRAIL-R1, TNF-α, disease activity indices, markers of systemic inflammation, and clinical features were evaluated. RESULTS Serum TRAIL-R1 and TNF-α levels were increased in patients with AS compared with healthy controls (4.5 ± 2.3 vs 3.5 ± 2.3 pg/mL, p = 0.036; 3.8 [1.6-7.7] vs 2.0 [0.21-5.7] pg/mL, p = 0.048, respectively). Serum TRAIL-R1 displayed a medium positive correlation with serum TNF-α concentrations (r = 0.412; p = 0.002). Serum TRAIL-R1 concentration was higher in human leucocyte antigen (HLA)-B27-positive patients compared with non-HLA-B27 patients (5.5 ± 2.2 vs 3.1 ± 1.6 pg/mL, p < 0.001). No relationship was found between serum TRAIL-R1 concentration and disease activity scores. CONCLUSIONS This study confirms that serum TRAIL-R1 levels are higher in AS patients than healthy controls. The persistence of significantly elevated serum TRAIL-R1 levels, even in patients with low disease activity or after excluding biologic treatment, and the association with HLA-B27 positivity, warrants further investigation due to the unclear role of TRAIL-R1 in the pathophysiology of AS.

The aim was to evaluate the left and right ventricular functions concurrently by two-dimensional speckle tracking echocardiography (STE) in systemic sclerosis (SSc) patients without overt cardiac disease. A total of 47 patients with SSc and 36 age- and sex-matched controls were evaluated cross-sectionally. Two-dimensional STE was used to assess the longitudinal peak systolic strains (PSS) of both ventricles including apical long-axis (APLAX), apical four-chamber (4-CH), apical two-chamber (2-CH), and global longitudinal measurements. Any association of metabolic, cardiac, and inflammatory biomarkers with PSS was investigated. The longitudinal PSS of the left ventricle [APLAX, 4-CH, 2-CH and global] were significantly lower in SSc patients than controls (− 18.2 ± 3.2 vs − 19.8 ± 2.7% p = 0.02; − 17.8 ± 3.5 vs. − 20.3 ± 3.3% p = 0.001; − 18.6 ± 3.1 vs. − 21.8 ± 3% p

The aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM).Our study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI).PON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p0.001). TOS and OSI were statistically higher in BC patients than HV group (p0.001).Our results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.Cilj studije bio je istraživanje veze polimorfizma paraoksonaze 1 (PON1), aktivnosti PON1/arilesteraze (ARE) i indeksa oksidativnog stresa (OSI) kod pacijentkinja sa rakom dojke (BC) i dijabetesom tip 2 (DM).Naša studijska grupa se sastojala od 30 zdravih žena (HV grupa) i 66 žena sa rakom dojke (BC). Pacijentkinje iz BC grupe su podeljene u dve grupe: one sa (n = 37) i bez DM (n = 29) (BDM i NBDM grupa). Genotipizacija PON1 K192R i L55M polimorfizama vršena je polimeraznom lančanom reakcijom (PCR) – metodom polimorfizma dužine restrikcionih fragmenta (RFLP). Enzimske aktivnosti serumske PON1/ARE, ukupni oksidativni status (TOS) i ukupni antioksidativni status (TAS) analizirani su spektrofotometrijskom metodom. Odnos TOS-a prema TAS-u je prihvaćen kao indeks oksidativnog stresa (OSI).Frekvencija distribucije genotipova PON1 K192R bila je značajno drugačija u BDM grupi u odnosu na NBDM grupu (p = 0,021). Kada je ispitana alelna distribucija, R i L aleli su bili značajno niži, K i M aleli su bili značajno viši u BDM grupi nego u NBDM grupi (p0,001). TOS i OSI su bili statistički viši kod pacijentkinja sa rakom dojke odnosu na HV grupu (p0,001).Naši rezultati ukazuju na to da PON1 gen Q i M aleli mogu biti faktori rizika koji predisponiraju razvoj raka dojke zbog povećanog oksidativnog oštećenja kod DM. Ipak, ovakva tvrdnja zahteva dalju potvrdu skriningom PON1 polimorfizma kod većeg broja pacijentkinja sa DM, a u istu svrhu su potrebne i dodatne studije širokog spektra.

Aim: Measurement of blood bilirubin levels is a crucial analysis because of the toxic effects of bilirubin on brain tissue, particularly in preterm neonates. The aim of this study was to investigate the consistency of the total bilirubin values obtained by the blood gas analyzer and the autoanalyzer. Material and Methods: In this study, we used total bilirubin data of 407 pediatric patients from Kocaeli University Medical Faculty Education and Research Hospital Central Laboratory System. Total bilirubin data, provided that it was measured simultaneously, was obtained from ABL 735 blood gas analyzer and Roche Cobas C8000 chemistry analyzer. Pediatric patients (neonates, infant and children under 17 years old) were selected retrospectively by year between 2015-2017. Results: Under a cut-off value (14.6 mg/dL) ABL 735 blood gas analyzer and Roche COBAS C8000 chemistry analyzer had strong correlation (r = 0.939) for total bilirubin measurements. It was found that 2-15 days old neonates give more scattered total bilirubin data by Bland Altman analysis in two measurements. Statistical analysis performed to compare whole total bilirubin data identity between two measurements: correlation coefficient was found r = 0.949 a statistically significant positive correlation (p < 0.001). Conclusion: According to our analysis which was supported by previous studies in the literature, we can say that the compatibility between the blood gas analyzer (multi-wave-length spectrophotometric technique) and the chemistry analyzer becomes weaker when the total bilirubin levels exceed 14.6 mg/dL.

Testicular torsion is an emergency urological disease, and the treatment is immediate surgery. Despite emergency surgery, testicular damage may occur due to reperfusion. Therefore, a medical treatment to prevent this damage may be a rational idea. We aimed to evaluate the protective effect of oltipraz in testicular ischaemia/reperfusion damage. Twenty-eight Wistar-Albino rats were randomly divided into four groups. In ischaemia/reperfusion group, testicular torsion was executed, and orchiectomy was done 4 hr after detorsion with no treatment. Second group performed torsion; intraperitoneal 50 mg/kg oltipraz was applied 30 min before detorsion, and orchiectomy was performed 4 hr after detorsion. Third group applied torsion; intraperitoneal 150 mg/kg oltipraz was applied 30 min before detorsion, and orchiectomy was performed 4 hr after detorsion. Last one was the sham group. We evaluated tissue malondialdehyde (MDA), transforming growth factor-β1 (TGF-β1), superoxide dismutase (SOD), reduced glutathione (GSH) and Johnsen testicular biopsy score. There was a significant decrease in TGF-β1, GSH and MDA values in oltipraz treatment groups compared with ischaemia/reperfusion group. Oltipraz treatment has significant protective effect in testicular ischaemia/reperfusion damage. However, more clinical studies are needed to demonstrate appropriate dose and its effects.

Breast cancer (BC) is the main cause of cancer-related death among women worldwide. Oxidative stress is a disturbance of balance between oxidant and antioxidants in favor of oxidants. Paraoxonase (PON) enzymes (PON1, PON2, and PON3) are calcium-dependent hydrolases that are involved in the antioxidation process and are the products of three genes: PON1, PON2, and PON3. The association of PON1 with BC was based on a number of PON1 polymorphisms leading to low serum PON1 activity. This low PON1 activity contributes to an increase in oxidative stress and may promote BC development. In addition, PON2 and PON3 show antiapoptotic activity and antioxidative effects by reducing the formation of reactive oxygen species (ROS). Thus, higher concentrations in healthy breast cells are beneficial for cellular homeostasis. However, their antiapoptotic function, by decreasing ROS in cancerous breast cells, makes treatment of BC more difficult. There is limited information about the regulation of PONs and associated-molecular mechanisms between ROS and PONs in BC. Therefore, it is essential to evaluate the present data concerning the relationship between PONs and ROS and possible PON-dependent molecular mechanisms of cancer induction, especially for BC.

Introduction: Naftidrofuryl and cilostazol are drugs with proven efficacy in the treatment of claudication in peripheral vascular disease. In this experimental study, we evaluated the effects of naftidrofuryl and cilostazol in ischemia-reperfusion (IR) injury on various tissues. Materials and Methods: 40 male albino Wistar rats (8-12 weeks old, 250-350 g.) are randomly divided into 4 groups: Control (Group 1), sham (group 2), cilostazol pre-treatment (group 3), naftidrofuryl pre-treatment (group 4). During 21 days placebo is given to group 2, 12 mg/kg/day cilostazol is given to group 3, 50 mg/kg/day naftidrofuryl is given to group 4 orally. Ischemia and reperfusion are induced at the lower hind limb in Groups 2, 3 and 4. Ischemic muscle, kidney, liver, heart, brain and blood samples are obtained. The total antioxidant capacity, oxidant levels and oxidative stress index are studied for each group. Results: Both drugs have protective effects of remote organ injury following IR. Systemic effects are similar to each other, both have protective effects of IR injury. It showed no statistical significance in the total antioxidant capacity. Total oxidant levels are significantly affected by cilostazol in the heart (p < 0.01) and by naftidrofuryl in the liver (p < 0.01). The effect on oxidative stress was only significant with cilostazol on the heart (p < 0.01). Conclusion: Cilostazol and naftidrofuryl had beneficial effects in all tissues against tissue damage caused by IR injury. In ischemic muscle, kidney and heart cilostazol had improved outcomes comparing to naftidrofuryl. Naftidrofuryl had benefits over cilostazol in liver tissue.

Epilepsy is a major pathological condition, characterized by recurrent seizures and affecting approximately 1% of the population. Many studies have shown a relationship between epilepsy and inflammation. The adenosinergic system contributes to inflammation and epilepsy by regulating the release of neurotransmitters through its various receptors. This study investigates the effect of agonist and antagonist of adenosinergic system on seizure activity and cytokine levels in the WAG/Rij strain, a genetic animal model of absence epilepsy. The WAG/Rij rats used in our study were assigned to saline, Tween 20, adenosine, and caffeine groups. Tripolar electrodes were implanted on the skull, and EEG activities recorded for 3 h. ELISA was used to determine the NFkB, TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions, as well as the TNF-α, IL-1β, and IL-6 levels in the blood samples. Administration of caffeine to rats resulted in a decreased SWD number at 30 and 60 min as determined by EEG recording after baseline (p .05), and a significant increase in NFkB and IL-6 levels in the thalamic tissue (p .05). Administration of adenosine to rats did not change seizures and cytokine levels. Our results show that an increase in thalamic IL-6 and NFkB levels may related with a decrement in absence epilepsy. This study clearly shows the contribution of adenosinergic system in absence seizure in WAG/Rij rats. These results also support the importance of the thalamus on occurrence of SWD in the thalamocortical loop.

BACKGROUND: This study aims to compare clopidogrel and rivaroxaban against ischemia-reperfusion injury after a long reperfusion time and to investigate its effects on various tissues. METHODS: A total of 40 Wistar rats were included in the study and were randomly divided into four groups (n=10 per group). Groups were defined as follows: control (Group 1), sham (Group 2), clopidogrel pre-treatment (Group 3), and rivaroxaban pre-treatment (Group 4). Ischemia (6 h) and reperfusion (8 h) were induced at the lower hind limb in Groups 2, 3, and 4. The ischemic muscle, heart, kidney, liver, and plasma tissues of the subjects were obtained to test for the oxidant (malondialdehyde) and antioxidants (glutathione, superoxide dismutase, and nitric oxide). RESULTS: Malondialdehyde levels were significantly higher in the sham group, compared to the controls in all tissues. Clopidogrel and rivaroxaban pre-treatment significantly decreased malondialdehyde levels, compared to the heart, ischemic muscle, liver, and blood tissues of the sham group. Kidney malondialdehyde levels were reduced only by rivaroxaban. Group 4 had significantly decreased malondialdehyde levels, compared to Group 3 in ischemic muscle (p

The pathophysiology of endometriosis is still unknown and treatment options remain controversial. Searches focus on angiogenesis, stem cells, immunologic and inflammatory factors. This study investigated the effects of etanercept and cabergoline on ovaries, ectopic, and eutopic endometrium in an endometriosis rat model. This randomized, placebo-controlled, blinded study included 50 rats, Co(control), Sh(Sham), Cb(cabergoline), E(etanercept), and E + Cb(etanercept + cabergoline) groups. After surgical induction of endometriosis, 2nd operation was performed for endometriotic volume and AMH level. After 15 days of treatment: AMH level, flow cytometry, implant volume, histologic scores, immunohistochemical staining of ectopic, eutopic endometrium, and ovary were evaluated at 3rd operation. All groups had significantly reduced volume, TNF-α, VEGF, and CD 146/PDGF-Rβ staining of endometriotic implants comparing to the Sh group (p 0.05). E and E + Cb groups significantly decreased TNF-α staining in the ovary comparing to Sh, Co, and Cb groups (p < 0.05). All treatment groups had significantly higher AFC compared to the Sh group. CD25+ Cells' median percentage was significantly increased in the E + Cb group compared to Co, Sh, Cb, and E group. E + Cb group had a significantly higher CD5+ Cells' level than the Co group (p = 0.035). In conclusion; Etanercept and/or Cabergoline decreased volume, TNF-α, VEGF, and CD 146/PDGF-Rβ staining of the ectopic endometrial implant. E and E + Cb treatment decreased TNF-α levels in the ovary. E + Cb also increased peripheral blood CD25+ & CD5+ Cell's.

The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80μg/kg)+PTZ, and Group 5: NPY (60μg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1β, IL-6, FGF-2, galanin, nitric oxide (NOֹ), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures.

Objective: It has been suggested that the adenosinergic system and cytokines play a role in the pathogenesis of epilepsy. Although the role of the adenosinergic system in the modulation of seizure activity is well known, the mechanism of this modulation needs to be described in detail. We performed this study to determine the contribution of the proinflammatory cytokines to the generalized seizure activity during adenosine and caffeine treatment. Methods: We induced generalized tonic-clonic seizures with the administration of 60 mg/kg pentylenetetrazole (PTZ) in male Wistar Albino rats. Adenosine (500 mg/kg) or caffeine (5 mg/kg) was administered before PTZ injection. We monitored seizure activity and then determined the TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions of rats by ELISA. Results: Adenosine pretreatment significantly extended seizure latency (p < 0.05), but did not affect seizure duration and entry time to stage 4 seizure. Caffeine pretreatment did not change seizure latency and seizure duration. PTZ treatment did not change brain cytokine levels significantly (p > 0.05) compared to the control group. Whereas adenosine pretreatment decreased brain TNF-α, IL-1β, and IL-6 levels significantly (p < 0.05), caffeine pretreatment reduced brain cytokine levels slightly but nonsignificantly (p > 0.05). Conclusion: Our results show that there is a clear relation between adenosinergic system and brain tissue cytokine levels. Our findings indicated that TNF-α, IL-1β, and IL-6 participate in the pathogenesis of generalized seizures, and the inhibition of TNF-α, IL-1β, and IL-6 with adenosinergic modulation may decrease seizure severity.

Diabetes is one of the risk factors for the development of vascular dementia (VD), leading to endothelial dysfunction and cognitive impairment. Resveratrol has been shown to have antioxidant, antiinflammatory, and neuroprotective effects. The previous studies have also reported that resveratrol improves cognitive and vascular endothelial functions in several pathological conditions. In the present study we aimed to evaluate the effect of resveratrol on cognitive and vascular endothelial function and to explore the mechanisms of its effects in the streptozotocin-induced diabetic rat model of VD. Male Wistar rats were divided into 3 groups (n = 10 in each group): Control, diabetes (DM), DM + resveratrol (DM + RSV) groups. Rats from the DM + RSV group received resveratrol (20 mg/kg/day, ip) for 4 weeks after induction of diabetes and then cognitive functions of the rats were tested by the Morris water maze and a passive avoidance tests. After behavioral tests, endothelial function of thoracic aorta (the endothelium-dependent and -independent vasorelaxant responses) was investigated. To explore the mechanisms of resveratrol, endothelial eNOS, aortic superoxide dismutase (SOD), NADPH oxidase, heme oxygenase-1 (HO-1) levels, TNF-α and IL-1β expressions; serum SOD and NADPH oxidase levels and, hippocampal BDNF, TNF-α and IL-1β expressions were measured. It was shown that DM resulted in severe learning and memory deficits associated with endothelial dysfunction, increased expression of TNF-α and IL-1β, increased oxidative stress levels and decreased expression of eNOS and BDNF. In contrast, resveratrol treatment improved the cognitive decline. It was also found that chronic treatment with resveratrol ameliorated the impaired vascular reactivity. Reveratrol significantly reversed diabetes-induced changes of protein expression. Our data suggest that resveratrol prevents memory deficits, endothelial dysfunction, increased oxidative stress, inflammation and impairment of neurotrophin expression in a VD rat model. Thus, the vasculoprotective and neuroprotective effects of resveratrol may be beneficial in DM patients.

Introduction Diabetes is associated with anxiety and depression. Resveratrol, one of the most potent natural polyphenols with antioxidant properties, has been demonstrated to have benefits against diabetes. In the current study, we investigated the effects of resveratrol on depression and anxiety-like behaviors in diabetic rats. Methods Adult male Wistar albino rats were assigned for control and diabetic groups, and these groups were divided into four subgroups as follows: Saline-treated, DMSO-treated, resveratrol-treated and imipramine-treated animals (n=10). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg), and 2 days after the STZ injection the rats having hyperglycemia (>300 mg/dl) were assigned to be diabetic. Rats in treatment groups were injected intraperitoneally with resveratrol (20 mg/kg) and imipramine (10 mg/kg) for 4 weeks. After 4-week-treatment period, tail suspension test (TST), forced swimming test (FST), elevated plus maze test (EPM) and locomotor activity test were performed. Blood samples were collected to estimate serum superoxide dismutase (SOD) and NADPH oxidase (Nox) levels. Results Diabetic rats displayed depressive-like behaviors in the FST and TST, and anxiety-like behaviors in the EPM. Resveratrol and imipramine decreased anxiety-like and depressive-like behaviors without affecting locomotor activity in diabetic rats. A significant reduction in SOD levels and a marked increase in Nox levels were observed in diabetic rats. Resveratrol treatment normalized these levels, while imipramine did not affect neither SOD nor Nox levels. Conclusion This study indicates that chronic resveratrol treatment may able to treat comorbid anxiety-and depressive-like behaviors in diabetes through inhibition of oxidative stress.

Schizophrenia, an important brain neurodevelopmental disorder, is observed in 1% of the global population. New-generation antipsychotics have been developed as alternatives to typical antipsychotics for more effective and safe therapy. Chronic administration of asenapine and paliperidone compared to haloperidol on depression, anxiety and analgesy in the forced swimming test (FST), elevated plus maze (EPM) and hot plate tests were examined in mice. Moreover effects of drugs, on expression levels of brain neurotrophic factors [brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB),nerve growth factor (NGF), synapsin and fibroblast growth factor 2 (FGF2)] in the hippocampus of mice, neurogenesis and neurodegeneration, and blood enzyme levels were also investigated. In FST, haloperidol (0.25 mg/kg) significantly increased immobility time while both asenapine (0.075 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly diminished this parameter. In EPM test, haloperidol significantly increased both %, time spent in open arms and % open arm entries. Asenapine (0.075 mg/kg) and paliperidone (0.50 mg/kg) significantly increased % time spent in the open arms. They also increased % open arm entries, but this parameter failed to reach a statistically significant value. In hot plate test, haloperidol (0.125 and 0.25 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly increased the latency to lick the hind paws but asenapine had no effect. Asenapine and paliperidone upregulated more neurotrophic factors in the brain and caused less neurodegeneration compared to haloperidol. Investigated drugs had no effect on liver enzymes and plasma glucose levels. Asenapine and paliperidone may be preferred over classical antipsychotics since they have antidepressant-like effect, upregulate more neurotrophic factors and cause less neurodegeneration in naive mice without having diabetogenic and liver damaging effects. Paliperidone seems to possess superior effects compared to asenapine since it also exerts analgesic-like effect.

Depression is one of the most commonly encountered psychiatric problems in peritoneal dialysis (PD) patients. Our aim was to investigate the associations between oxidative and nitrosative stress (ONS) and brain-derived neurotrophic factor (BDNF) in PD patients with elevated depressive symptoms (EDS).Eighty-three patients with PD and 84 healthy controls were enrolled in this study. In PD patients, two subgroups were formed: 28 with and 55 without EDS. EDS were defined as a Beck Depression Inventory (BDI) score ≥17 in patients. Serum malondialdehyde (MDA) erythrocyte, glutathione (GSH) levels measured spectrophotometrically. Serum superoxide dismutase (SOD) activity, nitric oxide (NO) and BDNF levels were determined by ELISA.While MDA and NO levels were higher, levels of SOD, GSH and BDNF were lower in PD patients compared to controls (p 0.001). The patients with EDS had higher levels of MDA and lower levels of BDNF as compared to those without EDS (p 0.005). In linear regression analysis, the BDNF levels were dependently associated with SOD levels in PD patients (B: 0.274, p: 0.043). In addition, while a negative correlation existed between BDI scores with BDNF levels (r = -0.312, p = 0.004), a positive correlation was present between BDI scores and MDA levels (r = 0.320, p = 0.005) in PD patients.Our results suggest the presence of high ONS and low antioxidant capacity accompanied with decreased levels of BDNF in PD patients, especially those with EDS were deeper. These may represent the risk factors for cellular injury and might reveal part of the mechanism causing the depressive state in PD patients.

Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a pro-apoptotic, multi-functional cytokine.Several studies have suggested that autoimmun diseases, diabetes mellitus, hyperlipidemia and cardiovascular diseases were associated with circulating TRAIL concentrations. Objectives The aim of this study was to investigate, whether TRAIL levels were associated with metabolic features in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Methods We compared the relationship between the serum levels of TRAIL with body mass index, waist circumference, fasting plasma glucose, insulin, HOMA, hemoglobin A1C, cholesterol levels in 53 patients with AS, 42 patients with PsA and 53 healthy controls. We also analysed the association ofTRAIL with inflammatory parameters (CRP, ESR, TNF-α)and disease acitivity (BASDAI, BASFI, DAS28-ESR). None of the patients included in this study had diabetes mellitus or CVD. Results Serum levels of TRAIL were not different in patients with PsA (5,06±3,23 pg/ml), AS (4,36±2,49 pg/ml) and HC (3,85±2,2 pg/ml, p=0,155 ).Serum TRAIL had a direct and significant correlation with waist circumference ( p=0,005 ), TNF-α ( p=0,000 ) and CRP ( p=0,021 ).When we analysed the results in patients with AS;serum TRAIL levels directly correlated with TNF-α ( p=0,003 ),LDL ( p=0,041 ) and total cholesterol ( p=0,026 ).Serum TRAIL levels were higher in HLAB-27 positive patients than negative patients ( p=0,001 ). TNF-α levels were higher in AS than PsA and healthy controls ( p=0,038 ).TNF-α was inversely associated with BASDAI ( p=0,029 ) and BASFI ( p=0,046 ). Conclusions Our results showed that, serum TRAIL levels were associated with TNF-α, LDL-cholesterol and total cholesterol in patients with AS.Serum TRAIL concentrations were higher in HLAB-27 positive patients.Further studies are needed to clarify the underlying basis, because it seems there is a complex interaction between inflammatory processes and metabolic disorders. References G.Zauli and P.Secchiero, The role of the TRAIL/TRAIL receptors system in hematopoiesis and endothelial cell biology. Cytokine and Growth Factor Reviews,vol.17,no.4,pp.245–257,2006. Harith HH DiBartolo BA,Insulin promotes VSMC proliferation and apoptosis via differential regulation of TNF-related apoptosis inducing ligand. JDiabetes.2015 doi:10.1111/1753-0407. Disclosure of Interest None declared

Peri-procedural Changes in Serum Arylesterase Acvitivity in Patients Undergoing Elective PCI for Stable CAD. H. Erman, H.A. Cakmak, B. Ikitimur, V. Sozer, Z. Ongen, B. Karadag, R. Gelisgen, G. Simsek, H. Uzun. Department of Biochemistry, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; Department of Cardiology, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Education and Research Hospital, Istanbul, Turkey; Department of Cardiology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; Department of Physiology, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; Department of Biochemistry, Yildiz Technical University, Istanbul, Turkey. Introduction: Oxidative stress, characterized by an imbalance between the generation ROS and the capacity of the intrinsic antioxidant defense system, may be implicated in the pathogenesis of cardiovascular diseases. Percutaneous transluminal coronary angioplasty (PTCA) and stent deployment induce production of vascular reactive oxygen species (ROS) and reactive nitrogen species (RNS) leading to post-procedural pathophysiological changes including restenosis, stent thrombosis, and endothelial dysfunction. Previous studies suggest that oxidative stress plays an important role in the pathophysiology of restenosis. Because of the actual mechanism accounting for the increased oxidative stress formation in circulation among patients undergoing PCI is still undefined, we aimed to investigate through the analysis of a novel parameter, namely ARE activity, whether early changes in oxidative stress takes place in stable coronary artery disease (CAD) patients undergoing elective PCI with implantation of stents. Methods: In this study 32 consecutive chronic stable angina patients (mean age 61 9.8 years, 75% male) undergoing PCI for management