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Objective: Opioid dependence is a chronic and complex disorder characterized by relapse and remission. Chronic administration of morphine causes symptoms of physical and psychological dependence. The purpose of the present study was to investigate the effect of anti-addictive drugs such as bupropion and varenicline on morphine dependence and naloxone precipitated withdrawal syndrome in a rat model. Materials and Methods: To assess the physical dependence of morphine, Wistar albino rats were intraperitoneal (i.p.) administered increasing doses of morphine twice daily for 5 days, 4 hours after a single dose of morphine on day 6, and 15 minutes before subcutaneous (s.c.) naloxone (2 mg/kg, s.c.) administration to elicit withdrawal symptoms. Physical dependence was evaluated by giving intraperitoneal bupropion (5, 10 and 20 mg/kg, i.p.) and varenicline (0.5. 1 and 2 mg/kg, s.c) for 15 minutes. Results: The morphine-dependent rats had significantly more withdrawal symptoms than naive control rats. The results demonstrated administration of bupropion and varenicline during induction of morphine dependence attenuated the most of the severity of withdrawal symptoms. Co-administration of bupropion reduced withdrawal symptoms such as jumping, wet dog shaking, weight loss and total withdrawal symptoms. Co-administration of varenicline was found to be effective on withdrawal symptoms such as bupropion, but had no effect on weight loss. Conclusion: These outcomes provide preliminary data that bupropion and varenicline could be used as a candidate drugs to attenuate morphine withdrawal symptoms.

Background and Objective: Coronary bypass operations are commonly performed for the treatment of ischemic heart diseases. Coronary artery bypass surgery with autologous human saphenous vein maintains its importance as a commonly used therapy for advanced atherosclerosis. Vascular inflammation-related intimal hyperplasia and atherosclerotic progress have major roles in the pathogenesis of saphenous vein graft disease. Methods: In our study, we investigated the effect of anacardic acid (AA), which is a bioactive phytochemical in the shell of Anacardium occidentale, on atherosclerosis considering its inhibitory effect on NF-κB. We observed relative ICAM-1 and NF-κB mRNA levels by qRT-PCR method in a TNF-α- induced inflammation model of saphenous vein endothelial cell culture after 0.1, 0.5, 1 and 5 μM of AA were applied to the cells. In addition, protein levels of ICAM-1 and NF-κB were evaluated by immunofluorescent staining. The results were compared between different concentrations of AA, and also with the control group. Results: It was found that 5 μM, 1 μM and 0.5 μM of AA had toxic effects, while cytotoxicity decreased when 0.1 μM of AA was applied both alone and with TNF-α. When AA was applied with TNF-α, there was a decrease and suppression in NF-κB expression compared with the TNF-α group. TNF-α-induced ICAM-1 expression was significantly reduced more in the AA-applied group than in the TNF-α group. Conclusion: In accordance with our results, it can be said that AA has a protective role in the pathogenesis of atherosclerosis and hence in saphenous vein graft disease.

Background. Tacrolimus, one of the immunosuppressive agents, is used to prevent tissue rejection in renal transplant recipients, but the relationship between the plasma concentrations of tacrolimus and female sexual dysfunction has not yet been elucidated. The aim of this study was to determine the effect of tacrolimus use on sexual dysfunction of women after renal transplant. Methods. Twenty-one female patients who successfully underwent transplant and were treated with tacrolimus were enrolled as the patient group, while 21 patients presented to the obstetrics and gynecology clinic for different reasons were included in the study as the control group. The Beck Depression Inventory, Beck Anxiety Inventory, and Female Sexual Function Index were applied. Plasma concentrations of tacrolimus were simultaneously measured in transplant recipients. Results. The scores of all scales did not differ among groups in terms of depression, anxiety, and sexual dysfunction. All transplant recipients had a plasma concentration of tacrolimus in the range of 3 to 7 ng/L. When the patients were compared by the scores of depression and anxiety scales, the drug levels showed no effect on the depression, anxiety, and female sexual functions. Conclusions. Sexual dysfunction appears to be ameliorated in women because of the hormone levels after renal transplant at the end of the dialysis process, hence enhancing the quality of life. Normal plasma levels of tacrolimus, which is known to cause sexual dysfunction, could not change this result.

Ozen, Deniz/0000-0002-3095-1208; Ozyazgan, Sibel/0000-0002-2511-3541 WOS:000480320200006 PubMed ID: 31423307 Endothelial and microvascular dysfunction serve important roles in the formation and pathogenesis of cardiac syndrome X (CSX). Expression of receptor for advanced glycation end products (RAGE) is suggested to be increased in several conditions, including diabetes, inflammation and vascular diseases. In the present study, RAGE gene polymorphisms in patients with CSX and healthy controls were investigated. A total of 114 patients, diagnosed with CSX using coronary angiography results following complaints of angina and objective ischemia, and 103 healthy controls participated in the study. Whether there was a difference in genotype distributions of RAGE gene -374T/A, -429T/C and Glys82Ser polymorphisms between patients with CSX and healthy controls was investigated. Following DNA isolation from blood samples of the participants, the polymorphic regions were examined by quantitative polymerase chain reaction, and the genotyping results were statistically analyzed. When the genotypic distributions of -374T/A, -429T/C and Gly82Ser polymorphisms were investigated in patients with CSX and healthy controls, no statistically significant differences were identified between the two groups (P>0.05). Likewise, no statistically significant differences were observed in the allelic distributions of all 3 polymorphic regions (P>0.05). To the best of our knowledge, the present study also investigated the association between CSX and RAGE gene polymorphisms for the first time. No statistically significant differences in RAGE gene polymorphisms between the CSX and control groups were observed. We hypothesized that significant results may be obtained by increasing the numbers of patients and healthy controls in future studies. Scientific Research Projects of Istanbul UniversityIstanbul University [3755] The present study was supported by the Scientific Research Projects of Istanbul University (project no. 3755).

Objective. To study pitavastatin’s effects on nuclear factor-kappa B (NF-κB ) and adhesion molecules in human saphenous vein graft endothelial culture indicating its pleotropic properties. Materials and Method. Low-dose (0.1 μM/L) and high-dose (1μM/L) pitavastatin calcium were administered as a frontline therapy in human saphenous endothelial cell culture, followed by induction of inflammation by TNF-α and determination of mRNA level alterations of ICAM-1 and NF-κB genes of endothelial cells using the qRT-PCR method. Additionally, immunofluorescence method was used to show the expression of NF-κB and ICAM-1. Finally, LDH levels were determined by the ELISA method to quantify cytotoxicity. Results. ICAM-1 mRNA expression in the low-dose pitavastatin+TNF-α group was significantly higher than that in the TNF-α group and significantly lower than that in the high-dose pitavastatin+TNF-α group (for all comparisons, P = 0.001). The low-dose pitavastatin+TNF-α group had a similar NF-κB mRNA expression with TNF-α and high-dose pitavastatin+TNF-α groups. Conclusion. Pitavastatin increases ICAM-1 mRNA expression in saphenous vein endothelial cells. Furthermore, the effect of pitavastatin on adhesion molecules appears independent of NF-κB. Novel studies are needed in this field.

Ozen, Deniz/0000-0002-3095-1208 WOS:000516543400006 Objective: Cardiac syndrome X (CSX) can be defined as experiencing chest pain with angina by patients with normal coronary arteries. Endothelial and microvascular dysfunction is responsible for the pathophysiology of the inflammatory CSX disease. Inflammation is especially an important factor in the progression of ischemic heart diseases. It is accepted that both the number of B and T lymphocytes and expression of various proinflammatory cytokines released from those cells increases during inflammatory response. Different proinflammatory cytokines are produced by activated macrophages and T lymphocytes. Since interleukin-17 (IL-17) induces many signaling molecules, which promote immune response and play a role in inflammation, it is assumed that IL-17 can play a role in the CSX pathogenesis. In our study, the relationship between CSX and IL-17 serum levels and the -152G/A polymorphism on IL-17 gene was investigated. Methods: Serum IL-17 levels of blood samples were analyzed from 100 patients with CSX and 101 healthy control individuals using the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. After the DNA isolation was performed from blood samples, the IL-17 gene-152G/A polymorphisms were detected based on the PCR-RFLP method for both patients and healthy individuals. The pomotor region of the IL-17 gene was amplified by the PCR method, and then, genotyping was performed using PCR products for the RFLP step. After that, obtained data for CSX patients and the healthy control group were compared using the statistical analysis. Results: When the IL-17 gene-152G/A polymorphism genotyping results of patients with CSX and healthy control individuals were compared, no statistically significant difference was observed in both genotypic and allelic distributions (p=0.218). The IL-17 serum levels were found to be significantly higher in patients with CSX than in healthy controls (p

Alzheimer's disease (EOAD, LOAD), mild cognitive impairment (MCI), Parkinson's disease (PD) and healthy controls were included to determine the serum interleukin-1s (IL-1α, IL-1β), IL-6 and alpha-2-macroglobulin (α2M) levels using ELISA. IL-6 might be a significant contributor to the inflammatory response in LOAD. The MCI data indicate that IL-1s, α2M and BDNF are somehow related, and this relationship might allow MCI patients to be more similar to the healthy controls. A correlation analysis of multiple biomarkers in different neurodegenerative disorders might be more useful than determining the levels of a single cytokine in a single disorder.

BackgroundDefinition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis. MethodsA total of 176 CSX patients and 196 healthy subjects with similar age and clinical features were compared in terms of C677T polymorphism of the MTHFR gene. Results and ConclusionThere was no significant difference in terms of MTHFR gene C677T polymorphism between CSX patients and controls. When genotypic distribution was compared based on gender in both patients and controls, no significant difference was found between male and female subjects (P>.05). As fasting blood sugar and urea values were significantly higher, alanine aminotransferase and gamma-glutamyl transferase levels were significantly lower in the patients than the controls (P

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)

Identifying early-detection biomarkers have become an increasingly important approach in the treatment and prevention of Alzheimer's disease (AD). In this study, we investigated the potential of brain-derived neurotrophic factor (BDNF), complement factor H (CFH), tumor necrosis factor-α (TNFα), interleukin 10 (IL-10), and heat shock protein 90 (Hsp90) as serum biomarkers for AD in a cohort of the Turkish population because they have been suggested to be associated with AD. Serum BDNF, CFH, TNFα, IL-10, and Hsp90 levels in three groups of patients, early-onset AD (EOAD; age of onset65; n = 22), late-onset AD (LOAD; age of onset65; n = 54), and mild cognitive impairment (MCI) (n = 30), were compared with age-matched healthy controls (age65, n = 18 and age65; n = 32) using ELISA. The serum BDNF levels significantly decreased and TNFα levels significantly increased in the EOAD and LOAD groups compared to the age-matched healthy controls. There was a correlation between serum TNFα and IL-10 levels in the LOAD and healthy control groups. Serum CFH levels in the LOAD and MCI patients were significantly decreased compared with controls. Serum Hsp90 levels in the EOAD, LOAD, and MCI patients were significantly decreased compared with controls. The protein misfolding, the inflammatory response, and decreased neurotrophic factor synthesis are all suggested to be related to AD type brain pathology, and our results indicate these alterations might be traced from serum samples. For accurate early diagnosis of AD, it is important to determine a profile of alterations in multiple biomarkers in large-scale population studies.

Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer's disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEɛ4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFα, IL-1β or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in ɛ4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEɛ4 non-carrier AD patients than for ɛ4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEɛ4 allele non-carrier AD patients.

We compared Turkish patients with cardiac syndrome X (CSX) and controls with respect to serum pro- and anti-inflammatory cytokine levels, as well as the single-nucleotide polymorphisms located in the promoter regions of their related genes. This study included 111 consecutive patients angiographically diagnosed with CSX and 111 healthy controls with similar demographic characteristics. Serum interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-10 levels were measured, and the genotypes of the patients and controls were determined using standard methods. Serum IL-6 and IL-10 levels were significantly higher in the CSX group than in the control group ( P < .01, respectively). Serum TNF-α level was lower in the CSX group than in the control group ( P < .001). On the other hand, participants with CSX and healthy controls were not significantly different with respect to the genotype distributions of IL-6, TNF-α, and IL-10 genes. As a result of our study, both pro-inflammatory and anti-inflammatory cytokines may play a role in the pathogenesis of CSX. In contrast, the studied gene polymorphisms did not influence CSX pathogenesis.

The present study investigates the release of cardiac troponin-I (cTnI) as a biomarker of cardiac injuries induced by doxorubicin (Doxo) alone and along with ciprofloxacin (Cipro), following acute and chronic dose protocol in Sprague Dawley rats. In chronic protocol, rats were given multiple intra-peritoneal (i.p) injections of Doxo (1 or 2.5 mg kg(-1)) alone or in combination with Cipro (20 mg kg(-1) daily) and a placebo control. Whereas in acute protocol, rats were subjected to receive single i.p. injection of Doxo (6 or 15 mg kg(-1)) alone or along with Cipro (20 mg kg(-1)) and placebo treatment with saline (control). The plasma levels of cTnI were measured by using Enzyme-linked Immuno Sorbent Assay (ELISA) technique. All the treated groups, following acute or chronic dose protocol showed significant increase in cTnI plasma level from 137-248% in comparison to control (p

BACKGROUND Behcet's disease (BD) is a chronic inflammatory vasculitis characterized by endothelial dysfunction, elevated reactive oxygen species (ROS), and neutrophil hyperfunction production including acute attacks and remission periods. Ischemia modified albumin (IMA), advanced oxidation protein products (AOPP), prooxidants-antioxidants balance (PAB), and ferric reducing antioxidant power (FRAP) were evaluated in regard to their role in the pathogenesis of BD as well as their relation to clinical presentation, uveitis attacks and remission periods, and healthy volunteers. METHODS The study included 28 BD cases and 27 healthy volunteers as the control group. Blood samples were taken twice from each patient; first during an attack and second about three months after an attack, during remission period. RESULTS AOPP, IMA and PAB levels were significantly increased in active periods of patients with BD compared with healthy control and remission periods of patients with BD (p < 0.0001, p < 0.0001, p < 0.0001, respectively). FRABP levels were found to be lower in active periods of patients with than healthy controls and remission periods of patients with BD (p < 0.001, p < 0.05, respectively). The AOPP levels were negatively correlated with the levels of FRAB in patients (r = -0.468, p = 0.012; r = -0.394, p = 0.038, respectively). The PAB levels were positively correlated with the levels of CRP in patients (r = -0.606, p = 0.001). CONCLUSIONS Our results show that these parameters play a major role in the inflammatory reactions observed in BD. Increased levels of IMA and PAB are likely to be a result of inflammation-induced oxidative stress and hence its potential significance as a new marker of oxidative stress in BD.