Ischemia is characterized by cataclysmic oxygen deficiency, but the reperfusion of an ischemic tissue paradox-ically causes more serious damage than the ischemia itself. Ischemia/reperfusion (I/R) triggers organ damage, which is frequently observed in organ transplantation surgery, specifically in heavily blooded organs, such as the lung and kidney. To understand the molecular underpinnings of organ damage in transplant surgery, we aimed to monitor autophagic flux, a cellular death pathway, in an organ transplantation scenario created by prolonged ischemia and reperfusion of the lung. We included a total of 48 adult Wistar-Albino rats weighing 250-300 g in this study. We implemented three different ischemia/reperfusion protocols in three different groups (n = 10) based on different reperfusion times, and we observed one randomly created control group for comparison (n = 10). We then probed the gene expression levels of autophagy mediators in normal and pathologic tissues. Autophagy, a cellular death pathway, is sensitive to intracellular oxidative stress, which is one of the most dramatic markers of reperfused-ischemic tissue. In keeping with this ground, we determined that as the duration of reperfusion increases, autophagy driving proteins, Atg5, Atg7, Atg10, Beclin1, and Ulk1, specifically surge. Reperfusion of an ischemic tissue triggers catastrophic cellular death pathway, autophagy, and thus gives rise to a ruinous result. Considering autophagy inhibitor usage might be prophylactic. We indicated that Atg7 and Atg10 are the most dramatically increased mediators of autophagy. Hence, targeting these mediators with specific agents could increase patient survival and shorten the post-surgical recovery period after transplant surgery.

OBJECTIVE:To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS:Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS:Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS:It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE:MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Objective: TRPM are integral membrane proteins that have broad range of cellular functions. Roles of TRPM2, TRPM3, TRPM4 and TRPM7 among these channels are very important and their roles in lung ischemia/reperfusion injury have not been evaluated yet. The aim this study is to investigate the contribution of these genes in lung ischemia/reperfusion injury and evaluate histopathology of tissues. Methods: Total number of 40 Wistar albino rats were enrolled for the study. Ischemia was performed by the application of an atramvatic clamp to pulmonary artery. Gene expressions were determined by semiquantitative RT-PCR method. Histopatholical evaluations were held by a standard hematoxyline–eosin staining. Results: The major histopathological tissue damage was observed in ischemia performed groups and expression of TRPM channels was found to be obviously down-regulated. Substantial changes were determined between TRPM2, TRPM3, TRPM4 and TRPM7 and lung ischemia reperfusion injury. In particular, expression of TRPM2 and TRPM7 were reversibly down-regulated in ischemia. Yet, the expression of TRPM3 and TRPM4 were irreversibly down-regulated after ischemia. Conclusion: Consequently, these results indicate that TRPM family of cation channels may have significant roles in the lung ischemia/reperfusion injury.

Background: Rhinitis medicamentosa, also known as ‘rebound congestion,’ is inflammation of the nasal mucosa caused by the overuse of topical nasal decongestants. Although local decongestants resolve the initial nasal obstruction, the overuse causes rebound obstruction. However, how the overuse of the decongestant causes rhinitis medicamentosa is not known. Objectives: Here, we show the intracellular effects of oxymetazoline, commonly used a local decongestant, on the cell death pathways. We also investigated the antioxidative effects of erdosteine suspension (175 mg/5mL), an antioxidative agent. Methods: Thirty Wistar-albino rats were used to form the rhinitis medicamentosa model. After rhinitis medicamentosa was clinically detected, we removed the whole lungs of animals to perform the molecular analyses of cell death pathways. Results: We found a statistically significant decrease in the expression levels of Atg5 (p=0.021), Atg7 (p=0.013) and Ulk1 (p=0.036) in the oxymetazoline group compared to the control group (p<0.05); however, Caspase 3 expression level was recorded to be significantly increased in the oxymetazoline group, and the expression level of Beclin1 recorded to be substantially increased in the erdosteine group (p=0.001). Conclusion: Based on these grounds, we suggest that vasoconstriction in capillary vessels caused by oxymetazoline could lead to a decrease in the blood supply, which triggers autophagy to ensure cellular homeostasis.

Background Fibromyalgia is the prototypical central sensitivity syndrome which is associated with increased sensitivity to pain and other stimuli. Somatosensory temporal discrimination (STD) is the perception of two discrete stimuli applied at short intervals as separate. The evaluation of STD ability essentially provides information about central processing of sensory stimuli.1 Objectives In this study, we aimed to evaluate whether STD ability, which requires an intact central sensory processing, is altered in patients with fibromyalgia. Methods Fifteen patients with fibromyalgia and 15 healthy subjects participated in the study. Demographic characteristics of participants and severity for fatigue, sleep quality, cognitive symptoms, somatic symptoms and health-related quality of life in fibromyalgia patients were recorded. STD thresholds were measured from the dorsum of the dominant hands of the participants by using a constant current stimulator.2 Results Patients with fibromyalgia had higher STD thresholds than healthy subjects (table 1). There were significant correlations between STD thresholds and pain intensity, fibromyalgia impact questionnaire scores and symptom severity scale scores in fibromyalgia group (p=0.006, r=0.68; p=0.037, r=0.54; p=0.017, r=0.61 respectively). Table 1 STDT measures and clinical characteristics of study participants Fibromyalgia group (n:15) mean±SD Control group (n:15) mean±SD Mean difference(95% CI) p Pain (VAS), cm 7.3±1.1 FIQ score 58.8±5.5 SSSS 7.7±1.4 STDT, ms 69.1±8.6 33.4±4.6 35.7 (30.6–40.8) <0.001 VAS: Visual analogue scale, FIQ: Fibromyalgia impact questionnaire, SSSS: Symptom severity scale score, STDT: Somatosensory temporal discrimination threshold, SD: Standard deviation, CI: Confidence interval Conclusions Somatosensory temporal discrimination ability is impaired in fibromyalgia patients compared to healthy subjects. Disrupted somatosensory temporal discrimination ability correlates with increased widespread pain and severity of other symptoms including fatigue, sleep quality, cognitive symptoms, somatic symptoms and decreased functional status. The impaired somatosensory temporal discrimination ability indicates an alteration in higher cognitive sensory processing in fibromyalgia. References [1] Vuralli D, Boran HE, Cengiz B, Coskun O, Bolay H. Somatosensory temporal discrimination remains intact in tension-type headache whereas it is disrupted in migraine attacks. Cephalalgia2017Nov;37(13):1241–1247. [2] Conte A, Modugno N, Lena F, Dispenza S, Gandolfi B, Iezzi E, Fabbrini G, Berardelli A. Subthalamic nucleus stimulation and somatosensory temporal discrimination in Parkinson’s disease. Brain 2010 Sep;133(9):2656–63. Disclosure of Interest: None declared

Objective: Migraine, a highly prevelant headache disorder, is regarded as a polygenic multifactorial disease. Serotonin (5 HT) and their respective receptors have been implicated in the patogenesis.Methods: We investigated the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor gene polymorphisms and their association with migraine in Turkish patients. The rs6295, rs1300060, rs1228814, rs6311, rs6313, rs6314, rs6318, rs3813929 (-759C/T) and rs518147 polymorphisms were analyzed in 135 patients with migraine and 139 healthy subjects, using a BioMark 96.96 dynamic array system.Results: We found no difference in the frequency of the analyzed eight out of nine polymorpisms between migraine and control groups. However, a significant association was found between the rs3813929 polymorphism in the promoter region of 5-HTR2C gene and migraine. Also, the allele of rs3813929 was more common in the migraine group.Conclusion: This result suggests that the 5-HTR2C rs3813929 polymorphism can be a genetic risk factor for migraine in a Turkish population.

Acute Myeloid Leukemia (AML) is a hematopoietic stem cell disorder. Many of the tumor development steps are processes regulated by Ca2+ dependent signaling pathways found in tumor growth. Calcium channels, which can be blocked by pharmacological agents such as verapamil, are important in the regulation of intracellular Ca2+ homeostasis. The failure to stop cell cycle and to achieve programmed cell death are the most important factors in AML or other types of cancers and are considered to be the real cause of cancer. Our aim in this study was to investigate the effect of verapamil on apoptosis and cell cycle in AML cell line, HL-60, using flow cytometry. The effective dose of verapamil was determined as 50 mg / ml by MTT method, and was applied to HL-60 cells, subsequently, they were assessed for apoptosis and cell cycle. After 50 mg / ml of verapamil application, apoptotic cell ratio was found to be 77.7% after 24 hours (p< 0.05). In cell cycle analysis, the ratio of diploid cells decreased in G1 phase and increased in S phase, and the ratio of aneuploid cells decreased in G1 phase (p< 0.05) and increased in S phase (p> 0.05) in verapamil-untreated group when compared to verapamil-treated group.

OBJECTIVES:Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue's life.MATERIALS AND METHODS:It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-β1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis.RESULTS:We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-β1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control.CONCLUSION:These findings suggest that I/R injury may trigger apoptotic mechanism in lung.

Migraine, a highly prevalent headache disorder, is regarded as a polygenic multifactorial disease. Single-nucleotide polymorphisms (SNPs) in the genes that involved in sex hormone metabolism may comprise risk for migraine, but the results of previous genetic association studies are conflicting. The aim of this study was to evaluate genetic variants in genes involved in oestrogen receptor and oestrogen hormone metabolism in a Turkish population. A total of 12 SNPs in the ESR1, ESR2, FSHR, CYP19A1, SHBG and NRIP1 genes were genotyped in 142 migraine cases and 141 nonmigraine controls, using a BioMark 96.96 dynamic array system. In addition, gene–gene interactions were analysed using generalized multifactor dimensionality reduction (GMDR) methods. According to GMDR analysis, our results indicated that there was a significant association between migraine and gene–gene interaction among the CYP19A1, FSHR, ESR1 and NRIP1. Single-gene variant analysis showed that a significant association was observed between the TT genotype of rs10046 and migraine susceptibility. When the analysis was performed only in women, the GG genotype of rs2229741 was different between migraineurs and controls. When the female migraine patients were divided into two groups, migraine related to menstruation (MRM) or migraine not related to menstruation (MNRM), GG genotype of rs726281 was significantly associated with MRM. These results suggested that rs10046 could play a potential role in migraine susceptibility in Turkish population. Also, the rare GG genotype of rs726281 appears to influence migraine susceptibility in a recessive manner in MRM subgroup of female patients. In addition, variant GG genotype of rs2229741 may reduce the risk of migraine in Turkish women.

BACKGROUND/AIMThe objective of this experimental study was to examine the effects of epinephrine, dexmedetomidine, and clonidine added as adjuvants to bupivacaine on block onset and effect times, as well as the effects on the Na+ and Ca+2 channel gene expressions, which may indicate cell damage in the sciatic nerve cell membrane.MATERIALS AND METHODSRats were divided into five groups: Group S (sham), saline solution; Group B, bupivacaine; Group BD, bupivacaine + dexmedetomidine; Group BC, bupivacaine + clonidine; and Group BE, bupivacaine + epinephrine. For each group, 0.2 mL of local anesthetic was injected into the sciatic nerve bifurcation point of the right leg. Sensory (proprioceptive and nociceptive block) and motor block onset and ending times were recorded.RESULTSThe shortest onset time for the examined sciatic block was observed in the BC group, whereas the longest sensory and motor block times were observed in the BD group. The present data suggest suppressed TRPM7 and increased TRPM2 in the groups other than the BE group.CONCLUSIONClonidine is more suitable for fast onset of peripheral nerve blocks, whereas the addition of dexmedetomidine is better in terms of duration. Because the SCN9A and TRPM2,4,7 expression ratios of the BE group showed the least amount of change, this group had the best cellular integrity.

Yavuz Y?cel, Salih Co?kun, Beyhan Cengiz, Hasan H. ?zdemir, Ertu?rul Uzar, Abdullah ?im, M. Akif Camkurt, and M. Ufuk Aluclu. Clin Psychopharmacol Neurosci 2016;14:250-5. https://doi.org/10.9758/cpn.2016.14.3.250

BACKGROUND/AIM:In this study, we investigated the effectiveness of antibiotic prophylaxis (ABP) with respect to the incidence of symptomatic urinary tract infections (UTIs) and evaluated the development of renal scarring in patients treated with clean intermittent catheterization (CIC).MATERIALS AND METHODS:A total of 22 patients were included in the study. The patients were administered ABP in the first year (the ABP-received period) but not in the second year (the ABP-discontinued period).RESULTS:Twenty-eight of all cultures taken in the ABP-received period (18.2%) and 25 (16.2%) of the ABP-discontinued cultures were considered to be indicative of symptomatic UTIs (P = 0.65). The multiple antibiotic resistance rate of microorganisms in cultures taken during the ABP-discontinued period (47; 30.5%) was lower than that in those taken in the ABP-received period (62; 40.3%), (P = 0.07). There was no difference between the ABP-received and ABP-discontinued periods with respect to the development of new lesions according to dimercaptosuccinic acid results (P = 0.14).CONCLUSION:Routine ABP usage is not protective against the development of symptomatic UTIs and new lesions in neurogenic bladder patients receiving CIC. Furthermore, the growth of resistant microorganisms increased in the ABP-received period.

Background: Inhibitor of growth (ING) tumor suppressor gene family has been discovered over the past decade and five different genes have been identified from ING1 to ING5. They have some functions like cell transcription regulation, cell cycle control, DNA repair and apoptosis. Because of the fact that ING3 gene expression has not been studied in breast cancer so far, we aimed to determine whether there was a relationship between ING3 gene expression and breast cancer prognostic factors. Methods: 46 female breast cancer patients in different stages were enrolled to our study. ING3 gene expressions obtained from tumoral and healthy breast tissue samples of patients were evaluated together with pathological and histological parameters. Results: The median age of the patients was 49 years. ING3 expression rate has been significantly higher in the tumor tissue compared to normal tissue and was statistically significant (p=0.001). In estrogen receptor (ER) and progesterone receptor (PR) positive patients, gene expression ratio was significantly higher than negative ones (p 0.05). Conclusions: This study was the first study on ING3 gene expression in breast cancer. ING3 gene expression has been shown to be associated with the receptor positivity and advanced stage disease. Further studies should be conducted on the prognostic significance of ING3 gene in breast cancer. Citation Format: Kalender ME, Cakir M, Ergun S, Oztuzcu S, Cengiz B, Ulasli M, Sevinc A, Camci C. Expression and role of ING3 gene in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-08.

Abstract Background: Inhibitor of growth (ING) tumor suppressor gene family has been discovered over the past decade and five different genes have been identified from ING1 to ING5. They have some functions like cell transcription regulation, cell cycle control, DNA repair and apoptosis. Because of the fact that ING3 gene expression has not been studied in breast cancer so far, we aimed to determine whether there was a relationship between ING3 gene expression and breast cancer prognostic factors. Methods: 46 female breast cancer patients in different stages were enrolled to our study. ING3 gene expressions obtained from tumoral and healthy breast tissue samples of patients were evaluated together with pathological and histological parameters. Results: The median age of the patients was 49 years. ING3 expression rate has been significantly higher in the tumor tissue compared to normal tissue and was statistically significant (p=0.001). In estrogen receptor (ER) and progesterone receptor (PR) positive patients, gene expression ratio was significantly higher than negative ones (p<0.001 and p<0.001, respectively). ING3 expression in tumor tissues of the patients with advanced disease (stage 3-4) was detected higher than ones with early stage disease and it was found to be statistically significant at the border (p=0.048). Moreover, there were no significant changes when ING3 gene expressions were compared with c-erbB2 (Receptor tyrosine-protein kinase erbB-2) status and tumor grade (p> 0.05). Conclusions: This study was the first study on ING3 gene expression in breast cancer. ING3 gene expression has been shown to be associated with the receptor positivity and advanced stage disease. Further studies should be conducted on the prognostic significance of ING3 gene in breast cancer. Citation Format: Kalender ME, Cakir M, Ergun S, Oztuzcu S, Cengiz B, Ulasli M, Sevinc A, Camci C. Expression and role of ING3 gene in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-08.

Cancer is a consequence of accumulation of genetic and epigenetic alterations in the cell which can lead to activation of oncogenes or inactivation of tumor suppressor genes (TSG). Since members of ING family were discovered as TSGs in different cancer types, it was aimed to analyze the chromosome 13q33-34 region, ING1 and p53 genes in bladder cancer. 30 paired normal and tumor tissues were investigated in terms of microdeletion of chromosome 13q33-34 region, ING1 expression and mutation status of ING1 and p53 genes. Because there is no data available about the transcription factors which bind to ING1 promoter, the promoter sequence was analyzed via Genomatix-MatInspector and TFSEARCH softwares. Used DS markers were D13S285, D13S1315, D13S796, D13S278, D13S158, and D13S779 where loss of heterozygosity (LOH) results were as 23.3, 20, 6.7, 3.3, 6.7, and 0 %, respectively. The highest LOH scores were obtained with markers D13S285 and D13S1315 which are flanking the ING1. Seven of 30 cases showed alteration in expression (p > 0.05). However, no mutation was detected in the exons of ING1. One patient showed a two-nucleotide deletion in p53 gene. However no significant TSG activity of ING1 was observed while higher activity was reported in different cancer types. As for the LOH data 13q33-34 region may contain different candidate TSGs like COL4A1, COL4A2 and SOX1. As a result of computational promoter analysis, some factors like ABL, E2F, HIF1, SOX, P53, BPTF, NRSF, c-Rel and c-ETS were associated with the promoter region. Molecular analysis of ING1 promoter warrants further analysis.