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New findings What is the central question of this study? Could different hormonally active substances, including oestrogen receptor (ER) agonists, protect against oxidative brain damage and memory impairment induced by a single epileptic seizure in rats? If so, which signalling mechanisms are involved in their anti-inflammatory effects? What is the main finding and its importance? Chronic administration of oestrogen, progesterone, ER modulators/agonists or blockade of testosterone exhibited anti-inflammatory and antioxidant actions on single seizure-induced neuronal injury, while ER agonists additionally improved memory function and up-regulated CREB signalling and hippocampal GABA(A)α1 receptor density, suggesting that ERα or ERβ receptor activation may be beneficial in protecting against seizure-related oxidative brain injury and cognitive dysfunction. Abstract The susceptibility to epileptic seizures is dependent on sex as well as fluctuations in oestrogen levels, while exogenous oestrogen was shown to have no effect or to facilitate or to inhibit seizure activity. Oestrogen receptors (ERs) mediate antioxidant and anti-inflammatory actions in several inflammatory models, but the involvement of ERs in seizure-induced neuronal injury has not been evaluated previously. In order to assess the effects of resveratrol, progesterone, oestradiol (E2), an anti-testosterone (cyproterone acetate; CPA), a selective ER modulator (tamoxifen; TMX) and ERα/ERβ agonists (propyl pyrazole triol (PPT), diarylpropionitrile (DPN)) on oxidative brain damage and memory impairment due to epileptic seizure, male Wistar rats (n = 120) received one of the treatment choices either in drinking water or intraperitoneally for 31 days, and epileptic seizure was induced on the 28th day by injection of a single-dose of pentylenetetrazole (45 mg kg-1 ). The results demonstrate that chronic pretreatment with resveratrol, progesterone, E2, CPA or TMX suppressed most of the inflammatory parameters indicative of oxidative neuronal injury, while treatment with the ER agonists DPN or PPT were found to be even more effective in limiting the oxidative damage. Treatment with DPN resulted in the up-regulation of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression, while PPT up-regulated expression of CREB without affecting BDNF levels. Moreover, both ER agonists provided protection against seizure-induced memory loss with a concomitant increase in hippocampal GABA(A)α1-positive cells. In conclusion, ER agonists, and more specifically ERβ agonist, appear to provide maximum protection against seizure-induced oxidative brain injury and associated memory dysfunction by up-regulating the expression of CREB, BDNF and GABA(A)α1 receptors.

Background: Plasminogen activator inhibitor-1 (PAI-1) antagonists are known for their neuroprotective effects. In this study, it was aimed to investigate the possible protective effects of PAI-1 antagonists in a rat mild traumatic brain injury (TBI) model.Method: Sprague Dawley male rats were grouped as sham (n=7), TBI (n=9), TBI + PAI-1 antagonist (5 and 10 mg/kg TM5441 and TM5484; n=6-7). Under anesthesia, TBI was induced by dropping a metal 300-gram weight from a height of 1 meter on the skull. Before and 24-hour after trauma neurological examination, tail suspension, Y-maze, novel object recognition tests were performed. Twenty-four hours after TBI, the rats were decapitated and activities of myeloperoxidase, nitric oxide release, luminol- and lucigenin-enhanced chemiluminescence were measured. Also, interleukin-1b, interleukin-6, tumor necrosis factor, interleukin-10, tumor growth factor-b, caspase-3, cleaved caspase-3, and PAI levels were measured with the ELISA method in the brain tissue. Brain injury was graded histopathologically following hematoxylin-eosin staining. Western blot and immunohistochemical investigation for low-density lipoprotein receptor, matrix metalloproteinase-3 and nuclear factor-kB were also performed. Data were analyzed using GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA) and expressed as means ± SEM. Values of p < 0.05 were considered to be statistically significant.Results: Higher levels of myeloperoxidase activity in the TBI group (pConclusion: PAI antagonists, especially TM5441, has antioxidant and anti-inflammatory properties against mild TBI in the acute period. Behavioral test results were also improved after PAI antagonist treatment after mild TBI.

Cancer as the leading cause of death worldwide has many issues that still need to be addressed. Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans. In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations. Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy. Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations. Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers. While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer. WOS:000628899900003 33404348 Q2

Aims: This study aims to evaluate medical students’ knowledge, thoughts, and awareness of the COVID-19 pandemic. Metho- ds: A questionnaire consisting of 31 questions was prepared for this descriptive study. In the questionnaire, medical students’ knowledge, attitudes and behaviors during the COVID-19 pandemic were investigated. Categorical variables are demonstrated as numbers and percentages, whereas continuous variables are presented as minimum, maximum, and mean values. Results: A total of 575 participants completed the questionnaire. The mean participant age was 21.7 years. Fifty-two percent of participants knew about the coronaviridae family before the outbreak and 38.8% were informed about COVID-19 in their medical schools. Of the students, 99.7% stated that the first case’s origin was in China. Eighty percent of the participants stated that droplet spread is the transmission route of COVID-19. The most common opinion about the incubation period of the SARS CoV-2 was two to twelve days. Being older than 65 years old, having a comorbidity, being immunosuppressed, or working in the healthcare sector were the most particular risk factors to get infected. The majority of the participants follow the vaccine developments from social media, radio and television. According to 75.83% of the participants, all people should wear a mask in daily life for protection. Conclusion: The epidemiology and diagnostic factors of COVID-19 are well known by medical students. To minimize informa- tion pollution and raise awareness, medical students should be educated about pandemic and management of it. Further evalu- ation with various methods and more participants may help to better understand the awareness of the COVID-19 pandemic in medical students.

AIM: To identify the copy number variations that are specific to myxopapillary ependymomas (MPEs) of the cauda equina. MATERIAL and METHODS: The patient cohort included five patients who underwent resection of histologically confirmed MPEs. Tumor samples collected during surgery and stored in liquid nitrogen as well as corresponding blood samples collected were analyzed. Genomic DNA from the venous blood and tumor samples was obtained using standard techniques and hybridized to a Cytoscan 750K Array in accordance with the manufacturer's introductions. RESULTS: As a novel finding, amplification on chromosome 14q32.33 was detected in all tumor and blood samples, except one tumor sample. All tumor tissues also showed amplification on chromosomes 5, 7, 9, and 16. CONCLUSION: Although further studies with larger cohorts are required to identify genes involved in MPE tumorigenesis and to validate our results, these findings provide a basis for advanced molecular biological and genetic studies of MPEs.

Background: Radiographic severity of ankylosing spondylitis (AS) shows such great variance that some patients never develop syndesmophytes throughout the entire disease span, whereas some develop bamboo spine relatively early. Objective: To study the association between ERAP1, IL23R and PTGER4 single nucleotide polymorphisms (SNPs) and radiographic severity in AS patients. Methods: rs27044 and rs30187 (ERAP1), rs11209032 (IL23R) and rs10440635 (PTGER4) SNPs were genotyped in 235 AS patients fulfilling the modified New York criteria. Patients were classified as mild- and severe-AS according to modified Stoke AS spinal score (mSASSS). Mild-AS is defined as having mSASSS of “0” following at least 10 years of disease duration. Severe-AS is defined as having mSASSS of >20 (patients with mild vertebral changes (i.e. squaring or erosions) were omitted for clear stratification) regardless of disease duration. Results: The genotype distributions and allele frequencies of ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs were similar in mild- (n=171, mSASSS=0, 55.6% HLA-B27 positive) and severe-AS patients (n=64, mSASSS=48.5±17.8, 73.4% HLA-B27 positive). After adjustment for clinical differences between groups (gender, disease duration, HLA-B27 and smoking status) by logistic regression analysis, none of the alleles in the investigated SNPs were found to be associated with radiographic severity of AS. Conclusion: In radiographically well-categorized AS patients, ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs are not found to be associated with radiographic severity of AS.

BACKGROUND: The insulin-like growth factor binding protein5 (IGFBP5) is often dysregulated in human cancers and considered neither a tumor suppressor nor an oncogene. OBJECTIVE: We aim to examine the reason of the changeable gene regulation of IGFBP5 in the case of methylation in breast cancer. METHODS: We used methyl-specific polymerase (MSP) chain reaction to detect CpG methylation of IGFBP5 promoter and exon-I in breast cancer and adjacent tissues. Gene expression is evaluated by quantative polymerase chain reaction (qPCR). RESULTS: IGFBP5 methylation was detected in 24 of 58 (41%) and 54 of 56 (96.5%) promoter and exon-I site respectively in tumor tissues. In adjacent tissues 17 of 58 (29%) and 53 of 56 (96.5%) was methylated. IGFBP5 expression was higher estrogene receptor (ER)(+) than ER(-) patients (p = 0:0549). Beside, we found a positive correlation between the expression of IGFBP5 and G2 tumor grade (p = 0:0131). However, no correlation was observed between IGFBP5 expression and age, menopause or the presence of lymph node metastasis (p > 0:05). CONCLUSIONS: In summary, our results showed that IGFBP5 promoter and exon-I methylation did not have any differences between tumor and adjacent tissues so that IGFBP5 methylation did not change IGFBP5 gene regulation in breast cancer. This is the first study investigating the IGFBP5 gene methylation in breast cancer. © 2016 - IOS Press and the authors.

Objective: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1 beta) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+- ATPase enzyme activities were analyzed to study tissue injury under light microscope. Results: While IR increased AST, ALT, TNF-alpha, and IL-1 beta levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values. Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

Background Cells detaching from the primary tumor site are metastasis initiator cells, and the detection of CTC, known as liquid biopsy, is an important test of biomarkers of cancer progression. We investigated the molecular characterization of circulating tumor cells (CTCs), profiled the plasma microRNA (miR) content, and analyzed the relationship with the clinical outcomes by sampling the peripheral blood from patients with locally advanced breast cancer before and after neoadjuvant chemotherapy. Patients and Methods Markers of breast cancer, epithelial–mesenchymal transition (EMT), drug resistance, and stem cells were used for CTC isolation and characterization. Plasma miR profiles were obtained from selected patients with CTC positivity determined using next-generation sequencing. Results The proportion of CTC, EMT, and stem cell marker positivity was 16.7%, 8.3%, and 25% before and 18.2%, 15.2%, and 9.1% after treatment, respectively. A significant correlation was found between the pretreatment CTCs and ALDH1 positivity (P = .0245). These CTCs with stemness properties were observed in most hormone receptor–positive, human epidermal growth factor receptor 2–negative cases and were also present with a high incidence in cases of early metastasis. miR-146b-5p and miR-199a-5p, which are involved in metastasis, invasion, and EMT, were accompanied by CTC positivity, and miR-4646-3p was associated with the development of early metastasis. Conclusions Molecular characterization of CTCs and miR profiling of serial samples from patients with locally advanced breast cancer during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course and might be a key to developing new targeted therapies.

Objective Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients. Material and method The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis. Results None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis ( p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04–16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69–197.13). Conclusions Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and nesfatin (n = 8). After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114). Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects.

Background Thermal injury may cause distant organ inflammation and multiorgan failure. Oxytocin (OT), a nonapeptide, modulates the immune and inflammatory processes. Materials and Methods To investigate the effects of oxytocin on burn-induced tissue injury, Sprague-Dawley rats were subjected to a partial thickness burn. Immediately after burn, half of the burned rats were placed single in the cages, while others were caged in groups. All the rats then were treated with either OT (5 μg/kg, s.c) or saline twice daily for 5 d. The control rats had no burn injury and received no treatments. On day 5, the rats were decapitated, tissue and serum samples were obtained to score the severity of damage and to assay TNF-α levels. Results Burn trauma resulted in oxidative ileal damage, as evidenced by increased apoptotic rate, increased neutrophil recruitment, and enhanced lipid peroxidation. OT treatment depressed the TNF-α level and alleviated dermal degeneration, while attenuating ileal damage. Although a higher degree of skin damage was observed in the animals kept isolated following burn injury, keeping the rats in groups did not affect the level of TNF-α or the severity of dermal or ileal injury, but abolished the burn-induced elevations in ileal lipid peroxidation and myeloperoxidase activity. Moreover, OT treatment reduced the ileal apoptosis when applied to rats housed in groups, while the treatment did not alter apoptotic ratio in the isolated rats. Conclusion Oxytocin can be considered as a potential agent in treating burn-induced distant organ injury.

To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis.

Transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in gastrointestinal tissues due to ischemia, which is followed by reperfusion injury. Oxytocin (OT), a hypothalamic nonapeptide, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in immune and inflammatory processes. To assess the possible protective effect of oxytocin (OT) against burn-induced gastric injury, Sprague–Dawley rats (250–300 g) were randomly divided into three groups as control (n = 8), OT-treated burn (n = 8) and saline-treated burn (n = 8) groups. Under anesthesia, the shaved dorsal skin of rats was exposed to 90 °C water for 10 s to induce burn injury covering 30% of total body surface area in a standardized manner. Either oxytocin (5 μg/kg) or saline was administered subcutaneously immediately after and at 24 h following burn, and the rats were decapitated at 48 h. Serum samples were assayed for TNF-alpha, and stomach was taken for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, DNA fragmentation rate (%) and histopathological examination. MDA and MPO were assayed for products of lipid peroxidation and as an index of tissue neutrophil infiltration, respectively. When compared to control group, burn caused significant increases in gastric MDA and MPO activity and increased microscopic damage scores at 48 h (p < 0.001). Oxytocin treatment reversed the burn-induced elevations in MDA and MPO levels and reduced the gastric damage scores (p < 0.001, p < 0.01), while TNF-alpha levels, which were increased significantly at 48th h after injury (p < 0.001), were abolished with OT treatment (p < 0.001). The results of this study suggest that oxytocin may provide a therapeutic benefit in diminishing burn-induced gastric inflammation by depressing tissue neutrophil infiltration and decreasing the release of inflammatory cytokines, but requires further investigation as a potential therapeutic agent in ameliorating the systemic effects of severe burn.

A 19-year-old woman presented with pain at the lateral side of the fifth toe of her left foot, which was separated from the adjacent toe. Initial examination suggested dislocation of the fifth metatarsophalangeal joint due to a past fracture. Radiographs showed a mass arising from the proximal phalanx of the little toe, with no medullary and cortical continuity. Excisional biopsy of the mass was performed, and a histologic diagnosis of bizarre parosteal osteochondromatous proliferation of bone (Nora’s lesion) was made. (J Am Podiatr Med Assoc 96(2): 158–161, 2006)

Traumatic injury to the central nervous system results in the delayed dysfunction and neuronal death. Impaired mitochondrial function, generation of reactive oxygen species (ROS), and lipid peroxidation occur soon after traumatic spinal cord injury (SCI), while the activation of compensatory molecules that neutralize ROS occurs at later time points. The aim of the current study was to investigate the putative neuroprotective effect of the COX2 inhibitor meloxicam in a rat model of SCI. In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10, was used. Injured animals were given either 2 mg/kg meloxicam or saline 30 min postinjury by intraperitoneal injection. At seven days postinjury, neurological examination was performed and rats were decapitated. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and DNA fragmentation. Formation of ROS in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in CL, MDA levels, MPO activity, and DNA damage. On the other hand, meloxicam treatment reversed all these biochemical parameters as well as SCI-induced histopathological alterations. Furthermore, impairment of the neurological functions due to SCI was improved by meloxicam treatment. The present study suggests that meloxicam, reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, GSH depletion, and DNA fragmentation.

Background: Oxidative stress is a mediator of secondary injury to the spinal cord following trauma. Objective: To investigate the putative neuroprotective effect of a-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI). Methods: Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. Results: SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SO-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged. Conclusion: The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.

Background Ankylosing spondylitis (AS) is an inflammatory disease predominantly affecting spine which may lead to syndesmophyte formation and disability. However, the new bone formation and the radiographic severity of AS shows great variance that some patients never develop syndesmophytes throughout the entire disease duration, whereas some develop spinal fusion. The genetic determinants of this variance has not been identified yet in a well-defined mild-radiograhic AS and severe-radiographic AS. Objectives To determine the association between ERAP1 , IL23R and PTGER4 polymorphisms and radiographic severity of AS and secondly to identify clinical characteristics associated with severe radiographic AS. Methods rs27044 and rs30187 ( ERAP1 gene), rs11209032 ( IL23R gene) and rs10440635 ( PTGER4 gene) single nucleotide polymorphisms (SNP) were genotyped in total of 199 AS patients (F/M: 83/116, mean age: 42.1±11.0 years, 62.8% HLA-B27 [+]) fulfilling the 1984 modified New York criteria for AS. Patients were classifed as severe-radiographic AS and mild-radiographic AS according to modified Stoke AS spinal score (m-SASSS). Mild AS is defined as having m-SASSS of “0” despite ≥10 years of disease duration. Whereas severe AS is defined as having m-SASSS of >20 (without counting scores “1”) regardless of the disease duration. Results Fifty eight patients (F/M=9/49, mean age 50.7±9.3, disease duration 21.9±7.0 years) were classified as severe AS, 141 patients (F/M=74/67, mean age 38.3±9.1, disease duration 13.6±4.9 years) were classified as mild AS. Severe group had significantly higher m-SASSS scores (48.5±18.3 vs 0) ( P ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNP genotypes between severe and mild AS (Table 2). The genotype frequencies did not change when severe and mild AS patients were categorized according to gender or HLA-B27 status. Concerning clinical and demographic characteristics, it was found that majority of severe AS patients were males (84.5%) and severe AS patients had significantly higher coxofemoral joint involvement (43.1% vs 22.2%, P =0.003), uveitis (25.9% vs 12.8%, P =0.024), anti-TNF usage (70.7% vs 39.7, P P =0.026) compared to mild AS. In multi-variate analysis male gender (OR=0.19, 95% CI [0.087-0.42], P P =0.033) were independently associated with severe AS. Conclusions Our data with a well-defined categorization of mild and severe-radiographic AS underline that ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs are not associated with radiographic severity of AS. Whereas male gender and coxofemoral joint involvement are associated with severe-radiographic AS. Disclosure of Interest None declared

Amac: Epidemiyolojik calismalar ulseratif kolitin sigara kullanmayanlarda daha sik goruldugunu bildirmektedir. Bu calismada kolitle olusan oksidan hasar ve anksiyete uzerine nikotin on tedavisinin ve/veya kolit sonrasi tedavinin olasi yararli etkilerinin arastirilmasi amaclanmistir. Gerec ve Yontem: Wistar Albino (250-300 g) sicanlar (n=40), serum fizyolojik (SF) verilen, on-tedavili, tedavili ve on-tedavi+ tedavili kolit grubu ve kontrol grubu olmak uzere bese ayrildi. Kolit oncesi 15 gun ve kolit sonrasinda 3 gun sicanlara intraperitoneal SF ya da nikotin (0,1 mg/kg/gun) uygulandi. Kolon orneklerinde oksidan hasari belirlemek icin malondialdehid (MDA), miyeloperoksidaz (MPO) aktivitesi, glutatyon (GSH), superoksit dismutaz (SOD), katalaz ve DNA fragmantasyonu olcumleri ile histolojik skorlama yapildi. Delikli kutu testi ile anksiyete seviyeleri belirlendi. Sonuclar ANOVA ve Mann Whitney U testi ile analiz edildi. Bulgular: Kolitte artan anksiyetenin nikotin ile degismedigi gozlendi. SF verilen kolit grubunda kolon MPO ve MDA duzeyleri ile DNA fragmantasyonunun ve hasar skorunun kontrol grubuna kiyasla arttigi, nikotin verilen tum kolit gruplarinda ise bu hasar gostergelerinin anlamli sekilde dustugu gozlendi. Histolojik doku hasari skorunun nikotin uygulanan kolit grubunda daha az oldugu gozlendi. SOD, katalaz ve GSH duzeylerindeki azalmanin nikotin tedavisiyle anlamli sekilde arttigi gozlendi. Sonuc: Calismada asetik asitle olusturulan kolit modelinde, nikotin tedavisinin doku antioksidan kapasitesini arttirarak, inflamasyon sonucu notrofil gocunu ve membran hasarini azaltarak antioksidan etki olusturdugu gosterildi.