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Objectives: The most diagnosed tumor among infiltrating tumors of the female genital tract is endometrial carcinoma. The Wnt/β-catenin signaling pathway has an important role in organogenesis, self-renewal of tissues, and adult stem cell maintenance. However aberrant activation of it causes many types of tumors and also related to the prognosis of patients. Therefore, we aimed to investigate whether Wnt/β-catenin pathway inhibitors have any effect on the proliferation and migration of tumor cells. Methods: As cancer cell line, HEC-1A endometrial adenocarcinoma was used. The Wnt/β-catenin pathway inhibitors effects on proliferation and migration were demonstrated by real-time cell analysis device and wound healing model respectively. Results: Wnt/β-catenin pathway inhibitors FH535 (25 μM at 36th hour, p < 0.05; 50μM at 48th hour p < 0.001) and niclosamide inhibited cell proliferation (10, 25 and 50μM at 60th hours; p < 0.01, p < 0.05 and p < 0.001, respectively) whereas ICRT14 and IWP-2 did not. However only niclosamide which is also an antihelmintic drug inhibited migration of the cells in all concentrations tested (10, 25 and 50μM, p < 0.05). Conclusions: The present study shows that the Wnt/β-catenin pathway has an substantial role in both proliferation and migration of endometrial adenocarcinoma. We suggest that the antihelmintic drug niclosamide could be further investigated for its potential therapeutic effect in endometrial adenocarcinoma.

Amaç: Bu çalışmada Mersin Üniversitesi Hastanesi’nde çalışan araştırma görevlilerinin akılcı ilaç kullanımı (AİK) konusunda bilgi ve yaklaşımlarını belirlemek amaçlanmıştır. Yöntem: Kesitsel ve tanımlayıcı tipte olan bu çalışmada Mersin Üniversitesi Hastanesi’nde çalışmakta olan araştırma görevlilerine demografik verilere ait 6 soru ve akılcı ilaçla ilgili bilgi düzeylerini ve yaklaşımlarını ölçmek üzere hazırlanan 46 soru olmak üzere toplam 52 sorudan oluşan bir anket uygulanmıştır. Bulgular: Bu çalışmaya Mersin Üniversitesi Hastanesi’nden 180 kişi dahili, 69 kişi cerrahi bölümlerden olmak üzere 249 araştırma görevlisi katıldı. 169’u (%67.9) daha önce AİK ile ilgili eğitim almış 80’i ise (%32.1) herhangi bir eğitim almamış olan katılımcıların %78.1’i tıp eğitimi sırasında, %22.5’i mezuniyet sonrası ve %43.8’i de asistanlık süreçlerinde teorik eğitimler aldıklarını ifade ettiler. Hastanın yaşını, kullanmakta olduğu diğer ilaçları ve kronik hastalıklarını soranlar ise sırası ile katılımcıların%96.8, %94.8ve %98.0’i dir. Hastanın gebeliğini sorgulayanlar katılımcıların %87.1 ve emzirip emzirmediğini soranlar ise %85.5'i idi. Katılımcıların sadece %67.9’u hastasına yazdığı ilacın adını söylerken, ilaca ait yan etkilerden hastaya bahsetmeyenlerin sadece %30’u AİK ile ilgili eğitim almayanlardı. Öte yandan katılımcıların %25.5’i ilaç seçerken maliyet kriterini hiç dikkate almazken etkinlik, güvenlik ve uygunluğu daha fazla önemsemekteydiler. Maliyeti dikkate almayanlardan ise akılcı ilaç konusunda eğitim almayanların oranı ise %39.7 idi. Sonuç: Araştırma görevlilerinin daha önce eğitimler almış olsalar da AİK konusunda gerek bilgi düzeyleri gerek se tutum ve yaklaşımları açısından geliştirilmesi gereken noktalar olduğu tespit edilmiştir. Bu nedenle AİK ile ilgili süre ve içerik açısından zenginleştirilmiş, özellikle de uygulamalı eğitimlerin yapılması akılcı ilaç reçeteleme davranışı ile ilgili tespit edilen eksikliklerin giderilmesi yönünde önemli katkılar sağlayacaktır., Aim: In this study, it was aimed to determine the knowledge and approaches of research assistants working in Mersin University Hospital on rational use of drug (RDU). Method: In this cross-sectional and descriptive study, a questionnaire consisting of 52 questions in total, including 6 questions on demographic data and 46 questions prepared to measure their knowledge and approaches about rational medicine, was applied to the research assistants working at Mersin University Hospital. Results: 249 research assistants from Mersin University Hospital, including 180 internal and 69 from the surgical departments, participated in this study. Participants, 169 (67.9%) of whom had previously received training on RDU and 80 (32.1%) had not received any training stated that they received theoretical training on rational drug use during medical education (78.1%), after graduation (22.5%) and during assistantship (43.8%). Those asking about the age of the patient, the other medications he is using, and his chronic diseases are 96.8%, 94.8% and 98.0% of the participants, respectively. Those questioning the pregnancy of the patient were 87.1% of the participants and 85.5% of them asked whether she was breastfeeding or not. While only 67.9% of the participants said the name of the drug they prescribed to their patients, only 30% of those who did not mention the side effects of the drug to the patient were those who did not receive training on RDU. On the other hand, while 25.5% of the participants did not consider the cost criteria when choosing drugs, they gave more importance to efficiency, safety and suitability. 39.7% of those who did not consider the cost did not receive any training about RDU. Although the research assistants have received training before, it has been determined that there are points that need to be improved in terms of both their level of knowledge and their attitudes and approaches on RDU. Conclusion: Although the research assistants have received training before, it has been determined that there are points that need to be improved in terms of both their level of knowledge and their attitudes and approaches on RDU. For this reason, enriched courses in terms of duration and content, and especially practical training on RDU will provide significant contributions to overcome the deficiencies identified in rational drug prescribing behavior.

Endometrial cancer is the most common gynecological cancer in developed countries. Potassium channels, which have many types, are suggested to play a major role in cancer progression. However, their role in endometrial cancer has not been fully investigated. We aimed to demonstrate whether the ATP-sensitive potassium channel blocker glibenclamide, voltage-sensitive potassium channel blocker 4-aminopyridine, non-selective (voltage-sensitive and calcium-activated) potassium channels blocker tetraethylammonium and potassium chloride (KCl) have any effect on the proliferation and migration of HEC1-A cells.Proliferation and migration were evaluated by real-time cell analysis (xCELLigence system) and wound healing assays, respectively. Proliferation was reduced by glibenclamide (0.1 and 0.2 mM, P 0.05 and P 0.01, respectively), 4-aminopyridine (10 and 20 mM, P 0.001) and tetraethylammonium (10 and 20 mM, P 0.01 and P 0.001, respectively). However, KCl did not change the proliferation. Migration was reduced by glibenclamide (0.01, 0.1 and 0.2 mM, P 0.001, P 0.001 and P 0.01, respectively) and 4-aminopyridine (10 and 20 mM, P 0.05 and P 0.01, respectively). Tetraethylammonium did not change migration. However, KCl reduced it (10, 25 and 50 mM, P 0.05, P 0.01 and P 0.01, respectively). Both proliferation and migration were reduced by glibenclamide and 4-aminopyridine. However, tetraethylammonium only reduced proliferation and KCl only reduced migration.Potassium channels have an important role in HEC1-A cell proliferation and migration and potassium channel blockers needs to be further investigated for their therapeutic effect in endometrial cancer.

It has been clearly indicated that osteoarthritis (OA) is an inflammatory and degenerative disease that could be promoted by Rho-kinase (ROCK); however, little is known about the role of ROCK/inhibitor κB alpha (IκB-α)/nuclear factor-κB (NF-κB) p65 pathway activation in interleukin-1β (IL-1β) induced inflammatory response and oxidative stress in primary human chondrocytes. To test this hypothesis, we focused on determining ROCK-II, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), p22phox, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subtype 4 (NOX4) protein expression, ROCK-II activity, NADPH oxidase levels, and total antioxidant capacity (TAC) in the presence and absence of ROCK-inhibitor fasudil. IL-1β (2 ng·mL–1, 24 h) increased the expression of ROCK-II, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, TNF-α, COX-2, and p22phox proteins, and decreased the expression of IκB-α, and the NOX4 protein level did not alter. ROCK activity and NADPH oxidase levels were increased, whereas the TAC was decreased by IL-1β. Fasudil (10−5–10−7 M) reversed all these changes induced by IL-1β. These results demonstrate that ROCK/IκB-α/NF-κB p65 pathway activation contributes to the IL-1β-induced inflammatory response and oxidative stress, and thus, ROCK inhibition might be a beneficial treatment option for OA patients mainly based on its anti-inflammatory and antioxidant effects.

Objective: Variant alleles in specific ethnic groups are important for personalized drug therapy regimens and adverse drug reactions. Therefore, the aim of this study was to investigate allelic frequencies of the CYP2D6*1, CYP3A4*5, CYP3A4*18, CYP3A5*2 and CYP3A5*4 in a group of Turkish population. Materials and methods: Three hundred and six unrelated healthy subjects who were accepted as blood donors to the Mersin University Blood Bank were included in the study after informed consent. Allelic frequencies of the CYP2D6*1 (rs3892097), CYP3A4*5 (rs55901263), CYP3A4*18 (rs28371759), CYP3A5*2 (rs28365083) and CYP3A5*4 (rs56411402) were determined by using polymerase chain reaction-restriction fragment length polymorphism assays. Results: CYP2D6 allele frequencies in detected group was 100% for CYP2D6*1 (WT/WT). CYP3A4 allele frequencies of subjects were 100% for CYP3A4*5 (C/C) and CYP3A4*18 (T/T). CYP3A5 allele were in Hardy-Weinberg equilibrium for CYP3A5*2 (p=0.142) and frequencies for C and A allele were 91% and 9% respectively. CYP3A5 allele frequencies of subjects was 100% for CYP3A5*4 (WT/WT). Conclusion: Screening of low frequency alleles by pharmacogenetic testing must not be omitted to optimize pharmacotherapy and avoid severe drug toxicities. Frequency distributions of the identified polymorphisms in the present study may contribute to the personalized drug therapy regimens and prediction of possible adverse drug reactions in the Turkish population.

Aim:Although detection and monitoring of adverse drugreactions is mandatory for drug safety, the reporting of adverse drug reactionsare insufficient in our country. On the other hand, raising awareness of theimportance of pharmacovigilance among nurses is important for reporting adversedrug reactions. The main purpose of this study is to evaluate the knowledge,attitudes and practices about pharmacovigilance of nurses working in auniversity hospital.Methods:In this cross-sectional and descriptive study, a25-question questionnaire was applied to evaluate their knowledge, attitudesand practices on pharmacovigilance to nurses working in Mersin UniversityHospital.Results:83.9% of the nurses defined the pharmacovigilancecorrectly and 40.7% knew that there was a pharmacovigilance contact point inthe hospital. 81.7% of nurses are aware that reporting adverse drug reactionsis a professional obligation. While 48.8% of the nurses reported that they hadexperienced an adverse drug reaction but only 0.2% of them had reported anadverse drug reaction. 75.1% of the nurses reported that it was difficult todecide on an adverse drug reactionand 36.6% of the nurses showed that there was not enough time to report anadverse drug reaction.Conclusions:In this study, it was observed that nursesparticipating in the study had deficiencies in knowledge, attitude andpractices related to pharmacovigilance. The rate of adverse drug reactionreporting among nurses is very low. Pharmacovigilance training should beorganized for nurses in hospitals and nurses should be involved in thisprocess. In this way, it could be ensured that nurses make the necessarycontribution to the reporting of adverse drug reactions., Amaç: Advers ilaç reaksiyonlarının tespit edilmesi ve izlenmesi ilaçgüvenliği açısından zorunlu olmasına rağmen, ülkemizde advers ilaç reaksiyonubildirimi yetersizdir. Öte yandan hemşirelerde farmakovijilansın önemi hakkındafarkındalık yaratmak advers ilaç reaksiyonu bildirimi için önem arz etmektedir.Bu çalışmanın temel amacı bir üniversite hastanesinde çalışan hemşirelerinfarmakovijilans konusundaki bilgi, tutum ve uygulamalarını değerlendirmektir.Yöntem: Kesitsel ve tanımlayıcı tipte yapılan bu çalışmada, MersinÜniversitesi Hastanesinde çalışan hemşirelerin farmakovijilans konusunda bilgi,tutum ve uygulamalarını değerlendirmek için 25 soruluk anket uygulanmıştır. Bulgular: Hemşirelerin %83,9’u farmakovijilansı doğru tanımlamış ve %40,7’sihastanede bir farmakovijilans irtibat noktasının olduğunu bilmiştir.Hemşirelerin %81,7’si advers ilaç reaksiyonu bildiriminin profesyonel biryükümlülük olduğunun farkındadır. Hemşirelerin %48,8’i yaşanan bir advers ilaçreaksiyonu gördüğünü bildirmekle birlikte sadece %0,2’si advers ilaç reaksiyonubildirimi yaptığını ifade etmiştir. Yaşanan bir advers ilaç reaksiyonunutanımlamada hemşirelerin %75,1’i karar vermenin zor olduğunu bildirmiş veadvers ilaç reaksiyonunu bildirmek için hemşirelerin %36,6’sı yeterlizamanlarının olmadığını sebep olarak göstermişlerdir.Sonuç: Bu çalışmada araştırmaya katılan hemşirelerin farmakovijilans ileilgili bilgi, tutum ve uygulamalarında eksiklikleri olduğu görülmüştür.Hemşireler arasında advers ilaç reaksiyonu bildirimi oranı çok düşüktür.Hastanelerde hemşireler için farmakovijilans ile ilgili eğitimler düzenlenmelive hemşirelerin bu süreçte yer almaları sağlanmalıdır. Bu şekilde advers ilaçreaksiyonlarının bidiriminde hemşirelerin gerekli katkıyı sunması sağlanabilir.

The aim of this study was to investigate the expression of RhoA/Rho-kinase in the uterus and the effect of Rho-kinase inhibitors on uterine contractions of dehydroepiandrosterone (DHEA) induced polycystic ovary syndrome (PCOS) rats. Forty-four female Sprague-Dawley (21 days old) rats divided into three groups: The control group (n = 14, any procedure was not performed), vehicle group (n = 14, 0.2 ml of sesame oil, subcutaneous injection, 20 days) and PCOS group (n = 16, DHEA 6 mg/100 g in 0.2 ml of sesame oil, subcutaneous injection, 20 days). The myometrium thickness and uterine wet weight were assessed. The mRNA and protein expressions of Rho A, the effect of Rho-kinase inhibitors (fasudil and Y-27632) on KCI, carbachol, and PGF2 alpha induced contractions were evaluated in the uterus. In the PCOS group, the myometrium thickness and uterine wet weight significantly increased compared to the control group and vehicle group. The mRNA expression level and the immunoreactive score of Rho A, ROCK 1, ROCK 2 were similar in all groups. In the PCOS group, KCI, carbachol, and PGF2 alpha induced uterine contractions significantly increased compared to the control group and vehicle group. Fasudil and Y-27632 significantly inhibited KCI, carbachol, and PGF2 alpha induced uterine contractions in all groups. In conclusion, the expression of Rho A, ROCK 1, ROCK 2 not changed although myometrium thickness, uterine wet weight and the contractile responses of uterus increased in the PCOS group. The results suggest that the Rho-kinase inhibitors effectively suppressed increased contractions in the PCOS group they might be potential therapeutic agents.

Klasik olarak kalsiyumve fosfat mekanizması üzerine olan etkilerinin yanı sıra antiproliferatif veimmünomodülatör gibi özellikleri de olan D vitamini aslında bir seko-steroidhormondur. Yakın dönem çalışmalar, D vitamini eksikliğinin otoimmün ve kardiyovaskülerhastalıkların yanı sıra kanser riskini artırabildiğini göstermiştir. D vitaminieksikliği dünyada küresel bir salgın olarak bildirilmiştir. Buna ek olarakosteoporoz ve düşme kırıkları için de bir risk faktörü olarak tanımlanmıştır. Diyetle alınan ve deride güneş aracılığı ile sentezlenenD vitamininin kandaki normal seviyelerinin sağlanması için doğru bilgi sahibiolmak çeşitli hastalıklardan ve kanserden korunmak açısından önemlidir. Bunedenle öncelikle D vitaminin sentezi, kandaki düzeyleri, günlük ihtiyaç, metabolizması ve reseptörlerin durumuderlendi. Buna ek olarak D vitaminininiyi bilinen kemik mineralizasyonu dışındaki etkilerinden olan özellikle kansergelişimi ile olan ilişkisine dair güncel bilgiler derlendi., In addition to its well known classical effect oncalcium and phosphate metabolism Vitamin D which is actually a secosteroidhormone also has antiproliferative and immunomodulatory properties. Recentstudies have shown that vitamin D deficiency may increase autoimmune andcardiovascular diseases as well as cancer risk. Vitamin D deficiency has beenreported as a global epidemic in the world. In addition it has been identifiedas a risk factor for osteoporosis and fall fractures. The right information toensure normal levels of vitamin D taken from the diet and synthesized by thesunlight is important for protecting against various diseases and cancer.Firstly, the synthesis, blood levels, the daily need, the metabolism and thestatus of the receptors of vitamin D have been presented. In addition, current informationon the association of vitamin D with cancer developments that those outside thewell-known bone mineralization, were particularly presented.

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation.

Akademisyen Yayinevi yoneticileri, yaklasik 30 yillik yayin tecrubesini, kendi tuzel kisiliklerine aktararak uzun zamandan beri, ticari faaliyetlerini surdurmektedir. Anilan sure icinde, basta saglik ve sosyal bilimler, kulturel ve sanatsal konular dahil 750 kitabi yayimlamanin gururu icindedir. Uluslararasi yayinevi olmanin alt yapisini tanimlayan Akademisyen, Turkce ve yabanci dillerde yayin yapmanin yaninda, kuresel bir marka yaratmanin pesindedir.Bilimsel ve dusunsel calismalarin kalici belgeleri sayilan kitaplar, bilgi kayit ortami olarak yuzlerce yilin taniklaridir. Matbaanin icadiyla varolusunu saglam temellere oturtan kitabin gelecegi, her ne kadar yeni buluslarin yorungesine tasinmis olsa da, daha uzun sure hayatimizda yer edinecegi muhakkaktir.

This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI).The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats' cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months.PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1-4 of MWM testing (p 0.001). On day 2-4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3-4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms.Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance.

Aim: The aim of the present study is to give a brief evaluation about plants used for the treatment of obstetric and gynecological conditions by using Cerrâhiyyetu’l-Hâniyye which has been written by Serefeddin Sabuncuoglu who was a famous surgeon in Anatolia in the 15th Century. Material and Methods: Based on the Cerrâhiyyetu’l-Hâniyye, we selected plants that used for women health, and systematically arranged plants according to diseases. Plant species that detected in this book compared with the plants of three works (Soranus’ On Gynecology, Paulus Aeginata’s The Seven Books, and Zahavi's At Tasrif). Results: Cerrâhiyyetu’l-Hâniyye contains 24 different medical plants for women health. Six plants were found in Cerrâhiyyetu’l-Hâniyye were different from the other books compared. Sabuncuoglu wrote 18 same plants which typed by other authors for women health. Conclusion: This study shade light on the Ottoman herbal remedy. Regard to plant treatment, difference between Cerrâhiyyetu’l-Hâniyye and other books submitted by the present study.