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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.

objective. Effect of estrogenic compounds and 17β-estradiol (E2), which induces endothelial cell motility, was investigated on ROCK-2 expression in rat coronary vascular endothelial cells (CVEC). Methods. The CVEC were isolated from the heart of Wistar rats by collagenase (0.04%) and incubated with E2 (1-100 nM), estrogen receptor α (ERα) agonist: propyl pyrazole triol (PPT, 10 nM); ERβ agonists: (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN, 10 nM) and E2-conjugate with bovine serum albumin (E2-BSA, 1 nM); and GPER1 agonist: G1 (100 nM). Furthermore, the effect of combination of E2 with estrogen receptors (ERs) antagonist and GPER1 agonist, ICI-182780 (10 µM), physiological estrogen antagonists: progesterone (P4, 10-100 nM) and testosterone (T, 10-100 nM); transcription inhibitor: actinomycin-D (1 µg/ml); GPER1 antagonist: G-15 (100 nM), superoxide dismutase, (SOD, 500 U/ml); G i/o protein inhibitor: pertussis toxin (PTX, 100 µg/ml); and epidermal growth factor receptor (EGFR) blocker: AG-1478 (10 µM) was tested. After 24h incubation, ROCK-2 and GPER1 protein expressions were detected in the CVEC by Western-blotting. results. E2, ICI-182780, and G1 but not E2-BSA significantly up-regulated ROCK-2 expression, which was suppressed by actinomycin-D, PTX, AG-1478, and G-15. However, PPT and DPN had no effects on the ROCK-2 expression. ICI-182780, P4, T or SOD did not antagonize the E2 action. GPER1 expression was demonstrated in the CVEC. Conclusions. Estrogens could up-regulate ROCK-2 in the rat CVEC through GPER1 and EGFR transactivation.

Rho/Rho-kinase signalling pathway plays a substantial role in vascular contractions. In this study, we investigated any roles of Rho/Rho-kinase pathway in the vasoconstriction of the rat conductance and capacitance vessels by hyperosmolar glucose solution. Isolated aortic, mesenteric and renal rings were suspended and exposed to hyperosmolar glucose, sucrose and NaCl in the organ chambers filled with Krebs solution gassed with 95% O2 and 5% CO2 and maintained at 37 °C. The effect of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 10(-5) M), was tested on the contraction induced by hypertonic solutions. Endothelial integrity was also assessed after hyperosmolar glucose exposure. Moreover, the activity and expression of Rho-kinase (ROCK-2) as well as RhoA translocation were detected by Western blotting and enzyme-linked immunosorbent assay-based RhoA activity detection method detection kit. The vessels produced substantial contractions in response to hyperosmolar solutions. Y-27632 significantly reduced hyperosmolarity-induced vasoconstrictions (P < 0.05). Phosphorylation of myosin-phosphatase target 1 increased after hyperosmolar glucose exposure, and this phosphorylation was significantly decreased by Y-27632 (P < 0.05) in the aorta. Furthermore, RhoA translocation but not ROCK-2 expression markedly increased by hyperosmolar glucose solution. These results may indicate that hyperosmolarity could induce vasoconstriction through Rho/Rho-kinase signalling.

OBJECTIVE To examine the effect of candesartan cilexetil with hydrochlorothiazide (6 mg and 12.5 mg, respectively) on blood pressure and ST-segment depression during daily life of patients with treated but not controlled arterial hypertension (blood pressure taken at doctor's practice (3)140/90 mmHg, despite being on at least two antihypertensive drugs) PATIENTS AND METHODS 51 patients (45 men, 17 women) with treated but reportedly uncontrolled hypertension were placed on self-measurement of blood pressure for 4 weeks of a run-in period and 8 weeks as a follow-up period. Combined 24-hour automatic blood pressure measurement (ABPM) and electrocardiography were done at the end of the run-in and the follow-up periods. Ten patients proved to be normotensive according to the self-measurement and ABPM after the run-in period (group A), while 41 were still uncontrolled according to both methods (group B). In group B the least efficacious component of the antihypertensive medication was replaced by candesartan with hydrochlorothiazide (C + HCT) and any changes in blood pressure and ST-segment depression analysed after 8 weeks of follow-up in both groups. RESULTS In group A no significant blood pressure change was observed between run-in- and follow-up periods. But in group B (n=41) the self-measured systolic blood pressure had significantly decreased (155/84 mmHg compared with [vs] 147/81 mmHg; p

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.

To investigate the antimuscarinic effect of oxybutynin in the rat detrusor muscle after estrogen pretreatment because, to our knowledge, no study has been done on the interaction of estrogen with antimuscarinic drugs. Estrogen has been shown to affect muscarinic receptors in the detrusor muscle of animals. In addition, oxybutynin has been shown to block muscarinic receptors in the bladder.Estradiol benzoate (150 microg/kg) or saline was given subcutaneously to virgin female Wistar albino rats (n = 6, each group) for 10 consecutive days. On the 11th day, isolated detrusor muscle strips were taken, and acetylcholine (ACh)-induced contractions were evaluated in the absence or presence of oxybutynin (10 and 100 nM).ACh induced concentration-dependent contractions in the detrusor muscle. In the estradiol-pretreated group, the maximum of the ACh-induced contractions was diminished compared with that in the control group (P0.05). Oxybutynin (10 and 100 nM) inhibited ACh-induced contractions competitively (pK(B) 8.85). In the estradiol-pretreated group, the concentration-response curve to ACh was shifted further to the right in the presence of oxybutynin (100 nM).We have demonstrated for the first time that oxybutynin further inhibits ACh-induced and muscarinic receptor-mediated contractions in rat detrusor muscle after pretreatment with estrogen.

In human internal mammary artery (IMA), testosterone induces vasodilation that shows marked variability among patients. We aimed to investigate the relationship of this variability with cardiovascular risk factors. Cumulative relaxations to testosterone after precontraction with KCl were examined in IMA segments from patients with identified cardiovascular risk factors such as hypercholesterolemia, diabetes, hypertension, smoking, age, gender, body mass index (BMI), and number of occluded vessels. Testosterone responses were significantly diminished in subjects with 3 compared with 1 risk factor. Hypercholesterolemia independently influenced testosterone responses by significantly decreasing its maximum, and smoking significantly decreased the sensitivity to testosterone. Thus, the variability observed in testosterone-induced vascular relaxations may in part be related to differences in risk factors present among the individuals studied.

Relaxant responses to two Rho-kinase inhibitors, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632) and fasudil, were compared in the corpus cavernosum obtained from diabetic and non-diabetic mice. Streptozotocin (100 mg kg(-1) day(-1), for 2 days) induced diabetes with a blood glucose level of 318+/-55.4 mg dl(-1); whereas it was 85.4+/-4.1 mg dl(-1) in control mice (P0.05). Electrical field stimulation (40 V, 0.5 ms, 1, 2, 4, 8, 16 Hz for 15 s) and acetylcholine-induced relaxations were markedly attenuated in the corpus cavernosum from streptozotocin-diabetic mice whereas responses to Y-27632 (10(-9)-3 x 10(-5) M) and fasudil (10(-9)-3 x 10(-5) M) were not altered. EC(50) values for Y-27632 were 2.98+/-0.89 and 4.19+/-2.71 microM in the corpus cavernosum from control and diabetic mice, respectively (P0.05). The values for fasudil were 7.42+/-4.91 and 3.53+/-1.41 microM in the corpus cavernosum from control and diabetic mice, respectively (P0.05). These results may suggest that, in diabetes, the relaxant effects of the Rho-kinase inhibitors may not be changed and thus, they may have a beneficial therapeutic effect in diabetic erectile dysfunction.

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.

Heat shock protein 90 (hsp90) regulates the NO-cGMP pathway in several vascular tissues. In the present study, we investigated the existence and functional significance of hsp90-eNOS interactions i...

Rho/Rho-kinase signalling pathway plays a substantial role in vascular contractions. In this study, we investigated any roles of Rho/Rho-kinase pathway in the vasoconstriction of the rat conductance and capacitance vessels by hyperosmolar glucose solution. Isolated aortic, mesenteric and renal rings were suspended and exposed to hyperosmolar glucose, sucrose and NaCl in the organ chambers filled with Krebs solution gassed with 95% O2 and 5% CO2 and maintained at 37 °C. The effect of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 10(-5) M), was tested on the contraction induced by hypertonic solutions. Endothelial integrity was also assessed after hyperosmolar glucose exposure. Moreover, the activity and expression of Rho-kinase (ROCK-2) as well as RhoA translocation were detected by Western blotting and enzyme-linked immunosorbent assay-based RhoA activity detection method detection kit. The vessels produced substantial contractions in response to hyperosmolar solutions. Y-27632 significantly reduced hyperosmolarity-induced vasoconstrictions (P0.05). Phosphorylation of myosin-phosphatase target 1 increased after hyperosmolar glucose exposure, and this phosphorylation was significantly decreased by Y-27632 (P0.05) in the aorta. Furthermore, RhoA translocation but not ROCK-2 expression markedly increased by hyperosmolar glucose solution. These results may indicate that hyperosmolarity could induce vasoconstriction through Rho/Rho-kinase signalling.

Objectives We aimed to investigate effects of the proton pump inhibitors (PPIs) omeprazole, lansoprazole and pantoprazole, which are currently used for the treatment of hyperacidity and gastro-oesophageal reflux, on the reactivity of the isolated rat lower oesophageal sphincter. Methods Omeprazole, lansoprazole and pantoprazole (all 10–9–10–3m, cumulatively) were tested on carbachol-induced (10–6m) contraction. In addition, the effects of PPI preincubation (all 10–3m) on the contractions induced by cumulative carbachol (10−9–10−5m), angiotensin-2 (10−9–10–5m) or electrical field stimulation (EFS; 40 V, 32 Hz, 1 ms, 10 s) were assessed. Finally, the effects of PPI on the spontaneous contractile activity of the tissue were also evaluated. Key findings PPI relaxed precontracted lower oesophageal sphincter in a concentration-dependent manner and suppressed carbachol-, angiotensin- and EFS-induced contractions. Furthermore, PPI attenuated spontaneous contractile activity of the tissue. Conclusions Omeprazole, lansoprazole and pantoprazole had a suppressor effect on lower oesophageal sphincter contractions.

The objective of the present study was to investigate the prevalence, the risk factors, the hemodynamic triggering mechanisms, the circadian variability of ST segment depression (ST depression) and the effect of day and night fall in blood pressure on the prevalence of ST depression in hypertensive patients.In a multicentric study in Germany, 1,244 CardioTens registrations (combined 24-h ambulatory blood pressure measurement/electrocardiography with ST segment triggering; Meditech, Budapest, Hungary) from patients with arterial hypertension were consecutively monitored and evaluated centrally at the University of Bonn. Inclusion criterion was treated or untreated arterial hypertension. The ST segment was measured in accordance with the "1 : 1 : 1 rule" (horizontal or descending ST depression by 1 mm, 1 min duration, 1 min interval from the previous episode).ST segment depression was observed in 250 (20.1%) patients; 90.3% of the transient ST-segment depression was silent (without angina pectoris). Ambulatory 24-h blood pressure measurement, but not office-based blood pressure measurement, was predictive for the occurrence of ST-segment depression. Risk factors for ST-segment depression were the Sokolow indexor =3.5 mV, smoking status, severity of coronary heart disease, use of diuretics, reduced left ventricular function, pulse pressureor =60 mmHg and increase of double product (1,000 mmHg/min). A significant rise of the systolic/diastolic blood pressure (+8+ or -18/+7+ or -10 mmHg), of the heart rate (+12+ or -13/min) and of the double product (+2,471+ or -2,517 mmHg/min) was found during the transient ST depression as compared with the corresponding 24-h ambulatory blood pressure measurement mean values (P0.0001 for all parameters specified). In most intermittent ST depressions, a rise of the double product was seen (n=789 episodes), and in the remaining 239 ST depressions, a fall of the double product was observed. ST depressions with fall of the double product showed a circadian distribution with a peak in the late evening. ST depression accompanied by a rise in double product showed two peaks (one in the early morning and one in the late evening). The prevalence of ST depression was significantly higher (28.6%) in extreme dippers than in dippers (18.2%), risers (21.8%) and non-dippers (19.6%).ST depressions have a high prevalence of 20.1% in hypertensive patients. Clinical predictors for the occurrence of ST-segment depression were classical risk factors and cardiac target organ damage. Office-based blood pressure measurement was not a useful measuring tool for forecasting the likelihood of ST-segment depression. ST depressions were triggered inter alia by variations of blood pressure and the heart rate. The circadian variability of the ST depressions is crucially affected by the pressure double product characteristics on which the ST depression is based.

PubMedID: 14757149 Rho-kinase expression was investigated in the rat mesenteric artery and the effects of its inhibitors, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632) and fasudil (HA-1077), were examined on the increase in perfusion pressure induced by two different receptor agonists, namely the ?-adrenoceptor agonist, phenylephrine and, the endothelin ETA and ETB receptor agonist, endothelin-1. Y-27632 and fasudil produced a concentration-dependent decrease in perfusion pressure. There was no difference between the concentration-response lines of these two inhibitors. The maximum decrease in the perfusion pressure induced by 10-5 M Y-27632 was 85.8±3. 7% when the tone was increased by phenylephrine. However, it was 48.1±5.4% (P

Isolated rabbit corpus cavernosum relaxed in response to ultraviolet (UV) light (365 nm). The UV light-induced relaxation (photorelaxation) was diminished on repeated UV irradiation from 30.5 +/- 4.0% (the first photorelaxation) to 15.5 +/- 2.7% (the last photorelaxation). Hydroxocobolamine of 100 muM and hemoglobin (Hb) of 10 muM, which are nitric oxide (NO) scavengers, and 10 muM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor, markedly reduced photorelaxation, However, 300 muM 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO) failed to inhibit photorelaxation. NaNO2 and N-G-nitro-L-arginine (L-NA) but not 3-nitro-L-tyrosine (3-NT),were found to be photosensitive in that these compounds are photolysed to release NO, as demonstrated by use of an amperometric NO probed NO signals produced by 500 muM NaNO2, and 500 muM L-NA were 133.3 +/- 28.9 and 54.4 +/- 10.4 pA, respectively, Not 3-NT but the other compounds (all 200 muM) also enhanced photorelaxation of the cavernosal tissue. Based on these findings, the substance, which mediates photorelaxation, could be NO released from putative stores in the rabbit corpus cavernosum, and L-NA as well as NaNO2 but not 3-NT produce NO under the influence of UV light. (C) 2002 Published by Elsevier Science B.V.