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5. Exploring integration in schools by using the lens of cultural diversity and multilingualism in policy documents from Finland, Scotland and Sweden.

Author

Tarnanen, Mirja, Oral, Didem, Niklasson, Emil, de Riba-Mayoral, Silvia, Vähäsantanen, Katja, Pantić, Nataša, and Manninen, Eveliina

Subjects
*MULTICULTURALISM, *ACCULTURATION, *CULTURAL pluralism, *IMMIGRANTS, *EMIGRATION & immigration
Abstract

AbstractEducation policies are legally and societally significant for framing how schools are expected to promote the integration of pupils with migration backgrounds into school communities. Approaches to integration in education are embedded in policies that reflect wider general understandings of diversity and specific arrangements that aim to accommodate the increasing cultural and linguistic diversity of school populations. This article explores how the integration, cultural diversity and multilingualism of pupils with migration backgrounds are conceptualised in education policy documents in Finland, Sweden and Scotland. Based on thematic analysis of 19 policy documents, this study provides comparative insights into how migrant integration is conceptualised in policy documents across three similar but different national contexts. In the policy documents, pupils with migration backgrounds are implicitly identified as migrants because of their language backgrounds. In the documents of each country, it seems that integration has been scantly addressed or is even a hidden construct. At the same time, the cultural diversity of pupils has been recognised and considered favourable across the countries. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Investigation of Possible Protective Effects of Resveratrol on Oxidative Stress and Ferroptosis in PFOA Exposure in HepG-2 Cells.

Author

Oral, Didem and Hacioglu, Ceyhan

Subjects
*EPITHELIAL cells, *STREPTOMYCIN, *RESEARCH funding, *ENZYME-linked immunosorbent assay, *OXIDATIVE stress, *DESCRIPTIVE statistics, *RESVERATROL, *CELL death, *ANTIOXIDANTS, *COMPARATIVE studies, *FLUOROCARBONS, *PENICILLIN
Abstract

Objective: Exposure to perfluorooctanoic acid (PFOA) is linked to adverse health effects, including cancer and hepatic diseases. PFOA induces reactive oxygen species generation in human hepatic cells, causing oxidative stress and cell death. Resveratrol (RSV) has garnered attention for its protective effects against xenobiotic-induced damage, yet its impact on PFOA-induced oxidative stress and ferroptosis in the liver remains understudied. This study investigates RSV's protective mechanisms against oxidative stress and ferroptosis in HepG2 cells exposed to PFOA. Method: HepG2 cells were cultured in DMEM with 10% FBS and 1% penicillin/streptomycin in a 5% CO2 incubator at 37°C. PFOA was added to the cells at concentrations ranging from 0 to 450 µM and incubated at 37°C for 24 hours. The IC50 was determined to be 457 μM. To examine RSV's protective effects, cells were treated with 60 μM RSV. Following treatment with PFOA, RSV, and the combination of PFOA+RSV, cell lysates were prepared for analysis. Oxidative stress and ferroptosis parameters were measured spectrophotometrically using ELISA. Results: In the PFOA+RSV group, antioxidant capacity increased, and ferroptosis was suppressed compared to the control. Conversely, the PFOA group showed decreased antioxidant capacity, increased oxidant capacity, and induced ferroptosis compared to the control and RSV-treated groups. Conclusion: PFOA exposure heightens oxidative stress and ferroptosis, whereas RSV treatment significantly reduces hepatic oxidative stress and protects against ferroptosis during PFOA exposure. [ABSTRACT FROM AUTHOR]

Published
2024
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10. How do teachers exercise relational agency for supporting migrant students within social networks in schools from Scotland, Finland, and Sweden?

Author

Pantić, Nataša, Sarazin, Marc, Coppe, Thibault, Oral, Didem, Manninen, Eveliina, Silvennoinen, Kaisa, Lund, Anna, Päivi, Hökkä, Vähäsantanen, Katja, Li, Shupin, Pantić, Nataša, Sarazin, Marc, Coppe, Thibault, Oral, Didem, Manninen, Eveliina, Silvennoinen, Kaisa, Lund, Anna, Päivi, Hökkä, Vähäsantanen, Katja, and Li, Shupin

Abstract

This study examines how teachers exercise relational agency - working flexibly with other actors in their social networks to support migrant students. Teachers and other staff members from 7 schools in Scotland, Finland and Sweden participated in social network surveys (n = 1116), online logs (n = 275) and interviews (n = 82). A mixed-method social network analysis shows how networks facilitate relational agency as teachers reach out to others to mobilise resources and tacit knowledge within their school communities. The findings point to the critical role of professional collaboration and suggest that social networks shape how teachers work with specialists to support migrant students.

Published
2024
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12. The Impact of Levothyroxine and Testosterone Administration on Bladder Contractility in the Rat Model of Propy lthio uraci l-Ind uced Hypothyroidism.

Author

Oral, Didem Yılmaz, Ciloğlu, Berna Güven, and Gür, Serap

Subjects
*BLADDER physiology, *THYROXINE, *TESTOSTERONE, *PARASYMPATHOMIMETIC agents, *ADENOSINE triphosphate, *TREATMENT effectiveness, *DESCRIPTIVE statistics, *RATS, *TRIIODOTHYRONINE, *ANIMAL experimentation, *COMBINED modality therapy, *ELECTRIC stimulation, *STAINS & staining (Microscopy), *COMPARATIVE studies, *COLLAGEN, *HYPOTHYROIDISM, *MUSCLE contraction
Abstract

Objective: To investigate the effects of testosterone (T) treatment, with or without levothyroxine, the most widely used and least effective medication for managing hypothyroidism, on the functional and histological changes in propylthiouracil (PTU)- induced hypothyroid rat bladders. Materials and Methods: Male rats (n = 35) were split into control, hypothyroid, hypothyroid rats treated with levothyroxine (20 µg/kg/day, oral, 2-weeks), hypothyroid rats treated with Sustanon (10 mg/kg,iIM, once/week, 2-weeks), and hypothyroid rats treated with combined treatment groups. Hypothyroidism was induced by PTU (0.05% in drinking water, 6 weeks). The serum concentration of triiodothyronine (T3), thyroxine (T4), total T, and the detrusor muscle's contractile responses were determined. A morphological study was conducted using Masson trichrome staining. Results: Triiodothyronine, T4, and T levels were considerably reduced in rats with hypothyroidism; however, these hormones were restored by levothyroxine and Sustanon. Compared to controls, the combination therapy improved the ratio of smooth muscle to collagen and the contractile responses to carbachol, electrical field stimulation, and adenosine triphosphate in the hypothyroid bladder. Conclusion: The authors' research suggests that hypothyroidism may affect the contractility and morphology of the bladder. In males with hypothyroidism and urogenital system dysfunction, combination therapy with thyroid hormones and T has a major impact on repairing detrusor smooth muscle contractility and bladder histomorphology. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy

Author

Yilmaz-Oral, Didem, primary, Sezen, Sena F., additional, Turkcan, Damla, additional, Asker, Heba, additional, Kaya-Sezginer, Ecem, additional, Kirlangic, Omer Faruk, additional, Kopru, Cagla Zubeyde, additional, Elci, Mualla Pınar, additional, Ozen, Fatma Zeynep, additional, Korkusuz, Petek, additional, Oren, Sema, additional, Oztekin, Cetin Volkan, additional, Ates, Ilker, additional, and Gur, Serap, additional

Published
2023
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17. Using mixed methods social network analysis to study teacher collaboration for migrant inclusion in a Swedish school

Author

Sarazin, Marc, Oral, Didem, Lund, Anna, Pantic, Natasa, Sarazin, Marc, Oral, Didem, Lund, Anna, and Pantic, Natasa

Abstract

Growing migration has changed student populations in many countries, challenging schools and educational systems to include students from migration backgrounds. Teacher collaboration has emerged as a key means to respond to this challenge, yet studying how teachers collaborate to mobilise support in this context poses difficult theoretical and methodological questions. This chapter presents an analytical approach which, drawing on the theory of inclusive pedagogy and mixed methods social network analysis (MMSNA), can elucidate the extent to which teacher collaborations are likely to support the inclusion of migrant students. The approach proceeds in three steps to examine: first, who collaborates to support migrant students? Second, what do inclusive forms of collaboration look like? And finally, how supportive of migrant student inclusion are collaborations likely to be? The approach, demonstrated with MMSNA data from a lower secondary school in a large Swedish city, advances knowledge on the role of collaboration for supporting diverse students and offers the potential to further theory and methods.

Published
2023
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18. Evaluation of possible cytotoxic, genotoxic and epigenotoxic effects of titanium dioxide nanoparticles and possible protective effect of melatonin.

Author

Balci-Ozyurt, Aylin, Yirün, Anıl, Cakır, Deniz Arca, Zeybek, N. Dilara, Oral, Didem, Sabuncuoğlu, Suna, and Erkekoğlu, Pınar

Subjects
MELATONIN, TITANIUM dioxide nanoparticles, GENETIC toxicology, POISONS, TITANIUM dioxide, DNA methylation, DNA damage
Abstract

Nanoparticles (NPs) are particles of matter that are between 1 to 100 nm in diameter. They are suggested to cause toxic effects in both humans and environment thorough different mechanisms. However, their toxicity profile may be different from the parent material. Titanium dioxide (TiO2) NPs are widely used in cosmetic, pharmaceutical and food industries. As a white pigment, the use of TiO2 is used in food coloring, industrial paints, clothing and UV filters has increased tremendously in recent years. Melatonin, on the other hand, is a well-known antioxidant and may prevent oxidative stress caused by a variety of different substances, including NPs. In the current study, we aimed to comparatively investigate the effects of normal-sized TiO2 (220 nm) and nano-sized TiO2 (21 nm) on cytopathology, cytotoxicity, oxidative damage (lipid peroxidation, protein oxidation and glutathione), genotoxicity (8-hydroxydeoxyguanosine), apoptosis (caspase 3, 8 and 9) and epigenetic alterations (global DNA methylation, H3 acetylation) on 3T3 fibroblast cells. In addition, the possible protective effects of melatonin, which is known to have strong antioxidant effects, against the toxicity of TiO2 were also evaluated. Study groups were: a. the control group; b. melatonin group; c. TiO2 group; d. nano-sized TiO2 group; e. TiO2 + melatonin group and f. nano-sized TiO2 + melatonin group. We observed that both normal-sized and nano-sized TiO2 NPs showed significant toxic effects. However, TiO2 NPs caused higher DNA damage and global DNA methylation compared to normal-sized TiO2 whereas normal-sized TiO2 led to lower H3 acetylation vs. TiO2 NPs. Melatonin showed partial protective effect against the toxicity caused by TiO2 NPs. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

Author

Yilmaz-Oral, Didem, Sezen, Sena F., Turkcan, Damla, Asker, Heba, Kaya-Sezginer, Ecem, Kirlangic, Omer Faruk, Kopru, Cagla Zubeyde, Elci, Mualla Pınar, Ozen, Fatma Zeynep, Korkusuz, Petek, Oren, Sema, Oztekin, Cetin Volkan, Ates, Ilker, and Gur, Serap

Subjects
*RADICAL prostatectomy, *STEM cells, *ARGININE, *NICOTINAMIDE adenine dinucleotide phosphate, *NITRIC-oxide synthases, *MUSCARINIC acetylcholine receptors
Abstract

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Ameliorative effect of cranberry on erectile function in diabetic rats.

Author

Oral, Didem Yilmaz, Onder, Alev, and Gur, Serap

Subjects
*PHARMACEUTICAL research, *CRANBERRY industry, *FRUIT extracts, *IMPOTENCE, *GUANYLATE cyclase
Abstract

Background and Aims: Cranberry products are beneficial in erectile dysfunction (ED). Therefore, we assessed the impact of Cranberry fruit extract (Cranberry-E) on in vivo erectile response and in vitro relaxant responses in the corpus cavernosum (CC). Methods: Rats (n=10) were divided into control and diabetic groups. In vivo erectile function was measured following intracavernosal injection of Cranberry-E. The relaxation responses to Cranberry-E were obtained after pre-contraction with phenylephrine (Phe, 10 M) and KCl (60 mM). Cranberry-E caused relaxant responses in the incubation with nitric oxide synthase (NOS) blocker (L-NAME, 100 M) and soluble guanylate cyclase (sGC) blocker (ODQ, 30 M), and relaxation responses of cavernosal tissue were calculated before and after the incubation with Cranberry-E. Results: Erectile responseswere significantly reduced in diabetic animals as compared to controls (p<0.001), whichwas normalized after the intracavernous administration of Cranberry-E. There was no difference in the relaxation responses to Cranberry-E between the control and diabetic groups. Cranberry-E induced the relaxation of cavernosal tissue, which remained unaltered in the presence of L-NAME and ODQ. Relaxation responses to Cranberry decreased after KCl-induced precontraction (p<0.001). The relaxation of cavernosal tissue increased after Cranberry-E incubation. Conclusion: Cranberry-E improved diabetes-induced ED and induced relaxation of cavernosal tissue via a nitric oxide-independent mechanism. Thus, cranberry consumption is likely to be effective as a potential strategy to prevent diabetes-induced ED. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Combined levothyroxine and testosterone treatment for restoring erectile dysfunction in propylthiouracil-induced hypothyroid rats

Author

Korkmaz, Fatma Nur, primary, Yilmaz-Oral, Didem, additional, Asker, Heba, additional, Guven, Berna, additional, Turkcan, Damla, additional, Kirlangic, Omer Faruk, additional, Oztekin, Cetin Volkan, additional, Çorapçıoğlu, Demet, additional, Demir, Özgür, additional, Ates, Ilker, additional, and Gur, Serap, additional

Published
2023
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25. Ethnobotany of medicinal plants used in dermatology in Türkiye: a review.

Author

DEMİRCİ KAYIRAN, Serpil, PARLAK, Meryem, and YILMAZ ORAL, Didem

Subjects
ETHNOBOTANY, SCIENTIFIC literature, STINGING nettle, HYPERICUM perforatum, DERMATOLOGY, MEDICINAL plants, WALNUT
Abstract

Medicinal plants are increasingly used to treat skin diseases and as cosmetics. Türkiye has a rich diversity of medicinal flora, and patients have a choice of ethnomedicines to manage various dermatology problems. This comprehensive review aims to summarize the primary information available on the dermatological properties of medicinal plants in Türkiye and provide a baseline for the detection of new plant species having efficacy against skin conditions. In this review, clinical and experimental data were researched using relevant search terms in scientific literature databases like PubMed, Web of Science, Google Scholar, ScienceDirect, Scopus, EBSCO, ProQuest, Cochrane Library, and HighWire Press. The results are presented in different tables along with a regional comparative analysis. The study revealed that 439 taxa belonging to 89 families are used for the ethnomedical treatment of skin diseases or as cosmetics. The most commonly mentioned species are Plantago lanceolata L., Malva neglecta Wallr., Plantago major L., Juglans regia L., Hypericum perforatum L., Rubus sanctus Schreb., Urtica dioica L., Juniperus oxycedrus L., Echium italicum L., and Rosa canina L. This is the first nationwide ethnopharmacological review conducted in Türkiye for the treatment of dermatological disorders. Moreover, it is a contributing resource for further studies on using herbal remedies for the treatment of skin diseases. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Mother Tongue Instruction : Between Assimilation and Multicultural Incorporation

Author

Oral, Didem, Lund, Anna, Oral, Didem, and Lund, Anna

Abstract

For many students with migrant backgrounds and newly arrived students, their mother tongue is not only a knowledge and a school grade issue, but also a reflection of their identity and a sense of belonging, which are shaped by political structures. In this article, we analyze the role of mother tongue in Swedish policy documents and the way teachers and students see the role mother tongue in two Swedish schools: how do school professionals and students view the importance of mother tongue? What measures are taken to encourage the mother tongues of students with a migration background and newly arrived students? What are the implications of and obstacles to studying one’s mother tongue? We will look at levers of integration where school staff, as well as policy documents, encourage modes of incorporation, but also do identify obstacles concerning the practice of mother tongue instruction. Our article shows that although students long for a double cultural belonging, the policy documents are ambiguous and create an unclear promise for migrant students and their mother tongue teachers concerning multicultural incorporation. In practice, they have little evidence that maintaining their cultural background represents a strong value in Sweden. Ambiguous attitude towards mother tongue can be seen as a symbolic response to Sweden as a country which took a turn regarding its migration policy. The integration of residents with a migrant background is constantly questioned in the media and became a central issue in political debates. The implementation of mother tongue instruction reflects Sweden’s current state of discussing migration concerning integration policies somewhere between recognition and stigmatization. The data are drawn from student interviews, interviews with mother tongue teachers, and field notes in two schools in one of the biggest cities in Sweden.

Published
2022
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36. THE BENEFICIAL EFFECT OF INTRACAVERNOSAL INJECTION OF SILDENAFIL ON ERECTILE DYSFUNCTION IN DUTASTERIDE TREATED RATS.

Author

YILMAZ-ORAL, Didem and GUR, Serap

Subjects
SILDENAFIL, IMPOTENCE, BENIGN prostatic hyperplasia, ENDOTHELIAL cells, IN vitro studies
Abstract

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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38. Evaluation of DNA Damage, DNA Repair, Oxidative Stress, and Cell Death Caused by Helicobacter pylori in Human Adenocarcinoma Cells

Author

ORAL, DİDEM, primary, SUR, ÜNZİLE, additional, özkemahlı, gizem, additional, Yirüna, Anıl, additional, ZEYBEK, N. DİLARA, additional, BACANLI, MERVE, additional, aydın, kübra simay, additional, Akyön, Yakut, additional, başaran, nurşen, additional, gümüşel, belma, additional, and ERKEKOĞLU, PROF.DR. PINAR, additional

Published
2021
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43. EPIGENETIC AND GENETIC CHANGES CAUSED BY HELICOBACTER PYLORI AND THEIR ROLES IN GASTRIC CARCINOGENESIS

Author

ORAL, Didem, YİRÜN, Anıl, and ERKEKOĞLU, Pınar

Subjects
Helicobacter pylori,epigenetik mekanizmalar,DNA hasarı,gastrik karsinojenez, epigenetic mechanisms,DNA damage,gastric carcinogenesis,Helicobacter pylori,Helicobacter pylori, Farmakoloji ve Eczacılık, Pharmacology and Pharmacy
Abstract

Amaç: Helicobacterpylori mide mukozasında kolonize olan bir bakteridir ve dünya genelinde enyaygın infeksiyon hastalıklarından birisidir. Helicobacter pylori’nin gastrikkanser ve mukoza-assosiye lenfoid doku (MALT) lenfomaya neden olduğuna dairbulgular vardır. Bu bakterinin gastrik karsinojenez gelişimindeki etkimekanizmaları ile ilgili pek çok çalışma yapılmış olup, hem epigenetik hem degenetik mekanizmaların bu süreçte etkili olduğu belirtilmektedir. Bu derlemede,Helicobacter pylori’nin neden olduğu gastrik karsinojenez sürecindeki epigenetikve genetik mekanizmalar değerlendirilecektir. Gereç ve Yöntem: Helicobacterpylori’nin neden olduğu epigenetik ve genetik değişiklikler ve gastrikkarsinojenez gelişimindeki rolünün tespiti için yapılan çalışmaların kapsamlıolarak derlenebilmesi için başta PUBMED olmak üzere sağlık bilimleri alanındakiveri tabanları kullanılmış ve özellikle de son on yılda bu konuda yayınlananmakalelerden yararlanılmıştır. Sonuç ve Tartışma: Helicobacterpylori’nin neden olduğu karsinojenezin gelişiminde kronik inflamasyonun yolaçtığı oksidatif stres, bakteriyel virülans faktörleri, konakçıya bağlıintrinsik ve ekstrinsik faktörlerin bir bütün olarak tetiklediği epigenetik vegenetik mekanizmalar rol oynamaktadır. Ancak, bu Helicobacter pylori’nin yolaçtığı tüm epigenetik ve genetik değişiklikler henüz tam olarak anlaşılmamışolup, daha fazla in vivo ve in vitro mekanistik çalışmaya gereksinimduyulmaktadır., Objective: Helicobacterpylori is a bacteria which colonizes in the gastric mucosa and it is one of themajor infectious diseases throughout the world. There are findings pointing outthat Helicobacter pylori can cause gastric cancer and mucosa-associatedlymphoid tissue (MALT) lymphoma. There are several studies on the mechanism ofaction of this bacterium and it is indicated that both epigenetic and geneticmechanisms are effective in this process. In this review, we will evaluateepigenetic and genetic mechanisms caused by Helicobacter pylori through gastriccarcinogenesis development. Material and Method: In order to review the epigenetic andgenetic mechanisms caused by Helicobacter pylori and their roles in gastriccarcinogenesis development comprehensively, the health sciences databasesincluding PUBMED were used and particularly the scientific papers on thsesbject published in the last ten years were used. Result and Discussion: The epigenetic and genetic mechanisms caused by chronicinflammation (like oxidative stress, bacterial virulance factors, intrinsic andextrinsic fators) may trigger the gastric carcinogenesis development byHelicobacter pylori as a whole. However, all of the epigenetic and geneticalterations caused by Helicobacter pylori are not yet fully understood and morein vivo ve in vitro mechanistic studies are needed.

Published
2019

44. Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model

Author

Oral, Didem Yılmaz, Bayatlı, Nur, Öztekin, Çetin Volkan, Lokman, Utku, Gür, Serap, Sezginer, Ecem Kaya, Oral, Didem Yılmaz, Bayatlı, Nur, Öztekin, Çetin Volkan, Lokman, Utku, Gür, Serap, and Sezginer, Ecem Kaya

Abstract

Aims: To evaluate the impacts of hydrogen sulfide (H2S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). Methods: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. Results: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2S levels, while combined therapy completely recovered. Conclusions: The combination therapy with H2S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms.

Published
2020

45. Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model

Author

Öztekin, Çetin Volkan, Lokman, Utku, Sezginer, Ecem Kaya, Oral, Didem Yılmaz, Bayatlı, Nur, Gür, Serap, Öztekin, Çetin Volkan, Lokman, Utku, Sezginer, Ecem Kaya, Oral, Didem Yılmaz, Bayatlı, Nur, and Gür, Serap

Abstract

Aims: To evaluate the impacts of hydrogen sulfide (H2S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). Methods: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. Results: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2S levels, while combined therapy completely recovered. Conclusions: The combination therapy with H2S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms.

Published
2020

47. İnsan mide adenokarsinoma hücrelerinde Helicobacter pylori'nin neden olduğu DNA çift sarmal kırıkları ve oksidatif strein değerlendirilmesi

Author

Oral, Didem, Erkekoğlu, Ülfet Pınar, and Farmasötik Toksikoloji Anabilim Dalı

Subjects
Helicobacter pylori, Pharmacy and Pharmacology, Oxidative stress, Stomach neoplasms, Autophagy, DNA damage, DNA repair, Apoptosis, Eczacılık ve Farmakoloji, Adenocarcinoma
Abstract

Çeşitli mikroorganizmaların oluşturduğu infeksiyonların reaktif oksijen bileşikleri (ROS) ve reaktif azot bileşiklerinin (RNS) oluşumuna yol açtığı iyi bilinmektedir. Bu bileşiklerin de intrasellüler oksidan/antioksidan dengeyi değiştirip oksidatif strese neden olduğu birçok çalışmada gösterilmiştir. Oksidatif stres, birçok farklı mekanizma ile DNA hasarı oluşturabilmektedir. DNA hasarı, basit ve onarılabilir baz lezyonlarından, en tehlikeli DNA hasarı olan DNA çift sarmal kırıklarına (DSB) dek oldukça geniş bir yelpazede görülebilir. Radyasyon ve bazı bakteri toksinleri DSB'yi indükleyerek, karsinojeneze yol açabilir. Helicobacter pylori gastrik mukozada kronik infeksiyona neden olan bir Gram negatif bakteridir. Helicobacter pylori infeksiyonu Uluslararası Kanser Araştırma Ajansı tarafından `Grup I karsinojen` olarak sınıflandırılmıştır. Helicobacter pylori'nin neden olduğu toksisite altında yatan mekanizmalar ve bu bakterinin yol açtığı gastrik karsinojenezin mekanizması henüz tam olarak anlaşılamamıştır. Çalışmalar Helicobacter pylori'nin hem doğrudan DNA hasarı yaparak, hem de epigenetik mekanizmalarla genetik instabiliteye neden olduğunu göstermektedir. Helicobacter pylori infeksiyonu konak DNA'sında oksidatif hasara neden olmaktadır. Literatürde, Helicobacter pylori infeksiyonunun oksidatif strese ve DSB'ye neden olduğu ve DSB onarım mekanizmalarını da etkileyebileceğini gösteren çalışmalar mevcuttur. Ancak, Helicobacter pylori infeksiyonu ile oksidatif stres arasındaki ilişkiyi inceleyen yeterli sayıda çalışma bulunmamaktadır. Bu verilerin ışığında gerçekleştirilen tez kapsamında, gastrik adenokarsinoma (AGS) hücrelerinin Helicobacter pylori'ye maruziyeti sonucu ortaya çıkabilecek olası sitotoksisite, intrasellüler ROS artışı ve oksidatif stres, DNA baz lezyonları, DNA onarım proteinlerindeki değişiklikler, apoptotik ve otofajik değişiklikler detaylı bir şekilde araştırılmıştır. Ayrıca, AGS hücrelerinin Helicobacter pylori'yle infekte olması sonucu, hücrelerde DSB'nin bir biyogöstergesi olan histon 2A ailesi üyesi X (H2AX) fosforilasyonunun (-H2AX) belirlenmiştir. Diğer taraftan, DSB onarım yolaklarıyla ile Helicobacter pylori maruziyeti sonucu ortaya çıkabilecek DSB'lerin onarılabileceği de düşünülerek çalışmaya bir DSB onarımında önemli rolü olan DNA-protein kinaz (DNA-PK) inhibitörü eklenmiş ve ilgili parametreler DNA-protein kinaz inhibitörü varlığında da ölçülmüştür. Bu şekilde, DSB onarımı bozulmuş bireylerde Helicobacter pylori infeksiyonunun neden olabileceği olası durumun öngörülmesi planlanmıştır. Elde edilen sonuçlar, Helicobacter pylori infeksiyonunun özellikle DNA-PK inhibitörü varlığında oksidatif streste önemli artışlara, DNA onarım proteinlerinde değişikliklere ve g-H2AX düzeylerinde belirgin artışlara yol açtığı ve apoptozu ve otofajiyi tetiklediği görülmüştür. Diğer taraftan, Helicobacter pylori ve DNA-PK inhibitörü birlikte maruz kalan grupta apoptoz ve otofajinin çok daha yüksek olduğu tespit edilmiştir. Sonuç olarak, Helicobacter pylori infeksiyonunun özellikle DSB onarımında sorun olan hücrelerde ciddi sorunlara yol açabileceği belirlenmiştir. It is well-known that infections caused by various microorganisms lead to the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Several studies have shown that these species can change the intracellular oxidant/antioxidant balance and cause oxidative stress. Oxidative stress can cause DNA damage by many different mechanisms. DNA damage can be observed in a wide range, from simple and repairable base lesions to DNA double-strand breaks (DSBs),which are the most dangerous DNA damage types. Radiation and some bacterial toxins can casue carcinogenesis by inducing DSBs. Helicobacter pylori is a gram negative bacterium that causes chronic infection in gastric mucosa. Approximately 50% of the world's population has been reported to be infected with chronic Helicobacter pylori infection which causes gastritis, peptic ulcer, stomach adenocarcinoma and gastric mucosal lymphoma. Helicobacter pylori infection is categorized as `Group I carcinogen` by the International Agency for Research on Cancer. The mechanisms underlying the toxicity of Helicobacter pylori infection and the mechanism of gastric carcinogenesis caused by this certain bacterium are not fully understood yet. Studies show that Helicobacter pylori infection can cause genetic instability both by direct DNA damage and by epigenetic mechanisms. Helicobacter pylori infection causes oxidative damage nuclear and mitochondrial DNA of the host. In addition, it can lead to chromosomal instability, microsatellite instability and mutations by affecting DNA methylation. There are studies in literature that show Helicobacter pylori infection can cause DSBs, oxidative stress and may also affect DSB repair mechanisms. However, there are not many studies that investigate the association between Helicobacter pylori infection and oxidative stress. Studies to date have generally been conducte on clinical specimens, and focused on the direct treatment of infection rather than focusing on the toxicity mechanisms of the bacterium. In the light of these data, the possible cytotoxicity, intracellular ROS elevations, and oxidative stress, DNA base lesions, changes in DNA repair proteins, apoptotic and autophagic changes caused by Helicobacter pylori in gastric adenocarcinoma (AGS) cell line were investigated in detail in this thesis. In addition, AGS cells which were infected with Helicobacter pylori were investigated for the presence of histone 2A family X (H2AX) phosphorilation (-H2AX), a biomarker of DSBs. On the other hand, by evaluating that DSBs caused by Helicobacter pylori can be repaired, a DNA-protein kinase (DNA-PK, an important DSB repair protein) inhibitor was also included to the study and the related parameters were measured. Thus, we planned to foresee the outcomes of Helicobacter pylori infection in people which disrupted DSB repairs. According to the results, Helicobacter pylori infection caused significant increases in oxidative stress, changes in DNA repair proteins and increases in g-H2AX levels, particularly in the presence of DNA-protein kinase inhibitor. Moreover, Helicobacter pylori infection triggered apoptosis and autophagy and cell death was significantly higher in both DNA-protein kinase inhibitor and Helicobacter pylori -exposed group. 231

Published
2019

49. Effect of aerial part and root extracts from Ferula orientalis L. growing in Turkey on erectile dysfunction in streptozotocin-ınduced diabetic rats

Author

KARAKAYA, Songül, YILMAZ ORAL, Didem, GÜR, Serap, and KILIÇ, Ceyda Sibel

Subjects
erektil disfonksiyon,Apiaceae,rat,Ferula, Biodiversity Conservation, Biyoloji Çeşitliliğinin Korunuması, erectile dysfunction,Apiaceae,rat,Ferula
Abstract

Apiaceae familyasına ait Ferula L. cinsinin Türkiye’de 22 türü yetişmekte olup bu türlerin 13'ü endemiktir ve bu cins zamk-reçine bakımından zengindir. Ferula türleri Türkiye’nin çeşitli yörelerinde “çakşır, çakşırotu, helizan, çağşır, kıngor, çağ vb.” adlarıyla bilinmektedir. Türkiye’de F. orientalis “heliz” adıyla bilinir ve karminatif, sedatif, antispazmotik, laksatif, dijestif, ekspektoran, diüretik, afrodizyak, antiseptik, antihelmentik, analjezik ve stimulan olarak kullanılmaktadır. Bu çalışmanın amacı, F. orientalis ekstrelerinin corpus cavernosum (CC) üzerindeki gevşetici etkisini in vitro göstermektir. 16 adet erkek Sprague-Dawley sıçan diyabetik ve kontrol olarak iki gruba ayrıldı. Diyabet grubuna tek doz intraperitoneal enjeksiyonla streptozotosin (40 mg/kg) verilerek diyabet oluşturuldu. Organ banyosu çalışmalarında, izole korpus kavernosum dokularında asetilkoline (ACh, 1 mM), elektrik alan stimülasyonuna (EFS, 20 Hz) and sodyum nitroprusite (SNP, 0.1 μM) bağlı gevşeme cevapları alınmış, bitkinin toprak üstü ve köklerinden elde edilen sulu ekstreler ile tekrarlanmıştır. Ekstrelerin her iki grupta aktif olduğu görülmüştür. Kök ekstrelerinin % 98.12 gevşeme sağladığı bulunmuştur. Kök ekstrelerinin en iyi aktivite gösterdiği tespit edilmiştir. Bunun yanısıra, toprak üstü kısımlarına ait ekstreler en kötü aktiviteyi göstermiştir. Bu bulgulara bağlı olarak, bu türün kökleri afrodizyak potansiyel bakımından daha fazla in vivo değerlendirmeyi hak etmektedir., Ferula L. belongs to Apiaceae family and 22 species of this genus grow in Turkey, of which 13 are endemic and this genus is found to be a rich resource of gum-resin. Ferula species are known in various regions of Turkey as “çakşır, çakşırotu, helizan, çağşır, kıngor, çağ etc. ”. F. orientalis is known as “heliz” in Turkey and has been utilised as carminative, sedative, antispasmodic, laxative, digestive, expectorant, diuretic, aphrodisiac, antiseptic, anthelminitic, analgesic and stimulants. The purpose of this study is to indicate in vitro the relaxant effect of F. orientalis extracts on corpus cavernosum (CC). Total of 16 adult male Sprague-Dawley rats were levelly divided down the middle control and diabetic ingroups. Diabetes was induced by a single intraperitoneial injection of streptozotocin (40 mg/kg). The relaxation responses to acetylcholine (ACh, 1 mM), electrical field stimulation (EFS, 10Hz) sodium nitroprusside (SNP, 0.1 μM) of corpus cavernosum (CC) strips were studied after the incubation with the aerial parts and roots in organ baths. The extracts were active in both groups. It was found that root extracts yielded 98.12% relaxation. Among the extracts of roots indicated the best activity. In other respects, aerial part extracts demonstrated the worst activity. Depending upon this findings, the roots of this species deserve further in vivo assessments for its aphrodisiac potential.

Published
2018

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