Estrogen and Progesterone Synthesis with Cellular Response in a C57BL/6 Mouse Model of Cuprizone-Induced Demyelination

Background: Demyelination refers to the degradation or loss of myelin sheath. In demyelination model studies, it has been reported that demyelination is regressed by giving steroid hormones such as estrogen and progesterone. However, there are not many studies investigating the synthesis of these two hormones by the brain during demyelination and remyelination. Neurosteroids are steroid hormones synthesized by the brain independently from peripheral tissues. In this study, it was aimed to have knowledge about the synthesis of these two hormones by the brain in experimentally formed demyelination process in brains of C57BL/6 mice and their role in the cellular response formed in the region.Materials, Methods & Results: In the study, 36 C57BL/6 mice were used: 12 mice were fed normal diet for 12 weeks as control group (Group I); 12 of them were fed 0.2% cuprizone diet for 12 weeks (Group II) and 12 mice were fed normal diet for 4 weeks after feeding cuprizone diet for 8 weeks (Group III). At the end of the experiment, mice were perfused with 4% paraformaldehyde and brain tissues were blocked in paraffin. 6 μm-thick section was taken from each block. Sections were stained histologically with LFB staining and immunohistochemically with MBP staining in order to determine the demyelination in sections. All sections were also immunohistochemically stained with GFAP to detect astrocytes, with NG2 to detect young OPCs, with aromatase for estrogen synthesis and with 3βHSD antibodies for progesterone synthesis. At the end of the study, complete myelination was observed in group I, while severe demyelination was determined in group II as a result of blind evaluation of LFB and MBP staining by two pathologists. In group III, demyelination was found to be mild. In immunostaining with GFAP and NG2 antibodies, the number of GFAP and NG2 positive cells in Group II was found to be increased compared to the control group. The difference between these two groups was statistically significant (P < 0.01). In group III, the number of GFAP and NG2 positive cells were found to be increased compared to the control group; however, it was found to be lower than that in experimental group II (P < 0.01). In immunohistochemical staining with aromatase and 3βHSD antibody, there was no staining observed in the control groups. While an intense staining was observed in experimental group II, fewer glial staining was noticed in experimental group III when compared to the experimental group II. The difference between these two groups was found to be statistically significant (P ˂ 0.01).Discussion: Aromatase is an enzyme that converts testosterone into estrogen. On the other hand, 3βHSD is an enzyme that converts pregnenolone to progesterone. Expression of aromatase from tissues refers to the synthesis of estrogen and expression of 3βHSD refers to progesterone synthesis. In previous demyelination studies carried out with cuprizone, it has been reported that demyelination is regressed by giving estrogen and progesterone during demyelination. In the presented study, we observed that enzyme levels that catalyze the synthesis of estrogen and progesterone increased during demyelination. In the study, it was determined that estrogen and progesterone levels were increased in the region by enzymes released from the glial cells of the brain as a response to damage formed during demyelination. Interestingly, during the period in which cuprizone was excluded from the diet, it was observed that remyelination began to be formed again and that enzyme levels synthesizing these hormones started to decrease. These results suggested that estrogen and progesterone may be synthesized in the brain after a damage and may contribute to remyelination by initiating a number of cell to cell signaling steps

Effects of Oral Propolis on Mucosal Wound Healing after Endoscopic Nasal Surgery in a Rabbit Model

Objective: If the respiratory nasal mucosa is damaged and the mucosa does not heal properly during nasal or paranasal sinus surgery, a revision surgery may be required. The aim of this study is to investigate the effects of oral propolis application on mucosal wound healing following endoscopic nasal surgery in a rabbit model.Methods: Twenty four New Zealand rabbits were randomly divided into three groups, namely the experimental group (EG), the control group (CG), and the negative control group (NCG). Mucosal resection was applied with 3-mm punch forceps in the bilateral ventral nasal concha in the experimental and control groups. 75 mg/kg/day propolis was added to the diet of the rabbits in the EG for 14 days. The CG continued with the standard diet postoperatively. In the NCG, no surgical intervention was made, and no dietary support was given. On postoperative day 14 all rabbits were sacrificed and left nasal specimens were examined histopathologically, hydroxyproline levels were measured in right nasal specimens.Results: There were no statistically significant differences in hydroxyproline level, epithelial and subepithelial thickness, ciliary and goblet cell count, subepithelial fibrosis and collagen density between EG and CG. Neutrophil count was statistically significantly lower in EG, compared to CG (p=0.019, Tamhane test).Conclusion: Although there are many studies that show the positive effects of propolis on wound healing, such effect was not observed in this study. This study is deemed to constitute a unique experimental study that can be a resource for future similar studies to be performed with higher numbers of subjects and higher dosage of propolis

Determination of Serum Adenosine Deaminase Activity in Bitch Diagnosed as Cystic Endometrial Hyperplasia (CEH)-pyometra Complex

Bu çalışmanın amacı, kliniğimize getirilen ve kistik endometriyal hiperplazi (KEH)-pyometra kompleks tanısı konulan köpeklerde serum adenozin deaminaz aktivitesinin belirlenmesi ve sonuçların kan lenfosit ve monosit sayılarıyla ilişkisinin araştırılmasıdır. Çalışmada açık serviks KEH- pyometrası bulunan 18 köpek ve diöstrus döneminin ortasında olan 7 sağlıklı köpek olmak üzere toplam 25 köpek kullanıldı. KEH-pyometra tanısı klinik, ultrasonografik ve hematolojik bulgulara dayanılarak konuldu. Kontrol köpeklerinin diöstrusun ortasında olduğu sitolojik muayeneyle belirlendi. Ovaryohisterektomi yapılmadan önce kan örnekleri alındı ve operasyon sonrası histopatolojik incelemeler için doku örnekleri alındı. ADA aktivitesi spektrofotometrik olarak ölçüldü. Serum ADA aktivitesi KEH-pyometralı köpeklerde 5.99±0.31 U/l, diöstrustaki kontrol köpeklerinde ise 3.50±0.64 U/l olarak belirlendi. Ortalama serum ADA aktivitesi (KEH)-pyometra kompleks tanısı konulan köpeklerde sağlıklı köpeklere göre daha yüksek bulundu (p<0.01). Sonuç olarak, KEH-pyometra kompleksinin köpeklerde hücre aracılı bağışıklık sistemini uyararak serum ADA aktivitesinde yükselmeye neden olduğu ve serum ADA aktivitesinin değerlendirilmesinin bu hastalığın tanısında ve tedavisinin izlenmesinde yararlı bir parametre olabileceği kanısına varılmıştır.The purpose of the study was to investigate serum ADA activity and blood lymphocyte and monocyte numbers in the bitch diagnosed as cystic endometrial hyperplasia (CEH)-pyometra complex. Twenty five female dogs were involved in the study. Samples from 18 bitches with open cervix CEH- pyometra and 7 mid-diestrus bitches were used. The diagnosis of CEH- pyometra was based on clinical, ultrasonographical and haematological findings. Mid-diestrus control bitches were diagnosed by vaginal cytologic examination. Blood samples were taken before the operation and tissue samples were collected at the time of surgery from the uteri of 18 adult bitch diagnosed as cystic endometrial hyperplasia (CEH)-pyometra complex and of 7 healthy mid- diestrus dogs presented for ovariohysterectomy for histopathological investigation. Serum ADA activity was measured by spectrophotometrically and determined to be 5.99±0.31 U/l in bitches with CEH-pyometra and 3.50±0.64 U/l in mid-diestrus bitches. Mean serum ADA activity were higher in bitches with CEH-pyometra complex compared with the concentrations in healthy mid-diestrus dogs (p<0.01). It was concluded that CEH-pyometra complex results in increase in serum ADA activity by cell-mediated immune system and evaluation of serum ADA activity could be an useful parameter for diagnosis and treatment follow-up of this complex

Determination of Serum Adenosine Deaminase Activity in Bitch Diagnosed as Cystic Endometrial Hyperplasia (CEH)-pyometra Complex

Bu çalışmanın amacı, kliniğimize getirilen ve kistik endometriyal hiperplazi (KEH)-pyometra kompleks tanısı konulan köpeklerde serum adenozin deaminaz aktivitesinin belirlenmesi ve sonuçların kan lenfosit ve monosit sayılarıyla ilişkisinin araştırılmasıdır. Çalışmada açık serviks KEH- pyometrası bulunan 18 köpek ve diöstrus döneminin ortasında olan 7 sağlıklı köpek olmak üzere toplam 25 köpek kullanıldı. KEH-pyometra tanısı klinik, ultrasonografik ve hematolojik bulgulara dayanılarak konuldu. Kontrol köpeklerinin diöstrusun ortasında olduğu sitolojik muayeneyle belirlendi. Ovaryohisterektomi yapılmadan önce kan örnekleri alındı ve operasyon sonrası histopatolojik incelemeler için doku örnekleri alındı. ADA aktivitesi spektrofotometrik olarak ölçüldü. Serum ADA aktivitesi KEH-pyometralı köpeklerde 5.99±0.31 U/l, diöstrustaki kontrol köpeklerinde ise 3.50±0.64 U/l olarak belirlendi. Ortalama serum ADA aktivitesi (KEH)-pyometra kompleks tanısı konulan köpeklerde sağlıklı köpeklere göre daha yüksek bulundu (p<0.01). Sonuç olarak, KEH-pyometra kompleksinin köpeklerde hücre aracılı bağışıklık sistemini uyararak serum ADA aktivitesinde yükselmeye neden olduğu ve serum ADA aktivitesinin değerlendirilmesinin bu hastalığın tanısında ve tedavisinin izlenmesinde yararlı bir parametre olabileceği kanısına varılmıştır.The purpose of the study was to investigate serum ADA activity and blood lymphocyte and monocyte numbers in the bitch diagnosed as cystic endometrial hyperplasia (CEH)-pyometra complex. Twenty five female dogs were involved in the study. Samples from 18 bitches with open cervix CEH- pyometra and 7 mid-diestrus bitches were used. The diagnosis of CEH- pyometra was based on clinical, ultrasonographical and haematological findings. Mid-diestrus control bitches were diagnosed by vaginal cytologic examination. Blood samples were taken before the operation and tissue samples were collected at the time of surgery from the uteri of 18 adult bitch diagnosed as cystic endometrial hyperplasia (CEH)-pyometra complex and of 7 healthy mid- diestrus dogs presented for ovariohysterectomy for histopathological investigation. Serum ADA activity was measured by spectrophotometrically and determined to be 5.99±0.31 U/l in bitches with CEH-pyometra and 3.50±0.64 U/l in mid-diestrus bitches. Mean serum ADA activity were higher in bitches with CEH-pyometra complex compared with the concentrations in healthy mid-diestrus dogs (p<0.01). It was concluded that CEH-pyometra complex results in increase in serum ADA activity by cell-mediated immune system and evaluation of serum ADA activity could be an useful parameter for diagnosis and treatment follow-up of this complex

Neuroprotective effects of epidermal growth factor

Epidermal büyüme faktörü (EGF), hücrelerin bölünmesini, farklılaşmasını, yaşamasını, çoğalmasını, büyümesini ve göçünü uyaran, organizmadaki pek çok fizyolojik ve patolojik süreçte görev alan protein yapıda bir büyüme faktörüdür. Epidermal büyüme faktörü, biyolojik etkilerini bir transmembran protein olan EGF reseptörü (EGFR) aracılığı ile göstermektedir. Epidermal büyüme faktörü reseptörü, akciğerde, midede, duodenumda, pankreasta, böbrekte, hipofiz bezinde, tiroid bezinde, meme bezinde, yumurtalıkta, uterusta, plasentada, korneada ve gliya hücrelerinde bulunmaktadır. Epidermal büyüme faktörü, EGFR'ye bağlanarak, hücre çoğalması ve sağ kalımında rol oynayan mitojen-aktiveli protein kinaz (MAPK), hücre dışı sinyalle düzenlenen kinaz (ERK) 1/2 ve fosfotidil inozitol 3-kinaz (PI3K)-Akt sinyalizasyon yolaklarını aktive etmektedir. Epidermal büyüme faktörü reseptörü, astrositlerin çoğalmasında, farklılaşmasında ve postmitotik nöronların sağ kalımında rol oynamaktadır. Epidermal büyüme faktörü reseptörünün oligodendrosit gelişiminde de önemli bir role sahip olduğu bilinmektedir. Akut omurilik yaralanmasında EGF uygulaması kan-omurilik bariyeri geçirgenliğindeki bozulmayı fosfotidil inozitol 3-kinaz /Akt/ Ras- ilişkili C3 botulinum toksin substrat 1 (PI3K/Akt/Rac1) yolağı ile hafifletmekte ve lokomotor aktiviteyi artırmaktadır. Yeni doğan beyin hasarı modelinde burun içi heparin-bağlı EGF tedavisi, progenitör hücrelerden yeni oligodendrositlerin oluşumunu artırmakta ve fonksiyonel iyileşmeyi uyarmaktadır. Plazma EGF düzeyinin, Parkinson ve Alzheimer hastalarında bilişsel gerilemenin biyobelirteçi olduğu ileri sürülmektedir. Epidermal büyüme faktörü, multiple skleroz hastalarında remiyelinasyon için anahtar bir molekül olarak değerlendirilmektedir. Sinir sistemi hastalıklarının tedavisinde EGF uygulaması yeni bir yaklaşım olarak görülmektedir. Bu derlemede, EGF'nin nöroprotektif etkileri hakkında bilgi sunulması amaçlanmıştır.Epidermal growth factor (EGF) is a growth factor in protein structure that stimulating division, differentiation, survival, proliferation, growth and migration of the cells and is involved in many physiological and pathological processes of the organism. EGF exerts its biological effects through EGF receptor (EGFR) which is a transmembrane protein. Epidermal growth factor receptors are located on the cell surface of many tissues that include lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus, placenta, cornea and glia. EGF activates the mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 and phosphatidylinositol 3 kinase (PI3K)-Akt signaling pathways stimulating cell proliferation and survival through binding to EGFR. EGFR plays a role in proliferation and differentiation of astrocytes and survival of postmitotic neurons. EGFR is also known to have an important role in oligodendrocyte development. In acute spinal cord injury, EGF treatment alleviates the deterioration in the blood-spinal cord barrier permeability via phosphatidylinositol 3 kinase/Akt/Ras-releated C3 botulinum toxin substrate 1 (PI3K/Akt/Rac1) pathway and increases locomotor activity. Intranasal heparin-bound EGF treatment increases the formation of new oligodendrocytes from progenitor cells and induces functional recovery in newborn brain injury model. Plasma EGF levels is suggested that a biological marker of cognitive decline in patients with Parkinson disease and Alzheimer disease. EGF is evaluated as a key molecule for remyelination in patient with multiple sclerosis. EGF treatment is considered as a novel approach to the treatment of nervous system diseases. In this review, it has been aimed to present a knowledge about neuroprotective effect of EGF

A flavonoid has neuroprotective effect : nobiletin

Nörodejeneratif hastalıkların tedavisinde flavonoidlerin kullanımı yeni umutlar vaad etmektedir. Nobiletin, narenciye kabuklarında bulunan bir polimetoksi flavonoiddir. Nobiletinin nöroprotektif etkiye sahip olduğu pek çok in vivo ve in vitro araştırma ile ortaya konulmuştur. Nobiletin, öğrenme ve hafıza ile ilişkili sinyalizasyon kaskadlarını etkilemekte, enflamasyon mediyatörlerini modüle ederek nörodejenerasyonu hafifletmekte, dopamin salınımını artırarak motor ve bilişsel işlev bozukluğunu engellemekte, duygusal ve yenilikleri tanıma belleğini geliştirmektedir. Güncel çalışmalar, nobiletinin nörodejeneratif hastalıkların tedavisi için yeni bir ilaç olma potansiyeline sahip olduğunu desteklemektedir. Bu derlemede, nobiletinin nöroprotektif etkileri üzerinde durularak, literatürden elde edilen sonuçlar özetlenmiştirThe use of flavonoids promises new approach for the treatment of neurodegenerative diseases. Nobiletine is a polymethoxy flavonoid found in the citrus peel. The neuroprotective effect of nobiletin has been demonstrated in vivo and in vitro. Nobiletine affects the signaling cascades associated with learning and memory, alleviates neurodegeneration by modulating inflammatory mediators, inhibits motor and cognitive dysfunction by increasing dopamine release and enhances memory and recognition of emotions and innovations. Recent studies suggest that nobiletine has the potential to be a new drug for the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of nobiletin was emphasized and the results obtained from the literature were summarize

Investigation of the effect of cornelian cherry (Cornus mas L.) fruit extract against cisplatin-induced renal cell injury in vitro

Amaç: Bu in vitro çalışmada, kızılcık meyva ekstraktının sisplatin indüklü nefrotoksisiteye karşı koruyucu etkisinin değerlendirilmesi amaçlanmıştır.Materyal ve Metot: Çalışmada Afrika yeşil maymun böbrek epitel hücreleri (Vero), 100 mg/mL kızılcık meyva ekstraktı, 50 ?mol/L sisplatin veya 50 ?mol/L sisplatin + 100 mg/mL kızılcık meyva ekstraktı ile 4 saat inkübe edildi. Herhangi bir ekleme yapılmayan, sadece hücre bulunan kuyucuklar kontrol grubu olarak kullanıldı. Hücre canlılığı, 3-(4,5-dimetil-thiazole-2-yl)-2,5-difenil tetrazolium bromide tayini ile belirlendi. Kültür medyumları toplandı ve santrifüj edildi. Malondialdehit (MDA), glutatyon (GSH), superoksit dismutaz (SOD) ve glutatyon peroksidaz (GPx) analizleri yapıldı.Bulgular: Sisplatine maruz bırakılan hücrelerde hücre canlılılığı %42, sisplatinle birlikte kızılcık meyva ekstraktı uygulanan hücrelerde ise hücre canlılılığı %59 bulundu. Sisplatin uygulanan hücrelerde hücresel hasar oranı yüksekti. Bununla birlikte kızılcık meyva ekstraktı ile kombine sisplatin grubunda, sisplatinin zararlı etkileri anlamlı derecede azalmıştı. Sisplatin grubu, kontrol grubu, kızılcık grubu ve sisplatin + kızılcık grupları ile karşılaştırıldığında MDA konsantrasyonu önemli decede yüksek, GSH konsantrasyonu, GPx ve SOD enzim aktiviteleri anlamlı derecede düşük bulundu (p < 0.05).Sonuç: Bu çalışma sisplatin ile uyarılan in vitro oksidatif hasar üzerine kızılcık meyva ektraktının koruyucu etkileri olduğunu göstermiştirObjective: The aim of this study was to evaluate the protective effects of cornelian cherry fruit extract against cisplatin-induced nephrotoxicity in vitro.Materials and methods: African green monkey kidney epithelial cells (Vero) were incubated with 100 mg/mL of cornelian cherry fruit extract, 50 ?mol/L of cisplatin or 50 ?mol/L of cisplatin plus 100 mg/mL of cornelian cherry fruit extract for 4  h. The wells containing cells without any supplementation served as control. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay. Culture mediums were collected, centrifuged and analyzed for malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx)Results: The cell viability was 59% in cells co-treated with cisplatin and cornelian cherry fruit extract simultaneously and 42% in cisplatin treated cells. The cellular damage ratio was elevated in cells treated with cisplatin. However, when cisplatin combined with cornelian cherry fruit extract the deleterious effects of cisplatin were significantly decreased. The MDA concentration was significantly higher (p?<?0.05), GSH concentration and GPx and SOD activities were significantly lower (p?<?0.05) in cisplatin treated group when compared with control group, cornelian cherry group, and cisplatin?+?cornelian cherry group. Conclusion: The present study indicated that cornelian cherry fruit extract exert protective effects on oxidative damage in vitro induced by cisplatin

Uludağ'ın eteklerinden Bursa halkına uzanan kişi : İhsan Uzer

Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2018.This work is a student project of the Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.The History of Turkey course (HIST200) is a requirement for all Bilkent undergraduates. It is designed to encourage students to work in groups on projects concerning any topic of their choice that relates to the history of Turkey. It is designed as an interactive course with an emphasis on research and the objective of investigating events, chronologically short historical periods, as well as historic representations. Students from all departments prepare and present final projects for examination by a committee, with 10 projects chosen to receive awards.Includes bibliographical references (pages 14-15).by İbrahim Mert Öztürk

Crystal Structure Of 4-(4-Bromophenyl)-1,7,7-Trimethyl-1,2,3,4,5,6,7,8-Octahydroquinazoline-2,5-Dione

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