HTK-Alcar, a modified organ transplantation solution, decreases ischemic injury in the rat kidney tissue

Objectives: Histidine-tryptophan-ketoglutarate (HTK) solution is the storage solution used in organ transplantation. However, such solutions cannot completely eliminate tissue damage. Acetyl L-carnitine (Alcar) is a strong antioxidant. In this study we aimed to determine the protective effects of HTK solution prepared with Alcar in kidney tissue. Methods: Twenty-four rats used in this study were divided into 4 groups. Kidneys of rats in groups 1 and 2 were stored for 4 hours in HTK and HTK+Alcar solutions, respectively. Kidneys of rats in groups 3 and 4 were stored for 24 hours in HTK and HTK+Alcar solutions, respectively. Histological and immunohistochemical examinations of the kidneys were performed. In addition, TUNEL analysis was performed for the evaluation of apoptosis. Results: The findings of histomorphological damage in short-term HTK and HTK+Alcar groups were mild, but it was found widely in long-term HTK and ong-term HTK+Alcar groups on histologic evaluation. When histological scoring was made from kidney sections stained with H&E, the scores in HTK+Alcar groups decreased significantly compared to HTK groups. It was also seen that the score level increased significantly in long-term groups. According to immunohistochemical evaluation, in short- and long-term HTK +Alcar groups, the acetyl-L-carnitine prevented the antiapoptotic mechanisms to be activated and the intense expression of Bcl-2 has not occurred. In short- and long-term HTK groups, osteopontin showed more immunopositive result. Conclusion: It was determined that the modified HTK solution prevented the increase of the activation of the expected oxidant mechanisms resulting in ischemia. This contribution of acetyl-L-carnitine was also found in long-term group findings. © Copyright 2020 by Gazi University Medical Faculty

A Comparison of Ramipril and Bevacizumab to Mitigate Radiation-Induced Brain Necrosis: An Experimental Study

Background: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is a new treatment approach for radionecrosis. In our study, we compared the prophylactic and therapeutic usage of a promising agent, ramipril (an angiotensin-converting enzyme inhibitor), with that of bevacizumab for reducing radiation-induced brain injury after high-dose stereotactic radiosurgery (SRS). Methods: A total of 60 Wistar rats were used. The rats were irradiated with a single dose of 50 Gy using a Leksell Gamma Knife device. Bevacizumab and ramipril were administered in the prophylactic protocol (starting the first day of SRS) and in the therapeutic protocol (starting the fourth week of SRS). Their usage was continued until 12 weeks, and the right frontal lobes of the rats were examined histologically (hematoxylin and eosin stain) and immunohistochemically (hypoxia-inducible factor [HIF]-1α, VEGF, and CD31 antibody expression). Results: The expression of VEGF, HIF-1α, and CD31 had significantly increased at 12 weeks after SRS compared with the control group. The addition of bevacizumab or ramipril to SRS significantly mitigated the histological severity of radiation injury and the expression of VEGF, HIF-1α, and CD31. However, the prophylactic use of bevacizumab and ramipril seemed to be more effective than therapeutic administration. Our results also revealed that the greatest benefit was achieved with the use of prophylactic administration of bevacizumab compared with other treatment protocols. Conclusions: Ramipril might be a promising agent for patients with radionecrosis. Clinical studies are required to investigate the effective and safe doses of ramipril, which is an inexpensive, well-tolerated drug that can cross the blood–brain barrier. © 2020 Elsevier Inc

Effects Of Uterus Derıved Mesenchymal Stem Cells And Theır Exosomes On Asherman S Syndrome

Asherman sendromu sezaryen ve endometrial cerrahi işlemler ile görülme sıklığı artan bir sorun haline gelmiştir. Yeni tedavi olanaklarının araştırılması amacıyla biz de Asherman modeli oluşturulan ratlarda uterus kaynaklı mezenkimal kök hücrelerin ve eksozomlarının etkilerini araştırmayı amaçladık. Endometriumun bazal tabakasına hasar verecek herhangi bir olay intrauterin adezyon olarak şekillenir ve Asherman Sendromu na sebep olabilir. İntrauterin adezyonu olan hastalarda anjiyogenez ve revaskülarizasyon yetenekleri azalmakta; adezyon ilişkili sitokinlerin ekspresyonları ise artış göstermektedir. Sonuç olarak da adezyonlar atrofik endometriuma sebep olmaktadır. Mezenkimal kök hücreler, non-immünojenik, anjiyogenik, antifibrotik, antiapoptotik ve antiinflamatuar özellikler gibi bazı özelliklerle karakterize edilirler ve aynı zamanda hücre terapilerinde çeşitli faktörlerin ve kemokinlerin salgılanması yoluyla doku onarımını desteklerler. Eksozomlar hasarlı doku tamirinde büyük bir potansiyele sahip, aktif parakrin bileşenlerdir. Eksozomlar rejenerasyon ve anjiyogenezden sorumlu birçok parakrin faktörleri içermektedir. Çalışmada 10 adet yeni doğan Wistar rat mezenkimal kök hücre eldesi için kullanıldı. Ayrıca toplam 24 adet yetişkin Wistar rat kullanıldı. Ratlar, kontrol grubu (Grup I; n=6); asherman grubu (Grup II; n=6); asherman + uterus kaynaklı mezenkimal kök hücre uygulanan grup (Grup III; n=6); asherman + uterus kaynaklı mezenkimal kök hücre eksozomları uygulanan grup (Grup IV; n=6) olmak üzere 4 gruba ayrıldı. Deney sonunda uterus dokuları histokimyasal ve immunohistokimyasal olarak değerlendirildi. Mezenkimal kök hücre ve eksozom tedavileri sonucunda uterus dokusunda proliferasyon belirteci olan PCNA ve anjiyogenez belirteci olan VEGFR-1 ekspresyonunun arttığı; masson ttrikrom boyaması ile fibrozisin azaldığı gösterildi. Ayrıca MMP-2 ekspresyonunun mezenkimal kök hücre ve eksozom uygulaması ile arttığı; ek olarak TIMP-2 ekspresyonunun azaldığı gösterilmiştir. Sonuç olarak, Asherman sendromunda ortaya çıkan fibrozis ve azalmış anjiyogenezis bulgularının uterus kökenli mezenkimal kök hücre ve eksozom tedavisi ile ortadan kalktığı gösterilmiştir. Tüm bulgular değerlendirildiğinde, eksozom tedavisi asherman sendromunun hasarını doku düzeyinde mezenkimal kök hücre grubuna kıyasla daha kısa sürede onarmıştır.Asherman's syndrome has become a growing problem with the incidence of cesarean and endometrial surgical procedures. In order to investigate new therapies, we also aimed to investigate the effects of uterine mesenchymal stem cells and their exosomes in the rat models of the Asherman. A surgical procedure that can damage to the basal layer of the endometrium is formed as intrauterine adhesion and can cause Asherman Syndrome. In patients with intrauterine adhesion, angiogenesis and revascularization abilities decrease; the expression of adhesion-associated cytokines increases. As a result, adhesions cause atrophic endometriosis. Mesenchymal stem cells are characterized by some characteristics such as non-immunogenic, angiogenic, antifibrotic, antiapoptotic and antiinflammatory properties, also they support tissue repair by secretion of various factors and chemokines in cellular therapy. Exosomes are active paracrine components with a great potential for repairing damaged tissue. Exosomes include many paracrine factors responsible for regeneration and angiogenesis. In the study, 10 newborn Wistar rats were used to obtain mesenchymal stem cells. A total of 24 adult Wistar rats were also used. The rats were divided into 4 groups: control group (Group I, n = 6); asherman group (Group II, n = 6); asherman + uterine derived mesenchymal stem cell group (Group III; n = 6); Asherman + uterine derived mesenchymal stem cell exosomes group (Group IV, n = 6). At the end of the experiment, uterine tissues were evaluated by histochemical and immunohistochemical. As a result of mesenchymal stem cells and exosomes treatments, expression of markers such as PCNA and VEGFR-1, which are the markers responsible for proliferation and vascularization respectively in uterine tissue was increased. It was also shown to reduce fibrosis with masson s trichrome staining. MMP-2 expression was enhanced by mesenchymal stem cell and exosomal therapy; in addition, TIMP-2 expression was decreased. In conclusion, it has been shown that the findings of fibrosis and decreased angiogenesis in Asherman's syndrome are resolved by uterine-derived mesenchymal stem cell and exosomal therapy. When all the findings are evaluated, the exosomal treatment restored the damage of asherman syndrome at tissue at a shorter time than the mesenchymal stem cell group

Ellagic Acid Inhibits TGF?1/Smad-Induced Renal Fibrosis in Diabetic Kidney Injury

Aim: Free radical formation increases due to hyperglycemia occurring in the pathogenesis of diabetes mellitus (DM), and as a result, oxidative stress occurs. Hyperglycemia-mediated oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The antihyperglycemic, antioxidative, anti-apoptotic, and anti-inflammatory effects of ellagic acid (EA) have been demonstrated by many studies. In this study, it was aimed to demonstrate the antifibrotic effect of EA on TGF?1/Smad signaling in rats with streptozotocin induced diabetic nephropathy. Material and Methods: A total of 24 male Sprague Dawley rats, weighing 200-250 g, were used in this study. The animals were divided into four groups as control, EA, DM, and DM+EA. The kidney tissues were used for histological and immunohistochemical procedures. While the collagen density in kidney tissues was revealed by Masson's trichrome staining, the expression levels of fibrotic markers TGF?1, p-Smad3, and ?SMA were determined by the immunocytochemical method. Results: It was shown that the collagen density in the renal tissue of the DM group increased significantly in the intertubular area, while the collagen density in the EA-treated DM group was statistically significantly decreased. When TGF?1, p-Smad3, and ?SMA immunopositivity in kidney tissue sections of all groups were evaluated, the highest staining intensity was in the DM group, while the intensity of staining was close to the control group in the treatment group. It was observed that ?SMA, TGF?1, and p-Smad3 protein expression were down-regulated with EA treatment. Conclusion: EA reduced fibrosis in diabetic nephropathy by returning profibrotic parameters to normal levels

The Effect of Isotretinoin on Oocyte Maturation in Adolescent Female Rats

Objective: Isotretinoin is used in acne vulgaris treatment for more than 20 years. Isotretinoin has serious side effects on many organs, but there are no comprehensive studies investigating its possible toxic effects on reproductive organs. Thus, we aimed to investigate the possible toxic effects of isotretinoin administration on oocyte maturation in female rat gonads in this study. Methods: Thirty-two adolescent female rats (Wistar Albino, 220 ± 35 g) were randomly divided into 4 groups with 8 subjects in each group: group 1, group 2, group 3, and group 4. Different doses of isotretinoin which was dissolved in sesame oil were given to rats by gavage: 7.5 mg/kg/day in group 3 and 15 mg/kg/day in group 4. The rats in group 2 received sesame oil by gavage. To create gavage stress, only gavage was administered to the rats in group 1. The gavages for each group continued once a day and at a certain time for 30 days. To determine the effect of isotretinoin on oocyte maturation, the periodic acid-Schiff reaction was performed for histochemical and histomorphometric evaluation of the zona pellucida, and staining of growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) was performed for immunohistochemical analysis. Results: When the thickness of the zona pellucida was evaluated, a statistically significant difference was found between group 1 and experimental groups (group 3 and group 4). In the experimental groups, it was determined that the thickness of the zona pellucida was decreased depending on the increase in dose. GDF-9 and BMP-15 expressions in oocytes of primordial and primary follicles decreased significantly in the experimental groups compared to group 1 and group 2. However, the expression of GDF-9 and BMP-15 in oocytes of secondary follicles was not significantly different between group 1 and group 2 and the experimental groups. Conclusions: In our study, we showed toxic effect of isotretinoin on oocyte maturation in female rats. © 2020 S. Karger AG, Basel

S-allylcysteine inhibits chondrocyte inflammation to reduce human osteoarthritis via targeting RAGE, TLR4, JNK, and Nrf2 signaling: comparison with colchicine

The discovery of new pharmacological agents is needed to control the progression of osteoarthritis (OA), characterized by joint cartilage damage. Human OA chondrocyte (OAC) cultures were either applied to S-allylcysteine (SAC), a sulfur-containing amino acid derivative, or colchicine, an ancient anti-inflammatory therapeutic, for 24 h. SAC or colchicine did not change viability at 1 nM-10 mu M but inhibited p-JNK/pan-JNK. While SAC seems to be more effective, both agents inhibited reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), lipid hydroperoxides (LPO), advanced lipoxidation end-products (ALEs as 4-hydroxy-2-nonenal, HNE), advanced glycation end-products (AGEs), and increased glutathione peroxidase (GPx) and type-II-collagen (COL2). IL-1 beta, IL-6, and osteopontin (OPN) were more strongly inhibited by SAC than by colchicine. In contrast, TNF-alpha was inhibited only by SAC, and COX2 was only inhibited by colchicine. Casp-1/ICE, GM-CSF, receptor for advanced glycation end-products (RAGE), and toll-like receptors (TLR4) were inhibited by both agents, but bone morphogenetic protein 7 (BMP7) was partially inhibited by SAC and induced by colchicine. Nuclear factor erythroid 2-related factor 2 (Nrf2) was induced by SAC; in contrast, it was inhibited by colchicine. Although they exert opposite effects on TNF-alpha, COX2, BMP7, andNrf2, SAC and colchicine exhibit anti-osteoarthritic properties in OAC by modulating redox-sensitive inflammatory signaling

Knowledge and Perception about Oocyte Donation in a Semirural Region of Turkey

Objective: To evaluate the general knowledge and perception of people living in a semi-rural area of Turkey where oocyte donation is currently illegal and to explore decision-making factors around the adoption of oocyte donation. Methods: This is a descriptive study of 320 participants who were selected using a cluster sampling method from two districts in Antalya, a migrant city heavily populated with Turkish people from other provinces. A standardized survey was administered by post-doctoral degree researchers during face-to-face interviews to capture participants’ responses. Results: The majority of participants reported that they did not know what oocyte donation was and were not able to correctly define it. Among those who reported knowing nothing or not knowing what oocyte donation was, once informed, almost half stated that donation should be legal in the presence of medical problems. The statement “oocyte donation could be performed in the presence of medical problems” was significantly more agreeable to participants under the age of 40 years than to those over the age of 40 years, to those who were single or widowed than to those who were married, to those had moderate income levels than to those who had low income levels, and to those who were more educated than to those who were less educated. Conclusion: In our study, support for the statement “oocyte donation should be legal in cases of medical necessity” was significantly influenced by demographic and descriptive factors such as sex, age, marital status, education, and income level among people living in a semi-rural Turkish region

Knowledge and perception about oocyte donation in a semirural region of Turkey

Objective: To evaluate the general knowledge and perception of people living in a semi-rural area of Turkey where oocyte donation is currently illegal and to explore decision-making factors around the adoption of oocyte donation. Methods: This is a descriptive study of 320 participants who were selected using a cluster sampling method from two districts in Antalya, a migrant city heavily populated with Turkish people from other provinces. A standardized survey was administered by post-doctoral degree researchers during face-to-face interviews to capture participants’ responses. Results: The majority of participants reported that they did not know what oocyte donation was and were not able to correctly define it. Among those who reported knowing nothing or not knowing what oocyte donation was, once informed, almost half stated that donation should be legal in the presence of medical problems. The statement “oocyte donation could be performed in the presence of medical problems” was significantly more agreeable to participants under the age of 40 years than to those over the age of 40 years, to those who were single or widowed than to those who were married, to those had moderate income levels than to those who had low income levels, and to those who were more educated than to those who were less educated. Conclusion: In our study, support for the statement “oocyte donation should be legal in cases of medical necessity” was significantly influenced by demographic and descriptive factors such as sex, age, marital status, education, and income level among people living in a semi-rural Turkish region