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Objective: Age brings about changes to the oxidant and antioxidant balance of male testis that give rise to loss of fertility. The Ferula elaeochytris root extract (FE), contents antioxidant and anti-inflammatory component, have been used to treat infertility by local people for centuries. The main objectives of this study were to determine whether FE was effective on sperm quality, spermatogenesis, apoptosis and oxidative stress in aged rat. Methods: Four groups were formed with 40 rats; young Control (YC), Aged Control (AC), Ferula elaeochytris administrated aged rat (A+FE) and vitamin E administrated aged rat (A+VE). Vitamin E and FE was administered orally for 8 weeks. Results: The administration of FE significantly increased serum TAS, testetorone levels and decreased testicular malondialdehyde (MDA) activity, that these changes were accompanied by the reduced serum TNF-α, and TOS levels. Also, the apoptosis germ cell, the tubular diameter, the germinal epithelium height and Johnson’s score a have been regulated after administration of FE (p < 0.05). Meanwhile, in the present context, in aged group the sperm count, motility, testicular weight declined significantly. FE showed showed significantly increased effect on the motility and sperm count. Conclusive: These findings support that aging induces stress oxidative and inflammation, and FE could protect the testis against these damaging effects via its anti-oxidative, anti-inflammatory action and modulate spermatogenesis. Keywords: Ferula elaeochytris, Aging, Antioxidant system, Spermatogenesis.

This study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin (CIS)-induced and gentamicin (GEN)-induced nephrotoxicity.The study consisted of five groups: control (saline solution only), CIS D2 (2.5 mg/kg for 2 days), CIS D7 (2.5 mg/kg for 7 days), GEN D2 (160 mg/kg for 2 days), and GEN D7 (160 mg/kg for 7 days). All rats were sacrificed 24 h after the last injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney.CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS), while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β)) and ER stress markers (GRP78 and PERK) was significantly increased in the kidney tissue of rats treated with CIS and GEN for 7 days.These findings suggest that CIS and GEN administration for 7 days aggravates nephrotoxicity through the enhancement of oxidative stress, inflammation, and ER stress-related markers. As a result, the recommended course of action is to utilize CIS and GEN as an immediate but brief induction therapy, stopping after 3 days and switching to other drugs instead.

Purpose: To evaluate the effect of Ferula elaeochytris (FE) at the prostatic and epididymal ends of rat vas deferens. Methods: The effects of cumulative concentrations of FE (10 μL; 31.25 mg/μL and 20 μL; 62.5 mg/μL) were investigated on prostatic and epididymal ends of rat vas deferens in the presence of prazosin (0.3 μM), suramin (100 μM), atropine (10 nM) and nitric oxide synthase inhibitor (L-NOARG; 100 μM). The muscle contractions were induced by electrical field stimulation (EFS; 4 Hz, 50 V, 0.15 ms). Calcium (3 and 6 mM) was added into the bath medium while electrical field stimulation (EFS) was in progress. Results: Ferula elaeochytris significantly inhibited the muscle contractions induced by electrical field stimulation (EFS) in a concentration-dependent manner. In the presence of prazosin or suramin, the contractile responses to EFS were significantly inhibited by FE at the prostatic and epididymal ends of vas deferens (p < 0.05). However, this inhibition was not affected by atropine and L- NOARG, suggesting that there is no direct interaction of FE with cholinergic and nitrergic responses. However, in the presence of prazosin or suramin, Ca2+ addition to the organ bath significantly reversed the inhibitory effect of FE at the prostatic and epididymal ends of vas deferens (p < 0.05). Conclusion: These results show an inhibitory effect for the extract of FE on neurogenic contractile activity of prostatic and epididymal ends of vas deferens. This effect of FE may be associated with Ca2+ channels. Keywords: Contractile activity; Electrical Field Stimulation (EFS); Ferula elaeochytris; Rat; Vas deferens

Purpose: The aim of this study was to determine the levels of irisin in the heart, which is a vital organ, in rats of different ages and to reveal whether Ferula elaeochytris (FE) has an effect on the expression of the irisin. Materials and Methods: Our study was designed in six groups, young (4 months), middle age (12 months), old (24 months) rats which were given FE extract for 8 weeks and their control groups. After that their heart tissues were taken and irisin levels were measured by immunohistochemical staining method. Results: The obtained results were analyzed by performing histoscoring. It was observed that the level of irisin in old rats was statistically significantly lower in young and middle age rats. In addition, irisin level of in all groups administered with FE extract was found significantly increased. Conclusion: FE extract increases the level of irisin through other pathways besides its protective effect against tissue damage.

Objectives This study was aimed to investigate the effects of garlic oil (GO), an important natural constituent used in alleviating diabetes and its complications, on the expression levels of irisin and related genes. Methods Thirty-two rats were divided into four groups: Control, Diabetes-Control, Diabetes+GO 100 mg/kg/day and Control+GO 100 mg/kg/day for 45 days. The measurements included: changes in liver Peroxisome proliferator-activated receptor-gamma-coactivator (PGC)-1α, Fibronectin Type-III-Domain-Containing5 (FNDC5), irisin expression, mRNA expression of p38 and TNF-α (Tumour necrosis factor-α), total-antioxidant-status (L-TAS; S-TAS), total-oxidant-status (L-TOS; S-TOS) in liver and serum, respectively. Key findings There was a significant reduction in serum levels of irisin and S-TAS and expression of PGC-1α and FNDC5 in liver in Diabetes-control compared to Control-group, while a significant increase in serum levels of fasting blood glucose (FBG) and TOS, also p38 and TNF-α expressions in liver. In Diabetes+GO group, there was a significant increase in serum irisin and S-TAS, also expression of PGC-1α and FNDC5 in liver, while serum FBG, S-TOS levels, and mRNA expression of p38 and TNF-α in liver were decreased compared to Diabetes-control group (P < 0.05). Conclusions GO alleviated the diabetic liver injury by decreasing Oxidative-Stress parameters and regulation PGC-lα, FNDC5, irisin and P38, keeping the balance of TAS/TOS and TNF-α.

Aim:The imbalance between production of reactive oxygen species and antioxidant defense determines the degree of oxidative toxicity and severity of subsequent myocardial damage.We aimed to evaluate the anti-oxidative effects of neprilysin and angiotensin inhibition on cardiovascular target tissues in dexhamethasone-induced hypertensive rats.Methods:Thirty-six Wistar rats were divided into six groups. Three groups received 30 μg/kg/day dexamethasone for 14 days to induce arterial hypertension. Mean arterial blood pressures were verified by carotid artery cannulation. Ramipril (10 mg/kg), and sacubitril/valsartan (80 mg/kg) were administered for 18 days to the hypertensive and normotensive groups. Glutathione peroxidase, superoxide dismutase and malondialdehyde levels were evaluated in cardiovascular target tissues.Results:Serum and cardiac malondialdehyde levels were lower, while cardiac glutathione peroxidase and superoxide dismutase were higher in treatment groups than in control groups. Aortic malondialdehyde in sacubitril/valsartan group was lower; aortic and renal superoxide dismutase in sacubitril/valsartan and ramipril groups were significantly higher than in control group. Serum glutathione peroxidase was higher in hypertensive sacubitril/valsartan group than in hypertensive control group.Conclusion:We demonstrated that neprilysin and/or angiotensin inhibition had protective properties against oxidative stress exerted by dexhamethasone-induced hypertension in cardiovascular target organs, which may be mediated by reversal of natriuretic peptides degradation.m, hypertension, oxidative stress, dexamethasone, rat

Doxorubicin is an anthracycline chemotherapeutic agent that causes cardiomyopathy as a side effect. Here, we aimed to investigate the effects of linagliptin and bisoprolol on the management of doxorubicin-induced cardiomyopathy in rats. Wistar rats were divided into six groups (n = 8). Group I received saline for 4 weeks; group II received 1 mg/kg bisoprolol for 8 weeks; group III received 3 mg/kg linagliptin for 8 weeks; group IV received 1.25 mg/kg doxorubicin for 4 weeks for the induction of cardiomyopathy; group V received 1.25 mg/kg doxorubicin for 4 weeks plus 1 mg/kg bisoprolol for 8 weeks; and group VI received 1.25 mg/kg doxorubicin for 4 weeks plus 3 mg/kg linagliptin for 8 weeks. Electrocardiography and isometric mechanography were conducted to measure ventricular contractile responses. Myocardial tissue and serum samples were analyzed for oxidative and cardiotoxic markers by ELISA. Electrocardiography revealed that QRS, QT and Tp intervals were longer in group IV than group I. Doxorubicin caused a significant decrease in ventricular contraction, which was significantly prevented by bisoprolol. Doxorubicin resulted in myocardial fiber disorganization and disruption, but bisoprolol or linagliptin improved this myocardial damage. Glutathione peroxidase was significantly decreased in groups IV and V. Bisoprolol or linagliptin treatment attenuated the significant doxorubicin-mediated increase in malondialdehyde. Doxorubicin and linagliptin provided significant elevations in CK-MB activity and troponin-I levels. Doxorubicin resulted in pronounced oxidative stress. The beneficial effects of bisoprolol and linagliptin on myocardial functional, histopathological and biochemical changes could be related to the attenuation of oxidative load.

This study aimed to investigate the role of caffeic acid phenethyl ester (CAPE), a compound found in propolis, on imidacloprid (IMI), a nicotinic acetylcholine receptor agonist that causes cerebral toxicity. 60 adult rats were randomly divided into five groups: control, IMI (100 mg/kg), and IMI+CAPE (1, 5, 10 mg/kg). Cerebral cortex tissue was examined histopathologically, biochemically, spectrophotometrically and immunohistochemically. The results showed that IMI caused toxicity in the cerebral cortex. However, CAPE (5 and 10 mg/kg) attenuated the deteriorated histopathological score and normalized the apoptotic markers (Bax and Caspase-3). Additionally, CAPE dose-dependently normalized the levels of TNF-α, dopamin, GFAP and NGF, and at the highest dose (10 mg/kg) also normalized the balance of oxidative parameters (MDA, SOD, CAT, and GSH). In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic effects of CAPE may be a promising treatment for acute IMI-induced cerebral cortex toxicity.

Background: Smooth muscle contraction and enlargement of the prostate are important targets for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia. The effect of Ferula elaeochytris (FE) root extract on tissues that play a role on fertility such as the prostate has not been demonstrated yet. The aim of this study is to investigate the effects of FE extract on isolated rat prostate tissue induced by electrical field stimulation (EFS) in vitro. Methods: In this experimental study, 48 male rats were randomly divided into 6 groups (n = 8). Groups were consisting FE (20 µl), FE + Adenosine triphosphate (ATP; 50 μM), FE + prazosin (0.3 μM), FE + Calcium (Ca2+; 3 mM and 6 mM), FE + suramin (100 μM), FE + phenylephrine and FE + carbachol. Result: In our study, FE extract inhibited the neurogenic contractions induced by EFS on isolated rat anterior prostate tissue. The presence of suramin and prazosin were not significantly increase the inhibition caused by the FE extract, while Ca2+ and ATP significantly increased the inhibition by the FE extract. (p less than 0.05). In addition, FE extract significantly inhibited phenylephrine and carbachol contractions (p less than 0.05).

Background We hypothesized that renin-angiotensin system and neprilysin (NEP) inhibition can modulate the nociceptive parameters on hypertensive rats. The aim of this study is to assess the preventive and therapeutic effects of ramipril and sacubitril on the pain hypersensitivities, and their interaction mechanisms with high blood pressure. Methods Antinociceptive effects of ramipril and sacubitril were compared with those of diclofenac. Threshold of pain assesments were recorded before drugs administration. After a 18 days treatment, normotensive and dexamethasone-induced hypertensive rats were evaluated on thermal hyperalgesia and mechanical allodynia tests. Blood pressure of rats were verified by mean arterial pressure measurement. Results Hypertensive rats showed significantly high pain threshold on thermal plantar test compared to that of normotensives. Among hypertensive rats, pain hypersensitivity was lowest in diclofenac group, followed by sacubitril group, while ramipril caused increased thermal and mechanical hypersensitivities. Conclusion We found that NEP inhibition may play a role in nociception in hypertensive rats. NEP inhibitors may be suitable choice for the management of hypertension and pain because of their therapeutic and preventive effects on nociception and arterial blood pressure.

Aim: The publication of theses is the main indicator in revealing the scientific efficiency of a country. To the best of our knowledge, the publication status of pharmacology specialty theses has not been reported before. The aim of this study is to evaluate the publication status of medical pharmacology theses published by the departments of medical pharmacology of medical faculties in our country between 2006 and 2016 in scientific journals.Methods: A total of 108 pharmacology residency theses published between 2006 and 2016 and registered into the system from all Medical Pharmacology departments of all medical faculties in our country, as accessed from in Higher Education Council National Thesis Center's Internet database (https://tez.yok.gov.tr/ulusaltezmerkezi/), were included in this observational study. These theses were analyzed and evaluated in terms of the year they were written in, the institution in which they were prepared, the academic title of the thesis advisor, research type, its publication status in scientific journals, publication features, author's gender and other features of the author of the thesis.Results: As a result of the research conducted, it was found that 61 (56.5%) of the 108 pharmacology specialty theses written between 2006-2016 had been published in thescientific journals. Forty-seven (77.0%) of these publications were published in a medical journal with Science Citation Index (SCI) / Science Citation Index-Expanded (SCI-E) indexes, 9 (14.8%) in other international indexes, 3 (4.9%) in TUBITAK TR index and 2 (3.3%) in national refereed journals.Conclusion: The rate of publication of the residency theses written after the completion of medical pharmacology residency training and publication as articles in the journals within the scope of SCI / SCI-E was quite high., Amaç: Tezlerin yayınlanması, bir ülkenin bilimsel etkinliğini ortaya çıkarmanın temel göstergesidir. Bildiğimiz kadarıyla farmakoloji uzmanlık tezlerinin yayınlanma durumu daha önce bildirilmemiştir. Bu çalışmada, ülkemizdeki tıp fakültelerinin tıbbi farmakoloji anabilim dalları tarafından 2006-2016 yılları arasında yayınlanan tıbbi farmakoloji tıpta uzmanlık tezlerinin bilimsel dergilerde yayına dönüştürülme durumunun değerlendirilmesi amaçlanmıştır.Yöntemler: Gözlemsel olan bu çalışmaya Mayıs 2020 tarihinde Yüksek Öğretim Kurulu Başkanlığı Ulusal Tez Merkezi internet veri tabanında (https://tez.yok.gov.tr/UlusalTezMerkezi/) yer alan, ülkemizdeki tüm tıp fakültelerinin tıbbi farmakoloji anabilim dalı birimlerinden sisteme girilmiş 2006-2016 yılları arasında yayınlanmış 108 adet farmakoloji uzmanlık tezi dahil edilmiştir. Bu tezler yapıldıkları yıl, yapıldıkları kurum, tez danışmanın akademik ünvanı, tezin hangi araştırma türü olduğu, yayınlanma durumu, yayına ait özellikler, yazar cinsiyeti ve tez yazarlarına ait diğer özellikler açısından incelenip değerlendirilmiştir.Bulgular: Çalışmamızda yapılan araştırmalar sonucunda 2006-2016 yılları arasında yapılmış 108 adet farmakoloji uzmanlık tezinin 61’i (%56,5) yayınlanmıştır. Bu yayınların 47’si (%77,0) Science Citation Index (SCI) / Science Citation Index-Expanded (SCI-E), 9’u (%14,8) uluslararası diğer indekslerde, 3’ü (%4,9) TUBİTAK TR dizin, 2’si (%3,3) ulusal hakemli dergilerde yayınlanmıştı.Sonuç: Bu çalışmada, Türkiye’de tıbbi farmakoloji uzmanlık eğitimi tamamlandıktan sonra yazılan uzmanlık tezlerinin yayına dönüşme oranı ve SCI/SCI-E kapsamındaki dergilerde makale olarak yayınlanma oranı oldukça yüksek bulunmuştur.

Nowadays, diabetes is a metabolic disease characterized by hyperglycemia by a problem in insulin secretion, insulin action, or both. It is known that oxidative damage plays an important role in the development of vascular and neurogenic complications of diabetes and antioxidants are effective on these pathologies. The aim of this study was to investigate the possible antidiabetic and antioxidant effects of Ferula elaeochytris root extract, commonly known as “ÇAKŞIR” in South and Southeastern Anatolia. Ferula elaeochytris was collected from the Engizek plateau of Kahramanmaraş. The plant root was prepared on a clean and dry surface and ground for grinding. The inhibitory effect of Ferula eleaochytris on glucose was determined electrochemically with the biosensor device, and total phenolic content was determined by Folin-Ciocalteu method as an indicator of antioxidant activity. In this study, according to electrochemical analysis with biosensor device, a linear decrease in glucose levels was observed depends on the decrease of enzyme-substrate interaction as a result of the addition of 100 µl cumulatively 1 minute (min) intervals of Ferula elaeochytris root extract (N=120). In addition, the total phenolic content of this plant was detected (41.45±2.38 mg GAE/g, n:3) by Folin-Ciocalteu method. It can be concluded that Ferula elaeochytris may have a hypoglycemic effect owing to its inhibitory effect on glucose levels and Ferula elaeochytris may also have a possible antioxidant source by means of the plant has a high capacity of total phenolic content. With the advanced studies to be done, it will be able to provide a more conscious utilization in accordance with the purpose of this unconsciously used plant by many people.

Ethnopharmacological relevance Ferula elaeochytris Korovin (FE) is a perennial medicinal plant of Apiaceae family. Ferula elaeochytris Korovin, known as ‘Caksir’ in Anatolia, is widely used as an aphrodisiac as well as antioxidant, anti-inflammatory, and anti-diabetic. Aim of the study: Erectile dysfunction (ED) is a serious public health problem that has a high prevalence and negatively affects the quality of life in elderly men. In the treatment and prophylaxis of many diseases, because of widely increasing use of plant extracts as therapeutic agents, preclinical studies related to plant extracts are becoming more important by the day. In this study, we aimed to investigate the protective effect of Ferula elaeochytris Korovin (FE) root extract on age-related ED. Materials and methods Seventy-two male Wistar albino rats were equally divided into four groups: 4-month aged rats (Y), 24-month aged rats (AG), and FE-administered (20 and 40 mg/kg/day; oral gavage; over 8 weeks) 24-month aged rats (AG + FE). The measurements included: changes in smooth muscle cells and collagen fibrils, tumor necrosis factor alpha (TNF-α), penile neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) expression, serum testosterone concentrations (ST), neurogenic- and endothelial-dependent relaxations of the corpus cavernosum (CC), intracavernosal pressure/mean arterial pressure (ICP/MAP), area under the curve (total ICP), total antioxidant status (TAS), and total oxidant status (TOS) on corpus cavernosal tissue. Results These results have an important role in the development of ED. ICP/MAP, total ICP, eNOS/nNOS expressions and ST levels increased in AG+40 mg FE group compared to the AG group, whereas TNF-α levels decreased and oxidative and antioxidant parameters balanced. Conclusions Our findings show that FE may have a useful effect on decelerating the development of age-related ED.

Amaç: Birçok hastalığın tedavisinde yerel halk tarafından yaygın olarak kullanılan Ferula elaeochytris kökü (FE), yağları ve oleoresinleri içermesi yönüyle güçlü bir aromatik kokuya sahiptir. Bu çalışmada, Ferula elaeochytris kök ekstresinin yağ asidi bileşenlerini ve insan vücudu için önemini belirlemek amaçlandı.Gereç ve Yöntemler: Bu çalışmada, Kahramanmaraş’ın Engizek platosundan toplanan Ferula elaeochytris bitkisinin kök kısmı kurutulup, öğütülerek hazırlanan kök ekstresinin yağ asidi profili, Alev İyonizasyon Dedektörleri (GC-FID) ile donatılmış bir Gaz Kromatografisi kullanılarak analiz edildi.Bulgular: Yapılan analiz sonucunda 9 adet doymamış, 7 adet doymuş toplam 16 yağ asidi belirlenmiştir. Doymamış (% 56,25) yağ içeriği, doymuş yağdan (% 43,75) daha yüksek bulundu. insan vücudunun besin ihtiyacının sağlanması için gereken doymamış yağ asidi olarak Omega-6'dan türetilmiş linoleik asit (% 39,25) ve omega-3 türevi alfa-linolenik asit (% 2,390) içeriği yüksek iken, omega-9 türevi oleik asit (15.79) en bol bulunan ikinci sıra yağ asidi olarak bulunmuştur. Bu bitki ayrıca sinir sisteminin gelişimi ve bozuklukları için önemli olan Nervonik asit (% 0.599) içermektedir. Palmatik asit (% 10,506), doymamış yağ asitleri arasında en yüksek seviyelerde bulundu.Sonuç: Yapılan bu çalışmada, insan sağlığında birçok yararlı etkileri gösterilen Ferula elaeochytris bitkisi içeriğindeki major komponentler, GC-FID ile yapılan analiz ile gösterilmiştir.

Objective Renin angiotensinogen system (RAS) inhibitors, ramipril and sacubitril/valsartan are frequently used in the treatment of cardiovascular diseases. Although they are known as contraindicated during pregnancy in hypertensive women, there is not any outcome of their safety in male fertility after exposure to ramipril or sacubitril/valsartan. In this study, we aimed to evaluate the effects of ramipril and sacubitril/valsartan to highlight their safety in the male fertility in normotensive and hypertensive rats. Methods Adult male normotensive and dexamethasone-induced hypertensive rats were treated with sacubitril/valsartan, ramipril and saline for 18 days. Arterial blood pressures were verified using carotid artery cannulation. Male fertility parameters, including the testis weights, histopathologic scoring of the testis, sperm count, sperm motility, morphology, and serum testosterone levels, were analyzed in treated and nontreated normotensive/hypertensive rats. Results Sacubitril/valsartan or ramipril treatments did not reveal a significant difference in sperm production, testicular morphology, and radioimmunoassay of serum testosterone levels compared to the control group. However, sperm motility was significantly reduced in rats under RAS inhibition. Conclusion This finding was likely mediated by the identification of Ang receptors in the tails of rat sperm given that Ang receptors may play a role in the modulation of sperm motility. Identification of RAS-related proteins involved in sperm motility may help to explain their roles in motility. Our data provide general safety evidence for the male fertilization ability after paternal sacubitril/valsartan and ramipril exposure.

We aimed to investigate the in vitro modulating effects of medicarpin on the PI3K/AKT signal pathway gene expressions in head and neck squamous cell carcinoma (HNSCC).The effect of medicarpin on PTEN and other associated genes in the PTEN/AKT signal pathway was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, real-time quantitative polymerase chain reaction, and Western blot analysis in the SCCL-MT1 (HNSCC) and control (HEK-293) cell lines.The IC50 dose was 80 μM as a result of medicarpin treatment on HNSCC cells (P = 0.0006). It was found that PTEN and AKT gene expressions increased after the medicarpin administration while PDK1 gene expression was decreased in SCCL-MT1 cells (P = 0.0002, P = 0.0003, and P = 0.05, respectively). Protein expression results showed that medicarpin-treated cells significantly increased in pAKT (P = 0.024), pPTEN (P = 0.032), and decreased pPDK1 (P = 0.059) in SCCL-MT1.Our data show that medicarpin modulates HNSCC cells by increasing the PTEN and decreasing PDK1 expressions. PDK1 gene expression effects mTOR pathway which may increase AKT gene. Our study suggests that both medicarpin extracts combination with the HNSCC drug may be more effective in cancer treatment. Future prospective studies that integrate molecular and pharmacogenetic studies are crucial for revealing the mechanism and preventive medical efforts.

Erectile dysfunction (ED) is an important complication of diabetes. The aim of our study was to determine whether Ferula elaeochytris (FE) root extract could affect ED in streptozotocin (STZ)-induced diabetic rats. Seventy-five adult male Wistar albino rats were equally divided into five groups; control (C), FE (40 mg/kg-d), STZ-induced diabetes (60 mg/kg) (DM), diabetes + F. elaeochytris (DM + FE), and ethanol (EtOH). After 8 weeks, in vitro and in vivo parameters (intracavernosal pressure [ICP]), testicle and body weight, serum glucose levels, and histopathology were assessed. In the STZ-induced diabetic group, acetylcholine-induced endothelium-dependent relaxation responses, and electrical field stimulation-induced neurogenic and nitrergic relaxation responses were decreased significantly, while FE administration to diabetic rats reversed the decreased nitrergic and neurogenic responses. In the diabetic group, ICP/MAP (0.1375 ± 0.02 cm/H 2 O), spermatogenesis in testicles (53.73 ± 0.81), and testicle weights (257.8 ± 20.63) were decreased significantly; however, FE administration to diabetic rats restored the decreased values (0.350 ± 0.019 cm/H 2 O, 75.07 ± 0.35, and 416 ± 24.11, respectively). In the DM group, blood glucose levels were increased (411.7 ± 18.30) compared to the C group. However, FE administration to diabetic rats reduced glucose levels (230.6 ± 25.60 mg/dL) compared to the DM group. In conclusion, FE recovered neurogenic and endothelial dysfunction and decreased glucose levels in diabetic rats. © 2019, Springer Nature Limited.

Methotrexate (MTX) is a frequently used anticancer drug in the treatment of several diseases. However, MTX therapy causes significant cytotoxicities in testicular tissue. In this experimental study, the therapeutic utility of vitamin D (VD) on MTX induced testicular injury was investigated. Twenty-eight Wistar rats were randomly divided into four equal groups; Control, VD, MTX, and MTX+VD. Following the treatment, the rats were sacrificed and testicular tissues were removed. Testicular tissues were analyzed for routine histopathology and apoptosis. The activities of glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were evaluated by enzyme-linked immunosorbent assay and malondialdehyde (MDA) levels were measured spectrophotometrically. MTX-treatment group exhibited degeneration of spermatogenic cells, desquamation of the epithelial cells into the lumen of the tubules, lack of spermatozoa in tubule lumen, edema at interstitial area, a statistically significant decrease in both height and diameter of the tubules (p < 0.05). These values were also concordant with the Johnsens testicular biopsy score (JTBS). In addition, a significantly increased caspase-3 immunoreactivity was observed. Serum and testicular tissue SOD, and GSH-Px enzyme activities were found to be decreased while MDA increased in the MTX group compared to control group (p < 0.05). In the MTX + VD group, the histological injury was reduced, the caspase-3 positivity and MDA level decreased whereas activities of SOD, and GP-x enzymes were significantly increased compared to those in MTX group (p < 0.05). VD supplement may have a therapeutic utility in reducing the MTX-induced cytotoxicities in testicular tissue. [Med-Science 2020; 9(4.000): 998-1003]

Aim: In this study benefits from different machine learning methods to analyze factors which affect young person’s scores of cognitive assessment. Material and Methods: This study was performed among 144 persons aged between 18 and 24 who study at Kahramanmaras Sutcu Imam University. Boosted Tree Regression (BTR), Random Forest Regression (RFR) and Support Vector Machine (SVM), which are among machine learning methods, were used in order to determine the factors affecting the score of cognitive assessment. K-10 fold cross validation method was also used. Mean Squared Error (MSE), Root Mean Squared Error (RMSE), Mean Absolute Error (MAE) and Correlation coefficients (R) metrics were used in order to measure prediction performances of machine learning methods.Results: MSE values were calculated as 9.66 for BTR, 9.78 for RFR, and 6.43 for SVM. MAE values were calculated as 2.06 for BTR, 2.05 for RFR, and 1.97 for SVM. RMSE values were calculated as 3.10 for BTR, 3.12 for RFR, and 2.53 for SVM. Finally, correlation coefficients were calculated as 0.289 for BTR, 0.371 for RFR and 0.546 for SVM. In addition, it was also found out that the most important variables which affected the scores of cognitive assessment were anti-depressant use, depression and obsession.Conclusion: It was demonstrated in this study that SVM displayed the lowest error rates and highest prediction performance in terms of determining the score of cognitive assessment. Therefore, SVM can be stated that it is the most suitable method for the prediction of cognitive impairment.

İnsan norovirüsü (HNoV), çevresel etkenlere oldukça dirençli bir RNA virüsüdür ve akut viral gastroenteritin nedeni olan ana etkenlerden birisidir. Hızlı evrim yeteneği nedeniyle 7 genogrubu vardır ve bunlardan GI, GII ve GIV insan enfeksiyonları ile ilişkilidir. Sular HNoV için salgın aracı olarak tanımlamaktadır. Bu bilgiler ışığında, çalışmamızda, lokal kuyular ve derelerden alınan su numunelerinde özellikle insanlarda enfeksiyonları ile ilişkili HNoV genogrup (G)I, GII ve GIV varlığının gerçek zamanlı polimeraz zincir reaksiyonu (real-time PCR) ile tanımlanarak moleküler epidemiyolojik bir veri sağlanması amaçlanmıştır.Çalışma için lokal kuyulardan ve derelerden, Ocak 2017 – Ocak 2018 döneminde toplanan 60 adet su numunesi çalışmamıza dahil edildi. RNA izolasyonu ve cDNA sentezi sonrası HNoV GI, GII ve GIV spesifik primer problar ile LightCycler 480 sisteminde real-time PCR yöntemi ile çalışıldı ve sonuçlar değerlendirildi.Çalışmamıza dâhil edilen 60 numunede, HNoV GII’nin %10 düzeyinde saptandığı, bunu sırasıyla GI (%5) ve GIV (%1.67) varlığının takip ettiği tespit edildi. 10 numunede (%16.67) HNoV GI, GII ve GIV pozitifliği bulundu. Lokal kuyulardan 3 (%8.57) tanesinde ve derelerden alınan numunelerden de 7 (%28) tanesinde pozitiflik saptandı.Sonuç olarak, ülkemizde ilk defa kuyu suları ve derelerden alınan sularla yaptığımız çalışmamızla, moleküler epidemiyolojik olarak HNoV varlığını saptadık. HNoV’lar arasında GII’nin ön planda tutulması gerektiğini ama GI ve GIV’ünde bulunduğunu tespit ettik. HNoV için salgınlarında sular göz önünde bulundurulmalı ve gelişen moleküler tekniklerle, sular gibi önemli enfeksiyon kaynaklarından epidemiyolojik veriler sağlanarak durum ortaya konabilir ve bu bilgiler ile bölgesel aşı geliştirme çalışmaları içinde ön veriler sağlanabileceği kanaatindeyiz.

The acute phase effects of toluene on the brain have been investigated in this study using rabbit brain via histopathological, immunohistochemical, and biochemical methods. A total of 20 male rabbits were used as control and experimental groups. Moreover, nerve growth factor (NGF), tumor necrosis factor-alpha (TNF-alpha), dopamine (DA), and glial fibrillary acidic protein (GFAP) tests were performed in order to designate the severity of the biochemical damage. In the biochemical evaluation of the prefrontal cortex, hippocampus, hypothalamus, substantia nigra, and entorhinal cortex, the TNF-alpha levels in the brain were found to be significantly higher than in the control group. Levels of dopamine, secreted from the substantia nigra, nerve growth factor (NGF) developed from the hippocampal neurons, and GFAP, secreted from astrocyte cells, were detected to be significantly lower in the toluene-administration group than in the control group (p<0.05). In addition, areas of focal vacuolar degeneration (abscess formation), gliosis, and perivascular demyelination, many pyknotic cells and necrosis were observed. In the toluene-administration group compared to the control group, distinct excessive expansions of the blood vessels and severe degeneration in the structure of cells and also dispersed cell borders were observed. Furthermore, abnormal malformations of the nuclei structure of the oligodendrocyte cells were seen. Bodies of the sequential neurons of the hippocampus in the toluene-administration group were distinctly structurally damaged compared to the control group. In addition, cytoplasm of the cortex cell showed serious immune reactivity in the experimental group.

Purpose : To determine the chemical composition of Ferula elaeochytris , a plant with traditional medicinal uses, and to investigate its potential benefits. Methods : Ferula elaeochytris specimens were collected from Engizek plateau of Kahramanmaras, Turkey in early June 2017, and dried in a cool and dry place at room temperature. Once dried, they were ground into a powder using a plant grinder. A Soxhlet extractor was employed for extraction of the powdered roots using diethyl ether solvent for 4 h, and then subsequently evaporated using a rotary evaporator. The extract was analysed by gas chromatography mass spectrometry (GC-MS) to reveal the components of F. elaeochytris. Results : Khusinol, ferutinin and beta-ionone, components with anti-inflammatory phytoestrogen, antiproliferative and antioxidant activities, were found in high levels (25.9, 13.9 and 22.9 %, respectively in F. elaeochytris root extract, In addition α-pinene, which has anti-inflammatory, bronchodilator, hypoglycaemic and anticarcinogenic effects, was found at lower levels (12.9 % or less). Conclusion : The results reveal the presence of some therapeutically beneficial components of F. elaeochytris root extract, including compounds with antioxidant and anti-inflammatory effects. Keywords : Ferula elaeochytris, Khusinol, Ferutinin, Beta-ionone, Anti-inflammatory Phytoestrogen, Antiproliferative, Antioxidant

Aim: To investigate whether prostatic inflammation affects the contractile responses of prostate tissue and then whether melatonin has any restorative effect on the contractile responses in a rat model of bacterial prostatitis at early stages. Materials and methods: We evaluated the nerve-evoked, adrenergic agonist-induced or cholinergic agonist-induced contractions of isolated prostate tissue at 24 and 72 h after intraurethrally instilled Escherichia coli-treatment. We also analyzed the histological changes in the prostate. Secondarily, we investigated the effect of melatonin pretreatment (7 days, 10 mg kg–1 day–1) on the contractile responses and the histopathologic changes. Results: The degrees of acute inflammatory cell infiltration, acinar changes, and interstitial fibrosis in the prostate glands indicated the development of acute prostatitis at 24 or 72 h after bacterial inoculation. These inflammatory changes were more pronounced at 72 h. Bacterial prostatitis attenuated contractile responses to electrical field stimulation, phenylephrine, or carbachol. The impairment in the contractions was more prominent at 72 h. Melatonin treatment reduced the pathologic changes and partially restored the contractile responses at 72 h of inflammation. Conclusion: Prostatic inflammation caused a diminution in the contractile mechanism of the prostate tissue and melatonin partially restored the contractile responses and histopathologic changes. Melatonin can be useful as an adjuvant to the main therapies for prostatitis to reduce the contractility problems. Aim: To investigate whether prostatic inflammation affects the contractile responses of prostate tissue and then whether melatonin has any restorative effect on the contractile responses in a rat model of bacterial prostatitis at early stages. Materials and methods: We evaluated the nerve-evoked, adrenergic agonist-induced or cholinergic agonist-induced contractions of isolated prostate tissue at 24 and 72 h after intraurethrally instilled Escherichia coli-treatment. We also analyzed the histological changes in the prostate. Secondarily, we investigated the effect of melatonin pretreatment (7 days, 10 mg kg–1 day–1) on the contractile responses and the histopathologic changes. Results: The degrees of acute inflammatory cell infiltration, acinar changes, and interstitial fibrosis in the prostate glands indicated the development of acute prostatitis at 24 or 72 h after bacterial inoculation. These inflammatory changes were more pronounced at 72 h. Bacterial prostatitis attenuated contractile responses to electrical field stimulation, phenylephrine, or carbachol. The impairment in the contractions was more prominent at 72 h. Melatonin treatment reduced the pathologic changes and partially restored the contractile responses at 72 h of inflammation. Conclusion: Prostatic inflammation caused a diminution in the contractile mechanism of the prostate tissue and melatonin partially restored the contractile responses and histopathologic changes. Melatonin can be useful as an adjuvant to the main therapies for prostatitis to reduce the contractility problems.

PubMedID: 22647456 The purpose of this study was to investigate the effects of silymarin, a phytotherapeutic agent, on bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model. Female Wistar Albino rats received a single intraperitoneal injection of CYP (150 mg/kg) or saline and after 72 h, bladder function was evaluated by in vitro preparations of whole bladders and cystometry with continuous saline infusion under urethane anesthesia. Silymarin or a vehicle was orally given for 7 days in rats. CYP was injected on the 5th day of silymarin or vehicle treatment and then the animals were killed on the 8th day. CYP-treatment dramatically potentiated the basal spontaneous contractions of isolated whole bladders compared to control rats. In anesthetized rats, during continuous infusion cystometry, intercontraction interval (ICI) was significantly shorter, but bladder voiding pressure was not significantly changed in CYP-injected rats compared to control rats. In the CYP-injected group, silymarin treatment significantly decreased the amplitude, frequency (contractions/min) and area under the curve of spontaneous contractions, but failed to change carbachol-induced contraction in isolated whole bladder. Also, silymarin treatment significantly increased the ICI in comparison to the vehicle treatment. In the saline-injected group, no significant changes in the bladder function were observed between the silymarin and vehicle-treated groups. Histopathological examination showed that CYP-induced bladder inflammation tended to be lower in the silymarin + CYP-treated group. In conclusion, the oral administration of silymarin suppressed CYP-induced bladder overactivity. Silymarin may be considered as an attractive treatment for CYP-induced bladder overactivity. © 2012 Elsevier GmbH. All rights reserved.

Aims The effect of a non-specific thiol-alkylating agent N-ethylmaleimide (NEM) was studied on neurogenic contractile mechanisms in rat ventral prostate gland. Methods Male Wistar albino rats were used. The rats were killed by cervical dislocation under sevoflurane anesthesia and ventral prostate gland was removed. Two preparations were obtained from each lobe. Neurally evoked isometric contractions were induced using trains of electrical field stimulation (EFS; 0.5, 1, 4, or 8 Hz). The effect of NEM on the contractions to EFS was examined in the absence or presence of adrenergic and/or purinergic antagonists. Results NEM enhanced the EFS-evoked contractions without altering the basal tone. These effects were significantly suppressed by an α1-adrenergic receptor antagonist (prazosin), a P2-purinergic antagonist (suramin), a specific P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS), an ATP analog (α,β-methylene ATP), or a calcium channel blocker (verapamil). This facilitating effect of NEM did not occur following the administration of L-cysteine or glutathione which saturated NEM with excess thiols. However, a thiol-oxidant diamide failed to affect the contractions to EFS. An adrenergic neuron blocker (guanethidine) completely suppressed the responses to NEM. On the other hand, an α2-adrenergic receptor blocker (yohimbine), a nitric oxide synthase inhibitor (Nω-nitro-L-arginine) or a cholinergic muscarinic receptor antagonist (atropine) did not significantly affect the facilitatory response of NEM. Conclusions These findings suggest that NEM has a prejunctional facilitatory action on the adrenergic nerves in rat prostate tissue to enhance release of transmitters, noradrenaline, and ATP. NEM sensitive proteins involved in transmitter release mechanisms can play a role in this effect. Neurourol. Urodynam. 31:579–585, 2012. © 2012 Wiley Periodicals, Inc.

The effect of a non-specific thiol-alkylating agent N-ethylmaleimide (NEM) was studied on neurogenic contractile mechanisms in rat ventral prostate gland.Male Wistar albino rats were used. The rats were killed by cervical dislocation under sevoflurane anesthesia and ventral prostate gland was removed. Two preparations were obtained from each lobe. Neurally evoked isometric contractions were induced using trains of electrical field stimulation (EFS; 0.5, 1, 4, or 8 Hz). The effect of NEM on the contractions to EFS was examined in the absence or presence of adrenergic and/or purinergic antagonists.NEM enhanced the EFS-evoked contractions without altering the basal tone. These effects were significantly suppressed by an α(1) -adrenergic receptor antagonist (prazosin), a P2-purinergic antagonist (suramin), a specific P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS), an ATP analog (α,β-methylene ATP), or a calcium channel blocker (verapamil). This facilitating effect of NEM did not occur following the administration of L-cysteine or glutathione which saturated NEM with excess thiols. However, a thiol-oxidant diamide failed to affect the contractions to EFS. An adrenergic neuron blocker (guanethidine) completely suppressed the responses to NEM. On the other hand, an α(2) -adrenergic receptor blocker (yohimbine), a nitric oxide synthase inhibitor (N(ω) -nitro-L-arginine) or a cholinergic muscarinic receptor antagonist (atropine) did not significantly affect the facilitatory response of NEM.These findings suggest that NEM has a prejunctional facilitatory action on the adrenergic nerves in rat prostate tissue to enhance release of transmitters, noradrenaline, and ATP. NEM sensitive proteins involved in transmitter release mechanisms can play a role in this effect.