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    Effects of N-acetylcysteine on sciatic nerve healing: A histopathological, functional, and biochemical study of the rat sciatic nerve
    (Turkish Joint Diseases Foundation, 2024) Saritas, Tahir Burak; Erturk, Cemil; Buyukdogan, Halil; Yildirim, Burak; Gunduz, Nermin; Selek, Sahabettin
    Objectives: This study aims to evaluate the histopathological, biochemical, and functional effects of N-acetylcysteine (NAC), which has antioxidant, anti-inflammatory, and cytoprotective activity, on nerve regeneration in rats with sciatic nerve crush (axonotmesis) injury. Materials and methods: This study used 16 male Wistar rats, which were divided into treatment and control groups. A standard axonotmesis-type surgical injury was induced in the left sciatic nerves of all rats. The treatment group was given 300 mg/kg of intraperitoneal NAC once a day, whereas the control group received an equal volume of saline solution. After conducting gait analyses, the sciatic functional index (SFI) was used for functional assessment. After gait analysis, all animals were euthanized. Blood samples were examined biochemically. The left sciatic nerves and left triceps surae muscles were examined histopathologically. Results: Histopathologically, the thickness of the perineurium, axonal degeneration, axonolysis, edema, inflammation, muscle atrophy, and muscle degeneration were all significantly lower in the treatment group (p<0.05). Functionally, SFI-1, SFI-2, and SFI-3 were significantly higher in the treatment group (p<0.05). Biochemically, while the native thiol level and native thiol/total thiol ratio were significantly higher in the treatment group (p<0.003), the disulfide/total thiol ratio was significantly higher in the control group (p<0.005). Significant correlations were found between six of the seven gait parameters and the histopathological findings (p<0.05). Conclusion: Our study results suggest that NAC may contribute positively to the histopathological and functional recovery of sciatic nerve injury in rats. Furthermore, NAC may have an antioxidant effect on thiol-disulfide homeostasis at a biochemical level. We believe that NAC has a stimulatory effect on healing following nerve injuries.
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    Kisspeptin: a potential therapeutic target in patients with unexplained infertility
    (Springer London Ltd, 2023) Atakul, Nil; Kilic, Berna Sermin; Selek, Sahabettin; Atamer, Yildiz; Unal, Fehmi
    Background Kisspeptin has recently emerged as a key regulator of the reproductive axis in women. Kisspeptin, acting centrally via the kisspeptin receptor, stimulates the secretion of the gonadotrophin-releasing hormone (GnRH). Aims To investigate serum kisspeptin levels in infertility patients for its clinical utilisation in management and understanding of the pathophysiology of infertility in a wide array of patients. Methods This prospective case-control study analysis involved 92 primary infertile women with PCOS, diminished ovarian reserve (DOR), unexplained infertility (UEI), and male factor infertility between 20 and 42 years of age. Serum samples were collected between the second and fifth day of the menstrual cycle. The kisspeptin level was determined using a human kisspeptin ELISA kit according to the manufacturer's procedure. Results The median value of serum kisspeptin in the PCOS infertility group was significantly higher than that in the UEI group (p = 0.011). There was a statistically significant (p = 0.015, r = -0.182) negative weak correlation found between serum kisspeptin levels and age. The optimal cutoff value obtained to differentiate the UEI from others (PCOS infertility + DOR + male factor infertility) according to the serum kisspeptin level was 214.3 ng/L with a sensitivity of 55% and specificity of 80.9%. Conclusions Understanding the role of kisspeptin may lead to its use as a biomarker in infertility diagnosis in UEI patients and might guide the use of kisspeptin analogues in selected patients for infertility management.
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    Levels of a novel metabolic marker, spexin in patients with hirsutism: metabolic syndrome risk in idiopathic and polycystic ovarian syndrome (PCOS) hirsutism
    (Via Medica, 2024) Atakul, Nil; Kilic, Berna Sermin; Selek, Sahabettin; Atamer, Yildiz
    Objectives: Polycystic ovarian syndrome (PCOS) disease the most common endocrinopathy among reproductive age women, and its association with metabolic syndrome is investigated in many reports. The most common cause of hirsutism worldwide is considered to be idiopathic hirsutism (IH) defined as clinical hirsutism without underlying hormonal imbalance. Spexin is a novel peptide and is mainly involved in energy homeostasis and, has not yet made its way into clinical practice. We aim to investigate spexin in an understudied population of hirsute patients. Material and methods: This prospective casecontrol study analysis involved 48 patients with hirsutism.and, was further divided into two groups: 26 had PCOS syndrome and 22 had IH. 40 healthy, age and BMImatched nonhirsute women enrolled as the control group. The spexin level was determined using a human spexin ELISA kit. Results: There was no statistically significant difference in spexin levels found between hirsutism and control patients 1514 vs 1425 ng/L, (p = 0.849). Spexin levels were found to be significantly higher in the PCOS hirsutism group than in the IH group (1668.5 ng/L vs 1021 ng/L), (p = 0.022). Correlations of spexin levels with total testosterone, lowdensity lipoprotein, and total cholesterol were found in hirsutism patients. Conclusions: Our findings conclude that both IH and PCOS hirsutism patients have an increased risk of metabolic syndrome; hyperandrogenemia and dyslipidemia contribute to the progression of upcoming research on metabolic syndrome. Low spexin levels in IH in hirsute patients could potentially elucidate the pathogenesis of the condition, consequently assisting in diminishing the risk of associated complications.
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    Maternal neuropeptide galanin levels in pregnancies with intra-uterine growth restriction (IUGR): neurohormonal regulation of fetal weight
    (Springer London Ltd, 2023) Kilic, Berna Sermin; Atakul, Nil; Selek, Sahabettin; Atamer, Yildiz
    Aim Galanin is a neuroendocrine peptide with diverse biological actions in humans. Here, we evaluated plasma galanin levels in pregnant women with intrauterine growth restriction (IUGR) to elucidate the mechanism underlying the causal link between regulatory neuropeptides and IUGR. Material and methods This prospective case-control study evaluated 40 IUGR pregnancies and 35 healthy body mass index (BMI) and age-matched second and third-trimester pregnant women at Istanbul Teaching and Research Hospital. Serums galanin levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's procedure. Results Median serum galanin levels were lower in the IUGR group (9.59 pg/ml) than in the control group (12.1 pg/ml), although statically insignificant. Galanin levels were significantly higher in the control group with a BMI >= 30 than in those with a BMI < 30; the IUGR group exhibited no significant difference. Galanin levels were higher in the control group premature births than in term pregnancies; the difference was insignificant in the IUGR group. Thus, IUGR minimally impacts circulating maternal galanin levels, indicating that while galanin might affect IUGR pathogenesis, it negligibly contributes to disease progression. Conclusion The lack of correlation between galanin levels and maternal BMI and preterm pregnancies suggests a blunted neuropeptide response to hormonal stimulus in IUGR pregnancies, compared with the positive association with maternal BMI and negative association with healthy preterm pregnancies.
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    Maternal Serum Levels of Zinc, Copper, and Thiols in Preeclampsia Patients: a Case-Control Study
    (Springernature, 2022) Gul, Ayse Zehra; Atakul, Nil; Selek, Sahabettin; Atamer, Yildiz; Sarikaya, Ufuk; Yildiz, Tugce; Demirel, Metin
    Preeclampsia is one of the leading causes of maternal mortality-morbidity, and environmental factors act as the main driving force for the development of disease in genetically lean women. Trace element levels (zinc, copper) and thiol state (total, native thiol) may affect involved risk factors and play a role in the pathogenesis. The objective of our study is to assess trace element and thiol levels in patient and control groups. A total number of 88 pregnant women (in their third trimester) included 43 preeclampsia patients and 45 normotensive pregnant women as controls. The main findings of this study were the significantly elevated copper levels and decreased thiol levels (native and total thiols) in the patient group compared to controls (p < 0.05). Disulfide levels were not statistically different between the groups (p > 0.05). In patients, the predictive cutoff value of copper was 224 mu g/dL and was 1.19 for the copper/native thiol ratio. Zinc levels were not statistically different between the two groups. Correlation analysis revealed no relationship between zinc-copper and zinc-total thiol levels in patients, while a positive correlation was evident in controls (zinc-copper, p < 0.05, r = 0.425, and zinc-total thiol levels, p < 0.05, r = 0.642). Patients had marginally high ALT and AST values in the normal range, and a significant difference was found between the two groups (p < 0.05). According to these results, elevated copper levels and decreased thiol levels may have a value for early prediction. The mechanisms that may be responsible for the altered element and thiol status have been discussed here in the context of oxidative stress.
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    Novel metabolic marker Afamin: A predictive factor for Large-for-Gestational-Age (LGA) fetus estimation in pregnancies with gestational diabetes mellitus?
    (Elsevier Masson, Corp Off, 2021) Atakul, Nil; Atamer, Yildiz; Selek, Sahabettin; Kilic, Berna Sermin; Unal, Fehmi
    Objective: Gestational diabetes mellitus (GDM) affects both maternal and fetal/infant outcomes during and after pregnancy. The reason for the high incidence of large-for-gestational-age (LGA) infants in GDM patients despite close monitorization of glucose levels with early detection of the disease remains unclear to date. Our study aims to investigate the levels of the third-trimester novel marker afamin in GDM versus non-GDM pregnancies in terms of glycemic control status and their utility in the prediction of LGA fetuses. Material and Methods: This prospective case-control study analysis involved 49 pregnant women with GDM diagnosed using the 75-g oral glucose tolerance test (75-g OGTT) and 40 randomly selected women with a similar body mass index (BMI) and gestational age (GA). Blood samples were collected in the third trimester of pregnancy. The afamin level was determined using a human afamin ELISA kit according to the manufacturer's procedure. Results: There was no significant difference found in BMI or GA of patients. Third-trimester afamin levels were 93.91 mg/L and 83.87 mg/L in the GDM and non-GDM groups, respectively (p=0.625). Afamin values of patients were not correlated with age, BMI, GA, HgA1c, 75-g OGTT fasting and 75-g OGTT 1-hour, or 75-g OGTT 2-hour values (p>0.05). GDM patients with LGA fetuses had significantly higher afamin values than patients with appropriate-for-gestational-age (AGA) fetuses (120.8 mg/L versus 91.26 mg/L, respectively). Between GDM patients with either LGA or AGA fetuses, there was no statistically significant difference found for age, BMI, GAs, insulin dose, 75-g OGTT results, or HgA1c values. Conclusion: Our findings conclude that novel marker afamin levels could predict the risk of LGA infants independently of glycemic control status and provide insight into the pathogenesis of LGA fetuses, thus helping to reduce the risk of associated complications. (C) 2021 Elsevier Masson SAS. All rights reserved.
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    ST2 and galectin-3 as novel biomarkers for the prediction of future cardiovascular disease risk in preeclampsia
    (Taylor & Francis Inc, 2022) Atakul, Nil; Atamer, Yildiz; Selek, Sahabettin; Kilic, Berna; Koktasoglu, Fatmanur
    The aim of this study was to investigate known cardiovascular disease (CVD) risk biomarkers galectin-3 (Gal-3) and human stromelysin-2 (ST2) levels in preeclampsia (PE) and normotensive pregnancies. A case-control study was conducted in a teaching and research hospital. We performed data analysis involving 45 pregnant women with PE and gestational week (GW) matched 35 normotensive pregnant women. The Gal-3 and ST2 levels were determined by using ELISA kit. Gal-3 values did not differ statistically between PE and control groups (535.1 ng/mL vs. 615.2 ng/mL) (p> .05). ST2 value in the PE group was statistically significantly lower than the control group (33.3 pg/mL vs. PE, 54.5 pg/mL, p < .05). >34 GW patients (late-onset PE) had statistically significantly lower Gal-3 values than the <= 34 GW patients (early-onset PE) (507.1 ng/mL vs. 769.6 ng/mL, p < .05). Late-onset PE patients had significantly lower ST2 values than early-onset patients (26.4 pg/mL vs. 57.9 pg/mL, p < .05). We assume that low Gal-3 values in early-onset PE show a higher risk of cardiac fibrosis although both early and late-onset PE patients had an increased CVD risk later in life. We found the superiority of ST2 levels to Gal-3 levels in PE pregnancies for CVD risk assessment.Impact Statement What is already known about this subject? Preeclampsia (PE) in pregnancy is a known risk factor for future cardiovascular disease (CVD) and is also associated with increased mortality from ischaemic heart disease later in life. Studies that investigate patients with a higher risk for CVD in PE pregnancies are lacking. What do the results of this study add? We found different levels of two novel cardiac markers with PE and normotensive pregnancies, and also with early and late-onset PE pregnancies. What are the implications of these findings for clinical practice and/or further research? Different adaptive responses from patients during PE pregnancies via altered levels of cardiac markers could help clinicians to identify women with a higher risk of CVD.