İbrahim Ömer Barlas İbrahim Ömer Barlas TIP FAKÜLTESİ TEMEL TIP BİLİMLERİ BÖLÜMÜ TIBBİ BİYOLOJİ ANABİLİM DALI
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Endoplasmic Reticulum Stress in Myometrial Smooth Muscle Cells and Spontaneous Contraction Changes in the Uterus of Dehydroepiandrosterone-induced Polycystic Ovary Syndrome Rats

Savas Aktas | Ismail Un | Ibrahim Omer Barlas

Myometrial changes in polycystic ovary syndrome (PCOS) are poorly investigated. Thus, we aimed to investigate endoplasmic reticulum (ER) stress in myometrial smooth muscle cells and changes in spontaneous uterine contraction in PCOS. Twenty-one female Sprague-Dawley rats (21 days old) were divided into control (n = 7), vehicle (n = 7) and PCOS (n = 7) groups. While the control group was not injected subcutaneously, the vehicle group was injected subcutaneously with sesame oil (0.2 ml/day) for 20 consecutive days. The PCOS group was injected subcutaneously with dehydroepiandrosterone (6 mg/100 g/day dissolved in 0.2 ml sesame oil) for 20 consecutive days. Blood samples were collected for the measurement of follicle stimulating-hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) and glucose-regulated protein 78 (GRP78). The mRNA expression of GRP78 in the uterine tissue samples was analysed by quantitative real-time polymerase chain reaction. GRP78 protein expression was assessed by immunohistochemistry. Myometrial smooth muscle cells were examined by transmission electron microscopy. Uterine contractions were evaluated with isolated organ bath experiments. In the PCOS group, T and LH levels increased significantly, although FSH and E2 levels decrea...

Endoplasmic Reticulum Stress in Myometrial Smooth Muscle Cells and Spontaneous Contraction Changes in the Uterus of Dehydroepiandrosterone-induced Polycystic Ovary Syndrome Rats

Aktaş, Savaş | Barlas, İbrahim Ömer | Ün, İsmail

Myometrial changes in polycystic ovary syndrome (PCOS) are poorly investigated. Thus, we aimed to investigate endoplasmic reticulum (ER) stress in myometrial smooth muscle cells and changes in spontaneous uterine contraction in PCOS. Twenty-one female Sprague-Dawley rats (21 days old) were divided into control (n = 7), vehicle (n = 7) and PCOS (n = 7) groups. While the control group was not injected subcutaneously, the vehicle group was injected subcutaneously with sesame oil (0.2 ml/day) for 20 consecutive days. The PCOS group was injected subcutaneously with dehydroepiandrosterone (6 mg/100 g/day dissolved in 0.2 ml sesame oil) for 20 consecutive days. Blood samples were collected for the measurement of follicle stimulating-hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) and glucose-regulated protein 78 (GRP78). The mRNA expression of GRP78 in the uterine tissue samples was analysed by quantitative real-time polymerase chain reaction. GRP78 protein expression was assessed by immunohistochemistry. Myometrial smooth muscle cells were examined by transmission electron microscopy. Uterine contractions were evaluated with isolated organ bath experiments. In the PCOS group, T and LH levels increased significantly, although FSH and E2 levels decreased, but th...

Evaluation of the Rho A/Rho-kinase pathway in the uterus of the rat model of polycystic ovary syndrome

Aktaş, Savaş | Ün, İsmail | Barlas, İbrahim Ömer | Öztürk, Ayla Batu

The aim of this study was to investigate the expression of RhoA/Rho-kinase in the uterus and the effect of Rhokinase inhibitors on uterine contractions of dehydroepiandrosterone (DHEA) induced polycystic ovary syndrome (PCOS) rats. Forty-four female Sprague-Dawley (21 days old) rats divided into three groups: The control group (n = 14, any procedure was not performed), vehicle group (n = 14, 0.2 ml of sesame oil, subcutaneous injection, 20 days) and PCOS group (n = 16, DHEA 6 mg/100 g in 0.2 ml of sesame oil, subcutaneous injection, 20 days). The myometrium thickness and uterine wet weight were assessed. The mRNA and protein expressions of Rho A, the effect of Rho-kinase inhibitors (fasudil and Y-27632) on KCl, carbachol, and PGF2α induced contractions were evaluated in the uterus. In the PCOS group, the myometrium thickness and uterine wet weight significantly increased compared to the control group and vehicle group. The mRNA expression level and the immunoreactive score of Rho A, ROCK 1, ROCK 2 were similar in all groups. In the PCOS group, KCl, carbachol, and PGF2α induced uterine contractions significantly increased compared to the control group and vehicle group. Fasudil and Y-27632 significantly inhibited KCl, carbachol, and PGF2α induced uterine contractions in all groups...

Harnessing Knowledge on Very Important Pharmacogenes CYP2C9 and CYP2C19 Variation for Precision Medicine in Resource-Limited Global Conflict Zones

Barlas, İbrahim Ömer | Sezgin, Orhan

Pharmacogenomics harnesses the utility of a patient’s genome (n = 1) in decisions on which therapeutic drugs and in what amounts should be administered. Often, patients with shared ancestry present with comparable genetic profiles that predict drug response. However, populations are not static, thus, often, population mobility through migration, especially enmasse as is seen for refugees, changes the pharmacogenetic profiles of resultant populations and therefore observed responses to commonly used therapeutic drugs. For example, in the aftermath of the Syrian civil war since 2011, millions have fled their homes to neighboring countries in the Middle East. The growing permanence of refugees and mass migrations is a call to shift our focus in the life sciences community from old models of pharmaceutical innovation. These seismic social changes demand faster decisions for ‘‘population-to-population bridging,’’ whereby novel drugs developed in or for particular regions/countries can meet with rational regulatory decisions/approval in world regions impacted by migrant/ refugee populations whose profiles are dynamic, such as in the Eastern Mediterranean region at present. Thus, it is important to characterize and report on the prevalence of pharmacogenes that affect commonly used medi...

The Association of Olanzapine-Induced Weight Gain with Peroxisome Proliferator–Activated Receptor-g2 Pro12Ala Polymorphism in Patients with Schizophrenia

Erdal, Mehmet Emin | Barlas, İbrahim Ömer

Olanzapine is a second-generation antipsychotic that may cause weight gain and metabolic syndrome in some cases. The peroxisome proliferator–activated receptor (PPAR)-g is an important gene in the progress of type II diabetes and metabolic syndrome. In recent studies the polymorphism of the PPAR-g has been studied in type II diabetes mellitus, polycystic ovary syndrome, and insulin resistance syndrome. It is aimed to evaluate the association between polymorphism of PPAR-g gene and olanzapine-induced weight gain. Our study comprised 95 unrelated subjects who strictly met Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSMIV) criteria for schizophrenia, and all were of Turkish origin. All patients were evaluated with rating scales, and genetic analyses were performed. We found statistically significant differences between pretreatment and posttreatment body mass index and weight change in Pro12Ala polymorphism of PPAR-g2. Our results suggest that genetic polymorphism of PPAR might be important in olanzapine-induced weight gain and that genetic variance of people might be considered in antipsychotic medication selection.

Lack of Association Between DRD3 Gene Polymorphism and Response to Clozapine in Turkish Schizoprenia Patients

Barlas, İbrahim Ömer | Erdal, Mehmet Emin | Ay, Mustafa Ertan

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N¼92) and healthy controls (N¼100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism ofDRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist