Asiye Ugras Dikmen

The role of interleukin-17 in intrahepatic cholestasis of pregnancy

Abstract Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease, is characterized by pruritus, abnormal liver function and elevated serum bile acid levels. The main cause of ICP has not yet been identified. We aimed to provide a new perspective to the pathogenesis of by investigating the possible association of circulating interleukin-17 (IL-17) that is a recently discovered proinflammatory cytokine levels with ICP. Materials and methods: In this controlled cross-sectional study, maternal venous blood samples were obtained from 33 consecutive pregnant women with ICP (15 with mild and 18 with severe forms of the disease) and 25 healthy women with uncomplicated pregnancies (as the control group) and IL-17 levels were compared among the groups. Results: Although serum IL-17 levels were significantly higher in the severe ICP group than in the control group (p = 0.022), there were no significant differences between the mild and severe ICP groups or between the control and mild ICP groups. Conclusion: Explaining the mechanisms of hepatocyte injury might contribute to the existing therapeutic strategies for treating cholestatic diseases. Changes in IL-17 levels may shed light on the pathogenesis of ICP.

Diagnostic value of sonography for detecting endometrial pathologies in postmenopausal women with and without bleeding

To investigate the diagnostic value of endometrial thickness measurement on sonography in predicting endometrial pathologies in postmenopausal women with vaginal bleeding and in those with asymptomatic thickened endometrium.

A New Diagnostic and Prognostic Marker in Endometrial Cancer: Neopterin

Objective In this study, we investigated the correlation between serum and urinary neopterin levels as well as the stage of the disease in women with endometrial cancer. Increased neopterin concentrations are reported in patients with activation of macrophages by interferon-γ, which includes the following: viral infections, autoimmune disorders, allograft rejection, and various malignant tumors. In patients with several types of cancer, high-neopterin concentrations in body fluids like serum/plasma, urine, ascites, and cerebrospinal fluid indicate the course of the disease, and it is associated with poor prognosis. In the light of foregoing, we aimed to investigate the role of neopterin as a prognostic biomarker in endometrial cancer. Materials and Methods Serum neopterin concentrations were determined by enzyme-linked immunosorbent assay and urinary neopterin by high-performance liquid chromatography in 41 patients with endometrial cancer (group 2) and 41 healthy women (group 1). Results Increased urinary neopterin levels were observed in patients with endometrial cancer (P < 0.001), and the difference in the urinary neopterin levels between low and high stages of endometrial cancer was significant (P < 0.01; stage I–II vs stage III–IV, respectively). Serum neopterin levels did not show a significant difference in each group. Conclusions This study suggests that urinary neopterin levels are relevant in evaluating the endometrial cancer stage and follow-up of the disease. As a result, using neopterin and cancer antigen 125 together would be useful in determining the prognosis of endometrial cancer and its posttreatment progression.

Do the expressions of epithelial–mesenchymal transition proteins, periostin, integrin-α4 and fibronectin correlate with clinico-pathological features and prognosis of metastatic castration-resistant prostate cancer?

Development of metastatic castration-resistant prostate cancer is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial–mesenchymal transition. Although there are several strongly recommended biomarkers for determining prognosis of metastatic castration-resistant prostate cancer, only few of them may help decide the selection of the optimal treatment option. The mode of treatment sequencing in metastatic castration-resistant prostate cancer will be based on the individual characteristics of the patient. In this study, we aimed to explain the correlation between the expression characteristics of periostin, integrin-α4, and fibronectin in metastatic castration-resistant prostate cancer patients and their clinico-pathological data comprising Gleason score, PSA levels, and metastatic sites in the process of epithelial–mesenchymal transition. We evaluated by using Western blotting, periostin, integrin-α4, and fibronectin expressions in peripheral blood samples of metastatic castration-resistant prostate cancer patients (n = 40), benign prostatic hyperplasia patients (n = 20), and the healthy control group (n = 20). Associations between changes in the protein expressions and clinico-pathological parameters were also analyzed in the metastatic castration-resistant prostate cancer group. When comparing BPH and healthy groups with the metastatic castration-resistant prostate cancer group, a reduced expression of integrin-α4 was found in metastatic patients, albeit being statistically insignificant (P > 0.05). Protein expressions of periostin and fibronectin in the metastatic castration-resistant prostate cancer group were higher than those in the BPH and heathy groups (P < 0.001). Increased periostin expression in metastatic patients was significantly associated with bone metastasis (P < 0.05). Elevated periostin and fibronectin levels in metastatic castration-resistant prostate cancer patients may be appropriate targets of therapeutic intervention in the future. Impact statement Prostate cancer is the third most common cancer in the world and the most common cancer among men. Development of metastatic castration-resistant prostate cancer (mCRPC) is a result of the lack of an apoptotic response by the tumor cells and loss of the ability to stick to adjacent cells through epithelial–mesenchymal transition (EMT). The present study analyzes for the first time the expressions of EMT marker proteins – periostin, integrin α4, fibronectin – in mCRPC and in benign prostatic hyperplasia (BPH) with the aim to determine the clinical relevance of changes in these three proteins vis-a-vis the PCa aggressive phenotype. In doing so, it sheds light on the molecular mechanism underlying the disease. We concluded that elevated periostin and fibronectin levels in mCRPC patients may be appropriate targets of therapeutic intervention in the future; hence, adopting methods that target these proteins may help treat prostate cancer effectively.

Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration for the determination of lung cancer subtypes

It is crucial to diagnose the subtype of lung cancer quickly and accurately for effective therapy. Conventional cytology staining sometimes provides limited information, and additional tissue is often required to diagnose lung cancer. Cell blocks (CB) recovered during endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) increases the diagnostic accuracy of the procedure and the likelihood of additional valuable histochemical and immunohistochemical staining.

Vitamin D receptor polymorphisms in immune thrombocytopenic purpura

Vitamin D receptor (VDR) polymorphisms have been studied in immune‐mediated disorders, but not yet in immune thrombocytopenic purpura (ITP). We investigated whether VDR variants were associated with ITP in children.

Analysis of MMP-7 and TIMP-2 gene polymorphisms in coronary artery disease and myocardial infarction: A Turkish case-control study

Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) have a significant role in tissue remodeling related to cardiac function. In earlier studies, MMP‐7 A‐181G (rs11568818), C‐153T (rs11568819), C‐115T (rs17886546), and TIMP‐2 G‐418C (rs8179090) polymorphisms have been studied in various diseases. However, association between coronary artery disease (CAD) and these polymorphisms has been poorly studied. The goal of this study is to investigate the association of CAD and myocardial infarction (MI) with MMP‐7 or TIMP‐2 polymorphisms. This study included 122 CAD patients and 132 control individuals. DNA was extracted from whole blood. Polymerase chain reaction‐restriction fragment length polymorphism and automated direct sequencing method were used for genotyping of these polymorphisms. No significant differences were found between MMP‐7 A‐181G, C‐115T, and TIMP‐2 G‐418C polymorphism and CAD or MI in a Turkish population. Despite the fact that the genotypes of MMP‐7 C‐153T polymorphism had no significant differences among MI and control groups, allele frequencies of C‐153T polymorphism were significantly different between the two groups. Our study is the first report to clarify the appreciable relationship between MMP‐7 C‐153T polymorphism and MI development in CAD patients. However, these findings also need to be confirmed in other populations so we can improve our knowledge about the genetic factors affecting the development of CAD.

The Retrospective Evaluation of the Effects of the Delivery Time Intervals on the Newborn During Elective Cesarean Sections Under Spinal Anesthesia

Aim : We aimed to investigate whether delivery time intervals are related to newborn outcome by evaluating Apgar scores and umbilical cord blood results during elective cesarean section under spinal anesthesia. Materials and Methods : Records of the 203 ASA I or ASA II pregnant women underwent elective cesarean section under spinal anesthesia during one-year period were evaluated retrospectively. Demographic properties of the parturients (age, weight, body mass index, gravidity, parity and gestational week) and newborns (birthweight and gender), and duration of surgery were presented. In order to demonstrate any possible relationship, time intervals from completion of spinal anesthesia (SA) to skin incision (SI), uterine incision (UI) and umbilical cord clamping (UCC) and from skin and uterine incisions to UCC, Apgar scores, umbilical artery and vein (UA and UV) blood gas analysis (UA-pH, UA-BE, UA-PO 2, UA-PCO 2, UV-pH, UV-BE, UV-PCO 2 and UV-PO 2 ) were also documented. Results : There was a significant correlation between delivery time intervals including SA-SI, SA-UI and SA-UCC to UA-pH, UA-BE, UV-pH and UV-BE (p=0.0001). There was also a correlation between SI-UCC and UI-UCC to UV-pH (p=0.0001 and p=0.02) but not with UV-BE. No correlation was observed between SA-SI, SA-UI and SA-UCC to mean Apgar scores at 1 min. However, relatively significant correlation was observed between the time interval SA-SI to mean Apgar scores at 5 min (r=0.13, p=0.04). Conclusion : We observed a strong correlation between the time intervals from SA to SI, UI, and UCC with the newborn outcome in terms of UV-pH and UV-BE. There was also a correlation between the time interval from SA to SI with Apgar score at 5 min. Therefore, prolongation of the delivery time interval particularly for parturients scheduled to undergo elective cesarean delivery under spinal anesthesia might possibly affect newborn outcome.

High neutrophil-lymphocyte ratio in schizophrenia independent of infectious and metabolic parameters

Abstract Background: Immunological and inflammatory mechanisms play an important role in schizophrenia. In the literature, there are studies investigating neutrophil-lymphocyte ratio (NLR) association with schizophrenia. Aims: The purpose of this study was to compare NLR values between patients with schizophrenia and healthy controls. In addition, the study aimed to investigate the relationship between NLR and disease severity and some metabolic/inflammatory parameters. Methods: Fifty-two patients diagnosed with schzophrenia and 53 healthy controls were included in the study. A socio-demographic information form was filled out by the clinician. Height, body weight, waist and hip circumference and blood pressure values of each patient were measured. Severity of disease was assessed by positive and negative syndrome scale (PANSS) and clinical global impression-severity scale (CGI-S). Complete blood count was performed to both patient and control groups. Fasting blood glucose, insulin, HbA1c, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, total cholesterol and C-reactive protein (CRP) were measured. Results: The number of leukocytes, neutrophils, monocytes and NLR values in patients with schizophrenia was significantly higher than in the control group. There was no significant relationship between NLR values and the number of hospitalisation, duration of ilness or disease severity in patients. There was no correlation between other laboratory findings and NLR values. Conclusion: NLR levels are high in schizophrenia independent of metabolic parameters according to the results. So, it can be considered that inflammatory processes may play a role in the etiology of the disease.

Memantine induces apoptosis and inhibits cell cycle progression in LNCaP prostate cancer cells

Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer’s drug. Drug repositioning studies offer wide range of benefits, such as reduced time, cost and risk over de novo drug discovery. Therefore, we aimed to target glucose and glutamine metabolism in androgen-dependent LNCaP cells by using metformin and memantine and investigate these agents’ effects on prostate cancer cell proliferation in vitro. We evaluated the effects of metformin and memantine on the protein expression levels of genes that play significant roles in apoptosis and cell cycle progression (Casp3, Casp9, Bcl-2, Survivin, Bax, c-Myc, HIF1A, CCND1, CDK4 and GAPDH) by Western blotting. Alzheimer’s drug memantine exerted cytotoxic effects at 0.25 mM and metformin at 2.5 mM. We identified for the first time that memantine exerts antineoplastic activity (0.25 mM) by triggering Bax-dependent pathway of apoptosis. In addition to that both molecules have shown similar patterns on pro- and anti-apoptotic protein expression levels, such as Bcl-2, Casp3, Survivin and Bax. Our preclinic results indicate that memantine might be used as a new repositioned drug in cancer treatment. Beyond targeting glucose metabolism, glutamine metabolism also holds great promise for a potential treatment option.