Işıl Albeniz

Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole-induced generalized seizures

Erythropoietin (EPO) suppresses epileptic seizures, but the mechanism is unclear. The search for novel targets in the therapy of epilepsy has focused recently on brain inflammation since brain inflammation and the associated blood–brain barrier (BBB) damage appears to be an integral part of epilepsy pathophysiology. We examined the effects of EPO on proinflammatory mediators in brain and serum in PTZ-induced generalized seizure model. The inflammation markers (IL-1β, TNF-α, IL-6, IL-10), BBB and neuron damage markers (S100B, Neuron specific enolase; NSE, respectively) in serum and brain of Sprague–Dawley male rats were examined with the ELISA method. Nitric oxide synthase (NOS) isoforms were investigated immunohistochemically in hippocampus. EPO treatment 4 h and 24 h before PTZ administration had diverse effects. EPO treatment 4 h before PTZ administration elongated the seizure latency, decreased the inflammation and damage markers in serum and brain significantly, whereas EPO treatment 24 h before PTZ administration lowered inflammation and damage markers to control levels and decreased the seizure stage. PTZ-induced seizures increased inducible NOS (iNOS) activity and decreased endothelial NOS (eNOS) activity in hippocampus. Both EPO pretreatments reversed these effects. These findings, i.e., decreased iNOS activity and increased eNOS activity by EPO suggest the first time that the favorable effect of EPO pretreatment on inflammatory mediators triggered by PTZ-induced seizures. This can provide further insight into epilepsy treatment and new prophylactic strategies against epilepsy risk.

Erythrocyte CD38 as a prognostic marker in cancer

Abstract Background: Surface antigen CD38 which is a multifunctional protein with enzymatic and receptorial properties is involved in many processes of cell proliferation and activation. It is widely expressed within the hematopoetic system, and its expression is stimulated by proinflammatory cytokines. CD38-associated enzymatic activities in erythrocytes from cancer patients were investigated in this context. Methods: Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities in normal individuals and cancer patients were compared and correlation of these activities to CEA values and anemia were determined. Changes in CD38-expression were followed by SDS-PAGE and Western blot analysis of erythrocyte membrane proteins. Results: Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities were significantly increased in cancer, in parallel to enhancement of CD38 expression and in correlation with CEA values and anemia. Conclusions: An increased expression of CD38 which may be due to action of proinflammatory cytokines produced in tumor–host reactions appears to account for the elevations in erythrocyte CD38-associated enzyme activities in cancer patients. The changes in these enzyme activities may provide a prognostic outlook in view of their apparently close correlation to tumor progressions.

ADP-ribosylation of serum proteins : Elevated levels in neoplastic cases due to altered NAD/ADP-ribose metabolism

ADP-ribosylation of human serum proteins was studied in various groups of disorders. In most of these groups, the extent of ADP-ribosylation did not show a divergence from the group of normal controls. Neoplastic diseases revealed, however, a unique group, with more than fivefold increases in ADP-ribosylation levels over the other groups. Blood samples with high levels of ADP-ribosylation revealed, in general, increased serum NAD glycohydrolase activities and low levels of serum NAD.

Cyclosporin A-Associated Changes in Red Blood Cell Membrane Composition, Deformability, Blood and Plasma Viscosity in Rats

Most of the studies concerning the effects of cyclosporin A (Cs A) on red blood cell (RBC) rheology were carried out in human transplant recipients who may still have residual insufficiency and concomitant administration of other immunosuppressive and antihypertensive drugs. The aim of this study is to evaluate the effects of Cs A on red cell rheology and membrane composition in nontransplant healthy rats. Female Wistar albino rats were divided into two groups of 10 animals each. Rats received 10 mg/kg Cs A, i.p. or saline for 4 weeks. Cs A administration significantly increased the RBC deformability, and plasma and blood viscosity (p < 0.001, p < 0.01 and p < 0.01, respectively). Cs A administration to the rats increased RBC membrane cholesterol (CHO) levels and the CHO/phospholipid (PL) ratio significantly (p < 0.01 and p < 0.05, respectively) but did not change RBC membrane proteins and membrane PL levels. These results suggest that Cs A changes the rheological functions of RBC and lipid content of RBC membrane in healthy rats and thereby it may play an important role in the regulation of microcirculation.

Clinical significance of serum ADP-ribosylation and NAD glycohydrolase activity in patients with colorectal cancer

The objective of this study was to evaluate the clinical significance of serum ADP-ribosylation and NAD glycohydrolase activity in patients with colorectal cancer (CRC). A total of 108 patients with CRC who underwent curative surgery and 20 healthy volunteers were enrolled in this study. ADP-ribosylation and NAD glycohydrolase activity levels were determined. The association of ADP-ribosylation and NAD glycohydrolase with clinical and laboratory factors and their impact on overall survival (OS) and disease free survival (DFS) were shown. The preoperative ADP-ribosylation and NAD glycohydrolase activity levels were significantly higher in patients with CRC than in the control group (p < 0.001). ADP-ribosylation and NAD glycohydrolase activity levels were correlated with tumor stage (p = 0.05, p = 0.001), stage of disease (p < 0.001, p < 0.001), serum CEA level (p < 0.001, p < 0.001), and site of lesion (p < 0.001, p < 0.001), respectively. Patients with high ADP-ribosylation had significantly unfavorable OS and DFS compared with those with lower levels (p < 0.001, p < 0.001), respectively. Moreover, the patients with high NAD glycohydrolase activity showed significantly worse OS and DFS rates, similar to ADP-ribosylation. Serum levels of ADP-ribosylation and NAD glycohydrolase activity correlate well with tumor stage, stage of disease, serum CEA level, and site of lesion. In conclusion, elevated levels of preoperative ADP-ribosylation and NAD glycohydrolase levels in serum are associated with poor prognosis in patients with CRC.

Nicotine reduces effectiveness of doxorubicin chemotherapy and promotes CD44+CD24‑ cancer stem cells in MCF‑7 cell populations

Breast cancer is the most common type of cancer in females and the second most common cause of cancer mortality after lung cancer. Cancer stem cells represent a novel approach to target cancer and reduce cancer recurrence and metastasis. Many patients with breast cancer continue to smoke after receiving their diagnosis. Nicotine is a key factor in tobacco addiction and also changes some cellular functions, such as activation of mitogenic pathways, angiogenesis and cell proliferation. In the present study, the impact of nicotine was assessed in a population of MCF-7 human breast cancer cells. Cluster of differentiation (CD)44+CD24− cancer stem cell population of MCF-7 cells were evaluated using flow cytometry and scanning electron microscopy. Chemoresistance effects of nicotine were demonstrated in these cells. These findings demonstrated harmful effects of nicotine following metastasis of cancer, owing to the chemoresistance produced through uninterrupted smoking, which may impact the effectiveness of treatment.

Induction of apoptosis by Centaurea nerimaniae extract in HeLa and MDA-MB-231 cells by a caspase-3 pathway

Abstract We investigated the cytotoxic and apoptotic effects of a methanol extract of Centaurea nerimaniae, a plant endemic in Turkey, on HeLa and MDA-MB-231 cells. Eight concentrations of C. nerimaniae extract were applied to cells, and cytotoxic effects were measured using the xCELLigence system. The TUNEL assay was used to assess apoptotic cell death and immunohistochemistry was used to determine active caspase-3 using the effective cytotoxic doses of the extract. Doses of 1.42 mg/ml C. nerimaniae inhibited the growth of HeLa cells and 3.67 mg/ml C. nerimaniae inhibited the growth of MDA-MB-231 cells in a dose- and time-dependent manner. The apoptotic indexes for HeLa and MDA-MB-231 cells were increased significantly compared to control groups. Immunohistochemistry showed that the number of caspase-3 immunostained cells increased in the extract treatment groups for both HeLa and MDA-MB-231 cells. In the MDA-MB-231 cell line, caspase-3 immunostaining was observed in nuclei and/or cytoplasm in the extract treated group. Caspase-3 activation was greater in HeLa cells than in MDA-MB-231 cells. We found that the extract of C. nerimaniae had a strong antiproliferative effect and induced apoptosis via caspase-3; MDA-MB-231 cancer cells were more resistant than HeLa cells.