Zahide Cavdar - Academia.edu (original) (raw)

Papers by Zahide Cavdar

Research paper thumbnail of Kistik Böbrek Hastalıklarının Genetiği ve Tanıda Kullanımı

Turkiye Klinikleri Journal of Nephrology Special Topics, 2012

Research paper thumbnail of Careers and Research Performance of PhD Program Graduates of Health Sciences in Turkey

Turkish Journal of Biochemistry, 2013

Research paper thumbnail of Pretreatment with Nebivolol Attenuates Level and Expression of Matrix Metalloproteinases in a Rat Model of Renal Ischemia-Reperfusion Injury

Nephrology, 2017

Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degrada... more Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a β1 -adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI. 20 Wistar albino rats were divided into three groups: sham-operated , ischemia-reperfusion, and nebivolol-pretreated . IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by gelatin zymography and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. Creatinine levels increased significantly in the ischemia-reperfusion group compared to sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group. Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.

Research paper thumbnail of The Effects of α -Lipoic Acid against Testicular Ischemia-Reperfusion Injury in Rats

The Scientific World Journal, 2012

Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adoles... more Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of αlipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.

Research paper thumbnail of Tavşan Erken Ateroskleroz Modelinde HSP47 ile Kolajen Arasındaki Endotelin Reseptöründen Bağımsız İlişki

Turkiye Klinikleri Journal of Medical Sciences, 2011

ABSTRACT Objective: Collagen in the extracellular matrix (ECM) plays an important role in modulat... more ABSTRACT Objective: Collagen in the extracellular matrix (ECM) plays an important role in modulation of response to the vascular injury during the progression of atherosclerosis and restenosis. Collagen can regulate smooth muscle cell (SMC) proliferation, migration and matrix metalloproteinase (MMP) production. Therefore, collagen turnover in the arteries is an important determinant of intimal thickening. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is thought to be essential for the processing and secretion of procollagen molecules. Endothelin (ET) is a strong chemoatractant and mitogen promoting SMC proliferation and migration. The aim of this study was to investigate the possible role of HSP47 and its relation to collagen synthesis, and the effects of a nonselective ETA/ETB receptor antagonist, TAK-044 in collar-induced early atherosclerosis model. Material and Methods: New Zealand white rabbits were divided into two groups. Both groups received vehicle (0.9% NaCl 0.8 ml/kg/day, s.c.) or TAK-044 (5 mg/kg/day, s.c.) for three weeks. On 8th day, a non-occlusive silicon collar was placed around the left carotid artery. The right carotid artery was sham-operated. HSP47 expression in carotid arteries were determined immunohistochemically. Furthermore, total collagen levels, collagen expression and type I procollagen expression were established. Results: HSP47 expression correlated with collagen expression did not change in collared arteries. TAK-044 treatment did not affect HSP47 and collagen levels. Conclusion: There was a correlation between HSP47 expression and collagen expression in carotid arteries. However, intimal thickening did not induce HSP47 expression and early collagen development. The ineffectivenes of TAK-044 suggests that ET-1 signaling may not be implicated in HSP47 and collagen in this model.

Research paper thumbnail of Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats

Molecular medicine (Cambridge, Mass.)

Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/rep... more Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/reperfusion (I/R) injury in several tissues. The aim of this study was to determine whether EPO could prevent intestinal tissue injury induced by I/R. Wistar rats were subjected to intestinal ischemia (30 min) and reperfusion (60 min). A single dose of EPO (5000 U/kg) was administered intraperitoneally at two different time points: either at five minutes before the onset of ischemia or at the onset of reperfusion. At the end of the reperfusion period, jejunum was removed for examinations. Myeloperoxidase (MPO), malondialdehyde (MDA), and antioxidant defense system were assessed by biochemical analyses. Histological evaluation was performed according to the Chiu scoring method. Endothelial nitric oxide synthase (eNOS) was demonstrated by immunohistochemistry. Apoptotic cells were determined by TUNEL staining. Compared with the sham, I/R caused intestinal tissue injury (Chiu score, 3+/-0.36 v...

Research paper thumbnail of The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model

Biotechnic & Histochemistry, 2014

Matrix metalloproteinases (MMPs) are enzymes that are responsible for degradation of extracellula... more Matrix metalloproteinases (MMPs) are enzymes that are responsible for degradation of extracellular matrix (ECM); they are involved in the pathogenesis of ischemia-re-perfusion (I-R) injury. We investigated the possible preventive effect of alpha-lipoic acid (LA) in a renal I-R injury model in rats by assessing its reducing effect on the expression and activation of MMP-2 and MMP-9 induced by I-R. Rats were assigned to four groups: control, sham-operated, I-R (saline, i.p.) and I-R+ LA (100 mg/kg, i.p.). After a right nephrectomy, I-R was induced by clamping the left renal pedicle for 1 h, followed by 6 h re-perfusion. In the sham group, a right nephrectomy was performed and left renal pedicles were dissected without clamping and the entire left kidney was excised after 6 h. LA pretreatment was started 30 min prior to induction of ischemia. Injury to tubules was evaluated using light and electron microscopy. The expressions of MMP-2 and MMP-9 were determined by immunohistochemistry and their activities were analyzed by gelatin zymography. Serum creatinine was measured using a quantitative kit based on the Jaffe colorimetric technique. Malondialdehyde (MDA) and glutathione (GSH) were analyzed using high performance liquid chromatography. Tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 were assessed using enzyme-linked immunosorbent assay (ELISA). I-R caused tubular dilatation and brush border loss. LA decreased both renal dysfunction and abnormal levels of MDA and GSH during I-R. Moreover, LA decreased significantly both MMP-2 and MMP-9 expressions and activations during I-R. TIMP-1 and TIMP-2 levels were increased significantly by LA administration. LA modulated increased MMP-2 and MMP-9 activities and decreased TIMP-1 and TIMP-2 levels during renal I-R.

Research paper thumbnail of Special-study modules in a problem-based learning medical curriculum: An innovative laboratory research practice suppporting introduction to research methodology in the undergraduate curriculum

Biochemistry and Molecular Biology Education, 2011

We describe the organization of wet-lab special-study modules (SSMs) in the Central Research Labo... more We describe the organization of wet-lab special-study modules (SSMs) in the Central Research Laboratory of Dokuz Eylü l Medical School, Izmir, Turkey with the aim of discussing the scientific, laboratory, and pedagogical aspects of this educational activity. A general introduction to the planning and functioning of these SSMs is given, along with specific examples. The wet-lab SSMs incorporate several innovative pedagogies: problem-based learning, research-based learning, practical laboratory education, team-based learning, and project-based learning. Oral and written evaluations show that the students find this activity rewarding. The wet-lab SSM model applied in the Research-Lab of Dokuz Eylü l School of Medicine represents a format which is effective in training the students in research methodology, practical laboratory work, and independent learning.

Research paper thumbnail of In vitro reoxygenation following hypoxia increases MMP-2 and TIMP-2 secretion by human umbilical vein endothelial cells

Acta biochimica Polonica, 2010

Endothelial cells lining the inner blood vessel walls play a key role in the response to hypoxia,... more Endothelial cells lining the inner blood vessel walls play a key role in the response to hypoxia, which is frequently encountered in clinical conditions such as myocardial infarction, renal ischemia and cerebral ischemia. In the present study we investigated the effects of hypoxia and hypoxia/reoxygenation on gelatinases (matrix metalloproteinase-2 and -9), their inhibitor (TIMP-2) and activator (MT1-MMP), in human umbilical vein endothelial (HUVE) cells. HUVE cells were subjected to 4 h of hypoxia or hypoxia followed by 4 and 24 h of reoxygenation. The pro- and active forms of MMP-2 and MMP-9 were analyzed by gelatin zymography; TIMP-2 protein level was assayed using ELISA, while MT1-MMP activity was measured using an activity assay. The secretion of MMP-2 proform increased significantly in cells subjected to 4 h of hypoxia followed by 4 or 24 h of reoxygenation, compared with the normoxic group. TIMP-2 protein level also increased significantly in the hypoxia/reoxygenation groups,...

Research paper thumbnail of MMP-2 and MMP-9 alteration in response to collaring in rabbits: the effects of endothelin receptor antagonism

Journal of cardiovascular pharmacology and therapeutics, 2009

Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been im... more Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels...

Research paper thumbnail of BIOCHEMICAL MARKERS IN CEREBROSPINAL FLUID (CSF) AND EVALUATION OF THE EFFECT OF CSF ON PC12 CELL LINE VIABILITY IN ALZHEIMER’S DISEASE

Research paper thumbnail of Effect of Intravenous Iron Sucrose on Oxidative Stress in Peritoneal Dialysis Patients

Renal Failure, 2007

Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continu... more Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 +/- 66.69 to 123.68 +/- 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100-400 and 400-800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.

Research paper thumbnail of Pioglitazone Reduces Peritoneal Fibrosis via Inhibition of TGF- β , MMP-2, and MMP-9 in a Model of Encapsulating Peritoneal Sclerosis

Renal Failure, 2012

Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-β) were increased in pe... more Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-β) were increased in peritoneal dialysis patients with encapsulating peritoneal sclerosis (EPS) and in chlorhexidine gluconate (CG)-induced peritoneal sclerosing animal models. Peroxisome proliferator-activated receptors (PPARs) are the major regulators of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The objective of this study was to investigate the effect of pioglitazone (Pio), a synthetic PPAR-γ ligand, on the development of peritoneal fibrosis in CG-induced EPS rats. Thirty-two Wistar albino rats were intraperitoneally injected with saline (C group n = 8) or with CG (1.5 mL/100 g; CG group, n = 8). Pio (30 mg/kg/day) was administered orally to another group of CG injected rats (the CG + Pio group, n = 8) and to another control group (Pio group, n = 8) from initiation to the end of this study. After 14 days of Pio administration, the rats were killed and the parietal and visceral peritoneum were harvested. TGF-β, MMP-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 activity assays and a morphological examination of the peritoneal tissues were performed. Pio significantly inhibited thickening of the submesothelial layer, fibrosis, and inflammation in the peritoneum. It also prevented increases in pro-MMP-2, pro-MMP-9, TIMP-1, and TGF-β activities. Pio, via MMP and TGF-β inhibition, may lessen accumulation of peritoneal extracellular matrix and fibrosis to some extent in an EPS model and might be a new approach to the amelioration of EPS.

Research paper thumbnail of The Effect of Renal Replacement Therapies on Serum Gastrointestinal System Hormones

Renal Failure, 2007

The kidney is a major site for the inactivation, degradation, and clearance of a variety of pepti... more The kidney is a major site for the inactivation, degradation, and clearance of a variety of peptide hormones. It has been shown that the uremia increases or decreases gastrointestinal system (GIS) hormones. Moreover, studies investigating the serum GIS hormones levels in chronic renal failure (CRF) were conducted mainly in a particular period of the renal replacement therapy, and the changes caused by continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) could not be fully demonstrated. In this study, we investigated the effect of CAPD and HD on serum GIS hormones (amylase, lipase, trypsinogen, and gastrin) levels in CRF patients who were diagnosed for the first time. Serum amylase, lipase, trypsinogen, and gastrin levels were measured in 36 patients who were just diagnosed with CRF, 22 patients with CAPD and 14 patients with HD. GIS hormones of these patients were measured before treatment and three months from the beginning of CAPD and HD treatment. As the control group, 20 normal healthy cases with well-matched age and gender were used. The mean serum amylase, lipase, secretin, and gastrin levels were found meaningfully decreased according to the beginning values at third months of the CAPD and HD treatment. However, they were higher than control group. In patients receiving CAPD or HD as renal replacement therapy, GIS hormone levels were found to be lower, albeit higher than the healthy control group.

Research paper thumbnail of TNF-related apoptosis-inducing ligand level in Alzheimer’s disease

Neurological Sciences, 2009

In the present study, we determined the significance of tumor necrosis factor-related apoptosis-i... more In the present study, we determined the significance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Alzheimer's disease (AD). We characterized the expression of TRAIL protein in the cerebrospinal fluid (CSF) and serum with ELISA and TRAIL mRNA in the peripheral blood mononuclear cells (PBMCs) with real-time PCR in 22 patients with AD and 20 control cases. We could not find TRAIL protein in the CSF samples. The concentration of TRAIL protein in sera from patients with AD was not different from controls. However, there was an inverse correlation between serum TRAIL levels and Mini-Mental State Examination scores in AD patients. Also we did not find significant difference in TRAIL mRNA in the PBMCs of patients with AD when compared with control group. Our data indicate that TRAIL serum level decreases in the late stage of disease.

Research paper thumbnail of Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

International Journal for Vitamin and Nutrition Research, 2012

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular u... more The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

Research paper thumbnail of Arginase in patients with breast cancer

Clinica Chimica Acta, 2003

The mean arginase activity in breast cancers (n = 80) was significantly higher than in control ti... more The mean arginase activity in breast cancers (n = 80) was significantly higher than in control tissues and it accounted for 0.31 +/- 0.23 U/g wet tissue and 0.083 +/- 0.061 U/g (P < 0.05), respectively. With the cutoff value of 0.1 U/g wet tissue, raised arginase activity was observed in 74% of tumors. The preoperative arginase activity in blood serum from women with breast cancer was 11.2 +/- 7.9 U/l (n = 115), and it was significantly higher than in 70 healthy controls, where it was 5.7 +/- 2.4 U/l (P < 0.05). With the cutoff value for normal serum arginase activity above 8.0 U/l, the activity was raised in 10% of control individuals, and in 63% of women with breast cancer. The sensitivity and specificity of the arginase test in blood serum were 63% and 60%, respectively. Two isoforms immunologically identical to human kidney arginases (L-arginine amidinohydrolase) were found in both normal and cancerous breast tissues. The level of anionic form was similar in control and cancerous tissues, whereas the cationic isoform predominated in breast cancer. The cationic isoform was the only one present in serum of both ill and healthy women, and its level was higher in patients with breast cancer. Thus, it can be concluded that the cationic isoform is responsible for the increase of arginase activity in serum of patients with breast cancer.

Research paper thumbnail of Biological markers in cerebrospinal fluid (CSF) and evaluation of in vitro effect of CSF on PC12 cell line viability in Alzheimer's disease

Cell Biochemistry and Function, 2009

The definite diagnosis of Alzheimer&a... more The definite diagnosis of Alzheimer's disease (AD) is based on post mortem pathological examination. To date, there is no laboratory test that can discriminate AD patients from healthy individuals. In the perspective of recent knowledge, there are three cerebrospinal fluid (CSF) markers which have the highest sensitivity and specificity: A beta(1-40), A beta(1-42), and p-tau. In the present study, 15 'Probable Alzheimer's Disease' (PAD) patients and 15 control subjects were included. PAD patients were selected from the patients of Dokuz Eylül University Neurology Department Dementia outpatient clinic and control subjects were selected from the patients who were undergone epidural anesthesia because of any surgical operation. The concentrations of Ab1-40, Ab1-42, and p-tau in CSF were quantified by using ELISA. Also, the effects of 'PAD patients' CSF on the survival of PC12 cell line were assessed. There was a significant decrease of Ab1-40 and increase of p-tau in patients with AD when compared with controls. Ab1-42 concentration was not significantly different between groups. There was a positive correlation between duration of the disease and CSF of p-tau concentration in patients with AD. There was no significant difference in cell line viability values between groups.

Research paper thumbnail of Original Article: Decrease in cell proliferation by an matrix metalloproteinase inhibitor, doxycycline, in a model of immune-complex nephritis

Nephrology, 2010

Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribut... more Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribute to the development of tubulointerstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). The aim of this study was to investigate the therapeutic effect of MMP inhibitor, doxycycline, administration in an experimental rat model of immune-complex nephritis (ICN). The induction of immune-complex glomerulonephritis was carried out by the administration of an i.v. dose of 2 mg bovine serum albumin (BSA) daily for 28 days after 8 weeks of s.c. immunization with 1 mg of BSA in complete Freund's adjuvant. Doxycycline (30 mg/kg) was given daily (in groups 2 and 4) by gavage for 28 days. Animals treated with doxycycline showed significant reduction in glomerular area and cell proliferation than non-treated controls. Glomerular deposition of immunoglobulin (Ig)G and C3 was less intense in treated rats than non-treated controls. Although not statistically significant, interstitial inflammation was less intense in treated rats than non-treated controls. Glomerular expression of MMP-9 by immunoflourescence was significantly inhibited in the treated group. In addition pro-MMP-2 on gelatin zymography was importantly suppressed by doxycycline in ICN. Doxycycline, in addition to its antibiotic property, may, following further investigation, provide a possible survival benefit in proliferative glomerulonephritis.

Research paper thumbnail of Kistik Böbrek Hastalıklarının Genetiği ve Tanıda Kullanımı

Turkiye Klinikleri Journal of Nephrology Special Topics, 2012

Research paper thumbnail of Careers and Research Performance of PhD Program Graduates of Health Sciences in Turkey

Turkish Journal of Biochemistry, 2013

Research paper thumbnail of Pretreatment with Nebivolol Attenuates Level and Expression of Matrix Metalloproteinases in a Rat Model of Renal Ischemia-Reperfusion Injury

Nephrology, 2017

Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degrada... more Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a β1 -adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI. 20 Wistar albino rats were divided into three groups: sham-operated , ischemia-reperfusion, and nebivolol-pretreated . IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by gelatin zymography and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. Creatinine levels increased significantly in the ischemia-reperfusion group compared to sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group. Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.

Research paper thumbnail of The Effects of α -Lipoic Acid against Testicular Ischemia-Reperfusion Injury in Rats

The Scientific World Journal, 2012

Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adoles... more Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of αlipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.

Research paper thumbnail of Tavşan Erken Ateroskleroz Modelinde HSP47 ile Kolajen Arasındaki Endotelin Reseptöründen Bağımsız İlişki

Turkiye Klinikleri Journal of Medical Sciences, 2011

ABSTRACT Objective: Collagen in the extracellular matrix (ECM) plays an important role in modulat... more ABSTRACT Objective: Collagen in the extracellular matrix (ECM) plays an important role in modulation of response to the vascular injury during the progression of atherosclerosis and restenosis. Collagen can regulate smooth muscle cell (SMC) proliferation, migration and matrix metalloproteinase (MMP) production. Therefore, collagen turnover in the arteries is an important determinant of intimal thickening. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is thought to be essential for the processing and secretion of procollagen molecules. Endothelin (ET) is a strong chemoatractant and mitogen promoting SMC proliferation and migration. The aim of this study was to investigate the possible role of HSP47 and its relation to collagen synthesis, and the effects of a nonselective ETA/ETB receptor antagonist, TAK-044 in collar-induced early atherosclerosis model. Material and Methods: New Zealand white rabbits were divided into two groups. Both groups received vehicle (0.9% NaCl 0.8 ml/kg/day, s.c.) or TAK-044 (5 mg/kg/day, s.c.) for three weeks. On 8th day, a non-occlusive silicon collar was placed around the left carotid artery. The right carotid artery was sham-operated. HSP47 expression in carotid arteries were determined immunohistochemically. Furthermore, total collagen levels, collagen expression and type I procollagen expression were established. Results: HSP47 expression correlated with collagen expression did not change in collared arteries. TAK-044 treatment did not affect HSP47 and collagen levels. Conclusion: There was a correlation between HSP47 expression and collagen expression in carotid arteries. However, intimal thickening did not induce HSP47 expression and early collagen development. The ineffectivenes of TAK-044 suggests that ET-1 signaling may not be implicated in HSP47 and collagen in this model.

Research paper thumbnail of Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats

Molecular medicine (Cambridge, Mass.)

Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/rep... more Previous studies have shown that erythropoietin (EPO) has protective effects against ischemia/reperfusion (I/R) injury in several tissues. The aim of this study was to determine whether EPO could prevent intestinal tissue injury induced by I/R. Wistar rats were subjected to intestinal ischemia (30 min) and reperfusion (60 min). A single dose of EPO (5000 U/kg) was administered intraperitoneally at two different time points: either at five minutes before the onset of ischemia or at the onset of reperfusion. At the end of the reperfusion period, jejunum was removed for examinations. Myeloperoxidase (MPO), malondialdehyde (MDA), and antioxidant defense system were assessed by biochemical analyses. Histological evaluation was performed according to the Chiu scoring method. Endothelial nitric oxide synthase (eNOS) was demonstrated by immunohistochemistry. Apoptotic cells were determined by TUNEL staining. Compared with the sham, I/R caused intestinal tissue injury (Chiu score, 3+/-0.36 v...

Research paper thumbnail of The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model

Biotechnic & Histochemistry, 2014

Matrix metalloproteinases (MMPs) are enzymes that are responsible for degradation of extracellula... more Matrix metalloproteinases (MMPs) are enzymes that are responsible for degradation of extracellular matrix (ECM); they are involved in the pathogenesis of ischemia-re-perfusion (I-R) injury. We investigated the possible preventive effect of alpha-lipoic acid (LA) in a renal I-R injury model in rats by assessing its reducing effect on the expression and activation of MMP-2 and MMP-9 induced by I-R. Rats were assigned to four groups: control, sham-operated, I-R (saline, i.p.) and I-R+ LA (100 mg/kg, i.p.). After a right nephrectomy, I-R was induced by clamping the left renal pedicle for 1 h, followed by 6 h re-perfusion. In the sham group, a right nephrectomy was performed and left renal pedicles were dissected without clamping and the entire left kidney was excised after 6 h. LA pretreatment was started 30 min prior to induction of ischemia. Injury to tubules was evaluated using light and electron microscopy. The expressions of MMP-2 and MMP-9 were determined by immunohistochemistry and their activities were analyzed by gelatin zymography. Serum creatinine was measured using a quantitative kit based on the Jaffe colorimetric technique. Malondialdehyde (MDA) and glutathione (GSH) were analyzed using high performance liquid chromatography. Tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 were assessed using enzyme-linked immunosorbent assay (ELISA). I-R caused tubular dilatation and brush border loss. LA decreased both renal dysfunction and abnormal levels of MDA and GSH during I-R. Moreover, LA decreased significantly both MMP-2 and MMP-9 expressions and activations during I-R. TIMP-1 and TIMP-2 levels were increased significantly by LA administration. LA modulated increased MMP-2 and MMP-9 activities and decreased TIMP-1 and TIMP-2 levels during renal I-R.

Research paper thumbnail of Special-study modules in a problem-based learning medical curriculum: An innovative laboratory research practice suppporting introduction to research methodology in the undergraduate curriculum

Biochemistry and Molecular Biology Education, 2011

We describe the organization of wet-lab special-study modules (SSMs) in the Central Research Labo... more We describe the organization of wet-lab special-study modules (SSMs) in the Central Research Laboratory of Dokuz Eylü l Medical School, Izmir, Turkey with the aim of discussing the scientific, laboratory, and pedagogical aspects of this educational activity. A general introduction to the planning and functioning of these SSMs is given, along with specific examples. The wet-lab SSMs incorporate several innovative pedagogies: problem-based learning, research-based learning, practical laboratory education, team-based learning, and project-based learning. Oral and written evaluations show that the students find this activity rewarding. The wet-lab SSM model applied in the Research-Lab of Dokuz Eylü l School of Medicine represents a format which is effective in training the students in research methodology, practical laboratory work, and independent learning.

Research paper thumbnail of In vitro reoxygenation following hypoxia increases MMP-2 and TIMP-2 secretion by human umbilical vein endothelial cells

Acta biochimica Polonica, 2010

Endothelial cells lining the inner blood vessel walls play a key role in the response to hypoxia,... more Endothelial cells lining the inner blood vessel walls play a key role in the response to hypoxia, which is frequently encountered in clinical conditions such as myocardial infarction, renal ischemia and cerebral ischemia. In the present study we investigated the effects of hypoxia and hypoxia/reoxygenation on gelatinases (matrix metalloproteinase-2 and -9), their inhibitor (TIMP-2) and activator (MT1-MMP), in human umbilical vein endothelial (HUVE) cells. HUVE cells were subjected to 4 h of hypoxia or hypoxia followed by 4 and 24 h of reoxygenation. The pro- and active forms of MMP-2 and MMP-9 were analyzed by gelatin zymography; TIMP-2 protein level was assayed using ELISA, while MT1-MMP activity was measured using an activity assay. The secretion of MMP-2 proform increased significantly in cells subjected to 4 h of hypoxia followed by 4 or 24 h of reoxygenation, compared with the normoxic group. TIMP-2 protein level also increased significantly in the hypoxia/reoxygenation groups,...

Research paper thumbnail of MMP-2 and MMP-9 alteration in response to collaring in rabbits: the effects of endothelin receptor antagonism

Journal of cardiovascular pharmacology and therapeutics, 2009

Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been im... more Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels...

Research paper thumbnail of BIOCHEMICAL MARKERS IN CEREBROSPINAL FLUID (CSF) AND EVALUATION OF THE EFFECT OF CSF ON PC12 CELL LINE VIABILITY IN ALZHEIMER’S DISEASE

Research paper thumbnail of Effect of Intravenous Iron Sucrose on Oxidative Stress in Peritoneal Dialysis Patients

Renal Failure, 2007

Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continu... more Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 +/- 66.69 to 123.68 +/- 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100-400 and 400-800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.

Research paper thumbnail of Pioglitazone Reduces Peritoneal Fibrosis via Inhibition of TGF- β , MMP-2, and MMP-9 in a Model of Encapsulating Peritoneal Sclerosis

Renal Failure, 2012

Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-β) were increased in pe... more Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-β) were increased in peritoneal dialysis patients with encapsulating peritoneal sclerosis (EPS) and in chlorhexidine gluconate (CG)-induced peritoneal sclerosing animal models. Peroxisome proliferator-activated receptors (PPARs) are the major regulators of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The objective of this study was to investigate the effect of pioglitazone (Pio), a synthetic PPAR-γ ligand, on the development of peritoneal fibrosis in CG-induced EPS rats. Thirty-two Wistar albino rats were intraperitoneally injected with saline (C group n = 8) or with CG (1.5 mL/100 g; CG group, n = 8). Pio (30 mg/kg/day) was administered orally to another group of CG injected rats (the CG + Pio group, n = 8) and to another control group (Pio group, n = 8) from initiation to the end of this study. After 14 days of Pio administration, the rats were killed and the parietal and visceral peritoneum were harvested. TGF-β, MMP-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 activity assays and a morphological examination of the peritoneal tissues were performed. Pio significantly inhibited thickening of the submesothelial layer, fibrosis, and inflammation in the peritoneum. It also prevented increases in pro-MMP-2, pro-MMP-9, TIMP-1, and TGF-β activities. Pio, via MMP and TGF-β inhibition, may lessen accumulation of peritoneal extracellular matrix and fibrosis to some extent in an EPS model and might be a new approach to the amelioration of EPS.

Research paper thumbnail of The Effect of Renal Replacement Therapies on Serum Gastrointestinal System Hormones

Renal Failure, 2007

The kidney is a major site for the inactivation, degradation, and clearance of a variety of pepti... more The kidney is a major site for the inactivation, degradation, and clearance of a variety of peptide hormones. It has been shown that the uremia increases or decreases gastrointestinal system (GIS) hormones. Moreover, studies investigating the serum GIS hormones levels in chronic renal failure (CRF) were conducted mainly in a particular period of the renal replacement therapy, and the changes caused by continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) could not be fully demonstrated. In this study, we investigated the effect of CAPD and HD on serum GIS hormones (amylase, lipase, trypsinogen, and gastrin) levels in CRF patients who were diagnosed for the first time. Serum amylase, lipase, trypsinogen, and gastrin levels were measured in 36 patients who were just diagnosed with CRF, 22 patients with CAPD and 14 patients with HD. GIS hormones of these patients were measured before treatment and three months from the beginning of CAPD and HD treatment. As the control group, 20 normal healthy cases with well-matched age and gender were used. The mean serum amylase, lipase, secretin, and gastrin levels were found meaningfully decreased according to the beginning values at third months of the CAPD and HD treatment. However, they were higher than control group. In patients receiving CAPD or HD as renal replacement therapy, GIS hormone levels were found to be lower, albeit higher than the healthy control group.

Research paper thumbnail of TNF-related apoptosis-inducing ligand level in Alzheimer’s disease

Neurological Sciences, 2009

In the present study, we determined the significance of tumor necrosis factor-related apoptosis-i... more In the present study, we determined the significance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Alzheimer's disease (AD). We characterized the expression of TRAIL protein in the cerebrospinal fluid (CSF) and serum with ELISA and TRAIL mRNA in the peripheral blood mononuclear cells (PBMCs) with real-time PCR in 22 patients with AD and 20 control cases. We could not find TRAIL protein in the CSF samples. The concentration of TRAIL protein in sera from patients with AD was not different from controls. However, there was an inverse correlation between serum TRAIL levels and Mini-Mental State Examination scores in AD patients. Also we did not find significant difference in TRAIL mRNA in the PBMCs of patients with AD when compared with control group. Our data indicate that TRAIL serum level decreases in the late stage of disease.

Research paper thumbnail of Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

International Journal for Vitamin and Nutrition Research, 2012

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular u... more The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

Research paper thumbnail of Arginase in patients with breast cancer

Clinica Chimica Acta, 2003

The mean arginase activity in breast cancers (n = 80) was significantly higher than in control ti... more The mean arginase activity in breast cancers (n = 80) was significantly higher than in control tissues and it accounted for 0.31 +/- 0.23 U/g wet tissue and 0.083 +/- 0.061 U/g (P < 0.05), respectively. With the cutoff value of 0.1 U/g wet tissue, raised arginase activity was observed in 74% of tumors. The preoperative arginase activity in blood serum from women with breast cancer was 11.2 +/- 7.9 U/l (n = 115), and it was significantly higher than in 70 healthy controls, where it was 5.7 +/- 2.4 U/l (P < 0.05). With the cutoff value for normal serum arginase activity above 8.0 U/l, the activity was raised in 10% of control individuals, and in 63% of women with breast cancer. The sensitivity and specificity of the arginase test in blood serum were 63% and 60%, respectively. Two isoforms immunologically identical to human kidney arginases (L-arginine amidinohydrolase) were found in both normal and cancerous breast tissues. The level of anionic form was similar in control and cancerous tissues, whereas the cationic isoform predominated in breast cancer. The cationic isoform was the only one present in serum of both ill and healthy women, and its level was higher in patients with breast cancer. Thus, it can be concluded that the cationic isoform is responsible for the increase of arginase activity in serum of patients with breast cancer.

Research paper thumbnail of Biological markers in cerebrospinal fluid (CSF) and evaluation of in vitro effect of CSF on PC12 cell line viability in Alzheimer's disease

Cell Biochemistry and Function, 2009

The definite diagnosis of Alzheimer&a... more The definite diagnosis of Alzheimer's disease (AD) is based on post mortem pathological examination. To date, there is no laboratory test that can discriminate AD patients from healthy individuals. In the perspective of recent knowledge, there are three cerebrospinal fluid (CSF) markers which have the highest sensitivity and specificity: A beta(1-40), A beta(1-42), and p-tau. In the present study, 15 'Probable Alzheimer's Disease' (PAD) patients and 15 control subjects were included. PAD patients were selected from the patients of Dokuz Eylül University Neurology Department Dementia outpatient clinic and control subjects were selected from the patients who were undergone epidural anesthesia because of any surgical operation. The concentrations of Ab1-40, Ab1-42, and p-tau in CSF were quantified by using ELISA. Also, the effects of 'PAD patients' CSF on the survival of PC12 cell line were assessed. There was a significant decrease of Ab1-40 and increase of p-tau in patients with AD when compared with controls. Ab1-42 concentration was not significantly different between groups. There was a positive correlation between duration of the disease and CSF of p-tau concentration in patients with AD. There was no significant difference in cell line viability values between groups.

Research paper thumbnail of Original Article: Decrease in cell proliferation by an matrix metalloproteinase inhibitor, doxycycline, in a model of immune-complex nephritis

Nephrology, 2010

Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribut... more Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribute to the development of tubulointerstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). The aim of this study was to investigate the therapeutic effect of MMP inhibitor, doxycycline, administration in an experimental rat model of immune-complex nephritis (ICN). The induction of immune-complex glomerulonephritis was carried out by the administration of an i.v. dose of 2 mg bovine serum albumin (BSA) daily for 28 days after 8 weeks of s.c. immunization with 1 mg of BSA in complete Freund's adjuvant. Doxycycline (30 mg/kg) was given daily (in groups 2 and 4) by gavage for 28 days. Animals treated with doxycycline showed significant reduction in glomerular area and cell proliferation than non-treated controls. Glomerular deposition of immunoglobulin (Ig)G and C3 was less intense in treated rats than non-treated controls. Although not statistically significant, interstitial inflammation was less intense in treated rats than non-treated controls. Glomerular expression of MMP-9 by immunoflourescence was significantly inhibited in the treated group. In addition pro-MMP-2 on gelatin zymography was importantly suppressed by doxycycline in ICN. Doxycycline, in addition to its antibiotic property, may, following further investigation, provide a possible survival benefit in proliferative glomerulonephritis.