Publications by authors named "Dildar Konukoglu"

44 Publications

Efficacy of Serum Angiotensin II Levels in Prognosis of Patients With Coronavirus Disease 2019.

Crit Care Med 2021 Feb 26. Epub 2021 Feb 26.

Cerrahpasa Faculty of Medicine, Department of Emergency Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey. Cerrahpasa Faculty of Medicine, Department of Medical Biochemistry, Istanbul University-Cerrahpasa, Istanbul, Turkey. Cerrahpasa Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul University-Cerrahpasa, Istanbul, Turkey. Cerrahpasa Faculty of Medicine, Department of Intensive Care, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Objectives: We aimed to determine serum angiotensin II levels in patients with coronavirus disease 2019 infection and to investigate the effect of these levels on the prognosis of the disease.

Design: The study was planned prospectively and observationally.

Setting: The study was conducted in a tertiary university hospital.

Patients: Coronavirus disease 2019 patients older than 18 years old, polymerase chain reaction test positive, with signs of pneumonia on tomography, and hospitalized were included in the study. ICU need, development of acute respiratory distress syndrome, and in-hospital mortality were considered as primary endpoints.

Interventions: Blood samples were taken from patients three times for angiotensin II levels.

Measurements And Main Results: Angiotensin II levels were studied by enzyme-linked immunosorbent assay method. The SPSS 24.0 program (Statistics Program for Social Scientists, SPSS, Chicago, IL) was used to analyze the data. A total of 112 patients were included in the study, of which 63.4% of the patients were men. The serum angiotensin II levels were statistically significantly lower in the patients with coronavirus disease 2019 compared with the healthy control group (p < 0.001). There was no statistical significance between the serum angiotensin II levels measured at three different times (p > 0.05). The serum angiotensin II levels of the patients with acute respiratory distress syndrome were found to be statistically significantly lower than those without acute respiratory distress syndrome in three samples collected at different clinical periods (p < 0.05). The angiotensin II levels of the patients who required admission to the ICU at all three times of blood sample collection were found to be statistically significantly lower than those who did not (p < 0.05). Although the serum angiotensin II levels of the patients who died were low, there was no statistically significant difference in mortality at all three times (p > 0.05).

Conclusions: The serum angiotensin II levels decrease significantly in patients with coronavirus disease 2019, and this decrease is correlated with lung damage.
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http://dx.doi.org/10.1097/CCM.0000000000004967DOI Listing
February 2021

Efficacy of Serum Angiotensin II Levels in Prognosis of Patients With Coronavirus Disease 2019.

Crit Care Med 2021 Feb 26. Epub 2021 Feb 26.

Cerrahpasa Faculty of Medicine, Department of Emergency Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey. Cerrahpasa Faculty of Medicine, Department of Medical Biochemistry, Istanbul University-Cerrahpasa, Istanbul, Turkey. Cerrahpasa Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul University-Cerrahpasa, Istanbul, Turkey. Cerrahpasa Faculty of Medicine, Department of Intensive Care, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Objectives: We aimed to determine serum angiotensin II levels in patients with coronavirus disease 2019 infection and to investigate the effect of these levels on the prognosis of the disease.

Design: The study was planned prospectively and observationally.

Setting: The study was conducted in a tertiary university hospital.

Patients: Coronavirus disease 2019 patients older than 18 years old, polymerase chain reaction test positive, with signs of pneumonia on tomography, and hospitalized were included in the study. ICU need, development of acute respiratory distress syndrome, and in-hospital mortality were considered as primary endpoints.

Interventions: Blood samples were taken from patients three times for angiotensin II levels.

Measurements And Main Results: Angiotensin II levels were studied by enzyme-linked immunosorbent assay method. The SPSS 24.0 program (Statistics Program for Social Scientists, SPSS, Chicago, IL) was used to analyze the data. A total of 112 patients were included in the study, of which 63.4% of the patients were men. The serum angiotensin II levels were statistically significantly lower in the patients with coronavirus disease 2019 compared with the healthy control group (p < 0.001). There was no statistical significance between the serum angiotensin II levels measured at three different times (p > 0.05). The serum angiotensin II levels of the patients with acute respiratory distress syndrome were found to be statistically significantly lower than those without acute respiratory distress syndrome in three samples collected at different clinical periods (p < 0.05). The angiotensin II levels of the patients who required admission to the ICU at all three times of blood sample collection were found to be statistically significantly lower than those who did not (p < 0.05). Although the serum angiotensin II levels of the patients who died were low, there was no statistically significant difference in mortality at all three times (p > 0.05).

Conclusions: The serum angiotensin II levels decrease significantly in patients with coronavirus disease 2019, and this decrease is correlated with lung damage.
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http://dx.doi.org/10.1097/CCM.0000000000004967DOI Listing
February 2021

An easy-to-use nomogram for predicting in-hospital mortality risk in COVID-19: a retrospective cohort study in a university hospital.

BMC Infect Dis 2021 Feb 5;21(1):148. Epub 2021 Feb 5.

Department of Infectious Diseases, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Kocamustafapasa, Fatih, 34098, Istanbul, Turkey.

Background: One-fifth of COVID-19 patients are seriously and critically ill cases and have a worse prognosis than non-severe cases. Although there is no specific treatment available for COVID-19, early recognition and supportive treatment may reduce the mortality. The aim of this study is to develop a functional nomogram that can be used by clinicians to estimate the risk of in-hospital mortality in patients hospitalized and treated for COVID-19 disease, and to compare the accuracy of model predictions with previous nomograms.

Methods: This retrospective study enrolled 709 patients who were over 18 years old and received inpatient treatment for COVID-19 disease. Multivariable Logistic Regression analysis was performed to assess the possible predictors of a fatal outcome. A nomogram was developed with the possible predictors and total point were calculated.

Results: Of the 709 patients treated for COVID-19, 75 (11%) died and 634 survived. The elder age, certain comorbidities (cancer, heart failure, chronic renal failure), dyspnea, lower levels of oxygen saturation and hematocrit, higher levels of C-reactive protein, aspartate aminotransferase and ferritin were independent risk factors for mortality. The prediction ability of total points was excellent (Area Under Curve = 0.922).

Conclusions: The nomogram developed in this study can be used by clinicians as a practical and effective tool in mortality risk estimation. So that with early diagnosis and intervention mortality in COVID-19 patients may be reduced.
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http://dx.doi.org/10.1186/s12879-021-05845-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862983PMC
February 2021

Factors influencing blood pressure and microalbuminuria in children with type 1 diabetes mellitus: salt or sugar?

Pediatr Nephrol 2020 07 24;35(7):1267-1276. Epub 2020 Mar 24.

Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey.

Background: The aim of the study is to identify the effect of salt intake and diabetes itself on blood pressure (BP) profile and microalbuminuria in children with type one diabetes mellitus (T1DM). Our hypothesis is that higher amount of salt consumption and/or hyperglycemia may impair blood pressure pattern in children with T1DM.

Methods: This cross-sectional study included 84 children and adolescents with T1DM (62% females, age 13.9 ± 3.2 years, disease duration 7.3 ± 3.1 years, 43% poorly controlled diabetes) and 54 aged- and sex-matched healthy children with an adequately collected 24-h urine samples. Urine sodium, creatinine, and microalbumin were measured and salt intake was assessed on the basis of sodium excretion in 24-h urine. Blood pressure profile of the children with T1DM was evaluated with 24-h ambulatory blood pressure monitoring.

Results: Compared to the children with well-controlled diabetes, children with poorly controlled diabetes had significantly higher standard deviation scores (SDS) of nighttime systolic BP (0.22 ± 1.28 vs - 0.87 ± 0.76, p = 0.003) and lower dipping in diastole (13.4 ± 5.9 vs 18.4 ± 8.1, p = 0.046). Among T1DM group, children with the highest quartile of salt intake had higher nighttime systolic and diastolic BP-SDS (0.53 ± 1.25 vs - 0.55 ± 0.73, p = 0.002 and 0.89 ± 1.19 vs 0.25 ± 0.63, p = 0.038, respectively) and lower dipping in systole compared to their counterparts (7.7 ± 5.0 vs 11.5 ± 6.1, p = 0.040). High averaged HbA1c was independently associated with higher both daytime and nighttime systolic BP-SDS (p = 0.010, p < 0.001) and nighttime diastolic BP-SDS (p = 0.001), and lower diastolic dipping (p = 0.001). High salt intake was independently associated with higher nighttime systolic BP-SDS (p = 0.002) and lower systolic dipping (p = 0.019). A 24-h MAP-SDS was the only independent risk factor for microalbuminuria (p = 0.035).

Conclusion: Beside poor diabetic control, high salt consumption appears to be an important modifiable risk factor for impaired BP pattern, which contributes to the development of diabetic kidney disease in children with T1DM.
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http://dx.doi.org/10.1007/s00467-020-04526-2DOI Listing
July 2020

Role of Alvarado score and biological indicators of C-reactive protein, procalicitonin and neopterin in diagnosis of acute appendicitis.

Ulus Travma Acil Cerrahi Derg 2019 May;25(3):229-237

Department of General Surgery, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul-Turkey.

Background: The determination of a definitive preoperative diagnosis of acute appendicitis (AA) remains a challenge; however, delays in diagnosis increase complication rates. The aim of this study was to investigate the contribution of the Alvarado score (AS) alone and the AS combined with the use of the biological indicators of C-reactive protein (CRP), procalcitonin (PCT) and neopterin (NP) in the diagnosis.

Methods: Serum was collected from 100 patients who were admitted to the general surgery clinic of Istanbul University, Cerrahpasa Medical Faculty between March 4, 2014 and July 29, 2015 with the pre-diagnosis of AA and who agreed to take part in the study. The serum samples were stored at -70°C. The patients were divided into 2 groups: AA-positive (n=60) and AA-negative (n=40). The AA positive group was divided into subgroups of complicated (n=11), uncomplicated AA (n=49) and the AS, CRP, PCT, NP levels were compared.

Results: The study population consisted of 45 men (45%) and 55 women (55%), with a mean age of 32.8+-13.7 years (range: 18-92 years). There was no significant difference between the groups in age and gender. There were 24 patients with an AS ≤4 (3 had surgery), 35 patients with an AS of 5-7 (22 had surgery), and 41 patients with an AS of 8-10 (38 had surgery). Three of the 63 patients who underwent surgery were diagnosed with a normal appendix. The serum CRP, PCT, and NP measures were found to be inadequate to make an AA diagnosis alone, these values increased the sensitivity and specificity of the AS. The biological indicators were also significant in differentiating between the complicated and uncomplicated AA groups (p<0.05).

Conclusion: Although the AS is useful, additional testing and clinical approaches are valuable to inform the diagnostic procedure. When considered alone, serum CRP, PCT and NP values are insufficient for a diagnosis of AA. However, they increased the diagnostic value of the AS and can be helpful in distinguishing complicated AA cases.
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http://dx.doi.org/10.5505/tjtes.2018.57362DOI Listing
May 2019

Effects of Cigarette Smoke on Fat Graft Survival in an Experimental Rat Model.

Aesthetic Plast Surg 2019 06 28;43(3):815-825. Epub 2019 Feb 28.

Department of Plastic Reconstructive and Aesthetics Surgery, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Introduction: A fat graft is the closest thing to being the ideal soft tissue filler. Although it has many advantages, reliability of late-term survival is a never-ending debate. Although there are observational studies that research the effect of cigarette smoke on fat graft take in clinical setting, there has not been an objective experimental animal study on the affect of smoking on fat graft survival. The aim of our study is to search if smoking has an affect on fat grafts.

Materials And Methods: Twenty-two Sprague-Dawley type rats were used. Exposure was maintained via a passive smoke exposure system. Rats were divided into three groups regarding their exposure period. At the end of the study, transferred fat grafts were extracted and weighed with a precision scale, an arterial blood sample was taken for biochemical analysis, and grafts were sent to the pathology laboratory for immunohistochemical assessment.

Results: There were meaningful differences between the control group and the other two groups in graft weight loss, serum cotinine, tissue MDA, adipose tissue/fibrosis ratio, stem cell counts, perilipin positive cell density and inflammation density. Furthermore, we detected meaningful correlations between serum cotinine, tissue MDA and graft weight loss.

Conclusion: Fat graft takes with the same mechanisms as a wound heals. So like wound healing, cigarette smoke has a negative affect on fat graft survival. A fat graft is by its nature an elective procedure so to improve our late-term success, cigarette smoke exposure should be kept to a minimum for increased reliability.

No Level Assigned: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-019-01327-3DOI Listing
June 2019

Glucagon-like peptide-1 levels and dipeptidyl peptidase-4 activity in type 2 diabetes.

Clin Invest Med 2017 10 19;40(5):E188-E199. Epub 2017 Oct 19.

University of Biruni, Medical Faculty, Department of Internal Medicine, Medicine Hospital, Istanbul, Turkey.

Purpose: Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes mellitus (T2DM) patients. This randomized controlled clinical trial aimed to investigate T2DM patients with microvascular complications with regard to possible relations among serum clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) activities.

Methods: Subject groups were defined as follows: T2DM without complications (n=25, F/M=9/16, age 53.9±11.1 years); T2DM+Retinopathy (n=25, F/M=13/12, age 63.8±7.1 years); T2DM+Nephropathy (n=25, F/M=13/12, age 58.7±14.4 years); T2DM+Neuropathy (n=25, F/M=15/10, age 63.2±9.6 years); and healthy control subjects (HC) (n=25). CLU, amylin, SFRP-4, DPP-4 and GLP-1 (total and active) activities were measured and compared in blood samples from type 2 diabetic patients with and without microvascular complications.

Results: Significantly lower levels of DPP-4 and GLP-1total (P.
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http://dx.doi.org/10.25011/cim.v40i5.28624DOI Listing
October 2017

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose.

Horm Metab Res 2017 Jun 28;49(6):434-439. Epub 2017 Mar 28.

Department of Medical Biochemistry, Cerrahpaşa Faculty of Medicine, Istanbul University, İstanbul, Turkey.

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)<27 kg/m. Subjects were categorized as normoglycemic (n=55), IFG (n=50), IGT (n=60), and DM (n=55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p<0.005), IFG (p<0.004), and IGT (p<0.001). Male subjects have significantly higher betatrophin levels than female subjects (p<0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p<0.04), IFG (p<0.01), and IGT (p<0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.
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http://dx.doi.org/10.1055/s-0043-104383DOI Listing
June 2017

Essential parameters and risk factors of the patients for diabetes care and treatment.

Diabetes Metab Syndr 2017 Nov 6;11 Suppl 1:S315-S320. Epub 2017 Mar 6.

Medipol International School of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Aim: The aim was to explore the association between Type 2 Diabetes Mellitus [T2DM] treatment satisfactions of patients regarding their socio-economic, life-style, history medication and clinical outcome in a Turkish population SUBJECT AND METHODS: A cross-sectional study conducted from February 2016 to September 2016. Of the total 1500 diabetic patients approached, 1094 (72.9%) gave their consent. Data analysis included, sociodemographic, serum lipid profiles (LDL, HDL), calcium, uric acid, blood pressure and glycated hemoglobin (HbA1c) at baseline and after six months. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) tools were used to measure the patient satisfaction.

Results: The mean and standard deviation of age among gender, there were significant differences between males (51.81±14.40) and females (49.76±13.99) (p=0.024). There were statistically significant differences between males and females regarding place of living (city 76% vs town 26%) p<0.001) and consanguinity (p=0.040). Almost of the patients with diabetes were overweight (males 44.5% vs females 41.8%) while more than a quarter (31.2%) males were obese. Among patients with diabetes, significantly larger proportion were treated for DM with insulin (females 28.8% vs males 22.5%) and 'insulin & oral anti diabetic drugs' (females 21.6% vs males 18.4%%; p<0.001) in comparison. Reported average sleeping haours was significantly more among males (6.5±1.1 vs. 6.1±1.2; p<0.001) than females. Males and females reported significantly greater improvements in mean values of blood glucose (-2.07 p<0.001; vs. -2.36; p=0.007), HbA1c (-1.72 p<0.001; vs. -1.47 p=0.038), potassium (+0.98 p<0.001; vs. +0.93 p<0.005); albumin (-3.38 p<0.001; vs. -3.60; p<0.001); billirubin (-0.69 p=0.049; vs. -0.98; p<0.001); uric acid (+11.9 p=0.017; vs. +14.3; p<0.001); systolic blood pressure (-3.86 p<0.001; vs. -3.2 p<0.001) and diastolic blood pressure (-3.17 p<0.001; vs. -3.2 p<0.001) in comparison to 6 months before. Multivariate stepwise regression analysis showed that the satisfaction DTSQ scores for HbA1c (p<0.001), h of sleep (p<0.001), neuropathy (p=0.007), diabetic education (p=0.014), SBP (mmHg) (p=0.021) DBP (mmHg) (p=0.028) were identified as significantly associated with higher treatment satisfaction.

Conclusion: The study confirms a positive correlation between diabetes patient's satisfaction with care and treatment. Females DM patients compared to males had a better satisfaction score with current treatment, unacceptably low blood glucose level, flexibility in treatment and understanding of DM.
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http://dx.doi.org/10.1016/j.dsx.2017.03.008DOI Listing
November 2017

Endothelial Dysfunction and Hypertension.

Adv Exp Med Biol 2017 ;956:511-540

Cerrahpasa Medical Faculty, Department of Biochemistry, Istanbul University, Istanbul, Turkey.

In the past, endothelium was thought to be only a mechanical barrier. Today, endothelium is known to be a tissue regulating vascular tone, cell growth and the interaction between the leukocytes, thrombocytes and the vessel wall. It also synthesizes growth factors and thrombo-regulatory molecules and responds to physical and chemical signals. Even though the term "endothelial dysfunction" is generally used for deterioration of endothelium-dependent vasodilatation; the term also includes the abnormalities between endothelium and leukocytes, thrombocytes and regulatory molecules and conditions resulting in aberrant endothelium activation. Healthy endothelium is essential for cardiovascular control. Thus, it plays an important role in pathogenesis of many diseases and cardiovascular problems such as atherosclerosis, systemic and pulmonary hypertension, cardiomyopathies and vasculitides. The aim of this chapter is to explain endothelial dysfunction and the circulating molecules of endothelial cells as they become potential targets of therapeutic approach for hypertension. This chapter reviews the roles of endothelial dysfunction in hypertension by addressing (1) the nature of endothelial function, (2) mechanisms of endothelial dysfunction and its relationship with the diseases (3) also endothelial function testing (4) the role of endothelial dysfunction and hypertension and (4) the effects of antihypertensive therapeutic options on the endothelial dysfunction. In addition to these, the role of endothelial dysfunction in white coat hypertension has been discussed. The key connections between hypertension and endothelial dysfunction are vitally important for future studies to permit new interventions to be designed and released.
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http://dx.doi.org/10.1007/5584_2016_90DOI Listing
October 2017

Oxidative stress parameters and inflammatory and immune mediators as markers of the severity of sepsis.

J Infect Dev Ctries 2016 Oct 31;10(10):1045-1052. Epub 2016 Oct 31.

Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey.

Introduction: Sepsis is a complex inflammatory syndrome with diverse etiology and wide spectrum of severity. The aim of this study was to investigate whether inflammatory mediators, in comparison with oxidative parameters, are associated with severity of sepsis.

Methodology: Plasma neopterin, adenosine deaminase (ADA), vascular cell adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-α), as inflammatory mediators, and serum nitric oxide (NOx), nitrotyrosine (NT), oxidized LDL (oxLDL) levels, serum paraoxonase 1 (PON1) activity, and erythrocyte glutathione (GSH) levels as oxidative stress parameters of 12 patients with mild sepsis, 25 patients with severe sepsis, and 20 healthy control subjects were evaluated. NOx, GSH levels and PON1 activity were determined by colorimetric methods, whereas neopterin, VCAM, ICAM, IL-1, IL-6, TNF-α, NT, and oxLDL levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: All parameters in mild and severe sepsis were significantly different from those of healthy subjects, except ADA activities. Patients with severe sepsis exhibited higher IL-6, TNF-α, NT, and oxLDL levels than patients with mild sepsis. GSH (98%, 98%), oxLDL (98%, 98%), VCAM-1 (99%, 99%), and ICAM-1 (99%, 99%) have much more sensitivitiy and specificity in sepsis.

Conclusions: Our results suggest that the oxidative stress and inflammatory response in patients with sepsis were increased and that serum IL-6, TNF-α, NT, and oxLDL levels were correlated with the severity of sepsis. Therefore, increases in these parameters may contribute to the dysfunction or failure of one or more organs, or even death, in sepsis.
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http://dx.doi.org/10.3855/jidc.7585DOI Listing
October 2016

Inflammatory hypothesis as a link between Alzheimer's disease and diabetes mellitus.

Geriatr Gerontol Int 2016 Oct 3;16(10):1161-1166. Epub 2015 Sep 3.

Department of Biochemistry, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey.

Aims: The aim of the present study was to evaluate whether there was an inflammation-mediated link between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) status.

Methods: An age-matched control group and patient groups designated as AD without treatment (AD); AD under cholinesterase inhibitors (AD-CEI); DM without treatment (DM); DM under oral antidiabetic agents (DM-OAD); AD under treatment, who had newly diagnosed DM (AD-CEI+DM); and DM under treatment, who had newly diagnosed probable AD (DM-OAD+AD) were studied. Serum inflammation status was evaluated by the determination of serum C-reactive protein (CRP), tumor necrosis factor-alpha, interleukin (IL)-1β and IL-6 levels. CRP levels were determined by an immunonephelometric method. The others were assayed by enzyme-linked immunosorbent assay methods.

Results: IL-1β levels were found to be significantly lower in the DM group than in the control group (P < 0.01). The AD group had significantly higher serum IL-1β levels than the DM group (P < 0.01). IL-6 levels were significantly higher in the AD and DM groups than in controls (P < 0.01 and P < 0.01). Serum tumor necrosis factor-alpha and CRP levels in the AD (P < 0.05 and P < 0.001, respectively) and DM groups (P < 0.05 and P < 0.001, respectively) were significantly higher when compared with the controls. The presence of AD or DM or therapies of the diseases did not significantly change in serum tumor necrosis factor-alpha levels. The AD-CEI + DM and DM-OAD+AD groups had significantly higher CRP levels than the AD-CEI group (P < 0.05) and DM-OAD groups (P < 0.001), respectively. Serum CRP levels showed a positive correlation with Mini-Mental State Examination scores (r = 0.339, P < 0.01).

Conclusion: Our findings support the presence of a low-grade systemic inflammation link between AD and DM. Geriatr Gerontol Int 2016; 16: 1161-1166.
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http://dx.doi.org/10.1111/ggi.12602DOI Listing
October 2016

Cardiovascular alterations do exist in children with stage-2 chronic kidney disease.

Clin Exp Nephrol 2016 Dec 28;20(6):926-933. Epub 2016 Jan 28.

Department of Pediatric Nephrology, Cerrahpaşa School of Medicine, İstanbul University, Cerrahpaşa, Kocamustafapaşa, İstanbul, 34098, Turkey.

Background: Cardiovascular disease (CVD) is an important complication of chronic kidney disease (CKD) in children. However, it is not well known when and how cardiovascular alterations start.

Methods: This cross-sectional, controlled study consisted of 25 patients and 28 healthy controls. 24-h ambulatory blood pressure monitoring, aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and carotid distensibility (distensibility coefficient and β stiffness index), and echocardiography were assessed to evaluate CVD. Routine biochemical parameters, fibroblast growth factor-23 (FGF23) and high sensitive C- reactive protein were measured to determine cardiovascular risk factors.

Results: Hypertension was found in 12 patients (48 %). Patients had higher FGF23 levels and aPWV-standard deviation score (SDS) as compared to the controls (p = 0.003 and p = 0.002, respectively). Aortic PWV-SDS was predicted by increased daytime systolic blood pressure load (β = 0.512, p = 0.009, R  = 0.262). Neither cIMT nor distensibility differed between the groups; however, older age and high level of FGF23 were independent predictors of β stiffness index in patients (β = 0.507, p = 0.005, R  = 0.461 and β = 0.502, p = 0.005, R  = 0.461, respectively). As compared to controls, patients had worse left ventricular diastolic function [lower E/A ratio p = 0.006) and increased left atrial dimension (p < 0.001)].

Conclusions: Cardiovascular deteriorations appear in children with stage-2 CKD. Good control of BP and decreasing the level of FGF23 may be useful to slow down the progression of cardiovascular complications.
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http://dx.doi.org/10.1007/s10157-016-1234-3DOI Listing
December 2016

The impact of depression and ghrelin on body weight in migraineurs.

J Headache Pain 2014 Apr 24;15:23. Epub 2014 Apr 24.

Neurology Department, Istanbul University Cerrahpaşa School of Medicine, Istanbul, Turkey.

Background: Comorbidity of migraine with anxiety and depression may play a role in the link between migraine and obesity. We examined the moderating and mediating roles of ghrelin in the relationship between depression (and anxiety) and body weight in newly diagnosed migraineurs.

Methods: Participants were 63 newly diagnosed migraine patients (using the ICHD-II criteria) and 42 healthy volunteers. Body mass index (BMI) was calculated by measuring height and weight. Ghrelin was assessed at fasting. Depression was assessed with the Hamilton Depression scale, and anxiety with the Hamilton Anxiety scale.

Results: The data did not support the mediating role of ghrelin in the relationship between depression (or anxiety) and BMI for either the migraine or the control group. The interaction between ghrelin and depression as well as anxiety was significant for the migraine group, but not for the control group. Depressed (or anxious) migraineurs had a positive association between ghrelin and BMI, whereas for the non-depressed (or non-anxious) migraineurs this association was negative.

Conclusions: Depression and anxiety moderated the effect of ghrelin on BMI for migraineurs. Management of anxiety and depression might be regarded as part of migraine treatment.
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http://dx.doi.org/10.1186/1129-2377-15-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016645PMC
April 2014

Total antioxidant status and markers of oxidative stress in subjects with normal or impaired glucose regulation (IFG, IGT) in diabetic patients.

Scand J Clin Lab Invest 2013 Dec 23;73(8):641-9. Epub 2013 Oct 23.

Kırklareli University, School of Health , Kırklareli.

Background: We investigated the ischemia-modified albumin (IMA), advanced oxidation protein products (AOPPs), prooxidants-antioxidants balance (PAB), and ferric reducing antioxidant power (FRAP) concentrations in patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM) and compared the results to those of normoglycemic individuals at baseline and 2 hours after glucose loading.

Methods: An oral glucose tolerance test was performed on age-matched subjects (n = 110) with a body mass index (BMI) < 27 kg/m(2). Subjects were categorized as normoglycemic (n = 35), IFG (n = 25), IGT (n = 30) and DM (n = 20) according to the WHO criteria. The IMA, AOPP, PAB, FRAP concentrations were determined by colorimetric methods.

Results: At baseline, the AOPP concentrations were significantly higher in subjects with IFG and DM compared to normoglycemic subjects (p < 0.01 for all cases). The IFG, IGT and DM patients had a significantly higher IMA at baseline when compared with the normoglycemic individuals (p < 0.001 for all cases). The IMA in IFG subjects was significantly elevated (p < 0.05), while in DM patients, the IMA was significantly decreased (p < 0.001) after glucose loading with respect to baseline concentrations. Following glucose loading, the PAB was significantly decreased from baseline concentrations in normoglycemic individuals (p < 0.001) and in the IFG (p < 0.001) and IGT (p < 0.001) patients.

Conclusion: In subjects with impaired glucose metabolism, the hyperglycemia is associated with increased IMA, AOPP and PAB concentrations. Increased IMA in subjects with IFG and decreased FRAP concentrations in subjects with IGT after glucose loading suggests that an increase in glucose concentrations can lead to tissue damage by increasing oxidative stress.
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http://dx.doi.org/10.3109/00365513.2013.846477DOI Listing
December 2013

The effects of atorvastatin on oxidative stress in L-NAME-treated rats.

Scand J Clin Lab Invest 2013 Oct 12;73(7):591-7. Epub 2013 Sep 12.

Department of Biochemistry, Yildiz Technical University , Istanbul.

Objectives: Current evidence suggests that the beneficial vascular effects of statins are not limited to the statins' lipid-lowering properties; these drugs can also improve vascular endothelial cell function. Nω-nitro-l-arginine methyl ester (L-NAME) is a potent synthetic nitric oxide inhibitor, and long-term oral L-NAME treatment is used to induce vascular lesions in experimental animal models.

Methods: We determined the effects of statins on protein carbonyl (PCO), lipid hydroperoxides (LHP), oxidized low-density lipoproteins (ox-LDL) and antioxidants such as paraoxonase 1 (PON1) and total thiols (T-SH) in long-term L-NAME-treated rats. Adult male Wistar rats were divided into three groups, namely, control, L-NAME-treated (1 mg/mL in drinking water for three weeks), and atorvastatin plus L-NAME-treated (4 mg/kg/day atorvastatin for 1 week during the third week of L-NAME treatment) groups.

Results: In the L-NAME group, the ox-LDL, LHP and PCO were higher and the PON1 and T-SH were lower than the concentrations observed for the controls. When compared with the L-NAME group, the L-NAME plus atorvastatin group had significantly lower ox-LDL and LHP and higher PON1 activities. Additionally, the elevated total cholesterol (TC) and low-density lipoprotein-C (LDL-C) in the L-NAME group were decreased by atorvastatin administration. TC and LDL-C were positively correlated with ox-LDL and LHP and negatively correlated with PON1 in all groups. High-density lipoprotein-C (HDL-C) was negatively correlated with ox-LDL.

Conclusion: PON1 prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids; its activity showed a pronounced decrease in the L-NAME treatment group and was increased in the atorvastatin group. Based on our findings, we concluded that the atorvastatin had HDL-related antioxidant activity as well as lipid-lowering properties.
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http://dx.doi.org/10.3109/00365513.2013.828241DOI Listing
October 2013

Serum neurotrophic factor levels in patients with type 2 diabetes mellitus: relationship to metabolic syndrome components.

Clin Lab 2013 ;59(3-4):369-74

Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Biochemistry, Istanbul, Turkey.

Background: It has been thought that neurotrophins have metabotrophic effects and take part in the carbohydrate and lipid metabolism. The aim of the present study is to examine the levels of neurotrophins in type 2 diabetes mellitus (T2DM) and whether the levels are linked to the components of metabolic syndrome.

Methods: 90 patients and 35 healthy controls were enrolled in this study. The brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 were measured using an enzyme-linked immunosorbent assay. Plasma glucose, insulin, systolic blood pressure, diastolic blood pressure, and body mass index were measured, and, for each subject, the homeostasis model assessment of insulin resistance was calculated as the index of metabolic syndrome.

Results: The serum levels of brain-derived neurotrophic factor and neurotrophin-3 levels were higher, nerve growth factor lower in the T2DM patients than those of healthy controls (p < 0.001, p < 0. 001, and p < 0.001, respectively). The neurotrophic factor levels did not display any difference with respect to gender. The brain-derived neurotrophic factor was correlated with neurotrophin-3 level in female T2DM patients. In the male patients, brain-derived neurotrophic factor was correlated positively with plasma insulin and the homeostasis model assessment of insulin resistance; neurotrophin-3 was correlated positively with both systolic blood pressure and diastolic blood pressure, and nerve growth factor was correlated negatively with plasma glucose.

Conclusions: We thought that the changes in the serum neurotrophic factor levels were associated with metabolic syndrome components in T2DM.
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http://dx.doi.org/10.7754/clin.lab.2012.120404DOI Listing
June 2013

Comparison of plasma viscosity as a marker of endothelial dysfunction with nitric oxide and asymmetric dimethylarginine in subjects with dyslipidemia.

Clin Hemorheol Microcirc 2014 ;57(4):315-23

Istanbul University, Cerrahpasa Faculty of Medicine, Department of Biophyshics, Istanbul, Turkey.

Objective: In this study, we aimed to investigate the alterations in plasma viscosity and whether there was a relationship between plasma viscosity and endothelial dysfunction markers such as nitric oxide (NOx), asymmetric dimethylarginine (ADMA) and oxidized Low Density Lipoprotein (oxLDL) in dyslipidemic subjects.

Material And Method: 35 subjects with normolipidemia and 30 subjects with hyperlipidemia were involved in this study. Dyslipidemia was defined as total cholesterol levels ≥200 mg/dL and/or triglyceride level ≥150 mg/dL. Plasma total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, total protein, albumin levels and NOx were determined by enzymatic methods using commercial kits. Plasma ADMA concentrations and serum levels of total oxLDL were determined by ELISA. Plasma viscosity was measured by Harkness capillary viscometer.

Result: Plasma viscosity, ADMA and oxLDL values were significantly higher in subjects with dyslipidemia than in subjects with normolipidemia. Plasma NOx concentration was decreased in dyslipidemic subjects compared to the normo-lipidemic subjects. We found that fibrinogen had no effect upon plasma viscosity in selected patients with dyslipidemia.

Conclusion: Our results demonstrated that the rheological impairment of dyslipidemic patients was related with endothelial dysfunction and this was a possible cause of both micro and macrovascular complications. Therefore, as plasma viscosity is also a sensitive parameter, it can add useful information about the diagnosis and treatment of various disorders, and it should be utilized more frequently in clinical medicine.
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http://dx.doi.org/10.3233/CH-131706DOI Listing
July 2015

Serum brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3 levels in dementia.

Acta Neurol Belg 2012 Sep 28;112(3):255-60. Epub 2012 Jun 28.

Ataköy Konakları, D2-1, Daire 10, Bakırköy, Istanbul, Turkey.

The aim of this study is to measure serum levels of neurotropic factor (NF) in patients with dementia. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) were determined in Alzheimer's dementia patients without medication (AD; n: 22), Alzheimer's dementia patients receiving cholinesterase inhibitor (CEI) treatment (AD + CEI; n: 32) and vascular dementia patients receiving CEI treatment (VaD + CEI; n: 27) and the age-matched control group (n: 20). NGF levels were detected to be significantly higher in the control group than in AD group (P < 0.001). BDNF and NT-3 levels in AD group were not significantly different from control group's levels. NGF levels in AD + CEI group were significantly higher than in AD group (P < 0.05). There was also no significant difference in serum neurotrophic factor levels between AD + CEI and VaD + CEI group. A positive correlation between BDNF and Mini Mental State Examination (MMSE) scores (r: 0.422, P < 0.01) in AD group and a negative correlation between BDNF and MMSE scores in the AD + CEI group (r: -0.357, P < 0.005) were obtained. In conclusion, our results suggest that while serum NGF levels are associated with the presence of dementia, serum BDNF levels may be associated with the severity of Alzheimer's dementia. However, future studies are required to determine the importance of NFs.
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http://dx.doi.org/10.1007/s13760-012-0101-6DOI Listing
September 2012

Plasma oxidative and inflammatory markers in patients with idiopathic Parkinson's disease.

Acta Neurol Belg 2012 Jun 9;112(2):155-9. Epub 2012 Feb 9.

Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Parkinson's disease (PD) is the most common neurodegenerative disorder after alzheimer's disease. Neuroinflammation and oxidative damage are implicated to be responsible for the pathogenesis of neurodegenerative diseases. However, there are a few studies showing the changes in the biomarkers for neuroinflammation and oxidative damage in neurodegenerative diseases. In our study we aimed to examine the role of the molecules that are involved in oxidative stress and inflammation in PD patients taking L: -dopa treatment. Oxidized-LDL (ox-LDL), high-sensitivity C-reactive protein (hs-CRP) and the soluble intracellular adhesion molecule (ICAM) were chosen as biomarkers for systemic inflammation and oxidative damage. The patients were classified according to the Hoehn-Yahr staging system. Forty-five idiopathic L: -dopa-given PD patients and 25 age-matched healthy controls were examined. Plasma ox-LDL and ICAM levels were significantly higher in PD patients when compared with controls (p < 0.001 and p < 0.05, respectively). PD patients at all stages had significantly higher plasma ox-LDL levels than controls (p < 0.001). Plasma ICAM levels at stage 1 and 2 and CRP levels at stage 2 patients were significantly higher than controls (p < 0.05, p < 0.05, and p < 0.01, respectively). We insist that further studies have to be conducted to establish neuroinflammation and oxidative damage in PD. Establishing the roles of these pathological processes in PD might be the key to effective therapy at an early stage by antioxidants and/or anti-inflammatory drugs.
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http://dx.doi.org/10.1007/s13760-012-0015-3DOI Listing
June 2012

Serum nitrosative stress levels are increased in Alzheimer disease but not in vascular dementia.

Alzheimer Dis Assoc Disord 2010 Apr-Jun;24(2):194-7

Department of Biochemistry, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.

The aim of this study was to investigate whether there is a difference between Alzheimer disease (AD) dementia and pure vascular dementia (VaD) in relation to nitrosative stress levels. We determined serum nitric oxide (NO), oxidized low-density lipoproteins (ox-LDL), and 3-nitrotyrosine levels (3-NT) in healthy elderly individuals (controls, n=15, mean age=73.4+/-7.9 y), AD patients (n=30; mean age=71.2+/-12.7 y) and VaD patients (n=20; mean age=75.2+/-7.5 y). Patients were under anticholinesterase drug therapy. Our results showed that serum NO and ox-LDL levels in AD patients group were significantly higher than in both controls (P<0.001 and P<0.001) and VaD patients (P<0.01 and P<0.001). However, no significant differences in plasma NO and ox-LDL levels were found between VaD and controls. Our study did not reveal significant differences in plasma 3-NT values of dementia patients when compared with controls. There was a significant negative correlation between Mini-Mental State Examination score and serum NO levels in dementia patients (r=-0.349, P<0.01). Serum NO levels were also positively correlated with serum ox-LDL levels (r=0.358, P<0.01). In conclusion, elevation in serum levels of NO was present in probable AD patients but not in VaD patients, and this seems to be related to both ox-LDL levels and cognitive status.
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http://dx.doi.org/10.1097/WAD.0b013e3181c53d0dDOI Listing
August 2010

Increased maternal serum and cord blood fibronectin concentrations in preeclampsia are associated with higher placental hyaluronic acid and hydroxyproline content.

Hypertens Pregnancy 2010 Jan;29(2):153-62

Istanbul University, Cerrahpaşa Medical Faculty, Department of Biochemistry, Istanbul, Turkey.

Background: Total or cellular fibronectin (FN) determinations have been used to differentiate between normal and preeclamptic pregnants. The purpose of this study was to examine the relationship between maternal serum FN levels and the extracellular matrix molecule contents of placental tissue, such as FN, hyaluronic acid (HA) and hydroxyproline (HP) levels.

Material And Methods: We obtained maternal blood samples and placental tissue samples from healthy (n = 17, controls) and preeclamptic pregnants (n = 29). We also obtained cord blood samples for FN and HA determination from the same patients. FN and HA concentrations in the placenta and maternal and cord blood were measured by and enzyme-linked immunosorbent assay and HP contents in the placenta were measured by a colorimetric assay.

Results: FN levels in maternal serum, cord blood, and placenta were significantly higher in preeclamptics than in controls (p<0.001, p<0.001 and p<0.05, respectively). HA concentrations in the cord blood and placenta were found to be elevated in preeclamptics (p<0.05 and p<0.01). Preeclamptics had significantly higher placental HP levels than controls (p<0.001). Similar statistically significant results were obtained when the pregnant subjects classified as nulliparous and multiparous. There was no difference in ECM molecule levels between nulliporous and multiparous women in preeclamptic pregnant group. In regression analysis maternal serum FN levels were correlated with placental HA and HP levels (p<0.01 and p<0.01). There was a positive correlation between cord blood FN and both placental HP (p<001) and HA levels (p<0.01). FN levels in maternal serum, cord blood, and placenta were also negative correlated with fetal birth weight (p<0.01, p<0.05 and p<0.05, respectively).

Conclusion: FN in maternal serum, cord blood, and placenta is increased with elevated placental HA and HP levels, probably reflecting placental basement membrane alterations during preeclampsia.
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http://dx.doi.org/10.3109/10641950902968619DOI Listing
January 2010

Relationship among plasma secretory phospholipase A2, oxidized low density lipoprotein & paraoxonase activities in hypertensive subjects treated with angiotensin converting enzyme inhibitors.

Indian J Med Res 2009 Apr;129(4):390-4

Istanbul University, Cerrahpasa Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.

Background & Objective: Secretory phospholipase A(2) (sPLA(2)) and oxidized low density lipoprotein (oxLDL) are considered as oxidative and inflammatory markers. The effects of oxLDL have been shown to be inhibited by paraoxonase (PON1). This study was undertaken to investigate the relationship between oxidative and inflammatory markers in hypertensive patients with or without antihypertensive drug treatment.

Methods: Newly diagnosed hypertensive patients (n=35) and hypertensive patients who had been taking angiotensin converting enzyme (ACE) inhibitors as antihypertensive therapy (10 or 20 mg/day for 9 +/- 2 wk; n=35) and age-matched normotensive subjects (controls; n=20) were included in this study. Plasma sPLA(2), oxLDL and PON1 activities were determined.

Results: Hypertensives had higher plasma oxLDL and sPLA(2) levels (P<0.01) and lower PON1 levels than the controls (P<0.01). Treated hypertensives had lower plasma sPLA< and oxLDL levels and higher PON1 activities than hypertensives (P<0.01). sPLA(2) was positively correlated with oxLDL (r=0.433, P<0.01) and negatively correlated with plasma PON1 (r=-0.540, P<0.01) in untreated hypertensives. In controls and treated hypertensives, plasma PON1 was positively correlated with oxLDL (r=0.455, r=0.429, P<0.01, respectively) and sPLA(2) (r=0.450, r=0.506, P<0.01, respectively).

Interpretation & Conclusion: Reduction in PON1 activity and elevation in both sPLA(2) activities and oxLDL levels might be involved in elevated oxidative stress and inflammation. ACE inhibitor treatment may help reduce inflammation and oxidative stress in hypertensives.
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April 2009

Preventive effects of curcumin on different aspiration material-induced lung injury in rats.

Pediatr Surg Int 2009 Jan 12;25(1):83-92. Epub 2008 Nov 12.

Department of Pediatrics, Trakya University Faculty of Medicine, Edirne, Turkey.

Purpose: We have studied whether curcumin protects different pulmonary aspiration material-induced lung injury in rats.

Materials And Methods: The experiments were designed in 60 Sprague-Dawley rats, randomly allotted into one of six groups (n=10): normal saline (NS, control), enteral formula (Biosorb Energy Plus, BIO), hydrochloric acid (HCl), NS+curcumin-treated, BIO+curcumin-treated, and HCl+curcumin-treated. NS, BIO, HCl were injected in to the lungs. The rats received curcumin twice daily only for 7 days. Seven days later, both lungs in all groups were examined histopathologically, immunohistochemically, and biochemically. Histopathologic examination was performed according to the presence of peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, alveolar exudate, alveolar histiocytes, interstitial fibrosis, granuloma, and necrosis formation. Immunohistochemical assessments were examined for the activity of inducible nitric oxide synthase (iNOS) and the expression of surfactant protein D (SP-D). Malondialdehyde (MDA), hydroxyproline (HP), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity were measured in the lung tissue.

Results: Our findings show that curcumin inhibits the inflammatory response reducing significantly (P<0.05) all histopathological parameters in different pulmonary aspiration models. Pulmonary aspiration significantly increased the tissue HP content, MDA levels and decreased the antioxidant enzyme (SOD, GSH-Px) activities. Curcumin treatment significantly decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px enzymes in the tissues. Furthermore, our data suggest that there is a significant reduction in the activity of iNOS and a rise in the expression of SP-D in lung tissue of different pulmonary aspiration models with curcumin therapy.

Conclusion: Our findings support the use of curcumin as a potential therapeutic agent in acute lung injury.
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http://dx.doi.org/10.1007/s00383-008-2282-xDOI Listing
January 2009

The effects of renal replacement therapy on plasma, asymmetric dimethylarginine, nitric oxide and C-reactive protein levels.

Clin Invest Med 2008 ;31(1):E1-7

Istanbul University, Cerrahpasa Medical Faculty, Department of Biochemistry, Istanbul, Turkey.

Purpose: Asymmetric dimethylarginine (ADMA), nitric oxide (NOx), and C-reactive protein (CRP) are important risk factors for endothelial dysfunction and mortality in the end stage renal diseases population. The aim of the study was to investigate the relationship between renal replacement therapy and endothelial dysfunction.

Methods: Plasma NOx, ADMA and CRP levels were examined in randomized selected 30 patients with chronic kidney diseases (CKD), 28 patients receiving continuous ambulatory peritoneal dialysis (PD) and 30 patients receiving regular hemodialysis (HD) and age-matched 20 healthy controls. The duration of dialysis was from 4, 5 to 11, and 6 years, respectively.

Results: CKD patients had higher plasma ADMA (1.26+/-0.53 micromol/L) and CRP levels (1.02+/-025 mg/L) and lower NOx levels (28.6+/-5.4 micromol/L) than controls (0.45+/-0.20; 0.65+/- 0.45; 32.5+/-37 respectively, P < 0.001). Plasma NOx and CRP levels were higher in HD patients (32.9+/-5.5 micromol/L, P < 0.05 and 4.59+/-3.18 mg/L, P < 0.001) and plasma ADMA and CRP levels were higher in PD patients (1.82+/-0.98 micromol/L, P < 0.001 and 2.40+/-1.53 mg/L, P < 0.001) than in CKD patients. PD patients had higher plasma ADMA levels (P < 0.05) and lower plasma NOx and CRP levels than HD patients (P < 0.001 and P < 0.001). Plasma ADMA levels were negatively correlated with NOx levels in all patient groups (P < 0.001). Plasma CRP levels in CKD and HD patients were positively correlated with plasma urea levels (r:0,437, P < 0,001) and duration of dialysis (r:0,370, P < 0.01), respectively.

Conclusion: CRP and ADMA may be emerging as important risk factors for atherosclerosis in dialysis patients. Reduced NO elaboration secondary to accumulation of ADMA and elevated inflammation may be important pathogenic factors for endothelial dysfunction in both dialysis treatment strategies.
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http://dx.doi.org/10.25011/cim.v31i1.3135DOI Listing
June 2008

The relationship between plasma asymmetrical dimethyl-L-arginine and inflammation and adhesion molecule levels in subjects with normal, impaired, and diabetic glucose tolerance.

Metabolism 2008 Jan;57(1):110-5

Istanbul University, Cerrahpasa Faculty of Medicine, Department of Biochemistry, Istanbul 34303, Turkey.

Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. To evaluate the effects of acute hyperglycemia on endothelial dysfunction and inflammation, plasma asymmetrical dimethyl-l-arginine (ADMA), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, and C-reactive protein (CRP) levels and secretory phospholipase A(2) (sPLA(2)) activities were measured in subjects with normal (n = 35), impaired (IGT) (n = 25), and diabetic (DGT) (n = 20) glucose tolerance. At baseline, plasma ADMA, sICAM-1, and CRP concentrations and plasma sPLA(2) activities were higher in both the IGT and DGT groups than in the normal glucose tolerance group (for each comparison, each P < .001). Patients with DGT have higher plasma ADMA and sICAM-1 concentrations than patients with IGT (for each, P < .001).Two hours after glucose loading, plasma ADMA and CRP concentrations and sPLA(2) activities were significantly elevated in the 3 groups when compared with baseline levels (for each comparison, P < .001). Plasma vascular cell adhesion molecule 1 and sICAM-1 concentrations were found to be elevated from baseline levels after glucose loading in the IGT and DGT groups (for each comparison, P < .001). Correlation analysis at baseline suggested that there was a significant relationship between ADMA and inflammation and soluble adhesion markers in the studied groups. In conclusion, plasma concentrations of ADMA and of inflammation and adhesion molecules were elevated in the prediabetic state. A complex interrelation could exist between ADMA and inflammation, and mechanisms involved in endothelial dysfunction are multifactorial at the prediabetic and diabetic state.
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http://dx.doi.org/10.1016/j.metabol.2007.08.013DOI Listing
January 2008

Plasma protein carbonyl and thiol stress before and after laparoscopic gastric banding in morbidly obese patients.

Obes Surg 2007 Oct;17(10):1367-73

Istanbul University, Cerrahpasa Medical Faculty, Department of Biochemistry, Turkey.

Background: The aim of this study is to examine the relationship between oxidative plasma protein and thiol stress and weight loss after laparoscopic adjustable gastric banding (LAGB).

Methods: Plasma protein carbonyl (PCO) concentration as a marker of protein oxidation, plasma thiol (P-SH) and erythrocyte glutathione concentration (GSH, major intracellular thiol), as an antioxidant and metabolic markers, such as Homeostatic Model Assessment - Insulin resistance (HOMA-IR), BMI and plasma lipids were determined in morbidly obese patients (n 22, mean age 34.7 +/- 11 years, BMI 48.4 +/- 6.4 kg/m2) at baseline and 1 and 6 months after operation. Baseline levels in patients were also compared with the levels in age-matched controls (n 20, BMI 21.3 +/- 1.8 kg/m2). Plasma PCO and thiols and erythrocyte GSH concentrations were determined spectrophotometrically.

Results: Plasma PCO were significantly higher and plasma and erythrocyte thiol concentrations were significantly lower in morbidly obese patients than in controls (for each comparison, P<0.01). BMI, plasma triglycerides and HOMA-IR were positively correlated with plasma PCO and negatively correlated with plasma P-SH and erythrocyte GSH (for each comparison, P<0.01). Plasma HDL-cholesterol levels were positively correlated with plasma erythrocyte GSH (r = 0.405, P<0.01) and negative correlated with plasma PCO (r = -0.273, P<0.01). One and 6 months after the LAGB operation, total weight loss was 13.2 +/- 6.3 and 35.5 +/- 7.5 kg, respectively. Plasma PCO concentrations were decreased and P-SH and erythrocyte GSH concentrations were elevated following weight loss (for each, P<0.01). Only plasma P-SH levels were restored to the control levels 6 months after LAGB.

Conclusions: Obesity and insulin resistance appear to be associated with plasma protein oxidation and thiol concentrations. Protein and thiol oxidative stress was improved by weight loss after LAGB in the short-term.
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http://dx.doi.org/10.1007/s11695-007-9242-8DOI Listing
October 2007

Relation of serum vascular endothelial growth factor as an angiogenesis biomarker with nitric oxide & urokinase-type plasminogen activator in breast cancer patients.

Indian J Med Res 2007 Jun;125(6):747-51

Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.

Background & Objective: The primary mediator of angiogenesis is vascular endothelial growth factor (VEGF). It is well documented that angiogenic activity in human cancer depends on nitric oxide (NO) levels in tissues. Additionally, urokinase type plasminogen activator (u-PA) plays a role in cell adhesion and migration. Serum VEGF and its relationship between NO and u-PA concentrations are poorly reported in breast cancer patients. The aim of this study was to investigate the relationship between serum levels of VEGF and NO and u-PA in patients with breast cancer.

Methods: Serum concentrations of VEGF, NO and u-PA were measured in groups of pre-operative breast cancer patients without metastasis (n=20), post-operative breast cancer patients without metastasis (four wk after the operation, n=20), breast cancer patients with metastasis (n=23), patients with benign breast disease (n=11) and healthy female controls (n=20).

Results: There was no difference in serum concentrations of VEGF, NO and u-PA between controls and patients with benign breast disease. Serum VEGF, NO and u-PA concentrations were significantly higher in pre-operative breast cancer patients than in controls and in patients with benign breast diseases (P<0.01). Post-operative breast cancer patients without metastasis had significantly lower serum VEGF and u-PA concentrations than the pre-operative patients (P<0.01). In breast cancer patients with metastasis, serum VEGF, and u-PA were significantly higher than post-operative nonmetastatic patients (P<0.01). Serum VEGF concentrations were positively correlated with serum uPA in all of the patients groups (r=0.886, P<0.01). Serum VEGF levels were positively correlated with serum NO levels in breast cancer patients with metastasis (r= 0.386, P<0.05).

Interpretation & Conclusion: Our results demonstrated that the angiogenic activity was increased in patients with breast cancer. Elevated VEGF levels as an angiogenesis marker may be associated with uPA. VEGF, NO and uPA seem to be associated with the angiogenetic and metastatic process of breast cancer.
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June 2007

Plasma adhesion and inflammation markers: asymmetrical dimethyl-L-arginine and secretory phospholipase A2 concentrations before and after laparoscopic gastric banding in morbidly obese patients.

Obes Surg 2007 May;17(5):672-8

Istanbul University, Cerrahpasa Medical Faculty, Department of Biochemistry, Istanbul, Turkey.

Background: The aim of this study was to examine the relationship between subclinical inflammation and weight loss by laparoscopic adjustable gastric banding (LAGB).

Methods: Plasma concentrations of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), sensitive C-Reactive Protein (sCRP), asymmetrical dimethyl-L-arginine (ADMA), Secretory Phospholipase A2 (sPLA2), and metabolic markers, such as homeostatic model assessment insulin resistance (HOMA-IR) and body mass index (BMI) were determined in morbidly obese patients (n=18, BMI 48.6 +/- 1.7 kg/m2) at baseline and 1 month after operations. Baseline levels in patients were also compared with age-matched controls (n=20, BMI 21.3 +/- 1.8 kg/m2). Plasma ICAM-1, VCAM, sCRP and ADMA, and sPLA2 concentrations were determined by enzyme-linked immunoassay methods and colorimetric method, respectively.

Results: Plasma sCRP, ICAM-1, ADMA and sPLA2 concentrations and HOMA-IR were significantly higher in morbidly obese patients than in controls (for each, P<0.01). Plasma VCAM-1 concentration was not changed in obese patients. HOMA-IR was significantly correlated with ICAM-1, ADMA and sPLA2 in the obese group at baseline (for each, P<0.01). There was a significant correlation between plasma sCRP and plasma glucose, VCAM-1, ICAM-1, ADMA and sPLA2 concentrations (for each, P<0.01). 1 month after LAGB, mean body weight loss was 13.2 +/- 6.3 kg, and plasma sCRP and ADMA concentrations and HOMA-IR and BMI were significantly decreased (for each, P<0.01). However, these levels cannot be decreased to the levels of the controls.

Conclusion: Obesity and insulin resistance appear to be associated with low-grade inflammation and endothelial dysfunction. Insulin resistance and endothelial dysfunction were improved by weight loss after LAGB.
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http://dx.doi.org/10.1007/s11695-007-9113-3DOI Listing
May 2007

Abdominal aortic aneurysm or aortic occlusive disease: role of trace element imbalance.

Angiology 2007 Apr-May;58(2):191-5

Department of Cardiovascular Surgery, Sureyyapasa Thoracic and Cardiovascular Disease Hospital, Istanbul, Turkey.

The nature of the relationship between atheromatous disease and degenerative aneurysm is yet to be defined. The purpose of this study was to compare tissue Fe, Cu, Zn, and thiobarbituric acid reactive substances (TBARS) levels (as a marker of lipid peroxidation) in the abdominal aorta in relation to the development of aneurysmal and occlusive disease in the infrarenal aorta. This was a prospective clinical study in an institutional referral center, in hospitalized patients. Eighty male patients who underwent surgery for abdominal aortic aneurysm (AAA) or aortic occlusive disease (AOD) were included in the study. Age, risk factors and comorbid conditions were recorded, including diabetes mellitus, hypertension, coronary artery disease, smoking, and chronic obstructive pulmonary disease. Aortic wall biopsies were collected at operation from the anterolateral section of the infrarenal aorta. Tissue Fe, Cu, Zn, and TBARS levels were determined. The mean age of the AAA group was 66.2 (56-75) years and of the AOD group 57.8 (47-72) years (p <0.001). There was a higher prevalence of hypertension in AAA patients compared to AOD patients (62.5%, 35% respectively; p <0.05). The comparison of tissue Zn levels showed no significant difference. Tissue levels of Fe, Cu, and TBARS were found to be higher in the AAA group, compared with the AOD group (p<0.001 for each). These results suggest that higher oxidative stress as a result of higher Fe and Cu levels in the AAA, compared with AOD, may be one of the contributing factors in aneurysmal formation as a result of promoted wall erosion.
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http://dx.doi.org/10.1177/0003319707300354DOI Listing
June 2007