Publications by authors named "Ferah Armutçu"

69 Publications

The relationship between obstructive sleep apnea syndrome and obesity: A new perspective on the pathogenesis in terms of organ crosstalk.

Clin Respir J 2020 Jul 5;14(7):595-604. Epub 2020 Mar 5.

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

Introduction: Obstructive sleep apnea syndrome (OSAS) is a common disorder that has a major impact on public health. The connection between OSAS and obesity is very complex and likely represents an interaction between biological and lifestyle factors. Oxidative stress, inflammation and metabolic dysregulation are both actors involved in the pathogenesis of OSAS and obesity. Also, the current evidence suggests that gut microbiota plays a significant role in the emergence and progression of some metabolic disorders. When the relationship between OSAS and obesity is evaluated extensively, it is understood that they show mutual causality with each other, and that metabolic challenges such as impaired microbiota affect this bidirectional organ interaction, and by ensuing organ injury.

Objectives: The aim of this study is to investigate the association between OSAS and obesity, and the effect of "organ crosstalk" on the pathogenesis of the relationship and to contribute to the diagnosis and treatment options in the light of current data.

Data Source: We performed an electronic database search including PubMed, EMBASE and Web of Science. We used the following search terms: OSAS, obesity, inflammation, metabolic dysregulation and gut microbiota.

Conclusion: Obesity and OSAS adversely affect many organs and systems. Besides the factors affecting the diagnosis of the OSAS-obesity relationship, mutual organ interactions among the respiratory system, adipose tissue and intestines should not be ignored for prevention and treatment of OSAS and obesity. Comprehensive clinical trials addressing the efficacy and efficiency of current or potential treatments on therapeutic applications in the OSAS-obesity relationship are needed.
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http://dx.doi.org/10.1111/crj.13175DOI Listing
July 2020

Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions.

Authors:
Ferah Armutcu

Inflamm Res 2019 Oct 20;68(10):825-839. Epub 2019 Jul 20.

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

Background: Organ crosstalk can be defined as the complex and mutual biological communication between distant organs mediated by signaling factors. Normally, crosstalk helps to coordinate and maintain homeostasis, but sudden or chronic dysfunction in any organ causes dysregulation in another organ. Many signal molecules, including cytokines and growth factors, are involved in the metabolic dysregulation, and excessive or inappropriate release of these molecules leads to organ dysfunction or disease (e.g., obesity, type 2 diabetes).

Aim And Method: The aim of this review is to reveal the impact of organ crosstalk on the pathogenesis of diseases associated with organ interactions and the role of inflammatory and fibrotic changes in the organ dysfunction. After searching in MEDLINE, PubMed and Google Scholar databases using 'organ crosstalk' as a keyword, studies related to organ crosstalk and organ interaction were compiled and examined.

Conclusion: The organ crosstalk and the functional integration of organ systems are exceedingly complex processes. Organ crosstalk contributes to metabolic homeostasis and affects the inflammatory response, related pathways and fibrotic changes. As in the case of interactions between adipose tissue and intestine, stimulation of inflammatory mechanisms plays an active role in the development of diseases including insulin resistance, obesity, type 2 diabetes and hepatic steatosis. The increased level of knowledge about the 'crosstalk' between any organ and distant organs will facilitate the early diagnosis of the disease as well as the management of the treatment practices in the short- and long-term organ dysfunction.
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http://dx.doi.org/10.1007/s00011-019-01271-7DOI Listing
October 2019

Hypoxia causes important changes of extracellular matrix biomarkers and ADAMTS proteinases in the adriamycin-induced renal fibrosis model.

Nephrology (Carlton) 2019 Aug 9;24(8):863-875. Epub 2019 May 9.

Department of Biochemistry, Turgut Ozal University, Faculty of Medicine, Ankara, Turkey.

Aim: Renal fibrosis is a common cause of renal dysfunction with chronic kidney diseases. This process is characterized by excessive production of extracellular matrix (ECM) or inhibition of ECM degradation. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteinases, which are widely presented in mammals, have very critical roles in ECM remodelling. We aimed to study the role of ADAMTS proteinases and some of the ECM markers in the pathogenesis of renal fibrosis and to investigate the effects of hypoxia on these biomarkers.

Methods: In addition to the control group, Adriamycin (ADR) treated rats were divided into four groups as ADR, sham and two hypoxia groups. Renal nephropathy was assessed biochemical assays, pathological and immunohistochemical staining methods. The expression of ADAMTSs and mRNA were determined using Western blotting and real-time PCR, respectively.

Results: Renal dysfuntion and tissue damage in favour of ECM accumulation and renal fibrosis were observed in the ADR group. This was approved by remarkable changes in the expression of ADAMTS such as increased ADAMTS-1, -12 and -15. In addition, it was found that hypoxia and duration of hypoxia enhanced markers of tubulointerstitial fibrosis in the rat kidney tissues. Also, expression differences especially in ADAMTS-1, -6 and -15 were observed in the hypoxia groups. The variable and different expression patterns of ADAMTS proteinases in the ADR-induced renal fibrosis suggest that ADAMTS family members are involved in the development and progression of fibrosis.

Conclusion: The expression changes of ADAMTS proteinases in kidney and association with hypoxia have potential clues to contribute to the early diagnosis and treatment options of renal fibrosis.
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http://dx.doi.org/10.1111/nep.13572DOI Listing
August 2019

The role of electronegative low-density lipoprotein in cardiovascular diseases and its therapeutic implications.

Trends Cardiovasc Med 2017 05 19;27(4):239-246. Epub 2016 Nov 19.

Vascular & Medicinal Research, Texas Heart Institute, 6770 Bertner Avenue, MC 2-255, Houston, TX 77030, USA; Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Cardiovascular disease (CVD) is a health problem of great concern to both the public and medical authorities. Low-density lipoprotein (LDL) has been reported to play an important role in both the development and progression of CVD, but studies are underway to determine how LDL exerts its effects. In recent years, it has been found that LDL has several subfractions, each of which affects endothelial function differently; L5, the most electronegative fraction, has been shown to be unique in that it induces an atherogenic response. This review examines the current knowledge concerning the relationships between L5 and CVD and highlights the role of L5 in the pathophysiology of CVD, especially with regards to atherosclerosis.
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http://dx.doi.org/10.1016/j.tcm.2016.11.002DOI Listing
May 2017

Increased Exhaled 8-Isoprostane and Interleukin-6 in Patients with Helicobacter pylori Infection.

Helicobacter 2016 Oct 8;21(5):389-94. Epub 2016 Apr 8.

Department of Internal Medicine, Tatvan State Hospital, Bitlis, Turkey.

Background: Helicobacter pylori (H. pylori) infection triggers both local inflammation, usually in gastric mucosa, and chronic systemic inflammation. It is assumed that this local and systemic inflammation is caused by extracellular products excreted by H. pylori. The aim of this study was to investigate the possible association between H. pylori infection and a local inflammatory response in the airway by using exhaled breath condensate technique.

Materials And Methods: This study includes 41 H. pylori seropositive patients who have gastric symptoms and 27 healthy control subjects. Pulmonary function tests (PFT), chest X ray, and physical examination were performed in all patients and interleukin-6 (IL-6), 8-isoprostane and nitrotyrosine levels were measured in exhaled breath condensate.

Results: Levels of IL-6 and 8-isoprostane in exhaled breath condensate (EBC) were significantly higher in H. pylori positive patients than control subjects (p < 0.05). Nitrotyrosine levels were also higher in H. pylori positive patients but the difference was not statistically significant. Both groups had similar leukocyte counts, C-reactive protein (CRP) levels and PFT parameters.

Conclusion: H. pylori infection causes an asymptomatic airway inflammation which can be detected by exhaled breath condensate. The clinical importance of this inflammation remains unclear.
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http://dx.doi.org/10.1111/hel.12302DOI Listing
October 2016

Melatonin and caffeic acid phenethyl ester in the regulation of mitochondrial function and apoptosis: The basis for future medical approaches.

Life Sci 2016 Mar 16;148:305-12. Epub 2016 Jan 16.

Vascular & Medicinal Research, Wafic Said Molecular Cardiology Research Laboratories, Texas Heart Institute, Houston, TX, United States; Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

The aim of this review article is to summarize and compare the effects of melatonin and caffeic acid phenethyl ester (CAPE) on the relationship between mitochondrial functioning and apoptosis. References in this article were selected with an approach based on a comprehensive literature review by using MEDLINE/PubMed and Google Scholar databases which were scanned in the last six months without any restrictions. For each database, the review terms used are 'melatonin', 'caffeic acid phenethyl ester, both together and associated with other key words such as apoptosis and mitochondria. Evidential mitochondrial molecular backgrounds for diseases make these two molecule competitors, since both of them use the same pathways to cope with fundamentals of the diseases such as nuclear factor κ-light-chain-enhancer of activated B (NF-κB inhibition, induction of mitochondrial apoptosis in cancer cells, free radical scavenging effects, and antioxidant activities. The data reviewed in this paper provide a useful background for the understanding of some molecular details of melatonin and CAPE on several medical situation and diseases. Mutual usage of these two tremendous molecules might have a capacity to open new therapeutic approaches in near future.
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http://dx.doi.org/10.1016/j.lfs.2016.01.026DOI Listing
March 2016

The comparison of caffeic acid and caffeic acid phenethyl ester against cisplatin-induced hair cell damage.

Int J Pediatr Otorhinolaryngol 2016 Feb 29;81:103-4. Epub 2015 Dec 29.

Vascular & Medicinal Research, Wafic Said Molecular Cardiology Research Laboratories, Texas Heart Institute, Houston, Texas; Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.1016/j.ijporl.2015.12.009DOI Listing
February 2016

Indices of Central and Peripheral Obesity; Anthropometric Measurements and Laboratory Parameters of Metabolic Syndrome and Thyroid Function.

Balkan Med J 2015 Oct 1;32(4):414-20. Epub 2015 Oct 1.

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

Background: Metabolic syndrome (MetS) and obesity are serious health problems in the World, including Turkey. Contemporary studies have suggested a meaningful association between insulin resistance (IR), MetS parameters, and thyroid function tests.

Aims: We aimed to elucidate the impact of fat distribution on the anthropometric and laboratory parameters, especially indices of MetS, IR and thyroid function, in obese women.

Study Design: Cross-sectional study.

Methods: Anthropometric measurements of all participants and biochemical tests in their serum samples were performed.

Results: Weight, waist circumference (WC), body mass index (BMI), and other parameters of fat distribution were significantly increased in all obese compared to control subjects; but there was no significant difference between central and peripheral obese groups. The central obese group had significantly higher insulin levels, components of MetS, the ratio free triiodothyronine (fT3) to free thyroxin fT4, and fT4 than those of peripheral obese and control groups.

Conclusion: Elevated triglyceride, glucose and insulin levels may be associated with increased IR, which in turn is related to MetS. Body fat composition may affect thyroid tests in the obese; the changes in fT3/fT4 could be the consequence of fat distribution.
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http://dx.doi.org/10.5152/balkanmedj.2015.151218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692343PMC
October 2015

The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis.

Inflammation 2016 Apr;39(2):700-5

Department of Biochemistry, Medical Faculty, Namik Kemal University, Namık Kemal Mahallesi Kampus Caddesi No:1, 59100, Merkez-Tekirdag, Turkey.

Experimental studies indicate that sepsis causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative damage, and inflammation on lung injury, following sepsis model by cecal ligation and puncture, and the effects of quercetin, antioxidant, and anti-inflammatory flavonoid, in the lung tissue were investigated. In the present study, we found that administration of single-dose quercetin before cecal ligation and puncture procedure, while markedly diminishing the levels of YKL-40 and oxidant molecules (xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA)), increases the antioxidant enzymes levels. Quercetin is beneficial to acute lung injury by decreasing the levels of oxidative stress markers and increasing the antioxidant enzyme activities. Quercetin also causes a decrease in the serum levels of YKL-40 and periostin in the oxidative lung injury induced by the experimental sepsis model.
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http://dx.doi.org/10.1007/s10753-015-0296-9DOI Listing
April 2016

Antiviral properties of caffeic acid phenethyl ester and its potential application.

J Intercult Ethnopharmacol 2015 Oct-Dec;4(4):344-7. Epub 2015 Nov 5.

Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Caffeic acid phenethyl ester (CAPE) is found in a variety of plants and well-known the active ingredient of the honeybee propolis. CAPE showed anti-inflammatory, anticarcinogenic, antimitogenic, antiviral, and immunomodulatory properties in several studies. The beneficial effects of CAPE on different health issues attracted scientists to make more studies on CAPE. Specifically, the anti-viral effects of CAPE and its molecular mechanisms may reveal the important properties of virus-induced diseases. CAPE and its targets may have important roles to design new therapeutics and understand the molecular mechanisms of virus-related diseases. In this mini-review, we summarize the antiviral effects of CAPE under the light of medical and chemical literature.
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http://dx.doi.org/10.5455/jice.20151012013034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665029PMC
December 2015

In vitro and in vivo neuroprotective effect of caffeic acid phenethyl ester.

J Intercult Ethnopharmacol 2015 Jul-Sep;4(3):192-3. Epub 2015 Jun 26.

Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.5455/jice.20150620024326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579495PMC
September 2015

Comment on 'Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model' by Choi J.H. et al. [Exp. Eye Res. 134 (2015) 53-62].

Exp Eye Res 2015 Sep 10;138:124-5. Epub 2015 Jul 10.

Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.1016/j.exer.2015.07.003DOI Listing
September 2015

Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review).

Exp Ther Med 2015 May 11;9(5):1582-1588. Epub 2015 Mar 11.

Department of Biochemistry, Medical Faculty, Fatih University, Istanbul 34500, Turkey.

Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent and study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-κB (NF-κB) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-κB represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects.
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http://dx.doi.org/10.3892/etm.2015.2346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471667PMC
May 2015

The possible preventive effect of caffeic acid phenethyl ester (CAPE) against myringosclerosis.

Eur Arch Otorhinolaryngol 2016 Mar 24;273(3):789-90. Epub 2015 Jun 24.

Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.1007/s00405-015-3690-xDOI Listing
March 2016

The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome.

Arch Gynecol Obstet 2014 Nov 20;290(5):929-35. Epub 2014 May 20.

Department of Endocrinology, Regional Education and Research Hospital, Erzurum, Turkey.

Purpose: To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients.

Methods: Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann-Whitney U tests were used for statistical analysis.

Results: PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group.

Conclusion: In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.
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http://dx.doi.org/10.1007/s00404-014-3275-8DOI Listing
November 2014

Markers in nonalcoholic steatohepatitis.

Adv Clin Chem 2013 ;61:67-125

Department of Biochemistry, Medical Faculty, Turgut Ozal University, Ankara, Turkey.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide, encompasses a spectrum of abnormal liver histology ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Population studies show that NAFLD is strongly associated with insulin resistance, obesity, type 2 diabetes mellitus, and lipid abnormalities. In the context of hepatic steatosis, factors that promote cell injury, inflammation, and fibrosis include oxidative stress, early mitochondrial dysfunction, endoplasmic reticulum stress, iron accumulation, apoptosis, adipocytokines, and stellate cell activation. The exact NASH prevalence is unknown because of the absence of simple noninvasive diagnostic tests. Although liver biopsy is the "gold standard" for the diagnosis of NASH, other tests are needed to facilitate the diagnosis and greatly reduce the requirement for invasive liver biopsy. In addition, the development of new fibrosis markers in NASH is needed to facilitate the assessment of its progression and the effectiveness of new therapies. The aim of this chapter, which is overview of biomarkers in NASH, is to establish a systematic approach to laboratory findings of the disease.
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http://dx.doi.org/10.1016/b978-0-12-407680-8.00004-xDOI Listing
November 2013

The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis.

Redox Rep 2013 5;18(4):127-33. Epub 2013 Jun 5.

Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common underlying causes of chronic liver injury. They are associated with a wide spectrum of hepatic disorders including basic steatosis, steatohepatitis, and cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in NAFLD and NASH are still unknown. This review describes the roles of oxidative stress and inflammatory responses in the pathogenesis of NAFLD and its progression to NASH.
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http://dx.doi.org/10.1179/1351000213Y.0000000050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837573PMC
February 2014

In vivo and in vitro antıneoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives.

Nutr Cancer 2013 ;65(4):515-26

Turgut Ozal University Vocational School of Medical Sciences, Division of Medical Laboratory Techniques, Ankara, Turkey.

Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at μM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.
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http://dx.doi.org/10.1080/01635581.2013.776693DOI Listing
December 2013

ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse.

Neurosci Lett 2013 Jun 2;544:25-30. Epub 2013 Apr 2.

Department of Medical Biology, Turgut Ozal University School of Medicine, Ankara, Turkey.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS) has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI.
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http://dx.doi.org/10.1016/j.neulet.2013.02.064DOI Listing
June 2013

APRI, the FIB-4 score, and Forn's index have noninvasive diagnostic value for liver fibrosis in patients with chronic hepatitis B.

Eur J Gastroenterol Hepatol 2013 Sep;25(9):1076-81

Departments of aClinical Biochemistry bPathology cGastroenterology, Diskapi Yildirim Beyazit Training and Research Hospital dDepartment of Clinical Biochemistry, Numune Training and Research Hospital eDepartment of Clinical Biochemistry, Faculty of Medicine, Fatih University fDepartment of Gastroenterology, Ankara Training and Research Hospital, Ankara, Turkey.

Objectives: The aim of this study was to evaluate the potential use of serum transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), fetuin-A, and fibroblast growth factor 21 (FGF21) in the detection of liver fibrosis in patients with chronic hepatitis B (CHB). The value of the noninvasive fibrosis models - that is, the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on the four factors (FIB-4) score, and Forn's index - was also examined.

Materials And Methods: CHB patients who underwent liver biopsy for the evaluation of fibrosis were included in the study. A total of 73 patients were divided into two groups according to their METAVIR scores (F0-1, no/minimal fibrosis; F2-4, significant fibrosis). Serum levels of TGF-β1, TIMP-1, fetuin-A, and FGF21 were measured besides APRI, FIB-4, and Forn's scores. The area under the receiver operating characteristic curve was measured for each parameter, followed by calculation of sensitivity, specificity, and positive and negative predictive values.

Results: APRI, FIB-4, and Forn's index scores were significantly higher in patients with significant fibrosis (P<0.05). There was no difference between no/minimal fibrosis and significant fibrosis groups in terms of serum levels of TGFβ-1, TIMP-1, fetuin-A, and FGF21 (P>0.05). The areas under the receiver operating characteristic curve for TGF-β1, TIMP-1, fetuin-A, FGF21, APRI, FIB-4, and Forn's index were 0.445, 0.483, 0.436, 0.585, 0.662, 0.687, and 0.680, respectively.

Conclusion: Our results suggest that serum TGF-β1, TIMP-1, fetuin-A, and FGF21 are not useful for the assessment of the extent of liver fibrosis in CHB in this patient group. However, APRI, FIB-4, and Forn's index have a better diagnostic value in patients with significant fibrosis than in those with no/minimal fibrosis.
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http://dx.doi.org/10.1097/MEG.0b013e32835fd699DOI Listing
September 2013

Protective effects of Ankaferd blood stopper on aspirin-induced oxidative mucosal damage in a rat model of gastric injury.

Toxicol Ind Health 2014 Nov 31;30(10):888-95. Epub 2012 Oct 31.

Department of Biochemistry, Faculty of Medicine, Fatih University, Ankara, Turkey

The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats.
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http://dx.doi.org/10.1177/0748233712466134DOI Listing
November 2014

Influence of CPAP treatment on airway and systemic inflammation in OSAS patients.

Sleep Breath 2014 May 4;18(2):251-6. Epub 2012 Sep 4.

Department of Respiratory Medicine, Fatih University Medical School, Ankara, Turkey.

Aim: Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent respiratory disorders in the upper airways during sleep. Although continuous positive airway pressure (CPAP) has been accepted to be the most effective treatment for OSAS, its role on inflammation remains debatable. In this study, our aim was to examine the influence of 3 months of CPAP treatment on tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), 8-isoprostane, and peroxynitrite levels in exhaled breathing condensates (EBC) and serum.

Methods: Thirty-five patients who were newly diagnosed as moderate or severe OSAS with full night polysomnography and used CPAP therapy regularly for 3 months were included in the study. Polysomnography, spirometric tests, fasting blood samples, and EBC were ascertained on entry into the study and after 3 months of treatment. All patients were assessed monthly for treatment adherence and side effects.

Results: We found that all polysomnographic parameters were normalized after CPAP therapy in the control polysomnogram. Also, all markers in EBC and nitrotyrosine and 8-isoprostane levels in serum were decreased significantly with CPAP treatment. Sedimentation rate, C-reactive protein, IL-6, and TNF-α remained unchanged in serum after treatment. We found that baseline nitrotyrosine levels were significantly correlated with apnea-hypopnea index, oxygen desaturation index, and percent time in SpO2 < 90 % (p < 0.01).

Conclusions: CPAP therapy has primarily a relevant impact on airways, and nitrotyrosine levels correlated well with severity of OSAS. This treatment decreases both inflammation and oxidative stress levels in airways in OSAS patients. Also, this treatment helps to decrease systemic oxidative stress levels in serum.
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http://dx.doi.org/10.1007/s11325-012-0761-8DOI Listing
May 2014

Lymphocyte subpopulations in Sheehan's syndrome.

Pituitary 2013 Jun;16(2):202-7

Department of Endocrinology and Metabolism, Ondokuz Mayis University Medical School, Kurupelit 55139, Samsun, Turkey.

The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p < 0.001), CD8(+)28(+) (p = 0.030), CD4(+)CD25(+) (p = 0.007), the ratio of CD3 (+) DR(+)/CD3 (p < 0.001) were higher; the percentage of CD3 (p = 0.020), CD4 (p < 0.001) and the ratio of CD4/CD8 (p = 0.006) were lower in patients with Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.
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http://dx.doi.org/10.1007/s11102-012-0405-9DOI Listing
June 2013

Effect of resveratrol on treatment of bleomycin-induced pulmonary fibrosis in rats.

Inflammation 2012 Oct;35(5):1732-41

Department of Pulmonary Diseases, Ordu State Hospital, Ordu, Turkey.

Resveratrol has a preventive potential on bleomycin-induced pulmonary fibrosis in prophylactic use; however, it was not studied in the treatment of the fibrosis. This study investigated the role of resveratrol on the treatment of bleomycin-induced pulmonary fibrosis. Intratracheal bleomycin (2.5 mg/kg) was given in fibrosis groups and saline in controls. First dose of resveratrol was given 14 days after bleomycin and continued until sacrifice. On 29th day, fibrosis in lung was estimated by Aschoft's criteria and hydroxyproline content. Bleomycine increased the fibrosis score (3.70 ± 1.04) and hydroxyproline levels (4.99 ± 0.90 mg/g tissue) as compared to control rats (1.02 ± 0.61 and 1.88 ± 0.59 mg/g), respectively. These were reduced to 3.16 ± 1.58 (P = 0.0001) and 3.08 ± 0.73 (P > 0.05), respectively, by resveratrol. Tissue malondialdehyde levels in the bleomycin-treated rats were higher (0.55 ± 0.22 nmol/mg protein) than that of control rats (0.16 ± 0.07; P = 0.0001) and this was reduced to 0.16 ± 0.06 by resveratrol (P = 0.0001). Tissue total antioxidant capacity is reduced (0.027 ± 0.01) by bleomycine administration when compared control rats (0.055 ± 0.012 mmol Trolox Equiv/mg protein; P = 0.0001) and increased to 0.041 ± 0.008 (P = 0.001) by resveratrol. We concluded that resveratrol has some promising potential on the treatment of bleomycin-induced pulmonary fibrosis in rats. However, different doses of the drug should be further studied.
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http://dx.doi.org/10.1007/s10753-012-9491-0DOI Listing
October 2012

The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity.

Cell Biochem Funct 2012 Jul 20;30(5):438-43. Epub 2012 Mar 20.

Department of Biochemistry, Fatih University Medical School, Ankara, Turkey.

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.
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http://dx.doi.org/10.1002/cbf.2817DOI Listing
July 2012

Investigation of oxidative balance in patients with dysmenorrhea by multiple serum markers.

J Turk Ger Gynecol Assoc 2012 1;13(4):233-6. Epub 2012 Dec 1.

Department of Biochemistry, Faculty of Medicine, Fatih University, Ankara, Turkey.

Objective: To investigate the level of oxidative stress in patients with dysmenorrhea by multiple serum markers including malondialdehyde (MDA), nitrotyrosine (3-NT), deoxyguanosine (8-OHdG) and superoxide dismutase (SOD).

Material And Methods: Fifty-eight women, aged between 20 and 34, who had had regular menses for at least six previous cycles, were involved. The women were divided into two groups. The study group consisted of 33 patients with primary dysmenorrhea, and the control group consisted of 25 healthy women.

Results: Demographic characteristics of patients were similar between the two groups. The serum MDA levels were 1.32±0.46 and 0.91±0.26 nmol/mL for the dysmenorrhea and control groups, respectively (p<0.001). The differences in plasma levels of 3-NT, SOD and serum 8-OhdG were similar in both groups (p>0.05). Also, no correlation was found between the severity of dysmenorrhea and the levels of oxidative markers.

Conclusion: Oxidative stress is slightly aggravated in patients with dysmenorrhea.
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http://dx.doi.org/10.5152/jtgga.2012.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881713PMC
March 2014

Association of serum calcitonin with coronary artery disease in individuals with and without chronic kidney disease.

Int Urol Nephrol 2012 Aug 1;44(4):1169-75. Epub 2011 Dec 1.

Department of Medicine, Division of Nephrology, Fatih University School of Medicine, Ankara, Turkey.

Background: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Recent data implicate disordered bone and mineral metabolism, including changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and fetuin A, as novel risk factors for arterial calcification. The potential role of calcitonin, another hormonal regulator of mineral and bone metabolism, has not been studied in detail.

Materials And Methods: We investigated the link between serum calcitonin and the total burden of coronary artery disease (CAD) using the validated Gensini score, in a cross-sectional study of 88 patients with estimated GFR (eGFR) between 46 and 87 ml/min/1.73 m² who underwent coronary angiography. We evaluated the associations between serum calcitonin, minerals (calcium, phosphate), calcium × phosphate product, and other factors that regulate mineral metabolism (intact PTH, 25-OH-vitamin D, FGF-23, and fetuin A) and the severity of CAD.

Results: The mean serum calcitonin was 11.5 ± 7.8 pg/ml. In univariate analysis, the Gensini CAD severity score correlated significantly with male gender, eGFR, and serum levels of 25-OH-vitamin D, iPTH, FGF-23, fetuin A, and calcitonin (R = 0.474, P = 0.001 for the latter). In multivariate analysis adjusted for calcium, phosphate, 25-OH-vitamin D, iPTH, FGF 23, fetuin A, and calcitonin, only calcitonin (β = 0.20; P = 0.03), FGF-23, fetuin A, and 25-OH-vitamin D emerged as independent predictors of Gensini score. In the second step, we adjusted for the presence of traditional risk factors, proteinuria, and GFR. After these adjustments, the FGF-23 and fetuin A remained statistically significant predictors of the Gensini score, while calcitonin did not.

Conclusions: Our study suggests that, in addition to other well-known components of mineral metabolism, increased calcitonin levels are associated with greater severity of CAD. However, this relation was not independent of traditional and nontraditional cardiovascular risk factors. Longitudinal studies in larger populations including patients with more advanced CKD are needed.
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http://dx.doi.org/10.1007/s11255-011-0076-xDOI Listing
August 2012

Some inflammatory cytokine levels, iron metabolism and oxidan stress markers in subjects with nonalcoholic steatohepatitis.

Clin Biochem 2011 Dec 8;44(17-18):1375-9. Epub 2011 Oct 8.

Fatih University Medical Faculty, Department of Biochemistry, Turkey.

Objectives: The relation between nonalcoholic steatohepatitis and iron metabolism is still controversial. Free fatty acids, iron, and other sources of oxidative stress probably result in cell damage, and necroinflammation mediated by various cytokines.

Design And Methods: Sixty patients were diagnosed with NASH were included in the study, and the patient group was divided into three subgroups. Iron metabolism markers, inflammatory cytokines, including TNF-α, IL-6 and IL-8, MDA and nitric oxide levels were measured.

Results: Serum ferritin, inflammatory cytokines, and oxidative stress markers were significantly higher in the patient group. Among three patient groups, divided according to the results of ultrasonic examination, there were significant changes with regard to these parameters.

Conclusion: The study results suggest that liver iron and fat accumulation, oxidant stres, and inflammatory cytokines are closely related. Therefore, levels of serum ferritin, MDA, IL-6, TNF-α and IL-8 could represent the indices of activity and progression of NASH.
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http://dx.doi.org/10.1016/j.clinbiochem.2011.09.017DOI Listing
December 2011

Uric acid and pentraxin-3 levels are independently associated with coronary artery disease risk in patients with stage 2 and 3 kidney disease.

Am J Nephrol 2011 10;33(4):325-31. Epub 2011 Mar 10.

Division of Nephrology, Department of Medicine, Fatih University School of Medicine, Ankara, Turkey.

Background And Objectives: Cardiovascular disease is prevalent in chronic kidney disease (CKD). Uric acid is increased in subjects with CKD and has been linked with cardiovascular mortality in this population. However, no study has evaluated the relationship of uric acid with angiographically proven coronary artery disease (CAD) in this population. We therefore investigated the link between serum uric acid (SUA) levels and (i) extent of CAD assessed by the Gensini score and (ii) inflammatory parameters, including C-reactive protein (CRP) and pentraxin-3, in patients with mild-to-moderate CKD.

Material And Methods: In an unselected population of 130 patients with estimated glomerular filtration rate (eGFR) between 90 and 30 ml/min/1.73 m(2), we measured SUA, serum pentraxin-3, CRP, urinary protein-to-creatinine ratio, lipid parameters and the severity of CAD as assessed by coronary angiography and quantified by the Gensini lesion severity score.

Results: The mean serum values for SUA, pentraxin-3 and CRP in the entire study population were 5.5 ± 1.5 mg/dl, 6.4 ± 3.4 ng/ml and 3.5 ± 2.6 mg/dl, respectively. The Gensini scores significantly correlated in univariate analysis with gender (R = -0.379, p = 0.02), uric acid (R = 0.42, p = 0.001), pentraxin-3 (R = 0.54, p = 0.001), CRP (R = 0.29, p = 0.006) levels, eGFR (R = -0.33, p = 0.02), proteinuria (R = 0.21, p = 0.01), and presence of hypertension (R = 0.37, p = 0.001), but not with smoking status, diabetes mellitus, and lipid parameters. After adjustments for traditional cardiovascular risk factors, only uric acid (R = 0.21, p = 0.02) and pentraxin-3 (R = 0.28, p = 0.01) remained significant predictors of the Gensini score.

Conclusions: SUA and pentraxin-3 levels are independent determinants of severity of CAD in patients with mild-to-moderate CKD. We recommend a clinical trial to determine whether lowering uric acid could prevent progression of CAD in patients with CKD.
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http://dx.doi.org/10.1159/000324916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064941PMC
August 2011

Association of serum fetuin-A with valvular calcium concentration in rheumatic mitral valve disease.

J Heart Valve Dis 2010 Sep;19(5):636-43

Department of Cardiology, Türkiye Yuksek Ihtisas Hospital, Ankara, Turkey.

Background And Aim Of The Study: Fetuin-A is an acute-phase glycoprotein that inhibits ectopic calcification. The study aim was to assess serum fetuin-A levels in patients with rheumatic mitral valve disease (RMVD), and to evaluate the association of fetuin-A with the extent of mitral valve calcification, determined either echocardiographically or by the measurement of calcium and phosphorus concentrations in the resected valve tissues.

Methods: The study group comprised 21 patients (14 females, seven males; mean age 48 +/- 12.4 years) with RMVD, who were scheduled for mitral valve replacement surgery, while 30 age- and gender-matched healthy subjects (17 females, 13 males; mean age 43.6 +/- 11.1 years) served as a control group. Baseline serum fetuin-A levels were measured using ELISA, and high-sensitivity C-reactive protein (hs-CRP) levels using immunonepholometry. A Wilkins score was calculated using transesophageal echocardiography, and the resected valve tissues were analyzed for concentrations of calcium and phosphorus.

Results: Serum fetuin-A levels were lower and hs-CRP levels higher in the study group than in controls (300.4 +/- 92.5 microg/ml versus 352.6 +/- 55.3 microg/ml, p = 0.028; and 1.9 +/- 1.2 mg/dl versus 0.3 +/- 0.2 mg/dl, p < 0.0001, respectively). An inverse correlation was found between serum fetuin-A and hs-CRP levels (r = -0.690, p = 0.001). A significant association of either serum fetuin-A or hs-CRP was also found to occur with calcium concentration in the mitral valve tissue (r = -0.684, p = 0.001, and r = 0.510, p = 0.018, respectively), but not with the Wilkins calcium score. Serum fetuin-A and phosphorus concentrations in the MV tissue were independent predictors of calcium concentration in the MV tissue.

Conclusion: Serum fetuin-A, which is significantly decreased in patients with RMVD, is an independent predictor of calcium concentration in the mitral valve tissue.
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September 2010